"One for Sorrow, Two for Joy?": American embryo transfer guideline recommendations, practices and outcomes for gestational surrogate patients

In January 2016, Melissa Cook, a California gestational surrogate experiencing a multiple birth pregnancy following the in vitro fertilization (IVF) transfer of three embryos comprised of donor eggs and sperm provided by the intended father went to the media when the intended father requested that she undergo a fetal reduction because twins were less expensive to raise than triplets. Much of the legal interest in this case to date has centered on the enforceability of surrogacy contracts. However, the Cook case also raises troubling issues about fertility treatment practices involving gestational surrogates, twin preference, and third-party reproduction medical decision-making. This paper focuses on multipleembryo transfers in the context of U.S. surrogacy arrangements. Offering an original analysis of data obtained from the U.S. national assisted reproduction registry, it examines single- and multiple-embryo transfer trends over an eleven-year period (2003 to 2014). Findings reveal that recommended guidelines were followed in less than 42% of cases in 2014. The paper argues that ensuring equitable medical treatment for all recipients of IVF requires the adoption of treatment guidelines tailored to, and offering protections for, specific patient groups, and that, once in place, guidelines must be robustly implemente

Preconception Care and Treatment with Assisted Reproductive Technologies

Couples with fertility problems seeking treatment with assisted reproductive technologies (ART) such as in vitro fertilization should receive preconception counseling on all factors that are provided when counseling patients without fertility problems. Additional counseling should address success rates and possible risks from ART therapies. Success rates from ART are improving, with the highest live birth rates averaging about 40% per cycle among women less than 35 years old. A woman’s age lowers the chance of achieving a live birth, as do smoking, obesity, and infertility diagnoses such as hydrosalpinx, uterine leiomyoma, or male factor infertility. Singletons conceived with ART may have lower birth weights. Animal studies suggest that genetic imprinting disorders may be induced by certain embryo culture conditions. The major risk from ovarian stimulation is multiple gestation. About one-third of live-birth deliveries from ART have more than one infant, and twins represent 85% of these multiple-birth children. There are more complications in multiple gestation pregnancies, infants are more likely to be born preterm and with other health problems, and families caring for multiples experience more stress. Transferring fewer embryos per cycle reduces the multiple birth rate from ART, but the patient may have to pay for additional cycles of ART because of a lower likelihood of pregnancy

Fertil Steril

ObjectiveTo evaluate assisted reproductive technology (ART) ET practices in the United States and assess the impact of these practices on multiple births, which pose health risks for both mothers and infants.DesignRetrospective cohort analysis using the National ART Surveillance System data.SettingUS fertility centers reporting to the National ART Surveillance System.Patient(s)Noncanceled ART cycles conducted in the United States in 2012.Intervention(s)None.Main Outcome Measure(s)Multiple birth (birth of two or more infants, at least one of whom was live-born).Result(s)Of 134,381 ART transfer cycles performed in 2012, 51,262 resulted in live births, of which 13,563 (26.5%) were multiple births: 13,123 twin and 440 triplet and higher order births. Almost half (46.1%) of these multiple births resulted from the following four cycle types: two fresh blastocyst transfers among favorable or average prognosis patients less than 35 years (1,931 and 1,341 multiple births, respectively), two fresh blastocyst transfers among donor-oocyte recipients (1,532 multiple births), and two frozen/thawed ETs among patients less than 35 years (1,452 multiple births). More than half of triplet or higher order births resulted from the transfer of two embryos (52.5% of births among fresh autologous transfers, 67.2% of births among donor-oocyte recipient transfers, and 42.9% among frozen/thawed autologous transfers).Conclusion(s)A substantial reduction of ART-related multiple (both twin and triplet or higher order) births in the United States could be achieved by single blastocyst transfers among favorable and average prognosis patients less than 35 years of age and donor-oocyte recipients.CC999999/Intramural CDC HHS/United States2016-04-01T00:00:00Z25637480PMC46070497184vault:1467

