22q11.2 Deletion Syndrome in Offspring Conceived via Assisted Reproductive Technology Versus Spontaneously

To evaluate uterine arteries Doppler pulsatile index (PI) and resistance index (RI) at 11 + 0 to 13 + 6 weeks of singleton pregnancies with good known outcome after natural and assisted reproductive technologies (ART) conception, to continue this work for later retrospective analysis in cases with obstetrical complications and poor neonatal outcome with the idea to use first trimester prenatal anomalies screening program for obstetrical goals. All patients both with natural pregnancies and with pregnancies after ART conception underwent transabdominal uterine artery Doppler flow velocimetry to measure the PI and RI in addition to a first-trimester prenatal chromosomal anomaly screening program in a one-stop clinic for assessment of risk (OSCAR). After delivery, a retrospective analysis was done to compare Doppler measurements in late first trimester in pregnancies with known good outcome. There were 36 cases after natural spontaneous conception and 48 cases after ART conception The mean PI were 1.46 in spontaneous pregnancies and 1.43 in ART pregnancies. The mean RI were 0.68 in spontaneous pregnancies and 0.66 in ART pregnancies. An average newborn weight and Apgar was, respectively, 3430 g and 9 in spontaneous conception group. An average newborn weight and Apgar was, respectively, 3320 g and 9 in ART pregnancies group. These results show no differences in uterine arteries Doppler indices between groups with spontaneous and ART conception in pregnancies with known good outcome. It suggests no major differences in trophoblastic invasions between ART and natural pregnancies with good outcome. It needs to evaluate the possible differences of uterine Doppler indices in pregnancies after natural spontaneous and ART pregnancies in cases of known late obstetrical complications.

Patients using assisted reproductive technology (ART) may need additional counseling about the increased risks of placental abruption and preterm delivery. Further investigation into the potential additive risk of ART and placental abruption is needed. To ascertain the risk of placental abruption in patients who conceived with ART and to evaluate if placental abruption and ART conception are associated with an increased risk of preterm delivery (<37 weeks' gestation) over and above the risks conferred by each factor alone. This cross-sectional study used data from the National Inpatient Sample, which includes data from all-payer hospital inpatient discharges from 48 states across the US. Participants included women aged 15 to 54 years who delivered from 2000 through 2019. Data were analyzed from January 17 to April 18, 2024. Pregnancies conceived with ART. Risks of placental abruption and preterm delivery in ART conception compared with spontaneous conceptions. Associations were expressed as odds ratios (ORs) and 95% CIs derived from weighted logistic regression models before and after adjusting for confounders. The relative excess risk due to interaction (RERI) of the risk of preterm delivery based on ART conception and placental abruption was also assessed. Of 78 901 058 deliveries, the mean (SD) maternal age was 27.9 (6.0) years, and 9 212 117 patients (11.7%) were Black individuals, 14 878 539 (18.9%) were Hispanic individuals, 34 899 594 (44.2%) were White individuals, and 19 910 807 (25.2%) were individuals of other races and ethnicities. Of the total hospital deliveries, 98.2% were singleton pregnancies, 68.8% were vaginal deliveries, and 52.1% were covered by private insurance. The risks of placental abruption among spontaneous and ART conceptions were 11 and 17 per 1000 hospital discharges, respectively. After adjusting for confounders, the adjusted OR (AOR) of placental abruption was 1.42 (95% CI, 1.34-1.51) in ART pregnancies compared with spontaneous conceptions, with increased odds in White women (AOR, 1.42; 95% CI, 1.31-1.53) compared with Black women (AOR, 1.16; 95% CI, 0.93-1.44). The odds of preterm delivery were significantly higher in pregnancies conceived by ART compared with spontaneous conceptions (AOR, 1.46; 95% CI, 1.42-1.51). The risk of preterm delivery increased when patients had both ART conception and placental abruption (RERI, 2.0; 95% CI, 0.5-3.5). In this cross-sectional study, patients who conceived using ART and developed placental abruption had a greater risk of preterm delivery compared with spontaneous conception without placental abruption. These findings have implications for counseling patients who seek infertility treatment and obstetrical management of ART pregnancies.

