Endometrial preparation using gonadotropin-releasing hormone agonist prior to frozen-thawed embryo transfer in women with repeated implantation failure: An RCT بررسی اثر GnRh-a در پروتکل آماده سازی آندومتر در سیکل های برگشت از فریز بیماران با شکست مکرر لانه گزینی 2 1 مقدمه: آماده سازی آندومتر در سیکلهای برگشت از فریزیک چالش بزرگ در بیماران با شکست مکرر لانه گزینی میباشد. هدف: هدف از این مطالعه بررسی تاثیر اضافه کردن آگونیست GnRH به پروتکل آمادهسازی آندومتر با استروژن و پروژسترون در سیکلهای برگشت از فریز در بیماران با سابقه شکست مکرر لانهگزینی بود. مواد و روش ها: مطالعه به روش کارآزمایی بالینی در پژوهشکده علوم تولیدمثل یزد انجام شد. 67 زن با سابقه شکست مکرر لانهگزینی در این مطالعه وارد و به صورت تصادفی به دو گروه تقسیم شدند. 34 نفر در گروه مصرف آگونیست (شروع 1/0 میلیگرم زیر جلدی از روز 21 سیکل قبل که از روز دوم سیکل به میزان 05/0 میلیگرم کاهش یافته وتا زمان شروع پروژسترون ادامه مییابد) و 33 نفر در گروه دریافتکننده استروژن و پروژسترون. به تنهایی پیامدهای باروری مورد بررسی شامل میزان بارداری شیمیایی و کلینیکی و میزان لانهگزینی بود. نتایج: خصوصیات پایه و دموگرافیک شرکتکنندگان دو گروه یکسان بود. هرچند پیامدهای باروری در گروه دریافتکننده GnRH آگونیست در مقایسه با گروه کنترل بالاتر بود اما از لحاظ آماری معنیدار نبود. نتیجه گیری: با توجه به اینکه نتایج این تحقیق نشان میدهد اضافه کردن آگونیست GnRH به پروتکل سیکلهای برگشت از فریز تمایل به بهبود پیامد بارداری داشته است شاید با اضافه کردن حجم نمونه نتایج از لحاظ آماری معنیدار شود و بتوان از این پروتکل در بیماران با سابقه شکست مکرر لانه گزینی استفاده کرد. 2 Background: Preparation of endometrial thickness in frozen-thawed embryo transfer (FET) is extremely important, particularly in repeated implantation failure (RIF) patients. Objective: This study aimed to investigate the clinical outcomes of FET cycles among RIF women, based on the effects of administering gonadotropin-releasing hormone (GnRH) agonist prior to estrogen-progesterone preparation of the endometrium. Materials and Methods: In this randomized clinical trial, 67 infertile women who were candidates for FET were divided into two groups: A) case group (n = 34), treated with GnRH agonist prior to endometrial preparation and B) control group (n = 33), which received the routine protocol.(6 mg daily estradiol started from second day) The clinical outcomes including chemical and clinical pregnancy, in addition to implantation rates, were compared between the two groups. Results: The results showed no significant differences in women’s age (p = 0.558), duration (p = 0.540), type (p = 0.562), and cause of infertility (p = 0.699). Regarding pregnancy and implantation rates, there was a trend toward an increase in the case group; however, differences were not statistically significant. Conclusion: Although our results showed no significant differences between groups. Because there are trends to better results in case group larger sample size may show significant difference. 319 326 2019/05/12 1398/2/22 2019/11/10 1398/8/19 Robab Davar Robab Davar Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران r_davar@yahoo.com Saeideh Dashti Saeideh Dashti Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران saeideh_dashti@yahoo.com Marjan Omidi Marjan Omidi Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران omidi.marjan@ymail.com Implantation failure Gonadotropin-releasing Hormone Embryo transfer Pregnancy Implantation. شکست مکرر لانه گزینی آگونیست GnRH آماده سازی آندومتر. 1. Gardner DK, Weissman A, Howles CM, Shoham Z. Textbook of assisted reproductive techniques. 5th Ed. Clinical Perspectives: CRC press; 2017.##2. Yarali H, Polat M, Mumusoglu S, Yarali I, Bozdag G. Preparation of endometrium for frozen embryo replacement cycle: a systematic review and meta-analysis. J Assist Reprod Genet 2016; 33: 1287-1304.##3. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril 2011; 96: 344‐348.