Assisted reproductive technology surveillance--United States, 2010

Problem/Condition: 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 both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely to deliver multiple-birth infants than those who conceive naturally because more than one embryo might be transferred during a procedure. Multiple births pose substantial risks to both mothers and infants, including pregnancy complications, preterm delivery, and low birthweight infants. This report provides state-specific information on U.S. ART procedures performed in 2010 and compares infant outcomes that occurred in 2010 (resulting from procedures performed in 2009 and 2010) with outcomes for all infants born in the United States in 2010.Reporting Period Covered: 2010.Description of System: In 1996, CDC began collecting data on all ART procedures performed in fertility clinics in the United States and U.S. territories, 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 collecting system developed by CDC.Results: In 2010, a total of 147,260 ART procedures performed in 443 U.S. fertility clinics were reported to CDC. These procedures resulted in 47,090 live-birth deliveries and 61,564 infants. The largest numbers of ART procedures were performed among residents of six states: California (18,524), New York (excluding New York City) (14,212), Illinois (10,110), Massachusetts (9,854), New Jersey (8,783), and Texas (8,754). These six states also had the highest number of live-birth deliveries as a result of ART procedures and together accounted for 48.0% of all ART procedures performed, 45.0% of all infants born from ART, and 45.0% of all multiple live-birth deliveries but only 34.0% of all infants born in the United States and U.S. territories. Nationally, the average number of ART procedures performed per 1 million women of reproductive age (15\u201344 years), which is a proxy indicator of ART use, was 2,331. In 13 states (California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Virginia), this proxy measure was higher than the national rate, and in four states (Connecticut, Massachusetts, New Jersey, and New York) and the District of Columbia, it exceeded twice the national rate. Nationally, among cycles in which at least one embryo was transferred, the average number of embryos transferred increased with increasing age (2.0 among women aged 40 years). Elective single-embryo transfer (eSET) rates decreased with increasing age (10.0% among women aged 40 years). ESET rates also varied substantially between states (range: 0 to 45.0% among women aged 3.5% of all infants born) observed in four states (Connecticut, Massachusetts, New Jersey, and New York), and the District of Columbia. The proportion of ART births was 642.5% in the remaining states and territories. Infants conceived with ART comprised 20.0% of all multiple-birth infants (range: 0 in Guam to 40.5% in Massachusetts), 19.0% of all twin infants (range: 0 in Guam to 40.0% in Massachusetts), and 33.0% of triplet or higher order infants (range: 0 in several states to 60.0% in Arizona). Among infants conceived with ART, 46.0% were born in multiple deliveries (range: 0 in Guam to 55.4% in Utah), compared with only 3.0% of infants among all births in the general population (range: 1.3% in Guam to 4.7% in Connecticut). A substantial proportion (43.4%) of ART-conceived infants were twin infants, and a smaller proportion (3.0%) were triplets and higher order infants. Nationally, infants conceived with ART comprised 5.6% of all low birthweight (1.5 times the national level. This type of mandated insurance has been associated with greater use of ART and might account for the differences observed in other states.Public Health Actions: Reducing the number of embryos transferred per ART procedure among all age groups and promotion of eSET procedures, when clinically appropriate, is needed to reduce multiple births, including twin births, and related adverse consequences of ART. Improved patient education and counseling on the risks of twins might be useful in reducing twin births because twins account for the majority of multiples. Although ART contributes to increasing rates of multiple births, it does not explain all of the increases, and therefore the possible role of non-ART fertility treatments warrants further study.201

