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عضویت

جستجوی مقالات مرتبط با کلیدواژه « premature ovarian failure » در نشریات گروه « پزشکی »

  • نگار پولادوند، مهناز آذرنیا، حدیث زینلی، روح الله فتحی، سمیه توانا*
    مقدمه

    شایع ترین عارضه شیمی درمانی، ناباروری ناشی از نارسایی زودرس تخمدان (POF) است. بیماریPOF به عنوان از دست دادن عملکرد طبیعی تخمدان قبل از 40 سالگی تعریف می شود که با افزایش سطح گنادوتروپین، کاهش سطح استرادیول و کاهش ذخیره تخمدان مشخص شده و اغلب منجر به ناباروری می شود. علی رغم تاثیر زیاد POF بر سلامت عمومی و کیفیت زندگی، پاتوفیزیولوژی این بیماری نامشخص است. برای این منظور مدل های حیوانی این فرصت را در اختیار ما قرار می دهند که به طور فرضی پاتوژنز بیماری را به طور جامع بررسی کنیم. رایج ترین روش ایجاد مدل حیوانی نارسایی زودرس تخمدان، استفاده از داروهای شیمی درمانی می باشد. در این مطالعه، انواع داروهای شیمی درمانی و نیز مسیرهای مولکولی مربوطه که در ایجاد مدل نارسایی زودرس تخمدان در موش نقش دارند،  مورد بررسی قرار خواهند گرفت.

    نتیجه گیری

    با توجه به مطالعات انجام شده، داروی سیکلوفسفامید به عنوان رایج ترین داروی گنادوتوکسیک به منظور ایجاد مدل POF در موش معرفی می گردد.

    کلید واژگان: نارسایی زودرس تخمدان, داروهای شیمی درمانی, ناباروری, موش}
    Negar Pouladvand, Mahnaz Azarnia, Hadis Zeinali, Rouhollah Fathi, Somayeh Tavana*
    Introduction

    The most common complication of chemotherapy is infertility due to premature ovarian failure (POF). POF is defined as the loss of normal ovarian function before age 40, characterized by increased gonadotropin levels, decreased estradiol levels, and diminished ovarian reserve, often leading to infertility. Despite the high impact of POF on general health and quality of life, the pathophysiology of this disease is unclear. For this purpose, animal models provide us with the opportunity to hypothetically investigate the pathogenesis of the disease comprehensively. The most common method of creating an animal model of premature ovarian failure is the use of chemotherapy drugs. In this study, the types of chemotherapy drugs and the relevant molecular pathways that play a role in creating the premature ovarian failure model in mice will be investigated

    Conclusion

    According to the studies, cyclophosphamide drug is introduced as the most common gonadotoxic drug in order to induce POF model in mice.

    Keywords: Premature Ovarian Failure, Chemotherapy Drugs, Infertility, Mouse}
  • Yahya Yahyavi, Abbas Karimi, Abbas Ebrahimi-Kalan, Fatemeh Ramezani, Mahdi Hasanzadeh, Soudabe Yousefi, Hourieh Sadrekarimi, Neda Abouasoltani, Mohammad Nouri, Mahdi Edalati*
    Background

     Chemotherapy-induced premature ovarian failure is a prevalent issue for cancer patients, and current treatment options are associated with limitations. Platelet-rich plasma (PRP) has emerged as a safe and straightforward treatment option for various medical conditions, including infertility. The study aims to assess the impact of PRP on the follicular function of granulosa cells damaged with Cyclophosphamide (CTX).

    Methods

     The study evaluated the biological characteristics of Human Granulosa Cells (HGrC1) that were damaged with 4 hydroxy-cyclophosphamide (4-HC) as the active form of CTX. Then, cells were treated with different concentrations of platelet-rich plasma (PRP), and the expression of PI3K, K-RAS, BCL-2, P27, and Caspase 3 genes were analyzed. Cell viability and apoptosis were also assessed.

    Results

     In the MTT assay, it was observed that cells treated with Cyclophosphamide had a faster growth rate when exposed to high concentrations of PRP. The results of the apoptosis assay using Annexin-V and propidium iodide (PI) revealed that PRP effectively inhibited apoptosis and enhanced cell proliferation across all incubation periods (24, 48, and 72 hours). Compared to untreated cells, those treated with different concentrations of PRP showed significantly lower levels of apoptosis, indicating higher cell viability. Real-time PCR results demonstrated that PRP treatment decreased the expression of apoptotic factors P27 and caspase 3 while increasing the expression of genes that promote cell survival and proliferation, such as BCL-2, PI3K, and K-RAS. These findings are consistent with previous research, which suggests that the growth factors present in platelets have anti-apoptotic effects and promote high rates of cell proliferation.

    Conclusion

     The study suggests that PRP therapy may have potential benefits in promoting follicular growth and repairing ovarian tissue. However, further research is necessary to establish novel therapeutic strategies based on PRP therapy for treating infertility.

    Keywords: 4-hydroxycyclophosphamide, Cyclophosphamide, Platelet-rich plasma (PRP), Premature ovarian failure}
  • غنچه صالحی، پروین فرزانگی*، عبدالرضا جعفری، فرزانه فرخی
    مقدمه

    ناباروری زنان، یک وضعیت پزشکی جهانی است که می تواند ناشی از اختلالات مختلف دستگاه تناسلی از جمله نارسایی زودرس تخمدان باشد. مطالعه حاضر با هدف بررسی اثر 8 هفته تمرین شنا و تزریق سلول بنیادی بر ژن های VEGF، TGF و HGF بافت تخمدان موش های مدل نارسایی زودرس تخمدان انجام شد.

    روش کار

    در این تحقیق تجربی، تعداد 30 سر موش صحرایی ماده 8-6 هفته ای انتخاب شدند. به منظور ایجاد مدل نارسایی زودرس تخمدان، از داروی سیکلوفسفامید و بیوسولفان به ترتیب به میزان 100 و 50 میلی گرم بر کیلوگرم، به صورت تزریق درون صفاقی استفاده شد. پس از القاء مدل، موش ها به صورت تصادفی به 6 گروه (5 سر در هر گروه) شامل: کنترل سالم، بیمار+ شم، بیمار+ سالین، بیمار+ سلول، بیمار+ ورزش و بیمار+ سلول+ ورزش تقسیم شدند. رت های گروه تمرین، در طی 8 هفته به شنا پرداختند. گروه های سلول، 2 هفته بعد از ایجاد مدل سلول های بنیادی به میزان یک میلیون سلول برای هر موش در تخمدان پیوند زده شد. تجزیه و تحلیل داده ها با استفاده از نرم افزار آماری SPSS (نسخه 22) و آزمون های آنالیز واریانس یک طرفه و تعقیبی توکی انجام شد. میزان p کمتر یا مساوی 05/0 معنی دار در نظر گرفته شد.

