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

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

Why are multiple pregnancy rates and single embryo transfer rates so different globally, and what do we do about it?

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.

Elective Single Embryo Transfer in the Setting of Funded In Vitro Fertilization: Two Years' Experience in an Ontario Hospital-Based Fertility Clinic.

OBJECTIVE: The objective of this study was to assess data from a fertility clinic and identify differences in patient and cycle characteristics, clinical pregnancy rates, and multiple gestation rates before and after fertility treatment funding and a policy of elective single embryo transfer were instituted by the Ontario government to reduce multiple gestations arising from fertility treatment. METHODS: This study was a retrospective database review of clinic and embryology laboratory data for all patients undergoing in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) cycles over a 4-year period. The investigators compared IVF and ICSI cycles before funding, from January 1, 2014 to December 31, 2015, with cycles after funding, from January 1, 2016 to December 31, 2017. RESULTS: The number of cycles performed over a 2-year period increased from 554 to 853, of which 76.2% were funded. Patient age, body mass index, and parity were similar before and after funding. Fewer patients receiving funded IVF or ICSI had had a previous cycle. Cycle cancellation rates were similar before and after funding; however, there were fewer embryo transfers per cycle start after funding (80.3% vs. 72.2%, P = 0.001). The clinical pregnancy rate was similar before and after funding (37.8% vs. 32.5%, P = 0.09), whereas the multiple gestation rate was significantly lower (13.1% vs. 3.5%, P = 0.001). CONCLUSION: Since the government of Ontario began funding IVF and ICSI cycles, more patients are accessing treatment, many for the first time. The clinical pregnancy rate was maintained, whereas multiple gestations were significantly reduced. These findings support the benefit of single embryo transfer in the context of funded IVF and ICSI and demonstrate the importance of government-funded assisted reproductive technology.

Factors associated with the use of elective single-embryo transfer and pregnancy outcomes in the United States, 2004-2012.

OBJECTIVE: To evaluate factors associated with elective single-embryo transfer (eSET) utilization and its effect on assisted reproductive technology outcomes in the United States. DESIGN: Historical cohort. SETTING: Not applicable. PATIENT(S): Fresh IVF cycles of women aged 18-37 years using autologous oocytes with either one (SET) or two (double-embryo transfer [DET]) embryos transferred and reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2004 and 2012. Cycles were categorized into four groups with ([+]) or without ([-]) supernumerary embryos cryopreserved. The SET group with embryos cryopreserved was designated as eSET. INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): The likelihood of eSET utilization, live birth, and singleton non-low birth weight term live birth, modeled using logistic regression. Presented as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULT(S): The study included 263,375 cycles (21,917 SET[-]cryopreservation, 20,996 SET[+]cryopreservation, 103,371 DET[-]cryopreservation, and 117,091 DET[+]cryopreservation). The utilization of eSET (SET[+]cryopreservation) increased from 1.8% in 2004 to 14.9% in 2012 (aOR 7.66, 95% CI 6.87-8.53) and was more likely with assisted reproductive technology insurance coverage (aOR 1.60, 95% CI 1.54-1.66), Asian race (aOR 1.26, 95% CI 1.20-1.33), uterine factor diagnosis (aOR 1.48, 95% CI 1.37-1.59), retrieval of ≥16 oocytes (aOR 2.85, 95% CI 2.55-3.19), and the transfer of day 5-6 embryos (aOR 4.23, 95% CI 4.06-4.40); eSET was less likely in women aged 35-37 years (aOR 0.76, 95% CI 0.73-0.80). Compared with DET cycles, the likelihood of the ideal outcome, term non-low birth weight singleton live birth, was increased 45%-52% with eSET. CONCLUSION(S): Expanding insurance coverage for IVF would facilitate the broader use of eSET and may reduce the morbidity and healthcare costs associated with multiple pregnancies.

Costs of achieving live birth from assisted reproductive technology: a comparison of sequential single and double embryo transfer approaches.

