Hormonal manipulation of endometrial maturation.

Three experimental protocols were devised to induce endometrial maturation in 12 women with ovarian failure. Each was planned to serve a dual purpose: to resolve a particular clinical situation related to synchronization between ovum donor and recipient and to answer a specific question about endometrial physiology. A fourth protocol of sequential estrace (2-6 mg/day) and progesterone (P4; 25-50 mg/day, im) simulating the 28-day natural cycle, served as a control protocol (18 cycles). A short follicular phase protocol consisted of only 6 days of estrogen (E) administration before addition of P4 (13 cycles). In the long follicular phase protocol (5 cycles), estrace was given for 3-5 weeks, and P4 administration was accordingly postponed. In 6 accelerated secretory transformation cycles, 150 mg/day P4 were administered, im, from day 15 onward. The adequacy of the induced endometrial cycles was evaluated by hormonal, morphological, and histochemical criteria relevant to endometrial normalcy and receptivity. Serum estradiol levels and the areas under the estradiol curves for the long and short follicular phase protocols differed significantly from those during the control cycles (P less than 0.005). Areas under the estradiol curves in the accelerated secretory transformation protocol yielded significantly higher P4 values than those in all other protocols (P less than 0.05). All biopsies in the 3 experimental protocols compared favorably with those of the control protocol. Glycocalyx intensity (periodic acid-Schiff) and the amount of galactose residues in the glycocalyx (Ricinus communis-I agglutinin) were greatest during the periimplantation interval. We conclude that a very short exposure of the human endometrium to E or, conversely, prolonged E stimulation will allow normal endometrial maturation with the addition of P4. Supraphysiological doses of P4 in the accelerated secretory transformation protocol significantly enhanced endometrial maturational processes.