Assisted Reproductive Technology Group Research Articles

O-087 Use and safety of assisted reproductive technology in young BRCA carriers with a pregnancy after treatment for breast cancer: results from an international cohort study

Abstract Study question Does assisted reproductive technology (ART) to achieve pregnancy after breast cancer (BC) adversely affect maternal or fetal outcomes in germline BRCA1/2 pathogenic variants (PVs) carriers? Summary answer This global study showed that ART is safe in BC survivors harboring BRCA1/2 PVs, with no apparent worsening of maternal prognosis or fetal outcomes. What is known already Very little information is currently available on the safety of fertility treatments in BC survivors harboring BRCA1/2 PVs. The previous published work on this topic included only 22 cases of patients who used any kind of ART to become pregnant; the small number of included patients did not allow for statistical analysis. Hence, concerns remain among physicians counseling young BRCA carriers with prior history of BC on the safety of using ART to attempt pregnancy Study design, size, duration International, multicenter, hospital-based, retrospective cohort study across 78 centers worldwide. The study included 4732 women harboring known BRCA1/2 PVs and diagnosed at ≤ 40 years with stage I-III BC between January 2000 and 2020 (Lambertini M et al., JAMA 2024;331:49-59). This specific analysis included 543 women with a pregnancy after prior history of BC harboring a BRCA1/2 PV. Participants/materials, setting, methods Among 543 young BRCA carriers with a pregnancy after BC, 436 conceived naturally and 107 using ART. ART procedures included embryo transfer under hormonal replacement therapy following oocyte or embryo cryopreservation at diagnosis, treatment with oocyte donation, ovulation induction and In-Vitro-Fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) carried out after anticancer treatments. Survival analyses compared patients achieving a pregnancy spontaneously (spontaneous pregnancy group) vs. using ART (ART group). Main results and the role of chance Of 107 pregnancies achieved through ART, 45 (42.1%) were obtained with oocytes or embryo cryopreserved at diagnosis, 33 (30.8%) with ovarian stimulation and IVF/ICSI after completion of anticancer therapies, 21 (19.6%) with embryo transfer following oocyte donation and for 8 ART type was missing. As compared to survivors in the spontaneous pregnancy group, those in the ART group were older at the time of conception (37.1 vs. 34.3 years, p < 0.001), had more often hormone receptor-positive BC (46 (43.4%) vs. 132 (30.8%), p = 0.016), and a longer median time from BC diagnosis to conception (4.2 vs. 3.3 years, p = 0.004). No statistically significant differences in pregnancy complications were observed between cohorts (p = 0.382). However, patients who conceived with ART had more miscarriages (12, 11.3%) than those who conceived spontaneously (38, 8.8%). The opposite was true for induced abortion (1 (0.9%) vs. 36 (8.3%), respectively). At a median follow up of 9.1 years (interquartile range 6.4-13.4), no detrimental effect of ART on disease-free survival (DFS) was observed with 13 DFS events observed among the 99 patients undergoing ART and 118 DFS events in patients with spontaneous pregnancy (log-rank p = 0.147). Limitations, reasons for caution Despite the global representation, this retrospective study included a small number of patients for this specific analysis. Nevertheless, this is the largest analysis to date investigating safety of ART in BC survivors harboring BRCA1/2 PVs. Wider implications of the findings Young BRCA carriers can be reassured that the use of ART to achieve pregnancy is safe. Oocyte/embryo cryopreservation in young BRCA carriers allows access to pre-implantation genetic testing, if the patients are interested. Trial registration number NCT03673306

P-772 Assisted reproductive technology and the risk of minor congenital heart defects in the newborn

