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Estradiol added to progesterone for luteal support improves IVF outcomes

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – In women undergoing in vitro fertilization, hormonal support with progesterone plus estradiol supplementation during the luteal phase after embryo transfer improves pregnancy and implantation rates compared to luteal support with progesterone alone.

That finding, reported online in Fertility and Sterility, comes from Turkish investigators at the Zekai Tahir Burak Woman’s Health Education and Research Hospital in Ankara.

Dr. Esra Aysin Tonguc and colleagues explain that the need for luteal phase support in IVF cycles suppressed with a GnRH agonist is well documented, and the value of progesterone supplementation in the luteal phase of downregulated cycles is widely accepted. However, the benefit of additional luteal supplementation with estradiol is controversial.

The team investigated the effect of three different luteal phase support protocols in 288 patients who were undergoing assisted reproduction (intracytoplasmic sperm injection) with a long protocol of controlled ovarian hyperstimulation.

Beginning on the day of oocyte pickup, the women were randomly assigned to treatment with 90 mg/d vaginal progesterone gel only, progesterone gel plus 4 mg/d oral estradiol, or progesterone gel plus 1500 IU hCG intramuscularly on days 0, 3 and 6. Treatment continued at least until the pregnancy test on day 14.

The implantation rate was 7.9% in the women treated with progesterone only, significantly lower than the 16.8% rate among those given supplemental estradiol and the 20.0% rate seen with hCG supplementation (p=0.001). Ongoing pregnancy rates followed a similar pattern — 21.6%, 40.6% and 38.9% in the three groups, respectively.

However, hCG supplementation was associated with ovarian hyperstimulation syndrome. Also, the risk of multiple pregnancies was highest in the hCG group (14.7%), compared with 2.3% among the women given estradiol, and 0% in the progesterone-only group.

Summing up, Dr. Tonguc and colleagues write: “In IVF cycles with GnRH agonist, supplementing progesterone with 4 mg of oral E2 (estradiol) in the luteal phase significantly increased the pregnancy rates and implantation rates and decreased the miscarriage rate compared with the use of progesterone alone. Although supplementing progesterone with hCG as a luteal support also yielded similar results to E2, the latter should be preferred because of ovarian hyperstimulation syndrome and multiple-pregnancy risks.”


A comparison of the effects of three different luteal phase support protocols on in vitro fertilization outcomes: a randomized clinical trial

Fertil Steril 2010.