Spontaneous Conception Group Research Articles

Maternal and Neonatal Perinatal Outcomes of Singleton Pregnancies in Advanced-Age Women Undergoing IVF/ICSI-ET Compared with Spontaneous Conception: A Retrospective Propensity Score Matched Cohort Study.

To assess the safety and efficiency of in vitro fertilization/ intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) on maternal and neonatal perinatal outcomes in women (≥40y) with singleton pregnancies. This multi-center retrospective cohort study, carried out from January 2018 to June 2023, enrolled 1762 women (≥40y) with singleton pregnancies of at least 28weeks. Participants were divided into two groups: the IVF/ICSI-ET group (204 cases) and the spontaneous conception (SC) group (1558 cases). After 1:2 propensity score matching (PSM), the two groups were compared for maternal and neonatal outcomes. The SC group (1558 cases) was further divided by age into the <43 years group (1195 cases) and the ≥43 years group (363 cases) for subgroup analysis. Adverse maternal and neonatal outcomes were comparable between the IVF/ICSI-ET group and the SC group, with a higher cesarean section rate (78% vs 67.5%, P =0.013), an increased maternal ICU admissions rate (5.5% vs 1.3%, P =0.008), and a lower birth defects rate (1.1% vs 4.6%, P =0.037) in the IVF/ICSI-ET group. Subgroup analysis showed that women aged ≥43 years had higher incidences of gestational diabetes, gestational hypertension, cesarean section, and neonatal asphyxia compared to women aged <43 years. This study indicated IVF/ICSI-ET is relatively safe for women ≥40 years with singleton pregnancies. However, advanced maternal age deteriorated maternal and neonatal outcomes, and IVF/ICSI-ET further heightened the risk of cesarean section and maternal ICU admissions. Therefore, enhanced care and vigilance are crucial for women over 40 undergoing IVF/ICSI-ET.

INFERTILITY AND IVF PREGNANCY: A CROSS-SECTIONAL STUDY AMONG NORTH INDIAN WOMEN

Objective: The aim of the study is to compare the reproductive, perinatal, and neonatal outcomes among women conceived by in vitro fertilization to those females conceived spontaneously. Methods: It is an observational descriptive cross-sectional study. The data were collected for 1 year and 6 months. The study population consisted of 82 term females admitted under the Department of Obstetrics and Gynecology of the hospital nearing termination who conceived after infertility. A semi-structured pre-designed questionnaire was used to collect the data. Results: There was a significant difference in the mean age at conception of the patients who conceived spontaneously versus those who conceived after infertility treatments (p&lt;0.001). The rate of cesarean section was higher in the group with a history of infertility (75%) with the rate being 35.7% in the spontaneous conception group (p=0.038). The neonatal outcomes were not significantly different in the two groups. Conclusion: There is a need to analyze and compare patients on a larger scale, so as to decide if special algorithms are required to treat pregnancies conceived after infertility treatments.

Depressive symptoms during pregnancy and postpartum: associations with mode of conception and demographic and obstetric factors

ABSTRACT An increasing number of women are conceiving through assisted reproductive technology; however, few studies have investigated their mental health after successful conception. This study investigated the changes in depressive symptoms in women using assisted reproductive technology and the association between the mode of conception and perinatal depressive symptoms. A longitudinal observational study was conducted from 2015 to 2019, 542 pregnant women completed questionnaires on depressive symptoms at eight timepoints during the prepregnancy, pregnancy and first-year postpartum periods. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. A generalized estimating equation regression model was employed for repeated measures. In the assisted reproductive technology group, depressive symptoms were more prevalent during early pregnancy and at 1 month postpartum than before pregnancy, and more prevalent before pregnancy and at 1 month after childbirth than in the spontaneous conception group. No significant association was identified between the mode of conception and depressive symptoms during the antenatal or postnatal period. The lack of full-time employment and prepregnancy depressive symptoms were associated with antenatal depressive symptoms. Primipara status and depressive symptoms during prepregnancy and pregnancy were associated with depressive symptoms during the first-year postpartum. Assisted reproductive technology was not a risk factor for depressive symptoms during the pregnancy and postpartum periods, whereas primipara status, lack of full-time employment and prepregnancy depressive symptoms were negative predictors. Therefore, targeted mental health interventions should address these specific factors to effectively support maternal mental health.

Comparative influence of inappropriate gestational weight gain on pregnancy outcomes in IVF-conceived and spontaneously conceived twin pregnancies.