##4. Ming L, Liu P, Qiao J, Lian Y, Zheng X, Ren X, et al. Synchronization between embryo development and endometrium is a contributing factor for rescue ICSI outcome. Reprod Biomed Online 2012; 24: 527-531.##5. Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycle? A systematic review and meta-analysis. Hum Reprod Updat 2013; 19: 458-470.##6. Ozgur K, Berkkanoglu M, Bulut H, Humaidan P, Coetzee K. Agonist depot versus OCP programming of frozen embryo transfer: a retrospective analysis of freeze-all cycles. J Assist Reprod Genet 2016; 33: 207-214.##7. Makrigiannakis A, BenKhalifa M, Vrekoussis T, Mahjub S, Kalantaridou SN, Gurgan T. Repeated implantation failure: a new potential treatment option. Eur J Clin Invest 2015; 45: 380-384.##8. Roque M, Lattes K, Serra S, Sola I, Geber S, Carreras R, et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril 2013; 99: 156-162.##9. Guo S, Zhang D, Niu Z, Sun Y, FengY. Pregnancy outcomes and neonatal outcomes after pituitary down-regulation in patients with adenomyosis receiving IVF/ICSI and FET. Results of a retrospective cohort study. Int J Clin Exp Med 2016; 9: 14313-14320.##10. Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril 2002; 78: 699-704.##11. Niu Z, Chen Q, Sun Y, Feng Y. Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis. Gynecol Endocrinol 2013; 29: 1026-1030.##12. Yang X, Dong X, Huang K, Wang L, Xiong T, Ji L, et al. The effect of accompanying dominant follicle development/ovulation on the outcomes of frozen-thawed blastocyst transfer in HRT cycle. Int J Clin Exp Pathol 2013; 6: 718-723.##13. Hebisha SA, Adel HM. GnRh agonist treatment improves implantation and pregnancy rates of frozen-thawed embryos transfer. J Obstet Gynaecol India 2017; 67: 133-136.##14. Tsai HW, Wang PH, Lin LT, Chen SN, Tsui KH. Using gonadotropin-releasing hormone agonist before frozen embryo transfer may improve ongoing pregnancy rates in hyperandrogenic polycystic ovary syndrome women. Gynecol Endocinol 2017; 33: 686-689.##15. Yang X, Huang R, Wang YF, Liang XY. Pituitary suppression before frozen embryo transfer is beneficial for patients suffering from idiopathic repeated implantation failure. J Huazhong Univ Sci Technolog Med Sci 2016; 36: 127-131.##16. Ferrero S, Gillott DJ, Remorgida V, Anserini P, Ragni N, Grudzinskas JG. Proteomic analysis of peritoneal fluid in fertile and infertile women with endometriosis. J Reprod Med 2009; 54: 32-40.##17. Ferrero S, Gillott DJ, Remorgida V, Anserini P, Ragni N, Grudzinskas JG. GnRH analogue remarkably down-regulates inflammatory proteins in peritoneal fluid proteome of women with endometriosis. J Reprod Med 2009; 54: 223-231.##18. Tremellen K, Russell P. Adenomyosis is a potential cause of recurrent implantation failure during IVF treatment. Aust N Z J Obstet Gynaecol 2011; 51: 280-283.##19. Dal Prato L, Borini A, Cattoli M, Bonu MA, Sciajno R, Flamigni C. Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist. Fertil Steril 2002; 77: 956-960.##20. Davar R, Eftekhar M, Tayebi N. Transfer of cryopreserved-thawed embryos in a cycle using exogenous steroids with or without prior gonadotropihin-releasing hormone agonist. J Med Sci 2007; 7: 880-883.## ##

Protective effect of melatonin against methotrexate-induced testicular damage in the rat model: An experimental study اثر محافظتی ملاتونین بر علیه آسیب بیضه توسط متوترکسایت در مدل موش صحرایی: یک مطالعه تجربی 2 1 مقدمه: نشان داده شده که متوترکسایت دارای اثرات سوِئی بر روی بیضه بخصوص اپیتلیوم سمینی فروس میباشد. همچنین نشان داده شده که ملاتونین که یک هورمون اندوکرین میباشد میتواند عملکرد بیضه را طبیعی کند لذا بهتر است توانایی ملاتونین در پیشگیری از عوارض ایجاد شده توسط متوترکسایت بر روی بیضه بررسی گردد. هدف: با توجه به اثرات آنتیاکسیدانی، ضد التهابی و ضد اپوپتوزیس ملاتونین، هدف این مطالعه بررسی اثر محافظتی ملاتونین بر علیه آسیب بیضه توسط متوترکسایت میباشد. مواد و روش ها: تعداد 40 موش