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Introduction: The 2024 Australian evidence‐based guideline for unexplained infertility provides clinicians with evidence‐based recommendations for the optimal diagnostic workup for infertile couples to establish the diagnosis of unexplained infertility and optimal therapeutic approach to treat couples diagnosed with unexplained infertility in the Australian health care setting. The guideline recommendations were adapted for the Australian context from the rigorous, comprehensive European Society of Human Reproduction and Embryology (ESHRE) 2023 Evidence‐based guideline: unexplained infertility, using the ADAPTE process and have been approved by the Australian National Health and Medical Research Council. Main recommendations: The guideline includes 40 evidence‐based recommendations, 21 practice points and three research recommendations addressing: definition — defining infertility and frequency of intercourse, infertility and age, female and male factor infertility;diagnosis — ovulation, ovarian reserve, tubal factor, uterine factor, laparoscopy, cervical/vaginal factor, male factor, additional testing for systemic conditions; andtreatment — expectant management, active treatment, mechanical‐surgical procedures, alternative therapeutic approaches, quality of life. Changes in assessment and management resulting from the guideline: This guideline refines the definition of unexplained infertility and addresses basic diagnostic procedures for infertility assessment not considered in previous guidelines on unexplained infertility. For therapeutic approaches, consideration of evidence quality, efficacy, safety and, in the Australian setting, feasibility, acceptability, cost, implementation and ultimately recommendation strength were integrated across multidisciplinary expertise and consumer perspectives in adapting recommendations to the Australian context by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, which had not been used in past guidelines on unexplained infertility to formulate recommendations. The Australian process also included an established data integrity check to ensure evidence could be trusted to guide practice. Practice points were added and expanded to consider the Australian setting. No evidence‐based recommendations were underpinned by high quality evidence, with most having low or very low quality evidence. In this context, research recommendations were made including those for the Australian context. The full guideline and technical report are publicly available online and can be accessed at https://www.monash.edu/medicine/mchri/infertility and are supported by extensive translation resources, including the free patient ASKFertility mobile application (https://www.askfertility.org/). [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does medroxyprogesterone acetate (MPA) exposure in progestin-primed ovarian stimulation (PPOS) cycles cause molecular perturbations in the steroidogenic function and gonadotropin responsiveness of the granulosa cells? SUMMARY ANSWER PPOS cycles are identical to traditional GnRH antagonist cycles not only for clinical IVF characteristics but also for gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level. WHAT IS KNOWN ALREADY PPOS is increasingly used as an alternative to GnRH antagonists due to the inhibitory effect of progesterone on LH release by reducing GnRH pulsatility at the hypothalamic level. Although a growing body of evidence from clinical studies did not indicate significant differences between PPOS and antagonist protocols for IVF cycle characteristics and obstetrical outcomes, it is still unknown whether exposure of the antral follicle cohort to progesterone or its synthetic derivatives during ovarian stimulation causes any subtle molecular aberrations in terms of steroidogenesis and gonadotropin responsiveness. To address this issue, detailed comparative molecular analyses were conducted in the luteinized mural granulosa cells (GCs) obtained from normal responding IVF patients undergoing PPOS and antagonist cycles. STUDY DESIGN, SIZE, DURATION A clinical translational research study was conducted with IVF patients. