Assisted Reproductive Technology Pregnancies Research Articles

Comparison of Fetal Crown-Rump Length Measurements between Thawed and Fresh Embryo Transfer.

Background and Objectives: Neonates born from thawed embryo transfers tend to have a significantly higher birthweight compared to those from fresh embryo transfers. The aim of this study was to compare the crown-rump length (CRL) between thawed and fresh embryos to investigate the potential causes of different growth patterns between them. Materials and Methods: This was a retrospective study (July 2010-December 2023) conducted at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. In total, 3082 assisted reproductive technology (ART) pregnancies (4044 embryos) underwent a routine scan at 11+0-13+6 gestational weeks and were included in the study. Maternal age, the type of embryo transfer (thawed vs. fresh, donor vs. their own oocytes), CRL, twin and singleton gestations were analyzed. Results: The mean maternal age in thawed was significantly higher than in fresh embryos (39.8 vs. 35.8 years, p-value < 0.001). The mean CRL z-score was significantly higher in thawed compared to fresh embryo transfers (0.309 vs. 0.199, p-value < 0.001). A subgroup analysis on singleton gestations showed that the mean CRL z-score was higher in thawed blastocysts compared to fresh (0.327 vs. 0.215, p-value < 0.001). Accordingly, an analysis on twins revealed that the mean CRL z-score was higher in thawed blastocysts (0.285 vs. 0.184, p-value: 0.015) and in oocytes' recipients compared to own oocytes' cases (0.431 vs. 0.191, p-value: 0.002). Conclusions: The difference in CRL measurements between thawed and fresh embryos may be a first indication of the subsequent difference in sonographically estimated fetal weight and birthweight. This finding highlights the need for additional research into the underlying causes, including maternal factors and the culture media used.

Prevalence of gestational diabetes mellitus risk factors in singleton pregnancies obtained by assisted reproductive technology: An observational, retrospective, real-world study from a pregnancy registry

AIMSSeveral studies showed that Assisted Reproductive Technology (ART) could affect gestational diabetes mellitus (GDM) onset. The aim of this study was to estimate the prevalence of GDM risk factors in a cohort of women with singleton pregnancy obtained by ART and complicated by GDM. Maternal and neonatal outcomes were explored. METHODSWe retrospectively collected data of pregnancies of women with singleton pregnancy obtained by ART and complicated by GDM consecutively cared for at a specialized center for diabetes and pregnancy care. Prevalence and combination of GDM risk factors, their combinations and maternal-fetal outcomes were estimated. RESULTSOverall, our cohort included 50 women (mean age of 40.4 ± 4.7 years, mean pre-pregnancy BMI 26.3 ± 6.2 kg/m2). The most frequent GDM traditional risk factors were age ≥ 35 years (94 %), family history of diabetes (44 %), overweight (29 %) and obesity (19 %). Combining risk factors, 5 groups were identified with 1, 2, 3, 4, or 5 risk factors with a prevalence respectively of 28 %, 46 %, 20 %, 4 %, and 2 %. Examining features of the above groups, pre-pregnancy weight (p < 0.0001) and pre-pregnancy BMI (p < 0.0001) statistically significant differed in the 5 groups, increasing with higher numbers of risk factors. Regarding neonatal outcomes only neonatal hypoglycemia (p = 0.03) differed significantly among the groups, with higher percentages in women with higher numbers of combined risk factors. CONCLUSIONPrevalence of GDM traditional risk factors in singleton ART pregnancies complicated by GDM is considerable. Such pregnancies need appropriate clinical attention because of the risk of adverse outcomes.

Is There a Cumulative Effect for Congenital Heart Defects in Monochorionic Twins after Assisted Reproduction? - A Retrospective Analysis at a Tertiary Referral Center.

