The optimal endometrial preparation for frozen-thawed single embryo transfer in a natural cycle: a retrospective analysis

Abstract

Single embryo transfer (SET) is the best method for preventing multiple births. The purpose of this study is to evaluate pregnancy outcomes with or without luteal phase support (LPS) of frozen-thawed single blastocyst transfer (SBT) treatment performed in natural cycles. The study retrospectively analyzed 966 frozen-thawed SBT in natural cycles with or without LPS performed between the periods January 2010 to April 2013. Oral chlomadinone acetate (Lutoral®) was given daily during the luteal phase. The outcomes of frozen-thawed SBT treatment including demographic data, clinical pregnancy rates and miscarriage rates, were compared with or without LPS. Ovulation was determined by the LH surge, progesterone (P4) levels and ultrasonography. And all patients underwent ovarian stimulation with human chorionic gonadotrophin (hCG). In order to determine whether the P4 levels after ovulation are associated with clinical pregnancy rate or miscarriage rate, we analyzed P4 levels 2 days after ovulation in 383 cycles out of 966cycles with or without LPS. Post ovulation P4 levels were divided into four groups (with (+), without (-) LPS): Low (L+, L-), 1.4-4.4ng/ml; Middle Low (ML+, ML-), 4.5-5.5ng/ml; Middle High P4 (MH+, MH-), 5.6-7.5ng/ml and High (H+, H-), 7.6-14.8ng/ml. There were no significant differences in the patients’ demographic data (age, basal FSH and embryo quality), clinical pregnancy rate (42.5% vs. 38.0%, p=0.150) and miscarriage rate (24.7% vs. 20.3%, P=0.296), between the groups. On the second comparison (383 cycles), a strong tendency of increased clinical pregnancy rates were observed in the high P4 levels group compared to the low P4 levels group (51.1% (H-) vs. 31.9%(L-), p = 0.059) and (42.1% (H+) vs. 28.0%(L+), p=0.131), but no difference in the miscarriage rates were noted (26.7% (H-) vs. 25.0% (L-), p=0.908) and (37.5% (H+) vs. 23.8% (L+), p=0.367). The pregnancy outcomes of natural cycle frozen-thawed SBT were similar regardless of LPS. Our results suggest that LPS with oral chlomadinone acetate may not improve the clinical pregnancy nor decrease miscarriage rate. Patients with low levels of P4 might need additional interventions in order to achieve higher pregnancy rates. Our findings suggest that 2-day post ovulation levels ≥ 7.6 ng/ml of P4 provide an optimal endometrial environment. However, we need further studies to determine the optimal treatment for patients with low P4 levels to undergo frozen thawed SBT in a natural cycle.