After Assisted Reproductive Technology Research Articles

Zygotic-splitting after in vitro fertilization and prenatal parenthood testing after suspected embryo mix-up - a case report.

After in vitro fertilization with a single embryo, the parents learned about being pregnant with twins in the 10th week with various indications that an embryonic mix-up could have taken place. The affected couple thus expressed the urgent desire for a clarification of parenthood considering an abortion. However, the prenatal test results would not have been available until the 14/15th week of pregnancy. Legally, then, severe physical or mental distress of the pregnant woman must be claimed by physicians to justify an abortion after the twelfth week. However, a lack of genetic relatedness could lead to serious psychological distress for the parents, making a pregnancy termination possible even after the twelfth week, which is discussed in this case study alongside the interdisciplinary team's ethical, legal, and medical considerations.For the invasive relationship testing, cultivated chorionic villi samples (CVS) from both unborn and saliva samples from the putative parents were genetically analyzed using classical short tandem repeats (STR) analysis. The perfect match of both CVS profiles suggested the occurrence of an unusual late twin shaft, for which, fortunately, parenthood could be confirmed. To our knowledge, this is the first report on a prenatal investigation of a suspected embryo mix-up after assisted reproductive technology (ART), in which parenthood should be fixed. We want to draw attention to this unthinkable scenario, which may increase in the future with ART-induced rising multiple pregnancies.

Decreased Serum Levels of the Insulin Resistance-Related microRNA miR-320a in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is often associated with metabolic abnormalities in the affected patients such as obesity or a dysregulated glucose metabolism/insulin resistance (IR). IR affects the serum levels of several circulating microRNAs; however, studies on the association between IR-related microRNAs and PCOS are scarce. Therefore, we quantified the serum levels of the IR-associated microRNAs miR-93, miR-148a, miR-216a, miR-224 and miR-320a via qPCR in a cohort of 358 infertility patients, of whom 136 were diagnosed with PCOS. In bivariate correlation analyses, the serum levels of miR-93 and miR-216a were inversely associated with dipeptidyl peptidase 4 serum concentrations, and the miR-320a serum levels were significantly downregulated in PCOS patients (p = 0.02, Mann-Whitney U test). Interestingly, in all patients who achieved pregnancy after Assisted Reproductive Technology (ART) cycles, the serum levels of the five IR-associated microRNAs were significantly elevated compared to those of non-pregnant patients. In cell culture experiments, we detected a significant upregulation of miR-320a expression following testosterone stimulation over 24 and 48 h in KGN and COV434 granulosa carcinoma cells. In conclusion, we demonstrated a significantly reduced serum level of the IR-associated miR-320a in our patient cohort. This result once again demonstrates the close relationship between metabolic disorders and the dysregulation of microRNA expression patterns in PCOS.

Pregnancy and obstetric outcomes of dichorionic triamniotic triplet pregnancies with selective foetal reduction after assisted reproductive technology

BackgroundIt is generally beneficial and recommended that dichorionic triamniotic (DCTA) triplet pregnancies be reduced to monochorionic (MC) twin or singleton pregnancies after assisted reproductive technology (ART). However, some infertile couples still have a firm desire to retain twins. For this reason, the best foetal reduction strategies need to be available for infertile couples and clinicians. Given that data on the elective reduction of DCTA triplet pregnancies to twin pregnancies are scarce, we investigated the outcomes of elective reduction of DCTA triplet pregnancies through the retrospective analysis of previous data.MethodPatients with DCTA triplet pregnancies who underwent elective foetal reduction between January 2012 and June 2020 were recruited. A total of 67 eligible patients with DCTA triplet pregnancies were divided into two groups: a DCTA-to-dichorionic diamniotic (DCDA) twin group (n = 38) and a DCTA-to-monochorionic diamniotic (MCDA) twin group (n = 29); the basic clinical data of the two groups were collected for comparison.ResultsCompared with the DCDA-to-MCDA twin group, the DCTA-to-DCDA twin group had lower rates of complete miscarriage (7.89% versus 31.03%, p = 0.014), early complete miscarriage (5.26% versus 24.14%, p = 0.034), late preterm birth (25.71% versus 65.00%, p = 0.009) and very low birth weight (0 versus 11.11%, p = 0.025). In addition, the DCTA-to-DCDA twin group had higher rates of full-term delivery (65.71% versus 25.00%, p = 0.005), survival (92.11% versus 68.97%, p = 0.023), and taking the babies home (92.11% versus 68.97%, p = 0.023) than did the DCTA-to-MCDA twin group. In terms of neonatal outcomes, a significantly greater gestational age (38.06 ± 2.39 versus 36.28 ± 2.30, p = 0.009), average birth weight (3020.77 ± 497.33 versus 2401.39 ± 570.48, p < 0.001), weight of twins (2746.47 ± 339.64 versus 2251.56 ± 391.26, p < 0.001), weight of the larger neonate (2832.94 ± 320.58 versus 2376.25 ± 349.95, p < 0.001) and weight of the smaller neonate (2660.00 ± 345.34 versus 2126.88 ± 400.93, p < 0.001) was observed in the DCTA-to-DCDA twin group compared to the DCTA-to-MCDA twin group.ConclusionThe DCTA-to-DCDA twin group had better pregnancy and neonatal outcomes than the DCTA-to-MCDA twin group. This reduction approach may be beneficial for patients with dichorionic triamniotic triplet pregnancies who have a strong desire to have DCDA twins.