    یافته ها

    القاء نارسایی زودرس تخمدان منجر به افزایش معنی دار ژن های VEGF، TGF و HGF بافت تخمدان رت ها نسبت به گروه کنترل- سالم شد (05/0≥p) که گروه های تمرین، سلول و تمرین+ سلول، بیان این ژن ها را نسبت به گروه بیمار و بیمار سالین کاهش دادند (05/0≥p).

    نتیجه گیری

    اثر هم افزایی تمرین هوازی و سلول بنیادی مزانشیمی مشتق از مغز استخوان باعث بهبود فاکتورهای رگ زایی رت های مدل تجربی نارسایی زودرس تخمدان می شود.

    کلید واژگان: آنژیوژنز, تمرین شنا, سلول بنیادی مزانشیمی, نارسایی زودرس تخمدان}
    Ghoncheh Salehi, Parvin Farzanegi *, Abdolreza Jafari, Farzane Farokhi
    Introduction

    Female infertility is a universal medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure. The present study was performed with aim to investigate the effect of 8 weeks of swimming training and stem cell injection on VEGF, TGF and HGF genes in the ovarian tissue of premature ovarian failure model rats.

    Methods

    In this experimental research, 30 female rats 6- to 8-week-old were selected. In order to create a model of premature ovarian failure, cyclophosphamide and biosulfan were used in the amount of 100 and 50 mg/kg, respectively, as an intraperitoneal injection. After model induction, rats were randomly divided into 6 groups (5 heads in each group) including: 1) healthy control, 2) patient+ sham, 3) patient+ saline, 4) patient+ cell, 5) patient +exercise and 6) patient+ cell+ exercise. The rats of the training group swam for 8 weeks. Cell groups, 2 weeks after creating the model stem cells were transplanted in the ovary at the rate of one million cells for each mouse. Data analysis was done using SPSS statistical software (version 22) and one-way ANOVA and Tukey's post hoc tests. P≤0.05 was considered significant.

    Results

    Induction of premature ovarian failure led to a significant increase in VEGF, TGF and HGF genes in the ovarian tissue of rats compared to the control-healthy group (P≤0.05) that the exercise, cell and exercise+ cell groups decreased the expression of these genes compared to the patient and patient-saline groups (P≤0.05).

    Conclusion

    The synergistic effect of aerobic exercise and bone marrow-derived mesenchymal stem cells improve angiogenic factors in experimental premature ovarian failure model rats.

    Keywords: Mesenchymal stem cells, Premature Ovarian Failure, Swimming training}
  • مرضیه لطفی، لیلا عضد، ملیحه لطفی، فاطمه توحیدی، سید حسین شاهچراغی*
    مقدمه

     نارسایی زودرس تخمدان یا Premature Ovarian Failure (POF)  بیماری است که قبل از 40 سالگی و به دلیل اختلال در عملکرد تخمدان ها رخ می دهد. در این افراد تولید و ترشح هورمون استروژن به درستی انجام نمی شود. چنین وضعیتی باعث نامنظم شدن یا قطع پریود واختلال در فرایند تخمک گذاری و بروز علایم یایسگی می شود. نارسایی زودرس تخمدان باردار شدن افراد را با مشکل مواجه می کند، لذا تحقیقات بیشتر در این زمینه ضروری است.

    نتیجه گیری

     یکی از راه های پیشنهادی برای ترمیم و بازسازی بافت تخمدان نارسا استفاده از پلاسمای غنی از پلاکت (PRP) است. اثرات مثبت PRP وابسته به غلظت بالای فاکتورهای رشد موجود در گرانول های الفای پلاکت ها می باشد. نتایج این مقاله مروری نشان دهنده این است که استفاده از پلاسمای غنی از پلاکت در بازگرداندن عملکرد تخمدان می تواند به عنوان یک روش درمانی در این بیماران مدنظر قرار گیرد.

    کلید واژگان: نارسایی زودرس تخمدان, پلاسمای غنی از پلاکت, جوان سازی تخمدان}
    Marzieh Lotfi, Leila Azod, Malihe Lotfi, Fatemeh Tohidi, Seyed Hossein Shahcheraghi*
    Introduction

     Premature Ovarian Failure (POF) is a disease that occurs before the age of 40 due to dysfunction of the ovaries. In these women، the production and secretion of estrogen hormone is not done properly. Such a situation causes irregular or interrupted periods، disturbances in the ovulation process and occurrence of menopausal symptoms. Premature ovarian failure makes it difficult for women to get pregnant، so more research in this field is necessary.

    Conclusion

     The results showed that one of the recommended ways to repair and regenerate the failing ovarian tissue was the use of platelet-rich plasma (PRP). The positive effects of PRP were dependent on the high concentration of growth factors in the alpha granules of platelets. The results of this review article showed that the use of platelet-rich plasma in restoring ovarian function could be considered as a treatment method in these patients.

    Keywords: Premature Ovarian Failure, Platelet-rich plasma, Ovarian rejuvenation}
  • Saman Moradi, Mozafar Khazaei, Zahra Rashidi *
    Objective

    Premature ovarian failure (POF) is a heterogeneous disorder. POF is defined as hypergonadotropic hypoestrogenism in women under 40 years. There is no effective treatment to cure POF patients. Antioxidants prevent ovarian damage by reducing the lipid peroxidation cascades affecting folliculogenesis, meiosis and ovulation. Hence; the aim of present study was to investigate the effects of Capsaicin (CAP) and Quercetin (QUR) on cyclophosphamide (CYC)-induced POF in rat model.

