P-412 Elevated progesterone levels after hormone replacement therapy (HRT) for frozen embryo transfer (FET) does not impair IVF outcomes, a retrospective study
Authors: Cozzolino M , Hervás I , Massaro M  G , Pellicer N , Rodríguez Valera C , De Angelis F , Pellegrini L , Labarta E , Galliano D 
Published: July 2024

Abstract

Study question
Does high serum progesterone (P) level on the day of FET after hormone replacement therapy affect IVF outcomes?

Summary answer
The supraphysiological serum progesterone levels on the day of FET after HRT do not impair reproductive outcomes.

What is known already
A proper synchronization between embryo and the endometrium is still required by controlling the timing and the dosage of exposure to exogenous hormones. Previous observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during FET cycles. However, based on existing research, the relationship between progesterone levels on FET day and pregnancy outcomes as well as the certain dose of progesterone ideally to achieve pregnancy and a live birth are debatable topics

Study design, size, duration
This is an observational, retrospective and cohort study including 7539 FET cycles that were performed under artificial endometrial preparation with HRT using exogenous estradiol and progesterone (vaginal, subcutaneous and intramuscular) between January 2017 and December 2022. Both euploid FET from autologous oocyte ICSI-PGT-A cycles (n = 1822) or FET from ICSI cycles using donated oocytes (n = 5724) were considered.

Participants/materials, setting, methods
Women were divided into three groups according to P4 level on the day of FET:P&lt;20 ng/ml (n = 6623),P≥20-40 ng/ml (n = 770) and P &gt; 40 ng/ml (n = 146).All ET were performed at the blastocyst stage.The primary outcome was live birth rate (LBR). Secondary outcomes evaluated were biochemical, clinical, and ongoing pregnancy, and miscarriage rate (MR) calculated per FET.Categorical variables were compared between groups with Fisher’s exact test. Logistic regression models adjusted (AOR) with several confounders.

Main results and the role of chance
There were no significant differences in baseline characteristics of the study population. The mean of P4 level was 15,66 ng/ml. Female age was P &lt; 20:38.7 ±3.1, P ≥ 20-40: 39.0 ±3.0, and P &gt; 40: 38.1 ±2.9 (p = 0.53) years old. The group with the highest progesterone levels always found lower biochemical pregnancy even no statistically significant [64.6% (P &lt; 20) vs 63.7% (P ≥ 20-&lt;40) vs 61.1% (P &gt; 40); p = 0.62]; in clinical pregnancy [56.3% (P &lt; 20) vs 56.8% (P ≥ 20-&lt;40) vs 51.4% (P &gt; 40); p = 0.5] and in ongoing [47.0% (P &lt; 20) vs 47.0% (P ≥ 20-&lt;40) vs 41.8% (P &gt; 40); p = 0.47] pregnancy rates. The MR was also higher in the group with higher progesterone, although not significantly: 16.2% (P &lt; 20) vs 15.0% (P ≥ 20-&lt;40) vs 18.0% (P &gt; 40) (p = 0.60). No statistically significant differences were reported for live birth rate, 41.8% (P &lt; 20) vs 40.3% (P ≥ 20-&lt;40) vs 34.2% (P &gt; 40) (p = 0.2). The multivariate analysis showed an increased risk of miscarriage when P &gt; 40ng/ml, aOR= 1.14 (0.75-1.74) (p = 0.55) whereas no such association was found with P4 ≥20-40 ng/ml, aOR=0.92 (0.74-1.15) (p = 0.46). Additionally, the probability of live birth is similar when the patient was P &gt; 40 (aOR= 0.77 (0.51-1,15) (p = 0.20)) than when P ≥ 20-&lt;40 (aOR=0.94 (0.79-1,11) (p = 0.47) compared with the references group.

Limitations, reasons for caution
The retrospective design and different female factors for IVF were included in the study leading to a possible biased population although the adjusted analysis. Different routes of progesterone administration were considered in the study. Currently, we don’t report the timing between the last P4 administration and dosage on the FET.

Wider implications of the findings
This information is useful for clinicians who monitor progesterone levels prior to FET to avoid reaching high levels that would undermine the chances of achieving a newborn.

Trial registration number
Not Applicable