Hysterosalpingo-foam sonography versus hysterosalpingography during fertility work-up: an economic evaluation alongside a randomized controlled trial.

STUDY QUESTION: What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER: During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference -1.2%, 95% CI: -3.4% to 1.5%; P = 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1160 infertile women (18-41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies-management based on HyfoSy results versus HSG results-the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference -1.2%; 95% CI: -3.4% to 1.5%). For the procedures itself, HyFoSy cost €136 and HSG €280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were €3307 for the HyFoSy strategy and €3427 for the HSG strategy (mean difference €-119; 95% CI: €-125 to €-114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was €10 042, meaning that by using HyFoSy instead of HSG we would save €10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION: When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS: Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S): FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting-and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

Oocyte cryopreservation versus ovarian tissue cryopreservation for adult female oncofertility patients: a cost-effectiveness study.

PURPOSE: In December 2019, the American Society for Reproductive Medicine designated ovarian tissue cryopreservation (OTC) as no longer experimental and an alternative to oocyte cryopreservation (OC) for women receiving gonadotoxic therapy. Anticipating increased use of OTC, we compare the cost-effectiveness of OC versus OTC for fertility preservation in oncofertility patients. METHODS: A cost-effectiveness model to compare OC versus OTC was built from a payer perspective. Costs and probabilities were derived from the literature. The primary outcome for effectiveness was the percentage of patients who achieved live birth. Strategies were compared using incremental cost-effectiveness ratios (ICER). All inputs were varied widely in sensitivity analyses. RESULTS: In the base case, the estimated cost for OC was $16,588 and for OTC $10,032, with 1.56% achieving live birth after OC, and 1.0% after OTC. OC was more costly but more effective than OTC, with an ICER of $1,163,954 per live birth. In sensitivity analyses, OC was less expensive than OTC if utilization was greater than 63%, cost of OC prior to chemotherapy was less than $8100, cost of laparoscopy was greater than $13,700, or standardized discounted costs were used. CONCLUSIONS: With current published prices and utilization, OC is more costly but more effective than OTC. OC becomes cost-saving with increased utilization, when cost of OC prior to chemotherapy is markedly low, cost of laparoscopy is high, or standardized discounted oncofertility pricing is assumed. We identify the critical thresholds of OC and OTC that should be met to deliver more cost-effective care for oncofertility patients.

Pregnancy outcome and cost-effectiveness comparisons of artificial cycle-prepared frozen embryo transfer with or without GnRH agonist pretreatment for polycystic ovary syndrome: a randomised controlled trial.

OBJECTIVE: To compare the live birth rate and cost effectiveness of artificial cycle-prepared frozen embryo transfer (AC-FET) with or without GnRH agonist (GnRH-a) pretreatment for women with polycystic ovary syndrome (PCOS). DESIGN: Open-label, randomised, controlled trial. SETTING: Reproductive centre of a university-affiliated hospital. SAMPLE: A total of 343 women with PCOS, aged 24-40 years, scheduled for AC-FET and receiving no more than two blastocysts. METHODS: The pretreatment group (n = 172) received GnRH-a pretreatment and the control group (n = 171) did not. Analysis followed the intention-to-treat (ITT) principle. MAIN OUTCOME MEASURES: The primary outcome measure was live birth rate. Secondary outcome measures included clinical pregnancy rate, implantation rate, early pregnancy loss rate and direct treatment costs per FET cycle. RESULTS: Among the 343 women randomised, 330 (96.2%) underwent embryo transfer and 328 (95.6%) completed the protocols. Live birth rate according to ITT did not differ between the pretreatment and control groups [85/172 (49.4%) versus 92/171 (53.8%), absolute rate difference -4.4%, 95% CI -10.8% to 2.0% (P = 0.45). Implantation rate, clinical pregnancy rate and early pregnancy loss rate also did not differ between groups, but median direct cost per FET cycle was significantly higher in the pretreatment group (7799.2 versus 4438.9 RMB, OR = 1.9, 95%CI 1.2-3.4, P < 0.001). Median direct cost per live birth was also significantly higher in the pretreatment group (15663.1 versus 8189.9 RMB, odds ratio [OR] = 1.9, 95% CI 1.2-3.8, P < 0.001). CONCLUSIONS: Pretreatment with GnRH-a does not improve pregnancy outcomes for women with PCOS receiving AC-FET, but significantly increases patient cost. TWEETABLE ABSTRACT: For women with PCOS, artificial cycle-prepared FET with GnRH agonist pretreatment provides no pregnancy outcome benefit but incurs higher cost.