    Materials and Methods

    In this experimental study, POF was induced by intraperitoneal injection of 200 mg/kg CYC on first day and then 8 mg/kg/day for the following 3 days. After 4 days of CYC administration, rats were randomly divided into five groups (n=6/group) as follows: POF, dimethyl sulfoxide (DMSO), CAP (0.5 mg/kg/day), QUR (100 mg/kg/day) and CAP+QUR. Biochemical, hormonal, gene expression, and histological evaluations were performed on blood serum and tissue samples after 14 days of treatment with the CAP and QUR.

    Results

    CAP, QUR and CAP+QUR groups showed signs of restored ovarian function in the form of a significant increase in serum total antioxidant capacity (TAC), estrogen, progesterone and anti-mullerian hormone (AMH) levels versus POF and DMSO groups and a significant improvement in histological parameters and follicle numbers in treatment groups compared to POF and DMSO groups. Polymerase chain reaction (PCR) analysis demonstrated that CAP and QUR upregulate the expression of BAX gene and decreased the expression of apoptosis inducing genes (BCL-2 and P53).

    Conclusion

    CAP and QUR treatment of CYC-induced POF rats showed a positive effect on reducing ovarian damage by improving TAC levels, expression of apoptotic genes, levels of ovarian reserve markers, and histological parameters. Our results suggest that treatment with CAP or QUR may be a conservative treatment approach for CYC -induced POF.

    Keywords: Capsaicin, Cyclophosphamide, Premature Ovarian Failure, Quercetin, Total Antioxidant Capacity}
  • لیلا علیزاده، فرشته قهرمانی، سیده مریم خلیلی، مرجان هوایی، الناز حاجی رفیعی، هدیه ریاضی، زهره کشاورز*
    مقدمه

    مهم ترین عامل آغازگر سرطان دهانه رحم، ابتلاء به عفونت ویروس پاپیلومای انسانی (HPV) است. اگرچه واکسن ساخته شده بر علیه این ویروس، می تواند به نحو چشمگیری از ابتلاء زنان پیشگیری نماید؛ اما یافته های متناقضی در مورد عوارض جانبی آن از جمله نارسایی زودرس تخمدان مطرح شده است. مطالعه حاضر با هدف مروری سیستماتیک بر مطالعات انجام شده در زمینه ارتباط این واکسن و نارسایی زودرس تخمدان انجام شد.

    روش کار: 

    مطالعه حاضر با جستجو در پایگاه های اطلاعاتی معتبر Embase، google scholar، web of science، PubMed و Scopus توسط دو محقق مستقل، بر اساس دستورالعمل PICO و استفاده از واژه های کلیدی Mesh شامل: Papillomavirus Vaccines،Human Papillomavirus Recombinant Vaccine Quadrivalent ، Primary ovarian Insufficiency و Premature Ovarian Failure انجام شد. جهت ارزیابی کیفیت مقالات از چک لیست نیوکاسل اوتاوا استفاده شد.

    یافته ها

    پس از بررسی و ارزیابی کیفی 128 مقاله اولیه، در نهایت 7 مقاله وارد مرور سیستماتیک شدند. طبق نتایج مطالعات جمعیت محور، ارتباط تایید شده ای بین واکسن HPV و بروز نارسایی زودرس تخمدان وجود نداشت؛ اما گزارشات مطالعات موردی که از ارتباط بین واکسن HPV و نارسایی زودرس تخمدان حمایت می کنند؛ علت بروز این عارضه را القاء پاسخ خودایمنی توسط واکسن و عوارض جانبی ناشی از ادجوانت به کار گرفته شده در آن ذکر می کنند.

    نتیجه گیری

    با توجه به اینکه در حال حاضر واکسن HPV، موثرترین رویکرد در پیشگیری از سرطان دهانه رحم می باشد، لذا بهره مندی از منافع پیشگیرانه این واکسن معقول تر به نظر می رسد. بدیهی است مطالعات بیشتر با تاکید بر عوارض جانبی احتمالی واکسن می تواند در آینده چالش های مرتبط با این واکسن را به حداقل برساند.

    کلید واژگان: نارسایی زودرس تخمدان, ویروس پاپیلومای انسانی, واکسن ویروس پاپیلومای انسانی}
    Leila Alizadeh, Fereshte Ghahremani, Seyedeh Maryam Khalili, Marjan Havaei, Elnaz Hajirafiei, Hedyeh Riazi, Zohreh Keshavarz *
    Introduction

    The most important factor initiating cervical cancer is human papilloma virus (HPV) infection; although the HPV vaccine can significantly prevent the infection in women, there is contradictory findings about its side effects such as premature ovarian failure (POF). The present systematic review was conducted with aim to determine the association between this vaccine and POF.

    Methods

    This study was conducted by search in the reliable databases of PubMed, Web of Science, Google Scholar, Embase, and Scopus by two researchers independently based on the PICO guidelines and the use of Mesh terms including Papillomavirus vaccine, Human Papillomavirus Recombinant Vaccine Quadrivalent, Primary Ovarian Insufficiency and Premature Ovarian Failure. Newcastle - Ottawa checklist was used to evaluate the quality of articles.

    Results

    After review and evaluation of the quality of 128 primary articles, finally 7 articles were included in the systematic review. According to the results of population-based studies, there was no significant relationship between the HPV vaccine and POF; but there are case series which support the association between the HPV vaccine and POF. They declared that the cause of this complication was the induction of autoimmune response by the vaccine and the side-effects of the adjuvant used in it.

    Conclusion

    Considering that the HPV vaccine is currently the most effective approach in preventing cervical cancer, it seems more reasonable to use preventive benefits of this vaccine. Further studies emphasizing the possible side effects of the vaccine can minimize the challenges associated with this vaccine in the future.

    Keywords: Human Papillomavirus Vaccine, Human papilloma virus, Premature Ovarian Failure}
  • مقدمه

    نارسایی زودرس تخمدان (POF) به یایسگی قبل از سن 40 سالگی اطلاق می گردد که 3-1% از زنان سراسر جهان را درگیر می کند. تغییرات ایمونولوژیکی مانند تغییر در ژن های FAS و FASL که نقش مهمی در تولید مثل و هموستاز سلولی دارند منجر به افزایش خطر ابتلا به POF می گردد.

