The impact of caesarean scar niche on fertility - a systematic review.

BACKGROUND: The trend of increasing caesarean section (CS) rates brings up questions related to subfertility. Research regarding the influence of CS on assisted reproduction techniques (ART) is conflicting. A potential mechanism behind CS-induced subfertility is intra uterine fluid resulting from a caesarean scar defect or niche. The vaginal microbiome has been repeatedly connected to negative ART outcomes, but it is unknown if the microbiome is changed in relation to a niche. METHODS: This systematic review describes literature investigating the effect of a niche on live birth rates after assisted reproduction. Furthermore, studies investigating a difference in microbial composition in subfertile persons with a niche compared to no niche are evaluated. Pubmed, Embase and Web of Science were searched on March 2023 for comparative studies on both study questions. Inclusion criteria were i.e., English language, human-only studies, availability of the full article and presence of comparative pregnancy data on a niche. The quality of the included studies and their risk of bias were assessed using the Newcastle-Ottawa scale for cohort studies. The results were graphically displayed in a forest plot. RESULTS: Six retrospective cohort studies could be included on fertility outcomes, with a total of 1083 persons with a niche and 3987 without a niche. The overall direction of effect shows a negative impact of a niche on the live birth rate (pooled aOR 0.58, 95% CI 0.48-0.69) with low-grade evidence. Three studies comparing the microbiome between persons with and without a CS could be identified. CONCLUSION: There is low-grade evidence to conclude that the presence of a niche reduces live birth rates when compared to persons without a niche. The theory that a caesarean has a negative impact on pregnancy outcomes because of dysbiosis promoted by the niche is interesting, but there is no sufficient literature about this.

The increasing number of caesarean deliveries has raised concerns about how it might affect a woman's ability to get pregnant afterwards. Some studies suggest that having a caesarean section (CS) could make it harder to conceive, particularly through in vitro fertilisation (IVF). The reason could be the scar or niche from a previous caesarean. This niche can cause fluid inside the uterus. We also know that the mix of bacteria in the vagina, called the vaginal microbiome, can affect a woman's chances of getting pregnant, especially with treatments like IVF. But we are not sure if having a caesarean affects the vaginal microbiome.To understand this better, van den Tweel's team looked at studies on whether having a niche from a caesarean affects a woman's chance of having a baby through IVF. They also looked at studies comparing the bacteria in the vagina of women who have had a caesarean with those who have not. They found that having a caesarean niche makes it harder for a woman to have a baby through IVF. However, the evidence from these studies is not very strong. We still do not know enough about whether having a caesarean niche affects the bacteria in the vagina.

Medically Assisted Reproduction and Risk of Cancer Among Offspring.

Importance: Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations. Objective: To assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally. Design, Setting, and Participants: For this cohort study, the French National Mother-Child Register (EPI-MERES) was searched for all live births that occurred in France between January 1, 2010, and December 31, 2021 (and followed up until June 30, 2022). The EPI-MERES was built from comprehensive data of the French National Health Data System. Data analysis was performed from December 1, 2021, to June 30, 2023. Exposure: Use of assisted reproduction technologies (ART), such as fresh embryo transfer (ET) or frozen ET (FET), and artificial insemination (AI). Main Outcomes and Measures: The risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or AI and children conceived naturally, using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth. Results: This study included 8 526 306 children with a mean (SD) age of 6.4 (3.4) years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation. There were 260 236 children (3.1%) born after MAR, including 133 965 (1.6%) after fresh ET, 66 165 (0.8%) after FET, and 60 106 (0.7%) after AI. A total of 9256 case patients with cancer were identified over a median follow-up of 6.7 (IQR, 3.7-9.6) years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively. The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12 [95% CI, 0.96 to 1.31]), FET (HR, 1.02 [95% CI, 0.78 to 1.32]), or AI (HR, 1.09 [95% CI, 0.86 to 1.38]). However, the risk of acute lymphoblastic leukemia was higher among children born after FET (20 case patients; HR 1.61 [95% CI, 1.04 to 2.50]; risk difference [RD], 23.2 [95% CI, 1.5 to 57.0] per million person-years) compared with children conceived naturally. Moreover, among children born between 2010 and 2015, the risk of leukemia was higher among children born after fresh ET (45 case patients; HR, 1.42 [95% CI, 1.06 to 1.92]; adjusted RD, 19.7 [95% CI, 2.8 to 43.2] per million person-years). Conclusions and Relevance: The findings of this cohort study suggest that children born after FET or fresh ET had an increased risk of leukemia compared with children conceived naturally. This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART.

