Saswati Sunderam

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.

Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010

IMPORTANCE Use of assisted reproductive technology (ART) has been associated with increased risks for birth defects. Variations in birth defect risks according to type of ART procedure have been noted, but findings are inconsistent. OBJECTIVES To examine the prevalence of birth defects among liveborn infants conceived with and without ART and to evaluate risks associated with certain ART procedures among ART-conceived infants. DESIGN, SETTING, AND PARTICIPANTS Used linked ART surveillance, birth certificates, and birth defects registry data for 3 states (Florida, Massachusetts, and Michigan). Methods for ascertaining birth defect cases varied by state. Resident live births during 2000 to 2010 were included, and the analysis was conducted between Feburary 2015 and August 2015. EXPOSURES Use of ART among all live births and use of certain ART procedures among ART births. MAIN OUTCOME AND MEASURES Prevalence of selected chromosomal and nonchromosomal birth defects that are usually diagnosed at or immediately after birth. RESULTS Of the 4 618 076 liveborn infants between 2000 and 2010, 64 861 (1.4%) were conceived using ART. Overall, the prevalence of 1 or more of the selected nonchromosomal defects was 58.59 per 10 000 for ART infants (n = 389) vs 47.50 per 10 000 for non-ART infants (n = 22 036). The association remained significant after adjusting for maternal characteristics and year of birth (adjusted risk ratio [aRR], 1.28; 95% CI, 1.15-1.42). Similar differences were observed for singleton ART births vs their non-ART counterparts (63.69 per 10 000 [n = 218] vs 47.17 per 10 000 [n = 21 251]; aRR, 1.38; 95% CI, 1.21-1.59). Among multiple births, the prevalence of rectal and large intestinal atresia/stenosis was higher for ART births compared with non-ART births (aRR, 2.39; 95% CI, 1.38-4.12). Among ART births conceived after fresh embryo transfer, infants born to mothers with ovulation disorders had a higher prevalence of nonchromosomal birth defects (aRR, 1.53; 95% CI, 1.13-2.06) than those born to mothers without the diagnosis, and use of assisted hatching was associated with birth defects among singleton births (aRR, 1.55; 95% CI, 1.10-2.19). Multiplicity-adjusted P values for these associations were greater than .05. CONCLUSIONS AND RELEVANCE Infants conceived after ART had a higher prevalence of certain birth defects. Assisted hatching and diagnosis of ovulation disorder were marginally associated with increased risks for nonchromosomal birth defects; however, these associations may be caused by other underlying factors.

Safe Conception for HIV Discordant Couples through Sperm-Washing: Experience and Perceptions of Patients in Milan, Italy

