Infertility affects an estimated 12 percent-15 percent of women of reproductive age. The use of fertility enhancing therapies, including Assisted Reproductive Technologies (ART), has risen steadily in the United States, with an estimated 1 percent-3 percent of births involving ART. Numerous studies have reported significantly higher risks of adverse perinatal outcomes in assisted-versus spontaneous-conception pregnancies. Infertility and sub fertility diagnoses, independent of ART, can also result in higher rates of adverse pregnancy outcomes. Documenting the added effect of ART, beyond underlying sub fertility, on child health outcomes remains a challenge. This applications describes an innovative collaboration between Boston University's School of Public Health, the Massachusetts Department of Public Health, the Society for Assisted Reproductive Technology, and the Centers for Disease Control and Prevention. The collaboration creates a unique longitudinal, population-based, source of data that combines detailed clinical information on ART treatment and infertility diagnoses for the resultant live births and fetal deaths from 2004 through 2011, with the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System. PELL contains longitudinal data on pregnancy, births, deaths, hospital utilization, birth defects and public program participation including Early Intervention. The resulting database will track reproductive and child health outcomes to 3 years of age among three groups: babies conceived through ART (~18,000), and those not conceived through ART to subfertile women (~5,000) and those conceived to fertile women (~354,000). This project addresses key limitations of prior ART research (limited subfertility comparison groups, and lack of population-based data and longitudinal child health measures). Two broad hypotheses will be tested: (1) children born from ART treatments are at significantly higher risk of compromised fetal, perinatal, infant, and early childhood health outcomes compared to the two comparison groups, and (2) risk of adverse infant and child health outcomes will vary by ART treatment parameters, infertility diagnoses, and their interaction. The treatment parameters will include source of gametes;state of oocytes or embryos;stage of the embryo;micromanipulation;number of embryos transferred;early fetal loss;and number and outcome of prior treatment cycles. In both cases we will test these hypotheses at three age periods: 1) fetal/perinatal;2) infant health to one year;and 3) child health to three years. The analyses will proceed in five stages: 1) univariate analyses;2) unadjusted bivariate analyses;3) multivariate analyses adjusted for known confounders;4) subgroup analyses;and 5) path analysis to assess the differential effect of ART treatment parameters and infertility diagnoses, as well as the magnitude of the overall effect of ART, and the direct and indirect effects of plurality on perinatal and child health outcomes in an eight-year, population-based sample. The result will be the largest, most refined analysis ever completed of child health outcomes associated with ART.

Public Health Relevance

Research has shown that children born after infertility and assisted reproductive technology (ART) treatments are at greater risk for adverse health outcomes, although the generalizability of prior studies has been hampered by small sample sizes and the lack of a subfertility comparison group. As the use of infertility treatments continue to rise, it is important to determine how much of this increased risk is related to the ART treatment rather than the underlying infertility, and if there are residual effects extending into early childhood. The proposed project will link ART clinical data from 2004 to 2011 to the Massachusetts Pregnancy to Early Life Longitudinal birth and fetal death file (resulting in approximately 18,000 ART assisted births, 5,000 births with no ART but other subfertility indicators, and 380,000 other births), facilitating the largest and most comprehensive U.S. study to date on infertility, ART and child health from birth to age three.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
King, Rosalind B
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Boston University
Other Health Professions
Schools of Public Health
United States
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Belanoff, Candice; Declercq, Eugene R; Diop, Hafsatou et al. (2016) Severe Maternal Morbidity and the Use of Assisted Reproductive Technology in Massachusetts. Obstet Gynecol 127:527-34
Diop, Hafsatou; Gopal, Daksha; Cabral, Howard et al. (2016) Assisted Reproductive Technology and Early Intervention Program Enrollment. Pediatrics 137:e20152007
Stern, Judy E; Gopal, Daksha; Liberman, Rebecca F et al. (2016) 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 106:717-722.e2
Luke, Barbara; Stern, Judy E; Kotelchuck, Milton et al. (2016) Birth Outcomes by Infertility Treatment: Analyses of the Population-Based Cohort: Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART). J Reprod Med 61:114-27
Luke, Barbara; Stern, Judy E; Hornstein, Mark D et al. (2016) Is the wrong question being asked in infertility research? J Assist Reprod Genet 33:3-8
Buck Louis, Germaine M; Druschel, Charlotte; Bell, Erin et al. (2015) Use of assisted reproductive technology treatment as reported by mothers in comparison with registry data: the Upstate KIDS Study. Fertil Steril 103:1461-8
Luke, Barbara; Stern, Judy E; Kotelchuck, Milton et al. (2015) Adverse pregnancy outcomes after in vitro fertilization: effect of number of embryos transferred and plurality at conception. Fertil Steril 104:79-86
Stern, Judy E; Luke, Barbara; Tobias, Michael et al. (2015) Adverse pregnancy and birth outcomes associated with underlying diagnosis with and without assisted reproductive technology treatment. Fertil Steril 103:1438-45
Luke, Barbara; Stern, Judy E; Kotelchuck, Milton et al. (2015) Birth Outcomes by Infertility Diagnosis Analyses of the Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART). J Reprod Med 60:480-90
Declercq, Eugene; Stern, Judy E; Luke, Barbara et al. (2015) Maternal Postpartum Hospitalization Following Assisted Reproductive Technology Births. Epidemiology 26:e64-5

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