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Natural Cycle Frozen Embryo Transfer: Evaluating Optimal Protocols for Preparation and Timing
Kai N Holder1, Jessica S Mormol2, Jennifer B Bakkensen3
1Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Journal of Human Reproductive Sciences
|February 7, 2024
Summary
Natural cycle frozen embryo transfer (NC-FET) protocols show varied approaches. Different ovulation induction, trigger, and timing methods did not significantly impact implantation, pregnancy, or live birth rates in this study.
Area of Science:
- Reproductive endocrinology
- Infertility treatments
- Assisted reproductive technologies
Background:
- Natural cycle frozen embryo transfer (NC-FET) is increasingly utilized.
- Significant practice variations exist in NC-FET protocols, including ovulation induction, trigger administration, and embryo transfer timing.
- There is no established consensus on the optimal NC-FET protocol.
Purpose of the Study:
- To evaluate the association between key NC-FET protocol aspects and cycle outcomes.
- To assess the impact of letrozole use, ovulation trigger method, and transfer timing on implantation, pregnancy, and live birth rates.
Main Methods:
- Retrospective cohort study of blastocyst stage NC-FET cycles (October 2019 - July 2021).
- Evaluated three primary predictors: letrozole use, exogenous trigger vs. spontaneous LH surge, and trigger-based vs. progesterone-based timing.
- Primary outcomes included implantation, clinical pregnancy, and ongoing pregnancy rates.
Main Results:
- 183 cycles from 170 patients were analyzed.
- Average implantation rate was 0.58; clinical pregnancy rate was 59.0%; ongoing pregnancy rate was 51.4%.
- No significant associations were found between any of the evaluated protocol variations and implantation, clinical pregnancy, ongoing pregnancy, or live birth rates after adjustment.
Conclusions:
- Various NC-FET preparation and timing protocols may yield comparable outcomes.
- Flexibility in protocol selection based on patient and physician preference may be possible.
- Findings require validation through larger, randomized trials.

