Sperm selection for ICSI using hylauronan binding in males with high DNA fragmentation does not appear to select against sperm chromosome aneuploidies

Abstract

Hyalyronic acid (HA) surrounding the human oocyte acts as a natural selector for morphologically normal sperm with hyaluronic acid receptors and minimal DNA fragmentation. An association between high sperm DNA fragmentation and pregnancy loss has been reported, however the clinical value of selecting sperm for intracytoplasmic sperm injection (ICSI) in conjunction with hyaluronic acid binding assays remains to be clarified. The objective of this study was to evaluate the IVF outcomes of sperm with low HA-binding ability (≤65%) following physiological ICSI (PICSI). Retrospective study. Infertility patients with high sperm DNA fragmentation (≥14%; TUNEL assay) that underwent in vitro fertilization (IVF) and PICSI with low HA-binding ability (≤65%; n=23) were evaluated for IVF outcomes including fertilization, blastocyst development and chromosome constitution. Euploid frozen embryo transfer (FET) outcomes which included implantation rate with fetal heart tone, miscarriage rates and live birth rates, were compared to maternally age-matched infertility patients with normal sperm DNA fragmentation that underwent IVF with ICSI. Statistical analysis was performed using Students t-test and Chi square test where appropriate, significance at P<0.05. Mean maternal and paternal ages for these PICSI patients with low HA-binding ability were 37.9±3.7 and 40.9±6.2 years, respectively. High sperm DNA fragmentation (mean 21.5±6.3%) was the only male factor variable significantly associated with these couples. Fertilization and usable blastocyst development with PICSI selected sperm was observed at acceptable rates of 78% and 46%, respectively. Following trophectoderm biopsy, 38% of blastocysts were identified as euploid, significantly less than maternally age-matched ICSI patients at 52% (P<0.05). To date, there have been 12 euploid FETs resulting in comparable good clinical outcomes to maternally age-matched ICSI patients: 66.7% implantation with fetal heart tone, 83.3% live birth and no clinical pregnancy losses. There were 7 cycles that resulted in all aneuploid blastocysts with no FET, thereby calculating a 45.5% live birth rate from oocyte retrieval for PICSI patients with high sperm DNA fragmentation and low HA-binding ability. No significant differences were observed for the chromosomes involved in the errors between the aneuploid blastocysts from the PICSI patients with low HA-binding ability and the maternally age-matched ICSI patients. In conclusion, this study revealed that PICSI patients with high sperm DNA fragmentation and low HA-binding ability have significantly higher blastocyst aneuploidy rates than maternally age-matched ICSI patients. Nevertheless, following a euploid FET these patients exhibited positive clinical outcomes and no pregnancy losses to date.