    هدف

    هدف از این مطالعه بررسی نقش ژن های FAS و FASL در احتمال بروز نارسایی زودرس تخمدان است.

    مواد و روش ها

    در این مطالعه مورد-شاهدی، پلی مورفیسم ژن های آپوپتوزی FAS-670A/G و FASLIVS2nt_124A/G بر روی 51 بیمار ایرانی مبتلا به نارسایی زودرس تخمدان و 61 فرد سالم به عنوان کنترل انجام گرفت. استخراج DNA به روش salting-out و تعیین ژنوتایپ با روش PCR-RFLP انجام گردید.

    نتایج

    طبق نتایج ما در ژن های هموزیگوت FAS-670A/A, G/G و هتروزیگوت FAS-670A/G بین دو گروه کیس و کنترل تفاوت معناداری وجود نداشت (99/0 = p). همچنین در پلی مورفیسم مدل های ژنوتایپی FASIVS2nt_124 نیز شاهد تفاوت معناداری بین دو گروه کیس و کنترل نبودیم       (23/0 = p).

    نتیجه گیری

    ارتباط آماری معناداری بین فراوانی پلی مورفیسم های مورد مطالعه و خطر ابتلا به نارسایی زودرس تخمدان در زنان مراجعه کننده به کلینیک های مشاوره ژنتیک مورد بررسی وجود نداشت.

    Zhima Akhavansales*, Alimohammad Mosadegh Mehrjardi, HamidReza Ashrafzadeh, Shadnaz Fakhteh Yavari, MohammadTaher Tahoori, Morteza Bitaraf Sani, Mahnaz Mohammadi, Fateme Montazeri, Nasrin Ghasemi
    Background

    Premature ovarian failure (POF), is menopause occurring before the age of 40, affecting 1-3% of women worldwide. The risk of POF increases with altered immunological parameters such as FAS and FASL genes, which play a fundamental role in embryogenesis and cellular homeostasis.

    Objective

    The study aimed to investigate the potential role of FAS and FASL genes in POF pathogenesis.

    Materials and Methods

    In this case-control study, the polymorphisms of FAS-670A/G and FASLIVS2nt_124A/G apoptotic genes were analyzed in 51 Iranian women suffering from POF, and 61 healthy controls. Isolation of DNA was done using the salting-out method, and genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method.

    Results

    Our results revealed that homozygous FAS-670A/A and G/G, and heterozygous FAS-670A/G are not significantly different between cases and controls (p = 0.99). Also, in different genotyping models of FASIVS2nt_124, polymorphisms were not related to POF risk (p = 0.23).

    Conclusion

    There is no statistical association between these polymorphisms and POF risk in women referred to genetic counseling clinics.

    Keywords: FAS, FASL, Polymorphism, Premature ovarian failure}
  • پروانه زرین، سیده نفیسه طباطبایی، سید محمد مشتاقیون*، علی فلاحتی، نسرین قاسمی
    مقدمه

    نارسایی زودرس تخمدان (POF)، به توقف فعالیت تخمدان ها قبل از سن 40 سالگی گفته می شود که با سطح پایین هورمون های جنسی و سطح بالای گنادوتروپین ها همراه است. عوامل ژنتیکی بیشترین نقش را درPOF ایفا می کنند. BMP15 و گیرنده ی آن BMPR1B از اعضای ابرخانواده ی TGFβ هستند که در بافت تخمدان بیان می شوند و در مسیر فولیکولوژنز دخالت دارند. هرگونه تغییر در این ژن ها ممکن است مسیر فولیکولوژنز را مختل کند. بنابراین هدف از این مطالعه بررسی 4 واریانت در اگزون 2 ژن BMP15 و دو واریانت در اگزون 9 ژن BMPR1B به عنوان واریانتی کاندید در زنان نابارور ایرانی مبتلا به POF می باشد.

    روش کار

    با استفاده از دیتابیس Uniprot و تکنیک PCR-SSCP ارتباط بین واریانت های 443T>C، 468G>A، 538G>A، 598C>T ژن BMP15 و 945G>A،1020A>G ژن BMPR1B در 45 زن مبتلا به POF و 45 زن سالم صاحب فرزند، بدون هیچگونه سابقه بیماری های مرتبط با فولیکولوژنز و تخمک گذاری به عنوان کنترل بررسی شد. سپس تعدادی از محصولات PCR با تغییر الگوی حرکتی باندها، تعیین توالی شدند و نتایج حاصل از آن با نرم افزار CLC تحلیل شد.

    نتایج

    نتایج ژل الکتروفورز، SSCP و گراف های تعیین توالی هیچ کدام از واریانت ها، تغییری را در توالی ژنوم افراد بیمار نسبت به افراد کنترل نشان ندادند.

    بحث و نتیجه گیری

    با توجه به نقش کلیدی BMP15 در مسیر فولیکولوژنز و گزارش مطالعات قبلی، احتمالا BMP15 در پیدایش POF موثر باشد. عدم مشاهده ی SNP در بیماران این مطالعه می تواند به علت کم بودن حجم نمونه های مورد مطالعه و تفاوت های ژنتیکی افراد باشد.

    کلید واژگان: نارسایی زودرس تخمدان, پلی مورفیسم تک نوکلئوتیدی, ناباروری زنان, BMP15, BMPR1B}
    Parvane Zarrin, Seyede Nafise Tabatabaei, Seyed Mohammad Moshtaghiun *, Ali Falahati, Nasrin Ghasemi
    Introduction

    Premature ovarian failure (POF) is the end of ovarian activity before the age of 40, which is associated with low levels of sex hormones and high levels of gonadotropins. Genetic factors play an essential role in POF. BMP15 and its receptor BMPR1B are members of the TGFβ superfamily that are expressed in the ovaries and are involved in folliculogenesis. Any changes in these genes may disrupt them. So, this study aimed to assess 4 SNPs in exon 2 of BMP15 and 2 SNPs in exon 9 of BMPR1B genes as candidate SNPs in infertile Iranian women with POF.

