O-092 Does embryo biosensing really determine endometrial fate decisions at implantation?

Abstract

Abstract Implantation depends on bi-directional communication between the blastocyst and endometrium. Encoded in this communication is information on maternal and embryonic fitness, which in turn can lead to the activation of species-specific reproductive suppression mechanisms. For example, blastocysts in over 130 mammals, although not humans, respond to the presence or absence of specific endocrine or endometrial cues by entering or exiting diapause, a state of suspended animation that leads to postponement of implantation. By contrast, embryo biosensing and selection depend on the endometrium first receiving and decoding fitness information from the conceptus and then either promoting implantation or initiating rapid tissue breakdown, thus limiting maternal investment into a failing pregnancy. Importantly, embryo selection relies on physiological mechanisms that sense deleterious (internal/external) cues, which is fundamentally different from reproductive failure caused by disease or trauma. Nevertheless, physiological embryo selection is easily conflated with pathology. For example, repeated implantation failure of low-fitness IVF embryos can lead to the diagnosis of ‘recurrent implantation failure’, an ill-defined clinical label, which often spurs uninformative investigations and ineffective ad-hoc treatments. On the other hand, pathological relaxation of embryo selection at implantation causes early pregnancy loss, with the frequency of affected cycles determining the age-independent recurrence risk of miscarriage. In this presentation, I will elaborate on the cellular mechanisms that control embryo biosensing and selection, highlight the clinical consequences, and discuss emerging strategies for pre-pregnancy optimisation of the endometrium. Trial registration number XXXX