Modified natural cycle for embryo transfer using frozen-thawed blastocysts: A satisfactory option

Abstract Objective To describe pregnancy outcomes of frozen-thawed blastocysts cycles using modified natural cycle frozen embryo transfers (NC-FET) and down-regulated hormonally controlled frozen embryo transfers (HC-FET) protocols. Study design This retrospective cohort study included all patients undergoing either modified NC-FET or down-regulated HC-FET using frozen-thawed day 5 embryos. Cycles with donor blastocysts were excluded. Four hundred twenty eight patients underwent a total of 493 FET cycles. Patients with regular menses and evidence of ovulation underwent modified NC-FET. These patients were given hCG 10,000 IU IM on the day of LH-surge. Vaginal progesterone (P4) was started two days later and blastocyst transfer was planned seven days after detecting the LH surge. Anovulatory patients and some ovulatory patients underwent down-regulated HC-FET. These patients were placed on medroxy-progesterone acetate (10 mg) for 10 days to bring on menses and were also given a half-dose of GnRH-agonist (GnRH-a) on the third day of medroxy-progesterone acetate. Exogenous estradiol was initiated on the third day of menses. Once serum E2 levels reached >500 pg/mL and endometrial lining reached >8 mm, intramuscular (IM) P4 in oil was administered. Blastocyst FET was planned 6 days after initiating P4. The primary outcomes included clinical pregnancy and delivery rates. Results There were 197 patients in the modified NC-FET protocol and 181 in the down-regulated HC-FET protocol. Mean age (years), day-3 FSH levels (mIU/mL) and percentage of patients with male factor infertility were significantly higher and mean BMI (kg/m 2 ) was significantly lower in modified NC-FET compared to HC-FET, respectively. Analysis of the first cycle pregnancy outcomes revealed no significant differences in clinical pregnancy rate (54.3% vs. 52.5%) and delivery rate (47.2% vs. 43.6%) between modified NC-FET and HC-FET. Logistic regression analysis showed age (OR = 0.939, 95% CI 0.894–0.989, p = 0.011), number of blastocysts transferred (OR = 1.414, 95% CI 1.046-1.909, p = 0.024), and the year of FET (OR = 1.127, 95% CI 1.029-1.234, p = 0.010) were significant factors impacting clinical pregnancy. An age analysis within three age groups (≤35, 36–39, ≥40) was performed, but no significant difference in clinical pregnancy was observed. Conclusion Our data suggests that modified NC-FET protocol has comparable pregnancy outcomes to down-regulated HC-FET when utilizing frozen-thawed day 5 embryos.