Donor Programs in Human Reproduction: Reviewing the Debate on Anonymity and Openness

To assess the effect on the human sex ratio at birth by assisted reproductive technology (ART) procedures. Retrospective population-based study. Fertility clinics in Australia and New Zealand. The study included 13,368 babies by 13,165 women who had a single embryo transfer (SET) between 2002 and 2006. Logistic regression was used to model the effect on the sex ratio at birth of ART characteristics [in vitro fertilisation (IVF) or intracytoplasmic sperm insemination (ICSI) SET, cleavage-stage or blastocyst SET, and fresh or thawed SET] and biological characteristics (woman's and partner's age and cause of infertility). Proportion of male births. The crude sex ratio at birth was 51.3%. Individual ART procedures had a significant effect on the sex ratio at birth. More males were born following IVF SET (53.0%) than ICSI SET (50.0%), and following blastocyst SET (54.1%) than cleavage-stage SET (49.9%). For a specific ART regimen, IVF blastocyst SET produced more males (56.1%) and ICSI cleavage-stage SET produced fewer males (48.7%). The change in the sex ratio at birth of SET babies is associated with the ART regimen. The mechanism of these effects remains unclear. Fertility clinics and patients should be aware of the bias in the sex ratio at birth when using ART procedures.

Is the risk of hypertensive disorders in pregnancies conceived following specific assisted reproductive technology (ART) procedures different from the risk in spontaneously conceived (SC) pregnancies? ART pregnancies had a higher risk of hypertensive disorders, in particular following cryopreservation, with the highest risk seen in twin pregnancies following frozen-thawed cycles. The risk of hypertensive disorders is higher in ART pregnancies than in SC pregnancies. The increased risk may be partly explained by multiple pregnancies and underlying infertility, but a contribution from specific ART procedures has not been excluded. Population-based cohort study, including sibling design with nationwide data from health registers in Sweden, Denmark and Norway. All registered ART pregnancies and a sample of SC pregnancies with gestational age ≥22 weeks from 1988 to 2007 were included. ART singleton pregnancies (n = 47 088) were compared with SC singleton pregnancies (n = 268 599), matched on parity and birth year. ART twin pregnancies (n = 10 918) were compared with SC twin pregnancies (46 674). We used logistic regression to estimate adjusted odds ratios and risk differences for hypertensive disorders in pregnancies following IVF, ICSI and fresh or frozen-thawed cycles. We also compared fresh and frozen-thawed cycles within mothers who had conceived following both procedures using conditional logistic regression (sibling analysis). Hypertensive disorders were reported in 5.9% of ART singleton and 12.6% of ART twin pregnancies. Comparing singleton pregnancies, the risk of hypertensive disorders was higher after all ART procedures. The highest risk in singleton pregnancies was seen after frozen-thawed cycles [risk 7.0%, risk difference 1.8%, 95% confidence interval (CI) 1.2-2.8]. Comparing twin pregnancies, the risk was higher after frozen-thawed cycles (risk 19.6%, risk difference 5.1%, 95% CI 3.0-7.1), but not after fresh cycles. In siblings, the risk was higher after frozen-thawed cycles compared with fresh cycles within the same mother (odds ratio 2.63, 95% CI 1.73-3.99). There were no clear differences in risk for IVF and ICSI. The number of ART siblings in the study was limited. Residual confounding cannot be excluded. In addition, we did not have information on all SC pregnancies in each woman's history, and could therefore not compare risk in ART versus SC pregnancies in the same mother. Pregnancies following frozen-thawed cycles have a higher risk of hypertensive disorders, also when compared with fresh cycle pregnancies by the same mother. The safety aspects in frozen-thawed cycles merit further attention. Funding was received from the European Society for Human Reproduction and Embryology, the University of Copenhagen, the Danish Agency for Science, Technology and Innovation, the Nordic Federation of Societies of Obstetrics and Gynecology and the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. None of the authors has any competing interests to declare.

Towards the global coverage of a unified registry of IVF outcomes.

This study examines the influence of assisted reproductive technology (ART) procedures on maternal and placental fatty acid status and their correlation with placental weight and birth outcome. Pregnant women were recruited at Gupte Hospital, Pune, India and grouped as those with natural pregnancy (non-ART) (n = 93) and those who underwent ART procedures (ART) (n = 64). Fatty acids were analyzed using gas chromatography. Group comparisons were performed using an independent t-test. Partial correlation test controlling for maternal age, body mass index, gestational age and baby sex was used for association of fatty acid status with placental weight and birth outcome. Maternal and placental total omega-3 fatty acids were significantly lower (P = 0.023 and P = 0.050 respectively) and the omega-6: omega-3 fatty acid ratio was higher (P = 0.041 and P = 0.050, respectively) in ART pregnancies in comparison to natural pregnancies. The ART group, further categorized as invitro fertilization (IVF) and intrauterine insemination (IUI), showed lower maternal dihomo-gamma-linolenic acid (DGLA) (P = 0.033) and placental docosapentaenoic acid (DPA) levels only in the IVF group (0.011) and not in the IUI group in comparison to the non-ART group. Placental arachidonic acid (AA), omega-6 and total polyunsaturated fatty acid (PUFA) levels were negatively associated, whereas placental monounsaturated fatty acid (MUFA) levels were positively associated with placental weight (P < 0.001 for others and P = 0.008 for MUFA) and birth weight (P < 0.001, P = 0.001, P = 0.004, P = 0.005, respectively). ART procedures, particularly IVF, are associated with disturbed maternal and placental fatty acid metabolism that influences placental weight and, thereby, birth outcome.

