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Objective: To identify any correlations between evidence levels, adoption rates, and additional costs of in vitro fertilization (IVF) add-ons., Design: Online survey., Subjects: The survey was conducted in 621 assisted reproductive technology-registered facilities that are members of the Japanese Society of Obstetrics and Gynecology from December 22, 2021, to February 13, 2022., Exposure: The survey included details regarding the specific add-on modalities employed and their associated costs; inquiries pertained to the fertility healthcare infrastructure in Japan before the implementation of the National Health Insurance scheme., Main Outcome Measures: The correlation between the adoption rate and cost of IVF add-ons and their evidence levels were analyzed. The evidence level of the add-on treatments was classified into Green, Amber, and Red categories based on the United Kingdom's Human Fertilisation and Embryology Authority and Cochrane systematic reviews., Results: A total of 438 eligible responses were analyzed, with clinics constituting 70.9% of the respondents' facilities. A total of 18 add-ons were assessed, and 96.5% (423/438) of facilities used at least one add-on. A positive correlation of the adoption rate and an inverse correlation of the cost with the evidence level of the IVF add-on treatment were observed (not significant). Outpatient clinics, defined as medical facilities with no beds, had a significantly higher adoption rate (Amber, 65.7%; Red, 52.0%) of add-ons than other facilities, regardless of the evidence rating, although the costs were similar across all site attributes., Conclusion: Accumulating evidence on the efficacy and safety of add-ons will lead to the development of medical care with a high-cost benefit, as an increase in the adoption rate and a decrease in cost are expected when limiting to medical care with a high level of evidence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shionoya, Yamada, Harada, Shirasawa, Jwa, Kuroda, Harada and Osuga.)

Study Question: How are ART and IUI regulated, funded, and registered in European countries, and how has the situation changed since 2018?, Summary Answer: Of the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding varies across and sometimes within countries (and is lacking or minimal in four countries), and national registries are in place in 33 countries; only a small number of changes were identified, most of them in the direction of improving accessibility, through increased public financial support and/or opening access to additional subgroups., What Is Known Already: The annual reports of the European IVF-Monitoring Consortium (EIM) clearly show the existence of different approaches across Europe regarding accessibility to and efficacy of ART and IUI treatments. In a previous survey, some coherent information was gathered about how those techniques were regulated, funded, and registered in European countries, showing that diversity is the paradigm in this medical field., Study Design, Size, Duration: A survey was designed using the SurveyMonkey tool consisting of 90 questions covering several domains (legal, funding, and registry) and considering specific details on the situation of third-party donations. New questions widened the scope of the previous survey. Answers refer to the situation of countries on 31 December 2022., Participants/materials, Settings, Methods: All members of the EIM were invited to participate. The received answers were checked and initial responders were asked to address unclear answers and to provide any additional information considered relevant. Tables resulting from the consolidated data were then sent to members of the Committee of National Representatives of ESHRE, requesting a second check. Conflicting information was clarified by direct contact., Main Results and the Role of Chance: Information was received from 43 out of the 45 European countries where ART and IUI are performed. There were 39 countries with specific legislation on ART, and artificial insemination was considered an ART technique in 33 of them. Accessibility is limited to infertile couples only in 8 of the 43 countries. In 5 countries, ART and IUI are permitted also for treatments of single women and all same sex couples, while a total of 33 offer treatment to single women and 19 offer treatment to female couples. Use of donated sperm is allowed in all except 2 countries, oocyte donation is allowed in 38, simultaneous donation of sperm and oocyte is allowed in 32, and embryo donation is allowed in 29 countries. Preimplantation genetic testing (PGT)-M/SR (for monogenetic disorders, structural rearrangements) is not allowed in 3 countries and PGT-A (for aneuploidy) is not allowed in 10; surrogacy is accepted in 15 countries. Except for marital/sexual situation, female age is the most frequently reported limiting criterion for legal access to ART: minimal age is usually set at 18 years and the maximum ranges from 42 to 54 with some countries not using numeric definition. Male maximum age is set in very few countries. Where third-party donors are permitted, age is frequently a limiting criterion (male maximum age ranging from 35 to 50; female maximum age from 30 to 37). Other legal restrictions in third-party donation are the number of children born from the same donor (or, in some countries, the number of families with children from the same donor) and, in 12 countries, there is a maximum number of oocyte donations. How countries deal with the anonymity is diverse: strict anonymity, anonymity just for the recipients (not for children when reaching legal adulthood age), a mixed system (anonymous and non-anonymous donations), and strict non-anonymity. Inquiring about donors' genetic screening showed that most countries have enforced either mandatory or scientific recommendations that exclude the most prevalent genetic diseases, although, again, diversity is evident. Reimbursement/compensation systems exist in more than 30 European countries, with around 10 describing clearly defined maximum amounts considered acceptable. Public funding systems are extremely variable. One country provides no financial assistance to ART/IUI patients and three offer only minimal support. Limits to the provision of funding are defined in the others i.e. age (female maximum age is the most used), existence of previous children, BMI, maximum number of treatments publicly supported, and techniques not entitled for funding. In a few countries reimbursement is linked to a clinical policy. The definitions of the type of expenses covered within an IVF/ICSI cycle, up to which limit, and the proportion of out-of-pocket costs for patients are also extremely dissimilar. National registries of ART are in place in 33 out of the 43 countries contributing to the survey and a registry of donors exists in 19 of them. When comparing with the results of the previous survey, the main changes are: (i) an extension of the beneficiaries of ART techniques (and IUI), evident in nine countries; (ii) public financial support exists now in Albania and Armenia; (iii) in Luxembourg, the only ART centre expanded its on-site activities; (iv) donor-conceived children are entitled to know the donor identity in six countries more than in 2018; and (v) four more countries have set a maximum number of oocyte donations., Limitations, Reasons for Caution: Although the responses were provided by well-informed and committed individuals and submitted to double checking, no formal validation by official bodies was in place. Therefore, possible inaccuracies cannot be excluded. The results presented are a cross-section in time, and ART and IUI frameworks within European countries undergo continuous modification. Finally, some domains of ART activity were deliberately left out of the scope of this survey., Wider Implications of the Findings: Our results offer a detailed updated view of the ART and IUI situation in European countries. It provides extensive answers to many relevant questions related to ART usage at the national level and could be used by institutions and policymakers at both national and European levels., Study Funding/competing Interest(s): The study has no external funding, and all costs were covered by ESHRE. There were no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: This paper uses health economics methods to discuss the cost-effectiveness value of long protocol and antagonist protocol for in vitro fertilisation and embryo transfer (ET) in the Chinese population., Design: Health economic evaluation study., Setting: The data needed to construct the model for this study were derived from published studies and other secondary sources in China., Participants: No patients participated in the study., Measures: The main outcomes were live birth rate (LBR) and cost. From the societal perspective, we considered the direct and indirect costs over the course of the treatment cycles. A cost-effectiveness was measured using the incremental cost-effectiveness ratio and the probability that a protocol has higher net monetary benefit. Sensitivity analysis was carried out to verify the reliability of the simulation results., Results: For the Chinese population, the long protocol resulted in a higher LBR than the antagonist protocol (29.33% vs 20.39%), but at the same time, it was more expensive (￥29 146.26 (US$4333.17) vs ￥23 343.70 (US$3470.51)), in the case of considering only one fresh ET cycle. It was the same when considering subsequent frozen ET (FET) cycles (51.78% vs 42.81%; ￥30 703.02 (US$4564.62) vs ￥24 740.95 (US$3678.24)). The results of most subgroups were consistent with the results of the basic analysis. However, for certain populations, the long protocol was the inferior protocol (less effective and more expensive)., Conclusion: For the Chinese population, when the monetary value per live birth was greater than ￥65 420 (US$9726) and ￥66 400 (US$9872), respectively, considering only one fresh cycle and considering subsequent frozen cycles, the long protocol is the preferred protocol. This threshold also varies for women of different ages and ovarian response capacities. For women in POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) group 2, group 3 and group 4, antagonist protocol is recommended as the preferred protocol. The results of this study need to be verified by further large-scale randomised controlled trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The decrease in assisted reproductive technology success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus on the optimal ovarian stimulation protocol for older women undergoing IVF exists. This retrospectively registered cohort study aimed to compare the cumulative live birth rate (CLBR), time to live birth (TTLB), and cost-effectiveness among women older than 35 years who were receiving either the gonadotropin-releasing hormone agonist (GnRHa) or clomiphene citrate and gonadotropin cotreatment with ovarian stimulation (CC cotreatment) protocol. To compare treatment outcomes, we performed propensity score matching (PSM) on 2871 IVF cycles in women older than 35 years who received either the GnRHa or CC cotreatment protocol, resulting in 375 cycles in each group. Additionally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Following PSM, both groups had similar baseline characteristics. The CC cotreatment protocol resulted in a greater rate of cycle cancellation (13.07% vs. 8.00%, p = 0.032), but the groups maintained comparable fertilization rates and embryo quality. Although the TTLB was longer in the CC cotreatment group, the CLBR per initial cycle (41.07% vs. 45.33%, p = 0.269) and delivery outcomes were similar between the two groups at the 24 months follow-up. Additionally, the average cost per live birth in the CC cotreatment group was 21.27% lower than in the GnRHa group (¥32,301.42 vs. ¥39,174.22). In conclusion, for women older than 35 years undergoing IVF, the CC cotreatment protocol offered a comparable CLBR to the GnRHa protocol but with reduced costs, indicating its potential as a viable and cost-effective ovarian stimulation option.Clinical trial registration: https://www.chictr.org.cn/ , identifier [ChiCTR2300076537]., (© 2024. The Author(s).)

