Dmitry M. Kissin

Assisted Reproductive Technology Surveillance - United States, 2014.

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). Women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks to both mothers and infants, including obstetric complications, preterm delivery, and low birthweight infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2014 and compares birth outcomes that occurred in 2014 (resulting from ART procedures performed in 2013 and 2014) with outcomes for all infants born in the United States in 2014. Period Covered 2014. Description of System In 1996, 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). 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 2014, a total of 169,568 ART procedures (range: 124 in Wyoming to 21,018 in California) with the intent to transfer at least one embryo were performed in 458 U.S. fertility clinics and reported to CDC. These procedures resulted in 56,028 live-birth deliveries (range: 52 in Wyoming to 7,230 in California) and 68,782 infants born (range: 64 in Wyoming to 8,793 in California). Nationally, the total number of ART procedures performed per million women of reproductive age (15–44 years), a proxy measure of the ART usage rate, was 2,647 (range: 364 in Puerto Rico to 6,726 in Massachusetts). ART use exceeded the national average in 13 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Virginia). Eight reporting areas (Connecticut, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, and New York) had rates of ART use exceeding 1.5 times the national average. 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 (1.7 among women aged <35 years, 1.9 among women aged 35–37 years, and 2.3 among women aged >37 years). Among women aged <35 years, who typically are considered to be good candidates for elective single embryo transfer (eSET) procedures, the national eSET rate was 28.5% (range: 4.3% in Puerto Rico to 67.9% in Delaware). In 2014, ART contributed to 1.6% of all infants born in the United States (range: 0.4% in Puerto Rico to 4.7% in Massachusetts) and 18.3% of all multiple-birth infants (range: 5.5% in Alaska and West Virginia to 37.3% in Hawaii), including 18.0% of all twin infants (range: 5.2% in some states to 36.2% in Hawaii) and 26.4% of all triplets and higher-order infants (range: 0% in some states to 65.2% in Hawaii). Percentages of live births that were multiple-birth deliveries were higher among infants conceived with ART (39.4%; range: 11.5% in Delaware to 55.6% in Puerto Rico) than among all infants born in the total birth population (3.5%; range: 2.2% in Puerto Rico to 4.4% in New Jersey). Approximately 38.0% of ART-conceived infants were twin infants, and 2.0% were triplets and higher-order infants. ART-conceived twins accounted for approximately 95.3% of all ART-conceived infants born in multiple deliveries. Nationally, infants conceived with ART contributed to 5.5% of all low birthweight (<2,500 g) infants (range: 1.2% in West Virginia to 14.2% in Massachusetts). Among ART-conceived infants, 27.8% were low birthweight (range: 10.6% in Delaware to 44.4% in Puerto Rico), compared with 8.0% among all infants (range: 5.9% in Alaska to 11.3% in Mississippi). ART-conceived infants contributed to 4.7% of all preterm (<37 weeks) infants (range: 1.2% in Puerto Rico to 13.4% in Massachusetts). Percentages of preterm births were higher among infants conceived with ART (33.2%; range: 18.9% in the District of Columbia to 45.9% in Puerto Rico) than among all infants born in the total birth population (11.3%; range: 8.5% in California to 16.0% in Mississippi). The percentage of ART-conceived infants who were low birthweight was 8.9% (range: 3.2% in some states to 16.1% in Vermont) among singletons and 55.2% (range: 38.5% in Delaware to 77.8% in Alaska) among twins; the corresponding percentages of low birthweight infants among all infants born were 6.3% for singletons (range: 4.6% in Alaska, North Dakota, and Oregon to 9.5% in Puerto Rico) and 55.2% for twins (range: 46.1% in Alaska to 65.6% in Mississippi). The percentage of ART-conceived infants who were preterm was 13.2% (range: 7.5% in Rhode Island to 23.4% in West Virginia) among singletons and 62.2% (range: 33.3% in some states to 81.4% in Mississippi) among twins; the corresponding percentages of preterm infants among all infants were 9.7% for singletons (range: 1.7% in the District of Columbia to 14.2% in Mississippi) and 56.6% for twins (range: 47.2% in Vermont to 66.9% in Wyoming). Interpretation The percentage of infants conceived with ART varied considerably by reporting area. Multiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born. Low birthweight and preterm infant birth rates were disproportionately higher among ART-conceived infants than among the overall birth population. Although women aged <35 years are typically considered good candidates for eSET, on average two embryos were transferred per ART procedure with women in this group. Compared with ART-conceived singletons, ART-conceived twins were approximately five times more likely to be born preterm and approximately six times more likely to be born with low birthweight. Singleton infants conceived with ART had higher percentages of preterm birth and low birthweight than all singleton infants born in the United States. ART use per population unit was geographically variable, with 13 reporting areas showing ART use higher than the national rate. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive statewide-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 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 Reducing the number of embryos transferred and increasing use of eSET when clinically appropriate could help reduce multiple births and related adverse health consequences. Because twins account for the majority of ART-conceived multiple births, improved provider practices and patient education and counseling on the maternal and infant health risks of having twins are needed. Although ART contributes to high percentages of multiple births, other factors not investigated in this report (e.g., delayed childbearing and use of non-ART fertility treatments) also contribute to multiple births and warrant further study.