OBJECTIVE: To assess treatment and pregnancy/infant-associated medical costs and birth outcomes for assisted reproductive technology (ART) cycles in a subset of patients using elective double embryo (ET) and to project the difference in costs and outcomes had the cycles instead been sequential single ETs (fresh followed by frozen if the fresh ET did not result in live birth). DESIGN: Retrospective cohort study using 2012 and 2013 data from the National ART Surveillance System. SETTING: Infertility treatment centers. PATIENT(S): Fresh, autologous double ETs performed in 2012 among ART patients younger than 35 years of age with no prior ART use who cryopreserved at least one embryo. INTERVENTION(S): Sequential single and double ETs. MAIN OUTCOME MEASURE(S): Actual live birth rates and estimated ART treatment and pregnancy/infant-associated medical costs for double ET cycles started in 2012 and projected ART treatment and pregnancy/infant-associated medical costs if the double ET cycles had been performed as sequential single ETs. RESULT(S): The estimated total ART treatment and pregnancy/infant-associated medical costs were $580.9 million for 10,001 double ETs started in 2012. If performed as sequential single ETs, estimated costs would have decreased by $195.0 million to $386.0 million, and live birth rates would have increased from 57.7%-68.0%. CONCLUSION(S): Sequential single ETs, when clinically appropriate, can reduce total ART treatment and pregnancy/infant-associated medical costs by reducing multiple births without lowering live birth rates.

Elective Single Embryo Transfer: an update to UK Best Practice Guidelines.

A significant number of multiple pregnancies and births worldwide continue to occur following treatment with Assisted Reproductive Technologies (ARTs). Whilst efforts have been made to increase the proportion of elective single embryo transfer (eSET) cycles, the multiple pregnancy rate or MPR remains at a level that most consider unacceptable given the associated clinical risks to mothers and babies, and the additional costs associated with neonatal care of premature and low birth weight babies. Northern Europe, Australia and Japan have continued to lead the way in the adoption of eSET. Randomised controlled trials or RCTs, meta-analyses and economic analyses support the implementation of an eSET policy, particularly in light of recent advances in ARTs. This paper provides a review of current evidence and an update to the eSET guidelines first published by Cutting et al. (2008) intended to assist ART clinics in the implementation of an effective eSET policy.

Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation?

STUDY QUESTION: What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?. SUMMARY ANSWER: Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child. WHAT IS KNOWN ALREADY: IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF. STUDY DESIGN, SIZE, DURATION: We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates. MAIN RESULTS AND THE ROLE OF CHANCE: There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were €7187 for IVF-SET, €8206 for IVF-MNC and €5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences €2117; 95% CI: €1544-€2657 and €3136, 95% CI: €2519-€3754, respectively).The ICER for IVF-SET compared with IUI-COH was €43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs. LIMITATIONS, REASONS FOR CAUTION: We only report on direct health care costs. The present analysis is limited to 12 months. WIDER IMPLICATIONS OF THE FINDINGS: Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a grant from ZonMw, the Netherlands Organization for Health Research and Development, (120620027) and a grant from Zorgverzekeraars Nederland, the Netherlands' association of health care insurers (09-003). TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.

Public health implications of a North American publicly funded in vitro fertilization program; lessons to learn.

PURPOSE: A retrospective study was conducted to determine trends in practice and outcomes that occurred since the implementation of the publicly funded in vitro fertilization (IVF) and single embryo transfer (SET) program in Quebec, in August, 2010. METHODS: Data presented was extracted from an advisory report by the Health and Welfare Commissioner, and from a report by the Ministry of Health and Social Services published in June 2014 and October 2013, respectively. This data is publicly available, and was collected from all six private and three public-assisted reproduction centers in Quebec providing IVF services. Data pertains to all IVF cycles performed from the 2009-2010 to 2012-2013 fiscal years. RESULTS: SET was performed in 71 % of cycles in 2012. The number of children born from IVF was 1057 in 2009-2010 and 1723 in 2012-2013 (p < 0.0001). Multiple birth rates from IVF were 24 % in 2009-2010 (before the program began) and 9.45 % in 2012-2013 (p < 0.0001). The proportions of IVF babies that were premature, that were the result of multiple births, or that required neonatal intensive care unit admission (NICU) all decreased by 35.5 % (p < 0.0001), 55 % (p < 0.0001), and 37 % (p < 0.0001), respectively, from 2009-2010 to 2012-2013. The cost per NICU admission for an IVF baby increased from $19,990 to $28,418 from 2009-2010 to 2011-2012. CONCLUSION: This first North American publicly funded IVF program with a SET policy shows that such a program contributes substantially to number of births. It has also succeeded in increasing access to treatment and decreasing perinatal morbidity by decreasing multiple birth rates from IVF. A substantial increase in global public health care costs occurred as well.

