P-787 Ovarian morphology and length of follicular phase differ between immediate and postponed modified natural-cycle frozen embryo transfer (mNC-FET) cycles – Sub-study of an ongoing RCT
Authors: Bergenheim S , Saupstad M , Wulff Bogstad J , La Cour Freiesleben N , Behrendt-Møller I , Englund A L , Nøhr B , Husth M , Sopa N , Løkkegaard E C L , Pinborg A , Løssl K 
Published: June 2023

Abstract

Study question
Does ovarian morphology and length of the follicular phase differ between immediate and postponed mNC-FET cycles?

Summary answer
More cystic follicular residue after oocyte pick-up was observed at cycle day 2-5 in immediate vs postponed mNC-FET. The immediate follicular phase was longer.

What is known already
Whether the optimal timing for treatment with mNC-FET is in the cycle immediately following ovarian stimulation (OS) and oocyte pick-up, or in a subsequent cycle, has been much debated. Recent evidence suggests that reproductive outcomes after immediate vs postponed FET are comparable or even better in programmed-cycle FET. Due to concerns about suboptimal ovarian and endocrinological conditions in the natural cycle immediately following an OS/IVF cycle, postponed FET has become the standard treatment in most settings. However, studies describing attributes of the immediate NC-FET are lacking and little is known about cycle characteristics and ovarian morphology shortly after oocyte pick-up.

Study design, size, duration
The present descriptive sub-study is based on data from an ongoing Danish, multicentre, randomised controlled trial (RCT), investigating if mNC-FET can be performed in the cycle immediately following OS and oocyte pick-up, without compromising pregnancy and live birth rates. Participants were randomized 1:1 to mNC-FET in the immediate vs a subsequent cycle. The first 102 participants were included in the present sub-study. Data was collected between April 2021 and December 2022.

Participants/materials, setting, methods
Women with a regular menstrual cycle, aged 18-40 years, undergoing single blastocyst mNC-FET were eligible for inclusion. Ovarian morphology and cycle length were compared between immediate and postponed mNC-FET using Chi-squared test for categorical variables, and independent sample T-test or Mann Whitney U-test for continuous variables. Categorical variables were reported as numbers and percentages, continuous variables as mean and standard deviation or median and range.

Main results and the role of chance
Background characteristics including age, BMI, AMH and normal cycle length were similar for women in the immediate and postponed group, apart from a lower rate of elective freeze all-transfers (30.2% vs 55.1%, p = 0.011) in the OS cycle preceding FET, in the immediate vs the postponed group. The total number of cystic follicular structures (hypo- and non-hypodense) &gt;10 mm (2 (range 0-11) vs 0 (range0-3), p = &lt;0.001) were higher in the immediate vs the postponed group on cycle day (CD) 2-5 of the treatment cycle. On the day of hCG-trigger, there was no significant difference in the total number of cystic follicular structures between the groups, but a higher number of non-hypodense structures was found in the immediate group (p = 0.021). Endometrial thickness was greater in the immediate vs postponed group (8.6 vs 7.8 mm, p = 0.031) while the mean size of the dominant follicle was similar 17.1 vs 17.3 mm between groups (p = 0.410). The average day of hCG-trigger was CD15 (range 9-24) in the immediate group compared to CD12 (range 5-28) in the postponed group (p = 0.001). More ultrasound scans of follicular development were needed in the immediate vs postponed group (3 vs 2, p = 0.012).

Limitations, reasons for caution
The proportion of elective freeze-all in the OS cycle preceding FET differed between the immediate and postponed group which may bias the results. The sample size limits stratified analyses.

Wider implications of the findings
The findings of this study indicate that cystic follicular ovarian structures shortly after oocyte pick-up are commonly occurring. However, most of these structures seems to regress before the time of ovulation. The follicular phase was longer in immediate cycles, and whether this effects pregnancy outcomes is yet unknown.

Trial registration number
NCT04748874