Fertility Treatments and Multiple Births in the United States

BACKGROUND The advent of fertility treatments has led to an increase in the rate of multiple births in the United States. However, the trends in and magnitude of the contribution of fertility treatments to the increase are uncertain. METHODS We derived the rates of multiple births after natural conception from data on distributions of all births from 1962 through 1966 (before fertility treatments were available). Publicly available data on births from 1971 through 2011 were used to determine national multiple birth rates, and data on in vitro fertilization (IVF) from 1997 through 2011 were used to estimate the annual proportion of multiple births that were attributable to IVF and to non-IVF fertility treatments, after adjustment for maternal age. Trends in multiple births were examined starting from 1998, the year when clinical practice guidelines for IVF were developed with an aim toward reducing the incidence of multiple births. RESULTS We estimated that by 2011, a total of 36% of twin births and 77% of triplet and higher-order births resulted from conception assisted by fertility treatments. The observed incidence of twin births increased by a factor of 1.9 from 1971 to 2009. The incidence of triplet and higher-order births increased by a factor of 6.7 from 1971 to 1998 and decreased by 29% from 1998 to 2011. This decrease coincided with a 70% reduction in the transfer of three or more embryos during IVF (P<0.001) and a 33% decrease in the proportion of triplet and higher-order births attributable to IVF (P<0.001). CONCLUSIONS Over the past four decades, the increased use of fertility treatments in the United States has been associated with a substantial rise in the rate of multiple births. The rate of triplet and higher-order births has declined over the past decade in the context of a reduction in the transfer of three or more embryos during IVF. (Funded by the Centers for Disease Control and Prevention.).

Adverse event reports after tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines in pregnant women

OBJECTIVE We sought to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) of pregnant women who received tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap). STUDY DESIGN We searched VAERS for reports of pregnant women who received Tdap from Jan. 1, 2005, through June 30, 2010. We conducted a clinical review of reports and available medical records. RESULTS We identified 132 reports of Tdap administered to pregnant women; 55 (42%) described no adverse event (AE). No maternal or infant deaths were reported. The most frequent pregnancy-specific AE was spontaneous abortion in 22 (16.7%) reports. Injection site reactions were the most frequent non-pregnancy-specific AE found in 6 (4.5%) reports. One report with a major congenital anomaly (gastroschisis) was identified. CONCLUSION During a time when Tdap was not routinely recommended in pregnancy, review of reports to VAERS in pregnant women after Tdap did not identify any concerning patterns in maternal, infant, or fetal outcomes.

Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure — United States, 2016

CDC has updated its interim guidance for U.S. health care providers caring for women of reproductive age with possible Zika virus exposure to include recommendations on counseling women and men with possible Zika virus exposure who are interested in conceiving. This guidance is based on limited available data on persistence of Zika virus RNA in blood and semen. Women who have Zika virus disease should wait at least 8 weeks after symptom onset to attempt conception, and men with Zika virus disease should wait at least 6 months after symptom onset to attempt conception. Women and men with possible exposure to Zika virus but without clinical illness consistent with Zika virus disease should wait at least 8 weeks after exposure to attempt conception. Possible exposure to Zika virus is defined as travel to or residence in an area of active Zika virus transmission ( http://www.cdc.gov/zika/geo/active-countries.html), or sex (vaginal intercourse, anal intercourse, or fellatio) without a condom with a man who traveled to or resided in an area of active transmission. Women and men who reside in areas of active Zika virus transmission should talk with their health care provider about attempting conception. This guidance also provides updated recommendations on testing of pregnant women with possible Zika virus exposure. These recommendations will be updated when additional data become available.

Adverse events following administration to pregnant women of influenza A (H1N1) 2009 monovalent vaccine reported to the Vaccine Adverse Event Reporting System

OBJECTIVE The objective of the study was to evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system, in pregnant women who received influenza A (H1N1) 2009 monovalent vaccine to assess for potential vaccine safety problems. STUDY DESIGN We reviewed reports of adverse events (AEs) in pregnant women who received 2009-H1N1 vaccines from Oct. 1, 2009, through Feb. 28, 2010. RESULTS VAERS received 294 reports of AEs in pregnant women who received 2009-H1N1 vaccine: 288 after inactivated and 6 after the live attenuated vaccines. Two maternal deaths were reported. Fifty-nine women (20.1%) were hospitalized. We verified 131 pregnancy-specific outcomes: 95 spontaneous abortions (<20 weeks); 18 stillbirths (≥20 weeks); 7 preterm deliveries (<37 weeks); 3 threatened abortions; 2 preterm labor; 2 preeclampsia; and 1 each of fetal hydronephrosis, fetal tachycardia, intrauterine growth retardation, and cleft lip. CONCLUSION Review of reports to VAERS following H1N1 vaccination in pregnant women did not identify any concerning patterns of maternal or fetal outcomes.

HIV seroprevalence in street youth, St Petersburg, Russia

Background:Reliable data on HIV infection among Russian street youth are unavailable. The purpose of this study was to assess HIV seroprevalence among street youth in St Petersburg and to describe social, sexual, and behavioral characteristics associated with HIV infection. Methods:A cross-sectional assessment conducted during January–May 2006 included city-wide mapping of 41 street youth locations, random selection of 22 sites, rapid HIV testing for all consenting 15–19-year-old male and female street youth at these sites, and an interviewer-administered survey. Adjusted odds ratios (AOR) were calculated using logistic regression, accounting for intracluster homogeneity. Results:Of 313 participants, 117 (37.4%, 95% confidence interval 26.1–50.2%) were HIV infected. Subgroups with the highest seroprevalences included double orphans (64.3%), those with no place to live (68.1%), those previously diagnosed with a sexually transmitted infection (STI; 70.5%), those currently sharing needles (86.4%), and those currently using inhalants (60.5%) or injection drugs (78.6%), including Stadol (82.3%) or heroin (78.1%). Characteristics independently associated with HIV infection included injecting drugs (AOR 23.0), sharing needles (AOR 13.3), being a double or single orphan (AOR 3.3 and 1.8), having no place to live (AOR 2.4), and being diagnosed with a STI (AOR 2.1). Most HIV-infected street youth were sexually active (96.6%), had multiple partners (65.0%), and used condoms inconsistently (80.3%). Discussion:Street youth aged 15–19 years in St Petersburg, Russia, have an extraordinarily high HIV seroprevalence. In street youth who are injection drug users, HIV seroprevalence is the highest ever reported for eastern Europe and is among the highest in the world.

