Infertility, Contraception, and Abortion

On completion of this chapter, the reader will be able to:

• Discuss the psychologic impact of infertility.

• Describe common diagnoses and treatments for infertility.

• Compare reproductive alternatives for couples experiencing infertility.

• Identify the advantages and disadvantages of the following methods of contraception: fertility awareness methods, barrier methods, hormonal methods, intrauterine devices, and sterilization.

• Explain common nursing interventions that facilitate contraceptive use.

• Describe the techniques used for medical and surgical interruption of pregnancy.

• Recognize ethical, legal, cultural, and religious considerations of infertility, contraception, and elective abortion.

Infertility is a serious concern that affects quality of life of 10% to 15% of reproductive-age couples (American Society for Reproductive Medicine [ASRM], 2012). 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 (Practice Committee of the ASRM, 2008). 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.

The prevalence of infertility is relatively stable among the overall population; although, as the U.S. population ages, the numbers of infertile women will decline with the decrease in numbers of reproductive-age women. Infertility increases with the age of the woman, with fertility rates in women ages 40 to 45 being 95% lower than women ages 20 to 24. 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. The origins of some of these feelings are myths, superstitions, misinformation, or magical thinking about the causes of infertility. Other feelings of anxiety and helplessness arise from the need to undergo many tests and examinations and from a perception of being “different” from others (RESOLVE, 2012). Nurses who care for infertile couples should consider the following four goals:

• 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 as a couple 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.

Nurses should also remember that among healthy women and men promotion of normal reproduction and prevention of infertility can be achieved if both partners 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. As they make plans for their future family, adults should also know that realistically fertility decreases with age.

Factors Associated with Infertility

Although exact percentages vary somewhat with populations, approximately 80% of couples have an identifiable cause of infertility, with about 40% of these causes related to factors in the female partner, 40% related to factors in the male partner, and 20% related to factors in both partners. About 20% or more couples will experience unexplained or idiopathic causes of infertility (ASRM, 2012). Nevertheless 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 fallopian 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 fallopian 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.

Box 5-1 Factors Affecting Female Fertility

Ovarian Factors

• Developmental anomalies

• Anovulation—primary

• Pituitary or hypothalamic hormone disorders

• Adrenal gland disorders (rare)

• Congenital adrenal hyperplasia (rare)

• Anovulation—secondary

• Disruption of hypothalamic-pituitary-ovarian axis

• Anorexia

• Insufficient body fat in athletic women

• Increased prolactin levels

• Thyroid disorders

• Premature ovarian failure

• Polycystic ovarian disorder

• Medications

• Oral contraceptives

• Progestins

• Antidepressant and antipsychotic drugs

• Corticosteroids

• Chemotherapy

Tubal/Peritoneal Factors

• Developmental anomalies of the tubes (see Fig. 5-1)

• Reduced tubal motility

• Inflammation within the tube

• Tubal adhesions

• Disruption caused by tubal pregnancy

• Endometriosis

Uterine Factors

• Developmental anomalies of the uterus (see Fig. 5-1)

• Endometrial and myometrial fibroid tumors

• Asherman’s syndrome (uterine adhesions or scar tissue)

Vaginal-Cervical Factors

• Vaginal-cervical infections

• Cervical mucus inadequate

• Isoimmunization (development of sperm antibodies)

Other Factors

• Nutritional deficiencies

• Obesity

• Thyroid dysfunction (hyperthyroidism and hypothyroidism)

• Idiopathic conditions

Box 5-2 Factors Affecting Male Fertility

Hormonal Disorders

• Congenital disorders

• Tumors of the pituitary and hypothalamus

• Trauma to the pituitary or hypothalamus

• Hyperprolactinemia

• Excess of androgens, estrogen, cortisol

• Drugs and substance abuse (recreational and prescribed drugs)

• Chronic illnesses

• Nutritional deficiencies

• Obesity

• Endocrine disorders (e.g., diabetes)

Testicular Factors

• Congenital disorders

• Undescended testes

• Hypospadias

• Varicocele

• Viral infections (e.g., mumps)

• Sexually transmitted infections (gonorrhea, chlamydial infection)

• Obstructive lesions of the epididymis and vas deferens

• Environmental toxins

• 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

• Antisperm antibodies

Factors Associated with Sperm Transport

• Drugs

• Sexually transmitted infections of the epididymis

• Ejaculatory dysfunction

• Premature ejaculation

Idiopathic Male Infertility

For ovulation 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 (Fritz and Speroff, 2011c). 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.

Care Management

The nurse 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. Box 5-3 describes some of the concerns related to religion that may affect the couple’s choices regarding infertility treatment. The Cultural Competence box notes cultural rituals and beliefs regarding fertility. 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 (see Cultural Competence box). 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 5-4 describes the status of insurance coverage for infertility treatment.

