P-252 Oolemma surface area impacts human pre-implantation embryo development and usage: The Rotterdam Periconception Cohort
Authors: Rubini E , Wiegel R , Rousian M , Schoenmakers S , Laven J.S.E , Willemsen S.P , Baart E.B , Steegers-Theunissen R.P.M 
Published: June 2022

Abstract

Study question
Does oolemma area change before the 2-cell stage? Is oolemma area associated with fertilization rate, embryo usage rate and preimplantation embryo development?

Summary answer
Oolemma area is associated with preimplantation embryo development, the odds of fertilizing and developing into a used or discarded embryo.

What is known already
Current morphological grading systems are based on embryo morphology and omit oocyte morphology. Fertilization and embryo potential are largely determined by the maturation and quality of the oocyte. Oocyte quality correlates to morphology, and the very early stages of embryo development are critical to changes in oocyte size. Larger oocyte size associates with higher quality blastocyst. This suggests that oocyte size can be a morphological marker of preimplantation embryo quality and assisted reproductive treatment (ART) outcomes.

Study design, size, duration
This study is embedded in the Rotterdam Periconceptional Cohort, an ongoing prospective tertiary hospital-based birth cohort study. From May 2017 to July 2020, a subcohort of 378 women that underwent ART was included comprising of 124 pregnancies after in vitro fertilization (IVF) and 254 after intracytoplasmic sperm injection (ICSI).

Participants/materials, setting, methods
Health, lifestyle and treatment factors were collected from detailed self-reported questionnaires and medical records. Oolemma area was measured at the time of fertilization (t0), pronuclear appearance (tPNa) and fading (tPNf). Oolemma area trajectories (slope surface t0-tPNf) were calculated with linear regression. Fertilization rate, embryo usage rate, and embryo morphokinetics were analyzed in association with oolemma area and trajectories. Analyses were performed with linear mixed models, mixed effects logistic regression, and adjusted for relevant confounders.

Main results and the role of chance
Oolemma area decreased from t0 to tPNf for oocytes that developed into both used or discarded embryos. Oolemma area at t0 was strongly associated with the rate of area shrinking, as larger oolemma areas had faster shrinking rates (Bshrinking -12.55 µm²/hour, 95%CI -14.55; -10.55, p &lt; 0.001). Oocytes that resulted in a usable embryo were larger and reached tPNf faster than oocytes that resulted in a discarded embryo (tPNf 9855±595 µm2 vs 9690±721 µm2, p &lt; 0.001, 24.4±3.6 h vs 26.5±5.8 h, p &lt; 0.001). Oolemma area at tPNf did not differ between ICSI and IVF oocytes, however ICSI oocytes reached tPNf faster than IVF oocytes (23.6±3.2h and 25.9±3.8h, p &lt; 0.001, respectively). In ICSI only, larger oolemma area showed lower odds of a successful fertilization (t0 OR 0.57, 95%CI 0.48; 0.67, p &lt; 0.001), but higher odds of being cryopreserved or transferred (tPNf OR 1.66, 95%CI 1.33; 2.08, p &lt; 0.001). For IVF and ICSI, larger oolemma area at tPNF was associated with faster preimplantation development up to the morula stage (t7 B -1.41, 95%CI -2.18; -0.63, p &lt; 0.001). Oolemma area shrinking rate was not associated with embryo morphokinetics.

Limitations, reasons for caution
Small number of embryos measured at the blastocyst stage, and oolemma area measurements were not possible at t0 and tPNa for IVF oocytes.

Wider implications of the findings
Oolemma area is a suggested morphological marker for oocyte competence and an early marker for the success of fertilization and embryo development. The relevance of oolemma area as predictor of ART success requires further research. Cryopreservation and PCOS, which influence oocyte size, could be studied in association with oolemma area.

Trial registration number
not applicable