Numerous medical conditions/pathologies can afflict male fertility both directly and indirectly. An in-depth history taking should comprehensively assess the patients (a) past fertility, (b) past investigations and treatments for infertility, (c) presence of associated systemic diseases and/or treatments for the same, (d) current and past medication history, (e) past and recent history of surgeries with particular emphasis to surgeries performed in the inguinal/pelvic/testicular region, (f) chemotherapies and/or radiotherapy, (g) the occupational exposure to potential toxins/chemicals, (h) personal lifestyle factors like smoking and alcohol consumption and/or drug abuse, (i) family history of infertility and other congenital defects, and finally (j) sexual history. An in-depth sexual history is very important in the workup of an infertile male since the coital frequency/week is significantly associated with the chance of conception (Macleod and Gold 1953). A chance of conception significantly increases when coital frequency approaches ≥3 time/week as compared to ≤2 times/week. History about the patient’s libido, erection, and ejaculation should also be elucidated as a pathology affecting any of these areas could reduce the number of successful sexual contacts leading to infertility. An outline of the various components in a male infertility clinical history taking is given in Table 4.2. An important point of noteworthy mention is that numerous medical drugs can potentially impair the male’s fertility. Their mechanism of action could be by either affecting spermatogenesis, sperm motility, or sperm fertilizing capacity. Commonly used antibiotics, proton pump inhibitors, antihypertensive medications, calcium channel blockers, statins, beta-blockers, and psychotropic medications can all potentially impair male fertility and/or sexual function leading to difficulties with achieving a conception (Pandiyan 2007). A clinical history should thoroughly elucidate as to whether the patient is or was on any medication for any comorbid illness.

Clinical examination of an infertile male forms an important initial tool in the assessment of male infertility. A general examination is as important as a genital exam. The patient’s height, weight, and BMI (body mass index) along with blood pressure should be documented before the systemic and local examination. The degree of androgenization can be assessed by looking for a male pattern of hair distribution and by questioning the patient on the frequency of shaving (to assess facial hair growth). An assessment of the distribution of body hair should also be made. Sparse hair distribution combined with gynecomastia and eunuchoidal body proportions is suggestive of Klinefelter’s syndrome which can be clinically picked by watchful observation of the patient’s phenotype. An assessment of the patient’s cardiovascular and respiratory system is also to be made routine. Here, the presence of bronchiectasis combined with situs inversus is suggestive of dyskinetic cilia syndrome where the semen picture would also show varying degrees of immotile spermatozoa (Schidlow 1994). Careful inspection of the abdomen and inguinal region may show up scars that may potentially indicate past hernia surgery and/or orchidopexy that the patient might have forgotten to mention during the clinical history taking. Pediatric hernia surgeries carry a potential risk of iatrogenic injury to the vas deferens (Sheynkin et al. 1998). Genital examination should include details of the penile anatomy. The penis is examined and the position of the external urethral meatus is noted. The presence of any hypospadias or epispadias should be documented. Phimosis should also be excluded. Palpation of the penile body may reveal hardened areas due to fibrous plaque formation within the cavernosal tissue that is suggestive of Peyronie’s disease (Gelbard 1995). This is followed by examination of the testes, for its size and consistency. Testicular size is estimated to calculate volume; the testicular size has a moderate degree of correlation to sperm production (Johnson et al. 1980).

The mean average testicular volume of South Indian men is 6 cc (Dupesh and Pandiyan 2015). Estimation of testicular volume can be done using a Prader orchidometer, and these measurements correlate well with ultrasound measurements, although a good correlation >0.8 is obtained only with good clinical experience (Behre and Nashan 1989). A simpler method for estimating testicular size involves the use of a washable steel scale; in this method, the testis is stabilized firmly between the index and thumb, length (l) is measured in centimeters (cm) from the upper pole to the lower pole, and breadth (b) and height (h) along the midaxis are recorded. Volume is estimated by l × b × h/2 (length × breadth × height the product divided by two). This method gives an excellent correlation with ultrasound-based measurements and is routinely used in our clinic (Shah and Pandiyan 2015). From the clinical perspective, a small but firm testis along with elevated FSH is suggestive of hypergonadotropic hypogonadism, while small soft testis with low FSH is suggestive of hypogonadotropic hypogonadism (Pandiyan 1999). For male patients with low FSH and low LH, cranial imaging with serum prolactin measurement should be done to rule out pituitary pathology (De Kretser 1979). The presence of maldescended testis and anorchia should be documented and warrant further investigation. The epididymis should also be palpated. One should also look out for the classical Bayle’s sign, where the epididymis is palpable and augmented and soft suggestive of an obstruction (Schoysman 1982). A normal epididymis is usually firm in consistency. Presence of nodularity is rare finding and could be due to a past history of tuberculous epididymo-orchitis.