Box 5-3

Religious Considerations Concerning Infertility

The health care provider must always be aware of civil laws and religious proscriptions about sexual activities. Conservative and reform Jewish couples accept most infertility treatment; however, the Orthodox Jewish husband and wife may face problems in infertility investigation and management because of religious laws that govern marital relations. For example, according to Jewish law the Orthodox couple may not engage in marital relations during menstruation and through the following seven “preparatory days.” The wife then is immersed in a ritual bath (Mikvah) before relations can resume. Fertility problems can arise when the woman has a short cycle (i.e., a cycle of 24 days or fewer, when ovulation would occur on day 10 or earlier).

The Roman Catholic Church regards the embryo as a human being from the first moment of existence. Therefore technical procedures such as in vitro fertilization (IVF), therapeutic donor insemination, and freezing embryos are not accepted or endorsed.

Other religious groups may have ethical concerns about infertility tests and treatments. For example, most Protestant denominations and Muslims usually support infertility management as long as IVF is done with the husband’s sperm, there is no reduction of fertilized embryos after implantation, and insemination is done with the husband’s sperm. These groups are less supportive of surrogacy and use of donor sperm and eggs. Christian Scientists do not permit surgical procedures or IVF but do permit insemination with husband and donor sperm.

Care providers should seek to understand the woman’s spirituality and how beliefs affect her perception of health care, especially in relation to infertility. Women may wish to seek infertility treatment but have questions about proposed diagnostic and therapeutic procedures because of religious proscriptions. These women are encouraged to consult their minister, rabbi, priest, or other spiritual leader for advice.

Data from D’Avanzo C: Mosby’s pocket guide to cultural health assessment, ed 4, St Louis, 2008, Mosby.

Box 5-4 Insurance Coverage for Infertility

As of October 2012, 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. For questions about an individual state, call the state Insurance Commissioner’s office. The website for the American Society for Reproductive Medicine (www.asrm.org) has more complete information.

Cultural Competence

Fertility and Infertility

Worldwide cultures continue to use symbols and rites that celebrate fertility. One fertility rite that persists today is the custom of throwing rice at the bride and groom. Other fertility symbols and rites include passing out congratulatory cigars, candy, or pencils by a new father and baby showers held in anticipation of a child’s birth.

In many cultures the responsibility for infertility is usually attributed to the woman. A woman’s inability to conceive may be caused by previous sins, evil spirits, or personal inadequacies. In some cultures male virility remains in question until a man demonstrates his ability to reproduce by having at least one child (D’Avanzo, 2008).

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 over 35. 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 (Fig. 5-1) as a result of congenital abnormalities during fetal development). These uterine abnormalities increase risk for early pregnancy loss.

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.

Laboratory data, including routine urine and blood tests, are collected. The initial clinic visit serves as a preconceptual 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.

Diagnostic Testing.

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. Previous status regarding ovulation can be evaluated through menstrual history, serum hormone studies, and use of an ovulation predictor kit. If the woman is over age 35, 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 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 5-5.

Box 5-5 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 presence of adequate ovarian follicles.

d. Day 3 estradiol levels are low enough to verify 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.

TABLE 5-1

GENERAL TESTS FOR IMPAIRED FERTILITY

TEST OR EXAMINATION	TIMING (MENSTRUAL CYCLE DAYS)	RATIONALE
Hysterosalpingogram (HSG) (uterine abnormalities, tubal patency)	7-10	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)	Variable	Negative antibody test may indicate tubal patency assessment (HSG); not needed in low risk women
Hysterosalpingo-contrast sonography (uterine abnormalities, tubal patency)	7-10	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)	Variable, ovulation	Cervical mucus should have low viscosity, high 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)	Variable, ovulation	Detects timing of lutein hormone surge before ovulation
Semen analysis (male factor)	2 to 7 days after abstinence	Detects ability of sperm to fertilize egg
Sperm penetration assay (male factor)	After 2 days but ≤1 wk of abstinence	Evaluation of ability of sperm to penetrate egg
Follicle-stimulating hormone (FSH) level (ovarian reserve)	Day 3	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 3 through 10	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

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 5-6. 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.

Box 5-6

Semen Analysis

• Semen volume at least 1.5 L

• 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.

Source: World Health Organization (WHO): Laboratory manual for the examination of human semen, ed 5, Geneva, 2010, WHO.

Hormone analyses are done for testosterone, gonadotropin, FSH, and luteinizing hormone (LH). The sperm penetration assay and other alternative tests can be used to evaluate the ability of sperm to penetrate an egg. Testicular biopsy may be warranted. Scrotal ultrasound can 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.

Psychosocial Considerations

Infertility is recognized as a major life stressor that can affect self-esteem; relations with the spouse, 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 proscriptions 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 a private act, lovemaking, 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 Critical Thinking Case Study).