Abstract Study question Are children conceived through assisted reproductive technology (ART) at higher risk of minor congenital heart defects (CHD) compared with naturally conceived (NC) children? Summary answer Contrary to previous studies children conceived through ART had similar risk of minor CHDs compared with children conceived naturally. What is known already Congenital heart defects (CHD) may precipitate cardiac arrhythmias, lead to thromboembolic events, culminate in heart failure or even sudden cardiac demise. A systematic review and meta-analysis showed an elevated odds ratio (OR) for diagnosis of any CHD among children conceived through in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compared with NC children. Other studies indicate that ART is associated with an increased arterial blood pressure and vascular dysfunction in the pulmonary and systemic arterial vasculature. This association persists throughout childhood, adolescence, and early adulthood in individuals conceived through ART; this indicates a lasting impact on the cardiovascular circulatory system. Study design, size, duration The present study is a sub-study to the Copenhagen Baby Heart Study (CBHS), a prospective population-based cohort study of > 25 000 children born in the three main maternity wards in Copenhagen, Denmark, in 2016–2018. Transthoracic echocardiography (TTE) was performed on all children within 60 days of delivery and diagnosis of CHD was reviewed by a specialist in paediatric cardiology. Information regarding parental health, pregnancy, delivery, and the newborn was collected through Danish patient registries. Participants/materials, setting, methods This study includes all children conceived by ART in the CBHS (n = 1 784), and a matched group (1:4 by maternal age at birth) of NC children (n = 7 141). Exclusion criteria were genetic or chromosomal syndromes and heart surgery. Minor CHD was defined as an atrial (ASD) or ventricular septum defects (VSD), bicuspid aortic valve, coarctation of the aorta, pulmonary stenosis, or patent ductus arteriosus. We calculated ORs using logistic regression analyses. Main results and the role of chance The mean maternal age at birth was 34.9 (standard deviation [SD] ±4.4) and 35.1 years (SD ± 4.6) and the newborn mean age at TTE was 12.1 (SD ± 9.3) and 12.2 days (SD ± 9.4) in the ART and NC population, respectively. Parental CHD was registered in 40 (2.2 %) children in the ART group and 121 (1.7 %) in the NC group. Overall, 165 (9.2%) children conceived by ART and 611 (8.6%) NC children were diagnosed with a minor CHD. The most prevalent CHDs were VSD and ASD which accounted for 38.8 % and 35.2 % in children with CHD in the ART group, respectively, and 36.8 % and 33.9 % in children with CHD in the NC group. The unadjusted OR for minor CHD was 1.09 (95% CI 0.91–1.30). Adjustments for maternal age and parental CHD did not change the OR. There were no differences in ORs when stratifying by minor CHD type. We stratified by the method of ART: ICSI and IVF and frozen embryo transfer and fresh embryo transfer, and calculated risk of minor CHD comparing the methods and with NC children. We found no difference in any ORs, crude or adjusted. Limitations, reasons for caution Children born preterm, and children with severe minor and major CHDs, were underrepresented in the cohort indicating parents of such children chose not to participate in a research project that would include another hospital visit. Residual confounding is plausible because parental CHD diagnoses were retrieved from patient registries. Wider implications of the findings The number of children conceived through ART is increasing each year and previous research have found an increased risk of CHD in children conceived through ART. Our findings indicate no increased risk of minor CHD, providing comforting and significant information for advising individuals considering or undergoing ART treatment. Trial registration number NCT02753348

The impact of assisted reproductive technologies on ADHD: A systematic review and meta-analysis

BackgroundThe escalating utilization of assisted reproductive technology (ART) in response to global infertility rates has spurred research into its complications. Short-term and long-term outcomes have been extensively studied, particularly the neurological concerns surrounding attention-deficit/hyperactivity disorder (ADHD) among ART-conceived children. This study aims investigate the association between ART and ADHD. MethodsMedline, Embase, Scopus, and Web of Science databases were searched through April 4, 2023. Cohort, case-control, and cross-sectional studies were eligible for inclusion. primary summary measures included the unadjusted relative risk (RR) and adjusted hazard ratio (HR) with 95 % confidence intervals. Both fixed-effects and random-effects models were utilized for meta-analysis data pooling to determine the overall effect size. The onset of ADHD in children conceived through ART compared to those conceived naturally. ResultsThe systematic search yielded 8 studies with 10,176,148 individuals included in the meta-analysis. The meta-analysis revealed a pooled RR of 0.93 (0.68–1.26) for cohort studies and a pooled RR of 0.97 (0.41–2.29) for cross-sectional studies, along with a pooled HR of 1.08 (1.03–1.13) for ADHD in the ART group compared to the non-ART group. ConclusionWhile this study identifies some potential association between ART and ADHD, the limited effect size and inherent heterogeneity underscore the need for cautious interpretation.

