472 CHAPTER 11 Infertility
Basic investigations
Semen analysis
Obtain 2 or 3 specimens over several weeks, collected after 2–7 days of sexual abstinence. Deliver specimens to the laboratory within 1 hour. Ejaculate volume, liquefaction time, and pH are noted (Table 11.1).
Microscopy techniques measure sperm concentration, total numbers, morphology, and motility (Table 11.2).
The mixed agglutination reaction (MAR test) is used to detect antiperm antibodies. The presence of leukocytes or round cells in the ejaculate (>1 x 106/mL of semen) suggests infection, and cultures should be requested.
Hormone measurement
Obtain serum FSH, LH, and testosterone (Table 11.3). Elevated serum FSH levels (2 x normal) suggest irreversible testicular failure. In cases of isolated low testosterone level, it is recommended that morning and free testosterone levels be tested.
Elevated prolactin is associated with sexual dysfunction and low serum testosterone levels, and usually indicates the presence of a pituitary adenoma.
Special investigations
•Chromosome analysis is indicated for clinical suspicion of an abnormality (azoospermia or oligospermia, small atrophic testes with iFSH).
•Fructose is produced in the seminal vescle and is a major source of energy for sperm metabolism. If semen fructose is low, an ejaculatory duct obstruction or seminal vesical abnormality should be suspected.
•Testicular biopsy is performed for azoospermic patients with normal FSH levels, to differentiate between idiopathic (e.g., maturation arrest, Sertoli cell only syndrome) and obstructive causes. It may also be used for sperm retrieval.
Sperm function tests
Postcoital test
Cervical mucus is taken just before ovulation and within 8 hours of intercourse, and microscopy is performed. Normal results shows >10 sperm per high-powered field, the majority demonstrating progressive motility. Abnormal results indicate inappropriate timing of the test; cervical mucus antisperm antibodies; abnormal semen; or inappropriately performed coitus.
Sperm penetration test
A sample of semen is placed directly onto preovulatory cervical mucus on a slide and the penetrative ability of spermatozoa is observed.
Sperm-cervical mucus test
A specimen of semen (control) and one mixed with cervical mucus are placed separately on a slide and observed for 30 minutes. More than 25% exhibiting jerking movements in the mixed sample (but not the control) is a positive test for antisperm antibodies.
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LAB INVESTIGATION OF MALE INFERTILITY |
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Table 11.1 Semen analysis: normal parameters* |
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Semen analysis |
Normal values |
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Semen volume |
>2.0 mL |
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pH |
7.2–7.8 |
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Total sperm count |
>40 x106/ejaculate |
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Sperm concentration |
>20 x106/mL |
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Sperm motility |
>50% with progressive motility (grades >2); |
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or >25% grade 4 |
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Sperm morphology |
>15% normal forms |
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Viability |
>75% viable sperm |
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Time to liquefy |
5–25 minutes |
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White blood cells |
<1 x106 WBC/mL |
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MAR test (for antisperm Ab) |
Negative (<10% with adherent particles) |
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Zinc |
>2.4 mol/ejaculate |
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Semen fructose |
120–145 mg/dL |
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*Adapted from World Health Organization (WHO) reference values for semen analysis.
Table 11.2 Grading of sperm motility
Grade |
Type of sperm motility |
0No motility
1Sluggish; no progressive movement
2Slow, meandering forward progression
3Moving in a straight line with moderate speed
4Moving in a straight line at high speed
Table 11.3 Clinical diagnosis on hormone assay
FSH* |
LH** |
Testosterone |
Diagnosis |
i |
Normal |
Normal |
Seminiferous tubule damage |
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(defective spermatogenesis) |
Normal |
Normal |
Normal |
Normal; or bilateral genital tract |
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obstruction |
i |
i |
Normal/d |
Testicular failure |
d |
d |
d |
Hypogonadotrophism |
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* Follicle stimulation hormone. ** Luteinizing hormone.
474 CHAPTER 11 Infertility
Imaging
Scrotal ultrasound
This is used to confirm a varicocele and assess testicular abnormalities.
Transrectal ultrasound
TRUS is indicated for low ejaculate volumes, to investigate seminal vesicle obstruction (>1.5 cm width) or absence and ejaculatory duct obstruction (>2 .3 mm).
Vasography
Vas deferens is punctured at the level of the scrotum and injected with contrast toward the prostate, never toward the epdidymis. Vasography is performed at the time of planned reconstruction.
A normal test shows the passage of contrast along the vas deferens, seminal vesicles, ejaculatory duct, and into the bladder, which rules out obstruction—indigo carmine is commonly used to confirm patency.
Formal radiographic vasography is only indicated to localize obstructions proximal to the inguinal ring.
Venography
This is used to diagnose and treat varicoceles (embolization).
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476 CHAPTER 11 Infertility
Oligospermia
Oligospermia is defined as a sperm concentration of <20 million/mL of ejaculate.
Etiology
It is often idiopathic. It is identified in ~60% of patients presenting with testicular cancer or lymphoma.
Associated disorders
It is often associated with abnormalities of morphology and motility (oligoasthenoteratospermia). Common causes include varicoceles, cryptorchidism, idiopathic, drug and toxin exposure, and febrile illness.
Investigations
Semen analysis: Severely low sperm counts (<5–10 million/mL) require hormone investigation, including FSH and testosterone. Severe oligospermia is associated with seminiferous tubular failure, small soft testes, and iFSH.
Treatment
Correct the underlying cause. Idiopathic cases may respond to empirical medical therapy. Clomiphene and tamoxifen are mild antiestrogens that work best for men with low to normal testosterone and FSH levels.
Consider assisted reproductive techniques, such as intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI).
Azoospermia
This is defined as a complete absence of sperm in the ejaculate fluid.
Etiology
•Obstructive: absent or obstructed vas deferens; epididymal or ejaculatory duct obstruction. The cystic fibrosis gene is located on chromosome 7 and the condition is associated with congenital absence of the vas deferens (CAVD).
•Nonobstructive: hypogonadotrophism (Kallmann’s syndrome, pituitary tumour); abnormalities of spermatogenesis (chromosomal anomalies, toxins, idiopathic, varicocele, orchitis, testicular torsion)
Investigations
Hormone assay
Elevated FSH indicates a nonobstructive cause; normal FSH with normal testes indicates an increased likelihood of obstruction. Low levels of FSH, LH, and testosterone indicate Kallmann’s syndrome (hypogonadotropic hypogonadism) due to hypothalamic dysfunction and absence of GnRH secretion.
Prader-Willi syndrome also has absent GnRH secretion. It is associated with obesity, mental retardation, and short stature, whereas Kallman’s syndrome is associated with anosmia.