A microfluidic device for selecting the most progressively motile spermatozoa yields a higher rate of euploid embryos

Abstract

We tested a novel approach for treating couples with complete and persistent embryo aneuploidy. Using a microfluidic device, we selected spermatozoa with the highest progressive motility and genomic integrity, capable of generating euploid embryos. In a 19-month period, seven couples with a history of high sperm chromatin fragmentation (SCF) and persistent embryo aneuploidy underwent a cycle of ICSI in which semen specimens were processed in a standard fashion or by microfluidics. SCF was assessed by TUNEL. Fertilization and clinical pregnancy rates were assessed and compared between the two preparation methods, and preimplantation genetic testing for aneuploidy (PGT-A) was performed on the resulting embryos. Consenting men had their ejaculates screened by standard semen analysis according to WHO 2010 criteria. Specimens were processed by density gradient and microfluidic sperm selection (MFSS). SCF was measured by TUNEL utilizing a commercial kit (In Situ Cell Death Detection Kit, Roche). At least 500 spermatozoa were counted under fluorescent microscopy, with an established threshold of 15%. Seven couples (average maternal age, 38.3±6 years; average paternal age, 44.2±11 years) underwent 19 ICSI cycles. An average semen concentration of 11.5±16x106/mL, 18.5±16% motility, 2.0±0% normal morphology, and an SCF of 29.2±10% were found. After selection by density gradient, the total motility of the sperm samples was 34.2±26%, resulting in a 60.4% fertilization rate. These cycles only generated 5 euploid embryos out of 23, which yielded two pregnancies, both resulting in miscarriage. Couples subsequently underwent 7 ICSI cycles in which the spermatozoa were processed by MFSS, which generated 98%±4 (P<0.0001) motility and an increased 4% morphology, while the SCF dropped to only 1.6±1 (P<0.0001). Although the fertilization rate was 67.1%, 7 euploid blastocysts out of 14 (50%) were obtained, yielding 5 out of 7 ongoing clinical pregnancies (71.4%; P<0.001). Selecting a genomically competent male gamete may enhance the chances of obtaining a euploid conceptus for transfer. Couples with a persistent number of aneuploid embryos that cannot be solely attributed to the female partner may benefit from the selection of spermatozoa with intact chromatin to increase the chances of conceiving a child.