Assisted reproductive technology surveillance--United States, 2009

PROBLEM/CONDITION: Since the birth of the first U.S. infant conceived with Assisted Reproductive Technology (ART) in 1981, use of advanced technologies to overcome the problem of infertility has increased steadily, as has the number of fertility clinics providing ART services in the United States. ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely to deliver multiple-birth infants than those who conceive naturally. Multiple births pose substantial risks to both mothers and infants, including pregnancy complications, preterm delivery, and low birthweight infants. This report presents the most recent data on ART use and birth outcomes for U.S. states and territories.REPORTING PERIOD COVERED: 2009.DESCRIPTION OF SYSTEM: In 1996, CDC began collecting data on all ART procedures performed 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]). ART data for 1995-2003 were obtained from the Society of Assisted Reproductive Technology (SART) through its proprietary Clinical Outcomes Reporting System data base (SART CORS). Since 2004, CDC has contracted with Westat, Inc., a statistical survey research organization, to obtain data from fertility clinics in the United States through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC.RESULTS: In 2009, a total of 146,244 ART procedures were reported to CDC. These procedures resulted in 45,870 live-birth deliveries and 60,190 infants. The largest numbers of ART procedures were performed among residents of California (18,405), New York (14,539), Illinois (10,192), Massachusetts (9,845), New Jersey (9,146), and Texas (8,244). Together, these six states reported the highest number of live-birth deliveries as a result of ART and accounted for 48% of all ART procedures initiated, 46% of all infants born from ART, and 45% of all ART multiple-birth deliveries but only 34% of all births in the United States. Nationally, the average number of ART procedures performed per 1 million women of reproductive age (15-44 years), which is a proxy indicator of ART utilization, was 2,361. In four states (Massachusetts, New York, New Jersey, and Connecticut) and the District of Columbia, this proxy measure of ART use exceeded twice the national average. Nationally, the average number of embryos transferred was 2.1 among women aged 40 years (and varied most in this age group from 1.7 in Maine to 3.5 in Missouri). Age-specific elective single-embryo transfer (eSET) rates were approximately 7% among women aged 40 years. The highest rates of eSET were observed among women aged 4%) with high rates also observed in New Jersey, New York, Connecticut, and the District of Columbia (>3% of all infants born). Infants conceived with ART accounted for 20% of all multiple-birth infants (ranging from 4% in Maine to 41% in New York), 19% of all twin births (ranging from 4% in Maine to 42% in New York) and 34% of triplet or higher order births (ranging from 0 in several states to 61.5% in New Jersey). Among infants conceived with ART, 47% were born as multiple-birth infants (ranging from 35% in Delaware to 60.8% in Wyoming), compared with only 3% of infants among the general birth population (ranging from 1% in New York to 5% in Connecticut). Nationally, infants conceived with ART contributed to approximately 6% of all low birthweight (<2,500 grams) infants, ranging from 1.3% in Mississippi to 15% in Massachusetts and to 6% of all very low birthweight (<1,500 grams) infants, ranging from 1% in Alaska to 15% in New Jersey. Overall, among ART-conceived infants, 32% were low birthweight (ranging from 20% in Alaska to 48% in Puerto Rico), compared with 8% among the general birth population (ranging from 5.8% in South Dakota to 12.2% in Mississippi), and 6% of ART infants were very low birthweight (ranging from 1.5% in Alaska to 13% in South Dakota), compared with 1% among the general birth population (ranging from 1% in Alaska to 2% in Mississippi and District of Columbia). Finally, ART-conceived infants accounted for 3.9% of all preterm (<37 weeks; range: 0.5% in Puerto Rico to 11.1% in Massachusetts) and 4.5% of all very preterm births (<32 weeks; range: 0.5% in Puerto Rico to 12% in New York). Overall, among infants conceived with ART, 33.4% were born preterm (ranging from 21.3% in Vermont to 47.1% in Wyoming), compared with 12.2% of the general birth population (ranging from 9.3% in Vermont to 18.0% in Mississippi), and 6.1% of ART infants were very preterm births (ranging from 1.5% in Alaska to 14.7% in South Dakota), compared with 2% among the general birth population (ranging from 1.4% in Alaska, Oregon, Utah, and Washington to 3% in Mississippi).INTERPRETATION: The proportion of births from ART varied considerably by state and territory (ranging from 0.2% to 4.3%) with substantial impact on perinatal outcomes in some states. In most states, multiple births from ART accounted for substantial proportions of twins and triplets and higher order infants, and the rates of low birthweight and preterm births were disproportionately higher among ART infants than in the general birth population. More than one embryo was transferred per procedure in most states and territories for all age groups, influencing the overall multiple birth rates in the United States. ART use was represented disproportionately in the United States, with only 13 states having above-average ART use. High rates of ART utilization were observed in Massachusetts and New Jersey, which have comprehensive statewide-mandated health insurance coverage for ART procedures. Insurance mandates might influence ART utilization and ART-related birth outcomes.PUBLIC HEALTH ACTIONS: Promotion of single-embryo transfer, where feasible, is needed to reduce multiple births and related adverse consequences of ART. Nevertheless, because ART accounts for a relatively small fraction of total births in most states and territories, the overall prevalence of low birthweight and preterm births cannot be explained solely by the use of ART, and therefore non-ART causes of these adverse outcomes must be examined. Monitoring the use of non-ART infertility treatments (e.g., ovulation stimulation medications without ART) in the general population might be useful because these treatments also might be associated with high rates of multiple births and adverse outcomes such as preterm delivery and infants born with low birthweight.201223114281701

