Dataset Information

Meta-analysis of ART outcomes in women with different preconception TSH levels.

ABSTRACT:

Background

To assess whether elevated thyroid-stimulating hormone (TSH) levels before conception can predict poor outcomes of assisted reproductive technology (ART).

Methods

Prior to July 2018, we searched the PubMed, EMBASE, COCHRANE, Google Scholar, and CNKI databases for studies. Retrospective or prospective reports that compared ART results in patients with subclinical hypothyroidism (SCH) with normal thyroid function were selected. Two reviewers separately reviewed each potential article for qualification, analyzed the quality of the studies according to the Newcastle-Ottawa scale, and extracted the data. The PRISMA guidelines were adopted.

Results

We selected a total of 18 publications that included 14,846 participants for this meta-analysis. When the TSH cut-off value for SCH was set at 2.5 mIU/L, no significant differences were observed in ART-related outcomes between SCH patients and normal women. The evaluated outcomes included the live birth rate (LBR) (OR: 0.93; 95% CI (0.77,1.12), P =?0.43), clinical pregnancy rate (CPR) (OR:1.02; 95% CI (0.90,1.17); P =?0.74), pregnancy rate (PR) (OR: 1.00; 95% CI (0.89,1.12); P =?0.99), and miscarriage rate (MR) (OR:1.24; 95% CI (0.85, 1.80); P =?0.26). Furthermore, when a higher TSH level was used as the cut-off value to diagnose SCH (i.e., 3.5-5 mIU/L), a significant difference was found in the MR (OR: 1.91; 95% CI (1.09, 3.35); P =?0.02) between the two groups of ART-treated women. However, when a broader cut-off value was used to define SCH, no significant differences were observed in the LBR (OR: 0.72; 95% CI (0.47,1.11); P =?0.14), CPR (OR: 0.82; 95% CI (0.66,1.00); P =?0.052), or PR (OR: 1.07; 95% CI (0.72,1.60); P =?0.74) between the two groups of ART-treated women.

Conclusion

No difference was observed in ART outcomes when a TSH cut-off value of 2.5 mIU/L was used. However, when a broader TSH cut-off value was used, preconception SCH resulted in a higher miscarriage rate than in normal women.

SUBMITTER: Zhao T

PROVIDER: S-EPMC6219175 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Meta-analysis of ART outcomes in women with different preconception TSH levels.

Zhao T T Chen B M BM Zhao X M XM Shan Z Y ZY

Reproductive biology and endocrinology : RB&E 20181105 1

<h4>Background</h4>To assess whether elevated thyroid-stimulating hormone (TSH) levels before conception can predict poor outcomes of assisted reproductive technology (ART).<h4>Methods</h4>Prior to July 2018, we searched the PubMed, EMBASE, COCHRANE, Google Scholar, and CNKI databases for studies. Retrospective or prospective reports that compared ART results in patients with subclinical hypothyroidism (SCH) with normal thyroid function were selected. Two reviewers separately reviewed each poten ...[more]

PMID: 30396353

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Project description:BackgroundSubtle abnormalities in children's intelligence, motor skills, and psychology from various assisted reproductive treatments (ARTs) might be underdiagnosed. Understanding the prognosis of intelligence, motor skills, and psychology in children from ART would provide parents with reasonable expectations and enable them to plan relevant support to achieve the optimum potential in ART children.MethodsWe searched PubMed, EMBASE, Ovid, Google Scholar, and Scopus databases until April 13, 2021, to identify relevant studies. Thirty-four studies met the inclusion and exclusion criteria. The meta-analysis employed a standardized mean difference model. The outcome of this study is to compare intelligence quotient (IQ), motoric ability, and behavioral problems between all ARTs, in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) to naturally conceived (NC) children. Subdomains of intelligence based on the Cattell, Horn, and Carroll Model (CHC Model) of cognitive architecture, including fluid reasoning, short-term and working memory, processing speed, visual-spatial ability, long-term memory retrieval, and crystalized intelligence (knowledge), were evaluated and summarized in details. Motor skill was stratified into two domains: gross motoric and fine motoric. Behavioral problem was categorized as externalizing and internalizing behavior.ResultsMeta-analysis showed that verbal intelligence score in IVF toddlers is significantly lower than NC toddlers (p = 0.02); conversely, ICSI toddlers scored significantly higher verbal intelligence score compared to NC toddlers (p = 0.005). Toddlers born after ART had significantly lower non-verbal intelligence score (p = 0.047). IVF toddlers scored significantly lower fine motor score (p = 0.01) compared to naturally conceived toddlers. Based on parent's CBCL, NC toddlers had higher total (p = 0.01) and externalizing behavior (p = 0.001) scores compared to ART toddlers. Evaluation of full scale IQ and all domains of intelligence in preschool and primary school children revealed that no significant differences exist between ART and NC children. Based on preschool and primary school parents' CBCL, IVF children had significantly lower externalizing behavior score compared to NC children (p = 0.04). Meta-analyses of studies on young adolescents revealed that ART young adolescents scored higher academically than their NC counterparts, including on mathematics (p < 0.00001) and reading or language (p < 0.00001).ConclusionsDespite differences in certain aspects, this finding suggests that ART is unlikely to cause negative impacts on children's neurodevelopment.