Objective: To assess the potential costs and benefits of preimplantation genetic testing for aneuploidy (PGT-A) across age groups, considering financial costs, total euploidy rates and the potential for morphology grading to predict a euploid embryo., Methods: This study is a blinded retrospective chart review of patients who incorporated PGT-A as part of their in vitro fertilization (IVF) treatment cycle at a university-affiliated fertility clinic. Patients between 25-44 years of age undergoing IVF with intracytoplasmic sperm injection and PGT-A with autologous oocytes (n = 220) were included in this study. Number of blastocysts achieved, euploidy rates and PGT-A costs were compared between 3 age groups: <35 years, 35-37, and ≥38. Additionally, agreement on the top-quality embryo based on morphology assessment alone versus PGT-A selection was analyzed and further compared based on the number of blastocysts achieved., Results: A significant negative correlation between patient age and number of embryos produced, PGT-A costs, and euploidy rates (P < 0.001) was observed. Additionally, morphology alone ratings were able to predict the top-quality euploid embryo 78% of the time in the <35 age group, but only 32% of the time in the ≥38 age group (P < 0.05), with a trend toward even lower agreement when 3 or fewer blastocysts were produced., Conclusion: Based on our cost analysis, it may be advantageous to incorporate PGT-A when maternal age is ≥38, given the lower financial costs associated with each cycle and the low likelihood of transferring a euploid embryo on the first attempt for this age group. Nevertheless, we acknowledge that PGT-A remains a complex decision influenced by a multitude of factors., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Importance: A publicly funded fertility program was introduced in Ontario, Canada, in 2015 to increase access to fertility treatment. For in vitro fertilization (IVF), the program mandated an elective single-embryo transfer (eSET) policy. However, ovulation induction and intrauterine insemination (OI/IUI)-2 other common forms of fertility treatment-were more difficult to regulate in this manner. Furthermore, prior epidemiologic studies only assessed fetuses at birth and did not account for potential fetal reductions that may have been performed earlier in pregnancy., Objective: To examine the association between fertility treatment and the risk of multifetal pregnancy in a publicly funded fertility program, accounting for both fetal reductions and all live births and stillbirths., Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative health databases at ICES to examine all births and fetal reductions in Ontario, Canada, from April 1, 2006, to March 31, 2021., Exposure: Mode of conception: (1) unassisted conception, (2) OI/IUI, or (3) IVF., Main Outcomes and Measures: The main outcome was multifetal pregnancy (ie, a twin or higher-order pregnancy). Modified Poisson regression generated adjusted relative risks (ARRs) and derived population attributable fractions (PAFs) for multifetal pregnancies attributable to fertility treatment. Absolute rate differences (ARDs) were used to compare the era before eSET was promoted (2006-2011) with the era after the introduction of the eSET mandate (2016-2021)., Results: Of all 1 724 899 pregnancies, 1 670 825 (96.9%) were by unassisted conception (mean [SD] maternal age, 30.6 [5.2] years), 24 395 (1.4%) by OI/IUI (mean [SD] maternal age, 33.1 [4.4] years), and 29 679 (1.7%) by IVF (mean [SD] maternal age, 35.8 [4.7] years). In contrast to unassisted conception, individuals who received OI/IUI or IVF tended to be older, reside in a high-income quintile neighborhood, or have preexisting health conditions. Multifetal pregnancy rates were 1.4% (95% CI, 1.4%-1.4%) for unassisted conception, 10.5% (95% CI, 10.2%-10.9%) after OI/IUI, and 15.5% (95% CI, 15.1%-15.9%) after IVF. Compared with unassisted conception, the ARR of any multifetal pregnancy was 7.0 (95% CI, 6.7-7.3) after OI/IUI and 9.9 (95% CI, 9.6-10.3) after IVF, with corresponding PAFs of 7.1% (95% CI, 7.1%-7.2%) and 13.4% (95% CI, 13.3%-13.4%). Between the eras of 2006 to 2011 and 2016 to 2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI (ARD, -3.8%; 95% CI, -4.2% to -3.4%) and from 29.4% to 7.1% with IVF (ARD, -22.3%; 95% CI, -23.2% to -21.6%)., Conclusions and Relevance: In this cohort study of more than 1.7 million pregnancies in Ontario, Canada, a publicly funded IVF program mandating an eSET policy was associated with a reduction in multifetal pregnancy rates. Nevertheless, ongoing strategies are needed to decrease multifetal pregnancy, especially in those undergoing OI/IUI.

Oxygen (O 2 ) concentration is approximately 5% in the fallopian tube and 2% in the uterus in humans. A "back to nature" approach could increase in vitro fertilization (IVF) outcomes. This hypothesis was tested in this monocentric observational retrospective study that included 120 couples who underwent two IVF cycles between 2014 and 2019. Embryos were cultured at 5% from day 0 (D0) to D5/6 (monophasic O 2 concentration strategy) in the first IVF cycle, and at 5% O 2 from D0 to D3 and 2% O 2 from D3 to D5/6 (biphasic O 2 concentration strategy) in the second IVF cycle. The total and usable blastocyst rates (44.4% vs. 54.8%, p = 0.049 and 21.8% vs. 32.8%, p = 0.002, respectively) and the cumulative live birth rate (17.9% vs. 44.1%, p = 0.027) were significantly higher with the biphasic (5%-2%) O 2 concentration strategy. Whole transcriptome analysis of blastocysts donated for research identified 707 RNAs that were differentially expressed in function of the O 2 strategy (fold-change > 2, p value < 0.05). These genes are mainly involved in embryo development, DNA repair, embryonic stem cell pluripotency, and implantation potential. The biphasic (5-2%) O 2 concentration strategy for preimplantation embryo culture could increase the "take home baby rate", thus improving IVF cost-effectiveness and infertility management., (© 2021. The Author(s).)

The goal of an IVF cycle is the birth of at least one baby per intention to treat. However, IVF cannot confer competence on an embryo, but only can provide each couple with a safe treatment to meet a predetermined chance of success. This commentary highlights how clinical, financial and patient-centred perspectives should be included in the definition of success in IVF. The primary outcome, which is the cumulative live birth delivery rate per intention to treat, must always be complemented by analyses of risks, costs and time invested, as well as by measures of patient satisfaction. Finally, it is essential, whenever clinical conditions exist, to limit treatment discontinuation after failed attempts. Constant monitoring of the data is pivotal and must be adjusted for patient characteristics and compared with national and international registers. The authors aimed to review all these aspects and highlight the points that are still open for discussion. Is it time for a consensus?, (Copyright © 2021. Published by Elsevier Ltd.)

Background: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception., Methods: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis., Results: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate., Conclusions: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers., (© 2021. The Author(s).)

