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Although street youth are at increased risk of lifetime pregnancy involvement (LPI), or ever becoming or getting someone pregnant, no reports to date describe the epidemiology of LPI among systematically sampled street youth from multiple cities outside of North America. The purpose of our assessment was to describe the prevalence of and risk factors associated with LPI among street youth from three Ukrainian cities. We used modified time-location sampling to conduct a cross-sectional assessment in Odesa, Kyiv, and Donetsk that included citywide mapping of 91 public venue locations frequented by street youth, random selection of 74 sites, and interviewing all eligible and consenting street youth aged 15-24 years found at sampled sites (n = 929). Characteristics of youth and prevalence of LPI overall and by demographic, social, sexual, and substance use risk factors, were estimated separately for males and females. Adjusted odds ratios (AORs) were calculated with multivariable logistic regression and effect modification by gender was examined. Most (96.6%) eligible youth consented to participate. LPI was reported for 41.7% of females (93/223) and 23.5% of males (166/706). For females, LPI was significantly elevated and highest (>70%) among those initiating sexual activity at ≤12 years and for those reporting lifetime anal sex and exchanging sex for goods. For males, LPI was significantly elevated and highest (>40%) among those who reported lifetime anal sex and history of a sexually transmitted infection. Overall, risk factors associated with LPI were similar for females and males. Among the total sample (females and males combined), significant independent risk factors with AORs ≥2.5 included female gender, being aged 20-24 years, having five to six total adverse childhood experiences, initiating sex at age ≤12 or 13-14 years, lifetime anal sex, most recent sex act unprotected, and lifetime exchange of sex for goods. Among street youth with LPI (n = 259), the most recent LPI event was reported to be unintended by 63.3% and to have ended in abortion by 43.2%. In conclusion, our assessment documented high rates of LPI among Ukrainian street youth who, given the potential for negative outcomes and the challenges of raising a child on the streets, are in need of community-based pregnancy prevention programs and services. Promising preventive strategies are discussed, which are likely applicable to other urban populations of street-based youth as well. [ABSTRACT FROM AUTHOR]

Abstract Background The HIV epidemic in Russia has increasingly involved reproductive-aged women, which may increase perinatal HIV transmission. Methods Standard HIV case-reporting and enhanced perinatal HIV surveillance systems were used for prospective assessment of HIV-infected women giving birth in St. Petersburg, Russia, during 2004-2008. Trends in social, perinatal, and clinical factors influencing mother-to-child HIV transmission stratified by history of injection drug use, and rates of perinatal HIV transmission were assessed using two-sided χ2 or Cochran-Armitage tests. Results Among HIV-infected women who gave birth, the proportion of women who self-reported ever using injection drugs (IDUs) decreased from 62% in 2004 to 41% in 2008 (P < 0.0001). Programmatic improvements led to increased uptake of the following clinical services from 2004 to 2008 (all P < 0.01): initiation of antiretroviral prophylaxis at ≤28 weeks gestation (IDUs 44%-54%, non-IDUs 45%-72%), monitoring of immunologic (IDUs 48%-64%, non-IDUs 58%-80%) and virologic status (IDUs 8%-58%, non-IDUs 10%-75%), dual/triple antiretroviral prophylaxis (IDUs 9%-44%, non-IDUs 14%-59%). After initial increase from 5.3% (95% confidence interval [CI] 3.5%-7.8%) in 2004 to 8.5% (CI 6.1%-11.7%) in 2005 (P < 0.05), perinatal HIV transmission decreased to 5.3% (CI 3.4%-8.3%) in 2006, and 3.2% (CI 1.7%-5.8%) in 2007 (P for trend Conclusions Reduced proportion of IDUs and improved clinical services among HIV-infected women giving birth were accompanied by decreased perinatal HIV transmission, which can be further reduced by increasing outreach and HIV testing of women before and during pregnancy.

Objective: To examine trends, characteristics, and outcomes of donor oocyte embryo transfer cycles by original oocyte and resultant embryo state and determine whether oocyte state (fresh or frozen) is differentially associated with clinical pregnancy, live birth, and term, healthy birthweight neonates among singleton live births., Design: Retrospective cohort study., Setting: National study., Patient(s): Patients undergoing donor oocyte embryo transfer cycles in the United States reporting to the National Assisted Reproductive Technology Surveillance System from 2013 to 2020 . INTERVENTION(S): Original donor oocyte and resultant embryo state (fresh or frozen)., Main Outcome Measure(s): Annual numbers and proportions of total donor oocyte embryo transfer cycles stratified by oocyte and embryo state and single embryo transfer cycles resulting in the live birth of term (≥37 weeks gestation), healthy birthweight (≥2,500 g) singletons during 2013-2020. Rates of live birth and term, healthy birthweight neonates among singleton live births for 2018-2020 are also reported. Relative risks examine associations between donor oocyte state and live birth and term, healthy birthweight neonates among singleton live births resulting from donor oocyte embryo transfer cycles., Result(s): From 2013 to 2020, there were 135,085 donor oocyte embryo transfer cycles, of which the proportions increased for frozen embryos (42.3%-76.6%), fresh embryos using frozen donor oocytes (19.9%-68.3%) and single embryo transfers (36.4%-85.5%). During 2018-2020, there were 48,679 donor oocyte embryo transfer cycles. Rates of live birth were lower with frozen compared with fresh donor oocytes for both fresh (46.2%, 55.9%; adjusted relative risk [aRR], 0.83; 95% confidence interval [CI], 0.79-0.87) and frozen (41.3%, 45.8%; aRR, 0.94; 95% CI, 0.91-0.98) embryo transfer cycles. Among singleton live births, rates of delivering a term, healthy birth weight neonate were similar for frozen compared with fresh donor oocyte transfer cycles among fresh (77.3%, 77.2%; aRR, 1.01; 95% CI, 0.98-1.03) and frozen (75.6%, 75.1%; aRR, 1.02; 95% CI, 0.99-1.04) embryos., Conclusion(s): In this national study of donor oocyte embryo transfer cycles, frozen embryo transfers, fresh embryo transfers using frozen oocytes, and single embryo transfers increased. Although frozen compared with fresh oocytes were associated with a slightly reduced rate of live birth, rates of term, healthy birthweight neonates among singleton live births were comparable between donor oocyte states., Competing Interests: Declaration of Interests C.B.B. reports funding from Marianne Ruby, MD Award from the Department of Gynecology and Obstetrics, Emory University School of Medicine for a senior medical student to conduct research in an area that will advance knowledge and understanding of issues impacting women from menarche through menopause; and the Pacific Coast Reproductive Society Scholarship for part of this research to be presented at the Annual Pacific Coast Reproductive Society Conference in Indian Wells, California, March 22–26, 2023. C.E.D. has nothing to disclose. J.C.L. has nothing to disclose. D.M.K. has nothing to disclose. J.F.K. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. All rights reserved.)

In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California's Department of Developmental Services from 2000 through November 2019. All 95 149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The hazard risk ratio for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