Our research explored the reproductive desires of HIV-negative women and their HIV-positive partners who underwent assisted conception based on sperm-washing and intrauterine insemination in Italy. Twenty-two semi-structured interviews were conducted with former patients (6 women, 5 men and 11 couples). Desire for children, perceived risk from treatment and acceptability of the insemination technique were some of the issues explored. Participants had the treatment for a mean duration of 3.5 years, with a mean number of cycles of 5.3. They were highly motivated to conceive a biological child to bring purpose to their lives, and strongly desired options to conceive safely. Most rejected spontaneous conception. Those who successfully conceived reported a positive impact on their quality of life, fulfilling their desire to be parents and restoring their sense of “normalcy”. Participants strongly supported extending assisted conception services to all HIV negative women living with HIV positive partners who wished to become pregnant and felt that withholding such treatment was not ethically justified. They perceived assisted conception services to be a safe and effective alternative to spontaneous conception, and felt that society has a moral obligation to provide such services. Résumé Nous avons étudié les souhaits de femmes séronégatives au VIH et de leurs partenaires séropositifs qui s’étaient soumis à une procréation assistée avec lavage du sperme et insémination intra-utérine en Italie. Vingt-deux entretiens semi-structurés ont été menés avec d’anciens patients (6 femmes, 5 hommes et 11 couples). Le désir d’enfant, la perception du traitement et l’acceptabilité de la technique d’insémination figuraient parmi les questions abordées. Les participants ont suivi le traitement en moyenne pendant 3,5 ans, avec un nombre moyen de 5,3 cycles. Ils étaient très motivés pour concevoir un enfant biologique afin de donner un sens à leur vie, et demandaient des options pour procréer en toute sécurité. La plupart rejetaient la conception spontanée. Ceux qui ont conçu un enfant ont indiqué que cela avait eu des retombées positives sur leur qualité de vie, en satisfaisant leur désir d’être parents et leur redonnant un sentiment de « normalité ». Les participants soutenaient énergiquement l’élargissement des services de procréation assistée à toutes les femmes séronégatives vivant avec des partenaires séropositifs et qui souhaitaient avoir un enfant, et ils pensaient qu’il était moralement injustifié de refuser ce traitement. Ils estimaient aussi que la procréation assistée était une option sûre et efficace à la conception spontanée, et jugeaient que la société avait l’obligation morale de fournir de tels services. Resumen Nuestra investigación exploró los deseos reproductivos de mujeres VIH-negativas y sus parejas VIH-positivas, que pasaron por la concepción asistida basada en el lavado de espermatozoides e inseminación intrauterina, en Italia. Se realizaron 22 entrevistas semiestructuradas con antiguos pacientes (6 mujeres, 5 hombres y 11 parejas). Algunos de los aspectos explorados fueron: el deseo de tener hijos, el riesgo percibido del tratamiento y la aceptación de la técnica de inseminación. Los participantes recibieron el tratamiento por una duración media de 3.5 años, con un número medio de ciclos de 5.3. Estaban muy motivados a concebir un hijo biológico para darle sentido a sus vidas, y muy deseosos de tener opciones para concebir de manera segura. La mayoría rechazó la concepción espontánea. Aquéllos que lograron concebir informaron un impacto positivo en calidad de vida, realizar su deseo de ser padres y restaurar su sentido de “normalidad”. Los participantes apoyaron enfáticamente extender los servicios de concepción asistida a todas las mujeres VIH-negativas que viven con parejas VIH-positivas, que desean quedar embarazadas y opinan que la denegación de dicho tratamiento no se justifica éticamente. Percibieron los servicios de concepción asistida como una alternativa segura y eficaz a la concepción espontánea, y afirmaron que la sociedad tiene la obligación moral de proporcionar dichos servicios.

Linking Birth and Infant Death Records With Assisted Reproductive Technology Data: Massachusetts, 1997–1998

Objectives: To link data from the US assisted reproductive technology (ART) registry with the Massachusetts birth–infant death file to create a comprehensive dataset on the circumstances surrounding conception and maternal and infant outcomes for a population of ART-conceived infants. Methods: The authors sought to link data for 3704 ART-conceived live-born infants from 2703 deliveries in 1997–1998 involving Massachusetts resident mothers who gave birth in Massachusetts, Rhode Island, New Hampshire, or Connecticut to their corresponding Massachusetts birth record using a two-stage algorithm. Maternal and infant dates of birth served as the primary linkage variables. Maternal names for a subset of the ART-conceived infants were obtained and used in the second stage of the algorithm to confirm a sample of records that matched in Stage I, to resolve duplicate matches, and to link unmatched records. Results: In Stage I, 78% of ART deliveries matched with only one Massachusetts record, 2% matched with two records, and 20% remained unmatched. Overall, the complete algorithm using maternal name data for a portion of records yielded an 89% linkage rate. Nearly all of the records that matched during Stage I that were evaluated with maternal name data in Stage II were confirmed as correctly linked. Conclusions: This project confirms that high-yield data linkage can be achieved in the absence of specific identifiers (e.g., name and social security number). Nonetheless, additional matches were achieved when name data were obtained. This linkage creates the first population-based file in the US capturing detailed information on ART births.

Embryo transfer practices and perinatal outcomes by insurance mandate status

OBJECTIVE To use linked assisted reproductive technology (ART) surveillance and birth certificate data to compare ET practices and perinatal outcomes for a state with a comprehensive mandate requiring coverage of IVF services versus states without a mandate. DESIGN Retrospective cohort study. SETTING Not applicable. PATIENT(S) Live-birth deliveries ascertained from linked 2007-2009 National ART Surveillance System and birth certificate data for a state with an insurance mandate (Massachusetts) and two states without a mandate (Florida and Michigan). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Number of embryos transferred, multiple births, low birth weight, preterm delivery. RESULT(S) Of the 230,038 deliveries in the mandate state and 1,026,804 deliveries in the nonmandate states, 6,651 (2.9%) and 8,417 (0.8%), respectively, were conceived by ART. Transfer of three or more embryos was more common in nonmandate states, although the effect was attenuated for women 35 years or older (33.6% vs. 39.7%; adjusted relative risk [RR], 1.46; 95% confidence interval [CI], 1.17-1.81) versus women younger than 35 (7.0% vs. 26.9%; adjusted RR, 4.18; 95% CI, 2.74-6.36). Lack of an insurance mandate was positively associated with triplet/higher order deliveries (1.0% vs. 2.3%; adjusted RR, 2.44; 95% CI, 1.81-3.28), preterm delivery (22.6% vs. 30.7%; adjusted RR, 1.31; 95% CI, 1.20-1.42), and low birth weight (22.3% vs. 29.5%; adjusted RR, 1.28; 95% CI, 1.17-1.40). CONCLUSION(S) Compared with nonmandate states, the mandate state had higher overall rates of ART use. Among ART births, lack of an infertility insurance mandate was associated with increased risk for adverse perinatal outcomes.