Purpose: To determine the frequency of and factors associated with a patient being declined from pursuing a cycle of in vitro fertilization with autologous oocytes (IVF-AO)., Methods: A cross-sectional study using a nationwide cohort of female respondents aged 35 or over, who visited a US fertility clinic from 1/2015 to 3/2020, responded to the online FertilityIQ questionnaire ( http://www.fertilityiq.com ). All respondents were asked if they were previously declined from pursuing a cycle of IVF-AO. Examined demographic and clinical predictors included age, race/ethnicity, education, income, clinic type, care received in a mandated state, insurance coverage for fertility treatment, and self-reported infertility diagnosis. Logistic regression was used to calculate the adjusted odds ratios for factors associated with being declined from pursuing IVF-AO., Results: Of 8660 women who met inclusion criteria, 418 (4.8%) reported previously being declined a cycle of IVF-AO. In the multivariate analysis, predictors of being declined from pursuing IVF-AO included increasing age, income of less than $50,000, and diagnoses of poor oocyte quality and diminished ovarian reserve. Predictors of being less likely to report decline included some college or college degree and diagnoses of male factor, unexplained or tubal infertility. Notably, diagnosis of PCOS or residence in a state with mandated fertility coverage was not predictive of patients being declined from pursuing IVF-AO., Conclusion: Nearly 5% of patients who pursued IVF reported being declined from pursuing IVF-AO. Further studies are needed to confirm our findings and explore whether patients being declined treatment meet the criteria for futile or very poor prognosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the use of a web-based application that assists in medication management during in vitro fertilization (IVF) treatment., Design: Multicenter randomized controlled trial., Setting: University hospitals., Patient(s): Women undergoing IVF., Intervention(s): Subjects were recruited to assess quality of life during IVF and were randomly assigned to use either the OnTrack application to assist with medication management or conventional medication management. Surveys were administered at four time points., Main Outcome Measure(s): Medication surplus, incidence of medication errors, amount of patient-initiated communication, and patient satisfaction., Result(s): A total of 153 women participated. The average number of portal messages and telephone calls was similar between groups. Twelve patients in the control group (12/69, 17.4%) and 8 patients in the case group (8/72, 11.1%) made medication errors. There were similar amounts of medication surplus in the two groups. The estimated cost of medication waste was $2,578 ± $2,056 in the control group and $2,554 ± $1,855 in the case group. Patient satisfaction was similar between the two groups., Conclusion(s): Use of a web-based application did not decrease medication errors, medication surplus, or patient-initiated messages. Many patients had a medication surplus, which can be an area of cost reduction during IVF., Clinical Trial Registration Number: Clinicaltrials.gov NCT03383848., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction : To study the impact of biosimilars in assisted reproductive treatments, we performed a review of the literature. Biosimilars are a bioequivalent chemical drug referred to the original. Their production is strongly requested in order to reduce drug cost and reduce health economic impact on national health system. In assisted reproductive treatments different gonadotropin biosimilars are being produced. Areas covered : For this reason, we performed a review of the literature on follitropin alfa Gonal-F biosimilar, Ovaleap and Bemfola, to assess their cost efficacy in national health system. Cost effective (CE) analysis and incremental cost-effectiveness ratio (ICER) were used as parameters for biosimilar impact evaluation in the national health system economy. In particular, they had only slight impact on cost reduction of recombinant follitropin alfa products in Europe. Expert opinion : considering cost-effective analysis, Gonal-F remains the first choice for national health systems. However, well-designed powered methods are strongly needed to assess biosimilars cost-effectiveness.

