scholarly journals The Role of Androgen Supplementation in Women With Diminished Ovarian Reserve: Time to Randomize, Not Meta-Analyze

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Raquel Neves ◽  
Pedro Montoya-Botero ◽  
Nikolaos P. Polyzos
Keyword(s):  
Ovarian Reserve ◽  
Clinical Studies ◽  
Animal Studies ◽  
Diminished Ovarian Reserve ◽  
Inclusion Criteria ◽  
Treatment Protocols ◽  
Challenging Tasks ◽  
Reserve Time ◽  
Androgen Supplementation

The management of patients with diminished ovarian reserve (DOR) remains one of the most challenging tasks in IVF clinical practice. Despite the promising results obtained from animal studies regarding the importance of androgens on folliculogenesis, the evidence obtained from clinical studies remains inconclusive. This is mainly due to the lack of an evidence-based methodology applied in the available trials and to the heterogeneity in the inclusion criteria and IVF treatment protocols. In this review, we analyze the available evidence obtained from animal studies and highlight the pitfalls from the clinical studies that prevent us from closing the chapter of this line of research.

scholarly journals Association of Germline BRCA Pathogenic Variants with Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data

2021 ◽  
Author(s):  
Volkan Turan ◽  
Matteo Lambertini ◽  
Dong-Yun Lee ◽  
Erica T Wang ◽  
Florian Clatot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Ovarian Reserve ◽  
Clinical Studies ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Diminished Ovarian Reserve ◽  
Pathogenic Variants ◽  
Repair Deficiency ◽  
Dna Repair Deficiency

AbstractPurposeTo determine whether germline BRCA pathogenic variants (gBRCA) are associated with decreased ovarian reserve.Materials and MethodsAn individual patient-data meta-analysis was performed using 5 datasets on 828 evaluable women who were tested for gBRCA. Of those, 250 carried gBRCA while 578 had tested negative and served as controls. Of the women with gBRCA, four centers studied those affected with breast cancer (n=161) and one studied unaffected individuals (n=89). The data were adjusted for the center, age, body mass index, smoking and oral contraceptive pill use before the final analysis. Anti-mullerian hormone (AMH) levels in affected women were drawn before pre-systemic therapy.ResultsMean ages of women with vs. without gBRCA1/2 (34.1± 4.9 vs. 34.3± 4.8 years; p=0.48), and with gBRCA1 vs gBRCA2 (33.7± 4.9 vs. 34.6± 4.8 years; p=0.16) were similar. After the adjustments, women with gBRCA1/2 had significantly lower AMH levels compared to controls (23% lower; 95% CI: 4-38%, p=0.02). When the adjusted analysis was limited to affected women (157 with gBRCA vs. 524 without, after exclusions), the difference persisted (25% lower; CI: 9-38%, p=0.003). The serum AMH levels were lower in women with gBRCA1 (33% lower; CI: 12-49%, p=0.004) but not gBRCA2 compared to controls (7% lower; CI: 31% lower to 26% higher, p=0.64).ConclusionsYoung women with gBRCA pathogenic variants, particularly of those affected and with gBRCA1, have lower serum AMH levels compared to controls. They may need to be preferentially counselled about the possibility of shortened reproductive lifespan due to diminished ovarian reserve.ContextKey objectiveDNA repair deficiency is emerging as a joint mechanism for breast cancer and reproductive aging. Recent studies showed that ovarian reserve maybe lower in women with BRCA pathogenic variants (gBRCA) due to DNA repair deficiency. However, clinical studies using the most sensitive serum ovarian reserve marker Anti-Mullerian-Hormone (AMH) provided mixed results. Given the heterogeneity of the data from clinical studies, we performed an individual patient data (IPD) meta-analysis to determine if gBRCA are associated with lower ovarian reserve.Knowledge generatedgBRCA are associated with diminished ovarian reserve, as determined by serum AMH and this association is restricted to gBRCA1. This finding is firmer for affected women as this IPD meta-analysis predominantly studied those with breast cancer.RelevanceWomen with gBRCA may have shortened reproductive life span due to diminished ovarian reserve and should be proactively counseled for fertility preservation especially if faced with chemotherapy or delaying childbearing.