The aim of our study was to compare maternal, chorionicity and neonatal complications in monochorionic (MC) twins between spontaneously conceived (SC) and assisted reproductive technologies (ART) pregnancies. This was a retrospective cohort study between January 2010 to December 2019 at a tertiary referral University center. All consecutive pregnancies with MC twins that delivered at our University hospital were included. Maternal, chorionicity and neonatal complications were recorded and compared between SC and ART pregnancies. 393 MC pregnancies were included for final analysis, including 353 (89.8%) SC and 40 (10.2%) pregnancies conceived after ART. Hypothyroidism was the only maternal condition seen significantly more often in ART pregnancies (35.0% vs 12.5%, p=0.001). There were no significant differences in chorionicity complications, such as twin-twin transfusion syndrome, selective fetal growth restriction and twin anemia-polycythemia sequence (40.0% in ART pregnancies vs 31.6% in SC pregnancies, p=0.291). At least one congenital anomaly in one twin was seen significantly more often in ART pregnancies (18.8% vs 8.1%, p=0.004), especially congenital heart defects (16.3% vs 6.2%, p=0.005). There were no other significant differences in neonatal outcomes between both groups, however, there were non-significant trends in gestational age at delivery (34 weeks in ART pregnancies vs 35 weeks, p=0.078) and birthweight (1951g±747 in ART pregnancies vs 2143g±579, p=0.066). This is the largest cohort study to date comparing maternal, chorionicity and neonatal complications between MC twin pregnancies after ART and after SC. Hypothyroidism was the only maternal condition occurring more frequently in pregnancies conceived after ART. There were no significant differences in chorionicity complications, in contrast to previously reported studies. While MC twins and ART pregnancies per se are known to be at risk for congenital heart defects, there seems to be a cumulative effect in MC pregnancies conceived after ART.

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

PurposeTo examine feto-maternal characteristics and outcomes of morbidly obese pregnant patients who conceived with assisted reproductive technology (ART).MethodsThis 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.ResultsPatients 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).ConclusionsThe 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.

Value of aspirin in assisted reproductive technology

Infertility affects at least 15% of couples worldwide, and its prevalence is higher in low- and middle-income countries (LMICs). Although expensive, especially in LMICs, the uptake of assisted reproductive technology (ART) services is on the rise. The cohort of patients who utilize these services tend to be older and prone to pregnancy-related complications, such as hypertension and early pregnancy loss. Aspirin is not only affordable and accessible but also widely used for its antithrombotic and anti-inflammatory effects, which may counteract implantation failure or miscarriage. Although this sounds logical, sufficient evidence has not been adduced. In addition, there is currently no consensus on the dosage of aspirin. It is important to consider the therapeutic advantages of aspirin in pregnancies conceived through ART to optimize pregnancy outcomes. There is a need for more research on the benefits that may be accrued using aspirin in ART and other high-risk pregnancies.

Combined effects of pre-pregnancy BMI and gestational weight gain on preterm birth: comparison between spontaneous and ART conception.

Inappropriate pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are both linked to preterm birth (PTB); however, which one plays a dominant role in PTB risk is not yet sure. We aimed to evaluate the combined effect of pre-pregnancy BMI and GWG on the risk of PTB in singleton pregnancies conceived both spontaneously and through assisted reproductive technology (ART). The data included all mothers (n = 17,540,977) who had a live singleton birth from the US National Vital Statistics System (NVSS) 2015-2019. Logistic regression models, quantile-g-computation, and generalized additive model were used to analyze the combined association of pre-pregnancy BMI and GWG with PTB. The singleton PTB rate was significantly higher in ART pregnancies (11.5%) than in non-ART pregnancies (7.9%). When compared to those women with pre-pregnancy normal weight and GWG within Institute of Medicine (IOM) guidelines, the highest PTB risk was observed in non-ART women with pre-pregnancy underweight and GWG below IOM guidelines (aOR 2.56; 95% CI 2.53-2.60) and in ART women with pre-pregnancy obese and GWG below IOM guidelines (aOR 2.56; 95%CI 2.36-2.78). GWG dominated the combined effect with its joint effect coefficient of - 0.281 (P < 0.05) in non-ART women and - 0.108 (P < 0.05) in ART women. Inappropriate GWG played a dominant role in increasing the risk of PTB in both non-ART and ART populations. Counseling regarding pre-pregnancy BMI and especially GWG appears to be even more crucial for pregnancies conceived via ART, given their impact on PTB.