Objective: To determine the dropout rate between the first and second in vitro fertilization (IVF) cycles in a controlled population derived from a funded and actively managed system of care in New Zealand, including the reason for dropout and associated cumulative live birth rate., Design: Retrospective cohort., Setting: Multicenter IVF practice., Patient(s): Couples qualifying for publicly funded IVF treatment under New Zealand's Clinical Priority Assessment Criteria. Couples (n = 974) started treatment between July 2011 and June 2013, used their own gametes, and were eligible for up to 2 IVF packages of funded care (including the transfer of surplus embryos)., Intervention(s): None., Main Outcome Measure(s): IVF dropout rate, reason for dropout, and cumulative live birth rate., Result(s): A low IVF dropout rate between the first and second IVF cycle was reported within this controlled IVF population, with 10% of couples discontinuing treatment for reasons related to stress. The cumulative live birth rate in this "low dropout" population was 59% at the end of treatment, ranging from 72% (≤30 years) to 42% (38-39 years) according to female age. Most patients who discontinued for stress had a good prognosis, and a third of patients still had embryos in cryostorage. Only 30% of those who discontinued used the funded counseling services., Conclusion(s): A low dropout rate (10%) can be achieved within an actively managed IVF population. This was lower than previously reported, suggesting that prognosis, cost, and treatment management are the significant causes of dropout within the general IVF population. Couples with many embryos also require psychological support because of treatment fatigue or repeated transfers., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Object: We have previously reported that cumulative live birth rates (CLBRs) are higher in the freeze-all group compared with controls (64.3% vs. 45.8%, p = 0.001). Here, we aim to determine if the freeze-all policy is more cost-effective than fresh embryo transfer followed by frozen-thawed embryo transfer (FET)., Materials and Methods: The analysis consisted of 704 ART (Assisted reproductive technology) cycles, which included in IVF (In vitro fertilisation) and ICSI (Intra Cytoplasmic Sperm Injection) cycles performed in Taichung Veterans General Hospital, Taiwan between January 2012 and June 2014. The freeze-all group involved 84 patients and the fresh Group 625 patients. Patients were followed up until all embryos obtained from a single controlled ovarian hyper-stimulation cycle were used up, or a live birth had been achieved. The total cost related to treatment of each patient was recorded. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-all strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed., Results: The total treatment cost per patient was significantly higher for the freeze-all group than in the fresh group (USD 3419.93 ± 638.13 vs. $2920.59 ± 711.08 p < 0.001). However, the total treatment cost per live birth in the freeze-all group was US $5319.89, vs. US $6382.42 in the fresh group. CEAC show that the freeze-all policy was a cost-effective treatment at a threshold of US $2703.57 for one additional live birth. Considering the Willingness-to-pay threshold per live birth, the probability was 60.1% at the threshold of US $2896.5, with the freeze-all group being more cost-effective than the fresh-ET group; or 90.1% at the threshold of $4183.8., Conclusion: The freeze-all policy is a cost-effective treatment, as long as the additional cost of US $2703.57 per additional live birth is financially acceptable for the subjects., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To examine whether Society for Assisted Reproductive Technology (SART) member in vitro fertilization (IVF) centers adhere to the Society's new advertising policy, updated in January 2018, and evaluate other services advertised by region, insurance mandate and university affiliation status. Historically, a large percentage of IVF clinics have not adhered to SART guidelines for IVF clinic website advertising and have had variability in how financial incentives and other noncore fertility services are advertised., Design: Cross-sectional study., Setting: Not applicable., Patient(s): None., Intervention(s): None., Main Outcome Measure(s): Adherence of SART participating websites to objective criteria from the 2018 SART advertising guidelines., Result(s): All 361 SART participating clinic websites were evaluated. Approximately one third of clinics reported success rate statistics directly on their websites, but only 52.6% of those clinics reported current statistics. Similarly, only 67.5% of SART member clinics included the required disclaimer statement regarding their outcome statistics. Only 10.5% of websites were wholly compliant with SART guidelines regarding presentation of supplemental data. There were no significant differences between academic and nonacademic centers, programs in mandated versus nonmandated states, or East versus West Coast clinics in any of these areas., Conclusion(s): Many of the SART member websites failed to adhere to core guidelines surrounding reporting IVF clinic success rates. Consideration for additional education and streamlining as well as simplifying success rate advertising guidelines is recommended., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Research Question: How do costs and effects of in-vitro maturation (IVM) compare to IVF in women with a high antral follicle count (AFC)?, Design: This cost-effectiveness analysis (CEA) was based on data of a previous retrospective cohort study at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. Between July 2015 and December 2017, 608 women underwent IVM and 311 women IVF. The effectiveness measure for the CEA was cumulative live birth rate (LBR) after one completed cycle including subsequent cryo-cycles within 12 months of inclusion. Data were collected on resource use related to treatment, medication and pregnancy from the case report forms. The mean costs and effects, average cost differences and incremental cost-effectiveness ratios (ICER) were calculated using non-parametric bootstrap resampling to assess the effect of uncertainty in the estimates., Results: Cumulative LBR after one completed cycle were 239/608 (39.3%) in the IVM group versus 155/311 (49.8%) in the IVF group (adjusted odds ratio 0.52, 95% confidence interval [CI] 0.30-0.89). Ovarian hyperstimulation syndrome (OHSS) did not occur in the IVM group versus 11/311 (3.5%) in the IVF group. The mean costs per couple were €4300 (95% CI €1371-18,798) for IVM and €6493 (95% CI €2204-20,136) for IVF. The ICER per additional live birth with IVF was €20,144 (95% CI €9116-50,418). Results were robust over a wide range of assumptions., Conclusions: IVM is less expensive than IVF in women with a high AFC undergoing treatment with assisted reproductive technology, while leading to a slightly lower effectiveness in terms of cumulative LBR., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the willingness to pay (WTP) of infertile couples for in vitro fertilization (IVF) treatment., Method: This was a prospective study with an anonymous questionnaire for infertile couples in an academic setting. Clinical characteristics were analyzed by a Student's t test or Mann-Whitney test, categorical variables were compared by a chi-square or Fisher exact test, and correlations were assessed using a Spearman's test. An alpha of 5% was adopted., Results: Mean female and male ages were 31.5 and 35.9 years, respectively; 80.2% were married; 19.8% were in consensual union; 48.1% of women had college degrees; and 49.4% of men had a high school education. Most women (77.8%) and men (75.3%) were white, with a household income of class C. Average duration of union was 8.5 years, and average infertility was 4.7 years. Using a willingness-to-pay (WTP) evaluation and the technique of "direct questioning," the average value was determined to be R$18 720.18 (by payment scale R$22 831.17). WTP positively correlated with household income and each woman's education level. Previous parenthood or use of public health system negatively correlated with WTP., Conclusion: We conclude that the higher the couple's monthly income and the woman's educational level, the higher the WTP for an IVF treatment; previous parenthood determined a lower WTP for an IVF treatment, and previous use of the Brazilian Unified Health System, determined a lower WTP for an IVF treatment., (Copyright © 2020 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Research Question: How are IVF clinic websites advertising three common IVF add-ons: assisted hatching, time-lapse embryo imaging and preimplantation genetic testing for aneuploidies (PGT-A)?, Design: The Human Fertilisation and Embryology Authority 'Choose a fertility clinic' website service was used to identify IVF clinics and their websites. Assisted hatching, time-lapse embryo imaging and PGT-A were examined to determine which websites advertised them, what price they charged and what claims they made in relation to the add-ons., Results: Eighty-seven eligible clinics were identified, with 72 unique websites; 37 (43%) clinics were part of one of nine groups of IVF clinics, of sizes ranging from two to eight clinics in the UK. Time-lapse imaging (TLI) was the most frequently advertised of the three add-ons (67% of clinics), followed by PGT-A (47%) and assisted hatching (28%). Very few websites stated that the effectiveness of the add-on was in doubt or unclear (four, two and one websites for TLI, PGT-A and assisted hatching, respectively), and none raised the possibility that an add-on might have negative effects. Claims of efficacy were often based on upstream outcomes (e.g. implantation, pregnancy). Some claims that PGT-A and TLI improved live birth rates were found. There was substantial variation in pricing., Conclusions: IVF clinic websites provide valuable information for patients seeking fertility treatment so it is key that the information is accurate and complete. There is a need for transparent information on interventions, including uncertainties and risks, to be made available by IVF clinics to support well-informed treatment decisions. The selected add-ons are widely advertised, and there is wide variation in pricing., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Commercial surrogacy is a highly controversial issue that leads to heated debates in the feminist literature, especially when surrogacy takes place in developing countries and when it is performed by local women for wealthy international individuals. The objective of this article is to confront common assumptions with the narratives and experiences described by Indian surrogates themselves., Methods: This qualitative study included 33 surrogates interviewed in India (Mumbai, Chennai and New Delhi) who were at different stages of the surrogacy process. They were recruited through five clinics and agencies. This 2-year field study was conducted before the 2018 surrogacy law., Results: Surrogates met the criteria fixed by the national guidelines in terms of age and marital and family situation. The commitment to surrogacy had generally been decided with the husband. Its aim was above all to improve the socioeconomic condition of the family. Women described surrogacy as offering better conditions than their previous paid activity. They had clear views on the child and their work. However, they declared that they faced difficulties and social condemnation as surrogacy is associated with extra-marital relationships. They also described a medical process in which they had no autonomy although they did not express complaints. Overall, surrogates did not portray themselves as vulnerable women and victims, but rather as mothers and spouses taking control of their destiny., Conclusions: The reality of surrogacy in India embraces antagonistic features that we analyze in this paper as "paradoxes". First, while women have become surrogates in response to gender constraints as mothers and wives, yet in so doing they have gone against gender norms. Secondly, while surrogacy was socially perceived as dirty work undertaken in order to survive, surrogates used surrogacy as a means to upward mobility for themselves and their children. Finally, while surrogacy was organized to counteract accusations of exploitation, surrogates were under constant domination by the medical system and had no decision-making power in the surrogacy process. This echoes their daily life as women. Although the Indian legal framework has changed, surrogacy still challenges gender norms, particularly in other developing countries where the practice is emerging.

In the early years of in vitro fertilization, overall pregnancy rates were low, and it was considered necessary to transfer more than one embryo to increase the chances of pregnancy. It was not until advances in assisted reproductive technologies resulting in increased pregnancy rates that the concept of transferring just one embryo was considered possible. A consequence of improvements in implantation rates was also an increase in multiple pregnancies when more than one embryo was transferred. Although some countries have reduced the number of embryos transferred, international data show that in many parts of the world high twin and higher order multiple pregnancy rates still exist. Even in developed countries these problems persist depending on clinical practice, funding of health services, and patient demands. Perinatal and other outcomes are significantly worse with twins compared with singleton pregnancies and there is an urgent need to reduce multiple pregnancy rates to at least 10%. This has been achieved in several countries and clinics by introducing single embryo transfer but there are many barriers to the introduction of this technique in most clinics worldwide. We discuss the background to the high multiple rate in assisted reproduction and the factors that contribute to its persistence even in excellent clinics and in high-quality health services. Practices that may promote single embryo transfer are discussed., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Assisted reproductive technologies (ARTs) are often considered luxury services by policy-makers and the general population, which are always susceptible of removal from public funding of health care. The analysis of the economic aspects of this scope seems essential due to the high prevalence of infertility in Iran and the high costs of infertility treatments. This study aimed to investigate the value put on IUI and IVF treatments by communities in Iran and the affordability of services based on community preferences. A cost-benefit analysis (CBA) was performed based on the WTP approach, and the contingent valuation method (CVM) was used to estimate WTP for IUI and IVF using a researcher-made survey in two cities of Kerman and Isfahan, Iran, in 2016-17. The sample size was 604, and the study sample frame to estimate WTP included two groups of couples who were/were not aware of their fertility statuses. The costs of one cycle of IUI and IVF were calculated according to the treatment protocols, tariffs of 2016-17, and medical information records of patients. The mean direct and indirect medical costs of one cycle of IUI and IVF were equivalent to 19561140 and 60897610 IRR, respectively. Also, the mean WTP for IUI and IVF treatments were obtained of 15941061 and 28870833 IRR, respectively. The demand for IUI and IVF treatments was elastic and the community was sensitive to price changes of these treatment methods. IUI and IVF treatments brought no positive net benefits, and economic variables had the highest impact on the WTP and community preferences, indicating the significant role of financial constraints in the community's valuation for advanced infertility treatments in Iran., Competing Interests: The authors have declared that no competing interests exist.

