The Endometrium as a Target for Contraception

Progesterone, the hormone "pro gestationem", plays a pivotal role in mammalian reproduction during almost all phases of the menstrual cyc1e and all stages of pregnancy. It is involved in the control of ovula- tion, prepares the endometrium for implantation, and, in later stages of pregnancy, is responsible for its maintenance by suppressing uterine contractility. The sudden withdrawal of progesterone action at the end of the nonfertile cycle leads to the constriction of spiral arteries and, in . turn, to menstruation in human beings and non human primates. The decrease in serum progesterone concentrations or its functional with- drawal in the myometrium and decidua are the most important events during parturition in various mammals. In the uterus, progesterone controls the growth and differentiation of endometrial and myometrial cells and regulates a variety of cell functions directly by either stimulating or inhibiting structural and functional proteins, but also indirectly by functionally opposing estra- diol action. In the nonpregnant uterus, there are different progesterone effects on uterine cell proliferation which vary among species. In the fertile cyc1e, progesterone regulates in synergism with estradiol the transport of the fertilized eggs and the c1eavage stage embryos through the oviduct and induces the secretory changes in the endometrium re- quired for implantation. During the period between ovulation and im- plantation, remarkable morphological and biochemical changes in the lumenal and glandular epithelial cells take pi ace under the influence of rising progesterone levels in the human and primate endometrium.

This book is a summary of the present state of the art in the physiology of both endometrial receptivity and implantation. Although these physiological processes are today considered as limiting factors responsible for both infertility and low gestation rates in patients undergoing assisted reproductive techniques, they may, on the other hand, represent future targets for contraception. Several aspects of endometrial receptivity and implantation are discussed in this book. In the first part, basic aspects of the cell biology of endometrial functions as well as the molecular aspects of endometrial receptivity and implantation are discussed. Subsequently the clinical and experimental approaches to endometrial contraception are considered. Finally, some basic questions are raised pointing to the need for further research in order to gain a better understanding of the implantation process and the development of new contraceptive strategies, including the inhibition of endometrial receptivity. The organizers of the workshop and the editors of the volume hope that this book will encourage both universities and the pharmaceutical industry to initiate and/or continue research on endometrial receptivity and implantation.