Chapter 34 Infertility and Assisted Reproductive Technologies
It is estimated that 10% to 15% of couples in the United States are involuntarily infertile. Newer reproductive technologies such as in vitro fertilization (IVF) and embryo transfer are increasing the success of treatment for this condition.
A couple is considered infertile after unsuccessfully attempting to achieve pregnancy for 1 year. Infertility is termed primary when it occurs without any prior pregnancy and secondary when it follows a previous conception. Some conditions, such as azoospermia, endometriosis, and tubal occlusion, are more common in women with primary infertility, but virtually all conditions occur in both settings, making the distinction of little clinical significance.
Physiology of Conception
Conception requires the juxtaposition of the male and female gametes at the optimal stage of maturation, followed by transportation of the conceptus to the uterine cavity at a time when the endometrium is supportive of its continued development and implantation (see Chapter 4). For these events to occur, the male and female reproductive systems must be both anatomically and physiologically intact, and coitus must occur with sufficient frequency and at the proper time (preferably a few hours before) to the release of the oocyte from the follicle. Even when fertilization occurs, it is estimated that more than 70% of resulting embryos are abnormal and fail to develop or become nonviable shortly after implantation.
General Principles of Evaluation
Conception requires adequate function of multiple physiologic systems in both partners. Infertility may result from either one major deficiency (e.g., tubal occlusion) or multiple minor deficiencies. Failure to realize this important dictum may lead the inexperienced practitioner to overlook additional factors that might be more amenable to treatment than the one that has been identified. Infertility in about 40% of infertile couples has multiple causes. Therefore, in general, a complete infertility evaluation should be performed on each couple.
Age substantially decreases the rate of conception because of lower embryo quality, reduced ovulation, and possibly decreased coital frequency. From a large study of donor insemination, the strictly age-related reduction appears to be about one third for women aged 35 to 45 years. It is reasonable to begin the basic evaluation at 6 months in older patients and to consider starting treatment for unexplained infertility earlier in women older than 35 years of age.
Basic Evaluations
Evaluation and therapy may be started earlier when obvious defects are identified, or they may be delayed, for instance, when a correctable factor, such as infrequent intercourse, is identified.
In general, the first 6 to 8 months of evaluation involve relatively simple and noninvasive tests and the performance of a radiologic evaluation of tubal patency (hysterosalpingography, or HSG), which can sometimes have a therapeutic effect. In some studies, use of an oil-based dye about doubled the success rate after HSG. Operative evaluation by laparoscopy is thus reserved for the small proportion of couples who have not conceived after 18 to 24 months or who have specific abnormalities or indications of a probable pelvic factor.
To keep the status of the evaluation in mind, it is helpful to arrange the workup under a series of five categories that can be mentally reviewed at each visit. Table 34-1 shows the approximate incidence and the tests involved in the evaluation of each category. Box 34-1 summarizes the treatment options for infertility. In 5% to 10% of couples, no explanation can be found (idiopathic infertility).
TABLE 34-1 COMMON INFERTILITY FACTORS
Factor | Incidence (%) | Basic Investigations |
---|---|---|
Male, coital | 40 | Semen analysis |
Postcoital test | ||
Ovulatory | 15-20 | Urinary luteinizing hormone self-test∗; serum progesterone∗ |
Cervical | 5 | Postcoital test |
Uterine, tubal | 30 | Hysterosalpingogram |
Laparoscopy | ||
Peritoneal | 40 | Laparoscopy |
∗ Investigations only when menses are regular (every 22 to 35 days); oligomenorrhea generally requires treatment.
Etiologic Factors
MALE COITAL FACTOR
History
The history from the male partner should cover any pregnancies previously sired; any history of genital tract infections, such as prostatitis or mumps orchitis; surgery or trauma to the male genitalia or inguinal region (e.g., hernia repair); and any exposure to lead, cadmium, radiation, or chemotherapeutic agents. Excessive consumption of alcohol or cigarettes or unusual exposure to environmental heat should be elicited. Some medications, such as furantoins and calcium channel blockers, reduce sperm quality or function.
Physical Examination
Physical examination is done on referral to a urologist when semen analysis is abnormal. The normal location of the urethral meatus should be ensured. Testicular size should be estimated by comparison with a set of standard ovoids. The presence of a varicocele should be elicited by asking the patient to perform Valsalva’s maneuver in the standing position.
Investigations
A semen analysis should be performed following a 2- to 4-day period of abstinence. The entire ejaculate should be collected in a clean, nontoxic container. Until relatively recently, the full range of normal variation was not appreciated. Characteristics of a normal semen analysis are shown in Table 34-2.
TABLE 34-2 CHARACTERISTICS OF NORMAL SEMEN ANALYSIS
Characteristics | Quantity |
---|---|
Semen volume | 2-5 mL |
Sperm count | Greater than 20 million/mL |
Sperm motility | Greater than 50%∗ |
Normal forms | Greater than 30% standard morphology or greater than 14% “strict” morphology |
White blood cells | Fewer than 10 per high-power field or 1 × 106/mL |
∗ At least 25% A motility or 40% A plus B motility.
An excessive number of leukocytes (more than 10 per high-power field) may indicate infection, but special stains are required to differentiate polymorphonuclear leukocytes from immature germ cells. Semen quality varies greatly with repeated samples. An accurate appraisal of abnormal semen requires at least three analyses. Periodic reassessment is necessary.
Endocrine evaluation of the male with subnormal semen quality may uncover a specific cause. Hypothyroidism can cause infertility, but there is no place for the empirical use of thyroxine. Low levels of gonadotropins and testosterone may indicate hypothalamic-pituitary failure. An elevated prolactin concentration may indicate the presence of a prolactin-producing pituitary tumor. An elevated level of follicle-stimulating hormone (FSH) generally indicates substantial parenchymal damage to the testes,

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