The Effect of Assisted Reproductive Technology on Morbidity and Mortality of Twin Premature — A Secondary Publication

Objective: It is thought that twin neonates born from pregnancies resulting from assisted reproductive technology (ART) are clinically riskier than twin neonates born from spontaneous pregnancy. However, information on the risks in premature infants born as a result of ART pregnancies is limited. In our study, premature twin infants born from ART and spontaneous pregnancies were compared to clinical outcomes. Method: All premature twin infants hospitalized in our unit between September 2017 and September 2019 and born under 32 weeks of gestation were included in our study. Demographic and clinical results of premature twins born as a result of spontaneous and ART pregnancies were compared. Results: A total of 142 premature twins, 116 (81.6%) in the spontaneous twin group and 26 (18.4%) in the ART twin group, were included in the study. Demographic and clinical features were similar between ART and spontaneous twin groups (P > 0.05). Conclusion: Our study determined that premature infants born due to ART pregnancies did not have any additional risk compared to spontaneous infants. This result shows that the main determinants of clinical outcomes in premature infants are gestational week and birth weight.

Congenital Heart Defects in Pregnancies Conceived by Assisted Reproductive Technology: Comparing Functional and Structural Defects.

Introduction Congenital heart defects (CHD) are one of the most common congenital anomalies, and their association with assisted reproductive technology (ART) is controversial in different populations. The purpose of this study was to evaluate this association and to provide information about the necessity of specialized echocardiography during pregnancy with ART. Methods This retrospective study was performed on all pregnancies conceived by ART and referred for fetal echocardiography to the Rasoul Akram and Akbar Abadi hospitalsin Tehran, Iran. A total of 109 patients were enrolled in the study (56 in the ART group and 53 in the non-ART). Two-dimensional and color Doppler echocardiography were performed on all patients to identify heart problems and anomalies and medical records of the patients were reviewed. The outcome was considered the presence of functional and structural heart defects on echocardiography. Results The study groups were similar in terms of maternal age and GA.The ART group consisted of 31 singletons (55%) and 25 multiples (45%). All pregnancies in the non-ART group were singletons. Following in vitro fertilization (33%), ovulation induction (25%) was the next most used method. The findings of echocardiography were one atrial septal defect (ASD) in ART and one in non-ART, six ventricular septal defects (VSD) in ART and three in non-ART, and one ASD and VSD in the ART group. These structural abnormalities showed no difference in the two groups (P value = 0.58). There was no significant difference in rhythm between the two groups (P = 0.51). Echocardiographic indices of both groups did not differ statistically except in the TR-PG index (P value = 0.02). Conclusions The structural defects of the two groups were not different, and no heart dysfunction was observed in ART fetuses. There was no association between ART and CHD in our study. We concluded that echocardiography by pediatric cardiologists is not necessary for these fetuses.

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.

Impact of assisted reproductive technology on birth weight discordance in twins

To explore the association between assisted reproductive technology (ART) and birth weight discordance in twins (BWDT). A retrospective analysis was conducted on twin infants born between January 2011 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University, with complete basic birth data. The impact of ART on the occurrence of BWDT was identified by the multivariate logistic regression analysis. A total of 3 974 pairs of twins were included, with 1 431 conceived naturally and 2 543 through ART. Neonates in the ART group had higher birth weights than those in the naturally conceived group (P<0.001). The incidence of BWDT was lower in the ART group compared to the naturally conceived group (16.17% vs 21.09%, P<0.001). The multivariate logistic regression analysis, adjusting for confounding factors such as maternal age, parity, pre-pregnancy body mass index, gestational diabetes, hypothyroidism, gestational age, and chorionic properties, showed no significant difference in the risk of BWDT between the ART and naturally conceived groups (P>0.05). ART is not associated with the risk of BWDT.

Визначення особливостей перебігу вагітності та пологів, стану плода і новонародженого у вагітних після застосування допоміжних репродуктивних технологій (дані ретроспективного аналізу)

