Risk factors associated with monozygotic twinning in offspring conceived by assisted reproductive technology
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PROVIDER: S-EPMC10570986 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Background and objectiveAn increasing number of children are born after assisted reproductive technology (ART), and monitoring their long-term health effects is of interest. This study compares cancer risk in children conceived by ART to that in children conceived without.MethodsThe Medical Birth Registry of Norway contains individual information on all children born in Norway (including information of ART conceptions). All children born between 1984 and 2011 constituted the study cohort, and cancer data were obtained from the Cancer Registry of Norway. Follow-up started at date of birth and ended on the date of the first cancer diagnosis, death, emigration, or December 31, 2011. A Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer risk between children conceived by ART and those not. Cancer risk was also assessed separately for all childhood cancer types.ResultsThe study cohort comprised 1 628 658 children, of which 25 782 were conceived by ART. Of the total 4554 cancers, 51 occurred in ART-conceived children. Risk of overall cancer was not significantly elevated (HR 1.21; 95% CI 0.90-1.63). However, increased risk of leukemia was observed for children conceived by ART compared with those who were not (HR 1.67; 95% CI 1.02-2.73). Elevated risk of Hodgkin's lymphoma was also found for ART-conceived children (HR 3.63; 95% CI 1.12-11.72), although this was based on small numbers.ConclusionsThis population-based cohort study found elevated risks of leukemia and Hodgkin's lymphoma in children conceived by ART.
| S-EPMC5178823 | biostudies-literature
Project description:STUDY QUESTION:Do children conceived by ART have an increased risk of cancer? SUMMARY ANSWER:Overall, ART-conceived children do not appear to have an increased risk of cancer. WHAT IS KNOWN ALREADY:Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce. STUDY DESIGN, SIZE, DURATION:A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS:All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers' questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]). MAIN RESULTS AND THE ROLE OF CHANCE:The median follow-up was 21 years (interquartile range (IQR): 17-25) and was shorter in ART-conceived children (20 years, IQR: 17-23) compared with naturally conceived children (24 years, IQR: 20-30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72-1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90-1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73-2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81-2.85; 1.80, 95% CI: 0.65-4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81-7.37) and melanoma (HR = 1.86, 95% CI: 0.66-5.27) were non-significantly increased for ART-conceived compared with naturally conceived children. LIMITATIONS, REASONS FOR CAUTION:Despite the large size and long follow-up of the cohort, the number of cancers was rather small for subgroup analyses as cancer in children and young adults is rare. WIDER IMPLICATIONS OF THE FINDINGS:Overall, ART-conceived children do not appear to have an increased cancer risk after a median follow-up of 21 years. This large study provides important results, enabling physicians to better inform couples considering ART about the long-term safety of ART for their children. However, larger studies with prolonged follow-up are needed to investigate cancer risk in adults and in children conceived by ICSI and/or from cryopreserved embryos. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by The Dutch Cancer Society (NKI 2006-3631) which funded the OMEGA-women's cohort and Children Cancer Free (KIKA;147) which funded the OMEGA-offspring cohort. We declare no competing interests.
| S-EPMC6443110 | biostudies-literature
Project description:Assisted reproductive technology (ART) may affect fetal development through epigenetic mechanisms as the timing of ART procedures coincides with the extensive epigenetic remodeling occurring between fertilization and embryo implantation. However, it is unknown to what extent ART procedures alter the fetal epigenome. Underlying parental characteristics and subfertility may also play a role. Here we identify differences in cord blood DNA methylation, measured using the Illumina EPIC platform, between 962 ART conceived and 983 naturally conceived singleton newborns. We show that ART conceived newborns display widespread differences in DNA methylation, and overall less methylation across the genome. There were 607 genome-wide differentially methylated CpGs. We find differences in 176 known genes, including genes related to growth, neurodevelopment, and other health outcomes that have been associated with ART. Both fresh and frozen embryo transfer show DNA methylation differences. Associations persist after controlling for parents' DNA methylation, and are not explained by parental subfertility.
