Victoria C. Wright

Perinatal outcome among singleton infants conceived through assisted reproductive technology in the United States

OBJECTIVE: To examine perinatal outcome among singleton infants conceived with assisted reproductive technology (ART) in the United States. METHODS: Subjects were 62,551 infants born after ART treatments performed in 1996–2000. Secular trends in low birth weight (LBW), very low birth weight (VLBW), preterm delivery, preterm LBW, and term LBW were examined. Detailed analyses were performed for 6,377 infants conceived in 2000. Observed numbers were compared with expected using a reference population from the 2000 U.S. natality file. Adjusted risk ratios were calculated. RESULTS: The proportion of ART singletons born LBW, VLBW, and term LBW decreased from 1996 to 2000. The proportion delivered preterm and preterm LBW remained stable. After adjustment for maternal age, parity, and race/ethnicity, singleton infants born after ART in 2000 had elevated risks for all outcomes in comparison with the general population of U.S. singletons: LBW standardized risk ratio 1.62 (95% confidence interval 1.49, 1.75), VLBW 1.79 (1.45, 2.12), preterm delivery 1.41 (1.32, 1.51), preterm LBW 1.74 (1.57, 1.90), and term LBW 1.39 (1.19, 1.59). Risk ratios for each outcome remained elevated after restriction to pregnancies with only 1 fetal heart or any of 7 other categories: parental infertility diagnosis of male factor, infertility diagnosis of tubal factor, conception using in vitro fertilization without intracytoplasmic sperm injection or assisted hatching, conception with intracytoplasmic sperm injection, conception in a treatment with extra embryos available, embryo culture for 3 days, and embryo culture for 5 days. CONCLUSION: Singletons born after ART remain at increased risk for adverse perinatal outcomes; however, risk for term LBW declined from 1996 to 2000, whereas preterm LBW was stable. LEVEL OF EVIDENCE: III

Are children born after assisted reproductive technology at increased risk for adverse health outcomes

As assisted reproductive technologies (ARTs) are increasingly used to overcome infertility, there is concern about the health of the children conceived. The empirical evidence for associations with outcomes related to child health is variable and should be evaluated with consideration of methodological shortcomings. Currently, there is convincing evidence that ART treatment may increase the risk of a few outcomes. Experimental laboratory studies document that various constituents in culture media affect various embryo characteristics both positively and negatively. Multiple-gestation pregnancy and birth are increased with ART, both because of multiple embryo transfer and embryo splitting. There is evidence of an increase in chromosomal abnormalities among pregnancies conceived using intracytoplasmic sperm injection and low birth weight and preterm delivery among singletons conceived with all types of ART; however, there remains uncertainty about whether these risks stem from the treatment or the parental infertility. For some outcomes, data of an increased risk with ART are suggestive at best largely because of lack of purposeful study of sufficient size and scope. These include specific perinatal morbidities, birth defects, developmental disabilities, and retinoblastoma. The evidence for an association between ART and spontaneous abortion is inconsistent and weak. There is inconclusive evidence that ART may be associated with genetic imprinting disorders. For childhood cancer, chronic conditions, learning and behavioral disorders, and reproductive effects there is insufficient empirical research to date, but given the data for more proximal outcomes, these outcomes merit further study. Future research needs to address the unique methodological challenges underlying study in this area.

Ectopic pregnancy risk with assisted reproductive technology procedures

OBJECTIVE: To assess the ectopic pregnancy risk among women who conceived with assisted reproductive technology (ART) procedures. METHODS: The ectopic rate for ART pregnancies was calculated from population-based data of pregnancies conceived with ART in U.S. clinics in 1999–2001. Variation in ectopic risk by patient and ART treatment factors was assessed by using bivariate analyses and multivariable logistic regression. RESULTS: Of 94,118 ART pregnancies, 2,009 (2.1%) were ectopic. Variation was observed by procedure type. In comparison with the ectopic rate (2.2%) among pregnancies conceived with in vitro fertilization and transcervical transfer of freshly fertilized embryos from the patient’s oocytes (fresh, nondonor IVF-ET), the ectopic rate was significantly increased when zygote intrafallopian transfer (ZIFT) was used (3.6%) and significantly decreased when donor oocytes were used (1.4%) or when a gestational surrogate carried the pregnancy (0.9%). Among fresh nondonor IVF-ET procedures, the risk for ectopic pregnancy was increased among women with tubal factor infertility (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.7–2.4; referent group = ART for male factor), endometriosis (OR 1.3, 95% CI 1.0–1.6), and other nontubal female factors of infertility (OR 1.4, 95% CI 1.2–1.6) and decreased among women with a previous live birth (OR 0.6, 95% CI 0.5–0.7). Transfer of embryos with an indication of high implantation potential was associated with a decreased ectopic risk when 2 or fewer embryos were transferred (OR 0.7, 95% CI 0.5–0.9), but not when 3 or more embryos were transferred. CONCLUSION: Ectopic risk among ART pregnancies varied according to ART procedure type, reproductive health characteristics of the woman carrying the pregnancy, and estimated embryo implantation potential. LEVEL OF EVIDENCE: II-2