    Materials and Methods

    Using the Uniprot database and PCR-SSCP methods, the link between SNPs 443T>C, 468G>A, 538G>A, 598C>T of BMP15, and 945G>A, 1020A>G of BMPR1B gene in 45 women with POF and 45 healthy women with children, without any history of diseases related to folliculogenesis and ovulation were examined as controls. Then, PCR products with mobility shift were sent for sequencing and the results were analyzed with CLC software

    Results

    The results of gel electrophoresis, SSCP, and sequencing graphs of none of the SNPs, did not show a change in the sequence of the patients compared to the control samples.

    Conclusion

    According to the key role of BMP15 in folliculogenesis and previous reports; BMP15 may be effective in the occurrence of POF. The absence of SNPs in these POF patients can be due to the small size of the studied samples and their genetic differences.

    Keywords: Premature Ovarian Failure, single nucleotide polymorphism, female infertility, BMP15, BMPR1B}
  • Sepideh Sheshpari, Mahnaz Shahnazi, Shahin Ahmadian, Mohammad Nouri, Mehran Mesgari Abbasi, Rahim Beheshti, Reza Rahbarghazi, Ali Honaramooz, Mahdi Mahdipour*
    Introduction

    Cell-based therapies with certain cell types are touted as novel and hopeful therapeutic intervention in the clinical setting. Here, we aimed to assess the regenerative potential of c-Kit+ cells in the rejuvenation of ovarian tissue and fertility rate in rat model of premature ovarian failure (POF).

    Methods

    Rats were treated with 160 mg/kg/BW of 4-vinylcyclohexene dioxide for 15 days. Freshly enriched rat bone marrow-derived c-Kit+ (MACS) and c-Kit- cells (4×105 cells/10 µL) were transplanted into the ovaries of treatment and control animals. Prior to transplantation as well as 2, 4, 6, and 8 weeks post-transplantation, randomly-selected rats were euthanized and ovarian tissues were subjected to pathophysiological examinations and real-time PCR analyses.

    Results

    POF status was confirmed by the presence of pathological features and a decreased number of immature and mature follicles compared with the control group (P < 0.05). Histological examination revealed a substantial reduction of atretic follicles in POF rats receiving c-Kit+ cells in comparison with POF rats that did not receive these cells (P < 0.05). Compared with the control samples, angiogenesis-related genes, Angpt2 and KDR, showed increased and decreased expressions in POF ovaries, respectively (P < 0.05). c-Kit+ cells had potential to restore angiogenesis in the ovarian tissue within normal ranges. Systemic levels of FSH did not significantly change in pre- or post-transplantation time points for any group (P > 0.05). Notable reduction of collagen deposition was found in c-Kit-treated rats. Transplantation of c-Kit+ cells also restored the reduced fertility rate (P < 0.05).

    Conclusion

    The administration of c-Kit+ cells can modulate angiogenesis and pathological changes, leading to the rejuvenation of ovarian function of a rat model of premature menopause.

    Keywords: Premature ovarian failure, Bone marrow c-Kit+ cells, Follicular competence, Angiogenesis, Fertility}
  • Shadan Navid *, Ali Talebi, Somayeh Solhjoo, Tayebeh Hadigol, Zahra Saadatian, Parastoo Noory
    Background

    In the last few decades, many studies have been done on the treatment of premature ovarian failure. This review was conducted to study different types of treatment with a focus on the 3D culture model of stem cells as a pluripotent source for repairment in regenerative medicine for this disease in recent decades.

    Methods

    To conduct this review, electronic databases of MEDLINE, Scopus, PubMed, and Web of Science were searched using MeSH terms. Only English articles were included, and case reports were excluded. The keywords used for the search were mentioned as the keywords of the paper.

    Results

    To transplant the stem cells into the patient's body, the 3D culture of these cells in vitro and the molecular and cellular aspects of these cells were considered, andtheir success rate and differentiation were compared to granulosa cells or oocytes.

    Conclusion

    The present study aimed to discuss the potential effects of stem cells for regeneration and recovery of ovarian function in premature ovarian failure as a useful therapy.

    Keywords: Premature Ovarian Failure, Stem Cell Therapy, Three-dimensional Culture}
  • Soophia Mehrjooy, Roshan Nikbakht, Javad Mohammadi Asl, Ata Ghadiri, Pegah Ghandil*
    Background

    Premature ovarian failure is a heterogeneous disorder, leading to early menopause. Several genes have been identified as the cause of non-syndromic premature ovarian failure (POF). Our aim was to explore the genetic defects in Iranian patients with POF.

    Methods

    We studied a family with three females exhibiting non-syndromic POF. WES was performed for one of the affected individuals after ruling out the presence of CGG repeat expansion at fragile X mental retardation 1 gene in the family. Sanger sequencing was used to confirm the candidate sequence variants in the proband, and screening of the detected mutation was performed for the other affected and unaffected members of the family.

    Results

    A homozygous frameshift mutation, c.349delC, was identified in ficolin-3 (FCN3) gene in the proband and two other patients. The parents and two healthy brothers were heterozygous for the mutation, and an unaffected sister was homozygous for wild type.

    Conclusion

    This is the first report of a mutation in FCN3 gene in a family with POF. Our findings can lead to the enhancement of genetic databases of patients with POF, specifically for families with high-risk background.

    Keywords: Ficolin-3, Premature ovarian failure, Whole exome sequencing}
  • Parvinsadat Eslamnik, Mana Moghaddasi, Ali Malmir, Bahar Sadeghi Goughari, MohammadReza Javan, Maryam Ebrahimi

    Today, young women infertility through chemotherapy has become a global challenge. Chemotherapy destructs the malignant cells by reactive oxygen species (ROS)productionand inflammatory factorssecretion; these factors can also destructthe ovarian and uterine cells. Infertility usuallyhappens as a result of ovarian and uterine cellsapoptosis, as well as dysfunctionin these organs. Signaling pathways activated by chemotherapy lead to increased activation of follicles and depletion of the follicular pool. In addition, excessive secretion of sex hormones leads to follicles activation and infertility in women. Mesenchymal stem cells(MSC) use havebeen reported to be a great help inrestoringthe function of ovarian and uterine cells.On the other hand, theycanregulate sex hormonesecretion. Finally, the use of MSCsas a suitable treatment strategy can help restore the function of reproductive cells and treat infertility.

