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A guide to understanding Frozen Embryo Transfer (FET)

The first successful birth from a frozen embryo occurred in 1984, with the birth of Zoe Leyland in Australia. This marked a major milestone in reproductive technology and paved the way for the widespread use of frozen embryo transfer (FET) we see today. While the first successful birth was in 1984, research and experimentation on embryo cryopreservation had been ongoing for some time prior. The development of effective freezing techniques, particularly vitrification (a rapid freezing method), has significantly improved the success rates of FET over the years.

Since then Frozen Embryo Transfer (FET) has revolutionized assisted reproductive technology (ART), offering hope and expanded options for individuals and couples facing infertility. This technique involves freezing and storing embryos created during an in-vitro fertilization (IVF) cycle for later use. Once considered experimental, FET is now a well-established and increasingly common practice, often yielding comparable, and in some cases even improved, pregnancy success rates compared to fresh embryo transfers. This advancement has provided greater flexibility in treatment planning, allowing for better control over the timing of embryo transfer and minimizing the risks associated with ovarian hyperstimulation syndrome (OHSS).  

Cryopreservation Techniques

The core principle of FET lies in cryopreservation, a process that uses extremely low temperatures to preserve embryos at a stage where their biological activity is essentially paused. These embryos are typically created through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and then frozen for future use. This allows for indefinite storage without significant degradation of embryo quality. The success of a frozen embryo transfer cycle relies on the quality and viability of the cryopreserved embryos. Prior to the FET cycle, the embryos undergo thorough assessment to ensure their viability and suitability for transfer. This includes evaluating their morphology, developmental stage, and genetic screening if performed during the initial IVF/ICSI cycle.

Vitrification Improves Embryo Survival Rates in Frozen Embryo Transfer:

Vitrification of embryos significantly improves FET outcomes compared to the older “slow freezing” method by addressing a key challenge: the formation of ice crystals. Embryo Vitrification minimizes the formation of ice crystals within the cells (a problem seen in older slow freezing method), which can damage the embryos during the freezing and thawing process. These ice crystals could damage cellular structures, such as membranes and organelles, reducing the embryo’s viability upon thawing. Vitrification, on the other hand, uses extremely rapid cooling rates and high concentrations of cryoprotectants (substances that protect cells during freezing) to essentially “flash freeze” the embryos. This rapid cooling prevents the formation of damaging ice crystals, resulting in much higher survival rates after thawing. This improvement has significantly enhanced the survival rates of frozen embryos and contributed to the increased success of FET procedures.  

IVF with a Frozen Embryo Transfer cycle offers several advantages:

The benefits of Froze Embryo Transfer extend beyond simply preserving embryos for future use. It offers several key advantages over fresh embryo transfers. Firstly, it allows for more thorough preimplantation genetic testing (PGT) of embryos. Because embryos can be frozen after biopsy, there is sufficient time to receive the PGT results before transfer, allowing for the selection of chromosomally normal embryos and potentially increasing implantation rates and reducing the risk of miscarriage.

Secondly, FET provides an opportunity to optimize the uterine environment for implantation. In some cases, the hormonal stimulation required for a fresh IVF cycle can temporarily create a less-than-ideal uterine lining. By transferring frozen embryos in a subsequent, more natural or controlled cycle, clinicians can ensure the endometrium is optimally receptive. This is particularly beneficial for women with conditions like polycystic ovary syndrome (PCOS) or those who experience elevated progesterone levels during the follicular phase of their fresh IVF cycle.  

Furthermore, FET offers greater flexibility for patients. It allows for postponing embryo transfer for medical or personal reasons, such as undergoing treatment for other health conditions or simply needing more time to prepare emotionally and logistically for pregnancy. This flexibility also reduces the pressure associated with coordinating the transfer with a fresh IVF cycle, which can be stressful and demanding.