Assisted reproductive techniques and subsequent risk of asthma and allergic rhinitis in offspring: a nationwide birth cohort study in South Korea.

OBJECTIVE: The relationship between assisted reproductive techniques (ART) and the risk of asthma and allergic rhinitis (AR) is controversial. Thus, we aimed to investigate the relationship between ART and the risk of asthma and AR in a nationwide, large-scale birth cohort. PATIENTS AND METHODS: This study utilized the National Health Insurance Service data in South Korea to conduct a nationwide, large-scale, population-based birth cohort. We included all infants born between 2017 and 2018. AR, asthma, food allergies, and atopic dermatitis were defined using the International Classification of Diseases tenth edition codes. Asthma was classified as allergic or non-allergic based on accompanying allergic diseases (AR, food allergy, or atopic dermatitis). Using 1:10 propensity score matching, we compared infants conceived through ART with those conceived naturally (non-ART). After matching, logistic regression was used to compare the hazard ratio for asthma and AR between the two groups. RESULTS: We included 543,178 infants [male infants, 280,194 (51.38%)]. After matching, 8,925 and 74,229 infants were selected for the ART and non-ART groups, respectively. The ART group showed a decreased risk of asthma in the offspring [adjusted hazard ratio (aHR), 0.45; 95% confidence interval (CI), 0.41-0.48]. Similarly, for AR, being conceived by ART was associated with a decreased risk of AR (aHR, 0.25; 95% CI, 0.12-0.37). ART offspring showed a decreased risk of asthma and AR in offspring compared to that observed in non-ART offspring. CONCLUSIONS: Our study offers important insights for clinicians, researchers, and parents regarding the health outcomes of ART-conceived infants and enhances our understanding of ART's impact on respiratory health.

Consumption of hookahs, e-cigarettes, and classic cigarettes and the impact on medically assisted reproduction treatment.

Smoking of classic cigarettes has been well-established as a health risk factor, including cardiovascular, neurological, and pulmonary diseases. Adverse effects on human reproduction have also been shown. Smokers are assumed to have a significantly lower chance of pregnancy, however, the impact of smoking on medically assisted reproduction (MAR) treatment outcomes is controversial. Moreover, smoking habits have changed during the last decades since e-cigarettes and hookahs, or water pipes, have become very popular, yet little is known regarding vaping or hookah-smoking patients undergoing MAR treatments. This prospective study aimed to examine the presence of benzo[a]pyrene, nicotine, and its main metabolite, cotinine, in human follicular fluid (FF) in non-smoking, smoking, and vaping/hookah-smoking patients and to evaluate the impact on female fertility. Human FF samples were collected from 320 women subjected to intracytoplasmic sperm injection (ICSI) cycles due to male subfertility. Gas chromatography combined with mass spectrometry was used to analyse the presence of benzo[a]pyrene, nicotine, and cotinine. A questionnaire was provided to assess patient consumption behaviour and to identify (1) non-smoking patients, (2) patients who consumed cigarettes, and (3) patients with exclusive consumption of e-cigarettes or hookahs. Data were analysed using linear and logistic regression, Fisher's exact test, and the Mann-Whitney U Test. Nicotine was present in 22 (6.8%) and cotinine in 65 (20.3%) of the 320 samples. The nicotine and cotinine concentrations per sample ranged from 0 to 26.3 ng/ml and 0-363.0 ng/ml, respectively. Benzo[a]pyrene was not detectable in any of the samples analysed. Nicotine and cotinine were also present in the FF of patients with exclusive consumption of e-cigarettes or hookahs. The clinical pregnancy rate, fertilization and maturation rates, and number of oocytes per oocyte pick-up were not statistically significantly different between non-smoking, smoking, or vaping/hookah-smoking patients. Smoking and the accumulation of smoking toxins in the FF have no impact on the outcome of MAR treatments-neither the clinical pregnancy rate, maturation and fertilization rates, nor the number of retrieved oocytes were affected. For the first time, nicotine and cotinine were quantified in the FF of patients exclusively vaping e-cigarettes or smoking hookahs. Since vaping liquids and hookah tobaccos contain potentially harmful substances, other adverse effects cannot be excluded.Trial registration ClinicalTrials.gov Identifier: NCT03414567.