Recurrent failure of ART, thrombosis and thrombophilia

In recent years, the number of risk factors for thrombosis associated with pregnancy has increased substantially due to the active introduction of new medical technologies not used 30 years ago or because their role in emerging thrombosis has not been studied, e.g., during pregnancy after assisted reproductive technologies (ART) particularly in vitro fertilization (IVF). The risk of venous thromboembolic complications (VTEС) related to ovarian hyperstimulation during ART is often overlooked. We present the case of a 37-year-old woman who developed thrombosis of the right internal jugular vein 3 weeks after embryo transfer within the IVF protocol. Ovarian hyperstimulation during hormonal IVF protocols provokes procoagulant changes in the hemostasis and fibrinolysis system able to result in venous and arterial thrombosis. The localization of VTEС typical to ART is more often located in the internal jugular vein being accompanied by neck pain and edema. Thrombosis risk factors should be assessed in all women in the IVF program, and appropriate thromboprophylaxis should be carried out to all high risk subjects.

Risk of stroke the year following a delivery after using assisted reproductive technologies.

Studies indicate that individuals who deliver after assisted reproductive technologies (ART) may have an increased risk of cardiovascular disease (CVD). A recent large study from the U.S. showed a higher risk of stroke during the first year after delivery. To compare the risk of stroke during the first year after delivery according to the use of ART in the Nordic countries. Registry-based cohort study using nationwide data from Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015) and Sweden (1985-2015). Data on ART conception were available from ART quality registries and/or Medical Birth Registries (MBRs). National data on stroke were available from hospital and cause-of-death registries. The risk of stroke during the first year after delivery was estimated with Cox proportional hazard regression, adjusting for age, calendar year of delivery, multiple births, and country. A total of 2,659,272 primiparous individuals had a registered delivery in the MBRs during the study period, and 91,466 (4%) of these gave birth after ART. We observed no overall increased risk of stroke during the first year after delivery among individuals conceiving after ART (adjusted hazard ratio [HR] 1.10, 95% CI 0.77, 1.57). Similarly, there was no convincing evidence that the short-term risk of stroke was higher within 1, 2, 3, or 6 months after delivery, with adjusted HRs ranging between 1.23 and 1.33 and confidence intervals including the null value for all time periods. A secondary analysis also including multiparous individuals (n = 3,335,478) at the start of follow-up yielded similar findings. We found no evidence of an increased short-term risk of stroke among individuals who delivered after using ART.

Early pregnancy bleeding after assisted reproductive technology: a systematic review and secondary data analysis from 320 patients undergoing hormone replacement therapy frozen embryo transfer.

Early pregnancy bleeding after assisted reproductive technology: a systematic review and secondary data analysis from 320 patients undergoing hormone replacement therapy frozen embryo transfer.

Long-term healthcare utilization and costs of babies born after assisted reproductive technologies (ART): a record linkage study with 10-years' follow-up in England.