صحرائی نر با وزن 200 تا 230 گرم به 5 گروه 8 تایی تقسیم شدند. به موشهای گروه 1 به عنوان گروه کنترل ماده بیاثر تزریق شد. به موشهای گروه 2 تزریق داخل صفاقی ملاتونین 8 میلیگرم به ازای هر کیلوگرم وزن بدن برای 15 روز متوالی انجام شد. به موشهای گروه 3 تزریق داخل وریدی ملاتونین 75 میلیگرم به ازای هر کیلوگرم وزن بدن برای 15 روز متوالی انجام شد. به موشهای دو گروه باقیمانده تزریق داخل صفاقی ملاتونین 8 میلیگرم به ازای هر کیلوگرم وزن بدن برای 15 روز متوالی (گروه 4) و 30 روز متوالی (گروه 5) انجام شد و سپس تزریق داخل وریدی ملاتونین 75 میلیگرم به ازای هر کیلوگرم وزن بدن در روزهای 8 و 15 مداخله انجام شد. پارامترهای تولیدمثل از جمله غلظت اسپرم اپیدیدمی، بیان پروتئین تیروزین فسفریله بیضوی، بیان پروتئین تنظیمکننده حاد استروئیدوژنیک (StAR) و کاسپاز 3 و سطح مالون دیالدئید مورد آزمایش قرار گرفتند. نتایج: غلظت اسپرم (ml/ 106×) در گروههای 4 (28/1±75/58) و 5 (57/2±93/55) به طور معنیداری (032/0p= ) در مقایسه با گروه 2 (14/2±92/32) بهبود یافته بود. اپیتلیوم سمینیفروس در گروههای 4 و 5 افزایش یافته بود در حالیکه بیان کاسپاز 3 کاهش یافته بود. در گروه درمان شده با ملاتونین در مقایسه با گروه متوترکسایت بیان پروتئین تیروزین فسفریله در 32 kDa کاهش و در 47 kDa افزایش یافته بود. بیان پروتئین StAR در گروههای مختلف تفاوتی را نشان نداد. نتیجه گیری: نتایج ما نشان داد که ملاتونین باعث بهبود غلظت اسپرم اپیدیدیمی به وسیله کاهش بیان کاسپاز 3 و افزایش بیان پروتئین تیروزین فسفریله در بیضههای آسیب دیده با متوترکسایت میشود. 2 Background: Methotrexate (MTX) has been shown to affect the testes adversely, especially the seminiferous epithelium. As melatonin, an endocrine hormone, has been shown to normalize testicular function, its ability to prevent MTX-induced testicular damage should be considered. Objective: Based on the antioxidant, anti-inflammatory, and antiapoptotic activities of melatonin, this study aimed to investigate its protective effect against testicular damage induced by MTX. Materials and Methods: Forty adult male rats (200-230 g) were divided into five groups (n = 8/each). The rats in group I were injected with vehicle as a control. In group II, the rats were received intraperitoneal injections of melatonin (8 mg/kg) for 15 consecutive days. The rats in group III were intravenously injected with MTX (75 mg/kg) for 15 consecutive days. The remaining two groups received melatonin (8 mg/kgBW) for 15 (group IV) and 30 (group V) consecutive days, intraperitoneally, and then intravenously received MTX (75 mg/kgBW) on days 8 and 15 of the experimental period. Reproductive parameters, including epididymal sperm concentration, testicular tyrosine-phosphorylated protein expression, steroidogenic acute regulatory (StAR) protein expression, and caspase-3 and malondialdehyde levels, were examined. Results: The sperm concentrations (×106/ml) of groups IV (58.75 ± 1.28) and V (55.93 ± 2.57) were improved significantly (p = 0.032) compared with that of group II (32.92 ± 2.14). The seminiferous epithelium in groups IV and V also increased, while caspase-3 expression decreased. In the melatonin-treated groups, the expression of tyrosine-phosphorylated proteins at 32 kDa was decreased and that of proteins at 47 kDa was increased compared with the MTX group. StAR protein expression was not altered in any of the groups. Conclusion: Our results indicate that melatonin improves the epididymal sperm concentration by decreasing the expression of caspase-3 and increasing that of tyrosine-phosphorylated proteins in MTX-treated testes. 327 338 2019/05/122019/06/18 1398/3/28 2019/11/102019/11/19 1398/8/28 Wannisa Sukhorum Wannisa Sukhorum School of Medicine, Mae Fah Luang University, Chiang Rai, Thailand. تایلند wannisa.suk@mfu.ac.th Jariya Umka Welbat Jariya Umka Welbat Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. تایلند Jariya@kku.ac.th Suchada Ktutsri Suchada Ktutsri Sitthichai Iamsaard; Department of Anatomy, Faculty of Medicine, Khon Kaen University. 