Adverse obstetric and perinatal outcomes of singleton pregnancies may be related to maternal factors associated with infertility rather than the type of assisted reproductive technology procedure used

Genomic imprinting refers to preferential allele-specific gene expression. DNA methylation-based molecular mechanisms regulate establishment and maintenance of parental imprints during early embryo development and gametogenesis. Because of the coincident timing, a potential association between assisted reproductive technology (ART) procedures and imprinting defects has been investigated in various studies. In this review, we provide an overview of genomic imprinting and present a summary of the relevant clinical data. ART procedures affect DNA methylation pattern, parental imprinting status, and imprinted gene expression in the mouse embryo. In humans, several case series suggested an association between ART and imprinting disorders, with a three-fold to six-fold higher prevalence of ART use among children born with Beckwith-Wiedemann syndrome compared to the general population. However, more recent studies failed to support these findings and could not demonstrate an association between imprinting disorders and ARTs, independent of subfertility. ART procedures may affect methylation status of imprinted regions in the DNA, leading to imprinting disorders. Although the low prevalence of imprinting disorders makes it challenging to perform conclusive clinical trials, further studies in large registries are required to determine the real impact of ARTs on their occurrence.

The article presents a literature review over the last few years devoted to the health status and development peculiarities of children born using assisted reproductive technologies (ART) procedures. The statistics shows an explosive increase in the frequency of ART application as a fertility treatment method. The presented data analysis reflects the perinatal outcomes after ART in children, the frequency of congenital malformations and genetic diseases in this population, possible long-term malconditions and pathologies in children born using ART. The overwhelming majority of investigators consider the adverse effect of ART on a child's body to be the result of prematurity and multiple pregnancy (transfer multiple embryos followed by partial reduction). It is stated that the widespread introduction of ART may contribute to the vertical transmission of parental infertility factors in the population. The application of ARTprocedures in some cases is associated with controversial ethical and legal issues (surrogacy, oocyte donation). Further improvements in ART procedures (preimplantation training, medical and genetic diagnosis, reducing the frequency of multiple pregnancy) cannot be stated as an alternative to the general medical and social prevention of reproductive disorders in adolescents and youth.

Assisted Reproductive Technology Surveillance - United States, 2013.

The aim of this study was to evaluate the influence of body mass index (BMI) and ultrasound-estimated visceral adipose tissue deposits on oocyte quality and pregnancy rate in women undergoing Assisted Reproductive Technology (ART) procedures. The study included 58 women who underwent ART procedures. According to their BMI, the women were divided into normal weight and overweight/obese; an ultrasound evaluation of preperitoneal fat thickness (PFT) was also performed for each patient. The oocyte quality was then assessed, and samples of follicular fluid were collected from each woman, in order to evaluate the intrafollicular concentration of reactive oxygen species (ROS) as markers of oxidative stress and pro-inflammatory cytokines (IL-1β and IL-6) as markers of chronic inflammation. A negative correlation was found between BMI (as well as PFT) and the number of retrieved oocytes (r = −0.3; p <0.05 and r = −0.5; p < 0.001, respectively), good quality oocytes (r = −0.4; p = <0.05) and obtained embryos (r = −0.3; p < 0.05). In women undergoing ART procedures, BMI and PFT negatively influence the number of oocytes retrieved and their quality. However, on multivariable analysis, only age, PFT and number of retrieved oocytes affect the success rate of ART procedures.

Monozygotic multiple gestation after intracytoplasmic sperm injection and preimplantation genetic diagnosis

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.