The rapid growth in the number of infertile couples leads to the development of assisted reproductive technologies (ART). Among the most common forms of infertility are tubo-peritoneal, endocrine, and caused by the male factor, and prevention of pregnancy complications caused by ART treatment cycles becomes one of the main tasks of practicing clinicians. Purpose - to determine the features of the course of pregnancy and childbirth; to assess the condition of the fetus and newborn in pregnant women after the application of ART to improve the perinatal outcomes of pregnancy and childbirth. Materials and methods. A retrospective clinical and statistical analysis of 334 histories of pregnancy and childbirth of women, as well as medical records of newborns from women, was conducted over the past five years, which formed the ART group - 221 history of pregnancy and childbirth, and the group of spontaneous pregnancy - 113 history of pregnancy and childbirth. Results. The structure of the subjects was statistically significant dominated by pregnant women over the age of 35 years and pregnant women in late reproductive age. The main characteristics of women after the ART application were a statistically significant predominance of somatic and gynecological pathology. The structure of pregnancy complications in women after ART application was dominated by threatening late spontaneous miscarriages, isthmic-cervical insufficiency and vaginitis, and in the structure of labor complications - anomalies of labor activity and premature rupture of fetal membranes. Among newborns from women in the ART group, perinatal mortality was 18.0%. Conclusions. The revealed features of somatic and gynecological anamnesis, as well as aspects of the course of pregnancy and childbirth and the condition of newborns in women after ART application are the basis for an in-depth examination of this category of pregnant women in order to improve approaches to predicting, diagnosing and optimizing preventive measures, as well as to improve the perinatal consequences of pregnancy and childbirth. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. No conflict of interests was declared by the authors.

Maternal and perinatal outcomes in women aged 42 years or older.

To describe maternal and fetal outcomes of pregnancies after 42 years and to compare maternal and fetal morbidities according to the conception mode; comparing pregnancies obtained spontaneously and those resulting from assisted reproductive technology (ART). This retrospective cohort study was conducted in a level 3 maternity hospital. This study covered all women, aged 42 years or older, who gave birth between January 1, 2014 and December 31, 2019. Univariate and multivariate analyses with logistic regression models were used to compare maternal and perinatal outcomes depending on conception mode: spontaneous or using ART. A sample of 532 women, including 335 spontaneous pregnancies (63%) and 147 pregnancies after ART (27.6%) were studied. Conception mode was missing for 50 (9.4%). We found increased rates not only of maternal complications such as maternal overweight and obesity, pre-eclampsia, and gestational diabetes, but also of interventions such as hospitalization during pregnancy, cesarean section, postpartum hemorrhage, and perinatal outcome like preterm birth. There were also more maternal and perinatal negative outcomes among the ART group. After multivariate analysis, pre-eclampsia was predominant in the ART group (odds ratio 0.25, 95% confidence interval 0.07-0.85, P = 0.02). While maternal and fetal risks increase for late pregnancies, there also appears to be a difference depending on the conception mode, with pregnancies resulting from ART having more pregnancy-related complications than those obtained spontaneously.

Does controlled ovarian hyperstimulation in women with a history of borderline tumor influence recurrence rate?

PurposeTo determine the recurrence rate in the women with controlled ovarian hyperstimulation after a history of borderline ovarian tumors (BOT).MethodsThis was a retrospective analysis of 275 patients with BOT undergoing surgery for fertility preservation in our hospital between 2001 and 2017. Cases were divided into an assisted reproductive technology (ART) treatment group (n = 15) and a non-ART treatment group (n = 260). We compared the recurrence rate, survival rate and pregnancy outcomes between these two groups.ResultsThe ART group had a higher recurrence rate (33.33% vs. 10.80%, P = 0.023). Survival analysis indicated that the recurrence time in patients undergoing ART was significantly shorter (P = 0.026). A low pregnancy rate before diagnosis, and high intraoperative blood loss, were associated with postoperative ART treatment (P < 0.05). Multivariate analysis showed that ART treatment and bilateral lesions both significantly increased the risk of recurrence (P < 0.05). The pathological type of recurrent tumors was often the same as the initial tumor.ConclusionThe postoperative use of ART in patients with BOT significantly increased the recurrence rate, but does not significantly affect the overall survival rate of patients. Therefore, ART in such patients should be individualized, and close follow-up is necessary after ART.