To investigate the influence of inappropriate gestational weight gain (GWG) on pregnancy outcomes in twin pregnant women with invitro fertilization (IVF) treatment. This retrospective cohort study included 2992 twin pregnant women and categorized the participants as follows: (i) they were classified into spontaneous conception (SC) or IVF groups based on whether they received IVF treatment, and (ii) they were categorized into inadequate, optimal, or excessive GWG groups according to the International Organization for Migration Twin Pregnancy Guidelines. Initially, the study investigated the separate effects of IVF treatment and different levels of GWG on the outcomes of twin pregnancies. Subsequently, after adjusting for confounding factors, multifactorial logistic regression analysis was performed to further investigate the impact of IVF treatment and high GWG on twin pregnancy outcomes. Based on this, the analysis was stratified by whether IVF was used to explore the effects of different GWG levels on each subgroup (those who underwent IVF and those who conceived spontaneously). Finally, potential multiplicative interactions between IVF and different GWG categories were examined to identify their combined effect on pregnancy outcomes. The results showed that women with twin gestations conceived via IVF exhibited significantly higher maternal age, pre-pregnancy body mass index, and a greater incidence of GWG beyond recommended guidelines compared to the SC group. Furthermore, both IVF treatment and inappropriate GWG increased the risk of adverse pregnancy outcomes, respectively. Following adjustments for confounding variables through multifactorial logistic regression, it was demonstrated that both IVF treatment and high GWG significantly elevated the risk of adverse outcomes in twin pregnancies, such as admission to the neonatal intensive care unit. It is noteworthy that inappropriate GWG, combined with IVF treatment, will stepwise increase the incidence of intrahepatic cholestasis of pregnancy, respiratory failure, respiratory distress, pre-eclampsia, maternal intensive care unit admission, and postpartum hemorrhage risk. However, these outcomes were less affected by inappropriate GWG in the SC group. Lastly, this study did not unveil a significant interaction between the IVF procedure and disparate levels of GWG in relation to the adverse outcomes. A high incidence of inappropriate GWG in twin pregnancies with IVF treatment and inappropriate GWG conferred more adverse twin pregnancy outcomes in the IVF group relative to the SC group. This study indicates that proper management of GWG may be a breakthrough in reducing adverse outcomes in twin pregnancies associated with IVF. Therefore, implementing proactive interventions such as supervised exercise programs, prescribed physical or dietary plans, enhanced weight management, or personalized counseling, holds promise for lowering the risks associated with inappropriate GWG in twin pregnancies resulting from IVF.

Effect of ART treatments on maternal and neonatal outcomes in singleton live births: A large-scale retrospective cohort study

BackgroundThe increased risk of pregnancy complications in the ART population has been reported, but the source of these risks remains controversial. The study aims to evaluate the association between ART treatments and patient characteristics with maternal and neonatal outcomes. MethodsThis was a retrospective analysis of 45,159 singleton pregnant women at a hospital between 2018 and 2021. The maternal and neonatal outcomes included pregnancy-induced hypertension (PIH), preeclampsia (PE), gestational diabetes mellitus (GDM), placental abruption (PA), placenta accreta spectrum (PAS), postpartum hemorrhage (PPH), cesarean section, iatrogenic and spontaneous preterm birth, small for gestational age (SGA), low birth weight (LBW), macrosomia, and birth defects. We assessed the outcomes among the fresh embryo transfer (ET), frozen embryo transfer (FET), and spontaneous conception (SC) groups. Potential risk factors were further analyzed in the ART population. ResultsFET was associated with higher risks for PIH (SC: AOR, 1.97(1.51–2.57); fresh ET: AOR, 1.68(1.03–2.72)), PE (SC: 2.28(1.86–2.80); fresh ET: AOR, 1.61(1.11–2.33)), PAS (SC: AOR, 3.89(3.39–4.46); fresh ET: AOR, 2.23(1.70–2.92)), PPH (SC: AOR, 3.46(2.76–4.34)); fresh ET: 2.09(1.39–3.14)), and macrosomia (SC: 1.53(1.25–1.86); fresh ET: AOR, 2.87(1.89–4.35). Fresh ET was associated with higher risks for PA (SC: AOR, 2.19(1.51–3.18); FET: AOR, 0.39(0.17–0.90)), SGA (SC: AOR, 1.56(1.06–2.31), FET: AOR, 0.42(0.19–0.91)), and LBW (SC: AOR, 2.24(1.82–2.77), FET: AOR, 0.63 (0.44–0.89)), and fresh ET is an independent risk factor for PA and SGA. Furthermore, the risk of GDM was associated with the biological characteristic of low-fertility patients. ConclusionsEmbryo status (fresh or frozen) is a key factor affecting the maternal and neonatal outcomes in ART treatments, while biological characteristics of infertile patients also play a certain role.

P-410 A modified artificial cycle-frozen embryo transfer(mAC-FET) protocol with evidence of corpus luteum(CL) formation as determined by serum relaxin-2 in early pregnancy :a prospective proof-of-concept study

