Obstetrics and Gynecology 7 Ed.

Chapter 42


This chapter deals primarily with APGO Educational Topic Area:


Students should be able to define and describe causes of infertility. They should be able to outline a basic approach to the evaluation and initial management of patients with infertility. They should be able to outline the complex psychosocial issues associated with this diagnosis.

Clinical Case

A 36-year-old G0 comes to see you regarding her concerns about infertility. She reports that she and her husband of 4 years have been trying to achieve pregnancy for the past 14 months without success. She is particularly frustrated because he has fathered children from his previous marriage. They have been timing intercourse using commercial ovulation predictor kits, but she is unsure whether she is using them correctly. She reports regular menses and no history of tubal surgery or tubal disease.

Infertility affects approximately 15% of reproductive-age couples in the United StatesReproductive age generally encompasses ages of 15 to 44 years, although pregnancy can occur outside of this age range. Infertility is the failure of a couple to conceive after 12 months of frequent, unprotected intercourse. The probability of achieving a pregnancy in one menstrual cycle is termed fecundability and is estimated to be 20% to 25% in healthy young couples. Similarly, fecundity is the probability of achieving a live birth in one menstrual cycle. Fecundability and fecundity both decrease over time; in other words, the probability of conceiving in a given menstrual cycle decreases as the duration of time to achieve conception increases (Fig. 42.1). After 12 months of unprotected intercourse, 85% of couples will achieve pregnancy. Of those who have not achieved pregnancy after 12 months without using contraception, approximately 50% of couples will conceive spontaneously within the following 36 months. If a couple does not conceive by this point, then infertility will likely persist without medical intervention.

Infertility is a condition that encompasses a wide spectrum of reversible and irreversible disorders, and many successful treatments are available. Today, greater numbers of men and women are seeking infertility treatment due to increased public awareness of infertility and changes in social acceptance of infertility, improvements in the availability and range of fertility treatments, and improvements in physicians’ ability to evaluate and diagnose infertility. Furthermore, many individuals and same-sex couples seek fertility treatments to conceive. Although this chapter discusses infertility from the standpoint of a heterosexual couple, it is recognized that fertility treatments offer the opportunity of parenthood to many nonheterosexual individuals and couples.

Today, 85% of infertile couples who undergo appropriate treatment can expect to have a child. However, fertility treatment can be a difficult experience for an individual or a couple. The inability to conceive or carry a pregnancy can be emotionally stressful, and fertility treatment can be a significant financial burden. The psychological stress associated with infertility must be recognized, and patients should be counseled accordingly.


Successful conception requires a specific series of complex events: 1) ovulation of a competent oocyte, 2) production of competent sperm, 3) juxtaposition of sperm and oocyte in a patent reproductive tract and subsequent fertilization, 4) generation of a viable embryo, 5) transport of the embryo into the uterine cavity, and 6) successful implantation of the embryo into the endometrium (Fig. 42.2). Any defect in one or more of the essential steps in reproduction can result in diminished fertility or infertility.

Conditions that affect fertility are divided into three main categories:

1. Female factors (65%)

2. Male factors (20%)

3. Unexplained or other conditions (15%)


FIGURE 42.1. Conception rates for fertile couples.


The most common causes of male and female infertility are investigated during the initial evaluation of infertility. It is important to recognize that more than one factor may be involved in a couple’s infertility; thus, comprehensive evaluation is often warranted (Table 42.1). As with any medical condition, a careful history and evaluation should reveal factors that may be involved in a couple’s infertility, such as medical disorders, medications, prior surgeries, pelvic infections or pelvic pain, sexual dysfunction, and environmental and lifestyle factors (e.g., diet, exercise, tobacco use, and drug use).

The timing of the initial evaluation depends primarily on the age of the female partner and a couple’s risk factors for infertility. Because there is a decline in fecundity with advancing maternal age, women over the age of 35 years may benefit from a preliminary evaluation after only 6 months of attempted conception. The initial assessment and treatment of infertility is commonly provided by an obstetrician–gynecologist. More specialized evaluation and treatment may be performed by a reproductive endocrinologist.


