Fluorescence in situ hybridization
detects increased sperm aneuploidy
in men with recurrent pregnancy loss
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.,
and Larry I. Lipshultz, M.D.
Department of Urology,
Center for Reproductive Medicine, and
Department of Molecular and Cellular Biology, Baylor
College of Medicine, Houston, Texas
To investigate, in men presenting with recurrent pregnancy loss (RPL), the prevalence of sperm autosome and sex chromo-
Male infertility clinic.
A total of 140 men with RPL provided semen samples, and
ve normozoospermic controls provided 140 semen samples for
comparison. Recurrent pregnancy loss, documented in the female partners, was de
ned as a prior miscarriage and/or recurrent IVF/in-
tracytoplasmic 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. (Fertil Steril
2015 by American Society for
Male infertility, genetics, aneuploidy, FISH
You can discuss this article with its authors and with other ASRM members at
Use your smartphone
to scan this QR code
and connect to the
discussion forum for
this article now.*
* Download a free QR code scanner by searching for
in your smartphone
s app store or app marketplace.
nfertility is the inability to produce
offspring despite actively attempt-
ing to do so for 1 year. It affects
approximately 15% of all couples,
with 50% of cases being ascribed to a
. Many factors that
fertility (i.e., oligozoospermia, astheno-
zoospermia) can be overcome with the
use of assisted reproductive technology
(ART), such as IVF with intracytoplas-
mic sperm injection (ICSI). These tech-
considered to be infertile to now father
children of their own.
Offspring conceived by ICSI have
been shown to be at increased risk for
aneuploidies, in particular of the sex
. Given that ICSI is
a relatively new technology (
old), the long-term effects are still
poorly understood. Indeed, one of the
primary shortcomings of ICSI is the
. Although close attention
is paid to selecting a sperm that dis-
plays the best possible combination of
sperm parameters (i.e., motility and
Received December 15, 2014; revised and accepted January 20, 2015; published online February 20,
R.R. has nothing to disclose. J.M.S. has nothing to disclose. J.R.K. has nothing to disclose. P.J.C. has
nothing to disclose. D.J.L. has nothing to disclose. L.I.L. has nothing to disclose.
R.R. and J.R.K. are K12 scholars supported by a Male Reproductive Health Research Career Develop-
ment Physician-Scientist Award (grant HD073917-01) from the
Eunice Kennedy Shriver
Institute of Child Health and Human Development Program (to D.J.L.).
Reprint requests: Larry I. Lipshultz, M.D., Department of Urology, Baylor College of Medicine, 6624
Fannin Street, Suite 1700, Houston, Texas 77030 (E-mail:
Fertility and Sterility® Vol. 103, No. 4, April 2015 0015-0282/$36.00
Copyright ©2015 American Society for Reproductive Medicine, Published by Elsevier Inc.
VOL. 103 NO. 4 / APRIL 2015
ORIGINAL ARTICLES: ANDROLOGY