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International and national oncofertility networks, including the US-led Oncofertility Consortium, FertiProtekt, and the Danish Network, have played pivotal roles in advancing the discipline of oncofertility over the last decade. Many other countries lack a shared approach to pediatric oncofertility health service delivery. This study aims to describe baseline oncofertility practices at Australian New Zealand Children's Haematology/Oncology Group centers in 2019–2021, describe binational priorities for care, and propose a 5-year action plan for best practice to be implemented by the newly formed Australian New Zealand Consortium in Children, Adolescents, and Young Adults (CAYA) Oncofertility (ANZCO).

PURPOSE: As a further step to elucidate the actual diverse spectrum of oncofertility practices for breast cancer around the globe, we present and discuss the comparisons of oncofertility practices for breast cancer in limited versus optimum resource settings based on data collected in the Repro-Can-OPEN Study Part I & II. METHODS: We surveyed 39 oncofertility centers including 14 in limited resource settings from Africa, Asia & Latin America (Repro-Can-OPEN Study Part I), and 25 in optimum resource settings from the United States, Europe, Australia and Japan (Repro-Can-OPEN Study Part II). Survey questions covered the availability of fertility preservation and restoration options offered to young female patients with breast cancer as well as the degree of utilization. RESULTS: In the Repro-Can-OPEN Study Part I & II, responses for breast cancer and calculated oncofertility scores showed the following characteristics: (1) higher oncofertility scores in optimum resource settings than in limited resource settings especially for established options, (2) frequent utilization of egg freezing, embryo freezing, ovarian tissue freezing, GnRH analogs, and fractionation of chemo- and radiotherapy, (3) promising utilization of oocyte in vitro maturation (IVM), (4) rare utilization of neoadjuvant cytoprotective pharmacotherapy, artificial ovary, and stem cells reproductive technology as they are still in preclinical or early clinical research settings, (5) recognition that technical and ethical concerns should be considered when offering advanced and innovative oncofertility options. CONCLUSIONS: We presented a plausible oncofertility best practice model to guide oncofertility teams in optimizing care for breast cancer patients in various resource settings.

Objective: To determine the causal effect of in-vitro fertilisation (IVF) on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. Design(s): Causal inference methods (based on the potential outcomes approach) were used to analyses observation data in a way that emulates the results of a target randomised clinical trial. Method(s): The study cohort comprised state-wide linked maternal and childhood administrative data from Victoria, Australia. The study included singleton infants conceived spontaneously or via IVF and born between 2005-2014, who had school-age developmental and educational outcomes assessed. The exposure of interest was conception via IVF, with those born after spontaneous conception as the control group. Two separate measures of childhood outcome were examined: The Australian Early Developmental Consensus (AEDC), a broad developmental assessment conducted for all children in their first year of primary school (age 4-6, n = 172,000); and the National Assessment Program -Literacy and Numeracy (NAPLAN), a school-based psychometric test first undertaken during their fourth year of primary school (grade three) at age 7-9 (n = 342,311). We combined inverse probability weighting with regression adjustment to estimate population average causal effects. Result(s): The final cohort included 412,713 children across the two outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC outcome data, and 8,976 cases and 333,335 controls for NAPLAN data. The mothers of IVF-conceived children were older, more highly educated mothers, who lived in more socio-economic advantaged areas and were less likely to be from non-English speaking backgrounds. There was no evidence against the null hypothesis that there is no causal effect of IVF-conception on the on the risk of developmental vulnerability at school-entry compared to spontaneously conceived chil

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.

PURPOSE: This study aims to examine whether blastocyst morphology post-warming correlates with live birth. METHODS: In this cohort study, morphological characteristics post-warming were reviewed in all single vitrified-warmed blastocyst transfer cycles performed between November 2016 and May 2017. Immediately before transfer, the degree of blastocoel re-expansion was graded as A, fully expanded; B, partially expanded ≥ 50%; C, partially expanded < 50%; and D, collapsed. The degree of post-warming cell survival was graded on a scale of 50 to 100% and was then classified into 4 groups: very low 50-70%, low 71-80%, moderate 81-90%, and high 91-100%. RESULTS: Overall, 612 cycles were reviewed, of which 196 included PGT-A tested embryos. The live birth rate (LBR) increased from 11.4% in the collapsed blastocysts group to 38.9% in the post-warming full re-expansion group (p < 0.001) and from 6.5% for blastocysts with a very low cell survival rate to 34.7% for blastocysts with high cell survival rate (p = 0.001). LBR was 6.7% for blastocysts with the worst post-warming morphological characteristics, namely, collapsed with very low cell survival rate. On multivariate analyses, partial blastocyst re-expansion ≥ 50%, full re-expansion, and high cell survival rate remained significantly associated with live birth, after controlling for female age, pre-vitrification morphological grading, and PGT-A. A sub-analysis of cycles using PGT-A tested embryos showed similar results. CONCLUSION: Post-warming re-expansion and high cell survival rate are associated with higher LBR in euploid and untested blastocysts. However, embryos with poor post-warming morphology still demonstrate a considerable probability of live birth, and they should not be discarded.

