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Current Treatment Options in Oncology Jan 2015All work referenced herein relates to treatment of epithelial ovarian carcinomas, as their treatment differs from ovarian germ cell cancers and other rare ovarian... (Review)
Review
All work referenced herein relates to treatment of epithelial ovarian carcinomas, as their treatment differs from ovarian germ cell cancers and other rare ovarian cancers, the treatments of which are addressed elsewhere. Fallopian tube cancers and primary peritoneal adenocarcinomatosis are also generally treated as epithelial ovarian cancers. The standard of care initial treatment of advanced stage epithelial ovarian cancer is optimal debulking surgery as feasible plus chemotherapy with a platinum plus a taxane agent. If this front-line approach fails, as it too often the case, several FDA-approved agents are available for salvage therapy. However, because no second-line therapy for advanced-stage epithelial ovarian cancer is typically curative, we prefer referral to clinical trials as logistically feasible, even if it means referring patients outside our system. Immune therapy has a sound theoretical basis for treating carcinomas generally, and for treating ovarian cancer in particular. Advances in understanding the immunopathogenic basis of ovarian cancer, and the immunopathologic basis for prior failures of immunotherapy for it and other carcinomas promises to afford novel treatment approaches with potential for significant efficacy, and reduced toxicities compared with cytotoxic agents. Thus, referral to early phase immunotherapy trials for ovarian cancer patients that fail conventional treatment merits consideration.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Female; Humans; Immunotherapy; Ovarian Neoplasms
PubMed: 25648541
DOI: 10.1007/s11864-014-0317-1 -
Reproductive Biology and Endocrinology... Mar 2010Young cancer patients may occasionally face infertility and premature gonadal failure. Apart from its direct effect on follicles and oocytes, chemotherapy may induce...
BACKGROUND
Young cancer patients may occasionally face infertility and premature gonadal failure. Apart from its direct effect on follicles and oocytes, chemotherapy may induce ovarian toxicity via an impact on the entire ovary. The role of doxorubicin in potential ovarian failure remains obscure. Our intention was to elucidate doxorubicin-related toxicity within ovaries.
METHODS
Female mice were injected intraperitoneally with 7.5 or 10 mg/kg doxorubicin and their ovaries were visualized in vivo by high resolution MRI, one day and one month following treatment. Ovaries of other treated mice were excised and weighed at the same post-treatment intervals. Ovarian histological sections were stained for TUNEL or active caspase-3 and follicles were counted and categorized. Ovulation rates were evaluated in superovulated female mice treated with doxorubicin.
RESULTS
A single injection of doxorubicin resulted in a major reduction in both ovarian size and weight that lasted even one month post treatment. A dramatic reduction in ovulation rate was observed one week after treatment, followed by a partial recovery at one month. Histological examination revealed positive staining of TUNEL and active caspase-3. We observed a significant reduction in the population of secondary and primordial follicles one month following treatment.
CONCLUSIONS
Our results may imply a mechanism of chemotherapy-induced ovarian toxicity, manifested by reduced ovulation and accompanied by a reduction in ovarian size, caused probably by an acute insult to the ovary.
Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Cell Count; Cytotoxins; Dose-Response Relationship, Drug; Doxorubicin; Drug Evaluation, Preclinical; Female; Mice; Mice, Inbred ICR; Organ Size; Ovarian Diseases; Ovarian Follicle; Ovary
PubMed: 20202194
DOI: 10.1186/1477-7827-8-20 -
Frontiers in Endocrinology 2023Ovarian dysfunction is one of the most common features of women with Turner syndrome. In these women, oocyte apoptosis is markedly accelerated from the early stage of... (Review)
Review
Ovarian dysfunction is one of the most common features of women with Turner syndrome. In these women, oocyte apoptosis is markedly accelerated from the early stage of fetal life. Reduction in the number of germ cells disturbs primordial follicle development and thereby leads to the formation of streak gonads. There are three possible causes of accelerated germ cell loss in 45,X ovaries. First, chromosomal pairing failure due to X chromosomal aneuploidy is believed to induce meiotic arrest. Indeed, it has been suggested that the dosage of the X chromosome is more critical for the survival of the oocytes than for other cells in the ovary. Second, impaired coupling between oocytes and granulosa cells may also contribute to germ cell apoptosis. Previous studies have shown that 45,X ovaries may tend to lose tight junctions which are essential for intercellular interactions. Lastly, ovarian dysfunction in women with Turner syndrome is partly attributable to the reduced dosage of several genes on the X chromosome. Specifically, , , and some other genes on the X chromosome have been implicated in ovarian function. Further studies on the mechanisms of ovarian dysfunction are necessary to improve the reproductive outcomes of women with Turner syndrome.