Congenital malformations after assisted reproduction: risks and implications for prenatal diagnosis and fetal medicine

Severity of prematurity risk in spontaneous and in vitro fertilization twins: does conception mode serve as a risk factor?

Study question Is the use of Assisted Reproductive Technologies (ART) associated with an increased risk of certain categories of major congenital anomalies compared with spontaneous conception ? Summary answer Within a population of conceptus with CA, only the use of ICSI was associated with an increased risk of some categories of major CA. What is known already The literature favours an increased risk of congenital anomalies (CA) when Assisted Reproductive Technologies are used, in comparison with spontaneous conception (SC). The risk seems to further increase with more invasive techniques, with the maximum risk reported for ICSI. Some categories of CA are more described, such as congenital heart diseases (CHD), congenital urogenital tract malformations including hypospadia, and genetic anomalies. Nevertheless, many confounding factors could influence the association between ART and CA, such as : difficulties to separate the self-effects of infertility and ART, choice of control group, the analysis of only live-birth, the use of different CA classifications. Study design, size, duration This was a cross-sectional cohort study. The data used were collected prospectively by a regional CA register called REMERA (Registre des Malformations En Rhône-Alpes). REMERA is the first national French register and monitors more than 55 000 births per year. The study included all the cases of major congenital anomalies for a ten-year period between 2012 and 2021, in four departments of the Auvergne-Rhône-Alpes region. Participants/materials, setting, methods A case was defined as a fetus or child with a major CA, diagnosed antenatally regardless of the term, or postnatally up to the end of the first year of life. All pregnancy outcomes were included. Cases were then divided between four groups: spontaneous (SC), IUI, IVF, ICSI. Adjustment on maternal age, BMI, twin pregnancy, primary or secondary infertility, gamete donation, and fresh or frozen embryo transfer were done in multivariate analysis with logistic regression. Main results and the role of chance During the study period, there was 19,794 cases in the SC group, 167 cases for the IUI group, 548 cases for the FIV group and 307 cases of ICSI. The most common CA categories in the ART groups were CHD (24,8%), genetic (21,4%) and urinary anomalies (17,4%). Same categories were observed in the SC group. In multivariate analysis, ART conception was significantly associated with an increase of gastrointestinal anomalies [aOR 1.380 (95% IC 1.088-1.731)] and ear/face/neck category [aOR 1.747 (95% IC 1.029-2.801)]. In comparison with FIV, ICSI was significantly associated with an increase risk of orofacial clefts [aOR 2.539 (95% IC 1.085-5.858], gastrointestinal [aOR 2.199 (95% IC 1.278-3.748], genetic [aOR 1.614 (95% IC 1.083-2.392)] and central nervous system anomalies [aOR 1.839 (95% IC 1.149-2.916)]. The risk of genetic anomalies was significantly reduced in case of oocyte donation, in comparison with autologous oocytes [aOR 0.134 (95% IC 0.056-0.296)]. Limitations, reasons for caution Limitations of this study were the limited size for some ART groups despite a large cohort, a possible bias for data collection e.g cases of ovulation induction in the SC group, and the impossibility to adjust for some variables because of missing data such as infertility duration or culture media. Wider implications of the findings The French legislation for ART and TOPFA is particularly interesting to analyze the risk of CA after ART. The objective would be the creation of a prospective register for ART data to precisely analyze each feature of an ART cycle and explore more precisely the risk of congenital anomalies. Trial registration number No