Objective: To study the contribution of ovulation induction and ovarian stimulation, in vitro fertilization (IVF), and unassisted conception to the increase in national plural births in the United States, a significant contributor to adverse maternal and infant health outcomes., Design: National and IVF-assisted plural birth data were derived from the Centers for Disease Control and Prevention's National Vital Statistics System (1967-2021, after introduction of Clomiphene Citrate in the United States) and the National Assisted Reproductive Technology Surveillance System (1997-2021), respectively., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): Not applicable., Main Outcome Measure(s): In addition to IVF-assisted plural births, the contributions of unassisted conception to plural births among women aged <35 and ≥35 years were estimated using plural birth rates from 1949-1966 and a Bayesian logistic model with race and age as independent variables. The contribution of ovulation induction and ovarian stimulation was estimated as the difference between national plural births and IVF-assisted and unassisted counterparts., Result(s): From 1967-2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1,000 live births), then declined to 31.2/1,000 live births; the triplet and higher order birth rate increased 6.7-fold to a 1998 high (1.9/1,000 live births), then declined to 0.8/1,000 live births. In 2021, the contribution of unassisted conception among women aged <35 years to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women aged ≥35 years (16.8%), and IVF (7.6%). During 2009-2021, the contribution of ovulation induction and ovarian stimulation has remained stable, the contribution of unassisted conception among women aged <35 and ≥35 years has increased, and the contribution of IVF has decreased., Conclusion(s): Ovulation induction and ovarian stimulation are leading iatrogenic contributors to plural births. They are, therefore, targets for intervention to reduce the adverse maternal and infant health outcomes associated with plural births. Maternal age of ≥35 years is a significant contributor to the national plural birth increase., Competing Interests: Declaration of interest E.Y.A. has nothing to report. A.S.P. has nothing to report. P.A.G. has nothing to report. A.D.K. has nothing to report. Y.Z. has nothing to report. D.M.K. has nothing to report. R.G. has nothing to report., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Missing race/ethnicity data are common in many surveillance systems and registries, which may limit complete and accurate assessments of racial and ethnic disparities. Centers for Disease Control and Prevention's National Assisted Reproductive Technology (ART) Surveillance System (NASS) has a congressional mandate to collect data on all ART cycles performed by fertility clinics in the United States and provides valuable information on ART utilization and treatment outcomes. However, race/ethnicity data are missing for many ART cycles in NASS. Materials and Methods: We multiply imputed missing race/ethnicity data using variables from NASS and additional zip code-level race/ethnicity information in U.S. Census data. To evaluate imputed data quality, we generated training data by imposing missing values on known race/ethnicity under missing at random assumption, imputed, and examined the relationship between race/ethnicity and the rate of stillbirth per pregnancy. Results: The distribution of imputed race/ethnicity was comparable to the reported one with the largest difference of 0.53% for non-Hispanic Asian. Our imputation procedure was well calibrated and correctly identified that 89.91% (standard error = 0.18) of known race/ethnicity values on average in training data. Compared to complete-case analysis, using multiply imputed data reduced bias of parameter estimates (the range of bias for stillbirth per pregnancy across race/ethnicity groups is 0.02%-0.18% for imputed data analysis, versus 0.04%-0.66% for complete-case analysis) and yielded narrower confidence intervals. Conclusions: Our results underscore the importance of collecting complete race/ethnicity information for ART surveillance. However, when the missingness exists, multiply imputed race/ethnicity can improve the accuracy and precision of health outcomes estimated across racial/ethnic groups.

Objective: This study aimed to compare trends and characteristics of assisted reproductive technology (ART) and non-ART perinatal deaths and to evaluate the association of perinatal mortality and method of conception (ART vs. non-ART) among ART and non-ART deliveries in Florida, Massachusetts, and Michigan from 2006 to 2011., Study Design: Retrospective cohort study using linked ART surveillance and vital records data from Florida, Massachusetts, and Michigan., Results: During 2006 to 2011, a total of 570 ART-conceived perinatal deaths and 25,158 non-ART conceived perinatal deaths were identified from the participating states. Overall, ART perinatal mortality rates were lower than non-ART perinatal mortality rates for both singletons (7.0/1,000 births vs. 10.2/1,000 births) and multiples (22.8/1,000 births vs. 41.2/1,000 births). At <28 weeks of gestation, the risk of perinatal death among ART singletons was significantly lower than non-ART singletons (adjusted risk ratio [aRR] = 0.46, 95% confidence interval [CI]: 0.26-0.85). Similar results were observed among multiples at <28 weeks of gestation (aRR = 0.64, 95% CI: 0.45-0.89)., Conclusion: Our findings suggest that ART use is associated with a decreased risk of perinatal deaths prior to 28 weeks of gestation, which may be explained by earlier detection and management of fetal and maternal conditions among ART-conceived pregnancies. These findings provide valuable information for health care providers, including infertility specialists, obstetricians, and pediatricians when counseling ART users on risk of treatment., Key Points: · ART use is associated with a decreased risk of perinatal deaths prior to 28 weeks of gestation.. · ART perinatal mortality rates were lower than that for non-ART perinatal mortality.. · This study used linked data to examine associations between use of ART and perinatal deaths.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: As the use of in vitro fertilization continues to increase in the United States, up-to-date models that estimate cumulative live birth rates after multiple oocyte retrievals and embryo transfers (fresh and frozen) are valuable for patients and clinicians weighing treatment options., Objective: This study aimed to develop models that generate predicted probabilities of live birth in individuals considering in vitro fertilization based on demographic and reproductive characteristics., Study Design: Our population-based cohort study used data from the National Assisted Reproductive Technology Surveillance System 2016 to 2018, including 196,916 women who underwent 207,766 autologous embryo transfer cycles and 25,831 women who underwent 36,909 donor oocyte transfer cycles. We used data on autologous in vitro fertilization cycles to develop models that estimate a patient's cumulative live birth rate after all embryo transfers (fresh and frozen) within 12 months after 1, 2, and 3 oocyte retrievals in new and returning patients. Among patients using donor oocytes, we estimated the cumulative live birth rate after their first, second, and third embryo transfers. Multinomial logistic regression models adjusted for age, prepregnancy body mass index (imputed for 18% of missing values), parity, gravidity, and infertility diagnoses were used to estimate the cumulative live birth rate., Results: Among new and returning patients undergoing autologous in vitro fertilization, female age had the strongest association with cumulative live birth rate. Other factors associated with higher cumulative live birth rates were lower body mass index and parity or gravidity ≥1, although results were inconsistent. Infertility diagnoses of diminished ovarian reserve, uterine factor, and other reasons were associated with a lower cumulative live birth rate, whereas male factor, tubal factor, ovulatory disorders, and unexplained infertility were associated with a higher cumulative live birth rate. Based on our models, a new patient who is 35 years old, with a body mass index of 25 kg/m 2 , no previous pregnancy, and unexplained infertility diagnoses, has a 48%, 69%, and 80% cumulative live birth rate after the first, second, and third oocyte retrieval, respectively. Cumulative live birth rates are 29%, 48%, and 62%, respectively, if the patient had diminished ovarian reserve, and 25%, 41%, and 52%, respectively, if the patient was 40 years old (with unexplained infertility). Very few recipient characteristics were associated with cumulative live birth rate in donor oocyte patients., Conclusion: Our models provided estimates of cumulative live birth rate based on demographic and reproductive characteristics to help inform patients and providers of a woman's probability of success after in vitro fertilization., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Insurance coverage for fertility services may reduce the financial burden of high-cost fertility care such as assisted reproductive technology and improve its utilization. Patients who exit care after failing to reach their reproductive goals report higher rates of mental health problems and a lower sense of well-being. It is important to understand the relationship between state-mandated insurance coverage for fertility services and assisted reproductive technology care discontinuation., Objective: This study aimed to assess whether state-mandated insurance coverage for fertility services is associated with lower rates of care discontinuation after an initial assisted reproductive technology cycle that did not result in a live birth., Study Design: This is a retrospective, population-based cohort study using data from United States fertility clinics reporting to the National Assisted Reproductive Technology Surveillance System during 2016 and 2018. Patients who began their first autologous assisted reproductive technology cycle during 2016 and 2017 and did not have a live birth were included. We describe the rate of assisted reproductive technology care discontinuation (no additional cycle within 12 months of the previous cycle's date of failure). Multivariable analyses were conducted to evaluate factors independently associated with care discontinuation, including the scope of fertility services included in state coverage mandate at assisted reproductive technology cycle initiation that were as follows: comprehensive (≥3 assisted reproductive technology cycles), limited (1, 2, or an unspecified number of assisted reproductive technology cycles), mandate not including assisted reproductive technology, and no mandate., Results: Among 91,324 patients who underwent their first autologous assisted reproductive technology cycle that did not result in live birth, 24,072 (26.4%) discontinued care. Compared with patients who lived in states with mandates for comprehensive assisted reproductive technology coverage, those in states with mandates for fertility services coverage that did not include assisted reproductive technology or states with no mandate were 46% (adjusted relative risk, 1.46; 95% confidence interval, 1.31-1.63) and 26% (adjusted relative risk, 1.26; 95% confidence interval, 1.15-1.39) more likely to discontinue care, respectively, after controlling for patient and cycle characteristics. Increasing patient age, distance from clinic ≥50 miles, previous live birth, fewer oocytes retrieved, and not having embryos cryopreserved were also associated with higher rates of discontinuation. Non-Hispanic Black, non-Hispanic Asian, and Hispanic patients had higher rates of care discontinuation than non-Hispanic White patients regardless of the existence or scope of state-mandated assisted reproductive technology coverage., Conclusion: Comprehensive state-mandated insurance coverage for assisted reproductive technology is associated with lower rates of assisted reproductive technology care discontinuation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To assess the benefit of frozen vs. fresh elective single embryo transfer using traditional and novel methods of controlling for confounding., Design: Retrospective cohort study using data from the National Assisted Reproductive Technology Surveillance System., Setting: Not applicable., Patient(s): A total of 44,750 women aged 20-35 years undergoing their first lifetime oocyte retrieval and embryo transfer in 2016-2017, who had ≥4 embryos cryopreserved., Intervention(s): Fresh elective single embryo transfer and frozen elective single embryo transfer., Main Outcome Measure(s): The primary outcome was a singleton live birth. Secondary outcomes included rates of total live birth (singleton plus multiple gestations), twin live birth, clinical intrauterine gestation, total pregnancy loss, biochemical pregnancy, and ectopic pregnancy. Outcomes for infants included gestational age at delivery, birth weight, and being small for gestational age., Result(s): The eligibility criteria were met by 6,324 fresh and 2,318 frozen cycles. Patients undergoing fresh and frozen transfer had comparable mean age (30.69 [standard deviation {SD} 0.08] years vs. 31.06 [SD 0.08] years) and body mass index (24.76 [SD 0.20] vs. 25.65 [SD 0.15]); however, women in the frozen cohort created more embryos (8.1 [SD 0.12] vs. 6.8 [SD 0.08]). Singleton live birth rates in the fresh vs. frozen groups were 51.4% vs. 48.8% (risk ratio 1.05; 95% confidence interval [CI], 1.00-1.10). After adjustment with a log-linear regression model and propensity score analysis, the difference in singleton live birth rates remained nonsignificant (adjusted risk ratio, 1.05; 95% CI, 0.97-1.14 and 1.02; 95% CI, 0.96-1.08, respectively). A novel dynamical model confirmed inherent fertility (probability of ever achieving a pregnancy) was balanced between groups (odds ratio, 1.23; 95% CI 0.78-1.95]). The per-cycle probability of singleton live birth was not different between groups (odds ratio 1.11 [95% CI 0.94-1.3])., Conclusion(s): In this retrospective cohort study of fresh vs. frozen elective single embryo transfer, there was no statistically significant difference in singleton live birth rate after adjustment using log-linear models and propensity score analysis. The successful application of a novel dynamical model, which incorporates multiple assisted reproductive technology cycles from the same woman as a surrogate for inherent fertility, offers a novel and complementary perspective for assessing interventions using national surveillance data., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To examine trends of frozen embryo transfer (FET) proportions and large-for-gestational-age (LGA) incidence and determine risk factors for LGA infants after FET., Design: Retrospective cohort study., Setting: Not applicable., Patients: Frozen embryo transfer cycles., Interventions: None., Main Outcome Measures: Singleton LGA infant., Results: The percentage of FETs increased from 20%-74% of transfers, whereas the rate of LGA among FET singleton births decreased from 18%-12% during 2004-2018. In a subanalysis of 127,525 FET-associated singleton live births during 2016-2018, patient factors associated with LGA were higher-than-normal maternal body mass index (body mass index [BMI], 25.0-29.9 kg/m 2 ; adjusted relative risk [aRR], 1.31; 95% confidence interval [CI], 1.26-1.36; BMI, 30.0-34.9 kg/m 2 ; aRR, 1.48; 95% CI, 1.41-1.55; and BMI, >35 Kg/m 2 ; aRR, 1.68; 95% CI, 1.59-1.77) and ≥1 prior birth vs. none. Low maternal BMI (<18.5 vs. 18.5-24.9 kg/m 2 ) and cycles involving patients who were non-Hispanic (NH) Asian/Native Hawaiian/Pacific Islander, NH Black, or Hispanic (compared with NH White) were at lower risk of LGA infants. Cycle factors associated with LGA included gestational carrier use (aRR, 1.25; 95% CI, 1.16-1.34) and donor sperm (aRR, 1.17; 95% CI, 1.10-1.25)., Conclusions: Although the number and proportion of FET cycles increased from 2004-2018, the rate of LGA after FET decreased. Maternal BMI, parity, and race/ethnicity were the strongest risk factors for LGA infants after FET.

