Frozen Embryo Transfer

A frozen embryo transfer (FET) is a cycle where embryos which were frozen in the previous fresh IVF cycle are thawed and transferred into a woman’s uterus. This avoids the need to undergo another cycle of hormone stimulation and egg collection.

1. Embryo freezing might be an option if the couple is not ready to become pregnant now but want to try later.
2. Sometimes during ovarian stimulation, hormones are produced in very high number due to the development of a large number of follicles. In this condition, embryos are frozen to avoid the development of a serious complication which is ovarian hyperstimulation syndrome (OHSS).
3. If during the IVF cycle, a large number of embryos are created, usually one or two embryos are transferred and remaining embryos are frozen to avoid achieving multiple pregnancy and associated risks.
4. Genetic disorders: If either couple is having some genetic disease, which can be inherited by the offspring, they are offered pre-implantation genetic screening. Here some cells are biopsied from the embryo and genetic analysis is done. Healthy embryos which are devoid of any disease are then transferred.
5. Fertility preservation: If a woman is undergoing cancer treatment such as radiation or chemotherapy that could harm your fertility, freezing embryos is an option. These can be transferred later after cancer treatment.

The procedure will be explained to the patient as it has multiple steps:

Ovarian stimulation: 

• Hormonal medicines (injection FSH/HMG) are given to stimulate the ovaries to produce multiple eggs rather than the single egg that normally develops each month. Multiple eggs are needed because some eggs won’t fertilize or develop normally after fertilization.
• Monitoring: Vaginal ultrasound of ovaries is used to monitor the development of follicles where eggs mature. Additionally, blood tests are done to measure the response to ovarian stimulation medications — estrogen levels typically increase as follicles develop, and progesterone levels remain low until after ovulation
• Medications to prevent premature ovulation: prevent the body from releasing the developing eggs too soon.

Medications for oocyte maturation: When the follicles are ready for egg retrieval, generally after eight to 14 days, human chorionic gonadotropin (HCG) or other medications are given to help the eggs mature.

Egg collection

Egg retrieval usually planned 34 to 36 hours after the final injection and before ovulation. This procedure is done under sedation to make it pain-free. 

• Transvaginal ultrasound aspiration is the usual retrieval method. Under ultrasound guidance, a thin needle is inserted into an ultrasound guide to go through the vagina and into the follicles to retrieve the eggs.
• The eggs are removed from the follicles through a needle connected to a suction device. Multiple eggs can be removed in about 20 minutes. The chances of conceiving increase with the number of eggs that are retrieved.
• After egg retrieval, the patient may experience cramping and feelings of fullness or pressure.
• Mature eggs are placed in a nutritive liquid (culture medium) and incubated. Eggs that appear healthy and mature will be mixed with sperm to attempt to create embryos.

Sperm retrieval

If a partner’s sperm is used, he’ll provide a semen sample through masturbation the morning of egg retrieval. Other methods, such as testicular aspiration — the use of a needle or surgical procedure to extract sperm directly from the testicle — are sometimes required or donor sperm also can be used.

Fertilization

Fertilization can be attempted using two common methods:

• Conventional insemination: In this, healthy sperms and mature eggs are mixed in a culture medium, where the sperm fertilizes the egg using its natural motility.

Intracytoplasmic sperm injection (ICSI): In ICSI, a single healthy sperm is injected directly into each mature egg. ICSI is often used when semen quality or number is a problem or if fertilization attempts during prior IVF cycles failed. 

Embryo freezing:

The process most commonly used for embryo freezing is called vitrification. In this process, the water inside the cell is replaced with substances known as cryoprotectant. It is followed by very rapid cooling that helps prevent ice crystals from forming inside the cells and thus increases the survival of embryos during the thawing process. Embryos are then placed in plastic straws and are labelled with the patient’s name and identification number. Embryos can be frozen for many years by this process in the tanks filled with liquid nitrogen.

Frozen Embryo transfer:

• Preparation of uterine lining: Hormonal medications are given for the growth of uterine lining. Progesterone supplement is added to make the lining receptive to the embryo. When the lining is found to be of favourable thickness with good blood flows, the embryo transfer procedure is planned. 
• A number of embryos to be transferred: The number of embryos transferred is typically based on age and number of eggs retrieved. Since the rate of implantation is lower for older women, more embryos are usually transferred. Extra embryos can be frozen and stored for future use for several years.
• Thawing: During this process embryos to be transferred are removed from the storage tank and gradually warmed up to room temperature.
• The embryo transfer procedure is usually painless, although the patient might experience mild cramping. A long, thin, flexible tube called a catheter is inserted in the vagina, through the cervix into the uterus. A syringe containing one or more embryos suspended in a small amount of fluid is attached to the end of the catheter. The contents of the syringe are then pushed inside the uterus.

After the embryo transfer, the patient can resume normal daily activities. 

Frozen embryo transfer is associated with very minimal risks as compared to fresh embryo transfer where the risk of OHSS is present.

 About 12 days to two weeks after embryo transfer, blood test (beta-hCG) is used to detect whether the patient is pregnant.

• If b-HCG positive i.e pregnant, the doctor will start or refer the woman for prenatal care.

If b-HCG negative i.e. not pregnant, a woman is advised to stop taking progesterone and is likely to get period within a week. If she has any remaining embryos frozen, then she will be offered frozen embryo transfer in next cycles.

There is a risk of losing embryos during the freezing and thawing process, which could reduce the success rates.

Multiple pregnancies: when more than one embryo is transferred, there is a risk of multiple pregnancies, which carry a risk of early labour and delivery of low birth weight babies.

Ectopic pregnancy: when the fertilized egg implants outside the uterus, usually in a fallopian tube. The fertilized egg can’t survive outside the uterus, and there’s no way to continue the pregnancy.

Birth defects: The age of the mother is the primary risk factor in the development of birth defects.