Is the long-term health care utilization of children born after ARTmore costly to the healthcare system in England than children born to mothers with no fertility problems? Children born after ART had significantly more general practitioner (GP) consultations and higher primary care costs up to 10 years after birth, and significantly higher hospital admission costs in the first year after birth, compared to children born to mothers with no fertility problems. There is evidence that children born after ART are at an increased risk of adverse birth outcomes and a small increased risk of rare adverse outcomes in childhood. We conducted a longitudinal study of 368088 mother and baby pairs in England using a bespoke linked dataset. Singleton babies born 1997-2018, and their mothers, who were registered at GP practices in England contributing data to the Clinical Practice Research Datalink (CPRD), were identified through the CPRD GOLD mother-baby dataset; this data was augmented with further linkage to the mothers' Human Fertilisation and Embryology Authority (HFEA) Register data. Four groups of babies were identified through the mothers' records: a 'fertile' comparison group, an 'untreated sub-fertile' group, an 'ovulation induction' group, and an ART group. Babies were followed-up from birth to 28 February 2021, unless censored due to loss to follow-up (e.g. leaving GP practice, emigration) or death. The CPRD collects anonymized coded patient electronic health records from a network of GPs in the UK. We estimated primary care costs and hospital admission costs for babies in the four fertility groups using the CPRD GOLD data and the linked Hospital Episode Statistics (HES) Admitted Patient Care (APC) data. Linear regression was used to compare the care costs in the different groups. Inverse probability weights were generated and applied to adjust for potential bias caused by attrition due to loss to follow-up. Children born to mothers with no fertility problems had significantly fewer consultations and lower primary care costs compared to the other groups throughout the 10-years' follow up. Regarding hospital costs, children born after ART had significantly higher hospital admission costs in the first year after birth compared to those born to mothers with no fertility problems (difference = £307 (95% CI: 153, 477)). The same pattern was observed in children born after untreated subfertility and ovulation induction. HFEA linkage uses non-donor data cycles only, and the introduction of consent for data use reduced the availability of HFEA records after 2009. The fertility groups were derived by augmenting HFEA data with evidence from primary care records; however, there remains some potential misclassification of exposure groups. The cost of neonatal critical care is not captured in the HES APC data, which may cause underestimation of the cost differences between the comparison group and the infertility groups. The findings can help anticipate the financial impact on the healthcare system associated with subfertility and ART, particularly as the demand for these treatments grows. C.C. and this work were funded by a UK Medical Research Council Career Development Award [MR/L019671/1] and a UK MRC Transition Support Award [MR/W029286/1]. X.H. is an Australia National Health and Medical Research Council (NHMRC) Emerging Leadership Fellow [grant number 2009253]. The authors declare no competing interest. N/A.

Cerebral palsy in children born after assisted reproductive technology in Norway: Risk, prevalence, and clinical characteristics.

The aim was to investigate the risk, prevalence, and clinical characteristics of cerebral palsy among children born after assisted reproductive technology (ART) in Norway. All liveborn children from 2002 to 2015 were included. Information was collected from the Medical Birth Registry of Norway, linked to the Norwegian Quality and Surveillance Registry for Cerebral Palsy as of December 31, 2022. Logistic regression analyses were used to calculate the prevalence of cerebral palsy per 1000 live births after ART and natural conception with birth year as covariate, crude odds ratios (OR) for cerebral palsy among children born after ART using children born after natural conception as reference, and OR adjusted for potential confounders, with 95% confidence intervals (CI). Potential mediators of the association were studied in stratified analyses. Descriptive statistics were used to compare proportions in clinical characteristics among children with cerebral palsy born after ART and natural conception. Among 833 645 livebirths, 23 645 children were born after ART and of the latter 97 were diagnosed with cerebral palsy. The overall prevalence of cerebral palsy after ART was 4.10 per 1000 live births (95% CI 3.36-5.00), decreasing from 7.79 per 1000 in 2002 to 3.55 in 2015. Compared with children born after natural conception, the OR for cerebral palsy was 2.01 (95% CI 1.63-2.47) adjusted for mother's age at birth, parity, and pre-pregnancy health. When restricted to singletons born at term, the adjusted OR for cerebral palsy was 1.13 (95% CI 0.76-1.69). The distribution of cerebral palsy subtypes and the severity of gross and fine motor function and associated impairments did not differ significantly between children with cerebral palsy born after ART and natural conception. Children born after ART had a risk of cerebral palsy that was twice that of children born after natural conception. The increased risk of cerebral palsy after ART is likely attributed to multiple pregnancies and preterm births. The prevalence of cerebral palsy after ART decreased significantly during the study period, despite an increased use of ART in the population. The distribution of clinical characteristics did not differ between children with cerebral palsy born after ART and those born after a natural conception, suggesting that the risk factors for, and causes of cerebral palsy were similar.

P-774 Congenital Heart Disease in Children Born after Assisted Reproductive Technology: A Nordic Cohort Study.