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.

© 2018 The Author(s). Uncertainty in mass-observable scaling relations is currently the limiting factor for galaxycluster-based cosmology. Weak gravitational lensing can provide direct mass calibration and reduce the mass uncertainty. We present new ground-based weak lensing observations of 19 South Pole Telescope (SPT) selected clusters at redshifts 0.29 = z = 0.61 and combine them with previously reported space-based observations of 13 galaxy clusters at redshifts 0.576 = z = 1.132 to constrain the cluster mass scaling relations with the Sunyaev-Zel'dovich effect (SZE), the cluster gas mass Mgas and YX, the product of Mgas and X-ray temperature. We extend a previously used framework for the analysis of scaling relations and cosmological constraints obtained from SPT-selected clusters to make use of weak lensing information. We introduce a new approach to estimate the effective average redshift distribution of background galaxies and quantify a number of systematic errors affecting the weak lensing modelling. These errors include a calibration of the bias incurred by fitting a Navarro-Frenk-White profile to the reduced shear using N-body simulations. We blind the analysis to avoid confirmation bias. We are able to limit the systematic uncertainties to 5.6% in cluster mass (68% confidence). Our constraints on the mass-X-ray observable scaling relation parameters are consistent with those obtained by earlier studies and our constraints for the mass-SZE scaling relation are consistent with the simulation-based prior used in the most recent SPT-SZ cosmology analysis. We can now replace the external mass calibration priors used in previous SPT-SZ cosmology studies with a direct, internal calibration obtained for the same clusters.

PURPOSE To quantify joint degeneration and the clinical outcome after curettage and cementation in subchondral giant cell tumors of the bone (GCTB) at the knee. METHODS We conducted a retrospective analysis of 14 consecutive patients (seven female, seven male) with a mean age of 34 years (range 19-51) who underwent curettage and subchondral cementation for a biopsy-confirmed GCTB at the distal femur or the proximal tibia between August 2001 and August 2017, with a mean follow-up period of 54.6 months (range 16.1-156 months). The Whole-Organ Magnetic Resonance Imaging Score (WORMS), Kellgren-Lawrence (KL) classification, and Musculo-Skeletal Tumor Society (MSTS) score were assessed. RESULTS Radiological degeneration progressed from preoperative to the latest follow-up, with a median WORMS from 2.0 to 4.0 (p = 0.006); meanwhile, the median KL score remained at 0 (p = 0.102). Progressive degeneration (WORMS) tended to be associated with the proximity of the tumor to the articular cartilage (mean 1.57 mm; range 0-12 mm) (p = 0.085). The most common degenerative findings were cartilage lesions (n = 11), synovitis (n = 5), and osteophytes (n = 4). Mean MSTS score increased from 23.1 (preoperatively) to 28.3 at the latest follow-up (p < 0.01). Seven patients (50%) were treated for a local recurrence, with six revision surgeries performed. Removal of the cement spacer and filling of the cavity with a cancellous autograft was performed in seven patients. Conversion to a total knee arthroplasty was performed in one patient for local tumor control. CONCLUSIONS Cementation following the curettage of GCTB around the knee is associated with slight degeneration at medium-term follow-up and leads to a significant reduction in pain. Removal of the cement and reconstruction with an autograft may be beneficial in the long term.

A diagnosis of endometriosis is associated with increased risks of adverse pregnancy outcomes including placenta praevia and preterm birth. Some studies have also suggested associations with gestational hypertension, foetal growth restriction, gestational diabetes, perinatal death, and obstetric haemorrhage. This review aims to assess the impact of pre-pregnancy surgical treatment of endometriosis on future obstetric outcomes. A search of the Medline, Embase and PubMed electronic databases was performed to identify studies reporting pre-pregnancy surgery for endometriosis and subsequent pregnancy outcome compared to controls with unresected endometriosis. Three studies met the inclusion criteria. The studies were heterogenous in design, definition of study groups and outcome measures. All three studies were judged at critical risk of bias. Pre-pregnancy excision of endometriosis was associated with an increased risk of caesarean section in one of two studies, OR 1.72 (95% CI 1.59-1.86) and OR 1.79 (95% CI 0.69-4.64). Placenta praevia rates were also increased in one of two studies OR 2.83 (95% CI 0.56-12.31) and OR 2.04 (95% CI 1.66-2.52). One study found increased risks of preterm birth, small for gestational age, gestational hypertension, and antepartum and postpartum haemorrhage (all p < 0.05) with pre-pregnancy excision of endometriosis. There is insufficient evidence examining the role of pre-pregnancy endometriosis surgery in ameliorating adverse pregnancy outcomes, and thus reliable conclusions cannot be drawn. Prospectively designed studies are needed to assess the relationship between surgical treatments for endometriosis and obstetric outcome and examine potential confounders such as comorbid adenomyosis and infertility.