P-452 A decrease in serum progesterone-levels (P4) during early luteal phase in modified-natural frozen embryo transfer (mNC-FET) is significantly associated with lower pregnancy rates
Authors: Alvarez M , Polyzos N  P , Rodríguez I , Sachs-Guedj N , Solé M , Coroleu B 
Published: July 2024

Abstract

Study question
Does a serum progesterone-level (P4) increase (+ΔP4) or decrease (-ΔP4) through luteal phase (LP) compromise ongoing pregnancy rate (OPR) or miscarriage rate (MR) in mNC-FET?

Summary answer
A P4 decrease (-ΔP4) through luteal phase in mNC-FET is significantly associated with lower OPR and higher MR compared to P4 increase (+ΔP4)

What is known already
Increasing evidence has been recently reported in literature according to the relevance of P4 round FET but also on b-HCG day in artificial and natural FET (AC-FET; NC-FET). Otherwise, mNC-FET gives the chance for triggering and scheduling FET, with less days of monitoring for patients, but keeping the advantages described according to lower risk of preeclampsia through the relaxin production by the corpus luteum. Nevertheless, no studies have been reported according to reproductive outcomes and P4 increase or decrease through the luteal-phase in mNC-FET, as it has been done in fresh embryo transfer (IVF-transfer)

Study design, size, duration
This is a retrospective observational study led at a single university-affiliated fertility center. Overall, 504 women undergoing mNC-FET between October 2019-October 2023 were included for the analysis. Among them 373 (74%) were homologous-FET cycles (hom-FET), 123 (24%) heterologous-FET cycles (oocyte donation) (het-FET) and 8 (1.6%) embryo donation-FET cycles (don-FET)

Participants/materials, setting, methods
mNC-FETs were performed seven days after HCG-trigger (HCG+7) and on the sixth day of vaginal progesterone treatment. P4-levels were measured on the day before FET (D5-P4) and on β-HCG day (β-P4). Pregnancy outcomes were analysed according to + ΔP4 or -ΔP4 between those two time intervals through the LP in mNC-FET. Progesterone treatment continued until the 10th week of pregnancy.Chi-squared test was used to compare proportions and ROC-curve analysis to identify the best cutoffs for outcomes

Main results and the role of chance
Patients’ age at oocyte retrieval was 33.5 and 38.4 at FET. No differences were described according to epidemiological features. Mean β-P4 and D5-P4 (ng/mL) were 25.15 ± 12.8 and 24.88 ± 6.9 respectively. ΔP4 was reported as positive (+ΔP4) in 52.2% (n = 263), and negative (-ΔP4) in 47.8% patients (n = 241). Mean ΔP4 was +0.26 ± 13 ng/mL. Overall reproductive outcomes were: OPR 47.8% and miscarriage rate (MR) 12.3%. OPR was significantly lower (15.8% vs 77.2%, p = 0.00) and MR significantly higher (19.1% vs 11%, p = 0.099) in case of -ΔP4 compared to + ΔP4. Predicting factors for OPR were b-HCG (ROC-AUC (95% CI) 0.920 (0.896-0.945)), β-P4 (ROC-AUC (95% CI) 0.860 (0.827-0.893)) and ΔP4 (ROC-AUC (95% CI) 0.859 (0.826-0.893)). The optimal cut-off value for OPR were β-HCG &gt; 45.15 UI, β-P4 &gt;22.6 ng/mL and ΔP4 &gt; 0.73 ng/mL, with a sensitivity and a specificity of 0.84-0.75, 0.97-0.78 and 0.83-0.78 respectively. OPR in patients with β-HCG &gt; 45.15 UI and β-P4 &gt;22.6 ng/mL was significantly higher (81.7%) compared to patients with β-HCG &gt; 45.15 UI or β-P4 &gt; 22.6 ng/mL (53%), and patients with β-HCG ≤ 45.15 UI and β-P4 ≤ 22.6 ng/mL (2.6%) (p &lt; 0.001)

Limitations, reasons for caution
The main limitation of this study is its retrospective nature and that conclusions cannot be extrapolated to other methods for endometrial preparation for FET, although conflicting pregnancy outcomes according P4-levels have also been described in either natural or artificial FET. No live birth rate was available at the period study

Wider implications of the findings
ΔP4 through LP seems to be relevant for pregnancy outcomes in mNC-FET as -ΔP4 significantly reduces OPR and increases MR compared to + ΔP4. Evaluation of ΔP4 between the day before FET (D5-P4) and on β-HCG day (β-P4) may be a useful biomarker to predict ongoing pregnancy rates in mNC-FET cycles

Trial registration number
Not applicable