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Infertility is a serious concern that affects 1 in 4 couples of reproductive age, with increasing incidence correlated with increased age (Crawford & Steiner, 2015; Lobo, 2017). Commonly infertility is considered to be a diagnosis for couples who have not achieved pregnancy after 1 year of regular, unprotected intercourse when the woman is less than 35 years of age or after 6 months when the woman is older than 35 years of age. Fecundity is the term used to describe the chance of achieving pregnancy and subsequent live birth within one menstrual cycle. Fecundity averages 20% in couples who are not experiencing reproductive problems (American Society of Reproductive Medicine [ASRM], 2012).
Probable causes of infertility include the trend toward delaying pregnancy until later in life, a time when fertility decreases naturally and the prevalence of diseases such as endometriosis and ovulatory dysfunction increases. Questions exist regarding whether there has been an increase in male infertility or whether male infertility is more readily identified because of improvements in diagnosis.
For the couple experiencing infertility, diagnosis and treatment strategies require considerable physical, emotional, and financial investment over an extended period of time. Feelings connected with infertility are many and complex, often interfering with quality of life. It is common for infertile couples to experience anxiety from the need to undergo many tests and examinations and from a perception of feeling “different” from their fertile friends and relatives. The following four goals provide a framework for nurses who care for infertile persons:
• Provide the couple with accurate information about human reproduction, infertility treatments, and prognosis for pregnancy. Dispel any myths or inaccuracies from friends or the mass media that the couple may believe to be true.
• Help the couple and the health care team accurately identify and treat possible causes of infertility.
• Provide emotional support. The couple may benefit from anticipatory guidance, counseling, and support group meetings, either face-to-face or online. The organization RESOLVE (www.resolve.org) provides online support, advocacy, and education about infertility for both the infertility community and health care providers.
• Guide and educate those who fail to conceive biologically about other forms of treatment such as in vitro fertilization (IVF), donor eggs or semen, surrogate motherhood, and adoption. Support the couple in their decisions regarding their future family.
It is important for nurses to encourage all healthy women and men to maintain a normal body mass index (BMI) and avoid sexually transmitted infections (STIs) and exposures to substances or habits (such as smoking) that impair reproductive ability. While these health-promoting activities will not ensure fertility, they will enhance overall health as the individual or couple is coping with the stresses of infertility.
Factors Associated With Infertility
Although exact percentages vary somewhat with populations, approximately 85% to 90% of couples seeking infertility care are treated with medication or surgery, with 3% being treated with in vitro fertilization or other assisted reproductive methods (ASRM, 2016). About 40% of infertility is related to a male factor or a combined male and female factor (ASRM, 2016). About 20% of infertility is unexplained (Lobo, 2017). For those couples and individuals for whom a specific cause of infertility is not detected, the focus of infertility treatment has shifted from attempting to correct a specific pathology to recommending and initiating the treatment that is most effective in achieving pregnancy for this unique couple at this time in their reproductive life span. Assisted reproductive technologies (ARTs) have proven to be effective, even in couples who experience unexplained infertility.
Unassisted human conception requires a normally developed reproductive tract in both the male and female partners. For simplification, each live birth necessitates synchronization of the following:
• The male must deposit semen with sperm that has the capacity to fertilize an egg close to the cervix at the time of ovulation. The sperm must be able to ascend through the uterus and uterine tubes (male factor). The cervix must be sufficiently open to allow semen to enter the uterus and provide a nurturing environment for sperm (cervical factor).
• The uterine tubes must be able to capture the ovum, transport semen to the ovum, and transport the fertilized embryo to the uterus (tubal factor).
• Ovulation of a healthy oocyte must occur, ideally within the parameters of a regular, predictable menstrual cycle (ovarian factor).
• The uterus must be receptive to implantation of the embryo and capable of nourishing the growth and development of the fetus throughout the normal duration of pregnancy (uterine factor).
An alteration in one or more of these structures, functions, or processes results in some degree of impaired fertility. Boxes 5.1 and 5.2 list factors affecting female and male infertility.
Factors Affecting Female Fertility
• Developmental anomalies
• Pituitary or hypothalamic hormone disorders
• Adrenal gland disorders (rare)
• Congenital adrenal hyperplasia (rare)
• Disruption of hypothalamic-pituitary-ovarian axis
• Insufficient body fat in athletic women
• Increased prolactin levels
• Thyroid disorders
• Premature ovarian failure
• Polycystic ovary syndrome
• Oral contraceptives
• Antidepressant and antipsychotic drugs
• Developmental anomalies of the tubes (see Fig. 5.1)
FIG 5.1 Abnormal uterus. A, Complete bicornuate uterus with vagina divided by a septum. B, Complete bicornuate uterus with normal vagina. C, Partial bicornuate uterus with normal vagina. D, Unicornuate uterus.
• Reduced tubal motility
• Inflammation within the tube
• Tubal adhesions
• Disruption caused by tubal pregnancy
• Developmental anomalies of the uterus (see Fig. 5.1)
• Endometrial and myometrial fibroid tumors
• Asherman’s syndrome (uterine adhesions or scar tissue)
• Vaginal-cervical infections
• Cervical mucus inadequate
• Isoimmunization (development of sperm antibodies)
• Nutritional deficiencies
• Thyroid dysfunction (hyperthyroidism and hypothyroidism)
• Idiopathic conditions
Factors Affecting Male Fertility
• Congenital disorders
• Tumors of the pituitary gland or hypothalamus
• Trauma to the pituitary gland or hypothalamus
• Excess of androgens, estrogen, or cortisol
• Drugs and substance abuse (recreational and prescribed drugs)
• Chronic illnesses
• Nutritional deficiencies
• Endocrine disorders (e.g., diabetes)
• Congenital disorders
• Undescended testes
• Viral infections (e.g., mumps)
• Sexually transmitted infections (e.g. gonorrhea, chlamydial infection)
• Obstructive lesions of the epididymis and vas deferens
• Environmental toxins
• Systemic illnesses
• Antisperm antibodies
• Changes in sperm from cigarette smoking or use of heroin, marijuana, amyl nitrate, butyl nitrate, ethyl chloride, or methaqualone
• Decrease in libido from use of heroin, methadone, selective serotonin reuptake inhibitors, or barbiturates
• Impotence from use of alcohol or antihypertensive medications
Factors Associated With Sperm Transport
• Sexually transmitted infections of the epididymis
• Ejaculatory dysfunction
• Premature ejaculation
Idiopathic Male Infertility
For conception to occur, both partners must have normal, intact hypothalamic-pituitary-gonadal hormonal axes that support the formation of sperm in the male and ova in the female. Sperm can remain viable within a woman’s reproductive tract for at least 3 days and for as long as 5 days. The oocyte can only be successfully fertilized for 12 to 24 hours after ovulation. The couple seeking pregnancy should be taught about the menstrual cycle and ways to detect ovulation (see Chapter 3). They should be counseled to have intercourse 2 to 3 times a week; or, if timed intercourse does not increase anxiety, they should be encouraged to engage in intercourse the day before and the day of ovulation. Fertility decreases markedly 24 hours after ovulation.
Infertility care management includes a team of health care providers, including an obstetric care provider, fertility specialist, embryologist, genetic counselor, and mental health provider or counselor. The nurse is a key member of the care management team and assists in the assessment and education of the infertile couple. As part of the assessment process, he or she obtains information from the couple through interview and physical examination, including if this couple’s situation is one of primary (never experienced pregnancy) or secondary (previous pregnancy) infertility. Religious, cultural, and ethnic data may place restrictions on use of available treatments.
In addition, the nurse obtains and monitors results of diagnostic testing. Some of the information and data needed to investigate impaired fertility are of a sensitive, personal nature. The couple may experience feelings of invasion of privacy, and the nurse must exercise tact and express concern for their well-being throughout the interview. The tests and examinations associated with infertility diagnosis and treatment are occasionally painful and often intrusive. The couple’s intimacy and feelings of romantic attachment are often impaired as they engage in this process. A high level of motivation is needed to endure the investigation and subsequent treatment. Because multiple factors involving both partners are common, the investigation of impaired fertility is conducted systematically and simultaneously for both male and female partners. Both partners must be interested in the solution to the problem. The medical investigation requires time (3 to 4 months) and considerable financial expense. Box 5.3 describes the status of insurance coverage for infertility treatment.
Insurance Coverage for Infertility
As of October 2016, only 15 states had mandated some form of insurance coverage for infertility. These mandates included in vitro fertilization in some states, whereas others only covered some diagnostic tests. Some states require health maintenance organizations (HMOs) to cover some costs, whereas in others HMOs are exempt. Patients need information about what they can expect from their insurers. The state Insurance Commissioner’s office can provide information about an individual state. The website for the American Society for Reproductive Medicine (www.asrm.org) has more complete information.
Assessment of Female Infertility
Evaluation for infertility should be offered to couples who have failed to become pregnant after 1 year of regular intercourse or after 6 months if the woman is older than 35 years of age. Investigation of impaired fertility begins for the woman with a complete history and physical examination. A complete general physical examination should include height and weight and estimation of BMI. Both obesity and being underweight are associated with anovulation disorders. Signs and symptoms of androgen excess such as excess body hair or pigmentation changes should be noted. The general physical examination is followed by a specific assessment of the reproductive tract. A history of infections of the genitourinary tract and any signs of infections, especially STIs that could impair tubal patency, should be assessed. Bimanual examination of internal organs may reveal lack of mobility of the uterus or abnormal contours of the uterus and tubes. A woman may have an abnormal uterus and tubes as a result of congenital abnormalities during fetal development). These uterine abnormalities increase risk for early pregnancy loss.
Laboratory data, including routine urine and blood tests, are collected. The initial clinic visit serves as a preconceptional visit and as initial assessment of possible causes of infertility. The woman should be taking folic acid supplements, and all immunizations should be current to prepare for possible pregnancy.
The basic infertility survey of the female involves evaluation of the cervix, uterus, tubes, and peritoneum; detection of ovulation; and hormone analysis. Timing and descriptions of common tests are presented in Table 5.1.
General Tests for Impaired Fertility
Test or Examination
Timing (Menstrual Cycle Days)
Hysterosalpingogram (HSG) (uterine abnormalities, tubal patency)
Late follicular, early proliferative phase; will not disrupt a fertilized ovum; may open uterine tubes before time of ovulation
Chlamydia immunoglobulin G antibodies (tubal patency)
Negative antibody test may indicate tubal patency assessment (HSG); not needed in low-risk women
Hysterosalpingo-contrast sonography (uterine abnormalities, tubal patency)
Late follicular, early proliferative phase; will not disrupt a fertilized ovum; evaluates tubal patency, uterine cavity, and myometrium
Serum progesterone (ovulation)
7 days before expected menses
Midluteal-phase progesterone levels; check adequacy of corpus luteum progesterone production
Assessment of cervical mucus (ovulation)
Cervical mucus should have low viscosity, spinnbarkeit (ability to stretch) during ovulation
Basal body temperature (ovulation)
Chart entire cycle
Elevation occurs in response to progesterone; documents ovulation
Urinary ovulation predictor kit (ovulation)
Detects timing of lutein hormone surge before ovulation
Semen analysis (male factor)
2–7 days after abstinence
Detects ability of sperm to fertilize egg
Sperm penetration assay (male factor)
After 2 days but ≤1 week of abstinence
Evaluates ability of sperm to penetrate egg
Follicle-stimulating hormone (FSH) level (ovarian reserve)
High FSH levels (>20) indicate that pregnancy will not occur with woman’s own eggs; value <10 indicates adequate ovarian reserve
Clomiphene citrate challenge test (CCCT) (ovarian reserve)
Administer clomiphene 100 mg days 5 through 9
Assess FSH on days 3 and 10 in presence of clomiphene stimulation; high FSH levels (>20) indicate that pregnancy will not occur with woman’s own eggs; FSH <15 suggestive of adequate ovarian reserve
From Genetics & IVF Institute. (2013). Fertility: Clomiphene citrate test. Retrieved from http://www.givf.com/fertility/clomidchallengetest.shtml.
Previous status regarding ovulation can be evaluated through menstrual history, serum hormone studies, and use of an ovulation predictor kit. If the woman is older than 35 years of age, the clinician may choose to assess “ovarian reserve” or how many potential ova remain within the ovaries. A common evaluation of ovarian reserve is measurement of follicle-stimulating hormone (FSH) levels on the third day of the menstrual cycle. The uterus and fallopian/uterine tubes can be visualized for abnormalities and tubal patency through hysterosalpingogram (x-ray film examination of the uterine cavity and tubes after instillation of radiopaque contrast material through the cervix). If the woman is at risk for endometriosis (implants of endometrial tissue outside of the uterus) or adhesions, diagnostic laparoscopy may be indicated. Test findings favorable for fertility are summarized in Box 5.4.
Summary of Findings Favorable to Fertility
1. Follicular development, ovulation, and luteal development are supportive of pregnancy:
a. Basal body temperature (presumptive evidence of ovulatory cycles) is biphasic, with temperature elevation that persists for 12 to 14 days before menstruation.
b. Cervical mucus characteristics change appropriately during phases of the menstrual cycle.
c. Days 3 to 10 follicle-stimulating hormone (FSH) levels are low enough to verify the presence of adequate ovarian follicles.
d. Day 3 estradiol levels are low enough to verify the presence of adequate ovarian follicles.
e. Woman reports a history of regular, predictable menses with consistent premenstrual and menstrual symptoms.
2. The luteal phase is supportive of pregnancy:
a. Levels of plasma progesterone are adequate to indicate ovulation.
b. Luteal phase of menstrual cycle is of sufficient duration to support pregnancy.
3. Cervical factors are receptive to sperm during expected time of ovulation:
a. Cervical os is open.
b. Cervical mucus is clear, watery, abundant, and slippery and demonstrates good spinnbarkeit and arborization (fern pattern) at time of ovulation.
c. Cervical examination reveals no lesions or infections.
4. The uterus and uterine tubes support pregnancy:
a. Uterine and tubal patency are documented by (1) spillage of dye into the peritoneal cavity, and (2) outlines of uterine and tubal cavities of adequate size and shape with no abnormalities.
b. Laparoscopic examination verifies normal development of internal genitals and absence of adhesions, infections, endometriosis, and other lesions.
5. The male partner’s reproductive structures are normal:
a. There is no evidence of developmental anomalies of penis, testicular atrophy, or varicocele (varicose veins on the spermatic vein in the groin).
b. There is no evidence of infection in prostate, seminal vesicles, and urethra.
c. Testes are more than 4 cm in largest diameter.
6. Semen is supportive of pregnancy:
a. Sperm (number per milliliter) are adequate in ejaculate.
b. Most sperm show normal morphology.
c. Most sperm are motile, forward moving.
d. No autoimmunity exists.
e. Seminal fluid is normal.
Assessment of Male Infertility
The systematic investigation of infertility in the male patient begins with a thorough history and physical examination. Assessment of the male patient proceeds in a manner similar to that of the female patient, starting with noninvasive tests.
Diagnostic Testing and Semen Analysis
The basic test for male infertility is semen analysis. A complete semen analysis, study of the effects of cervical mucus on sperm forward motility and survival, and evaluation of the ability of the sperm to penetrate an ovum provide basic information. Sperm counts vary from day to day and depend on emotional and physical status and sexual activity. Therefore, a single analysis may be inconclusive. A minimum of two analyses must be performed several weeks apart to assess male fertility.
Semen is collected by ejaculation into a clean container or a plastic sheath that does not contain a spermicidal agent. The specimen is usually collected by masturbation following 2 to 7 days of abstinence from ejaculation. The semen is examined at the collection site or taken to the laboratory in a sealed container within 2 hours of ejaculation. Exposure to excessive heat or cold is avoided. Commonly accepted values for semen characteristics are given in Box 5.5. If results are in the fertile range, no further sperm evaluation is necessary. If results are not within this range, the test is repeated. If subsequent results are still in the subfertile range, further evaluation is needed to identify the problem.
Semen Analysis: Normal Values
• Semen volume at least 1.5 mL
• Semen pH 7.2 or higher
• Sperm density greater than 15 million/mL
• Total sperm count greater than 39 million per ejaculate
• Normal morphologic features greater than 4% (normal oval)
• Motility (important consideration in sperm evaluation)—percentage of forward-moving sperm estimated with respect to abnormally motile and nonmotile sperm, 40%
• Liquification—usually within 15 minutes but no longer than 60 minutes
NOTE: These values are not absolute but are only relative to final evaluation of the couple as a single reproductive unit. Values also differ according to source used as a reference.
Data from World Health Organization. (2010). Laboratory manual for the examination of human semen (5th ed.). Geneva, Switzerland: Author.
Hormone analyses are done for testosterone, gonadotropin, FSH, and luteinizing hormone (LH). The sperm penetration assay and other alternative tests may be used to evaluate the ability of sperm to penetrate an egg. Testicular biopsy may be warranted. Scrotal ultrasound may be used to examine the testes for presence of varicoceles and identify abnormalities in the scrotum and spermatic cord. Transrectal ultrasound is used to evaluate the ejaculatory ducts, seminal vesicles, and vas deferens.
Infertility is recognized as a major life stressor that can affect self-esteem; relations with the spouse or partner, family, and friends; and careers. Psychologic responses to the diagnosis of infertility may tax a couple’s capacity for giving and receiving physical and sexual closeness. The prescriptions and taboos for achieving conception may add tension to a couple’s sexual functioning. They may report decreased desire for intercourse, orgasmic dysfunction, or midcycle erectile disorders.
To be able to deal comfortably with a couple’s sexuality, nurses must be comfortable with their own sexuality so they can better help couples understand why aspects of sexual intimacy need to be shared with health care professionals. Nurses need current factual knowledge about human sexual practices and must be accepting of the preferences and activities of others without being judgmental. They must be skilled in interviewing and therapeutic use of self, sensitive to the nonverbal cues of others, and knowledgeable regarding each couple’s sociocultural and religious beliefs (see Clinical Reasoning Case Study).
Clinical Reasoning Case Study
Diane is a 39-year-old accountant who has recently married for the first time. Charles is 41 years of age and has two children from a previous marriage. Diane has a history of amenorrhea dating back to when she was in college and a member of the track team. Currently her menstrual periods are irregular. She wants to have a baby “before it’s too late,” and she and Charles have been having unprotected sex for almost 1 year. They have come to the fertility clinic today for an evaluation. Diane tells the nurse that she has heard about the success of in vitro fertilization (IVF) and wants to know if she will be able to have it performed. How should the nurse respond to Diane’s comments and questions?
1. Evidence—Is evidence sufficient to draw conclusions about what response the nurse should give?
2. Assumptions—Describe underlying assumptions about the following issues:
a. Age and fertility: Is Diane’s age a factor in her concern regarding infertility?
b. Infertility as a major life stressor: To what extent can infertility or the fear of being infertile cause stress?
c. Success rates for IVF pregnancy and birth: Is IVF a reasonable treatment to consider (after having a thorough workup)?
d. Causes of female infertility: What are some of the reasons that Diane may be infertile?
3. What implications and priorities for nursing care can be drawn at this time?
4. Describe the roles and responsibilities of members of the interprofessional health care team who may be caring for Diana and Charles.
The couple facing infertility exhibits behaviors of the grieving process such as those associated with other types of loss. The loss of one’s genetic continuity with the generations to come can provoke decreased self-esteem, a sense of inadequacy as a woman or a man, and feelings of loss of control over personal destiny. Infertile individuals can perceive dissatisfaction with their marriages or partner relationships. Not all people have all the reactions described, nor can it be predicted how long any reaction will last for an individual. Often a mental health counselor with experience and expertise dealing with infertility can be very helpful to an individual or couple.
If the couple does not conceive, they should be assessed regarding their desire to be referred for help with adoption, donor eggs or semen, surrogacy, or other reproductive alternatives. The couple may choose to continue in a child-free state. Both health care providers and patients should have a list of agencies, support groups, and other resources within their community such as the ASRM (www.asrm.org) and RESOLVE (www.resolve.org).
Both men and women can benefit from healthy lifestyle changes that result in a BMI within the normal range; moderate daily exercise; and abstinence from alcohol, nicotine, and recreational drugs. For the woman with a BMI >27 and polycystic ovary syndrome, losing just 5% to 10% of body weight can restore ovulation within 6 months. Anovulatory women with a BMI <17 who have eating disorders or intense exercise regimens benefit from weight gain. Nevertheless, this population sometimes is reluctant to alter their behaviors, and counseling should be advised.
Simple changes in lifestyle may be effective in the treatment of subfertile men. Only water-soluble lubricants should be used during intercourse because many commonly used lubricants contain spermicides or have spermicidal properties. Instead of wearing briefs, the male should wear boxer shorts and loose pants because these tend to decrease scrotal temperature and may prevent a decrease in sperm count. High scrotal temperatures can be caused by daily hot tub baths or saunas that keep the testes at temperatures too high for efficient spermatogenesis. These conditions lead to only lessened fertility and should not be used as a means of contraception.
Most herbal remedies have not been proven clinically to promote fertility or to be safe in early pregnancy and should be taken by the woman only as prescribed by a physician or nurse-midwife who has expertise in herbology. Relaxation, osteopathy, stress management (e.g., aromatherapy, yoga), and nutritional and exercise counseling have been reported to increase pregnancy rates in some women. Herbs to avoid while trying to conceive include licorice root, yarrow, wormwood, ephedra, fennel, goldenseal, lavender, juniper, flaxseed, pennyroyal, passionflower, wild cherry, cascara, sage, thyme, and periwinkle. All supplements or herbs should be purchased from trusted sources to ensure that they do not contain contaminants.
One goal of infertility assessment and treatment is to determine which couples are likely to respond to conventional therapies in a timely manner. Another goal is early referral of couples who will need ARTs to concieve. In general, any fertility treatment is more likely to result in a live birth in women who are younger than 35 years of age, with successful outcomes decreasing for women older than 40 years of age.
Pharmacologic therapy for female infertility is often directed at treating ovulatory dysfunction by either stimulating or enhancing ovulation so more oocytes mature. These medications include (1) clomiphene citrate as initial therapy for many women with intermittent anovulation; (2) a combination of clomiphene and metformin for women with anovulation and insulin resistance; (3) human menopausal gonadotropin (HMG), FSH, and recombinant FSH (rFSH) to stimulate follicle formation in women who do not respond to clomiphene therapies; (4) human chorionic gonadotropin to induce ovulation when follicles are ripe; (5) gonadotropin-releasing hormone (GnRH) agonists at the beginning of a cycle to sequence HMG therapies; (6) progesterone to support the luteal phase of the cycle; and (7) bromocriptine (Parlodel) for women who have excess prolactin (Lobo, 2017).
Treatment of certain medical conditions may result in improved fertility. The woman who is hypothyroid benefits from thyroid hormone supplementation. Treatment of endometriosis could include trials of danazol, progesterone, continuous combined oral contraceptives, or GnRH agonists to suppress menstruation and shrink endometrial implants. This regimen would be followed by ovulation induction. Adrenal hyperplasia is treated with prednisone. Any infections present in the infertile couple should be treated with appropriate antimicrobial therapy.
Clomiphene citrate (with the possible addition of metformin) is often the initial pharmacologic treatment of the infertile woman because it is inexpensive and the side-effect profile is less than other medications that induce ovulation. There is an increased risk for giving birth to twins or higher order multiples with clomiphene therapy.
The more powerful medications used to induce ovulation include GnRH agonists followed by gonadotropin therapy. These medications are extremely potent and require daily ovarian ultrasonography and monitoring of estradiol levels to prevent hyperstimulation of the ovaries. Combinations of these medications are used with ART to stimulate ovulation before harvesting eggs.
Drug therapy may be indicated for male infertility. As with women, problems with the thyroid or adrenal glands are corrected with appropriate medications. Infections are identified and treated with antimicrobials. FSH, HMG, and clomiphene may be used to stimulate spermatogenesis in men with hypogonadism. Men who do not respond to these therapies are candidates for intracytoplasmic sperm injection (ICSI), which is a procedure that injects sperm directly into the egg as part of IVF. ICSI has enabled men with very low sperm counts to achieve biologic reproduction.
The infertility specialist is responsible for fully informing patients about the prescribed medications. The nurse must be ready to answer patients’ questions and confirm their understanding of the drug, its administration, potential side effects, and expected outcomes. Because information varies with each drug, the nurse must consult the medication package inserts, pharmacology references, health care provider, and pharmacist as necessary. The nurse should also provide anticipatory guidance regarding the time given for a medication trial before referral to a specialist in ART would be indicated if the couple wants to continue to attempt to become pregnant.
Table 5.2 includes information on selected medications for infertility treatment.
Medication Guide to Selected Infertility Medications
Mechanism of Action
Common Side Effects
Ovulation induction, treatment of luteal-phase inadequacy
Thought to bind to estrogen receptors in the pituitary gland, blocking them from detecting estrogen
Tablets, starting with 50 mg/day by mouth for 5 days beginning on fifth day of menses; if ovulation does not occur, may increase dose next cycle; variable dosage
Vasomotor flushes, abdominal discomfort, nausea and vomiting, breast tenderness, ovarian enlargement
Menotropins (human menopausal gonadotropins)
Ovarian follicular growth and maturation
LH and FSH in 1 : 1 ratio, direct stimulation of ovarian follicle; given sequentially with hCG to induce ovulation
IM injections; dosage regimen variable based on ovarian response
Initial dose is 75 International Units of FSH and 75 International Units of LH (1 ampule) daily for 7–12 days (not to exceed 12 days) followed by 5000 to 10,000 International Units hCG (if serum estradiol <2000 pg/mL
Ovarian enlargement, ovarian hyperstimulation, local irritation at injection site, multifetal gestations
Follitropins (purified FSH)
Treatment of polycystic ovary syndrome; follicle stimulation for assisted reproductive techniques
Direct action on ovarian follicle
Subcutaneous or IM injections; dosage regimen variable
Ovarian enlargement, ovarian hyperstimulation, local irritation at injection site, multifetal gestations
Human chorionic gonadotropin (hCG)
Direct action on ovarian follicle to stimulate meiosis and rupture of the follicle
5000–10,000 International Units IM 1 day after last dose of menotropins; dosage regimen variable
Local irritation at injection site; headaches, irritability, edema, depression, fatigue
GnRH agonists (nafarelin acetate, leuprolide acetate)
Treatment of endometriosis, uterine fibroids
Desensitization and downward regulation of GnRH receptors of pituitary gland, resulting in suppression of LH, FSH, and ovarian function
Nafarelin, 200 mcg (1 spray) intranasally twice daily for 6 months; leuprolide acetate 3.75 mg IM every month for 3–6 months
Both nafarelin and leuprolide—hot flashes, vaginal dryness, myalgia and arthralgia, headaches, mild bone loss (usually reversible within 12–18 months after treatment)
Treatment of luteal-phase inadequacy
Direct stimulation of endometrium
Vaginal gel 8%, 1 prefilled applicator per day; after ovulation induction, continue through 10–12 weeks of pregnancy
Breast tenderness, local irritation, headaches
GnRH antagonists (ganirelix acetate, cetrorelix acetate)
Controlled ovarian stimulation for infertility treatment
Suppress gonadotropin secretion, inhibit premature LH surges in women undergoing ovarian hyperstimulation
250 mcg daily subcutaneously, usually in the early to midfollicular phase of the menstrual cycle; usually followed by hCG administration
Abdominal pain, headache, vaginal bleeding, irritation at the injection site
Restores cyclic ovulation and menses in many women with polycystic ovary syndrome
Induces ovulation through reducing insulin resistance, thus affecting gonadotropins and androgens; simulates the ovary
Initial dose is 500 mg daily and titrated up over several weeks to 1500 mg/day; administered orally
Nausea, vomiting, diarrhea, lactic acidosis, liver dysfunction
Aromatase inhibitor that inhibits E2 production, which causes an increase in LH:FHS ratio
2.5- to 5-mg tablets administered orally for 5 days beginning on cycle day 3 to 7
Hot flashes, headaches, breast tenderness; may increase risk for congenital anomalies
Data from American Society for Reproductive Medicine. (2013). Medications for inducing ovulation: A patient guide. Retrieved from www.asrm.org/Factsheetsandbooklets; Facts and Comparisons. (2013). A to Z drug facts. Retrieved from www.factsandcomparisons.com; Casper, R.F., & Mitwally, M.F.M. (2016). Ovulation induction with letrozole. UpToDate. Retrieved from https://www.uptodate.com/contents/ovulation-induction-with-letrozole; Medscape. (2017). Menotropins. Retrieved from http://reference.medscape.com/drug/menopur-repronex-menotropins-342877; Lobo R. (2017). Infertility: Etiology, diagnostic evaluation, management, prognosis. In R. A. Lobo, D. M. Gershenson, G. M. Lentz, et al. (Eds.), Comprehensive gynecology (7th ed.). Philadelphia, PA: Elsevier.
