P-397 A retrospective analysis shows a high effect in reproductive outcomes as age increases associated to endometrial factor in IVF advanced maternal age (AMA) patients
Authors: Sebastian-Leon P , Sanz F  J , Diana M  G , Pellicer A , Diaz-Gimeno P 
Published: July 2024

Abstract

Study question
Is there an increasing risk of a negative reproductive outcomes with every passing year associated with endometrial factor in AMA patients?

Summary answer
The risk of implantation failure and pregnancy loss associated with endometrial factor increase in 2.0% and 1.2% respectively with each passing year in AMA patients.

What is known already
Nowadays, there is a delay in maternity due to lifestyle, leading to a progressive increase in the age of women at the first childbirth increasing infertility. However, no universal definition of AMA has been established yet. Typically, studies are performed between different groups of age, establishing arbitrary thresholds. Besides, studies about AMA infertility mainly focus on the decline in oocyte quality, but the effects of age on the endometrium are often overlooked. Therefore, there is a lack of studies centered on endometrial factor and considering age year-by-year to be able to strictly establish when fertility decline starts and its magnitude.

Study design, size, duration
This retrospective study included a total of 33,735 single embryo transfers from 21,506 IVF AMA patients (&gt;35 y.o, BMI 19-25 kg/m2) performed with high quality embryos (embryos from donated oocytes (donor &lt;35 y.o) or euploid embryos from their own oocyte cohort) transferred in day 5 in an endometrial Hormonal Replacement Therapy (HRT) cycle. Evaluated transfers were performed between 2001 and 2022 in 19 clinics in Spain. This study was approved by an IRB (2203-FIVI-030-PD).

Participants/materials, setting, methods
A logistic regression analysis was performed, considering the patient’s age (42.93±3.45 y.o.) as a continuous and dependent variable and the reproductive outcome as an independent variable. The risk of obtaining a negative pregnancy outcome was estimated as risk ratios at a 95% confidence interval. A p-value&lt;0.05 was considered as statistically significant. Reproductive rates (live birth and pregnancy loss) were calculated and compared each passing year in the studied range of ages (35-51 y.o).

Main results and the role of chance
The rates of live birth, Implantation failure and pregnancy loss associated to endometrial factor were affected as age increased in IVF AMA patients (&gt;35 y.o). The implantation failure risk was increased in each passing year a 2% (Risk Ratio (RR) = 1.020 (1.003, 1.021) 95% confidence interval (95%CI), p-value=6.0E-09) and pregnancy loss risk was increased in each passing year a 1.2% (RR = 1.012, (1.003, 1.021) 95%CI, p-value=0.0096). Live birth rate decreased progressively from 42% observed in 35 y.o. to 32% in 50 y.o. Nevertheless, the pregnancy loss rate increased progressively from 29% in 35 y.o. to 37% in 50 y.o. Moreover, results shown a more drastic decrease of implantation failure rate after 42 years old and a pregnancy loss rate after 45 years old.

Limitations, reasons for caution
Only transfers from Spanish population under a HRT cycle were included, decreasing the results variability. However, the results could not be generalized to other hormonal cycles. Moreover, biochemical and clinical pregnancy loss could not be distinguished in this study considering pregnancy loss as a term that includes both of them.

Wider implications of the findings
To our knowledge, this is the first study in which the endometrial factor in AMA patients was analyzed year by year, helping to define in a more reliable way the ages at which the sharpest changes occur to improve clinical practices on endometrial implantation failure in AMA patients.

Trial registration number
Not applicable