30 years of data: impact of the United States in vitro fertilization data registry on advancing fertility care

ORIGINAL ARTICLE: ASSISTED REPRODUCTION

30 years of data: impact of the United States in vitro fertilization data registry on advancing fertility care Tarun Jain, M.D.,a David A. Grainger, M.D., M.P.H.,b G. David Ball, Ph.D.,c William E. Gibbons, M.D.,d Robert W. Rebar, M.D.,e,f Jared C. Robins, M.D.,a and Richard E. Leach, M.D.f a Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; b Department of Obstetrics and Gynecology, University of Kansas-Wichita School of Medicine, Wichita, Kansas; c Seattle Reproductive Medicine, Seattle, Washington; d Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; e Department of Obstetrics and Gynecology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan; and f Departments of Obstetrics, Gynecology, Reproductive Biology and Women's Health, Michigan State University and the Spectrum Health Medical Group, Grand Rapids, Michigan

Objective: To summarize and assess the impact of key research generated through the Society of Assisted Reproductive Technology (SART)-initiated United States IVF registry and annual reporting system. Design: Review. Setting: Eligible studies included those that analyzed data generated by the National IVF data collection program (through SART or Centers for Disease Control and Prevention). Patient(s): Not applicable. Intervention(s): Not applicable. Main Outcome Measure(s): Summarize and report outcomes of research using National IVF registry data. Result(s): The Society of Assisted Reproductive Technology was founded in 1985 and published the first annual US IVF data report 30 years ago in 1988 in Fertility and Sterility. In 1995, the Centers for Disease Control and Prevention subsequently began collecting data from IVF programs and published their first report in 1997. This annual National IVF data collection and reporting is a significant responsibility and effort for IVF programs. Using these data sources, 199 articles have been published by clinicians and researchers from across the country. This research has guided the development of evidence-based assisted reproductive technology (ART) practice guidelines during the past 30 years, which have ultimately led to improved quality and patient care. Conclusion(s): Since the first SART National IVF data report publication 30 years ago, SART has achieved its original goals of creating a national IVF registry that successfully assesses clinical effectiveness, quality of care, and safety. (Fertil SterilÒ 2018;-:-–-. Ó2018 by American Society for Reproductive Medicine.) Key Words: In vitro fertilization, IVF outcomes, SART registry, disparities, infertility Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertilityand-sterility/posts/40928-27035

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nfertility is a disease that affects approximately 12% of women in the United States (1, 2). The first successful IVF cycle in the United States occurred in 1981 (3). The growth and advancement of IVF to treat infertile patients have

been significant (Fig. 1) (4, 5). Approximately 1.6% of all births in the United States now result from IVF pregnancies (6). The growth and success of IVF can be attributed, in part, to the foresight of the early pioneers of IVF in the United

Received September 24, 2018; revised and accepted November 14, 2018. T.J. has nothing to disclose. D.A.G. has nothing to disclose. G.D.B. has nothing to disclose. W.E.G. has nothing to disclose. R.W.R. reports he serves as chair on DSMBs for drugs under investigation by Myovant Inc, is a member of the ASRM Practice Committee, is Associate Editor of Clinical OB/Gyn Alert, and Journal Watch Women's Health, outside the submitted work. J.C.R. has nothing to disclose. R.E.J. has nothing to disclose. Reprint requests: Tarun Jain, M.D., Northwestern Fertility and Reproductive Medicine, 676 North Saint Clair Street, Suite 2310, Chicago, Illinois 60611 (E-mail: [email protected]). Fertility and Sterility® Vol. -, No. -, - 2018 0015-0282/$36.00 Copyright ©2018 American Society for Reproductive Medicine, Published by Elsevier Inc. https://doi.org/10.1016/j.fertnstert.2018.11.015 VOL. - NO. - / - 2018

States (7). In 1983, providers from the five existing IVF programs discussed establishing a national registry of IVF attempts and outcomes. The goals of the registry were to determine clinical effectiveness of care, monitor safety, and measure quality of care. To serve this purpose, the Society for Assisted Reproductive Technology (SART) was founded in 1985 (8). As part of their charter, SART developed a national patient health service registry, SART Clinical Outcome Reporting System (SART CORS), perhaps the first such registry in the United States (9). Starting that same 1

ORIGINAL ARTICLE: ASSISTED REPRODUCTION year, IVF clinic-specific outcome data were voluntarily submitted to SART, combined into a national report, and published in the journal Fertility and Sterility. The first such national IVF data report was published 30 years ago in 1988, and annually since that time (10). As IVF use increased during the late 1980s, there was growing public concern about the quality and comparability of IVF outcome information being received by patients (11). Responding to these concerns, the US Congress passed a law (Public Law 102-493) titled the Fertility Clinic Success Rate and Certification Act, or the Wyden Law, as it was sponsored by Oregon Representative Ron Wyden (12). On October 24, 1992, President George H.W. Bush signed the Fertility Clinic Success Rate and Certification Act into law. This unfunded federal law requires that each IVF program shall annually report successful pregnancy rates (PRs) and the identity of their embryology laboratory to the Secretary of the Department of Health and Human Services through the Centers for Disease Control and Prevention (CDC). In 1995, the CDC began collecting data from IVF programs, and published their first report in 1997 (there is an approximate 2-year lag time in publication to allow for collection of live-birth data) (4). From 1997-2003, to facilitate their data collection, the CDC contracted with SART to annually obtain a copy of their clinic-specific database (13). Starting in 2004, the CDC has maintained the National ART Surveillance System, a web-based data reporting system. Furthermore, each year, the CDC selects a random sample of 5%–10% of all reporting IVF programs, for an on-site data validation visit. In parallel, SART continues to collect, validate, and report clinic-specific IVF outcome data from their member clinics (representing 94% of all IVF cycles) (5). Important, and differing from strict data validation, SART validation site visits include adherence (or lack thereof) to American Society for Reproductive Medicine (ASRM)/SART practice guidelines. Furthermore, SART uses the data to annually identify and provide consulting services to help clinics with the highest multiple PRs and the lowest PRs. The amount of data collected and submitted by IVF programs for each IVF cycle attempted is significant. The IVF cycle-specific data fields are broadly broken down into categories that include patient demographics, patient history, prior treatment, medications, treatment details, embryology details/techniques, pregnancy details/outcomes, birth details/outcomes, birth defects, and treatment complications. A major benefit of this comprehensive national health data collection has been to conduct meaningful research. From nearly its beginning, SART formed a Research Committee. The SART members could submit a research proposal to the committee that, if approved, would allow them access to the national dataset. This relatively passive process was improved in 2005 with the hiring of an epidemiologist by SART. This quickly led the Research Committee to initiate a more active role in asking and answering questions from the dataset. The quality and quantity of publications from the data markedly increased. Individual SART members still request and are granted database access, which broadens the depth of research questions. 2

This research has guided the development of evidencedbased assisted reproductive technology (ART) practice guidelines during the past 30 years. The enormous potential in the knowledge gained from such research is recognized by the numerous National Institutes of Health grants awarded to these researchers. The present article aims to analyze and summarize the key research generated by this national IVF registry and reporting system.