A number of surgical procedures may be used for problems causing female infertility. Ovarian tumors must be excised. Whenever possible, functional ovarian tissue is left intact. Scar tissue adhesions caused by chronic infections may cover much of the ovary. These adhesions usually necessitate surgery to free and expose the ovary so ovulation can occur.
Hysterosalpingography is useful for identification of tubal obstruction and also for the release of blockage as demonstrated in Fig. 5.2. During laparoscopy, delicate adhesions may be divided and removed, and endometrial implants may be destroyed by electrocoagulation or laser, as illustrated in Fig. 5.3. Laparotomy and microsurgery may be required for extensive repair of the damaged tube. Prognosis depends on the degree to which tubal patency and function can be restored. In general, laparoscopic surgery for tubal patency is most effective in younger women with distal tubal damage. Older women or those with significant proximal disease should be referred for ARTs that bypass the uterine tube.
FIG 5.2 Hysterosalpingography. Note that the contrast medium flows through the intrauterine cannula and out through the uterine tubes.
FIG 5.3 Laparoscopy.
In women with uterine abnormalities, reconstructive surgery (e.g., the unification operation for bicornuate uterus) can improve the ability to conceive and carry a fetus to term. Surgical removal of tumors or fibroids involving the endometrium or muscular walls of the uterus may also improve the woman’s chance of conceiving and maintaining a pregnancy to viability, depending on the location and size of the fibroid or tumor. Surgical treatment of uterine tumors or maldevelopment that results in successful pregnancy usually necessitates birth by cesarean surgery near term gestation because the enlarging uterus can rupture as a result of weakness in the area of reconstructive surgery.
Chronic inflammation and infection can be eliminated by radial chemocautery (destruction of tissue with chemicals) or thermocautery (destruction of tissue with heat, usually electrical) of the cervix, cryosurgery (destruction of tissue by application of extreme cold, usually liquid nitrogen), or conization (excision of a cone-shaped piece of tissue from the endocervix). When the cervix has been deeply cauterized or frozen or when extensive conization has been performed, the cervix may produce less mucus. Therefore, the absence of a mucus bridge from the vagina to the uterus can make sperm migration difficult or impossible. Therapeutic intrauterine insemination may be necessary to carry the sperm directly through the internal os of the cervix.
Surgical procedures may also be used for problems causing male infertility. Surgical repair of varicocele has been relatively successful in increasing sperm count but not fertility rates. Microsurgery to reanastomose (restore tubal continuity) the sperm ducts after vasectomy may restore fertility.
Assisted Reproductive Therapies
The Centers for Disease Control and Prevention (CDC) (2014) defines ART as fertility treatments in which both eggs and sperm are handled. In general, these treatments involve removing the eggs from the woman, fertilizing the eggs in the laboratory, and returning the embryo or embryos to the woman or surrogate carrier. Births that were conceived through ART comprise over 1.5% of all infants born in the United States each year since 2013 (Kaplan, 2015).
Some of the ARTs for treatment of infertility include in vitro fertilization–embryo transfer (IVF-ET), gamete intrafallopian transfer (GIFT) (Fig. 5.4), zygote intrafallopian transfer (ZIFT), ovum transfer (oocyte donation), embryo adoption, embryo hosting and surrogate motherhood, therapeutic donor insemination (TDI), ICSI, assisted embryo hatching, and preimplantation genetic diagnosis (PGD).
FIG 5.4 Gamete intrafallopian transfer (GIFT). A, Through laparoscopy a ripe follicle is located, and fluid containing the egg is removed. B, The sperm and egg are placed separately in the uterine tube, where fertilization occurs.
Table 5.3 describes these procedures and the possible indications for ARTs. Donor sperm and donor eggs can be used with ARTs. In addition, surrogates may carry the couple’s biologic child. ARTs are associated with many ethical and legal issues (Box 5.6).
Assisted Reproductive Therapies
In vitro fertilization–embryo transfer (IVF-ET)
A woman’s eggs are collected from her ovaries, fertilized in the laboratory with sperm, and transferred to her uterus after normal embryo development has occurred.
Tubal disease or blockage; severe male infertility; endometriosis; unexplained infertility; cervical factor; immunologic infertility
Gamete intrafallopian transfer (GIFT)
Oocytes are retrieved from the ovary, placed in a catheter with washed motile sperm, and immediately transferred into the fimbriated end of the uterine tube. Fertilization occurs in the uterine tube.
Same as for IVF-ET, except there must be normal tubal anatomy, patency, and absence of previous tubal disease in at least one uterine tube
IVF-ET and GIFT with donor sperm
This process is the same as described previously except in cases where the male partner’s fertility is severely compromised and donor sperm can be used; if donor sperm are used, the woman must have indications for IVF and GIFT.
Severe male infertility; azoospermia; indications for IVF-ET or GIFT
Zygote intrafallopian transfer (ZIFT)
This process is similar to IVF-ET; after IVF the ova are placed in one uterine tube during the zygote stage.
Same as for GIFT
Eggs are donated by an IVF procedure, and the donated eggs are inseminated. The embryos are transferred into the recipient’s uterus, which is hormonally prepared with estrogen/progesterone therapy.
Early menopause; surgical removal of ovaries; congenitally absent ovaries; autosomal or sex-linked disorders; lack of fertilization in repeated IVF attempts because of subtle oocyte abnormalities or defects in oocyte-spermatozoa interaction
Donor embryo (embryo adoption)
A donated embryo is transferred to the uterus of an infertile woman at the appropriate time (normal or induced) of the menstrual cycle.
Infertility not resolved by less aggressive forms of therapy; absence of ovaries; male partner azoospermic or severely compromised
Gestational carrier (embryo host); surrogate mother
A couple undertakes an IVF cycle, and the embryo(s) is/are transferred to another woman’s uterus (the carrier), who has contracted with the couple to carry the baby to term. The carrier has no genetic investment in the child.
Surrogate motherhood is a process by which a woman is inseminated with semen from the infertile woman’s partner and then carries the baby to term.
Congenital absence or surgical removal of uterus; reproductively impaired uterus, myomas, uterine adhesions, or other congenital abnormalities; medical condition that might be life-threatening during pregnancy (e.g., diabetes; immunologic problems; or severe heart, kidney, or liver disease)
Therapeutic donor insemination (TDI)
Donor sperm are used to inseminate the female partner.
Male partner is azoospermic or has very low sperm count; couple has genetic defect; male partner has antisperm antibodies
Intracytoplasmic sperm injection
One sperm cell is selected to be injected directly into the egg to achieve fertilization. It is used with IVF.
Same as TDI
The zona pellucida is penetrated chemically or manually to create an opening for the dividing embryo to hatch and implant into the uterine wall.
Recurrent miscarriages; to improve implantation rate in women with previously unsuccessful IVF attempts; advanced age
Data from American Society for Reproductive Medicine. (2016). Assisted reproductive technologies: A guide for patients. Retrieved from https://www.asrm.org/BOOKLET_Assisted_Reproductive_Technologies/.
Issues to Be Addressed by Infertile Couples Before Treatment
• Risk for multiple gestation
• Possible need for multifetal reduction
• Possible need for donor oocytes, sperm, or embryos or for gestational carrier (surrogate mother)
• Whether or how to disclose facts of conception to offspring
• Freezing embryos for later use and what to do with extra embryos
• Possible risk for long-term effects of medications and treatment on women, children, and families
• Potential mental health effects (anxiety, depression) related to infertility treatment
The lack of or misleading information about success rates and the risks and benefits of treatment alternatives prevent couples from making informed decisions. Nurses can provide information so couples have an accurate understanding of their chances for a successful pregnancy and live birth. Nurses also can provide anticipatory guidance about the moral and ethical dilemmas regarding the use of ARTs. If a couple is fortunate enough to have multiple embryos available, they may choose to preserve these for later implantation, which has potential legal implications.
Cryopreservation of Human Embryos
Couples who have extra embryos frozen for possible transfer must be fully informed before consenting to the procedure. They must make decisions regarding the disposal of embryos in the event of death or divorce. If they no longer want the embryos, they may consider donating them to other couples, contributing them to research, or disposing of them.
Other than the established risks associated with laparoscopy and general anesthesia, few risks are associated with IVF-ET, GIFT, and ZIFT. The more common transvaginal needle aspiration for egg retrieval requires only local or intravenous analgesia. Congenital anomalies occur no more frequently than among naturally conceived embryos. Multiple gestations are more likely and are associated with increased risks for both the mother and fetuses. Nevertheless, ectopic pregnancies do occur more often and pose significant maternal risk (Lobo, 2017).
Preimplantation Genetic Diagnosis
PGD is a form of early genetic testing designed to allow identification of embryos with serious genetic abnormalities. Those embryos would not be used in ART. Genetic testing improves the likelihood of successful pregnancy. Micromanipulation allows removal of a single cell from a multicellular embryo for genetic study (i.e., embryo biopsy) (ASRM, 2014). PGD is used clinically in numerous centers around the world. Couples must be counseled about their options and choices and the implications of their choices when genetic analysis is considered.
Couples may choose to build their family by adopting children who are not their own biologically. With increased availability of birth control and abortion and an increase in single mothers who choose to keep their babies, the availability of healthy newborn infants in the United States is limited (Greenblatt, 2011). Infants with diverse ethnic and racial heritages, infants with special needs, older children, and foreign adoptions are other options (Fig. 5.5).
FIG 5.5 After two miscarriages, this couple chose foreign adoption. (Courtesy of Shannon Perry, Phoenix, AZ.)
The CDC noted that the capability of Americans to engage in effective family planning as a result of the modern era of contraception was one of the 10 greatest public health achievements of the 20th century (CDC, 2013). Nevertheless, nearly half of all pregnancies in the United States are not planned (Rivlin & Westhoff, 2017). Among adolescent women who were 19 years of age or younger, more than 80% of those who became pregnant did not intend to do so (CDC, 2015). The nurse can play a vital role in preventing unplanned and/or unwanted pregnancy through counseling and education regarding family planning, contraception, and effective birth control. Family planning is the conscious decision about when to conceive or to avoid pregnancy throughout the reproductive years. Contraception is defined as the intentional prevention of pregnancy during sexual intercourse. Birth control is the device and/or practice used to decrease the risk for conceiving or bearing offspring.
With the wide assortment of birth control options available, it is possible for a woman to use several different contraceptive methods at various stages throughout her fertile years. Nurses provide information about the various methods and help couples compare and contrast available contraceptive options. Providing adequate instruction about how to use a contraceptive method, when to use a backup method, and when to use emergency contraception (EC) can decrease the risk for unintended pregnancy. The Community Focus box presents information about contraceptive education.
Education for Contraceptive Use: Student Activity
A suggested activity to learn more about contraceptive use is to observe a nurse doing contraceptive counseling in a family planning clinic. An alternative suggestion is to prepare information on several common contraceptive methods to present to adolescents at a health course in school or at a group meeting, such as for the Girl Scouts, Girls Inc., or a church youth group.
An interprofessional approach may help a woman choose and correctly use an appropriate contraceptive method. Nurses, nurse-midwives, nurse practitioners, other advanced practice nurses, and physicians have the knowledge and expertise to help a woman make decisions about contraception that will satisfy her personal, social, cultural, and interpersonal needs.
Assessment for the couple desiring contraception involves assessment of the woman’s medical and reproductive history (menstrual, obstetric, gynecologic, contraceptive), physical examination, and sometimes current laboratory tests. The nurse must determine the woman’s knowledge about reproduction, contraception, and STIs and her sexual partner’s commitment to any particular method. Fig. 5.6 illustrates contraceptive counseling. The nurse obtains information about the frequency of coitus, number of sexual partners (present and past), and any objections that she or her partner might have about specific birth control methods. In addition, the nurse must determine a woman’s willingness to touch her genitals. Religious and cultural factors may influence a couple’s choice regarding a particular contraceptive method. The couple may believe in certain reproductive myths. Unbiased patient teaching is fundamental to initiating and maintaining any form of contraception. The nurse counters myths with facts, clarifies misinformation, and fills in gaps in knowledge. The ideal contraceptive should be safe, effective, easily available, economical, acceptable, simple to use, and promptly reversible. Although no method may ever achieve all of these objectives, significant advances in the development of new contraceptive technologies have occurred over the past 30 years.
FIG 5.6 Nurse counseling a woman about contraceptive methods. (Courtesy of Dee Lowdermilk, Chapel Hill, NC.)
Contraceptive failure rate refers to the percentage of contraceptive users expected to have an unplanned pregnancy during the first year even when they use a method consistently and correctly. Contraceptive effectiveness varies from couple to couple and depends on both the properties of the method and the characteristics of the user (Box 5.7). Effectiveness of a method can be expressed as theoretic (i.e., how effective the method is with perfect use) and typical (i.e., how effective the method is with typical use). Failure rates decrease over time, either because a user gains experience with and uses a method more appropriately or because the less effective users stop using the method. Safety of a method may be affected by a woman’s medical history (e.g., thromboembolic problems and contraceptive methods containing estrogen). Nevertheless, in most instances pregnancy would be more dangerous to the woman with medical problems than a particular contraceptive method. In addition, many contraceptive methods have health promotion effects. Barrier methods such as the male condom offer some protection from acquiring STIs, and oral contraceptives lower the incidence of ovarian and endometrial cancer.
Factors Affecting Contraceptive Method Effectiveness
• Frequency of intercourse
• Motivation to prevent pregnancy
• Understanding of how to use the method
• Adherence to the method
• Provision of short- or long-term protection
• Likelihood of pregnancy for the individual woman
• Consistent use of the method
Following assessment and analysis, the couple determines possible contraceptive methods that are appropriate for their unique situation. Factors to consider when determining a contraceptive method are effectiveness, convenience, affordability, duration of action of method, reversibility of method, time of return to fertility, effects on uterine bleeding patterns, side effects, adverse events, health promotion effects of methods, effect of method on transmission of STIs, and medical contraindications for use.
The most effective reversible contraceptive methods at preventing pregnancy are the long-acting, reversible contraceptive (LARC) methods (e.g., contraceptive implants, intrauterine contraception). With these methods, theoretic and typical pregnancy rates are the same because the method requires no user intervention after correct insertion. Effective methods include those that prevent pregnancy through exogenous hormones (estrogen and/or progestins) such as contraceptive injections, oral contraceptive pills, contraceptive patches, and vaginal rings. Each of these methods involves user interventions; thus typical-use pregnancy rates are higher than pregnancy rates with perfect use. The least effective contraceptive methods include the barrier methods and natural family planning. Examples include condoms, diaphragms, cervical caps, spermicides, withdrawal, and periodic abstinence during perceived ovulation. Effectiveness rates for these methods vary from user to user, depending on correct application of the method and consistency of use.
Expected outcomes related to contraceptive counseling are that the couple will verbalize understanding about appropriate contraceptive methods, state they are satisfied with the method chosen, use the method correctly and consistently, experience no adverse sequelae as a result of the chosen contraceptive method, and prevent unplanned pregnancy. The nurse assists with obtaining appropriate informed consent concerning contraception or sterilization, provides appropriate education to the couple, and documents the couple’s understanding of the contraceptive method chosen. Evaluation involves achievement of patient-centered outcomes when the couple engage in effective use of the chosen contraceptive device, experience no adverse sequelae, and achieve pregnancy only when they desire to do so.
Methods of Contraception
The following discussion of contraceptive methods provides the nurse with information needed for patient teaching. After implementing the appropriate teaching for contraceptive use, the nurse supervises return demonstrations and practice to assess patient understanding (see Clinical Reasoning Case Study). The couple is given written instructions, telephone numbers, and/or email contact information for questions. If the woman has difficulty understanding written instructions, she and her partner, if available, are offered graphic material, a telephone number to call as necessary, and an opportunity to return for further instruction.
Clinical Reasoning Case Study
Contraception for Adolescents
Maria is a 16-year-old Hispanic female who comes to the family planning clinic seeking contraception. She has recently become sexually active and tells the nurse that she is concerned that her mother will find out. She also has many questions about the type of contraception to use. She seeks the nurse’s advice to help in her decision making.
1. Evidence—Is there sufficient evidence to draw conclusions about advice to give Maria?
2. Assumptions—What assumptions can be made about contraception for adolescents:
a. Types of contraception: What methods are appropriate (safe and effective) for an adolescent young woman?
b. Legal issues: With whom is this young woman engaging in sexual intercourse? Is it consensual? Does she need parental consent to obtain contraception?
c. Implications of culture on choice: Are there any cultural issues?
3. What implications and priorities for nursing care can be drawn at this time?
4. Describe the roles and responsibilities of members of the interprofessional health care team who may be involved in caring for Maria.
Coitus interruptus (withdrawal) involves the male partner withdrawing his penis from the woman’s vagina before he ejaculates. Although coitus interruptus has been criticized as being an ineffective method of contraception, it is a good choice for couples who do not have another contraceptive available. Effectiveness is similar to barrier methods and depends on the man’s ability to withdraw his penis before ejaculation. The percentage of women who experience an unintended pregnancy within the first year of typical use (failure rate) of withdrawal ranges from 4% when used consistently and correctly to 22% as a typical failure rate (Rivlin & Westhoff, 2017). Coitus interruptus does not protect against STIs or human immunodeficiency virus (HIV) infection.
Fertility Awareness Methods
Fertility awareness methods (FAMs) of contraception depend on identifying the beginning and end of the fertile period of the menstrual cycle. When women who want to use FAMs are educated about the menstrual cycle, the following three phases are identified:
1. Infertile phase: Before ovulation
2. Fertile phase: About 5 to 7 days around the middle of the cycle, including several days before and during ovulation and the day after ovulation
3. Infertile phase: After ovulation
Although ovulation can be unpredictable in many women, teaching the woman about how she can directly observe her fertility patterns is an empowering tool. In addition, knowledge about the signs and symptoms of ovulation can be very helpful when the couple desires pregnancy. There are nearly a dozen categories of FAMs. To prevent pregnancy, each one uses a combination of charts, records, calculations, tools, observations, and either abstinence (natural family planning [NFP]) or barrier methods of birth control during the fertile period of the menstrual cycle. The charts and calculations associated with these methods can also be used to increase the likelihood of detecting the optimal timing of intercourse to achieve conception.
Advantages of these methods include low-to-no cost, absence of chemicals and hormones, and lack of alteration in the menstrual flow pattern. Disadvantages of FAMs include adherence needed for strict record keeping, unintentional interference from external influences that may alter the woman’s core body temperature and vaginal secretions, decreased effectiveness in women with irregular cycles (particularly adolescents who have not established regular patterns of ovulation), decreased spontaneity of coitus, and the necessity of attending possibly time-consuming training sessions by qualified instructors. The typical failure rate for most FAMs is 24% during the first year of use (Rivlin & Westhoff, 2017). FAMs do not protect against STIs or HIV infection.
FAMs involve several techniques to identify high-risk, fertile days. The following discussion includes the most common techniques.
Natural Family Planning (Periodic Abstinence)
Natural family planning (NFP), or periodic abstinence, provides contraception by using methods that rely on avoiding intercourse during fertile days. NFP methods are the only methods of contraception acceptable to the Roman Catholic Church. Signs and symptoms of fertility awareness most commonly used with abstinence are menstrual bleeding, cervical mucus, and basal body temperature. Development and marketing of ovulation predictor kits have also been very helpful for couples who choose NFP. Several application products have been developed for smart phones, which make FAM record tracking convenient and portable.
The human ovum can be fertilized no later than 16 to 24 hours after ovulation. Motile sperm have been recovered from the uterus and uterine tubes as long as 7 days after coitus. However, their ability to fertilize the ovum probably lasts no longer than 24 hours. Pregnancy is unlikely to occur if a couple abstains from intercourse for 4 days before and 3 or 4 days after ovulation (fertile period). Unprotected intercourse on the other days of the cycle (safe period) should not result in pregnancy. Nevertheless, the exact time of ovulation cannot be predicted accurately, and couples may find it difficult to abstain from sexual intercourse for several days before and after ovulation. Women with irregular menstrual periods have the greatest risk for failure with this form of contraception.
Calendar Rhythm Method
Practice of the calendar rhythm method is based on the number of days in each cycle, counting from the first day of the menstrual cycle (first day of menstrual vaginal bleeding). The fertile period is determined after accurately recording the lengths of menstrual cycles for 6 months. The beginning of the fertile period is estimated by subtracting 18 days from the length of the shortest cycle. The end of the fertile period is determined by subtracting 11 days from the length of the longest cycle. If the shortest cycle is 24 days and the longest is 30 days, application of the formula to calculate the fertile period is as follows:
To avoid conception the couple would abstain during the fertile period, days 6 through 19.
If the woman has very regular cycles of 28 days each, the formula indicates the fertile days to be as follows:
To avoid conception, the couple would abstain from days 10 through 17 because ovulation occurs on day 14 ± 2 days. A major drawback of the calendar method is that the couple is attempting to predict future events with past data. The unpredictability of the menstrual cycle is also not taken into consideration. The calendar rhythm method is most useful as an adjunct to the basal body temperature or cervical mucus method.
Standard Days Method
The standard days method (SDM) is essentially a modified form of the calendar rhythm method that has a “fixed” number of days of fertility for each cycle (i.e., days 8 to 19). A CycleBeads necklace (i.e., a color-coded string of beads) can be purchased as a concrete tool to track fertility (Fig. 5.7) or as a smart phone application. Day 1 of the menstrual flow is counted as the first day to begin counting. Women who use this device are taught to avoid unprotected intercourse on days 8 to 19 (white beads on CycleBeads necklace). Although this method is useful to women whose cycles are 26 to 32 days long, it is unreliable for those who have longer or shorter cycles (Contracept.org, 2016a).
FIG 5.7 CycleBeads. Red bead marks the first day of the menstrual cycle. White beads mark days that are likely to be fertile days; therefore unprotected intercourse should be avoided. Brown beads are days when pregnancy is unlikely and unprotected intercourse is permitted. (Courtesy of Dee Lowdermilk, Chapel Hill, NC.)
Basal Body Temperature Method
The basal body temperature (BBT) is the lowest body temperature of a healthy person, taken immediately after waking and before getting out of bed. The BBT usually varies from 36.2° C (97.16° F) to 36.3° C (97.34° F) during menses and for approximately 5 to 7 days afterward (Fig. 5.8).
FIG 5.8 A, Special thermometer for recording basal body temperature, marked in tenths to enable the person to read it more easily. B, Basal temperature record shows decrease and sharp increase at time of ovulation. Biphasic curve indicates ovulatory cycle. A digital thermometer may also be used.
About the time of ovulation a slight drop in temperature (approximately 0.5° C [35.8° F]) may occur in some women, but others may have no decrease at all. After ovulation, in concert with the increasing progesterone levels of the early luteal phase of the cycle, the BBT increases slightly (approximately 0.4° C [36.2° F] to 0.8° C [36.6° F]). The temperature remains on an elevated plateau until 2 to 4 days before menstruation. Then BBT decreases to the low levels recorded during the previous cycle unless pregnancy has occurred. In pregnant women, the temperature remains elevated. If ovulation fails to occur, the pattern of lower body temperature continues throughout the cycle.
To use this method the fertile period is defined as the day of first temperature drop, or first elevation, through 3 consecutive days of elevated temperature. Abstinence begins the first day of menstrual bleeding and lasts through 3 consecutive days of sustained temperature rise. The decrease and subsequent increase in temperature are referred to as the thermal shift. When the temperatures of the entire month are recorded on a graph, the pattern described is more apparent. It is more difficult to perceive day-to-day variations without the entire picture (see Guidelines box). Either a glass mercury thermometer or a digital thermometer may be used for BBT, but the thermometer must measure the temperature within one-tenth of a degree. The glass mercury thermometer needs no batteries but is fragile and can break. If a mercury thermometer does break, it is important to put on rubber, nitrile, or latex gloves and pick up all broken pieces and place on a paper towel. Put the folded paper towel with the contents in it securely into a zip-lock bag, label it, and contact the local health department regarding disposal. A digital thermometer requires batteries but may have a history recall function and an audible beep when the temperature assessment is finished. Digital thermometers that monitor temperature throughout the day combined with an accelerometer to monitor movement have been cleared for use by the Food and Drug Administration (FDA). These devices can be wirelessly uploaded to a computer through a companion device. Their use in FAM needs further research. Guidelines for BBT recording is included in the Guidelines box, and Fig. 5.8 depicts a graph of what a BBT recording looks like.
Basal Body Temperature
• Discuss basal body temperature (BBT) with the woman.
• Show the woman a diagram depicting the phases of the menstrual cycle.
• Discuss the hormones in the woman’s body that are responsible for her menstrual cycle and ovulation. Leave time for questions.
• Show the woman a sample BBT graph (see Fig. 5.8) and the biphasic line seen in ovulatory cycles.
• Show the woman the BBT thermometer and how it is calibrated.
• Provide a demonstration.
• Encourage the woman to demonstrate taking and reading the thermometer and graphing the temperature while the nurse watches.
• Encourage the woman to start a log to keep track of any other activity that might interfere with determining her true BBT.
Infection, fatigue, less than 3 hours of sleep per night, awakening late, and anxiety may cause temperature fluctuations and alter the expected pattern. If a new BBT thermometer is purchased, this fact is noted on the chart because the readings may vary slightly. Jet lag, alcohol taken the evening before, or sleeping in a heated waterbed must also be noted on the chart because each affects the BBT. Therefore the BBT alone is not a reliable method of predicting ovulation.
Cervical Mucus Ovulation-Detection Method
The cervical mucus ovulation-detection method (i.e., Billings method or Creighton model ovulation method) requires that the woman recognize and interpret the cyclic changes in the amount and consistency of cervical mucus that characterize her own unique pattern of changes at the time of ovulation. Cervical mucus changes before and during ovulation to facilitate and promote the viability and motility of sperm. Without adequate cervical mucus, coitus does not result in conception. This method requires that a woman check the quantity and character of mucus on the vulva or introitus with her fingers or tissue paper each day for several months. This way she can learn how her cervical mucus responds to ovulation during her menstrual cycles. To ensure an accurate assessment of changes, the cervical mucus should be free from semen, contraceptive gels or foams, and blood or discharge from vaginal infections for at least one full cycle. Other factors that create difficulty in identifying mucus changes include douches and vaginal deodorants, being in the sexually aroused state (which thins the mucus), and taking medications such as antihistamines (which dry the mucus). Intercourse is considered safe without restriction beginning the fourth day after the last day of wet, clear, slippery mucus, which would indicate that ovulation has occurred 2 to 3 days previously.
