Defining the LH surge in natural cycle frozen-thawed embryo transfer: the role of LH, estradiol, and progesterone

Objective: Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. In the present retrospective and observational study we aim to evaluate the hormonal changes round the LH surge, for better determination of the LH surge and improving the NC FET outcome. We reviewed the computerized files of all consecutive women admitted to our IVF Institute, between January 1, 2023 and June 30, 2024, who underwent NC FET cycles in our IVF Institute. The elimination of bias in this selection, for the purposes of this study, was achieved by including only patients who had two consecutive hormonal blood tests and transvaginal ultrasound evaluations prior to ovulation, on two days (D- 2) before and one day before ovulation (D- 1). Data on patient demographics and infertility-treatment-related variables were collected from the files. We studied and compared several variable between patients who conceived and those who did not, including the % changes in LH (D- 1 minus D- 2/D- 2), in estradiol (D- 2 minus D- 1/D- 2) and % change in progesterone (D- 1 minus D- 2/D- 2) levels. Results: Six hundreds and sixty-eight NC FET cycles were performed during the study periods. Pregnancy was achieved in 348 patients (pregnancy rate, 52% per cycle). Figure that is not-significantly higher than our previous reported outcome, when the LH surge was defined only by the rise in LH level (46% per cycle). Patients who conceived were significantly younger, with no in-between group differences in LH, E2 and progesterone levels. Moreover, while no differences were observed in the % changes in E2, nor LH levels, the % change in progesterone levels was significantly higher in those who conceived (1.9 + 1.5 vs 1.6 + 1.4, p < 0.013), as compared to those who did not. Conclusions: Patients undergoing NC FET should be monitored by LH, estradiol and progesterone levels. We suggest that the LH surge should be determined by an increase in LH, concomitant to a drop in estradiol and a threefold increase in progesterone levels between D- 2 to D- 1. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.