ABSTRACTASSISTED REPRODUCTIVE TECHNOLOGY AND ADVERSE PERINATAL OUTCOMES Since its introduction in 1981, Assisted Reproductive Technology (ART) has been the conventional therapy for infertile couples seeking a pregnancy. However, consistent reports linked ART with adverse perinatal and obstetric outcomes. To elucidate this association we examined the risk of preterm birth and suboptimal newborn size among ART-conceived and non-ART singletons. We expanded our analyses to evaluate the risk of preterm birth and suboptimal newborn size along the gestational age continuum and by detailed parental infertility diagnoses and extensive treatment modality. Our retrospective cohort was assembled using a population-based ART data collected by the National ART surveillance system. The ART data were probabilistically linked to vital records of all live births in Massachusetts and Florida 2000-2010 and Michigan 2000-2009. We restricted our sample to a subset of singleton live births of mothers age 15-60 between 22 and 44 weeks' gestation, resulting in 32,691 ART and 4,263,846 non-ART singletons. We confirmed previous reports that ART singletons have a significantly increased risk of poor perinatal outcomes, e.g. preterm birth, small for gestational age and suboptimal newborn size. Our results suggested a heterogeneous pattern of preterm birth along the gestational age continuum only for ART singletons born to mothers with diagnosed infertility, but not other infertility sources. Examination of preterm birth risk, across distinct categories of female infertility, indicated significantly increased preterm birth for all ART singletons, independent of their parental infertility source. However, we were able to detect a different risk magnitude by the underlying infertility cause, such that ART singletons born to mothers with a diagnosis of uterine factor or ovarian disorders had a statistically significant increased risk to be born prematurely compared with ART singletons of other parental infertility cause. Thus, it is plausible that the etiology of adverse perinatal outcomes observed among ART singletons is related to both the infertility cause and the technology of assisted reproduction.Several ART cycle types and techniques were associated with poor perinatal outcomes among ART-conceived compared with non-ART singletons. Two invasive ART techniques, assisted hatching and intra-cytoplasmic sperm injection, were not associated with an increase the risk of preterm birth and small newborn size among singletons compared with singletons born following the basic ART procedures. This information may be reassuring for infertile couples seeking pregnancy. However, other perinatal risks may be associated with these techniques. The use of frozen, autologous embryos in ART cycles was associated with better perinatal outcomes compared to frozen/donor, fresh/donor and fresh/non-donor ART modalities. The observed protective effect of ART therapy with frozen, autologous embryos on preterm birth and small newborn size may be attributed to the less invasive ART procedures that are associated with frozen embryos, to the immunologic tolerance of autologous cycles or to ART methods applied in embryo cryopreservation.
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