Assisted reproduction and congenital malformations: A systematic review and meta-analysis.

Prior studies have explored the links between congenital anomalies and assisted reproduction techniques, among other factors. However, it remains unclear whether a particular technique harbors an inherent risk of major congenital anomalies, either cumulatively or in an organ-specific manner. A meta-analysis was conducted using relevant studies from inception to February 2023 using six databases and two appropriate registers. Sources of heterogeneity were explored using sub-group analysis, using study weight, risk of bias and geographical location of original studies. Neonates conceived through assisted reproduction appear to have a higher risk of major congenital anomalies compared to naturally conceived neonates, OR 0.67 [95% CI 0.59, 0.76], I2 = 97%, p < 0.00001, with neonates conceived through intracytoplasmic sperm injection (ICSI) at a 9% higher chance of being affected in comparison to neonates conceived through in vitro fertilization (IVF). The increase in cardiac, gastrointestinal (GI), and neurological congenital anomalies appears to be independent of the assisted reproduction technique, while urogenital and musculoskeletal (MSK) anomalies were found to be increased in ICSI compared with IVF, OR 0.83 [95% CI 0.69, 0.98]; p = 0.03, I2 = 0%, and OR 0.65 [95% CI 0.49, 0.85]; p = 0.002, I2 = 80%, respectively. Neonates conceived using assisted reproduction techniques appear to be at higher risk of major congenital anomalies, with a higher risk attributable to conception using ICSI. The increase in cardiac, neurological, and GI congenital anomalies does not appear to be technique-specific, while the opposite held true for urogenital and MSK anomalies.

Assisted reproductive technology-associated risk factors for placenta accreta spectrum after vaginal delivery.

This study aimed to investigate assisted reproductive technology (ART) factors associated with placenta accreta spectrum (PAS) after vaginal delivery. This was a registry-based retrospective cohort study using the Japanese national ART registry. Cases of live singleton infants born via vaginal delivery after single embryo transfer (ET) between 2007 and 2020 were included (n = 224,043). PAS was diagnosed in 1412 cases (0.63% of deliveries), including 1360 cases (96.3%) derived from frozen-thawed ET cycles and 52 (3.7%) following fresh ET. Among fresh ET cycles, assisted hatching (AH) (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI] 1.4-4.7) and blastocyst embryo transfer (aOR, 2.2; 95% CI 1.3-3.9) were associated with a significantly increased risk of PAS. For frozen-thawed ET cycles, hormone replacement cycles (HRCs) constituted the greatest risk factor (aOR, 11.4; 95% CI 8.7-15.0), with PAS occurring in 1.4% of all vaginal deliveries following HRC (1258/91,418 deliveries) compared with only 0.11% following natural cycles (55/47,936). AH was also associated with a significantly increased risk of PAS in frozen-thawed cycles (aOR, 1.2; 95% CI 1.02-1.3). Our findings indicate the need for additional care in the management of patients undergoing vaginal delivery following ART with HRC and AH.

Time to childbirth and assisted reproductive treatment in women with congenital heart disease.

OBJECTIVE: To investigate the time to first childbirth and to compare the prevalence of assisted reproductive treatment (ART) in women with congenital heart disease (CHD) compared with women without CHD. METHODS: All women in the national register for CHD who had a registered first childbirth in the Swedish Pregnancy Register between 2014 and 2019 were identified. These individuals (cases) were matched by birth year and municipality to women without CHD (controls) in a 1:5 ratio. The time from the 18th birthday to the first childbirth and the prevalence of ART was compared between cases and controls. RESULTS: 830 first childbirths in cases were identified and compared with 4137 controls. Cases were slightly older at the time for first childbirth (28.9 vs 28.5 years, p=0.04) and ART was more common (6.1% vs 4.0%, p<0.01) compared with controls. There were no differences in ART when stratifying for the complexity of CHD. For all women, higher age was associated with ART treatment (OR 1.24, 95% CI 1.20 to 1.28). CONCLUSIONS: Women with and without CHD who gave birth to a first child did so at similar ages. ART was more common in women with CHD, but disease severity did not influence the need for ART. Age was an important risk factor for ART also in women with CHD and should be considered in consultations with these patients.