Sex-specific differences in head circumference of term singletons after assisted reproductive technology: a multicentre study in Japan

Research questionDoes fertility treatment, specifically assisted reproductive technology (ART), affect head circumference in term singletons? DesignA total of 32,651 women who delivered at term at 12 maternity hospitals in Japan between 2010 and 2018 were included in the analysis; of these, 1941 (5.9%) and 2984 (9.1%) women conceived through ART and non-ART fertility treatments (timed intercourse, ovulation induction or artificial insemination), respectively. The study evaluated the adjusted odds ratios of head circumference ≥90th percentile stratified by infant sex and type of ART procedure after adjusting for covariates, with natural conception as the reference group. ResultsART significantly increased the risk of head circumference ≥90th percentile (adjusted odds ratio 1.56 [95% confidence interval 1.25–1.96]), whereas non-ART fertility treatment did not increase the risk (1.14 [0.92–1.42]). This increased risk of head circumference ≥90th percentile was observed exclusively in male neonates (1.73 [1.33–2.26]) and not in female neonates (1.18 [0.76–1.85]) in the ART group. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC-FET) and blastocyst-stage embryo transfer were significantly associated with head circumference ≥90th percentile (1.60 [1.26–2.02], 1.70 [1.30–2.22] and 1.72 [1.33–2.24], respectively). ConclusionsThe use of ART, particularly FET, HRC-FET or blastocyst-stage embryo transfer, was linked with a heightened risk of head circumference ≥90th percentile compared with non-ART fertility treatment or natural conception. The increased risk was observed only in male neonates.

Pregnancy and neonatal outcomes of monozygotic twins resulting from assisted reproductive technology: a 10-year retrospective study

BackgroundMonozygotic twins (MZTs) are associated with high risks of maternal and fetal complications. Even with the widely used elective single embryo transfer (SET), the risk of MZTs following assisted reproductive technology (ART) treatments remains. However, most studies of MZTs focused on the relevant etiology, with few studies describing pregnancy and neonatal outcomes.MethodsThis retrospective cohort study included 19,081 SET cycles resulting from in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT) and testicular sperm aspiration (TESA) performed between January 2010 and July 2020 in a single university-based center. A total of 187 MZTs were included in this investigation. The main outcome measures were the incidence, pregnancy and neonatal outcomes of MZTs. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy loss.ResultsThe overall rate of MZTs from ART treatment in SET cycles was 0.98%. No significant difference was found in the incidence of MZTs among the four groups (p = 0.259). The live birth rate of MZTs in the ICSI group (88.5%) was significantly more favorable than in the IVF, PGT and TESA groups (60.5%, 77.2% and 80%, respectively). IVF resulted in a significantly increased risk of pregnancy loss (39.4%) and early miscarriage (29.5%) in MZT pregnancies compared to ICSI (11.4%, 8.5%), PGT (22.7%, 16.6%) and TESA (20%, 13.3%). The total rate of twin-to-twin transfusion syndrome (TTTS) in MZTs was 2.7% (5/187); however, the TESA group had the highest rate at 20% and was significantly higher than the PGT group (p = 0.005). The four ART groups had no significant effect on the occurrence of congenital abnormalities or other neonatal outcomes in newborns from MZT pregnancies. Multivariate logistic regression analysis revealed that infertility duration, cause of infertility, the total dose of Gn used, history of miscarriages, and the number of miscarriages were not related to the risk of pregnancy loss (p > 0.05).ConclusionsThe rate of MZTs was similar among the four ART groups. The pregnancy loss and the early miscarriage rate of MZTs was increased in IVF patients. Neither the cause of infertility nor the history of miscarriage was correlated with the risk of pregnancy loss. MZTs in the TESA group had a higher risk of TTTS, placental effects influenced by sperm and paternally expressed genes may play a role. However, due to the small total number, studies with larger sample sizes are still needed to validate these result. Pregnancy and neonatal outcomes of MZTs after PGT treatment seem to be reassuring but the duration of the study was short, and long-term follow-up of the children is needed.

Comparison of Genetic Profiles of Neonates in Intensive Care Units Conceived With or Without Assisted Reproductive Technology