MATERIALS AND METHODS The study did not require approval by the Institutional Review Board because it is a review of existing published studies. We performed a comprehensive search up until January 1, 2018 in MEDLINE. Our search combined terms and descriptors related to any full-length studies using the national IVF registry dataset. Comprehensive lists of published studies that used IVF Registry data were also obtained directly from the SART and CDC websites (14, 15). Reference lists from the included studies were investigated for additional articles that met the inclusion criteria. The studies were categorized into broad topics and subsequently analyzed for their main findings and potential impact on patient care.

RESULTS We found 199 peer-reviewed published studies from clinicians and researchers across the country who used the national IVF registry data. The main findings of the studies are broadly categorized and summarized.

Embryos Transferred, Multiple Gestations, and Impact of ASRM Guidelines In the 1990s embryology laboratories improved and multiple ET continued to achieve high PRs, leading to increasing multiple PRs. It became evident that the goal of infertility treatment is for a patient to have one healthy child at a time. The IVF treatment has been associated with increasing the risk of multiple gestations, primarily due to the transfer of more than one embryo. The effect of multiple gestations to the mother, fetuses, and society has been well documented. The most prevalent maternal complications include preeclampsia, gestational diabetes, placenta previa, placental abruption, postpartum hemorrhage, and preterm labor and delivery (16–20). The risks of fetal demise during the third trimester, perinatal mortality, preterm birth, and low birthweight increase with the number of fetuses in the pregnancy (21). The fetal consequences of preterm birth (cerebral palsy, retinopathy, and bronchopulmonary dysplasia) and fetal growth restriction (polycythemia, hypoglycemia, and necrotizing enterocolitis) are significant. The economic price to society from multiple gestations are substantial and include the immediate costs of maternal hospitalization and neonatal intensive care, along with lifetime costs for chronic illness, special education, and rehabilitation (16, 22, 23). In 1998, SART and ASRM published the first practice guidelines for the maximum numbers of embryos to transfer in IVF cycles based on maternal age (24). These guidelines, VOL. - NO. - / - 2018

Fertility and Sterility®

FIGURE 1

National Trends from 1985 to 2015. (A) Number of IVF clinics (reporting data) in the United States. (B) Number of assisted reproductive technology (ART) cycles initiated in the United States. Jain. IVF data registry for 30 years. Fertil Steril 2018.

based on accumulating evidence, were a direct effort to reduce multiple gestations resulting from IVF treatment (particularly high-order multiples). Trend analysis (from 1995 to 2001) using the IVF national registry data revealed the average number of embryos transferred per cycle began decreasing in 1997, with the steepest decline between 1998 and 1999 (25). Accompanying this decline was a steady increase in the number of pregnancies and live births per cycle (Fig. 2). Most important, starting in 1999, the national rate of high-order multiple births began to stabilize for the first time in at least 18 years. In the 10-year period from 1999 to 2008, the proportion of transfers with three or more embryos VOL. - NO. - / - 2018

declined from 70%–39%, with transfers of four or more embryos declining from 36%–14%. Given the positive influence of the SART/ASRM ET guidelines on multiple gestations, periodic guideline revisions have steadily reduced the maximum number of embryos to transfer without sacrificing live-birth rates (26–32). Recognizing twin pregnancies as a ‘‘high risk’’ outcome, SART/ASRM eventually promoted elective single ET. Continued analyses of the IVF national registry data show steady improvements in lowering multiple gestations along with more adoption of elective single ET (33–44). Before 2002, only 1% of transfers were an elective single ET (45). 3

ORIGINAL ARTICLE: ASSISTED REPRODUCTION Concomitant with evolving SART/ASRM guidelines, from 2005 through 2015, the percentage of elective single ET increased dramatically from about 2% to 35% for women younger than age 35 years and from about 1% to almost 21% for women aged 35–37 years (Fig. 3) (46). Overall, between 1995 and 2015 from all IVF treatments, the twin birth rate has declined from about 30% to 22%, and the high-order birth rate from about 7% to <1% (Fig. 4).

Economics of IVF and Disparities in Access and Outcomes Despite the growing use and success of IVF to treat infertility, in the United States, it primarily remains a privately funded treatment (47, 48). It is often excluded from health insurance plans on the grounds that it is not medically necessary. This is in contrast to the World Health Organization defining infertility as a disease in 2009 (49), followed by recent official concurrence by the American Medical Association (50). Many other developed countries (e.g., Australia, Austria, Denmark, Finland, France, Germany, Iceland, The Netherlands, Norway, and Sweden) have made provisions in their national health plans to cover infertility treatment, including IVF. The average cost of a single IVF cycle in the United States is approximately $12,400, not including IVF medications, which cost $2,000–6,000 in addition (51, 52). With the median United States household income in 2016 being $59,039 (53), many financially constrained infertile couples likely cannot afford such treatment and are excluded from care (54). Furthermore, many couples may need more than one IVF cycle to achieve a live birth, and therefore incur substantially higher costs (55).

To address this financial inequity in health care, advocates have lobbied their state legislatures to mandate private health insurance companies to cover the cost of infertility treatment for state residents. Since the 1980s, 15 states have passed laws mandating insurers to either cover or offer coverage for infertility diagnosis and treatment (56). At present, only eight of those states have a meaningful mandate that requires coverage of IVF treatment (Arkansas, Connecticut, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, Rhode Island). The availability of national IVF registry data has allowed for meaningful analysis of potential disparities created due to lack of uniform health insurance coverage for IVF. Analysis of national data has revealed a 2 to 3fold higher utilization of IVF services within states with a comprehensive mandate to cover IVF compared with states without a mandate (57–59). Similar more levels of IVF utilization are also seen in other countries with national health plans that subsidize IVF expenses (60). Further national IVF registry data studies have revealed important differences in IVF practice patterns and outcomes. Compared with states without mandated insurance coverage for IVF, states with a comprehensive mandate have fewer number of embryos transferred per cycle along with lower rates of multiple pregnancies (especially three or more) (57, 61–63). It has been hypothesized that because patients must pay out of pocket in states without mandated coverage, physicians are placed under pressure to obtain a ‘‘successful’’ outcome the first time and therefore transfer more embryos per cycle (57, 61, 64, 65). Such information continues to be used by advocates to lobby for states to adopt mandates to cover IVF services.

FIGURE 2

Number of live born deliveries and infants born in the United States from assisted reproductive technology (ART). Jain. IVF data registry for 30 years. Fertil Steril 2018.

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FIGURE 3

Percentage of elective single embryo transfer using fresh nondonor eggs or embryos (by age group). Jain. IVF data registry for 30 years. Fertil Steril 2018.

