PROBLEM/CONDITION: Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2016 and compares birth outcomes that occurred in 2016 (resulting from ART procedures performed in 2015 and 2016) with outcomes for all infants born in the United States in 2016.
DESCRIPTION OF SYSTEM: In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). RESULTS: In 2016, a total of 197,706 ART procedures (range: 162 in Wyoming to 24,030 in California) with the intent to transfer at least one embryo were performed in 463 U.S. fertility clinics and reported to CDC. These procedures resulted in 65,964 live-birth deliveries (range: 57 in Puerto Rico to 8,638 in California) and 76,892 infants born (range: 74 in Alaska to 9,885 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART use rate, was 3,075. ART use rates exceeded the national rate in 14 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Utah, and Virginia). ART use exceeded 1.5 times the national rate in nine states, including three (Illinois, Massachusetts, and New Jersey) that also had comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four oocyte retrievals). Nationally, among ART transfer procedures for patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age (1.5 among women aged <35 years, 1.7 among women aged 35-37 years, and 2.2 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 42.7% (range: 8.3% in North Dakota to 83.9% in Delaware). In 2016, ART contributed to 1.8% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.7% in Massachusetts). ART also contributed to 16.4% of all multiple-birth infants, including 16.2% of all twin infants and 19.4% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (21,455 of 22,233) of all ART-conceived infants born in multiple deliveries. The percentage of multiple-birth infants was higher among infants conceived with ART (31.5%) than among all infants born in the total birth population (3.4%). Approximately 30.4% of ART-conceived infants were twins and 1.1% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.0% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 23.6% had low birthweight compared with 8.2% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (29.9%) than among all infants born in the total birth population (9.9%). The percentage of ART-conceived infants who had low birthweight was 8.7% among singletons, 54.9% among twins, and 94.9% among triplets and higher-order multiples; the corresponding percentages among all infants born were 6.2% among singletons, 55.4% among twins, and 94.6% among triplets and higher-order multiples. The percentage of ART-conceived infants who were born preterm was 13.7% among singletons, 64.2% among twins, and 97.0% among triplets and higher-order infants; the corresponding percentages among all infants were 7.8% for singletons, 59.9% for twins, and 97.7% for triplets and higher-order infants.
INTERPRETATION: Multiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. For women aged <35 years, who typically are considered good candidates for eSET, on average, 1.5 embryos were transferred per ART procedure, resulting in higher multiple birth rates than could be achieved with single-embryo transfers. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health insurance coverage, three (Illinois, Massachusetts, and New Jersey) had rates of ART use >1.5 times the national average. Although other factors might influence ART use, insurance coverage for infertility treatments accounts for some of the difference in per capita ART use observed among states because most states do not mandate any coverage for ART treatment.
PUBLIC HEALTH ACTION: Twins account for almost all of ART-conceived multiple births born in multiple deliveries. Reducing the number of embryos transferred and increasing use of eSET, when clinically appropriate, could help reduce multiple births and related adverse health consequences for both mothers and infants. Because multiple-birth infants are at increased risk for numerous adverse sequelae that cannot be ascertained from the data collected through NASS alone, long-term follow-up of ART infants through integration of existing maternal and infant health surveillance systems and registries with data available from NASS might be useful for monitoring adverse outcomes.
Background: Singleton infants conceived using assisted reproductive technology have lower average birthweights than naturally conceived infants and are more likely to be born low birthweight (<2500 gr). Lower birthweights are associated with increased infant and child mortality and poor adult health outcomes, including cardiovascular disease, hypertension, and diabetes. Data from registry and single-center studies suggest that frozen/thawed embryo transfer may be associated with larger birthweights. To date, however, a nationwide, full-population study on United States infants born using frozen/thawed embryo transfer has not been reported.
Objectives: The objective of this study was to compare the effect of frozen/thawed vs fresh embryo transfer on birthweight outcomes for singleton, term infants conceived using in vitro fertilization in the United States between 2007 and 2014, including average birthweight and the risks of both macrosomia (>4000 g) and low birthweight (<2500 g).
Study Design: We used data from the Centers for Disease Control and Prevention's National Assisted Reproductive Technology Surveillance System to compare birthweight outcomes of live-born singleton, autologous oocyte, term (37-43 weeks) infants. Generalized linear models for all infants and stratified by infant sex were used to assess the relationship between frozen/thawed embryo transfer and birthweight, in grams. Infertility diagnosis, year of treatment, maternal age, maternal obstetric history, maternal and paternal race, and infant gestational age and sex were included in the models. Missing race data were imputed. The adjusted relative risks for macrosomia and low birthweight were evaluated using multivariable predicted marginal proportions from logistic regression models.