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 (37 years). Among 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.Suggested citation for this article: Sunderam S, Kissin DM, Zhang Y, et al. Assisted Reproductive Technology Surveillance \u2014 United States, 2016. MMWR Surveill Summ 2019;68(No. SS-4):1\u201323. DOI: http://dx.doi.org/10.15585/mmwr.ss6804a1ss6804a1-H.pdf2019726

Pregnant, Donor Oocyte Recipient Women Describe Their Lived Experience of Establishing the “Family Lexicon”

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72928/1/j.1552-6909.2007.00128.x.pd

SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH

Many studies estimate that chromosomal mosaicism within the cleavage-stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism has been overestimated due to technical inconsistency rather than the biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques. Thirteen arrested cleavage-stage embryos were studied. Each was biopsied into individual cells (n = 160). The cells from each embryo were randomized into two groups. Those destined for FISH-based aneuploidy screening (n = 75) were fixed, one cell per slide. Cells for SNP microarray-based aneuploidy screening (n = 85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P = 0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (31%) than by FISH (100%) (P = 0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2 ± 0.2) than microarray (1.3 ± 0.2) (P < 0.0001). This is the first prospective, randomized, blinded and paired comparison between microarray and FISH-based aneuploidy screening. SNP microarray-based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH. These results also suggest that FISH technology may overestimate the contribution of mitotic error to the origin of aneuploidy at the cleavage stage of human embryogenesis

Human embryonic mosaicism: single-cell whole-genome sequencing and hEPS cell conversion

Infertility affects nearly 10% of women globally, and many of these women seek Assisted Reproductive Technology (ART) therapies (Mascarenhas, Flaxman, Boerma, Vanderpoel, & Stevens, 2012). Despite the substantial clinical need for improvements in in vitro fertilization, embryo implantation, pregnancy and live birth rates following embryo transfer remain below 50% (CDC Division of Reproductive Health, 2017). This paper aims to review the driving factors behind IVF failures and the new technologies being utilized to improve IVF outcomes, while also outlining novel experimental approaches to address these challenges. While morphology, morphokinetics, time-lapse imaging, and embryo biopsy have all been studied to assess embryo quality, no method has proven to be uniquely effective in improving the outcomes of IVF treatments. Single-cell whole genome sequencing will be evaluated to determine if this alternative approach can provide better information about early embryonic events that may impede embryo viability in vivo. Conversion of human embryonic stem cells (hESCs) into human extended pluripotent stem cells (hEPS) will also be undertaken. Co-culture of hEPS cells with cells derived from human embryo trophectoderm biopsies will support further investigation of early embryonic events at the cellular level, as well as of culture conditions that could facilitate long-term culture of human embryonic trophectoderm cells. Ultimately, the results of both approaches will be used to improve outcomes for patients seeking successful IVF treatment and pregnancy

Genetic Factors in Pregnancy Loss

Pregnancy loss is the most common obstetric complication. Multiple factors have been associated with recurrent or sporadic pregnancy loss, and genetic factors, particularly at earlier gestational ages, are the most important ones. The proportion of miscarriages due to chromosomal factors decreases with increasing gestational age. The most common chromosomal abnormalities in early losses are autosomal trisomies, monosomy X and polyploidy. In later losses, aneuploidies are similar to those found in live newborns (trisomies 21,18 and 13, X monosomy and polysomy of sex chromosomes. In cases of recurrent miscarriage the most common cytogenetic changes are trisomies, polyploidy, monosomy X and unbalanced translocations. Identification of the causes of pregnancy loss facilitates the families’ grief and may indicate if there is the risk of repetition, in order to reduce recurrence. The investigation recommended in each case is far from consensual, and the cost/benefit analysis of diagnostic exams is essential. The determination of the karyotype of the products of conception is indicated in cases of fetal loss and recurrent miscarriage, while the parental karyotypes should be performed only in selected cases. Couples with identified genetic conditions should be counseled about reproductive options, including prenatal or pre-implantation diagnosis. Surveillance of a future pregnancy should be multidisciplinary and adjusted in each case. The cytogenetic factors, due to their high prevalence and complexity, have a fundamental, but still not completely clear, role in pregnancy loss