Abstract Study question Can a mAC-FET protocol for endometrial preparation in ovulatory patients lead to formation of a CL as evidenced by serum relaxin-2 in the pregnant patients? Summary answer CL forms in the mAC-FET protocol as serum relaxin-2 in early pregnancy was comparable to that in spontaneous conception.Late luteal rise of relaxin-2 wasn’t demonstrated. What is known already Clinical evidence points to increased incidence of preeclampsia in pregnancies by AC-FET cycles compared to ovulatory FET cycles-natural cycle(NC) and mNC. The absence of CL and it’s secretory products like relaxin-2 is a contributing factor. FET protocols for endometrial preparation in ovulatory patients need to be optimised. NC/mNC-FET protocols need frequent monitoring. Also there is a temporal variability between LH/hCG and progesterone levels. We studied a mAC-FET protocol in ovulatory patients with a delayed start(day3-5 of the cycle),low dose transdermal 17β estradiol gel to see the formation of CL as elucidated by the presence of serum relaxin-2 in early pregnancy. Study design, size, duration A proof-of- concept prospective study was conducted at a tertiary centre (July2023-Dec2023). Serum relaxin-2(R&amp;D/Quantikine/ELISA) was determined in 4 groups of patients- Group-A. mAC-FET(n = 34) 1.On the day of start of progesterone 2.Post-ET day5-9 (along with serum progesterone) 3.In pregnancy(6-9 weeks of gestation) Group-B. AC-FET(n = 8) 1.On the day of start of progesterone 2.In pregnancy(6-9 weeks) Group-C. Spontaneous conception (n = 9) 1.In pregnancy(6-9 weeks) Group-D. Infertility patients ( n = 24) 1.Preovulatory. All patients were ≤40 years with a BMI ≤30kg/m2. Participants/materials, setting, methods In the AC-FET cohort-oral estradiol 6mg/day was started from day1/2 of the cycle. When endometrial thickness was&amp;gt;7mm,progesterone&amp;lt;1ng/ ml then intramuscular progesterone was started- 50mg/day-3 days,100mg on day4-the day of ET(Day-3 embryos) and continued every alternate day.Progesterone gel was added post-ET. In the mAC-FET cohort-17β transdermal estradiol gel(0.06%) 3mg/day was started from day3-5,rest of the protocol was similar. Statistical analysis was performed using appropriate non-parametric tests.Pearson coefficient(r) was used to assess linear-relationship.Two-tailed P&amp;lt;.05 indicated statistical significance. Main results and the role of chance Mean age and BMI of the patients with mAC-FET was 33.3±4.7 years and 24.4±3.7 kg/ m2 which was comparable across all groups (P=.14,P=.52 respectively). Clinical pregnancy rate in the mAC-FET group was 52.94%(18/34). 3 patients had an early abortion. Baseline relaxin-2 levels, median[Interquartile range(IQR)] were comparable- AC-FET cohort-9.1pg/mL(8.6-16.8), mAC-FET cohort-11.5pg/mL(9.6-13.7) and the infertility cohort-10.9pg/mL(8.4-14.5) (P=0.74) The primary outcome was the comparable levels of serum relaxin-2, in early pregnancy in the mAC-FET group and spontaneous conception group - median (IQR) 449.8pg/mL(73.1-492.3) and 487.9pg/mL(419.1-497.8) respectively (P=.12) The relaxin-2 levels, in early pregnancy in the mAC-FET group were significantly higher than the AC-FET group median(IQR) 449.8pg/mL(73.1-492.3) and 7.9pg/mL(7.8-9.5) respectively (P=.0005). As secondary outcomes, we studied the late luteal rise of relaxin-2 in the mAC-FET group and the relationship of late luteal progesterone with relaxin-2 in early pregnancies in the mAC-FET cohort. A late luteal rise of relaxin-2 was not demonstrated in the mAC-FET cohort. The serum relaxin-2, on the day of start of progesterone and on day5-9 post ET- median(IQR) 11.5pg/mL(9.6-13.7) and 11.4pg/mL(9.0-18.5), respectively was comparable (P=.18). The relationship between serum relaxin-2 in early pregnancy and the progesterone levels on day5-9 post ET in the mAC-FET cohort was not significant r = -.059 (P=.07) Limitations, reasons for caution This was a small proof- of-concept single centre study. Due to the limited numbers and short duration of the study, we could not compare efficacy, cancellation rates and pregnancy outcomes of the mAC-FET protocol with other FET protocols. Wider implications of the findings The mAC-FET protocol studied for endometrial preparation was similar to the AC -FET protocol regarding monitoring,flexibility and consistent progesterone exposure with the added advantage of the presence of the CL.This may decrease the risk of maternal/neonatal complications. Larger studies are needed to confirm it’s efficacy and impact on pregnancy outcomes. Trial registration number Not Applicable

Racial/ethnic disparity in severe maternal morbidity among women who conceived by in vitro fertilization

