The number of pregnancies conceived with assisted reproductive technology (ART) has dramatically increased over the last 30 years. Additionally, techniques developed for in vitro fertilization (IVF) are now utilized without in vitro culture. These widely-used non-IVF fertility treatments (NIFT) have increased the number of children potentially at risk for adverse health effects. Increased short-term risks for perinatal complications and birth defects, following ART, are well-known. However, the risk of these adverse outcomes has been difficult to characterize as studies used different methodologies, varied age of detection, and did not have appropriate comparison groups. For example, when underlying parental factors and infertility are included in the analyses of birth defects, the association is substantially weakened or disappears completely. More importantly, while the long-term health of children born through these technologies is of critical public health interest, and of personal interest to families, only limited data exist. In order to evaluate the potential risk for long-term health of children conceived through ART and NIFT, rigorous epidemiological methods, appropriate characterization of the exposure, standardized collection of outcome data, and appropriate comparison groups are required. We propose to establish a Developmental Epidemiological Study of Children born through Reproductive Technology (DESCRT) by linking the electronic medical records (EMR) of patients treated at UCSF with birth outcomes and health data. In addition, as part of the longitudinal study, children, up to age 13, will be invited for examination and exploratory aims will investigate underlying mechanisms for increased risk. In particular, we plan to: 1) Establish an epidemiological cohort and biobank for future studies by searching the EMR from UCSF for all pregnancies achieved in patients who underwent infertility consult during 2001?2015. Laboratory and treatment data for eligible women will be linked with the data on the course of pregnancy. Families will be traced and children invited for screening. Pregnancies achieved during the course of the next 4 years (2016- 2019) will be enrolled prospectively; 2) Examine the effects of parental factors and different reproductive treatment strategies on childhood metabolic risk by analyzing the correlation between specific fertility treatments and parental factors, and parameters of glucose/insulin homeostasis and metabolomics in the offspring; and in an Exploratory Aim: Examine the effects of early uterine environment on the precursors of metabolic risk in the offspring by evaluating bio-analytes of placental function and investigating uterine vascular impedance and placental growth and function during prospectively collected pregnancies. Overall impact: The major strengths of the proposed study are the large population with complete and complex data regarding exposure risk, the formation of a valuable biobank, and the interdisciplinary team with prior research suggesting key clinical and translational areas to focus the study improving information for patients and guiding recommendations for clinicians regarding safety of fertility treatment.
Despite the rise in the number of births from fertility treatments, there are limited long-term data on health of the offspring. We propose to establish an epidemiological cohort of almost 4,000 pregnancies to address critical public health questions regarding potential metabolic risk to children conceived through fertility treatments. This information will inform parents and guide clinicians and scientists in developing new technologies that improve treatment outcome and decrease risk to children.