Beyond financial constraints, IVF registry data analysis has also revealed significant disparities in access and outcomes related to race/ethnicity. Analysis of 2014 national IVF registry data revealed that Asian/Pacific Islander women underwent the highest number of IVF procedures per million women aged 15–44 years (5,883), whereas Black nonHispanic, Hispanic, and American Indian/Alaska Native non-Hispanic women had lower than the average US IVF uti-

lization rates (1,434, 997, 807, respectively) (58). Even in states with an insurance mandate, utilization rates for Black non-Hispanic and Hispanic women were lower than the overall utilization rate (58, 65). Findings with regard to racial/ethnic disparities in IVF outcomes are equally striking. Numerous studies analyzing the IVF registry data have consistently found that White women consistently have the highest rates of live births,

FIGURE 4

Percent of single, twin, and triplet. or more live births from IVF transfers using fresh, nondonor eggs or embryos. Jain. IVF data registry for 30 years. Fertil Steril 2018.

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ORIGINAL ARTICLE: ASSISTED REPRODUCTION followed by Hispanic and Asian women, whereas African American women have the lowest rates of live birth (65– 70). These findings have led to researchers actively collaborating to find the underlying reasons for such health disparities. The ASRM has also recognized these disparities in utilization and outcome, and have included solutions to these disparities as part of its strategic plan (71, 72).

IVF and Pregnancy, Birth, and Infant Health Outcomes With the birth of thousands of babies annually from IVF (72,913 in 2015), the national IVF registry data have allowed researchers to analyze birthweight, length of gestation, and live-birth/stillbirth outcomes. In the collection of IVF data (SART and CDC), the unit of analysis is the ‘‘cycle’’ (not the patient). This fact, combined with a mobile patient population receiving care from disparate providers, complicates outcomes research. To study pregnancy, birth, and infant outcomes, researchers have linked the SART CORS to the birth certificate, the birth defects registries, and to hospital discharge data (73). One of the early studies examined whether singleton infants conceived with the use of IVF may have a higher risk of low birthweight compared with spontaneous conceptions (74). The researchers from CDC analyzed IVF registry data from 1996 to 1997 and used a comparison group of >3 million infants born in the United States. They found that among singleton infants born at 37 weeks of gestation or later, those following IVF had a risk of low birthweight that was 2.6 times (95% confidence interval [CI] 2.4–2.7) than in the general population (absolute risk of low birthweight with spontaneous vs. resulting from IVF was 2.5% vs. 6.5%). This finding was thought to be due primarily to early fetal loss (plurality at early pregnancy more than plurality at birth), a direct result of transferring more than one embryo. A similar analysis using IVF registry data from 2000 also found an increased risk of low birthweight, as well as preterm delivery (75). Subsequent analyses by other groups confirmed these findings, and also reported increased risks among women treated with non-IVF fertility treatments (76–78). Infertility is in itself a risk factor for adverse pregnancy outcomes, and the longer the duration of infertility the greater the risk (73). Given the increased risks for singleton neonates born after IVF, researchers analyzed registry data from 2004 to 2006 to assess whether the alteration of the periimplantation maternal environment resulting from ovarian stimulation may contribute to increased risk of low birthweight in IVF births (79). They found no difference in preterm delivery, but the odds of low birthweight was significantly higher after fresh ETs compared with frozen ETs. Separate studies examined the effect of paternal age, maternal age, or use of elective single ET, and found that none of those parameters correlated with increased risk for prematurity or low birthweight (80–82). Two early studies (83, 84) analyzed the impact of first trimester fetal loss on an early twin or triplet IVF pregnancy, which subsequently led to a singleton or twin 6

birth. Analysis of 2005 registry data revealed significantly increased lower birthweight and shortened gestation in the multiple gestation pregnancies that had experienced a first trimester fetal loss. The effect of excess embryos transferred, even when plurality at conception was the same as plurality at birth, was also demonstrated with analysis of SART CORS data (85). Given the increase in autism diagnoses, CDC researchers examined national IVF registry data from 1997 to 2007 and linked the records with California Birth Master Files (86). They did find an association between IVF and autism, but it was primarily explained by adverse prenatal and perinatal outcomes and multiple births. A follow-up analysis revealed that the incidence of autism diagnosis in children resulting from IVF was higher when intracytoplasmic sperm injection (ICSI) was used compared with conventional IVF (87). This analysis dealt with the first 5 years of life. The CDC researchers also linked national IVF registry data from 1997 to 2007 with birth defects registry data from three states (Florida, Massachusetts, and Michigan) (88). They found that singleton infants after IVF were 39% more likely (adjusted relative risk of 1.39, 95% CI 1.21–1.59) to have a nonchromosomal birth defect (particularly gastrointestinal and musculoskeletal) compared with all other singleton births. No single ART procedure (e.g., ICSI, fresh, or frozen ETs) was found to substantially increase the risk of birth defects. Analyses from the Massachusetts Outcome Study of ART reported a 50% increase (adjusted prevalence ratio of 1.5, 95% CI 1.3–1.6) in birth defects in infants after IVF versus spontaneous pregnancy, and a 30% increase (adjusted prevalence ratio of 1.3, 95% CI 1.1–1.5) in birth defects in infants after subfertility versus spontaneous pregnancy (89). These researchers concluded that a substantial portion of the excess risk is mediated through multiple births, along with subfertility contributing an important role.

Patient and Treatment Characteristics Impacting IVF Outcomes A major advantage of having the national IVF registry data has been for researchers to analyze IVF outcomes in relation to patient and treatment characteristics. These outcomes are commonly reported on a per-cycle basis (e.g., live birth per IVF cycle). Such clinic-specific data are published annually by SART and the CDC on their respective websites (4, 5). More detailed patient-specific data are made available by SART and CDC to qualified researchers who want to conduct specific analyses. The SART developed the methodology to link IVF cycles to individual women, thus allowing calculation of cumulative live-birth rates as a function of the method of treatment, and analyses adjusting for the outcome of prior cycles (90, 91). This linkage led to a seminal analysis of the registry data from 2004 to 2009 outlining cumulative live-birth rates from autologous and donor oocyte cycles (90). The study concluded that cumulative live-birth rates approaching natural fecundity can be achieved with IVF using autologous oocytes. Also, cumulative live-birth rates in older women were similar to younger women when donor oocytes were used. VOL. - NO. - / - 2018