Trends and Outcomes for Donor Oocyte Cycles in the United States, 2000-2010

IMPORTANCE The prevalence of oocyte donation for in vitro fertilization (IVF) has increased in the United States, but little information is available regarding maternal or infant outcomes to improve counseling and clinical decision making. OBJECTIVES To quantify trends in donor oocyte cycles in the United States and to determine predictors of a good perinatal outcome among IVF cycles using fresh (noncryopreserved) embryos derived from donor oocytes. DESIGN, SETTING, AND PARTICIPANTS Analysis of data from the Centers for Disease Control and Preventions National ART Surveillance System, to which fertility centers are mandated to report and which includes data on more than 95% of all IVF cycles performed in the United States. Data from 2000 to 2010 described trends. Data from 2010 determined predictors. MAIN OUTCOMES AND MEASURES Good perinatal outcome, defined as a singleton live-born infant delivered at 37 weeks or later and weighing 2500 g or more. RESULTS From 2000 to 2010, data from 443 clinics (93% of all US fertility centers) were included. The annual number of donor oocyte cycles significantly increased, from 10,801 to 18,306. Among all donor oocyte cycles, an increasing trend was observed from 2000 to 2010 in the proportion of cycles using frozen (vs fresh) embryos (26.7% [95% CI, 25.8%-27.5%] to 40.3% [95% CI, 39.6%-41.1%]) and elective single-embryo transfers (vs transfer of multiple embryos) (0.8% [95% CI, 0.7%-1.0%] to 14.5% [95% CI, 14.0%-15.1%]). Good perinatal outcomes increased from 18.5% (95% CI, 17.7%-19.3%) to 24.4% (95% CI, 23.8%-25.1%) (P < .001 for all listed trends). Mean donor and recipient ages remained stable at 28 (SD, 2.8) years and 41 (SD, 5.3) years, respectively. In 2010, 396 clinics contributed data. For donor oocyte cycles using fresh embryos (n = 9865), 27.5% (95% CI, 26.6%-28.4%) resulted in good perinatal outcome. Transfer of an embryo at day 5 (adjusted odds ratio [OR], 1.17 [95% CI, 1.04-1.32]) and elective single-embryo transfers (adjusted OR, 2.32 [95% CI, 1.92-2.80]) were positively associated with good perinatal outcome; tubal (adjusted OR, 0.72 [95% CI, 0.60-0.86]) or uterine (adjusted OR, 0.74 [95% CI, 0.58-0.94]) factor infertility and non-Hispanic black recipient race/ethnicity (adjusted OR, 0.48 [95% CI, 0.35-0.67]) were associated with decreased odds of good outcome. Recipient age was not associated with likelihood of good perinatal outcome. CONCLUSIONS AND RELEVANCE In the United States from 2000 to 2010, there was an increase in number of donor oocyte cycles, accompanied by an increase in good outcomes. Further studies are needed to understand the mechanisms underlying the factors associated with less successful outcomes.

Attitudes and practices of obstetrician-gynecologists regarding influenza vaccination in pregnancy.

OBJECTIVE: To assess knowledge, attitudes, and practices of obstetrician–gynecologists (ob-gyns) regarding vaccination of pregnant women during the 2009 H1N1 pandemic. METHODS: From February to July 2010, a self-administered mail survey was conducted among a random sample of American College of Obstetricians and Gynecologists (the College) members involved in obstetric care. To assess predictors of routinely offering influenza vaccination, adjusted prevalence ratios and 95% confidence intervals (CIs) were calculated from survey data. RESULTS: Among 3,096 survey recipients, 1,310 (42.3%) responded to the survey, of whom 873 were eligible for participation. The majority of ob-gyns reported routinely offering both seasonal and 2009 H1N1 influenza vaccination to their pregnant patients (77.6% and 85.6%, respectively) during the 2009–2010 season; 21.1% and 13.3% referred patients to other specialists. Reported reasons for not offering vaccination included inadequate reimbursement, storage limitations, or belief that vaccine should be administered by another provider. Seasonal and 2009 H1N1 influenza vaccination during the first trimester was not recommended by 10.6% and 9.6% of ob-gyns, respectively. Predictors of routinely offering 2009 H1N1 influenza vaccine included: considering primary care and preventive medicine a very important part of practice (adjusted prevalence ratio 1.2, CI 1.01–1.4); observing serious conditions attributed to influenza-like illness (adjusted prevalence ratio 1.1, CI 1.02–1.1); personally receiving 2009 H1N1 influenza vaccination (adjusted prevalence ratio 1.2, CI 1.1–1.4); and practicing in multispecialty group (adjusted prevalence ratio 1.1, CI 1.1–1.2). Physicians in solo practice were less likely to routinely offer influenza vaccine (adjusted prevalence ratio 0.8, CI 0.7–0.9). CONCLUSION: Although most ob-gyns routinely offered influenza vaccination to pregnant patients, vaccination coverage rates may be improved by addressing logistic and financial challenges of vaccine providers. LEVEL OF EVIDENCE: III

