Magnetic-activated cell sorting (MACS) can be used to separate apoptotic sperm with high proportions of fragmented DNA from the rest, thus improving the overall quality of the seminal sample. Therefore, the aim of this retrospective study was to investigate the efficiency of the MACS technique to increase reproductive outcomes in patients with high levels of sperm DNA fragmentation (SDF) undergoing intracytoplasmic sperm-injection (ICSI) cycles. In this study, we analyzed a total of 724 assisted-reproduction-technique (ART) cycles that were divided into two groups: the study group (n = 366) in which the MACS selection technique was performed after density-gradient centrifugation (DGC), and the control group (n = 358) in which only DGC was used for sperm selection. Reproductive outcomes were analyzed in both groups according to three different ART procedures: preimplantation genetic testing for aneuploidy (PGT-A), and autologous and oocyte-donation cycles. The MACS group showed significantly lower miscarriage rates in autologous ICSI cycles, higher pregnancy rates in oocyte-donation cycles, and a significant increase in live-birth rates in both autologous and oocyte-donation cycles. Overall, these results suggested that the MACS technique can be effectively used to eliminate sperm with high SDF levels, and therefore may help to improve reproductive outcomes in couples undergoing ART.

Clinical outcome in assisted reproduction techniques (ARTs) is mainly influenced by the quality of gametes used. It is known that a high percentage of sperm DNA fragmentation (DNAf) decreases the success of ART clinical results. Therefore, techniques such as magnetic-activated cell sorting (MACS) help to improve results in cases of patients with a high percentage of DNAf. Cryopreservation of sperm in donor intrauterine insemination (D-IUI) treatments increases sperm DNAf, so patients using these sperm samples can benefit from using this technique. This prospective randomized national multicenter study analyzed clinical outcomes of 181 D-IUI treatments. MACS was performed after density gradient centrifugation (DGC) in 90 thawed semen donor samples (MACSG), whereas only DGC was performed in 91 thawed semen donor samples (CG). To our knowledge, this is the first study analyzing the effect of MACS on D-IUI cycles. Our results show no significant differences in gestation, live birth, or miscarriage rates between the two groups. We believe that further studies with a larger sample size are needed to evaluate the application of MACS in combination with standard IUI donor sperm preparations in fertility clinics.

The application of MACS non-apoptotic sperm selection in infertility clinics is controversial since the published literature does not agree on its effect on reproductive outcomes. Therefore, it is not part of the routine clinical practice. Classical measures of reproductive success (pregnancy or live birth rates per ovarian stimulation) introduce a bias in the evaluation of a technique’s effect, since only the best embryo is transferred. This retrospective, multicenter, observational study evaluated the impact of MACS on reproductive outcomes, measuring results in classical parameters and cumulative live birth rates (CLBR). Data from ICSI cycles using autologous oocyte in Spanish IVIRMA fertility clinics from January 2008 to February 2020 were divided into two groups according to their semen processing: standard practice (reference: 46,807 patients) versus an added MACS sperm selection (1779 patients). Only when measured as CLBR per embryo transferred and per MII oocyte used was the difference between groups statistically significant. There were no significant differences between MACS and reference groups on pregnancy and live birth rates. In conclusion, results suggest that non-apoptotic sperm selection by MACS on unselected males prior to ICSI with autologous oocytes has limited clinical impact, showing a subtle increase in CLBR per embryo transferred.

This multicenter retrospective cohort study assesses the effect of high paternal DNA fragmentation on the well-being of the woman during pregnancy and the health of the newborn delivered. It was performed with clinical data from 488 couples who had a delivery of at least one newborn between January 2000 and March 2019 (243 used autologous oocytes and 245 utilized donated oocytes). Couples were categorized according to sperm DNA fragmentation (SDF) level as ≤15% or >15%, measured by TUNEL assay. Pregnancy, delivery, and neonatal outcomes were assessed. In singleton pregnancies from autologous cycles, a higher but non-significant incidence of pre-eclampsia, threatened preterm labor, and premature rupture of membranes was found in pregnant women from the >15%SDF group. Additionally, a higher proportion of children were born with low birth weight, although the difference was not statistically significant. After adjusting for potential confounders, these couples had lower odds of having a female neonate (AOR = 0.35 (0.1–0.9), p = 0.04). Regarding couples using donor’s oocytes, pregnancy and neonatal outcomes were comparable between groups, although the incidence of induced vaginal labor was significantly higher in the >15% SDF group (OR = 7.4 (1.2–46.7), p = 0.02). Adjusted analysis revealed no significant association of elevated SDF with adverse events. In multiple deliveries from cycles using both types of oocytes, the obstetric and neonatal outcomes were found to be similar between groups. In conclusion, the presence of an elevated SDF does not contribute to the occurrence of clinically relevant adverse maternal events during pregnancies, nor does it increase the risk of worse neonatal outcomes in newborns. Nevertheless, a higher SDF seems to be related to a higher ratio of male livebirths.