Assisted Reproductive Technology Surveillance Research Articles

O-123 Trends and challenges in the practice of ART in China

Abstract China is a large country with a population of over 1.4 billion. In 1988, the first in-vitro fertilization-embryo transfer (IVF-ET) baby was born in Peking University Third Hospital. In the following 3 decades, assisted reproductive technology (ART) has developed rapidly in China, and the availability and accessibility of the ART service have improved markedly. In 2004 totally, only 37 institutions had passed the administrative licensing procedure to carry out ART. While in 2020, 536 institutions obtained the ART license. Since 2016, the total number of ART service cycles(Artificial insemination included)has exceeded 1 million, and the number of babies born has exceeded 300,000, accounting for about 2% of the total live births in China in 2016. At present, assisted reproductive technology has become one of the important medical interventions for the treatment of infertility in China, which has brought good news to infertile couples and their families, and has made great contributions to social harmony and family happiness. Cycles per million population (C/M) in 2009 was 120. In 2020, it has increased to 668, with more and more infertile couples having access to this technique in China. The success rate of assisted reproductive technology remained stable. In 2020, the clinical pregnancy rates (CPR)of conventional IVF and ICSI fresh embryo transfer cycles reached 52.4% and 49.4%, respectively, and the live birth rates were 43.0% and 40.6%, respectively. The clinical pregnancy rate and live birth rate of frozen-thawed embryo cycle were 51.3% and 40.5% per transfer. With the widespread application of embryo freezing technology, the cumulative live birth rate was estimated to reach 49.5% (CLBR estimate) in 2020. The safety monitoring indicators of assisted reproductive technology showed that since 2015, the multiple pregnancy rates of conventional IVF, ICSI and FET have decreased year by year, and have dropped to 22.4%, 21.4% and 17.6% in 2020, respectively. The incidence of moderate-severe ovarian hyper-stimulation syndrome (OHSS) and severe bleeding were also under control, within a reasonable range. Assisted reproductive technology, which involves many medical, social, ethical and legal issues, is a special clinical technology with limit application for medical indication. The Chinese government attaches great importance to the quality and safety management of assisted reproductive technology. A series of management documents such as the Administrative Measures for Human Assisted Reproductive Technology, the Regulations for Human Assisted Reproductive Technology and so forth, have been issued since 2001. Further improvement of key performance indicators (KPIs) correlated with ART quality and safety control is of the top priority and also challenging. In addition, the ART surveillance data in China is still aggregated data, which does not include important indicators such as age stratification, infertile factors or indications and delivery gestational age, maternal and infant outcomes, with some limitations for surveillance. Continuous improvement of data quality, and initiation of cycle-based data collection and security measures of case information are also challenging for the next step.

The role of multiple birth and birth complications in the association between assisted reproductive technology conception and autism diagnosis.

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.

Multiple Imputation of Missing Race/Ethnicity Information in the National Assisted Reproductive Technology Surveillance System.

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.

State insurance mandates and racial and ethnic inequities in assisted reproductive technology utilization

ObjectiveTo 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. DesignNational cross-sectional, ecologic study. SubjectsWe 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). ExposureState mandates were classified by scope of required coverage for fertility services: Comprehensive, Limited, and No Mandate. Main Outcomes MeasuresRace 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. ResultsAcross 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. ConclusionsRacial/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.