A history of regular, predictable menses strongly suggests ovulatory cycles. Furthermore, many women experience characteristic symptoms associated with ovulation and the production of progesterone: unilateral pelvic discomfort (mittelschmerz), fullness and tenderness of the breasts, decreased vaginal secretions, abdominal bloating, slight increase in body weight, and occasional episodes of depression. These changes rarely occur in anovulatory women. Therefore, a history of regular menses with associated cyclic changes may be considered presumptive evidence of ovulation.

Secretion of progesterone by the corpus luteum dominates the luteal phase of the menstrual cycle and persists if conception occurs. Progesterone acts on the endocervix to convert the thin, clear endocervical mucus into a sticky mucoid material. Progesterone also changes the brain’s thermoregulatory center set point, resulting in a basal body temperature rise of approximately 0.6°F. In the absence of pregnancy, involution of the corpus luteum is associated with an abrupt decrease in progesterone production, normalization of the basal body temperature, shedding of the endometrium, and the commencement of menstruation.


FIGURE 42.2. Steps in successful conception: ovulation, production of viable sperm and fertilization, development of the zygote, early embryonic development, and implantation of the embryo into the endometrium.


Ovulation Tests

Two tests provide indirect evidence of ovulation and can help predict the timing of ovulation. Basal body temperature measurement reveals a characteristic biphasic temperature curve during most ovulatory cycles (Fig. 42.3). Special thermometers are available for this use. Upon awakening in the morning, the patient must take her temperature immediately before any physical activity. The temperature drops at the time of menses and then rises 2 days after the peak of the luteinizing hormone (LH) surge, coinciding with a rise in peripheral levels of progesterone. Oocyte release occurs 1 day before the first temperature elevation, and the temperature remains elevated for up to 14 days. This test for ovulation is readily available, although it is cumbersome to use; it can retrospectively identify ovulation and the optimal time for intercourse, but it can be difficult to interpret. Urine LH kits are also used to prospectively assess the presence and timing of ovulation based on increased excretion of LH in the urine. Ovulation occurs approximately 24 hours after urinary evidence of the LH surge. However, due to the pulsatile nature of LH release, an LH surge can be missed if the test is performed only once daily.

Other diagnostic tests assess ovulation using serum progesterone levels and the endometrial response to progesterone. A midluteal phase serum progesterone level can be used to retrospectively assess ovulation. A value above 3 ng/mL implies ovulation; however, values between 6 and 25 ng/mL may occur in a normal ovulatory cycle. Due to the pulsatile nature of hormone secretion, a single low progesterone assessment should be repeated. Another diagnostic procedure is the luteal phase endometrial biopsy. The identification of secretory endometrium consistent with the day of the menstrual cycle confirms the presence of progesterone; hence, ovulation is implied. However, this procedure is invasive, and histologic assessment of the endometrium does not reliably differentiate infertile and fertile women and may interrupt an early pregnancy. Therefore, the endometrial biopsy is no longer performed to assess ovulation or the endometrium.


FIGURE 42.3. Biphasic basal body temperature pattern that occurs with an ovulatory cycle. HSG, hysterosalpingography; LH, luteinizing hormone.

Ovulatory Dysfunction

If oligo-ovulation (sporadic and unpredictable ovulation) or anovulation (absence of ovulation) is established, usually based on clinical and laboratory data, further testing is indicated to determine the underlying cause. A common cause of ovulatory dysfunction in reproductive-age women is polycystic ovary syndrome (PCOS); other causes include thyroid disorders and hyperprolactinemia. Women with PCOS often present with oligomenorrhea and signs of hyperandrogenism such as hirsutism, acne, and weight gain (see Chapter 40).

Some infertile women present with amenorrhea, and this usually signifies anovulation. Important causes of amenorrhea include pregnancy (a pregnancy test should always be given), hypothalamic dysfunction (usually stress-related), ovarian failure, and obstruction of the reproductive tract. Laboratory testing for ovulatory dysfunction may include assessment of serum levels of human chorionic gonadotropin (hCG), thyroid-stimulating hormone, prolactin, total testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), LH, and estradiol. Treatment of the etiology of ovulatory dysfunction may lead to resumption of ovulation and improved fertility.

