P-154 Is there an impact of oocyte vitrification on embryological and clinical outcomes in PGT-A cycles? A propensity score matching-based study
Authors: Fabozzi G , Cimadomo D , Innocenti F , Albricci L , Amendola M G , Nastri G , Soscia D , Dovere L , Stoppa M , Sanges F , Maggiulli R , Capalbo A , Vaiarelli A , Ubaldi F M , Rienzi L 
Published: June 2023

Abstract

Study question
Does oocyte vitrification affect euploid blastocyst rate (EBR) per cohort of inseminated oocytes and/or clinical outcomes per euploid blastocyst transfer?

Summary answer
Vitrified-warmed oocytes are subject to ≈90% cryo-survival and lower blastulation rates than fresh cohorts, but similar euploidy and clinical outcomes per euploid blastocyst transfer.

What is known already
Cryopreservation was a game-changer in IVF. It is an essential step of the IVF journey with a plethora of clinical (e.g., reduction of OHSS while fully-exploiting the ovarian reserve, implementation of chromosomal/genetic testing, cumulative perspective in defining IVF success), logistic (e.g., higher flexibility), and social (e.g., fertility preservation) advantages. Vitrification represents the gold-standard protocol. Studies in sibling oocytes showed that vitrification may slightly reduce blastocyst development without impact on embryo chromosomal constitution. Here we aimed at measuring the impact (if any) of oocyte vitrification on EBR per cohort of inseminated oocytes and clinical outcomes per euploid blastocyst transfer.

Study design, size, duration
We gathered a dataset of first PGT-A cycles with vitrified-warmed (N = 54) or fresh (N = 3916) inseminated MII-oocytes (April-2013 to July-2022). Patients were matched 1:1 for maternal age at retrieval (37.2 ± 3.4 versus 37.1 ± 3.4 years) and MII-oocytes used (8.7 ± 4.1 versus 9.0 ± 5.1) through propensity-score-matching resulting in 49 cycles per arm. The primary outcome was EBR per cohort of inseminated MII-oocytes. The secondary outcomes were all embryological and clinical outcomes, including cumulative-live-birth-rate (CLBR) per concluded warming/fresh cycle.

Participants/materials, setting, methods
ICSI of all (cryo-survived) MII-oocytes, trophectoderm biopsy without day3 zona-drilling, and comprehensive-chromosome-testing to assess full-chromosome non-mosaic aneuploidies were performed. Cryopreservation was performed via vitrification. Only euploid blastocyst transfers were conducted. The groups were comparable also for BMI and sperm factor. The reasons for oocyte vitrification were supernumerary oocytes (N = 22, 45%; days between vitrification and warming: 573.7 ± 503.9), postponement of sperm collection (N = 7, 14%; 69.3 ± 113.4 days) and fertility preservation (N = 20, 41%; 1160 ± 779.7 days).

Main results and the role of chance
8.7 ± 4.1 oocytes were warmed and 7.9 ± 3.7 survived (survival rate: 90.3 ± 14.7%). The zygotes were 5.4 ± 2.9 and 6.5 ± 4.0 in the vitrified-warmed and fresh groups, respectively (p = 0.2; fertilization-rates: 69.7 ± 22.3% versus 73.6 ± 18.4%, p = 0.5). The blastocysts were 2.1 ± 1.8 and 3.0 ± 1.9 (p = 0.01; blastulation-rates per zygotes: 34.9 ± 26.2% versus 49.4 ± 26.7%, p = 0.02). The euploid blastocysts were 1 ± 1.2 and 1.4 ± 1.6 (p = 0.2; euploidy-rates per biopsied blastocysts: 49.7 ± 34.3% versus 45.7 ± 36.3%, p = 0.5). The EBR per inseminated oocytes were 12.7 ± 13.3% and 17.5 ± 18.1% (p = 0.3). AA-blastocyst rates were also similar (N = 48/101, 47.5% versus N = 77/149, 51.7%, p = 0.6), while the day5-blastocysts rate was lower among vitrified-warmed cohorts (N = 12/101, 11.9% versus N = 51/149, 34.2%, P &lt; 0.01). Nonetheless, the clinical outcomes per euploid transfer (LBR: N = 15/34, 44.1% versus N = 16/38, 42.1%, p = 0.99; miscarriage-rate per clinical pregnancy: N = 1/16, 6.3% versus N = 4/20, 20%, p = 0.4), gestational age (37.8 ± 1.5 versus 38.4 ± 1.4 weeks, p = 0.32) and birthweight (3471.7 ± 575 versus 3153.8 ± 449.3 g, p = 0.1) were comparable. 85.7% (N = 42/49) and 77.6% (N = 38/49) of the warming/fresh cycles were concluded with similar CLBR: 33.3% (N = 14/42) versus 39.5% (N = 15/38; p = 0.6). Among the 22 cohorts of vitrified-warmed oocytes because supernumerary, the EBR per inseminated oocytes was similar to their sibling fresh cohorts (11.7 ± 13.4% versus 13.8 ± 11.1%; p = 0.6). Also, 68.1% warming cycles were concluded (N = 15/22) eliciting 20% CLBR (N = 3/15), comparable to their sibling fresh cohorts (N = 4/22, 18.2%).

Limitations, reasons for caution
Retrospective design with limited sample size. About half of the patients in the vitrified-warmed group cryopreserved oocytes because supernumerary. These women were characterized by better ovarian reserve markers and response to ovarian stimulation than controls. Nonetheless, these parameters do not affect our primary outcome.

Wider implications of the findings
Oocyte vitrification is crucial in IVF. It involves higher flexibility with clinical (full ovarian reserve exploitation, oocyte accumulation), social (fertility preservation), and ethical (cryo-storage of supernumerary oocytes) benefits. Beyond a moderate impact (degeneration after warming, lower blastulation-rates), euploidy-rates and clinical outcomes are not affected by this procedure.

Trial registration number
not applicable