O-050 The impact of embryo biopsy on obstetric and neonatal outcomes

Abstract Background Preimplantation genetic testing of embryos (PGT) was performed first in 1990 to prevent the transmission of X-linked disease. Since then, the technique has improved to include couples who are both carriers of the same autosomal recessive disorder, to those with balanced translocations having recurrent pregnancy loss, and to women with advanced maternal age who are at higher risk for having aneuploid embryos. Originally, PGT involved biopsy of the polar body or of one blastomere of a cleavage stage embryo for diagnosis. The contemporary practice of PGT involves the culture of embryos to the blastocyst stage (5-7 days after fertilization), with biopsy of several trophectoderm cells that would become the placenta, transport of biopsy tissue off-site for genetic analysis, and cryopreservation of blastocysts until biopsy results are available. A single euploid embryo is then transferred into the uterus as a frozen embryo transfer. Objective We sought to determine if removal of these cells for preimplantation genetic testing was associated with adverse obstetrical or neonatal outcomes after frozen-thawed single embryo transfer compared to frozen-thawed single embryo transfer without biopsy. Further, we review other studies of contemporary practice of PGT to draw conclusions about the safety of the practice. Study design We linked assisted reproductive technology surveillance data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System to birth certificates and maternal and neonatal hospitalization discharge diagnoses in Massachusetts, USA, from 2014-2017, considering singleton births after frozen-thawed single embryo transfer. We compared outcomes of cycles having embryo biopsy (n = 585) to those having no biopsy (n = 2,191), adjusting for mother’s age, race, education, parity, body mass index, birth year, insurance, and all infertility diagnoses (Sites CK et al, Am J Obstet Gynecol 2021;225:285.e1-7). Results With no biopsy used as the reference, we found no differences between no biopsy and biopsy groups with respect to preeclampsia, pregnancy-induced hypertension, placental disorders (placental abruption, placenta previa, placenta accreta, placenta increta, and placenta percreta), preterm birth, low birthweight, cesarean delivery, gestational diabetes mellitus, or maternal or infant length of stay after delivery. Comparing our outcomes to 4 other studies of contemporary PGT practice of frozen-thawed embryo transfers (Zhang WY Fertil Steril 2019, Li M Am J Obstet Gynecol 2020, Makhijani R Hum Reprod 2021, He H Fertil Steril 2019), our data are consistent with no effect of biopsy on low birth weight, pregnancy-induced hypertension, gestational diabetes, placenta previa, and placenta accreta. A slight decrease in preterm delivery (RR 1.10, CI 1.02-1.18), slight reduction in cesarean section (RR 0.90, CI 0.82-0.99), and increase in intrauterine growth restriction (RR 1.21, CI 1.06-1.38) are reported with biopsy in a systematic review (Hou W, Fertil Steril 2021). The increase in risk for intrauterine growth restriction with biopsy was influenced by one study (Li M Am J Obstet Gynecol 2020). Conclusion Embryo biopsy of trophectoderm cells for PGT in contemporary practice appears to be safe generally with respect to maternal and neonatal outcomes. There is no clear increase in diagnoses related to placentation (preeclampsia, pregnancy-induced hypertension, placental disorders, preterm birth, low birthweight), cesarean delivery, gestational diabetes mellitus, or maternal or infant length of stay after delivery. Further study of a possible increase in intrauterine growth restriction with biopsy is indicated.

P-292 It is feasible to carry out a large-scale multi-national Assisted Reproductive Technology Real World Data (RWD) collection prospectively, encompassing collected patient and treatment cycle information

