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Are male chromosomal abnormalities associated with repeated implantation failure and pregnancy loss? By manara99 on August 18, 2015

 

Diagnosing male causes of recurrent pregnancy loss and repeated IVF failure can be quite difficult.  It is well understood that the standard semen analysis will fail to identify all males with abnormally functioning sperm.  Sperm count, motility, and microscopic assessment may all be quite normal in some men who have poor sperm quality and function.  When a specific technique called fluorescence in-situ hybridization (FISH) is used to evaluate the sperm of men whose partners have experienced repeated pregnancy losses or multiple failed IVF treatments, an increased incidence of sperm chromosomal abnormalities has been found.  If the sperm count, motility, and microscopic evaluation are abnormal in these patients, then the incidence of chromosomal abnormalities is even higher. 

 

Studies of products of conception have revealed that 50-80% are genetically abnormal, and approximately 8-12% of these are of paternal origin. Today, we have the capability of performing chromosomal analysis of sperm through fluorescence in-situ hybridization (FISH).  However, chromosomal sperm analysis is not yet part of the standard infertility evaluation for infertile couples or for couples who have experienced recurrent pregnancy loss.  Pre-implantation genetic screening of embryos for genetic abnormalities is available and is currently being offered to patients in some clinics.  A paper  published in the July 8, 2015 issue of “Reproductive BioMedicine Online” reviews the existing literature on this subject and addresses several important questions:

 

1)   What is the incidence of sperm chromosomal abnormality (aneuploidy) in cases of repeated abortion and implantation failure?

2)   Which patients would benefit from FISH analysis of spermatozoa?

3)   Is there any advantage to performing FISH before or instead of PGS?

 

 

FINDINGS

 

Studies have demonstrated that men with low sperm counts (less than 20 million/cc) do have an increased incidence of genetic abnormalities in their sperm.

If the sperm counts were extremely low (less than 5 million/cc), the incidence of sperm chromosomal abnormality was even greater.

 

Another study demonstrated that in men with low sperm counts (less than 20 million/cc) the percentage of chromosomal abnormality (aneuploidy) in sperm was greater than 3%. These findings were associated with 64.87% abnormal embryos.  In controls with normal sperm counts, the incidence of chromosomally abnormal embryos was 35.15%.

 

In one study, the results of FISH done on spermatozoa were not predictive of embryonic chromosomal abnormalities.  In this study, embryos were studied with PGD (pre-implantation screening) and the FISH study done on the men before the IVF treatment cycle did not contribute to treatment outcomes. PGD played an important part in transferring only chromosomally normal embryos.

 

DISCUSSION

 

A thorough evaluation will only identify the cause of recurrent pregnancy loss in 30% of couples.  Some studies have proven that pathologies such as recurrent pregnancy loss, repeated IVF failure, structural chromosomal abnormalities in the male, and low sperm counts are associated with increased miscarriage due to sperm chromosomal abnormalities.

 

The authors of this article conclude that the value of sperm chromosomal analysis lies primarily in diagnosis of infertility rather than in its treatment.

 

The studies done thus far looking at chromosomal analysis of sperm and its ability to provide beneficial information for couples have come to contradictory conclusions.  In one study, FISH before PGD did not improve outcomes.  In another study FISH did predict PGD and served as a good alternative to the more invasive test (PGD).  In another study, even PGD did not improve outcomes in patients with increased sperm chromosomal abnormalities. In yet another study in a population with increased sperm chromosomal abnormalities, the chances of a viable pregnancy were greater if PGD was done.

 

In summary, the advantages of doing FISH chromosomal analysis of sperm before PGD remain uncertain and additional randomized controlled trials are needed to address this question.  In couples with repeated pregnancy loss or recurrent IVF failure, sperm chromosomal testing may offer an explanation, but unfortunately does not provide a well-validated superior therapeutic pathway. 

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Dr. Louis R. Manara

Center for Reproductive Medicine and Fertility

Dr. Louis R. Manara and the Center for Reproductive Medicine and Fertility team are dedicated to helping families achieve parenthood through safe, versatile, and personalized treatment options. We are affiliated with several noteworthy organizations including:

  • American Society for Reproductive Medicine
  • Society for Assisted Reproductive Technology
  • American Osteopathic Association®

​If you are struggling with infertility, a professional diagnosis is the best way to explore your treatment options. Schedule your initial consultation today by contacting us online or calling us at (856) 767-0009.

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