Estimating the impact of bias in causal epidemiological studies: the case of health outcomes following assisted reproduction.

Researchers interested in causal questions must deal with two sources of error: random error (random deviation from the true mean value of a distribution), and bias (systematic deviance from the true mean value due to extraneous factors). For some causal questions, randomization is not feasible, and observational studies are necessary. Bias poses a substantial threat to the validity of observational research and can have important consequences for health policy developed from the findings. The current piece describes bias and its sources, outlines proposed methods to estimate its impacts in an observational study, and demonstrates how these methods may be used to inform debate on the causal relationship between medically assisted reproduction (MAR) and health outcomes, using cancer as an example. In doing so, we aim to enlighten researchers who work with observational data, especially regarding the health effects of MAR and infertility, on the pitfalls of bias, and how to address them. We hope that, in combination with the provided example, we can convince readers that estimating the impact of bias in causal epidemiologic research is not only important but necessary to inform the development of robust health policy and clinical practice recommendations.

Ovulation induction and subfertile untreated conception groups offer improved options for interpreting risks associated with ART.

PURPOSE: To identify and characterise appropriate comparison groups for population studies of health outcomes in ART-conceived births: ovulation induction (OI), subfertile untreated and fertile natural conceptions. Our secondary objective was to examine whether known risks of pregnancy complications and adverse birth outcomes in ART births are elevated in comparison with subfertile (untreated and OI) conception groups. METHODS: We linked State and Commonwealth datasets to identify all live and stillbirths (≥ 20 weeks) in Western Australia from 2003 to 2014 by method of conception. Demographic characteristics, maternal pre-existing conditions, adverse obstetric history and pregnancy complications were compared across conception groups. Generalised estimating equations were used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CI) for pregnancy complications and birth outcomes in singletons. RESULTS: We identified 9456 ART, 3870 OI, 11,484 subfertile untreated and 303,921 fertile naturally conceived deliveries. OI and subfertile untreated groups more closely resembled the ART group than the fertile group; however, some differences remained across parity, maternal age, pre-existing conditions and obstetric history. In multivariate analyses, ART singletons had greater risks of placental problems (e.g. placenta praevia aRR 2.42 (95% CI 1.82-3.20)) and adverse birth outcomes (e.g. preterm birth aRR 1.38 (95% CI 1.25-1.52)) than the subfertile untreated group, while OI singletons were more similar to the subfertile group with higher risk of preeclampsia and gestational diabetes. CONCLUSION: OI and subfertile untreated conception groups offer improved options for interpreting health outcomes in ART births. Pregnancy complications (particularly placental disorders) and adverse outcomes at delivery are more common following ART.

Pregnancy following assisted reproductive technology in morbidly obese patients: assessment of feto-maternal outcomes.

PURPOSE: To examine feto-maternal characteristics and outcomes of morbidly obese pregnant patients who conceived with assisted reproductive technology (ART). METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. Study population was 48,365 patients with ART pregnancy from January 2012 to September 2015, including non-obesity (n = 45,125, 93.3%), class I-II obesity (n = 2445, 5.1%), and class III obesity (n = 795, 1.6%). Severe maternal morbidity at delivery per the Centers for Disease and Control Prevention definition was assessed with multivariable binary logistic regression model. RESULTS: Patients in the class III obesity group were more likely to have a hypertensive disorder (adjusted-odds ratio (aOR) 3.03, 95% confidence interval (CI) 2.61-3.52), diabetes mellitus (aOR 3.08, 95%CI 2.64-3.60), large for gestational age neonate (aOR 3.57, 95%CI 2.77-4.60), and intrauterine fetal demise (aOR 2.03, 95%CI 1.05-3.94) compared to those in the non-obesity group. Increased risks of hypertensive disease (aOR 1.35, 95%CI 1.14-1.60) and diabetes mellitus (aOR 1.39, 95%CI 1.17-1.66) in the class III obesity group remained robust even compared to the class I-II obesity group. After controlling for priori selected clinical, pregnancy, and delivery factors, patients with class III obesity were 70% more likely to have severe maternal morbidity at delivery compared to non-obese patients (8.2% vs 4.4%, aOR 1.70, 95%CI 1.30-2.22) whereas those with class I-II obesity were not (4.1% vs 4.4%, aOR 0.87, 95%CI 0.70-1.08). CONCLUSIONS: The results of this national-level analysis in the United States suggested that morbidly obese pregnant patients conceived with ART have increased risks of adverse fetal and maternal outcomes.