A growing number of children are conceived with assisted reproductive technology (ART). However, there is a lack of studies systematically analyzing the genetic landscape of live-born children conceived through ART who need intensive care in the neonatal period. To investigate the incidence and type of molecular defects among neonates conceived through ART who are in intensive care units (NICUs) with suspected genetic conditions. This was a cross-sectional study using data from the China Neonatal Genomes Project, a multicenter national neonatal genome data set managed by the Children's Hospital of Fudan University. All participants were from level III and IV NICUs and included 535 neonates conceived through ART with suspected genetic conditions, with data collected between August 1, 2016, and December 31, 2021, and 1316 naturally conceived neonates with suspected genetic conditions in the same clinical settings, with data collected between August 1, 2016, and December 31, 2018. The data were analyzed between September 2021 and January 2023. Whole-exome sequencing or target clinical exome sequencing with pathogenic or likely pathogenic single-nucleotide variant (SNV) and copy number variation (CNV) detection was performed for each individual. The primary outcome was the molecular diagnostic yield, mode of inheritance, spectrum of genetic events, and incidence of de novo variants. A total of 535 neonates conceived through ART (319 boys [59.6%]) and 1316 naturally conceived neonates (772 boys [58.7%]) were included. A genetic diagnosis was established for 54 patients conceived through ART (10.1%), including 34 patients with SNVs (63.0%) and 20 with CNVs (37.0%). In the non-ART group, 174 patients (13.2%) received a genetic diagnosis, including 120 patients with SNVs (69.0%) and 54 with CNVs (31.0%). The overall diagnostic yield was comparable between the ART group and the naturally conceived neonates (10.1% vs 13.2%; odds ratio [OR], 0.74; 95% CI, 0.53-1.02), as was the proportion of SNVs (63.0% vs 69.0%; OR, 0.68; 95% CI, 0.46-1.00) and CNVs (37.0% vs 31.0%; OR, 0.91; 95% CI, 0.54-1.53) detected by sequencing. Furthermore, the proportions of de novo variants in the ART group and the non-ART group were similar (75.9% [41 of 54] vs 64.4% [112 of 174]; OR, 0.89; 95% CI, 0.62-1.30). This cross-sectional study of neonates in NICUs suggests that the overall genetic diagnostic yield and the incidence of de novo variants were similar between live-born neonates conceived through ART and naturally conceived neonates in the same settings.

The impact of assisted reproductive technology and ovulation induction on breech presentation: A whole of population-based cohort study.

Multiple studies have suggested a likely association between breech presentation and assisted reproductive technology (ART) for conception. The aims were to determine whether conception via in vitro fertilisation (IVF) and ovulation induction (OI) is associated with fetal malpresentation at birth and to ascertain what mediating factors most significantly contribute to fetal malpresentation. This whole-population-based cohort study included 355 990 singleton pregnancies born in Queensland, Australia, between July 2012 and July 2018. Multinomial logistic regression models estimated the adjusted odds of breech, transverse/shoulder and face/brow malpresentations in pregnancies conceived via spontaneous conception, OI (OI group) and IVF with or without intracytoplasmic sperm injection (ART group). After adjustment for potential confounding factors, breech presentation occurred approximately 20% more often in singleton pregnancies conceived via both ART (adjusted odds ratio: 1.20, 95% confidence interval: 1.10-1.30, P< 0.001) and OI (1.21, 95% confidence interval: 1.04-1.39, P< 0.05). No significant associations were observed between the three modes of conception and transverse/shoulder or face/brow presentations. Low birthweight was found to be the most significant mediating factor for breech presentation in pregnancies conceived via ART and OI. Similar levels of increased odds of breech presentation are present in pregnancies conceived via OI and ART, suggesting a shared underlying mechanism for the aetiology of breech presentation. For women who are considering or have conceived via these methods, counselling with respect to this increased risk is recommended.

Infantile Prognosis of Neonates Conceived by Assisted Reproductive Technology: A Prospective Study

Background: Neonates of infertile couples are golden babies, and taking care of them is of paramount importance. However, it is not yet clear if the prognosis is different between these neonates and those from fertile couples. Objectives: The present study aimed to assess neonates conceived by assisted reproductive technology (ART). Methods: In this cohort study, 165 newborns conceived by ART and 165 naturally conceived newborns were included. The prospective study was conducted from April 2020 to October 2021. A neonatologist examined all newborns after birth, and outcomes were followed up over one year and compared with neonates of fertile couples using appropriate statistical tests. Results: The preterm neonates (60% vs. 38%) were higher in ART cases (P &lt; 0.001) than in the other cases. Also, the mean gravid and parity were lower, but the nulliparity was higher in the ART group (P &lt; 0.001) than in the other cases. Moreover, multiple pregnancies (45% vs. 10%; P &lt; 0. 001) and the C/S rate (91% vs. 67%) were higher in ART cases (P &lt; 0.001) than in the other cases. Similarly, the preeclampsia rate (16 % vs. 6%; P = 0.004) and the number of females were higher in the ART group (P = 0.035) than in the other groups. However, birth weight (P = 0.002) and the Apgar were significantly lower (P = 0.002; P = 0.012) in the ART group than in the other groups. IUGR was significantly higher (17% vs. 7%) (P = 0.006), while NEC and RDS were more common in the ART group (P &lt; 0.001) than in the other groups. In addition, more extended hospital stay (P &lt; 0.001) and more common re-admission and weight &lt; the 5th percentile after one year were observed in the ART group (P = 0.021) than in the other groups. Conclusions: According to the findings, pregnancy after ART has more side effects before and after birth and in infancy, not only because of multistation but also due to manipulations in ART.