Abstract Study question Do children conceived after assisted reproductive technology (ART) have a higher risk of Congenital Heart Disease (CHD) in comparison with children born after spontaneous conception? Summary answer Children born after ART have a higher risk of a major CHD compared with children born after spontaneous conception. What is known already It is well-known that children born after ART have higher risk of birth defects compared to children born after spontaneous conception. Congenital heart disease (CHD) is the most common birth defect, accounting for almost 50% of all major birth defects. Several cohort studies and systematic reviews have also found an increased risk of CHD in children born after ART, a recent review included 41 studies and 25 856 ART children covering CHDs in ART children. Conflicting results have been reported for specific CHDs. Study design, size, duration This Nordic registry-based cohort study from CoNARTaS (Committee of Nordic ART and Safety) included 171 774 live births born after use of ART and 7 772 474 live births born after spontaneous conception during a study period of up to three decades (Denmark 1994-2014, Finland 1990-2014, Norway 1984-2015, and Sweden 1985-2015). National data from ART registries, medical birth registries, malformation registries, patient registries, cause of death registries, and population registries were crosslinked. Participants/materials, setting, methods International Classification of Diseases (ICD) versions 8, 9, 10 were used for CHD codes at birth and up to one year of age. Major CHDs were defined according to European Concerted Action on Congenital Anomalies and Twins (EUROCAT). According to EUROCAT, 26 of the major CHDs were considered as severe. All major CHDs were further classified into six different groups in a hierarchical order. Minor CHDs as well as stillbirths and pregnancy terminations were excluded. Main results and the role of chance Data from Sweden included a total of 3 228 526 singletons and multiples; 62 243 children conceived after use of ART and 3 166 283 children after spontaneous conception. Among ART children, 2.27% (n = 1411) were diagnosed with any major non-chromosomal CHD during their first year of life, corresponding figures for children born after spontaneous conception was 1.43% (n = 45 310) (Odds Ratio [OR] 1.60; 95% Confidence Interval (CI) 1.51 to 1.69, p &amp;lt; 0.0001). Severe CHD occurred in 0.40% (n = 249) in the ART group and 0.31% (n = 9 795) in the spontaneous conception group (OR 1.29; 95% CI 1.14 to 1.47, p &amp;lt; 0.0001). Ventricular septal defect was the most common CHD, 0.97% (n = 603) in the ART vs 0.64% (n = 20 343) in the spontaneous conception group (OR 1.51; 95% CI 1.39 to 1.64, p &amp;lt; 0.0001), followed by atrial septal defect; 0.84% (n = 525) in the ART and 0.42% (n = 13 363) in the spontaneous conception group (OR 2.00; 95% CI 1.83 to 2.19, p &amp;lt; 0.0001). Limitations, reasons for caution This analysis included only non-adjusted Swedish data. Further analysis will include Danish, Finnish, and Norwegian data with adjustments, and subgroup analysis on singletons and multiples. No data are available on prenatal diagnosis, or pregnancies not ending to a live birth. A skewed distribution in these outcomes might introduce a bias. Wider implications of the findings Pregnancies conceived after use of ART may benefit from screening with fetal echocardiography. Although most children with CHD reach adulthood, the mortality rate is still high for this group during the first years of life. Early detection with antenatal diagnosis and pre/postnatal intervention may be beneficial and improve the outcome. Trial registration number Not applicable

P-663 Serum anti-Müllerian hormone level to predict the chance of live birth after spontaneous or assisted conception: a systematic review and meta-analysis

Abstract Study question Is Serum anti-Müllerian hormone (AMH) level predictive of cumulative live birth (CLB) rate after assisted reproductive technologies (ART) or in women trying to conceive naturally? Summary answer Serum AMH level is linked to CLB after IVF/ICSI but data are lacking after intrauterine insemination (IUI) or in women trying to conceive without ART. What is known already Serum AMH level is a marker of ovarian reserve and a good predictor of ovarian response after controlled ovarian hyperstimulation. Literature is unclear whether its measurement can predict CLB in spontaneous or assisted conception. Study design, size, duration A systematic review and meta-analysis, following PRISMA guidelines, was undertaken to assess whether serum AMH level may predict chances of CLB in infertile women undergoing IVF/ICSI or IUI and/or chances of live birth in women having conceived naturally. Participants/materials, setting, methods A systematic review and meta-analysis was performed using the following keywords: “AMH”, “Anti-Müllerian Hormone”, “Live-Birth”, “Cumulative live birth”. Searches were conducted from January 2004 to May 2021 on PubMed and Embase. Two independent reviewers carried out study selection, quality assessment and bias assessment with QUIPS tool scale and data extraction. Odds ratio were estimated using random-effect model. Pre-specified sensitivity analyses and subgroup analyses were performed. The primary outcome was CLB. Main results and the role of chance A total of 32 studies were included in the meta-analysis. After IVF-ICSI, only 4 studies reported CLB rate according to AMH level. No statistically significant differences in mean serum AMH levels was shown between patients with and without CLB, but with a high heterogeneity [Difference in Means (95% CI) = 0.97 (-0.25;2.19) ng/mL; I² = 99%; p = 0.12; n = 4]. After exclusion of 2 studies with high risks of bias, there were no more heterogeneity [I²=0%] and the mean AMH level was statistically significantly higher in women with CLB [Difference in Means (95% CI)=0.86 (0.53;1.19) ng/mL; p &amp;lt; 0.00001; n = 2]. Overall, 27 articles were included in the meta-analysis of the relationship between AMH and CLB or AMH and LB after IVF/ICSI. A non-linear positive relationship was found in both cases. A polynomial fraction was the best model to describe it but no discriminant AMH threshold was shown. There were not enough articles/data to assess the ability of AMH to predict CLB rate or find an AMH threshold after IUI or in women without history of infertility trying to conceive without ART. Limitations, reasons for caution Systematic review and meta-analysis have some limitations due to the limits and bias of the studies included. In the present meta-analysis, heterogeneity may have been caused by different baseline characteristics in study participants, different stimulating protocols for ART, different serum AMH level threshold used and various assays of serum AMH. Wider implications of the findings Serum AMH level is linked to CLB rate after IVF/ICSI but no discriminating threshold can be established. Data are lacking concerning its predictive value after IUI or in women trying to conceive without ART. Our findings may be helpful to counsel candidate couples to IVF-ICSI. Trial registration number not applicable

