Infertile human endometrial organoid apical protein secretions are dysregulated and impair trophoblast progenitor cell adhesion.

Introduction: Embryo implantation failure leads to infertility. As an important approach to regulate implantation, endometrial epithelial cells produce and secrete factors apically into the uterine cavity in the receptive phase to prepare the initial blastocyst adhesion and implantation. Organoids were recently developed from human endometrial epithelium with similar apical-basal polarity compared to endometrial gland making it an ideal model to study endometrial epithelial secretions. Methods: Endometrial organoids were established using endometrial biopsies from women with primary infertility and normal fertility. Fertile and infertile organoids were treated with hormones to model receptive phase of the endometrial epithelium and intra-organoid fluid (IOF) was collected to compare the apical protein secretion profile and function on trophoblast cell adhesion. Results: Our data show that infertile organoids were dysregulated in their response to estrogen and progesterone treatment. Proteomic analysis of organoid apical secretions identified 150 dysregulated proteins between fertile and infertile groups (>1.5-fold change). Trophoblast progenitor spheroids (blastocyst surrogates) treated with infertile organoid apical secretions significantly compromised their adhesion to organoid epithelial cell monolayers compared to fertile group (P < 0.0001). Discussion: This study revealed that endometrial organoid apical secretions alter trophoblast cell adhesiveness relative to fertility status of women. It paves the way to determine the molecular mechanisms by which endometrial epithelial apical released factors regulate blastocyst initial attachment and implantation.

Surgical anatomy in obstetrics and gynaecology: the trainees' perspective.

BACKGROUND: The aim of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) Integrated and Elective Training Program is to ensure trainees have both clinical and surgical competence. The capacity to recognise important anatomical structures underpins this aim; however, quantification of RANZCOG trainees' anatomical knowledge and their training and assessment is not available. AIM: To survey trainees at all levels relating to applied anatomy, training and assessment within the RANZCOG training program. METHODS: All accredited RANZCOG trainees were invited to participate in an online survey relating to anatomy knowledge, application, assessment and means of improving anatomical training. RESULTS: At the commencement of training, 11% of trainees perceived their anatomical knowledge as adequate and this increased to 77% by the final year of training. For final-year trainees, 78% perceived their anatomy knowledge as sufficient to perform a total abdominal hysterectomy and 87% an ovarian cystectomy or salpingectomy. Eighty-four per cent of trainees perceived the RANZCOG training programme as providing inadequate anatomy teaching. 100% of respondents supported a RANZCOG approved anatomy training course. LIMITATIONS: This is a survey-based study and therefore subjective. Consequently, accurate determination of anatomical knowledge for RANZCOG trainees is inexact. CONCLUSION: Trainees perceive limitations in their anatomical knowledge. A formalised RANZCOG anatomy course would be of value in providing structured education and assessment of trainees' knowledge and establishing whether there are improvements in surgical competencies.