Risk factors for diminished ovarian reserve and the role of endometriosis

2010 ◽  
Vol 94 (4) ◽  
pp. S63 ◽  
Author(s):  
K. Lin ◽  
B. Samantha ◽  
M.D. Sammel ◽  
K.T. Barnhart
Keyword(s):  
Risk Factors ◽  
Ovarian Reserve ◽  
Diminished Ovarian Reserve

Fresh Osteochondral and Chondral Allograft Preservation and Storage Media: A Systematic Review of the Literature

2021 ◽  
pp. 036354652110168
Author(s):  
Suzanne M. Tabbaa ◽  
Farshid Guilak ◽  
Robert L. Sah ◽  
William D. Bugbee
Keyword(s):  
Systematic Review ◽  
Clinical Studies ◽  
Animal Studies ◽  
Storage Time ◽  
Ex Vivo ◽  
Inclusion Criteria ◽  
Osteochondral Repair ◽  
Storage Solutions ◽  
Key Variables ◽  
And Storage

Background: Storage procedures and parameters have a significant influence on the health of fresh osteochondral allograft (OCA) cartilage. To date, there is a lack of agreement on the optimal storage conditions for OCAs. Purpose: To systematically review the literature on (1) experimental designs and reporting of key variables of ex vivo (laboratory) studies, (2) the effects of various storage solutions and conditions on cartilage health ex vivo, and (3) in vivo animal studies and human clinical studies evaluating the effect of fresh OCA storage on osteochondral repair and outcomes. Study Design: Systematic review; Level of evidence, 5. Methods: A systematic review was performed using the PubMed, Embase, and Cochrane databases. The inclusion criteria were laboratory studies (ex vivo) reporting cartilage health outcomes after prolonged storage (>3 days) of fresh osteochondral or chondral tissue explants and animal studies (in vivo) reporting outcomes of fresh OCA. The inclusion criteria for clinical studies were studies (>5 patients) that analyzed the relationship of storage time or chondrocyte viability at time of implantation to patient outcomes. Frozen, cryopreserved, decellularized, synthetic, or tissue-engineered grafts were excluded. Results: A total of 55 peer-reviewed articles met the inclusion criteria. Ex vivo studies reported a spectrum of tissue sources and storage solutions and conditions, although the majority of studies lacked complete reporting of key variables, including storage solution formula and environmental conditions. The effect of various conditions (eg, temperature) and storage solutions on cartilage health were inconsistent. Although 60% of animal models suggest that storage time may influence outcomes and 80% indicate inferior outcomes with frozen OCA as compared with fresh OCA, 75% of clinical studies report no correlation between storage time and outcomes. Conclusion: Given the variability in experimental designs and lack of reporting across studies, it is still not possible to determine optimal storage conditions, although animal studies suggest that storage time and chondrocyte viability influence osteochondral repair outcomes. A list of recommendations was developed to encourage reporting of key variables, such as media formulation, environmental factors, and methodologies used. High-quality clinical data are needed to investigate the effects of storage and graft health on outcomes.

scholarly journals Role of botulinum neurotoxin–A in cerebral revascularization graft vasospasm prevention: current state of knowledge

2019 ◽  
Vol 46 (2) ◽  
pp. E13
Author(s):  
Kristine Ravina ◽  
Ben A. Strickland ◽  
Robert C. Rennert ◽  
Joseph N. Carey ◽  
Jonathan J. Russin
Keyword(s):  
Animal Studies ◽  
Cerebral Revascularization ◽  
Clinical Role ◽  
Treatment Protocols ◽  
Graft Stenosis ◽  
Physiological Variability ◽  
Neural Transmission ◽  
Mechanistic Basis ◽  
Stenosis And Occlusion

