Allostatic load, a measure of chronic physiological stress, is associated with pregnancy outcomes, but not fertility, among women with unexplained infertility.
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ABSTRACT:
SUBMITTER: Barrett ES
PROVIDER: S-EPMC6454470 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Allostatic load, a measure of chronic physiological stress, is associated with pregnancy outcomes, but not fertility, among women with unexplained infertility.
Barrett Emily S ES Vitek Wendy W Mbowe Omar O Thurston Sally W SW Legro Richard S RS Alvero Ruben R Baker Valerie V Bates G Wright GW Casson Peter P Coutifaris Christos C Eisenberg Esther E Hansen Karl K Krawetz Stephen S Robinson Randal R Rosen Mitchell M Usadi Rebecca R Zhang Heping H Santoro Nanette N Diamond Michael M
Human reproduction (Oxford, England) 20180901 9
<h4>Study question</h4>Among infertile women undergoing ovarian stimulation, is allostatic load (AL), a measure of chronic physiological stress, associated with subsequent fertility and pregnancy outcomes?<h4>Summary answer</h4>AL at baseline was not associated with conception, spontaneous abortion or live birth, however, it was significantly associated with increased odds of pre-eclampsia and preterm birth among women who had a live birth in the study.<h4>What is known already</h4>Several studi ...[more]
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Project description:ObjectiveTo determine whether biochemical or clinical markers of androgenic activity predict live birth rate with ovarian stimulation in the unexplained infertility population.DesignSecondary analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial.SettingMulticenter university-based clinical practices.Patient(s)Nine hundred couples with unexplained infertility were included. Women were 18-40 years old with regular menses, a normal uterine cavity, at least one patent fallopian tube, and a male partner with ≥5 million motile sperm. Women were randomized to receive gonadotropin, clomiphene, or letrozole with IUI for four or fewer four treatment cycles. Women were evaluated for biochemical (total testosterone, DHEAS, and free androgen index) and clinical markers of androgenic activity (sebum, acne, and hirsutism). Multivariable logistic regression models adjusting for treatment group, maternal age, and body mass index were performed.Intervention(s)None.Main outcome measure(s)The primary outcome was live birth. Secondary outcomes included conception, clinical pregnancy, and pregnancy loss.Result(s)When comparing 900 women in the AMIGOS trial based on quartiles of serum TT, women were of younger age, higher body mass index, and higher waist circumference with increasing TT. Increasing quartiles of TT also showed increasing DHEAS and free androgen index values. Serum androgens were not associated with outcomes of live birth, conception, clinical pregnancy, or pregnancy loss. Clinical androgen markers were not associated with pregnancy outcomes.Conclusion(s)In a randomized cohort of women with unexplained infertility, biochemical and clinical measures of androgens did not predict live birth rate after ovarian stimulation treatment.Clinical trial registration numberNCT 01044862.
| S-EPMC7088440 | biostudies-literature
Project description:ObjectiveTo assess the association between allostatic load, as an estimate of chronic stress, and adverse pregnancy outcomes.MethodsThis was a secondary analysis of nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort study. Our primary exposure was dichotomous high allostatic load in the first trimester, defined as 4 or more of 12 biomarkers in the "worst" quartile. The primary outcome was a composite adverse pregnancy outcome: hypertensive disorders of pregnancy (HDP), preterm birth, small for gestational age (SGA), and stillbirth. Secondary outcomes included components of the composite. Multivariable logistic regression was used to test the association between high allostatic load and adverse pregnancy outcomes, adjusted for potential confounders. Mediation and moderation analyses were conducted to assess the role of allostatic load along the causal pathway between racial disparities and adverse pregnancy outcomes.ResultsAmong 4,266 individuals, 34.7% had a high allostatic load. Composite adverse pregnancy outcome occurred in 1,171 (27.5%): 14.0% HDP, 8.6% preterm birth (48.0% spontaneous and 52.2% indicated), 11.0% SGA, and 0.3% stillbirth. After adjustment for maternal age, gravidity, smoking, bleeding in the first trimester, and health insurance, high allostatic load was significantly associated with a composite adverse pregnancy outcome (adjusted odds ratio [aOR] 1.5, 95% CI 1.3, 1.7) and HDP (aOR 2.5, 95% CI 2.0-2.9), but not preterm birth or SGA. High allostatic load partially mediated the association between self-reported race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race, but not for a composite adverse pregnancy outcome, preterm birth, or SGA.ConclusionHigh allostatic load in the first trimester is associated with adverse pregnancy outcomes, particularly HDP. Allostatic load was a partial mediator between race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race.
