Natural Compared With Artificial Cycle Endometrial Preparation for Frozen Embryo Transfer: A Systematic Review and...

Area of Science:

• Reproductive Endocrinology
• In Vitro Fertilization (IVF)
• Clinical Trials

Background:

• Endometrial preparation is crucial for successful frozen embryo transfer (FET).
• Two primary protocols exist: natural cycle and artificial cycle preparation.
• Comparing their efficacy in achieving live births is essential for optimizing fertility treatments.

Purpose of the Study:

• To compare live-birth rates between natural and artificial cycle endometrial preparation in women undergoing FET.
• To evaluate the impact of different natural cycle variations (true vs. modified) on pregnancy outcomes.

Main Methods:

• Systematic review and meta-analysis of randomized controlled trials (RCTs).
• Literature search across multiple databases up to July 2025.
• Inclusion of 11 RCTs (9,955 women) comparing natural vs. artificial cycles for FET.

Main Results:

• Natural cycle preparation demonstrated significantly higher live-birth rates (41.5% vs. 39.2%) compared to artificial cycles (moderate-quality evidence).
• Modified natural cycles, particularly with hCG trigger, showed a significant benefit (RR 1.11).
• Natural cycles were associated with lower miscarriage rates (13.4% vs. 17.5%).

Conclusions:

• Natural cycle endometrial preparation, especially modified natural cycles with hCG trigger, is linked to superior live-birth rates in FET.
• Artificial cycle preparation may be less effective in achieving live births.
• Further research may refine understanding of true natural cycles versus modified approaches.