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Infertility is defined as an inability to conceive within one year of unprotect4ed intercourse by an apparently healthy couple of reproductive age.

The cause for infertility can be broadly classified as due to female factor, male factor, combined factor, and unexplained factors. It is imperative that the couple must understand that infertility can obviously be due to male factors and also, in about 20% a cause may not be obvious with current investigation modalities.

Male factor infertility alone accounts for 20% of all infertility cases and also contributes in upto 30-40% cases.

What causes male infertility?

From a clinician’s point of view male infertility can be classified based on the causes as Pre-Testicular, Testicular, Post-Testicular and Semen related.

What are pre-testicular causes of male infertility?

As the name implies, the cause is not at testicular but at central nervous system level. There is reduced secretion of gonadotropins due to disruption of the hypothalamo-pituitary system resulting in secondary testicular failure and abnormal spermatogenesis. So, this results in hypogonadotropic, hypogonadism.

Pre-testicular causes can be Congenital or Acquired.

Congenital causes include Kallman syndrome which is associated with hypo-osmia or anosmia. There exist other rare causes of congenital disruption in gonadotropin secretions. These cases manifest with under-virilization, gynecomastia, cognitive impairment, Color-blindness/ cleft palate/Congenital deafness in phenotypic boys. Acquired causes of hypogonadotropic hypogonadism include infections trauma, tumors, chemotherapy, or radiation. It can also occur transiently after serious illness, exhaustion, severe exercises, alcohol/ drugs, AIDS etc.

What are testicular causes of male infertility?

Testicular causes include inflammation, genetic causes like Klinefelter’s syndrome, irradiation, tumors, varicocele, torsion, obstruction of the ejaculatory duct, absence, or surgical occlusion of the vas deferens, surgeries that can hamper blood supply to uterus and finally idiopathic.

Testicular dysgenesis syndrome is a heterogenous entity where intrauterine environment and genetics play their role and it results in a spectrum of abnormalities from cryptorchidism and abnormal spermatogenesis to cancer-in-situ and testicular cancer. It can also cause cryptorchidism, hypospadiasis and androgen insensitivity.

Klinefelter’s syndrome is characterized by the presence of 47 XXY chromosomes with azoospermia or severe oligozoospermia when it is due to a mosaic variant.

Y chromosome microdeletions are an important testicular cause of male infertility. The AZF gene (Azoospermia Factor) is located on the long arm of the Y chromosome. Deletion in the AZFa and AZFb regions result in azoospermia while sperms can be obtained with AFZc microdeletions.

CBAVD (Congenital bilateral absence of Vas deferens) and hence azoospermia occurs in patients with Cystic fibrosis.

Testicular tumors are not rare in young boys and may be a part of the Testicular dysgenetic syndrome. Testicular damage by chemotherapy and radiation is dose dependent and often irreversible. Antibiotics, anti-hypertensives, anti-psychotics can cause reversible damage to spermatogenesis unlike chemotherapeutics.

Lifestyle factors like obesity, smoking, drug abuse, chemicals, cell phone, global warming have all been implicated in affecting spermatogenesis.

What are the post-testicular causes of Infertility?

Obstruction to the path of sperms from the site of production to ejaculation are grouped as post-testicular causes of infertility. It could be epididymal obstruction, ejaculatory duct obstruction or obstruction of the vas deferens or even intra-testicular obstruction involving the rete testes or seminiferous tubules. Obstruction can be due to congenital causes like CBAVD (Congenital bilateral absence of Vas deferens occurring in patients with Cystic fibrosis) or CUAVD (Congenital unilateral absence of vas deferens). Acquired obstructions can occur because of genital tract infection.

How is the cause of male infertility diagnosed?

A case of oligospermia/ azoospermia merits correct evaluation as further management and counselling depends on the right diagnosis.

Initially a detailed history is elicited regarding duration of infertility, pre-existing diseases, medication, family history (of infertility/ genetic abnormalities in members), drugs/ medications/alcohol tobacco or any previous surgery for hernia/ testicular mass/ varicocelectomy or torsion testis. History also includes asking for any sexual difficulty (erectile dysfunction or retrograde ejaculation) and ascertaining frequency.

General examination includes measuring BMI and looking for signs of appropriate masculinization. Patients with Immotile cilia syndrome (Kartagener’s syndrome) and cystic fibrosis may have signs of bronchiectasis. Abdominal examination is done to exclude any mass/ hepatomegaly and look for any scars of previous surgery.

Genital examination is performed to look for any evidence of small testes, varicocele, lump, micropenis or hypospadiasis. The size of the testis may be determined by palpation or with the help of vernier calipers.

Semen analysis is the initial and most important investigation for male infertility. Azoospermia is diagnosed when there are zero sperms on two occasions of semen analysis.

Further testing depends on the suspected cause of male infertility and may include hormonal evaluation (FSH, TSH, Prolactin, Testosterone etc.) imaging (ultrasound of scrotum), genetic testing if indicated as also higher functions for seminal parameters.

Treatment of male infertility.

This obviously depends on the underlying cause. The aim is to restore correctible causes.

Cases of hypogonadotropic hypogonadism merit thorough evaluation to determine the cause. First line of hormonal replacement includes hCG therapy which restores spermatogenesis. The degree of response correlates with the size of testes prior to treatment. Secondary causes of hypogonadotropic hypogonadism like pituitary / suprasellar tumors, hyperprolactinemia, trauma, sarcoidosis etc. must be appropriately treated.

Patients undergoing gonadotoxic therapy-either chemotherapy or radiotherapy- must be offered sperm banking, after appropriate counselling.

Varicocele repair or Varicocelectomy (microsurgical) may be indicated when varicocele is palpable and is associated with abnormal seminal parameters. Varicocele repair cannot help if it is only evident on ultrasound and not palpable. There is no definitive evidence to suggest varicocele repair prior to ART when there exists non-obstructive azoospermia along with clinical varicocele. Artificial reproductive techniques may be resorted to if there is no conception within 6 months of varicocele repair.

Surgical extraction of sperms from testes or epididymis can be done in certain obstructive cases where there exists spermatogenesis.

Patients with azoospermia and Ejaculatory duct obstruction can be offered surgical sperm extraction or TURED(Trans-urethral resection of ejaculatory ducts)

Surgical reconstruction of Vas (post-vasectomy) and microsurgical reconstruction in cases of vasal/epididymal azoospermia can be tried.

There is no indication for routine testosterone replacement. However, aromatase inhibitors, hCG and SERMs (Selective Estrogen receptor Modulators) have been used to increase testosterone. Hyperprolactinemia can be corrected medically. Using FSH analogue in cases of idiopathic infertility can increase sperm concentration, pregnancy rates and live birth rates. Using SERMs in Idiopathic infertility has limited benefit when compared to ART.

IVF and ICSI is the artificial reproductive technology offered for cases of male infertility when there exists a possibility of retrieving sperms. In cases of Obstructive azoospermia, sperms are extracted from testis or epididymis. In cases of non-obstructive azoospermia, micro-TESE (Microdissection testicular sperm extraction) are offered.

As men with abnormal seminal parameters are at an increased risk of cancer, diabetes, hypertension, multiple sclerosis, coronary artery disease, Thyroid/auto-immune disorders, sexually transmitted diseases; they must be counselled for appropriate lifestyle modifications.

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