Economic evaluation of elective single-embryo transfer with subsequent single frozen embryo transfer in an in vitro fertilization/intracytoplasmic sperm injection program.

OBJECTIVE: To analyze the cost-effectiveness of IVF-ICSI cycles with elective single-embryo transfer (eSET), plus elective single frozen embryo transfer (eSFET) if pregnancy is not achieved, compared with double-embryo transfer (DET). DESIGN: Cost-effectiveness analysis. SETTING: Public hospital. PATIENT(S): A population of 121 women (<38 years old), undergoing their first or second IVF cycles. INTERVENTION(S): We conducted a cost-effectiveness analysis using the results of a prospective clinical trial. The women in group 1 received eSET plus eSFET, and those in group 2 received DET. A probabilistic sensitivity analysis was performed. MAIN OUTCOME MEASURE(S): Live birth delivery rate. RESULT(S): The cumulative live birth delivery rate was 38.60% in the eSET+eSFET group versus 42.19% in the DET group. The mean costs per patient were €5,614.11 in the eSET+eSFET group and €5,562.29 in the DET group. These differences were not statistically significant. The rate of multiple gestation was significantly lower in the eSET group than in the DET group (0 vs. 25.9%). CONCLUSION(S): This study does not show that eSET is superior to DET in terms of effectiveness or of costs. The lack of superiority of the results for the eSET+eSFET and the DET groups corroborates that the choice of strategy to be adopted should be determined by the context of the health care system and the individual prognosis.

In search of real autonomy for fertility patients.

Nearly one in eight infants in the United States is born preterm. A variety of factors are associated with preterm birth, including multiplicity. In the United States fertility treatments are currently associated with high rates of multiplicity, but these rates could be reduced significantly if changes can be made to fertility treatment policy and practice. These include reducing the financial pressure on patients to prioritize pregnancy chances over safety by expanding insurance coverage and altering the way we calculate success rates and insurance benefits so that two consecutive single embryo transfers is equivalent to one double embryo transfer.

Universal coverage of IVF pays off.

STUDY QUESTION: What was the clinical and economic impact of universal coverage of IVF in Quebec, Canada, during the first calendar year of implementation of the public IVF programme? SUMMARY ANSWER: Universal coverage of IVF increased access to IVF treatment, decreased the multiple pregnancy rate and decreased the cost per live birth, despite increased costs per cycle. WHAT IS KNOWN ALREADY: Public funding of IVF assures equality of access to IVF and decreases multiple pregnancies resulting from this treatment. Public IVF programmes usually mandate a predominant SET policy, the most effective approach for reducing the incidence of multiple pregnancies. STUDY DESIGN, SIZE, DURATION: This prospective comparative cohort study involved 7364 IVF cycles performed in Quebec during 2009 and 2011 and included an economic analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: IVF cycles performed in the five centres offering IVF treatment in Quebec during 2009, before implementation of the public IVF programme, were compared with cycles performed at the same centres during 2011, the first full calendar year following implementation of the programme. Data were obtained from the Canadian Assisted Reproductive Technologies Register (CARTR). Comparisons were made between the two periods in terms of utilization, pregnancy rates, multiple pregnancy rates and costs. MAIN RESULTS AND THE ROLE OF CHANCE: The number of IVF cycles performed in Quebec increased by 192% after the new policy was implemented. Elective single-embryo transfer was performed in 1.6% of the cycles during Period I (2009), and increased to 31.6% during Period II (2011) (P < 0.001). Although the clinical pregnancy rate per embryo transfer was lower in 2011 than in 2009 (24.9 versus 39.9%, P < 0.001), the multiple pregnancy rate was greatly reduced (6.4 versus 29.4%, P < 0.001). The public IVF programme increased government costs per IVF treatment cycle from CAD$3730 to CAD$4759. Despite increased costs per cycle, the efficiency defined by the cost per live birth, which factored in downstream health costs up to 1 year post delivery, decreased from CAD$49 517 to CAD$43 362 per baby conceived by either fresh and frozen cycles. LIMITATIONS, REASONS FOR CAUTION: The costs described in the economic model are likely an underestimate as they do not factor in many of the long-term costs that can occur after 1 year of age. The information collected in the Canadian ART register precludes the calculation of cumulative pregnancy rates. WIDER IMPLICATIONS OF THE FINDINGS: Our study confirms that the implementation of a public IVF programme favouring eSET not only sharply decreases the incidence of multiple pregnancy, but also reduces the cost per live birth. STUDY FUNDING/COMPETING INTEREST(S): M.P.V. holds a fellowship award from the Canadian Institutes of Health Research (CIHR). The economic analysis performed by M.P.C. was supported by an unrestricted grant from Ferring Pharmaceutical.

