When does sperm impact fertilization success? The incidence of sperm-related poor fertilization after ICSI in 13 632 matched oocyte donation cycles

Abstract STUDY QUESTION What is the true incidence of male factor-related poor fertilization in ICSI cycles when analyzed using a matched oocyte donation model to investigate the influence of sperm-related factors on fertilization outcomes? SUMMARY ANSWER In ICSI cycles with donor oocytes, male factor-related poor fertilization occurs in 3.1% of cases and contributes to 84.1% of all poor fertilization outcomes (≤30% fertilization rate). WHAT IS KNOWN ALREADY Opting for oocyte donation is a complex decision for couples, involving significant financial and long-term considerations. This decision is typically driven by presumed female infertility, as male fertility diagnostics remain limited. While ICSI is a highly effective treatment, cases of poor or complete fertilization failure can still occur, even when sperm parameters appear normal. This suggests the presence of unidentified male-related factors. However, the precise incidence of these factors remains poorly understood. This study aims to address this gap, offering a unique perspective, by employing a matched oocyte donation model to investigate the influence of sperm-related factors on fertilization outcomes. STUDY DESIGN, SIZE, DURATION This retrospective cohort study analyzed 13 632 oocyte donation ICSI cycles, derived from 7455 controlled ovarian stimulations of 2963 unique oocyte donors. The data were obtained from a single center from January 2015 to December 2022. Sibling oocytes (n ≥ 5) from each oocyte donor were utilized for at least two different recipients, allowing comparisons under varying paternal conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS Cases from the same oocyte lot with poor (≤30%) and high (>65%) fertilization rates were matched to isolate sperm-related factors influencing fertilization success. Paired t-tests were used to compare outcomes. Ordinary least squares regression was used to isolate variables associated with poor fertilization, such as oocyte status (fresh vs vitrified), sperm origin (partner vs donor) and cases involving severely altered semen parameters, defined as a sperm concentration of <1 million/mL and/or <1% progressive motility. MAIN RESULTS AND THE ROLE OF CHANCE The mean fertilization rate was 72.7% across all analyzed cycles. The incidence of poor fertilization (≤30% fertilization rate) was found to be 3.7% across the entire cohort (510 out of 13 632 cycles). Of the ≤30% fertilization rate cases, 84.1% (429/510) could be matched to cases using the same oocyte lot with high fertilization rates (>65%) in other recipient cycles (n = 1373), indicating that poor fertilization was male-related. We observed a small but significant difference in the number of inseminated oocytes between matched cases with high and poor fertilization (7.41 ± 1.40 and 7.18 ± 1.29, P = 0.0025). As expected, given the group stratification, the mean number of normally fertilized oocytes (6.10 ± 1.35 vs 1.44 ± 0.77, P < 0.001) and mean fertilization rates (83% vs 20%, P < 0.001) differed significantly, among the two groups. Notably, oocyte vitrification negatively affected fertilization outcomes (coeff. −0.0817, P < 0.001). Most poor fertilization cases (95.5%) occurred in the absence of these factors, underscoring the limitations of conventional semen diagnosis tests in accurately predicting poor fertilization outcomes. Across the entire cohort, male factor alone accounted for 3.1% (429/13 632) of cycles with poor, (≤30%, fertilization rates) and 0.4% (59/13 632) of cycles with severely poor fertilization (≤10% fertilization rates). LIMITATIONS, REASONS FOR CAUTION Certain variables were not analyzed due to the retrospective nature and extended timeframe of the study. The matched oocyte model may overlook certain non-male factor-related instances of poor fertilization, such as procedural or technical issues. WIDER IMPLICATIONS OF THE FINDINGS This extensive analysis emphasizes the clinical relevance of male factor in fertilization outcomes, highlighting the need for improved semen diagnosis. It also indicates the importance of considering male-related factors in treatment decisions and shifting the focus from female-centric to more balanced fertility evaluations. STUDY FUNDING/COMPETING INTEREST(S) None TRIAL REGISTRATION NUMBER N/A