History and Physical Examination

A thorough reproductive history ( Table 23.1 ) is a critical component of the initial screening evaluation of the infertile male and should cover coital frequency and timing, duration of infertility, prior fertility, developmental history and childhood illnesses (including hypospadias, congenital anomalies, and onset of puberty), current systemic illnesses (especially diabetes mellitus, cystic fibrosis, cancer, and infections), surgical history (with a focus on scrotal, pelvic, retroperitoneal, and inguinal surgeries), sexual history (with a history of sexually transmitted diseases), medications and allergies, and exposure to gonadotoxins (both chemical and environmental toxins, such as heat [ Table 23.2 ]). Additionally, a family history of cryptorchidism, infertility, disordered sexual differentiation, or hypogonadism, and/or a social history with frequent alcohol, tobacco, or recreational drug use may suggest potential etiologies for male infertility.

A general physical examination with an emphasis on the genitalia can also provide important information. Upon initial inspection, note should be taken of obesity, secondary sex characteristics, hair distribution, and gynecomastia. Specific examination of the genitalia should include the phallus, which should be examined for hypospadias, penile curvature, and plaques that may interfere with proper semen deposition within the vagina. Both testes should be examined for size, consistency, and the presence of masses. Eighty-five percent of testicular volume is made up of seminiferous tubules in which spermatogenesis occurs, and testicles smaller than the normal adult size of 20 mL (or 4 cm × 3 cm) may be associated with impaired spermatogenesis.

Careful attention should be paid to the presence, consistency, and nodularity of the epididymides, which may help to identify obstruction and/or infection, while palpation of both vasa deferens can diagnose vasal agenesis, atresia, or injury. More specifically, congenital bilateral absence of the vas deferens (CBAVD) is a clinical diagnosis that can be made on physical examination. Palpation of both spermatic cords in the supine and standing positions both with and without Valsalva enables the diagnosis of varicocele, which is also a clinical diagnosis. Scrotal ultrasound may be used to confirm the diagnosis of varicocele, but those subclinical varicoceles found only on ultrasound (and not on physical exam) are unlikely to be clinically relevant. Finally, a digital rectal exam may help identify dilated seminal vesicles, ejaculatory duct cysts, or utricular cysts that may contribute to obstructive etiologies of male infertility.

Semen Analysis

Along with a thorough history and physical examination, semen analysis has long been the pillar upon which male infertility is evaluated and managed. While an abnormal semen analysis (with the exception of azoospermia) cannot delineate between fertile and sterile, abnormal semen quality is associated with decreased chances of natural conception.

To account for the large degree of biological variability between semen samples, at least two semen analyses should be performed. Patients should be given specific instructions regarding the need for 2 to 5 days of abstinence prior to undergoing semen analysis with the two semen analyses preferably spaced at least 1 week apart. The semen sample can be collected either by masturbation into a specimen cup or by intercourse with the use of a special semen collection condom that does not contain any spermatotoxic agents. In particular, lubricants should be avoided. If a specimen cannot be produced at the laboratory for analysis, it should be kept at room or body temperature during transport and delivered to the laboratory for analysis within 1 hour. Further delays can affect semen and sperm parameters, such as sperm motility, which decreases dramatically after 2 hours.

Parameters examined in routine semen analysis can be broken up into macroscopic and microscopic parameters. Key macroscopic parameters include semen volume, viscosity, color, pH, and coagulation/liquefaction; key microscopic parameters include sperm count/concentration, sperm motility, and sperm morphology. After analyzing the semen analyses of 1859 new fathers from eight countries across three continents, the World Health Organization (WHO) established the normal reference ranges for most of the key parameters of semen analysis ( Table 23.3 ). To establish the reference ranges, the WHO applied a one-sided lower reference limit of the 5th percentile to the semen parameters of the 1859 new fathers. While this methodology does provide lower thresholds for semen parameters in fertile men, it fails to answer the more relevant clinical question of which specific semen parameters and cutoffs are able to delineate between male fertility and subfertility. Efforts to identify specific semen parameters that can distinguish between male fertility and subfertility have instead found that while semen parameters are associated with fecundity, neither sperm concentration, morphology, nor motility could be considered diagnostic of infertility either alone or in combination. Rather than a direct diagnostic test of male infertility, the semen analysis should instead be considered an important contributor to the overall picture of male fertility.

Endocrine Evaluation

While a specific endocrine cause of impaired sperm production is identified in only 2% of men with male factor infertility, an endocrine evaluation is still indicated in men with abnormal semen analyses (especially in those with sperm concentrations less than 10 million/mL), abnormal sexual function, or findings suggestive of endocrinopathy. At minimum, an endocrine evaluation for male infertility should include serum FSH and morning testosterone levels. A low serum testosterone level (<300 ng/dL) should prompt the testing of a second morning serum testosterone level alongside serum LH and prolactin levels. The importance of obtaining a second morning serum testosterone level should not be understated since gonadotropins and testosterone are typically released in a pulsatile manner, and testosterone levels commonly demonstrate a physiologic decline over the course of the day. The characteristic hormone profiles for various etiologies of male infertility are described in Table 23.4 . In particular, while normal FSH levels (≤7.6 IU/L) do not guarantee normal spermatogenesis, elevated FSH levels often indicate an abnormality with spermatogenesis.