Gender inequality and utilization of ART: an international cross-sectional and longitudinal analysis.

STUDY QUESTION: What is the association between a country's level of gender equality and access to ART, as measured through ART utilization? SUMMARY ANSWER: ART utilization is associated with a country's level of gender equality even after controlling for the level of development. WHAT IS KNOWN ALREADY: Although gender equality is recognized as an important determinant of population health, its association with fertility care, a highly gendered condition, has not been explored. STUDY DESIGN, SIZE, DURATION: A longitudinal cross-national analysis of ART utilization in 69 countries during 2002-2014 was carried out. PARTICPANTS/MATERIALS, SETTING, METHODS: The Gender Inequality Index (GII), Human Development Index (HDI), and their component indicators were modelled against ART utilization using univariate regression models as well as mixed-effects regression methods (adjusted for country, time, and economic/human development) with multiple imputation to account for missing data. MAIN RESULTS AND THE ROLE OF CHANCE: ART utilization is associated with the GII. In an HDI-adjusted analysis, a one standard deviation decrease in the GII (towards greater equality) is associated with a 59% increase in ART utilization. Gross national income per capita, the maternal mortality ratio, and female parliamentary representation were the index components most predictive of ART utilization. LIMITATIONS, REASONS FOR CAUTION: Only ART was used rather than all infertility treatments (including less costly and non-invasive treatments such as ovulation induction). This was a country-level analysis and the results cannot be generalized to smaller groups. Not all modelled variables were available for each country across 2002-2014. WIDER IMPLICATIONS OF THE FINDINGS: Access to fertility care is central to women's sexual and reproductive health, to women's rights, and to human rights. As gender equality improves, so does access to ART. This relation is likely to be reinforcing and bi-directional, with progress towards global, equitable access to fertility care also improving women's status and participation in societies. STUDY FUNDING/COMPETING INTEREST(S): External funding was not provided for this study. G.D.A. declares consulting fees from Labcorp and CooperSurgical. G.D.A. is the founder and CEO of Advanced Reproductive Care, Inc., as well as the Chair of the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) and the World Endometriosis Research Foundation, both of which are unpaid roles. G.M.C. is an ICMART Board Representative, which is an unpaid role, and no payments are received from ICMART to UNSW, Sydney, or to G.M.C. to undertake this study. O.F., S.D., F.Z.-H., and E.K. report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Does in vitro fertilization (IVF) treatment provide good value for money? A cost-benefit analysis.

Background: Using traditional health technology assessment (HTA) outcome metrics, such as quality-adjusted life-years, to assess fertility treatments raises considerable methodological challenges because the objective of fertility treatments is to create new life rather than extend, save, or improve health-related quality of life. Objective: The aim of this study was to develop a novel cost-benefit framework to assess value for money of publicly funded IVF treatment; to determine the number of cost-beneficial treatment cycles for women of different ages; and to perform an incremental cost-benefit analysis from a taxpayer perspective. Methods: We developed a Markov model to determine the net monetary benefit (NMB) of IVF treatment by female age and number of cycles performed. IVF treatment outcomes were monetized using taxpayers' willingness-to-pay values derived from a discrete choice experiment (DCE). Using the current funding environment as the comparator, we performed an incremental analysis of only funding cost-beneficial cycles. Similar outputs to cost-effectiveness analyses were generated, including net-benefit acceptability curves and cost-benefit planes. We created an interactive online app to provide a detailed and transparent presentation of the results. Results: The results suggest that at least five publicly funded IVF cycles are cost-beneficial in women aged <42 years. Cost-benefit planes suggest a strong taxpayer preference for restricting funding to cost-beneficial cycles over current funding arrangements in Australia from an economic perspective. Conclusions: The provision of fertility treatment is valued highly by taxpayers. This novel cost-benefit method overcomes several challenges of conventional cost-effectiveness methods and provides an exemplar for incorporating DCE results into HTA. The results offer new evidence to inform discussions about treatment funding arrangements.

