Should the modified natural cycle protocol for frozen embryo transfer be modified? A prospective case series proof of concept study

Modified natural cycles for frozen embryo transfer utilize an ovulation trigger which assists in embryo transfer scheduling and simplifies cycle monitoring. There have been conflicting results with this protocol and modifications may be sought. We wanted to ascertain whether a modified natural protocol for frozen embryo transfer without triggered ovulation but with luteal progesterone support disconnecting the timing of embryo transfer from the timing of the LH surge can achieve a high pregnancy rate. Candidates for frozen embryo transfer of 48-h cleavage cell embryos were recruited from May 2016 to April 2018. The patients were monitored for endometrial growth, follicle formation and estradiol, progesterone, and LH hormone levels. After meeting the predetermined criteria, embryo transfer was scheduled. The patients began progesterone treatment 48 h before embryo transfer, regardless of identification of the LH surge if ovulation had not commenced. The predetermined primary outcome was the biochemical pregnancy rate while the secondary outcome included the clinical pregnancy rate and the ongoing pregnancy rate. Patients were monitored to the eighth week of pregnancy, but data was collected from the medical records to provide the live birth rate as well. Fifty-six women were screened. Eleven women declined or did not meet the inclusion criteria. Three had anovulatory cycles and were excluded. Forty-two women were included in the statistical analysis. The implantation rate was 42.9 % [95 %CI 29.3 %–56.4 %). Of the 42 participants, 25 (59.5 %) conceived [95 % CI 44.0 %–75 %]. Two pregnancies ended in first trimester miscarriage leaving 23 (54.7 %) ongoing pregnancies [95 % CI 39.1 %–70.5 %]. One patient experienced a late abortion such that the live birth rate was 22 of 42 patients or 52.4 % [95 % CI 36.4 %–68.0 %]. The proposed modified natural protocol which utilizes progesterone luteal support but does not trigger ovulation, maintains a high pregnancy rate while providing flexibility regarding the day of transfer disconnected from the day of the LH surge. This was a prospective, proof of concept study. This protocol may be suitable for smaller or public in-vitro fertility units whose resources are limited and facilities are not available daily. The high pregnancy and live birth rate that we found provides confidence that this protocol can be part of the armament of protocols the clinician may offer to his patients. Larger studies should confirm these findi