P-707 Evaluating DualStim/PGTA in poor prognosis patients: Comparison of double ICSI-PGTA vs. oocyte cryopreservation plus single PGTA in luteal phase through laboratory, genetic and clinical results.
Authors: Herrero Grassa L , Cascales Romero L , Aparicio Gonzalez M , Boyano B , Garcia-Ajofrin Garcia-Lago C , Ortiz Salcedo J A , Castillo J C , Bernabeu A , Ten Morro J , Bernabeu R 
Published: June 2023

Abstract

Study question
Which strategy is best for poor-prognosis patients: Two ICSI-PGTA cycles fresh oocytes (follicular plus luteal phase) or one ICSI-PGTA cycle with vitrified and fresh oocytes?"

Summary answer
Laboratory outcomes, ploidy rates and clinical results after euploid blastocyst transfer are similar between the two DualStim/PGTA strategies.

What is known already
Luteal phase ovarian stimulation (LPOS) after follicular phase ovarian stimulation (FPOS) is an effective strategy to obtain more oocytes in a single cycle and reduce time-to-pregnancy. The main goal of controlled ovarian stimulation in PGTA patients is to obtain a sufficient number of oocytes to have at least one euploid blastocyst. The standard treatment for achieving this goal is DuoStim plus oocyte cryopreservation. However, this method may decrease oocyte competence in older patients. To address this, we propose comparing the outcomes of two consecutive fresh ICSI-PGTA cycles to our standard protocol in older patients, as an alternative approach.

Study design, size, duration
This multicentric retrospective study evaluated 91 poor-prognosis PGTA cycles (≤ 5 antral follicle count) using the DualStim approach (182 oocyte pick-ups) in the same menstrual cycle, from January to October 2022. Fifty-three patients (group 1; 746 oocytes retrieved) underwent two consecutive egg retrievals, ICSI, and blastocyst biopsy, after FPOS and LPOS, while 38 patients (group 2; 743 oocytes retrieved) underwent oocyte vitrification after FPOS, followed by LPOS, egg retrieval, oocyte warming, ICSI, and blastocyst biopsy.

Participants/materials, setting, methods
We compared various parameters including oocyte number, maturity, fertilization rates, blastocyst quality, biopsy rates, and genetic results between two groups after both egg retrievals. Additionally, clinical outcomes after euploid embryo cryotransfer were also compared. Oocytes were microinjected, cultured in Geri® time-lapse incubators, and underwent embryo biopsy on day 5/6. Statistical analysis was conducted using R software (v.4.2.0), including maternal age as a confounding factor. Results were considered significant with a p-value less than 0.05.

Main results and the role of chance
Patient age was found to be significantly different between groups (40.5±2.2 in group-1 vs 38.5±2.7 in group-2; p &lt; 0.001) and was used as a confounding factor in statistical comparisons. No significant differences were found in terms of oocytes retrieved per patient (14±7.1 vs 13.6±5.8), maturity rate (79.4 % vs 77.9%), fertilization rate (75.3 % vs 74.6%), or day-5 blastocyst rate (54.8% vs 51.7%). However, a significant difference was observed in the percentage of blastocysts biopsied per group (50.2% group-1 vs 43.0% group-2; p = 0.023). After genetic analysis, euploidy rate was found to be lower in group-1 compared to group-2 although not statistically significant (19.8% and 32.6%, respectively, p = 0.007/p=0.309 after adjusting for maternal age), and this led to similar average number of euploid embryos per DuoStim cycle (1.1±1.3 group-1 vs 1.3±1.4 group-2). Aneuploidy (73.9% vs 62%) and mosaicism rates (6.3% vs 5.4%) were also comparable between the two groups. No statistical differences were observed between the follicular and luteal phases in each group in terms of laboratory and genetic results. Preliminary clinical outcomes showed similar pregnancy rates with 12 pregnancies achieved in group 1 after 23 euploid embryo transfers (52.2%), and 14/20 in group 2 (70.0%) with no significant difference between groups.

Limitations, reasons for caution
This study is a retrospective analysis and further validation through prospective study is recommended. Additionally, while the average age of the study groups is statistically different due to bias in the clinical prescription of treatment, this difference was statistically corrected.

Wider implications of the findings
Cryopreserving oocytes obtained after FPOS and warming them after the subsequent LPOS does not negatively impact the quality or final results of a DuoStim PGTA cycle. This approach should be considered as it can reduce workload for the IVF laboratory and minimize costs for patients.

Trial registration number
none