Modified natural cycle versus controlled ovarian hyperstimulation IVF: a cost-effectiveness evaluation of three simulated treatment scenarios.

STUDY QUESTION: Can modified natural cycle IVF or ICSI (MNC) be a cost-effective alternative for controlled ovarian hyperstimulation IVF or ICSI (COH)? SUMMARY ANSWER: The comparison of simulated scenarios indicates that a strategy of three to six cycles of MNC with minimized medication is a cost-effective alternative for one cycle of COH with strict application of single embryo transfer (SET). WHAT IS KNOWN ALREADY: MNC is cheaper per cycle than COH but also less effective in terms of live birth rate (LBR). However, strict application of SET in COH cycles reduces effectiveness and up to three MNC cycles can be performed at the same costs as one COH cycle. STUDY DESIGN, SIZE, DURATION: The cost-effectiveness of MNC versus COH was evaluated in three simulated treatment scenarios: three cycles of MNC versus one cycle of COH with SET or double embryo transfer (DET) and subsequent transfer of cryopreserved embryos (Scenario 1); six cycles of MNC versus one cycle of COH with strictly SET and subsequent transfer of cryopreserved embryos (Scenario 2); six cycles of MNC with minimized medication (hCG ovulation trigger only) versus one cycle of COH with SET or DET and subsequent transfer of cryopreserved embryos (Scenario 3). We used baseline data obtained from two retrospective cohorts of consecutive patients (2005-2008) undergoing MNC in the University Medical Center Groningen (n = 499, maximum six cycles per patient) or their first COH cycle with subsequent transfer of cryopreserved embryos in the Academic Medical Center Amsterdam (n = 392). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 1994 MNC cycles (958 MNC-IVF and 1036 MNC-ICSI) and 392 fresh COH cycles (one per patient, 196 COH-IVF and 196 COH-ICSI) with subsequent transfer of cryopreserved embryos (n = 72 and n = 94 in MNC and COH cycles, respectively) in ovulatory, subfertile women <36 years of age served as baseline for the three simulated scenarios. To compare the scenarios, the incremental cost-effectiveness ratio (ICER) was calculated, defined as the ratio of the difference in IVF costs up to 6 weeks postpartum to the difference in LBR. Live birth was the primary outcome measure and was defined as the birth of at least one living child after a gestation of ≥25 weeks. MAIN RESULTS AND THE ROLE OF CHANCE: In the baseline data, MNC was not cost-effective, as COH dominated MNC with a higher cumulative LBR (27.0 versus 24.0%) and lower cost per patient (€3694 versus €5254). The simulations showed that in scenario 1 three instead of six cycles lowered the costs of MNC to below the level of COH (€3390 versus €3694, respectively), but also lowered the LBR per patient (from 24.0 to 16.2%, respectively); Scenario 2: COH with strict SET was less effective than six cycles MNC (LBR 17.5 versus 24.0%, respectively), but also less expensive per patient (€2908) than MNC (€5254); Scenario 3: improved the cost-effectiveness of MNC but COH still dominated MNC when medication was minimized in terms of costs, i.e. €855 difference in favor of COH and 3% difference in LBR in favor of COH (ICER: €855/-3.0%). LIMITATIONS, REASONS FOR CAUTION: Owing to the retrospective nature of the study, the analyses required some assumptions, for example regarding the costs of pregnancy and delivery, which had to be based on the literature rather than on individual data. Furthermore, costs of IVF treatment were based on tariffs and not on actual costs. Although this may limit the external generalizability of the results, the limitations will influence both treatments equally, and would therefore not bias the comparison of MNC versus COH. WIDER IMPLICATIONS OF THE FINDINGS: The combined results suggest that MNC with minimized medication might be a cost-effective alternative for COH with strict SET. The scenarios reflect realistic alternatives for daily clinical practice. A preference for MNC depends on the willingness to trade off effectiveness in terms of LBR against the benefits of a milder stimulation regimen, including a very low rate of multiple pregnancies and hyperstimulation syndrome and ensuing lower costs per live birth. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by research grants from Merck Serono and Ferring Pharmaceuticals. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Refuting a misguided campaign against the goal of single-embryo transfer and singleton birth in assisted reproduction.