Topics: Humans; Female; Turner Syndrome; Ovarian Follicle; Oocytes; Granulosa Cells; Ovarian Diseases; Membrane Proteins; Receptors, Progesterone
PubMed: 37033245
DOI: 10.3389/fendo.2023.1160258 -
Frontiers in Medicine 2023Premature ovarian failure (POF) is an insidious cause of female infertility and a devastating condition for women. POF also has a strong familial and heterogeneous... (Review)
Review
Premature ovarian failure (POF) is an insidious cause of female infertility and a devastating condition for women. POF also has a strong familial and heterogeneous genetic background. Management of POF is complicated by the variable etiology and presentation, which are generally characterized by abnormal hormone levels, gene instability and ovarian dysgenesis. To date, abnormal regulation associated with POF has been found in a small number of genes, including autosomal and sex chromosomal genes in folliculogenesis, granulosa cells, and oocytes. Due to the complex genomic contributions, ascertaining the exact causative mechanisms has been challenging in POF, and many pathogenic genomic characteristics have yet to be elucidated. However, emerging research has provided new insights into genomic variation in POF as well as novel etiological factors, pathogenic mechanisms and therapeutic intervention approaches. Meanwhile, scattered studies of transcriptional regulation revealed that ovarian cell function also depends on specific biomarker gene expression, which can influence protein activities, thus causing POF. In this review, we summarized the latest research and issues related to the genomic basis for POF and focused on insights gained from their biological effects and pathogenic mechanisms in POF. The present integrated studies of genomic variants, gene expression and related protein abnormalities were structured to establish the role of etiological genes associated with POF. In addition, we describe the design of some ongoing clinical trials that may suggest safe, feasible and effective approaches to improve the diagnosis and therapy of POF, such as Filgrastim, goserelin, resveratrol, natural plant antitoxin, Kuntai capsule et al. Understanding the candidate genomic characteristics in POF is beneficial for the early diagnosis of POF and provides appropriate methods for prevention and drug treatment. Additional efforts to clarify the POF genetic background are necessary and are beneficial for researchers and clinicians regarding genetic counseling and clinical practice. Taken together, recent genomic explorations have shown great potential to elucidate POF management in women and are stepping from the bench to the bedside.
PubMed: 37332766
DOI: 10.3389/fmed.2023.1194865 -
Frontiers in Immunology 2022Premature ovarian failure (POF) is a common female reproductive disorder and characterized by menopause, increased gonadotropin levels and estrogen deficiency before the...
Premature ovarian failure (POF) is a common female reproductive disorder and characterized by menopause, increased gonadotropin levels and estrogen deficiency before the age of 40 years old. The etiologies and pathogenesis of POF are not fully clear. At present, hormone replacement therapy (HRT) is the main treatment options for POF. It helps to ameliorate perimenopausal symptoms and related health risks, but can't restore ovarian function and fertility fundamentally. With the development of regenerative medicine, bone marrow mesenchymal stem cells (BMSCs) have shown great potential for the recovery of ovarian function and fertility based on the advantages of abundant sources, high capacity for self-renewal and differentiation, low immunogenicity and less ethical considerations. This systematic review aims to summarize the possible therapeutic mechanisms of BMSCs for POF. A detailed search strategy of preclinical studies and clinical trials on BMSCs and POF was performed on PubMed, MEDLINE, Web of Science and Embase database. A total of 21 studies were included in this review. Although the standardization of BMSCs need more explorations, there is no doubt that BMSCs transplantation may represent a prospective therapy for POF. It is hope to provide a theoretical basis for further research and treatment for POF.
Topics: Female; Humans; Adult; Primary Ovarian Insufficiency; Mesenchymal Stem Cells; Regenerative Medicine; Menopause
PubMed: 36389844
DOI: 10.3389/fimmu.2022.997808 -
Chinese Medical Journal Feb 2017Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons... (Review)
Review
OBJECTIVE
Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis.
DATA SOURCES
We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms.
STUDY SELECTION
Articles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases.
RESULTS
Many cytokines, such as MMPs, TIMPs, TGF-β1, CTGF, PPAR-γ, VEGF, and ET-1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst, PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide.
CONCLUSIONS
Patients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.
Topics: Animals; Cytokines; Female; Fibrosis; Humans; Infertility, Female; Ovary
PubMed: 28139522
DOI: 10.4103/0366-6999.198931 -
Journal of Reproduction & Infertility 2017Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles before the age of 40, representing one major cause of...
BACKGROUND
Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles before the age of 40, representing one major cause of female infertility. Mutations in bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) have been shown to be associated with POF.
METHODS
Genomic DNA was isolated from 52 idiopathic premature ovarian failure patients and 100 normal control individuals. Exons of BMP15 and GDF9 gene were amplified using PCR method and subjected to directed sequencing. Variants were identified by comparing the sequences obtained with normal sequences from NCBI database.