Fertility and Sterility® An analysis of data (92) from 2008 to 2010 did reveal that donor oocyte recipients have stable pregnancy outcomes before age 45 years, after which there is a small but steady decline. Given the ability to link IVF cycles to individual women, SART-supported research of registry data from 2004 to 2011 resulted in the development of a model predictive of live-birth rates and multiple birth rates for an individual considering IVF (93). This validated model (for autologous and donor oocyte cycles) has subsequently been implemented on the SART website, therefore patients considering initiating an IVF cycle can input their data on the website to generate their expected outcomes (5). This predictive model was also used to demonstrate that the cumulative live-birth rate is as good or better with a single ET during two IVF cycles than with a double ET in one cycle, yet greatly reducing the probability of a multiple birth (94). Another independent analysis (95) of data from 2004 through 2013 found that in patients with favorable prognostic factors, the gain in the live-birth rate from single ET to double ET was 10%–15%; however, the multiple birth rate increased from approximately 2% to >49% in both autologous and donor fresh and frozen-thawed IVF cycles. Linkage of IVF cycles to individual women also enabled analysis of the risk of breast and genital cancer with IVF. In a large study (96) of women who initiated IVF in New York, Texas, and Illinois between 2004 and 2009, there was no evidence of increased risk of cancers after nearly 5 years of follow-up relative to age-specific general population rates. The advantage of this study versus prior reports is the population-based design, follow-up of contemporary IVF regimens (2004 to 2009), large sample size (>50,000 women treated with IVF), and the use of a national IVF database with validated exposure data. Given the steady increase of obesity in the United States, the effect of a woman's body mass index (BMI) on IVF outcomes has been debated. In 2007, patient height and weight data were added to the national IVF registry system. Using these data, researchers found that increasing obesity was associated with a significant increase in failure to achieve a clinical pregnancy with the use of autologous oocytes, but no difference with the use of donor oocytes (97). Furthermore, in those women who did conceive, failure to achieve a live birth increased with more obesity, and to a greater extent for those individuals <35 years of age and with use of both autologous and donor oocytes (97). A further analysis (69) revealed significant disparities in pregnancy and live-birth rates by race and ethnicity, within BMI categories. Other investigators also found that preconception maternal obesity was associated with significantly increased risk of very early (<28 weeks) and early (<32 weeks) preterm birth from singleton and twin pregnancies conceived through IVF (98, 99). Moderate to severe ovarian hyperstimulation syndrome (OHSS) is a rare but serious complication of ovarian stimulation (100). Analysis of the national IVF registry for IVF cycles performed between 2004 and 2006 revealed that the risk of developing OHSS was increased for Black women when compared with White women. Although the presence of VOL. - NO. - / - 2018

OHSS increased the odds of achieving pregnancy, there is a concomitant increased risk of an adverse pregnancy outcome (stillbirth, low birthweight, or preterm birth) by 26% (adjusted odds ratio 1.26, 95% CI 1.13–1.40) and low birthweight among singletons by 40% (adjusted odds ratio 1.40, 95% CI 1.12–1.75) (101). Several approaches to diminish OHSS have subsequently been adopted including triggering with GnRH agonists and cryopreserving all embryos for a subsequent frozen ET in an unstimulated cycle. The incidence of ectopic pregnancy (EP) after IVF procedures was controversial with rates as high as 8% reported in small retrospective studies (102). Analysis of national IVF registry data for 2001, however, revealed that the EP rate to be 0.8% per transfer and 1.6% per pregnancy, which were comparable to the overall incidence of EP in the United States (103). Continued annual tracking and reporting of EP rates from fresh, nondonor IVF cycles have been stable, with the EP rate being 0.5% in 2015 (46). Another important parameter, which was initially missing from the national IVF registry, is embryo morphology, which is known to be associated with implantation potential and attaining live birth. In June 2006, SART decided to voluntarily begin collecting embryo morphology data through the national registry to assess patient reproductive potential; reporting of these data became mandatory in 2010. In addition, it was thought that such collection would help standardize grading systems among IVF clinics, helping not only in quality assurance and quality improvement activities, but also in reducing the number of embryos transferred. By establishing a standardized grading system and with associated live-birth rates from a large number of embryos, clinics may have greater assurance that PRs may not be compromised after transfer of fewer embryos. The morphology system for day 3 and day 5 embryos was put in place and successfully validated to confirm a significant association between embryo quality parameters and live birth after IVF (104–106). National IVF registry data also allowed for assessment of embryology laboratory techniques such as ICSI, assisted zona hatching, and preimplantation genetic testing (PGT). Although ICSI was developed to overcome male factor infertility, trend analyses of the registry data from 1995 onward revealed that ICSI use dramatically increased in the United States (from 11% in 1995 to 76% in 2012), with the largest relative increase among cycles without male factor infertility (107, 108). Furthermore, the analyses revealed that among cycles without male factor infertility, ICSI use was associated with lower rates of implantation and live births compared with conventional IVF. The utility of assisted zona hatching and ICSI for patients with diminished ovarian reserve as the primary diagnosis was also analyzed using national IVF registry data from 2004 to 2011 (109). The investigators found that assisted zona hatching and ICSI were associated with significantly lower odds of live birth. Another analysis of data from 2004 to 2010 found that assisted zona hatching on day 2–3 embryos more than doubled the risk of monozygotic twin pregnancy (110). The use of PGT in the United States has been analyzed with some interesting findings. Compared with a 2007 to 7

ORIGINAL ARTICLE: ASSISTED REPRODUCTION 2008 data analysis, a 2011 to 2012 analysis reveals relatively minimal change in PGT utilization (4.4% vs. 4.5% of all fresh IVF cycles) (111, 112). Aneuploidy was the most common indication for use of PGT. Use of PGT for aneuploidy was associated with decreased odds of miscarriage for women >35 years, and increased odds of a live-birth delivery among women >37 years. However, no significant improvement in clinical pregnancy or live births was found for women <35 years (112).

DISCUSSION Limitations of SART CORS data There are numerous limitations to the annual collecting and reporting of the national IVF registry data. Given the data are self-reported yearly by each IVF clinic, timely participation and accuracy are essential to allow meaningful use of the data. Although it is federally mandated, a small number of clinics do not report data to the CDC and are listed as nonreporters in the ART Report. However, because most nonreporting clinics are small, the CDC estimates that it still collects information from >95% of all IVF cycles in the United States (113). There have been growing concerns about some IVF clinics not reporting all IVF cycles initiated, especially those of poor responder patients who may have a cycle cancelled (114, 115). A lower IVF cycle cancellation rate would artificially inflate outcomes such as ‘‘percentage of live births per cycle initiated.’’ To ensure proper data entry of all cycles, starting 2011, SART began requiring all member IVF clinics to prospectively report their data (i.e., a patient's demographic data and cycle start date must be entered within 4 days of starting gonadotropin therapy) (116, 117). To ensure data accuracy, the CDC has an extensive quality control program (46, 118). After a clinic's online data submission to the CDC's National ART Surveillance System, or indirectly by SART CORS, each IVF clinic's medical director has to verify by signature that the submitted data are accurate. The CDC subsequently conducts a review of the data and contacts the clinics if corrections are necessary. This is followed by an annual registry data validation process. The CDC randomly chooses 7%–10% of IVF clinics to conduct a site visit. In 2015, 34 (about 7%) of the 464 reporting clinics were selected. A CDC Validation Team visits the clinic and reviews medical record data for a sample of the clinic's IVF cycles. The SART also has a parallel Validation Team that is present for the site visits (8). For each IVF cycle, the validation team abstracts information from the patient's medical record and compares it with the data submitted, to ensure accuracy. Data field discrepancy rates are annually published by the CDC and are usually low (<4% in 2015) (46). Recent analyses of national IVF registry data reveal that there are some important data fields needing improvement to be used for meaningful research. Given that patient race/ ethnicity fields were not required, early studies on racial/ ethnic disparities using registry data had >35% of cycles excluded from analysis due to missing race/ethnicity data (70). Analysis of the birth defects data field by matching 8