Evaluation of the holding-up uterus technique for placenta accreta spectrum cesarean hysterectomy in shocked patients with a high shock index: a case series study

BackgroundPlacenta accreta spectrum (PAS) cesarean hysterectomy is performed under conditions of shock and can result in serious complications. This study aimed to evaluate the usefulness of the “Holding-up uterus” surgical technique with a shock index (S.I.) > 1.5.MethodsTwelve patients who underwent PAS cesarean hysterectomy were included in the study.ResultsGroup I had S.I. > 1.5, and group II had S.I. ≤ 1.5. Group I had more complications, but none were above Grade 3 or fatal. Preoperative scheduled uterine artery embolization did not result in serious complications, but three patients who had emergency common iliac artery balloon occlusion (CIABO) and a primary total hysterectomy with S.I. > 1.5 had postoperative Grade 2 thrombosis. Two patients underwent manual ablation of the placenta under CIABO to preserve the uterus, both with S.I. > 1.5.ConclusionsThe study found that the “Holding-up uterus” technique was safe, even in critical situations with S.I. > 1.5. CIABO had no intervention effect. The study also identified assisted reproductive technology pregnancies with a uterine cavity length of less than 5 cm before conception as a critical factor.

Alterations of the gut microbiota and fecal short-chain fatty acids in women undergoing assisted reproduction.

The community structure of gut microbiota changes during pregnancy, which also affects the synthesis of short-chain fatty acids (SCFAs). However, the distribution of gut microbiota composition and metabolite SCFA levels are poorly understood in women undergoing assisted reproductive technology (ART). To evaluate the changes in gut microbiota composition and metabolic SCFAs in women who received assisted reproduction treatment. Sixty-three pregnant women with spontaneous pregnancy (SP) and nine with ART pregnancy were recruited to provide fecal samples. Gut microbiota abundance and SCFA levels were determined by 16S ribosomal RNA (rRNA) gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS). The ART group showed decreased alpha diversity (the species richness or evenness in a sample). The principal coordinates analysis (a method of analysing beta diversity) showed significant difference in gut microbiota between the ART group versus the SP group (unweighted UniFrac distance, R2=0.04, P=0.003). Proteobacteria, Blautia and Escherichia-Shigella were enriched in the ART group, whereas the relative abundance of beneficial intestinal bacteria Faecalibacterium was lower than in the SP group. Different modes of conception were associated with several SCFAs (valeric acid (r=-0.280; P=0.017); isocaproic acid (r=-0.330; P=0.005); caproic acid (r=-0.336; P=0.004)). Significantly different SCFAs between the two groups were synchronously associated with the differential gut microbiota. The diversity and abundance of gut microbiota and the levels of SCFAs in women undergoing ART decreased. The application of ART shaped the microbial composition and metabolism, which may provide critical information for understanding the biological changes that occur in women with assisted reproduction.

Deep machine learning applied to support clinical decision-making in the treatment of infertility using assisted reproductive technologies

Introduction. Machine learning (ML) applied to data analysis allows to more accurately and targetedly determine the most significant correctable and non-correctable predictors of onset of pregnancy in assisted reproductive technology (ART) programs in patients of different age groups. Analysis of data using various techniques and comparison of results obtained via two models will determine the most significant factors for onset of pregnancy in the ART program.Aim. To determine the most significant clinical and embryological predictors of onset of pregnancy using standard regression analysis and a decision tree algorithm to predict pregnancy in the ART program.Materials and methods. A total of 1,021 married couples were included in the retrospective study. The study analysed clinical and laboratory test findings and stimulated cycle parameters depending on the effectiveness of the ART program. A regression analysis was carried out and a decision tree algorithm was built using the Gini criterion to determine the most significant factors.Results. We identified “general” signs that require further validation on other models, including ML: the presence/absence of a history of pregnancies, stimulated cycle parameters (oocyte cumulus complex, number of metaphase II (MII) oocytes, number of zygotes), spermogram indicators on the day of puncture, number of high and good quality embryos, as well as the embryo grading.Conclusion. rFSH (follitropin-alpha, Gonal-f) gives a significant result in two of the five available age groups, follitropin-beta, corifollitropin alfa – in one of the five groups only. Building a model that includes not only the couple’s medical history data, but also molecular markers using machine learning methods will not only allow us to most accurately determine the most promising groups of patients for in vitro fertilization (IVF) programs, but also increase the efficiency of ART programs by selecting the highest quality embryo to be transferred.

