A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure

Objective To test a novel method to select spermatozoa with high chromatin integrity. Design Specimens with high sperm chromatin fragmentation (SCF) were selected by density gradient selection (DGS) and microfluidic sperm sorting (MSS). Setting Academic medical center. Patient(s) Ejaculates from consenting men were processed by DGS/MSS. Couples underwent ICSI cycles with spermatozoa processed by DGS/MSS. Clinical outcomes were evaluated after embryo transfer. Intervention(s) SCF was measured by TUNEL. ICSI with spermatozoa selected by DGS and MSS was performed. Main outcome measure(s) Fertilization, embryo implantation, and pregnancy outcomes were compared between DGS and MSS. Result(s) A total of 23 men had an average SCF of 20.7 +/- 10%. After DGS and MSS, the SCF was 12.5 +/- 5% and 1.8 +/- 1%, respectively. In couples who underwent ICSI, the average SCF was 28.8 +/- 9%, which fell to 21.0 +/- 9% after DGS and 1.3 +/- 0.7% after MSS. Four couples underwent 11 ICSI cycles with DGS and achieved one (25%) pregnancy that resulted in pregnancy loss. In four subsequent ICSI cycles with MSS, an ongoing clinical pregnancy rate of 50% was achieved. Five additional couples underwent 12 cycles of ICSI with DGS. After preimplantation genetic testing for aneuploidy, 30.3% of the embryos were euploid. One pregnancy was achieved, resulting in pregnancy loss. With MSS, 31.5% of the embryos were euploid and 4 couples obtained a pregnancy. Finally, sixteen couples underwent 20 ICSI cycles solely with MSS at our center. Of these couples, 8 had failed 13 ICSI cycles with DGS elsewhere. These couples achieved an overall implantation of 34.5% (10/29) and a pregnancy rate of 58.8% (10/17). Conclusion(s) Microfluidic selection yielded spermatozoa with optimal genomic integrity and improved chances of obtaining a euploid conceptus.