IVF registry data with the birth defects registry in Massachusetts found very poor agreement (38.6% sensitivity), necessitating linkage to State birth defects registries for accurate data (119). Similarly, analysis of length of gestation data fields (for infant prematurity studies) found variations in the method used for calculating gestational age (120). It is also important to note that an untoward effect of the well-intentioned public IVF outcome reporting has been for clinics to use it for advertising and competitive advantage. Despite the CDC and SART having disclaimers to prevent clinic data comparisons, referring doctors and patients routinely assess clinic quality by comparing pregnancy and live-birth rates between clinics (115). There have been commercial attempts to ‘‘rank’’ IVF clinics using the publicly reported data (118, 121). Even the government and thirdparty payors have been known to use the IVF outcome data to provide subsidies to better performing clinics (114). Recent evidence also suggests that some clinics may deny care for poor prognosis patients or recommend higher number of embryos to transfer, to report superior IVF results (122). In summary, since the first SART national IVF data report publication 30 years ago, it is clear that SART has achieved its original goals of creating a national IVF registry to assess clinical effectiveness, quality of care, and monitor safety. Thanks to the foresight of the early IVF pioneers, national data collection and reporting for the past 30 years has provided fundamental industry-wide feedback, which has documented improved quality and care. Credit must also be given to all the IVF Centers who fund, diligently collect, and annually report their data to SART and CDC. With continued improvements and refinements of the IVF data collection and reporting process (123), IVF providers and laboratory directors will continue to be informed of contemporary best practices. Such improvements lead to better patient counseling and informed decision making. The ultimate benefactors of the national IVF registry are the patients who seek effective fertility care and are provided safe and evidence-based infertility treatments.

REFERENCES 1.

2.

3. 4.

5. 6.

7. 8.

Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril 2013;99:63. Chandra A, Copen CE, Stephen EH. Infertility service use in the United States: data from the National Survey of Family Growth, 1982-2010. National Health Statistics Reports; 2014, No. 73. Jones HW Jr, Jones GS, Andrews MC, Acosta A, Bundren C, Garcia J, et al. The program for in vitro fertilization at Norfolk. Fertil Steril 1982;38:14–21. Centers for Disease Control and Prevention. ART success rates—archived ART reports. Available at: www.cdc.gov/art/reports/archive.html. Accessed August 25, 2018. Society for Assisted Reproductive Technology. IVF success. Available at: www.sart.org. Accessed August 25, 2018. Levine AD, Boulet SL, Kissin DM. Contribution of assisted reproductive technology to overall births by maternal age in the United States, 20122014. JAMA 2017;317:1272–3. Jones HW Jr. Howard & Georgeanna: sixty years of marriage & medicine. Williamsburg, Virginia: Jamestowne Bookworks; 2015. Toner JP, Coddington CC, Doody K, van Voorhis B, Seifer DB, Ball GD, et al. Society for assisted reproductive technology and assisted VOL. - NO. - / - 2018

Fertility and Sterility®

9. 10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21. 22.

23.

24.

25.

26.

27.

28.

reproductive technology in the United States: a 2016 update. Fertil Steril 2016;106:541–6. Doody KJ. Public reporting of ART cycle outcome data is not simple. Fertil Steril 2016;105:893–4. Medical Research International, The American Fertility Society Special Interest Group. In vitro fertilization/embryo transfer in the United States: 1985 and 1986 results from the National IVF-ET Registry. Fertil Steril 1988;49: 212–5. Centers for Disease Control and Prevention. National ART surveillance policy documents. Available at: www.cdc.gov/art/nass/policy.html. Accessed August 25, 2018. H.R. 4773, Public Law 102-493, Fertility Clinic Success Rate and Certification Act of 1992. Available at: https://www.gpo.gov/fdsys/pkg/STATUTE106/pdf/STATUTE-106-Pg3146.pdf. Accessed August 25, 2018. Department of Health and Human Services, Centers for Disease Control and Prevention. Reporting of Pregnancy Success Rates From Assisted Reproductive Technology (ART) Programs, Vol 80. Federal Register; 2015. No. 165. Available at: www.gpo.gov/fdsys/pkg/FR-2015-08-26/ pdf/2015-21108.pdf. Accessed August 25, 2018. Society for Assisted Reproductive Technology. Publications using SART CORS. Available at: https://www.sart.org/professionals-and-providers/ research/publications-using-sart-cors/. Accessed August 25, 2018. Centers for Disease Control and Prevention. Assisted reproductive technology key findings. Available at: https://www.cdc.gov/art/key-findings/ index.html. Accessed August 25, 2018. Practice Committee of the American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy: an American Society for Reproductive Medicine Practice Committee opinion. Fertil Steril 2012; 97:825–34. American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Practice Bulletin No. 169: Multiple gestations: twin, triplet, and higher-order multifetal pregnancies. Obstet Gynecol 2016;128:e131–46. American College of Obstetricians and Gynecologists' Committee on Obstetric Practice and Committee on Genetics. Committee Opinion No 671: perinatal risks associated with assisted reproductive technology. Obstet Gynecol 2016;128:e61–8. Luke B, Brown MB. Contemporary risks of maternal morbidity and adverse outcomes with increasing maternal age and plurality. Fertil Steril 2007;88: 283–93. Conde-Agudelo A1, Belizan JM, Lindmark G. Maternal morbidity and mortality associated with multiple gestations. Obstet Gynecol 2000;95:899– 904. Institute of Medicine. Preterm birth: causes, consequences, and prevention. Washington, DC: National Academies Press; 2007. Bromer JG, Ata B, Seli M, Lockwood CJ, Seli E. Preterm deliveries that result from multiple pregnancies associated with assisted reproductive technologies in the USA: a cost analysis. Curr Opin Obstet Gynecol 2011;23:168– 73. Sunderam S, Kissin DM, Crawford SB, Folger SG, Jamieson DJ, Warner L, et al. Assisted Reproductive Technology Surveillance—United States, 2014. MMWR Surveill Summ 2017;66:1–24. Guidelines on number of embryos transferred. ASRM Practice Committee report. Birmingham, Ala.: American Society for Reproductive Medicine, January 1998. Jain T, Missmer SA, Hornstein MD. Trends in embryo-transfer practice and in outcomes of the use of assisted reproductive technology in the United States. N Engl J Med 2004;350:1639–45. Guidelines on number of embryos transferred. ASRM Practice Committee report. Rev. ed. Birmingham, Ala.: American Society for Reproductive Medicine, November 1999. Practice Committee of American Society for Reproductive Medicine; Practice Committee of Society for Assisted Reproductive Technology. Guidelines on number of embryos transferred. Fertil Steril 2004;82:S1–2. Practice Committee of American Society for Reproductive Medicine; Practice Committee of Society for Assisted Reproductive Technology. Guidelines on number of embryos transferred. Fertil Steril 2006;86:S51–2.

