Assisted Reproductive Technologies

Transcription

1 Assisted Reproductive Technologies ADDENDUM TO THE STEP REPORT August, 26 Submitted to: The Alberta Health Technologies Decision Process Research & Innovation Branch Strategic Planning & Policy Development Division Alberta Health Submitted by: Health Technology & Policy Unit School of Public Health Department of Public Health Sciences University of Alberta Production of this document has been made possible by a financial contribution from Alberta Health under the auspices of the Alberta Health Technologies Decision Process: the Alberta model for health technology assessment and policy analysis. The views expressed herein do not necessarily represent the official policy of Alberta Health.

2 ADDENDUM TO THE ARTS STEP REPORT SUBMITTED TO THE ALBERTA HEALTH TECHNOLOGIES DECISION PROCESS (AHTDP) AUGUST, 26 PREAMBLE In 22, under the auspices of the AHTDP, the Health Technology and Policy Unit (HTPU) at the University of Alberta conducted a health technology assessment (HTA) on assisted reproductive technologies (ARTs) for the treatment of infertility. The HTA, which took the form of an S-T-E report, reviewed available clinical evidence on the safety and effectiveness of ARTS and examined economic implications of possible policy options through cost-effectiveness and budget impact analyses (BIA). Different regulation and funding scenarios, were developed from the results of a jurisdictional scan of ARTs regulatory and reimbursement policies in other parts of Canada and abroad. Decision analytic and economic modeling techniques were used to estimate the cost of each policy option over 8 years (following a single cohort of women receiving ARTs and their offspring up to the age of 8 years) from both a societal and healthcare payer/system perspective. Estimates for model inputs were based on publicly available information at the time of the analysis. Key information sources included 29-2 Canadian Assisted Reproductive Technologies Registry (CARTR) data, published studies, and Alberta Health administrative data (for healthcare utilization and costs other than those related to the ARTs procedures). Since ARTs are not provided through the public healthcare system in Alberta, the costs of these procedures were obtained from the two IVF clinics in Alberta at the time (one in Calgary and one in Edmonton). The final report was submitted to the AHTDP in June 23. It concluded that publicly funding ARTS (i.e., in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI)) with restrictive limitations (e.g., on the number of embryos transferred) could offer cost-savings to the healthcare system when compared to status quo. For the status quo approach, it was assumed that pregnancy rates for singletons, twins and higher order multiples and costs associated with the current state (no public funding and no regulations) would remain unchanged. The anticipated savings under a policy that comprises public funding with restrictive conditions on the number of embryos transferred (referred to in the report as the restrictive policy ) were attributable to a reduction in the rates of twins and higher order multiples born prematurely, who typically spend extended periods of time in neonatal intensive care units. Also, they are more likely to experience developmental delays and chronic health and social issues that require costly ongoing support from health and social systems. As part of its ongoing activities, the HTPU regularly monitors Canadian news sites and press releases from relevant healthcare professional societies, checks the websites of ministries of health across Canada and performs updated searches of electronic bibliographic databases in order to identify any 26 Government of Alberta 2

