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Society for Assisted Reproductive Technology and assisted reproductive technology in the United States: a 2016 update
ASRM PAGES
Society for Assisted Reproductive Technology and assisted reproductive technology in the United States: a 2016 update James P. Toner, M.D., Ph.D.,a Charles C. Coddington, M.D.,b Kevin Doody, M.D.,c Brad Van Voorhis, M.D.,d David B. Seifer, M.D.,e G. David Ball, Ph.D., H.C.L.D.,f Barbara Luke, ScD, M.P.H.,g and Ethan Wantman, M.B.A.h a Atlanta Center for Reproductive Medicine, Atlanta, Georgia; b Division of Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, Minnesota; c Center for Assisted Reproduction, Dallas, Texas; d University of Iowa Carver College of Medicine, Iowa City, Iowa; e The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; f Seattle Reproductive Medicine, Seattle, Washington; g Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, Michigan; and h Redshift Technologies, Inc., New York, New York
The Society for Assisted Reproductive Technology (SART) was established within a few years of assisted reproductive technology (ART) in the United States, and has not only reported on the evolution of infertility care, but also guided it toward improved success and safety. Moving beyond its initial role as a registry, SART has expanded its role to include quality assurance, data validation, practice and advertising guidelines, research, patient education and advocacy, and membership support. The success of ART in this country has greatly benefited from SART's role, as highlighted by a series of graphs. SART continues to set the standard and lead the way. (Fertil SterilÒ 2016;-:-–-. Ó2016 by American Society for Reproductive Medicine.) Key Words: SART, IVF, history of IVF, SART Registry Discuss: You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/tonerj-sart-art-us2016-update/
T
he progress made in infertility care in the United States is inextricably linked to the membership and activities of the Society for Assisted Reproductive Technology (SART), the professional organization formed 30 years ago to collect and report on its treatment outcomes. In this two-part paper, we first review the evolution of the society from its origin as a registry to its current multifaceted mission and then describe the
progression of care as captured by the registry.
PART 1: THE SOCIETY FOR ASSISTED REPRODUCTIVE TECHNOLOGY Founding In 1981, shortly after the birth of Elizabeth Carr, the first in vitro fertilization (IVF) child born in the United States, Dr. Howard Jones gathered the leading
Received May 19, 2016; accepted May 24, 2016. J.P.T. has nothing to disclose. C.C.C. is a member of the AbbVie Advisory Board. K.D. has nothing to disclose. B.V.V. has nothing to disclose. D.B.S. reports royalties paid by Beckman-Coulter to Rutgers University/Massachusetts General Hospital for a license to use AMH as a method to determine ovarian reserve. G.D.B. has nothing to disclose. B.L. has received consulting fees from the Society for Assisted Reproductive Technology. E.W. is an employee of Redshift (Society for Assisted Reproductive Technology's data vendor). Reprint requests: James P. Toner, M.D., Ph.D., Past President, SART, Atlanta Center for Reproductive Medicine, 5909 Peachtree Dunwoody Road, Atlanta, Georgia 30328 (E-mail: jim.toner@acrm. com). Fertility and Sterility® Vol. -, No. -, - 2016 0015-0282/$36.00 Copyright ©2016 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2016.05.026 VOL. - NO. - / - 2016
practitioners of the 5 existing US IVF programs (Norfolk, Vanderbilt, the University of Texas at Houston, University of Southern California, and Yale) to discuss establishing a national registry of IVF attempts and outcomes. Two years later, in 1985, Drs. Alan DeCherney and Richard Marrs founded the Society for Assisted Reproductive Technology (SART) as a special interest group in the American Fertility Society (now the American Society for Reproductive Medicine [ASRM]) for that purpose (1). Initially, the data were tabulated at the clinic level and reported at the national level. Individual clinics could measure comparisons to national outcomes and the public could see what was happening broadly within the United States. National reports were made public by way of annual publications in Fertility and Sterility. Subsequent modifications to reporting 1
ASRM PAGES included a transition to both cycle-specific reporting and public reporting of outcomes at the individual clinic level, as required by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law No. 102-493, October 24, 1992) (2). Over the years that followed, SART's activities have expanded well beyond the simple collection of assisted reproductive technology (ART) outcomes.
Current Scope As of 2014, SART had 375 member clinics in the United States accounting for 83% of all clinics required to report and 91% of all reported ART cycles. The organization is led by an executive council of 28 professionals who sit on 15 committees populated by another 80 professional volunteers. The senior executive roles are elected and term-limited, which enhances the credibility of SART's operations. The only permanent employee is an administrator. SART also has contracts with a researcher and database administrator. The company providing database administration is also an active participant in developing specifications and custom software to meet the current needs of comprehensive data collection. SART's mission is to ‘‘promote and advance the standards for the practice of assisted reproductive technology to the benefit of our patients, members, and society at large.’’
