Fluorescence in situ hybridization detects increased sperm aneuploidy in men with recurrent pregnancy loss

Men with recurrent pregnancy loss and normal semen parameters exhibit increased sperm aneuploidy detected by fluorescence in situ hybridization.

Ranjith Ramasamy, M.D., Jason M. Scovell, B.A., Jason R. Kovac, M.D., Ph.D., Peter J. Cook, B.A., Dolores J. Lamb, Ph.D., Larry I. Lipshultz, M.D.

Volume 103, Issue 4, Pages 906-909


To investigate, in men presenting with recurrent pregnancy loss (RPL), the prevalence of sperm autosome and sex chromosome aneuploidy.

Retrospective study.

Male infertility clinic.

A total of 140 men with RPL provided semen samples, and five normozoospermic controls provided 140 semen samples for comparison. Recurrent pregnancy loss, documented in the female partners, was defined as a prior miscarriage and/or recurrent IVF/intracytoplasmic sperm injection failure.

Fluorescence in situ hybridization (FISH) was used to detect numerical abnormalities in sex chromosomes (X, Y) and autosomes (13, 18, 21) in ejaculated sperm.

Main Outcome Measure(s):
Sperm aneuploidy in men with RPL and normozoospermic controls.

Men with RPL had a greater percentage of sperm aneuploidy within the sex chromosomes and chromosomes 18 and 13/21 (1.04% vs. 0.38%; 0.18% vs. 0.03%; 0.26% vs. 0.08%). In total, 40% of men with normal sperm density and motility had abnormal sperm aneuploidy in all the chromosomes analyzed. Men with abnormal sperm density and motility had a higher proportion of sperm sex chromosome aneuploidy than men with normal density/motility (62% vs. 45%). Men with normal strict morphology (>4%) had lower rates of sex chromosome and sperm aneuploidy than men with abnormal strict morphology (28% vs. 57%). There was no association between sperm DNA fragmentation and sperm aneuploidy.

Men with RPL have increased sperm aneuploidy compared with controls. A total of 40% of men with RPL and normal sperm density/motility had abnormal sperm aneuploidy. Men with oligoasthenozoospermia and abnormal strict morphology had a greater percentage of sperm aneuploidy compared with men with normal semen parameters.

  • Bob Brannigan

    Congratulations to the team at Baylor on this work. We had an interesting discussion about this research at our PG Course at AUA2015 last week. It will be interesting to see how this technique is increasingly integrated into clinical care moving forward.

  • Ali Dabaja

    Interesting and compelling data, any of these men underwent karyotyping?

    • ranjithrama

      Karyotyping was done only in men with severe oligospermia – none of them had abnormalities in this cohort

  • Additional specialized testing that be utilized to evaluate infertile men.

    This may explain the ever so frustrating scenario of the infertile man with bulk “normal” semen analysis parameters.

    Question: What do we do with this data? Can we treat this? Can we pre-screen the sperm and then have a way to select out the normal sperm for ICSI?

    • ranjithrama

      These men had either recurrent pregnancy loss or recurrent IVF failure. I think PGS is a good option if the couple undergoes another ART cycle (so embryos without aneuploidy can be implanted). If they attempt natural conception, then blood test (fetal DNA @ 10 weeks) or CVS @ 12 weeks could determine if there is an abnormality with the developing fetus.

  • msamplaski

    The role of sperm aneuploidy continues to emerge. I would be interested to know if the specific aneuploidy correlated with the timing of pregnancy loss. Regardless, these are compelling data.

    • ranjithrama

      Mary, we don’t have that data but would be interesting to look at. Most of RPL in this study was first trimester loss.

  • Sperm FISH has emerged as another way to assess male fertility beyond routine semen analysis. It is interesting that a high % of aneuploidy was observed in normospermic men with history of RPL. my question for the authors is how do you counsel these men with abnormal sperm aneuploidy?

    • ranjithrama

      Mike, I think we should counsel them about risks of aneuploidy in the developing fetus or in the embryo if they use ART. Please see response above to Ed for options that the couple have.

Translate »