P-636 Euploid blastocysts obtained in advanced maternal age women either in donor or autologous egg cycles showed similar live birth rates: a retrospective cohort study
Authors: Cozzolino M , Capalbo A , Pellicer A , Garcia-Velasco J A , Cimadomo D , Galliano D , Vaiarelli A , Levi-Setti P 
Published: June 2023

Abstract

Study question
Do euploid blastocysts have the same implantation and live birth rate in autologous and donor egg cycles in patients with advanced maternal age (AMA)?

Summary answer
Euploid blastocysts transferred in AMA patients showed that implantation and live birth rates (LBR) were not significantly different between reproductively younger and older women.

What is known already
Aneuploidy rates increase steadily with age, reaching &gt;80% in women &gt;42 years old. The high prevalence of aneuploidies may provide an explanation for the low LBR achieved by assisted reproductive treatments, especially for women with AMA. Similarly, among oocyte donors, age is critical to achieving reproductive success independently of the recipients’ age. In donor cycles, recipients using oocytes from older donors had a statistically significantly lower LBR than younger donors. Currently, it still remains unclear whether the LBR differs between young donors versus old infertile patients in the context of euploid blastocyst transfers.

Study design, size, duration
Multicenter retrospective study with the preimplantation genetic test for aneuploidies (PGT-A) in both autologous and donor oocytes cycles between January 2018 and January 2021 was conducted at three different institutions (IVI-RMA, GeneraLife and Humanitas Fertility Center). 556 patients were included and matched 1:1 for the age of recipients, euploid blastocyst morphological quality, and day of development. In the frozen embryo transfers, endometrial preparation was done using hormonal replacement therapy (HRT) or natural cycles (NC).

Participants/materials, setting, methods
AMA patients older than 39 years underwent IVF. 556 patients who underwent autologous or donor oocyte cycles with at least one euploid blastocyst transferred were matched for oocyte age, blastocyst morphological quality and day of development. Blastocyst ploidy was assessed by aCGH or NGS analysis. Patients with uterine pathologies reported in the dataset were excluded. The primary outcome was LBR per first euploid blastocyst transfer. Outcomes were adjusted for confounders via logistic regression analyses.

Main results and the role of chance
278 single euploid blastocysts tested by PGT-A were transferred in both autologous and donor oocyte cycles. No statistical differences were reported in the maternal age at transfer in the two groups (41.91 ± 2.03 and 41.75 ± 1.98, p = 0.55), endometrial thickness [(8.67, 95%CI: 8.45-8.88) and (8.36, 95%CI: 8.05-8.67)] and type of endometrial preparation (HRT or NC). Implantation rate and pregnancy rate were similar without statical difference in autologous or donor cycles, respectively [57.91%, (95%CI: 51.87-63.78) versus 56.83%, (95%CI: 50.79-62.74); p = 0.99)] and N = 158/278 (56.83%, 95%CI: 50.79-62.74) versus N = 161/278 (57.91%, 95%CI: 51.87-63.78), p = 0.86. The rate of ectopic pregnancy was not statistically different in both arms. Even the miscarriage rate was comparable in autologous N = 46/158, 16.55% (95%CI:12.38-21.45) versus donor group N = 45/161, 16.19%, (95%CI:12.06-21.05); p = 0.98. The LBR was not statistically different in autologous N = 111/278 (39.93%, 95%CI:34.13-45.95) and donor group 114/278 (41.01%, 95%CI:35.17-47.04), p = 0.86. No statistical difference was reported for gestational age and birthweight at delivery. The logistic regression analyzed as putative confounders: oocyte age, number of inseminated MII-oocytes, zygotes and euploid blastocysts, sperm parameters, endometrial preparation and endometrial thickness showed no statistical differences.

Limitations, reasons for caution
Despite the matched design, the retrospective nature is the major limitation of this study. Also, patients received PGT-A using NGS and CGH arrays technology. The aCGH analysis is less sensitive than more recent NGS technology. Lastly, the prevalence of adenomyosis could be underestimated due to retrospective data collection.

Wider implications of the findings
The dramatic decline in IVF treatment success is primarily caused by aneuploidies. Euploid blastocysts show LBR largely independent of oocyte age. Our study suggests no uterine effect of aging. The reproductive decline in women is mainly related to meiotic failure, therefore future insights should develop strategies to overcome chromosomal aneuploidies.

Trial registration number
NA