Maternal and perinatal outcomes in twin pregnancies following assisted reproduction: a systematic review and meta-analysis involving 802 462 pregnancies.

BACKGROUND: ART is associated with higher rates of twin pregnancies than singleton pregnancies. Whether twin pregnancies conceived following ART have additional maternal and neonatal complications compared with non-ART twin pregnancies is not known. OBJECTIVE AND RATIONALE: The objective was to quantify the risk of adverse maternal and perinatal outcomes among twin pregnancies conceived following ART compared with non-ART and natural conception. Existing reviews vary in the reported outcomes, with many studies including triplet pregnancies in the study population. Therefore, we aimed to perform an up-to-date review with an in-depth analysis of maternal and perinatal outcomes limited to twin pregnancies. SEARCH METHODS: We searched electronic databases MEDLINE and EMBASE from January 1990 to May 2023 without language restrictions. All cohort studies reporting maternal and perinatal outcomes following ART compared with non-ART twin pregnancies and natural conception were included. Case-control studies, case reports, case series, animal studies, and in vitro studies were excluded. The Newcastle-Ottawa Scale was used to assess the methodological quality of the studies. Using random-effects meta-analysis, the estimates were pooled and the findings were reported as odds ratios (OR) with 95% CI. OUTCOMES: We included 111 studies (802 462 pregnancies). Twin pregnancies conceived following ART were at higher risk of preterm birth at <34 weeks (OR 1.33, 95% CI 1.14-1.56, 29 studies, I2 = 73%), <37 weeks (OR 1.26, 95% CI 1.19-1.33, 70 studies, I2 = 76%), hypertensive disorders in pregnancy (OR 1.29, 95% CI 1.14-1.46, 59 studies, I2 = 87%), gestational diabetes mellitus (OR 1.61, 95% CI 1.48-1.75, 51 studies, I2 = 65%), and caesarean delivery (OR 1.80, 95% CI 1.65-1.97, 70 studies, I2 = 89%) compared with non-ART twins. The risks for the above maternal outcomes were also increased in the ART group compared with natural conception. Of the perinatal outcomes, ART twins were at significantly increased risk of congenital malformations (OR 1.17, 95% CI 1.05-1.30, 39 studies, I2 = 59%), birthweight discordance (>25% (OR 1.31, 95% CI 1.05-1.63, 7 studies, I2 = 0%)), respiratory distress syndrome (OR 1.32, 95% CI 1.09-1.60, 16 studies, I2 = 61%), and neonatal intensive care unit admission (OR 1.24, 95% CI 1.14-1.35, 32 studies, I2 = 87%) compared with non-ART twins. When comparing ART with natural conception, the risk of respiratory distress syndrome, intensive care admissions, and birthweight discordance >25% was higher among the ART group. Perinatal complications, such as stillbirth (OR 0.83, 95% CI 0.70-0.99, 33 studies, I2 = 49%), small for gestational age <10th centile (OR 0.90, 95% CI 0.85-0.95, 26 studies, I2 = 36%), and twin-twin transfusion syndrome (OR 0.45, 95% CI 0.25-0.82, 9 studies, I2 = 25%), were reduced in twin pregnancies conceived with ART versus those without ART. The above perinatal complications were also fewer amongst the ART group than natural conception. WIDER IMPLICATIONS: ART twin pregnancies are associated with higher maternal complications than non-ART pregnancies and natural conception, with varied perinatal outcomes. Women seeking ART should be counselled about the increased risks of ART twin pregnancies and should be closely monitored in pregnancy for complications. We recommend exercising caution when interpreting the study findings owing to the study's limitations.