Freeze-all embryos during treatment with assisted reproduction: Health economic aspects.

Assisted reproductive technologies are evolving, with the most recent example being the introduction of the freeze-all policy during which a fresh embryo transfer does not take place and all embryos of good quality are cryopreserved to be used in future frozen embryo transfers. As the freeze-all policy is becoming more prevalent, it is important to review the economic aspects of this approach, along with considerations of efficacy and safety, and the role of emerging freeze-all-specific ovarian stimulation strategies. Based on the available evidence, the freeze-all policy presents distinct clinical advantages, particularly for high responders. Available health economic evaluations are limited. Two good-quality cost-effectiveness analyses based on randomized controlled trials suggest that the freeze-all strategy is unlikely to be cost-effective in non-polycystic ovarian syndrome (non-PCOS), normally responding patients. However, the cost-effectiveness of the freeze-all strategy in different populations of patients and in different settings has not been evaluated, nor has the clinical and economic efficacy of modern freeze-all-specific ovarian stimulation protocols that are likely to simplify treatment and make it more affordable for patients. Economic evaluations that incorporate good practice health technology assessment (HTA) methods are needed to compare freeze-all with conventional embryo transfer strategies. Furthermore, future research should address the unique limitation of traditional HTA methods in valuing a life conceived through fertility treatment.

What Features of Fertility Treatment do Patients Value? Price Elasticity and Willingness-to-Pay Values from a Discrete Choice Experiment.

BACKGROUND: Infertility is a medical condition affecting an estimated 186 million people worldwide. Medically assisted fertility treatments allow many of these individuals to have a baby. Insights about preferences of patients who have experienced fertility treatment should be used to inform funding policies and treatment configurations that best reflect the patients' voice and the value of fertility treatment to patients. OBJECTIVE: To explore the preferences for fertility treatment attributes of infertile women who had previously undergone or were undergoing fertility treatments-ex post perspective. METHODS: We used data from a stated-preference discrete choice experiment (DCE) among 376 Australian women who had undergone or were undergoing fertility treatment. Respondents chose their preferred treatment choices in 12 hypothetical treatment choice scenarios described by seven attributes (success rates, side effects, counselling/peer support, treatment journey, continuity of care, availability of experimental treatment and out-of-pocket cost). We estimated random parameter logit (RPL) and latent class (LC) models that accounted for preference heterogeneity. The results were used to derive price elasticities of demand and marginal willingness-to-pay (WTP) values for the treatment attributes explored within the DCE survey. RESULTS: Income level did not have a significant effect on marginal WTP for fertility treatment attributes. The demand for fertility treatment from an ex post perspective was found to be highly inelastic (treatment cost changes had almost no impact on demand). Success rates and out-of-pocket costs were significant and important predictors of individuals' treatment choices conditional on the attributes and levels included in the study. These were followed by counselling/peer support, side effects, treatment journey, continuity of care, and availability of experimental treatment, in that order. Respondents were willing to pay $383-$524 per one percentage point increase in the treatment success rate and over $2000 and over $3500 to avoid moderate and significant side effects, respectively (values are reported in AU$). Latent class models revealed that the majority of respondents (51%) were risk-averse success-rate seekers. CONCLUSION: Infertile women who had previously undergone or were undergoing fertility treatment valued fertility treatment highly as reflected by highly price-inelastic demand. Success rate of treatment and out-of-pocket costs were the most important attributes and largely determined patients' WTP for fertility treatment relative to the attributes and levels used in the study. While further research should investigate the price sensitivity of women who have not experienced fertility treatment, these results might explain why women continue fertility treatment once they have commenced despite their financial capacity to pay. Future research should also determine patients' price elasticities for a fertility treatment program with multiple treatment cycles.

Economic Evaluation of Newborn Screening for Severe Combined Immunodeficiency.

