Frozen Embryo Transfer Protocols

What is a Frozen Embryo Transfer (FET)?

A frozen embryo transfer (FET) is a procedure where an embryo created and frozen during a previous IVF cycle is thawed and transferred into your uterus.

Why Are There Different FET Protocols?

The goal of any FET protocol is to prepare your uterus so the lining (endometrium) is optimal for embryo implantation. There are several ways to do this, depending on your menstrual cycle, medical history, and personal preferences.

Types of FET Protocols

1. Modified Natural Cycle FET

How does it work?

• Your natural cycle is monitored with transvaginal ultrasounds and blood tests.

• Ovulation is usually triggered with an hCG or Ovidrel injection to precisely time the release of the egg and schedule the embryo transfer.

• Progesterone supplementation (vaginal or intramuscular injection) is started after ovulation to support the uterine lining.

• The embryo transfer is timed according to your ovulation

Pros:

• Fewer medications – less side effects

• Creation of a corpus luteum (cyst in the ovary that supports a natural pregnancy)

• Lower risks of high blood pressure and pre-eclampsia in pregnancy compared to hormone replacement FET protocols

Cons:

• Requires 1-2 more monitoring appointments

• Less flexibility in scheduling.

2. Stimulated Cycle FET

How does it work?

• Ovulation is stimulated with medications (e.g., letrozole, clomiphene, injectable gonadotropins).

• Ovulation is monitored and triggered with hCG or Ovidrel.

• Progesterone supplementation is started after ovulation.

• Embryo transfer is timed accordingly.

Pros:

• Fewer daily medications (i.e. estrogen) – less side effects

• Creation of a corpus luteum (cyst in the ovary that supports a natural pregnancy)

• Possible lower risks of high blood pressure and pre-eclampsia in pregnancy compared to hormone replacement FET protocols

Cons:

• Possible side effects associated with letrozole/clomiphene/gonadotropins

• Less scheduling flexibility

  
  

3. Hormone Replacement Therapy (HRT) or Artificial Cycle FET

How does it work?

• Estrogen is given (as pills or patches) to build up the uterine lining.

• Progesterone is added to prepare the lining for embryo implantation.

• Embryo transfer is scheduled based on the day progesterone is started.

Pros:

• Flexible scheduling.

• No need to monitor for natural ovulation.

Cons:

• Daily medications (estrogen and progesterone).

• Rare side effects from hormones (e.g., bloating, mood changes).

• Possible higher risk of hypertension (high blood pressure) in pregnancy compared to natural cycle protocols.

4. Hormone Replacement Therapy (HRT) or Artificial Cycle FET with Lupron downregulation

How does it work?

• Lupron (a GnRH agonist) is given as an intramuscular injection on cycle day 21 of preceeding menstrual cycle

• Estrogen is then given (as pills or patches) to build up the uterine lining starting one-two weeks later

• Progesterone is added to prepare the lining for embryo implantation.

• Embryo transfer is scheduled based on the day progesterone is started.

Pros:

• Flexible scheduling.

• No need to monitor for natural ovulation.

• Possible treatment of adenomyosis/endometriosis to minimize negative effect on embryo transfer

Cons:

• Longer protocol (requires 2 menstrual cycles)

• Daily medications (estrogen and progesterone).

• Rare side effects from hormones (e.g., bloating, mood changes).

• Possible higher risk of hypertension (high blood pressure) in pregnancy compared to natural cycle protocols.

  
  

Progesterone Administration Options

Progesterone is essential for preparing and supporting the uterine lining for embryo implantation. It is typically started after ovulation or when estrogen has sufficiently prepared the lining. Your doctor will recommend the best option for you. The two main options are:

• Vaginal Progesterone:

  • Suppositories, gel, or capsules inserted into the vagina three times a day

  • Most commonly used; well-tolerated by most patients.

  • Cons : vaginal discharge, frequency of administration

• Intramuscular Progesterone (Progesterone in Oil, PIO):

  • Injections given into the muscle (usually the buttock).

  • Some studies have shown a benefit of PIO injections in terms of pregnancy outcomes, while others have not demonstrated a clear advantage over vaginal progesterone.

  • Cons : need for daily injections, pain with injections, muscle soreness

Additional Considerations

• Personalization: Dr. Dason will recommend the best protocol for you based on your medical history (i.e. history of PE/DVT or blood clots, history of prior miscarriages or failed transfers, history of hypertension, family history of hypertension, PCOS, endometriosis, adenomyosis), cycle regularity, and previous IVF outcomes.

• Success Rates: No protocol has been proven to be significantly superior for all patients; the choice is individualized.

  
  

This blog post is not intended to represent medical advice and is for education purposes only. Dr. Dason is happy to answer questions in consultation.