Some women find this method unacceptable if they are uncomfortable touching their genitals. Whether or not a woman wants to use this method for contraception, it is to her advantage to learn to recognize mucus characteristics at ovulation (see Guidelines box).
Cervical Mucus Characteristics
Setting the Stage
• Show charts of the menstrual cycle along with changes in the cervical mucus.
• Have the woman practice assessing mucus using raw egg white.
• Supply her with a basal body temperature (BBT) log and graph if she does not already have one.
• Explain that the assessment of cervical mucus characteristics is best when mucus is not mixed with semen, contraceptive jellies or foams, or discharge from infections.
Benefits of Noting Cervical Mucus Characteristics
• To alert the couple to the reestablishment of ovulation while breastfeeding and after discontinuation of oral contraception
• To note anovulatory cycles at any time and at the beginning of menopause
• To help couples plan a pregnancy
Content Related to Cervical Mucus
• Explain to the woman (or couple) how cervical mucus changes throughout the menstrual cycle.
• Right before ovulation the watery, thin, clear mucus becomes more abundant and thick. It feels like a lubricant and can be stretched approximately 5 cm between the thumb and forefinger; this is called spinnbarkeit. This characteristic indicates the period of maximum fertility. Sperm deposited in this type of mucus can survive until ovulation occurs.
• Stress that good hand washing is imperative to begin and end all self-assessment.
• Start observation from the last day of menstrual flow.
• Assess cervical mucus several times a day for several cycles. Mucus can be obtained from vaginal introitus; there is no need to reach into vagina to cervix.
• Record findings on the same record on which her BBT is entered.
The symptothermal method combines the BBT and cervical mucus methods with awareness of secondary phase–related symptoms of the menstrual cycle. The woman gains fertility awareness as she learns the psychologic and physiologic symptoms that mark the phases of her cycle. Secondary symptoms include increased libido, midcycle spotting, mittelschmerz (cramplike pain before ovulation), pelvic fullness or tenderness, and vulvar fullness.
The woman is taught to palpate her cervix to assess for changes indicating ovulation: the cervical os dilates slightly, the cervix softens and rises in the vagina, and cervical mucus is copious and slippery. The woman notes days on which coitus, changes in routine, illness, and other changes that might affect BBT have occurred (Fig. 5.9). Calendar calculations and cervical mucus changes are used to estimate the onset of the fertile period; changes in cervical mucus or the BBT are used to estimate the end of the fertile period.
FIG 5.9 Example of completed symptothermal chart.
TwoDay Method of Family Planning
Based on monitoring and the recording of cervical secretions, an algorithm for identifying the fertile window has been developed by the Institute for Reproductive Health at Georgetown University (Contracept.org, 2016b). The TwoDay algorithm appears to be simpler to teach, learn, and use than other natural methods. Results suggest that the algorithm can be an effective alternative for low-literacy populations or for programs that find current NFP methods too time-consuming or otherwise not feasible to incorporate within their services. Two questions are posed. Each day the woman is to ask herself, (1) “Did I note secretions today?” and (2) “Did I note secretions yesterday?” If the answer to either question is yes, she should avoid coitus or use a backup method of birth control. If the answer to both questions is no, her probability of getting pregnant is low. Further studies are needed to determine the efficacy of the TwoDay algorithm in avoiding pregnancy and to assess its acceptability to users and providers.
Home Predictor Test Kits for Ovulation
Although the methods previously discussed are characteristic of ovulation, they do not prove that ovulation actually occurred or indicate the exact timing. The urine predictor test for ovulation is a major addition to the NFP and fertility-awareness methods to help women who want to plan the time of their pregnancies and for those who are trying to conceive (Fig. 5.10). The urine predictor test for ovulation detects the sudden surge of LH that occurs approximately 12 to 24 hours before ovulation. Unlike BBT, this test is not affected by illness, emotions, or physical activity. For home use, a test kit contains sufficient material for several days’ testing during each cycle. A positive response indicating an LH surge is noted by a color change that is easy to interpret. Directions for use of urine predictor test kits vary with the manufacturer.
FIG 5.10 Examples of ovulation predictor tests.
The Marquette Model
The Marquette Model (MM) is a natural family planning method that was developed through the Marquette University College of Nursing Institute for Natural Family Planning. The MM uses cervical monitoring along with the ClearPlan Easy Fertility Monitor. The ClearPlan monitor is a handheld device that uses test strips to measure urinary metabolites of estrogen and LH. The monitor provides the user with “low,” “high,” and “peak” fertility readings. The MM incorporates the use of the monitor as an aid to learning NFP and fertility awareness.
Research continues on the efficacy of available home test kits and devices for the prevention of pregnancy (Leiva et al., 2014).With more research and development, women and men will have greater access to pregnancy prevention methods.
Breastfeeding: Lactational Amenorrhea Method
The lactational amenorrhea method (LAM) can be a highly effective, temporary method of birth control. The LAM is more popular in underdeveloped countries and traditional societies in which breastfeeding is used to prolong birth intervals. The method has seen limited use in the United States because most American women do not establish breastfeeding patterns that provide maximum protection against pregnancy, and therefore it is recommended that breastfeeding mothers consider another form of reliable contraception (Rivlin & Westhoff, 2017).
When the infant suckles at the mother’s breast, a surge of prolactin is released. Prolactin inhibits estrogen production and suppresses ovulation and the return of menses. LAM works best if the mother is exclusively breastfeeding, if she has not had a menstrual flow since birth, and if the infant is younger than 6 months of age. Effectiveness is enhanced by frequent feedings at intervals of less than 4 hours during the day and no more than 6 hours during the night, long duration of each feeding, and no bottle supplementation. The woman should be counseled that disruption of the breastfeeding pattern or formula supplementation can increase the risk for pregnancy. The typical failure rate is 2% if used correctly, which means exclusive breastfeeding for up to 6 months after birth (Rivlin & Westhoff, 2017).
Barrier contraceptives have gained in popularity not only as a contraceptive method but also as protection against the spread of STIs such as human papilloma virus and herpes simplex virus (HSV). Some male condoms and female vaginal methods provide a physical barrier to several STIs, and some male condoms provide protection against HIV. Spermicides serve as chemical barriers against semen and inhibit the ability of sperm to fertilize the ovum.
The nurse should remember that any user of a barrier method of contraception must also be aware of emergency contraception (EC) options in case there is a failure of the method. An example of a barrier method failure would be if a condom broke during intercourse. In this instance, EC would be indicated to prevent unplanned pregnancy.
Spermicides such as nonoxynol-9 (N-9) work by reducing the mobility of the sperm. The chemicals attack the sperm flagella and body, thereby preventing the sperm from reaching the cervical os. N-9, the most commonly used spermicidal chemical in the United States, is a surfactant that destroys the sperm cell membrane. Results from data analyses now suggest that frequent use (more than 2 times a day) of N-9 or the use of N-9 as a lubricant during intercourse may increase the transmission of HIV and can cause lesions (World Health Organization, 2016). There is no evidence that the addition of spermicides to male condoms decreases the risk for subsequent pregnancy. Women with high-risk behaviors that increase their likelihood of contracting HIV and other STIs are advised to avoid the use of spermicidal products containing N-9, including lubricated condoms, diaphragms, and cervical caps to which N-9 is added.
Intravaginal spermicides are marketed and sold without prescriptions as aerosol foams, tablets, suppositories, creams, films, and gels (Fig. 5.11). Preloaded, single-dose applicators small enough to be carried in a small purse are available. Effectiveness of spermicides depends on consistent and accurate use. Not more than 1 hour before sexual intercourse, the spermicide should be inserted high into the vagina so it makes contact with the cervix. Spermicide must be reapplied for each additional act of intercourse, even if a barrier method is used. Studies have shown varying effectiveness rates for spermicidal use alone. The typical failure rate is 15% to 29% (Rivlin & Westhoff, 2017). Some female barrier methods (e.g., diaphragm, cervical caps) offer more effective protection against pregnancy with the addition of spermicides.
FIG 5.11 Spermicides. (Courtesy of Marjorie Pyle, RNC, Life Circle, Costa Mesa, CA.)
The male condom is a thin, stretchable sheath that covers the penis before genital, oral, or anal contact and is removed when the penis is withdrawn from the partner’s orifice after ejaculation. Condoms are made of latex rubber, which, if intact, provides a barrier to sperm and STIs (including HIV); polyurethane (strong, thin plastic); or natural membranes (animal tissue). In addition to providing a physical barrier for sperm, nonspermicidal latex condoms also provide a barrier for STIs (particularly gonorrhea, chlamydia, and trichomonas) and HIV transmission. Condoms lubricated with N-9 are not recommended for preventing STIs or HIV and do not increase protection against pregnancy, as noted earlier. Latex condoms break down with oil-based lubricants (e.g., petroleum jelly and suntan oil) and should be used only with water-based or silicone lubricants. Because of the growing number of people with latex allergies, condom manufacturers have begun using polyurethane, which is thinner and stronger than latex.
All patients should be questioned about the potential for latex allergy. Latex condom use is contraindicated for patients with latex sensitivity.
Although polyurethane condoms are as effective for STI prevention as latex condoms, they are more likely to slip or lose contour when compared to latex condoms. Therefore, with perfect use latex condoms offer better protection against pregnancy as compared with polyurethane condoms. Polyurethane condoms do offer pregnancy protection equivalent to that of most barrier products. A small percentage of condoms are made from lamb cecum (natural skin). Natural skin condoms do not provide the same protection against STIs and HIV infection as latex condoms. Natural skin condoms contain small pores that may allow passage of viruses such as hepatitis B, HSV, and HIV and are not generally recommended.
A functional difference in condom shape is the presence or absence of a sperm reservoir tip. To enhance vaginal stimulation, some condoms are contoured and rippled or have ribbed or roughened surfaces. Thinner construction increases heat transmission and sensitivity; a variety of colors increases condom acceptability and attractiveness. A wet jelly or dry powder lubricates some condoms. The typical failure rate for the use of the male condom is approximately 15% (Rivlin & Westhoff, 2017). Effective condom use is a skill that must be taught.
Box 5.8 summarizes advantages and disadvantages of male condoms and nursing considerations.
Mechanism of Action
Sheath is applied over the erect penis before insertion or loss of preejaculatory drops of semen. If used correctly, condoms prevent sperm from entering the cervix. Spermicide-coated condoms cause ejaculated sperm to be immobilized rapidly, thus increasing contraceptive effectiveness.
• No side effects
• Readily available
• Premalignant changes in cervix can be prevented or ameliorated in women whose partners use condoms
• Method of male nonsurgical contraception
• Sexual activity must be interrupted to apply sheath.
• Sensation may be altered.
• If used improperly, spillage of sperm can result in pregnancy.
• Condoms occasionally may tear during intercourse.
Sexually Transmitted Infection Protection
If a condom is used throughout the act of intercourse and there is no unprotected contact with female genitals, a latex rubber condom, which is impermeable to viruses, can act as a protective measure against sexually transmitted infections.
Teach the male patient to do the following:
• Use a new condom (check expiration date) for each act of sexual intercourse or other acts between partners that involve contact with the penis.
• Place the condom after the penis is erect and before intimate contact.
• Place the condom on the head of the penis (A) and unroll it all the way to the base (B).
• Leave an empty space at the tip (A); remove any air remaining in the tip by gently pressing air out toward the base of the penis.
• If a lubricant is desired, use water-based products such as K-Y lubricating jelly. Do not use petroleum-based products because they can cause the condom to break.
• After ejaculation, carefully withdraw the still-erect penis from the vagina, holding onto the condom rim; remove and discard the condom.
• Store unused condoms in a cool, dry place.
• Do not use condoms that are sticky, brittle, or obviously damaged.
It is a false assumption that everyone knows how to use condoms. To prevent unintended pregnancy and the spread of STIs, it is essential that condoms be used correctly. Proper instruction in use must be provided. The sheath is applied over the erect penis before insertion and before the loss of preejaculatory drops of semen. All types of condoms must be discarded after each single use. Condoms are available without prescription from a variety of sources, including vending machines.
The female condom is a vaginal sheath made of nitrile, a nonlatex, synthetic rubber and has flexible rings at both ends (Fig. 5.12, A). The closed end of the pouch is inserted into the vagina and anchored around the cervix; the open ring covers the labia. A woman whose partner will not wear a male condom can use this device as a protective mechanical barrier. Rewetting drops or oil- or water-based lubricants may be used to help decrease the distracting noise that is produced while penile thrusting occurs. The female condom is available in one size, is intended for single use only, and is sold over the counter. Male condoms should not be used concurrently because the friction from both sheaths can increase the likelihood of either or both tearing. The typical failure rate in the first year of female condom use is 21% (Rivlin & Westhoff, 2017).
FIG 5.12 Barrier methods. A, Female condom (FC2). B, FemCap. C, Contraceptive sponge. (A, Courtesy of The Female Health Company, Chicago, IL. B, Courtesy of FemCap, Del Mar, CA. C, Courtesy of Allendale Pharmaceuticals, Allendale, NJ.)
The contraceptive diaphragm is a shallow, dome-shaped, latex or silicone device with a flexible rim that covers the cervix. The diaphragm is a mechanical barrier to the meeting of sperm with the ovum. By holding spermicide in place against the cervix for the 6 hours it takes to destroy the sperm, the diaphragm also provides a chemical barrier to pregnancy. Diaphragms are available in a wide range of diameters (50 to 95 mm) and differ in the inner construction of the circular rim. The types of rims are coil spring, arcing spring, and wide-seal rim. The diaphragm should be the largest size the woman can wear without being aware of its presence. The typical failure rate of the diaphragm combined with spermicide ranges from 13% to 17%, but it is possible that the failure rate can be reduced to 4% to 8% with correct and consistent use (Rivlin & Westhoff, 2017).
The woman using a diaphragm needs an annual gynecologic examination to assess its fit, seeking the largest size that does not cause discomfort. Rivlin & Westhoff (2017) note that no data exist that support a correlation between fit and effectiveness, despite the fact that it has commonly been believed that weight change (gain or loss), birth, miscarriage, or abdominal and pelvic surgery may change the appropriate fit. Because various types of diaphragms are on the market, the nurse uses the package insert when teaching the woman how to use and care for the diaphragm (see Patient Teaching box). A newer diaphragm, called Caya, that is sold over-the-counter and comes in only one size, has been approved by the FDA (Rivlin & Westhoff, 2017).
Use and Care of the Diaphragm
Positions for Insertion of Diaphragm
• Squatting is the most commonly used position, and most women find it satisfactory.
• Another position is to raise the left foot (if right hand is used for insertion) on a low stool and, while in a bending position, insert the diaphragm.
• Another practical method for diaphragm insertion is to sit far forward on the edge of a chair.
• You may prefer to insert the diaphragm while in a semireclining position in bed.
Inspection of Diaphragm
Your diaphragm must be inspected carefully before each use. The best way to do this is:
• Hold the diaphragm up to a light source. Carefully stretch it at the area of the rim, on all sides, to make sure that there are no holes. Remember, it is possible to puncture the diaphragm with sharp fingernails.
• Another way to check for pinholes is to carefully fill the diaphragm with water. If there is any problem, it will be seen immediately.
• If your diaphragm is puckered, especially near the rim, this could mean thin spots.
• The diaphragm should not be used if you see any of these; consult your health care provider.
Preparation of Diaphragm
• Rinse off cornstarch (see section, below, on care of diaphragm, noting that it should be dusted with cornstarch when stored). Your diaphragm must always be used with a spermicidal lubricant to be effective. Pregnancy cannot be prevented effectively by the diaphragm alone.
• Always empty your bladder before inserting the diaphragm. Place about 2 tsp of contraceptive jelly or contraceptive cream on the side of the diaphragm that will rest against the cervix (or whichever way you have been instructed). Spread it around to coat the surface and the rim. This aids in insertion and offers a more complete seal. Many women also spread some jelly or cream on the other side of the diaphragm (Fig. A).
Insertion of Diaphragm
• The diaphragm can be inserted as long as 6 hours before intercourse. Hold it between your thumb and fingers. The dome can be either up or down, as directed by your health care provider. Place your index finger on the outer rim of the compressed diaphragm (Fig. B).
• Use the fingers of the other hand to spread the labia (lips of the vagina). This will aid in guiding the diaphragm into place.
• Insert the diaphragm into the vagina. Direct it inward and downward as far as it will go to the space behind and below the cervix (Fig. C).
• Tuck the front of the rim of the diaphragm behind the pubic bone so the rubber hugs the front wall of the vagina (Fig. D).
• Feel for your cervix through the diaphragm to be certain that it is placed properly and covered securely by the rubber dome (Fig. E).
• Regardless of the time of the month, you must use your diaphragm every time intercourse takes place. It must be left in place for at least 6 hours after the last intercourse. If you remove it before the 6-hour period, your chance of becoming pregnant could be greatly increased. If you have repeated acts of intercourse, you must add more spermicide for each act.
Removal of Diaphragm
• The only proper way to remove the diaphragm is to insert your forefinger up and over the top side of the diaphragm and slightly to the side.
• Next turn the palm of your hand downward and backward, hooking the forefinger firmly on top of the inside of the upper rim of the diaphragm, breaking the suction.
• Pull the diaphragm down and out. This avoids the possibility of tearing it with the fingernails. You should not remove it by trying to catch the rim from below the dome (Fig. F).
Care of Diaphragm
• When using a vaginal diaphragm, avoid using oil-based products such as certain body lubricants, mineral oil, baby oil, vaginal lubricants, or vaginitis preparations. These products can weaken the rubber.
• A little care means longer wear for your diaphragm. After each use, wash it in warm water and mild soap. Do not use detergent soaps, cold-cream soaps, deodorant soaps, and soaps containing oil products because they can weaken the rubber.
• After washing, dry the diaphragm thoroughly. All water and moisture should be removed with a towel. Dust the diaphragm with cornstarch. Scented talc, body powder, baby powder, and the like should not be used because they can weaken the rubber.
• To clean the introducer (if one is used), wash with mild soap and warm water, rinse, and dry thoroughly.
• Place the diaphragm back in the plastic case for storage. Do not store it near a radiator or heat source or exposed to light for an extended period.
Disadvantages of diaphragm use include the reluctance of some women to insert and remove it. Although it can be inserted up to 6 hours before intercourse, a cold diaphragm and a cold gel temporarily reduce vaginal response to sexual stimulation if insertion occurs immediately before intercourse. Some women or couples object to the messiness of the spermicide. These annoyances associated with diaphragm use, along with failure to insert the device once foreplay has begun, are the most common reasons for failures of this method. Side effects may include irritation of tissues related to contact with spermicides.
The diaphragm is not a good option for women with poor vaginal muscle tone or recurrent urinary tract infections. For proper placement, the diaphragm must rest behind the pubic symphysis and completely cover the cervix. To decrease the chance of exerting urethral pressure, the woman should be reminded to empty her bladder before diaphragm insertion and immediately after intercourse. Diaphragms are contraindicated for women with pelvic relaxation (uterine prolapse) or a large cystocele. Women with a latex allergy should not use latex diaphragms.
The FemCap is the only type of cervical cap available in the United States (see Fig. 5.12, B). It comes in three sizes and is made of silicone rubber. The cap fits snugly around the base of the cervix close to the junction of the cervix and vaginal fornices. It is recommended that the cap remain in place no less than 6 hours and no more than 48 hours at a time. It is left in place at least 6 hours after the last act of intercourse. The seal provides a physical barrier to sperm; spermicide inside the cap adds a chemical barrier. The extended period of wear may be an added convenience for women.
Instructions for the actual insertion and use of the cervical cap closely resemble the instructions for use of the contraceptive diaphragm. Some of the differences are that the cervical cap can be inserted hours before sexual intercourse without a later need for additional spermicide, the cervical cap requires less spermicide than the diaphragm when initially inserted, and no additional spermicide is required for repeated acts of intercourse. Effectiveness of the first-generation FemCap has been found to be comparable to that of the diaphragm (Rivlin & Westhoff, 2017).
Although reported in very small numbers, toxic shock syndrome (TSS) can occur in association with the use of the contraceptive diaphragm and cervical caps. The nurse should instruct the woman about ways to reduce her risk for TSS. These measures include prompt removal 6 to 8 hours after intercourse, not using the diaphragm or cervical caps during menses, and learning and watching for danger signs of TSS.
The nurse should alert the woman who uses a diaphragm or cervical cap as a contraceptive method for signs of TSS. The most common signs include a sunburn type of rash, diarrhea, dizziness, faintness, weakness, sore throat, aching muscles and joints, sudden high fever, and vomiting.
The angle of the uterus, the vaginal muscle tone, and the shape of the cervix may interfere with the ease of fitting and use of the cervical cap. Correct fitting requires time, effort, and skill of both the woman and the clinician, although the FemCap may be easier to fit than previous types of cervical caps.
Because of the potential risk for TSS associated with the use of the cervical cap, another form of birth control is recommended for use during menstrual bleeding and up to at least 6 weeks after birth. The cap should be refitted after any gynecologic surgery or birth and after major weight losses or gains. Otherwise the size should be checked at least once a year.
Women who are not good candidates for wearing the cervical cap include those with abnormal Papanicolaou (Pap) test results, those who cannot be fitted properly with the existing cap sizes or who find the insertion and removal of the device too difficult, those with a history of TSS or with vaginal or cervical infections, and those who experience allergic responses to the cap or to spermicide.
The vaginal sponge is a small, round, polyurethane sponge that contains N-9 spermicide (see Fig. 5.12, C). It is designed to fit over the cervix (one size fits all). The side that is placed next to the cervix is concave for better fit. The opposite side has a woven polyester loop to be used for removal of the sponge.
The sponge must be moistened with water before it is inserted into the vagina to cover the cervix. It provides protection for up to 24 hours and for repeated instances of sexual intercourse. It should be left in place for at least 6 hours after the last act of intercourse and no more than 24 to 30 hours. Wearing it longer than 24 to 30 hours may put the woman at risk for TSS. The typical failure rate of the vaginal sponge is greater than that of the diaphragm (Center for Young Women’s Health, 2016).
Many different hormonal contraception therapies using different delivery methods are available in the United States today. General classes are described in Table 5.4. Because of the wide variety of preparations available, the woman and nurse must read the package insert for information about specific products prescribed. Formulations include combined estrogen-progestin steroidal medications or progestational agents. The formulations are administered orally, transdermally, vaginally, by implantation, or by injection.
Route of Administration
Duration of Effect
Combination Estrogen and Progestin
Synthetic estrogens and progestins in varying doses and formulations
24 hours (extended cycle possible with daily pill for 12 weeks)
Vaginal ring insertion
• Norethindrone, norgestrel
• Medroxyprogesterone acetate
Intramuscular or subcutaneous injection
Up to 3 years
Combined Estrogen-Progestin Contraceptives
The normal menstrual cycle is maintained through hormonal feedback mechanisms. FSH and LH are secreted in response to fluctuating levels of ovarian estrogen and progesterone. Regular ingestion of combined oral contraceptive pills (COCs) suppresses the action of the hypothalamus and anterior pituitary gland, leading to insufficient secretion of FSH and LH; therefore follicles do not mature, and ovulation is inhibited.
Other contraceptive effects are induced by the combined steroids. Maturation of the endometrium is altered, making the uterine lining a less favorable site for implantation. COCs also have a direct effect on the endometrium; thus from 1 to 4 days after the last COC is taken the endometrium sloughs and bleeds as a result of hormone withdrawal. The withdrawal bleeding is usually less profuse than that of normal menstruation and may last only 2 to 3 days. Some women have no bleeding at all. The cervical mucus remains thick from the effect of the progestin. Cervical mucus under the effect of progesterone does not provide as suitable an environment for sperm penetration as does the thin, watery mucus that the healthy reproductive woman produces before and during ovulation.
Monophasic pills provide fixed dosages of estrogen and progestin. They alter the amount of progestin and sometimes estrogen within each cycle. These preparations reduce the total dosage of hormones in a single cycle without sacrificing contraceptive efficacy. To maintain adequate hormone levels for contraception and enhance compliance, COCs should be taken at the same time each day. Taken exactly as directed, COCs prevent ovulation, and pregnancy cannot occur. The overall user effectiveness rate of COCs is 91% (CDC, 2011).
Because taking the pill does not relate directly to the sexual act, COC acceptability may be increased. Improvement in sexual response may occur once the possibility of pregnancy is not an issue. For many women, it is convenient to know when to expect the next menstrual flow.
Contraindications for COC use include a history of thromboembolic disorders, cerebrovascular or coronary artery disease, breast cancer, estrogen-dependent tumors, pregnancy, impaired liver function, liver tumor, lactation less than 6 weeks postpartum, smoking if older than 35 years of age, migraine with aura, surgery with prolonged immobilization or any surgery on the legs, hypertension (≥160/100), and diabetes mellitus (of more than 20 years’ duration) with vascular disease.
The effectiveness of oral contraceptives is decreased when the following medications are taken simultaneously:
• Anticonvulsants such as barbiturates, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, primidone, and topiramate
• Systemic antifungals such as griseofulvin
• Antituberculosis drugs such as rifampicin and rifabutin
• Anti-HIV protease inhibitors such as nelfinavir and amprenavir
After discontinuing oral contraception, fertility usually returns quickly, but fertility rates may be slightly lower the first 3 to 12 months after discontinuation.
Many different preparations of oral hormonal contraceptives are available. Because of these wide variations in pills, each woman must be clear about the unique dosage regimen for the preparation prescribed for her and follow directions on the package insert. Directions for care after missing one or two tablets also vary. A simple recommendation is to implement EC after two missed pills, regardless of dose.
Signs of potential complications associated with the use of oral contraceptives must be reviewed with the woman, as noted in Box 5.9. Oral contraceptives do not protect a woman against STIs. Male condoms used in combination with COCs provide protection against STIs, and this combination gives excellent protection against unplanned pregnancy.
Signs of Potential Complications: Oral Contraceptives
Before oral contraceptives are prescribed and periodically throughout hormone therapy, the woman is alerted to stop taking the pill and report immediately any of the following symptoms to the health care provider. The mnemonic ACHES helps in remembering this list:
A—Abdominal pain: may indicate a problem with the liver or gallbladder
C—Chest pain or shortness of breath: may indicate a possible clot problem within the lungs or heart
H—Headaches (sudden or persistent): may be caused by cerebrovascular accident or hypertension
E—Eye problems: may indicate vascular accident or hypertension
S—Severe leg pain: may indicate a thromboembolic process
Transdermal contraceptive system.
The contraceptive patch delivers continuous levels of progesterone and ethynyl estradiol. The patch can be applied to the lower abdomen, upper outer arm, buttock, or upper torso (except the breasts). Application is on the same day once a week for 3 weeks but not at the same site, followed by a week without the patch. Withdrawal bleeding occurs during the “no patch” week. Mechanisms of action, contraindications, and side effects are similar to those of COCs. The typical failure rate during the first year of use is less than 9% (CDC, 2011).
Vaginal contraceptive ring.
The vaginal ring (made of ethylene vinyl acetate co-polymer) delivers continuous levels of progesterone and ethynyl estradiol. Mechanisms of action, contraindications, and side effects are similar to those of COCs. One vaginal ring is worn for 3 weeks, followed by 1 week without the ring. Withdrawal bleeding occurs during the “no ring” week. The ring can be inserted by the woman and does not have to be fitted. Some wearers may experience vaginal discomfort, usually related to increased vaginal discharge; but other wearers report that the ring alleviates symptoms of vaginitis. Some couples say that the ring can be felt during intercourse. Although it is not recommended that the ring be removed for intercourse, contraceptive effectiveness would not decrease if it were replaced within 3 hours. The typical failure rate of the vaginal contraceptive ring is less than 9% during the first year of use (CDC, 2011).
