Assisted Reproductive Technology Pregnancies Research Articles

Retrospective Analysis of Obstetric Intensive Care Unit Admissions Reveals Differences in Etiology for Admission Based on Mode of Conception

(Anesth Analg. 2020;130:436–444) As births using assisted reproductive technology increase, the maternal and neonatal safety of these pregnancies continues to be of concern. There are established associations between assisted reproductive technology pregnancies and a number of adverse outcomes, including gestational diabetes, hypertensive disorders of pregnancy, obstetric hemorrhage, abnormal placentation, and cesarean delivery. There is a lack of studies examining the risk of intensive care unit (ICU) admission in women using assisted reproductive technology. This study compared parturients who conceived via in vitro fertilization (IVF) and those who did not in terms of etiology and course of ICU admission, particularly focusing on postpartum hemorrhage.

Assisted reproductive technologies (ART) and placental abnormalities.

Objectives Assisted reproductive technologies (ART) may be associated with placental abnormalities including placenta previa, umbilical cord abnormalities, and placental abruption. Our study evaluates the relationship between ART and placental abnormalities compared with spontaneously conceived controls. Methods An IRB-approved cohort study was conducted including women who delivered between January 2013 and December 2018. We excluded delivery prior to 23weeks and known fetal anomalies. Patients were matched with controls (2:1) for parity, age, and mode of delivery. Controls were women who had spontaneously conceived and delivered immediately preceding and following the index delivery. The primary outcome was placental abnormalities found on both antenatal ultrasound and pathology in ART gestations compared with spontaneously conceived gestations. Results There were 120 ART pregnancies and 240 matched control pregnancies identified. The groups were similar for parity, BMI, comorbidities, number of multiples, mode of delivery, and female newborns. The ART group had a higher maternal age (37.1±5y vs. 30.0±5y; p<0.001), greater preterm birth (29 vs. 6%; p<0.001), and lower BW (2,928±803g vs. 3,273±586g; p<0.001). The ART group had a higher incidence of placenta previa on ultrasound (4.0 vs. 0.4%, p=0.01), adherent placentas at delivery (3 vs. 0% p=0.014), placental abruption (2 vs. 0%; p=0.04), as well asan increased rate of velamentous cord insertion (12 vs. 3%, p<0.001) and marginal cord insertion (28 vs. 15%, p=0.002). ART demonstrated a two-fold likelihood of abnormal placental pathology. Conclusions ART is associated with increased rate of placental abnormalities, including abnormal umbilical cord insertion and increased rates of adherent placentation. This information may be beneficial in planning and surveillance in patients with ART pregnancies.

Reproductive Travel of Intended Parents for Delivery of Gestational Carrier Pregnancies.

To explore the role of reproductive travel (travel to another state or country for reproductive services) for intended parents at the time of delivery of gestational carrier pregnancies and to analyze the sociodemographic characteristics of those who build families through gestational surrogacy. We conducted a cross-sectional study of births involving gestational surrogacy in Utah from 2009 to 2018. Data were obtained from birth certificates. State and country of residence were collected for intended parents, and the legal climates of these locations were assessed by reviewing laws at the time. Sociodemographic characteristics were compared among intended parents, parents with pregnancies resulting from assisted reproductive technology (ART) without gestational surrogacy, and parents with spontaneous pregnancies. A total of 361 gestational carrier pregnancies resulted in the birth of at least one liveborn neonate during the study period, involving 715 intended parents. Additionally, 50,434 parents delivered children after nonsurrogacy ART, and 950,460 parents delivered children after spontaneous fertilization. Many intended parents (17.2%) lived in countries outside of the United States, the majority of which (69.9%) had laws against surrogacy. Of those who lived within the United States, 57.4% lived outside of Utah, but only 15.9% lived in states that banned compensated surrogacy. Statutes in Utah support compensated and uncompensated gestational surrogacy. Intended parents were significantly older than parents with both nonsurrogacy ART pregnancies and spontaneous pregnancies (median age 38, 31, and 29 years, respectively) and had higher levels of education; 70.2% of intended parents had a bachelor's degree or above, compared with 48.2% of parents with nonsurrogacy ART pregnancies and 33.1% of parents with spontaneous pregnancies. A majority of intended parents live outside of Utah, which may be an important consideration for health care professionals caring for women with gestational carrier pregnancies. However, most intended parents live in places that do not have laws banning surrogacy, suggesting that there may be other reasons that intended parents travel for delivery.