VOL. - NO. - / - 2018

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

46.

47.

Practice Committee of American Society for Reproductive Medicine; Practice Committee of Society for Assisted Reproductive Technology. Guidelines on number of embryos transferred. Fertil Steril 2008;90:S163–4. Practice Committee of American Society for Reproductive Medicine; Practice Committee of Society for Assisted Reproductive Technology. Guidelines on number of embryos transferred. Fertil Steril 2009;92:1518–9. Practice Committee of American Society for Reproductive Medicine; Practice Committee of Society for Assisted Reproductive Technology. Criteria for number of embryos to transfer: a committee opinion. Fertil Steril 2013;99:44–6. Practice Committee of the American Society for Reproductive Medicine. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril 2017;107:901–3. Stern JE, Cedars MI, Jain T, Klein NA, Beaird CM, Grainger DA, et al. Society for Assisted Reproductive Technology Writing Group. Assisted reproductive technology practice patterns and the impact of embryo transfer guidelines in the United States. Fertil Steril 2007;88:275–82. Gibbons W, Grainger D, Cedars M, Jain T, Klein N, Stern J, SART Research Committee Writing Group. Continuous quality improvement and assisted reproductive technology multiple gestations: some progress, some answers, more questions. Fertil Steril 2007;88:301–4. Dickey RP. The relative contribution of assisted reproductive technologies and ovulation induction to multiple births in the United States 5 years after the Society for Assisted Reproductive Technology/American Society for Reproductive Medicine recommendation to limit the number of embryos transferred. Fertil Steril 2007;88:1554–61. Stern JE, Goldman MB, Hatasaka H, MacKenzie TA, Racowsky C, Surrey ES. Optimizing the number of blastocyst stage embryos to transfer on day 5 or 6 in women 38 years of age and older: a Society for Assisted Reproductive Technology database study. Fertil Steril 2009;91:157–66. Stern JE, Goldman MB, Hatasaka H, MacKenzie TA, Surrey ES, Racowsky C. Optimizing the number of cleavage stage embryos to transfer on day 3 in women 38 years of age and older: a Society for Assisted Reproductive Technology database study. Fertil Steril 2009;91:767–76. Luke B, Brown MB, Grainger DA, Cedars M, Klein N, Stern JE. Practice patterns and outcomes with the use of single embryo transfer in the United States. Fertil Steril 2010;93:490–8. Practice Committee of Society for Assisted Reproductive Technology; Practice Committee of American Society for Reproductive Medicine. Elective single-embryo transfer. Fertil Steril 2012;97:835–42. 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. Kissin DM, Kulkarni AD, Kushnir VA, Jamieson DJ, National ART Surveillance System Group. Number of embryos transferred after in vitro fertilization and good perinatal outcome. Obstet Gynecol 2014;123:239–47. Kissin DM, Kulkarni AD, Mneimneh A, Warner L, Boulet SL, Crawford S, et al. National ART Surveillance System (NASS) group. Embryo transfer practices and multiple births resulting from assisted reproductive technology: an opportunity for prevention. Fertil Steril 2015;103:954–61. Keyhan S, Acharya KS, Acharya CR, Yeh JS, Provost MP, Goldfarb JM, et al. How compliant are in vitro fertilization member clinics in following embryo transfer guidelines? An analysis of 59,689 fresh first in vitro fertilization autologous cycles from 2011 to 2012. Fertil Steril 2016;106:645–52. Acharya KS, Keyhan S, Acharya CR, Yeh JS, Provost MP, Goldfarb JM, et al. Do donor oocyte cycles comply with ASRM/SART embryo transfer guidelines? An analysis of 13,393 donor cycles from the SART registry. Fertil Steril 2016;106:603–7. Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2009 Assisted Reproductive Technology Fertility Success Rates Report. Atlanta (GA): US Department of Health and Human Services; 2011. Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2015 Assisted Reproductive Technology Fertility Success Rates Report. Atlanta (GA): US Department of Health and Human Services; 2017. Jain T, Hornstein MD. To pay or not to pay. Fertil Steril 2003;80:27–9.

9

ORIGINAL ARTICLE: ASSISTED REPRODUCTION 48.

49.

50.

51.

52.

53.

54. 55.

56.

57. 58.

59.

60.

61.

62.

63.

64. 65.

66.

67.

10

Ethics Committee of the American Society for Reproductive Medicine. Disparities in access to effective treatment for infertility in the United States: an ethics committee opinion. Fertil Steril 2015;104:1104–10. Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril 2009;92:1520–4. Berg S. AMA backs global health experts in calling infertility a disease. American Medical Association News; 2017. Available at: wire.amaassn.org/ama-news/ama-backs-global-health-experts-calling-infertilitydisease. Accessed August 25, 2018. American Society for Reproductive Medicine. Is in vitro fertilization expensive?. Available at: http://www.reproductivefacts.org/faqs/frequentlyasked-questions-about-infertility/q06-is-in-vitro-fertilization-expensive/. Accessed August 25, 2018. Wu AK, Odisho AY, Washington SL, Katz PP, Smith JF. Out-of-pocket fertility patient expense: data from a multicenter prospective infertility cohort. J Urol 2014;191:427–32. United States Census Bureau. Income, poverty and health insurance coverage in the United States: 2016. Available at: https://www.census. gov/newsroom/press-releases/2017/income-povery.html. Accessed August 25, 2018. Jain T. Socioeconomic and racial disparities among infertility patients seeking care. Fertil Steril 2006;85:876–81. Katz P, Showstack J, Smith JF, Nachtigall RD, Millstein SG, Wing H, et al. Costs of infertility treatment: results from an 18-month prospective cohort study. Fertil Steril 2011;95:915–21. National Conference of State Legislatures. State Laws Related to Insurance Coverage for Infertility Treatment. Available at: www.ncsl.org/research/ insurance-coverage-for-infertility-laws.aspx. Accessed August 25, 2018. Jain T, Harlow BL, Hornstein MD. Insurance coverage and outcomes of in vitro fertilization. N Engl J Med 2002;347:661–6. Dieke AC, Zhang Y, Kissin DM, Barfield WD, Boulet SL. Disparities in assisted reproductive technology utilization by race and ethnicity, United States, 2014: a commentary. J Womens Health 2017;26:605–8. Crawford S, Boulet SL, Jamieson DJ, Stone C, Mullen J, Kissin DM. Assisted reproductive technology use, embryo transfer practices, and birth outcomes after infertility insurance mandates: New Jersey and Connecticut. Fertil Steril 2016;105:347–55. Chambers GM, Hoang VP, Sullivan EA, Chapman MG, Ishihara O, ZegersHochschild F, et al. The impact of consumer affordability on access to assisted reproductive technologies and embryo transfer practices: an international analysis. Fertil Steril 2014;101:191–8. Martin JR, Bromer JG, Sakkas D, Patrizio P. Insurance coverage and in vitro fertilization outcomes: a U.S. perspective. Fertil Steril 2011; 95:964–9. Boulet SL, Crawford S, Zhang Y, Sunderam S, Cohen B, Bernson D, et al, for the SMART Collaborative. Embryo transfer practices and perinatal outcomes by insurance mandate status. Fertil Steril 2015;104:403–9. Styer AK, Luke B, Vitek W, Christianson MS, Baker VL, Christy AY, et al. Factors associated with the use of elective single-embryo transfer and pregnancy outcomes in the United States, 2004-2012. Fertil Steril 2016;106: 80–9. Collins JA. Reproductive technology—the price of progress. N Engl J Med 1994;331:270–1. Seifer DB, Zackula R, Grainger DA, a Society for Assisted Reproductive Technology Writing Group. Trends of racial disparities in assisted reproductive technology outcomes in black women compared with white women: Society for Assisted Reproductive Technology 1999 and 2000 vs. 20042006. Fertil Steril 2010;93:626–35. Seifer DB, Frazier LM, Grainger DA. Disparity in assisted reproductive technologies outcomes in black women compared with white women. Fertil Steril 2008;90:1701–10. Fujimoto VY, Luke B, Brown MB, Jain T, Armstrong A, Grainger DA, et al. a Society for Assisted Reproductive Technology Writing Group. Racial and ethnic disparities in assisted reproductive technology outcomes in the United States. Fertil Steril 2010;93:382–90.