Anatomic Factors

The pelvic anatomy should be assessed as a part of the infertility evaluation. Abnormalities of the uterus, fallopian tubes, and peritoneum can all play a role in infertility.


Uterine abnormalities are commonly not sufficient to cause infertility; these disorders are usually associated with pregnancy loss. However, assessment of the uterus is particularly important if there is a history that causes concern, such as abnormal bleeding, pregnancy loss, preterm delivery, or previous uterine surgery. Potential uterine abnormalities include leiomyomas, endometrial polyps, intrauterine adhesions, and congenital anomalies (such as a septate, bicornuate, unicornuate, or didelphic uterus), as shown in Figure 42.4. Assessment of the uterus and endometrial cavity can be accomplished with several imaging techniques; sometimes, a combination of modalities is necessary to best assess pelvic anatomy (Box 42.1).

Fallopian Tubes and Peritoneum

The fallopian tubes are dynamic structures that are essential for ovum, sperm, and embryo transport and fertilization. At ovulation, the fimbriated end of the fallopian tube picks up the oocyte from the site of ovulation or from the pelvic culde-sac. The oocyte is transported to the ampullary portion of the fallopian tube where fertilization occurs (see Fig. 42.2). Subsequently, a zygote and then an embryo are formed. At 5 days following fertilization, the embryo enters the endometrial cavity, where implantation into the secretory endometrium occurs, followed by further embryo growth and development.


FIGURE 42.4. Uterine abnormalities. (A) X-ray hysterosalpingogram confirms a didelphic uterus, with paired contrastfilled cervical canals (arrowheads) and uterine cavities (arrows). (B) Three-dimensional sonogram indicating a septate uterus. The endometrium is separated into two components (short arrows) and the uterine fundus (long arrow) has a smooth external contour. Courtesy of Dr. Beryl Benacerraf. (From Doubilet PM, Benson CB. Atlas of Ultrasound in Obstetrics and Gynecology. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:291.)

The fallopian tubes and pelvis can be evaluated with hysterosalpingography (HSG) or laparoscopy.


There are several important characteristics of a normal HSG (Fig. 42.5). The uterine cavity should be smooth and symmetrical; indentations or irregularities of the cavity suggest the presence of leiomyomas, endometrial polyps, or intrauterine adhesions. The proximal two thirds of the fallopian tube should be thin, approximately 1 mm in thickness. The distal third comprises the ampulla and should appear dilated in comparison to the proximal portion of the tube. Free spill of dye from the fimbria into the pelvis is appreciated as the cul-de-sac and other structures such as bowel are outlined by the accumulating dye. Failure to observe dispersion of dye through a fallopian tube or throughout the pelvis suggests the possibility of pelvic adhesions that restrict normal fallopian tube mobility. Examples of abnormal HSGs are shown in Figure 42.6.

BOX 42.1 Procedures Used in the Evaluation of Female Infertility

Transvaginal Ultrasonography: Provides assessment of the cervix, uterus, and ovaries.

3D Transvaginal Ultrasonography: Provides reconstructed coronal views of the uterus, allowing easier diagnosis of uterine abnormalities.

Saline Infusion Sonography: Provides assessment of the myometrium, endometrium, and adnexa; sometimes used in conjunction with magnetic resonance imaging.

Hysterosalpingography: Provides information about the uterus and fallopian tubes’ structure and function.

Magnetic Resonance Imaging: Provides information about uterine abnormalities, including fibroids.

Hysteroscopy: Provides in vivo assessment and treatment of intrauterine abnormalities identified by imaging studies, such as removal of small leiomyomata, polyps, and adhesions.

Laparoscopy: Provides in vivo assessment and treatment of pelvic abnormalities, including endometriosis. Saline infusion of the fallopian tubes can also be performed to test their patency.