The Risks of Birth Defects and Childhood Cancer With Conception by Assisted Reproductive Technology

ABSTRACT As the proportion of births conceived with assisted reproductive technology (ART) continues to increase, a growing body of literature continues to examine the risks involved such as the higher risk of birth defects. Recently, several studies have suggested that ART-conceived children may have a greater risk of childhood cancer. This population-based cohort study aimed to evaluate the risk of childhood cancer as a function of birth defect status and method of conception. Data were obtained from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, birth certificates (2004–2013), birth defect registries, and cancer registries in 4 states. The Society for Assisted Reproductive Technology Clinic Outcome Reporting System contains comprehensive information on ART procedures from 86% of all clinics and more than 92% of all ART cycles in the United States. Assisted reproductive technology cycles reported from January 2004 to December 2017 that resulted in live births were included in this study. For each ART-conceived delivery, the subsequent 10 deliveries were selected as the non-ART comparison group, and siblings of each ART birth were selected as the ART sibling group. The ART group was divided into 4 subgroups based on the combination of oocyte source (autologous or donor) and embryo state (fresh or thawed). A host of independent variables with established associations on birth defects, cancer, and/or ART were selected a priori for inclusion in statistical models. The total study population included 165,125 ART-conceived children, 31,524 non-ART siblings, 12,451 children born as a result of infertility treatment without ART (ovulation induction/intrauterine insemination [OI/IUI]), and 1,353,440 naturally conceived children. A total of 29,571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect. Compared with naturally conceived children, risks for defects were increased for all other groups for nonchromosomal (adjusted odds ratios [AORs] ranged from 1.20 to 1.24, except for donor-fresh), blastogenesis (AORs, 1.22–1.74), cardiovascular (AORs, 1.04–1.26), gastrointestinal (AORs, 1.28–2.01), musculoskeletal (AORs, 1.10–1.48), and genitourinary among male children (AORs, 1.15–1.40, except for donor-fresh). Orofacial defects were increased in the OI/IUI and autologous-fresh and autologous-thawed groups (AORs, 1.26–1.42). The risk of any cancer was increased among ART autologous-fresh and non-ART siblings (hazard ratios [HRs], 1.31 and 1.34, respectively). A total of 127 children had both birth defects and cancer, with 53 (42%) of these children having leukemia. A Cox proportional hazards regression model identified 2 components for the risk of cancer: method of conception and type and number of birth defects. The presence of chromosomal defects was strongly associated with cancer risk (HRs, 8.70 for all cancers and 21.90 for leukemia), and this was further increased in the presence of both chromosomal and nonchromosomal defects (HRs, 21.29 for all cancers, 64.83 for leukemia, and 4.71 for embryonal tumors). The results of this study demonstrate that compared with naturally conceived children a significantly increased risk of nonchromosomal birth defects was found among children conceived with infertility treatment and that the risk of cancer was increased by greater than 30% among non-ART siblings and ART children born from autologous-fresh cycles. Among both naturally conceived and ART-conceived children, the presence of birth defects was associated with a greater risk of cancer.

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).

Prenatal diagnosis of fetuses conceived by assisted reproductive technology by karyotyping and chromosomal microarray analysis.