Progestin-only methods impair fertility by inhibiting ovulation, thickening and decreasing the amount of cervical mucus, thinning the endometrium, and altering cilia in the uterine tubes. Because progestin-only methods do not contain estrogen, they may be used in certain instances such as lactation, when estrogen would not be recommended.
Oral progestins (minipill).
Progestin-only pills are less effective than COCs. Because minipills contain such a low dose of progestin, they must be taken at the same time every day. If the pill is taken more than 3 hours late (27 hours after the last pill), a backup contraceptive method must be initiated. Much of the contraceptive effectiveness of the minipill depends on progestin-induced changes in cervical mucus, and this effect lasts about 24 hours after oral ingestion of the pill. Users often complain of irregular vaginal bleeding. Effectiveness is increased if minipills are taken correctly. There are two instances in which the minipill is quite effective: in lactating women and women older than 40 years of age. The reduced fecundity of lactation and the perimenopause period enhance the contraceptive effects of the minipill.
Depot medroxyprogesterone acetate (DMPA; Depo-Provera) is given subcutaneously or intramuscularly in the deltoid or gluteus maximus muscle. It should be initiated during the first 5 days of the menstrual cycle and administered every 11 to 13 weeks.
When administering an injection of progestin (e.g., DMPA), the site should not be massaged after the injection because this action can hasten the absorption and shorten the period of effectiveness.
Advantages of DMPA include a contraceptive effectiveness comparable to that of combined oral contraceptives, long-lasting effects, requirement of injections only 4 times a year, and the unlikelihood of lactation being impaired. Side effects at the end of 1 year include decreased bone mineral density, weight gain, lipid changes, increased risk for venous thrombosis and thromboembolism, irregular vaginal spotting, decreased libido, and breast changes. Other disadvantages include no protection against STIs (including HIV). Return to fertility may be delayed as long as up to 18 months after discontinuing DMPA, with the median time being 10 months. The typical failure rate is 6% in the first year of use (CDC, 2011).
Women who use DMPA may lose significant bone mineral density with increasing duration of use. It is unknown if this effect is reversible. It is unknown if use of DMPA during adolescence or early adulthood, a critical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporotic fracture in later life. Women who receive DMPA should be counseled about calcium intake and exercise.
Contraceptive implants consist of one or more nonbiodegradable flexible tubes or rods that are inserted under the skin of a woman’s arm. These implants contain a progestin hormone and are effective for contraception for at least 3 years. They must be removed at the end of the recommended time. The only available implant in the United States is a single-rod etonogestrel implant (Implanon, Nexplanon), which is FDA approved. Three other devices are also used globally, but they are unavailable in the United States. One of these implants is Norplant, which used to be commonly used in the United States, but due to difficulties in insertion and removal (because it contains 6 rods), it is no longer used (Rivlin & Westhoff, 2017).
Insertion and removal of the single-rod etonogestrel capsule are minor surgical procedures involving a local anesthetic, a small incision, and no sutures. The capsule is placed subdermally in the inner aspect of the nondominant upper arm. The progestin prevents some, but not all, ovulatory cycles and thickens cervical mucus. Other advantages of the single-rod implant are that it provides long-term continuous contraception that is not related to frequency of coitus and is quickly reversible. The single-rod implant can be inserted immediately after the birth in breastfeeding women without affecting lactation. Irregular menstrual bleeding is the most common side effect. Less common side effects include headache, nervousness, nausea, skin changes, and vertigo. The implant does not protect against STIs. As in other hormonal contraception methods, condoms should be used for protection against STIs. Implants are considered to be as effective or even more effective than sterilization and IUDs, making them some of the most effective contraceptive methods (Rivlin & Westhoff, 2017).
Emergency contraception (EC) offers protection against pregnancy after intercourse occurs in instances such as broken condoms, sexual assault, dislodged cervical cap, disruption of use of any other method, or any other case of unprotected intercourse. Methods that are available in the United States that could provide postcoital contraception include the following:
• Ella (Ulipristal): single 30-mg pill containing an antiprogestin
• Plan B One-Step: single progestin-only pill containing 1.5 mg levonorgestrel
• Next Choice: two levonorgestrel 0.75-mg tablets taken orally 12 hours apart or both together
• Combined oral: estrogen-progestin contraceptive pills (e.g., 100-mcg ethinyl estradiol plus 0.5 mg levonorgestrel); two doses given 12 hours apart (Yuzpe regimen)
• Copper intrauterine device (IUD) insertion within 120 hours of intercourse
Plan B One-Step and Next Choice are approved by the FDA for over-the-counter sale to women 17 years of age and older with proof of age. Adolescents 16 years of age and younger require a prescription. Ella is available only with a prescription. States vary in the ability of pharmacists to dispense EC, and some states have implemented refusal legislation (Guttmacher Institute, 2016a).
In general, for the most effectiveness, EC should be taken by a woman as soon as possible but within 72 hours of unprotected intercourse or a birth control mishap (e.g., broken condom, dislodged ring or cervical cap, missed oral contraceptive pills, late for injection) to prevent unintended pregnancy. Research has shown a moderate amount of effectiveness between 72 and 120 hours, but no data are available for effectiveness after 120 hours (Rivlin & Westhoff, 2017).
If taken before ovulation, EC prevents ovulation by inhibiting follicular development. If taken after ovulation occurs, there is little effect on ovarian hormone production or the endometrium. To minimize the side effect of nausea that occurs with high doses of estrogen and progestin (Yuzpe regimen), the woman can be advised to take an over-the-counter antiemetic 1 hour before each dose. Nausea is not as common with the Plan B (One-Step regimen). Women with contraindications for estrogen use should use progestin-only EC. No medical contraindications for EC exist, except pregnancy and undiagnosed abnormal vaginal bleeding. If the woman does not begin menstruation within 21 days after taking the pills, she should be evaluated for pregnancy. EC is ineffective if the woman is pregnant since the pills do not disturb an implanted pregnancy. Risk for pregnancy is reduced by approximately 75% with EC (Rivlin & Westhoff, 2017).
EC will not protect the woman against pregnancy if she engages in unprotected intercourse in the days or weeks that follow treatment. Because ingestion of EC pills may delay ovulation, the woman should be cautioned that she needs to establish a reliable form of birth control to prevent unintended pregnancy. Information about EC method options and access to providers is available on the Internet at www.NOT-2-LATE.com or by calling 888-NOT-2-LATE.
IUDs containing copper (see later discussion) provide another EC option. The IUD should be inserted within 5 days of unprotected intercourse, resulting in an estimated 99% effectiveness in preventing pregnancy (Rivlin & Westhoff, 2017). This method is suggested only for women who wish to have the benefit of long-term contraception. The risk for pregnancy is reduced by as much as 99% with emergency insertion of the copper-releasing IUD.
Contraceptive counseling should be provided to all women requesting EC, including a discussion of modification of risky sexual behaviors to prevent STIs and unwanted pregnancy.
An intrauterine device (IUD) is a small T-shaped device with bendable arms for insertion through the cervix into the uterine cavity. Two strings hang from the base of the stem through the cervix and protrude into the vagina for the woman to feel for assurance that the device has not been dislodged (Fig. 5.13). There is one FDA-approved copper-bearing IUD in the United States. This is the Copper T380A (ParaGard, Frazier, Pennsylvania) IUD, which is made of radiopaque polyethylene and fine solid copper and is approved for 10 years of use. The copper primarily serves as a spermicide and inflames the endometrium, preventing fertilization. Sometimes women experience an increase in bleeding and cramping within the first year after insertion, but nonsteroidal antiinflammatory drugs (NSAIDs) can provide pain relief. The cumulative failure rate over 12 years of use of the copper IUD is 1.7% (Rivlin & Westhoff, 2017).
FIG 5.13 Intrauterine devices. A, Copper T380A. B, Levonorgestrel-releasing intrauterine device.
Another type of IUD releases levonorgestrel from its vertical reservoir. This is the levonorgestrel intrauterine system (IUS) (Mirena, Bayer, New Jersey), which is effective for up to 5 years. It works by impairing sperm motility, irritating the lining of the uterus, and exerting some anovulatory effects. Uterine cramping and uterine bleeding are usually decreased with this device, although irregular spotting is common in the first few months following insertion. The cumulative failure rate over 5 years of use is 1.1% (Rivlin & Westhoff, 2017). IUDs offer constant contraception without the need to remember to take pills each day or engage in other manipulation before or between coital acts. If pregnancy can be excluded, either device (the Copper T380A or the levonorgestrel intrauterine system) can be placed at any time during the menstrual cycle. These devices may be inserted immediately after childbirth or following a first-trimester abortion. The contraceptive effects are reversible. When pregnancy is desired, the health care provider removes the device.
Disadvantages of IUD use include increased risk for pelvic inflammatory disease within the first 20 days after insertion, especially if infection is present at the time of insertion. There is also a slight risk for uterine perforation. Neither the Copper T380A nor the levonorgestrel intrauterine system offers protection against STIs or HIV. The Copper T380A is more likely to be associated with regular menses that may have heavier flow. Women who have the levonorgestrel intrauterine system are more likely to experience scant, irregular episodes of vaginal bleeding or amenorrhea.
The woman should be taught to check for the presence of the IUD thread after menstruation to rule out expulsion of the device. If pregnancy occurs with the IUD in place, the IUD should be removed immediately in the first trimester if the strings are visible. Later in pregnancy ultrasound examination should be used to localize the IUD and rule out placenta previa. Retention of the IUD during pregnancy increases the risk for septic miscarriage and ectopic pregnancy. Some women allergic to copper develop a rash, necessitating removal of the copper-bearing IUD. Signs of potential complications of intrauterine contraception are listed in Box 5.10.
Signs of Potential Complications: Intrauterine Devices
Signs of potential complications related to intrauterine devices can be remembered using the pains mnemonic:
P—Period late, abnormal spotting or bleeding
A—Abdominal pain, pain with intercourse
I—Infection exposure, abnormal vaginal discharge
N—Not feeling well, fever, or chills
S—String missing: shorter or longer
Sterilization refers to surgical procedures intended to render the person infertile. Most procedures involve the occlusion of the passageways for the ova and sperm (Fig. 5.14). For the woman the uterine tubes are occluded; for the man the sperm ducts (vas deferens) are occluded. Only surgical removal of the ovaries (oophorectomy) or uterus (hysterectomy) or both results in absolute sterility for the woman. All other sterilization procedures have a small but definite failure rate (i.e., pregnancy may result).
FIG 5.14 Sterilization. A, Uterine tubes ligated and severed (tubal ligation). B, Sperm duct ligated and severed (vasectomy).
Female sterilization (bilateral tubal ligation) may be done immediately after giving birth (within 24 to 48 hours), concomitantly with abortion, or as an interval procedure (during any phase of the menstrual cycle). Half of all female sterilization procedures are performed immediately after a pregnancy. Sterilization procedures can be done safely on an outpatient basis. The failure rate for methods of female sterilization vary by the method and the woman’s age, but this is a very effective and safe method, with one study demonstrating a failure rate of 57 out of 1000 in the first year. However, it is important to emphasize that this form of birth control is considered to be permanent (Rivlin & Westhoff, 2017).
A laparoscopic approach or a minilaparotomy may be used for tubal ligation (Fig. 5.15), tubal electrocoagulation, or the application of bands or clips. Electrocoagulation and ligation are considered to be permanent methods. Essure is another permanent method in which a soft insert is placed into each fallopian tube, forming a barrier that grows around the inserts. The couple is told to use a backup contraceptive method for the first 3 months. Another method, the bands or clips, has the theoretic advantage of possible removal and return of tubal patency (see Patient Teaching box).
FIG 5.15 Use of minilaparotomy to gain access to uterine tubes for occlusion procedures. Tenaculum is used to lift uterus upward (arrow) toward incision.
What to Expect After Tubal Ligation
• You should expect no change in hormones and their influence.
• Your menstrual period will be about the same as before the sterilization.
• You may feel pain at ovulation.
• It is highly unlikely that you will become pregnant.
• You should not have a change in sexual functioning; you may enjoy sexual relations more because you will not be concerned about becoming pregnant.
• Sterilization offers no protection against sexually transmitted infections; therefore, you may need to use condoms.
Restoration of tubal continuity (reanastomosis) and function is technically feasible except after laparoscopic tubal electrocoagulation. Sterilization reversal is costly, difficult (requiring microsurgery), and uncertain. The success rate varies with the extent of tubal destruction and removal. The risk for ectopic pregnancy after tubal reanastomosis is approximately 10%, significantly higher than the risk of 3% in the general population (Tubal Reversal, 2017).
Laws and regulations.
All states have strict regulations for informed consent. Many states permit voluntary sterilization of any mature, rational woman without reference to her marital or pregnancy status. Although the partner’s consent is not required by law, the woman is encouraged to discuss the situation with her partner, and health care providers may request the partner’s consent. Sterilization of minors or mentally incompetent individuals is restricted by most states and often requires the approval of a board of eugenicists or other court-appointed individuals.
If federal funds are used for sterilization, the person must be at least 21 years of age on the day the consent form is signed. Informed consent must include an explanation of the risks, benefits, and alternatives; a statement that describes sterilization as a permanent, irreversible method of birth control; and a statement that mandates a 30-day waiting period between giving consent and the sterilization. Informed consent must be in the person’s native language, or an interpreter must be provided to read the consent form to the person. Signed consent forms expire after 180 days, so they must be re-signed if the sterilization procedure is still desired but has not yet been performed.
Vasectomy is the sealing, tying, or cutting of a man’s vas deferens so the sperm cannot travel from the testes to the penis. Vasectomy is the easiest and most commonly used operation for male sterilization. The surgery can be performed with local anesthesia on an outpatient basis. Pain, bleeding, infection, and other postsurgical complications are considered to be possible disadvantages to the surgical procedure.
Two methods are used for scrotal entry: conventional and no-scalpel vasectomy. The surgeon identifies and immobilizes the vas deferens through the scrotum. Then the vas is ligated or cauterized (see Fig. 5.14, B). Surgeons vary in their techniques to occlude the vas deferens: ligation with sutures, division, cautery, application of clips, excision of a segment of the vas, fascial interposition, or some combination of these methods.
Vasectomy has no effect on potency (ability to achieve and maintain erection) or volume of ejaculate. Endocrine production of testosterone continues, so secondary sex characteristics are not affected. Sperm production continues, but sperm are unable to leave the epididymis and are lysed by the immune system. Vasectomy does not change the man’s transmission of the HIV virus if he is infected. He will need to be instructed to engage in a number of ejaculations until there are no viable sperm remaining above the area of the surgery. Until this occurs, as documented by semen analysis, the couple should use backup contraception.
Complications after bilateral vasectomy are uncommon and usually not serious. They include bleeding (usually external), suture reaction, and reaction to the anesthetic agent. Men occasionally develop a hematoma, infection, or epididymitis. Less common are painful granulomas from accumulation of sperm. Vasectomy is highly effective and safe. It is estimated that 5% to 7% of men in the United States request reversal of vasectomy (Rivlin & Westhoff, 2017), and although reanastomosis is possible, it is important to emphasize that men should view the decision to have vasectomy as permanent.
Microsurgery to reanastomose (restore tubal continuity) the sperm ducts can be accomplished successfully (i.e., sperm in the ejaculate) in 86% of cases; however, the fertility rate following reanastomosis is only about 50% (Baker & Sabanegh, 2013). The rate of success decreases as the time since the procedure was initially performed increases. The vasectomy may result in permanent changes in the testes that leave men unable to father children. The changes are those ordinarily seen only in older adults (e.g., interstitial fibrosis [scar tissue between the seminiferous tubules]). In addition, some men develop antibodies against their own sperm (autoimmunization).
The nurse plays an important role in helping people make decisions so all requirements for informed consent are met. The nurse also provides information about alternatives to sterilization such as contraception.
Information must be given about what is entailed in the various procedures, how much discomfort or pain can be expected, and what type of care is needed. Many individuals fear sterilization procedures because of imagined effects on sexual functioning. They need reassurance concerning the hormonal and psychologic basis of sexual functioning. The fact that uterine tube occlusion or vasectomy has no biologic sequelae in terms of sexual adequacy needs to be communicated and reinforced. If sex drive is affected, it can be a sign of emotional or other physical issues and should discussed with a physician or nurse practitioner.
Preoperative care includes health assessment, which includes a psychologic assessment, physical examination, and laboratory tests. The nurse confirms that the individual understands printed instructions. Ambivalence and extreme fear of the procedure should be reported to the health care provider.
Postoperative care depends on the procedure performed (e.g., laparoscopy, laparotomy for tubal occlusion, or vasectomy). General care includes recovery after anesthesia, vital signs, fluid-electrolyte balance (intake and output, laboratory values), prevention of or early identification and treatment of infection or hemorrhage, control of discomfort, and assessment of emotional response to the procedure and recovery.
Discharge planning depends on the type of procedure performed. In general, the patient is given written instructions about observing for and reporting symptoms and signs of complications, the type of recovery to be expected, and the date and time for a follow-up appointment.
Induced abortion is the purposeful interruption of a pregnancy before 20 weeks of gestation. (Spontaneous abortion or miscarriage is discussed in Chapter 12.) If the abortion is performed at the woman’s request, the term elective abortion is usually used; if performed for reasons of maternal or fetal health or disease, the term therapeutic abortion applies. Many factors contribute to a woman’s decision to have an abortion. Indications include (1) preservation of the life or health of the mother, (2) genetic disorders of the fetus, (3) rape or incest, and (4) the pregnant woman’s request. The control of birth, dealing as it does with human sexuality and the question of life and death, is one of the most emotional components of health care. It has been the most controversial social issue in the last half of the twentieth century and continues to be so today. Regulations exist to protect the mother from the complications of abortion.
Abortion is regulated in most countries, including the United States. Before 1970 legal abortion was not widely available in the United States. However, in January 1973 the US Supreme Court set aside previous antiabortion laws and legalized it. This decision established a trimester approach to abortion, but controversy remains, and there are continuing attempts to change this law.
Following the US Supreme Court ruling in 1973 in the case of Roe versus Wade, the decision of first-trimester abortion was deemed to be between the pregnant woman and her health care provider, and state laws determining abortion to be illegal were struck down. During the second trimester, abortion is left to the discretion of the individual states to regulate procedures as long as these regulations are reasonably related to the woman’s health. In the third trimester, abortions may be limited or even prohibited by state regulation unless the restriction interferes with the life or health of the pregnant woman (Roe v. Wade, 1973). Hospitals maintained by Roman Catholics and some of those maintained by strict fundamentalists forbid abortion (and often sterilization) despite legal challenges.
Currently 38 states legislate that abortion be performed by a licensed physician. Nurse practitioners can perform aspiration abortions in six states: California, Montana, New Hampshire, New York, Rhode Island, and Vermont. In these states plus six additional states, nurse practitioners can prescribe medication abortions (Guttmacher Institute, 2016b; Levi et al., 2015). Congress has legislated that Medicaid funds can only be used to pay for abortion when a woman’s life is endangered. States vary on the financing of abortions, with 17 states using their own funds to pay for them, depending on the circumstances surrounding the procedure. States also vary regarding parental notification and/or consent regarding abortion, with 37 states providing legislation for some type of parental involvement in the abortion of a pregnant daughter who is a minor. Individual health care providers may refuse to participate in abortion in 45 states (Guttmacher Institute).
In the United States it is estimated that 50% of pregnancies are unintended, with about 40% of those unintended pregnancies ending in elective abortion (Rivlin & Westhoff, 2017). The number of abortions in the United States has decreased by 13% since 2008 (Rivlin & Westhoff). Most abortions occur in women who already have children, and abortion rates tend to be higher in women whose income is below the poverty level.
The Association of Women’s Health, Obstetric and Neonatal Nurses (AWHONN, 2016) supports a nurse’s right to choose whether to participate in abortion procedures in keeping with her or his “personal, moral, ethical, or religious beliefs.” AWHONN also advocates that “nurses have a professional obligation to inform their employers, at the time of employment, of any attitudes and beliefs that may interfere with essential job functions.” Levi and colleagues (2015) describe why they choose to provide abortion services and why this is an important role for nursing.
Rates of biologic complications after abortions such as ectopic pregnancy, infection, or hemorrhage tend to be low if the woman aborts during the first trimester. Psychologic sequelae of induced abortion are uncommon and may be related to circumstances and support systems surrounding the pregnant woman such as the attitudes reflected by friends, family, and health care workers. The woman facing an abortion is pregnant and exhibits the emotional responses shared by all pregnant women, including the possibility of depression.
Nurses and other health care providers often struggle with the same values and moral convictions as those of the pregnant woman. The conflicts and doubts of the nurse can be readily communicated to women who are already anxious. Regardless of personal views on abortion, nurses who provide care to women seeking abortion have an ethical responsibility to counsel women about their options and make appropriate referrals.
Institutional Policies for Nurses’ Rights and Responsibilities Related to Abortion
Nurses’ rights and responsibilities related to caring for abortion patients should be protected through policies that describe how the institution accommodates the nurse’s ethical or moral beliefs and what the nurse should do to avoid patient abandonment in such situations. Nurses should know what policies are in place in their institutions and encourage such policies to be written. Nurses and nurse practitioners play an important role in the care of a woman choosing to have an elective abortion.
A thorough assessment is conducted through history, physical examination, and laboratory tests. The length of pregnancy and the condition of the woman must be determined to select the appropriate type of abortion procedure. An ultrasound examination should be performed before a second-trimester abortion is done. If the woman is Rh-negative, she is a candidate for prophylaxis against Rh isoimmunization. She should receive Rho(D) immune globulin within 72 hours after the abortion if she is D-negative and if Coombs’ test results are negative (if the woman is unsensitized or isoimmunization has not developed).
The woman’s understanding of alternatives, the types of abortions, and expected recovery is assessed. Misinformation and gaps in knowledge are identified and corrected. The record is reviewed for the signed informed consent, and the woman’s understanding is verified. General preoperative, operative, and postoperative assessments are performed.
Analysis of data leads to identification of the appropriate nursing diagnoses for the woman undergoing elective abortion. Potential nursing diagnoses are listed in Box 5.11. Counseling about abortion includes helping the woman identify how she perceives the pregnancy, providing information about the choices available (i.e., having an abortion or carrying the pregnancy to term and then either keeping the infant or placing the baby for adoption), and informing about the types of abortion procedures and risks.
Selected Nursing Diagnoses for Women Having Elective Abortion
• Decisional conflict related to
• Value system
• Fear related to
• Abortion procedure
• Potential complications
• Implications for future pregnancies
• What others might think
• Grieving related to
• Distress at loss or feelings of guilt
• Risk for infection related to
• Effects of the procedure
• Lack of understanding of preoperative and postoperative self-care
• Acute pain related to
• Effects of the procedure or postoperative events
Methods for performing early elective abortion (up to 10 weeks of gestation) include surgical (aspiration) and medical methods (mifepristone with prostaglandin and methotrexate with misoprostol). The earlier an abortion is performed, the safer it is, reducing the need for later-term abortions.
Surgical (Aspiration) Abortion
Aspiration (vacuum or suction curettage) is the most common procedure in the first trimester. Aspiration abortion is usually performed under local anesthesia in a health care provider’s office, a clinic, or a hospital. The ideal time for performing this procedure is 8 to 12 weeks after the last menstrual period (gestational age of 10 weeks) (Rivlin & Westhoff, 2017). The suction procedure for performing an early elective abortion usually requires less than 5 minutes.
A bimanual examination is done before the procedure to assess uterine size and position. A speculum is inserted, and the cervix is anesthetized with a local anesthetic agent. The cervix is dilated if necessary, and a cannula connected to suction is inserted into the uterine cavity. The products of conception are evacuated from the uterus.
During the procedure, the woman is kept informed about what to expect next (e.g., menstrual-like cramping and sounds of the suction machine). The nurse assesses the woman’s vital signs. The aspirated uterine contents must be inspected carefully to ascertain whether all fetal parts and adequate placental tissue have been evacuated. After the abortion, the woman rests on the table until she is ready to stand. She remains in the recovery area or waiting room for 1 to 3 hours for detection of excessive cramping or bleeding; then she is discharged.
Bleeding after the operation is normally about the equivalent of a heavy menstrual period, and cramps are rarely severe. Excessive vaginal bleeding and infection such as endometritis or salpingitis are the most common complications of induced abortion. Retained products of conception are the primary cause of vaginal bleeding. Evacuation of the uterus, uterine massage, and administration of oxytocin or methylergonovine (Methergine) may be necessary to decrease vaginal bleeding. Prophylactic antibiotics to decrease the risk for infection are commonly prescribed. Generally, postabortion pain can be relieved with NSAIDs such as ibuprofen.
Instructions following a surgical abortion differ among health care providers. For example, there is disagreement as to whether tampons should not be used for at least 3 days or should be avoided for up to 3 weeks, or whether resumption of sexual intercourse may be permitted within 1 week or discouraged for 2 weeks. The woman may shower daily. Instruction is given to watch for excessive bleeding and other signs of complications and to avoid douches of any type. The woman can expect her menstrual period to resume 4 to 6 weeks after the day of the procedure. The nurse offers information about the birth control method the woman prefers if contraceptive counseling has not been done during the counseling interview that usually precedes the decision to have an abortion. The woman must be strongly encouraged to return for her follow-up visit so complications can be detected and an acceptable contraceptive method prescribed. A pregnancy test may also be performed to determine if the pregnancy has been terminated successfully.
The woman who has an induced abortion should be given clear instructions to return immediately to the health care facility or emergency department for any of the following symptoms:
• Fever greater than 38° C (100.4° F)
• Bleeding greater than two saturated pads in 2 hours or heavy bleeding lasting a few days
• Foul-smelling vaginal discharge
• Severe abdominal pain, cramping, or backache
• Abdominal tenderness (when pressure applied)
Data from Paul, M., & Stein, T. (2011). Abortion. In R. A. Hatcher, J. Trussell, & A. L. Nelson (Eds.), Contraceptive technology. Atlanta, GA: Ardent Media.
Early abortion using medication rather than surgery has been popular in Canada and Europe for more than 15 years, but medical abortion is a relatively new procedure in the United States. Medical abortions are available for use in the United States for up to 9 weeks after the last menstrual period. Methotrexate, misoprostol, and mifepristone are the drugs used in the current regimens to induce early abortion. Medication abortions increased from 6% in 2011 to 31% in 2014. However, the overall abortion rate has declined (Guttmacher Institute, 2017).
Misoprostol and Mifepristone
Misoprostol (Cytotec) is a prostaglandin analog that acts directly on the cervix to soften and dilate and on the uterine muscle to stimulate contractions. Mifepristone, formerly known as RU 486, was approved by the FDA in 2000. It works by preventing progesterone from binding to receptors, thereby blocking the action of progesterone, which is necessary for maintaining pregnancy (Rivlin & Westhoff, 2017).
Mifepristone may be taken up to 7 weeks after the last menstrual period. The FDA-approved regimen is that the woman takes 600 mg of mifepristone orally; 48 hours later she returns to the office and takes 400 mcg of misoprostol orally (unless abortion has already occurred and been confirmed) (Rivlin & Westhoff, 2017). Two weeks after the administration of mifepristone, the woman must return to the office for a clinical examination or ultrasound to confirm that the pregnancy has been terminated.
With any medical abortion regimen, the woman usually experiences bleeding and cramping. Side effects of the medications include nausea, vomiting, diarrhea, headache, dizziness, fever, and chills. These are attributed to misoprostol and usually subside in a few hours after administration.
Because the great majority of induced abortions in the United States occur in the first trimester, only about 10% are performed in the second trimester. Second-trimester abortion is associated with more complications and costs than first-trimester abortions. Dilation and evacuation (D&E) accounts for almost all procedures performed in the United States. This term is also often referred to as dilation and curettage (D&C).