BackgroundIn vitro fertilization (IVF) as a fertility treatment is associated with adverse perinatal outcomes. Racial/ethnic disparity in severe maternal morbidity (SMM) in women who conceived by IVF is understudied. ObjectiveTo examine differences in the association between race/ethnicity and SMM between women who conceived spontaneously and those who conceived using IVF. MethodsWe included all singleton live births and stillbirths in the United States, 2016–2021; data were obtained from the National Center for Health Statistics. Maternal race/ethnicity included non-Hispanic White (NHW), non-Hispanic Black (NHB), American Indian and Alaska Native (AIAN), Asian, Pacific Islander (PI), Hispanic, and mixed-race categories. The SMM composite outcome included eclampsia, uterine rupture, peripartum hysterectomy, blood transfusion, and intensive care unit (ICU) admission. We used logistic regression to adjust for potential confounders (such as age, education, parity, prepregnancy body mass index, smoking during pregnancy, chronic hypertension, and preexisting diabetes) and to assess modification of the association between race/ethnicity and SMM by IVF. ResultsThe study population included 21,585,015 women: 52% were NHW, 15% NHB, 0.8% AIAN, 6% Asian, 0.2% PI, 24% Hispanic, and 2% were of mixed race. IVF was used by 183,662 (0.85%) women; the rate of the SMM composite outcome was 18.5 per 1000 deliveries and 7.9 per 1000 deliveries in the IVF and spontaneous conception groups, respectively (unadjusted rate ratio 2.34, 95% confidence interval [CI] 2.26–2.43). In women with spontaneous conception, NHB, Asian and mixed-race women had elevated odds of SMM compared with NHW women (adjusted odds ratio [aOR]=1.39, 95% CI 1.37–1.41; aOR=1.04, 95% CI 1.02–1.07; and aOR=1.42, 95% CI 1.38–1.46, respectively). Racial/ethnic disparities in SMM and its components were not different between the IVF and spontaneous conception groups for the mixed-race category. NHB and Hispanic women had significantly higher aORs for uterine rupture/intrapartum hysterectomy compared with NHW women in the IVF group, while Asian women had a higher aOR for ICU admission compared with NHW women in the IVF group. ConclusionWomen who conceived by IVF have a greater than two-fold higher risk of SMM and this higher risk is evident across all racial/ethnic groups. However, NHB and Hispanic women who conceived by IVF had a higher risk of uterine rupture/hysterectomy, and Asian women who conceived by IVF had a higher risk of ICU admission. Our results warrant further investigation examining pregnancy and postpartum care issues among racial/ethnic minority women who conceive using IVF.

Comparative cross-sectional study on sexual function of couples during pregnancy: Assisted reproductive techniques versus spontaneous conceptions.

This study aims to compare the sexual functions of couples undergoing assisted reproductive techniques (ART) with those conceiving spontaneously during pregnancy. A total of 102 couples participated in this cross-sectional study, with 68 couples in the spontaneous conception group and 34 couples in the ART group. Data collection was conducted face-to-face in the antenatal clinic using separate "Descriptive Information Form" for women and men, "Female Sexual Function Index (FSFI)" for women, and "Libido Scoring System (LSS)" for men. Descriptive statistical methods, Chi-square and Fisher exact tests, t-test, and Pearson correlation test were used for data analysis. It was observed that the mean FSFI total scores of women who conceived spontaneously and through ART during pregnancy were at a good level (≥30), while the mean LSS scores of their partners were at a moderate level (5-7). No statistically significant distinction existed among the groups. Further research is advisable by adjusting the sample selection criteria, such as gravida, duration of ART treatment, and gestational age.

Antenatal fetal growth patterns in uncomplicated pregnancies according to mode of conception and placental location

Newborns resulting from in-vitro fertilisation (IVF) had a significantly (P= 0.002) higher birthweight centile than those resulting from spontaneous conception (SC) but no significant changes were found in ultrasound estimated fetal weight (EFW) centile between 20-22 and 32–34 weeks between the IVF and SC groups. When stratified for the IVF methods used, significant (P = 0.02) fastest in-utero fetal growth (mean increase in centile of 5 between 2nd to 3rd trimester) was observed in the frozen embryo transfer (FET) subgroup compared to SC, and to IVF pregnancies resulting from fresh blastocyst transfer (FBT) or from oocyte donation (OD). Low placentation was significantly (P < 0.001) more common in the IVF group than in the SC group but was not associated with a change in growth pattern suggesting that fetal growth in-utero is independent of placental location but may be influenced by embryo freezing.

Comparison of maternal, fetal, obstetric and neonatal outcomes for 234 triplet pregnancies conceived in vivo versus IVF and ICSI conceptions

Research questionTriplet pregnancies have increased due to the rise in assisted reproductive techniques (ART). The objective of this study is to compare the results of natural versus ART triplet pregnancies. DesignThis is a single-center, retrospective cohort study that includes all triplet pregnancies followed up on at the La Paz University Hospital between 2000 and 2022. The characteristics of the pregnant women, maternal, fetal, obstetric, and perinatal outcomes were examined. Univariate and multivariate statistical analyses were performed. Results234 triplet pregnancies were analyzed: 92 triplet pregnancies in the spontaneous and artificial insemination conception group (natural conception) and 142 triplet pregnancies in the in vitro fertilization and intracytoplasmic sperm injection conception group (ART conception). Between 2000 and 2010, ART pregnancies were more frequent (p<0.01). The monochorionic triamniotic percentage was significantly higher (p<0.01) in the spontaneous group and the dichorionic triamniotic percentage (p=0.02) was higher in the ART group. After adjusting for confounders, the intrauterine growth restriction (IUGR) (p=0.01) result remained statistically significant with OR=8.65(1.66-45-03), being more frequent in the ART group. Maternal age (p=0.61; OR=1.08(0.99-1.18)) threatened preterm labor (p=0.10), Apgar test ≤5 at 5-minutes (p=0.99), pH<7.20 (p=0.99) and fetal death (p=0.99) differences disappearing upon adjustment for confounders. ConclusionTriplet pregnancies by ART had a higher rate of IUGR than natural triplet pregnancies. This could be related to the higher maternal age and the higher rates of lower Apgar test scores at 5-minutes and umbilical cord pH <7.20 in these pregnancies. In these cases, placental examination could provide valuable information.

The Impact of Assisted Reproductive Technology on Umbilical Cord Insertion: Increased Risk of Velamentous Cord Insertion in Singleton Pregnancies Conceived through ICSI.