Cumulative Live Birth Rate and Cost-Effectiveness Analysis of Gonadotropin Releasing Hormone-Antagonist Protocol and Multiple Minimal Ovarian Stimulation in Poor Responders.

Background: The overall cumulative live birth rate (CLBR) of poor ovarian responders (POR) is extremely low. Minimal ovarian stimulation (MOS) provides a relatively realistic solution for ovarian stimulation in POR. Our study aimed to investigate whether multiple MOS strategies resulted in higher CLBR compared to conventional gonadotropin releasing hormone (GnRH) antagonists in POR. Methods: This retrospective study included 699 patients (1,058 cycles) from one center, who fulfilled the Bologna criteria between 2010 and 2018. Overall, 325 women (325 cycles) were treated with one-time conventional GnRH antagonist ovarian stimulation (GnRH-antagonist). Another 374 patients (733 cycles) were treated with multiple MOS including natural cycles. CLBR and time-and-cost-benefit analyses were compared between these two groups of women. Results: GnRH antagonists provided more retrieved oocytes, meiosis II oocytes, fertilized oocytes, and more viable embryos compared to both the first MOS (p < 0.001) and the cumulative corresponding numbers in multiple MOSs (p < 0.001). For the first in vitro fertilization (IVF) cycle, GnRH antagonists resulted in higher CLBR than MOS [12.92 versus 4.54%, adjusted OR (odds ratio) 2.606; 95% CI (confidence interval) 1.386, 4.899, p = 0.003]. The one-time GnRH-antagonist induced comparable CLBR (12.92 versus 7.92%, adjusted OR 1.702; 95% CI 0.971, 2.982, p = 0.063), but a shorter time to live birth [9 (8, 10.75) months versus 11 (9, 14) months, p = 0.014] and similar financial expenditure compared to repeated MOS [20,838 (17,953, 23,422) ¥ versus 21,261.5 (15,892.5, 35,140.25) ¥, p = 0.13]. Conclusion: Both minimal ovarian stimulation (MOS) and GnRH-antagonists provide low chances of live birth in poor responders. The GnRH antagonist protocol is considered a suitable choice for PORs with comparable CLBR, shorter times to live birth, and similar financial expenditure compared to repeated MOS.

Disparities in accessing infertility care in the United States: results from the National Health and Nutrition Examination Survey, 2013-16.

OBJECTIVE: To investigate infertility rates and access to infertility care among women in the United States. DESIGN: Retrospective cross-sectional. SETTING: Not applicable. PATIENT(S): Women between 20 and 44 years-old who participated in the National Health and Nutrition Examination Survey between 2013 and 2016 and answered questions RHQ074 ("have you ever attempted to become pregnant over a period of at least a year without becoming pregnant?") and RHQ076 ("have you ever been to a doctor or other medical provider because you were unable to become pregnant?"). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of infertility and accessing infertility care. RESULT(S): Women reported infertility at a rate of 12.5% (95% confidence interval, 10.8-14.4). Higher infertility rates were noted with increasing age and body mass index. There were no differences in infertility rates by race/ethnicity, education, income, U.S. citizenship, insurance, or primary location of health care. However, women with less than a high school diploma accessed infertility care less than women with a college degree (5.0% vs. 11.6%). Women with incomes less than $25,000 sought infertility care less than those with incomes above $100,000 (5.4% vs. 11.6%). Non-U.S. citizens accessed infertility care less than U.S. citizens (6.9% vs. 9.4%), and uninsured women reported fewer visits for infertility than insured women (5.9% vs. 9.9%). Women who used the emergency department as their primary medical location reported accessing infertility care less than those who relied on a hospital outpatient unit (1.4% vs. 14.9%). CONCLUSION(S): These nationally representative findings highlight the need to address disparities in access to infertility care.

