Early pregnancy loss: the default outcome for fertilized human oocytes
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REVIEW
Early pregnancy loss: the default outcome for fertilized human oocytes The Annual Capri Workshop Group
Received: 2 March 2020 / Accepted: 12 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Early pregnancy loss is by far the most frequent outcome of human reproduction. It occurs when despite the timely interaction of gametes and initiation of embryogenesis and implantation of the conceptus, pregnancy continuance fails. From a clinical perspective, early pregnancy loss represents a neglected but relevant issue because of the high incidence, the evolving and yet not fully elucidated mechanism, the possible association with other relevant medical conditions, and the potential psychological sequelae. Our growing understanding of the dialog established between the embryo and the endometrium provides new insights into the etiology of pregnancy loss. Aneuploidies as a cause of early pregnancy loss are known for a long time, but there is now evidence that endometrium is not a passive player. An active selection aimed at impeding implantation of unhealthy embryos actually occurs at the endometrial interface. The concept of selectivity is substituting the one of mere receptivity. Keywords Endometrium . Pregnancy loss . Implantation . Genetic testing . Misoprostol . Miscarriage . Cardiovascular risks
Introduction Early pregnancy loss (EPL) is the spontaneous demise of the conceptus before ten gestational weeks. It is the result of the failure to meet requirements imposed by both the embryo, endometrium, and maternal fetal interface to initiate, sustain, and maintain the conceptus in a state conducive supporting the pregnancy to term. Because of the delicate balance of factors introduced by both the embryo and endometrium, spatial and temporal conditions that integrate embryo viability with the window of implantation must be achieved and recognized and tolerated by the maternal host if the pregnancy has a chance to survive to advanced stages of gestation. Since the default reaction of a failed pregnancy opportunity is menstruation, it has been proposed that only mammals exhibiting menses would be subject to the frequency of this reproductive outcome. The list of the Annual Capri Workshop Group contributors is given in the Appendix. * The Annual Capri Workshop Group [email protected] 1
IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital, Via M. Fanti, 6, 20122 Milan, Italy
While there is commonality between EPL and menstruation among higher primates, other menstruating species exist that do not show EPL as a prevalent outcome but do exhibit other interesting variations in reproductive physiology that may account for this basic aspect of failed fecundity [1]. On the other hand, recognizing menstruation as the default for a failed pregnancy carries great meaning as to the maternal investment required to obtain a full-term gestation and delivery [2]. Thus, most attempts to understand the cause of EPL in humans have been strikingly binary emphasizing the under
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