3 new information related to topics on which it has conducted an HTA. In the fall of 25, such scans picked up recently announced changes in IVF funding policies in two Canadian provinces, along with press releases containing January 24 to July 25 CARTR Plus data on overall pregnancy rates for singletons, twins and higher order multiples in provinces across Canada. As a result, the original economic model and values used for its parameters were revisited in order to generate updated costing results. No additional information affecting the validity of other findings in the original report was found, CURRENT CONTEXT Changes in IVF funding policies across Canada Quebec: In November 25, Quebec eliminated its publicly-funded IVF program. Established in 2, the program provided coverage for the full cost of IVF, which included up to three IVF attempts, even in couples who had already conceived a child through its support. 2 While the program successfully reduced multiple pregnancy rates from 3% to 5%, it ran over budget. Quebec now offers tax credits to eligible couples (i.e., childless). Those seeking IVF pay up front for the procedure, and depending on their income, a portion of their costs may be reimbursed. The portion is based on a sliding scale of tax credits. The scale ranges from 8 per cent of costs for couples with a family income of less than $5, to 2 per cent of costs for families who earn more than $2, a year. Ontario: On October, 25, the Ontario Ministry of Health announced its plans to fund IVF for approximately 5, women at an annual cost of $5 million. 3 The new coverage, which took effect in December 25, provides one cycle of IVF and unlimited rounds of intrauterine insemination (IUI) to women under the age of 43 years, regardless of their family status or sexual and gender orientation. The age limit was set based on recommendations from an expert advisory panel. One cycle of IVF is defined as the retrieval of an egg or eggs and the one-at-a-time transfer of all viable embryos, providing multiple chances of achieving a pregnancy. The $5 million fund is separate from the Ontario Health Insurance Plan. Fifty fertility clinics across Ontario have been allocated funds to provide a fixed number of publicly funded cycles per year. 4 Individual doctors and clinics are left to decide which eligible patients will receive those cycles. Many use lotteries to distribute them. In May 26, Ontario s fertility specialists reported that within weeks of implementing the new funding policy, clinics had reached their yearly cap, caseloads for some had doubled, and appointments for publicly funded treatment were being booked into 28. However, no information related to the effect of the policy on rates of multiple births was reported. 5 New Brunswick: In July 24, the New Brunswick Department of Health announced the creation of a Special Assistance Fund for Infertility Treatment. The fund, which provides one-time grants, allows individuals to claim 5% of eligible costs for IVF and IUI up to a maximum of $5,. 6 Manitoba: Manitoba continues to offer its fertility treatment tax credit, in which 4% of eligible costs of fertility treatments provided by a Manitoba licensed physician or infertility treatment clinic can be claimed for a yearly maximum tax credit of $8,. 26 Government of Alberta 3

4 Recent initiatives of the Canadian Fertility and Andrology Society In late 22, the Canadian Fertility and Andrology Society (CFAS) released a position statement about reducing multiple pregnancy risk associated with IVF/ICSI on behalf of IVF Medical Directors of all fertility clinics in Canada. 7 It contained a series of goals, which clinics had unanimously agreed to work towards over the next three years. The goals included reducing IVF/ICSI-related multiple pregnancy rates to 5% in Canada by the end of 25; redefining assisted human reproduction (AHR) success as a healthy singleton live birth ; and developing educational material for physicians and patients on the risks of multiple pregnancies to mothers, fetuses, newborns and children, as well as the social, emotional and financial implications. In the fall of 23, the CFAS Clinical Practice Guidelines Committee published the first set of Canadian guidelines for fertility physicians and clinics across Canada regarding the number of embryos to transfer in order to minimize multiple pregnancy rates (including twins) while maintaining acceptable live birth rates. 8 The guidelines, which incorporate findings from a systematic review of relevant published clinical studies and the experience of local fertility experts, provide the following recommendations: For women < 35 years of age - For cleavage and blastocyst stage embryos, a single embryo should be transferred - For women with a poor prognosis, transfer of up to two embryos is reasonable For women 35 to 37 years of age - For cleavage and blastocyst stage embryos, transfer of one embryo is reasonable - For women with a poor prognosis, transfer of up to two embryos is reasonable For women 38 to 39 years of age - For cleavage stage embryos, transfer of up to two embryos is reasonable - For women with a poor prognosis and cleavage stage embryos, transfer of up to three embryos may be reasonable - For blastocyst stage embryos, transfer of to two embryos is reasonable - For women with a poor prognosis and blastocyst stage embryos, transfer of up to two embryos may be reasonable For women 4 to 42 years of age - For cleavage stage embryos, transfer of up to three embryos may be considered - For women with a poor prognosis and cleavage stage embryos, transfer of up to four embryos may be considered - For blastocyst stage embryos, transfer of up to two embryos may be considered - For women with a poor prognosis and blastocyst stage embryos, transfer of up to three embryos may be considered For women > 42 years of age 26 Government of Alberta 4