Decision analysis about the cost-effectiveness of different in vitro fertilization-embryo transfer protocol under considering governments, hospitals, and patient.

OBJECTIVE: The aim of this study was to explore the benefits of in vitro fertilization (IVF) for patients and hospitals under different protocols and if IVF treatment should be incorporated into health care. PERSPECTIVE: The government should consider including IVF treatment in health insurance. Hospitals and patients could obtain the best benefit by following the hospital's recommended protocol. SETTING: This retrospective study was conducted from January 2014 to August 2017 at an academic hospital. METHODS: A total of 7440 patients used gonadotropin-releasing hormone agonists (GnRHa) protocol, 2619 patients used, gonadotropin-releasing hormone antagonists (GnRHant) protocol, and 1514 patients used GnRHa ultra-long protocol. Primary outcomes were live birth rate (LBR), cost-effectiveness, hospital revenue, and government investment. RESULTS: The cycle times for the GnRHa protocol and the GnRHa ultra-long protocol were significantly higher than the GnRHant protocol. Patients who were ≤29 years chose the GnRHant protocol. The cost of a successful cycle was 67,579.39 ±â€Š9,917.55 ¥ and LBR was 29.25%. Patients who were >30 years had the GnRHa protocol as the dominant strategy, as it was more effective at lower costs and higher LBR. When patients were >30 to ≤34 years, the cost of a successful cycle was 66,556.7 ±â€Š8,448.08 ¥ and the LBR was 31.05%. When patients were >35 years, the cost of a successful cycle was 83,297.92 ±â€Š10,918.05 ¥ and the LBR was 25.07%. The government reimbursement for a cycle ranged between 11,372.12 ±â€Š2,147.71 ¥ and 12,753.67 ±â€Š1,905.02 ¥. CONCLUSIONS: The government should consider including IVF treatment in health insurance. Hospitals recommend the GnRHant protocol for patients <29 years old and the GnRHa protocol for patients >30 years old, to obtain the best benefits. Patients could obtain the best benefit by using the protocol recommended by the hospital.

Septate uterus according to ESHRE/ESGE, ASRM and CUME definitions: association with infertility and miscarriage, cost and warnings for women and healthcare systems.

