P-156 A statistical model to pinpoint oocyte donors subject to IVF outcomes significantly poorer than expected: a tool for egg banks’ management and Research
Authors: Maggiulli R , Cimadomo D , Figliuzzi M , Badajoz V , Magro Bello L M , Mifsud L , Gallardo M , Redondo J , Picchetta L , Ubaldi F M , Metello J , Aura M , Llacer J , Rienzi L , Capalbo A 
Published: June 2023

Abstract

Study question
What is the prevalence of egg donors resulting in oocyte maturation/fertilization/blastulation rates significantly poorer than expected?

Summary answer
6.7% of the egg donors (N = 34/504) elicited outcomes significantly poorer than expected mostly due to low oocyte maturation rates (N = 27/34, 79.4%).

What is known already
5-10% of donor oocyte cycles produce no blastocyst involving challenging follow-up counseling. Recent research outlined a statistical model identifying women subject to IVF outcomes poorer than expected. These infertile women underwent whole-exome-sequencing (WES) to identify genes involved in oocyte-maturation-defects (OOMD) and/or preimplantation-embryo-lethality (PREMBL). Oocyte donors are the ideal population to apply this model, because they are young, theoretically-fertile, and undergo multiple retrievals of numerous oocytes. This model can find clinical application in improving egg banks’ management, social application in pinpointing young women potentially-infertile because of oocyte defects, and improving knowledge on the molecular pathways involved in human oocyte/embryo competence.

Study design, size, duration
Retrospective study involving oocyte donors recruited at three private IVF centers in 2020-2021. 504 donors (25.6 ± 4.7 years; range: 18-35) undergoing 1684 retrievals (N = 32056 cumulus-oocyte-complexes, 24288 metaphase-II) and whose metaphase-II were used (N = 6996 to date) in 487 fresh and 445 frozen ICSI cycles, respectively, were included. Recipient couples affected from severe-male-factor infertility were excluded. Blastocyst culture was systematically conducted. We leveraged clinical/embryological key-performance-indicators to pinpoint outliers subject to outcomes significantly poorer than expected.

Participants/materials, setting, methods
We quantitatively described donors’ performance as oocyte maturation, fertilization and blastulation rates. The outlier identification was based on the probabilistic modeling of the rates as independent binomial processes, whose baseline success probabilities were estimated from the whole dataset and accounted both for donor age and oocyte type (fresh/vitrified-warmed). The model assigns low probability to individuals with unusually large numbers of immature/unfertilized oocytes or arrested embryos. Donors with low probability (p &lt; 0.001) were designated as outliers.

Main results and the role of chance
Oocyte donors underwent 3.3 ± 1.9 retrievals (1-8) collecting 63.6 ± 44.4 cumulus-oocyte-complexes (5-241), of which 48.2 ± 34.6 (3-162) metaphase-II (maturation-rate: 75 ± 13%,19-100). 13.9 ± 10.5 (3-75) metaphase-II were used during 1.8 ± 1.3 (1-9) cycles per donor, 1.0 ± 1.0 (0-6) cycles with 7.1 ± 7.6 (0-45) fresh metaphase-II oocytes and 0.9 ± 1.0 (0-7) cycles with 6.8 ± 8.1 (0-59) vitrified-warmed metaphase-II oocytes. Overall, 10.1 ± 8.0 (0-58) 2PN-zygotes were obtained per donor (fertilization-rate: 72 ± 16%,0-100), 5.1 ± 5.8 (0-34) in fresh (fertilization-rate: 72 ± 17%,0-100) and 5.0 ± 6.1 (0-41) in frozen cycles (fertilization-rate: 74 ± 16%,20-100). Overall, 5.5 ± 5.0 (0-31) blastocysts were obtained per donor (blastulation-rate: 55 ± 25%,0-100), 3.0 ± 3.8 (0-25) in fresh (blastulation-rate: 59 ± 25%,0-100) and 2.5 ± 3.6 (0-31) in frozen cycles (50 ± 24%,0-100). The model applied to this dataset designated 34 outliers (N = 34/504,6.7%, p &lt; 0.001, FDR&lt;0.1%). Most of them (N = 27) showed oocyte maturation-rates significantly lower than expected (51 ± 10%,19-66). These women were 26.9 ± 5.1 years old (19-35) and underwent 4.3 ± 1.7 retrievals, collecting 91.2 ± 45.0 cumulus-oocyte-complexes (25-210), of which 49.1 ± 31 (8-127) were metaphase-II oocytes. Three outliers showed fertilization-rates significantly poorer than expected (19 ± 17%,0-31). They were 21 ± 4.4 years old (18-26) and their metaphase-II oocytes (12.7 ± 4.9,7-16) were inseminated in 1.3 ± 0.6 donation cycles (1-2) resulting in 3 ± 2.6 (0-5) 2PN-zygotes. Four outliers showed blastulation-rates significantly poorer than expected (13 ± 7%,7-22SAME). They were 26.3 ± 6.2 years old (19-34) and their oocytes resulted in 28.5 ± 20.5 (14-58) 2PN-zygotes across 4.5 ± 3.1 (2-9) donation cycles that developed into 4.5 ± 5.7 (1-13) blastocysts.

Limitations, reasons for caution
Euploidy, another pivotal measure of oocyte competence, was not assessed. Larger studies are warranted, also accounting for putative additional confounders on all embryological outcomes under investigation. Nonetheless, gathering well-structured data on the cumulative performance of donor oocytes collected across multiple retrievals and through multiple IVF cycles is challenging and remarkable.

Wider implications of the findings
These outlier oocyte donors could benefit from follow-up investigation aimed at underpinning OOMD/PREMBL-related genetic factors. The development of genetic prediction tools to this end will improve egg donation cycles’ management and equity and might pave the way to preventive screening strategies and precision reproductive interventions in theoretically-fertile young women.

Trial registration number
not applicable