Strategies for Preventing HIV Infection Among HIV-Uninfected Women Attempting Conception with HIV-Infected Men — United States

By the end of 2014, a total of 955,081 persons in the United States (299.5 per 100,000 population) had received a diagnosis of human immunodeficiency virus type 1 (HIV-1) infection (1). The annual estimated number of HIV infections and incidence rate in the United States decreased from 2010 to 2014, and the survival rate has increased over time (1). Effective highly active antiretroviral therapy (HAART) is helping persons with HIV to live longer, healthier lives. Many of these persons, including an unknown percentage in discordant relationships (i.e., one partner is HIV-infected, and the other is HIV-uninfected), might wish to have their own biologic children. When the female partner is HIV-infected and the male partner is not, a discordant couple can undergo autologous sperm intrauterine inseminations to achieve conception without placing the man at risk for infection. However, for HIV-discordant couples in which the man is HIV-infected and the woman is not, strategies to minimize the risk for sexual transmission are needed. In 1988, CDC recommended against insemination with semen from HIV-infected men (2). Since 1988, new information has emerged regarding prevention of HIV transmission in HIV-discordant couples. This report reviews laboratory and epidemiologic information regarding the prevention of HIV transmission for HIV-discordant couples, in which the male is HIV-infected and the female is HIV-uninfected, who would like to attempt conception.

Assisted Reproductive Technology Surveillance — United States, 2015

Problem/Condition Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g) infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART procedures performed in 2014 and 2015) with outcomes for all infants born in the United States in 2015. Period Covered 2015. Description of System In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102–493 [October 24, 1992]). Data are collected through the National ART Surveillance System, a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). Results In 2015, a total of 182,111 ART procedures (range: 135 in Alaska to 23,198 in California) with the intent to transfer at least one embryo were performed in 464 U.S. fertility clinics and reported to CDC. These procedures resulted in 59,334 live-birth deliveries (range: 55 in Wyoming to 7,802 in California) and 71,152 infants born (range: 68 in Wyoming to 9,176 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15–44 years), a proxy measure of the ART utilization rate, was 2,832. ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Virginia). Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.6 among women aged <35 years, 1.8 among women aged 35–37 years, and 2.3 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 34.7% (range: 11.3% in Puerto Rico to 88.1% in Delaware). In 2015, ART contributed to 1.7% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.5% in Massachusetts). ART also contributed to 17.0% of all multiple-birth infants, 16.8% of all twin infants, and 22.2% of all triplets and higher-order infants. The percentage of multiple-birth infants was higher among infants conceived with ART (35.3%) than among all infants born in the total birth population (3.4%). Approximately 34.0% of ART-conceived infants were twins and 1.0% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.1% of all low birthweight infants. Among ART-conceived infants, 25.5% had low birthweight, compared with 8.1% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (31.2%) than among all infants born in the total birth population (9.7%). Among singletons, the percentage of ART-conceived infants who had low birthweight was 8.7% compared with 6.4% among all infants born. The percentage of ART-conceived infants who were born preterm was 13.4% among singletons compared with 7.9% among all infants. Interpretation Multiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. For women aged <35 years, who are typically considered good candidates for eSET, the national average of 1.6 embryos was transferred per ART procedure. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four cycles of IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use exceeding 1.5 times the national rate. This type of mandated insurance coverage has been associated with greater use of ART and likely accounts for some of the difference in per capita ART use observed among states. Public Health Action Twins account for the majority of ART-conceived multiple births. Reducing the number of embryos transferred and increasing use of eSET when clinically appropriate could help reduce multiple births and related adverse health consequences for both mothers and infants. State-based surveillance of ART might be useful for monitoring and evaluating maternal and infant health outcomes of ART in states with high ART use.

Affordability of Fertility Treatments and Multiple Births in the United States

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