Background: Chlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3-enhanced serological (Pgp3) assay., Methods: In our case-control study of women 19 to 42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in 2 US infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios with 95% confidence intervals (CIs) stratified by race. We then estimated the adjusted chlamydia population-attributable fraction with 95% CI of TFI., Results: All Black (n = 107) and 618 of 620 non-Black women had Pgp3 results. Pgp3 seropositivity was 25.9% (95% CI, 19.3%-33.8%) for non-Black cases, 15.2% (95% CI, 12.3%-18.7%) for non-Black controls, 66.0% (95% CI, 51.7%-77.8%) for Black cases, and 71.7% (95% CI, 59.2%-81.5%) for Black controls. Among 476 non-Black women without endometriosis (n = 476), Pgp3 was associated with TFI (adjusted odds ratio, 2.6 [95% CI, 1.5-4.4]), adjusting for clinic, age, and income; chlamydia TFI-adjusted population-attributable fraction was 19.8% (95% CI, 7.7%-32.2%) in these women. Pgp3 positivity was not associated with TFI among non-Black women with endometriosis or among Black women (regardless of endometriosis)., Conclusions: Among non-Black infertile women without endometriosis in these clinics, 20% of TFI was attributed to chlamydia. Better biomarkers are needed to estimate chlamydia TFI PAF, especially in Black women., Competing Interests: Conflict of Interest and Sources of Funding: The authors have no conflict of interest. This study was supported by Centers for Disease Control and Prevention, Prevention Research Centers grants (5U48DP001915 and 5U48DP001918) and National Institutes of Health, Sexually Transmitted Infections Clinical Trials group (contract HHSN27220130012I)., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Objective: To describe the prevalence and treatment characteristics of assisted reproductive technology (ART) cycles involving specific male factor infertility diagnoses in the United States., Design: Cross-sectional analysis of ART cycles in the National ART Surveillance System (NASS)., Setting: Clinics that reported patient ART cycles performed in 2017 and 2018., Patients: Patients who visited an ART clinic and the cycles were reported in the NASS. The ART cycles included all autologous and donor cycles that used fresh or frozen embryos., Interventions: Not applicable., Main Outcome Measures: Analyses used new, detailed reporting of male factor infertility subcategories, treatment characteristics, and male partner demographics available in the NASS., Results: Among 399,573 cycles started with intent to transfer an embryo, 30.4% (n = 121,287) included a male factor infertility diagnosis as a reason for using ART. Of these, male factor only was reported in 16.5% of cycles, and both male and female factors were reported in 13.9% of cycles; 21.8% of male factor cycles had >1 male factor. Abnormal sperm parameters were the most commonly reported diagnoses (79.7%), followed by medical condition (5.3%) and genetic or chromosomal abnormalities (1.0%).Males aged ≤40 years comprised 59.6% of cycles with male factor infertility. Intracytoplasmic sperm injection was the primary method of fertilization (81.7%). Preimplantation genetic testing was used in 26.8%, and single embryo transfer was used in 66.8% of cycles with male factor infertility diagnosis., Conclusions: Male factor infertility is a substantial contributor to infertility treatments in the United States. Continued assessment of the prevalence and characteristics of ART cycles with male factor infertility may inform treatment options and improve ART outcomes. Future studies are necessary to further evaluate male factor infertility.

