P-066 The impact of male factor infertility on the chromosomal status of the pre-implantation embryo
Authors: Wirleitner B , Stecher A , Hruba M , Schuff M , Damko A.R , Murtinger M 
Published: June 2022

Abstract

Study question
Do poor sperm parameters and/or advance male age increase the rate of aneuploid blastocysts in PGT-A cycles?

Summary answer
In our study neither impaired semen quality nor advanced male age increased the rate of aneuploid blastocysts after PGT-A.

What is known already
The vast majority of aneuploidies in pre-implantation embryos arise from failures during the meiotic division of the oocyte. The extend of the paternal contribution to aneuploidies in the embryo is still discussed. It is known that that the rates of aneuploid spermatozoa increase from around 4.5% in normozoospermia by 2-6-fold in severe male factor infertility. Despite this fact, several studies reported no effect of sperm quality or male age on aneuploidy rates in IVF-embryos, however reports are controversial. Actually, severe male factor is still rated as an indication for PGT-A in several countries.

Study design, size, duration
In this retrospective multi-center study (2016-2018) we analyzed 298 PGT-A cycles from 179 patients. Calculations was performed for two groups according to female age (group 1 women ≤ 35 years; group 2 women ≥ 36 years). Sperm parameter were classified according to the WHO 2010 criteria and the motile sperm organelle morphology examination (MSOME) classification.

Participants/materials, setting, methods
Blastocyst culture was performed in a single step culture medium in a time-lapse incubator. Biopsy of 5-10 TE-cells was performed on culture day 5-6 on 1012 blastocysts. For whole genome amplification (WGA) PicoPlex (Rubicon Genomics) or SurPlex (BlueGenome/ Illumina) platforms were used. Next generation sequencing (NGS) was processed using the VeriSeq platform and data analysis by BlueFuse Multi (Illumina).

Main results and the role of chance
Comparing men with normozoospermia to men showing reduced sperm sperm parameters, we found in the group of women ≤ 35 years (group 1) a rate of 40.3% vs. 45.2% euploid blastocysts after TE biopsy. In the group of women ≥ 36 years (group 2) the rate of euploid blastocysts was 19.3% vs. 23.1% in normozoospermia vs. non-normozoospermia men. No difference in the number of blastocysts with uniform or mosaic chromosomal abnormalities were found between both groups. In a further analysis, no impact of sperm parameters on the number embryos with of sex chromosome aberrations was observed. With application of the MSOME-classification we found a similar picture. There was no difference in the rate of aneuploid blastocysts with o%, 1-3% or min. 4% normal forms in both groups. When focusing on male age by comparing men ≤ 49 years and ≥ 50 years, we found no difference in the rate of euploid blastocysts. In group the rate of euploid blastocysts was 42.1% vs. 47.5% and in group 2 the rates for euploid blastocysts were 21.8% vs. 19.8% in men ≤ 49 years and ≥ 50 years, respectively.

Limitations, reasons for caution
Chromosomal screening of all chromosomes using PGT-A will not detect small chromosomal aberrations such as small deletions, insertions or mutations. These small aberration could play an important role in male factor infertility. Focus if the present study was to test the efficiency of PGT-A in reduced sperm parameters.

Wider implications of the findings
In line with previous studies we found neither an impact of poor sperm quality, nor of advanced male age on the rate of euploid blastocysts after PGT-A. However, results published are controversial and male factor as indication for PGT-A has to be further evaluated.

Trial registration number
EK-2-8/2020