Modified natural cycles improve live birth

Natural cycle preparation modestly improves live birth and lowers miscarriage after frozen embryo transfer.
*Systematic review and meta-analysis of randomized trials; Level 1.

Citation

Lin LT, Chang R, Chen SN, et al. Natural Compared With Artificial Cycle Endometrial Preparation for Frozen Embryo Transfer: A Systematic Review and Meta-analysis. Obstet Gynecol. 2026;148:e92-e107. doi:10.1097/AOG.0000000000006347

Background

Frozen embryo transfer is common, but the best way to prepare the uterine lining remains debated. Natural cycles may better mimic normal hormones, while artificial cycles offer easier scheduling.

Patients

Women aged 18 to 45 years undergoing frozen embryo transfer. Exclusions included fresh transfers, donor egg cycles, surrogacy, severe uterine scarring, nonrandomized studies, abstracts, and non-English full texts.

Intervention

Natural cycle preparation, including true natural cycles or modified natural cycles using an ovulation trigger.

Control

Artificial cycle preparation using estrogen and progesterone, with or without ovarian suppression.

Outcome

Live birth, clinical pregnancy, miscarriage, and cycle cancellation.

Follow-up Period

Through pregnancy outcome after the frozen embryo transfer cycle.

Results

Outcome Natural cycle Artificial cycle Effect
Live birth (primary) 41.5% 39.2% RR 1.11 (95% CI 1.03 to 1.19); NNT 31
Miscarriage 13.4% 17.5% RR 0.78 (95% CI 0.68 to 0.88); NNT 23 to prevent one miscarriage
Modified natural cycle live birth 29.3% 26.8% RR 1.11 (95% CI 1.01 to 1.23)

RR, risk ratio; CI, confidence interval; NNT, number needed to treat.

Clinical pregnancy, true natural cycles, and cycle cancellation did not differ significantly. Results used intention-to-treat analysis.

Limitations

Many trials had some or high risk of bias, and treatment blinding was not feasible. Cancellation rates varied widely between centers, limiting practical prediction. Benefits were modest and mainly seen with modified natural cycles, so results may not apply to anovulatory patients or clinics without intensive monitoring.

Funding

No reported funding or conflicts of interest.

Clinical Application

Consider modified natural cycles for ovulatory women undergoing frozen embryo transfer; artificial cycles remain useful when scheduling or anovulation matters.