DNA methylation status of imprinted H19 and KvDMR1 genes in human placentas after conception using assisted reproductive technology.

Assisted reproductive technologies (ARTs), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are thought to destabilize genomic imprints. Previous studies examining the association between ART and aberrant DNA methylation have been inconclusive. The DNA methylation status of H19 and KvDMR1was compared between newborns conceived through ART and those conceived naturally to evaluate the safety of ART. Placental tissues from 6 full-term, naturally conceived pregnancies (no gestational comorbidities) and six full-term ART pregnancies (no gestational complication) were collected. Genomic DNA (gDNA) and RNA were extracted from both groups. Real-time PCR was used to analyze the mRNA expression levels of H19 and KvDMR1 in the placenta for both groups. A whole-genome DNA methylation microarray was used to examine three placentas from full-term, naturally conceived pregnancies and three placentas from full-term IVF pregnancies. The expression level of H19 in the IVF group was significantly higher than that in the natural pregnancy group, whereas the expression level of KvDMR1 was significantly lower in the ART group than in the natural pregnancy group. Also, human ART manipulation resulted in placental gDNA methylation modifications. Conclusion: Abnormal methylation patterns were detected in phenotypically normal phenotype conceived by ART, which may occur due to imprinting errors in sperm/oocyte cells or side effects of in vitro embryo culture procedures. Further investigation is necessary to determine whether imprinted gene expression and DNA methylation can be regulated through other mechanisms. Assisted reproductive technology (ART); placenta; methylation; H19; KvDMR1.

Родоразрешение пациентки с индуцированной беременностью в программе ВРТ (суррогатное материнство) и врастанием плаценты

Родоразрешение пациентки с индуцированной беременностью в программе ВРТ (суррогатное материнство) и врастанием плаценты

Association of Abnormal Placental Cord Insertion With Assisted Reproductive Technology [20A

INTRODUCTION: Abnormal placental cord insertion has been associated with an increase in preterm delivery, low birth weight, neonatal intensive care admissions and cesarean delivery. Assisted reproductive technology (ART) has been associated with some similar placenta-medicated pregnancy complications. We hypothesize an increase in abnormal placental cord insertion in pregnancies conceived using ART, thereby contributing to the increased association of adverse pregnancy outcomes. METHODS: We performed an IRB approved, retrospective chart review of 3728 singleton and twin placentas sent to pathology at the University of Massachusetts between January 2011-January 2016. Placental pathology reports were reviewed and evidence of abnormal placental cord insertion, either velamentous or marginal, were recorded. Chi-square test was used for categorical variables and student T-test for continuous. Logistic regression was used to control for potential confounders. P less than 0.05 was used for statistical significance. RESULTS: Of the 3728 pregnancies, 3615 were conceived via spontaneous conception, whereas 113 were conceived through ART. Women who conceived with ART were more likely to be married, of white race, older and have multiple gestations than those with spontaneous conception. ART pregnancies were over 2-fold more likely to have abnormal placental cord insertions (OR 2.1 [1.1–3.9], P=.03). After adjusting for confounding factors, statistical significance was no longer noted. CONCLUSION: Pregnancies conceived with ART were more likely to have abnormal placental cord insertion in our study. A larger sample size of women conceived using ART would be needed to fully understand the effect of ART on abnormal placental cord insertion beyond the confounding effect of multiple gestations.

