By Dr. Jessie Wai Leng Phoon, MRCOG
Medical Director, GenPrime Fertility Singapore
Last reviewed: January 2026
When preparing for a frozen embryo transfer (FET), many patients assume that the way the uterus is prepared doesn’t really matter—as long as the embryo is good.
In reality, the endometrial preparation method may influence not just whether pregnancy occurs, but whether it continues.
This article explains the difference between natural-cycle and medicated (hormone replacement therapy, or HRT) FET, and what clinical evidence tells us about miscarriage and live birth outcomes. It is based on a large study conducted at KK Women’s and Children’s Hospital in Singapore and published in Fertility & Reproduction.
What is a frozen embryo transfer (FET)?
A frozen embryo transfer involves placing a previously frozen embryo into the uterus in a later cycle, rather than transferring it immediately after IVF stimulation.
FET has become increasingly common because it:
- Allows safer IVF cycles
- Reduces the risk of ovarian hyperstimulation
- Offers flexibility in timing
- Uses improved freezing techniques with high survival rates
A key decision before FET is how the uterine lining (endometrium) is prepared.
The two main ways to prepare the uterus for FET
Natural-cycle FET
A natural FET uses your own menstrual cycle hormones.
What this involves:
- Monitoring ovulation with ultrasound and hormone tests
- Timing embryo transfer to your natural ovulation
- Usually adding progesterone support after transfer
This option is generally suitable for women with regular ovulatory cycles.
Medicated (HRT) FET
A medicated FET uses oestrogen and progesterone to prepare the uterine lining.
What this involves:
- No reliance on natural ovulation
- More predictable scheduling
- Fewer monitoring visits in some cases
This approach is often used for:
- Women with irregular cycles
- Women who do not ovulate
- Situations where timing flexibility is important
Does the type of FET cycle affect pregnancy outcomes?
This is the key question the study explored.
Researchers reviewed 2,752 frozen embryo transfer cycles over five years and compared outcomes between:
- Natural-cycle FET
- Medicated (HRT) FET
They looked specifically at:
- Miscarriage rates
- Live birth rates
What the study found?
Pregnancy rates were similar
- The chance of achieving a pregnancy was similar in both natural and medicated cycles
This means embryos were implanting at comparable rates.
Miscarriage rates were different
- Miscarriage occurred in about 22% of pregnancies after natural-cycle FET
- Miscarriage occurred in about 38% of pregnancies after medicated FET
Even after adjusting for factors such as age, BMI, embryo type, and fertility diagnosis, medicated cycles were associated with a significantly higher risk of miscarriage.
Live birth rates favoured natural cycles
- Live birth rates were higher in natural-cycle FET
- The higher miscarriage rate in medicated cycles translated into fewer babies born overall
In other words, while pregnancy may occur at similar rates, the chance of taking a pregnancy home was better in natural cycles when ovulation was possible.
Why might this happen?
The exact reason is not fully understood, but there are some leading theories.
In a natural cycle:
- The body produces luteinising hormone (LH) naturally
- LH may play a role in endometrial receptivity and early placental development
In medicated cycles:
- Natural LH production is suppressed
- The uterus relies entirely on external hormones
Some studies suggest this difference in hormonal signalling may affect implantation stability and early pregnancy development.
Does this mean medicated FET is “bad”?
No — and this is important.
Medicated FET:
- Is essential for women who do not ovulate
- Is often the only practical option in certain medical situations
- Can still result in healthy pregnancies and live births
The takeaway is not that medicated cycles should be avoided, but that natural cycles may be preferable when they are safely possible.
How this affects real-life decision-making?
If you have regular menstrual cycles, your fertility specialist may discuss:
- Whether a natural-cycle FET is suitable for you
- The pros and cons of predictability vs potential outcome differences
If you do not ovulate regularly, a medicated cycle remains a reliable and effective option.
The best approach is individualised, balancing:
- Medical suitability
- Convenience
- Monitoring burden
- Your personal priorities
Questions to ask your doctor
If you’re planning a frozen embryo transfer, consider asking:
- Do I ovulate regularly enough for a natural-cycle FET?
- What are the benefits and drawbacks of a natural vs medicated cycle in my case?
- How will my cycle be monitored?
- Does my diagnosis (e.g. PCOS, ovulatory disorder) affect which option is better?
- How many visits and medications are involved with each approach?
A simple next step
If you’re preparing for a frozen embryo transfer, start with a conversation about cycle type, not just embryo quality.
Understanding how your uterus is prepared—and why one approach may suit you better—can help you move forward with greater clarity and confidence.
About Author
Dr. Jessie Wai Leng Phoon, MRCOGDr is a leader in fertility innovation and integrated women’s health, blending advanced clinical training with a personal approach to care. A graduate of the University of Auckland, she is an MOH-accredited IVF specialist with expertise across assisted reproduction and minimally invasive surgery. She previously served as Director of KKIVF Centre and the National Sperm Bank, and co-founded Singapore’s pioneering OncoFertility Clinic.