Project description:ImportanceMaternal thyrotropin levels during gestation have a profound effect on pregnancy outcomes; however, few studies to date have evaluated the importance of preconception thyrotropin levels.ObjectiveTo investigate the associations between preconception thyrotropin levels and pregnancy outcomes.Design, setting, and participantsThis population-based cohort study enrolled Chinese women aged 20 to 49 years from the National Free Prepregnancy Checkups Project in China. Participants conceived within 6 months after the thyrotropin examination and completed follow-up for pregnancy outcomes between January 1, 2013, and December 31, 2017. Data were analyzed between May 1, 2019, and March 31, 2020.ExposuresLevels of thyrotropin within 6 months before pregnancy, measured as less than 0.10 mIU/L, 0.10 to 0.36 mIU/L, 0.37 to 2.49 mIU/L, 2.50 to 4.87 mIU/L, 4.88 to 9.99 mIU/L, and 10.00 mIU/L or greater.Main outcomes and measuresThe association of maternal preconception thyrotropin levels with the 4 primary adverse pregnancy outcomes was assessed, including preterm birth (PTB), small for gestational age (SGA), birth defect, and perinatal infant death. Logistic regression analyses were used to evaluate the association between preconception maternal thyrotropin levels and risk of adverse pregnancy outcomes. The dose-response associations were assessed using restricted cubic spline regression.ResultsThis study enrolled 5 840 894 women (mean [SD] age, 26.30 [4.10] years) in the primary analysis. The median (interquartile range [IQR]) thyrotropin level was 1.60 (1.06-2.37) mIU/L. The cumulative incidences for the adverse pregnancy outcomes were as follows: PTB, 6.56%; SGA, 7.21%; birth defect, 0.02%; and perinatal infant death, 0.33%. Compared with the reference group (thyrotropin range, 0.37-2.49 mIU/L), both low (<0.10 mIU/L and 0.10-0.36 mIU/L) and high (4.88-9.99 mIU/L and ≥10.00 mIU/L) maternal preconception thyrotropin levels were associated with higher risk of PTB (low: odds ratio [OR], 1.23 [95% CI, 1.19-1.27] and OR, 1.15 [95% CI, 1.13-1.18] vs high: OR, 1.13 [95% CI, 1.10-1.15] and OR, 1.14 [95% CI, 1.08-1.20]), SGA (low: OR, 1.37 [95% CI, 1.33-1.40] and OR, 1.14 [95% CI, 1.12-1.17] vs high: OR, 1.05 [95% CI, 1.03-1.08] and OR, 1.17 [95% CI, 1.11-1.23]), and perinatal infant death (low: OR, 1.26 [95% CI, 1.10-1.43] and OR, 1.14 [95% CI, 1.05-1.24] vs high: OR, 1.31 [95% CI, 1.20-1.43] and OR, 1.47 [95% CI, 1.21-1.80]). J-shaped associations between preconception thyrotropin levels and PTB (χ2 = 1033.45; nonlinear P < .001), SGA (χ2 = 568.90; nonlinear P < .001), and perinatal infant death (χ2 = 38.91; nonlinear P < .001) were identified.Conclusions and relevanceIn this cohort study, both low and high maternal thyrotropin levels were associated with a significantly increased risk of adverse pregnancy outcomes. Results suggest that the optimal preconception thyrotropin levels may be between 0.37 mIU/L and 2.50 mIU/L to prevent adverse pregnancy outcomes.

