Do sperm factors influence embryonic aneuploidy? Long live the oocyte
Authors: Fouks Yuval , Vaughan Denis , Sripada Veda , Penzias Alan S , Bortoletto Pietro , Sakkas Denny 
Published: October 2024

Abstract

STUDY QUESTION
What is the impact of male age- and sperm-related factors on embryonic aneuploidy?

SUMMARY ANSWER
Using a 3-fold analysis framework encompassing patient-level, embryo-level, and matching analysis, we found no clinically significant interactions between male age and sperm quality with embryo ploidy.

WHAT IS KNOWN ALREADY
While the effect of maternal age on embryo chromosomal aneuploidy is well-established, the impact of male age and sperm quality on ploidy is less well-defined.

STUDY DESIGN, SIZE, DURATION
This retrospective cohort study analyzed autologous preimplantation genetic testing for aneuploidy (PGT-A) and frozen embryo transfer cycles from December 2014 to June 2021. The study involved 11 087 cycles from 8484 patients, with a total of 35 797 embryos.

PARTICIPANTS/MATERIALS, SETTING, METHODS
The aneuploidy rate, calculated as the ratio of aneuploid blastocysts to the total number of blastocysts biopsied in a single treatment cycle, was evaluated. In the embryo-level analysis, the main outcome measure was the ploidy state of the embryos. The study employed a multifaceted analytical approach that included a patient-level analysis using generalized linear mixed models, an embryo-level analysis focusing on chromosomal ploidy, and a propensity score matching analysis contrasting groups with distinct ploidy rates (0% and 100%). There were no interventions as this was an observational study of PGT-A cycles.

MAIN RESULTS AND THE ROLE OF CHANCE
No clinically relevant factors influencing ploidy rate related to male and sperm quality were revealed. In contrast, female age (coefficient = −0.053), BMI (coefficient = 0.003), prior ART cycle (coefficient = −0.066), and number of oocytes retrieved (coefficient = −0.018) were identified at the patient level. Embryo analysis identified age (coefficient = −0.1244) and ICSI usage (coefficient = −0.0129) as significant factors. Despite these, no significant interactions between male and female assessed factors on the ploidy rate emerged. Propensity score matching between maximal (100% vs 0%) euploid rates did not reveal significant differences of influence by male age and sperm quality.

LIMITATIONS, REASONS FOR CAUTION
The focus on patients having blastocyst biopsy for PGT-A may not reflect the broader IVF population. Other semen quality parameters like DNA fragmentation were not included. Exclusion of embryo mosaicism from the analysis could affect aneuploidy rate interpretations. There may also be unmeasured influences like lifestyle or environmental factors.

WIDER IMPLICATIONS OF THE FINDINGS
Male age and sperm quality parameters were consistent across both maximal and minimal ploidy rate comparisons. No significant clinical characteristics related to the factors assessed for the male-influenced blastocyst ploidy status, confirming the dominancy of the oocyte and female age.

STUDY FUNDING/COMPETING INTEREST(S)
The study was not funded. There are no competing interests.

TRIAL REGISTRATION NUMBER
N/A.