P-620 First step for personalized luteal support in frozen-thaw embryo transfer: Understanding the factors associated with serum progesterone concentrations on embryo transfer day
Authors: Boynukalin F K , Tohma Y A , Yarkiner Z , Gultomruk M , Findikli N , Bahceci M , Demir B 
Published: June 2023

Abstract

Study question
What factors determine serum progesterone (P) concentration on embryo transfer (ET) day after artificially prepared (AP) cycles receiving intramuscular progesterone (IM-P)?

Summary answer
Lower serum P concentrations on ET day in AP frozen-thaw cycles are associated with high body mass index(BMI) and low estradiol(E2) levels on ET day.

What is known already
Large sample sized studies reported low serum P levels on ET day in AP cycles related to low success rates. There are limited studies evaluating the pregnancy rates in patients with low serum P on ET day after the rescue doses. These studies included the patients who received vaginal P. There is no study evaluating rescue doses with low serum P concentration after IM-P. Common sense is that personalization of luteal phase support may increase the success rates. To adjust the P dosages, patient and cycle characteristics need to be analyzed for prediction of low serum P concentration.

Study design, size, duration
This retrospective cohort study conducted at Bahçeci Ankara IVF Center between November 2019 and February 2022. The study included 637 single or double frozen-thawed blastocyst transfers undergoing AP endometrium receiving 100 mg IM-P after incremental oestrogen treatment. Serum P concentrations were evaluated from the blood samples which were obtained between 117-119 hours after the first IM-P administration and 21±2 hours after last IM-P administration.

Participants/materials, setting, methods
A total of 637 patients, first frozen-thawed blastocyst ET cycles were analyzed. The mean age, BMI, duration of oestrogen treatment, ET day E2 and ET day P concentration of the study population were 31.9±5.1 years, 26.7 ±4.7 kg/m2, 13.9±1.3 days, 266.1±90.9 pg/ml and 30.2±9.3 ng/ml respectively. Correlation analysis for patient and cycle characteristics and serum P concentrations were evaluated. Multivariate linear regression analysis was performed to determine the independent factors.

Main results and the role of chance
The overall live birth rate in total study group was 50.7% (323/637). Female age, serum P concentrations on ET day, and number of embryos transferred were significantly associated with live birth. Bivariate correlation analysis revealed that ET day P concentrations were negatively correlated to BMI (r:-0.12, p: 0.002) and positively correlated to ET day E2 concentrations (r:0.14, p:0.001). However, no correlation to female age, causes of infertility, E2, P and LH concentrations on P administration day, duration of oestrogen treatment and presence or absence of GnRH agonist suppression. When a multivariate linear regression was performed to correct potential confounders, increasing BMI presented a negative correlation to ET day serum P concentrations (p = 0.003; 95% CI -0.384 to -0.079 ). On the contrary, significant positive correlations to ET day serum P concentrations were shown with ET day E2 levels (p = 0.01; 95% CI 0.003 to 0.018). Other patient and cycle characteristics were not found to be an independent factor for ET day P concentration.

Limitations, reasons for caution
The retrospective nature of the study is the main limitation. Only patients with IM-P were included therefore the results cannot be extrapolated to other P administration forms and needs to be validated. After determining the low serum P threshold in large sample size, the parameters should be re-evaluated.

Wider implications of the findings
Monitoring P levels and adjusting the doses of P administration (via personalization) may have a positive impact on outcome. Not only patient and cycle characteristics, also pharmacokinetic and pharmacogenetic studies are warranted to optimize luteal phase support. Personalization of the luteal phase can be achieved by this way.

Trial registration number
NA