P-407 Exploring the effectiveness of tailoring estradiol supplementation duration to mimic the natural cycle length in artificial endometrial preparation for frozen embryo transfer cycles
Authors: Tadros T , Del Gallego Bonilla R , Kalafat E , Lawrenz B , Fatemi H 
Published: July 2024

Abstract

Study question
Is an estrogen supplementation duration similar in length to the follicular phase of a natural cycle associated with a better clinical pregnancy rate?

Summary answer
An estradiol supplementation duration, which is proportional to the natural follicular phase length, results in significantly better outcomes compared to shorter exposure durations

What is known already
The last decade witnessed a major increase in the use of single euploid frozen embryos. Artificial endometrial preparation (AEP) has proven to be effective to prepare the endometrium for implantation. However, several features of AEP need to be clarified mainly the duration of estrogen supplementation and until now no study took into consideration the difference between exogenous estrogen supplementation and the actual length of the follicular phase of each patient during AEP. Furthermore, most of the studies focused on upper limit of estrogen exposure while few considered the lower limit. Unfortunately, the results on pregnancy rates were mixed.

Study design, size, duration
663 single euploid frozen embryo transfer cycles were included. Patients underwent vaginal ultrasound and hormonal blood measurement (Estradiol, Progesterone) on day 2 of their cycle. Estradiol valerate (4 mg the first 2 days then 6 mg daily, Orally) was started on the same day and another control was done around day 10. When triple lining pattern of the endometrium was seen, vaginal progesterone was initiated (800 mg daily) and SET was done after 120 hours.

Participants/materials, setting, methods
Patients with reported regular menstrual cycle (25-35 days) were included and the difference between estrogen supplementation and the actual follicular phase was calculated for each patient. Patients were sorted into 2 groups as follows: 231 women with normal interval (±2 days of follicular phase length), and 432 women with short interval (-3 days or shorter). Only the first single euploid embryo transfer cycles were analyzed for these patients.

Main results and the role of chance
Whereas patients had similar characteristics in both groups, the corresponding clinical pregnancy rates in normal and short supplementation groups were 69.3% (160/231) and 64% (277/432), respectively. After balancing the groups for BMI, embryo quality and endometrial thickness with inverse treatment probability weighting, those who received estradiol supplementation proportional to their natural follicular phase length had significantly higher clinical pregnancy rates compared to those who received it for shorter durations (adjusted OR: 1.48, 95% CI: 1.16 – 1.89, P = 0.002). Serum estradiol levels were available for 523 cycles, the clinical pregnancy rate in those within the 1st quartile (&lt;155pmol/L), 2nd to 3rd quartile (155 to 275pmol/L) and 4th quartile (&gt;275pmol/L) were 70%, 64.7% and 63%. After adjusting for BMI and embryo quality, higher (&gt;275pmol/L) (adjusted OR: 0.84, 95% CI: 0.53-1.32, P = 0.442) and lower(&lt;155pmol/L) (adjusted OR: 1.37, 95% CI: 0.85-2.22, P = 0.202) estradiol levels were not significantly associated with clinical pregnancy.

Limitations, reasons for caution
The present study could not address the influence of very long estrogen supplementation on clinical pregnancy rate due to limited samples. Further prospective studies, including larger populations, are needed to confirm our findings

Wider implications of the findings
Our data indicate that mimicking individually the natural cycle regarding estrogen supplementation duration in AEP for single euploid embryo transfer cycles can produce significant improvement in clinical pregnancy rates.

Trial registration number
not applicable