Graft stenosis and occlusion remain formidable complications in cerebral revascularization procedures, which can lead to significant morbidity and mortality. Graft vasospasm can result in early postoperative graft stenosis and occlusion and is believed to be at least partially mediated through adrenergic pathways. Despite various published treatment protocols, there is no single effective spasmolytic agent. Multiple factors, including anatomical and physiological variability in revascularization conduits, patient age, and comorbidities, have been associated with graft vasospasm pathogenesis and response to spasmolytics. The ideal spasmolytic agent thus likely needs to target multiple pathways to exert a generalizable therapeutic effect. Botulinum toxin (BTX)–A is a powerful neurotoxin widely used in clinical practice for the treatment of a variety of spastic conditions. Although its commonly described paradigm of cholinergic neural transmission blockade has been widely accepted, evidence for other mechanisms of action including inhibition of adrenergic transmission have been described in animal studies. Recently, the first pilot study demonstrating clinical use of BTX-A for cerebral revascularization graft spasm prevention has been reported. In this review, the mechanistic basis and potential future clinical role of BTX-A in graft vasospasm prevention is discussed.

scholarly journals miR-106a Increases Granulosa Cell Viability and Is Downregulated in Women With Diminished Ovarian Reserve

2018 ◽  
Vol 103 (6) ◽  
pp. 2157-2166 ◽  
Author(s):  
Liming Hong ◽  
Sha Peng ◽  
Ying Li ◽  
Ying Fang ◽  
Qin Wang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Granulosa Cell ◽  
P38 Mapk ◽  
Granulosa Cells ◽  
Ovarian Reserve ◽  
Mirna Expression ◽  
Diminished Ovarian Reserve ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase

Abstract Context Women with diminished ovarian reserve (DOR) have reduced fertility, cardiovascular events, and osteoporosis. Although differential microRNA (miRNA) expression has been described in several ovarian disorders, little is known about the role of miRNAs in the pathogenesis of DOR. Objective Identify differentially expressed miRNAs in DOR and explore the role of miR-106a in human granulosa cell proliferation. Design miRNA microarray (n = 3) and quantitative reverse transcription polymerase chain reaction (n = 30) were used to examine miRNA expression in serum and granulosa cells from normal-cycling and women with DOR. Primary human granulosa cells were treated alone or in combination with miR-106a mimic, miR-106a inhibitor, apoptosis signal-regulating kinase 1 (ASK1) small interfering RNA (siRNA), or p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) before assessment of cell viability and apoptosis. Western blot was used to measure ASK1 protein and phosphorylation/activation of p38 MAPK. Binding of miR-106a to ASK1 mRNA was examined by 3′ untranslated region (3′UTR) luciferase analysis. Results Fifteen miRNAs were differentially expressed (n = 30), and miR-106a was downregulated in serum and granulosa cells of women with DOR. miR-106a mimic increased cell viability and attenuated apoptosis, whereas the converse occurred following treatment with miR-106a inhibitor. miR-106a suppressed ASK1 expression by directly targeting its 3′UTR. miR-106a inhibitor increased p38 MAPK phosphorylation/activation, and this effect was abolished by treatment with ASK1 siRNA. Whereas knockdown of ASK1 abolished the effects of miR-106a inhibitor on cell viability/apoptosis, pretreatment with SB203580 did not significantly alter the effects of miR-106a inhibitor. Conclusions Downregulation of miR-106a may contribute to the pathogenesis of DOR by reducing granulosa cell viability and promoting apoptosis via enhanced ASK1 signaling.

Calcium-Channel Antagonists for Prevention of Atherosclerosis

1993 ◽  
Vol 27 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Shawn M. Borcherding ◽  
Suzanne G. Meeves ◽  
Neil E. Klutman ◽  
Patricia A. Howard
Keyword(s):  
Clinical Trials ◽  
Calcium Channel ◽  
Calcium Antagonists ◽  
Clinical Studies ◽  
Animal Studies ◽  
English Language ◽  
Data Extraction ◽  
Calcium Channel Antagonists ◽  
Trial Duration