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 have multiple births because multiple embryos might be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth (<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 2018 and compares birth outcomes that occurred in 2018 (resulting from ART procedures performed in 2017 and 2018) with outcomes for all infants born in the United States in 2018., Period Covered: 2018., 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 (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 the 50 U.S. states, the District of Columbia, and Puerto Rico., Results: In 2018, a total of 203,119 ART procedures (range: 196 in Alaska to 26,028 in California) were performed in 456 U.S. fertility clinics and reported to CDC. These procedures resulted in 73,831 live-birth deliveries (range: 76 in Puerto Rico and Wyoming to 9,666 in California) and 81,478 infants born (range: 84 in Wyoming to 10,620 in California). Nationally, among women aged 15-44 years, the rate of ART procedures performed was 3,135 per 1 million women. ART use exceeded 1.5 times the national rate in seven states (Connecticut, Illinois, Maryland, Massachusetts, New Jersey, New York, and Rhode Island) and the District of Columbia. ART use rates exceeded the national rate in an additional seven states (California, Delaware, Hawaii, New Hampshire, Utah, Vermont, and Virginia). Nationally, among all ART transfer procedures, the average number of embryos transferred was similar across age groups (1.3 among women aged <35 years, 1.3 among women aged 35-37 years, and 1.4 among women aged >37 years). The national single-embryo transfer (SET) rate among all embryo-transfer procedures was 74.1% among women aged <35 years (range: 28.2% in Puerto Rico to 89.5% in Delaware), 72.8% among women aged 35-37 years (range: 30.6% in Puerto Rico to 93.7% in Delaware), and 66.4% among women aged >37 years (range: 27.1% in Puerto Rico to 85.3% in Delaware). In 2018, ART contributed to 2.0% of all infants born in the United States (range: 0.4% in Puerto Rico to 5.1% in Massachusetts) from procedures performed in 2017 and 2018. Approximately 78.6% of ART-conceived infants were singleton infants. Overall, ART contributed to 12.5% of all multiple births, including 12.5% of all twin births and 13.3% of all triplets and higher-order births. ART-conceived twins accounted for approximately 97.1% (15,532 of 16,001) of all ART-conceived multiple births. The percentage of multiple births was higher among infants conceived with ART (21.4%) than among all infants born in the total birth population (3.3%). Approximately 20.7% (15,532 of 74,926) of ART-conceived infants were twins, and 0.6% (469 of 74,926) were triplets and higher-order multiples. Nationally, infants conceived with ART contributed to 4.2% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 18.3% were low birthweight compared with 8.3% among all infants. ART-conceived infants contributed to 5.1% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (26.1%) than among all infants born in the total birth population (10.0%). The percentage of low birthweight among singletons was 8.3% among ART-conceived infants and 6.6% among all infants born. The percentage of preterm births among ART-conceived singleton infants was 14.9% compared with 8.3% among all singleton infants. The percentages of small for gestational age infants was 7.3% among ART-conceived infants compared with 9.4% among all infants., Interpretation: Although singleton infants accounted for the majority of ART-conceived infants, multiple births from ART varied substantially among states and nationally, contributing to >12% of all twins, triplets, and higher-order multiple infants born in the United States. Because multiple births are associated with higher rates of prematurity than singleton births, the contribution of ART to poor birth outcomes continues to be noteworthy. Although SET rates increased among all age groups, variations in SET rates among states and territories remained, which might reflect variations in embryo-transfer practices among fertility clinics and might in part account for variations in multiple birth rates among states and territories., Public Health Action: Reducing the number of embryos transferred and increasing use of SET, when clinically appropriate, can help reduce multiple births and related adverse health consequences for both mothers and infants. Whereas risks to mothers from multiple-birth pregnancy include higher rates of caesarean delivery, gestational hypertension, and gestational diabetes, infants from multiple births are at increased risk for numerous adverse sequelae such as preterm birth, birth defects, and developmental disabilities. 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 on a population basis., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Nearly 14% of US women report any lifetime infertility which is associated with health care costs and psychosocial consequences. Tubal factor infertility (TFI) often occurs as a result of sexually transmitted diseases and subsequent pelvic inflammatory disease. We sought to evaluate for and describe potential racial disparities in TFI and in vitro fertilization (IVF) prevalence., Methods: Records of women aged 19 to 42 years in our retrospective cohort from 2 US infertility clinics were reviewed. We calculated TFI prevalence, IVF initiation prevalence, and prevalence ratios (PRs), with 95% confidence intervals (CIs) for each estimate, overall and by race., Results: Among 660 infertile women, 110 (16.7%; 95% CI, 13.8-19.5%) had TFI which was higher in Black compared with White women (30.3% [33/109] vs 13.9% [68/489]; PR, 2.2 [95% CI, 1.5-3.1]). For women with TFI, IVF was offered to similar proportions of women by race (51.5% [17/33] vs 52.9% [36/68] for Black vs White women); however, fewer Black than White women with TFI started IVF (6.7% [1/15] vs 31.0% [9/29]; PR, 0.2 [95% CI, 0-1.0]), although the difference was not statistically different., Conclusions: Tubal factor infertility prevalence was 2-fold higher among Black than White women seeking care for infertility. Among women with TFI, data suggested a lower likelihood of Black women starting IVF than White women. Improved sexually transmitted disease prevention and treatment might ameliorate disparities in TFI., Competing Interests: Conflicts of Interest: K.R.H. is on the Speakers bureau for AbbVie, and W.M.G. has received research funds and consulting fees from Hologic and consulting fees from Roche. The other authors declare no conflicts of interest., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

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 have multiple-birth infants because multiple embryos may be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth (<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 2017 and compares birth outcomes that occurred in 2017 (resulting from ART procedures performed in 2016 and 2017) with outcomes for all infants born in the United States in 2017., Period Covered: 2017., 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 (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 the 50 states, the District of Columbia, and Puerto Rico., Results: In 2017, a total of 196,454 ART procedures (range: 162 in Alaska to 24,179 in California) with at least one embryo transferred were performed in 448 U.S. fertility clinics and reported to CDC. These procedures resulted in 68,908 live-birth deliveries (range: 67 in Puerto Rico to 8,852 in California) and 78,052 infants born (range: 85 in Puerto Rico to 9,926 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years) was 3,040. ART use rates exceeded the national rate in 14 states (Connecticut, Delaware, District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Utah, Vermont, and Virginia). ART use exceeded 1.5 times the national rate in seven states (Connecticut, the District of Columbia, Illinois, Maryland, Massachusetts, New Jersey, and New York). Nationally, among all ART transfer procedures, the average number of embryos transferred increased slightly with increasing age (1.3 among women aged <35 years, 1.4 among women aged 35-37 years, and 1.5 among women aged >37 years). This year, single-embryo transfer (SET) rates among all embryo-transfer procedures are presented instead of elective single-embryo transfer procedures previously reported. Nationally, SET rates were 67.3% (range: 38.9% in South Dakota to 90.4% in Delaware), 65.0% (range: 23.6% in Puerto Rico to 89.4% in Delaware), and 60.0% (range: 28.6% in Puerto Rico to 83.1% in Delaware) among women aged <35 years, aged 35-37 years, and aged >37 years, respectively. In 2017, ART contributed to 1.9% of all infants born in the United States (range: 0.4% in Puerto Rico to 5.0% in Massachusetts). Approximately 73.6% of ART-conceived infants were singleton infants. Overall, ART contributed to 14.7% of all multiple births, including 14.7% of all twin infants and 17.3% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (18,890 of 19,570) of all ART-conceived infants born in multiple deliveries. The percentage of multiple births was higher among infants conceived with ART (26.4%) than among all infants born in the total birth population (3.4%). Approximately 25.5% of ART-conceived infants were twins, and 0.9% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 4.5% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 20.2% had low birthweight, compared with 8.3% 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 (27.8%) than among all infants born in the total birth population (9.9%). The percentage of low birthweight among singletons was 8.1% among ART-conceived infants and 6.6% among all infants born. The percentage of preterm births among ART-conceived singleton infants was 14.0%, compared with 8.1% among all singleton infants. The percentages of small for gestational age infants was 7.6% among ART-conceived infants, compared with 9.9% among all infants., Interpretation: Although singleton infants accounted for the majority of ART-conceived infants, multiple births from ART still contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. Variations in SET rates among states and territories were noted, reflecting variations in embryo-transfer practices among fertility clinics, which might in part account for higher multiple birth from ART observed in some states and territories., Public Health Action: Reducing the number of embryos transferred and increasing use of SET, when clinically appropriate, can help reduce multiple births and related adverse health consequences for both mothers and infants. Because infants from multiple births are at increased risk for numerous adverse sequelae that cannot be ascertained from the data collected through NASS alone, long-term follow-up for 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 on a population basis., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objectives: To assess trends, predictors, and perinatal outcomes of ovarian hyperstimulation syndrome (OHSS) associated with in vitro fertilization (IVF) cycles in the United States., Design: Retrospective cohort study using National Assisted Reproductive Technology Surveillance System (NASS) data., Setting: Not applicable., Patient(s): Fresh autologous and embryo-banking cycles performed from 2000 to 2015., Interventions(s): None., Main Outcome Measure(s): OHSS, first-trimester loss, second-trimester loss, stillbirth, low birth weight, and preterm delivery., Result(s): The proportion of IVF cycles complicated by OHSS increased from 10.0 to 14.3 cases per 1,000 from 2000 to 2006, and decreased to 5.3 per 1,000 from 2006 to 2015. The risk of OHSS was highest for cycles with more than 30 oocytes retrieved (adjusted risk ratio [aRR] 3.85). OHSS was associated with a diagnosis of ovulatory disorder (aRR 2.61), tubal factor (aRR 1.14), uterine factor (aRR 1.17) and cycles resulting in pregnancy (aRR 3.12). In singleton pregnancies, OHSS was associated with increased risk of low birth weight (aRR 1.29) and preterm delivery (aRR 1.32). In twin pregnancies, OHSS was associated with an increased risk of second-trimester loss (aRR 1.81), low birth weight (aRR 1.06), and preterm delivery (aRR 1.16)., Conclusion(s): Modifiable predictive factors for OHSS include number of oocytes retrieved, pregnancy following fresh embryo transfer, and the type of medication used for pituitary suppression during controlled ovarian hyperstimulation. Patients affected by OHSS had a higher risk of preterm delivery and low birth weight. Clinicians should take measures to reduce the risk of OHSS whenever possible., (Copyright © 2020 American Society for Reproductive Medicine. All rights reserved.)