‘‘Setting the Standard’’ Setting the standard is a primary means by which SART achieves its mission. The committees involved with this activity include: Practice Committee. This committee develops and issues guidance for evidence based care. Currently more than 60 documents have been released and are accessible online in the members section of the SART website (www.sart.org/members). Quality Assurance Committee (QA). QA is one of the most direct ways through which SART accomplishes its stated mission. The registry allows for measurement of clinical effectiveness of care, measurement of safety and harm, and assessment of the quality of care. This committee surveys outcomes each year to identify clinics with below average performance. The committee reaches out to the identified clinics and offers remediation if the issue has not already been addressed. If performance does not improve over successive years, loss of membership can occur. QA metrics currently focus on low pregnancy rates and high rates of multiple pregnancies. Advertising Committee. SART has developed advertising guidelines to assure fairness and accuracy. One of the guidelines prohibits direct clinic-to-clinic comparisons of outcome data. This committee continually reviews member websites (155 were reviewed in 2015), and fields complaints of violations from members and patients. Current guidelines require the posting of the full Clinic Summary Report (CSR) to ensure fair and full outcome disclosures. With the expansion of the CSR, a new set of guidelines will be forthcoming. 2
Validation Committee. This committee works with the Centers for Disease Control and Prevention (CDC) to ensure that data reported by clinics to the registries (SART Clinical Outcomes Reporting System [CORS] or National ART Surveillance System [NASS]) are accurate. Twenty clinics are visited each year. Low error rates have been found. SART's validation process goes beyond CDC's validation efforts. SART collects additional data fields requiring independent validation. Moreover, the Executive Council has authorized the Validation Committee to develop ‘‘triggers’’ to perform on site validation of ‘‘outliers’’ not based solely on below average outcomes, but also inexplicable ones. Validation is an important part of any medical registry, but is exceedingly important when submitted data are publically reported at the clinic level. Membership Committee. This committee evaluates the credentials of the primary professionals in each practice to ensure reproductive endocrinology and infertility (REI) board certification, lab accreditation, and compliance with advertising guidelines. While SART works hard to retain all members, membership has been revoked for persistently poor clinical performance, loss of accreditation, violation of advertising guidelines, and failing to report outcomes.
Membership Support In addition to setting the standard, SART supports its members via: SART website. SART has developed a comprehensive website that serves the needs of both patients and members (in a members-only section). It has recently been updated to be more informative and patient focused. This redesign was done in coordination with ASRM's information technology team. Find a Clinic. The SART website includes a tool for patients to find SART member clinics throughout the United States and to request information from those clinics. Informed Consents. SART has developed model consents for routine IVF as well as its variants: egg donation, donor egg recipient, cryopreservation (both eggs and embryos), and gestational carrier. Disposition documents for eggs and embryos have also been developed. These are available in both English and Spanish in an editable format to permit adjustment for local needs. Research. SART makes its large dataset available to members upon approval of their research plan. It has developed an online ‘‘portal’’ to make requesting datasets easier. Twenty-five requests were received in 2015. Since 2006, SART has funded an epidemiologist to study ART outcomes and to develop National Institutes of Health (NIH)-funded research. Taken together, more than 60 publications have used the SART database. Findings from these studies have influenced practice guidelines, and is a primary means by which SART guides practice. Government relations. SART has collaborated with the CDC since the initiation of the Fertility Clinic Success Rate & Certification Act of 1992, and continues to strive for a VOL. - NO. - / - 2016
Fertility and Sterility® coordinated approach to data collection and outcome reporting. SART also participates in the National Coalition for the Oversight of Assisted Reproductive Technology (NCOART). Member advocacy. Under the direction of ASRM's Washington DC office of Public Affairs, SART has supported members in countering state or local legislation that is unfavorable for patient access to ART services. SART works with consumer advocates such as the National Infertility Association (RESOLVE) and the American Family Association (AFA), and the insurance industry, to foster shared goals. Expanding access to care remains an important goal. It is also a member of the Women's Health Registry Alliance of the American Congress of Obstetricians and Gynecologists (ACOG). ASRM has provided significant assistance in this arena. Quality Assurance Dashboard. SART is developing a tool for member clinics that would provide for real-time comparisons of QA metrics to historical trends within a clinic, and contemporaneous benchmarking to national performance. Physician Treatment Model. As an extension of the patient predictor models (discussed later), SART has also developed physician treatment models to predict the chances of live birth and multiple birth. These web-based tools, which will be piloted in 2016, utilize data from more than 1.4 million cycles in SART CORS from 2004–2013 and are planned to be a series of five models. All models will include year of treatment, maternal age, gravidity and reproductive history, infertility diagnoses, body mass index, and day of embryo transfer. The first cycle models will be based on the use of autologous oocytes and fresh embryos; number of oocytes retrieved, embryos transferred, and embryos cryopreserved; and a future model will also include embryo morphology. A second cycle model will be based on factors in the first cycle, which did not result in a live birth. Two additional models for any cycle will include factors in all prior cycles, and the use of either fresh or thawed embryos and other factors in the current cycle.
Patient Education/Advocacy SART also provides service to patients, via its recently enhanced website (http://sart.org). It features educational material on IVF, including an image gallery. It also provides access to these benefits: Clinic Summary Report (CSR). SART has evolved the federally-mandated clinic summary report to reflect changing practice and incent best practice. In response to the increased use of preimplantation genetic screening (PGS), delayed transfers, and embryo accumulation, the prior data collection system required revision (3–5). The new collection system links the embryo transfer back to the cycle in which the eggs were obtained, and allows for multiple retrieval cycles to be linked to one transfer cycle. The CSR also highlights the live-birth rate per cycle start, which is the required metric in the original law, VOL. - NO. - / - 2016
and appropriately aligns the outcome of interest to patients (a live-born baby) with patient choices (whether or not to initiate a cycle to obtain eggs). The CSR now permits a wide range of data filters, including preimplantation genetic diagnosis (PGD)/PGS, blastocyst transfer, first cycle, etc. Find a Clinic (http://sart.org/Find_A_Clinic/). This feature allows a patient to specify a state or zip code to identify SART member clinics in that area. The address and contact information are displayed, as well as a link to the clinic summary report. Patients can directly request follow-up calls or emails from target clinics. Patient Predictor (https://www.sartcorsonline.com/Predictor/Patient). Because the SART database has more than 1.4 million treatment cycles, the ability to create a preeminent prediction model is second to none. The first version of the predictor (implemented in 2014 and based on 2004– 2012 cycles) included 3 models, showing the chance for live birth after 1, 2, and 3 ‘‘fresh’’ IVF attempts based on age, body mass index (BMI), prior gravidity, and cause of infertility, as well as first cycle using donor oocytes. It also compares multiple pregnancy rates when one embryo is transferred over two cycles versus two embryos transferred in one cycle. The revised version (implemented in 2016 and based on 2006–2013 cycles standardized to 2013) includes day of transfer, and expands the donor model to include the chance of a live birth and a multiple birth with one or two embryos transferred. History of IVF (http://sart.org/History_of_IVF/). This links to a series of images featuring trends in IVF in the United States since reporting began in 1985. The graphs are updated annually. IVF4VETS (https://www.sartcorsonline.com/ServiceToVeterans.aspx). A federal bill to permit veterans to receive IVF care has not yet passed Congress. To remedy this deficiency, certain SART member clinics have pledged reduced fee IVF to assist veterans with injuries stemming from their service that affects their reproductive capacity. ReproductiveFacts.org (http://www.reproductivefacts.org). In concert with the ASRM, SART links to and support content at reprouctivefacts.org. Mobile App. SART is developing a mobile application for patients to assist them in estimating their success with IVF, finding a local clinic, estimating their due date once pregnant, and much more. Extending Access to Care. In concert with ASRM and patient advocacy groups, SART has engaged the insurance industry and legislators to expand access to care.
