A frozen embryo transfer (FET) is the transfer of an embryo which has been previously frozen, and subsequently thawed, into the uterus. Traditionally, IVF has involved ovarian stimulation followed by egg retrieval and fertilization of harvested eggs, followed by a fresh embryo transfer (ET) of an embryo into the uterus within 5 days of the egg retrieval procedure, also known as IVF-ET. With the advent of advanced embryo freezing and thawing techniques achieving extremely high embryo survival rates, traditional IVF-ET (using fresh embryos) has become less common, giving way to the more commonly practiced FET.
Frozen embryo transfer (FET) cycles have become essential components of the IVF process and therefore must be performed with great care to achieve a successful outcome. Several components make up a successful FET cycle. A proper evaluation of the uterine cavity to rule out the presence of an intracavitary lesion (such as a polyp or fibroid that may interfere with implantation) must be undertaken prior to the FET cycle. The majority of FET cycles are medicated FET cycles, where estrogen supplementation is first administered in order to build up the uterine lining (known as the endometrial echo complex under ultrasound evaluation), until an optimal thickness of the lining is achieved. This phase of the FET cycle is critical and the type of and method of estrogen supplementation used (oral estrogen pills, vaginal estrogen suppositories, injectable estrogen, subcutaneous estrogen), the dose of estrogen, and the length of time of estrogen supplementation are critical and must be customized and adjusted to each patient based on multiple factors, so that a receptive uterine lining is achieved. The second phase of a medicated FET cycle involves progesterone supplementation, introduced to support the lining, once an optimal uterine lining has been achieved. In medicated FET cycles, progesterone is introduced while the estrogen supplementation is adjusted and continued. As in the case of estrogen supplementation, the type, dose, and route of progesterone supplementation, is critical. Commonly, progesterone is introduced in the form of intramuscular daily injections five days prior to the embryo transfer of a frozen-thawed embryo. Progesterone can also be administered in the form of vaginal suppositories or a combination of intramuscular injections and vaginal suppositories. The frozen embryo transfer must timed accurately to the initiation of progesterone supplementation in order for the FET to be successful. Estrogen and progesterone supplementation is normally continued after the embryo transfer and through 10 weeks of gestation.
An unmedicated FET cycle, also known as a natural cycle FET, is normally performed without any estrogen or progesterone supplementation. Instead, the estrogen produced by a naturally growing ovarian follicle, followed by progesterone produced after spontaneous ovulation of that follicle; support the implantation of a frozen-thawed embryo, when the FET is timed properly to the time of ovulation. Natural cycle FETs do not allow for flexibility in the timing of the FET and are only appropriate for patients with normal menstrual cycles, where ovulation is easy to monitor and is predictable.
In certain clinical scenarios, a stimulated FET cycle is performed. In a stimulated FET cycle the patient administers gonadotropin hormone injections (or oral ovulation induction medications) to induce the growth of a follicle or follicles. The growth of follicles leads to the endogenous production of estrogen which then leads to the thickening of the uterine lining. Once follicles reach a mature size, they are triggered to ovulate, leading to the production of endogenous progesterone, which then sets the stage for the embryo transfer of a frozen-thawed embryo. Stimulated FET cycles may be used in patients who do not ovulate naturally or in cases where traditional medicated FET cycles have failed.
Frozen embryo transfer cycles allow for great flexibility in optimization of the uterine lining prior to thawing of embryos, so that embryos are not thawed until the uterine lining is receptive. The essential contributor needed to achieve an optimally thick and receptive uterine lining, is estrogen. In cases of an inadequate uterine lining during an FET cycle, in addition to variations in the type of estrogen medication, dose, and route of administration, several other supplements can be added to optimize the lining thickness (including baby aspirin, pentoxifylline, vitamin E, Viagra, G-CSF…).