Objective: To evaluate the effectiveness of intracytoplasmic sperm injection (ICSI) in improving fertilization rates compared to conventional in vitro fertilization rates (IVF) among women aged ≥38 years with a non-male factor diagnosis., Design: Systematic review and meta-analysis., Setting: Not applicable., Patient(s): Women aged ≥38 years with a non-male factor diagnosis receiving IVF or ICSI., Intervention(s): A systematic review of databases including PubMed and Embase was performed. Study protocol was registered at the International Prospective Register of Systematic Reviews. Studies were selected if they compared fertilization rates from ICSI with those from conventional IVF among women aged ≥38 years with a non-male factor infertility diagnosis. A random effects model was used. Meta-analysis of Observational Studies in Epidemiology guidelines were applied., Main Outcome Measure(s): Fertilization rate., Results: Seven studies including 8796 retrieved oocytes (ICSI: 4,369; IVF: 4,427) with mean female age ≥38 years met the inclusion criteria. There was no significant difference in fertilization rates between ICSI and conventional IVF (relative risk [RR] 0.99, 95% confidence interval [CI] 0.93-1.06; P = .8). Heterogeneity was observed between studies (I 2 = 58.2; P < .05). Heterogeneity was significant (I 2 = 57.1; P < .05) when cycles with prior fertilization failure were excluded; however, when analysis was restricted to poor responders (RR 1.01, 95% CI 0.97-1.05; P = .6), heterogeneity was no longer significant (I 2 = 0.0; P = .5)., Conclusions: No difference was found in fertilization rates between conventional IVF and ICSI. Further studies are needed to assess the impact of ICSI in this population, controlling for other indications such as preimplantation genetic testing., (Published by Elsevier Inc.)

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess national trends in the sex distribution of live-born infants in the assisted reproductive technology (ART) and general population and to identify factors correlated with offspring sex., Design: Retrospective cohort study., Setting: Fertility treatment centers., Patients: All live-born infants included in the National Vital Statistics System and resulting from ART cycles reported to the National ART Surveillance System during 2006-14., Interventions: Not applicable., Main Outcome Measure(s): Trends in the proportion of male infants in the general population and proportion of males from fresh ART cycles among all ART live-born infants and singletons after single ET., Result(s): There were 214,274 live-born infants resulting from fresh ART cycles; 53.5% (5,492/10,266) of infants resulting from PGD/PGS cycles were male, as compared with 50.6% (103,228/204,008) in the non-PGD/PGS group. Among non-PGD/PGS cycles, blastocyst transfer was positively associated with male infants (adjusted risk ratio [aRR] = 1.03; 95% confidence interval [CI], 1.02-1.04). Intracytoplasmic sperm injection was negatively associated with male infants (aRR = 0.94; 95% CI, 0.93-0.95) and for singletons after single ET (aRR = 0.93; 95% CI, 0.90-0.95), as was transfer of two embryos (aRR 0.98; 95% CI, 0.97-0.99) or three or more embryos (aRR = 0.98; 95% CI, 0.96-0.99) among all live births from cycles without PGD/PGS use., Conclusion(s): The proportion of male live-born infants among ART population did not change during 2006-14, ranging from 50.5% to 51.2%. Factors such as blastocyst transfer, intracytoplasmic sperm injection use, embryo stage, and number of embryos transferred may be associated with infant sex; further investigation is needed to understand possible underlying causes., (Published by Elsevier Inc.)

Objectives We aimed to examine the extent to which health plan expenditures for infertility services differed by whether women resided in states with mandates requiring coverage of such services and by whether coverage was provided through a self-insured plan subject to state mandates versus fully-insured health plans subject only to federal regulation. Methods This retrospective cohort study used individual-level, de-identified health insurance claims data. We included women 19-45 years of age who were continuously enrolled during 2011 and classified them into three mutually exclusive groups based on highest treatment intensity: in vitro fertilization (IVF), intrauterine insemination (IUI), or ovulation-inducing (OI) medications. Using generalized linear models, we estimated adjusted annual mean, aggregate, and per member per month (PMPM) expenditures among women in states with an infertility insurance mandate and those in states without a mandate, stratified by enrollment in a fully-insured or self-insured health plan. Results Of the 6,006,017 women continuously enrolled during 2011, 9199 (0.15%) had claims for IVF, 10,112 (0.17%) had claims for IUI, and 23,739 (0.40%) had claims for OI medications. Among women enrolled in fully insured plans, PMPM expenditures for infertility treatment were 3.1 times higher for those living in states with a mandate compared with states without a mandate. Among women enrolled in self-insured plans, PMPM infertility treatment expenditures were 1.2 times higher for mandate versus non-mandate states. Conclusions for Practice Recorded infertility treatment expenditures were higher in states with insurance reimbursement mandates versus those without mandates, with most of the difference in expenditures incurred by fully-insured plans.

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., Period Covered: 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., Competing Interests: No conflicts of interest were reported.

Background: Smoking near conception has adverse effects on pregnancy outcomes. We estimated the proportion of assisted reproductive technology (ART) cycles with smoking reported and associated clinical outcomes., Methods: We used a retrospective cohort study (2009-2013) using national data of ART cycles in the United States. We compared patient characteristics, infertility diagnoses, and treatment procedures by self-reported smoking in the 3 months before treatment. Using multivariable logistic regression accounting for clustering by state, clinic, and patient, we assessed adjusted odds ratios (aOR) and 95% confidence intervals (CI) between smoking and clinical outcomes: cycle cancellations among all cycles (cycle stopped before retrieval of eggs or transfer of embryos), treatment outcomes (implantation, ectopic pregnancy, intrauterine pregnancy, and live birth) among cycles with ≥1 fresh embryo transferred, and pregnancy outcomes (miscarriage, stillbirth, and live birth) among intrauterine pregnancies., Results: Smoking was reported in 1.9% of cycles. Higher proportions of cycles among smokers versus nonsmokers were younger, non-Hispanic White, multigravida women and had tubal factor and male factor infertility diagnoses; lower proportions had diagnoses of diminished ovarian reserve and unexplained infertility, and used donor eggs. Smoking was associated with higher adjusted odds of cycle cancellation with no embryo transfer (aOR: 1.10; 95% CI: 1.00-1.21) and cancellations before fresh oocyte retrieval or frozen embryo transfer (1.11; 1.02-1.21). Associations between other clinical outcomes were nonsignificant., Conclusions: Over 12,000 ART cycles in the United States were exposed to smoking during 2009-2013; smoking increased the odds of cycle cancellation. Providers should encourage women to quit smoking before ART treatments.

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.