Much recent progress has been made by assisted reproductive technology (ART) professionals toward minimizing the incidence of multiple pregnancy following ART treatment. While a healthy singleton birth is widely considered to be the ideal outcome of such treatment, a vocal minority continues a campaign to advocate the benefits of multiple embryo transfer as treatment and twin pregnancy as outcome for most ART patients. Proponents of twinning argue four points: that patients prefer twins, that multiple embryo transfer maximizes success rates, that the costs per infant are lower with twins and that one twin pregnancy and birth is associated with no higher risk than two consecutive singleton pregnancies and births. We find fault with the reasoning and data behind each of these tenets. First, we respect the principle of patient autonomy to choose the number of embryos for transfer but counter that it has been shown that better patient education reduces their desire for twins. In addition, reasonable and evidentially supported limits may be placed on autonomy in exchange for public or private insurance coverage for ART treatment, and counterbalancing ethical principles to autonomy exist, especially beneficence (doing good) and non-maleficence (doing no harm). Second, comparisons between success rates following single-embryo transfer (SET) and double-embryo transfers favor double-embryo transfers only when embryo utilization is not comparable; cumulative pregnancy and birth rates that take into account utilization of cryopreserved embryos (and the additional cryopreserved embryo available with single fresh embryo transfer) consistently demonstrate no advantage to double-embryo transfer. Third, while comparisons of costs are system dependent and not easy to assess, several independent studies all suggest that short-term costs per child (through the neonatal period alone) are lower with transfers of one rather than two embryos. And, finally, abundant evidence conclusively demonstrates that the risks to both mother and especially to children are substantially greater with one twin birth compared with two singleton births. Thus, the arguments used by some to promote multiple embryo transfer and twinning are not supported by the facts. They should not detract from efforts to further promote SET and thus reduce ART-associated multiple pregnancy and its inherent risks.

Rapid policy change to single-embryo transfer while maintaining pregnancy rates per initiated cycle.

Public financing of IVF aims at increasing access to treatment while decreasing the expenses associated with multiple pregnancies. Critics argue that it is associated with lower pregnancy rates. This study compared cycles performed during 2009 (before implementation of Quebec's public IVF programme; period I) to those performed in the year following implementation (period II) in a single IVF centre. First fresh cycles in period I (499 women) and first fresh cycles (815 women) along with their corresponding first vitrified-warmed transfer (271 women) in period II were evaluated. From period I to period II, single-embryo transfer increased from 17.3% to 85.0% (P<0.001), multiple ongoing pregnancy rate decreased from 25.8% to 1.6% (P<0.001) and ongoing pregnancy rate decreased from 31.9% to 23.3% (P=0.001). During period II, the ongoing pregnancy rate per vitrified-warmed embryo transfer was 19.2%, leading to a cumulative ongoing pregnancy rate per initiated cycle of 29.7%, which was not different to the pregnancy rate per fresh cycle during period I (31.9%). To conclude, Quebec's public IVF programme decreased multiple pregnancy rates while maintaining an acceptable cumulative ongoing pregnancy rate, a more precise outcome to evaluate the impact of public IVF programmes.

The diversity of regulation and public financing of IVF in Europe and its impact on utilization.