Importance: Infertility poses a substantial public health problem for women of reproductive age, in the United States and globally. Infertility can be overcome with a variety of emerging assisted reproductive technologies (ARTs). In vitro fertilization (IVF) currently represents the most commonly utilized method of ART and is typically associated with the highest clinical pregnancy rate and live birth rate compared with other infertility treatment options. However, proper preconception evaluation and counseling is paramount for optimizing IVF and pregnancy outcomes., Objective: This article aims to outline current guidelines and recommendations for comprehensive preconception evaluation before initiation of IVF., Evidence Acquisition: Articles were obtained from PubMed, ACOG committee opinions 781 and 762, and relevant textbook chapters., Results: A variety of recommendations and best practices exist for optimally managing patients seeking IVF. Special attention must be paid to the workup of certain patient populations, such as those with age older than 35 years, uterine abnormalities, comorbidities (especially hypertension, diabetes, and thrombophilias), and obesity. In addition, many lifestyle factors must be addressed before IVF initiation, such as smoking, illicit drug use, and inadequate nutrition. Preconception counseling and expectation management is key to optimizing pregnancy outcome., Conclusion and Relevance: A myriad of patient and environmental factors impact the potential success rates of IVF in treating infertility. Providers must be equipped to provide data-driven, patient-centered counseling before initiation of IVF.

The gonadotropin releasing hormone agonist (GnRH-a) long-protocols and the GnRH-antagonist protocols are two commonly used protocols for in vitro fertilization (IVF), but their cost-effectiveness has not been studied, especially in China. A retrospective study involving 1638 individuals in GnRH-a long-protocol and 621 in GnRH-antagonist protocol were conducted and a decision tree model analysis was used to analyze the cost-effectiveness. Both direct and indirect costs were calculated. As a result, during the fresh embryo transplantation cycles, there was no significant difference in the rate of ongoing pregnancy between the two protocols, the average cost of per ongoing pregnancy in the GnRH-antagonist protocol was $ 16970.85, and that in the GnRH-agonist long-protocol was $19902.24. The probability of cumulative ongoing pregnancy per start cycle was estimated at 60.65% for the GnRH-antagonist protocol and 71.6% for the GnRH-agonist long-protocol (P < 0.01). Considering the cumulative ongoing pregnancy rate, the mean costs per ongoing pregnancy were estimated at $8176.76 and at $7595.28 with GnRH-antagonist protocol and GnRH-agonist long protocol, respectively. In conclusion, in fresh embryo transplantation cycle, the GnRH-antagonist protocol has economic advantage. However, the GnRH-agonist long protocol is more cost effective considering the cumulative ongoing pregnancy rate in the fresh embryo and frozen embryo transplantation cycles.

This report is an ethical analysis based on both facts and values. In in vitro fertilization (IVF), there is an intricate interaction between rapid scientific development and changing societal values. In most countries, the ethical discussion is no longer on whether or not IVF in itself is ethically justifiable. Therefore, in this review, I discuss other ethical aspects that have emerged since IVF was first introduced, such as upper age limits, 'ownership' of gametes and embryos, IVF in single women and same-sex couples, preimplantatory genetic testing, social egg freezing, commercialization, public funding, and prioritization of IVF. Despite secularization, since religion still plays an important role in regulation and practices of IVF in many countries, positions on IVF among the world religions are summarized. Decision-making concerning IVF cannot be based only on clinical and economic considerations; these cannot be disentangled from ethical principles. Many concerns regarding the costs, effects, and safety of IVF subtly transcend into more complex questions about what it means to society to bear and give birth to children.

Objective: On December 21, 2015, the Province of Ontario created the Ontario Fertility Program to fund one cycle of in vitro fertilization (IVF) to improve IVF affordability and access for Ontarians below age 43. The objective of this study was to determine whether the Program was meeting this goal, based on the experiences of participating patients., Methods: Participation in an electronic survey was invited through posters and brochures placed within the waiting rooms of all 25 IVF clinics providing funded IVF in Ontario and by a survey link placed on websites focused on fertility issues., Results: The survey was carried out at the end of the second year of the Program (September to December 2017), with 514 participants completing >75% of it. Program strengths were noted as follows: decreases in financial inequities of family building for the infertile; lowering of the opportunity cost of accessing IVF; and destigmatizing and raising public awareness of infertility as a legitimate medical condition. Weaknesses were as follows: lack transparency and consistency in clinics' patient prioritization schemes; clinic concentration in cities leading to geographic inequities in access; and high ancillary costs being financially burdensome. The following opportunities were suggested: funding of more than one IVF cycle and its supporting medications; standardization of prioritization schemes; and tying Program access to means testing., Conclusion: Patients strongly support the Program and noted improved IVF affordability, but the Program's reliance on existing private clinics for treatment provision has meant unresolved geographic inequities and inconsistent prioritization schemes. Because this is the first Program study of patients' experience, the results will help policymakers determine areas to re-evaluate for continued or increased funding and opportunities to collaborate with health care providers and clinic owners to improve provision and access., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: To compare success rates, associated risks and cost-effectiveness between intrauterine insemination (IUI) and in vitro fertilisation (IVF)., Design: Retrospective observational study., Setting: The UK from 2012 to 2016., Participants: Data from Human Fertilisation and Embryology Authority's freedom of information request for 2012-2016 for IVF/ICSI (intracytoplasmic sperm injection)and IUI as practiced in 319 105 IVF/ICSI and 30 669 IUI cycles. Direct-cost calculations for maternal and neonatal expenditure per live birth (LB) was constructed using the cost of multiple birth model, with inflation-adjusted Bank of England index-linked data. A second direct-cost analysis evaluating the incremental cost-effective ratio (ICER) was modelled using the 2016 national mean (baseline) IVF and IUI success rates., Outcome Measures: LB, risks from IVF and IUI, and costs to gain 1 LB., Results: This largest comprehensive analysis integrating success, risks and costs at a national level shows IUI is safer and more cost-effective than IVF treatment.IVF LB/cycle success was significantly better than IUI at 26.96% versus 11.49% (p<0.001) but the IUI success is much closer to IVF at 2.35:1, than previously considered. IVF remains a significant source of multiple gestation pregnancy (MGP) compared with IUI (RR (Relative Risk): 1.45 (1.31 to 1.60), p<0.001) as was the rate of twins (RR: 1.58, p<0.001).In 2016, IVF maternal and neonatal cost was £115 082 017 compared with £2 940 196 for IUI and this MGP-related perinatal cost is absorbed by the National Health Services. At baseline tariffs and success rates IUI was £42 558 cheaper than IVF to deliver 1LB with enhanced benefits with small improvements in IUI. Reliable levels of IVF-related MGP, OHSS (ovarian hyperstimulation syndrome), fetal reductions and terminations are revealed., Conclusion: IUI success rates are much closer to IVF than previously reported, more cost-effective in delivering 1 LB, and associated with lower risk of complications for maternal and neonatal complications. It is prudent to offer IUI before IVF nationally., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Research Question: The cost of IVF treatment remains high, among other factors because of the medication needed for ovarian stimulation. This study investigated the effect of using low-dose human chorionic gonadotrophin (HCG) for the second phase of follicular maturation after corifollitropin alfa induction, to replace the more expensive, either recombinant or human menopausal gonadotrophin (HMG), on the cost of ovarian stimulation., Design: One hundred and five patients were randomly divided into two groups: patients in the HCG group (n = 50) received low-dose HCG from Day 7 until the diameter of at least three follicles reached 17 mm or more, while patients in the FSH group (n = 55) received conventional ovarian stimulation with highly purified HMG injections., Results: The clinical pregnancy rate in the HCG group was 38% higher than in the FSH group (number needed to treat, NNT = 13). The cost per pregnancy needed for ovarian stimulation was reduced from €4902 in the FSH group to €2684 in the HCG group. Hence, the cost of ovarian stimulation medication to obtain 10 pregnancies using the conventional FSH protocol is sufficient to attain 18 pregnancies when applying the low-dose HCG protocol., Conclusion: This study provides evidence that using HCG instead of HMG/FSH for ovarian stimulation results in a significant reduction in the cost of IVF with, at least, an equivalent pregnancy rate., (Copyright © 2019. Published by Elsevier Ltd.)

