CONVENTIONAL METHODS FOR THE DIAGNOSIS AND TREATMENTS FOR MALE INFERTILITY

The following is a summary of the key methods currently used to diagnose male infertility.

·         30% of the cases of male infertility the causative factors are idiopathic.

·         Standardized laboratory models for the diagnosis of male infertility are unavailable.

·         Conventional therapeutic strategies are based on speculative concepts and clinical observations

·         Consider female reproductive function in relation to male infertility treatments, (timing of ovulation)

·         Develop good clinical experimental trials are necessary that include endocrino-logical evaluation of reproductive hormones.

·         Continuous record of technician performance are mandatory for internal quality control.

·         Semen analysis only useful for determining azoospermia and oligospermia.

Additional analysis of semen parameters are necessary, e.g. evidence of reactive oxygen species, acrosome reaction, and sperm movement characteristics. All of these help predict IVF fertilisation rates.

·         Inter-rater reliability of analysis of samples from the same laboratory is questionable.

·         Determination of anti-sperm antibodies

·         Sperm function testing, the use of computer-assisted semen analysis is costly but accurate.

·         Acrosome testing (failure of spermatozoa to undergo the acrosome reaction - diagnostic index of very poor fertilisation rates).

·         Sperm chromatin packaging assays- chromomycin A_3.

·         Post-coital testing and in-vitro cervical mucus.

·         Use of molecular testing to detection of pathogens in semen such as Polymerase Chain Reaction (PCR), recombinant zone pellucida glycoprotein 3, analysis of sperm binding and acrosome reaction proteins, mitochrondrial mutations in Sertoli and Leydig cells - PCR, cytometric analysis of Y deletions in sperm DNA using PCR.

·         Secondary hypogonadism parameters (testosterone serum conc., testicular growth, appearance of spermatozoa in ejaculate. More controlled trials to estimate quantities of patients with idiopathic hypogondotrophic hypogonadism.

·         Testicular maldescent -use of intranasal GnRH (gonadotrophin releasing hormone) or IM HCG therapy, or orchidopexy.

·         Varicocele - occlusion of the spermatic by vein by ligation or embolization

·         Infections- treat leukocytospermia with antibiotics as appropriate.

·         Anti-sperm antibodies - Immunosuppressive therapy - glucocorticoids - results are inadequate.

·         Idiopathic male infertility- various studies with anti-oxidants (Vit.E & C), results inconclusive.

·         Oligoastheoteratozoospermia - HCG/HMG did not improve semen parameters. Use of FSH to stimulate spermatogenesis has been shown to be less efficacious than expected.

·         Use of testosterone undecanoate and mesterolone are ineffective in producing normal spermatogenesis.

·         It is proposed that the oestrogen antagonist tamoxifen increased luteinizing hormone and FSH thereby improving sperm production. Tamoxifen and clomiphene were used to block oestrogen binding at respective receptor sites, thus reduce feedback inhibition and elevate gonadotrophin and testosterone concentration. However, both compounds were shown to be ineffective in influencing hypophyseal gonadotrophin secretion.

·         Diagnostic testicular biopsy can be used with complete histological examination to differentiate pure from mixed forms of SCOS

·         Immunohistochemical analysis of Sertolic cell intermediate filament proteins in particular, the presence of antibodies to vimentin can be used to diagnose mixed SCOS.

·         Lipid granules are normally present within the Sertoli cell and occur as a result of digestion of the cytoplasmic residue of spermatids following spermiation. Pure and mixed forms of SCOS can be differentiated on the quantity of lipid granules found.

·         Quantitative analyses of the presence and viability of immature germ cells released from the Sertoli cell in ejaculate can be assessed as an indicator of testicular function and may be a diagnostic predictor of possibility of recovering spermatozoa from the testis (Ezeh et al.,1998)

·         Telomerase assays can be used as a marker of cellular proliferation of chromosomes responsible for cell replication. Tissue sections from biopsied testicular tissue are used to assess telomerase activity. In patients with SCOS, telomerase activity is negligible, however, activity is indicative of normal spermatogenesis, hypospermatogenesis or maturation arrest. Confirmation of SCOS can be achieved through immunohistochemical testing of tissues, immunolabeling and biochemical assessment (Anniballo, et al., 2000).

·         Azoospermia caused by obstructions of the genital tract or by testicular failure contributing to an absence of sperm in the semen.

Causes of obstruction include: epididymovasal occlusions caused by infections, congenital bilateral absence of the vas deferens.

Ligation and re-section of the vas deferens during hernia repair, prostatic, vesicle surgery or vasectomy.

Sperm retrieval methods for azoospermic males- microsurgical epipdidiymal sperm aspiration (MESA). Use of epididymal and testicular spermatozoa can be retrieved easily with microsurgical epididymal sperm aspiration (MESA) or percutaneous epididymal sperm aspiration (PESA).

Testicular spermatozoa can be retrieved using testicular sperm aspiration (TESA) or more easily obtained testicular sperm aspiration extraction (TESE) due to location of sperm within the testes in these patients (Ezeh et al., 1998). Frequent failure of sperm recovery is known to occur in up to 57% of patients with non-obstructive azoospermia, and results in the partner undergoing unnecessary ovulation stimulation (Ezeh et al., 1998). TESE is used to recover spermatozoa as a male therapeutic approach in intracytoplasmic sperm injection (ICSI).

Non-obstructive azoospermia due to hypogonadotrophic hypogonadism, treat pituitary and testicular failure via hormonal supplementation for the duration of time required for resumption of spermatogenesis.

·         Intracytoplasmic Sperm Injection (ICSI)- micro-fertilization technique used as a first choice for the following:

1.      No or poor fertilization occurred in 2 IVF cycles.

2.      Problems associated with epididymal / testicular spermatozoa.

3.      Immotile spermatozoa

4.      Globozoospermia

5.      Frozen-thawed spermatozoa with poor survival

6.      Pre-implantation genetic diagnosis.

7.      ? a thick zona pellucida

8.      ? acrosomal index of the sperm sample.

TESE is used to recover spermatozoa as a male therapeutic approach in intracytoplasmic sperm injection (ICSI). Conditions alleviated by ICSI:

azoospermia, abnormal spermatozoa, and immobile spermatozoa.

Need to assess spermatid injections in oocytes

Need for genetic screening and counselling of patients and also to follow-up development of children produced using this procedure.

 

Although, numerous diagnostic methods are available to determine a diagnosis of infertility in males, the accuracy of the methods continues to be questionable, particularly if multiple factors are involved. This problem is also limited by the discrepancies in the methods of analysis and choice of treatment options. Hopefully, this situation will be resolved by extensive research.