5 - For cleavage stage embryos, transfer of up to five embryos may be considered - For blastocyst stage embryos, transfer of up to three embryos may be considered In October25, at the annual meeting of CFAS, the most recent multiple pregnancy rates from the CARTR Plus registry were presented. They reflected data from 34 of the 36 fertility clinics across Canada (including both clinics in Alberta) for the reporting period from January, 24 to July 5, Treatment cycle and birth outcomes were also presented, but not for the same period. They relied on for the years 2, 22, and 23. The following findings were noted, since they related to key assumptions of the economic model used to estimate the costs of each policy option in the original HTA report: The proportion of embryos transferred at the blastocyst stage was % higher than that of embryos transferred at the cleavage stage (the original economic model assumed they were equal) (note: blastocyst stage embryo transfer is associated with higher pregnancy rates). The proportion of cycles involving ICSI was 73.4% (the original economic model assumed 55% of cycles would use ICSI) (note: ICSI is associated with higher pregnancy rates when compared to conventional IVF). The proportion of couples opting for preimplantation genetic diagnosis/screening was approximately 9% (almost double the assumption in the original economic model (5%)). The overall pregnancy rate one year after the launch of the clinical practice guidelines was 35% (an overall rate of 33% was assumed in the original model). The percentage of multiple births per ongoing clinical pregnancy (twins and higher order multiples) was 3.3% (significantly lower than the value used for the status quo option in the original model (3%)). Given the potential impact of the findings on estimates of the economic implications of each policy option considered in the HTA report, particularly that of status quo, a decision to re-run the economic model was made. Original model inputs were replaced with the most current available, published studies, and recommendations on embryo transfer number in the CFAS clinical practice guidelines mentioned above. FINDINGS BASED ON CURRENT CONTEXT Updated estimates of the proportion of IVF cycles involving single, double, and triple embryo transfers within each age group under the four policy options ( status quo, restrictive, permissive and Quebec ) are presented in Table. When the original HTA was conducted, no national or local data on the extent of use of single, double and triple embryo transfers were available for the status quo option. The updated estimates for this option reflect the experiences of clinics since voluntary compliance with the CFAS guidelines was implemented. 26 Government of Alberta 5

6 Using the updated estimates of embryo transfer numbers, overall pregnancy rates after one treatment cycle (fresh or frozen) were calculated for the status quo option (Table 2). Values were comparable to those in the initial HTA report, suggesting that it is possible to maintain pregnancy rates while adhering to guidelines on the appropriate number of embryos to transfer in women of different ages. Twin pregnancy rates were significantly lower than those calculated with the original model (less than half), while pregnancy rates for higher order multiples (triplets or greater) were similar between the original and updated models. The total healthcare costs of each of the four funding policy options, as well as a set of regulate but do not fund options, based on the updated model are presented in Table 3. The probability and cost inputs used are listed in Appendix A and Appendix B, respectively. For the do not fund but regulate options, the same conditions on the number of embryos transferred as those used in the three funding options were used. The total healthcare costs include those incurred by a single cohort of women receiving IVF under the four different policy options and any infants born up to the age of 8 years (i.e., a time horizon of 8 years). The status quo option was found to be less costly than any of the funding policy options. However, two of the three regulate but do not fund options were associated with lower costs than the status quo option. CONCLUSIONS Given recent changes in practice among IVF physicians and clinics in Canada, the introduction of public funding for IVF no longer offers a means of reducing healthcare costs. 26 Government of Alberta 6

