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.

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, normal birthweight neonates among singleton live births. DESIGN: Retrospective cohort study SUBJECTS: Patients undergoing donor oocyte embryo transfer cycles in the United States reporting to National Assisted Reproductive Technology Surveillance System (NASS) from 2013-2020 EXPOSURE: Original donor oocyte and resultant embryo state (fresh or frozen) MAIN OUTCOME MEASURES: Annual numbers and proportions of total donor oocyte embryo transfer cycles stratified by oocyte and embryo state and single embryo transfer cycles resulting in live birth of term (≥37 weeks gestation), normal birthweight (≥2500g) singletons during 2013-2020. Rates of live birth and term, normal birthweight neonates among singleton live births for 2018-2020 are also reported. Relative risks (RR) examine associations between donor oocyte state and live birth and term, normal birthweight neonates among singleton live births resulting from donor oocyte embryo transfer cycles. RESULTS: From 2013-2020, there were 135,085 donor oocyte embryo transfer cycles, of which the proportions increased for frozen embryos (42.3% to 76.6%), fresh embryos using frozen donor oocytes (19.9% to 68.3%) and single embryo transfer (SET) (36.4% to 85.5%). During 2018-2020, there were 48,679 donor oocyte embryo transfer cycles. Rates of live birth were lower with frozen compared to fresh donor oocytes for both fresh (46.2%, 55.9%; aRR 0.83 [95% 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, normal birthweight neonate were similar for frozen compared to 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: In this national study of donor oocyte embryo transfer cycles, frozen embryo transfers, fresh embryo transfers using frozen oocytes, and SET increased. Although frozen compared to fresh oocytes were associated with a slightly reduced rate of live birth, rates of term, normal birthweight neonates among singleton live births were comparable between donor oocyte states.

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 U.S., 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 U.S.) and the National Assisted Reproductive Technology Surveillance System (1997-2021), respectively. MAIN OUTCOME MEASURES: 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. RESULTS: From 1967-2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1000 live births), then declined to 31.2/1000 live births; the triplet and higher-order birth rate increased 6.7-fold to a 1998 high (1.9/1000 live births), then declined to 0.8/1000 live births. In 2021, the contribution of unassisted conception among women <35 to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women ≥35 (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 <35 and women ≥35 has increased, and the contribution of IVF has decreased. CONCLUSION: 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 ≥35 is a significant contributor to the national plural birth increase.

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: To examine whether the (1) scope of state-mandated insurance coverage for assisted reproductive technology (ART), and (2) proportion of the population eligible for this coverage, are associated with reductions in racial/ethnic inequities in ART utilization. DESIGN: National cross-sectional, ecologic study. SUBJECTS: We employed estimates from the U.S. Census Bureau of all women 20-44 years of age living in the U.S. in 2018. The number of women who initiated an ART cycle during that year that was reported to the U.S. Centers for Disease Control and Prevention (CDC) was obtained from the National ART Surveillance System (NASS). EXPOSURE: State mandates were classified by scope of required coverage for fertility services: Comprehensive, Limited, and No Mandate. MAIN OUTCOMES MEASURES: Race and ethnic-specific ART utilization rates, defined as number of women undergoing ≥1 ART cycles per 10,000 women, were the primary outcome. As state mandates do not apply to all insurance plans, Comprehensive Mandate utilization rates were recalculated using denominators corrected for the estimated proportions of populations eligible for coverage. RESULTS: Across all mandate categories, Non-Hispanic (NH) Asian and NH White populations had the highest ART utilization rates, whereas the lowest rates were among Hispanic, NH Black, and NH Other/Multiple Races populations. As compared to the NH Asian reference group, the NH Black population had smaller inequities in the Comprehensive Mandate group than the No Mandate group (Rate Ratio [RR 0.33 [0.28-0.38] versus RR 0.23 [0.22-0.24]). Using the Comprehensive Mandate group for each race/ethnicity as reference, the NH Black and NH Other/Multiple Races populations had the largest relative differences in utilization between the No Mandate and Comprehensive Mandate groups (RR 0.39 [0.37-0.41] and 0.33 [0.28-0.38], respectively). Within the Comprehensive Mandate group, the disparities in the Hispanic and NH Black populations moved towards the null after correcting for state-mandated insurance eligibility. CONCLUSIONS: Racial/ethnic inequities in ART utilization were reduced in states with comprehensive infertility coverage mandates. Inequities were further attenuated after correcting for mandate eligibility. Mandates alone, however, were not sufficient to eliminate disparities. These findings can inform future strategies aimed at improving ART access under a social justice framework.

