Male infertility:An overview

CAUSES OF MALE INFERTILITY



Infertility is defined as the failure to conceive after one year of unprotected intercourse. The condition affects about 15% of couples within the reproductive age group and the male partner is contributory in about half the cases.
Basic clinical evaluation of the infertile male should include detailed reproductive history, physical examination and at least two semen samples must be obtained, preferably about a month apart with a 3-5 day abstinence period prior to each sample .According to abnormality in seminal parameters the following categories are made:
A. Oligo/astheno/teratospermia (OATs):
Abnormality in sperm density, motility or morphology.
B. Azoospermia:
Azoospermia refers to total absence of sperm. The presence of even a single mature sperm changes the diagnosis to extreme oligospermia or cryptozoospermia.


Hormonal evaluation(FSH and Testosterone)
An endocrine evaluation should be performed if:
1. Sperm concentration is less than 10 million/ml
2. Impaired sexual function such as decreased libido, volume of ejaculate
Semen culture
Persistent pyospermia despite an initial course of empirical antibiotics is an indication for seminal culture.Cultures are often negative since the infecting organisms: Chlamydia and Mycoplasma cannot be grown on routine bacterial cultures.

Scrotal ultrasound and Doppler
• Scrotal ultrasound should be done in case a suspicious mass lesion is found on clinical examination or the scrotum is difficult to evaluate clinically due to previous trauma/ surgery/ infection.


Genetic testing
Genetic abnormalities may be present in upto 10% men with severe OATs. These are primarily deletions in the long arm of the Y chromosome (Yq microdeletions) or karyotypic abnormalities such as Klinefelter’s syndrome or it’s variants.CFTR gene testing is done in obstructive azoospermia with vassal agenesis. Detecting these abnormalities identifies the etiology of the infertility and allows counseling of the patients if they choose to undergo ART
Management options for OATS (non-varicocele related)
Specific treatment must be offered to men with a demonstrable specific cause for OATs.








• Life-style changes, avoidance of heat exposure, toxin exposure should form the initial non-drug therapy for OATs.
• Hypogonadotropic hypogonadism requires hormone supplementation.
• Pyospermia should be initially treated with a short course of agents effective against Chlamydia and Mycoplasma.
• Empiric therapies should be avoided in couples with advanced age or where the fertility potential of the female partner is compromised.
• There is no role of empirical androgens including Testosterone, GnRH, FSH, hCG, hMG.
• Men with total asthenospermia with normal counts require ART.
Indications and techniques for correcting a varicocele





• A varicocelectomy should be advised only if all the following criteria are met:
1. Documented infertility
2. Clinically palpable varicocele
3. Presence of OATs
4. Fertile female partner
• Adolescent boys with a demonstrably smaller ipsilateral testis or unmarried men with documented decline in semen parameters may also be counseled for a varicocelectomy
• Azoospermic men with no other cause for azoospermia may rarely benefit from varicocelectomy, particularly if the varicocele is large or bilateral. Such men should be counseled well before surgery.
• Microsurgical procedures have the lowest risk of complications and should be preferred.
• Subinguinal approach is preferable as the pain is less because muscle cutting is not involved.



Laparoscopy for varicocelectomy:
Laparoscopy for varicocelectomy is challenging because of damage to testicular artery and higher recurrence rate however with the use of papavarine and meticulous dissection testicular artery can be preserved.This method can be probably used for bilateral varicocele.


Azoospermia

Etiologies of azoospermia can be categorized into pre-testicular, testicular and post testicular. Pre-testicular azoospermia occurs in men with hormonal abnormalities and are uncommon. Testicular causes result in poor spermatogenesis. These are usually not amenable to corrective therapy and require ART. Post testicular causes are due to ductal obstruction or ejaculatory dysfunction. These are often correctable and the aim of evaluation of azoospermic men is primarily to identify such patients.