PART 2: TRENDS IN CLINICAL OUTCOMES IVF treatment has changed over the years as new methods and understandings have accrued. The first 20 years of progress in the United States were summarized in a prior article published in Fertility and Sterility in 2002 (6). This current article extends that overview of trends as reported via the SART Registry dataset. This is meant to highlight certain salient trends. The most recently available data are from 2014 treatment cycles. 3
ASRM PAGES
FIGURE 2
FIGURE 1
A
A # US ART clinics
400
45%
350
40%
300
35%
Live born delivery / cycle
30%
250 200
Report to SART
25%
150
Report to CDC only
20%
100
Do not Report
15%
Both Fresh Frozen
10%
50 5%
0 1985
1990
1995
2000
2005
0% 1985
2010
B # Treatment cycles and deliveries
B
200,000 180,000
1990
1995
2000
2005
2010
Live born delivery / cycle by Age
60%
160,000 140,000
50%
120,000 40%
100,000
< 35 yo
# cycles
80,000
# liveborn deliveries
60,000
35 - 37 yo
30%
38 - 40 yo
40,000
20% 41 - 42 yo
20,000 0 1985
10%
1990
1995
2000
2005
(A) Number of US assisted reproductive technology clinics that report to the Society for Assisted Reproductive Technology, the Centers for Disease Control and Prevention, or do not report, by year. (B) Total number of treatment cycles and live-born deliveries by year, inclusive of all assisted reproductive technology treatment types. Toner. SART and ART in the U.S. Fertil Steril 2016.
The number of ART clinics in the United States continues to rise, but at a slower rate since 2000. Most clinics (80%) still report through SART, but a few report directly to the CDC using the NASS system, and a some do not report at all (Fig. 1A). All SART clinics also report to CDC without the need for duplicate data entry. The number of treatment cycles and live born deliveries has likewise continued to rise (Fig. 1B). Best estimates suggest that about 1.5% of all children born in the United States are the result of ART, totaling 1.1 million children since 2006. The overall delivery rate per initiated treatment cycle has risen as well among women using autologous embryos (Fig. 2A). Note the success of frozen cycles now exceeds that of fresh, likely due to a combination of factors, including the more physiological endometrial development of a nonstimulated cycle, and the improved embryo selection following PGS/PGD. Also note a decline in the fresh delivery rate, likely due to increasing use of single blastocyst transfers, since the implantation rate has in fact been rising across age groups (data not shown). Maternal age continues to be the strongest influence on the success of a treatment cycle (Fig. 2B). This graph displays the live born delivery rates for autologous fresh IVF cycles 4
> 42 yo
2010 0% 1997
2002
2007
2012
(A) Live-born delivery rate in autologous cycles by year. As of 2002, outcomes were divided by fresh versus frozen embryo transfer. (B) Live-born delivery rates in autologous cycles by age of woman and year. Toner. SART and ART in the U.S. Fertil Steril 2016.
only. While steady progress has occurred in most age groups, no improvement has been seen in women over 42 years of age (per cycle start). In the early years of IVF, low implantation rates led to the routine practice of transferring multiple embryos, and a higher than desirable rate of multiple pregnancy (7). Due to guidance from ASRM and SART (8) and the increased use of blastocyst culture and hence improved implantation rates, the number of embryos transferred in autologous fresh cycles has been dramatically reduced, from an average of 4 at all ages in 1995 to well under 2 in women under 35 years of age at last report (Fig. 3A). Moreover, there has been a rapid increase in the number of single embryo transfers, especially among younger women. Figure 3B shows the rates among autologous fresh cycles. Taken together, these trends have led to a dramatic reduction in high-order multiple pregnancies in autologous fresh IVF cycles (Fig. 3C). Estimates suggest that more multiples now stem from ovulation induction/insemination cycles than from ART (9). Single-embryo transfers in young patients and egg recipients, and even the rates of twinning have been declining since about 2000 due, in part, to SART's advocacy (Fig. 3C). VOL. - NO. - / - 2016
Fertility and Sterility®
FIGURE 3
FIGURE 4 Risks
A # Embryos transferred
1.4%
4.5
1.2% 4.0 3.5 3.0 < 35 yo
2.5
Psychological
1.0%
Anesthe c Complica on
0.8%
Medica on Side Effect
0.6%
Infec on Hemorrhage
0.4%
Mod OHSS
35 - 37 yo 2.0
38 - 40 yo
1.5
41 - 42 yo
1.0
> 42 yo
0.5
0.2%
Severe OHSS
0.0% 2006
2008
2010
2012
2014
Percent of fresh autologous cycles in which specified complications were reported, by year. Toner. SART and ART in the U.S. Fertil Steril 2016.