Risk of Ectopic Pregnancy Associated With Assisted Reproductive Technology in the United States, 2001–2011

OBJECTIVE: To assess national trends in ectopic pregnancy incidence among assisted reproductive technology users and identify risk factors associated with ectopic pregnancy. METHODS: We identified 553,577 pregnancies reported to the National ART Surveillance System between 2001 and 2011. Of those, 9,480 were ectopic, of which 485 were heterotopic. As a result of small numbers, ectopic and heterotopic pregnancies were combined for analysis. We assessed temporal trends in annual ectopic pregnancy rates using Poisson regression. We used log-binomial regression models with generalized estimating equations for correlated outcomes within clinics to calculate unadjusted and adjusted risk ratios for the association between ectopic pregnancy and selected patient characteristics and treatment factors. RESULTS: The rate of ectopic pregnancy declined from 2.0% (n=735, 95% confidence interval [CI] 1.9–2.2) in 2001 to 1.6% (n=968, 95% CI 1.5–1.7) in 2011 (P for trend <.001). The ectopic pregnancy rate ranged from 2.0% (n=7,469, 95% CI 1.9–2.0) for fresh, nondonor cycles to 1.0% (n=641, 95% CI 0.9–1.1) for fresh, donor cycles. Among fresh, nondonor cycles, the rate of ectopic pregnancy was 1.6% (95% CI 1.4–1.7) when one embryo was transferred compared with 1.7% (95% CI 1.7–1.8), 2.2% (95% CI 2.1–2.3), and 2.5% (95% CI 2.4–2.6) when two, three, or four or more embryos were transferred, respectively (adjusted risk ratios 1.11, 95% CI 0.94–0.30; 1.33, 95% CI 1.12–1.56; and 1.49, 95% CI 1.25–1.78). CONCLUSION: Ectopic pregnancy incidence after assisted reproductive technology has decreased over time, but factors such as multiple embryo transfer increase the risk of ectopic pregnancy. LEVEL OF EVIDENCE: II

HIV seroprevalence among orphaned and homeless youth: no place like home.

Objectives:We evaluated the combined influences of orphaned status and homelessness on HIV seroprevalence and risk among street-involved Ukrainian youth in 2008. Design:Systematic, multicity, community-based, cross-sectional assessment. Methods:Time-location sampling was used to identify eligible youth aged 15–24 after city-wide mapping of 91 sites where street-involved youth gathered in Odessa, Kiev, and Donetsk. Universal sampling identified 961 youth in 74 randomly selected sites; 97% consented. Youth reporting one or both parents dead were classified as orphaned; those without a stable residence or sleeping outside their residence at least two nights per week were classified as homeless. Trained staff provided HIV counseling and rapid testing via mobile vans. Adjusted odds ratios (AORs) were calculated using logistic regression, accounting for intracluster homogeneity. Results:We found 32% (300 of 929) were both orphaned and homeless; 48% either (but not both) homeless [37% (343 of 929)] or orphaned [11% (104 of 929)]; and [20% (182 of 929)] neither orphaned nor homeless. HIV seroprevalences were 7% for neither orphaned/homeless; 16 and 17%, respectively, for either orphaned/homeless; 28% for both orphaned/homeless (P for trend <0.0001). AORs for HIV infection were 1 for neither; 2.3 and 2.4 for either homeless [95% confidence interval (CI) 1.7–2.9] or orphaned (CI 1.8–3.3); 3.3 for both orphaned/homeless (CI 2.3–4.4). Ever-use of injection drugs increased from 15 to 32 to 48% for those who neither, either, or both orphaned and homeless, respectively (P for trend <0.0001). Conclusions:One of four youths who were both homeless and orphaned was HIV-infected; these youths were significantly more likely to be HIV infected and to report injection drug use than those with adequate housing and living parents.