Factors Influencing Adverse Perinatal Outcomes in Pregnancies Achieved Through Use of Assisted Reproductive Technology (ART)

Abstract

ObjectiveThere is growing evidence that an increased risk of low birth weight (LBW) and preterm delivery (PTD) is associated with the use of ART. Mechanisms to explain the association are unknown, but may be related to the underlying infertility or to the infertility treatment. We sought to determine whether infertility etiology or aspects of ART treatment were associated with the risk of adverse outcomes in pregnancies achieved through ART.DesignCase control study.Materials and methodsThe study sample was comprised of couples from two local infertility practices, one university-based and one community-based. All viable pregnancies achieved by fresh, non-donor in vitro fertilization (IVF) between January 1999 and March 2004 were included. Cases were identified as those experiencing PTD (≤37 weeks), delivery of a LBW infant (≤2500 grams), or fetal demise occurring beyond the first trimester. Controls were defined as pregnancies that achieved normal weight, full term live births. Data on the treatment cycle were abstracted from standardized stimulation flow sheets. Assignment of the infertility etiology was adjudicated using pre-specified strict criteria to confirm the diagnosis. Bivariate analyses were performed to determine the association between perinatal outcome and exposures of interest based on a priori hypotheses. Multivariable logistic regression was used to determine the risk while adjusting for clinically significant potential confounders.ResultsOf the 455 viable pregnancies identified during the study period, 435 met inclusion criteria, yielding a final study sample of 159 cases and 276 controls. There were no significant differences in age, race, parity, previous IVF attempts, or body mass index (BMI) between cases and controls. In the final multivariable model adjusting for maternal age, race, parity, BMI, infertility center, and year of ART procedure, multiple gestations were associated with a 12-fold increased risk of poor perinatal outcome compared to singletons (OR 11.94, 95%CI 7.29-19.54). Ovarian hyperstimulation syndrome (OHSS) significantly increased the risk more than 3-fold (OR=3.14, 95%CI 1.08-9.14), while endometrial thickness was found to have a significant protective effect (OR=0.89, 95%CI 0.80-0.99). Multivariable analysis revealed no effect of embryo quality, type of medication, dose of medication, peak estradiol, use of ICSI or use of AH on perinatal outcome. There were no significant associations between categories of infertility diagnosis and outcome.ConclusionThrough analysis of a large cohort of patients achieving viable pregnancies through ART, and adjustment for clinically important confounding factors, we confirmed that multiple gestation has the strongest association with poor perinatal outcomes. Furthermore, we noted that OHSS and a thin endometrial stripe are also significantly associated with adverse outcomes. It is reassuring to report that ICSI, AH and the dose or use of recombinant versus urinary gonadotropin are not associated with adverse outcomes. Importantly, etiology of infertility does not appear to influence these outcomes. Our findings allow for insight into potential biologic mechanisms and perhaps, modification of current treatment practices to reduce adverse perinatal outcomes after ART. ObjectiveThere is growing evidence that an increased risk of low birth weight (LBW) and preterm delivery (PTD) is associated with the use of ART. Mechanisms to explain the association are unknown, but may be related to the underlying infertility or to the infertility treatment. We sought to determine whether infertility etiology or aspects of ART treatment were associated with the risk of adverse outcomes in pregnancies achieved through ART. There is growing evidence that an increased risk of low birth weight (LBW) and preterm delivery (PTD) is associated with the use of ART. Mechanisms to explain the association are unknown, but may be related to the underlying infertility or to the infertility treatment. We sought to determine whether infertility etiology or aspects of ART treatment were associated with the risk of adverse outcomes in pregnancies achieved through ART. DesignCase control study. Case control study. Materials and methodsThe study sample was comprised of couples from two local infertility practices, one university-based and one community-based. All viable pregnancies achieved by fresh, non-donor in vitro fertilization (IVF) between January 1999 and March 2004 were included. Cases were identified as those experiencing PTD (≤37 weeks), delivery of a LBW infant (≤2500 grams), or fetal demise occurring beyond the first trimester. Controls were defined as pregnancies that achieved normal weight, full term live births. Data on the treatment cycle were abstracted from standardized stimulation flow sheets. Assignment of the