Abstract

Abstract Study question Is there an optimal serum progesterone (P) threshold in frozen embryo transfer (FET) modified natural cycles when luteal phase support (LPS) is given? Summary answer Serum P measured on the day of ET is not related with ongoing pregnancy outcome when doing a modified natural cycle with LPS. What is known already Recent publications showed that there is a minimum threshold of serum P that needs to be reached in artificial cycles to optimize pregnancy rates. When using micronized vaginal P (MVP), about 30% of patients show low levels of serum P (<9 ng/mL) leading to a significant decrease in ongoing pregnancy; although this situation can be reverted by increasing and modifying the route of exogenous P. In pure natural cycles without LPS, serum P below 10 ng/mL impairs pregnancy outcome. Nevertheless, there is no data about the impact of serum P levels in modified natural cycles in which LPS is given. Study design, size, duration Prospective cohort unicentric study performed in IVI RMA Valencia (Spain), including 244 cycles from February 2020 to January 2021. Participants/materials, setting, methods Infertile patients <50 y.o. and BMI<40Kg/m2 undergoing a FET of a maximum of 2 blastocysts, from own or donated oocytes. FET were performed in the context of a modified natural cycle (single injection of rec-hCG when dominant follicle reached 17mm and endometrial thickness >6.5mm). MVP was used for LPS (200mg/12h). Ongoing pregnancy rate (OPR) was correlated with serum P levels on the FET day, measured within two hours before transfer. Main results and the role of chance A total of 241 patients were analyzed. Mean age was 38.1 + 3.8 years, with a mean BMI of 23.3 + 3.9. On the rec-hCG day the mean leading follicle size was 17.7±0.1 mm. The endometrium displayed a trilaminar pattern, with a mean thickness of 7.8±3.3 mm, and mean P and estradiol (E2) levels were 0.30±0.03 ng/ml and 249.39±11.03 pg/ml, respectively. A mean of 1.1 blastocysts were transferred (90.9% were single embryo transfers), 27.4% (66) from donated and 72.6 % (175) from own oocytes. On the day of FET, the mean serum P and E2 levels were 26.19 + 8.97ng/mL and 154.12 + 96.08pg/mL, respectively. The overall OPR was 51.5% (124). OPR according to quartiles of serum P (ng/mL) was 56.7% (Q1, P < 20.2), 47.5% (Q2, P > 20.2-24.8), 51.7% (Q3, P > 24.8-31.1), 50.0% (Q4, P > 31.1), p = 0.78). Multivariate logistic regression showed that serum P was not related with OPR after adjusting for age, BMI, E2 and origin of oocytes (aOR:0.98, 95% CI:0.93-1.04, p = 0.47). Only 2 patients had serum P levels below 10 ng/mL, with values of 8.6 and 8.8 ng/mL on the ET day and had a negative pregnancy test. Limitations, reasons for caution As part of our routine clinical practice, MVP (200mg/12h) is given for LPS in patients undergoing a FET in the context of a modified natural cycle. Thus, these results cannot be extrapolated to LPS-free or any other LPS protocol in FET modified natural cycles. Wider implications of the findings The majority of patients undergoing FET in modified natural cycles when using LPS have adequate levels of serum P and thus, do not have an impact on pregnancy outcome. According to our data, there is no need to measure serum P levels on the luteal phase of modified natural cycles. Trial registration number NCT04259996

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