spermatogenic impairment

–

. Even though men with

infertility have increased sperm aneuploidy

(10, 11)

, most

practical clinical genetic testing for men with infertility is

currently limited to detection of chromosomal abnormalities

using

karyotype

and

Y-chromosome

microdeletion

analysis

(12)

Furthermore, research in male factor infertility predomi-

nantly is focused on men with abnormal semen parameters.

Indeed, men with grossly normal semen parameters and

RPL/IVF failure usually are not counseled on any particular

causes and are not encouraged to undergo any further testing.

It is important to realize that sperm aneuploidy rates can be

high even in men with normal sperm morphology

(13)

. Herein

we demonstrate that increased sperm aneuploidy is present in

men with normal strict sperm morphology.

Additionally, the most interesting

nding in our study

was that up to 45% of men with normal sperm density and

motility had abnormal FISH results. We believe that sperm

aneuploidy testing is indicated in this particular subpopula-

tion of men

—

that is, in men with normal semen parameters

and RPL or recurrent ART failure.

It is noteworthy that although the overall mean aneu-

ploidy seems to be small (0.18%

–

1.04%), it is up to four times

higher than the aneuploidy observed in controls (0.03%

–

0.38%). We also demonstrated an increase in aneuploidy in

both sex chromosomes and autosomes. It is expected that

meiotic recombination errors would affect both sex chromo-

somes and autosomes equally. In fact, in a study of men with

Klinefelter syndrome, sperm had increased disomy in chro-

mosome 21

(14)

. The marked increase in disomy is concern-

ing considering that trisomy 13, 18, and 21 result in Patau

syndrome, Edwards syndrome, and Down syndrome, respec-

tively. XY disomies and aneuploidies will lead to Klinefelter

syndrome (47,XXY) and Turner syndrome (46,XO). Couples

with abnormal sperm FISH should be counseled regarding

these possibilities and be urged to make informed reproduc-

tive choices.

Our study has several strengths as well as limitations.

The present report describes a very large series of men

with RPL who have also had sperm aneuploidy testing.

Furthermore, during the laboratory testing process, each pa-

tient sperm FISH sample was compared with a fresh semen

sample from a control. Consequently, although we only

had

ve normospermic men to use as controls, our data

are made more valid by the presence of inter-test controls.

Unfortunately, none of our

ve normozoospermic controls

attempted a pregnancy.

Regrettably, there are no universally accepted standards

for abnormal FISH results compared with those that exist

for strict morphology and DNA fragmentation. We calculated

mean aneuploidies from our normozoospermic controls and

ned a cutoff for abnormal FISH as 2 SDs above this

mean. Given that the sperm aneuploidy rates in our control

population were similar to those rates in published studies,

we are con

dent that our de

nition of abnormal FISH can

be applied to other studies as well.

In summary, up to 45% of men presenting with RPL and

normal sperm density, motility, and morphology can have

abnormal sperm aneuploidy. Abnormal sperm aneuploidy

can result in increased miscarriages and abnormal fetuses.

There is a need to reduce the burden associated with repeated

pregnancy attempts through either natural conception or

ART. Therefore, men presenting with recurrent pregnancy

loss or recurrent unexplained ART failure should consider

sperm aneuploidy testing to determine an underlying etiology

to enable better-informed reproductive choices. Further

controlled studies are necessary to determine the bene

FISH testing in men with RPL.

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VOL. 103 NO. 4 / APRIL 2015

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