There are two kinds of FET-IVF cycles: hormonal support cycles and “natural” cycles. The most commonly performed FET-IVF cycle is a hormonally supported cycle, which is appealing to couples, clinics, and labs because the day of transfer is easy to control and hormonal support is available for any ovulatory problems.
Frozen Embryo Transfer Using Hormone Replacement: A Step-by-Step Guide
For patients with irregular cycles or ovulation disorders, and for patients who need to plan their therapy around time constraints, we can create an artificial menstrual cycle for FET. This involves treatment with an oral estrogen medication and progesterone (usually administered vaginally). This treatment is well established. Pregnancy rates are equivalent when compared to natural cycle FET. We sometimes recommend a trial (practice) cycle before the actual FET cycle so we can perform an endometrial biopsy to ensure that the medication dosages produce the proper development of the uterine lining.
In addition, if you have been pregnant, we recommend a repeat uterine measurement before FET. If you have never had an endometrial biopsy to evaluate the development of the lining of the uterine cavity or if it has been longer than a year or if you have risk factors for uterine structural abnormalities, we will recommend a uterine cavity evaluation prior to FET, either with a saline infusion sonohystogram, office hysteroscopy or a hysterosalpingogram.
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The steps involved in FET with hormone replacement include:
FET Cycle
Step 1 - Estrogen Therapy
It is important that you start estrogen therapy on the first day of your period. A dose of estrogen is usually administered for 14 days, although shorter or longer cycles may be used, Estrace® is the most common form of estrogen we use. This is a pill containing 2 mg of estradiol, the same hormone produced by the ovaries. We will have you take one pill twice a day for about 14 days. After about 14 days of Estrace®, (your physician may vary the dose or duration of therapy) progesterone is added. This may be administered vaginally or as an intramuscular injection.
Estrace® and progesterone are continued until the day of the pregnancy test (usually 12 days after embryo transfer). If the test is positive, these medications may be continued for several weeks. Depending upon the individual physician’s protocol you may also be treated with oral medications such as methylprednisolone and doxycycline prior to the transfer.
Step 2 - Embryo Transfer
Embryo transfer is usually performed on the third to fifth day of progesterone therapy. As with natural cycle FET, embryos are thawed on the morning of the scheduled frozen embryo transfer. In our laboratory, approximately 60-70 percent of embryos survive cryopreservation and thawing. We usually transfer 1 to 2 embryos during each FET cycle. However, this number is flexible, and your physician will discuss this issue with you.
Excellent FET pregnancy rates occur in most cases with the transfer of one to two embryos, which also minimizes the risk of multiples. The transfer of more embryos may increase the likelihood of a multiple pregnancy, which increases the pregnancy risks for the woman and the fetuses.
The actual embryo transfer itself is identical to the embryo transfer following in vitro fertilization-embryo transfer. Depending upon the physician’s protocol the embryo transfer may be accomplished under ultrasound guidance which will require the bladder to be full. A small plastic catheter is passed gently through the cervix into the uterus. After waiting for 1-2 minutes to allow any mild cramping to resolve, the embryos are deposited into the cavity along with a small amount of fluid. You will be discharged after resting for 20 minutes. No anesthesia is required for the embryo transfer.
Step 3 - Hormonal Studies - Pregnancy Test
We will usually perform a serum pregnancy test 12-14 days after the embryo transfer. If the test is positive, we may also measure serum progesterone. On occasion, we may repeat tests every two or three days. If the test is negative, hormone therapy is discontinued and a period usually begins in a few days. Near the end of that period, your physician may request a vaginal sonogram and/or serum progesterone level.
Step 4 - Follow-up Consultation
If the pregnancy test is positive, we will perform a vaginal sonogram about three weeks later. At this point, we are usually able to identify the number of embryos and can often see a heartbeat. The risk of pregnancy loss is low after this developmental milestone. If the procedure is unsuccessful, you should schedule a consultation with your physician. We will review the procedure and discuss further treatment options.
Natural Cycle Frozen Embryo Transfer: A Step-by-Step Guide
Each cycle of FET, like that of the other ART procedures, involves multiple steps, occurring at a specific time during a four-week period. An approximate timetable and overview are presented below. If you have been pregnant, or if it has been more than one year since your last embryo transfer, a repeat uterine measurement should be performed before FET. If you have never had an evaluation of the uterine cavity or if it has been longer than a year or if you have risk factors for uterine structural abnormalities, we will recommend a uterine cavity evaluation prior to FET, either with a saline infusion sonohystogram, office hysteroscopy or a hysterosalpingogram.
