Can a sperm selection technique improve embryo ploidy?
Academic Article
Overview
abstract
BACKGROUND: Spermatozoa with the highest motility retain a superior genomic integrity, while elevated sperm chromatin fragmentation (SCF) has been linked to a lower ability of the conceptus to develop and implant. Therefore, the utilization of a sperm selection method, such as microfluidic sperm selection (MFSS), is capable of reducing the SCF by yielding the most motile fraction of spermatozoa with highest embryo developmental competence. What remains unclear, however, is the causal mechanism that links SCF to an impaired embryo development. OBJECTIVES: To identify a relationship between SCF and an unexpectedly high proportion of embryo aneuploidy while addressing treatment options. MATERIALS AND METHODS: We identified couples with a high incidence of embryo aneuploidy in a previous Intracytoplasmic Sperm Injection (ICSI) cycle with preimplantation genetic testing for aneuploidy (PGT-A) using spermatozoa selected by density gradient (DG). Terminal deoxynucleotidyl dUTP transferase nick-end labeling (TUNEL) and neutral Comet assays were carried out on the semen specimens to assess total SCF and, specifically, double-stranded DNA (dsDNA) fragmentation. These couples underwent subsequent ICSI/PGT-A cycles with MFSS. Total SCF and dsDNA fragmentation was compared between the two sperm selection methods. Embryo aneuploidy, implantation, clinical pregnancy, delivery rates, as well as pregnancy losses were compared between the couples' historical DG and subsequent MFSS cycles. RESULTS: In 57 couples undergoing 71 ICSI/PGT-A cycles where DG sperm selection was carried out, a high incidence of aneuploid embryos (74.7%) resulted in poor implantation and no viable pregnancies. Testing for SCF inclusive of dsDNA breaks evidenced a SCF of 26.2% and dsDNA break of 3.6%. Following MFSS, total SCF and dsDNA fragmentation decreased to 1.9% and 0.3%, respectively (P<0.001). The embryo euploidy rate improved from 25.3% in the DG cycles to 42.5% in the MFSS cycles (P<0.001). The 6.7% implantation rate in the DG cycles increased to 65.5% in the MFSS cycles (P<0.001). Similarly, the clinical pregnancy rate rose from 10.5% (DG) to 64.6% (MFSS), resulting in a 62.5% delivery rate (P<0.001). DISCUSSION AND CONCLUSIONS: In couples with a relatively young female partner with a negative infertility work-up, and a male partner with semen parameters adequate for ICSI presenting with a high rate of embryo aneuploidy, an additional subtle male factor component may be the culprit. Thus, it is crucial to assess the SCF and test for the dsDNA breaks, which can eventually contribute to embryo chromosomal abnormalities. Given the inverse relationship between SCF and motility, selection of the most motile gamete by MFSS enhanced the proportion of spermatozoa with an intact genome contributing to the generation of more euploid embryos that are capable of implanting and yielding higher term pregnancies. This article is protected by copyright. All rights reserved.
