CHAPTER 22 Male Infertility
NUMBERS TO REMEMBER
What are the WHO reference values for count, concentration, motility, and morphology on semen analysis?
According to the recently revised WHO reference values (2010), a total sperm count ≥39 million per ejaculate, sperm concentration ≥15 million/mL, motility ≥40%, progressive motility ≥32%, and 4% or more normal forms define the lower limits for normal fertility.
What percentage of couples are infertile, and how often is a male factor present?
Fifteen percent of couples are infertile. A male factor is present in 50% of cases.
What percentage of infertile men have varicoceles?
30% to 45%.
What percentage of infertile men have no known cause for their infertility even after a thorough workup?
25% to 30%.
What percentage of infertile men have azoospermia, including obstructive or nonobstructive azoospermia?
Azoospermia is present in approximately 1% of the general male population, and in up to 10% to 15% of infertile men. Obstruction accounts for 40% of all cases of azoospermia, with the remaining 60% having a nonobstructive etiology.
What percentage of infertile men have chromosomal abnormalities?
6% to 7%.
What is the most common chromosomal abnormality in men?
Klinefelter syndrome (1 in 500 men).
What percentage of men with nonobstructive azoospermia have Y chromosome microdeletions?
Up to 13% of men with azoospermia have Y chromosome microdeletions.
What are the indications for performing a karyotype or Y chromosome microdeletion analysis?
A karyotype analysis in indicated in men with sperm concentration below 10 million/mL. Men with sperm concentration below 5 million/mL should undergo Y chromosome microdeletion testing in addition to karyotype analysis.
What percentage of men with unilateral and bilateral cryptorchidism have oligozoospermia on semen analysis?
Thirty percent of men with unilateral cryptorchidism, and 50% of men with bilateral cryptorchidism have oligozoospermia on semen analysis.
A couple has one 4-year-old child and is now having difficulty conceiving again. The male partner has oligoasthenozoospermia and normal hormonal testing. What abnormality can be expected on physical examination?
A varicocele is found in up to 80% of men with secondary infertility. Varicoceles have been shown to cause progressive worsening of semen parameters.
What percentage of patients undergoing varicocelectomy for infertility can expect to have improvement in semen parameters, and which parameters are most often improved?
Approximately 70% of patients have improvement in semen parameters after varicocelectomy. Sperm motility is most often improved followed by count and then morphology.
What is the live birth rate for in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) for male factor infertility?
Approximately 30% to 40% per cycle.
What is the most important predictor of IVF/ICSI outcomes?
Age of the female partner.
What percentage of men develop significant antisperm antibodies after vasectomy?
60%.
What percentage of men who have undergone vasectomy eventually seek reversal?
6% to 10%.
ANATOMY AND PHYSIOLOGY
The pituitary hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH) act on which cells in the testis and what are the specific mediators of feedback inhibition from these cells to the pituitary gland?
FSH acts on the Sertoli cell to promote spermatogenesis, while LH acts on Leydig cells to stimulate testosterone production. Inhibin, produced by Sertoli cells, provides negative feedback at the pituitary level to inhibit FSH production. Estradiol and testosterone provide negative feedback at the hypothalamic and pituitary levels to inhibit LH production.
Which cells in the testis form the blood–testis barrier and exclude sperm from recognition by the immune system?
Tight junctional complexes between adjacent Sertoli cells create the blood–testis barrier making the seminiferous tubule an immunologically privileged site.
Autonomic innervation of the testis is provided by which nerve or nerves?
The superior spermatic nerve and the inferior spermatic nerve.
A germ cell undergoes how many meiotic divisions before producing a mature sperm?
Germ cells undergo mitotic division to produce numerous primary spermatocytes, which then undergo meiosis I to secondary spermatocytes (2N), and meiosis II to produce spermatids (1N).
Aside from sperm transportation, what is the most important function of the epididymis?
Sperm maturation occurs along the length of the epididymis, resulting in mature sperm capable of fertilizing oocytes.
What role does prostate-specific antigen (PSA) play in male fertility?
The protein secreted by prostatic epithelium is a protease enzyme involved in semen liquefaction.
Which substance produced in the seminal vesicle is the major energy source for sperm metabolism?
Fructose.
What is the role of the acrosome and where is it located?
The acrosome forms a cap on the sperm head and contains the enzymes necessary for drilling into the zona pellucida of the oocyte.
Do the testis, epididymis, and vas deferens share the same embryological origin?
No. The testis develops from coelomic epithelium of the genital ridge and underlying mesenchyme. Primordial germ cells migrate to this area. The epididymis and vas deferens, however, develop from the Wolffian (mesonephric) duct.
What is the normal adult testicular size?
Testes measure 15 to 25 cm3 in volume and 4.5 to 5 cm in longitudinal length in young healthy men. A length of less than 4 cm is considered abnormal.
When evaluating the ejaculatory ducts by transrectal ultrasound (TRUS), what is their normal size?
They are usually 2- to 8-mm wide and 2- to 3-cm long.
In performing a subinguinal varicocelectomy, the internal spermatic artery is inadvertently ligated and divided. By what blood supply might the testis still survive?
The deferential artery and the cremasteric artery also supply blood flow to the testis.
A patient develops retrograde ejaculation after retroperitoneal lymph node dissection (RPLND) for testis cancer. Which nerves were likely injured and which class of medications may be used to treat the problem?
Thoracolumbar sympathetic nerves control closure of the bladder neck during seminal emission via norepinephrine. Alpha-adrenergic agonist drugs have been used to stimulate closure of the bladder neck.
Prolactin release is restricted by what natural chemical?
Dopamine (from the hypothalamus) inhibits the release of prolactin. Dopamine agonists (cabergoline, bromocriptine, etc) are the treatment of choice for prolactinomas.
What is the effect of thyrotropin-releasing hormone and vasoactive intestinal peptide on prolactin secretion?
They stimulate prolactin release.
What is the total length of the seminiferous tubules of a normal testis?
250 m. Seminiferous tubules also comprise 85% of total testicular volume.
At what age do men lose 50% of their Sertoli and Leydig cells?
Age 50 for Sertoli cells and age 60 for Leydig cells.
What are the glands of Littre?
Another name for the periurethral glands.
What is the average length of the vas deferens?
The average length is 30 to 35 cm.
What is the origin of the deferential artery?
The internal iliac (hypogastric) artery or its branches, the superior or inferior vesicle artery.
Blood entering the testis is 2°C to 4°C lower than rectal (body) temperature as a result of what mechanism?
Countercurrent heat exchange system of the testicular vasculature.
DIAGNOSIS
What physical finding is most predictive of active sperm production in the testis?
Testicular size and consistency.
What is the most common finding, on physical examination, which is suggestive of infertility in men?
Varicocele.
A patient presents with azoospermia, low ejaculatory volume, and a semen pH of 6.5. Postejaculation urine is negative for sperm. The vasa deferentia are palpable. What is the next test that should be performed and what is the most likely diagnosis?
Transrectal ultrasound of the prostate should be performed to rule out ejaculatory duct obstruction.
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