Even the strictest laboratories and clinics are prone to the occurrence of microbial contamination. In the case of in vitro fertilization (IVF) research and practice facilities, the number of possible sources is particularly vast. In addition to ambient air, personnel, and non-sterilized materials, follicular fluid and semen from patients are a very common gateway for a diverse range of bacteria and fungi into embryo cultures. Even so, reports of contamination cases are rare, what leads many clinics to see the issue as a negligible risk. Microbiological contamination may result in the demise of the patient's embryos, leading to additional costs to both the patient and the clinics. Regardless of financial loss, emotional costs, and stress levels during IVF are highly distressing. Other worrisome consequences include DNA fragmentation, poor-quality embryos, early pregnancy loss or preterm birth, and possible long-term damages that need further investigation. In this review, we aimed to shed a light on the issue that we consider largely underestimated and to be the underlying cause of poor IVF outcomes in many cases. We also discuss the composition of the microbiome and how its interaction with the reproductive tract of IVF-seeking patients might influence their outcomes. In conclusion, we urge clinics to more rigorously identify, register, and report contamination occurrences, and highlight the role of the study of the microbiome to improve overall results and safety of assisted reproduction.

Research Question: What is the cost-effectiveness of gonadotrophins compared with clomiphene citrate in couples with unexplained subfertility undergoing intrauterine insemination (IUI) with ovarian stimulation under strict cancellation criteria?, Design: A cost-effectiveness analysis alongside a randomized controlled trial (RCT). Between July 2013 and March 2016, 738 couples were randomized to gonadotrophins (369) or clomiphene citrate (369) in a multicentre RCT in the Netherlands. The direct medical costs of both strategies were compared. Direct medical costs included costs of medication, cycle monitoring, insemination and, if applicable, pregnancy monitoring. Non-parametric bootstrap resampling was used to investigate the effect of uncertainty in estimates. The cost-effectiveness analysis was performed according to intention-to-treat. The incremental cost-effectiveness ratio (ICER) between gonadotrophins and clomiphene citrate for ongoing pregnancy and live birth was assessed., Results: The mean costs per couple were €1534 for gonadotrophins and €1067 for clomiphene citrate (mean difference of €468; 95% confidence interval [CI] €464-472). As ongoing pregnancy rates were 31% in women allocated to gonadotrophins and 26% in women allocated to clomiphene citrate (relative risk 1.16, 95% CI 0.93-1.47), the ICER was €21,804 (95% CI €11,628-31,980) per additional ongoing pregnancy with gonadotrophins and €17,044 (95% CI €8998-25,090) per additional live birth with gonadotrophins., Conclusions: Gonadotrophins are more expensive compared with clomiphene citrate in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria, without being significantly more effective., (Copyright © 2019. Published by Elsevier Ltd.)

Background and Objectives: Since 2009, the decline of the Greek economy has been in the spotlight of the world's financial agenda. This study assesses the economic crisis' impact on assisted reproduction demand dynamics., Materials and Methods: Patient records were recruited between 2005-2017. In 2013 the clinic proceeded with a cost reduction. The studied time-frames were defined accordingly: Period A: Prior to economic crisis, Period B: During the economic crisis-prior to cost reduction, and Period C: During the economic crisis-following cost reduction. Analysis focused on parameters reflecting on patient characteristics, decision to inquire on IVF treatment, embarking on it, and proceeding with multiple cycles., Results: The mean annual number of first visit patients was significantly decreased during Period B (1467.00 ± 119.21) in comparison to period A (1644.40 ± 42.57) and C (1637.8 ± 77.23). Furthermore, Period C in comparison to B and A, refers to women of more advanced age (37.27 ± 5.62 vs 36.04 ± 5.76 vs 35.53 ± 5.28), reporting a longer infertility period (8.49 ± 6.25 vs 7.01 ± 5.66 vs 6.46 ± 5.20), being inclined to abandon IVF treatment sooner (2.78 ± 2.51 vs 2.60 ± 1.92 vs 4.91 ± 2.28)., Conclusions: A decline regarding assisted reproduction techniques (ART) demand was noted as anticipated. Redefining the cost of infertility treatments may contribute towards overcoming the troubling phenomenon of postponing pregnancy due to financial concerns.

In vitro fertilization and embryo transplantation (IVF-ET) technology is one of the main treatments for infertility. But IVF-ET is expensive and has not be covered by health insurance in most developing countries. Therefore, how to obtain the maximum success rate with the minimum cost is a common concern of clinicians and patients. At present, the economic studies on IVF-ET mainly focus on different ovulation stimulating drugs, different ovulation stimulating protocols, different transplantation methods and the number of transplants. But the process of IVF-ET is complex, the relevant methods of economic study are diverse, and there are no unified standard for outcome indicators, so there is no unified conclusion for more economical and effective protocol by now. Therefore, to analyze the economic studies of IVF-ET, and to explore appropriate evaluation methods and cost-effective protocols will be helpful for reasonable allocation of medical resources and guidance of clinical selection. It would provide policy reference to include the costs of IVF-ET treatment in health insurance in the future.

Objective: To investigate factors associated with early IVF treatment discontinuation., Design: Retrospective cohort study., Setting: Academic medical center., Patient(s): Six hundred sixty-nine first-attempt IVF patients who did not have a live birth., Intervention(s): None., Main Outcome Measure(s): Treatment discontinuation and time to return for a second IVF cycle., Result(s): Women without IVF insurance coverage were more likely to discontinue treatment than women with insurance coverage (adjusted odds ratio [aOR] = 3.12; 95% confidence interval [CI], 2.22-4.40). African-American women were more likely to discontinue treatment (aOR = 2.95; 95% CI, 1.54-5.66) and returned for treatment more slowly (adjusted hazard ratio [aHR] = 0.44; 95% CI, 0.28-0.71) than non-Hispanic white women, regardless of IVF insurance coverage or income. Women with a poor prognosis were more likely to discontinue treatment than women with a good prognosis. Older women with IVF insurance coverage or a good prognosis had a shorter time to return for a second IVF cycle than older women without IVF insurance coverage or with a poor prognosis. Estimated income, distance to clinic, fertility diagnosis, number of oocytes retrieved, and history of previous live birth were not associated with treatment discontinuation or time to return for a second IVF cycle after adjustment for covariates., Conclusion(s): IVF insurance coverage, race, age, and future treatment prognosis are associated with IVF treatment discontinuation and time to return., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the economical benefit of preimplantation genetic testing of aneuploidies (PGT-A) when applied in an extended culture and stringent elective single ET framework., Design: Theoretical cost-effectiveness study., Setting: Not applicable., Patients/animal(s): None., Intervention(s): Comparison of the cost-effectiveness between two IVF treatment strategies: serial transfer of all available blastocysts without genetic testing (first fresh transfer and subsequent frozen-thawed transfer); and systematic use of genetic testing (trophectoderm biopsy, freeze-all, and frozen-thawed transfers of euploid blastocysts). The costs considered for this analysis are based on regional public health system provider., Main Outcome Measure(s): Costs per live birth., Result(s): Cost-effectiveness profile of PGT-A improves with female age and number of available blastocysts. Sensitivity analyses varying the costs of ET, the costs of genetic analyses, the magnitude of the detrimental impact of PGT-A on live birth rate, and the crude live birth rates change to some extent the thresholds for effectiveness but generally confirm the notion that PGT-A can be economically advantageous in some specific subgroups., Conclusion(s): PGT-A can be cost-effective in specific clinical settings and population groups. Economic considerations deserve attention in the debate regarding the clinical utility of PGT-A., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to determine the healthcare professionals knowledge and opinions of egg sharing and does this potentially effect egg sharing numbers in the UK?, Study Design: 304 healthcare professionals undertook a large, in-depth survey about various topics related to egg sharing. This included ranking key benefits and issues related to egg sharing. Statistical analysis was performed using SPSS., Results: 63.1% of respondents had little or no knowledge of egg sharing, although the majority supported the scheme once a short description was provided. Although attitudes towards egg sharing were positive, there was more support for voluntary donation. The issues surrounding egg sharing of most concern were the psychological well-being of the egg sharer if her own treatment is unsuccessful and the concern that giving away half her eggs reduces IVF success rates. Only 16.5% of respondents had previously referred a patient for egg sharing, with the majority citing lack of knowledge for the reason they hadn't referred., Conclusions: Egg sharing allows women to receive free or subsidised IVF in exchange for donating half their oocytes collected to a recipient. Although egg sharing was intended to solve the current donor oocyte shortage, egg sharing numbers have fallen over recent years. Education of healthcare professionals about the egg sharing programme and the research that supports it could improve their perceptions of egg sharing, increasing referral rates and egg sharing numbers., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

