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BACKGROUND. Oocyte competence for maturation and embryogenesis is associated with oocyte diameter in many mammals. This study aimed to test whether such a relationship exists in humans and to quantify its impact upon in vitro maturation (IVM). METHODS. We used computer-assisted image analysis daily to measure average diameter, zona thickness and other parameters in oocytes. Immature oocytes originated from unstimulated patients with polycystic ovaries, and from stimulated patients undergoing ICSI. They were cultured with or without meiosis activating sterol (FF-MAS). Oocytes maturing in vitro were inseminated using ICSI and embryo development was monitored. A sample of freshly collected in vivo matured oocytes from ICSI patients were also measured. RESULTS. Immature oocytes were usually smaller at collection than in vivo matured oocytes. Capacity for maturation was related to oocyte diameter and many oocytes grew in culture. FF-MAS stimulated growth in ICSI derived oocytes, but only stimulated growth in PCO derived oocytes if they eventually matured in vitro. Oocytes degenerating showed cytoplasmic shrinkage. Neither zona thickness, perivitelline space, nor the total diameter of the oocyte including the zona were informative regarding oocyte maturation capacity. CONCLUSIONS. Immature oocytes continue growing during maturation culture. FF-MAS promotes oocyte growth in vitro. Oocytes from different sources have different growth profiles in vitro. Measuring diameters of oocytes used in clinical IVM may provide additional non-invasive information that could potentially identify and avoid the use of oocytes that remain in the growth phase.

Funder: Warwick-Wellcome Trust Translational Partnership, Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into a robust matrix that accommodates the placenta throughout pregnancy. To gain insights into the underlying mechanisms, we established and characterized endometrial assembloids, consisting of gland-like organoids and primary stromal cells. Single-cell transcriptomics revealed that decidualized assembloids closely resemble midluteal endometrium, harbouring differentiated and senescent subpopulations in both glands and stroma. We show that acute senescence in glandular epithelium drives secretion of multiple canonical implantation factors, whereas in the stroma it calibrates the emergence of anti-inflammatory decidual cells and pro-inflammatory senescent decidual cells. Pharmacological inhibition of stress responses in pre-decidual cells accelerated decidualization by eliminating the emergence of senescent decidual cells. In co-culture experiments, accelerated decidualization resulted in entrapment of collapsed human blastocysts in a robust, static decidual matrix. By contrast, the presence of senescent decidual cells created a dynamic implantation environment, enabling embryo expansion and attachment, although their persistence led to gradual disintegration of assembloids. Our findings suggest that decidual senescence controls endometrial fate decisions at implantation and highlight how endometrial assembloids may accelerate the discovery of new treatments to prevent reproductive failure.