OBJECTIVES: To estimate the differences in frequency of diagnosis of septate uterus using three different definitions and determine whether these differences are significant in clinical practice, and to examine the association between diagnosis of septate uterus, using each of the three definitions, and infertility and/or previous miscarriage as well as the cost of allocation to surgery. METHODS: This was a secondary analysis of data from a prospective study of 261 consecutive women of reproductive age attending a private clinic focused on the diagnosis and treatment of congenital uterine malformations. Reanalysis of the datasets was performed according to three different means of defining septate uterus: following the recommendations of the American Society for Reproductive Medicine (ASRM), a 2016 update of those of the American Fertility Society from 1988 (ASRM-2016: internal fundal indentation depth ≥ 1.5 cm, angle of internal indentation < 90° and external indentation depth < 1 cm); following the recommendations of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE/ESGE), published in 2013 and reaffirmed in 2016 (ESHRE/ESGE-2016: internal fundal/uterine indentation depth > 50% of uterine-wall thickness and external indentation depth < 50% of uterine-wall thickness, with uterine-wall thickness measured above interostial/intercornual line); and using a definition published last year which was based on the decision made most often by a group of experts (Congenital Uterine Malformation by Experts; CUME) (CUME-2018: internal fundal indentation depth ≥ 1 cm and external fundal indentation depth < 1 cm). We compared the rate of diagnosis of septate uterus using each of these three definitions and, for each, we estimated the association between the diagnosis and infertility and/or previous miscarriage, and anticipated the costs associated with their implementation using a guesstimation method. RESULTS: Although 32.6% (85/261) of the subjects met the criteria for one of the three definitions of septate uterus, only 2.7% (7/261) of them were defined as having septate uterus according to all three definitions. We diagnosed significantly more cases of septate uterus using ESHRE/ESGE-2016 than using ASRM-2016 (31% vs 5%, relative risk (RR) = 6.7, P < 0.0001) or CUME-2018 (31% vs 12%, RR = 2.6, P < 0.0001) criteria. We also observed frequent cases that could not be classified definitively by ASRM-2016 (gray zone: neither normal/arcuate nor septate; 6.5%). There were no significant differences (P > 0.05) in the prevalence of septate uterus in women with vs those without infertility according to ASRM-2016 (5% vs 4%), ESHRE/ESGE-2016 (35% vs 28%) or CUME-2018 (11% vs 12%). Septate uterus was diagnosed significantly more frequently in women with vs those without previous miscarriage according to ASRM-2016 (11% vs 3%; P = 0.04) and CUME-2018 (22 vs 10%; P = 0.04), but not according to ESHRE/ESGE-2016 (42% vs 28%; P = 0.8) criteria. Our calculations showed that global costs to the healthcare system would be highly dependent on the criteria used in the clinical setting to define septate uterus, with the costs associated with the ESHRE/ESGE-2016 definition potentially being an extra US$ 100-200 billion over 5 years in comparison to ASRM-2016 and CUME-2018 definitions. CONCLUSIONS: The prevalence of septate uterus according to ESHRE/ESGE-2016, ASRM-2016 and CUME-2018 definitions differs considerably. An important limitation of the ASRM classification, which needs to be addressed, is the high proportion of unclassifiable cases originally named, by us, the 'gray zone'. The high rate of overdiagnosis of septate uterus according to ESHRE/ESGE-2016 may lead to unnecessary surgery and therefore unnecessary risk in these women and may impose a considerable financial burden on healthcare systems. Efforts to define clinically meaningful and universally applicable criteria for the diagnosis of septate uterus should be encouraged. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Útero septo según las definiciones de ESHRE/ESGE, ASRM y CUME: la relación con la infertilidad y el aborto espontáneo, el costo y advertencias para las mujeres y los sistemas de salud OBJETIVO: Evaluar el rendimiento de la velocidad sistólica máxima de la arteria cerebral media fetal (MCA-PSV, por sus siglas en inglés) ≥1,5 múltiplos de la mediana (MdM) para la predicción de la anemia moderada-severa en fetos sometidos a transfusión y no sometidos. MÉTODOS: Se realizó una búsqueda sistemática para identificar estudios observacionales relevantes reportados en el período 2008-2018 que evaluaron el rendimiento de la MCA-PSV, utilizando un umbral de 1,5MdM para la predicción de la anemia fetal. El diagnóstico de la anemia fetal mediante la toma de muestras de sangre fue el estándar de referencia. Se utilizaron modelos de efectos aleatorios para la elaboración de una curva jerárquica resumen de las características operativas del receptor (hSROC, por sus siglas en inglés). Se realizaron análisis de subgrupos y metarregresión, según el número de transfusiones intrauterinas previas. RESULTADOS: En el metaanálisis se incluyeron doce estudios y 696 fetos. El área bajo la curva (ABC) hSROC para la anemia moderada-severa fue del 83%. La sensibilidad y especificidad agrupadas (IC 95%) fueron del 79% (70-86%) y 73% (62-82%), respectivamente, y los cocientes de verosimilitud positivos y negativos fueron 2,94 (IC 95%: 2,13-4,00) y 0,272 (IC 95%: 0,188-0,371). Cuando solo se consideraron los fetos no sometidos a transfusión, la predicción mejoró, pues se logró un ABC del 87%, una sensibilidad del 86% (IC 95%: 75-93%) y una especificidad del 71% (IC 95%: 49-87%). Se observó una disminución en la sensibilidad de la predicción de la anemia moderada-severa mediante la MCA-PSV ≥1.5MdM (estimación, -5,5% (IC 95%: -10,7 a -0,3%), P=0,039) en función del aumento del número de transfusiones previas. CONCLUSIONES: El uso de la MCA-PSV ≥1.5MdM para la predicción de la anemia moderada-severa en fetos no sometidos a transfusión muestra una precisión moderada (86% de sensibilidad y 71% de especificidad), que disminuye con el aumento del número de transfusiones intrauterinas.

Is infertility a disease and does it matter?