Changes in the perinatal outcomes of twin pregnancies delivered at a tertiary referral center in Korea during a 24-year period from 1995 to 2018.

ObjectiveTo analyze the changes in the clinical characteristics and perinatal outcomes of twin pregnancies delivered at a tertiary referral center in Korea during a 24-year period.MethodsThis was a retrospective cohort study of twin pregnancies delivered at 24–40 weeks of gestation, from 1995 to 2018. The subjects were divided into 4 groups according to the year of delivery: 1995–2000, 2001–2006, 2007–2012, and 2013–2018. The trends in the changes in the twin birth rate, maternal age, assisted reproductive technology (ART) pregnancy rate, chorionicity, obstetric complications, delivery outcomes, and neonatal outcomes over the periods were analyzed.ResultsA total of 2,133 twin pregnancies were included in the study. The twin birth rate increased from 16.7/1,000 in 1995–2000 to 42.2/1,000 in 2001–2006, 49.5/1,000 in 2007–2012, and 61.8/1,000 in 2013–2018. The maternal age and ART pregnancy and dichorionic twin rates increased, while the monochorionic twin rate decreased over the periods. The incidence of fetal congenital anomalies, cervical incompetence, gestational diabetes mellitus, preeclampsia, and placental abruption increased over the periods. The preterm birth (PTB) rate significantly decreased owing to the decreasing elective late-PTB rate; however, the early-PTB rate significantly increased.ConclusionThis study found that twin pregnancies increased steadily over the last 24 years and that the increase was related to increased maternal age and ART pregnancy rate. The incidence of obstetric complications increased over the periods; however, the neonatal intensive care unit admission rate decreased, along with decreases in the elective late-PTB rate.

Children Conceived by Assisted Reproductive Technology Prone to Low Birth Weight, Preterm Birth, and Birth Defects: A Cohort Review of More Than 50,000 Live Births During 2011-2017 in Taiwan.

Objectives: The use of assisted reproductive technology (ART) has increased rapidly in Taiwan. The purpose of this study is to discuss the risks of low birth weight, preterm birth, and birth defect for children conceived by assisted reproductive technology in Taiwan.Methods: Both National ART report database and National birth reports were obtained from the Health Promotion Administration in the Ministry of Health and Welfare in Taiwan. The cohort included live births (n = 1,405,625) and children conceived by ART (n = 50,988/172,818 cycles) from 2011 to 2017. The prevalence of low birth weight, preterm birth, and birth defect were compared between the ART and natural pregnancy groups.Results: Children conceived by ART displayed a higher rate of low birth weight as compared to those in the natural pregnancy group (p < 0.001), even when analyses were restricted to singleton births (p < 0.001). A higher rate of preterm birth (p < 0.001) was also observed in children conceived by ART even when analyses were restricted to singleton births (p < 0.05). A significant increased rate of birth defects was noted from children conceived by ART (p < 0.05).Conclusions: With the increasing need for and use of ART-conceptions, the likelihood of risks induced or related to Assistant Reproductive Technology (ART) has drawn considerable attention in recent years. Taiwan, as one of the leading countries with outstanding ART performances and modern medical care, the result of the current study suggests that further consideration and tighter regulations and policy are needed with regard to the use of ART.

Time trends in placenta-mediated pregnancy complications after assisted reproductive technology in the Nordic countries