O-200 Cardiometabolic health in Danish children aged 7-10 years born after assisted reproductive technology with frozen and fresh embryo transfer

Abstract Study question Is cardiometabolic health in children conceived after frozen embryo transfer (FET) different from children conceived after fresh embryo transfer (fresh-ET) and natural conception (NC)? Summary answer FET-children had similar anthropometrics, glucose- and lipid profile in childhood compared to fresh-ET and NC. Blood pressure was higher in FET-girls compared to fresh-ET-girls. What is known already Children conceived after assisted reproductive technology (ART) with FET are more often born large-for-gestational age (LGA) while children born after fresh-ET are at risk of being small-for-gestational age (SGA).In general, children born LGA or SGA are at increased risk of obesity, diabetes and cardiovascular disease later in life. Smaller studies on the whole ART-population have raised concerns about premature vascular aging, increased risk of insulin resistance and higher blood pressure. The long-term cardiometabolic health of children born after ART and especially FET is scarcely explored. Study design, size, duration This study was part of the large cohort study “Health in Childhood following Assisted Reproductive Technology” (HiCART) which included 606 singletons (292 boys) born between December 2009 and December 2013: 200 children were conceived after FET; 203 children were conceived after fresh-ET; and 203 children were conceived naturally and matched for birth year and sex. The study period lastet from January 2019 to September 2021. Participants/materials, setting, methods The children were 7-10 years of age at examination and underwent a clinical examination with anthropometric measurements, pubertal staging and blood pressure measurement. Furthermore a whole-body dual-energy x-ray absorptiometry-scan (DXA) was performed and a fasting blood sample was drawn. Anthropometric measurements and blood pressure were converted to standard deviation scores (SDS) using a Danish reference. The three study groups were compared pairwise using univariate linear regression model. Main results and the role of chance Data is presented as mean (SD). Children conceived after FET had significantly higher birth weight (SDS) (0.20 SDS (1.09)) compared to children conceived after fresh-ET (-0.22 SDS (1.00), mean difference: 0.42 SDS (95% CI: 0.21; 0.62)) and NC-children (-0.16 SDS (1.09), mean difference: 0.35 SDS (95% CI: 0.14; 0.57)). At 7-10 years height (SDS), weight (SDS) and BMI (SDS) were similar between the groups. Fat percentage (DXA) and waist-to-height ratio were also comparable between the groups. Markers of glucose metabolism were similar in the groups including fasting glucose, C-peptide, HbA1c and insulin resistance (HOMA-IR). Lipid profiles including, cholesterol, LDL and HDL were also similar. Blood pressure was comparable between the three groups, but stratified on sex girls conceived after FET had significantly higher systolic blood pressure (SDS) (0.75 SDS (0.84)) compared to girls concieved after fresh-ET (0.49 SDS (0.61), mean difference: 0.25 SDS (95% CI: 0.05; 0.45)) and significantly higher diastolic blood pressure (SDS) (FET: 0.54 SDS (0.57), fresh-ET: 0.38 (0.58), mean difference: 0.16 SDS (0.00; 0.31)). Puberty had started in 17% of the girls, equally distributed in the three groups. Limitations, reasons for caution As the participation rate was between 18-42% in the three groups, selection bias cannot be excluded. We currently do not have information regarding endometrial preparation protocol in the FET-cycles which may bias the results. Due to multiple testing type I errors cannot be excluded. Wider implications of the findings Higher birth weight in children conceived after FET did not translate into differences in anthropometrics, glucose- or lipid profile in children ages 7-10 years. However, the higher systolic- and diastolic blood pressure (SDS) found in girls concieved after FET compared to fresh-ET is of concern and should be further explored. Trial registration number NNF18OC0034092, NFF19OC0054340