Claims about whether or not infertility is a disease are sometimes invoked to defend or criticize the provision of state-funded treatment for infertility. In this paper, I suggest that this strategy is problematic. By exploring infertility through key approaches to disease in the philosophy of medicine, I show that there are deep theoretical disagreements regarding what subtypes of infertility qualify as diseases. Given that infertility's disease status remains unclear, one cannot uncontroversially justify or undermine its claim to medical treatment by claiming that it is or is not a disease. Instead of focusing on disease status, a preferable strategy to approach the debate about state-funded treatment is to explicitly address the specific ethical considerations raised by infertility. I show how this alternative strategy can be supported by a recent theoretical framework in the philosophy of medicine which avoids the problems associated with the concepts of health and disease.

Health Care Access, Costs, and Treatment Dynamics: Evidence from In Vitro Fertilization.

We study public policies designed to improve access and reduce costs for in vitro fertilization (IVF). High out-of-pocket prices can deter potential patients from IVF, while active patients have an incentive to risk costly high-order pregnancies to improve their odds of treatment success. We analyze IVF's rich choice structure by estimating a dynamic model of patients' choices within and across treatments. Policy simulations show that insurance mandates for treatment or hard limits on treatment aggressiveness can improve access or costs, but not both. Insurance plus price-based incentives against risky treatment, however, can together improve patient welfare and reduce medical costs.

Oil-based or water-based contrast for hysterosalpingography in infertile women: a cost-effectiveness analysis of a randomized controlled trial.

OBJECTIVE: To determine the cost effectiveness of the use of oil-based versus water-based contrast in infertile women undergoing hysterosalpingography (HSG). DESIGN: Economic evaluation alongside a multicenter randomized trial. SETTING: Hospitals. PATIENT(S): Infertile women with an ovulatory cycle, 18-39 years of age, low risk of tubal pathology. INTERVENTION(S): Use of oil-based versus water-based contrast during HSG. MAIN OUTCOME MEASURE(S): Costs per additional ongoing pregnancy and per live birth within 6 months of randomization, incremental cost-effective ratios (ICERs). RESULT(S): A total of 1,119 women were randomized to HSG (oil-based contrast, n = 557; water-based contrast, n = 562). After HSG, most women had no additional treatment; a minority had IUI or IVF. In the oil group, 39.7% women had an ongoing pregnancy within 6 months of randomization versus 29.1% women in the water group. There was a 10.7% increase in the live birth rate in the oil group. For ongoing pregnancy, the mean costs per couple were US$2,014 in the oil group and US$1,144 in the water group, with a corresponding ICER of US$8,198 per additional ongoing pregnancy. For live birth, the mean costs per couple were US$11,532 in the oil group and US$8,310 in the water group, with a corresponding ICER of US$30,112 per additional live birth. CONCLUSION(S): Hysterosalpingography with oil-based contrast results in higher 6-month ongoing pregnancy and live birth rate. If society is willing to pay US$8,198 for an additional ongoing pregnancy, HSG with oil-based contrast is a cost-effective strategy compared with HSG with water-based contrast for infertile, ovulatory women at low risk for tubal pathology. CLINICAL TRIAL REGISTRATION NUMBER: Dutch Trial Register, NTR 6577 (www.trialregister.nl).

Intracytoplasmic sperm injection use in states with and without insurance coverage mandates for infertility treatment, United States, 2000-2015.

OBJECTIVE: To compare indications and trends in intracytoplasmic sperm injection (ICSI) use for in vitro fertilization (IVF) cycles among residents of states with and without insurance mandates for IVF coverage. DESIGN: Cross-sectional analysis of the National Assisted Reproductive Technology Surveillance System from 2011 to 2015 for the main outcome and from 2000 to 2015 for trends. SETTING: IVF cycles performed in U.S. fertility clinics. PATIENT(S): Fresh IVF cycles. INTERVENTION(S): Residency in a state with an insurance mandate for IVF (n = 8 states) versus no mandate (n = 43 states, including DC). MAIN OUTCOME MEASURE(S): ICSI use by insurance coverage mandate status stratified by male-factor infertility diagnosis. RESULT(S): During 2000-2015, there were 1,356,377 fresh IVF cycles, of which 25.8% (n = 350,344) were performed for residents of states with an insurance coverage mandate for IVF. ICSI use increased significantly during 2000-2015 in states both with and without a mandate; however, for non-male-factor infertility cycles, the percentage increase in ICSI use was greater among nonmandate states (34.6% in 2000 to 73.9% in 2015) versus mandate states (39.5% in 2000 to 63.5% in 2015). For male-factor infertility cycles, this percentage increase was ∼7.3% regardless of residency in a state with an insurance mandate for IVF. From 2011 to 2015, ICSI use was lower in mandate versus nonmandate states, both for cycles with (91.5% vs. 94.5%), and without (60.3% vs. 70.9%) male-factor infertility. CONCLUSION(S): Mandates for IVF coverage were associated with lower ICSI use for non-male-factor infertility cycles.

