INFERTILITY AND RELATED ISSUES

INFERTILITY AND RELATED ISSUES Infertility is defined as the failure to conceive after one year of attempting pregnancy. Primary...

INFERTILITY AND RELATED ISSUES INFERTILITY Infertility is defined as the failure to conceive after one year of at- tempting pregnancy. Primary infertility denotes those patients who have never conceived. Secondary infertility applies to patients who have conceived previously. Approximately 15% of couples experi- ence infertility, which may result from subfertility or sterility (the innate inability to conceive) in either partner or both. The female is responsible in 40%–50% of cases. The male is responsible in 30% and is contributory in another 20%–30% of couples. However, it is crucial to recall that multiple etiologies are found in 40% of infer- tile couples. The incidence of infertility has increased (perhaps 100% over the past 20 years) in developed countries because of increasing sexually transmitted disease (especially gonorrhea and Chlamy- dia, causing subsequent tubal damage), an increased number of sexual partners (increasing the potential for acquiring STDs), intentionally delaying pregnancy, the contraceptive(s) used, and smoking (Ͼ1 pack/day decreases the chance of pregnancy by Ͼ20%). Infertility accounts for 10%–20% of all gynecologic office visits. Fertility rates are established using fecundibility (the chance of pregnancy per month of exposure). Only 25% of young healthy cou- ples having frequent intercourse will conceive per month (60% by 6 months, 75% by 9 months, and 90% by 18 months). Fecundibil- ity declines with age, and the effect is more pronounced in women than in men. By 36–37 years of age, the chance of pregnancy is less than half that at 25–27 years of age. 29 INFERTILITY AND RELATED ISSUES (SPECIAL FERTILITY PROCEDURES, HYPERANDROGENISM) CHAPTER 769 Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use. BENSON & PERNOLL’S 770 HANDBOOK OF OBSTETRICS AND GYNECOLOGY Careful evaluation should detect probable cause(s) for infertil- ity in 85%–90%. Happily, even without therapy, 15%–20% of in- fertile couples may be expected to achieve pregnancy over time. Therapy, excluding in vitro fertilization, will result in pregnancy in 50%–60%. ETIOLOGY The causes of infertility may be classified as male-coital factors (40%), cervical (5%–10%), uterine-tubal (30%), ovulatory factors (15%–20%), and peritoneal or pelvic factors (40%). A few genetic causes (e.g., primary amenorrhea) are recognized. MALE-COITAL FACTORS Male factors include abnormal spermatogenesis, abnormal motil- ity, anatomic disorders, endocrine disorders, and sexual dysfunc- tion. The anatomic abnormalities possibly responsible are congen- ital absence of the vas deferens, obstruction of the vas deferens, and congenital abnormalities of the ejaculatory system. Abnormal spermatogenesis may occur as the result of mumps orchitis, chromosomal abnormalities, cryptorchidism, chemical or radiation exposure, or varicocele. Abnormal motility is seen with absent cilia (Kartagener’s syndrome), varicocele, and antibody for- mation. The male factor endocrine disorders include thyroid disorders, adrenal hyperplasia, exogenous androgens, hypothalamic dysfunc- tion (Kallmann’s syndrome), pituitary failure (tumor, radiation, sur- gery), and hyperprolactinemia (tumor, drug-induced). An elevated FSH commonly indicates parenchymal testicular damage, since in- hibin, produced by the Sertoli cells, is the primary feedback con- trol of FSH secretion. CERVICAL FACTORS Cervical factors of female infertility may be congenital (DES ex- posure, mullerian duct abnormality) or acquired (infection, surgi- cal treatment). UTERINE-TUBAL FACTORS Uterine-tubal factors are most commonly structural abnormalities (e.g., DES exposure, myoma, failure of normal fusion of the re- productive tract, infections, previous ectopic pregnancy). OVULATORY FACTORS Ovulatory factors involve CNS function, metabolic disease, or pe- ripheral defects. CNS defects include chronic hyperandrogenemic anovulation, hyperprolactinemia (empty sella, tumor, or drug- induced), hypothalamic insufficiency (including Kallmann’s syn- drome), and pituitary insufficiency (trauma, tumor, or congenital). Metabolic diseases causing ovulatory factor defects are thyroid dis- ease, liver disease, renal disease, obesity, and androgen excess (ad- renal or neoplastic). Peripheral defects may be gonadal dysgenesis, premature ovarian failure, ovarian tumor, or ovarian resistance. PERITONEAL OR PELVIC FACTORS The two most common pelvic or peritoneal factors are endometrio- sis and sequelae or infection (e.g., appendicitis, pelvic inflamma- tory disease). Laparoscopy in women with unexplained infertility will reveal previously unsuspected pathology in at least 30% of pa- tients. Endometriosis exerts a greater pejorative effect on fertility