Objective: To compare live birth rates (LBRs) and multiple birth rates (MBRs) between elective single-embryo transfer (eSET) and double-embryo transfer (DET) in donor oocyte in vitro fertilization (IVF) treatments in both a cycle-level and clinic-level analysis., Methods: Donor oocyte IVF treatments performed by US IVF clinics reporting to the Centers for Disease Control and Prevention in 2013-2014 were included in the analysis. Primary outcomes included LBR and MBR. Secondary outcomes included gestational age at delivery (GA) and birth weight (BW) of offspring. These outcomes were evaluated on an individual cycle level as well as on the clinic level., Results: In multivariable models, LBR did not change significantly as clinics utilized eSET more frequently. MBR decreased significantly as utilization of eSET increased, from 39% MBR in clinics that utilized eSET 0-9% of the time to 7% MBR in clinics that used eSET 70% of the time (P < .0001). Mean BW and GA of IVF-conceived offspring both increased as clinics utilized eSET more frequently (2778 to 3185 g [P < .0001] and 37.5 to 38.5 weeks [P = .02] for clinics with the lowest and highest eSET utilization, respectively)., Conclusions: US IVF clinics utilizing eSET with higher frequencies have clinically comparable LBRs and significantly lower MBRs than clinics with lower-frequency eSET utilization. Mean offspring BW and GA increased with higher eSET utilization, further confirming the improved safety of this practice.

Zika virus infection can occur as a result of mosquitoborne or sexual transmission of the virus. Infection during pregnancy is a cause of fetal brain abnormalities and other serious birth defects (1,2). CDC has updated the interim guidance for men with possible Zika virus exposure who 1) are planning to conceive with their partner, or 2) want to prevent sexual transmission of Zika virus at any time (3). CDC now recommends that men with possible Zika virus exposure who are planning to conceive with their partner wait for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) before engaging in unprotected sex. CDC now also recommends that for couples who are not trying to conceive, men can consider using condoms or abstaining from sex for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) to minimize their risk for sexual transmission of Zika virus. All other guidance for Zika virus remains unchanged. The definition of possible Zika virus exposure remains unchanged and includes travel to or residence in an area with risk for Zika virus transmission (https://wwwnc.cdc.gov/travel/page/world-map-areas-with-zika) or sex without a condom with a partner who traveled to or lives in an area with risk for Zika virus transmission. CDC will continue to update recommendations as new information becomes available., Competing Interests: No conflicts of interest were reported.

We used 2006-2015 US National Assisted Reproductive Technology Surveillance System data to compare preterm birth and fetal growth for liveborn singletons (24-42 weeks' gestation) following in vitro fertilization with donor versus autologous oocytes. Using binary and multinomial logistic regression, we computed adjusted odds ratios and 95% confidence intervals for associations between use of donor oocytes and preterm delivery, being small for gestational age (SGA), and being large for gestational age (LGA), stratified by fresh and thawed embryo status and accounting for maternal characteristics and year of birth. There were 204,855 singleton births from fresh embryo transfers and 106,077 from thawed embryo transfers. Among fresh embryo transfers, donor oocyte births had higher odds of being preterm (adjusted odd ratio (aOR) = 1.32, 95% confidence interval (CI): 1.27, 1.38) or LGA (aOR = 1.27, 95% CI: 1.21, 1.33) but lower odds of being SGA (aOR = 0.81, 95% CI: 0.77, 0.85). Among thawed embryo transfers, donor oocyte births had higher odds of being preterm (aOR = 1.57, 95% CI: 1.48, 1.65) or SGA (aOR = 1.22, 95% CI: 1.14, 1.31) but lower odds of being LGA (aOR = 0.87, 95% CI: 0.82, 0.92). Use of donor oocytes was associated with increased odds of preterm delivery irrespective of embryo status; odds of being SGA were increased for donor versus autologous oocyte births among thawed embryo transfers only.

Purpose: To compare national trends and perinatal outcomes following the use of ejaculated versus surgically acquired sperm among IVF cycles with male factor infertility., Methods: This retrospective cohort includes US fertility clinics reporting to the National ART Surveillance System between 2004 and 2015. Fresh, non-donor IVF male factor cycles (n = 369,426 cycles) were included. We report the following outcomes: (1) Trends in surgically acquired and ejaculated sperm. (2) Adjusted risk ratios comparing outcomes for intracytoplasmic sperm injection (ICSI) cycles using surgically acquired (epididymal or testicular) versus ejaculated sperm. (3) Outcomes per non-canceled cycle: biochemical pregnancy, intrauterine pregnancy, and live birth (≥ 20 weeks). (4) Outcomes per pregnancy: miscarriage (< 20 weeks) and singleton pregnancy. (5) Outcomes per singleton pregnancy: normal birthweight (≥ 2500 g) and full-term delivery (≥ 37 weeks)., Results: Percentage of male factor infertility cycles that used surgically acquired sperm increased over the study period, 9.8 (2004) to 11.6% (2015), p < 0.05. The proportion of cycles using testicular sperm increased significantly over the study period, 4.9 (2004) to 6.5% (2015), p < 0.05. Among fresh, non-donor male factor ART cycles which used ICSI (n = 347,078 cycles), cycle, pregnancy, and perinatal outcomes were statistically significant but clinically similar with confidence intervals approaching one between cycles involving epididymal versus ejaculated sperm and between testicular versus ejaculated sperm. Results were similar among cycles with a sole diagnosis of male factor (no female factors), and for the subset in which the female partner was < 35 years old., Conclusion: Among couples undergoing ART for treatment of male factor infertility, pregnancy and perinatal outcomes were similar between cycles utilizing ejaculated sperm or surgically acquired testicular and epididymal sperm.

Purpose: In vitro fertilization (IVF) infants have lower birthweights than their peers, predisposing them to long-term health consequences. Blastocyst transfer (BT), at day 5-6 post-fertilization, is increasing in usage, partially due to improved pregnancy outcomes over cleavage-stage transfer (CT, day 2-3). Data to date, however, have been inconclusive regarding BT's effects on birthweight., Methods: Participants included all US autologous, single-gestation, fresh embryo transfer cycles initiated from 2007 to 2014 that resulted in a term infant (N = 124,154) from the National Assisted Reproductive Technology Surveillance System. Generalized linear models including obstetric history, maternal demographics, and infant sex and gestational age were used to compare birthweight outcomes for infants born following BT (N = 67,169) with infants born following CT (N = 56,985) and to test for an interaction between transfer stage and single embryo transfer (SET)., Results: Infants born following BT were 6 g larger than those born following CT (p = 0.04), but rates of macrosomia (RR 1.00, 95% CI 0.96-1.04) and low birthweight (LBW, RR 1.00, 95% CI 0.93-1.06) were not different between the groups. The interaction between SET and transfer stage was significant (p = 0.02). Among SET infants, BT was associated with 19.26 g increased birthweight compared to CT (p = 0.008)., Conclusions: The increase in birthweights identified following BT is unlikely to be clinically relevant, as there were no differences in rates of macrosomia or LBW. These findings are clinically reassuring and indicate that the increasing use of BT is unlikely to further decrease the on average lower birthweights seen in IVF infants compared to their naturally conceived peers.

[This corrects the article DOI: 10.1371/journal.pone.0169869.].

Objective: To compare associations between interpregnancy intervals (IPIs) and adverse perinatal outcomes in deliveries following IVF with deliveries following spontaneous conception or other (non-IVF) fertility treatments., Design: Cohort using linked birth certificate and assisted reproductive technology surveillance data from Massachusetts and Michigan., Setting: Not applicable., Patient(s): 1,225,718 deliveries., Intervention(s): None., Main Outcomes Measure(s): We assessed associations between IPI and preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) according to live birth or nonlive pregnancy outcome in the previous pregnancy., Result(s): In IVF deliveries following previous live birth, risk of PTB was 22.2% for IPI 12 to <24 months (reference); risk of PTB was higher for IPI <12 months (adjusted relative risk [aRR] 1.24, 95% confidence interval [CI] 1.09-1.41) and IPI ≥60 months (aRR 1.12, 95% CI 1.00-1.26). In non-IVF deliveries following live birth, risk of PTB was 6.4% for IPI 12 to <24 months (reference); risk of PTB was higher for IPI <12 and ≥60 months (aRR 1.19, 95% CI 1.16-1.21, for both). In both populations, U-shaped or approximately U-shaped associations were observed for SGA and LBW, although the association of IPI <12 months and SGA was not significant in IVF deliveries. In IVF and non-IVF deliveries following nonlive pregnancy outcome, IPI <12 months was not associated with increased risk of PTB, LBW, or SGA, but IPI ≥60 months was associated with significant increased risk of those outcomes in non-IVF deliveries., Conclusion(s): Following live births, IPIs <12 or ≥60 months were associated with higher risks of most adverse perinatal outcomes in both IVF and non-IVF deliveries., (Copyright © 2018 American Society for Reproductive Medicine. All rights reserved.)