OBJECTIVE: To critically evaluate the current literature regarding the role of calcium-channel antagonists in preventing atherosclerosis. DATA SOURCES: English language clinical studies, abstracts, conference proceedings, and review articles pertaining to calcium-channel antagonists and atherosclerosis. STUDY SELECTION: Relevant animal and human studies examining the role of calcium-channel antagonists in atherosclerosis prevention and treatment. DATA EXTRACTION: Potential mechanisms for the development of atherosclerosis and the use of calcium antagonists for preventing and treating coronary artery disease are discussed. Animal studies are summarized; next, significant data from human clinical studies are presented. DATA SYNTHESIS: Available studies are described and discussed. CONCLUSIONS: Results from animal and clinical trials in humans suggest that calcium antagonists may retard the development and progression of atherosclerosis. However, most clinical trials to date have been conducted in patients with proven atherosclerotic plaques. Further studies examining the role of calcium-channel antagonists in preventing and treating atherosclerosis are needed, but may be difficult to conduct because of the large numbers of patients required, long trial duration, and associated costs.

scholarly journals Ovarian Reserve Assessment for Infertility Investigation

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Bruno Ramalho de Carvalho ◽  
David Barreira Gomes Sobrinho ◽  
Andréa Duarte Damasceno Vieira ◽  
Manoela Porto Silva Resende ◽  
Antônio César Paes Barbosa ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Reproductive Medicine ◽  
Sufficient Evidence ◽  
Dynamic Tests ◽  
Treatment Protocols ◽  
Important Place ◽  
Current Trends ◽  
Financial Burdens ◽  
Ovarian Reserve Markers

The current trends to postpone motherhood and the increase in demand for assistance in reproductive medicine highlight the need for seeking guidelines for the establishment of individualized treatment protocols. Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, but they may occupy important place in initial counseling, predicting unsatisfactory results that could be improved by individualized induction schemes and reducing excessive psychological and financial burdens, and adverse effects. In this paper, we revise the role of hormonal basal and dynamic tests, as well as ultrasonographic markers, as ovarian reserve markers, in order to provide embasement for propaedeutic strategies and their interpretation in order to have reproductive success.

scholarly journals Cadmium Exposure and Ovarian Reserve in Women Aged 35–49 Years: The Impact on Results From the Creatinine Adjustment Approach Used to Correct for Urinary Dilution

2020 ◽  
Vol 190 (1) ◽  
pp. 116-124 ◽  
Author(s):  
Kristen Upson ◽  
Katie M O’Brien ◽  
Janet E Hall ◽  
Erik J Tokar ◽  
Donna D Baird
Keyword(s):  
Ovarian Reserve ◽  
Animal Studies ◽  
Elevated Serum ◽  
Careful Consideration ◽  
Diminished Ovarian Reserve ◽  
Covariate Adjustment ◽  
Relative Risks ◽  
Causal Pathway ◽  
Using Data ◽  
The Impact

Abstract Cadmium is toxic to the ovaries in animal studies, but its association with diminished ovarian reserve in women is not established. We investigated urinary cadmium, a biomarker of long-term exposure, in relation to diminished ovarian reserve, as indicated by elevated serum follicle-stimulating hormone concentrations (≥10 IU/L), in women aged 35–49 years (unweighted n = 1,681). Using data from the Third National Health and Nutrition Examination Survey (1988–1994), we conducted Poisson regression to estimate adjusted relative risks and 95% confidence intervals. Because the best approach to correcting for urinary dilution in spot samples with creatinine remains controversial, we employed 3 approaches: standardization, covariate adjustment, and covariate-adjusted standardization. Our data suggested a modest association with standardization (highest quartile vs. lowest: relative risk (RR) = 1.3, 95% confidence interval (CI): 0.8, 1.9; P for trend = 0.06) and covariate-adjusted standardization (highest quartile vs. lowest: RR = 1.3, 95% CI: 0.9, 1.9; P for trend = 0.05) and a stronger association with covariate adjustment (highest quartile vs. lowest: RR = 1.8, 95% CI: 1.2, 2.9; P for trend = 0.01). The stronger association with covariate adjustment may reflect bias from conditioning on urinary creatinine, a collider in the hypothesized causal pathway. We conclude that cadmium may contribute to ovarian aging in women and that careful consideration of the creatinine adjustment approach is needed to minimize bias.

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