As noted in earlier questions, the ovary produces both estrogen and progesterone until production of these hormones is taken over by the placenta at approximately 8 to 10 weeks of pregnancy. Estrogen and progesterone are critical hormones for the normal development of the endometrial lining of the uterus. Both medications are frequently used in patients undergoing a frozen embryo transfer (FET) or donor-egg IVF. Estrogen thickens the lining and then progesterone causes the lining to mature, ultimately allowing for the embryo’s implantation. Without these hormones, all FET cycles would have to be performed during spontaneous menstrual cycles (see Question 73) and donor-egg IVF would be possible only using frozen embryos, as there would be no way to synchronize the reproductive cycles of the donor and the recipient. There is no evidence that the estrogen used to synchronize these cycles presents any risk to the developing fetus or baby.

If there are no risks, then why do the labels of these medications carry such a strong warning? The labeling is an overreaction to previous experience in the United States with the use of a synthetic estrogen called diethylstilbestrol (DES).

During the 1950s to 1960s, this synthetic estrogen (which is not the natural estrogen used today) was given to women who were threatening to miscarry. Unfortunately, DES did not function in a normal fashion in terms of how it interacted with the estrogen receptors in the cells of the developing female reproductive tract in the unborn daughters of mothers who were prescribed DES. As a result, many of those women whose mothers took DES during their pregnancy were found to have significant reproductive tract abnormalities. In addition to cervical and uterine abnormalities, they were at a higher risk for an unusual form of vaginal cancer called clear cell carcinoma. Appropriately, DES was taken off the market. At this point in time, the impact of previous DES exposure in the U.S. population has greatly waned as most of the DES daughters have passed beyond child bearing age.

Following the DES debacle, the U.S. government decided that all reproductive steroids should be labeled as being contraindicated in pregnancy. This mandate applies to both progesterone and estrogen compounds. Today, however, the estrogens and progesterones prescribed by fertility physicians are exactly equivalent to the body’s own natural estrogen and progesterone produced by the ovary and by the placenta. Women who are prescribed these medications by their physician can take them without any worry that somehow these medications will have an adverse impact on their unborn children.