7 Table. Estimated proportion of cycles involving single (), double () and triple () embryo transfers by age and policy option Policy option Status quo a Restrictive policy Permissive policy Quebec policy b Description IVF remains unfunded and unregulated Age of female < 35 years (all cycles) - Fresh: Frozen:.699 (all cycles) - Fresh: Frozen:.288 (all cycles) - Fresh: 8 - Frozen: 3 35 to 39 years (all cycles) - Fresh: Frozen:.64 (all cycles) - Fresh: Frozen:.369 (all cycles) - Fresh:.75 - Frozen: 8 4 years (all cycles) - Fresh:.29 - Frozen:.464 (all cycles) - Fresh: Frozen:.42 (all cycles) - Fresh: Frozen:.6 IVF is funded but with the most restrictive conditions on the number of embryos transferred - Fresh:. (all cycles) - Frozen:. (all cycles) - Fresh:. (first two cycles) - Frozen:. (first two cycles) - Fresh:. (third cycle) - Frozen:. (third cycle) - Fresh:. (first cycle) - Frozen:. (first cycle) - Fresh:. (second and third cycles - Frozen:. (second and third cycles) IVF is funded with the most permissive conditions on the number of embryos transferred - Fresh:. (first cycle) - Frozen:. (first cycle) - Fresh:. (second and third cycles) - Frozen:. (second and third cycles) - Fresh:. (first cycle) - Frozen:. (first cycle) - Fresh:. (second and third cycles) - Frozen:. (second and third cycles) - Fresh:. (all cycles) - Frozen:. (all cycles) IVF is funded based on embryo transfer policies in Quebec s IVF program (no longer in existence) - Fresh:.89 (all cycles) - Frozen:.89 (all cycles) - Fresh:. (all cycles) - Frozen:. (all cycles) - Fresh:.59 (all cycles) - Frozen:.59 (all cycles) - Fresh:.38 (all cycles) - Frozen:.38 (all cycles) - Fresh: (all cycles) - Frozen: (all cycles) - Fresh:.3 (all cycles) - Frozen:.3 (all cycles) - Fresh:.56 (all cycles) - Frozen:.56 (all cycles) - Fresh:.4 (all cycles) - Frozen:.4 (all cycles) a. From presentation: Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus). The 6st annual meeting of the Canadian Fertility and Andrology Society (CFAS). Halifax, Nova Scotia. October 25. b. From recent study of Quebec experience: Velez, M.P., Kadoch, I.J., Phillips, S.J., Bissonnette, F. Rapid policy change to single-embryo transfer while maintaining pregnancy rates per initiated cycle. Reprod Biomed Online. 23;26: Government of Alberta 7

8 Table 2. Updated estimates of pregnancy rates after one treatment cycle under the status quo policy option Age Pregnancy rate (%) after one treatment cycle a Fresh Cycle Frozen Cycle Per embryo Per embryo Per cycle start transfer cycle Per thaw transfer cycle <35 years years years years > 43 years a. From presentation: Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus). The 6st annual meeting of the Canadian Fertility and Andrology Society (CFAS). Halifax, Nova Scotia. October 25. Table 3. Estimated total healthcare costs incurred by a single cohort of women receiving IVF under different policy scenarios and infants born up to 8 years of age Category of healthcare cost (Cdn) Total Policy Scenario Treatment Pregnancy & delivery c Neonatal & postnatal care d healthcare costs (Cdn) Maintain status quo/no change Status Quo (No Regulation, No Funding) N=,7 $3,55,342 a $2,268,782 $8,22,258 $97,5,382 Regulate and fund (i.e., fund with restrictions/criteria) Fund with Restrictive ET Policy $8,938,76 b $8,9,542 $93,673,598 $93,522,846 N=2,793 Fund with Permissive ET Policy $77,82,442 b $22,455,56 $93,823,254 $294,99,22 N=2,793 Fund with Quebec s ET Policy $8,33,59 b $9,263,625 $7,742,462 $27,39,246 N=2,793 Regulate but do not fund No Funding, Restrictive ET Policy $3,573,38 a $,577,883 $57,35,82 $72,52,446 N=,7 No Funding, Permissive ET Policy $3,59,733 a $3,748,269 $8,667,298 $36,6,3 N=,7 No Funding, Quebec s ET Policy N=,7 $3,58,2 a $,794,56 $65,964,772 $8,277,39 a. Includes costs related to pregnancy confirmation (e.g., ultrasound, blood tests and urine analysis) and miscarriage which are covered by the publicly funded healthcare system b. Includes costs related to fertility treatment, as well as those related to pregnancy confirmation and miscarriage c. Includes costs related to ongoing pregnancy and delivery for mom and infant d. Includes costs of infant from birth to 8 years of age 26 Government of Alberta 8