P-447 Gestational weight gain in relation to time-to-pregnancy and conception by assisted reproductive technology

Abstract Study question Does the gestational weight gain trajectory differ across levels of time-to-pregnancy (TTP) for spontaneously conceived pregnancies and pregnancies conceived by assisted reproductive technology (ART)? Summary answer Women with ART pregnancies had lower weekly weight gain during the third trimester compared with women with spontaneous conceptions with TTP ≤3. What is known already Studies suggest that both prolonged TTP and conception by ART may increase the risk of pregnancy complications and affect perinatal outcomes such as birthweight. Suboptimal gestational weight gain might further increase the risk of adverse pregnancy outcomes. However, it remains unclear whether there may be differences in gestational weight gain according to TTP and ART, which contribute to the subsequent risk of adverse pregnancy outcomes. Study design, size, duration We studied 69,121 singleton planned pregnancies contributed by 60,847 women participating in the Norwegian Mother, Father and Child Cohort Study. Participants completed questionnaires at 15 weeks’ gestation (study entry), 30 weeks’ gestation, and six months postpartum on sociodemographic, reproductive, and behavioral factors. Participants reported their TTP, and up to four weight measurements and corresponding gestational age from preconception through delivery. We identified use of ART in the Medical Birth Registry of Norway. Participants/materials, setting, methods We fitted gestational weight gain trajectories using mixed-effects linear regression models and included an interaction term between time (gestational weeks) and the exposure groups, TTP ≤3 (reference); TTP 4-6; TTP 7-11, TTP ≥12 months, and ART, to assess differences across levels of TTP and conception by ART. The analyses were adjusted for maternal age at start of pregnancy, pre-pregnancy height, educational attainment, pre-pregnancy smoking, parity, and gestational age at birth. Main results and the role of chance The adjusted average weekly weight gain was -15g (95% CI: −19; −12) during the first trimester, 620g (95% CI: 615; 624) during the second trimester, and 491g (95% CI: 489; 494) during the third trimester. When we compared differences in average weekly weight change during the first trimester, we observed little difference between the exposure groups. During the second trimester, compared with TTP≤3 months women with TTP 4-6 months, TTP 7-11 months or TTP ≥12 months gained on average 7g (95% CI: −18; 3), 19g (95% CI: −33; −5) and 15g (95% CI: −29; −1) less per week, respectively, whereas women with ART pregnancies gained 11g more per week (95% CI: −13; 34). However, the results for TTP 4-6 and ART pregnancies were imprecise. During the third trimester, average weekly weight gain did not differ according to TTP for spontaneous conceptions, while women who conceived after ART gained 35g (95% CI: −49; −22) less than women with TTP≤3 each week. Limitations, reasons for caution Because TTP and gestational weight gain were self-reported, non-differential misclassification may have influenced our results. Wider implications of the findings Decelerated weight gain during the third trimester in ART pregnancies compared with women who conceived spontaneously within 3 months might be associated with adverse pregnancy outcomes. Although our findings are imprecise and need to be replicated, monitoring gestational weight gain trajectories might support identification of pregnancies at increased risk. Trial registration number Not applicable

Increased Risk of Preeclampsia with Assisted Reproductive Technologies.