Project description:Background: Serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) change dynamically during pregnancy. Differences in geographic regions, populations, and manufacturer's methodologies can affect the reference intervals for thyroid function tests. The 2017 guidelines of the American Thyroid Association (ATA) recommended 4.0 mU/L as the cut-off point for the upper limit of serum TSH in early pregnancy. A systematic review is called for to establish practical, gestational-specific TSH and FT4 reference intervals for pregnant Chinese women and to explore whether the criteria are suitable for China. Methods: English and Chinese articles published from inception to Aug 2017 were searched in the PubMed, EMBASE, and SCIE English-language databases and the CNKI, WanFang, and CQVIP Chinese databases. The relative descent or ascent rates of serum TSH and FT4 were calculated, after which Comprehensive Meta-Analysis V2.0 software was used to analyze the data. Results: Eleven studies (6 in English and 5 in Chinese), five kits and 11,629 Chinese women from nine cities were considered in this meta-analysis. Compared with the reference ranges provided by manufacturers, serum TSH decreased in the first trimester, with the upper limit declining by 21.7% (5.0-36.6%), to a value close to 4.0 mU/L, and the lower limit declining by 85.7% (73.5-97.1%). It continued decreasing in the second trimester, with the upper limit declining by 24.0% (6.4-40.9%) and the lower limit declining by 40.7% (9.0-85.7%). For FT4, the upper limit fluctuated slightly, and the lower limit increased by 6.8% (1.0-14.6%) in the first trimester. Serum FT4 dropped gradually, with the upper limit declining by 21.8% (2.5-31.8%) and the lower limit declining by 12.7% (2.6-19.6%) in the second trimester. During the third trimester, the upper limit decreased by 25.1% (12.7-35.0%), while the lower limit decreased by 20.9% (14.8-27.3%). Conclusions: Various regions, kits and test methods affect the gestational TSH and FT4 levels. The non-pregnant serum TSH upper limit minus 22% is very close to 4.0 mU/L, which can be used as a sub-optimal approach to represent the cut-off value for pregnant Chinese women in the first trimester.

Project description:Objective:Obesity has become a major, worldwide public health issue and is associated with a greater risk of adverse pregnancy outcomes. Leptin, a hormone produced by adipocytes, is elevated in individuals with obesity and may mediate the association between obesity and pregnancy outcomes. Though leptin levels during pregnancy have been associated with pregnancy outcomes, less is understood regarding preconception levels. Therefore, the objective of this study was to evaluate associations between preconception leptin levels and adverse pregnancy outcomes. Methods:This was a prospective cohort study nested within a large randomized controlled trial conducted at four medical centres in the United States. A total of 1078 women completed the parent study; this analysis involved women who became pregnant during that study (n = 776). Patients were healthy women, ages 18 to 40, attempting to conceive, with 1 to 2 prior pregnancy losses. Participants were followed for less than or equal to 6 cycles while trying to conceive and throughout pregnancy if they conceived. Preconception leptin concentrations were measured in serum collected at baseline then categorized by tertiles (using the lowest as reference group). Weighted log-binomial regression estimated risk ratios (RR) and 95% confidence intervals (CIs) for pregnancy loss, preterm delivery (PTD), gestational diabetes (GDM), and hypertensive disorders in pregnancy, adjusting for age, waist-to-hip ratio (WHR), and body mass index (BMI). Results:The mean (SD) BMI in this cohort was 25.4 ± 6.0. GDM (RR 18.37; 95% CI, 2.39-141.55) and hypertensive disorders of pregnancy (RR 2.35; 95% CI, 1.20-4.61) risks were higher among women in the high tertile after adjusting for age and WHR. The associated risk persisted when adjusting for BMI for GDM but was attenuated for hypertensive disorders in pregnancy. Leptin levels were not associated with risk of pregnancy loss or PTD. Conclusions:Women with higher baseline preconception leptin levels had a higher likelihood of experiencing some adverse pregnancy outcomes including GDM and hypertensive disorders of pregnancy. These findings warrant further evaluation, especially in light of the association between leptin and obesity.

Project description:BackgroundWhile previous studies identified risk factors for diverse pregnancy outcomes, traditional statistical methods had limited ability to quantify their impacts on birth outcomes precisely. We aimed to use a novel approach that applied different machine learning models to not only predict birth outcomes but systematically quantify the impacts of pre- and post-conception serum thyroid-stimulating hormone (TSH) levels and other predictive characteristics on birth outcomes.MethodsWe used data from women who gave birth in Shanghai First Maternal and Infant Hospital from 2014 to 2015. We included 14,110 women with the measurement of preconception TSH in the first analysis and 3,428 out of 14,110 women with both pre- and post-conception TSH measurement in the second analysis. Synthetic Minority Over-sampling Technique (SMOTE) was applied to adjust the imbalance of outcomes. We randomly split (7:3) the data into a training set and a test set in both analyses. We compared Area Under Curve (AUC) for dichotomous outcomes and macro F1 score for categorical outcomes among four machine learning models, including logistic model, random forest model, XGBoost model, and multilayer neural network models to assess model performance. The model with the highest AUC or macro F1 score was used to quantify the importance of predictive features for adverse birth outcomes with the loss function algorithm.ResultsThe XGBoost model provided prominent advantages in terms of improved performance and prediction of polytomous variables. Predictive models with abnormal preconception TSH or not-well-controlled TSH, a novel indicator with pre- and post-conception TSH levels combined, provided the similar robust prediction for birth outcomes. The highest AUC of 98.7% happened in XGBoost model for predicting low Apgar score with not-well-controlled TSH adjusted. By loss function algorithm, we found that not-well-controlled TSH ranked 4th, 6th, and 7th among 14 features, respectively, in predicting birthweight, induction, and preterm birth, and 3rd among 19 features in predicting low Apgar score.ConclusionsOur four machine learning models offered valid predictions of birth outcomes in women during pre- and post-conception. The predictive features panel suggested the combined TSH indicator (not-well-controlled TSH) could be a potentially competitive biomarker to predict adverse birth outcomes.