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 …

Objective: To explore the effects of environmental, genetic factors as well as the interactions in early life on the short-term and long-term health of offspring and to systematically evaluate the pregnancy outcomes and health of offspring after birth between families with assisted reproductive technology (ART) conception and families with spontaneous conception. Methods: The China National Birth Cohort (CNBC), a multicenter prospective birth cohort study, includes both families with ART conception and families with spontaneous conception. Since 2016, CNBC has recruited families from 24 hospitals located in 12 provinces, municipalities and autonomous regions throughout China. Information and biospecimens were collected before ART treatment, embryo transfer, at early, second, third trimester and delivery, and at 42 days, 6, 12 and 36 months after birth. Results: By June 2020, CNBC had included 27 044 families with ART conception and 29 589 families with spontaneous conception. The majority of the participants are urban residents. Among the families with ART conception, 65.5% of the men and 63.7% of the women had college degrees or higher. The mean age distribution of men and women was (33.83±5.52) and (32.38±4.67) years. 83.2% of women were primiparas, and the prevalence rates of current regular smokers and current alcohol drinkers were 0.8% and 2.1% in women. Among the families with spontaneous conception, 81.5% of the men and 86.5% of the women had college degrees or higher. The mean age distribution of men and women was (32.06±5.09) and (30.40±4.27) years. 67.2% of women were primiparas, and the prevalence rates of current regular smokers and current alcohol drinkers were 0.1% and 2.2% in women. The baseline characteristics were different between the families with ART conception and spontaneous conception in different regions. Conclusion: CNBC provides a powerful and rich resource in studying the impact of genetic, environmental factors and interactions in early life and ART treatment on the health of offspring after birth.

Background/Introduction Survival rates for patients with congenital heart disease have improved, leading to more pregnancies among women with adult congenital heart disease (ACHD). Many patients now seek fertility treatments, including assisted reproductive technology (ART), but the short-term cardiovascular safety remains largely unknown. Purpose We sought to study the fertility rate and proportion of ART, as well as related complications and outcome among women with ACHD, in a large national retrospective matched case-control study. Methods We studied all women &amp;gt;18 years of age with ACHD in The Swedish Registry of Congenital Heart Disease compared to matched controls in Medical Birth Registry, respectively, the national registry of ART, the National Patient Register and the Cause of Death register between 2007 and 2020. Major adverse cardiovascular events (MACE) were studied from the start of first ART until 6 months after delivery, stillbirth/miscarriage or last treatment. MACE was defined as the presence of at least one of the following: CVD mortality, arrhythmia, thromboembolism (either during hospitalisation or in outpatient care), hospitalisation with a main diagnosis of either ischaemic heart disease, ischaemic stroke, peripheral artery disease, heart failure or aortic dissection. We excluded ART cycles due to preimplantation genetic diagnosis and due to sperm insemination and/or sperm donation (as a proxy for male factor infertility). Results We studied cycles of ART in women with ACHD (720 cycles) and controls (6221 cycles) from 2007 through 2020 (Table 1, Figure 1). More pregnancies in women with ACHD were facilitated by ART (3.9%) compared to controls (3.2%), but time from the start of the first treatment until delivery of a neonate did not differ. The total number of neonates, regardless of ART or spontaneous conception, was the same in women with ACHD and controls (1.7 neonates per woman). More women with ACHD gave birth prematurely before week 28 (2.5%) compared to controls (0.3%). Pregnancies in women with ACHD had an increased risk of congenital malformations (6.3%) compared to controls (3.2%). During and 6 months after ART, women with ACHD had an increased risk of MACE (n=9, 3.6%), odds ratio 2.84 (95% CI 1.15- 6.97), compared to controls (n=17, 1.1%). This was primarily driven by hospitalisation due to arrhythmias, mostly consisting of supraventricular tachyarrhythmias. No women died of cardiovascular mortality. Conclusion This is the first large national study investigating complications due to ART in women with ACHD compared to matched controls. Women with ACHD conceiving by ART may have an increased risk of prematurity, congenital malformations and non-fatal adverse cardiovascular events compared to controls. However, caution and careful optimism are still warranted, as our results cannot be applied directly to women with more complex ACHD.Table 1.