    Keywords: Chemotherapy, Infertility, Gestational Trophoblastic Disease, Premature Ovarian Failure, Mesenchymal Stem Cell}
  • Suada Tinjić *, Džihan Abazović, Dušica Ljubić, Danilo Vojvodić, Tatjana Božanović, Mirza Ibrišimović, Sergije Marković, Aleksandar Ljubić
    Background
    Premature ovarian failure (POF) can be found in 1% of women at the age of 35-40, mostly due to unknown causes. PI3K-Akt signaling is associated with both ovarian function and growth of primordial follicles. In this study, we examined the effects of autologous in vitro ovarian activation with stem cells and autologous growth factors on reproductive and endocrine function in patients with ovarian impairment.
    Materials and Methods
    The longitudinal prospective observational study included 50 patients (between 30 and 50 years) with a diagnosis of POF and infertility. This multicenter study was performed at Jevremova Special Hospital in Belgrade, Saint James Hospital (Malta), and Remedica Skoplje Hospital, between 2015 and 2018. All patients went through numerous laboratory testings, including hormonal status. The autologous bone marrow mesenchymal stem cells (BMSCs) and growth factors were used in combination for activation of ovarian tissue before its re-transplantation. The software package SPSS 20.0 was used for statistical analysis of the results.
    Results
    Differences in follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (PG) hormone concentrations before and after 3, 6, and 12 months post-transplantation were tested in correlation with the volume of transplanted ovarian tissue. A significant correlation (P=0.029) was found between the change in E2 level after 3 months and the volume of re-transplanted tissues. Also after re-transplantation, 64% of the patients had follicles resulting in aspiration of oocytes in 25% of positive women with follicles.
    Conclusion
      The SEGOVA method could potentially solve many human reproductive problems in the future due to the large number of patients diagnosed with POF, as well asthe possibility of delaying menopause, thus improving the quality of life and general health (Registration number: NCT04009473).
    Keywords: Growth factors, Ovarian, Premature Ovarian Failure, Stem cells}
  • مریم مهاجرانی راد، سید امیرحسین لطیفی، مهدی صالحی*
    سابقه و هدف

    نارسایی زودرس تخمدان با شیوع 1% از زنان زیر 40 سال، منجر به مشکلات جدی در سلامتی زنان در سنین باروری می شود .از آنجا که علل آن کاملا مشخص شده نیست و درمان های موجود نیز با عوارضی همراه هستند، طب های مکمل از جمله طب ایرانی، می توانند کمک کننده باشند. هدف از مطالعه حاضر گزارش یک مورد حاملگی به دنبال درمان موفقیت آمیز نارسایی زودرس تخمدان می باشد.

    گزارش مورد

     بیمار یک خانم 38 ساله با سابقه 16ماه آمنوره بود که در سونوگرافی تخمدان های آتروفیک داشت، به دلیل افزایش گنادوتروپین ها، کاهش استرادیول و هورمون آنتی مولرین، متخصص زنان نارسایی زودرس تخمدان را تشخیص داد. در مراجعه به کلینیک طب ایرانی و پس از گرفتن شرح حال و معاینه، درمان شامل اصلاح سبک زندگی و دارو (کپسول رها هر 12 ساعت 2 عدد، شربت سکنجبین بزوری 2 قاشق غذاخوری در روز، جوشانده پونه و بابونه 200 سی سی در روز و آبزن با چهار گیاه خطمی، بابونه، گل سرخ و پنیرک دوبار در هفته) آغاز شد .بیمار به مدت 18 ماه پیگیری شد. قاعدگی بعد از 3 ماه اتفاق افتاد و تخمدان ها در سونوگرافی دوم بعد از 8 ماه اندازه طبیعی داشتند و 10 ماه پس از شروع درمان نیز بیمار باردار شد و حاصل بارداری یک نوزاد پسر سالم بود.

    نتیجه گیری

    طبق نتایج مطالعه حاضر، طب ایرانی می تواند در درمان نازایی ناشی از نارسایی زودرس تخمدان موثر باشد.

    کلید واژگان: گزارش مورد, طب ایرانی, نارسایی زودرس تخمدان}
    M. Mohajeranirad, SA .Latifi, M. Salehi*
    BACKGROUND AND OBJECTIVE

    Premature ovarian failure, with a prevalence of 1% in women under the age of 40, leads to serious health problems for women of childbearing age. Since the causes are not fully understood and the available treatments are associated with side effects, complementary medicine, including Persian medicine, can be helpful. The aim of this study was to report a case of pregnancy following successful treatment of premature ovarian failure.

    CASE REPORT

     The patient was a 38-year-old woman with a history of 16 months of amenorrhea who had atrophic ovaries on ultrasound. Due to increased gonadotropins, decreased estradiol and anti-mullerian hormone, the gynecologist diagnosed premature ovarian failure. After referring to the Persian Medicine Clinic and after getting a history and examination, her treatment started which included lifestyle modification and medication (2 Raha capsules every 12 hours, 2 tablespoons of Sekanjabin-e-Bazoori [oxymel] a day, decoction of Chamomile and Pennyroyal 200 cc per day and Abzan [a human-sized container filled with hot water] with four plants of Hollyhocks, Chamomile, Rose, and Mallow twice a week). The patient was followed for 18 months. Menstruation occurred after 3 months and the ovaries were normal size after 8 months on the second ultrasound and 10 months after starting treatment, the patient became pregnant and the result was a healthy male baby.

    CONCLUSION

    According to the results of the present study, Persian medicine can be effective in treating infertility caused by premature ovarian failure.

    Keywords: Case Report, Persian Medicine, Premature Ovarian Failure}
  • فاطمه عابدی قهی، روح الله فتحی*، نعیمه سادات ابطحی، فریده عیوض خانی، خدیجه بهره بر، الهام عابدحیدری، سمیه توانا، لیلا راشکی قلعه نو، حسین ایمانی، لیلا منتظری
    هدف

    نارسایی زودرس تخمدان عارضه ای است که منجر به آمنوره، ناباروری و افزایش سطح گنادوتروپین قبل از سن 40 سالگی می شود. به کارگیری داروهای شیمی درمانی می تواند یکی از عوامل ایجاد این اختلال باشد. هدف از این مطالعه بررسی حضور سلول های زایا در موش های مدل نارسایی زودرس تخمدان به دنبال استفاده از داروهای شیمی درمانی بود.