| S-EPMC9712159 | biostudies-literature
Project description:Background: Allostatic load is the physiological deterioration that accumulates as the body responds to stress, resulting in disparities in chronic disease. Although perceptions of stress vary, marginalization and social disadvantage are associated with elevated allostatic load. Allostatic load is understudied in the multiply marginalized populations of sexual minority Black women. Methods: We used data from six waves of the National Health and Nutrition Examination Survey (2001-2010, 2015-2016) to identify heterosexual (n = 78), lesbian (n = 21), and bisexual (n = 57) Black women. We quantified allostatic load using nine biomarkers, and compared mean allostatic load across the three groups, adjusting for age, educational attainment, income, and country of birth to account for possible confounding. Results: We found no significant differences in allostatic load among heterosexual, lesbian, and bisexual Black women. Conclusions: These findings suggest that sexual orientation may not contribute to within-group differences in allostatic load among Black women, a group previously noted to have elevated allostatic load.
| S-EPMC8403173 | biostudies-literature
Project description:IL-17 signaling is an important candidate pathway that may contribute to dysregulated immune function in the endometrium of women with unexplained infertility after ART who are not pregnant
2021-01-06 | GSE144895 | GEO
Project description:ObjectiveTo study decidualization-associated endometrial factors.DesignRetrospective cohort study to compare endometrial gene expression patterns in women experiencing reproductive failure including recurrent pregnancy loss or unexplained infertility versus fertile controls.SettingUniversity Reproductive Medicine Center.PatientsWomen experiencing recurrent reproductive failure including recurrent pregnancy loss or unexplained infertility (n = 42) and fertile controls (n = 18).InterventionsEndometrial biopsy samples were analyzed with targeted ribonucleic acid sequencing via next-generation sequencing.Main outcome measuresThe primary end point measurements were the expression of genes important for endometrial transformation during decidualization measured singly and in a combined/cumulative score approach. The secondary end point measurements were receiver operating curve analysis and comparisons between the specific biomarkers.ResultsThe comparison revealed differential expression of factors associated with decidualization, tissue homeostasis, and immune regulation: FOXO1, GZMB, IL15, SCNN1A, SGK1, and SLC2A1. A combined evaluation of these 6 signature factors was designated as a decidualization score in which the maximal score was "6" and the minimal was "0". Among controls, 89% of the samples had a score ≥5 and 11% had a score of "4". A total of 76% of samples in the patient group had scores ≤4 and 19% had the lowest score of "0". A decidualization score <4 provided evidence of abnormality in the decidualization process with a sensitivity of 76% (95% CI 61%-88%) and specificity of 89% (95% CI 65%-99%).ConclusionsDecidualization scoring can determine whether the endometrial molecular profile is implantation-friendly. Further validation of this testing approach is necessary to determine a particular patient population in whom it could be used for selecting patients that require therapeutic actions to improve endometrial conditions prior to the in vitro fertilization procedure.
| S-EPMC8244268 | biostudies-literature
Project description:Up to 30% of men with normal semen parameters suffer from infertility and the reason for this is unknown. Altered expression of sperm proteins may be a major cause of infertility in these men. Proteomic profiling was performed on pooled semen samples from eight normozoospermic fertile men and nine normozoospermic infertile men using LC-MS/MS. Furthermore, key differentially expressed proteins (DEPs) related to the fertilization process were selected for validation using Western blotting. A total of 1139 and 1095 proteins were identified in normozoospermic fertile and infertile men, respectively. Of these, 162 proteins were identified as DEPs. The canonical pathway related to free radical scavenging was enriched with upregulated DEPs in normozoospermic infertile men. The proteins associated with reproductive system development and function, and the ubiquitination pathway were underexpressed in normozoospermic infertile men. Western blot analysis revealed the overexpression of annexin A2 (ANXA2) (2.03 fold change; P = 0.0243), and underexpression of sperm surface protein Sp17 (SPA17) (0.37 fold change; P = 0.0205) and serine protease inhibitor (SERPINA5) (0.32 fold change; P = 0.0073) in men with unexplained male infertility (UMI). The global proteomic profile of normozoospermic infertile men is different from that of normozoospermic fertile men. Our data suggests that SPA17, ANXA2, and SERPINA5 may potentially serve as non-invasive protein biomarkers associated with the fertilization process of the spermatozoa in UMI.