The use of assisted reproductive technology is increasing worldwide and conception after assisted reproduction currently comprises 3%-6% of birth cohorts in the Nordic countries. The risk of placenta-mediated pregnancy complications is greater after assisted reproductive technology compared with spontaneously conceived pregnancies. Whether the excess risk of placenta-mediated pregnancy complications in pregnancies following assisted reproduction has changed over time, is unknown. To investigate whether time trends in risk of pregnancy complications (hypertensive disorders in pregnancy, placental abruption and placenta previa) differ for pregnancies after assisted reproductive technology compared with spontaneously conceived pregnancies during 3 decades of assisted reproduction treatment in the Nordic countries. In a population-based cohort study, with data from national health registries in Denmark (1994-2014), Finland (1990-2014), Norway (1988-2015) and Sweden (1988-2015), we included 6,830,578 pregnancies resulting in delivery. Among these, 146,998 (2.2%) were pregnancies after assisted reproduction (125,708 singleton pregnancies, 20,668 twin pregnancies and 622 of higher order plurality) and 6,683,132 (97.8%) pregnancies were conceived spontaneously (6,595,185 singleton pregnancies, 87,106 twin pregnancies and 1,289 of higher order plurality). We used logistic regression with post-estimation to estimate absolute risks and risk differences for each complication. We repeated analyses for singleton and twin pregnancies, separately. In subsamples with available information, we also adjusted for maternal body mass index, smoking during pregnancy, previous cesarean delivery, culture duration, and cryopreservation. The risk of each placental complication was consistently greater in pregnancies following assisted reproductive technology compared with spontaneously conceived pregnancies across the study period, except for hypertensive disorders in twin pregnancies, where risks were similar. Risk of hypertensive disorders increased over time in twin pregnancies for both conception methods, but more strongly for pregnancies following assisted reproductive technology (risk difference, 1.73 percentage points per 5 years; 95% confidence interval, 1.35-2.11) than for spontaneously conceived twins (risk difference, 0.75 percentage points; 95% confidence interval, 0.61-0.89). No clear time trends were found for hypertensive disorders in singleton pregnancies. Risk of placental abruption decreased over time in all groups. Risk differences were -0.16 percentage points (95% confidence interval, -0.19 to -0.12) and -0.06 percentage points (95% confidence interval, -0.06 to -0.05) for pregnancies after assisted reproduction and spontaneously conceived pregnancies, respectively, for singletons and multiple pregnancies combined. Over time, the risk of placenta previa increased in pregnancies after assisted reproduction among both singletons (risk difference, 0.21 percentage points; 95% confidence interval, 0.14-0.27) and twins (risk difference, 0.30 percentage points; 95% confidence interval, 0.16-0.43), but remained stable in spontaneously conceived pregnancies. When adjusting for culture duration, the temporal increase in placenta previa became weaker in all groups of assisted reproductive technology pregnancies, whereas adjustment for cryopreservation moderately attenuated trends in assisted reproductive technology twin pregnancies. The risk of placenta-mediated pregnancy complications following assisted reproductive technology remains higher compared to spontaneously conceived pregnancies, despite declining rates of multiple pregnancies. For hypertensive disorders in pregnancy and placental abruption, pregnancies after assisted reproduction follow the same time trends as the background population, whereas for placenta previa, risk has increased over time in pregnancies after assisted reproductive technology.

Maternal and child-health outcomes in pregnancies following Assisted Reproductive Technology (ART): a prospective cohort study

BackgroundStudies comparing the outcome of spontaneous versus assisted reproductive technologies (ART) pregnancies report heterogeneous results. Despite the success of ART to overcome infertility, concern is growing regarding both its safety and its effect on maternal and child health. The objective of this study was to compare maternal and child-health outcomes after ART relative to natural conception.MethodsA population-based birth cohort study was carried out among pregnant women expected to deliver in 2015 in Pelotas, southern Brazil. Maternal outcomes included pregnancy complications and gestational weight gain. Gestational age, weight, intrauterine growth restriction, length and head circumference, and 1-min and 5-min Apgar, as well as health problems at birth and breastfeeding were defined as offspring outcomes. Statistical analyses were performed using linear and logistic regression. G-formula was used to perform mediation analysis.ResultsThe study included 4252 babies born by spontaneously pregnancies and 23 babies born after ART. Adjusted analyses showed that children conceived from ART presented lower means of gestational age (p = 0.001), birth weight (p = 0.002), length (p < 0.001), and head circumference at birth (p = 0.02). However, more than 90% of the effect of ART over these outcomes was mediated by multiple pregnancy.ConclusionOur findings suggest that the possible negative effect on the child-health outcomes is due mainly to the higher incidence of multiple pregnancies and not because of ART. The reasons for the increase in adverse pregnancy outcomes associated with ART singleton pregnancies are still uncertain and warrants further research. Further large-population studies are needed to confirm these results.