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 55 normal responding IVF patients who underwent ovarian stimulation with either PPOS using MPA (5 mg twice daily) or GnRH antagonist cetrorelix acetate. Recombinant forms of FSH and hCG were used for ovarian stimulation and ovulation triggering, respectively. Luteinized mural GCs obtained during the oocyte retrieval procedure were used for the experiments. Cell culture, quantitative real-time PCR, immunoblotting, confocal time-lapse live cell imaging, and hormone assays were used. MAIN RESULTS AND THE ROLE OF CHANCE Demographic and IVF cycle characteristics of the patients undergoing ovarian stimulation with PPOS and GnRH antagonist were similar, including ovarian response, mature oocyte yield, and fertilization rates. Molecular analyses revealed that the expression of the enzymes involved in sex-steroid synthesis (StAR, SCC, 3β-HSD, 17β-HSD, aromatase) and the uptake/storage/utilization of cholesterol (LDL receptor, Hormone-sensitive lipase, hydroxy-methyl glutaryl Co-enzyme-A reductase, and Sterol O-acyltransferase1) in the GCs of the PPOS cycles were comparable to those of the antagonist cycles. The expression of the receptors for gonadotropins, estrogen, and progesterone hormones was also similar. Basal and hCG-induced increases in 3β-HSD expression and progesterone production and basal and FSH-induced increases in aromatase expression and E2 output of the GCs from PPOS patients did not exhibit any meaningful differences when compared with GCs from antagonist cycles. Furthermore, basal and hCG-induced up-regulation in the LDL receptor expression and cholesterol uptake did not differ between the groups. Confocal imaging also revealed similar patterns of expression for the steroidogenic enzymes and their co-localization with mitochondria. Lastly, the expression of the other important genes regulating cumulus expansion, ovulation, and luteal function [Relaxin, ADAMTS-1, and epidermal growth factor (EGF)-like growth factor amphiregulin] in the GCs of the PPOS and antagonist cycles were similar. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Caution should be exercised when interpreting our data which was derived from normally responding patients whose ovulation was triggered with hCG. It is unclear whether the molecular parameters assessed vary according to infertility etiologies, magnitude of ovarian response, mode of trigger, and any other underlying ovarian pathologies or systemic diseases. MPA was the progestin used for PPOS and whether these findings can be generalized to other progestins is unknown. WIDER IMPLICATIONS OF THE FINDINGS This study provides reassuring molecular evidence that exposure of antral follicle cohorts to MPA during the follicular growth phase does not have any detrimental effects on steroidogenic, ovulatory, and luteal functions when compared with GnRH antagonist cycles. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), and equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Managing Volunteer Engagement Non-profit organizations that provide food, shelter, and other services to people in need, rely on volunteers to deliver their services. Unlike paid labor, non-profit organizations have less control over unpaid volunteers' schedules, efforts, and reliability. However, these organizations can invest in volunteer engagement activities to strive for a steady and adequate supply of volunteer labor. The paper, "A Dynamic Model for Managing Volunteer Engagement", models the volunteer management process. The paper derives a dynamic control policy that judiciously uses the non-profit's resources for volunteer engagement activities depending on explicit congestion thresholds, thereby lowering the overall cost of the non-profit operation. Nonprofit organizations that provide food, shelter, and other services to people in need, rely on volunteers to deliver their services. Unlike paid labor, nonprofit organizations have less control over unpaid volunteers' schedules, efforts, and reliability. However, these organizations can invest in volunteer engagement activities to ensure a steady and adequate supply of volunteer labor. We study a key operational question of how a nonprofit organization can manage its volunteer workforce capacity to ensure consistent provision of services. In particular, we formulate a multiclass queueing network model to characterize the optimal engagement activities for the nonprofit organization to minimize the costs of enhancing volunteer engagement, while maximizing productive work done by volunteers. Because this problem appears intractable, we formulate an approximating Brownian control problem in the heavy traffic limit and study the dynamic control of that system. Our solution is a nested threshold policy with explicit congestion thresholds that indicate when the nonprofit should optimally pursue various types of volunteer engagement activities. A numerical example calibrated using data from a large food bank shows that our dynamic policy for deploying engagement activities can significantly reduce the food bank's total annual cost of its volunteer operations while still maintaining almost the same level of social impact. This improvement in performance does not require any additional resources—it only requires that the food bank strategically deploy its engagement activities based on the number of volunteers signed up to work volunteer shifts. Supplemental Material: The e-companion is available at https://doi.org/10.1287/opre.2021.0419. [ABSTRACT FROM AUTHOR]