P-599 Oestradiol/Progesterone ratio Impact on Frozen Embryo Transfer (FET) and pregnancy outcomes
Authors: Hernandez Hernandez M , Domínguez Arroyo J  A , Álvarez Miguel I  S , Llamas Chicote M , Dominguez Piriz J , Ortiz Benítez A 
Published: July 2024

Abstract

Study question
Are oestradiol (E2) levels and oestradiol/progesterone (P4) ratio related to higher implantation rates and reduced risk of miscarriage?

Summary answer
We concluded that higher E2 levels and an increased E2/P4 ratio on the day before FET were associated with lower implantation rates.

What is known already
A progesterone threshold &lt; 9.2 ng/ml on the day of FET has been related to lower rates of clinical pregnancy. Progesterone is responsible for increasing endometrial vascularization and exerting an immunomodulator effect that allows blastocyst implantation. How oestradiol affects implantation is not well described yet. An appropriate luteal phase support is essential to synchronize the endometrium, ensure proper implantation and reduce the risk of abortion. However, no studies exist regarding E2 levels and E2/P4 ratios related to pregnancy outcomes in the first weeks of pregnancy.

Study design, size, duration
This is a prospective cohort study. From February 2023 to July 2023, 35 patients who underwent IVF in a private ART medical center were enrolled. Only euploid embryos after PGT- A were transferred and only the first single FET per patient was included. All embryos were transferred in blastocyst stage. Mosaic embryos, fresh cycles, patients with no PGT-A, miscarriages beyond 10 weeks and chemical pregnancies (no evidence of gestational sac) were excluded.

Participants/materials, setting, methods
35 patients who underwent IVF-ICSI were retrospectively analyzed. Serum oestradiol, serum progesterone and E2/P4 ratios were measured the day before embryo transfer and later in three moments: 15 days after positive BHCG test, when gestational sac was visualized; 10-15 days after visualization of the gestational sac, when positive embryo heart rate was verified, and in any moment of vaginal bleeding until the 10th week of pregnancy.

Main results and the role of chance
Our study supported the hypothesis that E2/P4 ratio before FET may be an important factor to predict the risk of threatened abortion considering that all patients had P4 levels &gt; 10 ng/ml before FET. Multiple logistic regression revealed that E2 and E2/p4 ratio on the day before FET are variables related to the risk of threat of abortion. The resulting adjusted OR for E2 on the day before FET in patients who suffered a threatened abortion vs patients who did not experience threat of abortion was 1,025 (95% CI: 1,001-1,049), p value 0,041. The OR for E2/p4 ratio before FET in patients with treat of abortion vs those without threat of abortion was 1,235 (95% CI: 1,035-1,472), p value 0,019. ROC curves showed a significant predictive value for E2 levels &gt;220 pg/ml [AUC of 0,88 (95% CI: 0,73-1,0), p value 0,009] and E2/P4 ratio &gt; 23 [AUC 0,91 (95% CI: 0,78-1,0), p &lt; 0,05], the day before FET indicating a higher risk of threat of miscarriage and loss of pregnancy.
Multiple logistic regression did not find significant statistical differences, either E2 or E2/P4 ratio, between the two groups of patients in subsequent determinations at 4 and 6 weeks after transfer.

Limitations, reasons for caution
The main limitation of this study is the sample size with the lack of further serial measurements of oestradiol and p4 in patients that presented threat of abortion/ miscarriage before the 10th week of pregnancy.

Wider implications of the findings
E2/P4 ratio the day before FET seems to be the most important factor to decrease threat of abortion in patients with P4&gt; 10 ng/ml. Our study may hold predictive value regarding endometrial receptivity and provide clinicians a guide to individualise FET protocols and to prevent early pregnancy losses

Trial registration number
N/A