Results: In total, 180,184 singleton, term infants were included, with 55,898 (31.02%) having been conceived from frozen/thawed embryos. Frozen/thawed embryo transfer was associated with, on average, a 142 g increase in birthweight compared with infants born after fresh embryo transfer (P <.001). An interaction between infant sex and embryo transfer type was significant (P <.0001), with frozen/thawed embryo transfer having a larger effect on male infants by 16 g. The adjusted risk of a macrosomic infant was 1.70 times higher (95% confidence interval, 1.64–1.76) following frozen/thawed embryo transfer than fresh embryo transfer. However, adjusted risk of low birthweight following frozen/thawed embryo transfer was 0.52 (95% confidence interval, 0.48–0.56) compared with fresh embryo transfer.
Conclusion: Frozen/thawed embryo transfer, in comparison with fresh embryo transfer, was associated with increased average birthweight in singleton, autologous oocytes, term infants born in the United States, with a significant interaction between frozen/thawed embryo transfer and infant sex. The risk of macrosomia following frozen/thawed embryo transfer was greater than that following fresh embryo transfer, but the risk of low birthweight among frozen/thawed embryo transfer infants was significantly decreased in comparison with fresh embryo transfer infants.
Background: Venous thromboembolism (VTE) is a complication in children with chronic pediatric heart disease (CPHD). The influence of acute VTE risk factors and the health care burden associated with VTE in CPHD is unknown.
Methods: Children <18 years of age with a CPHD diagnostic code were identified from the 2003-2013 MarketScan Commercial Databases. VTE diagnoses were identified either concomitantly with initial CPHD diagnoses or during a 6-month follow-up. The associations between demographic and clinical characteristics and VTE among children with CPHD, stratified by recent cardiac surgery, were assessed by multivariable logistic regression models. Estimates of health care utilization were compared using Wilcoxon rank-sum tests.
Results: VTE events occurred in 957 of 120 884 children with CPHD (0.8%). In-hospital mortality was significantly higher in children with VTE. Single-ventricle physiology had the highest VTE rate (2.3%). All comorbid conditions were significantly associated with VTE, but the prevalence was highest in children with recent cardiac (11.1%) or noncardiac surgery (7.8%). The magnitude of association between noncardiac comorbidities and acquired acute cardiovascular conditions and VTE were larger for children without a recent cardiac surgery. Children with VTE had significantly higher health care utilization.
Conclusions: VTE in CPHD is associated with significantly increased health care resource utilization and in-hospital mortality. All of the comorbid conditions examined were significantly associated with VTE, but a recent surgical procedure, especially cardiac surgery, conferred the highest VTE risk. Although confounding inherently limits observational studies, these findings provide practical information about the health care costs among patients with CPHD and VTE.
Twin births among users of assisted reproductive technology (ART) pose serious risks to both mothers and infants. However, patients may prefer twins and may be unaware of the risks of twin pregnancies. Increasing use of elective single embryo transfers (eSET) through improved patient education could help to reduce twin births and related adverse health consequences. A systematic review of PUBMED and EMBASE databases was conducted to evaluate the effectiveness of patient education among ART users on knowledge of twin pregnancy risks, desire for twins, preference for or use of eSET, and twin pregnancy rates. Of 187 references retrieved, six met the selection criteria. Most focused on patients undergoing their first ART cycle aged < 35 years. Patient education was delivered via written materials, DVDs or discussion. Four studies reporting on knowledge of risks or desire for twins showed significant effects of oral and written descriptions of multiple pregnancy complications, risks of twins versus singletons, and DVDs with factual information. Five studies showed increased eSET use or preference after patients were educated on the risks of multiple pregnancy and success rates associated with different types of ART procedures, when combined with clinic policies that supported single blastocyst transfers or provided options for insurance. In younger ART users, patient education on twin pregnancy risks and success rates of eSET may improve knowledge of twin pregnancy risks and increase use of eSET, and may be important for wider implementation of eSET in countries such as the USA where the use of eSET remains low. Clinic policies of single blastocyst transfers or financial incentives may strengthen these effects.
Background
Sexually transmitted diseases (STDs) including chlamydia and gonorrhea, cause pelvic inflammatory disease and infertility. We estimated the prevalence of infertility and infertility healthcare seeking.
