Natural cycle versus hormone replacement cycle for transferring vitrified-warmed embryos in eumenorrhoeic women. A retrospective cohort study

Abstract

Objective: To compare pregnancy, miscarriage and live birth rates and cycle monitoring parameters between Natural Cycle (NC-FET) and Hormone replacement cycle (HRC-FET) in eumenorrhoeic women undergoing vitrified-warmed autologous embryo transfer.

Study design: Single-centre retrospective cohort study analyzed 173 NC-FET and 507 HRC-FET cycles with transfer of day2/3/5/6 embryos. Natural cycle monitoring occurred with serial ultrasound with the first day of the scan determined by the shortest cycle frequency. Serum progesterone was ordered when ultrasound was ambiguous in ascertaining ovulation. For HRC-FET oral estradiol valerate was used in fixed or escalating doses with maximum daily dose of 12 mg. Transdermal estradiol gel was added when desired endometrial thickness was not achieved. Vaginal progesterone was introduced with Endometrial thickness(ET)> = 7 mm. Embryos were transferred after stage-appropriate progesterone exposure. Luteal support was given with vaginal progesterone in NC-FET and vaginal and oral progesterone in HRC-FET. Primary outcome was live-birth-rate. Secondary outcomes were ET, length-of-estrogenic-phase, numbers-of-ultrasounds&hormone-monitoring, pregnancy&miscarriage rate. The odds ratio for live-birth was adjusted for age, embryo number, previous-live-births, previous-losses, past-negative-ET-cycles, IVF-indication and embryo-developmental-stage. Quantitative variables were compared using unpaired-t-test and qualitative variables with chi-square test. Two tailed p-value < 0.05 was considered significant. Binary logistic regression was used to calculate adjusted odds for live-births.

Results: The two cohorts were comparable in age, infertility-duration, previous-live-births, previous-losses, past-negative-ET-cycles, IVF-indication and embryo-developmental-stage. Length-of-estrogenic-phase was significantly shorter for NC-FET than HRC-FET 14.32 ± 2.83vs.18.18 ± 4.48; p = 0.0001) as was mean ultrasound-monitoring-scans (2.73 ± 0.95vs. 3.3 ± 1.04; p = 0.0001). Mean-endometrial-thickness (8.75 ± 1.83vs. 8.5 ± 1.25; p = 0.25) and mean-hormonal-tests (1.75 ± 1.28 vs. 1.88 ± 0.69; p = 0.09) did not differ significantly between NC-FET vs HRC-FET. Significantly higher live births took place in NC-FET vs. HRC-FET (87/173 = 50.3%vs.204/507 = 40.2%;p = 0.026). No significant difference was found in pregnancy rate (66.5% vs. 58%; p = 0.058) or in the pregnancy loss rate (24.3%vs30.6%; p = 0.23). The odds ratio for live-births adjusted for relevant variables was 1.48 (1.03-2.13) in NC-FET compared to HRC-FET.

Conclusions: NC-FET is a superior method of endometrial preparation compared to HRC-FET in eumenorrhoeic women since it has a shorter estrogenic phase, reduces patient visits to the hospital and improves live birth rates. Future adequately powered studies should look at antenatal and perinatal outcomes, patient satisfaction rates and cost-effectiveness in the two endometrial preparation regimes.

Keywords: Frozen embryo transfer; Hormone replacement cycle; In-vitro-fertilization; Live births; Natural cycle.