Pelvic Adhesions

Pelvic adhesions that affect the fallopian tubes or peritoneum may occur because of pelvic infection (e.g., pelvic inflammatory disease and appendicitis); endometriosis; or abdominal or pelvic surgery, particularly tubal surgery. The sequelae of any of these processes or events can include fallopian tube scarring and obstruction. Pelvic infections are usually associated with sexually transmitted infections that cause acute salpingitis; commonly implicated organisms are Chlamydia trachomatis and Neisseria gonorrhea (see Chapter 29). Endometriosis occurs with higher frequency in infertile women compared with fertile women and can cause scarring and distortion of the fallopian tubes and other pelvic organs (see Chapter 31).

Hysteroscopy and Laparoscopy

The HSG detects approximately 70% of anatomic abnormalities of the genital tract. When there are abnormalities, further diagnostic evaluation and treatment can be performed with hysteroscopy and laparoscopy. Hysteroscopy evaluates the endometrium and the architecture of the uterine cavity. Laparoscopy assesses pelvic structures, including the uterus, ovaries, and fallopian tubes as well as the pelvic peritoneum. During laparoscopy, chromotubationshould be performed: similar to the HSG, a catheter is placed in the uterus, and colored dye is injected into the uterus while tubal patency and function is directly assessed by laparoscopy. Laparoscopy also allows the diagnosis and treatment of any pelvic abnormalities, such as adhesions and endometriosis.


FIGURE 42.5. A hysterosalpingogram demonstrating a patent female reproductive tract with normal anatomy.


FIGURE 42.6. Abnormal hysterosalpingograms. (A) Bilateral hydrosalpinges (dilated fallopian tubes) with distal obstruction at the fimbriated ends; no free spill of dye seen. (B) Bilateral proximal tubal occlusion; uterus overdistended with radiopaque dye.


Because male infertility is common, it is important to also perform a semen analysis when evaluating the female partner.

Semen Analysis

The semen specimen is usually obtained by masturbation after 2 to 3 days of abstinence; frequent ejaculation may lower the sperm concentration. It is important to collect the entire ejaculate, because the first part contains the greatest density of sperm. Analysis of the specimen should be performed within 1 hour of ejaculation (see Table 42.1). The standard semen analysis evaluates the quantity and quality of seminal fluid, sperm concentration, and sperm motility and morphology. Normal semen measurements have been established by the World Health Organization (Table 42.2). A normal semen analysis excludes a male cause for infertility in more than 90% of heterosexual couples. Certain abnormalities identified by the semen analysis are associated with specific etiologies of male infertility (Table 42.3). Sperm function can be further evaluated with specialized diagnostic tests, but these tests are not routinely used.


Besides the semen analysis, the postcoital test originally used to assess the viability of sperm contained in ovulatory cervical mucus is now considered of limited diagnostic and therapeutic usefulness. Furthermore, conventional fertility treatments, such as intrauterine insemination (IUI) and in vitro fertilization (IVF), bypass any abnormalities of the cervix or cervical mucus.

Causes of Male Infertility

If the results of the semen analysis are abnormal, the test should be repeated in 1 to 2 weeks. Persistent abnormalities in the semen necessitate further investigation. The male partner should be evaluated by a urologist or reproductive endocrinologist who specializes in male infertility. Occasionally, male infertility may be the presenting sign of a serious medical condition, such as testicular cancer or a pituitary tumor. Etiologies of male infertility include congenital, acquired, and systemic disorders that can be grouped into the following categories: hypothalamic–pituitary disease that causes gonadal dysfunction (1%–2%), testicular disease (30%–40%), post-testicular defects that cause disorders of sperm transport or ejaculation (10%–20%), and unexplained infertility (40%–50%).


Abnormalities in spermatogenesis are a major cause of male infertility. Unlike oocytes, which undergo development in a cyclic fashion, sperm are being produced constantly by the testes. As sperm develop within the germinal epithelium of the testis, they are released into the epididymis where maturation occurs before ejaculation. Sperm production and development takes approximately 70 days. Therefore, abnormal results of the semen analysis reflect events that occurred more than 2 months before the specimen collection. Alternatively, a minimum of 70 days is required to observe changes in sperm production following initiation of any therapy.