| S-EPMC8989983 | biostudies-literature
Project description:Background Assisted reproductive technology (ART) has emerged as a common treatment option for infertility, a problem that affects an estimated 48 million couples worldwide. Advancing maternal age with increasing prepregnancy cardiovascular risk factors, such as chronic hypertension, obesity, and diabetes, has raised concerns about pregnancy complications associated with ART. However, in-hospital complications following pregnancies conceived by ART are poorly described. Methods and Results To assess the patient characteristics, obstetric outcomes, vascular complications and temporal trends of pregnancies conceived by ART, we analyzed hospital deliveries conceived with or without ART between January 1, 2008, and December 31, 2016, from the United States National Inpatient Sample database. We included 106 248 deliveries conceived with ART and 34 167 246 deliveries conceived without ART. Women who conceived with ART were older (35 versus 28 years; P<0.0001) and had more comorbidities. ART-conceived pregnancies were independently associated with vascular complications (acute kidney injury: adjusted odds ratio [aOR], 2.52; 95% CI 1.99-3.19; and arrhythmia: aOR, 1.65; 95% CI, 1.46-1.86), and adverse obstetric outcomes (placental abruption: aOR, 1.57; 95% CI, 1.41-1.74; cesarean delivery: aOR, 1.38; 95% CI, 1.33-1.43; and preterm birth: aOR, 1.26; 95% CI, 1.20-1.32), including in subgroups without cardiovascular disease risk factors or without multifetal pregnancies. Higher hospital charges ($18 705 versus $11 983; P<0.0001) were incurred compared with women who conceived without ART. Conclusions Pregnancies conceived by ART have higher risks of adverse obstetric outcomes and vascular complications compared with spontaneous conception. Clinicians should have detailed discussions on the associated complications of ART in women during prepregnancy counseling.
| S-EPMC9075081 | biostudies-literature
Project description:ObjectiveTo identify independent risk factors for placenta accreta spectrum among pregnancies conceived with assisted reproductive technology.DesignRetrospective cohort study.SettingTertiary hospital.PatientsIndividuals who conceived with assisted reproductive technology and reached 20 weeks' gestation or later from 2011 to 2017.InterventionsPatient and cycle data was abstracted from hospital records and supplemented with state-level data. Poisson regression was used for multivariate analyses and reported as adjusted relative risks (aRR).Main outcome measuresClinical or histologic placenta accreta spectrum.ResultsOf 1,975 qualifying pregnancies, 44 (2.3%) met criteria for accreta spectrum at delivery. In the multivariate model, significant risk factors included low-lying placenta at delivery (aRR, 15.44; 95% CI 7.76-30.72), uterine factor infertility or prior uterine surgery (aRR, 4.68; 95% CI, 2.72-8.05), initial low-lying placentation that resolved (aRR, 3.83; 95% CI, 1.90-7.73), and use of frozen embryos (aRR, 3.02; 95% CI, 1.66-5.48). When the fresh vs frozen variable was replaced with controlled ovarian hyperstimulation, the final model did not change (aRR, 2.40 for unstimulated cycles, 95% CI, 1.32-4.38). With frozen transfers, the accreta rate was 16% when the endometrial thickness was < 6mm vs 3.8% with thicker endometrium (P=.02).ConclusionsAmong pregnancies conceived with assisted reproductive technology, accreta spectrum is associated with low placental implantation (even when resolved), uterine factor infertility and prior uterine surgery, and the use of frozen embryo transfer or unstimulated cycles.
| S-EPMC10504550 | biostudies-literature
Project description:BackgroundWith the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring.MethodsA total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads.ResultsCompared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P < 0.05 and P = 0.08 for IVF; P < 0.05 and P < 0.05 for ICSI, respectively). These alterations in IL-4 concentrations and the ratio of IFN-γ to IL-4 were statistically significantly correlated with supra-physical E2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = - 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05).ConclusionsImmunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.
| S-EPMC8620159 | biostudies-literature
Project description:BackgroundPregnancies following assisted reproductive technology (ART) may have elevated potential risk of pregnancy loss (PL) when compared to natural conception. However, rare studies comprehensively analyzed the IVF/ICSI cycle-dependent factors for loss of clinical pregnancy. Therefore, we aimed to determine the ART subgroup-specific risks of PL throughout pregnancy and explore different risk factors for early miscarriage and late miscarriage among pregnancies conceived through ART.MethodsA retrospective cohort study was launched in two infertility treatment centers in Nanjing and Changzhou including 5485 IVF/ICSI embryo transfer cycles with known outcomes after clinical pregnancy by the end of 2015. Cox proportional hazards regression analysis was performed to estimate the hazard ratios and their 95% confidence intervals. The associations between survival time during pregnancy and demographics and clinical characteristics of clinical pregnancies were estimated using the Kaplan-Meier method and the Log-rank test.ResultsThe overall PL rate in current ART population was 12.5%. Among the 685 pregnancy loss cycles, a total of 460 ended as early miscarriage, 191 as late miscarriage. We found couples in ART pregnancies demonstrated a significantly increased risk of PL as maternal age (HR = 1.31, Ptrend < 0.001) grows. Pregnancies received controlled ovarian hyperstimulation (COH) protocol like GnRH antagonist protocol (HR = 3.49, P < 0.001) and minimal stimulation protocol (HR = 1.83, P < 0.001) had higher risk of PL than GnRH-a long protocol. Notably, in contrast to fresh cycle, women who received frozen cycle embryo had a significant increased risk of early miscarriage (P < 0.001), while frozen cycle was linked with lower risk of late miscarriage (P = 0.045). In addition, four factors (maternal age, COH protocol, cycle type and serum hCG level 14 days after transfer) had independent impact on miscarriage mainly before 12 weeks of gestational age.ConclusionsWith these findings in this study, clinicians may make it better to evaluate a patient's risk of PL based on the maternal age at the time of treatment, COH protocol, cycle type and serum hCG level 14 days after transfer and the gestational week of the fetus, and we hope that it contributes to future study on its etiology and guide the clinical prevention and treatment.