RESULTS
Four BMP15 gene variants were identified in 6 patients in heterozygous condition. Out of these 4 variants, 3 variants namely, c.165A>T (p.Glu55Asp), c.538 G>T (p.Aln180 Ser) and c. 510_512 delT were novel variants. In silico analysis using SIFT, Provean and Polyphen 2 score predicted the non-deleterious effect of c.165A>T and c.538 G>T variant. 788insTCT variant was identified in 3 patients. No variant was identified in GDF9 gene in any patients and controls.
CONCLUSION
Although the variant has been identified in BMP15 gene but it may not be associated with the premature ovarian failure.
PubMed: 28377898
DOI: No ID Found -
Current Opinion in Obstetrics &... Aug 2006To summarize current knowledge about premature ovarian failure (POF) with an emphasis on recent developments regarding its management. (Review)
Review
PURPOSE OF REVIEW
To summarize current knowledge about premature ovarian failure (POF) with an emphasis on recent developments regarding its management.
RECENT FINDINGS
The incidence of POF is increasing largely due to improved survival rates of cancer patients treated with radiation and chemotherapy. Delayed diagnosis and management of POF leads to suboptimal outcomes. Anticipation and early detection of this condition in high-risk women by means of ovarian function testing, followed by early institution of appropriate management could improve outcomes. Choice of strategies should vary depending on the age of onset, associated symptoms and fertility aspirations of the individual, and should change with the patient's advancing age.
SUMMARY
Early assessment of the individual's risk of developing POF, development of a strategic management plan, and timely commencement of infertility and hormone deficiency treatment, together with counselling in an integrated management plan should improve both the short and long-term health of those with POF.
Topics: Female; Hormone Replacement Therapy; Humans; Infertility, Female; Ovarian Follicle; Primary Ovarian Insufficiency; Reproductive Techniques, Assisted
PubMed: 16794423
DOI: 10.1097/01.gco.0000233937.36554.d3 -
Journal of Traditional Chinese Medicine... Jun 2023Premature ovarian failure (POF) is a female reproductive system disease caused by many factors and systems, which has seriously affected the quality of life of women of... (Review)
Review
Premature ovarian failure (POF) is a female reproductive system disease caused by many factors and systems, which has seriously affected the quality of life of women of childbearing age. Clinically, the disease is difficult to treat while its incidence rate shows an increasing trend. In recent years, natural products used as multi-pathway, multi-target and efficient drugs, have become the focus of many research and clinical studies in China and abroad, and the effect of phytochemicals derived from edible plants and Chinese medicine herbs on POF were investigated in several papers. Using "premature ovarian failure" or "ovary" and related natural products as keywords, we retrieved and reviewed research articles from China National Knowledge Infrastructure Database, Wanfang, PubMed, Web of Science and other literature databases. Up to October, 2021, natural compounds with prophylactic or interference inhibition effects on POF mainly included flavonoids, polysaccharides, saponins, and polyphenols. Their effect on POF and ovarian function was closely related to their antioxidant, antiapoptotic, antiaging, immunoregulatory and estrogen-like activities.
Topics: Female; Humans; Quality of Life; Primary Ovarian Insufficiency; China
PubMed: 37147765
DOI: 10.19852/j.cnki.jtcm.20230227.002 -
Genes Dec 2023Primary ovarian failure (POF) is caused by follicle exhaustion and is associated with menstrual irregularities and elevated gonadotropin levels, which lead to... (Review)
Review
Primary ovarian failure (POF) is caused by follicle exhaustion and is associated with menstrual irregularities and elevated gonadotropin levels, which lead to infertility before the age of 40 years. The etiology of POI is mostly unknown, but a heterogeneous genetic and familial background can be identified in a subset of cases. Abnormalities in the fragile X mental retardation 1 gene () are among the most prevalent monogenic causes of POI. These abnormalities are caused by the expansion of an unstable CGG repeat in the 5' untranslated region of . Expansions over 200 repeats cause fragile X syndrome (FXS), whereas expansions between 55 and 200 CGG repeats, which are defined as a fragile X premutation, have been associated with premature ovarian failure type 1 (POF1) in heterozygous females. Preimplantation genetic testing for monogenic diseases (PGT-M) can be proposed when the female carries a premutation or a full mutation. In this narrative review, we aim to recapitulate the clinical and molecular features of POF1 and their implications in the context of PGT-M.
Topics: Female; Humans; 5' Untranslated Regions; Alleles; Fragile X Mental Retardation Protein; Fragile X Syndrome; Genetic Testing; Mutation; Primary Ovarian Insufficiency
PubMed: 38275588
DOI: 10.3390/genes15010006