Development of the Technique of Oocyte Donation and Hormonal Replacement Therapy: is Oestrogen Really Necessary for the Establishment and Maintenance of Pregnancy?

Abstract

The technique for oocyte donation to women with hypergonadotrophic hypogonadism was modelled on the requirements for ovarian steroid replacement therapy in ovariectomized ewes. In the sheep, it is apparent that a period of priming progesterone, follicular-phase oestrogen and luteal-phase progesterone is required to enable embryo development following embryo transfer; the timing of embryo transfer is governed by the actual dose of luteal-phase progesterone. The horse, on the other hand, requires only progesterone to establish a receptive uterus for transferred embryos. Although a sequential regimen of oestrogen and progesterone that mimics the hormonal profiles in a normal menstrual cycle is very efficient in effecting pregnancy by oocyte donation in women, much simpler regimens have been devised that produce a variable-length follicular phase by using a constant dose of oestrogen and a constant dose of progesterone for the luteal phase and early pregnancy. It is suggested that ovarian oestrogen is not essential for the luteal phase and early pregnancy, and may not even be required for the establishment of pregnancy. It is also apparent that progesterone replacement may cease before the luteoplacental shift is detected, without necessarily interrupting pregnancy, suggesting that local embryo or placenta-derived steroids may effectively maintain early pregnancy in the human.