Project description:Study questionIs preconception leukocyte telomere length associated with fecundability, pregnancy loss and live birth among women attempting natural conception with a history of 1-2 prior pregnancy losses?Summary answerPreconception leukocyte telomere length is not associated with fecundability, pregnancy loss or live birth.What is known alreadyAs women increasingly delay childbearing, accessible preconception biomarkers to predict pregnancy outcomes among women seeking natural conception could improve preconception counseling. Findings of small case-control or cross-sectional studies suggest that telomere attrition is associated with adverse pregnancy outcomes among women undergoing fertility treatment, but prospective studies in non-clinical populations are lacking.Study design, size, durationParticipants included 1228 women aged 18-40 years with a history of 1-2 prior pregnancy losses who were recruited at four university medical centers (2006-2012).Participants/materials, setting, methodsPreconception leukocyte telomere length was measured at baseline using PCR and reported as a ratio (T/S) in relation to population-specific standard reference DNA. Women were followed for up to six cycles while attempting to conceive. Associations of telomere length with fecundability, live birth and pregnancy loss were estimated using discrete Cox proportional hazards models and log-binomial models.Main results and the role of chanceAfter adjustment for age, BMI, smoking and other factors, preconception telomere length was not associated with fecundability (Q4 vs Q1 FOR = 1.00; 95% CI = 0.79, 1.27), live birth (Q4 vs Q1 RR = 1.00; 95% CI = 0.85, 1.19), or pregnancy loss (Q4 vs Q1 RR = 1.12; 95% CI = 0.78, 1.62).Limitations, reasons for cautionTelomere length was measured in leukocytes, which is an accessible tissue in women attempting natural conception but may not reflect telomere length in oocytes. Most women were younger than 35 years, limiting our ability to evaluate associations among older women. Participants had a history of 1-2 prior pregnancy losses; therefore, our findings may not be widely generalizable.Wider implications of the findingsDespite prior research suggesting that telomere length may be associated with pregnancy outcomes among women seeking fertility treatment, our findings suggest that leukocyte telomere length is not a suitable biomarker of pregnancy establishment or maintenance among women attempting natural conception.Study funding/competing interest(s)This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD, USA; contract numbers HHSN267200603423, HHSN267200603424 and HHSN267200603426). The authors have no conflicts of interest to disclose.Trial registration numberThe trial was registered with ClinicalTrials.gov, number NCT00467363.

Project description:BackgroundPreconception care is the provision of biomedical, behavioural, and social health interventions provided to women and couples before conception. However, in Ethiopia, little is known and practised to support preconception care. Therefore, this study aimed to assess women's knowledge and utilisation of preconception care and its associated factors in Ethiopia using systematic review and meta-analysis.MethodIn the current meta-analysis, variables were searched from different electronic database systems, which included PubMed, Google Scholar, EMBASE, HINAR, Scopus, Web of Sciences, and Grey literature. Data were extracted using a standardised data collection measurement tool. The data were analysed by using STATA 14 statistical software. I2 tests assessed heterogeneity between the studies. A random-effect model was used to forecast the pooled knowledge and utilisation of preconception care.ResultsThirteen full-text studies were included. The pooled prevalence of knowledge and utilisation of preconception care among women in Ethiopia was 30.95% and 16.27% respectivelly. Secondary education (OR = 2.78, 95% CI,2.01-3.85), college and above (OR = 5.05, 95% CI,2.70-9.44), and antenatal care (OR = 3.89, 95% CI, 1.69-8.98) were significantly associated with knowledge level whereas; age (OR = 2.43, 95% CI, 1.30-4.53) and knowledge on preconception care (OR = 3.95, 95% CI,2.35-6.62) were positively associated with utilisation of preconception.ConclusionsWomen's level of knowledge and utilisation of preconception care was significantly low. Educational status and antenatal care follow-up were factors shown to affect knowledge of preconception care. Age and having a sound knowledge of preconception care indicated a significant association towards utilisation of preconception care. Thus, integrating preconception care strategies and policies that can address all the components of preconception care services with other maternal and child health services will be essential when designing effective implementation strategies to improve preconception care uptake. Besides this, advocating for better education for women, awareness creation, and increasing antenatal care services are essential. Prospero registration: CRD42020218062.

Dataset Information

Meta-analysis of ART outcomes in women with different preconception TSH levels.

Background

Methods

Results

Conclusion

Publications

Meta-analysis of ART outcomes in women with different preconception TSH levels.

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