History and Physical

The comprehensive history should include all past and current medical problems related to reproductive function. Men who have previously fathered children or a pregnancy with the same or different partner are said to have secondary infertility. Men who have never fathered a child are considered to have primary infertility. The length of time the couple has been attempting a pregnancy and the frequency of intercourse should be ascertained. The ideal frequency of intercourse is every day to every other day. Use of artificial lubricants, even water soluble or natural sources, should be discouraged as they may impair sperm motility

Men should be asked about exposures to pesticides, chemicals, organic solvents, or heat (tanning booths, short order cooks, and foundry workers). Men who smoke tobacco or marijuana are at risk for infertility as these drugs decrease sperm concentration (oligospermia) and effect motility. Illicit drug and copious alcohol use can disrupt the hypothalamic-pituitary axis and adversely affect testicular function. Anabolic steroids can result in testicular atrophy and abnormal or absent spermio-genesis. Many medications can affect sperm concentrations and function including: prescription and over-the-counter medications, vitamin and protein supplements and herbal remedies. A list of pharmacological and environmental causes of infertility is given in Table Pharmacological and environmental causes of infertility.

Table Pharmacological and environmental causes of infertility

Diethylstilbesterol (DES) Radiation
Testosterone Chemotherapy
Ketoconazole Heat
Nitrofurantoin Pesticides
Calcium channel blockers Lead
Cigarettes Alcohol
Cocaine Marijuana
Sulfa drugs Solvents

The surgical history should include questions regarding a history of cryptorchid-ism (undescended testis) and patient s age at the time of repair. Cryptorchidism can cause oligospermia or even azoospermia, if bilateral. Correction of hypospadias, chordee or hernia should also be ascertained as well as any surgery on the bladder neck, urethra, rectum or pelvis. A history of urethral strictures and/or STDs may result in urethral and ductal obstruction causing reduced sperm counts. Men who have been treated for testicular cancer or Hodgkin’s lymphoma may have reduced sperm counts related to their disease as well as treatments such as chemotherapy and radiation. Surgery for testicular cancer may include retroperitoneal lymph node dissections and this can injure the sympathetic nerves involved in ejaculation.

The review of systems should include questions regarding diabetes (partial or retrograde ejaculation), cystic fibrosis (CF) — pertinent positives include: history of pneumonia, recurrent sinusitis or bronchitis — (congenital absence of the vas defer-ens), multiple sclerosis (impaired ejaculation), and spinal cord injuries (erectile dysfunction). There are several rare conditions which impact fertility that can be uncovered during the review of systems. Recurrent respiratory infections can be associated with nonmotile sperm and may suggest primary ciliary dyskinesia (Kartagener’s syndrome). Congenital anosmia (inability to smell) may be associated with Kallmann’s syndrome — hypogonadotropic hypogonadism.

Emphasis is placed on a thorough genitourinary examination. The male patient should be examined in a warm room. Normal virilization should be noted. The presence of gynecomastia should prompt questions regarding marijuana use or an evaluation for a prolactin producing pituitary tumor. Normal testicular size is 20 cm3 and the testicle should be firm but not hard,not unlike the feel of a hard boiled egg. An orchidometer can be used to assess size or it can be approximated by measuring. A normal testicle is at least 2.5 x 3 x 4 cm. The epididymis and vas deferens should be palpated and any thickening should suggest the possibility of obstructive causes of infertility.

The spermatic cords should be examined in the upright position to evaluate the man for a varicocele-dilation of the spermatic pampiniform plexus. It is thought that varicoceles may impact sperm quality by increasing testicular temperature or perhaps by causing reflux of adrenal metabolites via incompetent veins. However, 15% of the general male population has a varicocele, and up to 45% of men with infertility present with a varicocele. Grading of varicoceles is based on physical exam alone though occasionally ultrasound may be used as a confirmatory study or if body habitus makes examination difficult. Absence of the vas deferens is found in 1-2% of all infertile men and 10% of men with low sperm counts. It can be unilateral or bilateral. It is often associated with other genitourinary abnormalities such as absence of the ipsilateral kidney or incomplete epididymis formation. Importantly, 80% of men with bilateral congenital absence of the vas (CBAVD) have at least one cystic fibrosis mutation. Men with CBAVD and their partners should undergo genetic testing and counseling regarding possible CF gene carrier status.