BACKGROUND: As the use of in vitro fertilization (IVF) continues to increase in the US, up-to-date models that estimate cumulative live birth rates following multiple oocyte retrievals and embryo transfers (fresh and frozen) are valuable for patients and clinicians weighing treatment options. OBJECTIVE: To develop models that generate predicted probabilities of live birth in individuals considering IVF based on demographic and reproductive characteristics. STUDY DESIGN: Our population-based cohort study utilized data from the National Assisted Reproductive Technology Surveillance System 2016-2018, 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 IVF cycles to develop models that estimate a patient's cumulative live birth rate (CLBR) following all embryo transfers (fresh and frozen) within 12 months after one, two, and three oocyte retrievals in new and returning patients. Among patients using donor oocytes, we estimated CLBR after their first, second, and third embryo transfers. Multinomial logistic regression models adjusted for age, pre-pregnancy body mass index (BMI, imputed for 18% of missing values), parity, gravidity, and infertility diagnoses were used to estimate CLBR. RESULTS: Among new and returning patients undergoing autologous IVF, female age had the strongest association with CLBR. Other factors associated with higher CLBRs were lower BMI and parity or gravidity ≥1 although results were inconsistent. Infertility diagnoses of diminished ovarian reserve, uterine factor, and other reasons were associated with lower CLBR while male factor, tubal factor, ovulatory disorders, and unexplained infertility were associated with higher CLBR. Based on our models, a new patient who is 35 years, with a BMI of 25 kg/m(2), no previous pregnancies, and unexplained infertility diagnoses has a 48%, 69%, and 80% CLBR following first, second, and third oocyte retrieval. CLBRs are 29%, 48%, 62% respectively if the patient had diminished ovarian reserve; and 25%, 41%, and 52% if the patient was 40 years (with unexplained infertility). Very few recipient characteristics were associated with CLBR in donor oocyte patients. CONCLUSIONS: Our models provide estimates of CLBR based on demographic and reproductive characteristics to help inform patients and providers of a woman's likelihood of success following IVF.

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.

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. Patient(s): Frozen embryo transfer cycles. Intervention(s): None. Main Outcome Measure(s): Singleton LGA infant. Result(s): 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/m2; adjusted relative risk [aRR], 1.31; 95% confidence interval [CI], 1.26–1.36; BMI, 30.0–34.9 kg/m2; aRR, 1.48; 95% CI, 1.41–1.55; and BMI, &gt;35 Kg/m2; aRR, 1.68; 95% CI, 1.59–1.77) and ≥1 prior birth vs. none. Low maternal BMI (&lt;18.5 vs. 18.5–24.9 kg/m2) 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). Conclusion(s): 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. © 2022

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.

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. Patient(s): 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. Intervention(s): 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. Result(s): 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. Conclusion(s): 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. 2022

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.

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..

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 19-42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in two U.S. infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios (aOR) with 95% confidence intervals (CI) stratified by race. We then estimated the adjusted chlamydia population attributable fraction (aPAF) 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% (19.3-33.8%) for non-black cases, 15.2% (12.3-18.7%) for non-black controls, 66.0% (95% CI 51.7-77.8%) for black cases, and 71.7% (59.2-81.5%) for black controls. Among 476 non-black women without endometriosis (n=476), Pgp3 was associated with TFI (aOR 2.6 [1.5-4.4]), adjusting for clinic, age, and income; chlamydia TFI aPAF 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 nor 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.

BACKGROUND: Nearly 14% of US women report any lifetime infertility which is associated with healthcare 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 19-42 years in our retrospective cohort from two US infertility clinics were reviewed. We calculated TFI prevalence, IVF initiation prevalence, and prevalence ratios (PR), with 95% confidence intervals for each estimate, overall and by race. RESULTS: Among 660 infertile women, 110 (16.7%; 95% confidence interval [CI] 13.8-19.5%) had TFI which was higher in black compared to 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] versus 52.9% [36/68] for black versus white women); however, fewer black than white women with TFI started IVF (6.7% [1/15] versus 31.0% [9/29]; PR 0.2 [95% CI 0-1.0]), although the difference was not statistically different. CONCLUSIONS: TFI prevalence was two-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.

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.

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.

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.

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.

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 mum (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.

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.

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.

We read with interest the article by Zagadailov et al in the August 2018 issue describing temporal trends in the use of intracytoplasmic sperm injection by geographic region. The article used publically available data on clinic-specific success rates that are collected through the Centers for Disease Control and Prevention's (CDC's) National Assisted Reproductive Technology Surveillance System.1 | | Zagadailov et al report a 100% increase in the mean rate of male factor infertility diagnosis between 2000 and 2014, with a twofold increase occurring between 2010 and 2011 (from 18.4% to 36.8%). We note that a change in the calculation of male factor infertility diagnosis occurred in the Fertility Clinic Success Rates Report data between 2010 and 2011. Before 2011, the CDC reported the percentage of cycles with a diagnosis of male factor infertility absent any other diagnoses, including female infertility diagnoses; therefore, categories of male and female infertility were mutually exclusive. From 2011 onward, the CDC has reported the percentage of cycles with a diagnosis of male factor infertility, irrespective of whether a female factor diagnosis was reported. This change explains the drastic increase in male factor diagnoses identified by Zagadailov et al. When trends in male factor diagnosis are assessed separately for cycles with male factor infertility with or without other diagnoses, compared with cycles with male factor infertility only, there is no evidence of increasing rates of male factor diagnosis (Fig. 1).

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.

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.

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.

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.

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.

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.

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.