Subfertility, defined as delayed time-to-conception, affects an estimated 12% of women of reproductive age. The use of fertility-enhancing therapies, including assisted reproductive technologies (ART), has risen steadily in the United States due to several factors, including childbearing at older maternal ages and increasing insurance coverage. Prior studies of women's and children's health after ART have been limited by small sample sizes, non-US populations, or ART treatments performed more than a decade ago, and the lack of appropriate control groups. An important understudied area is that of non-ART fertility treatments and the perinatal, infant, and child health outcomes of these pregnancies. Our original pair of grants was the first population-based analysis of women's and children's health after ART to be conducted in the US. These studies, which had the unique strength of including a non-ART-treated subfertility comparison group, yielded a series of analyses suggesting that underlying subfertility, rather than the treatment modality, is the foundation for most maternal and child morbidity. In this renewal, we will expand this understanding through increased information on subfertility-related diagnoses, underlying non-subfertility medical conditions, non-ART treatment parameters, and outcome measures present in the All Payers Claims Database, as well as inclusion of new information on fathers. We will evaluate the health of mothers during pregnancy and for five years post-delivery, and their children through age four. The study population will include all Massachusetts women who delivered pregnancies between 2004 and 2011 (our original birth cohort) and their children, and will add study subjects who delivered between 2012 and 2017. The total study population will include more than one million families. Reference groups will include ART and non-ART pregnancies with only male factor infertility, and pregnancies without indicators or treatment of subfertility. The study aims and hypotheses are:
Aim 1 : To evaluate the effect of maternal subfertility diagnoses on long-term health; Hypothesis: Women with a history of subfertility diagnoses, independent of treatment, have higher risks of compromised health outcomes compared to women without indicators or treatment of subfertility;
Aim 2 : To evaluate the health of children born to women and men with subfertility diagnoses; Hypothesis: Children born to women and/or men with subfertility diagnoses, independent of treatment, have a higher risk of compromised health outcomes compared to children born to women without indicators of subfertility;
and Aim 3 : To develop a cost-of-subfertility measure for women and their children; Hypothesis: Women with a history of subfertility-related diagnoses and their children have higher healthcare costs compared to their counterparts without indicators or treatment of subfertility.

Public Health Relevance

This study evaluates the effect of parental subfertility-related diagnoses on the health of women and their children and the associated healthcare costs. The original project developed a cohort through linkage of assisted reproductive technology data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and vital records data in Massachusetts. In this renewal we have enhanced the study with the following innovations: addition of comprehensive, detailed diagnostic and treatment outpatient data from the newly available Massachusetts All Payers Claims Database (APCD): increasing the cohort to approximately one million women and their children; addition of the contribution of the male parent to child health; and development of a detailed cost estimate.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
6R01HD067270-09
Application #
9835329
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
King, Rosalind B
Project Start
2011-06-17
Project End
2021-03-31
Budget Start
2018-11-01
Budget End
2019-03-31
Support Year
9
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Dartmouth-Hitchcock Clinic
Department
Type
DUNS #
150883460
City
Lebanon
State
NH
Country
United States
Zip Code
Hwang, Sunah S; Dukhovny, Dmitry; Gopal, Daksha et al. (2018) Health of Infants After ART-Treated, Subfertile, and Fertile Deliveries. Pediatrics 142:
Luke, Barbara; Brown, Morton B; Liu, Chia-Ling et al. (2018) Validation of Severe Maternal Morbidity on the US Certificate of Live Birth. Epidemiology 29:e31-e32
Stern, Judy E; Liu, Chia-Ling; Cabral, Howard J et al. (2018) Factors associated with increased odds of cesarean delivery in ART pregnancies. Fertil Steril 110:429-436
Stern, Judy E; Liu, Chia-Ling; Cabral, Howard J et al. (2018) Birth outcomes of singleton vaginal deliveries to ART-treated, subfertile, and fertile primiparous women. J Assist Reprod Genet :
Dukhovny, Dmitry; Hwang, Sunah S; Gopal, Daksha et al. (2018) Length of stay and cost of birth hospitalization: effects of subfertility and ART. J Perinatol 38:1457-1465
Stern, Judy E; Gopal, Daksha; Diop, Hafsatou et al. (2017) Inpatient hospitalizations in women with and without assisted reproductive technology live birth. J Assist Reprod Genet 34:1043-1049
Luke, Barbara; Gopal, Daksha; Cabral, Howard et al. (2017) Pregnancy, birth, and infant outcomes by maternal fertility status: the Massachusetts Outcomes Study of Assisted Reproductive Technology. Am J Obstet Gynecol 217:327.e1-327.e14
Luke, Barbara; Gopal, Daksha; Cabral, Howard et al. (2017) Adverse pregnancy, birth, and infant outcomes in twins: effects of maternal fertility status and infant gender combinations; the Massachusetts Outcomes Study of Assisted Reproductive Technology. Am J Obstet Gynecol 217:330.e1-330.e15
Liberman, Rebecca F; Getz, Kelly D; Heinke, Dominique et al. (2017) Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births. Birth Defects Res 109:1144-1153
Luke, Barbara; Gopal, Daksha; Cabral, Howard et al. (2016) Perinatal outcomes of singleton siblings: the effects of changing maternal fertility status. J Assist Reprod Genet 33:1203-13

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