Fluorescence in situ hibridization (FISH) studies in carriers of microdeletions in the Y-chromosome

Abstract

OBJECTIVE: To assess the incidence of chromosomal abnormalities in embryos and spermatozoa from patients with microdeletions in the SRY and AZF regions of the Y chromosome. DESIGN: Retrospective study. MATERIALS AND METHODS: A total of 24 couples diagnosed as severe male factor infertility were included. All of them had normal karyotype and they were checked for microdeletions in the SRY, AZF regions of the Y chromosome. Five of them showed microdeletions, whereas in the remaining 19 no microdeletions were found. FISH analysis for chromosomes 13, 18, 21, X and Y were performed in sperm samples from 8 patients. All couples underwent a Preimplantation Genetic Diagnosis cycle for Aneuploidy Screening (PGD-AS). Embryo biopsy was performed on day-3 and chromosomes 13, 15, 16, 18, 21, 22, X and Y were analysed. PGD-AS results were compared between two groups of patients, with and without Y-microdeletions and a control group of fertile patients undergoing PGD due to sex-linked diseases. RESULTS: In the group of patients with Y-microdeletions, the percentage of cycles with embryo transfer and blastocyst rates were half than in patients without Y-microdeletions and the control group. Five out of seven patients without Y-microdeletions had abnormal FISH results in sperm. Only one patient with Y-microdeletions had a FISH study in sperm and was extremely abnormal with 29.8% of aneuploidies for the sex chromosomes. In this patient four out of six embryos analysed displayed sex chromosome abnormalities.Tabled 1Patients without Y-microdeletionsPatients with Y-microdeletionsControlsMean age (SD)34.2 (2.2)32.4 (1.2)33.0 (2.4)No. of cycles19533% Cycles with transfer79.040.087.5% Pregnancies53.310042.9Implantation rate45.850.034.4% Miscarriages12.50.016.7No. of analysed embryos7817200% Abnormal embryos61.5aStatistical differences with control group. P<0.05.70.6aStatistical differences with control group. P<0.05.34.0Blastocyst rate66.7bStatistical differences between the two groups of patients. P<0.05.35.3bStatistical differences between the two groups of patients. P<0.05.50.25% Sex chromosome abnormalities17.3aStatistical differences with control group. P<0.05.bStatistical differences between the two groups of patients. P<0.05.41.2aStatistical differences with control group. P<0.05.bStatistical differences between the two groups of patients. P<0.05.7.5a Statistical differences with control group. P<0.05.b Statistical differences between the two groups of patients. P<0.05. Open table in a new tab CONCLUSIONS: Patients with severe male factor infertility have an increased risk of chromosomally abnormal embryos. In the patients with Y-microdeletions this increase was more remarkable, mostly for sex chromosomes. The presence of microdeletions in the Y chromosome could have an effect in male meiosis, as can be deduced from the fact that in one of these patients an extremely high incidence of aneuploidies for the sex chromosomes was observed.