This article will delve into the specifics of the FET process, explore its success rates, and elaborate on the various benefits it offers, providing a comprehensive overview of this important advancement in reproductive medicine.  

  • Better Outcomes with FET
  • Why FET is done?
  • FET VS Fresh Embryo Transfer
  • IVF with FET Success Rate

Better Outcomes with FET

How Synchronized events lead to successful pregnancy

An optimal uterine environment and endometrial receptivity is essential to the success of embryo transfer. Lets understand how this is achieved in a natural cycle. Estrogen levels naturally peak soon before ovulation during the menstrual cycle. Ovulation is triggered by an increase in estrogen, which causes the ovaries to begin releasing progesterone. The endometrial lining of the uterus is then triggered by progesterone.

A fertilized egg must be implanted in the endometrial lining and continue to expand in order for a pregnancy to develop. Because the body produces progesterone in response to ovulation, the endometrial lining develops at the appropriate rate to nurture the fertilized egg in an ideal environment. The optimum environment for implantation is when the progesterone response and endometrial lining development are in sync.

How desynchronization happens during IVF cycle.

During IVF treatment ,the ovaries are stimulated via hormonal medications, and estrogen levels peak at significantly higher levels than in normal cycles. Progesterone production is triggered by this artificially generated estrogen peak.

Progesterone levels can become too high too soon, causing the endometrial lining to mature too quickly. The possibility of successful implantation is reduced when an embryo and endometrial lining are out of sync. The suppression of progesterone production is one of the reasons why IVF patients use medicines. However, these drugs may not work in some people, and they may still have problems with cycle desynchronization.

How does FET overcome IVF desynchronization

One technique to avoid desynchronization is to use frozen embryo transfer. Delaying embryo transfer until a later cycle allows your hormones to return to normal before starting, which may improve your chances of becoming pregnant. Embryos are generated and frozen rather than implanted while the body is still healing from IVF. The embryos are frozen and implanted once the body has recovered from the stress of IVF and has returned to a more normal cycle. Embryos are generated, biopsied, tested, and frozen during the first cycle. Once the biopsy findings have been received and the female partner has recovered from her egg retrieval, an embryo transfer will be scheduled.

  • Desynchronization can be avoided by using frozen embryo transfer.
  • Delaying embryo transfer until a later cycle allows your hormones to return to normal before starting, which may improve your chances of getting pregnant.

Why FET is done?

Frozen Embryo Transfer is recommended to get pregnant to those couples who have specific health issues or circumstances as:

  • Considering genetic screening (PGT) (most common indication)
  • Considering an elective procedure
  • When the consulting fertility specialist considers that a couple has a high chance of getting Ovarian hyperstimulation syndrome (OHSS)
  • Transfer of fresh embryos not possible due to any medical reason
  • Couples considering another child with the embryos created during one IVF cycle

FET VS Fresh Embryo Transfer

Fresh embryo transfer takes place during the same IVF cycle as IVF. In the lab, the eggs are extracted and fertilised. The embryos are allowed to mature before being returned to the woman’s uterus 3-5 days after being removed. Whereas, a woman undergoes IVF, her eggs are extracted and fertilised in the lab, and the resulting embryos are allowed to develop in a frozen embryo transfer cycle. Instead of being transferred back into her uterus on day 5 or 6, the embryos are frozen.

Benefits of FET over Fresh Embryo Transfer

Less Medication: Most patients are kept on a natural cycle with no medication and Frozen Embryo Transfer is carried out at the appropriate time. In others, minimal oral estrogen is good enough to prepare her endometrium.

Less Stress: Patients who use high-quality blastocyst-stage frozen embryos have a better chance of a successful FET cycle. With fewer cycle cancellations, cycles are also more predictable.

Better IVF planning: An IVF cycle including Preimplantation Genetic Testing (PGT) or ERA can be better planned with frozen embryo transfer. Preimplantation genetic testing can be done on embryos before they are frozen to screen for chromosomal problems. Once these results were received, the transfer would take place. In women with displaced window of Implantation, an ERA procedure can be done in the cycle that the embryos are frozen to find out the right time to transfer embryos in future FET cycles.

