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Infertile patients cannot afford to wait for treatment while their eggs get older.

Dr. Sherman Silber, Infertility Center of St. Louis, is offering video consultations for patients who need to plan now for their treatment while stay-at-home orders are in place. He is talking to and evaluating patients in their home to comply with social distancing measures.

Dr. Silber is discovering that patients actually prefer this method of telemedicine consultation over the conventional office visit. Patients have conveyed that “it is so much more convenient and less stressful” to have a telemedicine personal consultation than to take a day off from work to travel to the doctor’s office and sit with other nervous patients in the waiting room.

The COVID-19 pandemic is thus changing much of the way we will do things in the future, and for the better. “Our patients are surprisingly much happier with this approach. Of course, at some point we need to perform hands on treatment. But with this new manner of seeing patients, we can come to the right diagnosis and treatment plan for most patients more efficiently, quickly, and painlessly, with no loss of personal one-on-one communication.” This is a very welcome new era of telemedicine that has been forced on us by the current difficult times.

Transmitting Y deletions by ICSI


Transmission of Y deletions by ICSI makes genetic counseling necessary

IVF News, Volume 9, No 3&4, 1998

The role of the Y chromosome in male-germ-cell development continues to pose important challenges for researchers and clinicians alike, but the picture appeared to become even more challenging with reports from the groups of Dr Sherman Silber in St Louis, USA, and Dr David Page in Boston, USA, that there are probably several genes on the target region of the Y chromosome which have an effect on sperm production.

In a plenary lecture, Dr Page, reviewing what we so far seem to be sure of, reported that “nearly all” men with AZF (azoospermia factor) deletions on the c region of the long arm of the Y chromosome are infertile. He described a study in which 46 out of 49 men observed with AZFc deletions were all azoospermic.

Dr Silber has also shown (in a study reported below) that such deletions occur in 12% of azoospermic men and 7% of severely oligospermic men; these deletions are not found in normal fertile men.

The relevance of such findings, of course, is that now, with the routine availability of TESE and MESA, ICSI enables the transmission of such genetic mutations to all sons born as a result of treatment. So, while most of the father’s deletions are found to be de novo – and not inherited from his father—ICSI now makes these mutations transmissible. “The risk of transmission is very real,” said Dr Page, “and the implications for genetic counselling are considerable.”

So far, the main target of interest in the c region of the Y chromosome is a subregion expressing the DAZ gene cluster (deleted in azoospermia), but it seems, according to a poster presented by Dr Silber and colleagues, that genes on the Y chromosome likely to affect spermatogenesis are not simply confined to the DAZ region. In a study of 180 infertile men with either azoospermia or severe oligospermia, 19 were found to have Y deletions (15/125 azoospermic, 4/55 oligospermic). Among these 19, 14 had deletions limited to the DAZ region and 12 of these had some degree of spermatogenesis (“however minute”). However, the remaining five of the Y-deleted men had deletions which extended proximal to the DAZ region, and none of these had any spermatogenesis whatsoever. Hence Dr Silber’s proposal that genetic activity beyond the DAZ region is likely to affect spermatogenesis.

“It is the total effect of deletions or mutations in all of these spermatogenesis genes on the Y chromosome that determines sperm production rates,” Dr Silber reported. “This is consistent with the view that the Y chromosome has collected many previous autosomal spermatogenesis genes, during evolution of higher primates, with resultant amplification and subsequent degeneration. This can explain why the human male has relatively poor spermatogenesis compared to other animals.”

A similar study from the group of Pellicer in Valencia, Spain, also found Y deletions outside the DAZ region—and indeed outside the c region. This group screened 128 men with severe sperm disorders who appeared candidates for ICSI for Y deletions. No deletions were found in any man whose sperm count was above 200,OOOIml.

However, among those in whom mutations were found, testicular biopsy revealed a variety of disorders (maturation arrest, Sertoli cell only, severe oligospermia) which appeared unrelated to the pattern of deletions. The Spanish group also proposed that the absence of DAZ appears to cause azoospermia, but that other genes outside that region may also modif’ the effects. And they also agreed that genetic screening for Y deletions in men with severe oligospermia or azoospermia prior to ICSI would now seem a wise decision, noting like Dr Page that “men with somatic Y deletion are likely to have boys with similar defects after treatment.”

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