scholarly journals Fertility and Ovarian Function in High-Dose Estrogen-Treated Tall Women

2011 ◽  
Vol 96 (4) ◽  
pp. 1098-1105 ◽  
Author(s):  
A. E. J. Hendriks ◽  
J. S. E. Laven ◽  
O. Valkenburg ◽  
S. Lie Fong ◽  
B. C. J. M. Fauser ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Final Height ◽  
Later Life ◽  
Antral Follicle ◽  
High Dose ◽  
Duration Of Treatment ◽  
Ovarian Aging ◽  
Increased Risk ◽  
Tall Girls ◽  
Antral Follicle Counts

Abstract Background/Objective: High-dose estrogen treatment to reduce final height of tall girls has been shown to interfere with fertility. Ovarian function has not been studied. We therefore evaluated fertility and ovarian function in tall women who did or did not receive such treatment in adolescence. Methods: This was a retrospective cohort study of 413 tall women aged 23–48 yr, of whom 239 women had been treated. A separate group of 126 fertile, normoovulatory volunteers aged 22–47 yr served as controls. Results: Fertility was assessed in 285 tall women (157 treated, 128 untreated) who had attempted to conceive. After adjustment for age, treated women were at increased risk of experiencing subfertility [odds ratio (OR) 2.29, 95% confidence interval (CI) 1.38–3.81] and receiving infertility treatments (OR 3.44, 95% CI 1.76–6.73). Moreover, fecundity was notably affected because treated women had significantly reduced odds of achieving at least one live birth (OR 0.26, 95% CI 0.13–0.52). Remarkably, duration of treatment was correlated with time to pregnancy (r = 0.23, P = 0.008). Ovarian function was assessed in 174 tall women (119 treated, 55 untreated). Thirty-nine women (23%) exhibited a hypergonadotropic profile. After adjusting for age category, treated women had significantly higher odds of being diagnosed with imminent ovarian failure (OR 2.83, 95% CI 1.04–7.68). Serum FSH levels in these women were significantly increased, whereas antral follicle counts and serum anti-Müllerian hormone levels were decreased. Conclusion: High-dose estrogen-treated tall women are at risk of subfertility in later life. Their fecundity is significantly reduced. Treated women exhibit signs of accelerated ovarian aging with concomitant follicle pool depletion, which may be the basis of the observed subfertility.

scholarly journals Prediction of ovarian aging using ovarian expression of BMP15, GDF9, and C-KIT

2020 ◽  
Vol 245 (8) ◽  
pp. 711-719
Author(s):  
Min Jung Park ◽  
Jun-Woo Ahn ◽  
Ki Hyung Kim ◽  
Junghee Bang ◽  
Seung Chul Kim ◽  
...  
Keyword(s):  
Embryo Development ◽  
Ovarian Function ◽  
Antral Follicle ◽  
Antral Follicle Count ◽  
Development Rate ◽  
Ovarian Aging ◽  
Age Related ◽  
Morphogenetic Protein ◽  
New Information ◽  
Potential Biomarkers

This study investigated ovarian expressions of bone morphogenetic protein 15 (BMP15), growth differentiation factor 9 (GDF9), and C-KIT according to age in female mice to determine whether these factors can be served as new potential biomarkers of ovarian aging. Ovaries were collected from mice aged 10, 20, 30, and 40 weeks, and ovarian expressions of BMP15, GDF9, and C-KIT were examined by real-time PCR, Western blot, and immunohistochemistry. Follicle counts were measured on histological hematoxylin and eosin staining. In the second experiment to evaluate ovarian function, after superovulation with PMSG and hCG, the numbers of zygotes retrieved and embryo development rate were examined. Ovarian expressions of BMP15, GDF9, and C-KIT decreased with age. Follicle counts, numbers of retrieved zygotes, and embryo development rate were also significantly reduced in old mice over 30 weeks compared with young mice. These results indicate that these factors could be served as new potential biomarkers of ovarian aging. Impact statement Ovarian aging is becoming a more important issue in terms of fertility preservation and infertility treatment. Serum anti-Mullerian hormone (AMH) level and antral follicle count (AFC) are being practically used as markers of ovarian aging as well as ovarian reserve in human. However, these factors have some drawbacks in assessing ovarian aging and reserve. Therefore, the identification of ovarian expressions of BMP15, GDF9, and C-KIT according to female could be applied as a potent predictor of ovarian aging. This work provides new information on the development of diagnosis and treatment strategy of age-related fertility decline and premature ovarian insufficiency.