Effects of Vitrification on the Imprinted Gene Snrpn in Neonatal Placental Tissue

Objective: To investigate the effects of vitrification on the expression of the imprinted gene Snrpn in neonatal placental tissue.Methods: Neonatal placental tissue was collected from women with natural pregnancy (control group) and from women in assisted reproductive technology (ART) pregnancy group, following fresh and vitrified embryo transfer (fresh group and vitrified group, respectively). Snrpn mRNA expression and SNRPN protein levels in placental tissue from these three groups were assessed by real-time reverse transcription polymerase chain reaction and Western blot, respectively. DNA methylation in the Snrpn promoter region was analyzed by bisulfite-pyrosequencing.Results: The expression of Snrpn mRNA and SNRPN protein was found to be higher in placental tissue from the fresh and vitrified ART groups, compared to the control group. There was no significant difference in SNRPN gene or protein expression between the fresh and vitrified groups. DNA methylation at the Snrpn promoter region was not significantly different between these three groups.Conclusions: Human ART may alter the transcriptional expression and protein levels of the imprinted gene Snrpn. However, compared to other ART methods, vitrification may not aggravate or reduce this effect. Moreover, the altered expression of Snrpn is likely not directly related to DNA methylation of the Snrpn promoter region.

Perinatal and neonatal outcome in poor ovarian responders in assisted reproductive technology (ART) pregnancy

Perinatal and neonatal outcome in poor ovarian responders in assisted reproductive technology (ART) pregnancy

Association between serum homocysteine level and unexplained infertility in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): A retrospective, hospital-based, case-control study.

BackgroundLower serum homocysteine (Hcy) levels are found to correlate with a better chance of clinical pregnancy and better embryo grades in assisted reproductive technology (ART). However, there is little knowledge on the association between Hcy level and unexplained infertility until now.MethodsA total of 388 infertile women undergoing IVF/ICSI treatments were recruited, including 129 women with unexplained causes (case group) and 259 women with known causes (control group), and the case group was further divided into subgroups A (≤8 μmol/L), B (>8 and <15 μmol/L), and C (≥15 μmol/L) based on the serum Hcy level. The associations between serum Hcy level and IVF/ICSI pregnancy outcomes were examined in infertile women with unknown causes.ResultsA significantly higher serum Hcy level was measured in the case group than in the control group (P = .008). Subgroup analysis revealed a significant difference in the total number of oocytes retrieved among subgroups A, B, and C (P = .031), and no significant difference was seen among these three groups in terms of age, BMI, E2 level on the hCG day, number of M‐II oocytes, number of fertilized oocytes, or total number of high‐quality embryos (P > .05). Spearman correlation analysis revealed a negative correlation between serum Hcy level and total number of oocytes retrieved (r = −.406, P = .019). Univariate and multivariate linear regression analyses revealed that serum Hcy level had no correlations with any IVF/ICSI outcomes.ConclusionSerum Hcy level has no associations with IVF/ICSI pregnancy outcomes.