Prevalence of Low and High BMI in Patients with Infertility

Background: The number of individuals who are underweight as well as overweight is increasing worldwide and is known to lead to menstrual disorders and subfertility. Data regarding the prevalence of infertility in Austrian women are lacking. This study aimed to determine the prevalence of a pathologically low and high body mass index (BMI) in Austrian patients with infertility and to evaluate the live birth rate (LBR) after assisted reproductive technologies (ARTs) compared with normal weight patients. Methods: A total of 585 couples with infertility who sought treatment at a single center between April 2017 and April 2019 were included in this retrospective study. The patients were categorized into study group 1 (BMI &lt;19 kg/m2, n = 35), study group 2 (BMI &gt;30 kg/m2, n = 40), and control group (BMI 19–30 kg/m2, n = 95. They were randomly selected from the n = 522 women within these BMI values). Results: The prevalence rates of BMI &lt;19 kg/m2 and BMI &gt;30 kg/m2 were 5.9% and 6.7%, respectively. Baseline clinical and laboratory characteristics as well as the prevalence of pathospermia in their male partners were similar in all study groups. In women undergoing ART (n = 112), LBR was comparable between the study groups (27.3% vs. 31.9% and 22.2%, p = 0.4). Conclusions: The prevalence of low and high BMI in Austrian patients seeking fertility treatment was almost 13%. Although LBR was not reduced, physicians should be more attentive to the BMI values of patients with infertility because pregnancy-related complications are linked to being underweight and obese.

Long-term outcomes for children conceived by assisted reproductive technology

Worldwide, more than 10 million children have been born after Assisted Reproduction Technology (ART) and comprised up to 7.9% of children born in Europe and up to 5.1 % of children born in the US in 2018 (1, 2). The short-term outcome for children born after ART is well-known from numerous publications, with higher rates of preterm birth and low birth weight in children born after fresh embryo transfer and higher rates of large for gestational age and high birth weight in children born after frozen embryo transfer compared to children born after spontaneous conception (3, 4). Higher rates of birth defects in children born after ART have also been shown consistently over time (5). Studies on long-term health outcomes after ART are scarcer but suggest an increased risk of altered blood pressure and cardiovascular function in children born after ART. In this review we summarize long-term health outcomes in children born after ART and discuss if the increased health risks are associated with intrinsic maternal or paternal factors related to sub fertility or to the ART treatments per se. Finally, we speculate where the future will bring us with regards to ART treatment strategies and safety of the mother and child.

Pregnancy incidence and associated risk factors of dichorionic triamniotic triplet under assisted reproduction: A large sample of clinical data analysis.

Dichorionic triamniotic (DCTA) triplet pregnancies are rare in spontaneous pregnancy. The aim was to characterize the incidence and risk factors of DCTA triplet pregnancies after assisted reproductive technology (ART). A retrospective analysis of 10,289 patients, including 3,429 fresh embryo transfer (ET) cycle and 6,860 frozen ET cycle, was performed from January 2015 to June 2020. The effect of different ART parameters on the incidence of DCTA triplet pregnancies was evaluated by multivariate logistic regression analyses. Among all clinical pregnancies after ART, the incidence of DCTA was 1.24%. 1.22% occurred in the fresh ET cycle, while 1.25% occurred in the frozen ET cycle. The number of ET and cycle type has no effect on the occurrence of DCTA triplet pregnancies (p = 0.987; p = 0.056, respectively). There were significant differences in DCTA triplet pregnancies rate among receiving intracytoplasmic sperm injection (ICSI) and receiving in vitro fertilization (IVF) [1.92% vs. 1.02%, p < 0.001, OR = 0.461, 95% confidence interval (CI) 0.315-0.673], blastocyst transfer (BT) versus cleavage-ET (1.66% vs. 0.57%, P < 0.001, OR = 0.329, 95% CI 0.315-0.673), and maternal age ≥ 35 years versus maternal age < 35 years (1.00% vs. 1.30%, P = 0.040, OR = 1.773, 95% CI 1.025-3.066). Based on the regression analysis of cycle type, DCTA triplet pregnancies rate was higher in maternal age < 35 years than in maternal age ≥ 35 years (1.35% vs. 0.97%, P < 0.001, OR = 5.266, 95% CI 2.184-12.701), BT versus cleavage-ET (1.47% vs. 0.94%; P = 0.006, OR = 0.346, 95% CI 0.163-0.735), and receiving ICSI was higher than receiving IVF (3.82% vs. 0.78%, p < 0.001, OR = 0.085, 95% CI 0.039-0.189) in fresh ET cycle. However, DCTA triplet pregnancies rate did not show difference in maternal age, insemination methods, and number of ET, and only BT was found to be associated with a higher DCTA triplet pregnancies rate in the frozen ET cycle (1.73% vs. 0.30%, p < 0.001, OR = 0.179, 95% CI 0.083-0.389). The prevalence of DCTA triplet pregnancies has increased after ART. Maternal age < 35 years, BT, and receiving ICSI are risk factors for DCTA triplet pregnancies, also in fresh ET cycle. However, in frozen ET cycle, BT is an independent risk factor for increased DCTA triplet pregnancies rate.