Further evaluation of the infertile male includes endocrine testing. Endocrine evaluation is appropriate for individuals with abnormal sperm concentrations or signs of androgen deficiency. Serum testosterone, FSH, and LH levels will identify primary hypogonadism (low testosterone, or elevated FSH and LH) or secondary hypogonadism (low testosterone, FSH, and LH). A low LH level in the presence of oligospermia (sperm concentration < 5 million/mL) and a normal testosterone level may indicate exogenous steroid use. A serum prolactin level should be assessed in men with low testosterone levels.


Genetic abnormalities may affect sperm production or transportGenetic testing is indicated in men with azoospermia (no sperm) and severe oligospermia. The most common abnormalities identified include gene mutations in the cystic fibrosis transmembrane conductase regulator (CFTR), somatic and sex chromosome abnormalities, and microdeletions of the Y chromosome. Men with mutations in one or both copies of the CFTR gene often exhibit congenital bilateral absence of the vas deferens or other obstructive defects but have no pulmonary symptoms. A karyotype may reveal abnormalities, such as Klinefelter syndrome (47 XXY) or chromosome inversions and translocations. Special testing must be performed to search for Y chromosome microdeletions because they are not detected by routine karyotype analysis; these microdeletions are associated with altered testicular development and spermatogenesis. If a genetic condition is identified, genetic counseling is strongly recommended prior to conception. Advanced paternal age has been shown to be associated with increased rates of spontaneous autosomal-dominant mutations with risk progressively increasing with increasing age; however, currently there are no standardized protocols in place to screen for these. There is also data to suggest increased miscarriage rates and pregnancy loss rates with paternal age over 40 years.

Diagnostic Procedures

Men with azoospermia can be further evaluated by two diagnostic procedures. If an obstructive process is suspected (obstructive azoospermia), then sperm should accumulate just before the obstruction. For example, men with congenital absence of the vas deferens or those who underwent a vasectomy have a swollen epididymis where constant production of sperm results in a small collection. Percutaneous epididymal sperm aspiration and microsurgical epididymal sperm aspiration procedures can retrieve motile, healthy sperm. If no obstruction is present (nonobstructive azoospermia) and a testicular abnormality is suspected, a testicular biopsy may identify a few sperm present in the seminiferous tubules. With either procedure, small numbers of sperm are obtained compared with a normal ejaculated specimen. These retrieved sperm are used to fertilize a single oocyte obtained from the female partner via IVF, a technology called intracytoplasmic sperm injection (ICSI).


For some couples, comprehensive evaluation of both partners does not identify an etiology for their infertility. Specifically, test results identify a normal semen analysis, evidence of ovulation, a normal uterine cavity, and patent fallopian tubes. Approximately 15% of infertile couples are considered to have unexplained infertility. This diagnosis usually signifies the presence of one or more mild abnormalities in the highly orchestrated sequence of events that results in successful conception. These abnormalities may lie below the level of detection of current tests. These couples have a low rate of spontaneous conception, approximately 1% to 3% each month; this rate is influenced by the age of the female partner and the duration of infertility. If laparoscopy is performed on the female partner, subtle abnormalities such as pelvic adhesions and mild endometriosis may be identified and treated. However, it is reasonable to proceed with medical treatment of infertility without performing laparoscopy.


A couple’s infertility may be related to one or several abnormalities in one or both partners. Numerous medical, surgical, and assisted reproductive technology (ART) therapies are available for treating the infertile couple. For couples with unexplained infertility, empiric treatment may overcome the negative effects of one or more mild abnormalities. These couples, as well as the majority of infertile couples, tend to proceed through fertility treatment in a stepwise fashion, starting with conservative and then with more aggressive ovarian stimulation, inseminations, and eventually proceeding to IVF (explained below).