Perinatal outcomes of twin births conceived using assisted reproduction technology: a population-based study†

BACKGROUND Approximately 18% of multiple births in the USA result from assisted reproduction technology (ART). Although many studies comparing ART and naturally conceived twins report no difference in risks for perinatal outcomes, others report slight to moderate positive or protective associations. METHODS We selected twin deliveries with and without indication of ART from Massachusetts live birth-infant death records from 1997 to 2000 linked to the US ART surveillance system. The sample was restricted to deliveries by mothers with increased socioeconomic status, private health insurance and intermediate/plus prenatal care use. Our final sample included 1446 and 2729 ART and non-ART twin deliveries, respectively. Odds ratios (OR) for associations between ART and perinatal outcomes were adjusted for maternal demographic factors, smoking, prenatal care and hospital care level. RESULTS ART twin deliveries were less likely than non-ART to be very preterm (adjusted OR 0.75; 95% confidence interval 0.58-0.97) or include a very low birthweight (<1500 g) infant (0.75; 0.58-0.95) or infant death (0.55; 0.35-0.88). In stratified analyses, these findings were observed among primiparous deliveries, but there were no risk differences among multiparous ART and non-ART twin deliveries. CONCLUSIONS ART treatment was not a risk factor for adverse perinatal outcome, and risks for several outcomes were somewhat lower among ART twin deliveries. Nonetheless, ART is strongly associated with twinning and twins remain a high-risk group, relative to singletons. Promoting singleton gestation in assisted conception is an important strategy for reducing adverse outcomes.

Accuracy of assisted reproductive technology information on the Massachusetts birth certificate, 1997–2000

OBJECTIVE To evaluate the accuracy of assisted reproductive technology (ART) reporting on the Massachusetts birth certificate and to explore the individual and hospital-level characteristics associated with ART reporting. DESIGN Validity analysis of population-based data. SETTING Live-birth deliveries by Massachusetts-resident mothers during 1997-2000. PATIENT(S) Live births and delivery mothers. INTERVENTION(S) The ART data maintained by the Centers for Disease Control and Prevention were linked with the live birth-infant death records in Massachusetts. Successfully linked records were used as the gold standard for ART-related deliveries in evaluating the validity of the ART information reported on the Massachusetts birth certificate. MAIN OUTCOME MEASURE(S) Sensitivity and specificity. RESULT(S) The sensitivity of ART reporting on the birth certificate was 27% and the specificity >99%. Sensitivity of ART reporting was higher among women with multiple deliveries (twins: 32%; triplets+: 43%) and preterm deliveries (36%). CONCLUSION(S) During the period evaluated, reporting of ART information on the birth certificate was incomplete, and ART births identified through the birth certificate were a biased sample of the population of ART births. Using delivery hospital data as the sole source of ART information for the standard birth certificate may yield inaccurate information.

Linking Birth and Infant Death Records With Assisted Reproductive Technology Data: Massachusetts, 1997–1998

Objectives: To link data from the US assisted reproductive technology (ART) registry with the Massachusetts birth–infant death file to create a comprehensive dataset on the circumstances surrounding conception and maternal and infant outcomes for a population of ART-conceived infants. Methods: The authors sought to link data for 3704 ART-conceived live-born infants from 2703 deliveries in 1997–1998 involving Massachusetts resident mothers who gave birth in Massachusetts, Rhode Island, New Hampshire, or Connecticut to their corresponding Massachusetts birth record using a two-stage algorithm. Maternal and infant dates of birth served as the primary linkage variables. Maternal names for a subset of the ART-conceived infants were obtained and used in the second stage of the algorithm to confirm a sample of records that matched in Stage I, to resolve duplicate matches, and to link unmatched records. Results: In Stage I, 78% of ART deliveries matched with only one Massachusetts record, 2% matched with two records, and 20% remained unmatched. Overall, the complete algorithm using maternal name data for a portion of records yielded an 89% linkage rate. Nearly all of the records that matched during Stage I that were evaluated with maternal name data in Stage II were confirmed as correctly linked. Conclusions: This project confirms that high-yield data linkage can be achieved in the absence of specific identifiers (e.g., name and social security number). Nonetheless, additional matches were achieved when name data were obtained. This linkage creates the first population-based file in the US capturing detailed information on ART births.