The XYZ of Male Infertility

Hi Dr G,

I’ve been married for three years now and actively trying to conceive. Sad to say, although the attempts have been pleasurable, there has been no successful outcome over the years.

As I understand it, male factor infertility can be a major cause for concern. About a year back I did my semen analysis, and true enough, I discover I have no sperms in my ejaculates. From the interpretation of the blood and scan investigations, I was told I have NOA (Non Obstructive Azoospermia).

Now, upon further analysis through my genetic karyotype, I discovered I have a micro-deletion of AZFb and AZFc genes. Apparently, these are the results of some form of mutations in the sperm cells, inherited from my parents during conception.

The urologist told me that this might have caused a maturation arrest in the spermatogenesis or I don’t even have any sperm germ cells to begin with.

I would like to put Dr. G on the spot on the origin of such mutation? What kind of effects does it have on spermatogenesis? Will such deletion of the genes cause any other problems in health?

I read an article on germ cells implantation on rats and it had favorable outcome, would it work in humans? If this work, will my child have my genetic codes or the donor genetic codes?

And realistically, what options do I have to father a child?

X-men

Infertility is the inability for a person to reproduce by natural means. According to global statistics, it is estimated 5% of heterosexual couples face unresolved fertility problems in their lifetime. The rates of couples facing involuntary childlessness for at least one year ranges from 12% to 28%. Around one third of the causes of infertility are due to male factors, one third of the etiology is due to female issues, and the rest are caused by both male and female problems.

The commonest reason why a man is unable to cause pregnancy in a fertile female is due to sexual dysfunction or deficiencies in semen and its quality. Therefore, semen analysis has become a surrogate measure of male fecundity.

The simple analysis of the quality of the ejaculated fluid in men can determine the exact causes of male factor infertility. Scientific data has determined the minimum number of sperm required, the activeness and its normal morphology required to ensure fecundity. When the parameters have declined to less than the baseline of fifteen millions of sperms, with motility of less than 40% and morphology of less than 4%, the chances of pregnancy diminish significantly.

When there is no sperms detected in the ejaculate, the sufferer faces the problem of azoospermia. The absence of sperms can be caused by the occlusion of the sperm delivery, OA (Obstructive Azoospermia) and also NOA (Non Obstructive Azoospermia). In the latter form of the infertility, genetic damage caused by the environment or congenital forms are expected.

The most studied hereditary defect associated with male infertility is Y Chromosome Microdeletion (YCM), commonly known as Micro-Y-Deletion. This is a family of genetic disorders caused by a mutation or missing genes in the Y Chromosome that is only passed from father to son.

As there is no pairing of the Y chromosome like the rest of the X gene pool, such mutation is not protected by the error corrections of recombining genetic information from mother to son. Hence the natural selection leaves the repair mechanism to chances. Unfortunately, one of the affected genes in Y chromosome is the male fertility.

In recent years, many studies have been focused on the AZF (Azoospermia Factor Locus) of the Y Chromosome. The various forms of mutation (a, b and c) can result in a spectrum of defects in spermatogenesis. This can range from the reduction in sperm quality (Oligo-astheno-teratospermia) or even complete absent of the gametes. Many men who are affected by Micro-Y-deletion are completely oblivious to such deficiency, as they exhibit no symptoms and live a normal life.

As the understanding of the science behind human reproduction become more apparent in recent decades, the avenue of interventions to correct the defects caused by mutations in natural selection has become closer to reality. Although the success of stem cells reactivating the germ cells in infertility male rats has created a buzz in the scientific world, it has also caused significant concerns venturing into the unknown world of human medical ethics in the years to come!

Dean Ornish, the American physician and researcher who founded the Preventive Medicine Research Institute once said: “No one has all the answers, so whatever a woman who has the BRCA mutation chooses to do requires courage and an element of faith. And a lot of love and support.” Facing the reality of male factor infertility itself is often devastating, and the dilemma of how much to push to get the answers and solutions is often harder. For men with the diagnosis of YCM and mutation on the AFZ, the only solution to retrieve sperms is through an operation. Often times such intervention may also turn out to be pointless.

When Dr. G is put on the spot to give guidance to world of “XYZ” mutations of the reproductive genes, he agrees: “No one has all the answers, so whatever an infertile man who has AFZ mutation chooses to do requires courage and element of faith. Definitely a lot of love and support.” On that note, wishing the X men an Xcellent outcome in whatever decision made!