Assisted reproductive technology (ART) includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART procedures are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). This report presents the most recent national data and state-specific results.2005.In 1996, CDC initiated data collection regarding 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]). Beginning with 2004, CDC has contracted with a statistical survey research organization, Westat, Inc., to obtain data from ART medical centers in the United States. Westat, Inc., maintains CDC's web-based data collection system called the National ART Surveillance System (NASS).In 2005, a total of 134,260 ART procedures were reported to CDC. These procedures resulted in 38,910 live-birth deliveries and 52,041 infants. Nationwide, 73% of ART procedures used freshly fertilized embryos from the patient's eggs, 15% used thawed embryos from the patient's eggs, 8% used freshly fertilized embryos from donor eggs, and 4% used thawed embryos from donor eggs. Overall, 42% of ART transfer procedures resulted in a pregnancy, and 35% resulted in a live-birth delivery (delivery of one or more live-born infants). The highest live-birth rates were observed among ART procedures that used freshly fertilized embryos from donor eggs (52%). The highest numbers of ART procedures were performed among residents of California (18,655), New York (12,032), Illinois (9,449), New Jersey (9,325), and Massachusetts (8,571). These five states also reported the highest number of live-birth deliveries. Of 52,041 infants born through ART, 49% were born in multiple-birth deliveries. The multiple-birth risk was highest for women who underwent ART transfer procedures that used freshly fertilized embryos from either donor eggs (41%) or their own eggs (32%). Approximately 1% of U.S. infants born in 2005 were conceived through ART. Those infants accounted for 17% of multiple births nationwide. Approximately 9% of ART singletons, 57% of ART twins, and 95% of ART triplets or higher-order multiples were low birthweight. Similarly, 15% of ART singletons, 66% of ART twins, and 97% of ART triplets or higher-order multiples were born preterm.Whether an ART procedure resulted in a pregnancy and live-birth delivery varied according to different patient and treatment factors. ART poses a major risk for multiple births that are associated with adverse maternal and infant outcomes (e.g., preterm delivery, low birthweight, and infant mortality). This risk varied according to the patient's age, the type of ART procedure performed, the number of embryos available for transfer to the uterus, the number actually transferred, and the day of transfer (day 3 or day 5).ART-related multiple births represent a sizable proportion of all multiple births nationwide and in selected states. To minimize the adverse maternal and child health effects that are associated with multiple pregnancies, ongoing efforts to limit the number of embryos transferred in each ART procedure should be continued and strengthened. Adverse maternal and infant outcomes (e.g., low birthweight and preterm delivery) associated with ART treatment choices should be explained fully when counseling patients who are considering ART.

Assisted reproductive technology (ART) procedures are associated with placental dysfunction involving dysregulation of several molecular factors and pathways. MicroRNAs (miRNAs) are crucial epigenetic regulators involved in placental development and function. The objective was to identify differential miRNAs in the placentae of women conceived by ART procedures and explore their role by pathway analysis. Fifty pregnant women who underwent ART procedure and 50 pregnant women with natural pregnancy (Non-ART group) were included in the study. Qiagen miRCURY LNA PCR Array was used to identify differential miRNAs from placental samples using qRT-PCR. Pathway enrichment analysis was performed for differentially expressed miRNAs using Enrichr integrated within ShinyGO v0.80. Placental expression of 11 hsa-miRNAs (from 28 tested hsa-miRNAs) differed (5 upregulated and 6 downregulated) in the ART group. Pathway enrichment analysis revealed that upregulated miRNAs are associated with pathways such as vasculature development, and downregulated miRNAs were associated with xenobiotic stimulus, stress-activated MAPK cascade, circadian rhythm, insulin stimulus and secretion, cellular response to oxygen levels and fibroblast proliferation. Validation of miRNAs on larger sample size demonstrated that hsa-miR-30c-5p and hsa-miR-140a-5p were downregulated in the ART group. miRNA-mRNA target network analysis revealed that these miRNAs target 58 genes associated with regulation of VEGFA receptor signaling pathway, glomerulus vasculature development, long chain fatty-acyl-CoA biosynthesis, and apoptosis. ART procedures are associated with altered placental miRNA expression, possibly contributing to disturbed placental angiogenesis. This study identified two essential miRNAs (hsa-miR-30c-5p and hsa-miR-140a-5p) associated with ART procedures that regulate placental and fetal growth and development.

After completing this article, readers should be able to: 1. Describe the outcomes of assisted reproductive technologies (ART) for singleton, twin, and other multiple births. 2. Describe the role of fertility in adverse outcomes seen with ART births. 3. Review the association of birth defects with ART. 4. Delineate the association of disease of genomic imprinting with ART. 5. Describe the relationship between ART and the subsequent incidence of neurodevelopmental sequelae. In the 1977 ruling “Carey v. Population Services International,” the United States Supreme Court ruled that the decision to bear children is constitutionally protected. (1) Significant interest already had been shown in the development and improvements of in vitro fertilization (IVF) for infertile couples. The first human pregnancy and human birth using IVF were reported by Steptoe and Edwards in the United Kingdom. (2) Their work resulted in the first baby born via reproductive technologies, Louise Brown, born on July 25, 1978, at Oldham General Hospital in Oldham, United Kingdom. (3) She was born via a planned cesarean section, and her birthweight was 2.61 kg. The first successful viable IVF in the United States was performed by Jones and Seager-Jones in 1981 in Norfolk, Virginia. (4) Assisted reproductive technologies (ART) have seen a recent surge in popularity. The Centers for Disease Control and Prevention (CDC) reported that 122,872 cycles of ART were initiated in 2003, resulting in the delivery of 48,756 neonates, (5) accounting for approximately 1% of all neonates delivered in the United States. The percentage is higher in many countries, including Denmark, where it is estimated that 5% of all deliveries are with the assistance of ART. (6) Couples pursue ART for myriad reasons, including tubal transport factors, ovulatory dysfunction, uterine factors, endometriosis, male- and female-specific factors, and when a cause of infertility is unknown. (5) It would be very …

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