In vitro fertilisation (IVF) 'add-ons' are therapeutic or diagnostic tools developed in an endeavour to improve the success rate of infertility treatment. However, there is no conclusive evidence that these interventions are a beneficial or effective adjunct of assisted reproductive technologies. Additionally, IVF add-ons are often implemented in clinical practice before their safety can be thoroughly ascertained. Yet, patients continue to request and pay large sums for such additional IVF tools. Hence, this essay set out to examine if it is ethical to provide IVF add-ons when there is no evidence of a benefit if the patient requests it. In order to determine what is ethical-namely, morally good and righteous, the question was considered in relation to three key values of medical ethics-autonomy, beneficence and non-maleficence. It was determined that providing IVF add-ons might be morally acceptable in specific circumstances, if true informed consent can be given, there is a potential of cost-effective physiological or psychological benefit and the risk of harm is minimal, particularly with regard to the unborn child., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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 ± 9,917.55 ¥ 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 ± 8,448.08 ¥ and the LBR was 31.05%. When patients were >35 years, the cost of a successful cycle was 83,297.92 ± 10,918.05 ¥ and the LBR was 25.07%. The government reimbursement for a cycle ranged between 11,372.12 ± 2,147.71 ¥ and 12,753.67 ± 1,905.02 ¥., 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.

Objective(s): The aim of this study was to compare the patient characteristics, type of genetic disease and inheritance, volume of activity, practice patterns and pregnancy outcomes, in private versus publically funded IVF pre-implantation genetic testing (PGT) for translocation (IVF-PGT-SR) and aneuploidy (PGT-A) periods., Study Design: This study retrospectively analyzed data during both privately funded period (PRP) and publically funded period (PUP) of assisted reproductive technology (ART) for a total of 275 patients. 83 patients underwent IVF-PGT-SR and 192 patients underwent IVF-PGT-A. Given that PGT-SR is a chromosomal abnormality hereditary in nature, whereas PGT-A is sporadic in addition to the contrasting funding policies, the two cohorts were analyzed separately. To achieve the proposed objective, the two groups under analysis were grouped in accordance with their respective coverage systems for infertility., Results: Among translocation patients, 94 normal/balanced embryos were obtained from 47 IVF-PGT cycles in PRP whereas 145 embryos were obtained from 92 IVF-PGT cycles in PUP. The average number of embryos transferred per embryo transfer cycle was significantly lower in PUP in comparison to PRP (1.13 vs. 1.74, p < 0.0001). 13 singletons and 2 sets of twins were conceived in PRP. 14 singletons were conceived in PUP. Regardless of funding period, there were more reciprocal translocation carriers (79.4% in PRP and 76.4% in PUP) and more male carriers (82.4% in PRP and 60% in PUP), of which the majority had abnormal sperm parameters. Among aneuploidy patients, on average 2.5 embryos in PRP and 1.4 embryos in PUP were transferred per ET cycle (p = 0.05). There was a 13.3% increase in number of IVF-PGT-A attempts per patient in PRP compared to PUP. Live birth rate per IVF-PGT-A was higher in PRP (29.7% vs. 15%, P = 0.02), which consisted of 48 singletons and 18 multiparous pregnancies in PRP and 9 singletons in PUP., Conclusion(s): Public coverage of ART is associated with a greater utilization ART, as well as a reduced number in embryo transfer (ET) per cycle, a lower proportion of cycles resulting in successful pregnancy and a lower multiple birth rate. Our study ultimately shines light on the effect of providers' and patients' monetary conscious on pregnancy outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The contingent valuation (CV) method is an alternative approach to typical health economic methods for valuing interventions that have both health and non-health outcomes. Fertility treatment, such as in vitro fertilisation (IVF), fall into this category because of the significant non-health outcomes associated with having children., Aim: To estimate the general population's willingness to pay (WTP) for one cycle of IVF and one year of IVF treatment, and to test the reliability and validity of a CV instrument., Methods: Three online CV surveys were administered to a total of 1870 participants from the Australian general population using an ex-post perspective, that is, they assumed they were infertile and needed IVF to conceive a child. Participants answered questions with starting point WTP bids of 2018 Australian dollars (AU$) 4000 or $10,000 for the cost of one IVF cycle, and treatment success rates of 10%, 20% and 50% per IVF cycle. Tests for reliability, internal construct validity, starting point bias, and external validity were performed., Results: Depending on the success rate and the starting point WTP bid, the mean WTP for one IVF cycle ranged from $6135 to $13,561, while the mean WTP for one year of IVF treatment varied from $17,080 to $31,006. The CV method was reliable and satisfied internal construct and external criterion validity. However strong starting point bias was evident, rendering the mean WTP values highly imprecise., Conclusion: The CV method holds promise for eliciting the value of interventions, such as fertility treatment, that have significant health and non-health outcomes. Survey instruments that prevent starting point bias are essential. Comparing the results of CV methods to other value elicitation methods is needed to confirm convergent validity.

Purpose: The number of in vitro fertilization (IVF) cycles is increasing and the majority of patients undergoing IVF pay out of pocket. Reproductive endocrinology and infertility practitioners employ different business models to help create financial pathways for patients needing IVF but details regarding the different types of business models being used and physician satisfaction with those models have not been described previously., Methods: A cross-sectional survey was sent to members of the Society of Reproductive Endocrinology and Infertility. The survey included 30 questions designed to assess demographics, practice patterns, and business models utilized., Results: A total of 222/736 (30%) physicians responded to the survey. The majority of physicians offer a-la-carte (67%), bundled services (69%), grants (57%), and cost/risk-sharing (50%). The majority answered that the single ideal business model is bundled services (53%). There was no significant association between financial package offered and region of practice or state-mandated insurance. The largest barrier to care reported was cost with or without state-mandated coverage (94% and 99%, respectively). The majority of practices are satisfied with their business model (75%). Higher physician satisfaction was associated with private practice [69% vs 27%; OR (95%CI) = 3.8 (1.7, 8.6)], male gender [59% vs 30%; OR = 2.4 (1.1, 5.4)], and offering bundled services [83% vs 59%; OR = 2.8 (1.2, 6.7)]., Conclusions: Physicians utilize a variety of business models and most are satisfied with their current model. Cost is the major barrier to care in states with and without mandated coverage.

IUI has been practiced for five decades but only three unconvincing trials attempted to demonstrate the superiority of IUI over sexual intercourse (SI). In the absence of evidence of its effectiveness, the National Institute for Clinical Excellence (NICE) recommended IVF over IUI after 2 years of unprotected SI. High-quality recent data in well-constructed studies suggest that biases against IUI procedures and in favour of IVF are invalid. It is unethical to continue to misinform patients and stakeholders. The well-constructed randomised controlled trials (RCT) show IUI procedure to be efficient, with minimal risk, and above all improved cost-effectiveness when compared to IVF for live birth. IUI as first-line treatment should be offered to most patients, while funding agencies and stakeholders need to be urgently informed of the cost-benefit in offering IUI. Fertility clinics, IVF interest groups, and regulatory bodies should amend their patient information and guidance to state that IUI should be the first line treatment and that IVF should be offered only when essential. Reappraising and promoting IUI based on evidence enhances patient autonomy, choices, and trust, while allowing the fertility industry to operate within an ethical and acceptable framework not seen as exploitative toward vulnerable patients.

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.