22q11.2 Distal Deletion: A Recurrent Genomic Disorder Distinct from DiGeorge Syndrome and Velocardiofacial Syndrome

BackgroundGrowing evidence indicates that the risk of obstetric and perinatal outcomes is higher in women with assisted reproductive technology (ART). However, there is little known about pregnancy related complications and co-morbidity in gestational diabetes mellitus (GDM) following singleton pregnancies achieved by ART in comparison with spontaneous conception (SC).MethodsTwo hundred sixty singleton pregnant women conceived by ART and 314 pregnant women conceived by spontaneous conception (SC) were participated in this prospective cohort study. All participants were enrolled after GDM screening through one-step oral glucose tolerance test (OGTT) and then grouped into GDM and non-GDM groups. Women were followed for pregnancy outcomes including pregnancy-induced hypertension (PIH), preeclampsia, antepartum hemorrhage (APH), cesarean section (CS), preterm birth (PTB), intrauterine growth restriction (IUGR), being small or large for gestational age (SGA or LGA), macrosomia, low birth weight (LBW), respiratory distress, neonatal hypoglycemia, NICU admission and perinatal mortality from antenatal visits to delivery. Confounding factors were adjusted in logistic regression model in order to estimate adjusted odds ratios (aORs).ResultsAmong 260 ART and 314 SC, 135 and 152 women were GDM women, respectively. Higher maternal age and pre-gravid BMI, shorter duration of gestation and lower gestational weight gain were observed in GDM groups (ART-GDM and SC-GDM) compared to those of the SC group. ART-GDM group had a higher risk (95% confidence interval) of obstetric complications including PIH [aOR:7.04 (2.24–22.15)], preeclampsia [aOR:7.78 (1.62–37.47)], APH [aOR:3.46 (1.28–9.33)], emergency CS [aOR:2.64 (1.43–4.88)], and perinatal outcomes such as PTB [aOR:3.89 (1.51–10.10)], LBW [aOR:3.11 (1.04–9.30)] and NICU admission [aOR:4.36 (1.82–10.45)], as well as neonatal hypoglycemia [aOR: 4.91 (1.50–16.07)], compared to SC group. SC-GDM group showed a higher risk of PIH [aOR: 4.12 (1.31–12.89)], emergency CS [aOR: 2.01 (1.09–3.73] and LGA [aOR: 5.20 (1.07–25.20)], compared to SC group. Additionally, ART group had a higher risk of PIH [aOR: 3.46(1.02–11.68), preeclampsia 5.29 (1.03–27.09), and NICU admission [aOR: 2.53 (1.05–6.09)] compared to SC. Insulin requirement (41.8% vs. 25.7%) was significantly higher in ART-GDM group compared to SC-GDM group.ConclusionThe findings of this study suggest that GDM occurring after ART conception increases the risk of adverse obstetric and perinatal outcomes.

How much worse, really, are neonatal and maternal outcomes of infertility treatment?