Cost-effectiveness analysis of lifestyle intervention in obese infertile women.

STUDY QUESTION: What is the cost-effectiveness of lifestyle intervention preceding infertility treatment in obese infertile women? SUMMARY ANSWER: Lifestyle intervention preceding infertility treatment as compared to prompt infertility treatment in obese infertile women is not a cost-effective strategy in terms of healthy live birth rate within 24 months after randomization, but is more likely to be cost-effective using a longer follow-up period and live birth rate as endpoint. WHAT IS KNOWN ALREADY: In infertile couples, obesity decreases conception chances. We previously showed that lifestyle intervention prior to infertility treatment in obese infertile women did not increase the healthy singleton vaginal live birth rate at term, but increased natural conceptions, especially in anovulatory women. Cost-effectiveness analyses could provide relevant additional information to guide decisions regarding offering a lifestyle intervention to obese infertile women. STUDY DESIGN, SIZE, DURATION: The cost-effectiveness of lifestyle intervention preceding infertility treatment compared to prompt infertility treatment was evaluated based on data of a previous RCT, the LIFEstyle study. The primary outcome for effectiveness was the vaginal birth of a healthy singleton at term within 24 months after randomization (the healthy live birth rate). The economic evaluation was performed from a hospital perspective and included direct medical costs of the lifestyle intervention, infertility treatments, medication and pregnancy in the intervention and control group. In addition, we performed exploratory cost-effectiveness analyses of scenarios with additional effectiveness outcomes (overall live birth within 24 months and overall live birth conceived within 24 months) and of subgroups, i.e. of ovulatory and anovulatory women, women <36 years and ≥36 years of age and of completers of the lifestyle intervention. Bootstrap analyses were performed to assess the uncertainty surrounding cost-effectiveness. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Infertile women with a BMI of ≥29 kg/m2 (no upper limit) were allocated to a 6-month lifestyle intervention programme preceding infertility treatment (intervention group, n = 290) or to prompt infertility treatment (control group, n = 287). After excluding women who withdrew informed consent or who were lost to follow-up we included 280 women in the intervention group and 284 women in the control group in the analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Total mean costs per woman in the intervention group within 24 months after randomization were €4324 (SD €4276) versus €5603 (SD €4632) in the control group (cost difference of -€1278, P < 0.05). Healthy live birth rates were 27 and 35% in the intervention group and the control group, respectively (effect difference of -8.1%, P < 0.05), resulting in an incremental cost-effectiveness ratio of €15 845 per additional percentage increase of the healthy live birth rate. Mean costs per healthy live birth event were €15 932 in the intervention group and €15 912 in the control group. Exploratory scenario analyses showed that after changing the effectiveness outcome to all live births conceived within 24 months, irrespective of delivery within or after 24 months, cost-effectiveness of the lifestyle intervention improved. Using this effectiveness outcome, the probability that lifestyle intervention preceding infertility treatment was cost-effective in anovulatory women was 40%, in completers of the lifestyle intervention 39%, and in women ≥36 years 29%. LIMITATIONS, REASONS FOR CAUTION: In contrast to the study protocol, we were not able to perform the analysis from a societal perspective. Besides the primary outcome of the LIFEstyle study, we performed exploratory analyses using outcomes observed at longer follow-up times and we evaluated subgroups of women; the trial was not powered on these additional outcomes or subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS: Cost-effectiveness of a lifestyle intervention is more likely for longer follow-up times, and with live births conceived within 24 months as the effectiveness outcome. This effect was most profound in anovulatory women, in completers of the lifestyle intervention and in women ≥36 years old. This result indicates that the follow-up period of lifestyle interventions in obese infertile women is important. The scenario analyses performed in this study suggest that offering and reimbursing lifestyle intervention programmes in certain patient categories may be cost-effective and it provides directions for future research in this field. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The department of obstetrics and gynaecology of the UMCG received an unrestricted educational grant from Ferring pharmaceuticals BV, The Netherlands. B.W.J.M. is a consultant for ObsEva, Geneva. TRIAL REGISTRATION NUMBER: The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530). http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 1530.

