DETERMINANTS OF IMPLANTATION FAILURE IN ENDOMETRIOSIS: A SYSTEMATIC REVIEW OF EMBRYO MORPHOKINETICS AND ENDOMETRIAL RECEPTIVITY IN ASSISTED REPRODUCTIVE TECHNOLOGY CYCLES

Abstract

Objective: To synthesize scientific evidence on how endometriosis compromises reproductive success, by analyzing delays in embryonic developmental milestones (morphokinetics), reduced implantation rates in in vitro fertilization (IVF) cycles, and the influence of systemic factors, such as sleep quality and endometrial receptivity. Methodology: This is a systematic review conducted in accordance with PRISMA and MOOSE guidelines, using the PECO framework to formulate the research question. Observational studies published between 2016 and 2023 were included following a search of the databases specified in the methodology. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: Nine high-quality studies were selected, comprising a total sample of over 1,100 women with endometriosis and 2,300 controls. Morphokinetic analysis via time-lapse imaging revealed that embryos from patients with the condition exhibit significant chronological delays in critical milestones—such as the extrusion of the second polar body (tPB2), intermediate cleavage stages (t5 to t8), and progression to the expanded blastocyst stage—with the latter occurring approximately 2 hours later in the exposed group. A higher rate of multinucleation was also observed (50.0% vs. 44.5% in the control group). Although fertilization and live-birth rates in autologous cycles remained comparable, there was a statistically significant reduction in the implantation rate (OR 0.85; 95% CI: 0.74–0.97) and in the live-birth rate in oocyte donation models (OR 0.89), suggesting an impairment in endometrial receptivity. Additionally, a severe deterioration in sleep quality was identified in these patients (mean PSQI score of 10.6 vs. 7.1; p < 0.001), which correlated with chronic pelvic pain. Conclusion: Endometriosis exerts a deleterious and multifactorial impact on reproductive function, rooted in a threefold failure involving embryonic competence, uterine receptivity, and systemic homeostasis. These findings underscore the need for personalized assisted reproductive technology (ART) protocols and a multidisciplinary clinical management approach that integrates sleep hygiene strategies and pain control to optimize pregnancy outcomes.