infertility etiology was adjudicated using pre-specified strict criteria to confirm the diagnosis. Bivariate analyses were performed to determine the association between perinatal outcome and exposures of interest based on a priori hypotheses. Multivariable logistic regression was used to determine the risk while adjusting for clinically significant potential confounders. The study sample was comprised of couples from two local infertility practices, one university-based and one community-based. All viable pregnancies achieved by fresh, non-donor in vitro fertilization (IVF) between January 1999 and March 2004 were included. Cases were identified as those experiencing PTD (≤37 weeks), delivery of a LBW infant (≤2500 grams), or fetal demise occurring beyond the first trimester. Controls were defined as pregnancies that achieved normal weight, full term live births. Data on the treatment cycle were abstracted from standardized stimulation flow sheets. Assignment of the infertility etiology was adjudicated using pre-specified strict criteria to confirm the diagnosis. Bivariate analyses were performed to determine the association between perinatal outcome and exposures of interest based on a priori hypotheses. Multivariable logistic regression was used to determine the risk while adjusting for clinically significant potential confounders. ResultsOf the 455 viable pregnancies identified during the study period, 435 met inclusion criteria, yielding a final study sample of 159 cases and 276 controls. There were no significant differences in age, race, parity, previous IVF attempts, or body mass index (BMI) between cases and controls. In the final multivariable model adjusting for maternal age, race, parity, BMI, infertility center, and year of ART procedure, multiple gestations were associated with a 12-fold increased risk of poor perinatal outcome compared to singletons (OR 11.94, 95%CI 7.29-19.54). Ovarian hyperstimulation syndrome (OHSS) significantly increased the risk more than 3-fold (OR=3.14, 95%CI 1.08-9.14), while endometrial thickness was found to have a significant protective effect (OR=0.89, 95%CI 0.80-0.99). Multivariable analysis revealed no effect of embryo quality, type of medication, dose of medication, peak estradiol, use of ICSI or use of AH on perinatal outcome. There were no significant associations between categories of infertility diagnosis and outcome. Of the 455 viable pregnancies identified during the study period, 435 met inclusion criteria, yielding a final study sample of 159 cases and 276 controls. There were no significant differences in age, race, parity, previous IVF attempts, or body mass index (BMI) between cases and controls. In the final multivariable model adjusting for maternal age, race, parity, BMI, infertility center, and year of ART procedure, multiple gestations were associated with a 12-fold increased risk of poor perinatal outcome compared to singletons (OR 11.94, 95%CI 7.29-19.54). Ovarian hyperstimulation syndrome (OHSS) significantly increased the risk more than 3-fold (OR=3.14, 95%CI 1.08-9.14), while endometrial thickness was found to have a significant protective effect (OR=0.89, 95%CI 0.80-0.99). Multivariable analysis revealed no effect of embryo quality, type of medication, dose of medication, peak estradiol, use of ICSI or use of AH on perinatal outcome. There were no significant associations between categories of infertility diagnosis and outcome. ConclusionThrough analysis of a large cohort of patients achieving viable pregnancies through ART, and adjustment for clinically important confounding factors, we confirmed that multiple gestation has the strongest association with poor perinatal outcomes. Furthermore, we noted that OHSS and a thin endometrial stripe are also significantly associated with adverse outcomes. It is reassuring to report that ICSI, AH and the dose or use of recombinant versus urinary gonadotropin are not associated with adverse outcomes. Importantly, etiology of infertility does not appear to influence these outcomes. Our findings allow for insight into potential biologic mechanisms and perhaps, modification of current treatment practices to reduce adverse perinatal outcomes after ART. Through analysis of a large cohort of patients achieving viable pregnancies through ART, and adjustment for clinically important confounding factors, we confirmed that multiple gestation has the strongest association with poor perinatal outcomes. Furthermore, we noted that OHSS and a thin endometrial stripe are also significantly associated with adverse outcomes. It is reassuring to report that ICSI, AH and the dose or use of recombinant versus urinary gonadotropin are not associated with adverse outcomes. Importantly, etiology of infertility does not appear to influence these outcomes. Our findings allow for insight into potential biologic mechanisms and perhaps, modification of current treatment practices to reduce adverse perinatal outcomes after ART.