Abstract Study question Is it feasible to carry out a large-scale multi-national Assisted Reproductive Technology Real World Data (RWD) collection prospectively, encompassing collected patient and treatment cycle information? Summary answer The creation of an international database collecting RWD is feasible. The quality and quantity of the data allow them to be used for research purposes. What is known already Real World Evidence (RWE) may help to answer clinical research questions that are relevant to a broad population of patients. For 40 years, Assisted Reproductive Technology (ART) treatment cycle data have been collected in national registries. The aggregated national data are further collated on an international level. These data are useful for describing secular trends in ART utilization and associated outcomes. However, registries often fall short in providing patient-level and treatment-cycle-level information for data collation and analysis. Furthermore, national registries may restrict access of raw data for open research, for political, infrastructural, or legal reasons. Study design, size, duration In a first phase, the OPERA database (Observational retrospective ProjEct for a Research database for ART procedures) included data from cycles recorded between January 2016 and December 2020 in eighteen clinics, providing a robust sample size for Real World Data analyses. Fondazione per la Ricerca Ospedale di Bergamo (FROM), together with expert clinicians in the ART field, promoted the OPERA project with the financial support from two pharmaceutical companies (Merck KGaA, IBSA SA). Participants/materials, setting, methods The Eighteen clinics located in Germany and Italy joining the OPERA data collection, have proven expertise in ART procedures and use MedITEX® DB. The study protocol was reviewed by the competent Ethic Committees and Data Protection Officers. Among the outcomes collected were the mean number of cycles, the pregnancy and birth rate per Embryo Transfer, and the pregnancy and birth rates as a function of female age. The first extraction was scheduled for December 2022. Main results and the role of chance Around 75,000 ART cycles were collected from the first ten participating centers. Among the around 45,000 cycles that have available fertilization information , 11,553 (25.7%) were the In-Vitro Fertilization treatments (IVF), 31,202 (69.3%) Intracytoplasmic Sperm Injection treatments (ICSI), and 2,282 (5.1%) a combination of the two techniques. Of the adopted stimulation protocols, 38.43% (10,538) of the total were with variable antagonists, 31.27% (8,574) were with a single antagonist, 24.31% (6,665) were with a long agonist, 5.51% (1,511) were with a short agonist, and 0.35% (96) were with fixed antagonists. The average number of oocytes retrieved is 11.28, with a median of 10.0. The average number of 2 Pronuclear Oocytes (2PN) obtained is 3.7, with a median of 3.0. Moreover, the average number of 8 cell embryos at day 3 is 2.0, with a median of 2.0. It was also recorded the rate of unsuccessful cycles with no oocytes retrieved (4.8%). Among the cycles collected, 2.9% of the total were from frozen oocytes. Most of the ET (40.0%) were performed 5 days after the oocyte retrieval. Limitations, reasons for caution Amassing ART cycle information does not compensate for the well-known insufficiencies of primary data quality, of information on confounders and of access to patient level data. Moreover, the technical risk of this project is the potential loss of participant confidentiality, mitigated through a full anonymization. Wider implications of the findings The OPERA project may facilitate the transition of ART surveillance from a national aggregate level to a large-scale individual patient and treatment cycle level. Furthermore, as an evolutionary path, the OPERA project may help building large and longitudinal databases, suitable for appropriate epidemiological research in ART. Trial registration number not applicable

The time has come for harmonized international ART registration

For more than two decades, the European IVF-Monitoring Consortium has collected data on IVF in Europe with the aim of monitoring the quality and safety of assisted reproductive technology (ART) treatments, to ensure the highest performance with the lowest risk for patients and their offspring. Likewise, the Society for Assisted Reproductive Technology in the USA and the Australia/New Zealand Assisted Reproduction Database collect, process and publish data in their regions. The better the legal framework for ART surveillance, the more complete and reliable are the datasets. Worldwide, the landscape of ART regulation is fragmented, and until there is a legal obligation to report ART data in all countries, with an appropriate quality control of the data collected, the reported outcomes should be interpreted with caution. Once uniform and harmonized data are achieved, consensus reports based on collective findings can begin to address key topics such as cycle segmentation and complications. Improved registration systems and datasets allowing optimized surveillance should be developed in collaboration with patient representatives to consider patients’ needs, especially aiming to provide higher transparency around ART services. Support from national and international reproductive medicine societies will also be essential to the future evolution of ART registries.

Assisted reproductive technology cycles involving male factor infertility in the United States, 2017–2018: data from the National Assisted Reproductive Technology Surveillance System

ObjectiveTo describe the prevalence and treatment characteristics of assisted reproductive technology (ART) cycles involving specific male factor infertility diagnoses in the United States.DesignCross-sectional analysis of ART cycles in the National ART Surveillance System (NASS).SettingClinics 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 MeasuresAnalyses 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.

Assisted Reproductive Technology Surveillance - United States, 2018.

Assisted Reproductive Technology Surveillance - United States, 2018.

Assisted Reproductive Technology and Perinatal Mortality: Selected States (2006-2011).

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. Retrospective cohort study using linked ART surveillance and vital records data from Florida, Massachusetts, and Michigan. 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). 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. · 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..