Trends in the incidence of major birth defects after assisted reproductive technologies in Lombardy Region, Northern Italy

PurposeThe incidence of birth defects is increased in children born after assisted reproductive technologies (ART). However, changes in ART over time could influence this incidence. To investigate this issue, we present the frequency and trends of birth defects in ART and natural pregnancies in Lombardy, Northern Italy, during the period 2014–2020.MethodsThis is a population-based study using automated system of healthcare utilization (HCU) databases. ART pregnancies included only those obtained with conventional IVF or ICSI. After identifying the total number of deliveries, the rate of newborns with birth defects was compared between natural and ART pregnancies. A logistic regression model was used to calculate the adjusted odd ratio (OR). Analyses were repeated for every calendar year.ResultsOverall, 508,421 deliveries were identified, of which 14,067 (2.8%) were achieved after IVF-ICSI. A decreasing trend in birth defects over time was highlighted. The adjusted OR dropped from 1.40 (95%CI: 1.03–1.91) in 2014 to 0.92 (95%CI: 0.69–1.22) in 2020. During the study period, a significant reduction in multiple pregnancy and in the ratio of ICSI to conventional IVF was also observed, explaining at least in part the positive trend observed for birth defects.ConclusionThe increased risk of birth defects in children born after IVF-ICSI is not steady over time. A decline of this risk emerged in our region. Policy changes in ART may explain this beneficial effect.

The challenges of selective fertility and carryover effects in within-sibship analyses: the effect of assisted reproductive technology on perinatal mortality as an example.

Within-sibship analyses show lower perinatal mortality after assisted reproductive technology (ART) compared with natural conception (NC), a finding that appears biologically unlikely. We investigated whether this may be attributed to bias from selective fertility and carryover effects. Using data from national registries in Denmark (1994-2014), Finland (1990-2014) and Norway and Sweden (1988-2015), we studied 5 722 826 singleton pregnancies, including 119 900 ART-conceived and 37 590 exposure-discordant sibships. Perinatal mortality at the population level and within sibships was compared using multilevel logistic regression with random and fixed intercepts, respectively. We estimated selective fertility as the proportion of primiparous women with and without perinatal loss who had a second delivery, and carryover effects through bidirectional and crosswise associations. Population analysis showed higher perinatal mortality among ART conception compared with NC (odds ratio 1.21, 95% CI 1.13 to 1.30), whereas within-sibship analysis showed the opposite (OR 0.36, 95% CI 0.31 to 0.43). Primiparous women with perinatal loss were more likely to give birth again (selective fertility) and to use ART in this subsequent pregnancy (carryover effects), resulting in strong selection of double-discordant sibships with death of the naturally conceived and survival of the ART-conceived sibling. After controlling for conception method and outcome in the first pregnancy, ART was not consistently associated with perinatal mortality in the second pregnancy. Whereas population estimates may be biased by residual confounding, within-sibship estimates were biased by selective fertility and carryover effects. It remains unclear whether ART conception contributes to perinatal mortality.

Expectant treatment for angular pregnancy after assisted reproduction technology: a safe and patient-friendly treatment strategy.

Currently, the treatment strategies for angular pregnancy in the first trimester after assisted reproduction technology (ART) are unclear. Improper treatment will cause unnecessary losses to patients, especially infertile patients, after ART. The purpose of this study was to clarify the pregnancy outcomes of expectant treatment for angular pregnancy post-ART and to provide a basis for the formulation of clinical treatment strategies. This retrospective case series study was performed at the Reproductive Medicine Center of a university hospital. Maternal data and pregnancy outcomes were collected and analyzed for all patients diagnosed with angular pregnancies after ART between January 2016 and August 2021. The outcomes included live birth, term birth, premature birth, early pregnancy loss, fetal death, placental abruption, uterine rupture, maternal death, and hysterectomy. A total of 78 patients were analyzed in this study, of whom 54 (69.2%) had live births, 44 (56.4%) had term births, 21 (26.9%) had an early pregnancy loss, 1 (1.3%) had mid-trimester missed abortion, 1 (1.3%) underwent mid-trimester labor induction due to fetal malformation, and 1 (1.3%) underwent uterine rupture. There were no cases of maternal death, placental abruption, or hysterectomies. Angular pregnancy after ART is not as dangerous as that described in previous studies; most cases could be treated expectantly under close-interval follow-up and obtain live birth.

Risk of ovarian cancer in women who give birth after assisted reproductive technology (ART)-a registry-based Nordic cohort study with follow-up from first pregnancy.