Surgical procedures are indicated in certain circumstances. If a woman presents with pelvic pain and infertility, laparoscopy may be used to identify and treat the cause of her pelvic pain as well as evaluate pelvic anatomy from a fertility standpoint. If an obstructed fallopian tube is identified with HSG, it may be possible to correct the obstruction surgically. For these operations to be successful, the endosalpinx must be healthy. If the tubal damage is significant enough to impair gamete transport, then an ART such as IVF may be necessary. When indicated, abnormalities of the uterine cavity, such as submucosal leiomyomas, endometrial polyps, intrauterine adhesions, and a septum, can be surgically corrected with a hysteroscopic procedure.

Ovarian Stimulation

Ovulation induction is indicated in women with anovulation or oligo-ovulation. However, any identified condition associated with ovulatory disorders should be treated before initiating ovulation induction therapy. Such conditions include thyroid disorders, hyperprolactinemia, PCOS, and high levels of stress (including psychologic stress, intense exercise, and eating disorders).


The most commonly used medication for ovulation induction is clomiphene citrate. Clomiphene is a selective estrogen receptor modulator that competitively inhibits estrogen binding to the estrogen receptors at the hypothalamus and pituitary. The anti-estrogen effects of clomiphene induce gonadotropin release from the pituitary, which stimulates follicle development in the ovaries. Clomiphene is administered daily for 5 days in the follicular phase of the menstrual cycle, starting between cycle days 3 and 5. If ovulation does not occur, the dose is increased for the subsequent month. Women with ovulatory disorders associated with oligomenorrhea may not have regular menses and may require a progesterone-induced menses to start their clomiphene cycle. When used in women who are already ovulatory, clomiphene may stimulate development of several mature follicles.

With clomiphene, ovulation can occur between 5 and 12 days after the last pill, and it can be monitored in several ways. Urine LH kits can be used each day starting on cycle day 10; when ovulation occurs, exposure to sperm through intercourse or IUI should occur. Transvaginal ultrasound performed on cycle day 11 or 12 may identify a developing follicle. When ultrasound is used and a mature follicle is identified (average diameter > 18 mm), ovulation can be triggered by administering a subcutaneous injection of hCG. The exogenous hCG effectively simulates the LH surge and ovulation occurs; this practice enables the proper timing of intercourse or insemination. Some couples prefer to not monitor ovulation and have regular midcycle intercourse. In this situation, a serum progesterone level on cycle day 21 may suggest that ovulation has occurred. The use of clomiphene is associated with a 10% risk of multiple gestations, the majority of which are twin gestations, and a small risk of ovarian hyperstimulation and cyst formation.

Controlled Ovarian Hyperstimulation

Alternatively, exogenous gonadotropins can be given to stimulate follicular development. The use of gonadotropins is commonly referred to as controlled ovarian hyperstimulation (COH). This therapy aims to achieve monofollicular ovulation in anovulatory women (particularly those who do not respond to clomiphene) and ovulation of several mature follicles in other infertile women. Available preparations include purified human menopausal gonadotropins (FSH and LH are extracted from the urine of postmenopausal women) and recombinant human FSH. The dose of medication is tailored to a woman’s age, body weight, infertility diagnosis, and response to previous fertility treatments. These medications are more potent than clomiphene and require frequent monitoring of follicle growth that usually includes transvaginal ultrasonography and serum estradiol measurements. When at least one mature follicle is identified (average follicle diameter of 18 mm and serum estradiol concentration > 200 pg/mL), hCG is administered to trigger ovulation. Timed inseminations are commonly performed within 12 to 36 hours from hCG administration. The risks of this therapy include ovarian hyperstimulation syndrome, which can require intensive therapy; a 25% incidence of multiple gestations; and an increased risk of ectopic pregnancy.