We summarized recent available data to assess the association between assisted reproductive technology (ART) and risk for preeclampsia. The majority of clinical studies supporting the association of preeclampsia and ART are retrospective. Published data from both clinical and pre-clinical studies suggest specific ART procedures may contribute to the increased risk, including in vitro embryo handling and development, hormone stimulation, transfer cycle types, and use of donor oocytes/embryos. Potential mechanisms include epigenetic aberrations leading to abnormal placentation, absence of factors secreted by the corpus luteum, and immunologic responses to allogenic gametes. There is an increased risk of preeclampsia following ART. Treatment plans that favor reduced preeclampsia risk should be considered for ART pregnancies. To make ART pregnancies safer, additional clinical and animal model studies are needed to elucidate the underpinnings of this risk association.

Birth Outcomes Following Assisted Reproductive Technology Conception Among Same-Sex Lesbian Couples vs Natural Conception and Assisted Reproductive Technology Conception Among Heterosexual Couples

This study uses registry data to compare birth outcomes, including birth weight, gestational age, low birth weight, and preterm delivery, in assisted reproductive technology (ART) pregnancies among same-sex lesbian couples vs natural conceptions and ART pregnancies among heterosexual couples.

Leukocyte Telomere Length in Children Born Following Blastocyst-Stage Embryo Transfer

ABSTRACT Several recent studies have suggested an association between children conceived by assisted reproductive technology (ART) and a distinct growth pattern in early life, which has been linked to diseases of older age. Telomere shortening, specifically a shorter leukocyte telomere length (LTL), has also been linked to age-related diseases including cardiometabolic diseases and cancer. Initial telomere length is shaped by a telomere reset process during gamete fertilization and the early stages of preimplantation development. Given that ART involves the in vitro manipulation of oocytes and embryos, this study aimed to evaluate the association between ART-related factors and LTL in children. Whole genome-sequencing (WGS) data from the Nanjing and Suzhou centers of the China National Birth Cohort (CNBC) were obtained from 1137 individuals from 365 parent-children families, including 202 children conceived using ART and 205 conceived spontaneously. The association was determined between blastocyst-stage transfer and shorter telomere length in 180 children conceived by ART in the same centers. In addition, qPCR was used to perform validation on fingerstick blood samples from 406 children conceived using ART at 3 different centers in China. Data from qPCR were then compared with data obtained from WGS in 70 children in the discovery cohort with sufficient DNA samples. Associations between parental factors and demographics with LTL were examined in the discovery cohort. LTL attribution with aging was calculated using data from the discovery cohort, 1185 individuals aged 40–69 years from healthy controls in the Nanjing Lung Cancer Cohort with LTL measured using WGS, and 1452 East Asian adults aged 40–69 years in the UK biobank with LTL measured using qPCR. Results of association analyses found paternal LTL (β = 0.27, P = 3.26 × 10−8), maternal LTL (β = 0.26, P = 2.41 × 10−7), plurality (twins vs singletons; β = −0.34, P = 0.010), sex of children (male vs female; β = −0.22, P = 0.032), gestational age (β = 0.05, P = 0.026), and conception type (ART-conceived pregnancy vs spontaneously conceived, β = −0.35, P = 5.98 × 10−4) were all significantly associated with LTL in children. Multivariate regression analysis revealed that children conceived by ART had a significantly shorter LTL than those conceived spontaneously, even when adjusting for parental age at conception (adjusted β = −0.41, P = 3.33 × 10−4). Transfer of blastocyst-stage embryos was found to be significantly associated with shorter LTL (β = −0.54, P = 2.69 × 10−3). In addition, when LTL in children from spontaneous pregnancies was compared with LTL in children from ART pregnancies through cleavage-stage versus blastocyst-stage transfer, the LTL of the cleavage-stage group was comparable to the spontaneous pregnancy group, whereas the LTL of the blastocyst-stage group was shorter (β = −0.67, P = 7.81 × 10−8). This result suggests that the difference in LTL between transfer stages might explain the difference between the ART-conceived and spontaneous pregnancy groups. No associations between COS protocols, fertilization methods, or embryo transfer cycles on shorter LTL in children were observed. The multicenter validation cohort had similar associations between blastocyst-stage transfer and shorter LTL. Shortened LTL associated with blastocyst transfer was equivalent to 13.93 years (95% CI, 4.64–23.22 years), 13.42 years (95% CI, 4.52–22.21 years), and 10.85 years (95% CI, 1.03–20.67 years) of aging between 40–69 years in the discovery and 2 validation cohorts, respectively. The results of this study demonstrate that children conceived by ART are associated with a shorter LTL compared with those conceived spontaneously, and transfer of blastocyst-stage embryos was associated with shorter LTL in children than is the transfer of cleavage-stage embryos.