Background and Objectives: Vasa previa (VP) is a significant perinatal complication that can have serious consequences for the fetus/neonate. Velamentous cord insertion (VCI) is a crucial finding in prenatal placental morphology surveillance as it is indicative of comorbid VP. Assisted reproductive technology (ART) has been identified as a risk factor for VCI, so identifying risk factors for VCI in ART could improve VP recognition. This study aims to evaluate the displacement of umbilical cord insertion (CI) from the placental center and to examine the relationship between the modes of conception. Materials and Methods: We conducted a retrospective study at the Obstetrics Department of Osaka Metropolitan University Hospital in Japan between May 2020 and June 2022. The study included a total of 1102 patients who delivered after 22 weeks of gestation. They were divided into three groups: spontaneous pregnancy, conventional in vitro fertilization (cIVF), and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We recorded patient background information, perinatal complications, perinatal outcomes, and a numerical "displacement score", indicating the degree of separation between umbilical CI and the placental center. Results: The displacement score was significantly higher in the cIVF and IVF/ICSI groups compared with the spontaneous conception group. Additionally, the IVF/ICSI group showed a significantly higher displacement score than the cIVF group. Conclusions: Our study provides the first evidence that the methods of ART can affect the location of umbilical CI on the placental surface. Furthermore, we found that IVF/ICSI may contribute to greater displacement of CI from the placental center.

Subfertility versus ART: unraveling the origins of fetal cardiac programming.

Do spontaneously conceived (SC) fetuses from subfertile couples show the same signs of cardiac remodeling as those observed after IVF treatments? As opposed to fetuses from IVF, SC fetuses from subfertile couples do not show cardiac remodeling and present a similar cardiac structure and function to those of SC fetuses from fertile couples. Subjects conceived by IVF present signs of cardiac remodeling and suboptimal function in utero and during childhood, including larger atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation as compared to SC individuals from fertile couples. There are no previous publications investigating the independent cardiac programming effects of infertility in SC fetuses from subfertile couples (with time-to-pregnancy (TTP) over 12 months). A prospective cohort study of 289 singleton pregnancies exposed and not exposed to subfertility recruited from 2019 to 2021, including 96 SC pregnancies from fertile couples (TTP under 12 months), 97 SC from subfertile couples (TTP over 12 months), and 96 from IVF after fresh embryo transfer. Fetal echocardiography was performed in all pregnancies. Epidemiological data and perinatal outcomes were collected in all pregnancies. The overall attrition rate was 15.7%. SC from subfertile couples and IVF pregnancies were identified as eligible at pregnancy diagnosis, and eligible SC pregnancies from fertile couples who attended our maternal-fetal unit were invited to participate at third trimester, being matched to the other groups by maternal age. Fetal echocardiography was performed at 29-34 weeks of pregnancy to assess cardiac structure and function, and results were adjusted by parental age, maternal smoking status, child's birth order, birthweight centile, gestational age, and estimated fetal weight at scan. Parental age, ethnicity, BMI, and smoking exposure, median gestational age and estimated fetal weight were similar in all study groups. There were no significant differences in infertility duration or etiology between the subfertile and the IVF populations (TTP: subfertile median 35 months (interquartile range 20-48) versus IVF: 47 (25-61); P-value = 0.051). While both fertile and subfertile SC groups presented similar fetal cardiac results, IVF fetuses showed larger atria (right atria-to-heart ratio: IVF mean 18.9% (SD 3.4) versus subfertile 17.8% (3.5) versus fertile 17.6% (3.3); adjusted P-value < 0.001), more globular ventricles (right ventricular sphericity index: IVF 1.56 (0.25) versus subfertile 1.72 (0.26) versus fertile 1.72 (0.26); <0.001), and thicker myocardial walls (relative wall thickness: IVF 0.86 (0.22) versus subfertile 0.64 (0.13) versus fertile 0.64 (0.18); <0.001). Whereas SC fetuses from fertile and subfertile couples had preserved cardiac function, IVF fetuses showed signs of suboptimal systolic and diastolic function, with reduced tricuspid ring displacement (IVF 7.26 mm (1.07) versus subfertile 8.04 mm (1.18) versus fertile 7.89 mm (1.51); <0.001) and increased left myocardial performance index (IVF 0.49 (0.08) versus subfertile 0.45 (0.09) versus fertile 0.45 (0.10); <0.001). A sub-analysis including only unexplained infertility cases in subfertile SC and IVF groups showed similar results. The fetal cardiac changes reported here are subclinical, and most of the cardiovascular parameters were within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with long-term cardiovascular disease remains to be demonstrated. Subfertility per se does not seem to be associated to fetal cardiac remodeling, which has been previously described in IVF fetuses. Future studies are warranted to further investigate other factors related to the observed fetal cardiac changes associated with ART. This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI16/00861, PI17/00675, PI18/00073, INT21/00027)-co-funded by the European Union, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant no 1531. The authors have no conflicts of interest to declare. N/A.

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

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

Is Conception by Means In Vitro Fertilization Associated With Increased Risk of Antenatal Anxiety and Depression?