scholarly journals TNF-Alpha Inhibitors for Chronic Urticaria: Experience in 20 Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Freja Lærke Sand ◽  
Simon Francis Thomsen
Keyword(s):  
Side Effects ◽  
Chronic Urticaria ◽  
Treatment Options ◽  
Significant Proportion ◽  
Response Duration ◽  
Immunosuppressive Drugs ◽  
Tnf Alpha ◽  
High Dose ◽  
Duration Of Treatment ◽  
Durable Response

Patients with severe chronic urticaria may not respond to antihistamines, and other systemic treatment options may either be ineffective or associated with unacceptable side effects. We present data on efficacy and safety of adalimumab and etanercept in 20 adult patients with chronic urticaria. Twelve (60%) patients obtained complete or almost complete resolution of urticaria after onset of therapy with either adalimumab or etanercept. Further three patients (15%) experienced partial response. Duration of treatment ranged between 2 and 39 months. Those responding completely or almost completely had a durable response with a mean of 11 months. Six patients (30%) experienced side effects and five patients had mild recurrent upper respiratory infections, whereas one patient experienced severe CNS toxicity that could be related to treatment with TNF-alpha inhibitor. Adalimumab and etanercept may be effective and relatively safe treatment options in a significant proportion of patients with chronic urticaria who do not respond sufficiently to high-dose antihistamines or in whom standard immunosuppressive drugs are ineffective or associated with unacceptable side effects.

scholarly journals Long term alterations of growth after antenatal steroids in preterm twin pregnancies

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Thorsten Braun ◽  
Vivien Filleböck ◽  
Boris Metze ◽  
Christoph Bührer ◽  
Andreas Plagemann ◽  
...  
Keyword(s):  
Early Childhood ◽  
Disease Risk ◽  
Later Life ◽  
Ponderal Index ◽  
Childhood Growth ◽  
Antenatal Steroids ◽  
Increased Risk ◽  
Infancy And Early Childhood ◽  
Twin Pregnancies

AbstractObjectivesTo compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth.MethodsA retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children’s examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years.ResultsOverall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%.ConclusionsANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease.SynopsisFirst-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk.

scholarly journals Adjuvant brachytherapy for FIGO stage I serous or clear cell endometrial cancer

2021 ◽  
pp. ijgc-2020-002217
Author(s):  
Elizabeth B Jeans ◽  
William G Breen ◽  
Trey C Mullikin ◽  
Brittany A Looker ◽  
Andrea Mariani ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Clear Cell ◽  
Early Stage ◽  
Figo Stage ◽  
Stage I ◽  
High Dose ◽  
Vaginal Cuff ◽  
Locoregional Failure ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

ObjectivesOptimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy.MethodsFrom April 1998 to January 2020, women with FIGO stage IA–IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes.ResultsA total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3–12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology.ConclusionAdjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.

scholarly journals Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome After High-Dose Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2558
Author(s):  
Malte Roerden ◽  
Stefan Wirths ◽  
Martin Sökler ◽  
Wolfgang A. Bethge ◽  
Wichard Vogel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Clinical Decision Making ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Mantle Cell ◽  
Autologous Grafts

