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Frozen embryo transfer (FET) can be performed through a natural cycle or a medicated (HRT) cycle. Both prepare the uterus for embryo implantation, but in different ways. For intended parents and surrogates, understanding these differences can help you and your doctor choose the safest, most effective path to pregnancy.
🧭 Key Takeaways
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Success rates for live birth are overall comparable between Natural Cycle FET (NC-FET) and Medicated FET, though some studies report slightly higher outcomes with natural cycles.
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Natural cycles rely on the body’s corpus luteum (CL) and skip pre-ovulation estrogen medication.
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Medicated cycles offer precise, predictable timing—helpful for surrogacy coordination and travel.
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Modified natural cycles use an hCG trigger to mimic the LH surge, preserving physiological benefits while improving scheduling control.
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Evidence suggests that cycles without a corpus luteum (as in medicated FET) may have a higher risk of preeclampsia, while natural or modified-natural cycles could be safer for maternal health.
What Is a Natural Cycle FET?
In a Natural Cycle FET, the surrogate’s own menstrual cycle drives the process. The clinic monitors follicle growth and hormone levels; when ovulation is confirmed—naturally or after an hCG trigger—the embryo is transferred about 5–6 days later, matching the uterus’s optimal implantation window.
The modified natural cycle (mNC-FET) is increasingly popular because it combines the body’s own hormonal environment with the precision of an induced LH surge.
In contrast, a Medicated (programmed) FET suppresses natural ovulation entirely, and estrogen plus progesterone are administered to create and maintain the endometrial lining. This method offers full control over timing and is ideal for surrogates or patients with irregular cycles.
Success Rates and Evidence
Most large studies—including analyses of thousands of transfers—show that pregnancy and live birth rates are similar between natural and medicated FET cycles.
Some research, particularly those focusing on single euploid embryo transfers, has found slightly higher ongoing pregnancy rates with natural cycles, while others show no significant difference.
Overall, both methods are considered equally effective when cycles are carefully monitored and luteal support is properly provided.
Recent data also highlight that maternal outcomes may differ between protocols. Pregnancies achieved in cycles without a corpus luteum—as occurs in medicated or fully programmed FET—appear to have a higher risk of hypertensive complications such as preeclampsia. The corpus luteum’s natural secretion of relaxin and vascular growth factors may play a protective role in natural and modified-natural cycles.
The Role of the Corpus Luteum — and Why It Matters
A key biological difference between natural and medicated cycles lies in the presence of the corpus luteum, the temporary gland formed after ovulation.
In natural or modified-natural cycles, the corpus luteum produces progesterone, estrogen, and vasoactive hormones that stabilize the endometrium and support early pregnancy. This provides a more physiologic hormonal environment, similar to natural conception.
In medicated FET, no ovulation occurs—hence, no corpus luteum forms. The pregnancy depends entirely on externally supplied hormones until the placenta takes over around the end of the first trimester.
Luteal Support in Natural Cycle FET
In modern fertility practice, luteal phase support (LPS) is commonly recommended in both natural and medicated cycles.
The true “natural” advantage lies before ovulation, when the uterine lining develops without synthetic estrogen.
After ovulation, most clinics still provide progesterone supplementation—via vaginal or intramuscular administration—to ensure adequate hormone levels. The dosage and duration vary according to clinic protocol and the surrogate’s hormone monitoring, typically continuing until 10–12 weeks of gestation.
Thus, natural cycles do not necessarily mean “no medication” but rather a more physiologically aligned process.
Pros and Cons at a Glance
| Aspect | Natural / Modified-Natural FET | Medicated (Programmed) FET |
|---|---|---|
| Hormone Source | Endogenous (has corpus luteum) | Exogenous (no ovulation) |
| Medication Use | No pre-ovulation estrogen; progesterone after ovulation/trigger | Estrogen before transfer (oral or patch) + progesterone for luteal support |
| Monitoring | More frequent hormone checks and ultrasounds to track ovulation | Fewer visits once the medication plan starts |
| Timing Control | Natural or hCG-triggered; moderately flexible | Fully clinic-controlled; fixed transfer window |
| Cycle Cancellation | Possible if ovulation mistimed | Rarely canceled |
| Cost | Comparable overall (less medication but more monitoring) | Comparable overall (more medication but fewer visits) |
| Patient Experience | Feels more “natural”; uses fewer synthetic hormones before ovulation | Predictable, convenient scheduling; easier coordination for surrogacy |
How to Choose the Right Protocol
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Menstrual regularity: Natural FET suits surrogates or patients with regular ovulation; medicated cycles fit those with irregular or absent cycles.
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Scheduling needs: Medicated cycles offer flexibility and control—useful when multiple parties are involved.
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Hormone sensitivity: Surrogates sensitive to hormones may prefer natural cycles.
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Health considerations: If minimizing hypertensive risks is a concern, natural or modified-natural cycles may offer an advantage.
Ultimately, the best choice is a personalized decision made with your fertility doctor.
At Ivy Surrogacy, we work closely with your chosen clinic and physician to ensure smooth coordination, transparent communication, and personalized support—no matter which protocol your doctor recommends.
🤍 Whether you are a surrogate exploring your next journey or intended parents planning your embryo transfer, our team is here to guide and coordinate every step.
Contact us today to discuss how we can support your natural or medicated FET plan.
FAQs About Natural Cycle FET
1. Is Natural Cycle FET as successful as Medicated FET?
Yes. Most large studies show similar pregnancy and live birth rates, though a few report slightly higher success with natural cycles.
2. Who is a good candidate for Natural or Modified-Natural FET?
Those with regular ovulation and reliable hormone monitoring. Medicated cycles are better for irregular or anovulatory patterns.
3. Does Natural Cycle FET require progesterone support?
Yes. Most clinics recommend luteal phase progesterone after ovulation or hCG trigger to maintain stable hormone levels.
4. Why do some clinics prefer medicated FETs?
Because they allow predictable scheduling and fewer monitoring visits—especially convenient in surrogacy.
5. Are there maternal health differences between the two methods?
Yes. Research shows programmed cycles (without a corpus luteum) may have higher rates of preeclampsia, whereas natural cycles appear to have a more favorable vascular profile.
📚 References
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Alur-Gupta S, et al. Impact of method of endometrial preparation for frozen blastocyst transfer on pregnancy outcome. Fertility and Sterility. 2018;110(4):680–686.
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Wang A, et al. Hormone replacement versus natural frozen embryo transfer for euploid embryos. Archives of Gynecology and Obstetrics. 2019;300(4):1053–1060.
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Wolfe EL, et al. Modified natural and optimized programmed frozen embryo transfers have equivalent live birth rates: an analysis of 6,682 cycles. Fertility and Sterility. 2023;120:80–88.
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von Versen-Höynck F, et al. Increased preeclampsia risk and reduced aortic compliance with IVF cycles in the absence of a corpus luteum. Hypertension. 2019;73(3):640–649.
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Zaat TR, et al. Obstetric and neonatal outcomes after natural vs artificial cycle FET and the role of luteal phase support: a systematic review and meta-analysis. Human Reproduction Update. 2023;29(5):634–654.