Evidence on the cost-effectiveness of newborn screening (NBS) for severe combined immunodeficiency (SCID) in the Australian policy context is lacking. In this study, a pilot population-based screening program in Australia was used to model the cost-effectiveness of NBS for SCID from the government perspective. Markov cohort simulations were nested within a decision analytic model to compare the costs and quality-adjusted life-years (QALYs) over a time horizon of 5 and 60 years for two strategies: (1) NBS for SCID and treat with early hematopoietic stem cell transplantation (HSCT); (2) no NBS for SCID and treat with late HSCT. Incremental costs were compared to incremental QALYs to calculate the incremental cost-effectiveness ratios (ICER). Sensitivity analyses were performed to assess the model uncertainty and identify key parameters impacting on the ICER. In the long-term over 60 years, universal NBS for SCID would gain 10 QALYs at a cost of US $0.3 million, resulting in an ICER of US$33,600/QALY. Probabilistic sensitivity analysis showed that more than half of the simulated ICERs were considered cost-effective against the common willingness-to-pay threshold of A$50,000/QALY (US$35,000/QALY). In the Australian context, screening for SCID should be introduced into the current NBS program from both clinical and economic perspectives.

Modelling the Cost-Effectiveness and Budget Impact of a Newborn Screening Program for Spinal Muscular Atrophy and Severe Combined Immunodeficiency.

Spinal muscular atrophy (SMA) and severe combined immunodeficiency (SCID) are rare, inherited genetic disorders with severe mortality and morbidity. The benefits of early diagnosis and initiation of treatment are now increasingly recognized, with the most benefits in patients treated prior to symptom onset. The aim of the economic evaluation was to investigate the costs and outcomes associated with the introduction of universal newborn screening (NBS) for SCID and SMA, by generating measures of cost-effectiveness and budget impact. A stepwise approach to the cost-effectiveness analyses by decision analytical models nested with Markov simulations for SMA and SCID were conducted from the government perspective. Over a 60-year time horizon, screening every newborn in the population and treating diagnosed SCID by early hematopoietic stem cell transplantation and SMA by gene therapy, would result in 95 QALYs gained per 100,000 newborns, and result in cost savings of USD 8.6 million. Sensitivity analysis indicates 97% of simulated results are considered cost-effective against commonly used willingness-to-pay thresholds. The introduction of combined NBS for SCID and SMA is good value for money from the long-term clinical and economic perspectives, representing a cost saving to governments in the long-term, as well as improving and saving lives.

Biologics for severe, chronic plaque psoriasis: An Australian cost-utility analysis.

BACKGROUND: Biologics are a good therapeutic option for severe, chronic plaque psoriasis; however, they come with significant cost to the health care system. OBJECTIVE: To conduct a cost-utility analysis of outpatient biologics (adalimumab, etanercept, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab) available to adults with severe, chronic plaque psoriasis from the perspective of the Australian health care system. METHODS: A Markov cohort model was constructed to estimate the quality-adjusted life years (QALYs) and costs accrued for treatment pathways commencing with different first-line biologics, over a 96-week time horizon. The model adhered to the Australian Pharmaceutical Benefits Scheme eligibility criteria and guidelines. RESULTS: A biologic treatment pathway commencing on tildrakizumab was the most cost-effective first-line treatment (Australian dollar 39,930; total utility of 1.57 QALYs over 96 weeks). First-line secukinumab and risankizumab had incremental cost-utility ratios of Australian dollar 194,524/QALY and Australian dollar 479,834/QALY, respectively, when compared with first-line tildrakizumab. LIMITATIONS: The efficacy and utility input parameters were derived from international randomized control trials and patients from the United Kingdom, respectively. Findings from this study cannot be generalized beyond Australia. CONCLUSION: Tildrakizumab may be considered as first-line treatment for adult patients with severe, chronic plaque psoriasis embarking on biologic therapy, from the economic perspective of the Australian health care system.