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FET Cycle
Step 1 - Monitoring of Follicle Development
Monitoring of follicle development is often performed during a FET cycle by using transvaginal sonography. To determine the day on which you should begin monitoring, subtract seventeen days from the length of your menstrual cycle. For example, if it is 30 days from the first day of one menstrual cycle to the first day of the next, you should have your first ultrasound on approximately cycle day 13 (30-17=13). You will have other ultrasounds as your dominant follicle nears maturity. These ultrasounds will continue until we have documented ovulation.
Step 2 - Monitoring for LH Surge
As the growing follicle nears maturity, the level of the hormone LH in the blood and urine rises dramatically. This is known as the LH surge. For the purpose of frozen embryo transfer, we define the day of the LH surge as the day the urine LH test turns positive. It is important that the LH be monitored on a daily basis, as the frozen embryo transfer will be timed from the date of the LH surge. The timing of the embryo transfer will depend upon the stage at which your embryos were frozen. Embryos frozen at a more advanced stage of development (blastocysts) will be transferred later than embryos frozen at an earlier stage of development.
Step 3 - Documentation of Ovulation
In addition to monitoring your LH, your physician may also confirm ovulation with ultrasonography through the time of ovulation. If ovulation does not occur, as evidenced by failure of the dominant follicle to collapse on ultrasound, then the frozen embryo transfer may be canceled. Alternatively, hormonal supplementation may be provided during the remainder of the transfer cycle. Depending upon the individual physician’s protocol you may also be treated with oral medications such as methylprednisolone and doxycycline prior to the transfer.
Step 4 - Embryo Transfer
Embryos are thawed on the morning of the scheduled frozen embryo transfer. In our laboratory, approximately 60-70 percent of embryos survive cryopreservation and thawing. We usually transfer 1-2 embryos during each FET cycle. However, this number is flexible, and your physician will discuss this issue with you. Excellent FET pregnancy rates occur in most cases with the transfer of one to two embryos, which also minimizes the risk of multiples. The transfer of more embryos may increase the likelihood of a multiple pregnancy, which increases the pregnancy risks for the woman and the fetuses.
The actual embryo transfer itself is identical to the embryo transfer following in vitro fertilization-embryo transfer. Depending upon the physician’s protocol the embryo transfer may be accomplished under ultrasound guidance which will require the bladder to be full. A small plastic catheter is passed gently through the cervix into the uterus. After waiting 1-2 minutes to allow any mild cramping to resolve, the embryos are deposited in the cavity along with a very small amount of fluid. No anesthesia is required for the embryo transfer. You will be discharged after resting for 20 minutes.
Step 5 - Hormonal Supplements
Patients undergoing FET may not require hormonal supplementation when we document normal follicular development and ovulation. Unlike the initial IVF-ET procedure during which the progesterone-producing granulosa cells are aspirated, those cells remain functional within the corpus luteum during your FET cycle. Progesterone supplementation may be administered to patients with ovulatory dysfunction or luteal phase inadequacy. In these cases, progesterone injections or suppositories begin before the embryo transfer and continue until the pregnancy test is performed.
Step 6 - Pregnancy Test
We will usually perform a serum pregnancy test 12-14 days following the embryo transfer. If the test is positive, we may measure the serum progesterone level and recommend that you continue taking progesterone for several additional weeks. If the pregnancy test is negative, progesterone is discontinued and a period begins in a few days.
Step 7 - Follow-up Consultation
If the pregnancy test is positive, we will perform a vaginal sonogram about three weeks later. At this point, we are able to identify the number of embryos and can often see a heartbeat in the developing embryo. The risk of pregnancy loss is low after this developmental milestone. If the FET procedure is unsuccessful, you should schedule a consultation with your physician to review the procedure and discuss future treatment options.
About Iranian Surgery
Iranian surgery is an online medical tourism platform where you can find the best gynaecologists and obstetricians in Iran. The price of a FET-IVF in Iran can vary according to each individual’s case and will be determined based on in-person assessment with the doctor. For more information about the cost of FET-IVF in Iran and to schedule an appointment in advance, you can contact Iranian Surgery consultants via WhatsApp number 0098 901 929 0946. This service is completely free.