9 REFERENCES. IVF drug funding could be reduced in Quebec. CBC News [Internet]. 26 Feb 5. Available: 2. Quebec in-vitro fertilization: A breakdown of new restrictions on treatment. CBC News [Internet]. 25 Nov 3. Available: 3. Ontario offering 5 government-funded fertility treatment clinics. CBC News [Internet]. 25 Dec. Available: 4. Ferguson R. Ontario to cover in-vitro fertilization treatments. Toronto Star [Internet]. 25 Oct. Available: 5. Blackwell T. Huge demand for IVF treatment in Ontario- where it s fully funded has wait lists stretching to 28. National Post [Internet]. 26 May 2. Available: 6. New Brunswick Government. Infertility treatment fund announced [Internet]. 24 Jul 4. Available: 7. Reduction of multiple pregnancy risk associated with IVF/ICSI: IVF medical directors of Canada position statement 22 [Internet]. Canadian Fertility and Andrology Society. 22. Available: 8. Min J, Sylvestre C. Guidelines on the number of embryos transferred [Internet]. Canadian Fertility and Andrology Society. 23. Available: 9. Lanes A, Fell D, Guo YM, Elliott M, et al. Canadian assisted reproductive technologies register plus (CARTR Plus). Canadian Fertility and Andrology Society 6st annual meeting. Halifax; 25 Oct. 26 Government of Alberta 9

10 Appendix A. Probability inputs used in the updated model Probability Restrictive ET Policy Permissive ET Policy Status Quo Quebec ET Policy (N=,7) Variable < < < < Source Age (p. 35) Pregnancy after fresh cycle : - Pregnancy - No pregnancy Ongoing pregnancy after fresh cycle : - Ongoing pregnancy - Miscarriage & 8) Pregnancy after frozen cycle : - Pregnancy - No pregnancy Ongoing pregnancy after frozen cycle : - Ongoing pregnancy - Miscarriage & 8) Government of Alberta

11 Appendix A. Probability inputs used in the updated model Probability Status Quo Restrictive ET Policy Permissive ET Policy Quebec ET Policy (N=,7) Variable < < < < Source Pregnancy after fresh cycle 2: - Pregnancy - No pregnancy Ongoing pregnancy after fresh cycle 2: - Ongoing pregnancy - Miscarriage Pregnancy after frozen cycle 2: - Pregnancy - No pregnancy Ongoing pregnancy after frozen cycle 2: - Ongoing pregnancy - Miscarriage Pregnancy after fresh cycle 3: - Pregnancy - No pregnancy Ongoing pregnancy after fresh cycle 3: - Ongoing pregnancy - Miscarriage Pregnancy after frozen cycle 3: - Pregnancy - No pregnancy Ongoing pregnancy after frozen cycle 3: - Ongoing pregnancy - Miscarriage Order of pregnancy after fresh cycle : - Singleton - Twin pregnancy - HOM pregnancy & 8) 5 & 8) 5 & 8) 5 & 8) 7 & 8) Government of Alberta

12 Appendix A. Probability inputs used in the updated model Probability Status Quo Restrictive ET Policy Permissive ET Policy Quebec ET Policy (N=,7) Variable < < < < Source Order of pregnancy after frozen cycle : - Singleton pregnancy - Twin pregnancy - HOM pregnancy , 7 & 8) Order of pregnancy after fresh cycle 2: - Singleton - Twin pregnancy - HOM pregnancy Order of pregnancy after frozen cycle 2: - Singleton - Twin pregnancy - HOM pregnancy Order of pregnancy after fresh cycle 3: - Singleton - Twin pregnancy - HOM pregnancy Order of pregnancy after frozen cycle 3: - Singleton & 8) 5, 7 & 8) 7 & 8) 26 Government of Alberta 2