The Predictive Value of Serum ß-HCG Levels in The Detection of Ectopic Pregnancy Sixteen Days after Embryo Transfer: A Cross-Sectional Study.

To detect the predictive value of beta human chorionic gonadotropin (β-hCG) levels 16 days post embryo transfer (ET) regarding detection of an ectopic pregnancy (EP) in assisted reproductive technology (ART) cycles. In this cross-sectional study, we reviewed the database of Royan Institute from January 2011 to December 2014 and from January 2017 to December 2019 retrospectively. All cases with positive β-hCG levels sixteen days after ET were screened (n=4149). The pregnancies with oocyte or embryo donation and the multiple pregnancies based on the first ultrasound were excluded. All eligible singleton pregnancies with documented serum β-hCG levels at Royan institute laboratory (n=765) were included and then classified according to the type of pregnancy: EP (n=189) or non-EP (n=576). The data of the treatment cycle was extracted from the patients' files. A receiver operating characteristic (ROC) curve was used to detect the predictive power of the first measurement of β-hCG level in distinguishing EP from ongoing pregnancy in the ART and intrauterine insemination (IUI) cycles separately. Sensitivity, specificity, area under the ROC curve and 95% confidence intervals (CI) were calculated for each of the estimates. The mean levels of β-hCG 16 days after ET were remarkably higher in the ongoing pregnancy group than the EP group (1592.35 ± 87 IU/L vs. 369.69 ± 50.61 IU/L, P<0.001). The β-hCG thresholds predictive of ongoing pregnancy were 278 IU/L as the most suitable cut-off to predict viable pregnancy with a sensitivity of 72.8%, a specificity of 67.5%, a positive predictive value of 77.8%, standard error of 0.02, and a confidence interval of 73.8- 81.7%. However, this relationship was not found in IUI cycles. Based on these findings, if β-hCG levels 16 days after ET are below 278 IU/l, close follow-up is recommended, until either the diagnosis of EP or miscarriage is established.

Complications in pregnancies achieved by assisted reproduction.

Pregnancies resulting from assisted reproductive technologies (ART) have been documented to have a higher risk of adverse effects. To provide evidence on obstetric and perinatal complications associated with conceptions by ART versus spontaneous pregnancies. Comprehensive review of original articles published between 2010 and 2018 addressing the more common obstetric and perinatal complications in pregnancies resulting from in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), in comparison with spontaneous conceptions. Thirty-seven original articles, which reported on 26 cohort studies and 11 case-control trials, were included. IVF and ICSI conceptions were associated with a larger number of obstetric and perinatal complications such as low birth weight, prematurity, low weight for gestational age, admission to the neonatal intensive care unit, congenital malformations, C-sectionand premature rupture of membranes, among others. Pregnancies by ART are associated with an increased risk of obstetric and perinatal complications in comparison with spontaneous conceptions. Further research is needed to determine which aspects result in higher risk.