In general, medical administration of second-trimester abortions involves the same drugs (misoprostol and mifepristone) used in medical termination of pregnancy during the first trimester. The D&E procedure is often chosen by patients because it has a lower risk for retained products of conception and a decreased hospitalization time (Rivlin & Westhoff, 2017).
Dilation and Evacuation
D&E can be performed at any point up to 20 weeks of gestation, although it is more often performed between 13 and 16 weeks. After 16 weeks, the cervix requires more dilation because the products of conception are larger. Often laminaria are inserted several hours or several days before the procedure, or misoprostol can be applied to the cervix to soften the tissue. The procedure is similar to that of vaginal aspiration, except that a larger cannula is used and other instruments may be needed to remove the fetus and placenta. Nursing care includes monitoring vital signs, providing emotional support, administering analgesics, and postoperative monitoring. Disadvantages of D&E include possible long-term harmful effects on the cervix.
The woman considering an abortion will need help to explore the meaning of the various alternatives for elective abortion and consequences to herself and her significant others. It is often difficult for a woman to express her true feelings (e.g., what abortion means to her now and in the future and what support or regret her friends and peers may demonstrate). A calm, matter-of-fact approach on the part of the nurse can be helpful. Clarifying, restating, and reflecting statements; open-ended questions; and feedback are communication techniques that can be used to maintain a realistic focus on the situation and bring the woman’s problems into the open. Sometimes the partner or family are involved and may also need support as there may be conflicting feelings among family members of the partner. The woman may have been a victim of human trafficking (see Chapter 3). If family or friends cannot be involved, scheduling time for nursing personnel to give the necessary support is an essential component of the care plan.
Information about alternatives to abortion such as referral to adoption agencies or support services if the woman chooses to keep her baby is provided. If a decision is made to have an abortion, the woman must be assured of continued support. Information about what is entailed in various procedures, how much discomfort or pain can be expected, and what type of care is needed must be given. A discussion of the various feelings, including depression, guilt, regret, and relief, that the woman might experience after the abortion is needed. Information about community resources for postabortion counseling may be needed.
Evidence of long-term depression after elective abortion has been inconclusive. Guilt and anxiety may occur more with young women, women with poor social support, multiparous women, and women with a history of psychiatric illness. Women having second-trimester abortions may have more emotional distress than women having abortions in the first trimester. Because symptoms can vary among women who have had abortions, nurses must assess women for grief reactions and facilitate the grieving process through active listening and nonjudgmental support and care.
American Society for Reproductive Medicine. Age and fertility. [Retrieved from] https://www.asrm.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/agefertility.pdf; 2012.
American Society for Reproductive Medicine. Preimplantation genetic testing. [Retrieved from] http://www.asrm.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/PGT_2014.pdf; 2014.
American Society for Reproductive Medicine. Quick facts about infertility. [Retrieved from] https://www.asrm.org/detail.aspx?id=2322; 2016.
Association of Women’s Health, Obstetric and Neonatal Nurses. Position statement: Midwifery. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2016;45(3):454–457.
Baker K, Sabanegh E. Obstructive azoospermia: Reconstructive techniques and results. Clinics (Sao Paulo). 2013;68(1 suppl):61–73 [Retrieved from] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583161/.
Center for Young Women’s Health. Contraceptive sponge. [Division of Adolescent and Young Adult Medicine, Division of Gynecology, Boston Children’s Hospital; Retrieved from] http://youngwomenshealth.org/2013/08/22/contraceptive-sponge/; 2016.
Centers for Disease Control and Prevention. Effectiveness of family planning methods. [Retrieved from] https://www.asrm.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/agefertility.pdf; 2011.
Centers for Disease Control and Prevention. Ten great public health achievements in the 20th century. [Retrieved from] https://www.cdc.gov/about/history/tengpha.htm; 2013.
Centers for Disease Control and Prevention. What is assisted reproductive technology?. [Retrieved from] https://www.cdc.gov/art/whatis.html; 2014.
Centers for Disease Control and Prevention. Unintended pregnancy prevention. [Retrieved from] https://www.cdc.gov/reproductivehealth/unintendedpregnancy/; 2015.
Contracept.org. Fertility awareness methods: Standard days method. [Retrieved from] http://www.contracept.org/calendar.php; 2016.
Contracept.org. Fertility awareness methods: The TwoDay method. [Retrieved from] http://www.contracept.org/twoday-method.php; 2016.
Crawford NM, Steiner AZ. Age-related infertility. Obstetrics and Gynecology Clinics of North America. 2015;42(1):15–25.
Greenblatt A. Fewer babies available for adoption by US parents. National Public Radio. [Retrieved from] http://www.npr.org/2011/11/17/142344354/fewer-babies-available-for-adoption-by-u-s-parents; 2011.
Guttmacher Institute. Emergency contraception. [Retrieved from] https://www.guttmacher.org/sites/default/files/pdfs/spibs/spib_EC.pdf; 2016.
Guttmacher Institute. An overview of abortion laws, as of August 1, 2016. [Retrieved from] https://www.guttmacher.org/state-policy/explore/overview-abortion-laws; 2016.
Guttmacher Institute. Induced abortion in the US. [Retrieved from] https://www.guttmacher.org/fact-sheet/induced-abortion-united-states; 2017.
Kaplan K. More than 1.5% of American babies owe their births to IVF, report says. [Los Angeles Times; Retrieved from] http://www.latimes.com/science/sciencenow/la-sci-sn-ivf-live-births-success-rate-20150303-story.html; 2015.
Leiva R, Burhan U, Kyrillos E, Fehring R, McLaren R, Dalzell C, et al. Use of ovulation predictor kits as adjuncts when using fertility awareness methods (FAMs): A pilot study. Journal of the American Board of Family Medicine. 2014;27(3):427–429.
Levi AJ, Banks E, Dieseldorff J, Tueros VS. The clinician speaks: Why I am an abortion provider. [Women’s Healthcare, May, 46-49; Retrieved from] http://npwomenshealthcare.com/wp-content/uploads/2015/05/Comm_M15.pdf; 2015.
Lobo RA. Infertility: Etiology, diagnostic evaluation, management, prognosis. Lobo RA, Gershenson DM, Lentz GM, Valea FA. Comprehensive gynecology. 7th ed. Mosby: Philadelphia, PA; 2017.
Rivlin K, Westhoff C. Family planning. Lobo RA, Gershenson DM, Lentz GM, Valea FA. Comprehensive gynecology. 7th ed. Mosby: Philadelphia, PA; 2017.
Roe v. Wade, 410 US 113, 154 (1973).
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Genetics, Conception, and Fetal Development
Ellen F. Olshansky
This chapter presents a brief discussion of genetics and the role of the nurse in genetics. It also provides an overview of the process of fertilization and of the development of the normal embryo and fetus.
Recent advances in molecular biology and genomics have revolutionized the field of health care by providing the tools needed to determine the hereditary component of many diseases as well as improve our ability to predict susceptibility to disease, onset and progression of disease, and response to medications (Calzone, Jenkins, Nicoli, et al., 2013; McCarthy, McLeod, & Ginsburg, 2013).
Since the human genome was sequenced, there has been a gradual shift from genetics to genomics. Genetics refers to the study of a particular gene, whereas genomics refers to the study of the entire genome. Genes are the basic physical units of inheritance that are passed from parents to offspring and contain the information needed to specify traits. The genome is the entire set of genetic instructions found in a cell. For these and other definitions of genetic terms, check out the Talking Glossary of Genetic Terms (www.genome.gov/Glossary).
With growing public interest in personalized genomic information (information about much or all of an individual’s genome), increasing development of practice guidelines, mounting commercial pressures, and ever-increasing opportunities for individuals, families, and communities to participate in the direction and design of their genomic health care, genetic services are rapidly becoming an integral part of routine health care (Manolio, Chisholm, Ozenberger, et al., 2013). Moreover, many individuals and families have participated in direct-to-consumer genetic testing (testing marketed directly to consumers through television, print advertisements, and websites). Although much of the information provided by direct-to-consumer testing companies is recreational (ancestry information, information about types of ear wax, and bitter taste perception), some of the information provided is health related and could be interpreted as diagnostic. Because of this, direct-to-consumer testing that is provided without the involvement of competent health care professionals may be not only unhelpful, but also harmful (Beery, 2013). However, recently it has been reported that more negotiation is occurring between direct-to-consumer testing and the FDA to create regulations (Gever, 2015).
More recently, attention has turned toward “precision medicine” or “personalized medicine,” which emphasizes a focus away from the notion that “one size fits all” and toward the understanding that each individual’s uniqueness influences how best to determine medical treatment (US Food and Drug Administration [FDA], 2016). Personalized medicine holds promise for tailored treatments for individuals based on their own personal makeup.
Epigenetics is another more recent concept. Epigenetics refers to the variations in phenotype that occur due to the influence of the environment and our lifestyle on genetics. Moore (2015) has written eloquently on this new concept that he believes is key to understanding an individual’s development as a unique human being.
Genetic disorders affect people of all ages, from all socioeconomic levels, and from all racial and ethnic backgrounds. Genetic disorders affect not only individuals but also families, communities, and society. Advances in genetic testing and genetically based treatments have altered the care provided to affected individuals. Improvements in diagnostic capability have resulted in earlier diagnosis and enabled individuals who previously would have died in childhood to survive into adulthood. However, for most genetic conditions, therapeutic or preventive measures do not exist or are very limited. Consequently, the most useful means of reducing the incidence of these disorders is by preventing their transmission. It is standard practice to assess all pregnant women for heritable disorders to identify potential problems.
Nursing Expertise in Genetics and Genomics
Because of their front-line position in the health care system and their long-standing history of providing holistic family-centered care, nurses are likely to be one of the first health care professionals to whom individuals and families turn with questions about genetic risk and susceptibility and to seek guidance regarding the complexities of genetic testing and interpretation. Nowhere is this more apparent than in maternity and women’s health care. A growing number of maternity and women’s health nurses provide information about the availability of genetic tests, answer questions about them, and order and interpret genetic tests. Although most of these tests are used to determine a patient’s risk for having a child affected by a genetic condition such as Down syndrome (DS), cystic fibrosis (CF), or sickle cell disease, the number of genetic tests used to determine the presence of, or susceptibility to, adult-onset disorders (e.g., hereditary colorectal cancer, hereditary breast and ovarian cancer, and Huntington’s disease [HD]) continues to rise. Additionally, nurses working in maternity and women’s health are caring for an increasing number of individuals and families who are dealing with complex ethical, legal, and social issues associated with genetic testing and the experience of living with someone who has a genetic condition (Wilke, Gallo, Yao, et al., 2013).
Essential Competencies in Genetics and Genomics for All Nurses
Nearly 50 organizations, including the Association of Women’s Health, Obstetric and Neonatal Nurses (AWHONN) and the National Association of Neonatal Nurses (NANN), have endorsed the Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics (www.genome.gov/17517146). According to these guidelines, which were developed by an independent panel of nurse leaders (consensus panel) from clinical, research, and academic settings and published by the American Nurses Association and the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) (Greco, Tinley, & Seibert, 2011), all nurses need to have minimal competencies in genetics and genomics regardless of their academic preparation, practice setting, or specialty. Some of the competencies most relevant to nurses in the area of maternity and women’s health include the following:
• Construct a pedigree from collected family history information using standardized symbols and terminology
• Develop a plan of care that incorporates genetic and genomic assessment information
• Recognize when one’s own attitudes and values related to genetics and genomic science may affect care provided to patients
• Provide patients with credible, accurate, appropriate, and current genetic and genomic information, resources, services, and/or technologies that facilitate decision making
• Demonstrate in practice the importance of tailoring genetic and genomic information and services to patients based on their culture, religion, knowledge level, literacy, and preferred language
• Assess patients’ knowledge, perceptions, and responses to genetic and genomic information
• Facilitate referrals for specialized genetic and genomic services for patients as needed
Expanded Roles for Maternity and Women’s Health Nurses
Expanded roles for nurses with expertise in genetics and genomics are developing in many areas of maternity and women’s health nursing. These areas include but are not limited to prenatal screening and testing; carrier testing during pregnancy; newborn screening; palliative care for infants with life-threatening genetic conditions and their families; the identification and care of individuals with genetic conditions and their families; and the care of women with genetic conditions who require specialized care during pregnancy, such as women with neuromuscular disease, CF, and factor V Leiden deficiency (DeLuca, Zanni, Bonhomme, et al., 2013; Frazer, Porter, & Gross, 2013; Johnson, Giarelli, Lewis, et al., 2013; Prows, Hopkin, Barnoy, et al., 2013; Wilke et al., 2013). As an example, the Oncology Nursing Society (ONS) (www.ons.org) has taken an active role in providing oncology nurses with the education and resources they need to integrate genetics and genomics into all phases of care for individuals and families affected by cancer, including information specifically related to cancers affecting women.
Human Genome Project and Implications for Clinical Practice
The Human Genome Project was a publicly funded international effort coordinated by the NIH and the US Department of Energy (www.doegenomes.org). When the Human Genome Project was initiated in 1990, the ultimate goal of the project was to map the human genome (the complete set of genetic instructions in the nucleus of each human cell) by 2005. Considering that the human genome consists of approximately 3 billion base pairs of DNA, many people regarded this as an impossible task. However, by 2003 a substantially complete version of the human genome was announced.
The Human Genome Project found that all human beings are 99.9% identical at the DNA level (NHGRI, 2016). This finding that human beings are 99.9% identical at the DNA level should help discourage the use of science as a justification for drawing precise racial boundaries around certain groups of people. A more recent effort by the NHGRI called the Encyclopedia of DNA Elements, or the ENCODE Project, was organized to identify the genome’s functional elements (ENCODE, 2016). Researchers found that more than 80% of the human genome is linked to a specific biologic function, and that proteins interact with DNA in more than 4 million regulatory regions. This finding made clearer the active genome in which genes are turned on and off by proteins using sites that may be at a great distance from the genes. Identification of regulatory regions will help explain varied functions of different types of cells. (www.genome.gov/pfv.cfm?pageID=27549810).
Importance of Family History
Completion of the Human Genome Project and the resultant identification of the inherited causes for many diseases has resulted in renewed interest in family history. Although it is easy to be impressed by the more than 3600 genetic tests currently available through the Genetic Testing Registry (GTR), which can be accessed at its website (www.ncbi.nlm.nih.gov/gtr), family history will most likely continue to be the single most cost-effective piece of genetic information. In 2008, Solomon, Jack, and Feero described a complete three-generation family history that includes ancestry information concerning both sides of family as the best genetic “test” applicable to preconception care. When nurses and other clinicians conduct a family history, they can gain not only valuable information about the structure of the family and diseases that affect various individuals in the family, but also a rich understanding of family relationships, social context, occupations, lifestyle, and health habits (American College of Obstetricians and Gynecologists [ACOG], 2011a). The process of collecting this information often facilitates the development of a relationship between the patient/family and the clinician. In 2004, the US Department of Health and Human Services launched the Family History Initiative by designating Thanksgiving Day as National Family History Day. The US Surgeon General encouraged families to use their family gatherings as a time to talk about and collect important family health history. A number of family history tools are available free of charge online. One of the most widely used family history tools is the My Family Health Portrait (https://familyhistory.hhs.gov). Another helpful tool is the family health history tool, Does it run in the family? that was developed by the Genetic Alliance (www.doesitruninthefamily.org). The Centers for Disease Control and Prevention (CDC) also provides links to family history resources (https://www.cdc.gov/genomics/famhistory/index.htm).
The preconception period is an ideal time to review family history and provide personalized recommendations based on family history (ACOG, 2011a). It is also one of the best times to counsel couples about carrier testing options that are based on known population-specific risks (Bodurtha & Strauss, 2012). Finally, the preconception period is an optimal time to refer couples, when appropriate, to specialists in high-risk pregnancy and genetics.
Gene Identification and Testing
Initial efforts to sequence and analyze the human genome have proven invaluable in the identification of genes involved in disease and in the development of genetic tests. In an effort to bridge the transition from discovery to diagnostics and treatments, the NIH launched the Genetic Testing Registry (GTR) in 2012. The GTR (www.ncbi.nlm.nih.gov/gtr) is a free online tool that can be used to obtain a list of available genetic tests. The GTR website also includes links to other resources such as GeneReviews and Online Mendelian Inheritance in Man (OMIM). GeneReviews is a collection of expert-authored, peer-reviewed disease descriptions presented in a standardized format and focused on clinically relevant and medically actionable information on the diagnosis, management, and genetic counseling of individuals and families with specific inherited conditions. OMIM is an online catalog of human genes and genetic disorders.
Genetic testing involves the analysis of human DNA, ribonucleic acid (RNA), which has a major role in protein synthesis, chromosomes (threadlike packages of genes and other DNA in the nucleus of a cell), or proteins to detect abnormalities related to an inherited condition. Genetic tests can be used to directly examine the DNA and RNA that make up a gene (direct or molecular testing), look at markers that are coinherited with a gene that causes a genetic condition (linkage analysis), examine the protein products of genes (biochemical testing), or examine chromosomes (cytogenetic testing). Cytogenetic analysis of malignant tissue has become a mainstay of oncology.
Most of the genetic tests now offered in clinical practice are tests for single-gene disorders in patients with clinical symptoms or who have a family history of a genetic disease (http://iml.dartmouth.edu/education/cme/Genetics). Some of these genetic tests are prenatal tests or tests used to identify the genetic status of a pregnancy at risk for a genetic condition. Current prenatal testing options include maternal serum screening (a blood test used to see if a pregnant woman is at increased risk for carrying a fetus with a neural tube defect or a chromosomal abnormality such as DS, trisomy 18, or trisomy 13), fetal ultrasound or sonogram (an imaging technique using high-frequency sound waves to produce images of the fetus inside the uterus), invasive procedures (chorionic villus sampling and amniocentesis), and noninvasive prenatal testing for fetal aneuploidy (a blood test that uses cell-free DNA from the plasma of pregnant women to screen for DS and, in some cases, trisomy 13 and trisomy 18 (see Chapter 10 for more in-depth information).
Another type of genetic test is the carrier screening test used to identify individuals who have a gene mutation for a genetic condition but do not show symptoms of the condition because it is an autosomal recessive condition (e.g., CF, sickle cell disease, and Tay-Sachs disease). A third type of genetic testing is predictive testing, which is used to clarify the genetic status of asymptomatic family members. The two types of predictive testing are presymptomatic and predispositional. Mutation analysis for Huntington disease (HD), a neurodegenerative disorder, is an example of presymptomatic testing. If the gene mutation for HD is present, symptoms of HD are certain to appear if the individual lives long enough. Testing for a BRCA1 gene mutation to determine breast cancer susceptibility is an example of predispositional testing. Predispositional testing differs from presymptomatic testing in that a positive result (indicating that a BRCA1 mutation is present) does not indicate a 100% risk for developing the condition (breast cancer).
In addition to using genetic tests to test for single-gene disorders in patients with clinical symptoms or who have a family history of a genetic disease, genetic tests are used for population-based screening. For example, each year in the United States, approximately 4 million infants undergo newborn screening (Bodurtha & Strauss, 2012). Newborn screening is a mandatory, state-supported public health program. Initially, newborn screening in the United States was only concerned with a few conditions such as phenylketonuria (PKU). However, with the advent of tandem mass spectrometry, the number of conditions included in newborn screening grew rapidly (DeLuca et al., 2013). Currently, most states test newborns for 31 core disorders and 26 secondary disorders (McCarthy et al., 2013). A complete list of conditions tested for in each state is available on the National Newborn Screening and Genetics Resource website (http://genes-r-us.uthscsa.edu). (See Chapter 23.)
Another type of population-based screening is carrier screening for single-gene disorders such as CF, sickle cell disease, and Tay-Sachs disease either preconceptionally or prenatally. In 2001, ACOG and the American College of Medical Genetics (ACMG) recommended that clinicians offer carrier screening for CF to individuals with a family history of CF, reproductive partners of individuals who have CF, and couples in whom one or both partners are Caucasian and are planning a pregnancy or seeking prenatal care. Ten years later, in 2011, ACOG updated its recommendations and emphasized that it is not a straightforward or easy task to assign an ethnicity to a person and, therefore, the recommendation was updated to offer to screen all women of reproductive age to determine if they are carriers of CF (ACOG, 2011b). Recommendations for newborn screening for CF appeared in 2004, and soon after this many newborn screening programs in the United States began offering newborn screening for CF. One outcome of this broader carrier and newborn screening for CF is that more and more individuals are being informed they have a CF mutation. However, the correlation between genotype (an individual’s collection of genes) and phenotype (an individual’s observable traits) is poor for many of the more than 1900 CF mutations identified to date. That is, whereas some CF mutations are associated with significant health problems (poor growth, greasy stools, and chronic respiratory problems), others are not. Because of this, the significance of many CF mutations is uncertain. As a result, nurses and other health care professionals are increasingly being asked to communicate results with uncertain significance to individuals and families during the preconception, prenatal, and newborn periods. A coherent and systematic approach is needed for the introduction of new tests into population-based screening programs.
The use of genome sequencing (e.g., whole-genome sequencing and next-generation sequencing) has entered the clinical setting (Conley, Biesecker, Gonsalves, et al., 2013; McCarthy et al., 2013; Wade, Tarini, & Wilfond, 2013). It is difficult to determine the cost for sequencing a particular genome as there are many factors to consider (National Human Genome Research Institute, 2016).
One of the most promising clinical applications of the Human Genome Project has been pharmacogenomic testing (the use of genetic information to guide a patient’s drug therapy). Associations between genetic variation and drug effect have been observed for a number of commonly used drugs, including warfarin, an anticoagulant commonly used to reduce the risk for thromboembolic events in patients with a history of deep vein thrombosis, pulmonary embolism, myocardial infarction, or atrial fibrillation (McCarthy et al., 2013). Warfarin is a drug with a narrow therapeutic index; it can result in serious bleeding with supratherapeutic doses and thromboembolic events with subtherapeutic doses. Because of this and the fact that there is a great deal of interpatient and intrapatient dose variation, warfarin is one of the most common causes of serious adverse drug reactions. There is mounting evidence that genotype-guided warfarin dosing may not only help reduce the serious adverse drug reactions commonly associated with its use, but also increase dosing accuracy, shorten the time to dose stabilization, and help identify individuals who may require more frequent monitoring. In August 2007, the FDA approved updated labeling for warfarin. The updated labeling acknowledges that individuals with variations in their CYP2C9 and VKORC1 genes may require a lower initial dose of warfarin. However, there are not enough clinical data yet to recommend that this type of testing be mandatory, but there are some FDA-approved drugs with pharmacogenomic labeling (US Department of Health and Human Services, 2016).
Pharmacogenomic testing can also be used to target therapies. Trastuzumab (Herceptin), a monoclonal antibody that specifically targets HER2/neu overexpressing breast tumors, is an example of a drug for which an obligatory genetic test has been developed (McCarthy et al., 2013). The purpose of this obligatory genetic test is to identify the subset of women with breast cancer who overexpress HER2/neu. Women who overexpress HER2/neu are most likely the only breast cancer patients who will benefit from taking trastuzumab (www.herceptin.com/index.jsp).
The aim of gene therapy is to correct defective genes that are responsible for disease development. Generally, gene therapy involves inserting a healthy copy of the defective gene into the somatic cells (any cell of the body except sperm and egg cells) of the affected individual. Although the early optimism about gene therapy was probably never fully justified, gene therapy has now moved from preclinical to clinical studies for many diseases. These diseases range from hemophilia and other single-gene disorders to complex disorders such as cancer, HIV, and cardiovascular disorders. Major challenges to gene therapy include determining how to target the right gene to the right location in the right cells, expressing the transferred gene at the right time, and minimizing adverse reactions.
Ethical, Legal, and Social Implications
Because of widespread concern about misuse of the information gained through genetics research, a percentage of the Human Genome Project budget was designated for the study of the ethical, legal, and social implications (ELSI) of human genome research (Genetics Home Reference, 2017a). Two large ELSI programs were created to identify, analyze, and address the ELSIs of human genome research at the same time that the basic science issues were being studied. During the past decade, issues of high priority for these programs were as follows:
• Privacy and fairness in the use and interpretation of genetic information
• Clinical integration of new genetics technologies
• Issues surrounding genetics research, such as possible discrimination and stigmatization
• Education for professionals and the general public about genetics, genetics health care, and ELSI of human genome research
Both ELSI programs have excellent websites that include much educational information, as well as links to other informative sites (www.genome.gov/10001618; www.ornl.gov/sci/techresources/Human_Genome/elsi/elsi.shtml; https://www.genome.gov/elsi/).The major risk associated with genetic testing concerns what happens with the information gained through testing.It may result in increased anxiety and altered family relationships; it may be difficult to keep confidential; and it may result in discrimination and stigmatization. More important, there is a large gap between the ability to test for a genetic condition and the ability to treat that same condition. Informed consent is difficult to ensure when some of the outcomes, benefits, and risks of genetic testing remain unknown.
Factors Influencing the Decision to Undergo Genetic Testing
The decision to undergo genetic testing is seldom autonomous and based solely on the needs and preferences of the individual being tested. Instead, it is often a decision based on feelings of responsibility and commitment to others. For example, a woman who is receiving treatment for breast cancer may undergo BRCA1/BRCA2 mutation testing not because she wants to find out if she carries a BRCA1 or BRCA2 mutation but, instead, because her two unaffected sisters have asked her to be tested and she feels a sense of responsibility and commitment to them. A female airline pilot with a family history of HD, who has no desire to find out if she has the gene mutation associated with HD, may undergo mutation analysis for HD because she feels she has an obligation to her family, her employer, and the people who fly with her.
Decisions about genetic testing are shaped and, in many instances, constrained by factors such as social norms where care is received and socioeconomic status. Most pregnant women in the United States now have at least one ultrasound examination, many undergo some type of multiple-marker screening, and a growing number undergo other types of prenatal testing (see Chapter 8). The range of prenatal testing options available to a pregnant woman and her family may vary, based on where the pregnant woman receives prenatal care and her socioeconomic status. Certain types of prenatal testing may not be available in smaller communities and rural settings (e.g., chorionic villus sampling and fluorescent in situ hybridization [FISH] analysis). In addition, certain types of genetic testing may not be offered in conservative medical communities (e.g., preimplantation diagnosis). Some types of genetic testing are expensive and typically not covered by health insurance. Because of this, these tests may be available only to a relatively small number of individuals and families—those who can afford to pay for them (Badzek, Henaghan, Turner, et al., 2013). (See Chapter 10 for more information on prenatal testing).
Cultural and ethnic differences also have a significant impact on decisions about genetic testing. When prenatal diagnosis was first introduced, the principal constituency was a self-selected group of Caucasian, well-informed, middle- to upper-class women. Today the widespread use of genetic testing has introduced prenatal testing to new groups of women, women who had not previously considered genetic services. The fact that many of the women currently undergoing prenatal testing may not share mainstream US views about the role of medicine and prenatal care, the meaning of disability, or how to respond to scientific risks and uncertainties, further amplifies the complexity of ethical issues associated with prenatal testing.
Human development is a complicated process that depends on the systematic unraveling of instructions found in the genetic material of the egg and the sperm. Development from conception to birth of a normal, healthy baby occurs without incident in most cases; occasionally, however, some anomaly in the genetic code of the embryo creates a birth defect or disorder.
Genes and Chromosomes
The hereditary material carried in the nucleus of each of the somatic cells determines an individual’s characteristics. This material, called DNA (deoxyribonucleic acid), forms threadlike strands known as chromosomes. Each chromosome is composed of many smaller segments of DNA referred to as genes. Genes or combinations of genes contain coded information that determines an individual’s unique characteristics. The code is found in the specific linear order of the molecules that combine to form the strands of DNA. Genes control both the types of proteins that are made and the rate at which they are produced. Genes never act in isolation; they always interact with other genes and the environment.