0.0 1995
2000
2005
2010
B % Single embryo transfers 35% 30% 25% < 35 yo 20%
35 - 37 yo
15%
38 - 40 yo
10%
41 - 42 yo > 42 yo
5% 0% 2000
C
2005
2010
MulƟple pregnancy / delivery 35% 30% 25% 20% Twins 15%
Triplets
10%
Quads+
5% 0% 1995
2000
2005
2010
(A) Mean number of embryos transferred in fresh autologous cycles by age of woman and year. (B) Percent of fresh transfers among autologous cycles that involved elective transfer of a single embryo by age of woman and year. (C) Percent of live-born deliveries among fresh autologous cycles that were twin, triplets, or more, by year. Toner. SART and ART in the U.S. Fertil Steril 2016.
Moreover, the recent rate of decline suggests we may be at a tipping point among patients and practitioners, in recognizing that there is preventable risk associated with twin pregnancy so that ‘‘one baby at a time’’ really is best. The SART data collection system has also inquired about certain complications of treatments, particularly as they relate to ovarian stimulation and egg retrieval. As is shown in Figure 4, the overall chance for any complication is now about 1 in 200 cycles. Ovarian hyperstimulation VOL. - NO. - / - 2016
syndrome (OHSS) was reported in 5 per 1,000 cycles (moderate in 4 per 1,000 cycles and severe in 1 per 1,000 cycles) (9), hemorrhage in 2 per 10,000 cycles, infection in 1 per 10,000 cycles, and anesthetic complications in 7 per 100,000 cycles. Rates of OHSS have been steadily declining over the past 10 years, probably due to decreased use of human chorionic gonadotropin (hCG) to trigger final oocyte maturation.
Recent Trends Not yet Manifest in Reporting As noted previously, some recent changes in clinical practice have led to a major update of the data collection and reporting system. Some of these practices were captured beginning with 2014 treatment cycles, and some will not be captured until 2016. Since there is a two-year delay between the treatment and its report, we cannot yet say much about the impact of these changes. The new practices captured for the first time in 2014 cycles include: PGS for aneuploidy screening in thawed embryos. In recent years PGS has become more widespread, and most screened embryos are transferred in subsequent embryo-thaw cycles. The data reporting software was adjusted to permit identification of thawed embryos as having undergone PGS. Embryo accumulation. Before 2014 cycles were reported, it was not possible to report embryo transfers in which eggs from more than one retrieval were utilized. Clinics employing a strategy of embryo accumulation were unable to report this practice, leading to cases of ‘‘hidden cycles’’ (3). Reason for freezing all embryos. Before 2014, no information was requested about the reason all embryos were frozen. Now we ask whether it was for genetic testing, concerns about endometrial receptivity, and avoidance of OHSS. SART and the CDC had discussions about the need for updated reporting in 2014 and 2015. This collaborative process led to the addition of some new fields, modification of others, and deletion of a few. The CDC has published its updated rules 5
ASRM PAGES for reporting in the Federal Register (10). The new system of reporting to the CDC will commence with 2016 cycles. Enhancements of both the CDC and SART systems include the ability to link the source of all eggs with their ultimate use, additional male factor fields, and more.
2.
3. 4.
SUMMARY SART was established within a few years of ART in the United States, and has not only reported on the evolution of infertility care, but also guided it toward improved success and safety. The success of ART in the United States has greatly benefited from SART's role. SART continues to set the standard and lead the way. Acknowledgments: We thank the SART member clinics who have submitted their data through the SART CORS system over its many years, which has improved practice and patient education.
REFERENCES 1.
6
Jones HW Jr. Howard & Georgeanna: sixty years of marriage & medicine. Williamsburg, Virginia: Jamestowne Bookworks; 2015:212–3.
5. 6. 7. 8.
9.
10.
Centers for Disease Control and Prevention, American Society for Assisted Reproduction. 2013 Assisted Reproductive Technology Fertility Success Rates Report. Atlanta: U.S. Department of Health and Human Services; 2015. Doody KJ. Public reporting of ART cycle outcome data is not simple. Fertil Steril 2016;105:893–4. Kulak D, Jindal SK, Cheongeun O, Morelli SS, Kratka S, McGovern PG. Reporting in vitro fertilization cycles to Society for Assisted Reproductive Technologies (SART) database: where have all the cycles gone? Fertil Steril 2016; 105:927–31. Ball D, Coddington C, Doody K, Schattman GL, Toner J, Van Voorhis BJ, et al. The playing field is changing.. Fertil Steril 2014;101:e29. Toner JP Jr. Progress we can be proud of: U.S. trends in assisted reproduction over the first 20 years. Fertil Steril 2002;78:943–50. Jones HW Jr. Iatrogenic multiple births: a 2003 checkup. Fertil Steril 2007; 87:453–5. Practice Committee of the American Society for Reproductive Medicine, Practice Committee of the Society for Assisted Reproductive Technology. Criteria for number of embryos to transfer: a committee opinion. Fertil Steril 2013;99:44–6. Kulkarni AD, Jamieson DJ, Jones HW Jr, Kissin DM, Gallo MF, Macaluso M, et al. Fertility treatments and multiple births in the United States. N Engl J Med 2013;369:2218–25. Reporting of pregnancy success rates from assisted reproductive technology (ART) programs; Centers for Disease Control and Prevention, Department of Health and Human Services, 80 Fed. Reg. 51811 (August 26, 2015). Available at: https://federalregister.gov/a/2015-21108. Accessed June 13, 2016.