Ethics in pre-ART genetics: a missed X-linked Menkes disease case

Assisted reproductive technology (ART) has experienced dramatic progress over the last 30 years, and gamete donation is routine in fertility clinics. Major advances in genetic diagnostics are part of this development due to the ability to analyze multiple genes or whole genomes fast and to an affordable prize. This requires knowledge and capability to evaluate genetic variants correctly in a clinical setting. Here we report a Menkes disease case, born after ART, where genetic screening and variant scoring failed to identify an egg donor as carrier of this fatal X-linked disorder. The gene variant is a deletion of a single base pair leading to a frameshift and premature termination of the protein, predicted to result in no or severely diminished function. The variant would be classified as likely pathogenic (class 4) and should be readily detectable by molecular genetic screening techniques. We wish to highlight this case to prevent future similar cases. IVI Igenomix has developed and embarked on an ambitious screening program to detect and prevent a large number of inherited severe childhood disorders in ART pregnancies. The company has recently achieved ISO 15189 certification with competence to evaluate and deliver timely, accurate, and reliable results. Failure to identify a pathogenic variant in the ATP7A gene leading to birth of two boys with Menkes disease invokes the required procedures to screen and detect disease-causing gene variants. This calls for ethical and legal considerations in ART diagnostics to prevent fatal errors like the present.

Anti-Müllerian hormone and live birth in unexplained recurrent pregnancy loss

Research questionIs anti-Müllerian hormone (AMH) associated with live birth rate (LBR) in women with unexplained recurrent pregnancy loss (RPL)? DesignCohort study of women with unexplained RPL attending the RPL Unit, Copenhagen University Hospital, Denmark, between 2015 and 2021. AMH concentration was assessed upon referral, and LBR in the next pregnancy. RPL was defined as three or more consecutive pregnancy losses. Regression analyses were adjusted for age, number of previous losses, body mass index, smoking, treatment with assisted reproductive technology (ART) and RPL treatments. ResultsA total of 629 women were included; 507 (80.6%) became pregnant after referral. Pregnancy rates were similar for women with low and high AMH compared to women with medium AMH (81.9, 80.3 and 79.7%, respectively) (low AMH: adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 0.84–2.47, P = 0.18; high AMH: aOR 0.98, 95% CI 0.59–1.64, P = 0.95). AMH concentrations were not associated with live birth. LBR was 59.5% in women with low AMH, 66.1% with medium AMH and 65.1% with high AMH (low AMH: aOR 0.68, 95% CI 0.41–1.11, P = 0.12, high AMH: aOR 0.96, 95% CI 0.59–1.56, P = 0.87). Live birth was lower in ART pregnancies (aOR 0.57, 95% CI 0.33–0.97, P = 0.04) and with higher numbers of previous losses (aOR 0.81, 95% CI 0.68–0.95, P = 0.01). ConclusionIn women with unexplained RPL, AMH was not associated with the chances of live birth in the next pregnancy. Screening for AMH in all women with RPL is not supported by current evidence. The chance of live birth among women with unexplained RPL achieving pregnancy by ART was low and needs to be confirmed and explored in future studies.

The impact of assisted reproductive technology on the risk of postpartum hemorrhage: Difference by the mode of delivery and embryo transfer.

The frequency of postpartum hemorrhage (PPH) is increasing in developed countries, and some reports suggest that assisted reproductive technology (ART) increases various perinatal complications, including PPH. We investigated whether the effect of ART pregnancies on the incidence of PPH is modified by the mode of delivery. A retrospective cohort study was performed. We analyzed the medical records of 2914 pregnant women, including 411 pregnancies achieved by ART, which were delivered in our hospital from 2017 to 2020. PPH was defined as hemorrhage exceeding the 90th percentile of blood loss per the mode of delivery and number of fetuses. Multivariable logistic regression analysis was used to assess the association between ART and PPH. Propensity score-matched analyses were used to assess the difference in the incidence of PPH by the mode of delivery. As previously reported, multivariable logistic regression analysis showed that ART pregnancy is an independent risk factor for PPH. Propensity score-matched analysis for with and without ART showed a 3.39-fold higher incidence of PPH for ART pregnancy in the vaginal delivery group (p < 0.001). The effect of ART pregnancies on the incidence of PPH differed depending on the mode of delivery. Only in vaginal delivery, ART pregnancy increased the incidence of PPH.