than can be explained on the basis of physical alterations (p. 755). DIAGNOSIS Infertility evaluations should follow a progression of testing and procedures that takes into account probability (including individu- alization for the couple), invasiveness, risks, and expense. The ba- sic evaluation usually requires 6–8 weeks to complete. Even if the history suggests a probable cause of infertility, completion of the evaluation of all major factors should be accomplished to avoid overlooking a secondary or contributory factor. The initial assessment should include medical history for female infertility factors, including pubertal development, present menstrual cycle characteristics, contraceptive history, prior pregnancy and out- come, previous surgery (especially pelvic), prior infection, abnormal Pap smears and therapy, drugs and therapy, diet, weight stability, ex- ercise, and history of in utero DES exposure (now rare). EVALUATION OF MALE FACTORS The initial test for male infertility is the semen analysis because a normal semen analysis usually excludes a significant male factor (Table 29-1). The specimen should be obtained after 2–3 days abstinence and evaluated in the laboratory within 30–60 min of ejaculation. CHAPTER 29 INFERTILITY AND RELATED ISSUES 771 BENSON & PERNOLL’S 772 HANDBOOK OF OBSTETRICS AND GYNECOLOGY The frequency of male factors (as well as risk and cost effec- tiveness) mandates male diagnosis in the initial phase of infertility investigation. The medical history for male factor infertility should include frequency of intercourse, difficulty with erection or ejacu- lation, prior paternity, past history of genital tract infections (e.g., mumps orchitis or chronic prostatitis), congenital anomalies, sur- gery or trauma (e.g., hernia repair, direct testicular trauma), expo- sure to toxins (medications, lead, cadmium, or radiation), diet, ex- ercise, alcohol consumption, smoking Ͼ1 pack/d), illicit drug use, in utero exposure to DES, and unusual exposure to high environ- mental heat. The physical examination should consider habitus and hair dis- tribution (e.g., testosterone effect). The urethral meatus should be in the normal location. Testicular size may be compared to standard ovoids. Eliciting a Valsalva maneuver in the standing position should aid in the detection of a varicocele. Transrectal prostatic mas- sage generally will produce sufficient secretions for microscopic examination. Excessive leukocytes in this or the semen analysis in- dicate infection. If the semen analysis is abnormal or borderline, the man’s med- ical history over the past 2–3 months should be reviewed, recalling that spermogenesis requires 74 d. A repeat semen analysis should be performed 1–2 weeks later for comparison. Consider referral to a urologist specializing in infertility if a significant abnormality per- sists. Because sperm must reach the ovum before fertilization can oc- cur, infertility in the presence of normal semen values suggests that TABLE 29-1 NORMAL SEMEN ANALYSIS VALUES Parameter Normal Value Volume 2–5 ml Viscosity Full liquefication Ͻ60 min Count 40–250 M/ml (previously, down to 20 M/ml) Motility 1st h Ն60%; 2–3 h Ն50% Normal morphology Ͼ60% Dead sperm Ͻ35% White blood cells Ͻ10/hpf there may be an abnormally high attrition of sperm. Cervical mu- cus studies may clarify this problem. In vitro fertilization is the ultimate test for male factor infertil- ity. A sperm penetration test may be useful. This uses a hamster egg to demonstrate the ability of the sperm to penetrate a zona-free oocyte using a known fertile donor as control. Abnormality is in- dicated by Ͻ10% penetration. Negative penetration of healthy ap- pearing, mature ova by partner sperm with simultaneous positive penetration by donor sperm may provide the diagnosis. EVALUATION OF CERVICAL FACTORS Cervical factors are evaluated by physical examination and an ap- propriately timed postcoital mucus test. History of in utero DES ex- posure, abnormal Pap smears, cryotherapy, postcoital bleeding, or conization is suggestive of persistent cervical problems. Normal cervical mucus in the preovulatory phase is thin, wa- tery and acellular and dries in a ferning pattern. Mucus in this state acts as a facilitative reservoir for sperm. Cervical mucus is best evaluated on days 12–14 of a 28 d cycle. The amount and clarity of the mucus are recorded, and the pH should be Ն6.5. Spinnbarkeit (the stretchability of a strand of mucus) is ascertained by drawing out the mucus vertically (it should stretch to Ն6 cm). The Sims-Huhner test evaluates the initial interaction of the sperm with cervical mucus. The test should be conducted in the periovular interval. Timing of the test may be enhanced using vagi- nal ultrasound to determine the presence or absence of a dominant follicle. Mucus is collected 2–4 h after intercourse. The mucus is placed on