O-243 Progesterone levels measured on the day of blastocyst transfer in modified natural cycle frozen-thawed embryo transfer (mNC-FET) cycles: a sub-study of an ongoing RCT
Authors: Saupstad M , Bogstad J.W , Bergenheim S.J , Petersen M.R , Klajnbard A , Freiesleben N.L.C , Andersen L.F , Knudsen U.B , Englund A.L , Husth M , Alsbjerg B , Pinborg A , Løssl K 
Published: June 2022

Abstract

Study question
What is the serum progesterone level on blastocyst transfer day in mNC-FET and is the level related to the ongoing pregnancy rate?

Summary answer
One-quarter of all women had a progesterone level below 29.4 nmol/L on blastocyst transfer day, but the ongoing pregnancy rate was not compromised.

What is known already
It is widely recognized that a serum progesterone level above a certain threshold (30-35 nmol/L), at the time of blastocyst transfer improves ongoing pregnancy rates in artificial cycle FET (AC-FET). However, some studies have indicated that the progesterone level may also become too high. Similar results have been found in natural cycle FET; a recent retrospective study reported that low progesterone levels the day before blastocyst transfer was negatively associated with live birth. As for mNC-FET, data on optimal luteal phase progesterone levels are still missing.

Study design, size, duration
We present data from an ongoing multicentre, randomised, controlled, single-blinded trial planned to include 604 women undergoing mNC-FET with a single good-quality blastocyst. Women are randomised (1:1:1:1) to:
1) Luteal phase support (LPS) and transfer day 6 following hCG trigger
2) LPS and transfer day seven
3) No LPS and transfer day six
4) No LPS and transfer day seven
Only women randomized to the groups not receiving LPS were included in this sub-study.

Participants/materials, setting, methods
The RCT is still ongoing and by the end of December 2021, 188 normo-ovulatory women aged 18-41 had been randomized to study groups 3) and 4). Of these, 170 had blood drawn on the day of blastocyst transfer and were included in this sub-study. All blastocysts transferred were derived from the patient’s oocytes and had a Gardner score ≥3BB at vitrification. No preimplantation genetic testing for aneuploidies was performed.

Main results and the role of chance
The study participants had the following characteristics: The median (IQR) age was 34 years (30-37), BMI 22.6 kg/m2 (21.0-25.8 kg/m2), cycle length 28 days (27-30 days), and serum AMH level 19 pmol/L (13-29 pmol/L).
In mNC-FET without LPS, the median progesterone level on the day of transfer was 36.6 nmol/L, ranging from 9.6 to 91.8 nmol/L (except two outliers). The 25th, 10th, and 5th percentiles were 29.4, 22.0, and 17.7 nmol/L respectively, which means that 25% of the women had a progesterone level below 29.4 nmol/L. The pregnancy rate was 56.1% (23/41) among women with a progesterone level &lt;29.4 nmol/L compared to 60.6% (77/127) among women with a progesterone level above 29.4 nmol/L (P = 0.715). The ongoing pregnancy rate below and above the lowest progesterone quartile was 41.5% (17/41) and 43.8% (53/121) respectively (P = 0.856). Multivariate logistic regression analyses showed no effect of progesterone level on ongoing pregnancy rate, neither in simple analysis nor when adjusting for age and BMI.

Limitations, reasons for caution
The serum progesterone level on the day of transfer in mNC-FET without LPS was not a primary endpoint of the RCT. Thus, the number of women included might be too small to draw firm conclusions on progesterone levels and ongoing pregnancy rate in mNC-FET.

Wider implications of the findings
Optimal serum progesterone levels on the day of blastocyst transfer in mNC-FET have yet to be determined and seem to differ substantially from levels in AC-FET. Ongoing pregnancy rates in mNC FET without LPS are good even with progesterone levels in the lowest quartile.

Trial registration number
2018-002207-34