All normal human somatic cells contain 46 chromosomes arranged as 23 pairs of homologous (matched) chromosomes; one chromosome of each pair is inherited from each parent. There are 22 pairs of autosomes, which control most traits in the body, and one pair of sex chromosomes. The larger female chromosome is called the X; the smaller male chromosome is the Y. Whereas the Y chromosome is primarily concerned with sex determination, the X chromosome contains genes that are involved in much more than sex determination. Generally, the presence of a Y chromosome causes an embryo to develop as a male; in the absence of a Y chromosome, the individual develops as a female. Thus in a normal female, the homologous pair of sex chromosomes are XX, and in a normal male, the homologous pair are XY.
Homologous chromosomes (except the X and Y chromosomes in males) have the same number and arrangement of genes. In other words, if one chromosome has a gene for hair color, its partner chromosome also will have a gene for hair color and these hair-color genes will have the same loci or be located in the same place on the two chromosomes. Although both genes code for hair color, they may not code for the same hair color. Genes at corresponding loci on homologous chromosomes that code for different forms or variations of the same trait are called alleles. An individual having two copies of the same allele for a given trait is said to be homozygous for that trait. With two different alleles, the individual is heterozygous for the trait.
The term genotype typically is used to refer to the genetic makeup of an individual when discussing a specific gene pair, but at times, genotype is used to refer to an individual’s entire genetic makeup or all the genes that the individual can pass on to future generations. Phenotype refers to the observable expression of an individual’s genotype, such as physical features, a biochemical or molecular trait, and even a psychologic trait. A trait or disorder is considered dominant if it is expressed or phenotypically apparent when only one copy of the gene is present. It is considered recessive if it is expressed only when two copies of the alleles associated with the trait are present.
As more is learned about genetics and genomics, the concepts of dominance and recessivity have become more complex, especially in X-linked disorders. For example, traits considered to be recessive may be expressed even when only one copy of a gene located on the X chromosome is present. This occurs frequently in males because males have only one X chromosome; thus they have only one copy of the genes located on the X chromosome. Whichever gene is present on the one X chromosome determines which trait is expressed. Females, conversely, have two X chromosomes, so they have two copies of the genes located on the X chromosome. However, in any female somatic cell, only one X chromosome is functioning (otherwise there would be inequality in gene dosage between males and females). This process, known as X-inactivation or the Lyon hypothesis, is generally a random occurrence. That is, there is a 50-50 chance as to whether the maternal X or the paternal X is inactivated. Occasionally the percentage of cells that have the X with an abnormal or mutant gene is very high. This helps explain why hemophilia, an X-linked recessive disorder, can clinically manifest itself in a female known to be a heterozygous carrier (a female who has only one copy of the gene mutation). It also helps explain why traditional methods of carrier detection are less effective for X-linked recessive disorders; the possible range for enzyme activity values can vary greatly, depending on which X chromosome is inactivated.
Chromosomal abnormalities are a major cause of reproductive loss, congenital problems, and gynecologic disorders. Errors resulting in chromosomal abnormalities can occur in mitosis (cell division occurring in somatic cells that results in two identical daughter cells containing a diploid number of chromosomes) or meiosis (division of a sex cell into two and four haploid cells). These errors can occur in either the autosomes or the sex chromosomes. Even without the presence of obvious structural malformations, small deviations in chromosomes can cause problems in fetal development.
The pictorial analysis of the number, form, and size of an individual’s chromosomes is known as a karyotype. Cells from any nucleated, replicating body tissue (not red blood cells, nerves, or muscles) can be used. The most commonly used tissues are white blood cells and fetal cells in amniotic fluid. The cells are grown in a culture and arrested when they are in metaphase (during metaphase, the chromosomes are condensed and visible with a light microscope), and then the cells are dropped onto a slide. This breaks the cell membranes and spreads the chromosomes, making them easier to visualize. Next, the cells are stained with special stains (e.g., Giemsa stain) that create striping or “banding” patterns. These patterns aid in the analysis because they are consistent from person to person. Once the chromosome spreads are photographed or scanned by a computer, they are cut out and arranged in a specific numeric order according to their length and shape. The chromosomes are numbered from largest to smallest, 1 to 22, and the sex chromosomes are designated by the letter X or Y. Each chromosome is divided into two “arms” designated by p (short arm) and q (long arm). A female karyotype is designated as 46,XX, and a male karyotype is designated as 46,XY. Fig. 6.1 illustrates the chromosomes in a body cell and a karyotype.
FIG 6.1 Chromosomes during cell division. A, Example of a photomicrograph. B, Chromosomes arranged in karyotype; female and male sex-determining chromosomes.
Autosomal abnormalities involve differences in the number or structure of autosome chromosomes (pairs 1 to 22). They result from unequal distribution of the genetic material during gamete (egg and sperm) formation.
Abnormalities of Chromosome Number
A euploid cell is a cell with the correct or normal number of chromosomes within the cell. Because most gametes are haploid (1N, 23 chromosomes) and most somatic cells are diploid (2N, 46 chromosomes), they are both considered euploid cells. Deviations from the correct number of chromosomes per cell can be one of two types: (1) polyploidy, in which the deviation is an exact multiple of the haploid number of chromosomes or one chromosome set (23 chromosomes); or (2) aneuploidy, in which the numeric deviation is not an exact multiple of the haploid set. A triploid (3N) cell is an example of a polyploidy. It has 69 chromosomes. A tetraploid (4N) cell, also an example of a polyploidy, has 92 chromosomes.
Aneuploidy is the most commonly identified chromosome abnormality in humans and the leading genetic cause of intellectual disability. A monosomy is the product of the union between a normal gamete and a gamete that is missing a chromosome. Monosomic individuals have only 45 chromosomes in each of their cells. The product of the union of a normal gamete with a gamete containing an extra chromosome is a trisomy. The most common autosomal aneuploid conditions involve trisomies. Trisomic individuals have 47 chromosomes in most or all of their cells.
The vast majority of trisomies occur during oogenesis (the process by which a premeiotic female germ cell divides into a mature egg); the incidence of these types of chromosomal errors increases exponentially with advancing maternal age. Although variation exists among trisomies with regard to the parent and stage of origin of the extra chromosome, most trisomies are maternal meiosis I (MI) errors. This means that most trisomies are caused by nondisjunction during the first meiotic division. The first meiotic division involves the segregation of homologous or similar chromosomes. One pair of chromosomes fails to separate. One resulting cell contains both chromosomes, and the other contains none. The fact that most trisomies are maternal MI errors is not that surprising, because maternal MI occurs over a long time span. It is initiated in precursor cells during fetal development, but it is not completed until the time those cells undergo ovulation after menarche.
The most common trisomy abnormality is DS. Approximately 1 in every 691 newborns has DS; there are over 400,000 individuals with DS living in the United States (Prows et al., 2013; CDC, 2016; www.cdc.gov/ncbddd/birthdefects/DownSyndrome.html; http://ndsccenter.org; www.ndss.org). Ninety-five percent of individuals with DS have trisomy 21 (nondisjunction) or an extra chromosome 21 (47,XX+21, female with DS; or 47,XY+21, male with DS) (CDC, 2016). Another type of DS, translocation, occurs when extra chromosome 21 material is present in every cell of the individual but it is attached to another chromosome. In the third type of DS, mosaicism, extra chromosome 21 material is found in some but not all of the cells.
Although the risk for having a child with DS increases with maternal age (incidence is approximately 1 in 1200 for a 25-year-old woman; 1 in 350 for a 35-year-old woman; and 1 in 10 for a 49-year-old woman), children with DS can be born to mothers of any age. The risk for a mother over age 40 of having a second child with DS is about 1% (Sole-Smith, 2014).
Other autosomal trisomies that maternity nurses might see are trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). Trisomy 18 is more common than trisomy 13; it occurs in about 1 of 5000 live births versus 1 of 16,000 live births for trisomy 13 (Genetics Home Reference, 2017b). Infants with trisomy 18 and trisomy 13 usually have severe to profound intellectual disabilities. Although both conditions have a poor prognosis, with the vast majority of affected infants dying before they reach their first birthday, a growing number of infants with these trisomies are living longer, and a small number are actually living into their 40s and 50s.
Nondisjunction can also occur during mitosis. If this occurs early in development, when cell lines are forming, the individual has a mixture of cells, some with a normal number of chromosomes and others either missing a chromosome or containing an extra chromosome. This condition is known as mosaicism. The most common form of mosaicism in autosomes is mosaic DS.
Abnormalities of Chromosome Structure
Structural abnormalities can occur in any chromosome. Types of structural abnormalities include translocation, duplication, deletion, microdeletion, and inversion. Translocation results when there is an exchange of chromosomal material between two chromosomes. Exposure to certain drugs, viruses, and radiation can cause translocations, but often they arise for no apparent reason.
The two major types of translocation are reciprocal and robertsonian. Reciprocal translocations are the most common. In a reciprocal translocation, either the parts of the two chromosomes are exchanged equally (balanced translocation) or a part of a chromosome is transferred to a different chromosome, creating an unbalanced translocation because there is extra chromosomal material—extra of one chromosome but correct amount or deficient amount of the other chromosome. In a balanced translocation, the individual is phenotypically normal because there is no extra chromosome material; it is just rearranged. In an unbalanced translocation, the individual will be both genotypically and phenotypically abnormal.
In a robertsonian translocation, the short arms (p arms) of two different acrocentric chromosomes (chromosomes with very short p arms) break, leaving sticky ends that then cause the two long arms (q arms) to stick together. This forms a new, large chromosome that is made of the two long arms. The individual with a balanced robertsonian translocation has 45 chromosomes. Because the short arm of acrocentric chromosomes contains genes for ribosomal RNA and these genes are represented elsewhere, the individual usually does not show any symptoms. The individual may produce an unbalanced gamete (sperm or egg with too many or two few genes). This can lead to reproductive difficulties such as miscarriages or birth defects.
In duplication, there is an extra chromosomal segment within the same homologous or another nonhomologous chromosome. Clinical findings are highly variable and depend on which of the chromosomal segments are involved.
Deletions result in the loss of chromosomal material and partial monosomy for the chromosome involved. Microdeletions are deletions too small to be detected by standard cytogenetic techniques. Whenever a portion of a chromosome is deleted from one chromosome and added to another, the gamete produced may have either extra copies of genes or too few copies. The clinical effects produced may be mild or severe depending on the amount of genetic material involved. Two of the more common conditions are the deletion of the short arm of chromosome 5 (cri du chat syndrome) and the deletion of the long arm of chromosome 18.
Inversions are deviations in which a portion of the chromosome has been rearranged in reverse order. Few birth defects have been attributed to the presence of inversions, but it is suspected that inversions may be responsible for problems with infertility and miscarriages.
Sex Chromosome Abnormalities
Several sex chromosome abnormalities are caused by nondisjunction during gametogenesis in either parent. The most common deviation in females is Turner syndrome, or monosomy X (45,X). The affected female exhibits juvenile external genitalia with undeveloped ovaries. She is short in stature and often has webbing of the neck, a low hairline in the back, low-set ears, and lymphedema of her hands and feet. Intelligence may be impaired. Most affected embryos miscarry spontaneously. In most cases of Turner syndrome, it is the paternal X or Y that is lost. Turner syndrome is a common cause of infertility (Genetics Home Reference, 2017c).
The most common deviation in males is Klinefelter syndrome, or trisomy XXY. The affected male has poorly developed secondary sexual characteristics and small testes. He is infertile, usually tall, and effeminate and may be slow to learn. Males who have mosaic Klinefelter syndrome may be fertile.
Patterns of Genetic Transmission
Heritable characteristics are those that can be passed on to offspring. The patterns by which genetic material is transmitted to the next generation are affected by the number of genes involved in the expression of the trait. Many phenotypic characteristics result from two or more genes on different chromosomes acting together (referred to as multifactorial inheritance); others are controlled by a single gene (unifactorial inheritance). Specialists in genetics (e.g., geneticists, genetic counselors, and nurses with advanced expertise in genetics) predict the probability of the presence of an abnormal gene from the known occurrence of the trait in the individual’s family and the known patterns by which the trait is inherited.
Most common congenital malformations result from multifactorial inheritance, a combination of genetic and environmental factors. Examples are cleft lip, cleft palate, congenital heart disease, neural tube defects, and pyloric stenosis. Each malformation can range from mild to severe, depending on the number of genes for the defect present or the amount of environmental influence. A neural tube defect can range from spina bifida (a bony defect in the lumbar region of the vertebrae with little or no neurologic impairment) to anencephaly (absence of brain development, which is always fatal). Some malformations occur more often in one sex. For example, pyloric stenosis and cleft lip are more common in males, and cleft palate is more common in females.
If a single gene controls a particular trait or disorder, its pattern of inheritance is referred to as unifactorial mendelian or single-gene inheritance. The number of single-gene disorders far exceeds the number of chromosomal abnormalities. Potential patterns of inheritance for single-gene disorders include autosomal dominant, autosomal recessive, and X-linked dominant and recessive modes of inheritance (Fig. 6.2).
FIG 6.2 Possible offspring in three types of matings. A, Homozygous-dominant parent and homozygous-recessive parent. Children: all heterozygous, displaying dominant trait. B, Heterozygous parent and homozygous-recessive parent. Children: 50% heterozygous, displaying dominant trait; 50% homozygous, displaying recessive trait. C, Both parents heterozygous. Children: 25% homozygous, displaying dominant trait; 25% homozygous, displaying recessive trait; 50% heterozygous, displaying dominant trait.
Autosomal Dominant Inheritance
Autosomal dominant inheritance disorders are those in which only one copy of a variant allele is needed for phenotypic expression. The variant allele may be a result of a mutation—a spontaneous and permanent change in the normal gene structure in which case the disorder occurs for the first time in the family. Usually an affected individual comes from multiple generations having the disorder. An affected parent who is heterozygous for the trait has a 50% chance of passing the variant allele to each offspring (see Fig. 6.2, B and C). There is a vertical pattern of inheritance (i.e., there is no skipping of generations; if an individual has an autosomal dominant disorder such as HD, so must one of his or her parents). Males and females are equally affected.
Autosomal dominant disorders are not always expressed with the same severity of symptoms. For example, a woman who has an autosomal dominant disorder may show few symptoms and may not become aware of her diagnosis until after she gives birth to a severely affected child. Predicting whether an offspring will have a minor or severe abnormality is not possible. Sometimes an individual can acquire a de novo mutation (new mutation that spontaneously occurred in a gene carried by an individual germ cell) that can result in an autosomal dominant disorder (Prows et al., 2013). Examples of autosomal dominant disorders are HD, Marfan syndrome, neurofibromatosis, myotonic dystrophy, Stickler syndrome, Treacher Collins syndrome, and achondroplasia (dwarfism).
Autosomal Recessive Inheritance
Autosomal recessive inheritance disorders are those in which both genes of a pair associated with the disorder must be abnormal for the disorder to be expressed. Heterozygous individuals have only one variant allele and are unaffected clinically because their normal gene overshadows the variant allele. They are known as carriers of the recessive trait. Because these recessive traits are inherited by generations of the same family, an increased incidence of the disorder occurs in consanguineous matings (closely related parents). For the trait to be expressed, two carriers must each contribute a variant allele to the offspring (see Fig. 6.2, C). The chance of the trait occurring in each child is 25%. A clinically normal offspring may be a carrier of the gene. Autosomal recessive disorders have a horizontal pattern of inheritance rather than the vertical pattern seen with autosomal dominant disorders. That is, autosomal recessive disorders are usually observed in one or more siblings but not in earlier generations. Males and females are equally affected.
Inborn Errors of Metabolism
More than 350 inborn errors of metabolism have been recognized. Most inborn errors of metabolism (IEMs), such as phenylketonuria, galactosemia, maple syrup urine disease, Tay-Sachs disease, sickle cell anemia, and CF, are autosomal recessive inherited disorders. IEMs occur when a gene mutation reduces the efficiency of encoded enzymes to a level at which normal metabolism cannot occur. Defective enzyme action interrupts the normal series of chemical reactions from the affected point onward. The result may be an accumulation of a damaging product, such as phenylalanine in PKU, or the absence of a necessary product, such as the lack of melanin in albinism caused by lack of tyrosinase. Diagnostic and carrier testing is available for a growing number of IEMs. In addition, many states in the United States have started screening for specific IEMs as part of their expanded newborn screening programs using tandem mass spectrometry. However, many of the deaths caused by IEMs are the result of enzyme variants not currently screened for in many of the newborn screening programs. (See discussion of IEMs in Chapter 25.)
X-Linked Dominant Inheritance
X-linked dominant inheritance disorders occur in males and heterozygous females, but because of X inactivation, affected females are usually less severely affected than affected males and they are more likely to transmit the variant allele to their offspring. Heterozygous females (females who have one wild-type allele and one variant allele) have a 50% chance of transmitting the variant allele to each offspring. The variant allele is often lethal in affected males since, unlike affected females, they have no normal gene (wild-type allele). Mating of an affected male and an unaffected female is uncommon as a result of the tendency for the variant allele to be lethal in affected males. Relatively few X-linked dominant disorders have been identified. Two examples are vitamin D–resistant rickets and Rett syndrome.
X-Linked Recessive Inheritance
Abnormal genes for X-linked recessive inheritance disorders are carried on the X chromosome. Females may be heterozygous or homozygous for traits carried on the X chromosome because they have two X chromosomes. Males are hemizygous because they have only one X chromosome, which carries genes with no alleles on the Y chromosome. Therefore X-linked recessive disorders are most commonly manifested in the male with the abnormal gene on his single X chromosome. Hemophilia, color blindness, and Duchenne muscular dystrophy are X-linked recessive disorders.
The male with an X-linked recessive disorder receives the disease-associated allele from his carrier mother on her affected X chromosome. Female carriers (those heterozygous for the trait) have a 50% probability of transmitting the disease-associated allele to each offspring. An affected male can pass the disease-associated allele to his daughters but not to his sons. The daughters will be carriers of the trait if they receive a normal gene on the X chromosome from their mother. They will be affected only if they receive a disease-associated allele on the X chromosome from both their mother and their father.
It is standard practice in obstetrics to determine whether a heritable disorder exists in a couple or in anyone in either of their families. The goal of screening is to detect or define risk for disease in low-risk populations and identify those for whom diagnostic testing may be appropriate. A nurse can obtain a genetics history using a questionnaire or checklist such as the one in Fig. 6.3.
FIG 6.3 Questionnaire for identifying couples having increased risk for offspring with genetic disorders. (Courtesy of American College of Obstetricians and Gynecologists. . Your pregnancy and childbirth month to month [5th ed.]. Washington, DC: Author.)
Genetic counseling is a professional service that provides genetics information, education, and support to individuals and families with ongoing or potential genetic health concerns. It is typically provided by a team of genetics specialists that includes clinical geneticists (physicians), medical geneticists, genetics fellows, genetics counselors, and, advanced practice genetics nurse specialists. Cytogeneticists, biochemical geneticists, and molecular geneticists support the clinical genetics team by providing laboratory expertise that helps with the diagnosis and management of individuals and families affected by genetic conditions.
Genetic counseling occurs in regional genetics centers, major medical centers, outreach or satellite genetics clinics, public health clinics, some community hospitals, and now that genetics has entered the mainstream of health care, in a wide variety of other settings. These include but are not limited to managed health care organizations, commercial facilities, and private practices. A number of specialized groups provide genetics education and counseling for individuals and families affected by specific genetic disorders, such as DS, CF, diabetes, muscular dystrophy, HD, and cancer. Genetic counseling also is offered over the Internet.
Individuals and families seek out or are referred for genetic counseling for a wide variety of reasons and at all stages of their lives. Some seek preconception or prenatal information; others are referred after the birth of a child with a birth defect or a suspected genetic condition or after a pregnancy loss. Still others seek information because they have a family history of a genetic condition. Regardless of the setting or the individual’s and family’s stage of life, genetic counseling should be offered and available to all individuals and families who have questions about genetics and their health. However, there is a shortage of appropriately trained genetics professionals who can provide genetic counseling. This means that many individuals and families will not be offered genetic counseling when they undergo genetic testing. Moreover, some of the genetics education and counseling that is provided will be inadequate (see Community Focus box).
Resources for Genetic Disorders
• Select a hereditary disorder such as CF, muscular dystrophy, hemophilia, Tay-Sachs disease, or sickle cell anemia. Visit the website of the national organization. Locate accredited care centers that are in your community. Do the centers offer preconception counseling?
• Visit the Genetic Alliance website at www.geneticalliance.org. Select a disorder, and go to the disease information search link. Review the patient information sections about clinical description, insurance issues, research, and treatment.
• Share your findings with your classmates in a clinical conference.
• Existing genetics resources include the following:
• Centers for Disease Control and Prevention (www.cdc.gov/genetics/activities/ogdp.htm)
• Genetic Alliance (www.geneticalliance.org/)
• National Coalition for Health Professional Education in Genetics (www.nchpeg.org/)
• Genetics Education Program for Nurses at Cincinnati Children’s Hospital Medical Center (www.cincinnatichildrens.org/ed/clinical/gpnf/default.htm)
• NHGRI Education (www.genome.gov/Education/)
• National Center for Biotechnology Information (www.ncbi.nlm.nih.gov/)
• Other websites, such as www.hsl.unc.edu/Services/Guides/focusonclingen.cfm
Some of these resources may be in health care professionals’ own communities, but others are regional, national, and international resources.
Estimation of Risk
Most families with a history of genetic disease want an answer to the following question: What is the chance that our future children will have this disease? Because the answer to this question may have profound implications for individual family members and the family as a whole, health care professionals must be able to answer this question as accurately as they can in a timely manner. In some cases, estimation of risk is rather straightforward; in other cases, it is complicated.
If a couple has not yet had children but they are known to be at risk for having children with a genetic disease, they will be given an occurrence risk. Once the mating of a couple has produced one or more children with a genetic disease, the couple will be given a recurrence risk. Both occurrence and recurrence risks are determined by the mode of inheritance for the genetic disease in question. For genetic diseases caused by a factor that segregates during cell division (genes and chromosomes), risk can be estimated with a high degree of accuracy by application of mendelian principles.
In an autosomal dominant disorder, both the occurrence and recurrence risk is 50%, or one in two, that a subsequent offspring will be affected when one parent is affected and the other is not. The recurrence risk for autosomal recessive disorders is 25%, or 1 in 4, if both parents are carriers (they each have one recessive disease gene and one normal gene). Occasionally an individual homozygous for a recessive disease gene mates with an individual who is a carrier of the same recessive gene. In this case, the recurrence risk is 50%, or 1 in 2. If two individuals affected by an autosomal recessive disorder mate, all of their children will be affected. For X-linked disorders, recurrence risk is related to the sex of the child. Translocation chromosomes have a high risk for recurrence.
A number of autosomal disorders display fairly complex patterns of inheritance, making estimation of risk somewhat difficult. For example, if a child is born with a genetic disease and there has been no history of the disease in the family, the disease may have been caused by a new mutation (this is more likely if the disease in question is an autosomal dominant disorder, such as achondroplasia). If the child’s genetic disease has been caused by a new mutation, the recurrence risk for the parents’ subsequent children is low (1% to 2%), but it is not as low as that for the general population. Offspring of the affected child may have a substantially elevated occurrence risk.
The risk for recurrence for multifactorial conditions can be estimated empirically. An empiric risk is based not on genetics theory but, rather, on experience and observation of the disorder in other families. Recurrence risks are determined by applying the frequency of a similar disorder in other families to the case under consideration.
An important concept to be emphasized to individuals and families during a genetic counseling session is that each pregnancy is an independent event. For example, in monogenic disorders in which the risk factor is 1 in 4 that the child will be affected, the risk remains the same no matter how many affected children are already in the family. Families may maintain the erroneous assumption that the presence of one affected child ensures that the next three will be free of the disorder. However, “chance has no memory.” The risk is 1 in 4 for each pregnancy. Conversely, in a family with a child who has a disorder with multifactorial causes, the risk increases with each subsequent child born with the disorder.
Interpretation of Risk
The guiding principle for genetics counselors has traditionally been nondirectiveness. According to the principle of nondirectiveness, the individual who is providing genetic counseling respects the right of the individual or family being counseled to make autonomous decisions. Counselors using a nondirective approach avoid making recommendations, and they try to communicate genetics information in an unbiased manner. The first step in providing nondirective counseling is becoming aware of one’s own values and beliefs. Another important step is recognizing how one’s values and beliefs can influence or interfere with the communication of genetics information.
If the individual who is providing genetic counseling has difficulty being nonjudgmental and objective, he or she may either intentionally or unintentionally influence the decision-making process. Individuals and families also may pressure the counselor to make decisions for them with questions such as “What would you do if you were me?” Families and individuals need education, guidance, and support throughout the counseling process. They should be given the facts and possible consequences as well as all of the assistance they need in problem solving, but the final decision regarding a course of action must be their own.
Multiple Roles for Nurses in Genetics
Nurses play many roles in genetics. Some nurses play a key role in the identification of families in need of genetic counseling, and they collaborate with other health care professionals as part of interprofessional teams to make referrals to specialists in genetics. Other nurses take a more active role in genetic counseling.
Probably the most important of all nursing functions is to provide emotional support during all aspects of the counseling process. Feelings that are generated under the real or imagined threat posed by a genetic disorder are as varied as the individuals being counseled. Responses may include a variety of stress reactions, such as apathy, denial, anger, hostility, fear, embarrassment, grief, and loss of self-esteem. Guilt and self-blame are universal reactions. Many look on the disorder as a stigma, especially if the disorder is visible to others. Old wives’ tales, superstitions, and long-held misconceptions may influence a family’s reaction to a genetic disorder.
Nurses are ideally positioned to help individuals and families maximize the benefits of the genetics revolution, but first, nurses need (1) a working knowledge of human genetics, (2) an awareness of recent advances in genetics and genomics, and (3) an understanding of the potential effects of genomic discoveries on individual and family well-being. More research is needed concerning the family experience of genetic testing. Nurses must understand why individuals and families decide to undergo or to forgo genetic testing. Nurses also need to be aware of how individuals and families define and manage ethical, legal, and social issues that emerge during the genetic testing experience.
Cell Division and Conception
Cells are reproduced by two different methods: mitosis and meiosis. In mitosis, the body cells replicate to yield two cells with the same genetic makeup as the parent cell. First the cell makes a copy of its DNA, and then it divides. Each daughter cell receives one copy of the genetic material. Mitotic division facilitates growth and development or cell replacement.
Meiosis, the process by which germ cells divide and decrease their chromosomal number by half, produces gametes (eggs and sperm). Each homologous pair of chromosomes contains one chromosome received from the mother and one from the father; thus meiosis results in cells that contain one of each of the 23 pairs of chromosomes. Because these germ cells contain 23 single chromosomes, half of the genetic material of a normal somatic cell, they are called haploid. This halving of the genetic material is accomplished by replicating the DNA once and then dividing twice. When the female gamete (egg or ovum) and the male gamete (spermatozoon) unite to form the zygote, the diploid number of human chromosomes (46, or 23 pairs) is restored.
The process of DNA replication and cell division in meiosis allows different alleles (genes on corresponding loci that code for variations of the same trait) for genes to be distributed at random by each parent and then rearranged on the paired chromosomes. The chromosomes then separate and proceed to different gametes. Because the two parents have genotypes derived from four different grandparents, many combinations of genes on each chromosome are possible. This random mixing of alleles accounts for the variation of traits seen in the offspring of the same two parents.
