P-694 Dosage of exogenous gonadotropins is not related to blastocyst aneuploidy or cumulative live-birth rates in PGT-A cycles
Authors: Cozzolino M , Mossetti L , Mariani G , Pellicer A , Garrido N 
Published: June 2022

Abstract

Study question
Does dosage of gonadotropins affect aneuploidy rate rates or cumulative live birth rates (CLBRs) after the transfer of euploid embryos?

Summary answer
We did not find evidence that dosage gonadotropin influenced significantly the rate of aneuploidy and CLBRs after transfer of euploid embryos.

What is known already
Aneuploidy rates increase steadily with age, reaching &gt;80% in women &gt;42 years old. The goal of controlled ovarian stimulation obtaining more embryos to biopsy through the recruitment of several follicles, reaching more euploid embryos. However, several studies have suggested that a high response to stimulation might be embryotoxic and/or increase aneuploidy rates by enhancing the abnormal segregation of chromosomes during meiosis. Furthermore, a study on young donors showed differences in the euploidy rates, suggesting an iatrogenic etiology resulting from different stimulation methods.

Study design, size, duration
A multicenter retrospective study, with the preimplantation genetic test for aneuploidy (PGT-A) between January 2013 and January 2020 collected from clinics IVIRMA in Europe. 6832 cycles of in vitro fertilization (IVF) with PGT-A were included in the study

Participants/materials, setting, methods
A total of 62131 embryos were analyzed for ploidy status. Embryos that were subjected to chromosomal analysis were performed blastomere by aCGH (array Comparative Genomic Hybridization) or NGS (Next-Generation Sequencing) analysis. The embryos were biopsied on days 5 and 6. Women were divided into two age groups (&lt;37 and ≥37 years old). Outcomes were compared between different total gonadotropin dosages (&lt;3000 and ≥3000 IU), the dosage of hMG, and numbers of oocytes retrieved.

Main results and the role of chance
The total number of aneuploid embryos was 28336 of the 62131 embryos genetically screened using PGT-A. The embryonic aneuploidy rate was 59.4% (95%CI 58.5-60.3). In the group of women with gonadotropins dosage &lt;3000 IU the embryonic aneuploidy rate was 59.7% (95%CI 58.7-60.8) and in the group with gonadotropins dosage ≥3000 IU was 58.7% (95%CI 57.1-60.3) with no significant difference between them (P = 0.279). In the group of younger patients (&lt;37 y.o) the aneuploidy rate demonstrated no significant differences between patients who received low gonadotropin dosages and patients with high gonadotropin dosages (P = 0.06). Aneuploidy rates in the group of older patients (≥37 y.o) were similar regardless of gonadotropin dosing (P = 0.21). Dividing the according to the number of oocytes retrieved (10, 11-15, &gt;15), the analysis of aneuploidy rate revealed no association between the gonadotropin dosages administrated depending on the total number of retrieved oocytes and age. The aneuploidy rate was also analyzed considering the administration of hMG, there was no statistical difference in the aneuploidy rate with low or high hMG dosages also when it was stratified by age. The cumulative live-birth rate in the groups of different gonadotropins dosage and different ages of patients was similar across the group.

Limitations, reasons for caution
The retrospective nature is the major limitation of this study, also patients included in the study received PGT-A using NGS and CGH arrays technology. The aCGH analysis used is less sensitive than more recent NGS technology.

Wider implications of the findings
Our study demonstrated that gonadotropin dosage did not affect aneuploidy rate or cumulative live-birth rates suggesting that the high doses of gonadotropins used in ART cycles may be safe.

Trial registration number
not applicable