The presence or absence of the vas deferens must be carefully examined on both sides. The vas deferens can be palpated with the patient in a supine position, within the vessels of the spermatic cord, as a firm threadlike structure that snaps between the examiner’s fingers. The bilateral absence of vas deferens is suggestive of congenital bilateral absence of vas deferens (CBAVD) and is an extreme phenotypic variant of CFTR gene mutations (Costes et al. 1994). Unnecessary surgical exploration can be avoided in these cases. CBAVD is commonly associated with agenesis of the seminal vesicles, absence of sperm in the ejaculate with absent fructose in semen. In both unilateral and bilateral absence of vas deferens, an abdominal ultrasound for renal anomalies is warranted (McCallum et al. 2001). A varicocele is defined as distension of the venous pampiniform plexus in the spermatic cord, and assessment should be done only in the upright position. Grade 3 varicoceles are usually easily identified; however, to diagnose smaller grades accurately, Doppler studies are necessary.

Semen analysis remains the cornerstone test in the workup of an infertile male. A conventional semen analysis gives information about the male’s testicular germ cell function, secretory function of the male’s accessory sex organs, and also about the patency of the male reproductive tract. It is very important to understand that semen parameters of concentration, motility, and morphology show a high degree of variance with time, place, and region both among individuals and also within the same individual. Semen analysis remains a controversial but necessary test and has numerous pitfalls: (a) it is a subjective test, with results varying between technical personnel and within the same personnel who are assessing the sample (Barroso et al. 1999); (b) semen parameters of both fertile and infertile men show considerable degree of overlap between parameters, and very low sperm counts have led to documented spontaneous pregnancies (Thomson et al. 1993); (c) none of current semen parameters, namely, sperm concentration, motility, and morphology, have good predictive power in estimating a couple’s fertility potential (Ford 2010); and (d) it is important to understand that the relation between sperm concentration, sperm motility, and fertility is not a simple one. The role of the female partner and her fertility play a key role in deciding whether a conception would occur. It is now well known that a reproductive pathology in the female can reduce the fertility potential of a male presenting with a so-called “normal” spermiogram.

The clinical utility of semen analysis however cannot be overemphasized in extreme presentations like azoospermia, total asthenozoospermia, necrozoospermia, and globozoospermia. We still do not understand the molecular basis to male infertility; pathological changes resulting in subfertility rarely reflect onto a conventional semen analysis. The World Health Organization (WHO) has published over five editions so far reviewing diagnostic criteria and protocols for semen analysis in different times. It recently published the fifth edition of the Laboratory Manual for the Examination and Processing of Human Semen in 2010 (WHO manual, 5th edition. 2010). On an interesting note, while the first four editions were “consensus” based on expert opinions, the latest edition was published after a multicenter study. Numerous men who were previously diagnosed with oligozoospermia, asthenozoospermia, and teratozoospermia have now been included in the normal range as per the new manual’s diagnostic cutoffs. Thus, many men might have been subjected to unwanted and unwarranted surgeries/therapies for infertility based on these criteria (Pandiyan 2012). Semen analysis thus remains a number game.

The aforementioned facts do not mean that a semen analysis is a redundant test, but it is important to take a deep look at the patient from a clinical perspective and listen to his story and only then can the right diagnosis be made from a clinical standpoint. Common instructions given to the male patient before a semen analysis are as follows: a] Patients are advised to abstain from sexual intercourse for a period ranging from 2 to 7 days before a semen analysis as per the WHO criteria. However, a retrospective analysis of our data from over 2130 patients clearly showed that all the three semen parameters, namely, concentration, motility, and morphology do not vary significantly as a result of ejaculatory abstinence. Any variation noted was still within the normal range (Shah and Pandiyan ISAR 2015).