Embryo biopsy and maternal and neonatal outcomes following cryopreserved-thawed single embryo transfer

Contemporary embryo biopsy in the United States involves the removal of several cells from a blastocyst that would become the placenta for preimplantation genetic testing. Embryos are then cryopreserved while patients await biopsy results, with transfers occurring in a subsequent cycle as a single frozen-thawed embryo transfer, if euploid. We sought to determine if removal of these cells for preimplantation genetic testing was associated with adverse obstetrical or neonatal outcomes after frozen-thawed single embryo transfer. We linked assisted reproductive technology surveillance data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System to birth certificates and maternal and neonatal hospitalization discharge diagnoses in Massachusetts from 2014 to 2017, considering only singleton births after frozen-thawed single embryo transfers. We compared outcomes of cycles having embryo biopsy (n=585) to those having no biopsy (n=2191) using chi-square for categorical and binary variables and logistic regression for adjusted odds ratios and 95% confidence intervals, adjusting for mother's age, race, education, parity, body mass index, birth year, insurance, and all infertility diagnoses. Considering no biopsy as the reference, there was no difference between groups with respect to preeclampsia (adjusted odds ratio, 0.82; 95% confidence interval, 0.42-1.61; P=.5685); pregnancy-induced hypertension (adjusted odds ratio, 0.85; 95% confidence interval, 0.46-1.59; P=.6146); placental disorders, including placental abruption, placenta previa, placenta accreta, placenta increta, and placenta percreta (adjusted odds ratio, 1.16; 95% confidence interval, 0.60-2.24; P=.6675); preterm birth (adjusted odds ratio, 1.22; 95% confidence interval 0.73-2.03; P=.4418); low birthweight (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.15; P=.7355); cesarean delivery (adjusted odds ratio, 1.04; 95% confidence interval, 0.79-1.38; P=.7762); or gestational diabetes mellitus (adjusted odds ratio, 0.83; 95% confidence interval, 0.50-1.38; P=.4734). In addition, there was no difference between the groups for prolonged hospital stay for mothers (adjusted odds ratio, 1.23; 95% confidence interval, 0.83-1.80; P=.3014) or for infants (95% confidence interval, 1.29; 95% confidence interval, 0.72-2.29; P=.3923). Embryo biopsy for preimplantation genetic testing does not increase the odds for diagnoses related to placentation (preeclampsia, pregnancy-related hypertension, placental disorders, preterm delivery, or low birthweight), maternal conditions (gestational diabetes mellitus), or maternal or infant length of stay after delivery.

Assisted Reproductive Technology Surveillance - United States, 2017.

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 ( 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 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 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 ( 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.

Number of embryos transferred and diagnosis of preeclampsia

BackgroundMultiple births and first pregnancy are associated with higher preeclampsia risk. It is unknown if the transfer of multiple embryos or first embryo transfer with assisted reproductive technology (ART) is also associated with greater preeclampsia risk.MethodsWe performed a retrospective cohort study of IVF clinics and hospitals in Massachusetts. We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data for 21,188 births, considering resident singleton (12,810) and twin (8378) live-births from autologous or donor eggs from 2005 to 2012. We used log binomial and Poisson regression to calculate adjusted relative risks (aRRs) and 95% confidence intervals (CI) for the association between preeclampsia and predictors of preeclampsia. Outcomes were stratified by singleton and twin birth, donor versus autologous cycles, and use of fresh versus cryopreserved embryos.ResultsConsidering all singleton births, the transfer of multiple embryos increased the risk of preeclampsia [aRR = 1.10 (95% CI: 1.01–1.19)]. Relative risks were greatest for fresh non-donor cycles [aRR = 1.14 (95% CI: 1.03–1.26)]. Vanishing twin and number of prior ART cycles was not associated with preeclampsia among singleton births [aRR = 1.18 (95% CI: 0.91–1.53)], and aRR = 1.01 (95% CI: 0.96–1.05)], respectively. Considering all twin births, the transfer of > 2 embryos increased the risk of preeclampsia [aRR = 1.09 (95% CI: 1.001–1.19)]. Vanishing triplet and number of prior ART cycles were not associated with preeclampsia among twin births [aRR = 0.93 (95% CI: 0.69–1264), and aRR = 0.98 (CI: 0.95–1.02)], respectively.ConclusionsAmong ART births, the transfer of more than 1 embryo for singleton gestations and more than 2 embryos for twin gestations increased the risk for preeclampsia diagnosis.