Objectives Mental health during pregnancy is a very important public health issue with negative effects on both maternal and child outcomes. The aim of our study is to examine the possible association between conception via in vitro fertilization (IVF) and anxiety or depression during the third pregnancy trimester in the Greek population during the years of financial crisis. Materials and Methods This single-center prospective cohort study was conducted in a tertiary university hospital during the period 2017-2018. Pregnant women attending the Antenatal Care Program between 30th-32nd gestational week were asked to complete Hamilton Anxiety Rating Scale (HAM-A) and Beck Depression Inventory (BDI). A propensity score match for 10 variables was conducted in a 1:3 ratio. Results Of the 521 eligible patients, 446 women were included in our study. Four hundred fourteen of them conceived spontaneously, and 32 via IVF. After propensity score matching, 76 remained in the analysis, of whom 57 conceived spontaneously and 19 with IVF. The IVF group had a higher rate of anxiety (18.8%) and a lower rate of depression (9.4%) than the spontaneous conception group (13.5% and 13.5%, respectively), but the differences were not statistically significant before and after propensity score matching. Conclusion Our study showed that pregnancies after IVF had a higher incidence of antenatal anxiety and a lower incidence of antenatal depression in comparison to pregnancies that were conceived naturally, although the differences did not reach statistical significance.

To study the obstetrical and neonatal outcomes in spontaneous conception v/s IVF conception

Objective: Our study aims to study the overall obstetrical and neonatal outcomes in spontaneous conception v/s IVF conception. Study design: Hospital based prospective study. Methods and Materials: The study was conducted at our hospital over a period of one and a half years from September 2014 to April 2016. It was a hospital based prospective study. A total of 100 (50 spontaneous conception and 50 IVF conception) women who were admitted for safe confinement at Obstetrics and gynecology department of hospital were included in the study. For the purpose of the study, the study group was divided in two groups IVF conception group and spontaneous conception group for comparison of obstetrical and neonatal outcome. A detailed history was taken and thorough examination findings were noted. The antenatal course was noted and also the obstetric and neonatal outcomes were noted. Results: It was observed that the obstetrical outcomes were poorer in IVF conception group than in the spontaneous conception group. Significant association was found between gestational duration, mode of delivery, NICU stay requirement with mode of conception. Association was also found between ante-partum haemorrhage (APH), preeclampsia, gestational diabetes, post-partum haemorrhage (PPH) with mode of conception. Conclusion: Maternal age, gestational duration, pre term delivery, LSCS deliveries, low birth weight babies, low APGAR score, and requirement of NICU stay in IVF conception group was significantly higher than in spontaneous conception group. Association was also found between ante-partum haemorrhage, pre-eclampsia, gestational diabetes mellitus, preterm premature rupture of membranes, post-partum haemorrhage with mode of conception.

Racial and Ethnic Disparities in the Perinatal Health of Infants Conceived by ART.

Although racial and ethnic disparities in adverse birth outcomes have been well documented, it is unknown whether such disparities diminish in women who use medically assisted reproduction (MAR). We examined differences in the association between maternal race and ethnicity and adverse birth outcomes among women who conceived spontaneously and those who used MAR, including assisted reproduction technology (ART), eg, in-vitro fertilization, and also non-ART MAR, eg, fertility drugs. We conducted a population-based retrospective cohort study using data on all singleton births (N = 7 545 805) in the United States from 2016 to 2017. The outcomes included neonatal and fetal death, preterm birth, and serious neonatal morbidity, among others. Modified Poisson regression was used to estimate adjusted rate ratios (aRR) and 95% confidence intervals (CI) and to assess the interactions between race and ethnicity and mode of conception. Overall, 93 469 (1.3%) singletons were conceived by MAR. Neonatal mortality was twofold higher among infants of non-Hispanic Black versus non-Hispanic White women in the spontaneous-conception group (aRR = 1.9, 95% CI: 1.8-1.9), whereas in the ART-conception group, neonatal mortality was more than fourfold higher in infants of non-Hispanic Black women (aRR = 4.1, 95% CI: 2.9-5.9). Racial and ethnic disparities between Hispanic versus non-Hispanic White women were also significantly larger among women who conceived using MAR with regard to preterm birth (&lt;34 weeks) and perinatal mortality. Compared to women who conceived spontaneously, racial and ethnic disparities in adverse perinatal outcomes were larger in women who used MAR. More research is needed to identify preventive measures for reducing risks among vulnerable women who use medically assisted reproduction.

Risk of Higher Blood Pressure in 3 to 6 Years Old Singleton Born From OHSS Patients Undergone With Fresh IVF/ICSI

