Do the different luteal progesterone support regimens affect the serum progesterone levels and live birth rates in frozen-thawed embryo transfer cycles? a randomized prospective study

To determine the ideal luteal progesterone support regimen and serum progesterone level on the day of embryo transfer to achieve a live birth in hormone replacement treatment - frozen-thawed embryo transfer (HRT-FET) cycles The present randomized prospective study including 237 infertile women was performed between January 2021 and June 2022 in the IVF center of a tertiary university hospital. Patients who underwent HRT-FET (single – good quality blastocyst-Gardner A/B) were randomized into three groups depending on the luteal phase progesterone regimen; Group 1 (incrementally increased vaginal progesterone doses; 400mg-600mg-800 mg), Group 2 (600 mg vaginal) and Group 3 (on the day of ET subcutaneous progesterone 25 mg added to 600 mg vaginal). Serum progesterone levels were measured on the day of starting progesterone administration, on the day of embryo transfer and on the day of pregnancy testing. A total of 237 patients were included (67 in Group1, 95 in Group2, 75 in Group3). The median serum progesterone levels on the day of ET in Group 1 were significantly higher than the other groups [Respectively - with interquartile ranges; 12.9 ng/ml (6.6-24.5), 10.5 ng/ml (0.20-25.9), 9.8 ng/ml (3-25.5), p<0.01]. Live birth rates (LBR) were similar between the groups (Respectively; 37%, 34.8%, 28.3%, p=0.345). The ROC analysis showed a significant correlation between progesterone level on ET day and LBRs (Area under curve: 0.65, p= 0.004) and a threshold of progesterone to predict the LB was found at 10.65 ng/ml (71% sensitivity and 51% specificity). There were different reported threshold levels for progesterone on the day of embryo transfer to predict the live birth (8.8 ng/ml, 9.2 ng/ml and 10 ng/ml). Our results (10.65 ng/ml) were similar to the existing evidence that low serum progesterone levels could be detrimental to HRT-FET success rates. However, the relationship between serum progesterone levels and the different progesterone routes and doses appears to be nonlinear. Different types and doses of progesterone routes could exhibit different patterns of progesterone release. Systemic serum progesterone measurements could not truly be representative for each LPS progesterone administration regimen and to decide rescue regimen.