Spontaneous ovulation and corpus luteal activity in natural proliferative phase frozen embryo transfer protocol with natural progesterone as luteal phase support: A prospective study

Background The preferred frozen embryo transfer (FET) protocols for ovulatory patients are those where ovulation is preserved as they are associated with better obstetric and perinatal outcomes. The natural proliferative phase (NPP)-FET protocol is a recent, simple and effective protocol for ovulatory patients. As progesterone is initiated prior to ovulation in the NPP–FET protocol, evidence is required to confirm ovulation and the presence of the corpus luteum (CL). Objective To study the evidence for ovulation and CL activity in NPP-FET cycles when natural progesterone is used as luteal phase support (LPS) by estimating serum relaxin-2 levels in NPP-FET pregnancies. Design A prospective cohort study Methods This study included three cohorts of patients-NPP-FET pregnancies (n=28), artificial cycle (AC)-FET pregnancies (n=11) and spontaneous conceptions (SC) (n=24). In the NPP-FET cycles when endometrial thickness was > 7 mm, trilaminar and serum progesterone <1 ng/ml, then intramuscular progesterone was initiated. Vaginal progesterone was added from the day of ET. Day 3 or day 5 embryos were transferred. Serum relaxin-2 levels were estimated prior to initiation of progesterone in the NPP-FET and AC-FET cohorts and again in early pregnancy at 6–8 weeks of gestation in all the patients. Outcome measures Evidence for spontaneous ovulation in NPP-FET cycles and CL activity in NPP-FET pregnancies Results A significant increase in serum relaxin-2 levels were observed in 25/28 (89.3%) patients with NPP-FET pregnancies. Median serum relaxin-2 levels in NPP-FET pregnancies were significantly lower compared with those in spontaneously conceived pregnancies (368.4 pg/ml and 494.4 pg/ml, respectively; p= 0.0003). Conclusion Ovulation is preserved in most of the NPP-FET cycles where natural progesterone is used for LPS. However, the CL activity appears to be altered or suboptimal. Further studies are required to determine whether this translates into adverse clinical outcomes, and if LPS needs to be adjusted accordingly to optimize outcomes in the NPP-FET cycles.