Effect of stay in a postpartum care institution on postpartum depression in women

IntroductionPregnancy and childbirth can cause substantial psychological and social changes and may lead to mental disorders. Women who are discharged directly from the maternity hospital after delivery without social support may have postpartum psychological health issues. Rarely have studies focused on the effect of postpartum care institutions on postpartum depression in women. MethodsWe conducted a longitudinal study in Taiwan from January 2017 to July 2018. The data were collected via questionnaires administered at four time points: the first trimester of pregnancy (n = 309), the second trimester of pregnancy (n = 269), the third trimester of pregnancy (n = 257) and six weeks postpartum (n = 252). Among the participants, 130 women stayed in e postpartum care institutions, while 122 did not stay in an institution. Analysis included student t test, chi-square test, and difference in differences analysis. Linear regression analysis was used to determine the independence of the related factors for postpartum depression. ResultsThe women who stayed at postpartum care institutions (n = 130) had a higher education status, higher income, higher percentage of assisted reproductive technology (ART) treatment, higher cesarean section rate, and lower postpartum Edinburgh Perinatal Depression Scale (EPDS) scores (14.6% vs. 27.8%) compared with those who did not stay at postpartum care institutions. Among the women who stayed in postpartum care institutions, the average EPDS scores were 8.74 ± 0.46 and 8.15 ± 0.49 in the ART and natural pregnancy groups at baseline (3rd month), respectively, and there was no significant difference (p = 0.59). The EPDS scores in the ART group significantly declined at the 6th month (difference = −0.67, p<0.05), 9th month (difference = −2.00, p<0.01) and postpartum (difference = −4.01, p<0.01). Multivariate linear regression analysis indicated that postpartum care institutions was the main factor (r = 1.38, p = 0.014) correlating to postpartum depression in women. ConclusionProviding maternal and infant care in postpartum care institutions allows the mother to rest; and the professional guidance from the medical staff can provide the necessary support and help mothers to learn. Postpartum care institutions can decrease the incidence and severity of postpartum depression.

A case report of the expectant management for uterine arteriovenous malformation after loss of assisted reproductive technology pregnancy

A case report of the expectant management for uterine arteriovenous malformation after loss of assisted reproductive technology pregnancy

In-utero stress and mode of conception: impact on regulation of imprinted genes, fetal development and future health.

Genomic imprinting is an epigenetic gene regulatory mechanism; disruption of this process during early embryonic development can have major consequences on both fetal and placental development. The periconceptional period and intrauterine life are crucial for determining long-term susceptibility to diseases. Treatments and procedures in assisted reproductive technologies (ART) and adverse in-utero environments may modify the methylation levels of genomic imprinting regions, including insulin-like growth factor 2 (IGF2)/H19, mesoderm-specific transcript (MEST), and paternally expressed gene 10 (PEG10), affecting the development of the fetus. ART, maternal psychological stress, and gestational exposures to chemicals are common stressors suspected to alter global epigenetic patterns including imprinted genes. Our objective is to highlight the effect of conception mode and maternal psychological stress on fetal development. Specifically, we monitor fetal programming, regulation of imprinted genes, fetal growth, and long-term disease risk, using the imprinted genes IGF2/H19, MEST, and PEG10 as examples. The possible role of environmental chemicals in genomic imprinting is also discussed. A PubMed search of articles published mostly from 2005 to 2019 was conducted using search terms IGF2/H19, MEST, PEG10, imprinted genes, DNA methylation, gene expression, and imprinting disorders (IDs). Studies focusing on maternal prenatal stress, psychological well-being, environmental chemicals, ART, and placental/fetal development were evaluated and included in this review. IGF2/H19, MEST, and PEG10 imprinted genes have a broad developmental effect on fetal growth and birth weight variation. Their disruption is linked to pregnancy complications, metabolic disorders, cognitive impairment, and cancer. Adverse early environment has a major impact on the developing fetus, affecting mostly growth, the structure, and subsequent function of the hypothalamic-pituitary-adrenal axis and neurodevelopment. Extensive evidence suggests that the gestational environment has an impact on epigenetic patterns including imprinting, which can lead to adverse long-term outcomes in the offspring. Environmental stressors such as maternal prenatal psychological stress have been found to associate with altered DNA methylation patterns in placenta and to affect fetal development. Studies conducted during the past decades have suggested that ART pregnancies are at a higher risk for a number of complications such as birth defects and IDs. ART procedures involve multiple steps that are conducted during critical windows for imprinting establishment and maintenance, necessitating long-term evaluation of children conceived through ART. Exposure to environmental chemicals can affect placental imprinting and fetal growth both in humans and in experimental animals. Therefore, their role in imprinting should be better elucidated, considering the ubiquitous exposure to these chemicals. Dysregulation of imprinted genes is a plausible mechanism linking stressors such as maternal psychological stress, conception using ART, and chemical exposures with fetal growth. It is expected that a greater understanding of the role of imprinted genes and their regulation in fetal development will provide insights for clinical prevention and management of growth and IDs. In a broader context, evidence connecting impaired imprinted gene function to common diseases such as cancer is increasing. This implies early regulation of imprinting may enable control of long-term human health, reducing the burden of disease in the population in years to come.

