5th International Conference on Gynecology and Obstetrics

Nathalie Ledee, MD, PhD, received her medical degree in obstetrics and gynecology from Paris VI University in 1993, a Master’s degree in experimental surgery from McGill University in 1995, and a PhD in reproductive immunology from Paris VI University in 2003. She obtained her Habilitation à diriger des recherches (HDR), a French qualification recognizing the ability to lead independent research and supervise doctoral candidates, in 2006. She became assistant professor in reproductive medicine in 2004 and subsequently held academic and research positions at the University of Liège and Inserm in Paris. She is currently a Maître de conférences des universités–praticien hospitalier (MCU-PH) at Université de Versailles-Saint-Quentin-en-Yvelines, currently on secondment for an innovation mission. Since 2010, she has coordinated the Assisted Reproductive Technology (ART) Center at Hôpital Les Bluets in Paris, where she has served as Head of R&D since 2023. She is President of MatriceLab Innove, a company dedicated to innovation in reproductive immunology, and will become President of the European Society for Reproductive Immunology (ESRI) in 2027. Her research focuses on the endometrial immune microenvironment and its role in embryo implantation and reproductive outcomes. She has contributed to the development of endometrial immune profiling approaches aimed at characterizing immune dysregulation and guiding personalized treatment strategies in assisted reproductive technology. Her work seeks to improve reproductive outcomes through a better understanding of the immune dialogue between the embryo and the endometrium.

Background: Despite major advances in assisted reproductive technologies (ART), implantation failure remains a major clinical challenge. Embryo quality is central to current clinical practice, yet successful implantation also requires a receptive endometrium capable of establishing a coordinated dialogue with the embryo. The endometrial immune environment is an integral part of this process, but it is rarely considered in routine embryo-transfer decisions. Can characterizing and adapting this environment improve reproductive outcomes?

Study design and approach: We investigated this question in a prospective randomized controlled trial involving 493 good-prognosis IVF/ICSI patients younger than 38 years. Before embryo transfer, endometrial immune profiling was performed using cytokine biomarkers. Patients with a balanced profile received conventional care, whereas those with immune dysregulation were randomized to conventional management, without consideration of their immune profile, or to profile-guided precision care. The primary endpoint was live birth rate (LBR) after the first embryo transfer. Prespecified secondary analyses explored whether the clinical relevance of endometrial immune status varied according to embryo morphology and transfer strategy (fresh versus frozen embryo transfer, FET).

Results: Endometrial immune dysregulation was identified in approximately 80% of these good-prognosis patients, demonstrating that deviations from the reference immune profile are common even in patients with a favorable reproductive prognosis. In the primary randomized comparison, profile-guided precision care significantly increased LBR compared with conventional management (41.4% vs. 29.7%; OR 1.68, 95% CI 1.04–2.73; p=0.036).

Secondary analyses highlighted the importance of considering embryo morphology and endometrial immune status together. Under conventional management, LBR after transfer of non-Top embryos was higher in patients with a balanced immune profile than in those with immune dysregulation (38.4% vs. 21.2%). In contrast, LBR was similar between the two groups following transfer of Top embryos (46.3% vs. 45.8%). The difference was particularly striking in FET cycles: LBR was 52.4% in patients with a balanced profile and 14.7% in patients with immune dysregulation receiving conventional management. Among patients with immune dysregulation, profile-guided precision care was associated with an LBR of 48.6%.

Conclusions: These findings position the endometrial immune environment as a potentially modifiable component of reproductive success and support extending personalized ART beyond embryo selection alone. The randomized results demonstrate the clinical relevance of profile-guided management in good-prognosis patients with immune dysregulation. The secondary analyses further suggest that the relevance of endometrial immune status may depend on the embryo–uterine context, with particularly marked differences in FET cycles and following transfer of non-Top embryos. For clinicians, this perspective raises an important question: should embryo-transfer decisions consider not only the embryo's developmental potential, but also the endometrial environment in which implantation must occur? Integrating endometrial immune profiling into a broader model of personalized ART may offer a complementary strategy to optimize the conditions for implantation while preserving embryo quality as a central determinant of success.