Effects of hormone replacement therapy on endometrial hormone concentrations and progesterone receptor expression in recurrent pregnancy loss: a self-controlled study

Aim: To investigate the differential effects of endometrial preparation approaches, natural cycle (NC) and hormone replacement therapy (HRT), on the endometrial hormone conditions in patients with recurrent pregnancy loss (RPL).

Methods: 42 RPL patients were recruited, and a self-controlled trial was conducted to compare the effectiveness of NC to HRT on the same patient. The estradiol (E2) and progesterone (P) levels in both serum and endometrial tissue were measured in NC and HRT, respectively. Meanwhile, the expression levels of endometrial progesterone receptor A (PRA) and progesterone receptor B (PRB) were also compared between NC and HRT cycles during the window of receptivity. All statistical analyses were performed using GraphPad Prism 5, and data were averaged across subjects and tested for significance by pair-samples t-test.

Results: Hormone replacement slightly decreased serum E2 and P levels (0.9- and 0.8-fold in average, respectively), significantly elevated endometrial E2 and P (2.1- and 14.5-fold in average, respectively), and reduced endometrial E2/P ratio (0.34-fold in average) compared to the NC condition. However, no correlation was found between serum and endometrial hormone concentrations. Further, the PRA/PRB ratios of both stromal and glandular cells were comparable between HRT and NC conditions, even though stromal PRA expression was slightly elevated by HRT compared to NC (1.63±0.96 vs 1.18±0.99, p =.0173).

Conclusion: The effects of HRT for endometrial preparation are similar or slightly superior to NC in RPL patients.