Perinatal complications and live-birth outcomes following assisted reproductive technology: a retrospective cohort study.

BackgroundWith the development of assisted reproductive technology (ART) and its increasing success rate in the mainland of China, more attention has been paid to the safety of ART. In this study, we explored the associations between conception by ART and pregnancy/perinatal complications, and neonatal outcomes compared with similar outcomes following spontaneous conception.MethodsThis retrospective cohort study of pregnancies over a 3-year period (2013–2015) was performed at Beijing Obstetrics and Gynecology Hospital, Beijing, China. Subjects were divided into two groups: conception by ART (n = 2256) or spontaneous conception (n = 6768). According to different fertilization modes, the ART group was divided into in vitro fertilization (IVF, n = 1873) and intracytoplasmic sperm injection (ICSI, n = 383) subgroups. The ART group was also divided into two different embryo transfer methods; fresh embryo transfer (ET, n = 1583) and frozen embryo transfer (FET, n = 673) subgroups. Pregnancy complications, perinatal complications, and neonatal outcomes of the enrolled subjects were investigated and analyzed by univariate analysis and multivariate logistic regression.ResultsAfter adjustment for maternal age, gravidity, parity, maternal education, smoking, alcohol consumption, and body mass index (BMI), pregnancies conceived by ART were associated with a significantly increased incidence of gestational diabetes mellitus (GDM; OR 1.88, 95% CI 1.56–2.27), gestational hypertension (OR 2.18, 95% CI 1.83–2.60), and intrahepatic cholestasis of pregnancy (ICP) (OR 2.79, 95% CI 2.15–3.64), compared with spontaneous conception. These associations were similar for the singleton group. In the twin group, only the incidence of ICP was significantly higher than in controls. We found that pregnancies conceived by ART were associated with perinatal complications, including placental abruption (OR 2.14, 95% CI 1.33–3.45), premature rupture of membranes (PROM; OR 1.24, 95% CI 1.06–1.45), postpartum hemorrhage (OR 2.89, 95% CI 2.33–3.59) and polyhydramnios (OR 2.01, 95% CI 1.29–3.16). The singleton group had a similar result with placental abruption, but not with fetal membranes ruptures before labor and polyhydramnios. There were no significant differences in the incidence of these perinatal complications in the twin group. Some neonatal outcomes, including preterm labor (OR 4.29, 95% CI 3.84–4.80) and low birth weight (OR 1.72, 95% CI 1.42–2.08), were more likely to occur with singleton births after ART. However, there were no significant differences for these outcomes from twin pregnancies. Perinatal complications and neonatal outcomes were consistent between the IVF and ICSI subgroups. The FET and ET subgroups showed a similar increase in complications, except for the incidence of placental abruption. After taking into account the effects of parity, birth plurality and maternal age, the ART group still exhibited increased maternal and neonatal complications, although some differences narrowed or disappeared.ConclusionsThis retrospective cohort study demonstrated that patients who underwent ART were at increased risk of several adverse pregnancy outcomes compared with women who conceived spontaneously. These complications may be attributed in part to the relatively high multiple pregnancy rate after ART. Elective single embryo transfer should be promoted in China to reduce the obstetrical risks of ART pregnancy. Singletons of ART pregnancy exhibited increased maternal and neonatal complications as well, suggesting that underlying infertility or other maternal or parental factors may contribute to the adverse outcomes.