STUDY QUESTION: How do the different forms of regulation and public financing of IVF affect utilization in otherwise similar European welfare state systems? SUMMARY ANSWER: Countries with more liberal social eligibility regulations had higher levels of IVF utilization, which diminished as the countries' policies became more restrictive. WHAT IS KNOWN ALREADY: Europe is a world leader in the development and utilization of IVF, yet surveillance reveals significant differences in uptake among countries which have adopted different approaches to the regulation and and public financing of IVF. STUDY DESIGN, SIZE, DURATION: A descriptive and comparative analysis of legal restrictions on access to IVF in 13 of the EU15 countries that affirmatively regulate and publicly finance IVF. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using 2009 data from the European Society of Human Reproduction and Embryology study of regulatory frameworks in Europe and additional legislative research, we examined and described restrictions on access to IVF in terms of general eligibility, public financing and the scope of available services. Multiple correspondence analysis was used to identify patterns of regulation and groups of countries with similar regulatory patterns and to explore the effects on utilization of IVF, using data from the most recent European and international IVF monitoring reports. MAIN RESULTS AND THE ROLE OF CHANCE: Regulations based on social characteristics of treatment seekers who are not applicable to other medical treatments, including relationship status and sexual orientation, appear to have the greatest impact on utilization. Countries with the most generous public financing schemes tend to restrict access to covered IVF to a greater degree. However, no link could be established between IVF utilization and the manner in which coverage was regulated or the level of public financing. LIMITATIONS, REASONS FOR CAUTION: Owing to the lack of data regarding the actual level of public versus private financing of IVF it is impossible to draw conclusions regarding equity of access. Moreover, the regulatory and utilization data were not completely temporally matched in what can be a quickly changing regulatory landscape. WIDER IMPLICATIONS OF THE FINDINGS: Whether motivated by cost, eligility restrictions or the availability of particular services, cross-border treatment seeking is driven by regulatory policies, underscoring the extra-territorial implications of in-country political decisions regarding access to IVF. STUDY FUNDING/COMPETING INTEREST(S): There was no funding source for this study. The authors have no conflicts of interest to declare.

Impact of an educational intervention and insurance coverage on patients' preferences to transfer multiple embryos.

Multiple gestations resulting from IVF continue to be a major problem associated with maternal/neonatal morbidity and mortality including preterm labour/delivery, pre-eclampsia and post-partum haemorrhage. A prospective survey at a university IVF clinic evaluated the effect of education and insurance coverage on patients' preferences for single-embryo transfer (SET) versus double-embryo transfer (DET). Patients undergoing IVF treatment from September 2008 to October 2009 were included. The main outcome measure was patients' preference of SET versus DET. Patients were sent an educational handout describing maternal and fetal risks of twin gestation. A total of 163 patients (32.6% response rate) returned the pre- and post-education surveys regarding preferences for SET versus DET based on three different IVF insurance coverage scenarios (no coverage, two cycles covered and unlimited coverage). There were statistically significant differences in the preference for SET before and after education across all insurance scenarios (scenario 1, 42.0% versus 61.1%; scenario 2, 50.6% versus 71.0%; and scenario 3, 61.7% versus 79.6%; P<0.001 for all scenarios). Before education, patients preferred SET more in the unlimited coverage scenario (61.7%) versus no coverage (42.0%; P<0.001). An educational handout and increasing the amount of insurance coverage significantly increased a patient's preference for SET.

Elective single-embryo transfer.

As in vitro fertilization implantation rates have improved, the practice of transfering multiple embryos must be evaluated. The purpose of this document is to reassess the literature on elective single-embryo transfer, to provide guidance for patient selection, and to discuss barriers to utilization.

Assisted reproductive technology: public funding and the voluntary shift to single embryo transfer in Australia.

OBJECTIVES: To calculate cost savings to the Australian federal and state governments from the reduction in twin and triplet birth rates for infants conceived by assisted reproductive technology (ART) since 2002, and to determine the number of ART treatment programs theoretically funded by means of these savings. DESIGN AND SETTING: Costing model using data from the Australia and New Zealand Assisted Reproduction Database, the National Perinatal Data Collection and Medicare Australia on ART treatment cycles undertaken in Australia between 2002 and 2008. MAIN OUTCOME MEASURES: Annual savings in maternal and infant inpatient birth-admission costs resulting from the reduction in ART multiple birth rate; theoretical number of ART treatment programs funded and infants born by means of these savings. RESULTS: The reduction in the ART multiple birth rate from 18.8% in 2002 to 8.6% in 2008 resulted in estimated savings to government of $47.6 million in birth-admission costs alone. Theoretically, these savings funded 7042 ART treatment programs comprising one fresh plus one frozen embryo transfer cycle, equating to the birth of 2841 babies. Fifty-five per cent of the increased use of ART services since 2002 has been theoretically funded by the reduction in multiple birth infants. CONCLUSIONS: Against a backdrop of supportive public funding of ART in Australia, a voluntary shift to single embryo transfer by fertility clinicians and ART patients has resulted in substantial savings in hospital costs. Much of the growth in ART use has been theoretically cross-subsidised by the move to safer embryo transfer practices.