Male factor infertility
The male partner is directly responsible for 25% of cases of infertility and is thought to play a contributory role in another 25%. Male factor infertility implies a lack of sufficient numbers of competent sperm, resulting in failure to fertilize the normal ovum.
Spermatogenesis requires testicular growth & differentiation & it is under endocrine control by FSH & paracrine control by androgens produced by LH-stimulated Leydig cells. Spermatogenesis comprises the mitotic division of spermatogonia & meiotic division of spermatocytes. These will develop into spermatids which then transform into mature spermatozoa in a process called spermiogenesis. Genes involved in spermatogenesis are expressed on the Y chromosome. In human this process takes 74 days.
Causes of male infertility:
• Disorders of spermatogenesis:
Impaired spermatogenesis could result from defect in any of the above mechanisms. The normal scrotal temperature is 1 degree lower than the rest of the body temperature and a rise in scrotal temperature is found in undescended testes and varirocele wherein increased scrotal temperature may impair spermatogenesis. Micro deletions of Y chromosomes may lead to defective spermatogenesis. Impaired sperm production and sexual function may result from the intake of certain drugs such as some psychotropic drugs, anti-epileptic and antihypertensive agents, antibiotics and chemotherapeutic agents which adversely affect sperm production and sexual function.
• Sperm transport:
immotile spermatozoa are released into the lumen of the seminiferous tubules and travel to the ampulla of the vas deferens where they acquire motility. During ejaculation the semen is released by adrenergically mediated contractions of the distal epididymis and vas deferens. Spermatozoa are then mixed with the secretions of the accessory glands, prostate seminal vesicles, Cowpers and urethral glands.
Impairment of sperm transport can be seen in men with epididymal malformation, obstruction due to inflammation, enlargement or absence of vas deferens or immobile cilia syndrome. Sperm transport is blocked or impaired after vasectomy.
Ejaculatory dysfunction
Ejaculatory dysfunction only occurs in 1-2 per cent of males with infertility. It could be due to anejaculation, premature ejaculation or retrograde ejaculation and could be drug induced or idiopathic. Metabolic and systemic conditions like diabetes and multiple sclerosis may lead to impotence.
Other causes
Immunological factors such, as antisperrn antibodies (IgG or IgA) and general infections may affect sperm function and lead to infertility.
Seminal Fluid Analysis: The World Health Organization (WHO) has proposed a set of criteria for normal semen parameters:
• Volume: 2-5 mL
• Liquifaction time: within 30 minutes
• Sperm concentration: 20 million/mL
• Sperm motility: >50% progressive motility
• Sperm morphology: >30% normal forms
• White blood cells: <1million/mL
Nomenclature for some semen variables:
Oligozoospermia: Sperm concentration less than the reference value
Asthenozoospermia: less than the reference value for motility
Teratozoospermia: less than the reference value for morphology
Azoospermia: no spermatozoa in the ejaculate
Aspermia: no ejaculate
Further investigations of male infertility:
Endocrine tests: In men with azoospermia FSH level help to differentiate between obstructive & non-obstructive causes. Normal levels indicate obstructive azoospermia where surgical sperm retrieval may be considered while elevated levels are suggestive of failure of spermatogenesis. In rare cases undetectable levels of FSH can be suggestive of hypogonadotrophic hypogonadism where treatment with exogenous FSH may be effective. Testosterone and LH measurements are helpful in the assessment of men where androgen deficiency is suspected or steroid secreting tumours of the testes or adrenals. As men with hyperprolactinaernia have sexual dysfunction, it is necessary to exclude elevated prolactin levels in men with loss of libido and impotence. Persistently elevated prolactin levels warrant further investigations such as imaging of the pituitary gland.
CHROMOSOMAL AND GENETIC STUDIES
Men with azoospermia or severe oligozoospermia should undergo chromosomal analysis. A cystic fibrosis screen should be performed for men with congenital bilateral of the vas deferens (CBAVD) which is associated with defects in the cystic fibrosis gene.
MICROBIOLOGY OF SEMEN: Semen culture is indicated in men with microscopic evidence of infection. Male partners of women with chlamydia infection should be screened.
IMAGING OF THE MALE GENITAL TRACT:
A number of techniques have been used for imaging varicoceles. Tests include ultrasound and Doppler, angiography and thermog-raphy. Scrotal ultrasound scans are helpful if testicular tumours are suspected.
TESTICULAR BIOPSY
This is used in the past as a diagnostic tool to differentiate between obstructive and non-obstructive azoospermia. There is limited scope for the use of this invasive technique whose benefits are outweighed by potential risks such as reduction of testicular mass, devascularization, fibrosis and autoimmune response.
ANTISPERM ANTIBODIES
Tests for antisperm antibodies are not routine. The presence of sperm agglutination should alert the laboratory to the potential presence of antisperm antibodies. Subsequent tests to be done on a fresh sample should include MAR (mixed agglutinin reaction) and the immunobead test.
Management of male factor infertility:
Intrauterine insemination (IUI): using washed sperm may be considered in cases where semen parameters show mild or moderate abnormalities. Although IUI increases the relative odds of pregnancy, the absolute chances of conception remain low.
In Vitro Fertilization/ Intracytoplasmic Sperm Injection IVF/ICSI
Where semen parameters are poor, it may be appropriate to consider IVF treatment straightaway. In men with grossly reduced sperm concentrations (below 5 million/ml) ICSI is the treatment of choice. Obstructive azoospermia, in the presence of normal testicular volume and FSH levels can be treated by surgical sperm retrieval followed by ICSI. The prognosis for non-obstructive azoospermia associated with small atrophied testes and high FSH levels is poor and donor insemination (DI) may be considered.
Conventional treatment for male infertility:
GONADOTROPHINS
Hypogonadotrophic hypogonadism responds to gonadotrophin treatment. Administration of FSH and hCG is well tolerated and effective in achieving an acceptable sperm count in 80% of men. Pulsatile GnRH may be effective in improving sperm production in these situations.
SURGICAL TREATMENT
Include surgical procedures for post-infective block, including epididymovasotomy & surgical repair of varicoceles.
EJACULATORY FAILURE
Sildenafil is an effective treatment in men with erectile dysfunction. Medical treatment of anejaculation has included the use of alpha-agonists like imipramine and pseudoephedrine or parasympathomimetic drugs such as neostigmine. Medical treatment of retrograde ejaculation has relied on measures to increase sympathetic stimulation of the bladder and decrease parasympathetic stimulation, but no clear difference in effectiveness has been found between alpha-agonists and anticholinergic drugs. In the absence of other options, surgical sperm retrieval followed by IVF/ICSI may be considered.