Oogenesis, the process of egg (ovum) formation, begins during fetal life of the female. All the cells that may undergo meiosis in a woman’s lifetime are contained in her ovaries at birth. The majority of the estimated 2 million primary oocytes (the cells that undergo the first meiotic division) degenerate spontaneously. Only 400 to 500 ova will mature during the approximately 35 years of a woman’s reproductive life. The primary oocytes begin the first meiotic division (i.e., they replicate their DNA) during fetal life, but they remain suspended at this stage until puberty (Fig. 6.4, A). Then, usually monthly, one primary oocyte matures and completes the first meiotic division, yielding two unequal cells: the secondary oocyte and a small polar body. Both contain 22 autosomes and one X sex chromosome.
FIG 6.4 Gametogenesis and fertilization. A, Oogenesis. Gametogenesis in the female produces one mature ovum and three polar bodies. Note relative difference in overall size between ovum and sperm. B, Spermatogenesis. Gametogenesis in the male produces four mature gametes, the sperm. C, Fertilization results in the single-cell zygote and restoration of the diploid number of chromosomes.
At ovulation, the second meiotic division begins. However, the ovum does not complete the second meiotic division unless fertilization occurs. At fertilization, when the sperm is united with the mature ovum, a second polar body and the zygote (the united egg and sperm) are produced (see Fig. 6.4, C). The three polar bodies degenerate.
When a male reaches puberty, his testes begin the process of spermatogenesis. The cells that undergo meiosis in the male are called spermatocytes. The primary spermatocyte, which undergoes the first meiotic division, contains the diploid number of chromosomes. The cell has already copied its DNA before division, so four alleles for each gene are present. The cell is still considered diploid because the copies are bound together (i.e., one allele plus its copy on each chromosome).
During the first meiotic division, two haploid secondary spermatocytes are formed. Each secondary spermatocyte contains 22 autosomes and one sex chromosome; one contains the X chromosome (plus its copy) and the other, the Y chromosome (plus its copy). During the second meiotic division, the male produces two gametes with an X chromosome and two gametes with a Y chromosome, all of which will develop into viable sperm (see Fig. 6.4, B).
Conception, defined as the union of a single egg and sperm, marks the beginning of a pregnancy. Conception occurs not as an isolated event but as part of a sequential process. This sequential process includes gamete (egg and sperm) formation, ovulation (release of the egg), union of the gametes (which results in an embryo), and implantation in the uterus.
Meiosis occurs in the female in the ovarian follicles and produces an egg, or ovum. Each month one ovum matures with a host of surrounding supportive cells. At ovulation, the ovum is released from the ruptured ovarian follicle. High estrogen levels increase the motility of the uterine tubes so that their cilia can capture the ovum and propel it through the tube toward the uterine cavity. An ovum cannot move by itself.
Two protective layers surround the ovum (Fig. 6.5). The inner layer is a thick, acellular layer called the zona pellucida. The outer layer, called the corona radiata, is composed of elongated cells.
FIG 6.5 Ovum and sperm.
Ova are considered fertile for about 24 hours after ovulation. If unfertilized by a sperm, the ovum degenerates and is resorbed.
Ejaculation during sexual intercourse normally propels about a teaspoon of semen containing as many as 200 to 500 million sperm into the vagina. The sperm swim by means of the flagellar movement of their tails. Some sperm can reach the site of fertilization within 5 minutes, but average transit time is 4 to 6 hours. Sperm remain viable within the woman’s reproductive system for an average of 2 to 3 days. Most sperm are lost in the vagina, within the cervical mucus, or in the endometrium; or they enter the tube that contains no ovum.
As sperm travel through the female reproductive tract, enzymes are produced to aid in their capacitation. Capacitation is a physiologic change that removes the protective coating from the heads of the sperm. Small perforations then form in the acrosome (a cap on the sperm) and allow enzymes (e.g., hyaluronidase) to escape (see Fig. 6.5). These enzymes are necessary for the sperm to penetrate the protective layers of the ovum before fertilization.
Fertilization takes place in the ampulla (the outer third) of the uterine tube. When a sperm successfully penetrates the membrane surrounding the ovum, both sperm and ovum are enclosed within the membrane and the membrane becomes impenetrable to other sperm; this process is termed the zona reaction. The second meiotic division of the secondary oocyte is then completed, and the nucleus of the ovum becomes the female pronucleus. The head of the sperm enlarges to become the male pronucleus, and the tail degenerates. The nuclei fuse and the chromosomes combine, restoring the diploid number (46) (Fig. 6.6). Conception, the formation of the zygote (the first cell of the new individual), has been achieved.
FIG 6.6 Fertilization. A, Ovum fertilized by X-bearing sperm to form female zygote. B, Ovum fertilized by Y-bearing sperm to form male zygote.
Mitotic cellular replication, called cleavage, begins as the zygote travels the length of the uterine tube into the uterus. This voyage takes 3 to 4 days. Because the fertilized egg divides rapidly with no increase in size, successively smaller cells, called blastomeres, are formed with each division. A 16-cell morula, a solid ball of cells, is produced within 3 days and is still surrounded by the protective zona pellucida (Fig. 6.7, A). Further development occurs as the morula floats freely within the uterus. Fluid passes through the zona pellucida into the intercellular spaces between the blastomeres, separating them into two parts: the trophoblast (which gives rise to the placenta) and the embryoblast (which gives rise to the embryo). A cavity forms within the cell mass as the spaces come together, forming a structure called the blastocyst cavity. When the cavity becomes recognizable, the whole structure of the developing embryo is known as the blastocyst. Stem cells are derived from the inner cell mass of the blastocyst. The outer layer of cells surrounding the cavity is the trophoblast. The trophoblast differentiates into villous and extravillous trophoblast (Fig. 6.8).
FIG 6.7 First weeks of human development. A, Follicular development in ovary, ovulation, fertilization, and transport of early embryo down uterine tube and into uterus, where implantation occurs. B, Blastocyst embedded in endometrium. Germ layers forming. (A, From Carlson, B.M. . Human embryology and developmental biology [5th ed.]. St. Louis, MO: Mosby; B, Adapted from Langley, L.L., Telford, I.R., Christensen, J.B. . Dynamic human anatomy and physiology [5th ed.]. New York, NY: McGraw-Hill.)
FIG 6.8 Extravillous trophoblasts are found outside the villus and can be subdivided into endovascular and interstitial categories. Endovascular trophoblasts invade and transform spiral arteries during pregnancy to create low-resistance blood flow that is characteristic of the placenta. Interstitial trophoblasts invade the decidua and surround spiral arteries. (From Cunningham, F., Leveno, K., Bloom, S., et al. . Williams obstetrics [24th ed.]. New York, NY: McGraw-Hill.)
The zona pellucida degenerates, the trophoblast cells displace endometrial cells at the implantation site, and the blastocyst embeds in the endometrium, usually in the anterior or posterior fundal region. Between 6 and 10 days after conception, the trophoblast secretes enzymes that enable it to burrow into the endometrium until the entire blastocyst is covered. This is known as implantation. Endometrial blood vessels erode, and some women have implantation bleeding (slight spotting and bleeding at the time of the first missed menstrual period). Chorionic villi, fingerlike projections, develop out of the trophoblast and extend into the blood-filled spaces of the endometrium. These villi are vascular processes that obtain oxygen and nutrients from the maternal bloodstream and dispose of carbon dioxide and waste products into the maternal blood.
After implantation, the endometrium is called the decidua. The portion directly under the blastocyst, where the chorionic villi tap into the maternal blood vessels, is the decidua basalis. The portion covering the blastocyst is the decidua capsularis, and the portion lining the rest of the uterus is the decidua vera (Fig. 6.9).
FIG 6.9 Development of fetal membranes. Note gradual obliteration of intrauterine cavity as decidua capsularis and decidua vera meet. Also note thinning of uterine wall. Chorionic and amnionic membranes are in apposition to each other but may be peeled apart.
The Embryo and Fetus
Pregnancy lasts approximately 10 lunar months, 9 calendar months, 40 weeks, or 280 days. Length of pregnancy is computed from the first day of the last menstrual period (LMP) until the day of birth. However, conception occurs approximately 2 weeks after the first day of the LMP. Thus the postconception age of the fetus is 2 weeks less, for a total of 266 days or 38 weeks. Postconception age is used in the discussion of fetal development.
Intrauterine development is divided into three stages: ovum or preembryonic, embryo, and fetus (see Fig. 6.19). The stage of the ovum lasts from conception until day 14. This period covers cellular replication, blastocyst formation, initial development of the embryonic membranes, and establishment of the primary germ layers.
Primary Germ Layers
During the third week after conception, the embryonic disk differentiates into three primary germ layers: the ectoderm, the mesoderm, and the endoderm (or entoderm) (see Fig. 6.7, B). All tissues and organs of the embryo develop from these three layers.
The ectoderm, the upper layer of the embryonic disk, gives rise to the epidermis, glands (anterior pituitary, cutaneous, and mammary), nails and hair, central and peripheral nervous systems, lens of the eyes, tooth enamel, and floor of the amniotic cavity.
The mesoderm, the middle layer, develops into the bones and teeth, muscles (skeletal, smooth, and cardiac), dermis and connective tissue, cardiovascular system and spleen, and urogenital system.
The endoderm, the lower layer, gives rise to the epithelium lining the respiratory tract and digestive tract, including the oropharynx, liver and pancreas, urethra, bladder, and vagina. The endoderm forms the roof of the yolk sac.
Development of the Embryo
The stage of the embryo lasts from day 15 until approximately 8 weeks after conception, when the embryo measures approximately 3 cm from crown to rump. The embryonic stage is the most critical time in the development of the organ systems and the main external features. Developing areas with rapid cell division are the most vulnerable to malformation caused by environmental teratogens (substances or exposure that causes abnormal development). At the end of the eighth week, all organ systems and external structures are present and the embryo is unmistakably human. (See Fig. 6.19 and Visible Embryo, www.visembryo.com, for a pictorial view of normal and abnormal development.)
At the time of implantation, two fetal membranes that will surround the developing embryo begin to form. The chorion develops from the trophoblast and contains the chorionic villi on its surface. The villi burrow into the decidua basalis and increase in size and complexity as the vascular processes develop into the placenta. The chorion becomes the covering of the fetal side of the placenta. It contains the major umbilical blood vessels that branch out over the surface of the placenta. As the embryo grows, the decidua capsularis stretches. The chorionic villi on this side atrophy and degenerate, leaving a smooth chorionic membrane.
The inner cell membrane, the amnion, develops from the interior cells of the blastocyst. The cavity that develops between this inner cell mass and the outer layer of cells (trophoblast) is the amniotic cavity (see Fig. 6.7, B). As it grows larger, the amnion forms on the side opposite the developing blastocyst (see Fig. 6.7, B, and Fig. 6.9). The developing embryo draws the amnion around itself to form a fluid-filled sac. The amnion becomes the covering of the umbilical cord and covers the chorion on the fetal surface of the placenta. As the embryo grows larger, the amnion enlarges to accommodate the embryo/fetus and the surrounding amniotic fluid. The amnion eventually comes in contact with the chorion surrounding the fetus (see the Critical Reasoning Case Study).
Clinical Reasoning Case Study
Ingestion of Alcohol During Pregnancy
Sandra is 12 weeks pregnant, confirmed by ultrasound, and has just come for her first prenatal visit. She stated that she drinks wine with dinner almost every night. Now that she has a confirmed pregnancy, she is worried about her alcohol and medication intake during the first trimester of pregnancy. What information should the nurse provide Sandra?
1. Evidence—Is there sufficient evidence to draw conclusions about what information the nurse should provide Sandra?
2. Assumptions—Describe an underlying assumption about the following factors:
a. Sandra’s motivation to learn about fetal development
b. Sandra’s understanding of fetal development
c. Sandra’s knowledge about alcohol intake and medication use during pregnancy
d. Why dating the pregnancy is important
e. Sandra being worried about possible negative effects on the fetus of alcohol intake and medications
3. What implications and priorities for nursing care can be drawn at this time?
4. What are the opportunities for interprofessional practice? Which members of the interprofessional health care team might be involved in providing care for Sandra?
The amniotic cavity initially derives its fluid by diffusion from the maternal blood. Fluid secreted by the respiratory and gastrointestinal tracts of the fetus also enters the amniotic cavity (Moore, Persaud, & Torchia, 2013). The amount of fluid increases weekly, and 700 to 1000 mL of transparent liquid is normally present at term. The volume of amniotic fluid changes constantly. The fetus swallows fluid, and fluid flows into and out of the fetal lungs. Beginning in week 11, the fetus urinates into the fluid, increasing its volume.
Amniotic fluid serves many functions. It helps maintain a constant body temperature. It serves as a source of oral fluid and as a repository for waste and assists in maintenance of fluid and electrolyte homeostasis. It cushions the fetus from trauma by blunting and dispersing outside forces. It allows freedom of movement for musculoskeletal development. It acts as a barrier to infection and allows fetal lung development (Moore et al., 2013). The fluid keeps the embryo from tangling with the membranes, facilitating symmetric growth. If the embryo does become tangled with the membranes, amputations of extremities or other deformities can occur from constricting amniotic bands.
When the amniotic cavity and amnion are forming, another blastocyst cavity forms on the other side of the developing embryonic disk (see Fig. 6.7, B). This cavity becomes surrounded by a membrane, forming the yolk sac. The yolk sac aids in transferring maternal nutrients and oxygen, which have diffused through the chorion, to the embryo. Blood vessels form to aid transport. Blood cells and plasma are manufactured in the yolk sac during the second and third weeks while uteroplacental circulation is being established and is forming primitive blood cells until hematopoietic activity begins. At the end of the third week, the primitive heart begins to beat and circulate the blood through the embryo, the connecting stalk, the chorion, and the yolk sac.
The folding in of the embryo during the fourth week results in incorporation of part of the yolk sac into the embryo’s body as the primitive digestive system. Primordial germ cells arise in the yolk sac and move into the embryo. The shrinking remains of the yolk sac degenerate (see Fig. 6.7, B), and by the fifth or sixth week, the remnant has separated from the embryo.
By day 14 after conception, the embryonic disk, the amniotic sac, and the yolk sac are attached to the chorionic villi by the connecting stalk. During the third week, the blood vessels develop to supply the embryo with maternal nutrients and oxygen. During the fifth week, the embryo has curved inward on itself from both ends, bringing the connecting stalk to the ventral side of the embryo. The connecting stalk becomes compressed from both sides by the amnion and forms the narrower umbilical cord (see Fig. 6.7). Two arteries carry blood from the embryo to the chorionic villi, and one vein returns blood to the embryo. Approximately 1% of umbilical cords contain only two vessels: one artery and one vein. This occurrence is sometimes associated with congenital malformations (Kaiser Permanente, 2017).
The cord rapidly increases in length. At term, the cord is 2 cm in diameter and ranges from 30 to 90 cm in length (with an average of 55 cm). It twists spirally on itself and loops around the embryo/fetus. A true knot is rare, but false knots occur as folds or kinks in the cord and may jeopardize circulation to the fetus. Connective tissue called Wharton’s jelly prevents compression of the blood vessels and ensures continued nourishment of the embryo/fetus. Compression can occur if the cord lies between the fetal head and the pelvis or is twisted around the fetal body. When the cord is wrapped around the fetal neck, it is called a nuchal cord.
Because the placenta develops from the chorionic villi, the umbilical cord is usually located centrally. A peripheral location is less common and is known as a battledore placenta (see Chapter 12 for more information). The blood vessels are arrayed out from the center to all parts of the placenta (Fig. 6.10).
FIG 6.10 Term placenta. A, Maternal (or uterine) surface, showing cotyledons and grooves. B, Fetal (or amniotic) surface, showing blood vessels running under amnion and converging to form umbilical vessels at attachment of umbilical cord. C, Amnion and smooth chorion are arranged to show that they are (1) fused and (2) continuous with margins of placenta. (Courtesy of Marjorie Pyle, RNC, Lifecircle, Costa Mesa, CA.)
The placenta begins to form at implantation. During the third week after conception, the trophoblast cells of the chorionic villi continue to invade the decidua basalis. As the uterine capillaries are tapped, the endometrial spiral arteries fill with maternal blood. The chorionic villi grow into the spaces with two layers of cells: the outer syncytium and the inner cytotrophoblast. A third layer develops into anchoring septa, dividing the projecting decidua into separate areas called cotyledons. In each of the 15 to 20 cotyledons, the chorionic villi branch out and a complex system of fetal blood vessels forms. Each cotyledon is a functional unit. The whole structure is the placenta (see Fig. 6.10).
The maternal-placental-embryonic circulation is in place by day 17, when the embryonic heart starts beating. By the end of the third week, embryonic blood is circulating between the embryo and the chorionic villi. In the intervillous spaces, maternal blood supplies oxygen and nutrients to the embryonic capillaries in the villi (Fig. 6.11). Waste products and carbon dioxide diffuse into the maternal blood.
FIG 6.11 Schematic drawing of placenta illustrating how it supplies oxygen and nutrition to embryo and removes its waste products. Deoxygenated blood leaves fetus through the umbilical arteries and enters placenta, where it is oxygenated. Oxygenated blood leaves placenta through the umbilical vein, which enters the fetus via the umbilical cord.
The placenta functions as a means of metabolic exchange. Exchange is minimal at this time because the two cell layers of the villous membrane are too thick. Permeability increases as the cytotrophoblast thins and disappears; by the fifth month, only the single layer of syncytium is left between the maternal blood and the fetal capillaries. The syncytium is the functional layer of the placenta. By the eighth week, genetic testing may be done on a sample of chorionic villi obtained by aspiration biopsy; however, limb defects have been associated with chorionic villi sampling done before 10 weeks. The structure of the placenta is complete by the twelfth week. The placenta continues to grow wider until 20 weeks, when it covers about half of the uterine surface. It then continues to grow thicker. The branching villi continue to develop within the body of the placenta, increasing the functional surface area.
One of the early functions of the placenta is as an endocrine gland that produces four hormones necessary to maintain the pregnancy and support the embryo/fetus. The hormones are produced in the syncytium.
The protein hormone human chorionic gonadotropin (hCG) can be detected in the maternal serum by 8 to 10 days after conception, shortly after implantation. This hormone is the basis for pregnancy tests. The hCG preserves the function of the ovarian corpus luteum, ensuring a continued supply of estrogen and progesterone needed to maintain the pregnancy. Miscarriage occurs if the corpus luteum stops functioning before the placenta can produce sufficient estrogen and progesterone. The hCG reaches its maximum level at 50 to 70 days and then begins to decrease.
The other protein hormone produced by the placenta is human chorionic somatomammotropin (hCS) or human placental lactogen (hPL). This substance is similar to a growth hormone and stimulates maternal metabolism to supply needed nutrients for fetal growth. hCS increases the resistance to insulin, facilitates glucose transport across the placental membrane, and stimulates breast development to prepare for lactation (Fig. 6.12).
FIG 6.12 Distinct profile for the concentrations of human chorionic gonadotropin (hCG) and human chorionic somatomammotropin (hCS) in serum of women through normal pregnancy. IU, International units. (Adapted from Cunningham, F., Leveno, K., Bloom, S., et al. . Williams obstetrics [24th ed.]. New York, NY: McGraw-Hill.)
The placenta eventually produces more of the steroid hormone progesterone than the corpus luteum does during the first few months of pregnancy. Progesterone maintains the endometrium, decreases the contractility of the uterus, and stimulates maternal metabolism and development of breast alveoli.
By 7 weeks after fertilization, the placenta is producing most of the maternal estrogens, which are steroid hormones. The major estrogen secreted by the placenta is estriol, whereas the ovaries produce mostly estradiol. Estriol levels may be measured to determine placental functioning. Estrogen stimulates uterine growth and uteroplacental blood flow. It causes a proliferation of the breast glandular tissue and stimulates myometrial contractility. Placental estrogen production increases greatly toward the end of pregnancy. One theory for the cause of the onset of labor is the decrease in circulating levels of progesterone and the increased levels of estrogen (Fig. 6.13).
FIG 6.13 Plasma levels of progesterone, estradiol, estrone, and estriol in women during the course of gestation. (From Cunningham, F., Leveno, K., Bloom, S., et al. . Williams obstetrics [24th ed.]. New York, NY: McGraw-Hill.)
The metabolic functions of the placenta are respiration, nutrition, excretion, and storage. Oxygen diffuses from the maternal blood across the placental membrane into the fetal blood, and carbon dioxide diffuses in the opposite direction. In this way, the placenta functions as lungs for the fetus.
Carbohydrates, proteins, calcium, and iron are stored in the placenta for ready access to meet fetal needs. Water, inorganic salts, carbohydrates, proteins, fats, and vitamins pass from the maternal blood supply across the placental membrane into the fetal blood, supplying nutrition. Water and most electrolytes with a molecular weight less than 500 readily diffuse through the membrane. Hydrostatic and osmotic pressures aid in the flow of water and some solutions. Facilitated and active transport assist in the transfer of glucose, amino acids, calcium, iron, and substances with higher molecular weights. Amino acids and calcium are transported against the concentration gradient between the maternal blood and fetal blood.
The fetal concentration of glucose is lower than the glucose level in the maternal blood because of its rapid metabolism by the fetus. This fetal requirement demands larger concentrations of glucose than simple diffusion can provide. Therefore maternal glucose moves into the fetal circulation by active transport.
Pinocytosis is a mechanism used for transferring large molecules, such as albumin and gamma globulins, across the placental membrane. This mechanism conveys the maternal immunoglobulins that provide early passive immunity to the fetus.
Metabolic waste products of the fetus cross the placental membrane from the fetal blood into the maternal blood. The maternal kidneys then excrete them. Many viruses can cross the placental membrane and infect the fetus. Some bacteria and protozoa first infect the placenta and then infect the fetus. Drugs can also cross the placental membrane and may harm the fetus. Caffeine, alcohol, nicotine, carbon monoxide and other toxic substances in cigarette smoke, and prescription and recreational drugs (e.g., marijuana, cocaine) readily cross the placenta (Box 6.1).
Developmentally Toxic Exposures in Humans
• Angiotensin-converting enzyme inhibitors
• Cigarette smoking
• Coumarin anticoagulants
• Ethanol (>1 drink/day)
• Ionizing radiation (>10 rads)
• Methyl mercury
• Parvovirus B19
• Valproic acid
Although no direct link exists between the fetal blood in the vessels of the chorionic villi and the maternal blood in the intervillous spaces, only one cell layer separates them. Breaks occasionally occur in the placental membrane. Fetal erythrocytes then leak into the maternal circulation, and the mother may develop antibodies to the fetal red blood cells. This is often the way the Rh-negative mother becomes sensitized to the erythrocytes of her Rh-positive fetus (see the discussion of isoimmunization in Chapter 19).
Although the placenta and fetus are analogous to living tissue transplants, they are not destroyed by the host mother (Mor & Abrahams, 2014). Either the placental hormones suppress the immunologic response, or the tissue evokes no response.
Placental function depends on the maternal blood pressure supplying the circulation. Maternal arterial blood, under pressure in the small uterine spiral arteries, spurts into the intervillous spaces (see Fig. 6.11). As long as rich arterial blood continues to be supplied, pressure is exerted on the blood already in the intervillous spaces, pushing it toward drainage by the low-pressure uterine veins. At term gestation, 10% of the maternal cardiac output goes to the uterus.
If there is interference with the circulation to the placenta, the placenta cannot supply the embryo or fetus. Vasoconstriction, such as that caused by hypertension or cocaine use, diminishes uterine blood flow. Decreased maternal blood pressure or decreased cardiac output also diminishes uterine blood flow.
When a woman lies on her back with the pressure of the uterus compressing the vena cava, blood return to the right atrium is diminished (see Fig. 16.5 and the discussion of supine hypotension in Chapter 16). Excessive maternal exercise that diverts blood to the muscles away from the uterus compromises placental circulation. Optimum circulation is achieved when the woman is lying at rest on her side. Decreased uterine circulation may lead to intrauterine growth restriction of the fetus and infants who are small for gestational age.
Braxton Hicks contractions seem to enhance the movement of blood through the intervillous spaces, aiding placental circulation. However, prolonged contractions or intervals that are too short between contractions during labor can reduce the blood flow to the placenta.
This stage of the fetus lasts from 9 weeks (when the fetus becomes recognizable as a human being) until the pregnancy ends. Changes during the fetal period are not as dramatic, because refinement of structure and function is taking place. The fetus is less vulnerable to teratogens except for those that affect central nervous system functioning.
Viability refers to the capability of the fetus to survive outside the uterus. With modern technology and advances in maternal and neonatal care, infants who are 22 to 25 weeks of gestation are now considered to be on the threshold of viability (Cunningham, Leveno, Bloom, et al., 2014). The limitations on survival outside the uterus when an infant is born at this early stage are based on central nervous system function and oxygenation capability of the lungs.
Fetal Circulatory System
The cardiovascular system is the first organ system to function in the developing human. Blood vessel and blood cell formation begins in the third week and supplies the embryo with oxygen and nutrients from the mother. By the end of the third week, the tubular heart begins to beat and the primitive cardiovascular system links the embryo, connecting stalk, chorion, and yolk sac. During the fourth and fifth weeks, the heart develops into a four-chambered organ. By the end of the embryonic stage, the heart is developmentally complete.
The fetal lungs do not function for respiratory gas exchange, so a special circulatory pathway, the ductus arteriosus, bypasses the lungs. Oxygen-rich blood from the placenta flows rapidly through the umbilical vein into the fetal abdomen (Fig. 6.14). When the umbilical vein reaches the liver, it divides into two branches; one branch circulates some oxygenated blood through the liver. Most of the blood passes through the ductus venosus into the inferior vena cava. There it mixes with the deoxygenated blood from the fetal legs and abdomen on its way to the right atrium. Most of this blood passes straight through the right atrium and through the foramen ovale, an opening into the left atrium. There it mixes with the small amount of deoxygenated blood returning from the fetal lungs through the pulmonary veins.
FIG 6.14 Schematic illustration of fetal circulation. The colors indicate the oxygen saturation of the blood, and the arrows show the course of the blood from the placenta to the heart. The organs are not drawn to scale. Observe that three shunts permit most of the blood to bypass the liver and lungs: (1) ductus venosus, (2) foramen ovale, and (3) ductus arteriosus. A small amount of highly oxygenated blood from the inferior vena cava remains in the right atrium and mixes with poorly oxygenated blood from the superior vena cava. This medium oxygenated blood then passes into the right ventricle. The poorly oxygenated blood returns to the placenta for oxygen and nutrients through the umbilical arteries. (From Moore, K.L., Persaud, T.V.N., Torchia, M.G. . The developing human: Clinically oriented embryology [10th ed.]. Philadelphia, PA: Elsevier.)
The blood flows into the left ventricle and is squeezed out into the aorta, where the arteries supplying the heart, head, neck, and arms receive most of the oxygen-rich blood. This pattern of supplying the highest levels of oxygen and nutrients to the head, neck, and arms enhances the cephalocaudal (head-to-rump) development of the embryo/fetus.
Deoxygenated blood returning from the head and arms enters the right atrium through the superior vena cava. This blood is directed downward into the right ventricle, where it is squeezed into the pulmonary artery. A small amount of blood circulates through the resistant lung tissue, but the majority follows the path with less resistance through the ductus arteriosus into the aorta, distal to the point of exit of the arteries supplying the head and arms with oxygenated blood. The oxygen-poor blood flows through the abdominal aorta into the internal iliac arteries, where the umbilical arteries direct most of it back through the umbilical cord to the placenta. There the blood gives up its wastes and carbon dioxide in exchange for nutrients and oxygen. The blood remaining in the iliac arteries flows through the fetal abdomen and legs, ultimately returning through the inferior vena cava to the heart.