There is concern that assisted reproductive technology (ART) may increase ovarian cancer risk, but previous studies are inconclusive. We compared ovarian cancer risk for women who gave birth after ART vs natural conception. Through linkage of nationwide registry data, we followed 3,303,880 initially nulliparous women in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015) and Sweden (1985-2015) from first pregnancy ≥22 weeks to ovarian cancer, emigration, death or end of follow-up (2014/2015). We estimated hazard ratios (HRs), adjusting for age, parity, maternal birth year and country, and for body mass index and smoking in subsamples. Mean age at first birth was 27.7 years. During a mean follow-up of 14.4 person-years, 2683 participants (0.08%) developed ovarian cancer; 135 after ART and 2548 after natural conception only (incidence rates 11.6 and 5.5 per 100,000 person-years, respectively). The risk was higher for women who ever gave birth after ART (HR 1.70, 95% confidence interval 1.42-2.03) compared to natural conception. Associations were stronger for conventional in vitro fertilisation than for intracytoplasmic sperm injection. Among parous women, ART-conception was associated with a higher risk of ovarian cancer than natural conception. Further studies should decipher whether this is causal or confounded by infertility or other factors.

Association between Abortion History and Perinatal and Neonatal Outcomes of Singleton Pregnancies after Assisted Reproductive Technology

At present, few people have studied the associations between abortion history before pregnancy on the outcomes of women and their infants after assisted reproductive technology (ART). To explore the association between the history of abortion and the outcomes of singleton pregnancies after ART. This was a retrospective study in a hospital from 2015 to 2020 in Shanghai, China. Pregnant women with live singleton births through ART were included (n = 3043). Abortion was classified into spontaneous abortion (SAB) and induced abortion. We compared the maternal and fetal outcomes of singleton pregnancies obtained through ART with different abortion histories. Logistic regression analysis was used to evaluate the associations between the history of pre-pregnancy abortion with perinatal complications and neonatal outcomes. We observed that compared with those who had no abortion history and obtained singleton pregnancies through ART, women who had an abortion history before pregnancy (including SAB or induced abortion history) and only SAB history were more likely to have gestational diabetes mellitus (GDM), thyroid-related diseases, and placenta-related diseases. After adjusting the potential confounding factors, these differences still existed. The adjusted odds ratios (ORs) and 95% confidence interval (CI) of GDM, thyroid-related diseases, and placenta-related diseases in women with a history of abortion and only a history of SAB were 1.239 (1.030-1.492) and 1.240 (1.010-1.522), 1.589 (1.261-2.002) and 1.724 (1.344-2.213), 1.465 (1.183-1.815) and 1.433 (1.132-1.814), respectively. However, we did not observe the association between the history of induced abortion and GDM and thyroid-related diseases. Our research showed that pregnant women with singleton pregnancies through ART who had a history of abortion or only a history of SAB were more likely to have GDM, thyroid-related diseases, and placenta-related diseases. Pregnant women who had both SAB and induced abortion before pregnancy had a higher risk of thyroid-related diseases and placenta-related diseases, while women who had only a history of induced abortion had a higher risk of placenta-related diseases. Further research is needed to explore the biological mechanism of different types of abortion related to subsequent pregnancy.

Effect of a 60-day weight reduction intervention prior to IVF/ICSI on perinatal outcomes in overweight or obese infertile women.

The aim of this study was to determine whether a 60-day weight reduction intervention prior to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and a higher weight loss ratio effectively improved perinatal outcomes for infertile overweight or obese women. This was a retrospective cohort study conducted at a university-affiliated fertility center. Two thousand three hundred and eighty-one overweight or obese infertile women who underwent or did not undergo a 60-day weight reduction intervention prior to IVF/ICSI between February 27, 2017 and November 11, 2020 were included in this study. All of these women achieved clinical pregnancy and delivered a single child after assisted reproductive technology (ART). Primary outcomes included neonatal birth weight and the incidence of pregnancy complications, premature delivery, and low birth weight. The body mass index (BMI), blood glucose concentration, serum insulin level, and homeostasis model assessment of insulin resistance (HOMA-IR) of the intervention group decreased significantly after the weight reduction intervention. Neonatal birth weight was significantly higher in the intervention group (3519.6g ±484.8 g) than the control group (3406.8g ± 554.2g; P < 0.001). There was no significant difference in the incidence of pregnancy complications between the two groups. Linear regression analysis found that the weight reduction intervention prior to IVF/ICSI and lower HOMA-IR at ovulation induction were associated with increased birth weight. As the weight loss ratio increased, the incidence of hypertensive disorders of pregnancy, premature membrane rupture, premature delivery, stillbirth, and low birth weight showed a downward trend. A 60-day weight reduction intervention prior to IVF/ICSI may increase neonatal birth weight, reduce maternal blood glucose concentration, and improve maternal insulin resistance in infertile overweight or obese women. This results require to be further verified by prospective randomized controlled trials with a larger sample size.