BackgroundA large registry-based study found the increasing disorders of cardiovascular and metabolism in IVF children but underlying mechanism is still unknown. Few studies have investigated any association between OHSS and cardiovascular or metabolic function in subsequent children.ObjectiveTo evaluate the effect of ovarian hyperstimulation syndrome (OHSS) on blood pressure of singletons after in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI).Study DesignThe singlet-center corhort study included 1780 singletons born with IVF/ICSI and 83 spontaneously conceived children from 2003 to 2014. Follow-up has lasted more than 10 years, and is still ongoing. This study analyzed data from follow-up surveys at 3 to 6 years of age.Participants, Setting and MethodsWe recruited 83 children (Group E) spontaneously conceived (SC) as control group and 1780 children born with IVF/ICSI including 126 children born to OHSS-fresh embryo transfer (ET) women (Group A), 1069 children born to non OHSS-ET women (Group B), 98 children conceived by women who developed into moderate or severe OHSS after oocyte retrieval and selected the frozen-thawed embryo transfer (FET) (Group C), 487 children conceived with non OHSS-FET (Group D). We evaluated cardiometabolic function, assessed BP in mmHg, heart rate, anthropometrics, and metabolic index including glucose, serum lipid (triglyceride, total cholesterol, low density lipoprotein, high density lipoprotein), thyroid function, of those children. The BP and heart rate were measured twice on the same day. We applied several multiple regression analyses to investigate the effect of OHSS in the early pregnancy.Main FindingsBy the single factor analysis, the SBP and DBP in the SC group (SBP: 99.84 ± 8.9; DBP: 55.27 ± 8.8) were significantly lower than OHSS-ET group’s, while the blood pressure was similar between the SC group and other three ART groups. Children had higher BP in the OHSS-ET group (SBP: 101.93 ± 8.17; DBP: 58.75 ± 8.48) than in the non OHSS-ET (SBP: 99.49 ± 8.91; DBP: 56.55 ± 8.02) or OHSS-FET group (SBP: 99.38 ± 8.17; DBP: 55.72 ± 7.94). After using multiple regression analysis to adjust current, early life, parental and ART characteristics, the differences in the SBP and DBP (B (95% confidence interval)) between OHSS-ET and non OHSS-ET remained significant (SBP: 3.193 (0.549 to 2.301); DBP: 3.440 (0.611 to 2.333)). And the BP showed no significant difference complementarily when compared non OHSS-FET group with non OHSS-ET group. In addition, the anthropometrics, fast glucose, serum lipid, and thyroid index did not differ among the ART groups.Principal ConclusionsOHSS might play an independent key role on offspring’s BP even cardiovascular function. Electing frozen-thawed embryo transfer for high risk of OHSS population may reduce the risk of the high BP trend.Wider Implications of the FindingsIt is a large sample study to investigate the effect of OHSS on offspring’s health. These findings provide a clinic evidence of the impact of early environment (embryo even oocyte stage) on the offspring’s cardiovascular health. Our study emphasis the importance of the accuracy of IVF clinic strategy and preventing the OHSS after fresh embryo transfer.

P-771 Subfertility versus in vitro fertilization procedures: unravelling the origins of fetal cardiac remodeling in assisted reproductive technologies

Abstract Study question Do spontaneously conceived (SC) fetuses from subfertile couples present signs of cardiac remodeling as those observed after in vitro fertilization (IVF) treatments? Summary answer SC fetuses from subfertile couples do not associate cardiac remodeling, and their cardiac structure and function are similar to those of SC from fertile couples. What is known already Fetuses and children from IVF associate cardiac remodeling and suboptimal function, including dilated atria, more globular and thicker ventricles, reduced longitudinal motion and impaired relaxationin uteroand after birth. Fetal cardiac changes have been demonstrated both after fresh and frozen embryo transfer. The SC fetuses used as ‘controls’ in our previous publications were conceived by fertile couples thus making it difficult to separate the contribution of infertilityper sefrom the IVF procedures on cardiac programming. There are no previous cardiovascular studies investigating the independent effects of infertility in SC fetuses from subfertile couples (time-to-pregnancy (TTP) over 12 months). Study design, size, duration Prospective cohort study of 289 singleton pregnancies recruited from 2017 to 2021, including 96 SC pregnancies from fertile couples (TTP less than 12 months), 97 SC from subfertile couples (TTP over 12 months) and 96 from IVF after fresh ET. Fetal echocardiography was performed in all pregnancies. Epidemiological data and perinatal outcomes were collected in all pregnancies. Participants/materials, setting, methods IVF pregnancies from our centre were identified as eligible at pregnancy diagnosis. Eligible SC pregnancies from fertile and subfertile couples who attended our Maternal-Fetal Unit were invited to participate at third trimester, being matched to the IVF pregnancies by maternal age. Fetal echocardiography was performed at 29-34 weeks of pregnancy to assess cardiac structure and function. Echocardiographic comparisons were adjusted by nulliparity, birthweight centile, gestational age and estimated fetal weight at scan. Main results and the role of chance Parental age, ethnicity, body mass index and smoking exposure, median gestational age and estimated fetal weight were similar in all study groups. There were no significant differences in infertility duration or aetiology between the subfertile and the IVF populations (TTP: subfertile median 30 months [IQR 20-54] versus IVF: 47 [25-61]; p-value=0.052). While both fertile and subfertile SC groups presented similar fetal cardiac results, IVF fetuses showed larger atria (right atria-to-heart ratio: IVF mean 18.9% [SD 3.4] versus subfertile 17.8% [3.5] versus fertile 17.6% [3.3]; adjusted P-value&amp;lt;0.001), more globular ventricles (right ventricular sphericity index: IVF 1.56 [0.25] versus subfertile 1.72 [0.26] versus fertile 1.72 [0.26]; &amp;lt;0.001), and thicker myocardial walls (relative wall thickness: IVF 0.86 [0.22] versus subfertile 0.64 [0.13] versus fertile 0.64 [0.18]; &amp;lt;0.001). Whereas SC fetuses from fertile and subfertile couples had preserved cardiac function, IVF fetuses showed signs of suboptimal systolic and diastolic function with reduced tricuspid ring displacement (IVF 7.26 mm [1.07] versus subfertile 8.04 mm [1.18] versus fertile 7.89 mm [1.51]; &amp;lt;0.001) and increased left myocardial performance index (IVF 0.49 [0.08] versus subfertile 0.45 [0.09] versus fertile 0.45 [0.10]; &amp;lt;0.001). A sub-analysis including only unexplained infertility cases in subfertile SC and IVF groups showed similar results. Limitations, reasons for caution The fetal cardiac changes reported here are subclinical, with most cardiovascular parameters lying within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with long-term cardiovascular disease remains to be proven. Wider implications of the findings Subfertility per se does not seem to be associated to fetal cardiac remodeling, which have been previously described in IVF fetuses. Future studies are warranted to further investigate the factors related to fetal cardiac changes associated to ART. Trial registration number Not a trial

