**8. Estrogen**

The use of a GnRH agonist is an integral part of long protocols used in IVF/ICSI cycles and it results in pituitary suppression and luteal phase deficiency with decline in serum E2 and progesterone 8 days after hCG administration for oocyte maturation. Earlier reports indicated that serum E2 concentrations severely drop at the end of the luteal phase [61]; therefore,a concern has been raised about an additional supply of E2 during luteal phase of IVF cycles. The role of E2 luteal support is still debated after more than a decade of use. Previous meta analysis [18] and an update [62] and more recent randomized trials [63, 64] reported beneficial effects of adding E2 to luteal progesterone support. In our study [63] two hundred seventy-four women undergoing first ICSI cycles were randomized after ovum pickup into three groups of luteal support . Group I received IM progesterone only, group II received progesterone plus oral E2 valerate, group III received progesterone plus hCG. Outcome measures were pregnancy rate, implantation rate, rates of multiple pregnancy and miscarriage, and midluteal serum E2 and progesterone, and midluteal E2: progesterone ratio. The results showed that the pregnancy and implantation rates were significantly higher in group II (E2 plus progesterone) compared to group I (I.M. progesterone only) and the miscarriage rate was significantly lower in group II compared with group I. Midluteal E2 was significantly higher in group II compared with group I. The decline in E2 after ovum pickup was lowest in group II, highest in group I.

On the other hand two meta- analyses [65, 66] has shown that the addition of E2 to progesterone for luteal phase support in IVF/ICSI cycles has no beneficial effects on pregnancy rates. The last meta- analyses commented that the data in the literature are limited and heterogeneous, precluding the extraction of clear and definite conclusions. Therefore further studies are needed to clarify the exact role of E2 luteal support in long agonist vs. antagonist , normal responder vs. high responder and low responders.