| S-EPMC6678187 | biostudies-literature
Project description:Study questionAre mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility?Summary answerWe found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility.What is known alreadyMutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS).Study design, size, and durationNinety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK.Participants/materials, setting, methodsPatients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT).Main results and the role of chanceNo disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL.Limitations, reasons for cautionDue to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations.Wider implications of the findingsThe present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility.Study funding/competing interestsThis study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared.
| S-EPMC4262469 | biostudies-literature
Project description:BackgroundAllostatic load (AL) measures the cumulative impact of chronic stress and is associated with adverse health outcomes. A novel scoring system has previously been developed for AL in early pregnancy that is associated with pre-eclampsia. It was hypothesized that AL, as identified by the present model, is associated with psychosocial stressors and, specifically, poor sleep quality.MethodsWomen were selected from a low-risk, community-dwelling study population who enrolled at <15 weeks gestation. Nine physiologic components were divided among the domains of cardiovascular, metabolic, and inflammatory function. Spearman's rank correlations were used to examine the association of AL with age, income, the Revised Prenatal Distress Questionnaire (NuPDQ), Inventory of Depressive Symptoms (IDS), and Pittsburgh Sleep Quality Index (PSQI). The Wilcoxon rank-sum test was used to compare AL by race and educational attainment.ResultsA total of 103 women were identified, with: a mean age of 29.8 ± 5.0 years, 17.5% black, and mean gestational age 12.2 ± 1.1 weeks. Allostatic load was positively correlated with the PSQI (ρ = 0.23, p = 0.018). There were no associations with age, income, prenatal distress, race, or depression scores. College-educated women had lower AL compared with those with less education (0.57 ± 0.43 vs 0.81 ± 0.55, p = 0.045).ConclusionHigher AL, measured by the pregnancy-specific model, was associated with poorer sleep quality and lower educational attainment, both of which were considered to be chronic stressors. These relationships were consistent with previous findings in non-pregnant populations, and suggest that AL may be useful for capturing the physiologic impact of chronic stress in early pregnancy.
| S-EPMC5501183 | biostudies-literature
Project description:Recent studies are directed to decode the genetic signature of endometrial receptivity for better outcomes in assisted reproductive technologies. In this study, we aimed to understand the transcriptomic profile of midsecretory phase endometria of patients with recurrent pregnancy losses (RPL) and unexplained infertility (UI) by comparing with the endometria of healthy fertile women (Controls). In this prospective cohort study, we took endometrial samples from 24 patients with RPL, 24 patients with UI and 24 Controls at day 19-21 of the menstrual cycle. By performing genomic analysis, we assessed for differentially expressed genes (DEGs) and pathway analysis.
2021-01-18 | GSE165004 | GEO
Project description:BackgroundResearch suggests that non-Hispanic Black (henceforth, Black) women and people with lower educational attainment have higher levels of allostatic load (AL). This study sought to determine the association between educational attainment and AL among a large sample of Black women.MethodsWe analyzed data among 4177 Black women from the National Health and Nutrition Examination Survey years 1999-2018. AL score was defined as the total for abnormal measures of eight biomarkers. We further categorized participants with AL score greater than or equal to 4 as having high AL. We calculated mean estimates of total allostatic load scores using generalized linear models. We performed modified Poisson Regression models with robust variance estimation to estimate prevalence ratios (PRs) of high allostatic load and their associated 95% confidence intervals (CIs) by educational attainment.ResultsBlack women with a college degree or higher had the lowest prevalence of high allostatic load (31.8% vs. 42.7%, 36.3%, 36.6%), and age adjusted mean allostatic load scores (mean = 1.90 vs. mean = 2.34, mean = 1.99, mean = 2.05) when compared to Black women with less than a high school diploma, high school diploma or GED, and some college or associates degree respectively. Even after accounting for age, poverty-to-income ratio, smoking, congestive heart failure, and heart attack, Black college graduates had an 14.3% lower prevalence of high allostatic load (PR = 0.857, 95% CI 0.839-0.876) when compared to Black women with lower educational attainment.ConclusionsBlack women with a baccalaureate degree or higher educational attainment had lower allostatic load compared to Black women with less than a high school education. This finding further confirms higher education is a social determinant of health. Future research should explore differences in AL by more granular degree types.
| S-EPMC8928016 | biostudies-literature