BackgroundWith the development of assisted reproductive technology (ART) and its increasing success rate in the mainland of China, more attention has been paid to the safety of ART. In this study, we explored the associations between conception by ART and pregnancy/perinatal complications, and neonatal outcomes compared with similar outcomes following spontaneous conception.MethodsThis retrospective cohort study of pregnancies over a 3-year period (2013–2015) was performed at Beijing Obstetrics and Gynecology Hospital, Beijing, China. Subjects were divided into two groups: conception by ART (n = 2256) or spontaneous conception (n = 6768). According to different fertilization modes, the ART group was divided into in vitro fertilization (IVF, n = 1873) and intracytoplasmic sperm injection (ICSI, n = 383) subgroups. The ART group was also divided into two different embryo transfer methods; fresh embryo transfer (ET, n = 1583) and frozen embryo transfer (FET, n = 673) subgroups. Pregnancy complications, perinatal complications, and neonatal outcomes of the enrolled subjects were investigated and analyzed by univariate analysis and multivariate logistic regression.ResultsAfter adjustment for maternal age, gravidity, parity, maternal education, smoking, alcohol consumption, and body mass index (BMI), pregnancies conceived by ART were associated with a significantly increased incidence of gestational diabetes mellitus (GDM; OR 1.88, 95% CI 1.56–2.27), gestational hypertension (OR 2.18, 95% CI 1.83–2.60), and intrahepatic cholestasis of pregnancy (ICP) (OR 2.79, 95% CI 2.15–3.64), compared with spontaneous conception. These associations were similar for the singleton group. In the twin group, only the incidence of ICP was significantly higher than in controls. We found that pregnancies conceived by ART were associated with perinatal complications, including placental abruption (OR 2.14, 95% CI 1.33–3.45), premature rupture of membranes (PROM; OR 1.24, 95% CI 1.06–1.45), postpartum hemorrhage (OR 2.89, 95% CI 2.33–3.59) and polyhydramnios (OR 2.01, 95% CI 1.29–3.16). The singleton group had a similar result with placental abruption, but not with fetal membranes ruptures before labor and polyhydramnios. There were no significant differences in the incidence of these perinatal complications in the twin group. Some neonatal outcomes, including preterm labor (OR 4.29, 95% CI 3.84–4.80) and low birth weight (OR 1.72, 95% CI 1.42–2.08), were more likely to occur with singleton births after ART. However, there were no significant differences for these outcomes from twin pregnancies. Perinatal complications and neonatal outcomes were consistent between the IVF and ICSI subgroups. The FET and ET subgroups showed a similar increase in complications, except for the incidence of placental abruption. After taking into account the effects of parity, birth plurality and maternal age, the ART group still exhibited increased maternal and neonatal complications, although some differences narrowed or disappeared.ConclusionsThis retrospective cohort study demonstrated that patients who underwent ART were at increased risk of several adverse pregnancy outcomes compared with women who conceived spontaneously. These complications may be attributed in part to the relatively high multiple pregnancy rate after ART. Elective single embryo transfer should be promoted in China to reduce the obstetrical risks of ART pregnancy. Singletons of ART pregnancy exhibited increased maternal and neonatal complications as well, suggesting that underlying infertility or other maternal or parental factors may contribute to the adverse outcomes.

The aim of this study was to provide a comprehensive follow-up of fetal and perinatal outcome and the incidence of congenital anomalies in babies born after fresh embryo transfers compared to those conceived spontaneously in infertile couples. Retrospective comparative analysis of all clinical pregnancies from fresh cleavage-stage embryo transfer cycles (IVF and ICSI) compared with infertile patients who conceived spontaneously in the same time period (control). Congenital anomalies were classified following the European Surveillance of Congenital Anomalies (EUROCAT) classification. A total of 2414 assisted reproductive technology (ART) pregnancies were compared to 582 spontaneous conceptions in the control infertile group representing 2306 deliveries. No significant differences were found in pregnancy outcome between the two groups (delivery rate, abortion rate, ectopic pregnancies, medical abortions for fetal anomalies, single and twins mean gestational age, and weight at delivery). A significant difference (p < 0.001) was found in the twin (21.3 vs 2.3%) and triplet rates (2.3 vs 0%). A total of 2351 babies were delivered in the ART group and 449 in the control group. A total of 90 babies (3.8%) were diagnosed with a major congenital anomaly in the ART group and 15 (3.3%) in the control group (p = ns). The overall rate of major congenital anomalies (105/2800) in ART and spontaneous pregnancies in infertile couples was significantly higher when compared to the EUROCAT 2.0 versus 3.75% (p = 0.0002). Babies born after ART treatments and from spontaneous conception in infertile couples had rates of congenital anomalies higher than those recorded by the EUROCAT. However, the rates of anomalies were not different within the infertile population whether conceived by ART or spontaneously. These data suggest that the diagnosis of infertility in itself is the common denominator for the increase in the rates of anomalies seen in both ART and spontaneous conceptions.