Perinatal outcomes among young donor oocyte recipients.

Is the use of donor oocytes in women <35years of age associated with an increased risk of adverse perinatal outcomes compared to use of autologous oocytes? 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. Previous studies demonstrated elevated risk of poor perinatal outcomes with donor versus autologous oocytes during ART, primarily among older women. 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. 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. 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). 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. 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. None. N/A.

Trends and correlates of the sex distribution among U.S. assisted reproductive technology births

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. Retrospective cohort study. Fertility treatment centers. 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. Not applicable. 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. 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. 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.

Assisted Reproductive Technology Surveillance - United States, 2016.

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 ( 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 37 years). Among women aged 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 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.

Assisted Reproductive Technology and Stillbirth Risk: Selected States, 2006–2011 [15OP

INTRODUCTION: To examine trends and characteristics of stillbirths among pregnancies (live births and stillbirths) following assisted reproductive technology (ART) and to evaluate the association between ART and risk of stillbirth using linked ART surveillance and vital records from Connecticut, Florida, Massachusetts, and Michigan. METHODS: We examined trends of stillbirth rate (number of stillbirths/1,000 live births and stillbirths) and estimated the adjusted risk ratios (aRR) for associations between ART and stillbirth (adjusting for maternal characteristics, pregnancy history, and pre-pregnancy medical conditions), stratified by plurality and gestational age (&lt;28 and &gt;28 weeks). We also used ICD-10 to examine causes of stillbirth. RESULTS: During 2006–2011, 282 ART stillbirths and 15,540 non-ART stillbirths were identified. ART stillbirth rates were lower than the non-ART stillbirth rates for both singleton (3.1 versus 6.0) and multifetal pregnancies (9.4 versus 18.3). At &lt;28 weeks, the risk of stillbirth among ART-pregnancies was significantly lower than for non-ART pregnancies, aRR 0.38, 95% confidence interval (CI) 0.22–0.65 among singletons and aRR 0.63, 95% CI 0.42–0.94 among multiples. The leading causes of stillbirth were similar for both ART and non-ART pregnancies; maternal conditions (16.6%) (eg, hypertensive disorders, infections, respiratory diseases, periodontal diseases, incompetent cervix, etc), followed by placental abnormalities (9.8%), umbilical cord conditions (9.2%), chorioamnionitis (3.8%), and low birth weight (2.7%). CONCLUSION: ART was associated with a decreased stillbirth risk prior to 28 weeks of gestation. Earlier detection and management of fetal and maternal conditions among ART-conceived pregnancies may explain the lower rates of early fetal death observed in this study.

PD01-01 SURGICALLY ACQUIRED SPERM USE FOR ASSISTED REPRODUCTIVE TECHNOLOGY: TRENDS AND PERINATAL OUTCOMES, UNITED STATES, 2004-2015