Additional Adverse Perinatal Outcomes With No Effect on Neonatal Mortality and Birth Defects in Pregnancies Conceived by Assisted Reproductive Technology.

BackgroundPregnancy outcomes and perinatal diseases of children conceived by assisted reproductive technology (ART) and spontaneous conception (SC) are still unclear. We sought to compare the effects of ART and SC on adverse neonatal outcomes.MethodsWe included 5,913 neonates admitted to the neonatal intensive care unit (NICU) of the First Affiliated Hospital of the University of Science and Technology of China between January 2017 and December 2020. There were 1,112 (18.8%) ART pregnancies and 4,801 (81.2%) SC pregnancies. Data on maternal characteristics, comorbidities during pregnancy, and neonatal outcomes were collected and analyzed. Logistic regression models estimated the odds ratios (ORs) and 99% CIs of neonatal outcomes according to ART pregnancy. Neonatal outcomes primarily included neonatal respiratory distress syndrome (NRDS), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), neonatal anemia, birth defects, and mortality.ResultsAmong 5,913 neonates, 485 (8.2%) had NRDS, 165 (2.8%) had BPD, 113 (1.9%) had ROP, 602 (10.2%) had neonatal anemia, and 1,112 (18.8%) were ART infants. The incidence of pregnancy-related complications, such as gestational diabetes mellitus (GDM), gestational hypothyroidism, and rheumatic immune diseases, in mothers receiving ART, was higher than that in the SC group. On multivariate analysis, ART was independently associated with NRDS (OR = 1.46; 95% CI, 1.11–1.93; p = 0.008) and ROP (OR = 1.79; 95% CI, 1.06–3.05; p = 0.031). Moreover, the association persisted after adjustment for maternal age, history of cesarean section, preconception factors, and pregnancy complications. For BPD (OR = 1.44; 95% CI, 0.91–2.27; p = 0.117) and neonatal anemia (OR = 1.12; 95% CI, 0.87–1.45; p = 0.373), the associations were attenuated substantially when adjusting for pregnancy complications. ART was associated with neither birth defects (OR = 0.98; 95% CI, 0.77–1.25; p = 0.889) nor mortality (OR = 0.98; 95% CI, 0.51–1.91; p = 0.961).ConclusionART was independently associated with adverse neonatal outcomes, including NRDS and ROP. Therefore, women who conceive by ART must improve their perinatal health and management of pregnancy-related comorbidities to enhance the quality of life of their offspring.

The size, number and bilaterality of endometriomas do not affect spontaneous conception chance following surgical removal.

Endometrioma surgery is associated with a reduction in ovarian reserve. However, removal of an endometrioma may increase the likelihood of a spontaneous conception. The objective of this study was to assess the pre-operative and operative variables affecting spontaneous conception following endometrioma surgery. Data from 211 women ≤40 years of age who underwent an endometrioma surgery at a university-based infertility clinic between January 2005 and June 2020 were reviewed retrospectively. The main outcome measure was spontaneous clinical pregnancy. We had 84 women with and 127 women without a successful spontaneous conception making up the case and control groups. The median ages of the cases and controls were 27 and 32 years, respectively (p<0.001). The rate of recurrence was significantly lower in the spontaneous conception group when compared to controls (29.8% vs. 52.8%, respectively; p=0.001). Our results showed no differences in the number, size, or side of the endometriomas in both groups. Multivariate logistic regression analysis showed significant independent effects of age (B: -.166, OR {odds ratio}: 0.847, 95% CI {confidence interval}: 0.791-0.907, p<0.001), recurrence (B: -1.030, OR: 0.357, 95% CI: 0.188-0.678, p=0.002), and laparoscopic surgery rather than laparotomy (B: 1.585, OR: 4.879, 95% CI: 1.029-23.133, p=0.046) for spontaneous conception. The size, number and bilaterality of the endometrioma did not affect the spontaneous conception likelihood following surgical removal. However, increasing age and recurrence are negatively associated with the likelihood of spontaneous conception. Laparoscopic surgery may increase the chance of spontaneous conception when compared to laparotomy.