Assisted reproductive technologies in Africa: The African Network and Registry for ART, 2018 and 2019

Research questionWhat were the utilization, practices and outcomes of assisted reproductive technology (ART) in Africa in 2018 and 2019? DesignCycle-based data (CBD) and retrospective summary data were collected cross-sectionally from voluntarily participating ART centres. ResultsDuring 2018, 43,958 ART procedures were reported by 67 centres in 16 countries, increasing to 45,185 procedures reported by 70 centres in 18 countries in 2019. Autologous fresh procedures predominated at 70%, whereas autologous frozen embryo transfers (FET) increased from 21.2% to 23.1% and oocyte donation cycles remained below 10%. In 2019, the mean age of women undergoing autologous fresh embryo transfer was 33.9 years and received a mean number of 2.4 embryos per transfer. The clinical pregnancy rate (CPR) per fresh embryo transfer was 42.8% in 2018 and 38.4% in 2019, with corresponding rates of 38.3% and 31.8% after FET. In both years, most ART procedures, excluding single embryo transfer (SET), were associated with a multiple delivery rate above 20%, reaching over 30% after elective dual embryo transfer in autologous cycles and after fresh oocyte donation. Multiples were predominantly born preterm with a substantially increased perinatal mortality rate. The CBD for both years showed that elective SET (eSET) achieved a high CPR without compromising safety. ConclusionThis third report of The African Network and Registry for Assisted Reproductive Technology documents the prevailing practice of multiple embryo transfers in a cohort of relatively young women while highlighting the importance of disaggregating eSET, non-eSET and double embryo transfer. The high CPR after eSET and the increase in cryopreservation cycles are encouraging trends towards decreasing the number of embryos transferred without compromising effectiveness. Improved follow-up of ART pregnancies is required.

Maternal gestational diabetes in singleton pregnancies conceived by ART may be modified by periconceptional B vitamins.

The risk of maternal gestational diabetes mellitus (GDM) may be influenced by pregnancies conceived through assisted reproductive technology (ART). However, the influence of the dosage of B vitamins (folate, vitamin B6 and vitamin B12) on GDM weren't considered. Thus, we hypothesized that periconceptional B vitamins could modify maternal GDM in singleton pregnancies conceived by ART. This study is a prospective cohort study using data from 3,252 women with singleton pregnancies and received a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. We included an interaction term in the multivariable logistic and linear regression models, respectively, to test our hypothesis. Women who underwent ART were significantly associated with the incidence of GDM compared with spontaneous pregnancy women. The adjusted odds ratio (aOR) was 1.59, and the 95% confidence interval (CI) was 1.08-2.34. ART pregnancies also elevated OGTT (oral glucose tolerance test) 1-h blood glucose levels and OGTT 2-h blood glucose levels (P < 0.05). A positive association between dietary vitamin B6 (aOR = 1.60, 95% CI: 1.13-2.27), dietary vitamin B12 (aOR = 1.88, 95% CI: 1.34-2.64) and dietary folate (aOR = 1.66, 95% CI: 1.19-2.32) with GDM risk comparing the highest to the lowest quartile (all P trend < 0.001). The aORs of GDM for inadequate (< 400 μg/day), adequate (400-800 μg/day), and excessive (> 800 μg/day) supplemental folate intake were 1.00, 0.93, and 1.30, respectively (P trend = 0.033). Since only the supplemental folate illustrates a statistically significant interaction with ART (P for interaction < 0.05), the association between ART and GDM and OGTT blood glucose levels stratifying by supplemental folate were further evaluated. These increased risks of GDM (aOR = 1.62, 95% CI: 1.39-3.39) and the regression coefficients (β) of 1-h blood glucose (β = 0.76, 95% CI: 0.39-1.13) and 2-h blood glucose (β = 0.60, 95% CI: 0.29-0.92) in the multiple linear regression model were significant only in the ART group with excessive supplemental folate (> 800 μg/day). The risk of GDM is significantly elevated, particularly among those women who conceived ART with the intake of excessive supplemental folate (> 800 μg/day).