Novel predictive factors are needed to identify mantle cell lymphoma (MCL) patients at increased risk for relapse after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT/Auto-HSCT). Although bone marrow and peripheral blood involvement is commonly observed in MCL and lymphoma cell contamination of autologous stem cell grafts might facilitate relapse after Auto-HSCT, prevalence and prognostic significance of residual MCL cells in autologous grafts are unknown. We therefore performed a multiparameter flow cytometry (MFC)-based measurable residual disease (MRD) assessment in autologous stem cell grafts and analyzed its association with clinical outcome in an unselected retrospective cohort of 36 MCL patients. MRD was detectable in four (11%) autologous grafts, with MRD levels ranging from 0.002% to 0.2%. Positive graft-MRD was associated with a significantly shorter progression-free and overall survival when compared to graft-MRD negative patients (median 9 vs. 56 months and 25 vs. 132 months, respectively) and predicted early relapse after Auto-HSCT (median time to relapse 9 vs. 44 months). As a predictor of outcome after HDCT/Auto-HSCT, MFC-based assessment of graft-MRD might improve risk stratification and support clinical decision making for risk-oriented treatment strategies in MCL.

scholarly journals Association between early bronchiolitis and the development of childhood asthma: a meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e043956
Author(s):  
Guizuo Wang ◽  
Dong Han ◽  
Zhengdong Jiang ◽  
Manxiang Li ◽  
Shumei Yang ◽  
...  
Keyword(s):  
Early Life ◽  
Fixed Effects ◽  
Late Onset ◽  
Meta Analysis ◽  
Later Life ◽  
Analysis Data ◽  
Fixed Effects Model ◽  
Case Control Studies ◽  
Increased Risk ◽  
Registration Number

ObjectiveEarly life bronchiolitis has been hypothesised to be associated with the subsequent risk of persistent wheezing or asthma. However, the link remains controversial. The objective of our study was to evaluate the association between bronchiolitis before 2 years of age and the late-onset wheezing/asthma.DesignSystematic review and meta-analysis.MethodsPubMed, Embase and Web of Science databases were systematically searched for studies published between 1955 and January 2020. Meanwhile, we also checked through the reference lists of relevant articles to see whether these references included reports of other studies that might be eligible for the review. Cohort and case–control studies assessing the association between early-life bronchiolitis and late-onset wheezing/asthma were included in this meta-analysis. Data were extracted by two independent reviewers. Results were pooled using a random-effects model or fixed-effects model according to the heterogeneity among studies.Results32 original articles with 292 844 participants, which met the criteria, were included in this meta-analysis. Bronchiolitis before 2 years of age was associated with an increased risk of subsequent wheezing/asthma (relative risk=2.46, 95% CI 2.14 to 2.82, p<0.001). After categorising studies into different groups based on age at the end of follow-up, geographical region and study quality, the association still remained significant.ConclusionsThe meta-analysis indicates an association between bronchiolitis before 2 years of age and the wheezing/asthma in later life. Well-designed and highly standardised prospective studies that better address bias due to potential confounding factors are needed to validate the risk identified in our meta-analysis.PROSPERO registration numberCRD42018089453.

scholarly journals Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

2021 ◽  
Vol 10 (4) ◽  
pp. 835
Author(s):  
Manoja P. Herath ◽  
Jeffrey M. Beckett ◽  
Andrew P. Hills ◽  
Nuala M. Byrne ◽  
Kiran D. K. Ahuja
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fat Mass ◽  
Metabolic Disorders ◽  
Later Life ◽  
Therapeutic Interventions ◽  
Increased Risk ◽  
The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

scholarly journals A rodent model of human dose-equivalent progestin-only implantable contraception

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heather C. M. Allaway ◽  
Roger A. Pierson ◽  
Jesse Invik ◽  
Susan A. Bloomfield
Keyword(s):  
Repeated Measures ◽  
Ovarian Function ◽  
Virgin Female ◽  
Rodent Model ◽  
High Dose ◽  
Corpora Lutea ◽  
Average Dose ◽  
Estrus Cycle ◽  
Human Dose ◽  
Dose Dependent

Abstract Background Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use. Methods Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30μg/d, medium-0.17μg/d, low-0.09μg/d, placebo-0.00μg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA. Results Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation. Conclusion Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.

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