The China Family-Based Birth Cohort: A Study of Both Assisted Reproductive Technology and Spontaneous Pregnancies

Background: More than 1·0% of all births in China are through Assisted reproductive technology (ART). Concern is mounting over the safety of ART and the health impacts of ART on maternal and fetal health. Well-designed longitudinal cohort aiming to address the concern is yet sparse. The China National Birth Cohort (CNBC) Study is a family-based and prospective birth cohort study consisting of both Assisted reproductive technology (ART) pregnancies and spontaneous pregnancies. Which was set to comprehensively describe the incidence of birth outcomes from ART and spontaneous-conceived pregnancies and to systematically evaluate the environmental and genetic factors that may influence the birth outcomes of these pregnancies. Methods: CNBC was launched at 22 centers (located in 15 cities of China) in November 2016, and aims to complete recruitment of 10,000 couples who plan to have invitro fertilization or intra-cytoplasmic sperm injection (IVF/ICSI) treatments and 10,000 couples who have spontaneous pregnancies. The cohort data is collected from the biological parents and the offspring from the ART centers and obstetrics departments, respectively. Findings: By December 2018, CNBC had recruited 10,954 ART families and 10,618 spontaneous conceived families. Questionnaires (demographic, occupational, behavioral, environmental, nutritional and psychosocial factors, etc.), clinical data (obstetric and pediatric examination, and laboratory tests, etc.), and biospecimens (blood, urine, cord blood, follicular fluid, sperm, and seminal plasma, etc.) were collected respectively before embryo transfer, at the 1st, 2nd and 3rd trimester during pregnancy, and approximately 42 days, 6 months, 12 months, and 36 months after birth. Interpretation: The CNBC provided comprehensive data and bio-specimen resources from ART-received pregnancy and spontaneous pregnancy family, which will help identify the risk factors for ART pregnancies, and to elucidate heterogeneity of maternal and child health consequences between ART- and spontaneous-conceived populations. The CNBC data will be available on line, and researchers can apply with formal proposals. Funding: China National Key Research & Development (RD The Key Project of National Natural Science Foundation of China; The Innovation Capability Development Project of Jiangsu Province. Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: This study was approved by the institutional review board of CNBC, and written informed consent was obtained from all subjects.

Obstetric and neonatal risks in term-singleton assisted reproductive technology (ART) pregnancies: a single-center report in a period of 9 years

Obstetric and neonatal risks in term-singleton assisted reproductive technology (ART) pregnancies: a single-center report in a period of 9 years

The role of the growth hormone in assisted reproductive technologies cycles

The paper analyzes the literature data on the use of the growth hormone (GH) in ovarian stimulation in assisted reproductive technologies (ART). Routine use of GH in ovarian stimulation in patients with a normal GH level does not increase pregnancy and childbirth rates in ART. Also, no benefits of using GH have been identified for patients with polycystic ovary syndrome, despite the increase in insulin and IGF-1 blood levels. The main research focus is to study the use of GH in patients with poor ovarian response. According to the meta-analysis conducted by X.-L. Li et al. (2017), GH in ovarian stimulation of poor ovarian responders increases the number of received oocytes, mature oocytes number, reduces the embryo transfer cancellation rate and does not affect the fertilization rate. The pregnancy and live birth rates are significantly higher in the group of GH use - by 1.65 (95% CI 1.23-2.22) and 1.73 (95% CI 1.25-2.40) times, respectively. Thus, it is advisable to use GH in ovarian stimulation in poor ovarian responders, since it allows to increases live birth rate in ART. However, further studies should determine the optimal GH dose and assesse it`s safety in ART programs.