    مواد و روش ها

     در این مطالعه از 24 سر موش ماده بالغ برای ایجاد مدل نارسایی زودرس تخمدان و از مقادیر مختلف سیکلوفسفامید و بیوسولفان (گروه های آزمایشی یک تا پنج) استفاده شد. تغییرات وزن بدن، اسمیر واژن، تغییرات ساختاری بافت تخمدان در همه گروه های آزمایشی و گروه کنترل (بدون دریافت دارو) بررسی و بهترین مدل، تحت ارزیابی های هورمونی (FSH و استرادیول) و بیان عامل های سلول زایا (Oct-4 و Dazl) قرار گرفت.

    یافته ها

    از آنجایی که در گروه دوم اختلال در چرخه استروس و کاهش معنی دار در متغیرهای وزن و ذخیره تخمدانی (˂0/05p) نسبت به گروه کنترل مشاهده شد، بنابراین این گروه به عنوان بهترین مدل انتخاب شد. افزایش سطح FSH و کاهش سطح استرادیول در گروه دوم نسبت به گروه کنترل (˂0/05p) نیز تاییدی بر ایجاد مدل POF بود. همچنین بیان ژن های Oct-4 و Dazl در گروه دوم نسبت به گروه کنترل افزایش (˂0/05p) نشان داد.

    نتیجه گیری

    حضور عوامل سلول های زایا در مدل نارسایی زودرس تخمدان موش به دنبال استفاده از داروهای شیمی درمانی می تواند امید تازه ای در درمان ناباروری بیماران مبتلا به سرطان پس از شیمی درمانی باشد.

    کلید واژگان: نارسایی زودرس تخمدان, ذخیره تخمدان, فولیکولوژنز, شیمی درمانی, رده زایا}
    F. Abedy Ghehi, R. Fathi *, N.S. Abtahi, F. Eivazkhani, Kh. Bahrehbar, E. Abed Heidari, S. Tavana, L. Rashki Ghaleno, H. Imani, L. Montazeri
    Aims

    Premature ovarian failure is a syndrome causing amenorrhea, infertility, and increases gonadotropin levels before age 40. The use of chemotherapy drugs can be one of the reasons that lead to this disorder. The purpose of this study was to evaluate the presence of germ cells markers in mice model of premature ovarian failure following chemotherapy drugs.

    Materials and Methods

    In this study, 24 mature female mice were used to create a premature ovarian failure model, different amount of cyclophosphamide and busulfan were applied (experimental groups 1 to 5). Bodyweight change, vaginal smear, morphological alternation of ovarian tissue in both experimental and control (without treatment) groups were evaluated and for the best model, hormonal evaluation (FSH, E2), and expression of germline markers (Oct4, Dazl) were examined.

    Findings

    Since, in the second group estrus cycle disorder, the significant decrease in weight and ovarian reserve (p˂0.05) were observed, compared to the control group, so this group was chosen as the best model. An increase in FSH level and reduction in estradiol level in the second group, compared with the control group (p˂0.05), confirmed creation of the POF model. Also, genes expression of Oct-4 and Dazl showed an increase (p˂0.05) in the second group compared with the control one.

    Conclusion

    The presence of germ cells markers in a mouse model of premature ovarian failure following the use of chemotherapy drugs can be a new hope in the treatment of infertility in cancer patients after chemotherapy.

    Keywords: Premature ovarian failure, Ovarian reserve, Folliculogenesis, Chemotherapy, Germ line}
  • Ladan Jalalie, Mohammad Jafar Rezaie*, Ali Jalili, Mohammad Ali Rezaee, Zakaria Vahabzadeh, Mohammad Reza Rahmani, Mojtaba Karimipoor, Mohammad Saeed Hakhamaneshi
    Background
    Mesenchymal stem cells (MSCs) can be used to treat premature ovarian failure (POF). Different methods have already been applied to detect MSCs in tissues. This study aimed to investigate the quantitative distribution of CM-DiI-labeled human umbilical cord vein MSCs (hUCV-MSCs) in different regions of the ovarian tissue of the cyclophosphamide ( CTX )-induced POF in mice.
    Methods
    Adult female C57BL/6 mice (n = 40) were divided into four groups: (1) Mice receiving PBS as control (Ctrl) group; (2) mice receiving hUCV-MSCs intravenously as Ctrl + hUCV-MSCs group; (3) mice receiving CTX intraperitoneally (i.p.) as CTX group; (4) mice receiving CM-DiI-labeled hUCV-MSCs after CTX injection as CTX + hUCV-MSCs group. Histological changes and CM-DiI-labeled hUCV-MSCs distribution were analyzed in the ovarian tissues. Quantitative real-time PCR was performed to detect human mitochondrial cytochrome b (MTCYB) gene in the ovarian tissues of the mice.
    Results
    The mean number of the fluorescent hUCV-MSCs was 20 ± 2.5 (57.1%) in the medulla, 11.3 ± 2.8 (32.2%) in the cortex, and 5.5 ± 1 (15%) in the germinal epithelium of the ovarian tissue (p < 0.05). Moreover, MTCYB gene was detected in the mice ovaries of the CTX + hUCV-MSCs group, but not in other groups.
    Conclusion
    Our findings suggest that the distribution of the transplanted hUCV-MSCs in different regions of the ovarian tissue is not equal, and it is greater in the medulla than the cortex and germinal epithelium. This is the first report of quantitative distribution of MSCs in different regions of ovarian tissue in the POF model.
    Keywords: Cyclophosphamide, Mesenchymal stem cells, Premature ovarian failure, Transplantation}
  • Nasim Behnoud, Rosita Bahrami, Gholamreza Kordafshari, Farahnaz Farzaneh, Hoorieh Mohammadi Kenari *
    Interruption of the activity of ovary before the age of forty is called premature ovarian failure (POF) in which ovaries lose their follicular and hormonal functions. A decline in the number of ovules before the age of menopause is a physiologic phenomenon. In the present case report, treatment of a patient by POF was reported using traditional Persian medicine principles. In Persian medicine, each humor has its own temperament. A change in the temperament and quality or quantity of these humors causes the disease and therefore modifying the temperament is the milestone of treatment. The patient was a 39-year-old married woman with irregular menstruation cycles and finally, cessation of menstruation. In this period, the patient had vaginal dryness, severe dyspareunia, gastritis, and parasomnia. At first, some instructions were ordered to change her lifestyle, for example, a change in food intakes, enough sleep, and exercise. In addition, several medications were ordered including the digestive system electuary (Majoun Jahaz Hazemeh), Eyaraj Fighara capsule and powder containing Glycyrrhiza glabra roots, Foeniculum vulgare and white sugar, oil massage of the abdomen and flanks, and cupping of the uterus. At the end of treatment, complete rehabilitation was achieved and menstruation irregularity, gastritis, and parasomnia were resolved. Based on the results, if a patient follows the rules and has a healthy lifestyle, inappropriate humor is unable to appear, the healing can be stable, and this disease or similar melancholic disorders fail to occur.
    Keywords: Premature ovarian failure, Menopause, Persian medicine}
  • Nooshin Asgari, MohammadTaghi Akbari *, Faravareh Khordadpoor Deilamani, Gholamreza Babamohammadi
    Background