VOL. - NO. - / - 2016
Society for Assisted Reproductive Technology and assisted reproductive technology in the United States: a 2016 update James P. Toner, M.D., Ph.D.,a Charles C. Coddington, M.D.,b Kevin Doody, M.D.,c Brad Van Voorhis, M.D.,d David B. Seifer, M.D.,e G. David Ball, Ph.D., H.C.L.D.,f Barbara Luke, ScD, M.P.H.,g and Ethan Wantman, M.B.A.h a Atlanta Center for Reproductive Medicine, Atlanta, Georgia; b Division of Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, Minnesota; c Center for Assisted Reproduction, Dallas, Texas; d University of Iowa Carver College of Medicine, Iowa City, Iowa; e The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; f Seattle Reproductive Medicine, Seattle, Washington; g Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, Michigan; and h Redshift Technologies, Inc., New York, New York
The Society for Assisted Reproductive Technology (SART) was established within a few years of assisted reproductive technology (ART) in the United States, and has not only reported on the evolution of infertility care, but also guided it toward improved success and safety. Moving beyond its initial role as a registry, SART has expanded its role to include quality assurance, data validation, practice and advertising guidelines, research, patient education and advocacy, and membership support. The success of ART in this country has greatly benefited from SART's role, as highlighted by a series of graphs. SART continues to set the standard and lead the way. (Fertil SterilÒ 2016;-:-–-. Ó2016 by American Society for Reproductive Medicine.) Key Words: SART, IVF, history of IVF, SART Registry Discuss: You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/tonerj-sart-art-us2016-update/
T
he progress made in infertility care in the United States is inextricably linked to the membership and activities of the Society for Assisted Reproductive Technology (SART), the professional organization formed 30 years ago to collect and report on its treatment outcomes. In this two-part paper, we first review the evolution of the society from its origin as a registry to its current multifaceted mission and then describe the
progression of care as captured by the registry.
PART 1: THE SOCIETY FOR ASSISTED REPRODUCTIVE TECHNOLOGY Founding In 1981, shortly after the birth of Elizabeth Carr, the first in vitro fertilization (IVF) child born in the United States, Dr. Howard Jones gathered the leading
Received May 19, 2016; accepted May 24, 2016. J.P.T. has nothing to disclose. C.C.C. is a member of the AbbVie Advisory Board. K.D. has nothing to disclose. B.V.V. has nothing to disclose. D.B.S. reports royalties paid by Beckman-Coulter to Rutgers University/Massachusetts General Hospital for a license to use AMH as a method to determine ovarian reserve. G.D.B. has nothing to disclose. B.L. has received consulting fees from the Society for Assisted Reproductive Technology. E.W. is an employee of Redshift (Society for Assisted Reproductive Technology's data vendor). Reprint requests: James P. Toner, M.D., Ph.D., Past President, SART, Atlanta Center for Reproductive Medicine, 5909 Peachtree Dunwoody Road, Atlanta, Georgia 30328 (E-mail: jim.toner@acrm. com). Fertility and Sterility® Vol. -, No. -, - 2016 0015-0282/$36.00 Copyright ©2016 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2016.05.026 VOL. - NO. - / - 2016
practitioners of the 5 existing US IVF programs (Norfolk, Vanderbilt, the University of Texas at Houston, University of Southern California, and Yale) to discuss establishing a national registry of IVF attempts and outcomes. Two years later, in 1985, Drs. Alan DeCherney and Richard Marrs founded the Society for Assisted Reproductive Technology (SART) as a special interest group in the American Fertility Society (now the American Society for Reproductive Medicine [ASRM]) for that purpose (1). Initially, the data were tabulated at the clinic level and reported at the national level. Individual clinics could measure comparisons to national outcomes and the public could see what was happening broadly within the United States. National reports were made public by way of annual publications in Fertility and Sterility. Subsequent modifications to reporting 1
ASRM PAGES included a transition to both cycle-specific reporting and public reporting of outcomes at the individual clinic level, as required by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law No. 102-493, October 24, 1992) (2). Over the years that followed, SART's activities have expanded well beyond the simple collection of assisted reproductive technology (ART) outcomes.
Current Scope As of 2014, SART had 375 member clinics in the United States accounting for 83% of all clinics required to report and 91% of all reported ART cycles. The organization is led by an executive council of 28 professionals who sit on 15 committees populated by another 80 professional volunteers. The senior executive roles are elected and term-limited, which enhances the credibility of SART's operations. The only permanent employee is an administrator. SART also has contracts with a researcher and database administrator. The company providing database administration is also an active participant in developing specifications and custom software to meet the current needs of comprehensive data collection. SART's mission is to ‘‘promote and advance the standards for the practice of assisted reproductive technology to the benefit of our patients, members, and society at large.’’