Assessing reproductive choices of women and the likelihood of oocyte cryopreservation in the era of elective oocyte freezing.

OBJECTIVE: To assess reproductive choices of reproductive-age women in the United States and factors that influence consideration of elective egg freezing (EF). DESIGN: Cross-sectional internet-based survey. SETTING: Not applicable. PATIENTS: One thousand women aged 21-45 years. INTERVENTION(S): An anonymous 63-item self-administered questionnaire was distributed to a representative cross-section of women aged 21-45 years, stratified by age <35 years. One-half of the sample had at least one child, and the other one-half did not. All of the participants were interested in having children. MAIN OUTCOME MEASURE(S): Ordinal logistic regression was performed to characterize the association of population characteristics and reproductive knowledge with likelihood to consider EF. Willingness to pay was assessed with the use of a linear prediction model that calculated dollar amounts at varying success rates. RESULT(S): Overall, 87.2% of the sample reported awareness of EF for fertility preservation and 25% would consider this option, yet only 29.8% knew what the EF process entails. Once informed of the process, 30% of women changed their level of consideration. In a multivariable model, Asian race, single status, and infertility increased the likelihood of considering EF. Women likely to consider egg freezing would be willing to pay $3,811.55 (95% confidence interval $2,862.66-$4,760.44). If the total cost were $10,000, 91% of the cohort would accept at minimum a 50% chance of successful delivery. CONCLUSION(S): This study is one of the largest cohorts of reproductive-age women in the United States addressing reproductive choices and factors associated with the importance of having a biologically related child and the likelihood of considering EF to preserve fertility. This study provides important insight into the willingness to pay for this elective endeavor.

Chlamydia sequelae cost estimates used in current economic evaluations: does one-size-fit-all?

BACKGROUND: Current evidence suggests that chlamydia screening programmes can be cost-effective, conditional on assumptions within mathematical models. We explored differences in cost estimates used in published economic evaluations of chlamydia screening from seven countries (four papers each from UK and the Netherlands, two each from Sweden and Australia, and one each from Ireland, Canada and Denmark). METHODS: From these studies, we extracted management cost estimates for seven major chlamydia sequelae. In order to compare the influence of different sequelae considered in each paper and their corresponding management costs on the total cost per case of untreated chlamydia, we applied reported unit sequelae management costs considered in each paper to a set of untreated infection to sequela progression probabilities. All costs were adjusted to 2013/2014 Great British Pound (GBP) values. RESULTS: Sequelae management costs ranged from £171 to £3635 (pelvic inflammatory disease); £953 to £3615 (ectopic pregnancy); £546 to £6752 (tubal factor infertility); £159 to £3341 (chronic pelvic pain); £22 to £1008 (epididymitis); £11 to £1459 (neonatal conjunctivitis) and £433 to £3992 (neonatal pneumonia). Total cost of sequelae per case of untreated chlamydia ranged from £37 to £412. CONCLUSIONS: There was substantial variation in cost per case of chlamydia sequelae used in published chlamydia screening economic evaluations, which likely arose from different assumptions about disease management pathways and the country perspectives taken. In light of this, when interpreting these studies, the reader should be satisfied that the cost estimates used sufficiently reflect the perspective taken and current disease management for their respective context.

Cost-Benefit Analysis of Hysteroscopic Polypectomy Before Controlled Ovarian Hyperstimulation and Intrauterine Insemination in Infertile Women.