Additional investigations
Hormone analysis
• Bilaterally small testis with FSH raised more than 2x normal is diagnostic for testicular impairment and these men may not need a diagnostic testicular biopsy/FNAC.
• Serum FSH estimation is optional in men with obstructive azoospermia..
Testicular biopsy
• Testicular biopsy is mandatory before diagnosing obstructive azoospermia in men with a normal volume ejaculate and at least one palpable vas deferens.
• Testicular FNAC/ needle biopsy provides diagnostic information as good as an open biopsy. Where feasible, FNAC/ needle biopsy should be used instead of an open biopsy.
Vasography
• Vas patency may be confirmed by saline infusion or similar tests that do not result in inflammation of the vas. This should usually be combined with a reconstructive procedure and should not be performed as a separate diagnostic test.
Trans rectal ultrasonography (TRUS)
• TRUS is indicated in men with low-volume ejaculate and a palpable vas deferens.
• TRUS with injection of dye into the seminal vesicles is performed immediately prior to a trans-urethral resection of ejaculatory ducts (TURED) in men with ejaculatory duct obstruction.
Post-ejaculate urine examination
• Post-ejaculate urine should be checked for sperms in men with low-volume azoospermia, normal TRUS and normal spermatogenesis.
• Urine should be alkalinized for 2 days prior to the test.
Abdominal ultrasound
• Ultrasound of the abdomen, particularly the kidneys should be obtained in men with CBAVD. These men have a higher incidence of renal agenesis.

Diagnosis and management
Vasoepididymal junction obstruction (VEJO)
• Most cases of VEJO are idiopathic.
• Diagnosis is to be made if all the following are present:
o At least one palpable vas deferens
o Normal volume ejaculate with positive fructose
o Normal spermatogenesis on FNAC
• Should be treated with a microsurgical vasoepididymal anastomosis
• The possible patency rates must be discussed with the patient before the surgery(30-50%)



Ejaculatory duct obstruction
1. Diagnosis is to be made if all the following are present:
• At least one palpable vas deferens
• Low volume ejaculate
• Absent of sperms on post-ejaculate urine examination
• Normal spermatogenesis on FNAC testis
2. Men with EDO and dilated ejaculatory ducts may benefit from Trans-urethral resection of the ejaculatory ducts (TURED) or seminal vesiculoscopy.
3. Results in the appearance of sperm in the ejaculate in about one-half to three-fourths of cases. The pregnancy rate achieved by this surgery is about 25 percent
4. Retrograde ejaculation and recurrent Urinary Tract Infections are complications usually encountered.
5. Seminal vesiculoscopy liberally,safely deroofs seminal vesicles and bypasses the ejaculatory duct that too under direct vision.So the chance of restenosis is less likely.







Vasectomy, vasal injury
• The diagnosis is usually evident from the history and examination.
• In patients with a long history of injury, spermatogenesis should be confirmed prior.
• Microsurgical reconstruction treatment of choice.
• The results in our setting is around 80-85%(patency rate).



Microsurgical vasectomy reversal with Goldstein technique
Testicular Sperm Retrieval:

1. For patients with nonobstructive azoospermia, recommend open testicular sperm extraction.
2. For cases of obstructive azoospermia, either open or percutaneous techniques may be used.
The modalities of sperm extraction:
Obstructive azoospermia:
Percutaneous epididymal sperm aspiration:The idea behind epididymal sperm acquisition is that higher yield of bankable sperms from the epididymis than the testis.As the percutaneous technique is unreliable the Microsurgical Epididymal Sperm Aspiration(MESA)has been method of choice for the sperm aqusition.It involves microsurgically exposing and incising epididymal tunic and aspirating epididymal fluid.MESA leads to extraction of large number of motile mature sperms which can be cryopreserved.

Non-obstructive azoospermia:

Two methods have been described:Percutaneous(Fine needle aspiration or percutaneous aspiration with 18 G needle)or testicular biopsyBut the yield is scanty or none in Sertoli cell only syndrome or early maturation arrest.In these cases either Random multiple biopsies or microdissection TESE have been employed with reasonable success rate.Microdissection technique employs inspection of individual seminiferous tubules under operating microscope and selcting opaque yellowish tubules and dissecting them out and examining them under microscope for spermatogenesis.The yield in this method more with very less testicular tissue damage.





Assisted reproduction

• Assisted reproduction should be the primary treatment modality in men with:
o Testicular failure with severe OATs or azoospermia
o CBAVD
o All immotile sperms
o Partners who have an indication for ART