Objective: To compare indications and trends in intracytoplasmic sperm injection (ICSI) use for in vitro fertilization (IVF) cycles among residents of states with and without insurance mandates for IVF coverage., Design: Cross-sectional analysis of the National Assisted Reproductive Technology Surveillance System from 2011 to 2015 for the main outcome and from 2000 to 2015 for trends., Setting: IVF cycles performed in U.S. fertility clinics., Patient(s): Fresh IVF cycles., Intervention(s): Residency in a state with an insurance mandate for IVF (n = 8 states) versus no mandate (n = 43 states, including DC)., Main Outcome Measure(s): ICSI use by insurance coverage mandate status stratified by male-factor infertility diagnosis., Result(s): During 2000-2015, there were 1,356,377 fresh IVF cycles, of which 25.8% (n = 350,344) were performed for residents of states with an insurance coverage mandate for IVF. ICSI use increased significantly during 2000-2015 in states both with and without a mandate; however, for non-male-factor infertility cycles, the percentage increase in ICSI use was greater among nonmandate states (34.6% in 2000 to 73.9% in 2015) versus mandate states (39.5% in 2000 to 63.5% in 2015). For male-factor infertility cycles, this percentage increase was ∼7.3% regardless of residency in a state with an insurance mandate for IVF. From 2011 to 2015, ICSI use was lower in mandate versus nonmandate states, both for cycles with (91.5% vs. 94.5%), and without (60.3% vs. 70.9%) male-factor infertility., Conclusion(s): Mandates for IVF coverage were associated with lower ICSI use for non-male-factor infertility cycles., (Published by Elsevier Inc.)

Background: Information regarding the use of donor sperm in assisted reproductive technology, as well as subsequent treatment and perinatal outcomes, remains limited. Outcome data would aid patient counseling and clinical decision making., Objectives: The objectives of the study were to report national trends in donor sperm utilization and live birth rates of donor sperm-assisted reproductive technology cycles in the United States and to compare assisted reproductive technology treatment and perinatal outcomes between cycles using donor and nondonor sperm. We hypothesize these outcomes to be comparable between donor and nondonor sperm cycles., Study Design: This was a retrospective cohort study using data from all US fertility centers reporting to the Centers for Disease Control and Prevention's National Assisted Reproductive Technology Surveillance System, accounting for ∼98% of assisted reproductive technology cycles (definition excludes intrauterine insemination). The number and percentage of assisted reproductive technology cycles using donor sperm and rates of pregnancy, live birth, preterm birth (<37 weeks), and low birthweight (<2500 g) were the primary outcomes measured. Treatments assessed include use of donor vs nondonor sperm. The trends analysis included all banking and fresh assisted reproductive technology cycles using donor and autologous oocytes performed between 1996 and 2014 (n = 1,710,034). The outcomes analysis was restricted to include only fresh autologous cycles performed between 2010 and 2014 (n = 437,569) to focus on cycles with a potential outcome and cycles reflective of current practice, thereby improving the clinical relevance. Cycles canceled prior to retrieval were excluded. Statistical analysis included linear regression to explore polynomial trends and log-binomial regression to estimate relative risk for outcomes among cycles using donor and nondonor sperm., Results: Of all banking and fresh donor and autologous oocyte assisted reproductive technology cycles performed between 1996 and 2014, 74,892 (4.4%) used donor sperm. In 2014, 7351 assisted reproductive technology cycles using donor sperm were performed, as compared with 1763 in 1996 (6.2% vs 3.8% of all cycles). Among all autologous oocyte cycles performed between 2010 and 2014, the live birth rate was lower for donor sperm (27.9%) than nondonor sperm cycles (32.5%); however, after adjustment for maternal age, donor sperm use was associated with an increased likelihood of live birth (adjusted relative risk, 1.06, 95% confidence interval, 1.01-1.10). Per transfer, there was no significant difference in live birth rates for donor vs nondonor sperm (31.9% vs 36.8%; adjusted relative risk, 1.04, 95% confidence interval, 0.998-1.09). Per singleton live birth, there was no significant difference in preterm birth (11.5% vs 11.8%; adjusted relative risk, 0.98, 95% confidence interval, 0.90-1.06); however, low birthweight delivery was slightly lower in donor sperm cycles (8.8% vs 9.4%; adjusted relative risk, 0.91, 95% confidence interval, 0.83-0.99)., Conclusion: Donor sperm use in assisted reproductive technology has increased in the United States, accounting for approximately 6% of all assisted reproductive technology cycles in 2014. Assisted reproductive technology treatment and perinatal outcomes were clinically similar in donor and nondonor sperm cycles., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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) infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART procedures performed in 2014 and 2015) with outcomes for all infants born in the United States in 2015., Period Covered: 2015., 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, 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 2015, a total of 182,111 ART procedures (range: 135 in Alaska to 23,198 in California) with the intent to transfer at least one embryo were performed in 464 U.S. fertility clinics and reported to CDC. These procedures resulted in 59,334 live-birth deliveries (range: 55 in Wyoming to 7,802 in California) and 71,152 infants born (range: 68 in Wyoming to 9,176 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 utilization rate, was 2,832. ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Virginia). Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.6 among women aged <35 years, 1.8 among women aged 35-37 years, and 2.3 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 34.7% (range: 11.3% in Puerto Rico to 88.1% in Delaware). In 2015, ART contributed to 1.7% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.5% in Massachusetts). ART also contributed to 17.0% of all multiple-birth infants, 16.8% of all twin infants, and 22.2% of all triplets and higher-order infants. The percentage of multiple-birth infants was higher among infants conceived with ART (35.3%) than among all infants born in the total birth population (3.4%). Approximately 34.0% of ART-conceived infants were twins and 1.0% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.1% of all low birthweight infants. Among ART-conceived infants, 25.5% had low birthweight, compared with 8.1% 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 (31.2%) than among all infants born in the total birth population (9.7%). Among singletons, the percentage of ART-conceived infants who had low birthweight was 8.7% compared with 6.4% among all infants born. The percentage of ART-conceived infants who were born preterm was 13.4% among singletons compared with 7.9% among all 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 are typically considered good candidates for eSET, the national average of 1.6 embryos was transferred per ART procedure. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four cycles of IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use exceeding 1.5 times the national rate. This type of mandated insurance coverage has been associated with greater use of ART and likely accounts for some of the difference in per capita ART use observed among states., Public Health Action: Twins account for the majority of ART-conceived multiple births. 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. State-based surveillance of ART might be useful for monitoring and evaluating maternal and infant health outcomes of ART in states with high ART use.

Purpose: The purpose of this study is to examine the spectrum of infertility diagnoses and assisted reproductive technology (ART) treatments in relation to risk of preterm birth (PTB) in singletons., Methods: Population-based assisted reproductive technology surveillance data for 2000-2010 were linked with birth certificates from three states: Florida, Massachusetts, and Michigan, resulting in a sample of 4,370,361 non-ART and 28,430 ART-related singletons. Logistic regression models with robust variance estimators were used to compare PTB risk among singletons conceived with and without ART, the former grouped by parental infertility diagnoses and treatment modalities. Demographic and pregnancy factors were included in adjusted analyses., Results: ART was associated with increased PTB risk across all infertility diagnosis groups and treatment types: for conventional ART, adjusted relative risks ranged from 1.4 (95% CI 1.0, 1.9) for male infertility to 2.4 (95% CI 1.8, 3.3) for tubal ligation. Adding intra-cytoplasmic sperm injection and/or assisted hatching to conventional ART treatment did not alter associated PTB risks. Singletons conceived by mothers without infertility diagnosis and with donor semen had an increased PTB risk relative to non-ART singletons., Conclusions: PTB risk among ART singletons is increased within each treatment type and all underlying infertility diagnosis, including male infertility. Preterm birth in ART singletons may be attributed to parental infertility, ART treatments, or their combination.

