Estrogen may be administered late in the IVF cycle, usually by skin patches, in order to support the development of the embryo and stabilize the uterine lining. The most active form is that estrogen is estradiol, typically in the form of 17-beta estradiol. Currently this medication is available in an oral (Estrace), injectable (Estradiol valerate), vaginal (Estrace Cream) and transdermal (Estraderm) preparations.

The largest group of women achieving pregnancy with the use of supplemental estrogen is the group who utilized super-ovulation in association with IVF, GIFT, or ZIFT. During a cycle that is stimulated to produce multiple follicles, natural estrogen (estradiol) levels are 3-10 times higher than a normal cycle. Exposure to such high levels of estrogen has not been associated with an increase in the rate of fetal anomalies. French researchers have also published higher implantation and pregnancy rates with the use of supplemental estrogen before ovulation and in the luteal phase that occurs after ovulation.

Many doctors recommend the use of estrogen in the follicular phase (before ovulation) of development with additional estrogen that starts 4-5 days after the LH surge or "trigger shot" of hCG. In a normal spontaneous cycle, estrogen drops following the LH surge and slowly increase during the luteal phase. With ART cycles, we attempt to imitate this process and improve the development of the lining of the uterus through the use of vaginal, transdermal, or injectable estrogen. (The bioavailability–amount the body can use–is greater when the medication is given by one of these routes rather than when taken orally.)

Experience has shown that there is a significant difference in estrogen levels in women who experience recurrent spontaneous miscarriages. It is not clear if factors leading to miscarriage also caused a reduction on the production of estrogen, or if low estrogen somehow played a role in causing the miscarriage.

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