Invasive prenatal evaluation by chromosomal microarray analysis (CMA) and karyotyping might represent an important option in pregnant women, but limited reports have applied CMA and karyotyping of fetuses conceived by assisted reproductive technology (ART). This study aimed to examine the value of CMA and karyotyping in prenatal diagnosis after ART. This retrospective study included all singleton fetuses conceived by ART from January 2015 to December 2021. Anomalies prenatally diagnosed based on karyotyping and CMA were analyzed. Prevalence rates for various CMA and karyotyping results were stratified based on specific testing indications including isolated-and non-isolated ART groups. The rates of CMA findings with clinical significance (pathogenic/likely pathogenic) and karyotype anomalies were assessed and compared to those of local control individuals with naturally conceived pregnancies and without medical indications. In total, 224 subjects were assessed by karyotyping and CMA. In the examined patients, chromosomal and karyotype abnormality rates were 3.57% (8/224) and 8.93% (20/224), respectively. This finding indicated a 5.35% (12/224)-incremental rate of abnormal CMA was obtained over karyotype analysis (p=0.019). The risk of CMA with pathogenic findings for all pregnancies conceived by ART (5.80%, 13/224) was markedly elevated in comparison with the background value obtained in control individuals (1.47%, 9/612; p=0.001). In addition, risk of CMA with clinically pathogenic results in isolated ART groups was significant higher compared to the background risk reported in the control cohort (p=0.037). Prenatal diagnosis including karyotyping and CMA is recommended for fetuses conceived by ART, with or without ultrasound findings.

Living with the Threat of Covid-19: Exploring the Psychological Impact of Covid-19 in Those who Conceived Through ART Versus Spontaneously.

To explore and compare anxiety relating to the threat of Covid-19 in pregnancy by women who conceived through assisted reproductive technology (ART) and spontaneously. We also examined the psychological coping strategies used and lived experience for both groups. A total of 21 women who conceived through ART at a private university based IVF and a matched sample of women who conceived spontaneously were enrolled from July 2020 to February 2021. This was a mixed methods study. Covid-19-specific anxiety was measured using the coronavirus anxiety scale (CAS) as well as a validating qualitative data model with the use of open-ended questions to expand on quantitative findings. In both groups of women the level of anxiety detected by the CAS was low and mixed coping strategies (emotion-focused and problem-solving) were utilized. The ART group expressed more positive feelings towards pregnancy during the Covid-19 pandemic. The vulnerable ART group is no more at risk for negative emotional well-being during the Covid-19 pandemic. Additionally, healthcare providers ought to be knowledgeable of various Covid-19 coping strategies that may provide emotionally protective measures for all women of reproductive age. This is of particular importance as effective coping may ultimately prevent disruptions that could compromise prenatal care during the covid-19 pandemic.

Assisted reproductive technology causes reduced expression of amino acid transporters in human full-term placentas.

In the mouse model, manipulations of assisted reproductive technology (ART) can lead to enlarged placentas and influence the expression of amino acid transporters in placentas during mid-to late-gestation. However, it is uncertain whether those abnormal changes presented in ART mouse placentas also occur in human ART placentas. We choose the placenta tissue of pregnant woman by ART in term birth (ART group) and by natural pregnancy in term birth (control group) to compare the birth weight of the baby, placental weight and ratio of the fetal/placental weight of these two groups. We then detect the mRNA and protein expression of placental amino acid transporter genes (SNAT1, SNAT2, SNAT4, LAT1 and LAT2) in these two groups by real-time quantitative PCR, Western blot and immunofluorescence staining. Additionally, the PI3K-AKT-mTOR signaling activity was also analyzed. There were no statistical differences in new birth weight between the ART group and the control group. Compared with the control group, the placenta weight of baby was significantly higher in ART group and ratio of the fetal/placental weight was significantly lower in ART group. We found that the mRNA and protein expression of A system of amino acid transporter SNAT1, SNAT2 and SNAT4 in placenta were significantly down-regulated in ART group compared with placentas from natural pregnancies. Additionally, there were no statistical differences of the mRNA and protein expression of L system of amino acid transporter LAT1 between these two groups, but amino acid transporter LAT2 in placenta was significantly down-regulated in ART group. Furthermore, the PI3K-AKT-mTOR signaling activity was inhibited in ART group. ART leads to the expressions of amino acid transporter genes SNAT1, SNAT2, SNAT4 and LAT2 significantly down-regulated in placenta accompanied by the PI3K-AKT-mTOR signaling inhibition, which suggests that ART may affect the function of placenta amino acid transporter during the late pregnancy, leading to enlarged placentas and probably low birth weight.