P-490 Impact of follicular phase characteristics on mid-luteal progesterone and ongoing pregnancy rates: Lessons learned from true natural cycle frozen embryo transfer
Authors: Erden M , Polat M , Mumusoglu S , Yarali Ozbek I , Esteves S , Humaidan P , Yarali H 
Published: June 2023

Abstract

Study question
Is there an association between follicular phase endocrine and ultrasonographic characteristics and ongoing pregnancy rates (OPRs) in true-natural cycle (t-NC) frozen embryo transfers (FETs)?

Summary answer
Endometrial thickness one day before ovulation is the only independent predictor of ongoing pregnancy (OP) in t-NC FET cycles.

What is known already
In ovulatory women, NC FET is currently being proposed instead of the hormonal replacement treatment (HRT) protocol since HRT is associated with increased maternal and obstetric risk factors, most probably due to the absence of a corpus luteum. However, the presence of ovulation in regularly cycling women does not guarantee a receptive endometrium. Currently, there is a lack of data regarding the impact of follicular phase endocrine and ultrasonographic parameters on mid-luteal progesterone (P4) levels and OPRs in t-NC FET cycles.

Study design, size, duration
A cohort study of 229 women who underwent warmed blastocyst transfer employing t-NC. Three strategies were adopted. During January 2017-June 2017, serum P4 was not monitored. During July 2017-June 2020, serum P4 was routinely monitored on the FET-1 day. During July 2020-August 2022, a rescue strategy with daily 25-mg subcutaneous progesterone was adopted for patients with P4 levels between 7-10 ng/mL. In patients with serum P4&lt;7 ng/mL FET was cancelled.

Participants/materials, setting, methods
Staying in-town and having regular menstrual cycles, permitting intensive endocrine and ultrasonographic monitoring (daily serum estradiol [E2], luteinizing hormone [LH], P4, and transvaginal ultrasonography), starting mid-cycle until confirmation of ovulation was the only inclusion criteria. Only the first FET cycle per patient was included. The primary outcome measure was OPR. The impact of follicular phase endocrine and ultrasonographic parameters on serum P4 levels on the FET-1 day and OPRs were evaluated using regression analysis.

Main results and the role of chance
Follicular phase parameters, including follicular phase length, late follicular phase E2, LH, P4 levels, and maximal follicle diameter before ovulation, were not significant predictors of ongoing pregnancy (OP) in t-NC FET. In contrast, the endometrial thickness one day prior to ovulation was a significant independent predictor of OP (adjusted OR = 1.29, 95% CI:1.06-1.56). When endometrial thickness before ovulation was assessed in quartiles, univariate OPRs in the 25th (&lt;9.1 mm), 25-50th (9.1-10.1mm), 51-75th (10.2-11.6 mm) and &gt;75th (&gt;11.6 mm) percentiles were 43.3%, 47.3%, 71.7%, and 54.7%, respectively (p=0.016). Following logistic regression analysis, the adjusted ORs for OPR of the 51-75th (3.69, 95% CI:1.42-9.56) and &gt;75th (2.86, 95% CI: 1.06-7.73) percentiles were significantly higher when compared with that of &lt; 25th. The three strategies for monitoring/acting (rescue if needed) based on serum P4 levels on the FET-1 day were associated with similar adjusted ORs for OP. Notably, cancellation of cycles with serum P4 &lt;7 ng/mL and adopting a rescue policy for those with 7-10 ng/mL did not increase OPRs. After multivariate linear regression analysis, late follicular E2 levels (ß-coefficient: 0.399 ng/mL, 95% CI:0.007;0.021) and BMI (ß-coefficient: −0.292 ng/mL, 95% CI: −0.730;-0.222) were the only significant predictors of P4 levels on the FET-1 day.

Limitations, reasons for caution
Limitations include the cohort study design evaluating three different policies, the single point serum P4 assessment, and adopting an arbitrary lower cut-off of &lt; 7 ng/mL for cycle cancellation and 7-10 ng/mL for a rescue strategy.

Wider implications of the findings
Endometrial thickness one day before ovulation was the only significant predictor of OP in t-NC FET cycles. Apart from endometrial thickness, none of the follicular phase parameters were significant predictors of OP. Single-point assessment of serum P4 may not be reliable when assessing reproductive outcomes in t-NC FET.

Trial registration number
Not applicable