Research Question: Does delaying IVF for 6 months in couples with unexplained infertility, compared with immediate IVF treatment, decrease the cost of IVF without compromising success rates?, Design: Decision modelling was used to evaluate the cost and outcomes of immediate IVF versus delayed IVF for a cohort of women aged <40 years suffering unexplained infertility. Australian data and costs were used in the analysis. For different age groups, three scenarios were tested where 10%, 50% and 90% of couples with unexplained infertility delayed IVF for 6 months if they had a good prognosis for natural conception. The study included a total of 8781 couples aged <40 years, diagnosed with unexplained infertility and who had IVF in 2013., Results: The studied couples underwent 27,648 fresh and frozen embryo transfers, for an estimated total cost of $141 million. Potential out-of-pocket cost savings if 90% of couples delayed IVF ranged from $4.7 to $12.2 million, with Medicare cost savings of up to $15.1 million. The impact on the total pregnancy and live birth rates after 18 months was minimal., Conclusions: In couples with unexplained infertility and a good prognosis for natural conception, delaying IVF for 6 months could substantially decrease out-of-pocket costs without compromising pregnancy and live birth rates over an 18-month period., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Question: Is a freeze-only strategy more cost-effective from a patient perspective than fresh embryo transfer (ET) after one completed In Vitro Fertilization/ Intracytoplasmic Sperm Injection (IVF/ICSI) cycle in women without polycystic ovary syndrome (PCOS)?, Summary Answer: There is a low probability of the freeze-only strategy being cost-effective over the fresh ET strategy for non-PCOS women undergoing IVF/ICSI., What Is Known Already: Conventionally, IVF embryos are transferred in the same cycle in which oocytes are collected, while any remaining embryos are frozen and stored. We recently evaluated the effectiveness of a freeze-only strategy compared with a fresh ET strategy in a randomized controlled trial (RCT). There was no difference in live birth rate between the two strategies., Study Design, Size, Duration: A cost-effectiveness analysis (CEA) was performed alongside the RCT to compare a freeze-only strategy with a fresh ET strategy in non-PCOS women undergoing IVF/ICSI. The effectiveness measure for the CEA was the live birth rate. Data on the IVF procedure, pregnancy outcomes and complications were collected from chart review; additional information was obtained using patient questionnaires, by telephone., Participants/materials, Setting, Methods: For all patients, we measured the direct medical costs relating to treatment (cryopreservation, pregnancy follow-up, delivery), direct non-medical costs (travel, accommodation) and indirect costs (income lost). The direct cost data were calculated from resources obtained from patient records and prices were applied based on a micro-costing approach. Indirect costs were calculated based on responses to the questionnaire. Patients were followed until all embryos obtained from a single controlled ovarian hyperstimulation cycle were used or a live birth was achieved. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-only strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were also performed., Main Results and the Role of Chance: Between June 2015 and April 2016, 782 couples were randomized to a freeze-only (n = 391) or a fresh ET strategy (n = 391). Baseline characteristics including mean age, Body Mass Index (BMI), anti-Mullerian hormone, total dose of Follicle Stimulating Hormone (FSH), number of oocytes obtained, good quality Day 3 embryos, fertility outcomes and treatment complications were comparable between the two groups. The live birth rate (48.6% vs. 47.3%, respectively; risk ratio, 1.03; 95% Confidence Interval [CI], 0.89, 1.19; P = 0.78) and the average cost per couple (3906 vs. 3512 EUR, respectively; absolute difference 393.6, 95% CI, -76.2, 863.5; P = 0.1) were similar in the freeze-only group versus fresh ET. Corresponding costs per live birth were 8037 EUR versus 7425 EUR in the freeze-only versus fresh ET group, respectively. The incremental cost for the freeze-only strategy compared with fresh ET was 30 997 EUR per 1% additional live birth rate. The direct non-medical costs and indirect costs of infertility treatment strategies represented ~45-52% of the total cost. PSA shows that the 95% CI of ICERs was -263 901 to 286 681 EUR. Out of 1000 simulations, 44% resulted in negative ICERs, including 13.0% of simulations in which the freeze-only strategy was dominant (more effective and less costly than fresh ET), and 31% of simulations in which the fresh embryo strategy was dominant. In the other 560 simulations with positive ICERs, the 95% CI of ICERs ranged from 2155 to 471 578 EUR. The CEAC shows that at a willingness to pay threshold of 300 000 EUR, the probability of the freeze-only strategy being cost-effective over the fresh ET strategy would be 58%., Limitations, Reasons for Caution: Data were collected from a single private IVF center study in Vietnam where there is no public or insurance funding of IVF. Unit costs obtained might not be representative of other settings. Data obtained from secondary sources (medical records, financial and activity reports) could lack authenticity, and recall bias may have influenced questionnaire responses on which direct costs were based., Wider Implications of the Findings: In non-PCOS women undergoing IVF/ICSI, the results suggested that the freeze-only strategy was not cost-effective compared with fresh ET from a patient perspective. These findings indicate that other factors could be more important in deciding whether to use a freeze-only versus fresh ET strategy in this patient group., Study Funding/competing Interest(s): This study was funded by My Duc Hospital; no external funding was received. Ben Willem J. Mol is supported by an NHMRC Practioner Fellowship (GNT 1082548) and reports consultancy for Merck, ObsEva and Guerbet. Robert J. Norman has shares in an IVF company and has received support from Merck and Ferring. All other authors have no conflicts of interest to declare., Trial Registration Number: Not applicable.

Assisted reproductive technology has evolved tremendously since the emergence of in vitro fertilization (IVF). In the course of the recent decade, there have been significant efforts in order to minimize multiple gestations, while improving percentages of singleton pregnancies and offering individualized services in IVF, in line with the trend of personalized medicine. Patients as well as clinicians and the entire IVF team benefit majorly from 'knowing what to expect' from an IVF cycle. Hereby, the question that has emerged is to what extent prognosis could facilitate toward the achievement of the above goal. In the current review, we present prediction models based on patients' characteristics and IVF data, as well as models based on embryo morphology and biomarkers during culture shaping a complication free and cost-effective personalized treatment. The starting point for the implementation of prediction models was initiated by the aspiration of moving toward optimal practice. Thus, prediction models could serve as useful tools that could safely set the expectations involved during this journey guiding and making IVF treatment more effective. The aim and scope of this review is to thoroughly present the evolution and contribution of prediction models toward an efficient IVF treatment., Abbreviations: IVF: In vitro fertilization; ART: assisted reproduction techniques; BMI: body mass index; OHSS: ovarian hyperstimulation syndrome; eSET: elective single embryo transfer; ESHRE: European Society of Human Reproduction and Embryology; mtDNA: mitochondrial DNA; nDNA: nuclear DNA; ICSI: intracytoplasmic sperm injection; MBR: multiple birth rates; LBR: live birth rates; SART: Society for Assisted Reproductive Technology Clinic Outcome Reporting System; AFC: antral follicle count; GnRH: gonadotrophin releasing hormone; FSH: follicle stimulating hormone; LH: luteinizing hormone; AMH: anti-Müllerian hormone; DHEA: dehydroepiandrosterone; PCOS: polycystic ovarian syndrome; NPCOS: non-polycystic ovarian syndrome; CE: cost-effectiveness; CC: clomiphene citrate; ORT: ovarian reserve test; EU: embryo-uterus; DET: double embryo transfer; CES: Cumulative Embryo Score; GES: Graduated Embryo Score; CSS: Combined Scoring System; MSEQ: Mean Score of Embryo Quality; IMC: integrated morphology cleavage; EFNB2: ephrin-B2; CAMK1D: calcium/calmodulin-dependent protein kinase 1D; GSTA4: glutathione S-transferase alpha 4; GSR: glutathione reductase; PGR: progesterone receptor; AMHR2: anti-Müllerian hormone receptor 2; LIF: leukemia inhibitory factor; sHLA-G: soluble human leukocyte antigen G.

Background: The association of recombinant FSH plus recombinant LH in 2:1 ratio may be used not only to induce ovulation in anovulatory women with hypogonadotropic hypogonadism but also to achieve multiple follicular developments in human IVF. The aim of this analysis was to estimate the cost-effectiveness of Controlled Ovarian Stimulation (COS) with recombinant FSH (rFSH) plus recombinant LH (rLH) in comparison with highly purified human menopausal gonadotropin (HP-hMG) in the woman undergoing in vitro fertilization (IVF) in Italy., Methods: A probabilistic decision tree was developed to simulate patients undergoing IVF, either using r-FSH + r-LH or HP-hMG to obtain COS. The model considers the National Health System (NHS) perspective and a time horizon equal to two years. Simulations were reported considering the number of retrieved oocytes (5-9, 10-15 and > 15) and transition probabilities were estimated through specific analyses carried out on the population of 848 women enrolled in the real-life., Results: The model estimated that patients undertaking therapeutic protocol with r-FSH + r-LH increase the general success rate (+ 6.6% for pregnancy). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of r-FSH + r-LH was below the willingness to pay set at €20,000 for all the considered scenarios., Conclusions: The cost-utility analysis demonstrated that the r-FSH + r-LH is a cost-effective option for the Italian National Health System (NHS).