13 Appendix A. Probability inputs used in the updated model Probability Status Quo Restrictive ET Policy Permissive ET Policy Quebec ET Policy (N=,7) Variable < < < < Twin pregnancy - HOM pregnancy Singleton pregnancy: - Complicated - Uncomplicated Dropout after failure (left over embryos): - Failure & continue frozen cycle - Failure & dropout Dropout after failure (no left over embryos): - Failure & continue fresh cycle - Failure & dropout Type of delivery for singletons: - Vaginal - Caesarean Type of delivery for twins: - Vaginal Caesarean Type of delivery for HOMs: - Vaginal - Caesarean Birth outcome for singletons: - Live - Still Birth outcome for twins: - Both live - One live - Both still Birth outcome for HOMs: - Three live - Two live - One live - Three still Neonatal outcome for singletons: - Death - Survival Neonatal outcome for twins: - Death - Survival Neonatal outcome for HOMs: - Death Government of Alberta Source 5, 7 & 8) Expert opinion 22 Expert opinion 22 Expert opinion 22 Alberta Perinatal Health Program Data April 29 - Dec

14 Appendix A. Probability inputs used in the updated model Probability Restrictive ET Policy Permissive ET Policy Status Quo Quebec ET Policy (N=,7) Variable < < < < Survival Postnatal health status for singletons -4 yrs: - Healthy - Unhealthy Postnatal health status multiples -4 yrs: - Healthy - Unhealthy Postnatal health status multiples -4 yrs: - Healthy - Unhealthy Postnatal health status for singletons 5-8 yrs: - Healthy - Unhealthy Postnatal health status multiples 5-8 yrs: - Healthy - Unhealthy Postnatal health status multiples 5-8 yrs: - Healthy Source 22 (Table 4) Unhealthy: birthweight <,5 grams Published literature (proportions of unhealthy infants increased by.5-expert opinion) - Unhealthy Number of patients in status quo based on 22 : 9% of all cycles in 22 data were from Alberta. Assumption: 9% of individual women (8,995) in 22 were from Alberta (N =.9*8,995 =,7). Gunby J. 22. Assisted reproductive technologies (ART) in Canada: 22 results from the Canadian ART Register. Increase in number of patients in publicly funded scenarios based on 23 Quebec data: 85 women accessed IVF after introduction of public funding in comparison to 499 women before public funding. Assumption: same increases would be seen in Alberta (N =,7 * 85/499 = 2,793). Velez, M.P., Kadoch, I.J., Phillips, S.J., Bissonnette, F. Rapid policy change to single-embryo transfer while maintaining pregnancy rates per initiated cycle. Reprod Biomed Online. 23;26: Government of Alberta 4

15 Appendix B. Cost inputs used in the updated model Variable Cost (25 $Cdn) Source One-time registration fee $3 Calgary Regional Fertility Program Costs/Fees (regionalfertilityprogram.ca/ivficsi- Fresh cycle $4,34 program/ivf-2/costsfees/). Includes: 73.6% ICSI (7% with sperm retrieval and 3% with Cryopreservation $925 ejaculated sperm) and 2.7% PGD/PGS. Frozen cycle after OHSS $6 Frozen cycle after failed fresh $,28 Pregnancy confirmation $837 Alberta Health billing data (physician claims, ambulatory care, and inpatient databases) No pregnancy confirmation $45 Miscarriage $4,2 Pregnancy: - Singleton complicated - Singleton uncomplicated - Twin - Higher order multiple (HOM) Delivery: - Singleton vaginal - Singleton caesarean - Twin vaginal - Twin caesarean - HOM vaginal - HOM caesarean Postnatal health care up to 4 years: - Healthy singleton - Unhealthy singleton - Healthy multiple - Unhealthy multiple Health care 5-8 years of age: - Healthy singleton - Unhealthy singleton - Healthy multiple - Unhealthy multiple $3,764 $6,735 $,8 $8,59 $4,83 $5,828 $6,334 $5,674 $2,97 $9,889 Cost per child $8,893 $8,54 $22,52 $,398,56 Cost per child $2,24 $67,48 $27,824 $2,67 for mothers of infants born between April, 25 to March 3, 26 (costs inflated using CPI to obtain 25 dollars) Alberta data from Canadian Institutes for Health Information National Health Expenditures Report 2 (costs inflated using CPI to obtain 25 dollars) 26 Government of Alberta 5