Andrologist The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine New York, New York
Objective: To determine whether the best way to retrieve spermatozoa with an intact genome is to obtain specimens directly from the testicle or from the ejaculate through a microfluidic device. DESIGN: During the course of 48 months, men with high DNA fragmentation in their ejaculate and related ART failure were offered testicular biopsy or microfluidic selection in order to identify spermatozoa with the highest genomic integrity. Spermatozoa from these two different origins were used for ICSI while controlling for maternal age. Fertilization, implantation, and pregnancy outcomes according to the sperm source used were recorded and compared. MATERIALS AND
Methods: A total 111 consenting men had their ejaculated spermatozoa screened for SCF by TUNEL using a commercial kit on a minimum of 500 cells with a normal threshold of £15%. Testicular biopsy was carried out by micro-TESE. Ejaculated spermatozoa were selected by microfluidic processing. Both sources of spermatozoa were used for ICSI.
Results: A total of 111 men (paternal age 36.6±5) with normal semen parameters (concentration of 41.5±25 x 106/mL, 42.1±14% motility, and increased SCF (22.4 ± 9%)) underwent 167 ICSI cycles with their female partners (maternal age 33.7±3) without achieving pregnancy. Subsequently, 22 couples underwent testicular biopsy. Those testicular specimens (concentration of 1.8±4 x 106/mL (P<0.01) and 5.0±11% motility (P<0.01), and an SCF of 12.6 ± 6% (P<0.0001)) were used in 37 ICSI cycles, yielding a fertilization rate of 61.6% (204/331, P<0.01), a superior implantation rate of 10.6% (9/85, P<0.01), a CPR of 23.5% (8/34, P<0.01), and a delivery rate of 17.6% (6/34, P<0.01). Another 22 couples underwent 28 ICSI cycles with ejaculated spermatozoa processed by a microfluidic device (concentration of 1.5±13 x 106/mL (P<0.01), 97.4±5% motility (P<0.01), and an SCF of 1.2 ±1%, lower than both raw and testicular specimens (P<0.0001)), resulting in a fertilization rate of 76% (203/266, P<0.01), an implantation rate of 26% (15/57, P<0.05), and a CPR of 50% (13/26, P<0.01), of which 2 patients delivered and 10 pregnancies are ongoing.
Conclusions: Our study demonstrates that sperm DNA fragmentation can severely lower the chances of achieving pregnancy by impairing embryonic development with consequent implantation failure. While retrieving spermatozoa directly from the germinal epithelium represents a valuable option, microfluidic sperm selection provides an optimal alternative by reducing surgical risks and costs.