O-021 The dose of micronised vaginal progesterone prior to frozen embryo transfer in artificially prepared cycles: the more the better?
Authors: Bumbul-Mazurek E , Roelens C , Mackens S , Van Landuyt L , Drakopoulos P , Tournaye H , Blockeel C 
Published: June 2023

Abstract

Study question
Does a higher daily dose of micronized vaginal progesterone (MVP) increase live birth rates (LBR) or diminishes risk of early pregnancy loss (EPL)?

Summary answer
An increased dose of MVP does not affect reproductive outcomes.

What is known already
Endometrial preparation in frozen embryo transfer (FET) cycles can be achieved either in a natural cycle (NC), a stimulated cycle or an artificial cycle (AC). Despite growing advocacy for utilization of NC for FET mainly because of pregnancy complications, there are still numerous indications and strengths of AC, such as convenient monitoring and planning. In AC-FET cycles exogenous estradiol (E2) and progesterone (P) are administered consecutively in order to mimic a natural cycle. Although MVP still being the most widely used medication for LPS in AC-FET cycles, dose finding studies are lacking.

Study design, size, duration
This is a retrospective study performed at a university-affiliated centre including patients performing a single blastocyst transfer from January 2016 till June 2021. Pregnancy outcomes were compared between patients receiving 600mg (3x200mg) or 800mg (2x200mg) of MPV in the second phase of an AC-FET cycle. The time period was chosen to incorporate the empiric change made in the inner guidelines regarding artificial cycles LPS in autumn 2018.

Participants/materials, setting, methods
Patients aged 19-39, who underwent the first frozen single blastocyst transfer were included. Only HRT cycles, where after exogenous estradiol endometrium preparation LPS was started with MVP 600mg or 800mg were included. Patients lost to follow-up, with missing data, with known uterine pathology, recurrent miscarriages, with switch to MNC, with more than one progesterone route planned or modified LPS were excluded.

Main results and the role of chance
1825 artificial cycles for FET were included. 827 supplemented with 600mg of MVP -MVP600 group and 998 with 800mg of MVP – MVP800 group. The MVP600 and MVP800 groups did not differ in BMI 24.02 (SD 4.73) vs 23.81 (SD 4.6) (p = 0.37), rank of embryo transfer 1.93 (SD 1.41) vs 1.77 (SD1.19) (p = 0.11), or the thickness of the endometrium at planning 8.67mm (SD1.79) vs 8.51mm (SD 1.7) (p = 0.06). Yet, MVP 800mg group was slightly older than MVP600 group 31.99 (SD 3.72) vs 30.84 (SD 3.9) (p &lt; 0.001). Positive hCG was 58.65% (485 out of 827) for MVP600 and in 62.12% (620 out of 998) for MVP800 group (p = 0.13). LBR per positive hCG 64.18% (292 out of 455) in MVP600 and 67.17% (397 out of 591) in MVP800 group (p = 0.31). Early pregnancy loss per positive hCG did not differ between the groups, and including biochemical losses, was 32.75% in MVP600 (149 out of 455) vs 30.8% in MVP800 (182 out of 591) (p = 0.5). Multivariable regression analysis adjusting for relevant confounders (eg. BMI, endometrium thickness) revealed that the dose of MVP 600mg vs 800mg is not significantly associated with EPL OR 0.92 (95% CI 0.71-1.22) p &gt; 0.592.

Limitations, reasons for caution
The main limitation is the retrospective design of our study, with an inherent risk of bias. Furthermore, we could not compare the blood progesterone values at the day of the transfer as in MVP600 they were not routinely performed, so the need for additional LPS could not be compared.

Wider implications of the findings
This is the largest study dose finding study comparing the two progesterone administration doses. The higher dose of MVP does not improve reproductive outcomes, but might be more convenient due to a twice daily application.

Trial registration number
BUN: 1432022000074 EC number: EC-2022-102