This study aimed to compare sperm parameters and reproductive outcomes after sperm selection using microfluidic chips versus conventional techniques (swim-up/density gradients). A systematic review and meta-analysis were performed after the extraction of relevant data from thirty-nine studies that met the inclusion criteria. Mean difference or odds ratio was calculated for each outcome. The analysis revealed that sperm selection using microfluidics yields lower sperm DNA fragmentation (MD = −9.98 [−13.19, −6.76], p < 0.00001), increased progressive motility (MD = 14.50 [7.84, 21.71], p = 0.04), total motility (MD = 10.68 [6.04, 15.31], p < 0.00001) and morphology (MD = 1.41 [0.67, 2.16], p = 0.0002). Significant differences were also found in the fertilization rate/MII oocyte microinjected (OR = 1.22 [1.01, 1.46], p = 0.04), implantation rate/embryo transfer (ET) (OR = 4.51 [1.42, 14.37], p = 0.01), clinical pregnancy/ET (OR = 1.73 [1.22, 2.45], p = 0.002), ongoing pregnancy/ET (OR = 1.99 [1.03, 3.83], p = 0.04), live birth rate/first cycle (OR = 1.59 [1.12, 2.24], p = 0.009) and per all embryo transfer (OR = 1.65 [1.06, 2.55], p = 0.03). No significant differences were found in embryo euploidy/number of biopsied blastocysts (OR = 1.34 [0.88, 2.04], p = 0.77), biochemical pregnancy/ET (OR = 1.23 [0.84, 1.80], p = 0.29), miscarriage rate/cycle (OR = 0.84 [0.54, 1.31], p = 0.35) and per pregnancy (OR = 0.71 [0.50, 1.02], p = 0.07), live birth rate/first embryo transfer (OR = 1.60 [0.80, 3.22], p = 0.18) and per concluded cycle (OR = 1.03 [0.53, 2.00], p = 0.92). To summarize, microfluidics may offer a beneficial approach in certain situations, particularly for patients with elevated sperm DNA fragmentation (SDF) levels. However, its integration into routine clinical practice cannot be justified yet in terms of cost-effectiveness. Additional research is needed to provide more comprehensive data on reproductive outcomes, especially live birth rates, which remain the ultimate goal of assisted reproductive technologies.

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 study aimed to compare sperm DNA fragmentation (SDF) levels between ejaculate and testicular sperm and evaluate clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles using testicular sperm (T-ICSI) versus ejaculate sperm (E-ICSI) in males with high ejaculate SDF, prior ICSI failures, or severe male infertility. A systematic review of major databases and a subsequent meta-analysis were performed to compare clinical outcomes in men with high SDF, oligozoospermia, or prior ICSI failures undergoing T-ICSI or E-ICSI. Thirteen studies met the inclusion criteria. Outcomes analyzed included SDF levels, fertilization rate (FR), clinical pregnancy rate (CPR), live birth rate (LBR) per embryo transfer (ET), and miscarriage rate (MR) per pregnancy. The mean difference (MD) and odds ratio (OR) were calculated for each outcome. Paired assessments of SDF showed significantly lower levels in testicular sperm compared to ejaculated sperm (MD = −25.42 [−31.47, −17.30], p < 0.00001). While no significant difference in FR was observed in T-ICSI cycles overall (OR = 0.94 [0.74, 1.20]), a subgroup analysis revealed significantly higher FR with E-ICSI in men with oligozoospermia and no prior ICSI failures (OR = 0.61 [0.52, 0.71], p < 0.00001). CPR was significantly higher in T-ICSI cycles (OR = 2.13 [1.35, 3.36], p < 0.001; n = 540 ET), along with a significantly lower MR (OR = 0.31 [0.14, 0.70], p = 0.004; n = 35) and increased LBR (OR = 2.40 [1.32, 4.36], p = 0.004; n = 446 ET). In conclusion, using testicular sperm in cases of elevated ejaculate SDF, oligozoospermia, or prior failed ICSI cycles enhances the selection of sperm with lower DNA damage, leading to improved pregnancy rates, reduced miscarriage rates, and higher live birth rates. However, the studies included were rated as having a moderate to serious risk of bias. Further well-designed randomized controlled trials are necessary to confirm these findings with stronger evidence.

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.

Background: Concomitant with delays in childbearing, concerns have been raised of whether advanced paternal age is associated with adverse reproductive outcomes, but the evidence is controversial in part due to the uncertain threshold in which to consider advanced paternal age and confounding maternal factors. This retrospective study aimed to evaluate the effect of paternal age on reproductive outcomes related to the pregnancy and perinatal health of the offspring. Methods: We retrospectively evaluated 16,268 cases of patients who underwent IVF or ICSI (using autologous sperm and donated oocytes, between January 2008 and March 2020, at Spanish IVIRMA clinics. Patients were divided based on paternal age at conception [≤30 (n = 204), 31–40 (n = 5752), and >40 years (n = 10,312)], and the differences in obstetrical and perinatal outcomes were analyzed by descriptive analysis, followed by univariate and multivariate analysis. Results: Fathers 31–40 and >40 years old were associated with lower odds of caesarean delivery [AOR 0.63 (95% CI, 0.44–0.90; p = 0.012) and AOR 0.61 (95% CI, 0.41–0.91; p = 0.017), respectively] and longer pregnancies [ARC 5.09 (95% CI, 2.39–7.79; p < 0.001) and ARC 4.54 (95% CI, 1.51–7.58; p = 0.003), respectively] with respect to fathers ≤30 years old. Furthermore, fathers aged 31–40 years old had lower odds of having a female infant (AOR, 0.70; 95% CI, 0.49–0.99; p = 0.045) than those ≤30. The rest of obstetrical and perinatal outcomes, which we deemed more medically-relevant as they were considered serious for health, were comparable between groups with our adjusted model. Conclusions: Despite this hopeful message to fathers of advanced paternal age, future studies should consider the short- and long-term outcomes of the offspring and try to better elucidate the associations of advanced paternal age with reproductive outcomes and the molecular mechanisms underlying the observed associations.