Methods
We analyzed self-reported lifetime infertility and infertility healthcare-seeking in women aged 18–49 years in the 2013 and 2015 National Health and Nutrition Examination Surveys. Weighted prevalence of infertility and infertility healthcare seeking, prevalence ratios (PRs), and 95% confidence intervals (CIs) were calculated.
Results
Among 2,626 eligible women, 13.8% had self-reported infertility [95% CI 12.3–15.3] with higher prevalence by age: 6.4% [95% CI 4.8–8.0], n=960 18–29 year olds; 14.8% [95 % CI 12.2–17.3], n=799 30–39 year olds; and 20.8% [95% CI 17.2–24.4], n=867 40–49 year olds. Non-Hispanic white women (15.4% [95% CI 13.0–17.8]; n=904) and non-Hispanic black women (12.9% [95% CI 10.3–15.5]; n=575) had the highest infertility prevalences. Women reporting PID treatment (n=122) had higher infertility prevalence (24.2% [95% CI 16.2–32.2]) than women without PID treatment (13.3% [95% CI 11.6–15.0], n=2,485), especially among 18–29 year old women (PR 3.8 [95% CI 1.8–8.0)]. Of 327 women with infertility, 60.9% (95% CI 56.1–65.8) sought healthcare. Women without healthcare insurance sought care less frequently than women with insurance.
Conclusions
In a nationally-representative sample, 13.8% of reproductive-age women reported a history of infertility, of whom 40% did not access healthcare. Self-reported PID was associated with infertility, especially in young women. Annual chlamydia and gonorrhea screening to avert PID may reduce the burden of infertility in the US.
Previous studies report associations between conception with assisted reproductive technology (ART) and autism. Whether these associations reflect an ascertainment or biologic effect is undetermined. We assessed diagnosis age and initial autism symptom severity among >30,000 children with autism from a linkage study of California Department of Developmental Services records, birth records, and the National ART Surveillance System. Median diagnosis age and symptom severity levels were significantly lower for ART-conceived than non-ART-conceived children. After adjustment for differences in the socio-demographic profiles of the two groups, the diagnosis age differentials were greatly attenuated and there were no differences in autism symptomatology. Thus, ascertainment issues related to SES, not ART per se, are likely the driving influence of the differences we initially observed.
Objective: To estimate uptake of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), and COVID-19 vaccines during pregnancy and describe vaccine attitudes and beliefs among predominantly racial and ethnic minority individuals delivering at a publicly funded hospital. Methods: We collected survey and electronic medical record data for English-speaking postpartum individuals who delivered a live-born infant from July 7, 2022, through August 21, 2022, and agreed to participate in our study. The 58-item survey included questions about general vaccine attitudes and beliefs as well as vaccine-specific questions. We calculated rates of influenza, Tdap, and COVID-19 vaccinations and compared distributions of survey responses by number (no vaccines, one vaccine, or two or three of the recommended vaccines) and type of vaccines received during pregnancy. Results: Of the 231 eligible individuals, 125 (54.1%) agreed to participate. Rates of influenza, Tdap, and COVID-19 vaccination were 18.4%, 48.0%, and 5.6% respectively. A total of 61 (48.8%) did not receive any recommended vaccines during pregnancy, 40 (32.0%) received one vaccine, and 24 (19.0%) received two or three vaccines. Approximately 66.1% of the no vaccine group, 81.6% of the one vaccine group, and 87.5% of the two or three vaccine group strongly agreed or agreed that they trusted the vaccine information provided by their obstetrician or midwife. While most (>69.2%) agreed that the vaccine-preventable diseases were dangerous for pregnant women, only 24.0%, 29.3%, and 40.3% agreed that they were worried about getting influenza, whooping cough, or COVID-19, respectively, while pregnant. Discussion: Vaccine uptake in our population was low and may be due, in part, to low perceived susceptibility to vaccine-preventable diseases. Obstetricians and midwives were trusted sources of vaccine information, suggesting that enhanced communication strategies could be critical for addressing maternal vaccine hesitancy, particularly in communities of color justifiably affected by medical mistrust.