‘‘Setting the Standard’’ Setting the standard is a primary means by which SART achieves its mission. The committees involved with this activity include: Practice Committee. This committee develops and issues guidance for evidence based care. Currently more than 60 documents have been released and are accessible online in the members section of the SART website (www.sart.org/members). Quality Assurance Committee (QA). QA is one of the most direct ways through which SART accomplishes its stated mission. The registry allows for measurement of clinical effectiveness of care, measurement of safety and harm, and assessment of the quality of care. This committee surveys outcomes each year to identify clinics with below average performance. The committee reaches out to the identified clinics and offers remediation if the issue has not already been addressed. If performance does not improve over successive years, loss of membership can occur. QA metrics currently focus on low pregnancy rates and high rates of multiple pregnancies. Advertising Committee. SART has developed advertising guidelines to assure fairness and accuracy. One of the guidelines prohibits direct clinic-to-clinic comparisons of outcome data. This committee continually reviews member websites (155 were reviewed in 2015), and fields complaints of violations from members and patients. Current guidelines require the posting of the full Clinic Summary Report (CSR) to ensure fair and full outcome disclosures. With the expansion of the CSR, a new set of guidelines will be forthcoming. 2
Validation Committee. This committee works with the Centers for Disease Control and Prevention (CDC) to ensure that data reported by clinics to the registries (SART Clinical Outcomes Reporting System [CORS] or National ART Surveillance System [NASS]) are accurate. Twenty clinics are visited each year. Low error rates have been found. SART's validation process goes beyond CDC's validation efforts. SART collects additional data fields requiring independent validation. Moreover, the Executive Council has authorized the Validation Committee to develop ‘‘triggers’’ to perform on site validation of ‘‘outliers’’ not based solely on below average outcomes, but also inexplicable ones. Validation is an important part of any medical registry, but is exceedingly important when submitted data are publically reported at the clinic level. Membership Committee. This committee evaluates the credentials of the primary professionals in each practice to ensure reproductive endocrinology and infertility (REI) board certification, lab accreditation, and compliance with advertising guidelines. While SART works hard to retain all members, membership has been revoked for persistently poor clinical performance, loss of accreditation, violation of advertising guidelines, and failing to report outcomes.
Membership Support In addition to setting the standard, SART supports its members via: SART website. SART has developed a comprehensive website that serves the needs of both patients and members (in a members-only section). It has recently been updated to be more informative and patient focused. This redesign was done in coordination with ASRM's information technology team. Find a Clinic. The SART website includes a tool for patients to find SART member clinics throughout the United States and to request information from those clinics. Informed Consents. SART has developed model consents for routine IVF as well as its variants: egg donation, donor egg recipient, cryopreservation (both eggs and embryos), and gestational carrier. Disposition documents for eggs and embryos have also been developed. These are available in both English and Spanish in an editable format to permit adjustment for local needs. Research. SART makes its large dataset available to members upon approval of their research plan. It has developed an online ‘‘portal’’ to make requesting datasets easier. Twenty-five requests were received in 2015. Since 2006, SART has funded an epidemiologist to study ART outcomes and to develop National Institutes of Health (NIH)-funded research. Taken together, more than 60 publications have used the SART database. Findings from these studies have influenced practice guidelines, and is a primary means by which SART guides practice. Government relations. SART has collaborated with the CDC since the initiation of the Fertility Clinic Success Rate & Certification Act of 1992, and continues to strive for a VOL. - NO. - / - 2016
Fertility and Sterility® coordinated approach to data collection and outcome reporting. SART also participates in the National Coalition for the Oversight of Assisted Reproductive Technology (NCOART). Member advocacy. Under the direction of ASRM's Washington DC office of Public Affairs, SART has supported members in countering state or local legislation that is unfavorable for patient access to ART services. SART works with consumer advocates such as the National Infertility Association (RESOLVE) and the American Family Association (AFA), and the insurance industry, to foster shared goals. Expanding access to care remains an important goal. It is also a member of the Women's Health Registry Alliance of the American Congress of Obstetricians and Gynecologists (ACOG). ASRM has provided significant assistance in this arena. Quality Assurance Dashboard. SART is developing a tool for member clinics that would provide for real-time comparisons of QA metrics to historical trends within a clinic, and contemporaneous benchmarking to national performance. Physician Treatment Model. As an extension of the patient predictor models (discussed later), SART has also developed physician treatment models to predict the chances of live birth and multiple birth. These web-based tools, which will be piloted in 2016, utilize data from more than 1.4 million cycles in SART CORS from 2004–2013 and are planned to be a series of five models. All models will include year of treatment, maternal age, gravidity and reproductive history, infertility diagnoses, body mass index, and day of embryo transfer. The first cycle models will be based on the use of autologous oocytes and fresh embryos; number of oocytes retrieved, embryos transferred, and embryos cryopreserved; and a future model will also include embryo morphology. A second cycle model will be based on factors in the first cycle, which did not result in a live birth. Two additional models for any cycle will include factors in all prior cycles, and the use of either fresh or thawed embryos and other factors in the current cycle.
Patient Education/Advocacy SART also provides service to patients, via its recently enhanced website (http://sart.org). It features educational material on IVF, including an image gallery. It also provides access to these benefits: Clinic Summary Report (CSR). SART has evolved the federally-mandated clinic summary report to reflect changing practice and incent best practice. In response to the increased use of preimplantation genetic screening (PGS), delayed transfers, and embryo accumulation, the prior data collection system required revision (3–5). The new collection system links the embryo transfer back to the cycle in which the eggs were obtained, and allows for multiple retrieval cycles to be linked to one transfer cycle. The CSR also highlights the live-birth rate per cycle start, which is the required metric in the original law, VOL. - NO. - / - 2016
and appropriately aligns the outcome of interest to patients (a live-born baby) with patient choices (whether or not to initiate a cycle to obtain eggs). The CSR now permits a wide range of data filters, including preimplantation genetic diagnosis (PGD)/PGS, blastocyst transfer, first cycle, etc. Find a Clinic (http://sart.org/Find_A_Clinic/). This feature allows a patient to specify a state or zip code to identify SART member clinics in that area. The address and contact information are displayed, as well as a link to the clinic summary report. Patients can directly request follow-up calls or emails from target clinics. Patient Predictor (https://www.sartcorsonline.com/Predictor/Patient). Because the SART database has more than 1.4 million treatment cycles, the ability to create a preeminent prediction model is second to none. The first version of the predictor (implemented in 2014 and based on 2004– 2012 cycles) included 3 models, showing the chance for live birth after 1, 2, and 3 ‘‘fresh’’ IVF attempts based on age, body mass index (BMI), prior gravidity, and cause of infertility, as well as first cycle using donor oocytes. It also compares multiple pregnancy rates when one embryo is transferred over two cycles versus two embryos transferred in one cycle. The revised version (implemented in 2016 and based on 2006–2013 cycles standardized to 2013) includes day of transfer, and expands the donor model to include the chance of a live birth and a multiple birth with one or two embryos transferred. History of IVF (http://sart.org/History_of_IVF/). This links to a series of images featuring trends in IVF in the United States since reporting began in 1985. The graphs are updated annually. IVF4VETS (https://www.sartcorsonline.com/ServiceToVeterans.aspx). A federal bill to permit veterans to receive IVF care has not yet passed Congress. To remedy this deficiency, certain SART member clinics have pledged reduced fee IVF to assist veterans with injuries stemming from their service that affects their reproductive capacity. ReproductiveFacts.org (http://www.reproductivefacts.org). In concert with the ASRM, SART links to and support content at reprouctivefacts.org. Mobile App. SART is developing a mobile application for patients to assist them in estimating their success with IVF, finding a local clinic, estimating their due date once pregnant, and much more. Extending Access to Care. In concert with ASRM and patient advocacy groups, SART has engaged the insurance industry and legislators to expand access to care.