Critical Thinking Case Study

Infertility

Diane is a 39-year-old accountant who has recently married for the first time. Charles is 41 and has two children from a previous marriage. Diane has a history of amenorrhea 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 a year. They have come to the fertility clinic today for an evaluation. Diane tells the nurse that she has heard a lot 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

b. Infertility as a major life stressor

c. Success rates for IVF pregnancy and birth

d. Causes of female infertility

3. What implications and priorities for nursing care can be drawn at this time?

4. Does the evidence objectively support your conclusion?

The couple facing infertility exhibit 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 greater dissatisfaction with their marriages. Not all people have all the reactions described, nor can it be predicted how long any reaction will last for an individual.

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 childfree 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).

Nonmedical Treatments

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. 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.

Medical Therapy

One goal of infertility assessment and treatment is to determine which couples could respond to conventional therapies in a timely manner. Another goal is to refer couples who will need ARTs to conceive early in the process. In general, any fertility treatment is more likely to result in a live birth in women who are younger than age 35, with successful outcomes decreasing for women over age 40.

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 (a) clomiphene citrate as initial therapy for many women with intermittent anovulation; (b) a combination of clomiphene and metformin for women with anovulation and insulin resistance; (c) human menopausal gonadotropin (HMG), FSH, and recombinant FSH (rFSH) to stimulate follicle formation in women who do not respond to clomiphene therapies; (d) human chorionic gonadotropin to induce ovulation when follicles are ripe, (e) gonadotropin-releasing hormone (GnRH) agonists at the beginning of a cycle to sequence HMG therapies, (f) progesterone to support the luteal phase of the cycle, and (g) bromocriptine (Parlodel) for women who have excess prolactin (see Medication Guide).

Medication Guide

Selected Infertility Medications

DRUG	INDICATION	MECHANISM OF ACTION	DOSAGE	COMMON SIDE EFFECTS
Clomiphene citrate	Ovulation induction, treatment of luteal-phase inadequacy	Thought to bind to estrogen receptors in the pituitary, 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 followed by 10,000 International Units hCG	Ovarian enlargement, ovarian hyperstimulation, local irritation at injection site, multifetal gestations
Follitropins (purified FSH)	Treatment of polycystic ovarian disease; 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)	Ovulation induction	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, 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 to 6 months	Nafarelin—irritation, nosebleeds Both nafarelin and leuprolide—hot flashes, vaginal dryness, myalgia and arthralgia, headaches, mild bone loss (usually reversible within 12-18 months after treatment)
Progesterone	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
Metformin	Restores cyclic ovulation and menses in many women with polycystic ovary disease	Induces ovulation through reducing insulin resistance, thus affecting gonadotropins and androgens; simulates the ovary	Initial dose is 500 mg and titrated up over several weeks to 1500 mg/day; administered orally	Nausea, vomiting, diarrhea, lactic acidosis, liver dysfunction
Letrozole	Ovulation induction	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 5	Hot flashes, headaches, breast tenderness; may increase risk of congenital anomalies

Data from American Society for Reproductive Medicine (ASRM). Medications for inducing ovulation: A patient guide, 2012, www.asrm.org/Factsheetsandbooklets/; Facts and Comparisons. A to Z drug facts, 2013, www.factsandcomparisons.com; and Lobo, R: Infertility: Etiology, diagnostic evaluation, management, prognosis. In Lentz G, Lobo R, Gershenson D, Katz V, editors: Comprehensive gynecology, ed 6, Philadelphia, 2012, Mosby.

Treatment of certain medical conditions can 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 formulations.

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 of twins 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. The incidence of multiple pregnancies with the use of these medications is greater than 25%. 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 primary care provider 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.

Surgical Therapies

A number of surgical procedures can 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 fallopian tube.

FIG 5-2 Hysterosalpingography. Note that the contrast medium flows through the intrauterine cannula and out through the uterine tubes.

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 could 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 can restore fertility.

Assisted Reproductive Therapies

The Centers for Disease Control and Prevention (CDC) (2012) defines assisted reproductive technology (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. The CDC reported that in 2010 there were approximately 147,260 ART cycles with 47,090 births and 61,564 infants (some multiple births) from these cycles. Although the use of ART is still relatively rare compared to the potential demand, its use has doubled over the past decade. Births that were conceived through ART comprise over 1% of all infants born in the United States every year.

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), intracytoplasmic sperm injection (ICSI), assisted embryo hatching, and preimplantation genetic diagnosis (PGD). Table 5-2 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 5-7).

Box 5-7 Issues to Be Addressed by Infertile Couples before Treatment

• Risks of 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

• Possible risks of long-term effects of medications and treatment on women, children, and families

TABLE 5-2

ASSISTED REPRODUCTIVE THERAPIES

PROCEDURE	DEFINITION	INDICATIONS
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 husband’s fertility is severely compromised and donor sperm can be used; if donor sperm are used, the wife 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
Donor oocyte	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 until birth.	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
Assisted hatching	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