Assisted Reproductive Technology Surveillance — United States, 2012.
OBJECTIVE
Since the first U.S. infant conceived with Assisted Reproductive Technology (ART) was born in 1981, both the use of advanced technologies to overcome infertility 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). Because more than one embryo might be transferred during a procedure, women who undergo ART procedures, compared with those who conceive naturally, are more likely 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 Puerto Rico) on ART procedures performed in 2012 and compares infant outcomes that occurred in 2012 (resulting from ART procedures performed in 2011 and 2012) with outcomes for all infants born in the United States in 2012.


METHODS
2012.


METHODS
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, a web-based data collecting system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia [DC], and Puerto Rico).


RESULTS
In 2012, a total of 157,635 ART procedures performed in 456 U.S. fertility clinics were reported to CDC. These procedures resulted in 51,261 live-birth deliveries and 65,151 infants. The largest numbers of ART procedures were performed among residents of six states: California (20,241), New York (19,618), Illinois (10,449), Texas (10,281), Massachusetts (9,754), and New Jersey (8,590). These six states also had the highest number of live-birth deliveries as a result of ART procedures, and together they accounted for 50.1% of all ART procedures performed, 48.3% of all infants born from ART, and 48.3% of all ART multiple live-birth deliveries. Nationally, the total number of ART procedures performed per 1 million women of reproductive age (15-44 years), which is a proxy indicator of ART use, was 2,483. This indicator of ART use exceeded the national ratio in 13 reporting areas (California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Virginia, and DC) and was more than twice the national ratio in three reporting areas (Massachusetts, New Jersey, and DC). Nationally, among ART cycles with patients using fresh embryos from their own eggs, in which at least one embryo was transferred, the average number of embryos transferred increased with the increasing age of the woman (1.9 among women aged <35 years, 2.2 among women aged 35-40 years, and 2.7 among women aged >40 years). The percentage of elective single-embryo transfer (eSET) procedures varied substantially between reporting areas for all ages. Among women aged <35 years, who are typically considered to be good candidates for eSET procedures, the national eSET rate was 15.3% (range: 2.1% in Oklahoma to 60.4% in Delaware). Overall, ART contributed to 1.5% of all infants born in the United States (range: 0.2% in Puerto Rico to 4.7% in Massachusetts) with the highest rates (≥3.0% of all infants born) observed in four reporting areas (Connecticut, Massachusetts, New Jersey, and DC). Infants conceived with ART comprised 19.6% of all multiple-birth infants (range: 5.5% in Maine to 39.3% in Massachusetts), 19.2% of all twin infants (range: 4.4% in Puerto Rico to 39.1% in Massachusetts), and 29.6% of all triplet or higher order infants (range: 0 in West Virginia to 69.7% in Idaho). Among infants conceived with ART, 43.6% were born in multiple-birth deliveries (range: 18.7% in Delaware to 56.0% in Idaho), compared with only 3.4% among all infants born in the general population (range: 2.1% in Puerto Rico to 4.5% in New Jersey). Approximately 41% of ART-conceived infants were twin infants, and 2% were triplet and higher order infants. Nationally, infants conceived with ART comprised 5.7% of all low birthweight (<2,500 grams) infants (range: 0.8% in Puerto Rico to 15.3% in Massachusetts) and 5.8% of all very low birthweight (<1,500 grams) infants (range: 0 in West Virginia to 15.1% in New Jersey). Overall, among ART-conceived infants, 30.2% were low birthweight (range: 18.8% in DC to 45.1% in New Mexico), compared with 8.0% among all infants (range: 5.6% in Alaska to 11.6% in Mississippi and Puerto Rico); 5.5% of ART infants were very low birthweight (range: 0 in West Virginia to 12.9% in Puerto Rico), compared with 1.4% among all infants (range: 0.9% in Alaska and Idaho to 2.1% in Mississippi). ART-conceived infants comprised 4.6% of all preterm (<37 weeks) infants (range: 0.7% in Puerto Rico to 13.4% in Massachusetts) and 5.2% of all very preterm (<32 weeks) infants (range: 1.0% in Puerto Rico to 14.9% in Vermont). Overall, among infants conceived with ART, 34.9% were born preterm (range: 20.8% in Delaware and DC to 49.4% in Puerto Rico), compared with 11.6% among all infants born in the general population (range: 8.7% in Vermont to 17.1% in Mississippi); 6.5% of ART infants were born very preterm (range: 3.3% in Nevada to 14.8% in South Dakota), compared with 1.9% among all infants born in the general population (range: 1.1% in Vermont to 2.9% in Mississippi). The percentage of infants conceived with ART who were low birthweight varied from 9.3% (range: 4.1% in South Carolina to 20.9% in Puerto Rico) among singletons, to 55.2% (range: 41.5% in New Hampshire to 83.3% in South Dakota) among twins, and 95.3% (range: 85.2% in Oklahoma to 100% in several reporting areas) among triplets or higher-order multiples; comparable percentages for all infants were 6.3% (range: 4.5% in Alaska to 10.3% in Puerto Rico), 55.4% (range: 46.0% in Alaska to 69.0% in Puerto Rico), and 91.6% (range: 80.6% in Missouri to 100% in several reporting areas), respectively. The percentage of ART infants who were preterm varied from 13.2% (range: 9.4% in West Virginia to 25.4% in North Dakota) among singletons, to 61.0% (range: 47.8% in DC to 80.0% in Maine and West Virginia) among twins, and 97.7% (range: 92.7% in Massachusetts to 100% in several reporting areas) among triplets or higher-order multiples; comparable percentages for all infants were 9.9% (range: 7.3% in Vermont to 15.8% in Puerto Rico), 56.8% (range: 47.2% in Connecticut to 67.2% in Puerto Rico), and 92.6% (range: 36.4% in Oregon to 96.8% in Ohio), respectively.