STUDY QUESTION: Is air pollution associated with IVF treatment outcomes in the USA? SUMMARY ANSWER: We did not find clear evidence of a meaningful association between reproductive outcomes and average daily concentrations of particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) and ozone (O3). WHAT IS KNOWN ALREADY: Maternal exposure to air pollution such as PM2.5, nitrogen oxides, carbon monoxide or O3 may increase risks for adverse perinatal outcomes. Findings from the few studies using data from IVF populations to investigate associations between specific pollutants and treatment outcomes are inconclusive. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of 253 528 non-cancelled fresh, autologous IVF cycles including 230 243 fresh, autologous IVF cycles with a transfer of ≥1 embryo was performed between 2010 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: We linked 2010-2012 National ART Surveillance System data for fresh, autologous IVF cycles with the ambient air pollution data generated using a Bayesian fusion model available through the Centers for Disease Control and Prevention's Environmental Public Health Tracking Network. We calculated county-level average daily PM2.5 and O3 concentrations for three time periods: cycle start to oocyte retrieval (T1), oocyte retrieval to embryo transfer (T2) and embryo transfer +14 days (T3). Multivariable predicted marginal proportions from logistic and log-linear regression models were used to estimate adjusted risk ratios (aRR) and 95% CI for the association between reproductive outcomes (implantation rate, pregnancy and live birth) and interquartile increases in PM2.5 and O3. The multipollutant models were also adjusted for patients and treatment characteristics and accounted for clustering by clinic and county of residence. MAIN RESULTS AND THE ROLE OF CHANCE: For all exposure periods, O3 was weakly positively associated with implantation (aRR 1.01, 95% CI 1.001-1.02 for T1; aRR 1.01, 95% CI 1.001-1.02 for T2 and aRR 1.01, 95% CI 1.001-1.02 for T3) and live birth (aRR 1.01, 95% CI 1.002-1.02 for T1; aRR 1.01, 95% CI 1.004-1.02 for T2 and aRR 1.02, 95% CI 1.004-1.03 for T3). PM2.5 was not associated with any of the reproductive outcomes assessed. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is the use of aggregated air pollution data as proxies for individual exposure. The weak positive associations found in this study might be related to confounding by factors that we were unable to assess and may not reflect clinically meaningful differences. WIDER IMPLICATIONS OF THE FINDINGS: More research is needed to assess the impact of air pollution on reproductive function. STUDY FUNDING/COMPETING INTEREST(S): None.
STUDY QUESTION: Is the use of donor oocytes in women <35 years of age associated with an increased risk of adverse perinatal outcomes compared to use of autologous oocytes? SUMMARY ANSWER: Among fresh assisted reproductive technology (ART) cycles performed in women under age 35, donor oocyte use is associated with a higher risk of preterm birth, low birth weight and stillbirth (when zero embryos were cryopreserved) as compared to autologous oocytes. WHAT IS KNOWN ALREADY: Previous studies demonstrated elevated risk of poor perinatal outcomes with donor versus autologous oocytes during ART, primarily among older women. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study using data reported to Centers for Disease Control and Prevention's National ART Surveillance System (NASS) during the period from 2010 to 2015 in order to best reflect advances in clinical practice. Approximately 98% of all US ART cycles are reported to NASS, and discrepancy rates were <6% for all fields evaluated in 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all non-banking fresh and frozen ART cycles performed between 2010 and 2015 in women under age 35 using autologous or donor eggs. Cycles using cryopreserved eggs, donated embryos or a gestational carrier were excluded. Among fresh embryo transfer cycles, we calculated predicted marginal proportions to estimate the unadjusted and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for the association between donor versus autologous oocyte use and stillbirth, spontaneous abortion, preterm delivery and low birth weight among singleton pregnancies or births. Stillbirth models were stratified by number of embryos cryopreserved. All models were adjusted for patient and treatment characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 71 720 singleton pregnancies occurring during 2010-2015, singletons resulting from donor oocytes were more likely to be preterm (15.6% versus 11.0%; aRRs 1.39: CI 1.20-1.61) and have low birth weight (11.8% versus 8.8%; aRRs 1.34; CI 1.16-1.55) than those resulting from autologous oocytes. With zero embryos cryopreserved, donor versus autologous oocyte use was associated with increased risk for stillbirth (2.1% versus 0.6%; aRRs 3.73; CI 1.96-7.11); no association with stillbirth was found when ≥1 embryo was cryopreserved (0.54% versus 0.56%; aRR 1.15; CI 0.59-2.25). LIMITATIONS, REASONS FOR CAUTION: The data come from a national surveillance system and is thus limited by the accuracy of the data entered by individual providers and clinics. There may be unmeasured differences between women using donor eggs versus their own eggs that could be contributing to the reported associations. Given the large sample size, statistically significant findings may not reflect clinically important variations. WIDER IMPLICATIONS OF THE FINDINGS: Risks of preterm birth, low birth weight and stillbirth among singleton pregnancies using donor oocytes were increased compared to those using autologous oocytes. Further study regarding the pathophysiology of the potentially increased risks among donor oocyte recipient pregnancy is warranted. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.