Association of Assisted Reproductive Technology and Stroke During Hospitalization for Delivery in the United States.

INTRODUCTION: Infertility treatment with assisted reproductive technologies (ARTs) has been associated with adverse vascular events in some but not all previous studies. Endothelial damage, prothrombotic factor release, and a higher prevalence of cardiovascular risk factors in those receiving ART have been invoked to explain this association. We sought to explore the relationship between ART and stroke risk using population-level data. METHODS: We conducted a retrospective cohort study using data from the National Inpatient Sample registry from 2015 to 2020, including all delivery hospitalizations for patients aged 15 to 55 years. The study exposure was use of ART. The primary end point was any stroke defined as ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or cerebral venous thrombosis during index delivery hospitalization. Individual stroke subtypes (ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral venous thrombosis) were evaluated as secondary end points. Standard International Classification of Diseases, Tenth Revision, Clinical Modification algorithms were used to define study exposure, comorbidities, and prespecified end points. In addition to reporting population-level estimates, propensity score adjustment by inverse probability weighting was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between ART and non-ART users. RESULTS: Among 19 123 125 delivery hospitalizations identified, patients with prior ART (n=202 815, 1.1%) experienced significantly higher rates of any stroke (27.1/100 000 versus 9.1/100 000), ischemic stroke (9.9/100 000 versus 3.3/100 000), subarachnoid hemorrhage (7.4/100 000 versus 1.6/100 000), intracerebral hemorrhage (7.4/100 000 versus 2.0/100 000), and cerebral venous thrombosis (7.4/100 000 versus 2.7/100 000) in comparison to non-ART users (all P<0.001 for all unadjusted comparisons). Following inverse probability weighting analysis, ART was associated with increased odds of any stroke (adjusted odds ratios, 2.14 (95% CI, 2.02-2.26); P<0.001). CONCLUSIONS: Using population-level data among patients hospitalized for delivery in the United States, we found an association between ART and stroke after adjustment for measured confounders.

The association of assisted reproductive technology with fetal malpresentation: a systematic review and meta-analysis.

BACKGROUND: Since its introduction, assisted reproductive technology (ART) has developed into a common clinical practice around the world; yet it still raises a lot of questions. Throughout time, many researchers have investigated its association with several obstetric incidences and its consequences on perinatal outcomes. The aim of the current meta-analysis was to estimate the correlation between ART procedures and malpresentation of the fetus in singleton pregnancies. METHODS: The study was conducted according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines and prospectively registered under the PROSPERO database (CRD42023458084). Five databases (Embase, MEDLINE®, APA PsycInfo, Global Health, Health Management Information Consortium (HMIC)) and two additional sources were searched from inception to 31 May 2023. Quality of the included studies was assessed using the ROBINS-1 scale, whilst quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Summative and subgroup data as well as heterogeneity were generated by the Cochrane platform RevMan Web. RESULTS: Overall, 11 studies were included in the study with a total of 3,360,134 deliveries. Results indicate a higher risk of malpresentation at delivery in fetuses conceived through ART than those conceived naturally (RR: 1.50, (95% confidence interval (CI):1.30, 1.73)). This risk decreased when adjustments for potential confounders were applied (RR = 1.12, 95% CI 1.02, 1.23). CONCLUSIONS: Based on observational studies, this meta-analysis indicated that singleton pregnancies conceived through ART are associated with higher risk of malpresentation than those conceived naturally, albeit the difference was lower when potential confounders were examined. Thus, future large studies are required to better understand possible reversible and irreversible factors of this relationship.

Association Between Anti-Müllerian Hormone and Early Spontaneous Abortion in Assisted Reproduction Treatment: A Case-Control Study Integrated with Biological Evidence.