PART 2: TRENDS IN CLINICAL OUTCOMES IVF treatment has changed over the years as new methods and understandings have accrued. The first 20 years of progress in the United States were summarized in a prior article published in Fertility and Sterility in 2002 (6). This current article extends that overview of trends as reported via the SART Registry dataset. This is meant to highlight certain salient trends. The most recently available data are from 2014 treatment cycles. 3
ASRM PAGES
FIGURE 2
FIGURE 1
A
A # US ART clinics
400
45%
350
40%
300
35%
Live born delivery / cycle
30%
250 200
Report to SART
25%
150
Report to CDC only
20%
100
Do not Report
15%
Both Fresh Frozen
10%
50 5%
0 1985
1990
1995
2000
2005
0% 1985
2010
B # Treatment cycles and deliveries
B
200,000 180,000
1990
1995
2000
2005
2010
Live born delivery / cycle by Age
60%
160,000 140,000
50%
120,000 40%
100,000
< 35 yo
# cycles
80,000
# liveborn deliveries
60,000
35 - 37 yo
30%
38 - 40 yo
40,000
20% 41 - 42 yo
20,000 0 1985
10%
1990
1995
2000
2005
(A) Number of US assisted reproductive technology clinics that report to the Society for Assisted Reproductive Technology, the Centers for Disease Control and Prevention, or do not report, by year. (B) Total number of treatment cycles and live-born deliveries by year, inclusive of all assisted reproductive technology treatment types. Toner. SART and ART in the U.S. Fertil Steril 2016.
The number of ART clinics in the United States continues to rise, but at a slower rate since 2000. Most clinics (80%) still report through SART, but a few report directly to the CDC using the NASS system, and a some do not report at all (Fig. 1A). All SART clinics also report to CDC without the need for duplicate data entry. The number of treatment cycles and live born deliveries has likewise continued to rise (Fig. 1B). Best estimates suggest that about 1.5% of all children born in the United States are the result of ART, totaling 1.1 million children since 2006. The overall delivery rate per initiated treatment cycle has risen as well among women using autologous embryos (Fig. 2A). Note the success of frozen cycles now exceeds that of fresh, likely due to a combination of factors, including the more physiological endometrial development of a nonstimulated cycle, and the improved embryo selection following PGS/PGD. Also note a decline in the fresh delivery rate, likely due to increasing use of single blastocyst transfers, since the implantation rate has in fact been rising across age groups (data not shown). Maternal age continues to be the strongest influence on the success of a treatment cycle (Fig. 2B). This graph displays the live born delivery rates for autologous fresh IVF cycles 4
> 42 yo
2010 0% 1997
2002
2007
2012
(A) Live-born delivery rate in autologous cycles by year. As of 2002, outcomes were divided by fresh versus frozen embryo transfer. (B) Live-born delivery rates in autologous cycles by age of woman and year. Toner. SART and ART in the U.S. Fertil Steril 2016.
only. While steady progress has occurred in most age groups, no improvement has been seen in women over 42 years of age (per cycle start). In the early years of IVF, low implantation rates led to the routine practice of transferring multiple embryos, and a higher than desirable rate of multiple pregnancy (7). Due to guidance from ASRM and SART (8) and the increased use of blastocyst culture and hence improved implantation rates, the number of embryos transferred in autologous fresh cycles has been dramatically reduced, from an average of 4 at all ages in 1995 to well under 2 in women under 35 years of age at last report (Fig. 3A). Moreover, there has been a rapid increase in the number of single embryo transfers, especially among younger women. Figure 3B shows the rates among autologous fresh cycles. Taken together, these trends have led to a dramatic reduction in high-order multiple pregnancies in autologous fresh IVF cycles (Fig. 3C). Estimates suggest that more multiples now stem from ovulation induction/insemination cycles than from ART (9). Single-embryo transfers in young patients and egg recipients, and even the rates of twinning have been declining since about 2000 due, in part, to SART's advocacy (Fig. 3C). VOL. - NO. - / - 2016
Fertility and Sterility®
FIGURE 3
FIGURE 4 Risks
A # Embryos transferred
1.4%
4.5
1.2% 4.0 3.5 3.0 < 35 yo
2.5
Psychological
1.0%
Anesthe c Complica on
0.8%
Medica on Side Effect
0.6%
Infec on Hemorrhage
0.4%
Mod OHSS
35 - 37 yo 2.0
38 - 40 yo
1.5
41 - 42 yo
1.0
> 42 yo
0.5
0.2%
Severe OHSS
0.0% 2006
2008
2010
2012
2014
Percent of fresh autologous cycles in which specified complications were reported, by year. Toner. SART and ART in the U.S. Fertil Steril 2016.