The following three special characteristics enable the fetus to obtain sufficient oxygen from the maternal blood:
• Fetal hemoglobin carries 20% to 30% more oxygen than maternal hemoglobin.
• The hemoglobin concentration of the fetus is about 50% greater than that of the mother.
• The fetal heart rate (FHR) is 110 to 160 beats/min, making the cardiac output per unit of body weight higher than that of an adult.
Hematopoiesis, the formation of blood, occurs in the yolk sac (see Fig. 6.7, B) beginning in the third week. Hematopoietic stem cells seed the fetal liver during the fifth week, and hematopoiesis begins there during the sixth week. This accounts for the relatively large size of the liver between the seventh and ninth weeks. Stem cells seed the fetal bone marrow, spleen and thymus, and lymph nodes between weeks 8 and 11. (For more information about stem cells, see https://stemcells.nih.gov.)
The antigenic factors that determine blood type are present in the erythrocytes soon after the sixth week. For this reason, the Rh-negative woman is at risk for isoimmunization in any pregnancy that lasts longer than 6 weeks after fertilization.
The respiratory system begins development during embryonic life and continues through fetal life and into childhood. The development of the respiratory tract begins in week 4 and continues through week 17 with formation of the larynx, trachea, bronchi, and lung buds. Between 16 and 24 weeks, the bronchi and terminal bronchioles enlarge and vascular structures and primitive alveoli are formed. Between 24 weeks and term birth, more alveoli form. Specialized alveolar cells, type I and type II cells, secrete pulmonary surfactants to line the interior of the alveoli. After 32 weeks, sufficient surfactant is present in developed alveoli to provide infants with a good chance of survival.
The detection of the presence of pulmonary surfactants, surface-active phospholipids, in amniotic fluid has been used to determine the degree of fetal lung maturity, or the ability of the lungs to function after birth. Lecithin (L) is the most critical alveolar surfactant required for postnatal lung expansion. It is detectable at approximately 21 weeks and increases in amount after week 24. Another pulmonary phospholipid, sphingomyelin (S), remains constant in amount. Thus the measure of lecithin in relation to sphingomyelin, or the L/S ratio, is used to determine fetal lung maturity. When the L/S ratio reaches 2 : 1, the infant’s lungs are considered to be mature. This occurs at approximately 35 weeks of gestation (Mercer, 2014).
Certain maternal conditions that cause decreased maternal placental blood flow, such as maternal hypertension, placental dysfunction, infection, or corticosteroid use, accelerate lung maturity. This apparently is caused by the resulting fetal hypoxia, which stresses the fetus and increases the blood levels of corticosteroids that accelerate alveolar and surfactant development.
Conditions such as gestational diabetes and chronic glomerulonephritis can slow fetal lung maturity. The use of intrabronchial synthetic surfactant in the treatment of respiratory distress syndrome in the newborn has greatly improved the chances of survival for preterm infants (see Chapter 25).
Fetal respiratory movements have been seen on ultrasound as early as week 11. These fetal respiratory movements may aid in development of the chest wall muscles and regulate lung fluid volume. The fetal lungs produce fluid that expands the air spaces in the lungs. The fluid drains into the amniotic fluid or is swallowed by the fetus.
Shortly before birth, secretion of lung fluid decreases. Absorption of lung fluid begins during labor as fetal catecholamines and endogenous steroids are released in response to labor. The normal birth process squeezes out approximately one third of the fluid. Infants born by cesarean do not benefit from this squeezing process; thus they may have more respiratory difficulty at birth. The fluid remaining in the lungs at birth is usually resorbed into the infant’s bloodstream within 2 hours of birth.
During the fourth week, the shape of the embryo changes from being almost straight to a C shape as both ends fold in toward the ventral surface. A portion of the yolk sac is incorporated into the body from head to tail as the primitive gut (digestive system).
The foregut produces the pharynx, part of the lower respiratory tract, the esophagus, the stomach, the first half of the duodenum, the liver, the pancreas, and the gallbladder. These structures evolve during the fifth and sixth weeks. Malformations that can occur in these areas include esophageal atresia, hypertrophic pyloric stenosis, duodenal stenosis or atresia, and biliary atresia (see Chapter 41).
The midgut becomes the distal half of the duodenum, the jejunum and ileum, the cecum and appendix, and the proximal half of the colon. The midgut loop projects into the umbilical cord between weeks 5 and 10. A malformation, omphalocele, results if the midgut fails to return to the abdominal cavity, causing the intestines to protrude from the umbilicus. Meckel diverticulum is the most common malformation of the midgut. It occurs when a remnant of the yolk stalk that failed to degenerate attaches to the ileum, leaving a blind sac.
The hindgut develops into the distal half of the colon, the rectum and parts of the anal canal, the urinary bladder, and the urethra. Anorectal malformations are the most common abnormalities of the digestive system.
The fetus swallows amniotic fluid beginning in the fifth month. Gastric emptying and intestinal peristalsis occur. Fetal nutrition and elimination needs are taken care of by the placenta. As the fetus nears term, fetal waste products accumulate in the intestines as dark-green to black, tarry meconium. Normally this substance is passed through the rectum within 24 hours of birth. Sometimes with a breech presentation or fetal hypoxia, meconium is passed in utero into the amniotic fluid. The failure to pass meconium after birth may indicate atresia somewhere in the digestive tract; an imperforate anus (Fig. 6.15); or meconium ileus, in which a firm meconium plug blocks passage (seen in infants with CF).
FIG 6.15 Anorectal malformation (imperforate anus). (From Moore, K.L., Persaud, T.V.N., Torchia, M.G. . The developing human: Clinically oriented embryology [10th ed.]. Philadelphia, PA: Elsevier.)
The metabolic rate of the fetus is relatively low, but the infant has great growth and development needs. Beginning in week 9, the fetus synthesizes glycogen for storage in the liver. Between 26 and 30 weeks, the fetus begins to lay down stores of brown fat in preparation for extrauterine cold stress. Thermoregulation in the neonate requires increased metabolism and adequate oxygenation (see Chapter 22).
The gastrointestinal system is mature by 36 weeks. Digestive enzymes (except pancreatic amylase and lipase) are present in sufficient quantity to facilitate digestion. The neonate cannot digest starches or fats efficiently. Little saliva is produced.
The liver and biliary tract develop from the foregut during the fourth week of gestation. Hematopoiesis begins during the sixth week and requires that the liver is large. The embryonic liver is prominent, occupying most of the abdominal cavity. Bile, a constituent of meconium, begins to form in the twelfth week.
Glycogen is stored in the fetal liver beginning at week 9 or 10. At term, glycogen stores are twice those of the adult. Glycogen is the major source of energy for the fetus and for the neonate stressed by in utero hypoxia, extrauterine loss of the maternal glucose supply, the work of breathing, or cold stress.
Iron is also stored in the fetal liver. If maternal intake is sufficient, the fetus can store enough iron to last for 5 months after birth.
During fetal life, the liver does not have to conjugate bilirubin for excretion because the unconjugated bilirubin is cleared by the placenta. Therefore the glucuronyl transferase enzyme needed for conjugation is present in the fetal liver in amounts less than those required after birth. This predisposes the neonate, especially the preterm infant, to hyperbilirubinemia.
Coagulation factors II, VII, IX, and X cannot be synthesized in the fetal liver because of the lack of vitamin K synthesis in the sterile fetal gut. This coagulation deficiency persists after birth for several days and is the rationale for the prophylactic administration of vitamin K to the newborn (see Chapter 23).
The kidneys form during the fifth week and begin to function approximately 4 weeks later. Urine is excreted into the amniotic fluid and forms a major part of the amniotic fluid volume. Oligohydramnios is indicative of renal dysfunction. Because the placenta acts as the organ of excretion and maintains fetal water and electrolyte balance, the fetus does not need functioning kidneys while in utero. At birth, however, the kidneys are required immediately for excretory and acid-base regulatory functions.
A fetal renal malformation can be diagnosed in utero. Corrective or palliative fetal surgery may treat the malformation successfully, or plans can be made for treatment immediately after birth.
At term, the fetus has fully developed kidneys. However, the glomerular filtration rate (GFR) is low, and the kidneys lack the ability to concentrate urine. This makes the newborn more susceptible to both overhydration and dehydration.
The nervous system originates from the ectoderm during the third week after fertilization. The open neural tube forms during the fourth week. It initially closes at what will be the junction of the brain and spinal cord, leaving both ends open. The embryo folds in on itself lengthwise at this time, forming a head fold in the neural tube at this junction. The cranial end of the neural tube closes, and then the caudal end closes. During week 5, different growth rates cause more flexures in the neural tube, delineating three brain areas: the forebrain, the midbrain, and the hindbrain.
The forebrain develops into the eyes (cranial nerve II) and cerebral hemispheres. The development of all areas of the cerebral cortex continues throughout fetal life and into childhood. The olfactory system (cranial nerve I) and thalamus also develop from the forebrain. Cranial nerves III and IV (oculomotor and trochlear) form from the midbrain. The hindbrain forms the medulla, the pons, the cerebellum, and the remainder of the cranial nerves. Brain waves can be recorded on an electroencephalogram by week 8.
The spinal cord develops from the long end of the neural tube. Another ectodermal structure, the neural crest, develops into the peripheral nervous system. By the eighth week, nerve fibers traverse throughout the body. By week 11 or 12, the fetus makes respiratory movements, moves all extremities, and changes position in utero. The fetus can suck his or her thumb, swim in the amniotic fluid pool, and turn somersaults and can occasionally tie a knot in the umbilical cord.
At term, the fetal brain is approximately one-fourth the size of an adult brain. Neurologic development continues. Stressors on the fetus and neonate (e.g., chronic poor nutrition or hypoxia, drugs, environmental toxins, trauma, disease) damage the central nervous system long after the vulnerable embryonic time for malformations in other organ systems. Neurologic insult can result in cerebral palsy, neuromuscular impairment, intellectual disability, and learning disabilities.
Purposeful movements of the fetus have been demonstrated in response to a firm touch transmitted through the mother’s abdomen. Because it can feel, the fetus requires anesthesia when invasive procedures are done.
Fetuses respond to sound by 24 weeks. Different types of music evoke different movements. The fetus can be soothed by the sound of the mother’s voice. Acoustic stimulation can be used to evoke a fetal heart rate response. The fetus becomes accustomed (habituates) to noises heard repeatedly. Hearing is fully developed at birth.
The fetus is able to distinguish taste. By the fifth month, when the fetus is swallowing amniotic fluid, a sweetener added to the fluid causes the fetus to swallow faster. The fetus also reacts to temperature changes. A cold solution placed into the amniotic fluid can cause fetal hiccups.
The fetus can see. Eyes have both rods and cones in the retina by the seventh month. A bright light shone on the mother’s abdomen in late pregnancy causes abrupt fetal movements. During sleep time, rapid eye movements (REMs) have been observed similar to those occurring in children and adults while dreaming.
The thyroid gland develops along with structures in the head and neck during the third and fourth weeks. The secretion of thyroxine begins during the eighth week. Maternal thyroxine does not readily cross the placenta; therefore the fetus that does not produce thyroid hormones will be born with congenital hypothyroidism. If untreated, hypothyroidism can result in severe intellectual disability. Screening for hypothyroidism is typically included in newborn screening after birth.
The adrenal cortex is formed during the sixth week and produces hormones by the eighth or ninth week. As term approaches, the fetus produces more cortisol. This is believed to aid in initiation of labor by decreasing the maternal progesterone and stimulating production of prostaglandins.
The pancreas forms from the foregut during the fifth through eighth weeks. The islets of Langerhans develop during the twelfth week. Insulin is produced by week 20. In fetuses of mothers with uncontrolled diabetes, maternal hyperglycemia produces fetal hyperglycemia, stimulating hyperinsulinemia and islet cell hyperplasia. This results in a macrosomic (large) fetus. The hyperinsulinemia also blocks lung maturation, placing the neonate at risk for respiratory distress and hypoglycemia when the maternal glucose source is lost at birth. Control of the maternal glucose level before and during pregnancy minimizes problems for the fetus and infant.
Sex differentiation begins in the embryo during the seventh week. Female and male external genitalia are indistinguishable until after the ninth week. Distinguishing characteristics appear around the ninth week and are fully differentiated by the twelfth week. When a Y chromosome is present, testes are formed. By the end of the embryonic period, testosterone is being secreted and causes formation of the male genitalia. By week 28, the testes begin descending into the scrotum. After birth, low levels of testosterone continue to be secreted until the pubertal surge.
The female, with two X chromosomes, forms ovaries and female external genitalia. By the sixteenth week, oogenesis has been established. At birth, the ovaries contain the female’s lifetime supply of ova. Most female hormone production is delayed until puberty. However, the fetal endometrium responds to maternal hormones, and withdrawal bleeding or vaginal discharge (pseudomenstruation) may occur at birth when these hormones are lost. The high level of maternal estrogen also stimulates mammary engorgement and secretion of fluid (“witch’s milk”) in newborn infants of both sexes.
Bones and muscles develop from the mesoderm by the fourth week of embryonic development. At that time, the cardiac muscle is already beating. The mesoderm next to the neural tube forms the vertebral column and ribs. The parts of the vertebral column grow toward each other to enclose the developing spinal cord. Ossification, or bone formation, begins. If there is a defect in the bony fusion, various forms of spina bifida can occur. A large defect affecting several vertebrae may allow the membranes and spinal cord to pouch out from the back, producing neurologic deficits and skeletal deformity.
The flat bones of the skull develop during the embryonic period, and ossification continues throughout childhood. At birth, connective tissue sutures exist where the bones of the skull meet. The areas where more than two bones meet (called fontanels) are especially prominent. The sutures and fontanels allow the bones of the skull to mold, or move during birth, enabling the head to pass through the birth canal.
The bones of the shoulders, arms, hips, and legs appear in the sixth week as a continuous skeleton with no joints. Differentiation occurs, producing separate bones and joints. Ossification will continue through childhood to allow growth. Beginning in the seventh week, muscles contract spontaneously. Arm and leg movements are visible on ultrasound examination, although the mother does not perceive them until sometime between 16 and 20 weeks.
The epidermis begins as a single layer of cells derived from the ectoderm at 4 weeks. By the seventh week, there are two layers of cells. The cells of the superficial layer are sloughed and become mixed with the sebaceous gland secretions to form the white, cheesy vernix caseosa, the material that protects the skin of the fetus. The vernix is thick at 24 weeks but becomes scant by term.
The basal layer of the epidermis is the germinal layer, which replaces lost cells. Until 17 weeks, the skin is thin and wrinkled, with blood vessels visible underneath. The skin thickens, and all layers are present at term. After 32 weeks, as subcutaneous fat is deposited under the dermis, the skin becomes less wrinkled and red in appearance.
By 16 weeks, the epidermal ridges are present on the palms of the hands, the fingers, the bottoms of the feet, and the toes. These handprints and footprints are unique to that infant.
Hairs form from hair bulbs in the epidermis that project into the dermis. Cells in the hair bulb keratinize to form the hair shaft. As the cells at the base of the hair shaft proliferate, the hair grows to the surface of the epithelium. Very fine hairs, called lanugo, appear first at 12 weeks on the eyebrows and upper lip. By 20 weeks, they cover the entire body. At this time, the eyelashes, eyebrows, and scalp hair are beginning to grow. By 28 weeks, the scalp hair is longer than the lanugo, which thins and may disappear by term gestation.
Fingernails and toenails develop from thickened epidermis at the tips of the digits beginning during the tenth week. They grow slowly. Fingernails usually reach the fingertips by 32 weeks, and toenails reach toe tips by 36 weeks.
During the third trimester, albumin and globulin are present in the fetus. The only immunoglobulin (Ig) that crosses the placenta, IgG, provides passive acquired immunity to specific bacterial toxins. The fetus produces IgM by the end of the first trimester. This is produced in response to blood group antigens, gram-negative enteric organisms, and some viruses. IgA is not produced by the fetus; however, colostrum, the precursor to breast milk, contains large amounts of IgA and can provide passive immunity to the neonate who is breastfed.
The normal term neonate can fight infection, but not as effectively as an older child. The preterm infant is at much greater risk for infection.
Table 6.1 summarizes embryonic and fetal development.
Milestones in Human Development Before Birth Since Last Menstrual Period (LMP)
Body flexed, C shaped; arm and leg buds present; head at right angles to body
Body fairly well formed; nose flat, eyes far apart; digits well formed; head elevating; tail almost disappeared; eyes, ears, nose, and mouth recognizable
Nails appearing; resembles a human; head erect but disproportionately large; skin pink, delicate
Crown-to-Rump Measurement; Weight
0.4–0.5 cm; 0.4 g
2.5–3 cm; 2 g
6–9 cm; 19 g
Stomach at midline and fusiform; conspicuous liver; esophagus short; intestine a short tube
Intestinal villi developing; small intestines coil within umbilical cord; palatal folds present; liver very large
Bile secreted; palatal fusion complete; intestines have withdrawn from cord and assume characteristic positions
All somites present
First indication of ossification—occiput, mandible, and humerus; fetus capable of some movement; definitive muscles of trunk, limbs, and head well represented
Some bones well outlined, ossification spreading; upper cervical to lower sacral arches and bodies ossify; smooth muscle layers indicated in hollow viscera
Heart develops, double chambers visible, begins to beat; aortic arch and major veins completed
Main blood vessels assume final plan; enucleated red cells predominate in blood
Blood forming in marrow
Primary lung buds appear
Pleural and pericardial cavities forming; branching bronchioles; nostrils closed by epithelial plugs
Lungs acquire definite shape; vocal cords appear
Rudimentary ureteral buds appear
Earliest secretory tubules differentiating; bladder-urethra separates from rectum
Kidneys able to secrete urine; bladder expands as a sac
Well-marked midbrain flexure; no hindbrain or cervical flexures; neural groove closed
Cerebral cortex begins to acquire typical cells; differentiation of cerebral cortex, meninges, ventricular foramina, cerebrospinal fluid circulation; spinal cord extends entire length of spine
Brain structural configuration almost complete; cord shows cervical and lumbar enlargements; fourth ventricle foramina are developed; sucking present
Eye and ear appearing as optic vessel and otocyst
Primordial choroid plexuses develop; ventricles large relative to cortex; development progressing; eyes converging rapidly; internal ears developing
Earliest taste buds indicated; characteristic organization of eyes attained
Genital ridge appears (fifth week)
Testes and ovaries distinguishable; external genitalia sexless but begin to differentiate
Sex recognizable; internal and external sex organs specific
Head still dominant; face looks human; eyes, ears, and nose approach typical appearance on gross examination; arm/leg ratio proportionate; scalp hair appears
Vernix caseosa appears; lanugo appears; legs lengthen considerably; sebaceous glands appear
Body lean but fairly well proportioned; skin red and wrinkled; vernix caseosa present; sweat glands forming
Crown-to-Rump Measurement; Weight
11.5–13.5 cm; 100 g
16–18.5 cm; 300 g
23 cm; 600 g
Meconium in bowel; some enzyme secretion; anus open
Enamel and dentine depositing; ascending colon recognizable
Most bones distinctly indicated throughout body; joint cavities appear; muscular movements can be detected
Sternum ossifies; fetal movements strong enough for mother to feel
Heart muscle well developed; blood formation active in spleen
Blood formation increases in bone marrow and decreases in liver
Elastic fibers appear in lungs; terminal and respiratory bronchioles appear
Nostrils reopen; primitive respiratory-like movements begin
Alveolar ducts and sacs present; lecithin begins to appear in amniotic fluid (weeks 26–27)
Kidneys in position; attain typical shape
Cerebral lobes delineated; cerebellum assumes some prominence
Brain grossly formed; cord myelination begins; spinal cord ends at level of first sacral vertebra (S-1)
Cerebral cortex layered typically; neuronal proliferation in cerebral cortex ends
General sense organs differentiated
Nose and ears ossify
Testes in position for descent into scrotum; vagina open
Testes at inguinal ring in descent to scrotum
36 and 40 Weeks
Lean body, less wrinkled and red; nails appear
Subcutaneous fat beginning to collect; more rounded appearance; skin pink and smooth; has assumed birth position
Skin pink, body rounded; general lanugo disappearing; body usually plump
Skin smooth and pink; scant vernix caseosa; moderate to profuse hair; lanugo on shoulders and upper body only; nasal and alar cartilage apparent
Crown-to-Rump Measurement; Weight
27 cm; 1100 g
31 cm; 1800–2100 g
35 cm; 2200–2900 g
40 cm; 3200+ g
Astragalus (talus, ankle bone) ossifies; weak, fleeting movements, minimum tone
Middle fourth phalanxes ossify; permanent teeth primordia seen; can turn head to side
Distal femoral ossification centers present; sustained, definite movements; fair tone; can turn and elevate head
Active, sustained movement; good tone; may lift head
Lecithin forming on alveolar surfaces
L/S ratio = 1.2 : 1
L/S ratio ≥2 : 1
Pulmonary branching only two-thirds complete
Formation of new nephrons ceases
Appearance of cerebral fissures, convolutions rapidly appearing; indefinite sleep-wake cycle; cry weak or absent; weak suck reflex
End of spinal cord at level of third lumbar vertebra (L-3); definite sleep-wake cycle
Myelination of brain begins; patterned sleep-wake cycle with alert periods; cries when hungry or uncomfortable; strong suck reflex
Eyelids reopen; retinal layers completed, light receptive; pupils capable of reacting to light
Sense of taste present; aware of sounds outside mother’s body
Testes descending to scrotum
Testes in scrotum; labia majora well developed
The incidence of twinning is 1 in 43 pregnancies. There has been a steady rise in multiple births since 1973, partly attributed to the availability of assisted reproductive technologies and the increasing age at which women give birth (Benirschke, 2014). The twin rate was at its highest incidence in 2014 but then declined in 2015 (Martin, Hamilton, Osterman, et al., 2017) . This is partly attributed to the availability of assisted reproductive technologies and the increasing age at which women give birth as well as use of ovulation-enhancing drugs (Benirschke, 2014).
When two mature ova are produced in one ovarian cycle, both have the potential to be fertilized by separate sperm. This results in two zygotes, or dizygotic twins (Fig. 6.16). There are always two amnions, two chorions, and two placentas that may be fused (Fig. 6.17). These dizygotic or fraternal twins may be the same sex or different sexes and are genetically no more alike than siblings born at different times. Dizygotic twinning occurs in families with a history of twinning, more often among African-American women than Caucasian women, and least often among Asian-American women. Dizygotic twinning increases in frequency with maternal age up to 35 years, with parity, and with the use of fertility drugs.
FIG 6.16 Formation of dizygotic twins. There is fertilization of two ova, two implantations, two placentas, two chorions, and two amnions.
FIG 6.17 Diamniotic dichorionic (separate) twin placentas. (From Benirschke, K. . Multiple gestation: The biology of twinning. In Creasy, R., Resnik, R., Iams, J., et al. [eds.]. Creasy & Resnik’s maternal-fetal medicine: Principles and practice [7th ed.] Philadelphia, PA: Saunders.)
Identical or monozygotic twins develop from one fertilized ovum, which then divides (Fig. 6.18). They are the same sex and have the same genotype. If division occurs soon after fertilization, two embryos, two amnions, two chorions, and two placentas that may be fused will develop. Most often, division occurs between 4 and 8 days after fertilization, and there are two embryos, two amnions, one chorion, and one placenta. Rarely, division occurs after the eighth day after fertilization. In this case, there are two embryos within a common amnion and a common chorion with one placenta. This often causes circulatory problems because the umbilical cords may tangle together and one or both fetuses may die. If division occurs very late, cleavage may not be complete and conjoined or “Siamese” twins may result. Monozygotic twinning occurs in approximately 3.5 to 4 per 1000 births (Benirschke, 2014). There is no association with race, heredity, maternal age, or parity. Fertility drugs increase the incidence of monozygotic twinning.
FIG 6.18 Formation of monozygotic twins. A, One fertilization: blastomeres separate, resulting in two implantations, two placentas, and two sets of membranes. B, One blastomere with two inner cell masses, one fused placenta, one chorion, and separate amnions. C, One blastomere with incomplete separation of cell mass resulting in conjoined twins.
Conjoined twins are a type of monozygotic twins in which there is incomplete embryonic division at 13 to 15 days postconception (see Fig. 6.18). The estimated frequency is 1.5 in 100,000 births (Malone & D’Alton, 2014). Prenatal diagnosis is possible with three-dimensional ultrasonography. Cesarean birth minimizes trauma to mother and fetuses.
Other Multifetal Pregnancies
The occurrence of multifetal pregnancies with three or more fetuses has increased with the use of fertility drugs and in vitro fertilization, but in 2015 it decreased by 9% from the previous year to 103.6 triplets per 100,000 births (Martin et al., 2017). They can occur from the division of one zygote into two, with one of the two dividing again, producing identical triplets. Triplets can also be produced (1) from two zygotes, one dividing into a set of identical twins and the second zygote a single fraternal sibling or (2) from three zygotes. Quadruplets, quintuplets, sextuplets, and so on have similar possible derivations.
Nongenetic Factors Influencing Development
Congenital disorders may be inherited or may be caused by environmental factors or by inadequate maternal nutrition. Congenital means that the condition was present at birth. Some congenital malformations may be the result of teratogens, that is, environmental substances or exposures that result in functional or structural disability. In contrast to other forms of developmental disabilities, disabilities caused by teratogens are theoretically totally preventable. Known human teratogens are drugs and chemicals, infections, exposure to radiation, and certain maternal conditions such as diabetes and PKU (Box 6.2). A teratogen has the greatest effect on the organs and parts of an embryo during its periods of rapid growth and differentiation. This occurs during the embryonic period, specifically from days 15 to 60. During the first 2 weeks of development, teratogens either have no effect on the embryo or have effects so severe that they cause miscarriage. Brain growth and development continue during the fetal period, and teratogens can severely affect mental development throughout gestation (Fig. 6.19).
Etiology of Human Malformations
• Maternal conditions
• Alcoholism, diabetes, endocrinopathies, phenylketonuria, smoking, nutritional problems
• Infectious agents
• Rubella, toxoplasmosis, syphilis, herpes simplex, cytomegalic inclusion disease, varicella, Venezuelan equine encephalitis
• Mechanical problems (deformations)
• Amniotic band constrictions, umbilical cord constraint, disparity in uterine size and uterine contents
• Chemicals, drugs, radiation, hyperthermia
• Single-gene disorders
• Chromosomal abnormalities
• Polygenic/multifactorial (gene-environment interactions)
• “Spontaneous” errors of development
• Other unknowns
Modified from Parikh, A.S., Mitchell, A.L. (2015). Congenital anomalies. In Martin, R.J., Fanaroff, A.A., Walsh, M.C. (Eds.), Fanaroff and Martin’s neonatal-perinatal medicine: Diseases of the fetus and infant (10th ed.). Philadelphia, PA: Saunders.
FIG 6.19 Critical periods in human development. Dark color denotes highly sensitive periods; light color indicates stages that are less sensitive to teratogens. CNS, Central nervous system. (From Moore, K.L., Persaud, T.V.N., Torchia, M.G. . Before we are born: Essentials of embryology and birth defects [8th ed.]. Philadelphia, PA: Saunders.)
In addition to genetic makeup and the influence of teratogens, the adequacy of maternal nutrition influences development. The embryo and fetus must obtain the nutrients they need from the mother’s diet; they cannot tap the maternal reserves. Malnutrition during pregnancy produces low–birth-weight (LBW) newborns who are susceptible to infection. Malnutrition also affects brain development during the latter half of gestation and can result in learning disabilities in the child. Inadequate folic acid is associated with neural tube defects.
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