Laboratory Studies

All men undergoing infertility evaluation and counseling should have a semen analysis. Two samples should be given one week apart with two or three days of abstinence prior to the sample for optimal analysis. Masturbation without use of lubricants is preferred. Normal semen parameters, based on World Health Organization criteria, are given in Table Classification of semen abnormalities. More than one abnormal parameter is common. If ejaculate volume is low, the man should give a urine sample within minutes of ejaculation to look for sperm in the urine after ejaculate collection errors are ruled out (spilled specimen, incomplete collection). If sperm are found in the urine and his history is not indicative of obstruction, the man is considered to have retrograde ejaculation. Low sperm volume with no sperm in the post ejaculatory urine sample may be secondary to ejaculatory duct obstruction or ejaculatory duct absence. Both can be further evaluated by transrectal ultrasound.

Table Classification of semen abnormalities*

Oligospermia <20 million sperm/ml
Azoospermia Absence of sperm in the ejaculate
Teratospermia <30 % normal morphology
Asthenospermia <50% sperm motile
Leukocyto(Pyo)spermia >1 million/ml WBCs

*Based on WHO criteria.

A reduced sperm count, or oligospermia, is defined as an ejaculate with <20 million sperm per milliliter. Azoospermia is defined as the absence of sperm in the ejaculate. Men with either should undergo hormonal analysis to determine if the source of low sperm count is pretesticular — the hypothalamic-pituitary axis, testicular — primary testicular failure, or post testicular — obstruction or absence of the vasa. Treatment ultimately depends on the source: medical intervention for hypothalamic abnormalities, sperm cryopreservation for severe oligospermia with primary testicular failure versus surgical correction for post testicular obstruction.

Sperm should have tail movement regardless of motility Asthenospermia or poor motility is most often seen in the setting of other semen abnormalities. Movement of the tails without progression may be secondary to presence of sperm antibodies or agglutination (clumping) of the sperm. If antibodies are present, couples have successfully had pregnancies after in vitro fertilization and intracytoplasmic sperm injection (intracytoplasmic sperm injection).

Teratozospermia is the presence of a disproportionate concentration of morphologically abnormal sperm. According to the World Health Organization (WHO), 30% of the sperm should be classified as structurally normal. Others who advocate for more stringent histologic grading use strict criteria to examine the sperm head. Using the so-called strict criteria, only four percent of sperm are typically defined as Bl normal. Morphologically abnormal sperm are less likely to fertilize an egg.

Pyospermia ― white blood cells in the ejaculate is often treated with antibiotics though often without a documented source of infection. Patients are instructed to ejaculate frequently and a repeat semen analysis is completed after antibiotic treatment. There are various tests to analyze sperm function (such as electron microscopy for 0% motility) if the semen analysis appears normal. As a practical matter, these tests are not frequently performed as couples usually proceed to in vitro fertilization (IVF) and intracytoplasmic sperm injection (intracytoplasmic sperm injection) if a functional problem is suspected.

Depending on the history, physical exam and semen analysis, a patient may require hormone analysis. Useful serum tests include follicle stimulating hormone, luteinizing hormone, testosterone, and prolactin. Endocrine evaluation will often assist in distinguishing between pretesticular and testicular causes of infertility though endocrine causes of male infertility are fairly rare.

In clinical practice, the initial consult is sometimes performed without the required two semen analyses. Laboratory tests and sperm testing can be performed at a future date with follow up scheduled to review all results and formulate a possible treatment plan.

Radiologic Studies

If an abnormality is noted on the testicular exam, an ultrasound should be performed immediately to look for testicular masses consistent with cancer. Men with testicular cancer can have reduced sperm counts and will often present seeking consultation for infertility. Men with a low ejaculate volume and a negative post-ejaculatory urinalysis, normal testosterone and palpable vasa should undergo transrectal ultrasound. Findings of dilated seminal vesicles (>1.5 cm in AP diameter) are suggestive of partial or complete obstruction. Patients with CBAVD may also have dilation of the seminal vesicles, but diagnosis of vasal agenesis is made by clinical examination alone and does not require ultrasound. Scrotal ultrasound is not indicated for nonpalpable varicocele as these are of little clinical significance.

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