0.0 1995
2000
2005
2010
B % Single embryo transfers 35% 30% 25% < 35 yo 20%
35 - 37 yo
15%
38 - 40 yo
10%
41 - 42 yo > 42 yo
5% 0% 2000
C
2005
2010
MulƟple pregnancy / delivery 35% 30% 25% 20% Twins 15%
Triplets
10%
Quads+
5% 0% 1995
2000
2005
2010
(A) Mean number of embryos transferred in fresh autologous cycles by age of woman and year. (B) Percent of fresh transfers among autologous cycles that involved elective transfer of a single embryo by age of woman and year. (C) Percent of live-born deliveries among fresh autologous cycles that were twin, triplets, or more, by year. Toner. SART and ART in the U.S. Fertil Steril 2016.
Moreover, the recent rate of decline suggests we may be at a tipping point among patients and practitioners, in recognizing that there is preventable risk associated with twin pregnancy so that ‘‘one baby at a time’’ really is best. The SART data collection system has also inquired about certain complications of treatments, particularly as they relate to ovarian stimulation and egg retrieval. As is shown in Figure 4, the overall chance for any complication is now about 1 in 200 cycles. Ovarian hyperstimulation VOL. - NO. - / - 2016
syndrome (OHSS) was reported in 5 per 1,000 cycles (moderate in 4 per 1,000 cycles and severe in 1 per 1,000 cycles) (9), hemorrhage in 2 per 10,000 cycles, infection in 1 per 10,000 cycles, and anesthetic complications in 7 per 100,000 cycles. Rates of OHSS have been steadily declining over the past 10 years, probably due to decreased use of human chorionic gonadotropin (hCG) to trigger final oocyte maturation.
Recent Trends Not yet Manifest in Reporting As noted previously, some recent changes in clinical practice have led to a major update of the data collection and reporting system. Some of these practices were captured beginning with 2014 treatment cycles, and some will not be captured until 2016. Since there is a two-year delay between the treatment and its report, we cannot yet say much about the impact of these changes. The new practices captured for the first time in 2014 cycles include: PGS for aneuploidy screening in thawed embryos. In recent years PGS has become more widespread, and most screened embryos are transferred in subsequent embryo-thaw cycles. The data reporting software was adjusted to permit identification of thawed embryos as having undergone PGS. Embryo accumulation. Before 2014 cycles were reported, it was not possible to report embryo transfers in which eggs from more than one retrieval were utilized. Clinics employing a strategy of embryo accumulation were unable to report this practice, leading to cases of ‘‘hidden cycles’’ (3). Reason for freezing all embryos. Before 2014, no information was requested about the reason all embryos were frozen. Now we ask whether it was for genetic testing, concerns about endometrial receptivity, and avoidance of OHSS. SART and the CDC had discussions about the need for updated reporting in 2014 and 2015. This collaborative process led to the addition of some new fields, modification of others, and deletion of a few. The CDC has published its updated rules 5
ASRM PAGES for reporting in the Federal Register (10). The new system of reporting to the CDC will commence with 2016 cycles. Enhancements of both the CDC and SART systems include the ability to link the source of all eggs with their ultimate use, additional male factor fields, and more.
2.
3. 4.
SUMMARY SART was established within a few years of ART in the United States, and has not only reported on the evolution of infertility care, but also guided it toward improved success and safety. The success of ART in the United States has greatly benefited from SART's role. SART continues to set the standard and lead the way. Acknowledgments: We thank the SART member clinics who have submitted their data through the SART CORS system over its many years, which has improved practice and patient education.
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6
Jones HW Jr. Howard & Georgeanna: sixty years of marriage & medicine. Williamsburg, Virginia: Jamestowne Bookworks; 2015:212–3.
5. 6. 7. 8.
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Centers for Disease Control and Prevention, American Society for Assisted Reproduction. 2013 Assisted Reproductive Technology Fertility Success Rates Report. Atlanta: U.S. Department of Health and Human Services; 2015. Doody KJ. Public reporting of ART cycle outcome data is not simple. Fertil Steril 2016;105:893–4. Kulak D, Jindal SK, Cheongeun O, Morelli SS, Kratka S, McGovern PG. Reporting in vitro fertilization cycles to Society for Assisted Reproductive Technologies (SART) database: where have all the cycles gone? Fertil Steril 2016; 105:927–31. Ball D, Coddington C, Doody K, Schattman GL, Toner J, Van Voorhis BJ, et al. The playing field is changing.. Fertil Steril 2014;101:e29. Toner JP Jr. Progress we can be proud of: U.S. trends in assisted reproduction over the first 20 years. Fertil Steril 2002;78:943–50. Jones HW Jr. Iatrogenic multiple births: a 2003 checkup. Fertil Steril 2007; 87:453–5. Practice Committee of the American Society for Reproductive Medicine, Practice Committee of the Society for Assisted Reproductive Technology. Criteria for number of embryos to transfer: a committee opinion. Fertil Steril 2013;99:44–6. Kulkarni AD, Jamieson DJ, Jones HW Jr, Kissin DM, Gallo MF, Macaluso M, et al. Fertility treatments and multiple births in the United States. N Engl J Med 2013;369:2218–25. Reporting of pregnancy success rates from assisted reproductive technology (ART) programs; Centers for Disease Control and Prevention, Department of Health and Human Services, 80 Fed. Reg. 51811 (August 26, 2015). Available at: https://federalregister.gov/a/2015-21108. Accessed June 13, 2016.
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