a clean glass slide under a coverslip and observed. There should be Ͼ20 sperm/hpf, and large numbers of active sperm will be seen in the thin, acellular mucus. Lower numbers (Ͻ20/hpf) of motile sperm in favorable mucus may be present in normally fertile couples due to the stress of coitus at a prescribed time. The absence of sperm suggests aspermia or improper coital technique or specimen collection. Finding an adequate number of immobile sperm in favorable mucus requires an investigation for autoantibodies in the male or serum antibodies in the female. If a sufficient number of sperm are present but poorly motile, further assessment of the mucus and timing of the test is indicated. If the mucus tests are repeatedly abnormal despite apparently favorable mucus, a crosscheck using donor mucus and donor sperm is rea- sonable. Antibody studies may determine the antigenic site (sperm head, midpiece, or tail) and are more likely to be positive in men who have a history of trauma, infection, or previous surgery. CHAPTER 29 INFERTILITY AND RELATED ISSUES 773 BENSON & PERNOLL’S 774 HANDBOOK OF OBSTETRICS AND GYNECOLOGY DIAGNOSIS OF UTERINE-TUBAL FACTORS Both history and careful pelvic examination are essential initial steps in detection of uterine-tubal factors. Key details of the history include menstrual problems, pelvic infections (pelvic pain), STD, appendicitis, and abdominal trauma or surgery. Suggestive findings on pelvic examination include uterine irregularities, pelvic masses, and uterine deviation or fixation. It is uncommon for submucous myomata, endometrial polyps, or bicornuate uterus to cause infertility, although each of these is associated with an enhanced rate of abortion. Tubal fimbrial occlu- sion is the most common of the three usual locations, followed by midsegment and isthmus-cornual occlusion. Midsegment occlusion is nearly always due to tubal sterilization but may be secondary to tuberculosis. The major causes of isthmic-cornual occlusions are infection, maldevelopment, endometriosis, adenomyosis, or salpin- gitis isthmica nodosum. Hysterosalpingography (HSG) (Fig. 29-1), hysteroscopy, la- paroscopy, or a combination of these is required to determine pa- tency of the tubes. HSG is performed as an outpatient procedure us- ing a radiopaque dye (first water-soluble and, after patency is assured, an oil-based contrast medium) instilled into the uterine cav- ity via a small transcervical catheter. Radiographs should document FIGURE 29-1. Hysterosalpingography. the fluoroscopically observed findings. Uterine contour, tubal pa- tency, and ability of the dye to freely transit the tubes to enter the pelvis are evaluated. The oil-based dye provides a better image but has a greater risk of retention and granuloma formation. The wa- ter-based dye causes less cramping and allows better definition of the rugae. Abnormal findings include intrauterine synechiae (Ash- erman’s syndrome), congenital malformations of the uterus, polyps, submucous leiomyomas, proximal or distal tubal occlusion, and salpingitis isthmica nodosa. The major risk of HSG is infection. Thus, HSG should not be performed during even suspected active inflammation or when there is an adnexal mass. Broad-spectrum antibiotic therapy (e.g., doxycyline) may be prudent if recent STD screening has not been performed. The test is also contraindicated if there is allergy to the dye. Laparoscopy may demonstrate tubal abnormalities (e.g., agglu- tinated fimbria, endometriosis) that probably would not be seen on HSG. Hysteroscopy performed concomitantly with laparoscopy may give further information regarding uterine contour or polyps. En- dometriosis (Chapter 28) is an important cause of infertility and is suggested by a history of worsening dysmenorrhea or dyspareunia but usually cannot be diagnosed short of visual inspection. Some endometriosis may be eliminated during laparoscopic diagnosis if informed consent has been obtained and preparations have been made for laser surgery or operative pelviscopy. Laparoscopy may be indicated relatively early in the investi- gation of infertility if pelvic factors are suggestive or in older patients, whereas it may be the last test performed in a young woman when all other studies are negative. It may be considered together with ovarian stimulation and ovum collection in long- standing infertility using in vitro fertilization or by placing sperm and ovum directly into the tube to allow a trial of normal transport to the uterus. EVALUATION OF OVULATORY FACTORS Ovulating women usually have regular cycles (22–35 d). Substan- tiating symptoms may be useful, especially premenstrual (breast changes, bloating, and mood change). The physical examination and proper timing, coupled with cervical mucus evaluation, may determine ovulation. Some affirmation of ovulation may be ob- tained by basal body temperatures (BBTs, see Fig. 26-1) and en- dometrial biopsy. Currently, measurements of the midluteal serum progesterone (attempting to detect the surge), as well as serial CHAPTER 29 INFERTILITY AND RELATED ISSUES 775 FIGURE 29-2. Dating the endometrium. Approximate relationship of useful morphologic factors. (Modified after J.P.A. Latour. From Noyes, Hertig, and Rock, Dating the endometrial biopsy. Fertil Steril 1:3, 1950.) 