Intrauterine Insemination

Before performing IUI, an ejaculated semen specimen is washed to remove prostaglandins, bacteria, and proteins. The sperm is then suspended in a small amount of medium. To perform IUI, a speculum is inserted into the vagina, the specimen is placed in a thin flexible catheter, and the catheter is advanced through the cervix into the uterine cavity where the specimen is deposited (Fig. 42.7). A total motile sperm count (concentration multiplied by motility) of at least 1 million must be present, insofar as pregnancy is rarely achieved with lower counts. In couples with infertility, and particularly in those with mild male infertility, pregnancy rates are increased with IUI. However, more severe male infertility may necessitate the use of ART to achieve pregnancy. If the male partner is azoospermic and no sperm are identified during testicular biopsy, or if a woman does not have a male partner, IUI with an anonymous donor sperm is an available alternative.


FIGURE 42.7. Intrauterine insemination technique.

Assisted Reproductive Technologies

All fertility procedures that involve manipulation of gametes, zygotes, or embryos to achieve conception comprise the ARTs. In the United States, IVF accounts for more than 99% of all ART procedures. The process of IVF involves ovarian stimulation to produce multiple follicles, retrieval of the oocytes from the ovaries, oocyte fertilization in vitro in the laboratory, embryo incubation in the laboratory, and transfer of embryos into a woman’s uterus through the cervix. The required medications for IVF include gonadotropins to stimulate follicle development, a gonadotropin-releasing hormone analogue (agonist or antagonist) to prevent premature ovulation during follicle development, and hCG to initiate the final maturation of oocytes prior to their retrieval. As with COH, the IVF process necessitates careful monitoring of ovarian response with transvaginal ultrasonography and serum estradiol measurements.

Depending on the etiology of infertility, fertilization can be achieved “naturally,” by placing tens of thousands of sperm together with a single oocyte, or with ICSI (Fig. 42.8). Therefore, IVF provides the tools necessary to bypass the normal mechanisms of gamete transport, fertilization, and embryo transport. After oocyte retrieval, daily progesterone supplementation is necessary to insure the appropriate secretory changes in the endometrium and to support the potential pregnancy; if conception occurs, supplementation is continued until at least 10 weeks of gestation.


FIGURE 42.8. Intracytoplasmic sperm injection. (A) An oocyte is being held by a holding pipette. The injection pipette contains a single sperm. (B) The injection pipette has penetrated the zona pellucida and plasma membrane of the oocyte, and the sperm has been microinjected into the oocyte. (Courtesy of James H. Liu, MD. From Fritz MA, Dodson WC, Meldrum D, Johnson JV. Infertility. In: Precis, An Update in Obstetrics and Gynecology: Reproductive Endocrinology. 3rd ed. Washington, DC: American College of Obstetricians and Gynecologists; 2007:161.)

Indications for IVF include absent or blocked fallopian tubes, tubal sterilization, failed surgery to achieve tubal patency, severe pelvic adhesions, severe endometriosis, poor ovarian response to stimulation, oligo-ovulation, severe male factor infertility, unexplained infertility, and failed treatment with less aggressive therapies. Success rates with IVF depend on the etiology of infertility and the age of the female partner. The chance of conception with one IVF cycle depends on the number and quality of embryos transferred and can be as high as 40% to 50%, with a 30% rate of multiple gestations and at least a 15% rate of spontaneous abortion. In certain situations, embryo quality and number and, thus, chance of conception can be improved using donor gametes.


A team approach is frequently helpful in ensuring that patients receive an adequate workup and appropriate counseling. Counseling of patients who are treated with ART should include information regarding the risk of multiple gestation, ethical issues surrounding multifetal pregnancy reduction, the stress associated with undergoing ART, and adoption. Clinicians should also be familiar with any state laws regarding infertility services and treatment and insurance coverage insofar as the cost of these treatments is very high and most often covered in a limited way or not at all by third-party payers.

Clinical Follow-Up

Because the couple has excellent health care coverage, they agree to undergo a comprehensive workup, which demonstrates a normal Day 21 progesterone, normal hysterosalpingogram, and a normal semen analysis. When given the option of expectant management or clomiphene ovulation induction with intrauterine insemination, they opt for the latter and achieve pregnancy in 3 months. They ultimately deliver a healthy baby girl at term.

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