Objective: To study cross-border reproductive care (CBRC) by assessing the frequency and nature of assisted reproductive technology (ART) care that non-U.S. residents receive in the United States., Design: Retrospective study of ART cycles reported to the Centers for Disease Control and Prevention's National ART Surveillance System (NASS) from 2006 to 2013., Setting: Private and academic ART clinics., Patient(s): Patients who participated in ART cycles in the United States from 2006 to 2013., Intervention(s): None., Main Outcome Measure(s): Frequency and trend of ART use in the U.S. by non-U.S. residents, countries of residence for non-U.S. residents, differences by residence status for specific ART treatments received, and the outcomes of these ART cycles., Result(s): A total of 1,271,775 ART cycles were reported to NASS from 2006 to 2013. The percentage of ART cycles performed for non-U.S. residents increased from 1.2% (n = 1,683) in 2006 to 2.8% (n = 5,381) in 2013 (P<.001), with treatment delivered to residents of 147 countries. Compared with resident cycles, non-U.S. resident cycles had higher use of oocyte donation (10.6% vs. 42.6%), gestational carriers (1.6% vs. 12.4%), and preimplantation genetic diagnosis or screening (5.3% vs. 19.1%). U.S. resident and non-U.S. resident cycles had similar embryo transfer and multiple birth rates., Conclusion(s): This analysis showed that non-U.S. resident cycles accounted for a growing share of all U.S. ART cycles and made higher use of specialized treatment techniques. This study provides important baseline data on CBRC in the U.S. and may also prove to be useful to organizations interested in improving access to fertility treatments., (Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.)

Introduction: Information on the health-related quality of life (HRQOL) for women with infertility is limited and does not account for the co-occurrence of chronic conditions or emotional distress., Methods: We used data from state-added questions on reproductive health included in the 2013 Behavioral Risk Factor Surveillance System in seven states. HRQOL indicators included: self-reported health status; number of days in the past 30 days when physical and mental health was not good; number of days in the past 30 days that poor physical or mental health limited activities. We computed rate ratios for HRQOL for women ever experiencing infertility or difficulty staying pregnant compared with women never reporting these conditions; interactions with chronic conditions and depressive disorders were assessed., Results: Of 7,526 respondents aged 18-50 years, 387 (4.9%) reported infertility only and 339 (4.3%) reported difficulty staying pregnant only. Infertility was associated with an increase in average number of days with poor physical health for women with chronic conditions [rate ratio (RR) 1.85, 95% confidence interval (CI) 1.04-3.29] but was protective for women without chronic conditions (RR 0.47, 95% CI 0.29-0.75). Difficulty staying pregnant was associated with an increase in average number of days of limited activity among both women with chronic conditions (RR 2.14, 95% CI 1.32-3.45) and women with depressive disorders (RR 1.72 95% CI 1.14-2.62)., Discussion: Many HRQOL measures were poorer for women who had infertility or difficulty staying pregnant compared to their counterparts; the association was modified by presence of chronic conditions and depressive disorders.

Gestational surrogacy policy in the USA varies by state, but information on state differences is lacking. This study used data from the National Assisted Reproductive Technology Surveillance System from 2010 to 2014 to calculate state differences in gestational carrier cycle characteristics. Of the 662,165 in-vitro fertilization cycles in the USA between 2010 and 2014, 16,148 (2.4%) used gestational carriers. Non-USA residents accounted for 18.3% of gestational carrier cycles, and 29.1% of gestational carrier cycles by USA residents were performed in a state other than the state of residence of the intended parent. USA gestational surrogacy practice varies by state, potentially impacting patients' access to surrogacy services.

Background: Affordability plays an important role in the utilisation of in vitro fertilisation (IVF) and non-IVF fertility treatments. Fertility treatments are associated with increased risk of multiple births. The objective of this study was to investigate the association between the affordability of fertility treatments across US states and the percentage of multiple births due to natural conception, non-IVF treatments, and IVF, and the association between these percentages and state-specific multiple birth rates., Methods: State-specific per capita disposable personal income and state-specific infertility insurance mandates were used as measures of affordability. Maternal age-adjusted percentages of multiple births due to natural conception, non-IVF treatments, and IVF were estimated for each state using birth certificate and IVF data. Scatter plots and regression analysis were used to explore associations between state-level measures of affordability, the percentage of multiple births due to natural conception and fertility treatments, and state-specific multiple birth rates., Results: In 2013, age-adjusted contributions of natural conception, non-IVF fertility treatments, and IVF to multiple births in US were 58.2, 22.8, and 19.0% respectively. States with greater affordability of fertility treatments had higher percentages of multiples due to IVF and lower percentages due to natural conception. Higher percentages of multiples due to IVF and lower percentages due to natural conception were associated with higher state-specific multiple birth rates., Conclusion: Increasing affordability of fertility treatments may increase state-specific multiple birth rates. Policies and treatment practices encouraging single-gestation pregnancies may help reduce multiple births resulting from these treatments., (© 2017 John Wiley & Sons Ltd.)

Background: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility., Objectives: The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates., Study Design: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis-tubal factor infertility odds ratios and population-attributable fraction, stratified by race., Results: We enrolled 107 Black women (47 cases, 60 controls) and 620 non-Black women (140 cases, 480 controls). Chlamydia trachomatis seropositivity by either assay was 81% (95% confidence interval, 73-89%) among Black and 31% (95% confidence interval, 28-35%) among non-Black participants (P < .001). Using the primary Chlamydia trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among Blacks (odds ratio, 1.22, 95% confidence interval, 0.45-3.28) or non-Blacks (odds ratio, 1.41, 95% confidence interval, 0.95-2.09), and the estimated population-attributable fraction was 15% (95% confidence interval, -97% to 68%) among Blacks and 11% (95% confidence interval, -3% to 23%) among non-Blacks. Use of alternate serological measures and tubal factor infertility definitions had an impact on the magnitude of the chlamydia-tubal factor infertility association and resulted in a significant association among non-Blacks., Conclusion: Low population-attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background Chlamydia trachomatis seropositivity among controls, most striking among Black participants, could have obscured an association with tubal factor infertility and resulted in a population-attributable fraction that underestimates the true etiological role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also has an impact on the odds ratio and population-attributable fraction estimates., (Published by Elsevier Inc.)

Existing U.S. guidelines recommend that men with human immunodeficiency virus (HIV) infection should achieve virologic suppression* with effective antiretroviral therapy (ART) before attempting conception (1). Clinical studies have demonstrated that effective ART profoundly reduces the risk for HIV transmission (2-4). This information might be useful for counseling couples planning a pregnancy in which the man has HIV infection and the woman does not (i.e., a mixed HIV-status couple, often referred to as a serodiscordant couple).

Purpose: The purpose of the study was to describe trends in and investigate variables associated with clinical pregnancy and live birth in autologous in vitro fertilization (IVF) cycles among women ≥40 years., Methods: We used autologous IVF cycle data from the National ART Surveillance System (NASS) for women ≥40 years at cycle start. We assessed trends in fresh and frozen cycles (n = 371,536) from 1996 to 2013. We reported perinatal outcomes and determined variables associated with clinical pregnancy and live birth in fresh cycles between 2007 and 2013., Results: From 1996 to 2013, the total number of cycles in women ≥40 years increased from 8672 to 28,883 (p < 0.0001), with frozen cycles almost tripling in the last 8 years. Cycles in women ≥40 years accounted for 16.0% of all cycles in 1996 and 21.0% in 2013 (p < 0.0001). For fresh cycles from 2007 to 2013 (n = 157,890), the cancelation rate was 17.1%. Among cycles resulting in transfer (n = 112,414), the live birth rate was 16.1%. The following were associated with higher live birth rates: multiparity, fewer prior ART cycles, use of standard agonist or antagonist stimulation, lower gonadotropin dose, ovarian hyperstimulation syndrome, more oocytes retrieved, use of pre-implantation genetic screening/diagnosis, transferring more and/or blastocyst stage embryos, and cryopreserving more supernumerary embryos. Of the singleton infants born (n = 14,992), 86.9% were full term and 88.3% normal birth weight., Conclusions: The NASS allows for a comprehensive description of IVF cycles in women ≥40 years in the USA. Although live birth rate is less than 20%, identifying factors associated with IVF success can facilitate treatment option counseling.