P-058 Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF: not just ICSI failure

Abstract Study question How does sperm phospholipase C zeta (PLCζ) affect fertilization in conventional vitro (cIVF)? Summary answer Absence of PLCζ causes polyspermy, and a decline the proportion expressing is correlated with low rate (FR) after cIVF. What known already key sperm-borne factor that triggers Ca2+ oscillations subsequent oocyte activation following gamete fusion. Mutations PLCZ1, gene encoding PLCζ, cause male infertility intra-cytoplasmic injection (ICSI) failure; expression localization patterns are significantly ICSI FR. However, few studies have been published on relationship between cIVF, an insemination procedure involving several events bypassed ICSI, e.g., sperm-zona binding penetration, as well polyspermy blocking. It possible may different manner from ICSI. design, size, duration Sixty couples who underwent cIVF treatments were recruited Reproductive Genetic Hospital CITIC-Xiangya February 2019 January 2022. Participants/materials, setting, methods We performed whole-exome sequencing two unrelated males exhibited Immunofluorescence staining oocyte-activation testing employed to evaluate effects candidate variants protein. Subsequent analysis was additional 58 The Pearson correlation coefficient relationships FRs. receiver operating characteristic curve Youden’s index used indicate cutoff value. Main results role chance identified one previously reported novel PLCZ1 associated characterized by excessive sperm–zona delay pronuclear (PN) formation. In functional analyses revealed virtually all patients lacked thus unable evoke physiologic pattern oscillations. artificial treatment successfully rescued polyspermic phenotype resulted live birth. males, allocated three groups according outcomes: multiple (MPN) group (no. PN ≥ 3, MPN 50%, n = 9) (LF, total FR ≤ 30%, 18) normal (NF, 2PN 1PN + < 31). found expressed positively both (P 0.0005) 0.0008) optimal value below which likely experience (total 30%) 56.7% (area under ROC curve, 0.705; P 0.0176). Limitations, reasons for caution Precise mechanisms underly roles outcomes still uncovered. Follow-up larger numbers required validate sensitivity, specificity, accuracy diagnostic biomarker outcomes. Wider implications findings Our study causative humans,highlighting potential fertility marker Trial registration number nor applicable