     Blepharophimosis-ptosis-epicanthus syndrome (BPES) is a rare genetic disorder with autosomal dominant inheritance. There are two distinct phenotypes: BPES type I, which is associated with eyelid abnormalities as well as female infertility or premature menopause due to ovarian resistance to gonadotropins, whereas in type II only eyelid abnormalities are present. Mutations in the forkhead transcription factor 2 (FOXL2) gene are responsible for both types of BPES.

    Objectives

     The purpose of this study was to identify mutations in FOXL2 in two Iranian families (from Tehran) with BPES who were referred to Tehran Medical Genetics laboratory.

    Methods

     The peripheral blood was collected from the affected members of two BPES families and genomic DNA was extracted using salting out method. Then, direct sequencing of whole exon of FOXL2 genewas performed.

    Results

     Two frameshift mutations were identified in FOXL2 gene in two familial cases including NM_023067:c.102_103insA (p.G35Rfs*61)as a novel mutation and NM_023067:c.855_871dup (p.H291Rfs*71) (17-bp insertion). Both mutations cause the protein to be truncated and are responsible for a severe phenotype (BPES type I) which was in harmony with our finding.

    Conclusions

     Our results increased the spectrum of FOXL2 mutations and confirm the mutations associated with BPES type I.

    Keywords: BPES, FOXL2, Premature Ovarian Failure, Eyelid Abnormalities}
  • Occult Form of Premature Ovarian Insufficiency in Women with Infertility and Oligomenorrhea as Assessed by Poor Ovarian Response Criteria
    Rubina Izhar, Samia Husain, Suhaima Tahir, Sonia Husain
    Background

    The purpose of this study was to evaluate the ability of poor ovarian response criteria to classify women presenting with infertility and oligomenorrhea as having "occult" premature ovarian insufficiency.

    Methods

    This was a cross sectional study conducted at Aziz Medical Center, Karachi, Pakistan from 1st August 2015 to 31st July 2016. Women with infertility and oligomenorrhea were included. All eligible women underwent day 2 FSH level and an early follicular phase transvaginal ultrasound to assess the antral follicular count (AFC). All women then underwent the confirmatory test, of Anti- Mullerian Hormone (AMH) level. The main outcome measure was assignment to occult premature ovarian insufficiency (POI) after screening that used the criteria set out in fertility guideline for predicting the likely ovarian response to gonadotrophin stimulation. Another measure was to compare the sensitivity and specificity of the two index criteria, of FSH and AFC, relative to the emerging reference standard, of the AMH criterion.

    Results

    The three criteria together classified 59 (34.91%) women as occult POI in those with oligomenorrhea. The sensitivity, specificity, negative predictive value and positive predictive value of FSH relative to AMH for these women were 77.8%, 95.7%, 90.2% and 89.4%, respectively whereas the same values of AFC relative to AMH were 92.6%, 99.1 %, 96.6% and 98%, respectively.

    Conclusion

    Women with menstrual irregularity and infertility are at a higher risk for satisfying criteria of poor ovarian response irrespective of age. A policy incorporating these surrogate markers can be used to screen these women for occult premature ovarian insufficiency.

    Keywords: Female infertility, Occult premature ovarian insufficiency, Oligomenorrhea, Ovarian reserve, Premature ovarian ageing, Premature ovarian failure}
  • Zeinab Ghezelayagh, Mehdi Totonchi, Shabnam Zarei-Moradi, Ommolbanin Asadpour, Saman Maroufizadeh, Poopak Eftekhari-Yazdi, Hamid Gourabi, Anahita Mohseni-Meybodi*
    Objective
    Ovarian reserve is defined as the capacity of the ovary to provide fertile oocytes. Diminished ovarian reserve (DOR) is a disorder in which ovaries are prone to go through early menopause. Where this loss of function occurs before the age of 40, it results in the premature ovarian failure (POF) disease. Throughout folliculogenesis, the follicle-stimulating hormone receptor (FSHR) starts a signaling cascade in the granulosa cells where its inactivation leads to the arrest of follicle maturation and therefore adversely affects ovarian reserve. The aim of this study was to investigate the association of genetic variation (polymorphisms and inactivating mutations) of FSHR with POF and DOR.
    Materials And Methods
    This case-control study comprised 84 POF, 52 DOR and 80 fertile Iranian women. To determine the presence of the 566C>T mutation and the -29G>A polymorphism in FSHR, PCR-RFLP method was used. SSCP-sequencing was used to identify any allelic variants in exon 10. The expression of human FSHR at the transcript level was also compared between DOR and fertile controls by real time polymerase chain reaction (PCR).
    Results
    The 566C>T polymorphism was normal in all the cases. All genotypes of -29G>A and 919G>A (exon 10) polymorphisms were observed. Statistically significant differences were seen in the genotypic distribution of both polymorphisms when comparing the control group with the DOR patient group. A decrease was observed in FSHR expression of DOR patients compared with the control group but was not significant.
    Conclusion
    We conclude that the -29G>A and 919G>A polymorphisms in FSHR may be associated with DOR. Although these polymorphisms had significant differences at the genic level, no significant variation was found at the transcript level.
    Keywords: Allelic Variants, Follicle Stimulating Hormone Receptor, Premature Ovarian Failure}
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