How long should estrogen be supplemented after embryo transfer?

This study evaluated how long estrogen should be used during artificial cycle frozen embryo transfer (FET). It found that stopping estrogen at 6 weeks of pregnancy reduced miscarriages compared to continuing to 12 weeks. Stopping at 6 weeks also led to fewer pregnancy complications.

FET is a common infertility technique, in which a frozen embryo is transferred to the uterus. FET uses embryos preserved from an earlier cycle of in vitro fertilization (IVF). In order for a FET to be successful, the lining of the uterus must be receptive to an embryo implanting. One way to do this is to time the FET for after ovulation when the uterus is receptive. Alternately, artificial cycle FET uses injections of hormones including estrogen to prepare the uterus. Estrogen is a hormone which is high in the early part of the menstrual cycle, and causes changes throughout the body. One role of estrogen is to thicken the lining of the uterus. The body has several types of estrogen. Estradiol is the type of estrogen used to prepare for a FET.

Around when the embryo is transferred, supplements of progesterone are used in addition to estradiol. This hormone maintains the lining of the uterus. When using an artificial cycle, the ovary does not release its own progesterone. If the woman becomes pregnant, the developing placenta begins to release estrogen and progesterone around the fifth week. For women using artificial cycle FET, estradiol and progesterone are typically taken until 10 to 12 weeks. However, it is not clear how long estradiol should be used in artificial cycle FET.

This study recruited 291 patients who were undergoing FET using an artificial cycle. All of the patients had their body’s own hormone levels reduced using the GnRH agonist buserelin (Suprefact). Then they received estradiol valerate to prepare the lining of the uterus. After the FET, all patients received progesterone, and continued taking estradiol.

6 weeks after the FET, 64 patients had a pregnancy visible on ultrasound. 32 patients were randomly assigned to the 6-week estrogen (6WE) group. This group continued to take progesterone but stopped taking estradiol after 6 weeks. The other half continued taking both medications until 12 weeks after the FET.

After 12 weeks, the 6WE patients had a significantly lower miscarriage rate (3.13% vs. 18.75%). The average blood levels of estradiol and progesterone were similar in the two groups. There were significantly fewer pregnancy complications for the 6WE group. 92.6% of 6WE patients did not have any complications, versus 54.5% of the comparison group. These complications included cerclage, a procedure to sew the entrance of the uterus shut to prevent preterm birth. They also included preeclampsia and diabetes.

This study found that stopping estradiol after the pregnancy is visible on ultrasound reduced miscarriage for women undergoing artificial cycle FET. It also found that stopping estradiol early reduced pregnancy complications.

This study had a small number of patients and should be confirmed with larger trials. Also, artificial cycle FET has a higher rate of miscarriage than other types of FET which include ovulation.