You have accessJournal of UrologyInfertility: Therapy I1 Apr 2018PD01-01 SURGICALLY ACQUIRED SPERM USE FOR ASSISTED REPRODUCTIVE TECHNOLOGY: TRENDS AND PERINATAL OUTCOMES, UNITED STATES, 2004-2015 Jennifer Kawwass, Jeani Chang, Sheree Boulet, Ajay Nangia, Akanksha Mehta, and Dmitry Kissin Jennifer KawwassJennifer Kawwass More articles by this author , Jeani ChangJeani Chang More articles by this author , Sheree BouletSheree Boulet More articles by this author , Ajay NangiaAjay Nangia More articles by this author , Akanksha MehtaAkanksha Mehta More articles by this author , and Dmitry KissinDmitry Kissin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.214AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The impact of mode of semen acquisition on reproductive outcomes among couples undergoing treatment with assisted reproductive technology (ART) has not been well characterized. We investigated national trends, and compared pregnancy and perinatal outcomes between surgically acquired and ejaculated sperm use among fresh, non-donor in vitro fertilization cycles in which the male partner has infertility. METHODS This retrospective cohort study used data from U.S. fertility clinics reporting to the National ART Surveillance System (NASS) between 2004 and 2015 (n=369,426 fresh non-donor cycles with male factor infertility). We assessed trends in use of surgically acquired (testicular and epididymal) and ejaculated sperm using the Cochran-Armitage test. To the subset of these ART cycles that used intracytoplasmic sperm injection (ICSI) (n=347,078 cycles), we applied multivariable log binomial regression to compare pregnancy and perinatal outcomes for cycles that used surgically acquired versus ejaculated sperm. Outcomes examined included biochemical pregnancy, intrauterine pregnancy, and live birth (>20 weeks) per embryo transfer cycle; miscarriage (<20 weeks) and singleton live birth per pregnancy; and normal birthweight (>2500g) and full term delivery (>37 weeks) per singleton pregnancy. We performed subgroup analyses for cycles with a sole diagnosis of male factor infertility (no female factors) and for the subset of such cycles in which the female partner was under 35 years old. RESULTS Percentage of cycles in which the male partner had male factor infertility that used surgically acquired sperm increased over the study period (9.8% in 2004 to 11.6% in 2015, p<0.05). The proportion of cycles using testicular sperm also increased significantly over the study period (4.9% in 2004 to 6.5% in 2015, p<0.05); no change was detected for epididymal sperm use. Among fresh, non-donor ICSI cycles for patients with male factor infertility, outcomes were similar between cycles involving epididymal sperm and cycles involving testicular sperm versus those using ejaculated sperm. Results were similar for both subgroup analyses. CONCLUSIONS Surgically acquired sperm use increased over the study period. Mode of semen acquisition does not appear to significantly impact pregnancy and perinatal outcomes among couples undergoing IVF ICSI for treatment of male factor infertility. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e60 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Jennifer Kawwass More articles by this author Jeani Chang More articles by this author Sheree Boulet More articles by this author Ajay Nangia More articles by this author Akanksha Mehta More articles by this author Dmitry Kissin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Assisted Reproductive Technology Surveillance - United States, 2015.

Problem/ConditionSince 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 Covered2015.Description of SystemIn 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).ResultsIn 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.InterpretationMultiple 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 ActionTwins 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.

Embryo cryopreservation and preeclampsia risk

To determine whether assisted reproductive technology (ART) cycles involving cryopreserved-warmed embryos are associated with the development of preeclampsia. Retrospective cohort study. IVF clinics and hospitals. A total of 15,937 births from ART: 9,417 singleton and 6,520 twin. We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data, considering resident singleton and twin births from autologous or donor eggs from 2005-2010. We compared the frequency of preeclampsia diagnosis for cryopreserved-warmed versus fresh ET and used multivariable logistic regression to adjust for confounders. Among pregnancies conceived with autologous eggs resulting in singletons, preeclampsia was greater after cryopreserved-warmed versus fresh ET (7.51% vs. 4.29%, adjusted odds ratio = 2.17 [95% CI 1.67-2.82]). Preeclampsia without and with severe features, preeclampsia with preterm delivery, and chronic hypertension with superimposed preeclampsia were more frequent after cryopreserved-warmed versus fresh ET (3.99% vs. 2.55%; 2.95% vs. 1.41%; 2.76 vs. 1.48%; and 0.95% vs. 0.43%, respectively). Among pregnancies from autologous eggs resulting in twins, the frequency of preeclampsia with severe features (9.26% vs. 5.70%) and preeclampsia with preterm delivery (14.81% vs. 11.74%) was higher after cryopreserved versus fresh transfers. Among donor egg pregnancies, rates of preeclampsia did not differ significantly between cryopreserved-warmed and fresh ET (10.78% vs. 12.13% for singletons and 28.0% vs. 25.15% for twins). Among ART pregnancies conceived using autologous eggs resulting in live births, those involving transfer of cryopreserved-warmed embryos, as compared with fresh ETs, had increased risk for preeclampsia with severe features and preeclampsia with preterm delivery.