CONCLUSIONS
The percentage of infants conceived with ART varied considerably by reporting area. In most reporting areas, multiples from ART comprised a substantial proportion of all twin, triplet, and higher-order infants born, and the rates of low birthweight and preterm infants were disproportionately higher among ART infants than in the birth population overall. Among women aged <35 years, eSET procedures warrant consideration because these patients might have extra embryos available for cryopreservation, which is a good predictor of embryo quality, and might have a more favorable prognosis for a live birth than older patients. However, on average, two embryos were transferred per cycle in ART procedures among women aged <35 years, influencing the overall multiple-birth rates in the United States. Compared with ART singletons, ART twins were approximately four and a half 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 slightly higher rates of preterm delivery and low birthweight than all singleton infants born in the United States. ART use per population unit was geographically varied, with 12 states showing ART use above the national rate. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive statewide-mandated health insurance coverage for ART procedures (e.g., coverage for at least four cycles of in vitro fertilization), two states (Massachusetts and New Jersey) had rates of ART use exceeding twice the national level. This type of mandated insurance has been associated with greater use of ART and might account for some of the difference in per capita ART use observed among states.


CONCLUSIONS
Reducing the number of embryos transferred per ART procedure and increasing use of eSET, when clinically appropriate (typically age <35 years), might reduce multiple births and related adverse consequences of ART. Improved patient education and counseling on the maternal and infant health risks of having twins are needed given that twins account for the majority of ART-conceived multiple births. Although ART contributes to increasing rates of multiple births, it does not explain all of the increases. Other explanations for multiple births not investigated in this report might include age-related factors and the role of non-ART fertility treatments, and warrant further study.
Saswati
S
Sunderam
Dmitry M
DM
Kissin
Sara B
SB
Crawford
Suzanne G
SG
Folger
Denise J
DJ
Jamieson
Lee
L
Warner
Wanda D
WD
Barfield
D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D011159:Population Surveillance; D011247:Pregnancy; D011256:Pregnancy Outcome; D011272:Pregnancy, Multiple / Q000706:statistics & numerical data; D047928:Premature Birth / Q000453:epidemiology; D027724:Reproductive Techniques, Assisted / Q000706:statistics & numerical data*; D014481:United States / Q000453:epidemiology; D055815:Young Adult