776 777 FIGURE 29-2. (Continued) [...]... for infertility (e.g., Denmark), IVF has been utilized up to 6500 cycles per 1 million women in the reproductive age HYPERANDROGENISM The primary androgen produced by the ovaries is androstenedione, and the primary androgen from adrenal glands is dehydroepiandrostene sulfate (DHEAS) Androgen production in the ovary is stimulated by pituitary LH and in the adrenal is stimulated by pituitary ACTH Most androgens... than testosterone The sebaceous glands are very sensitive to androgens, and oily skin and acne are early signs of hyperandrogenism The hair follicle is moderately responsive CHAPTER 29 INFERTILITY AND RELATED ISSUES 787 to androgens, and hirsutism is a further response to increasing androgenicity Finally, with marked androgenicity, signs of masculinization appear in the woman (virilization) These include... nonpigmented, and not responsive to hormones) Whereas the amount of terminal hair is hereditarily determined, endocrine factors influencing the sebaceous gland and hair follicle include: androgen secretion (amount and duration), concentration of sex hormone-binding globulin, peripheral conversion of weaker to stronger androgens, and sensitivity to androgens Hirsutism is but one manifestation of hyperandrogenism... a-reductase) Adrenal causes of excessive androgen production include: dysfunctional excesses, congenital adrenal hyperplasia, Cushing syndrome and androgen secreting neoplasms Ovarian causes of excess androgen production include: PCO, sertoli-Leydig cell tumors, granulose cell tumors, and gynandroblastomas Only free androgen is biologically active and almost all androgens in the circulation are bound... female body contour, male type pubic hair pattern, and cliteromegaly The total testosterone produced by a mature female is 0.35 mg/day Ovarian secretion accounts for 0.1 mg, 0.2 mg comes from peripheral conversion of androstenedione, and 0.05 mg is from peripheral conversion of DHEAS The ovary and adrenal gland secrete about equal amounts of androstenedione and DHEA Thus, about two thirds of a woman’s daily... (GnRH) pulse frequency and tonically elevated levels of LH (generally Ͼ20 mIU/mL) Estradiol not bound to sex hormone-binding globulin (SHBG) is increased (total estradiol is not) because of a decreased SHBG (due to increased androgen levels and obesity), which stimulates GnRH pulsatility This results in androgen excess (from both ovaries and adrenals) and anovulation However, the hyperandrogenism is mild... follicle-stimulating hormone; E2, estradiol; T, testosterone; A2, androstenediol; SHBG, sex hormone-binding globulin CHAPTER 29 INFERTILITY AND RELATED ISSUES 789 Ovaries of PCO patients do not produce more estradiol from androstenedione (in fact, because of less FSH, the ovaries have lower aromatase levels) The increased circulating androstenedione is peripherally converted to estrone, resulting in... ovarian color and a honeycombed appearance The cysts are lined by luteinized thecal lutein cells from the ovarian connective tissue CHAPTER 29 INFERTILITY AND RELATED ISSUES 791 A luteoma of pregnancy is a unilateral or occasionally bilateral (30%) benign solid ovarian tumor (50%) caused by a hyperplastic reaction of ovarian theca lutein cells They are discrete and brown to reddish brown and may have... hyperandrogenic, some produce high levels of testosterone and androstenedione Thus, the mother is virilized in 30%, and a female fetus is at risk of virilization HYPERANDROGENISM OF ADRENAL ORIGIN Excess androgens from the adrenal glands may be the result of neoplasia, inborn errors of biosynthesis of adrenal hormones, or inappropriate stimulation of the adrenal gland Adrenal neoplasias typically produce DHEA... TREATMENT MALE AND COITAL FACTORS Smoking, alcohol, and drug use should be stopped Eliminate sources of increased scrotal temperature (e.g., saunas, hot tubs, or jockey shorts underwear) with their adverse effect on spermatogenesis Lubricants and douching should be eliminated The woman should lie on her back for at least 15 min following coitus (to CHAPTER 29 INFERTILITY AND RELATED ISSUES 779 facilitate . INFERTILITY AND RELATED ISSUES INFERTILITY Infertility is defined as the failure to conceive after one year of at- tempting pregnancy. Primary infertility. the laboratory. CHAPTER 29 INFERTILITY AND RELATED ISSUES 783 BENSON & PERNOLL’S 784 HANDBOOK OF OBSTETRICS AND GYNECOLOGY Ova Identification and Classification The