Background/Objectives: Uterine artery pulsatility index (UtA-PI) is a key biomarker of placental function, but its clinical interpretation in assisted reproductive technology (ART) pregnancies is uncertain. This meta-analysis aimed to assess trimester- and method-specific UtA-PI differences between ART and spontaneous conceptions (SC) and to examine associated risks for preeclampsia (PE) and small-for-gestational-age (SGA) neonates to contextualize its findings. Methods: A systematic search of MEDLINE, Scopus, and the Cochrane Library was conducted through 25 June 2025. We included observational studies comparing UtA-PI and perinatal outcomes in singleton ART versus SC pregnancies. The primary outcome was the standardized mean difference (SMD) in first (until the 13+6 gestational week) and second trimester (14+0–23+6 gestational weeks) UtA-PI measurements; secondary outcomes were PE and SGA rates. Analyses were stratified by ART modalities. Random-effects models were used, and study quality was evaluated using the Newcastle–Ottawa Scale and risk of bias with QUIPS tool (INPLASY registration: INPLASY202560104). Results: Thirteen cohort studies were included. Overall, ART pregnancies had significantly lower UtA-PI values than SC in both the first (SMD = −0.28; 95% CI: −0.53 to −0.03) and second trimesters (SMD = −0.20; 95% CI: −0.36 to −0.04). These reductions were driven by oocyte donation (first-trimester SMD = −0.70; 95% CI: −1.21 to −0.18; second-trimester SMD = −0.46; 95% CI: −0.65 to −0.26) and artificial cycle frozen embryo transfers (ET) (first-trimester SMD = −0.69; 95% CI: −1.00 to −0.39). These lower UtA-PI values typically suggest better placental perfusion and a lower risk of placental related complications. However, ART pregnancies had an elevated overall risk for PE (risk ratio [RR] = 2.32; 95% CI: 1.72 to 3.12), with the highest risk in oocyte donation (RR = 6.11; 95% CI: 3.35 to 11.17) and artificial cycle frozen ET (RR = 3.45; 95% CI: 1.51 to 7.90). Conclusions: ART pregnancies, particularly from oocyte donation and artificial cycle frozen ET, show lower UtA-PI values despite a significantly elevated risk for PE. This finding suggests that mechanisms other than placental perfusion contribute to PE development. Clinically, the ART method is an independent risk factor for PE, and UtA-PI interpretation should be adjusted accordingly. Further research is crucial to elucidate the underlying pathophysiology.

IntroductionPregnancies at very and extremely advanced maternal age (VAMA, 45–49 years and EAMA, ≥50 years) are increasingly common, particularly regarding the influence of assisted reproductive technology (ART), yet their obstetric and perinatal outcomes remain underexplored. This study aimed to investigate maternal and neonatal outcomes in singleton pregnancies among women aged ≥45 years, with a specific focus on ART conception and oocyte source.Material and MethodsThis multicenter retrospective cohort study included women aged ≥45 years with singleton pregnancies delivered ≥22 weeks' gestation between 2016 and 2022 across five Italian academic hospitals. Pregnancies were categorized by mode of conception (spontaneous conception [SC] vs. ART), and ART pregnancies were further stratified by oocyte origin (homologous [ART‐HO] vs. heterologous [ART‐HE]). Multivariable logistic regression was used to evaluate associations between mode of conception and obstetric outcomes, adjusting for key confounders.ResultsAmong 557 included pregnancies, 495 (88.9%) involved women aged 45–49 years, and 62 (11.1%) women aged ≥50. Compared to SC, ART pregnancies were associated with higher adjusted odds of cesarean delivery (aOR 4.20, 95% CI 2.99–4.92; p < 0.001) and postpartum hemorrhage (aOR 2.72, 95% CI 1.75–4.23; p < 0.001). No significant differences in neonatal outcomes were observed. In the ART subgroup analysis, ART‐HE was associated with increased odds of gestational diabetes (aOR 1.97, 95% CI 1.10–3.55; p = 0.024) and manual placental removal (aOR 10.45, 95% CI 1.23–88.46; p = 0.031) compared to ART‐HO.ConclusionsART pregnancies in women ≥45 years are associated with increased maternal morbidity, particularly when involving heterologous oocytes. These findings underscored the need for tailored counseling and multidisciplinary perinatal care in this growing population.