Early spontaneous abortion (ESA) is a common adverse pregnancy outcome mainly attributed to embryo chromosomal abnormalities. However, as a quantitative marker, whether the anti-Müllerian hormone (AMH) can reflect oocyte quality is still controversial. By integrating biological evidence and adjusting many cofounders, this study aimed to clarify the controversies about the association between AMH and ESA caused by embryo aneuploidy during assisted reproductive technology (ART) treatment. We strictly preselected 988 patients receiving first ART treatment for analyzing clinical data, while 55 of them acquired chorionic villi karyotype results. In addition, 373 biopsied embryos from 126 patients receiving preimplantation genetic diagnosis (PGT) were tracked to compare embryo karyotypes. Univariate and multiple factor regressions were applied to analyze the risk factors leading to ESA. As covariates unadjusted, AMH (odds ratio 0.87, 95% CI 0.82-0.93) was the significant variable contributing to ESA. However, AMH played no significant role in the following regression models after age was adjusted. Also, AMH had no significant association with ESA in most age-adjusted subgroups, except in the male factors engaged subgroup. Additionally, compared to the patients with euploid chorionic villi karyotypes, those with aneuploid karyotypes were older and acquired fewer oocytes, yet their AMH levels were not significantly different. Furthermore, the embryo aneuploidy was independent of AMH while associated with maternal age, retrieved oocyte number, and embryo quality. This study suggested that AMH was unassociated with the ESA caused by embryo aneuploidy in ART therapy. As a critical cofounder, age remains the variable closely related to ESA.

Association Between Assisted Reproductive Technology and Cerebral Palsy: A Meta-Analysis.

BACKGROUND: Since 1978 many children are born thanks to assisted reproductive technology (ART). However, the long-term effects of these therapies are still not fully known. Our objective is to evaluate the risk of cerebral palsy (CP) after ART compared with that in those spontaneously conceived (SC) and to examine this risk in single, multiple, and preterm births and the evolution of the risk over the years. METHODS: PubMed, Embase, and Web of Science databases were searched until December 2022. Studies were included if they studied CP cases in children born through ART. 16 studies were finally selected. Quality of studies was assessed using Newcastle Ottawa Scale. Pooled OR was estimated by weighting individual OR/RR by the inverse of their variance. A random-effect model was applied. To assess the causes of heterogeneity, we performed meta-regression analyses. RESULTS: A significantly high risk of CP was found (OR = 1.27; 95% CI 1.12 to 1.43) in children born through ART compared with those SC. This risk increased in singletons (OR = 1.48; 95% CI 1.23 to 1.79) but disappeared in multiple (OR = 1.05; 95% CI 0.93 to 1.18) and preterm births (OR = 1.09; 95% CI 0.87 to 1.37). We found a higher risk of CP in children born before the year 2000 (OR = 3.40; 95% CI 2.49 to 4.63). CONCLUSIONS: ARTs slightly increase the risk of CP once the effect of multiple gestation is controlled. Further studies are needed to clarify whether the techniques themselves, fertility problems, or associated maternal comorbidities are responsible for this risk.

Evidence based management of patients with endometriosis undergoing assisted conception: British fertility society policy and practice recommendations.

Endometriosis is a chronic inflammatory condition in women of reproductive age, which can lead to infertility and pelvic pain. Endometriosis associated infertility is multifactorial in nature adversely affecting each step of the natural reproductive physiology and thereby processes and outcomes of Assisted Reproductive Technology (ART) cycles. These outcomes are further complicated by the subtype of endometriosis, being peritoneal, deep infiltrating and ovarian, which bear negative effects on ovarian reserve, response to stimulation, accessibility for oocyte retrieval, intraoperative safety and endometrial receptivity. There is still a lack of clear guidance about the role of surgery for ovarian endometriosis/endometriomas. This guideline evaluates the evidence of the impact of pelvic endometriosis and endometriomas on the outcome of ART and provides recommendations for management options before and during ART including intra-uterine insemination. Recommendations are made based on the current evidence for the management of patients with endometriosis across each step of ART with the primary aim of improving ART outcomes.

Placentation and complications of ART pregnancy. An update on the different possible etiopathogenic mechanisms involved in the development of obstetric complications.