| S-EPMC6081896 | biostudies-literature
Project description:Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. Results. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of H19 CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD -0.81 (-1.53; -0.09), I2 = 89%, p = 0.03). In contrast, H19 CCCTC-binding factor 6 (CTCF6), Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1OT1), Paternally-expressed gene 3 (PEG3), and Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) were not differently methylated in ART vs. SC offspring. Conclusion: The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring.
| S-EPMC9457481 | biostudies-literature
Project description:BackgroundCaesarean section rates are higher among pregnancies conceived by assisted reproductive technology (ART) compared to spontaneous conceptions (SC), implying an increase in neonatal and maternal morbidity. We aimed to compare caesarean section rates in ART pregnancies versus SC, overall, by indication (elective versus emergent), and by type of ART treatment (in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), fresh embryo transfer, frozen embryo transfer) in a systematic review and meta-analysis.MethodsWe searched Medline, EMBASE and CINAHL databases using the OVID Platform from 1993 to 2019, and the search was completed in January 2020. The eligibility criteria were cohort studies with singleton conceptions after in-vitro fertilization and/or intracytoplasmic sperm injection using autologous oocytes versus spontaneous conceptions. The study quality was assessed using the Newcastle Ottawa Scale and GRADE approach. Meta-analyses were performed using odds ratios (OR) with a 95% confidence interval (CI) using random effect models in RevMan 5.3, and I-squared (I2) test > 75% was considered as high heterogeneity.ResultsOne thousand seven hundred fifty studies were identified from the search of which 34 met the inclusion criteria. Compared to spontaneous conceptions, IVF/ICSI pregnancies were associated with a 1.90-fold increase of odds of caesarean section (95% CI 1.76, 2.06). When stratified by indication, IVF/ICSI pregnancies were associated with a 1.91-fold increase of odds of elective caesarean section (95% CI 1.37, 2.67) and 1.38-fold increase of odds of emergent caesarean section (95% CI 1.09, 1.75). The heterogeneity of the studies was high and the GRADE assessment moderate to low, which can be explained by the observational design of the included studies.ConclusionsThe odds of delivering by caesarean section are greater for ART singleton pregnancies compared to spontaneous conceptions. Preconception and pregnancy care plans should focus on minimizing the risks that may lead to emergency caesarean sections and finding strategies to understand and decrease the rate of elective caesarean sections.
| S-EPMC7986269 | biostudies-literature
Project description:BackgroundInvasive prenatal evaluation by chromosomal microarray analysis (CMA) and karyotyping might represent an important option in pregnant women, but limited reports have applied CMA and karyotyping of fetuses conceived by assisted reproductive technology (ART). This study aimed to examine the value of CMA and karyotyping in prenatal diagnosis after ART.MethodsThis retrospective study included all singleton fetuses conceived by ART from January 2015 to December 2021. Anomalies prenatally diagnosed based on karyotyping and CMA were analyzed. Prevalence rates for various CMA and karyotyping results were stratified based on specific testing indications including isolated-and non-isolated ART groups. The rates of CMA findings with clinical significance (pathogenic/likely pathogenic) and karyotype anomalies were assessed and compared to those of local control individuals with naturally conceived pregnancies and without medical indications.ResultsIn total, 224 subjects were assessed by karyotyping and CMA. In the examined patients, chromosomal and karyotype abnormality rates were 3.57% (8/224) and 8.93% (20/224), respectively. This finding indicated a 5.35% (12/224)-incremental rate of abnormal CMA was obtained over karyotype analysis (p = 0.019). The risk of CMA with pathogenic findings for all pregnancies conceived by ART (5.80%, 13/224) was markedly elevated in comparison with the background value obtained in control individuals (1.47%, 9/612; p = 0.001). In addition, risk of CMA with clinically pathogenic results in isolated ART groups was significant higher compared to the background risk reported in the control cohort (p = 0.037).ConclusionsPrenatal diagnosis including karyotyping and CMA is recommended for fetuses conceived by ART, with or without ultrasound findings.
| S-EPMC9854383 | biostudies-literature