68.

69.

70.

71.

72.

73.

74.

75.

76.

77.

78.

79.

80.

81.

82.

83.

84.

85.

86.

Baker VL, Luke B, Brown MB, Alvero R, Frattarelli JL, Usadi R, et al. Multivariate analysis of factors affecting probability of pregnancy and live birth with in vitro fertilization: an analysis of the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Fertil Steril 2010;94: 1410–6. Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. Racial and ethnic disparities in assisted reproductive technology pregnancy and live birth rates within body mass index categories. Fertil Steril 2011;95:1661–6. Wellons MF, Fujimoto VY, Baker VL, Barrington DS, Broomfield D, Catherino WH, et al. Race matters: a systematic review of racial/ethnic disparity in Society for Assisted Reproductive Technology reported outcomes. Fertil Steril 2012;98:406–9. Fujimoto VY, Jain T, Alvero R, Nelson LM, Catherino WH, Olatinwo M, et al. Proceedings from the Conference on Reproductive Problems in Women of Color. Fertil Steril 2010;94:7–10. American Society for Reproductive Medicine. White Paper: access to care summit. September 10–11, 2015. Available at: http://www.asrm.org/glob alassets/asrm/asrm-content/news-and-publications/news-and-research/ press-releases-and-bulletins/pdf/atcwhitepaper.pdf. Accessed August 25, 2018. Luke B. Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies. Am J Obstet Gynecol 2017;217:270–81. Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with the use of assisted reproductive technology. N Engl J Med 2002;346:731–7. Schieve LA, Ferre C, Peterson HB, Macaluso M, Reynolds MA, Wright VC. Perinatal outcome among singleton infants conceived through assisted reproductive technology in the United States. Obstet Gynecol 2004;103: 1144–53. Declercq E, Luke B, Belanoff C, Cabral H, Diop H, Gopal D, et al. Perinatal outcomes associated with assisted reproductive technology: the Massachusetts outcomes study of assisted reproductive technologies (MOSART). Fertil Steril 2015;103:888–95. Luke B, Gopal D, Stern JE, Diop H. Pregnancy, birth, and infant outcomes by maternal fertility status: The Massachusetts Outcomes Study of Assisted Reproductive Technology. Am J Obstet Gynecol 2017;217:327.e1–14. Luke B, Gopal D, Stern JE, Diop H. Adverse pregnancy, birth, and infant outcomes in twins: effects of maternal fertility status and infant gender combination. The Massachusetts Outcomes Study of Assisted Reproductive Technology. Am J Obstet Gynecol 2017;217:330.e1–15. Kalra SK, Ratcliffe SJ, Coutifaris C, Molinaro T, Barnhart KT. Ovarian stimulation and low birthweight in newborns conceived through in vitro fertilization. Obstet Gynecol 2011;118:863–71. Stern JE, Luke B, Hornstein MD, Cabral H, Gopal D, Diop H, et al. The effect of father's age in fertile, subfertile, and assisted reproductive technology pregnancies: a population based cohort study. J Assist Reprod Genet 2014;31:1437–44. Xiong X, Dickey RP, Pridjian G, Buekens P. Maternal age and preterm births in singleton and twin pregnancies conceived by in vitro fertilization in the United States. Paediatr Perinat Epidemiol 2015;29:22–30. Fechner AJ, Brown KR, Onwubalili N, Jindal SK, Weiss G, Goldsmith LT, et al. Effect of single embryo transfer on the risk of preterm birth associated with in vitro fertilization. J Assist Reprod Genet 2015;32:221–4. Luke B, Brown MB, Grainger DA, Stern JE, Klein N, Cedars MI. The effect of early fetal losses on singleton assisted conception pregnancy outcomes. Fertil Steril 2009;91:2578–85. Luke B, Brown MB, Grainger DA, Stern JE, Klein N, Cedars MI. The effect of early fetal losses on twin assisted conception pregnancy outcomes. Fertil Steril 2009;91:2586–92. Luke B, Brown MB, Stern JE, Grainger DA, Klein N, Cedars M. Effect of embryo transfer number on singleton and twin implantation pregnancy outcomes after assisted reproductive technology (ART). J Reprod Med 2010; 55:387–94. Fountain C, Zhang Y, Kissin DM, Schieve LA, Jamieson DJ, Rice C, et al. Association between ART conception and autism in California 1997-2007. Am J Public Health 2015;105:96371.

VOL. - NO. - / - 2018

Fertility and Sterility® 87.

88.

89.

90.

91.

92.

93.

94.

95.

96.

97.

98.

99.

100.

101.

102.

103.

104.