How Much Is a Human Life Worth? A Systematic Review.

OBJECTIVES: To systematically review studies eliciting monetary value of a statistical life (VSL) estimates within, and across, different sectors and other contexts; compare the reported estimates; and critically review the elicitation methods used. METHODS: In June 2019, we searched the following databases to identify methodological and empirical studies: Cochrane Library, Compendex, Embase, Environment Complete, Informit, ProQuest, PubMed, Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reporting and a modified Consolidated Health Economic Evaluation Reporting Standards checklist to assess the quality of included studies. RESULTS: We identified 1455 studies, of which we included 120 in the systematic review. A stated-preference approach was used in 76 articles, with 51%, 41%, and 8% being contingent valuation studies, discrete-choice experiments, or both, respectively. A revealed-preference approach was used in 43 articles, of which 74% were based on compensating-wage differentials. The human capital approach was used in only 1 article. We assessed most publications (87%) as being of high quality. Estimates for VSL varied substantially by context (sector, developed/developing country, socio-economic status, etc), with the median of midpoint purchasing power parity-adjusted estimates of 2019 US$5.7 million ($6.8 million, $8.7 million, and $5.3 million for health, labor market, and transportation safety sectors, respectively). CONCLUSIONS: The large variation observed in published VSLs depends mainly on the context rather than the method used. We found higher median values for labor markets and developed countries. It is important that health economists and policymakers use context-specific VSL estimates. Methodological innovation and standardization are needed to maximize comparability of VSL estimates within, and across, sectors and methods.

Is there an optimal number of oocytes retrieved at which live birth rates or cumulative live birth rates per aspiration are maximized after ART? A systematic review.

The association between the number of oocytes retrieved and fresh live birth rate (LBR) or cumulative LBR (CLBR), and whether an optimal number of oocytes are retrieved when LBR or CLBR are maximized, are highly relevant clinical questions; however published results are conflicting. A systematic review of all eligible studies (n = 16) published until January 2020 on MEDLINE, Embase, Scopus, CINAHL and Web of Science was conducted. Five studies evaluated only LBR from fresh cycles, five studies evaluated only CLBR from stimulated cycles and six evaluated both. A marked difference was observed between the oocyte yields at which LBR and CLBR were reportedly maximized in the individual studies. On the basis of nine studies, the optimal number of oocytes at which fresh LBR seems to be maximized is proposed to be between 12 and 18 oocytes (15 oocytes was the most common suggestion). On the other hand, CLBR continues to increase with the number of oocytes retrieved. This is the first systematic review on the topic, and it suggests that the retrieval of 12-18 oocytes is associated with maximal fresh LBR, whereas a continuing positive association is present between the number of oocytes retrieved and CLBR.

Funding and public reporting strategies for reducing multiple pregnancy from fertility treatments.

The health of children born through assisted reproductive technologies (ART) is particularly vulnerable to policy decisions and market forces that play out before they are even conceived. ART treatment is costly, and public and third-party funding varies significantly between and within countries, leading to considerable variation in consumer affordability globally. These relative cost differences affect not only who can afford to access ART treatment, but also how ART is practiced in terms of embryo transfer practices, with less affordable treatment creating a financial incentive to transfer more than one embryo to maximize the pregnancy rates in fewer cycles. One mechanism for reducing the burden of excessive multiple pregnancies is to link insurance coverage to the number of embryos that can be transferred; another is to combine supportive funding with patient and clinician education and public reporting that emphasizes a "complete" ART cycle (all embryo transfers associated with an egg retrieval) and penalizes multiple embryo transfers. Improving funding for fertility services in a way that respects clinician and patient autonomy and allows patients to undertake a sufficient number of cycles to minimize moral hazard improves outcomes for mothers and babies while reducing the long-term economic burden associated with fertility treatments.

Early sacral neuromodulation ameliorates urinary bladder function and structure in complete spinal cord injury minipigs.

