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Comparative Effectiveness Review Number 217 R Management of Infertility Comparative Effectiveness Review Number 217 Management of Infertility Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov Contract No. 290-2015-00004-I Prepared by: Duke Evidence-based Practice Center Durham, NC Investigators: Evan R. Myers, M.D., M.P.H. Jennifer L. Eaton, M.D., M.S.C.I. Kara A. McElligott, M.D., M.P.H. Patricia G. Moorman, Ph.D., M.S.P.H. Ranee Chatterjee, M.D., M.P.H. Arthurine K. Zakama, M.D. Karen Goldstein, M.D., M.S.P.H. Jennifer Strauss, Ph.D. Remy R. Coeytaux, M.D., Ph.D. Adam Goode, D.P.T., Ph.D. Ethan Borre, B.A. Geeta K. Swamy, M.D. Amanda J. McBroom, Ph.D. Kathryn Lallinger, M.S.L.S. Robyn Schmidt, B.A. J. Kelly Davis, B.A. Victor Hasselblad, Ph.D. Gillian D. Sanders, Ph.D. AHRQ Publication No. 19-EHC014-EF May 2019 Key Messages Purpose of Review Evaluate the comparative effectiveness and safety of treatments for common causes of infertility. Key Messages • The ability to compare the effectiveness of treatments would be enhanced by greater consistency in reporting of outcomes, particularly live birth rates, as well as reporting of diagnosis-specific outcomes for treatments, such as assisted reproductive technology, that are used for multiple diagnoses. • Letrozole most likely results in more live births with lower multiple births than clomiphene alone in women with polycystic ovary syndrome. • For women with unexplained infertility, there is most likely shorter time to pregnancy for women with immediate in vitro fertilization (IVF) than for those who undergo other treatments prior to IVF. For the outcomes of live birth, multiple births, ectopic pregnancy, miscarriage, low birthweight, and ovarian hyperstimulation syndrome however, there may be no difference between the two groups. • Across all diagnoses, elective single-embryo transfer results in slightly lower live birth rates but substantially lower reductions in multiple birth rates than multiple-embryo transfer. ii This report is based on research conducted by the Duke Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00004-I. The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. The information in this report is intended to help healthcare decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients. This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders. AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied. This report may periodically be assessed for the currency of conclusions. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program website at www.effectivehealthcare.ahrq.gov. Search on the title of the report. Persons using assistive technology may not be able to fully access information in this report. For assistance contact [email protected]. Suggested citation: Myers ER, Eaton JL, McElligott KA, Moorman PG, Chatterjee R, Zakama AK, Goldstein K, Strauss J, Coeytaux RR, Goode A, Borre E, Swamy GK, McBroom AJ, Lallinger K, Schmidt R, Davis JK, Hasselblad V, Sanders GD. Management of Infertility. Comparative Effectiveness Review No. 217. (Prepared by the Duke Evidence-based Practice Center under Contract No. 290-2015-00004-I.) AHRQ Publication No. 19-EHC014-EF. Rockville, MD: Agency for Healthcare Research and Quality; May 2019. Posted final reports are located on the Effective Health Care Program search page. DOI: https://doi.org/10.23970/AHRQEPCCER217. iii Preface The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and private-sector organizations in their efforts to improve the quality of healthcare in the United States. These reviews provide comprehensive, science-based information on common, costly medical conditions, and new healthcare technologies and strategies. Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for practice, systematic reviews can help clarify whether assertions about the value of the intervention are based on strong evidence from clinical studies. For more information about AHRQ EPC systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm. AHRQ expects that these systematic reviews will be helpful to health plans, providers, purchasers, government programs, and the healthcare system as a whole. Transparency and stakeholder input are essential to the Effective Health Care Program. Please visit the website (www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an email list to learn about new program products and opportunities for input. If you have comments on this systematic review, they may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 5600 Fishers Lane, Rockville, MD 20857, or by email to [email protected]. Gopal Khanna, M.B.A. Arlene S. Bierman, M.D., M.S. Director Director Agency for Healthcare Research and Quality Center for Evidence and Practice Improvement Agency for Healthcare Research and Quality Stephanie Chang, M.D., M.P.H. Suchitra Iyer, Ph.D. Director Task Order Officer Evidence-based Practice Center Program Center for Practice Improvement Center for Evidence and Practice Agency for Healthcare Research and Quality Improvement Agency for Healthcare Research and Quality iv Acknowledgments The authors thank Megan von Isenburg, M.S.L.S., for help with the literature search and retrieval; Samantha Bowen, Ph.D., for project leadership; Megan Chobot, M.S.L.S., for assistance with project coordination; and Liz Wing, M.A., and Rebecca Gray, Ph.D., for editorial assistance. Key Informants In designing the study questions, the EPC consulted several Key Informants who represent the end-users of research. The EPC sought the Key Informant input on the priority areas for research and synthesis. Key Informants are not involved in the analysis of the evidence or the writing of the report. Therefore, in the end, study questions, design, methodological approaches, and/or conclusions do not necessarily represent the views of individual Key Informants. Key Informants must disclose any financial conflicts of interest greater than $5,000 and any other relevant business or professional conflicts of interest. Because of their role as end-users, individuals with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any conflicts of interest. The list of Key Informants who provided input to this report follows: Sheree Boulet, Dr.P.H., M.P.H. Dmitry Kissin, M.D., M.P.H. Centers for Disease Control and Prevention Centers for Disease Control and Prevention Atlanta, GA Atlanta, GA Barbara Collura, M.A. Dan I. Lebovic, M.D. RESOLVE: The National Fertility Center for Reproductive Medicine and Association Advanced Reproductive Technologies McLean, VA Minneapolis, MN Esther Eisenberg, M.D. Richard S. Legro, M.D. National Institute of Child Health and Pennsylvania State University Human Development State College, PA National Institutes of Health Bethesda, MD Bradley J. Van Voorhis, M.D. Carver College of Medicine Tina Groat, M.D., M.B.A., FACOG University of Iowa UnitedHealthcare Iowa City, IA Minneapolis, MN v Technical Expert Panel In designing the study questions and methodology at the outset of this report, the EPC consulted several technical and content experts. Broad expertise and perspectives were sought. Divergent and conflicting opinions are common and perceived as healthy scientific discourse that results in a thoughtful, relevant systematic review. Therefore, in the end, study questions, design, methodologic approaches, and/or conclusions do not necessarily represent the views of individual technical and content experts. Technical Experts must disclose any financial conflicts of interest greater than $5,000 and any other relevant business or professional conflicts of interest. Because of their unique clinical or content expertise, individuals with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any potential conflicts of interest identified. The list of Technical Experts who provided input to this report follows: Sheree Boulet, Dr.P.H., M.P.H.* Tina Groat, M.D., M.B.A., FACOG Centers for Disease Control and Prevention UnitedHealthcare Atlanta, GA Minneapolis, MN Barbara Collura, M.A.
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