P–332 Endometrium thickness is increased in gonadotropin stimulated IVF compared to unstimulated cycles, but this increase does not have a positive effect on pregnancy rate
Authors: Magaton I M , Helmer A , Vo. Wolff M , Stute P , Roumet M C 
Published: August 2021

Abstract

Study question
Is endometrial growth and endometrial thickness different in controlled ovarian stimulation (COS)-IVF compared to unstimulated cycles and does this have an effect on pregnancy rates?

Summary answer
Endometrial growth dynamic is different and endometrium is thicker in COS-IVF but this does not have a positive effect on pregnancy and live birth rates.

What is known already
Endometrial growth and endometrial thickness are a function of duration and concentration of estradiol (E2) stimulation. Endometrial thickness &lt;8mm is related with lower pregnancy rates in IVF treatments. It is commonly assumed that an increase of endometrial thickness by increasing estrogen stimulation could have a positive effect on pregnancy rate. However, such a relationship has never been systematically analysed. Natural Cycle IVF (NC-IVF) is an ideal model to analyse the effect of high dose gonadotropin stimulation on several parameters such as thickness of endometrium and pregnancy rate.

Study design, size, duration
Retrospective single center, University based study including 235 COS-IVF and 616 NC-IVF cycles from 2015 to 2019. Polyfollicular COS-IVF cycles were only analysed until 09 2017 as embryo selection was introduced in Switzerland afterwards. Limiting the analysis to cycles without embryo selection enabled us to compare embryos derived from cIVF and NC-IVF. 1550 endometrial and 1068 E2 measurements were included in the analysis.

Participants/materials, setting, methods
Mean female age at the time when the cycles were performed was in NC-IVF 35.8±3.9y and in COS-IVF 34.9±4.2y (maximum 42y). Each woman performed on average 1.96±1.45 IVF cycles. Endometrial thickness and E2 serum concentrations were evaluated daily between day –4 and –2 (0=day of aspiration). Pregnancy and live birth rate were evaluated per transferred embryo. Statistically, student test and a repeated measure model and a logistic regression model both adjusted for age were used.

Main results and the role of chance
Endometrial thickness was different in COS-IVF and NC-IVF. At each time point endometrial thickness was found to be higher in COS-IVF compared to NC-IVF (p &lt; 0.001 on days –4,–3, and –2). On day –2, the day when ovulation was triggered, mean endometrial thickness was 9.75 ±2.05mm in COS-IVF and 8.12 ±1.66mm in NC-IVF.
Endometrial growth dynamic was also different in COS-IVF and NC-IVF. Endometrial thickness increased significantly faster in NC-IVF cycles (0.58mm/day [0.43,0.73]) than in cIVF cycles (0.22mm/day [–0.12, 0.55], Pval= 0.034). The increase of endometrial thickness per day was less pronounced if E2 concentrations were high (–0.19 [–0.34, 0.05]). Therefore it can be assumed that the observed differences in growth dynamics in both treatments are caused by differences in E2.
Increased endometrial thickness in COS-IVF was not associated with higher success rate. There was no significant effect of endometrium thickness on pregnancy (Pval=0.318) and Live birth rate (Pval=0.461).

Limitations, reasons for caution
Pregnancy and live birth rates might be affected by more than just endometrial thickness. The study was only based on the thickness of the endometrium but not on its ultrasound pattern.
Wider implications of the findings: Postponing the aspiration to allow endometrium to further proliferate has only a limited effect in COS-IVF. Increasing gonadotropin stimulation dosage just to increase endometrial thickness is not a feasible strategy to improve pregnancy rate. The need to apply high dosages of estrogen supplementation in thawing cycles need to be questioned.

Trial registration number
“not applicable”