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Genetic Disorders

Acknowledgement of the importance of genetic anomalies to the cause of male infertility is growing. Chromosomal or monogenic disorders, mitochondrial DNA (mtDNA) abnormalities, Y chromosome deletions, multifactorial disorders, imprinting disorders or endocrine disorders of genetic origin may indeed be genetic contributing factors in male infertility. Around 10 percent of genes are linked to spermatogenesis in the genome. Increasing knowledge of the genetic basis of male infertility seems to have a significant effect not only on identifying the elements of infertility, but also on deciding the diagnosis and treatment of such couples with the increased use of assisted reproduction technology (ART). They account for 5%-10% of oligozoospermia cases, to 15%-25% of non-obstructive azoospermia cases.

Sex-chromosome defects are prominent in azoospermia. The key genetic trigger of oligozoospermia, however, is autosomal structural chromosomal defects and may be balanced (no benefit or loss of genetic material) or unbalanced. A common complication of masculine infertility is numerical chromosome errors. The occurrence is inversely proportional to the sum of ejaculated sperm.  The most common numerical chromosomal abnormality is Klinefelter syndrome [KFS], and is the most major condition of azoospermia. Men with 47,XXY chromosomal complement are azoospermic attributable to dysgenesis of seminiferous tubules, while oligozoospermic may be mosaic cases with regular 46,XY cell line. Aberrant translocation of Y material, such as the sex determining region (SRY) to the X chromosome, contributes to the 46,XX male chromosomal complement throughout paternal meiosis. The involvement of the SRY gene results in testicular differentiation, however due to the lack of a long arm of the Y chromosome, there is no spermatogenesis.

These men have normal sexual growth with normal external genitalia, but the occurrence of hypospadias and cryptorchidism has increased. Cystic fibrosis is a genetic condition that affects the lungs and digestive tract, which may be life-threatening. Abnormality in the gene called CFTR (cystic fibrosis transmembrane conductance regulator) of the cystic fibrosis gene is closely correlated with the absence of vas deferens, the tube that carries sperm for ejaculation to the urethra. Typically, men with this CFTR mutation do not have cystic fibrosis but are gene carriers. A blockage of the ejaculatory duct or blockage of the epididymis, a coiled tube behind each testicle which transports sperm to the vas deferens, might be present in men with the CFTR mutation.

The microdeletion location on the Y chromosome indicates the type of impact it has on the production of sperm. In the Azoospermia Factor (AZF) region on the long arm of the Y chromosome, most of the microdeletions that cause azoospermia or oligospermia happen. The strategy to possible fertility treatment can impact where the microdeletion is detected. 

Mutations in more than eight genes cause Noonan syndrome. It is usually evident at birth and can include a range of physical effects that vary from individual to individual. In the facial shape, head, sternum, elbows and spine, these can often include abnormalities. In a child with Noonan syndrome, heart defects are also feasible, as are blood disorders and intellectual difficulty. Infertility can also be encountered in boys with Noonan syndrome. This is especially the case if one or both of their testicles have not fallen into the scrotum before or after their first year of birth (cryptorchidism).

The lack of supply of normal viable ejaculate sperm for IVF treatment is one of the reasons of male infertility.

Any of the explanations for that may be:

  • With azoospermia (No sperms)
  • Low count of sperm (Oligospermia),
  • Poor motility of sperm (Asthenospermia).

Therapy with TESA and PESA requires sperm recovery procedures via a minor medical surgical phase.

Testicular Sperm Aspiration (TESA)

For men who are getting sperm extracted for IVF/ICSI, TESA is a procedure performed. The testicle is fitted with a needle and the tissue/sperm is aspirated. Individuals with obstructive azoospermia (s/p vasectomy), TESA is undertaken. Azoospermia is a disorder in which a male’s ejaculate does not contain sperm. It normally consists of 2 forms. Obstructive and non-obstructive azoospermia, both of which, on their own, are curable. There are, indeed, simple and non-obstructive surgical procedures which can be done by artificial means to either treat the disease or assist in childbirth. TESA sometimes does not have adequate tissue/sperm and it involves an open biopsy of the testis. TESA’s combined influence with artificial reproductive technology has proved to be a blessing to a high percentage of couples facing natural conception difficulties. There is usually some mild discomfort and swelling in the region of needle aspiration procedures, which goes away in a relatively short period of time. Sperm extraction through TESA has a really high rate of success by giving 80% success.

PESA (Percutaneous Epididymal Sperm Aspiration)

PESA is a treatment performed for men who have sperm collected for IVF/ICSI who have either a previous vasectomy or infection with obstructive azoospermia. It is a medical procedure requiring the use, as with a needle biopsy, of needle and syringe method, except the needle is inserted straight into the epididymis. If there is a blockage in the vas deferens, but the testis releases sperm, this also provides good results. The sperm retrieval (SR) technique of choice is depending on the nature of azoospermia, which could be obstructive or non-obstructive, and the preferences and experience of the attending surgeon. Obstructive azoospermia (OA) is correlated with a failing to recognize spermatozoa after centrifugation in the ejaculate and post-ejaculate urine due to bilateral seminal duct obstruction.

Microdissection TESE (MicroTESE)

MicroTESE is a process that is carried out for men who seem to have a problem with sperm production and are azoospermic. MicroTESE is executed with general anesthesia underneath the operating microscope in the operating room. MicroTESE is managed appropriately with the egg retrieval of the female partner, and is carried out the day before egg retrieval. This enables for the other’s procedure to be there for each partner. In the event of sperm not being spotted in the male partner, patients often have donor sperm backup. MicroTESE in azoospermic men has markedly increased sperm retrieval rates, and is a safe and secure procedure as less testicular tissue is removed. For future IVF/ICSI, patients cryopreserve sperm during this procedure.

Microepididymal Sperm Aspiration (MESA)

In men who have vasal or epididymal obstruction (s/p vasectomy, congenital bilateral absence of vas deferens), MESA is a procedure that is performed. It is either performed as a scheduled procedure or integrated with the egg retrieval of our female partner. MESA is done with local anaesthetic using the operating microscope in the operating room. For long term IVF/ICSI, patients typically cryopreserve sperm throughout that procedure. Especially in comparison to aspiration techniques, MESA enables for an extensive collection of mature sperm, and it is the method of choice of recovery for men with congenital bilateral absence of vas deferens as it does not affect the testis’ steroid production.

Sperm DNA Fragmentation

Sperm DNA fragmentation (SDF) is associated with male infertility, and reproductive outcomes are adversely affected. The scope of DNA damage is determined by both chromatin integrity and protamination status. In the seminal fluid, oxidative stress leading to excessive levels of reactive oxygen species impairs sperm DNA. A DNA fragmentation index is continually linked to poorer fertility prognosis of >30 percent (increased risk of spontaneous abortion, failure to achieve pregnancy, longer time to successful pregnancy, and more IVF cycles). The higher the levels of DNA fragmentation, the greater the chances of failure of assisted conception therapy and miscarriage. In subfertile men with abnormal sperm parameters, the SDF is higher. Also reported to have significant SDF are men with standard sperm parameters. While semen analysis is by far the most commonly used test in the male infertility workup, study has shown that findings of semen analysis tests can not accurately determine whether a male is fertile or whether an infertility treatment will occur during pregnancy