INTRODUCTION: Infertile couples' percentage is increasing all over the world, especially in Italy, with high number of children born in our country through assisted reproductive techniques (ART). However, pregnancies obtained by ART have increased potential obstetrical risks which could be caused by fetus-placenta unit development, most of all due to placentation's evolution. These can be reassumed into miscarriage, chromosomal abnormalities, preterm delivery, multiple pregnancy, IUGR, placenta previa, abruptio placentae, preeclampsia and hypertensive disorders, postpartum hemorrhage. METHODS: The aim of this article is to evaluate hypothetic mechanism involved in placentation process and in the etiopathology of ART pregnancies disorders, giving an updating overview of different etiopathogenetic pathways and features. On this scenario, we create an updated review about the etiopathogenesis of abnormal placentation in ART pregnancies. RESULTS: Several features and different etiopathogenetic characteristic might impact differently such as advanced maternal age, poor ovarian reserve, oocyte quality and causes of subfertility themselves, and the ART techniques itself, as hormonal medical treatments and laboratory techniques such as gamete and embryo laboratory culture, cryopreservation versus fresh ET, number of embryos transferred. CONCLUSION: To further explore the molecular mechanisms behind placentation in ART pregnancies, further studies are necessary to gain a better understanding of the various aspects involved, particularly those which are not fully comprehended. This could prove beneficial to clinicians in both ART care and obstetric care, as it could help to stratify obstetrical risk and decrease complications in women undergoing ART, as well as perinatal disorders in their children. Correct placentation is essential for a successful pregnancy for both mother and baby.

What is the impact of endometriosis and the AFS stage on cumulative pregnancy rates in IVF programs?

BACKGROUND: Endometriosis is commonly observed in infertile women and can be staged with regard to severity [e.g. according to the American Fertility Society (AFS) classification]. This condition can cause infertility through impaired oocyte quality, fertilization disorders, tubal lesions, adhesions, deep infiltration, and adenomyosis. Although women with endometriosis often turn to in vitro fertilization (IVF) programs, the literature data on IVF outcomes are sometimes contradictory (i.e. the same as in other etiologies of infertility, or worse). The objective of the present study was to assess and compare pregnancy rates in women with and without endometriosis and according to the endometriosis stage. METHODS: We retrospectively studied clinical and ongoing pregnancy rates in IVF and the cumulative pregnancy rates after frozen/thawed embryo transfers, in women without endometriosis (group A) or with endometriosis (group B). We further compared groups in which endometriosis was staged according to the revised AFS classification: stage 1/2 (group C), stage 3/4 (group D, without endometrioma), and endometrioma alone (group E). RESULTS: We documented 430 cycles in group A and 460 in group B (including 56 in group C, 88 in group D and 316 in group E). After fresh or frozen/thawed embryo transfers, the differences in ongoing pregnancy rates between groups A and B were not significant. However the cumulative rates per couple were significantly lower (p < 0.05) in group D. CONCLUSIONS: We recommend IVF for women with endometriosis because the pregnancy rates are similar to those observed for women with other types of infertility. This approach is in line with the international guidelines issued by assisted reproductive technology societies. These results again raise the question of whether surgical resection of deep infiltrating endometriosis (stage 3/4) should be recommended before admission to an IVF program. Trial registration This study was approved by an institutional review board (CPP Ouest VI, Brest, France): reference: B2020CE.43.

The Association between Assisted Reproductive Technologies and Neurodevelopmental Disorders in Offspring: An Overview of Current Evidence.

The utilization of assisted reproductive technologies (ART) is on the rise, resulting in a growing population of ART-conceived offspring. The health concerns of this unique population have attracted significant attention. During ART procedures, gametes and early-stage embryos are exposed to various non-physiological conditions, such as manipulation, culture media, and cryopreservation, which may disrupt embryonic development and potentially impact the health of offspring. Notably, the potential impact of ART on neurodevelopment and its association with an increased risk of neurodevelopmental disorders (NDD) later in life remains a subject of debate. This review aims to summarize the current research advancements concerning the effects of ART on neurodevelopment, specifically focusing on the evidence of the relationship between ART, epigenetic modifications, and NDD, including autism spectrum disorder, intellectual disability, attention deficit hyperactivity disorder, and cerebral palsy. Future studies should prioritize large sample sizes, rigorous adjustment for confounding factors, and the use of interdisciplinary approaches to effectively monitor the neurodevelopmental outcomes of ART-conceived children.