AIMS: To determine the effects of early sacral neuromodulation (SNM) and pudendal neuromodulation (PNM) on lower urinary tract (LUT) function, minipigs with complete spinal cord injury (cSCI) were analyzed. SNM and PNM have been proposed as therapeutic approaches to improve bladder function, for example after cSCI. However, further evidence on efficacy is required before these methods can become clinical practice. METHODS: Eleven adults, female Göttingen minipigs with cSCI at vertebral level T11-T12 were included: SNM (n = 4), PNM (n = 4), and SCI control (SCIC: n = 3). Tissue from six healthy minipigs was used for structural comparisons. Stimulation was started 1 week after cSCI. Awake urodynamics was performed on a weekly basis. After 16 weeks follow-up, samples from the urinary bladder were taken for analyses. RESULTS: SNM improved bladder function with better capacities and lower detrusor pressures at voiding and avoided the emergence of detrusor sphincter dyssynergia (DSD). PNM and untreated SCI minipigs had less favorable outcomes with either DSD or constant urinary retention. Structural results revealed SCI-typical fibrotic alterations in all cSCI minipigs. However, SNM showed a better-balanced distribution of smooth muscle to connective tissue with a trend towards the reduced progression of bladder wall scarring. CONCLUSION: Early SNM led to an avoidance of the emergence of DSD showing a more physiological bladder function during a 4 month follow-up period after cSCI. This study might pave the way for the clinical continuation of early SNM for the treatment of neurogenic LUT dysfunction after SCI.

The impact of a sugar-sweetened beverages tax on oral health and costs of dental care in Australia.

Background: Despite a clear causal link between frequent consumption of sugar-sweetened beverages (SSBs) and dental disease, little is known about the implications of a tax on SSBs in the context of oral health. The aim of our study was to estimate the impacts of a SSB tax on the Australian population in the context of oral health outcomes, dental care utilisation and associated costs. Methods: We designed a cohort model that accounted for the consequences of the tax through the mechanisms of consumer response to price increase, the effect on oral health due to change in sugar intake, and the implications for dental care use. Results: Our results indicate that in the adult population an ad valorem tax of 20% would lead to a reduction in decayed, missing and filled teeth (DMFT) by 3.9 million units over 10 years, resulting in cost savings of A$666 million. Scenario analyses show that the outcomes are sensitive to the choice of the time horizon, tax rate, price elasticity of demand for SSBs, and the definition of target population. Conclusion: We found that the total and per-person consequences of SSB tax were considerable, both in terms of dental caries (tooth decay) averted and dental care avoided. These results have to be compounded with the implications of SSB tax for other aspects of health and health care, especially in the context of chronic diseases. On the other hand, the improved outcomes have to be weighted against a welfare loss associated with introducing a tax.

Incarcerated inguinal hernia in the presence of Fournier's gangrene: a novel approach to a complex problem.

Fournier's gangrene is an aggressive, polymicrobial soft tissue infection that specifically affects the genital and perineal region. Treatment requires early recognition, broad-spectrum intravenous antibiotics, and radical surgical debridement of all infected tissues. Optimal therapy may necessitate multiple debridements that leave the patient with large tissue defects that require skin grafting for scrotal and perineal reconstruction. The presence of other surgical emergencies, such as an incarcerated inguinal hernia, in the face of Fournier's gangrene presents a rare and challenging dilemma to the general surgeon. With the widespread acceptance of tension-free repair utilizing prosthetic mesh in uncomplicated hernia surgery, outcomes have been improved. However, surgical options for hernia repair may become limited in the face of a regional necrotizing soft tissue infection, for which mesh use in an open repair after debridement of infected tissues is generally contraindicated. In this report, the authors describe three consecutive cases of incarcerated inguinal hernia in the presence of concomitant Fournier's gangrene using a laparoscopic approach and natural biomaterial mesh for abdominal wall reinforcement.