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Background: The use of frozen embryo transfers (FET) in assisted reproduction has increased worldwide. Controlled ovarian hyperstimulation in a fresh transfer may impair endometrial-embryo synchronicity. However, there is conflicting evidence on live birth rates (LBR) and clinical pregnancy rates (CPR). Objective: To compare LBRs and CPRs between single autologous day 5 fresh vs. vitrified blastocyst transfer cycles, to investigate the impact of controlled ovarian hyperstimulation on embryo-endometrium asynchrony. Materials and Methods: A large cross-sectional analysis of 6002 embryo transfers (ET) comprised 3774 fresh and 2228 FET cycles from 2016 to 2019. Multivariate and subgroup analysis were performed for high responders (> 20 oocytes). Results: Univariate analysis showed no difference in LBR (28.3% vs. 27.4%, p = 0.43) and CPR (32.2% vs. 30.9%, p = 0.30); however, multivariate analysis demonstrated significantly lower LBR (OR 0.864, p = 0.046, 95% CI 0.749-0.997) and CPR (OR 0.852, p = 0.024, 95% CI 0.742-0.979) in FET compared to fresh ETs. Younger participant age, previous in vitro fertilization pregnancy, advanced blastocyst expansion, higher trophectoderm quality, and lower cumulative number of ETs all improved the odds of LBR and CPR. Conventional in vitro fertilization, rather than intracytoplasmic sperm injection, improved CPR but not LBR. Body mass index affected neither LBR nor CPR. In the subgroup, multivariate analysis of high responders showed no difference in LBR or CPR. Conclusion: This study demonstrates relatively higher LBR and CPR of nearly 14% for fresh ETs compared to FETs, in multivariate analysis. A universal freeze-all strategy, without appropriate indication, may lead to suboptimal outcomes. In high responders, freeze-all cycles may be beneficial, as outcomes appear similar. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Suboptimal endometrial receptivity is a key factor behind in vitro fertilisation (IVF) implantation failure. Direct clinical tests of the endometrium of natural killer (NK) cells and endometrial receptivity analysis (ERA) are controversial. Aims: To examine the current practice of endometrial receptivity tests (NK cells and ERA) and immunological treatments (corticosteroids, anticoagulants, antiplatelets, intravenous immunoglobulin, Intralipid, other) among fertility specialists in Australia and New Zealand. Methods: A prospective 23‐item web‐based survey was distributed by email via the Fertility Society of Australia and New Zealand, between August and October 2020. Data were collected and analysed using Qualtrics. Results: Of 238 fertility specialists, 90 completed the survey (response rate 37.8%). ERA (48/90, 53.3%) was most commonly ordered, followed by uterine NK (uNK) (36/90, 40.0%) and peripheral blood NK (pNK) (12/90, 13.3%). For all tests, the most common indication was recurrent implantation failure (RIF) (41/48, 22/36, 6/12; 85.4%, 61.1%, and 50.0%, respectively for ERA, uNK and pNK). Of those that did not offer these tests, the main reason cited was insufficient evidence (30/42, 47/54, 68/78; 71.4%, 87.0%, and 87.0%). A third of specialists offered empirical immunological treatment for RIF (30/90, 33.3%): anticoagulants (28/30, 93.3%), antiplatelets (27/30, 90.0%), and corticosteroids (25/30; 83.3%). The majority of specialists (56/90, 62.2%) stated they had refused a patient request for endometrial testing or treatment. Conclusions: Tests for presumed endometrial receptivity pathology are often used in Australia and New Zealand. Immunological treatments for RIF are commonly employed empirically, without strong evidence of their effectiveness or safety. Further studies should focus on education and clinical adherence to evidence‐based guidelines. [ABSTRACT FROM AUTHOR]