Increased Flexibility: With frozen embryo transfer, embryos can be stored and used at a later time, allowing flexibility in treatment planning. This is particularly beneficial for individuals or couples who may require multiple attempts to achieve pregnancy or who need to delay embryo transfer due to medical or personal reasons.

Higher Success Rates: FET cycles often yield higher success rates compared to fresh embryo transfers. The frozen embryo transfer allows for better synchronization of the embryo with the recipient’s uterine lining, providing an optimal environment for implantation and reducing the risk of certain complications associated with ovarian stimulation.

Multiple Transfer Attempts: Frozen embryo transfer cycles offer the opportunity for multiple transfer attempts from a single IVF or ICSI cycle. This can potentially improve the chances of pregnancy without undergoing additional stimulation and egg retrieval procedures.

IVF with FET Success Rate

Freezing techniques like vitrification have evolved significantly in recent years to resemble spontaneous conception, resulting in higher pregnancy and live birth rates, fewer miscarriages, and healthier kids. The new vitrification approach significantly reduces loss rates compared to older slow freezing technology, which delivered few viable embryos.

High grade blastocysts have up to 40% chance of giving an ongoing pregnancy.

Procedure

Step-by-Step Process of Frozen Embryo Transfer cycle

1Preparing the Uterine Lining

Prior to the FET cycle, the recipient’s uterine lining is prepared using hormone medications. This involves taking estrogen to thicken the lining and progesterone to support implantation. This helps create an ideal environment for embryo implantation.

2Hormone Supplementation

The recipient undergoes hormonal therapy to prepare the uterine lining for embryo transfer.

3Monitoring and Synchronization

The recipient’s hormone levels and uterine lining are closely monitored using ultrasound scans and blood tests to ensure proper synchronization with the embryo transfer.

4Embryo Thawing

The frozen embryos are carefully thawed in the laboratory under controlled conditions. The embryologists monitor the survival and viability of the thawed embryos. Typically, not all frozen embryos survive the thawing process.

The thawing process for embryos during a frozen embryo transfer (FET) cycle is carefully performed to minimize the risk of damage. However, it is important to note that there is a small chance of embryo damage during the thawing process.

Embryos are cryopreserved using specialized techniques and cryoprotectant solutions that help protect them during freezing and storage. The thawing process involves gradually warming the embryos to body temperature, typically in a controlled laboratory environment. This process is conducted by experienced embryologists who closely monitor and ensure the optimal conditions for embryo survival.

While the vast majority of embryos survive the thawing process successfully, there is a slight risk of damage or loss. Some factors that can affect the survival rate include the quality of the embryos, the expertise of the laboratory, and the specific freezing and thawing techniques employed.

To mitigate this risk, fertility clinics and embryologists follow established protocols and employ best practices to maximize the chances of embryo survival. Quality control measures, strict temperature control, and precise timing are implemented during the thawing process to minimize any potential harm to the embryos.

It’s important to remember that fertility specialists and embryologists have extensive experience in handling and thawing embryos, and their primary goal is to ensure the best possible outcome for the FET procedure. They will take every precaution to minimize the risk of damage and optimize the chances of a successful transfer.

During the initial consultation with your fertility specialist, you can discuss the clinic’s specific protocols, success rates, and any concerns you may have regarding the thawing process. They will provide you with accurate and detailed information tailored to your individual circumstances and offer guidance throughout the FET cycle.

5Embryo Transfer

The selected and viable embryos are transferred to the recipient’s uterus using a catheter. This is a relatively quick and painless procedure performed under ultrasound guidance.

6Progesterone Support

Following the embryo transfer, the recipient continues taking progesterone to support the development of the uterine lining and pregnancy.

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