Revisiting oolemma characteristics during ICSI in relation to fertilization patterns and embryo development and implantation

Abstract

The oolemma response during ICSI has been linked to membrane and cytoplasmic maturity. The former is evidenced by the depth of the funnel and can manifest in the unextrusion of the second polar body and oocyte lysis, while the latter in absent fertilization. We investigate the occurrence of normal and abnormal fertilization patterns, as well as oocyte survival in relation to ovarian stimulation and eventual reproductive outcomes. In couples with an adequate cohort of mature oocytes and varying degrees of fertilization, we measured the occurrence of immature membrane and ooplasm (as evident by oocyte lysis), impaired cytoplasmic maturity (as evident by no fertilization), lower membrane maturity (as evident by 3PN embryos) and complete membrane and cytoplasmic maturity (2PN). Only ICSI cycles with >5 oocytes at MII stage were included. Unextrusion of the second polar body, characterized by digynic 3PN, is associated with sudden breakage of the membrane, short funnel, and indicates ooplasmic maturity but membrane dysmaturity. Oocyte lysis is characterized by absence of funnel development and therefore severe membrane dysmaturity. Absent fertilization presented with adequate funnel development up to the center of the oocyte therefore allowing oocyte survival, but unfortunately with ooplasmic immaturity. ICSI cycles were stratified by fertilization rates, in increments of 20%. The rates of 3-PN embryos and oocyte lysis were plotted against increasing fertilization rates. Demographics and ovarian stimulation parameters were compared across fertilization groups. 11911 ICSI cycles were identified. The rate of digynic 3PN embryos decreased with increasing fertilization rate [7.19% (<20%) to 1.10% (81-100%)]. Similar trends in the rate of oocyte lysis were observed as well. There was no difference in the median age of patients (36), number of oocytes (9), or total stimulation days (10) across different fertilization groups. Patients with oocyte lysis had a progressively lower dose of gonadotropins (P=0.007) and peak E2 levels (P<0.001) in comparison to those that had no fertilization, digynic 3PN embryos, and both membrane and cytoplasmic maturity (all 2PN). To assess the impact of oolemma/ooplasmic maturity within the cohort of oocyte injected on the embryo developmental outcome, we compared patients with oocyte lysis to those who had normal fertilization (n=384). Lower implantation (16.7% vs. 32.4%; P<0.001) and clinical pregnancy rates (7.01% vs. 34.6%; P<0.001) were noted in the former group compared to the latter. During ICSI, membrane funnel characteristics may provide insight into oolemma maturity. Oocyte survival, absent/abnormal fertilization provides invaluable information about ooplasmic maturity and embryo developmental competence. Our study highlights the potential link between oolemma behavior, absent/abnormal fertilization and ovarian stimulation.