O-195 Decreased embryo developmental potential and lower cumulative pregnancy rate in males with multiple morphological abnormalities of the sperm flagella

Abstract

Abstract Study question Is there any association between the multiple morphological abnormalities of the sperm flagella (MMAF) patients and the comprehensive outcomes of assisted reproductive technology (ART) cycles? Summary answer Patients with MMAF presented compromised ART outcomes, including lower embryo developmental potential and impaired clinical outcomes, compared with the cohort of oligoasthenospermia. What is known already Several studies have reported a positive intracytoplasmic sperm injection (ICSI) outcome in the MMAF cohort, and others have opposite opinions. The association between MMAF and ART outcomes is still controversial and open for debate. Furthermore, the neonatal outcomes and the information regarding the mutations of MMAF patients were incomplete. Study design, size, duration A retrospective cohort study of MMAF patients was performed at a reproductive medicine center in China between January 2014 and July 2022. Participants/materials, setting, methods Thirty-eight MMAF individuals were recruited based on a typical MMAF phenotype (abnormal sperm flagella, including short, absent, coiled, bent, and/or irregular flagella) and 131 couples with male infertility undergoing in vitro fertilization (IVF)/ICSI treatments over the same period were included as the control pool. Whole exome sequencing (WES) was performed to confirm the genetic pathogenesis of MMAF. Main results and the role of chance Pathogenic variants in known genes of DNAH1, DNAH11, CFAP43, FSIP2, and SPEF2 were identified in MMAF patients. The ART outcomes, including the fertilization rate, 2PN cleavage rate, blastocyst formation rate, and available blastocyte rate, were all significantly lower in the MMAF group than those in the control group (P<0.05). Moreover, the CLPR in the MMAF group was lower than that in the control group according to the embryo transfer times (68.6% vs. 86.5%, P=0.033) and complete cycles (66.7% vs. 84.2%, P=0.020), while no significant differences were found in the neonatal outcomes. Limitations, reasons for caution The sample size was limited due to the low incidence of MMAF and WES was not performed in all MMAF patients. Further exploration of the potential genetic mutations or underlying mechanisms in patients without identified mutations was needed. Moreover, long-term follow-up of neonates needs to be addressed in the future. Wider implications of the findings The current study identified the causative genetic mutations which were partly obligated to the pathogenesis of MMAF and presented the relationship between MMAF and compromised ART outcomes. These results may provide evidence support for clinicians in genetic counseling and clinical instruction in specific MMAF patients. Trial registration number the National Key Research & Development Program of China (2021YFC2700603)