Kissin DM, Zhang Y, Boulet SL, Fountain C, Bearman P, Schieve L, et al. Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children. Hum Reprod 2015;30:454–65. Boulet SL, Kirby RS, Reefhuis J, Zhang Y, Sunderam S, Cohen B, et al. Assisted reproductive technology and birth defects among liveborn infants in Florida, Massachusetts, and Michigan, 2000-2010. JAMA Pediatr 2016; 170:e154934. Liberman RF, Getz KD, Heinke D, Luke B, Stern JE, Declerq ER, et al. Assisted reproductive technology and birth defects: Effects of subfertility and multiple births. Birth Defects Res 2017;109:1144–53. Luke B, Brown MB, Wantman E, Lederman A, Gibbons W, Schattman GL, et al. Cumulative birth rates with linked assisted reproductive technology cycles. N Engl J Med 2012;366:2483–91. Luke B, Brown MB, Wantman E, Baker VL, Grow DR, Stern JE. Second try: who returns for additional ART treatment and the effect of a prior ART birth. Fertil Steril 2013;100:1580–4. Yeh JS, Steward RG, Dude AM, Shah AA, Goldfarb JM, Muasher SJ. Pregnancy outcomes decline in recipients over age 44: an analysis of 27,959 fresh donor oocyte in vitro fertilization cycles from the Society for Assisted Reproductive Technology. Fertil Steril 2014;101:1331–6. Luke B, Brown MB, Wantman E, Stern JE, Baker VL, Widra E, et al. A prediction model for live birth and multiple births within the first three cycles of assisted reproductive technology. Fertil Steril 2014;102:744–52. Luke B, Brown MB, Wantman E, Stern JE, Baker VL, Widra E, et al. Application of a validated prediction model for in vitro fertilization: comparison of live birth rates and multiple birth rates with 1 embryo transferred over 2 cycles vs 2 embryos in 1 cycle. Am J Obstet Gynecol 2015;212:676.e107. Mersereau J, Stanhiser J, Coddington C, Jones T, Luke B, Brown MB. Patient and cycle characteristics predicting high pregnancy rates with single-embryo transfer: an analysis of the Society for Assisted Reproductive Technology outcomes between 2004 and 2013. Fertil Steril 2017;108: 750–6. Luke B, Brown MB, Spector LG, Missmer SA, Leach RE, Williams M, et al. Cancer in women after assisted reproductive technology. Fertil Steril 2015;104:1218–26. Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod 2011;26:245–52. Dickey RP, Xiong X, Gee RE, Pridjian G. Effect of maternal height and weight on risk for preterm birth in singleton and twin births resulting from in vitro fertilization: a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Fertil Steril 2012;97:349–54. Dickey RP, Xiong X, Xie Y, Gee RE, Pridjian G. Effect of maternal height and weight on risk for preterm singleton and twin births resulting from IVF in the United States, 2008-2010. Am J Obstet Gynecol 2013;209:349.e1–6. Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril 2016;106:1634–47. Luke B, Brown MB, Morbeck DE, Hudson SB, Coddington CC 3rd, Stern JE. Factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect on assisted reproductive technology (ART) treatment and outcome. Fertil Steril 2010;94:1399–404. Verhulst G, Camus M, Bollen N, van Steirteghem A, Devroey P. Analysis of the risk factors with regard to the occurrence of ectopic pregnancy after medically assisted procreation. Hum Reprod 1993;8:1284–7. Society for Assisted Reproductive Technology, American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 2001 results generated from the American Society for Reproductive Medicine/Society for Assisted Reprodutive Technology registry. Fertil Steril 2007;87:1253–66. Racowsky C, Stern JE, Gibbons WE, Behr B, Pomeroy KO, Biggers JD. National collection of embryo morphology data into Society for Assisted Reproductive Technology Clinic Outcomes Reporting System: associations among day 3 cell number, fragmentation and blastomere asymmetry, and live birth rate. Fertil Steril 2011;95:1985–9.

VOL. - NO. - / - 2018

105.

106.

107. 108.

109.

110.

111.

112.

113.

114.

115.

116.

117. 118.

119.

120.

121. 122.

123.

Vernon M, Stern JE, Ball GD, Wininger D, Mayer J, Racowsky C. Utility of the national embryo morphology data collection by SART: correlation between day 3 morphology grade and live birth outcome. Fertil Steril 2011; 95:2761–3. Luke B, Brown MB, Stern JE, Jindal SK, Racowsky C, Ball GD. Using the Society for Assisted Reproductive Technology Clinic Outcome System morphological measures to predict live birth after assisted reproductive technology. Fertil Steril 2014;102:1338–44. Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med 2007;357:251–7. Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA 2015;313:255–63. Butts SF, Owen C, Mainigi M, Senapati S, Seifer DB, Dokras A. Assisted hatching and intracytoplasmic sperm injection are not associated with improved outcomes in assisted reproduction cycles for diminished ovarian reserve: an analysis of cycles in the United States from 2004 to 2011. Fertil Steril 2014;102:1041–7. Luke B, Brown MB, Wantman E, Stern JE. Factors associated with monozygosity in assisted reproductive technology pregnancies and the risk of recurrence using linked cycles. Fertil Steril 2014;101: 683–9. Ginsburg ES, Baker VL, Racowsky C, Wantman E, Goldfarb J, Stern JE. Use of preimplantation genetic diagnosis and preimplantation genetic screening in the United States: a Society for Assisted Reproductive Technology Writing Group paper. Fertil Steril 2011;96:865–8. Chang J, Boulet SL, Jeng G, Flowers L, Kissin DM. Outcomes of in vitro fertilization with preimplantation genetic diagnosis: an analysis of the United States Assisted Reproductive Technology Surveillance Data, 2011–2012. Fertil Steril 2016;105:394–400. Centers for Disease Control and Prevention. National ART Surveillance. Available at: www.cdc.gov/art/nass/index.html. Accessed August 25, 2018. Kushnir VA, Vidali A, Barad DH, Gleicher N. The status of public reporting of clinical outcomes in assisted reproductive technology. Fertil Steril 2013; 100:736–41. Kulak D, Jindal SK, Oh C, Morelli SS, Kratka S, McGovern PG. Reporting in vitro fertilization cycles to the Society for Assisted Reproductive Technology database: where have all the cycles gone? Fertil Steril 2016;105:927– 31. Society for Assisted Reproductive Technology. Newsletter: Summer/ Fall 2011. Available at: www.sart.org/globalassets/__sart/members-onlydocuments/sart-newsletters/sart-newsletter-summer-fall-2011.pdf. Accessed August 25, 2018. Kissin DM, Jamieson DJ, Barfield WD. Assisted reproductive technology program reporting. JAMA 2011;306:2564–5. Adashi EY, Wyden R. Public reporting of clinical outcomes of assisted reproductive technology programs: implications for other medical and surgical procedures. JAMA 2011;306:1135–6. Stern JE, Gopal D, Liberman RF, Anderka M, Kotelchuck M, Luke B. Validation of birth outcomes from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS): population-based analysis from the Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART). Fertil Steril 2016;106:717–22. Stern JE, Kotelchuck M, Luke B, Declercq E, Cabral H, Diop H. Calculating length of gestation from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database versus vital records may alter reported rates of prematurity. Fertil Steril 2014;101: 1315–20. Fertility Success Rates. Available at: www.fertilitysuccessrates.com. Accessed August 25, 2018. Gunderson S, Jungheim E, Callen K, Omurtag K. Public reporting of IVF outcomes influences medical decision making. Fertil Steril 2018;109: e28–9. Williams RS, Doody KJ, Schattman GL, Adashi EY. Public reporting of assisted reproductive technology outcomes: past, present, and future. Am J Obstet Gynecol 2015;212:157–62.

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