Objective: To examine the cost benefit of performing hysteroscopic polypectomy (HP) in infertile women with endometrial polyp(s) before controlled ovarian hyperstimulation with intrauterine insemination (COH/IUI). Study Design: Decision analytic model comparing costs and clinical outcomes. Results: HP and COH/IUI costs ranged from $537­$12,530 and $800­$7,600, respectively. Performing an HP before COH/IUI lowered fertility cost by $7,652 per clinical pregnancy. When COH/IUI costs remained constant, HP was most cost beneficial when the cost of HP was below a threshold value of $9,452. When HP costs remained constant, the threshold value at which HP was no longer cost beneficial was at COH/IUI costs below $704. The cost benefit was greatest when an office-based HP is performed. Conclusion: HP before COH/IUI is more cost beneficial than fertility treatment alone, particularly when office-based hysteroscopy is performed.

There is a Positive Correlation Between Socioeconomic Status and Ovarian Reserve in Women of Reproductive Age.

BACKGROUND The purpose of this study was to investigate the potential association between socioeconomic status and ovarian reserve, anti-Mullerian hormone level, antral follicle count, and follicle stimulating hormone level in women of reproductive age. MATERIAL AND METHODS A total of 101 married women between 20-35 years of age who presented to the Department of Obstetrics and Gynecology, Health Research System In Vitro Fertilization (HRS IVF) Center between October 2014 and November 2015 and met the inclusion criteria were included in this study. The participants were divided into three socioeconomic groups using Kuppuswamy's socioeconomic status scale. Thirty-one participants were assigned to the low socioeconomic status group, 37 to the middle socioeconomic status group, and 33 to the high socioeconomic status group. On days 3-6 of the menstrual cycle, 10 mL of blood was collected from the participants for follicle stimulating hormone and anti-Mullerian hormone measurements. Transvaginal ultrasonography was performed for both ovaries for the purpose of counting antral follicles measuring 2-10 mm in diameter. RESULTS Both ovarian reserve parameters, namely anti-Mullerian hormone level and antral follicle count, exhibited a significant association with socioeconomic status (p=0.000 and p=0.000, respectively). The association between follicle stimulating hormone level and socioeconomic status was also significant (p=0.000). CONCLUSIONS A low socioeconomic status aggravated by sources of stress such as undernutrition and financial hardships affects ovarian reserve, which should be remembered in approaching infertile patients.

Racial and ethnic disparities in assisted reproductive technology access and outcomes.

Infertility is a global problem affecting all ethnic, racial, and religious groups. Nevertheless, only a minority of the U.S. population has access to treatment. Additionally, for those who do engage in treatment, outcomes are disparate among various ethnic and racial groups. This article addresses racial and ethnic disparities regarding rates of fecundity and infertility, access to care, and assisted reproductive technology outcomes.

Inequity between male and female coverage in state infertility laws.

OBJECTIVE: To analyze state insurance laws mandating coverage for male factor infertility and identify possible inequities between male and female coverage in state insurance laws. DESIGN: We identified states with laws or codes related to infertility insurance coverage using the National Conference of States Legislatures' and the National Infertility Association's websites. We performed a primary, systematic analysis of the laws or codes to specifically identify coverage for male factor infertility services. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The presence or absence of language in state insurance laws mandating coverage for male factor infertility care. RESULT(S): There are 15 states with laws mandating insurance coverage for female factor infertility. Only eight of those states (California, Connecticut, Massachusetts, Montana, New Jersey, New York, Ohio, and West Virginia) have mandates for male factor infertility evaluation or treatment. Insurance coverage for male factor infertility is most specific in Massachusetts, New Jersey, and New York, yet significant differences exist in the male factor policies in all eight states. Three states (Massachusetts, New Jersey, and New York) exempt coverage for vasectomy reversal. CONCLUSION(S): Despite national recommendations that male and female partners begin infertility evaluations together, only 8 of 15 states with laws mandating infertility coverage include coverage for the male partner. Excluding men from infertility coverage places an undue burden on female partners and risks missing opportunities to diagnose serious male health conditions, correct reversible causes of infertility, and provide cost-effective treatments that can downgrade the intensity of intervention required to achieve a pregnancy.