Increased chromosome X, Y, and 18 nondisjunction in sperm from infertile patients that were identified as normal by strict morphology: implication for intracytoplasmic sperm injection
Hm. Ryu et al., Increased chromosome X, Y, and 18 nondisjunction in sperm from infertile patients that were identified as normal by strict morphology: implication for intracytoplasmic sperm injection, FERT STERIL, 76(5), 2001, pp. 879-883
Objective: To determine the incidence of nondisjunction for chromosomes X,
Y, and 18 using fluorescence in situ hybridization (FISH) on morphologicall
y normal sperm from infertile men who are candidates for ICSL.
Design: After standard hematoxylin staining, sperm with normal morphology w
ere identified using Kruger's strict morphology criteria. The location of e
ach normal-appearing sperm was recorded using an electronic microstage loca
tor. Slides were subsequently subjected to FISH for detection of chromosome
s X, Y, and 18 (control probe). Nuclei were relocated and analyzed under th
e fluorescent microscope.
Setting: University-affiliated IVF and intracytoplasmic sperm injection pro
gram.
Patient(s): Men classified as infertile on the basis of abnormal strict mor
phology (<4% by Kruger's criteria). For controls, normal fertile men (n=6)
were also analyzed.
Intervention(s): Semen smears were obtained retrospectively from infertile
(n=8) and fertile (n=6) men.
Main Outcome Measure(s): Ploidy of each cell was determined according to th
e number of signals detected for each probe.
Result(s): Approximately 100-150 morphologically normal sperm were identifi
ed and located in each case. Subsequent FISH analysis of these normal sperm
showed aneuploidy to range from 1.8% to 5.5% in the infertile group as com
pared with 0 to 2.6% among the control fertile group. Statistically signifi
cant differences in the incidence of aneuploidy for the sex chromosomes as
well as for all three (X, Y, and 18) chromosomes was observed.
Conclusion(s): Although 95% to 98% of the sperm were found to be normal for
X, Y, and 18, our findings show that infertile couples undergoing ICSI are
likely to be at an increased risk for having a genetically abnormal concep
tus as compared with the fertile controls. These results demonstrate that n
ormal morphology is not an absolute indicator for the selection of genetica
lly normal sperm. Hence, observed pregnancy failures among ICSI patients ma
y in part be due to the selection of aneuploid sperm. (C) 2001 by American
Society for Reproductive Medicine.