Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer cycles: a randomized clinical trial

To compare the pregnancy outcomes between four regimens of luteal phase support (LPS), including vaginal progesterone, oral dydrogesterone, combination of oral dydrogesterone and gonadotropin releasing hormone analog (GnRH-alpha), and combination of oral dydrogesterone and human chorionic gonadotrophin (hCG), in Frozen-thawed Embryo Transfer (FET) cycles. This randomized clinical trial was performed during a 6-month period, including candidates for FET. Patients were randomly assigned to four groups for LPS: 400 mg vaginal progesterone suppository twice daily, 10 mg oral dydrogesterone twice daily, 10 mg oral dydrogesterone twice daily combined with injection of 0.1 mg GnRH-alpha, and 10 mg oral dydrogesterone twice daily combined with injection of 1500 IU hCG. Primary endpoint included clinical pregnancy rate, ongoing pregnancy rate (OPR), and miscarriage rate (MR). A total of 400 FET cycles were analyzed. CPR was significantly lower in dydrogesterone group (9 %) when compared to vaginal progesterone (20 %), dydrogesterone and GnRH-alpha (25 %), and dydrogesterone and hCG (17 %). Logistic regression showed that only dydrogesterone group had significantly lower CPR in comparison with vaginal progesterone (OR = 0.39; p = 0.03), while it was comparable between other three groups. There were no significant difference between four groups regarding to OPR and MR. Vaginal progesterone provides appropriate LPS. Yet, combination of oral dydrogesterone and GnRH-alpha or hCG can be more suitable option compared to vaginal progesterone for LPS in women with vaginal irritation or discharge at a lower cost.