123 Mitraparp Road, Ampoe Muang, Khon Kaen 40002, Thailand. تایلند suchada_pt34@gmail.com Sitthichai Iamsaard Sitthichai Iamsaard Research Institute for Human High Performance and Health Promotion (HHP & HP), Khon Kaen, Thailand. تایلند sittia@kku.ac.th Melatonin Testis Sperm Methotrexate Caspase-3 Tyrosine phosphorylation فسفوریلاسیون تیروزین ملاتونین بیضه اسپرم متوترکسات کاسپاز 3 تیروزین. 1. 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Andrologia 2018; 50: e13077.##32. Brydøy M, Fosså SD, Dahl O, Bjøro T. Gonadal dysfunction and fertility problems in cancer survivors. Acta Oncol 2007; 46: 480-489.##33. Maneesh M, Jayalekshmi H. Role of reactive oxygen species and antioxidants on pathophysiology of male reproduction. Indian J Clin Biochem 2006; 21: 80-89.##34. Sheikhbahaei F, Khazaei M, Rabzia A, Mansouri K, Ghanbari A. Protective effects of thymoquinone against methotrexate-induced germ cell apoptosis in male mice. Int J Fertil Steril 2016; 9: 541-547.##35. Pınar N, Çakırca G, Özgür T, Kaplan M. The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats. Biomed Pharmacother 2018; 97: 1486-1492.##36. Wang Y, Zhao TT, Zhao HY, Wang H. Melatonin protects methotrexate-induced testicular injury in rats. Eur Rev Med Pharmacol Sci 2018; 22: 7517-7525.##37. Kolli VK, Abraham P, Isaac B, Kasthuri N. Preclinical efficacy of melatonin to reduce methotrexate-induced oxidative stress and small intestinal damage in rats. Dig Dis Sci 2013; 58: 959-969.##38. Iamsaard S, Arun S, Burawat J, Sukhorum W, Wattanathorn J, Nualkaew S, et al. Phenolic contents and antioxidant capacities of Thai- Makham Pom (Phyllanthus emblica L.) aqueous extracts. J Zhejiang Univ Sci B 2014; 15: 405-408.##39. Arun S, Burawat J, Sukhorum W, Sampannang A, Uabundit N, Iamsaard S. Changes of testicular phosphorylated proteins in response to restraint stress in male rats. J Zhejiang Univ Sci B 2016; 17: 21-29.## ##

Maternal and neonatal outcomes among pregnant women with different polycystic ovary syndrome phenotypes: A cross-sectional study پیامدهای نامطلوب حاملگی و نوزادی در فنوتیپ‌های مختلف زنان حامله مبتلا به سندرم تخمدان پلی کیستیک 2 1 مقدمه: بارداری فرایندی است که با تغییرات متابولیکی و هورمونی مختلف همراه است و سندرم تخمدان پلیکیستیک (PCOS) میتواند بر این فرآیند تاثیر گذارد. هدف: هدف از این مطالعه بررسی و مقایسه نتایج مادر و نوزاد در فنوتیپهای مختلف سندرم تخمدان پلیکیستیک بود. مواد و روش ها: 200 زن باردار مبتلا به PCOS طبق معیارهای ESHRE / ASRM 2003 در چهار گروه فنوتیپی (A-D) مورد بررسی قرار گرفتند. پیامدهای مادری شامل دیابت حاملگی، فشار خون بالا ناشی از بارداری، پارگی زودرس غشاها، زایمان زودرس، وزن کم نسبت به سن حاملگی (SGA)، محدودیت رشد داخل رحمی، مرگ و میر داخل رحمی، پرهاکلامپسی، سقط جنین، اختلالات مایع آمنیوتیک، روش زایمان و علت سزارین بین گروهها همچنین، پیامدهای نوزادی از جمله وزن نوزاد، بهبودی نوزاد، نمره 5 دقیقه Apgar، زردی نوزاد، نیاز به بستری در NICU، علت بستری و میزان مرگ و میر نوزادان بین گروهها بررسی و مقایسه شدند. نتایج: نتایج این مطالعه شایعترین فنوتیپ در بین زنان مبتلا به PCOS را فنوتیپ D با 37% شیوع نشان دادند. خطر دیابت حاملگی در فنوتیپ A و فشار خون ناشی از بارداری در فنوتیپ B بیشتر از سایر فنوتیپها بود. از نظر عوارض نوزادی بین فنوتیپهای PCOS اختلاف معنیداری مشاهده نشد. نتیجه گیری: با توجه بالاتر بودن شیوع دیابت حاملگی و فشار خون ناشی از بارداری به ترتیب در فنوتیپهای A و B ، این زنان نیاز به مراقبت دقیقتر در دوران بارداری دارند. 2 Background: Pregnancy is a process associated with various metabolic and hormonal changes, and polycystic ovary syndrome (PCOS) can affect this process. Objective: This study aimed to evaluate and compare the maternal and neonatal outcomes among pregnant women with different polycystic ovary syndrome phenotypes. Materials and Methods: In this cross-sectional study, 200 pregnant women with PCOS according to the 2003 ESHRE/ASRM criteria were categorized into four phenotype groups (A-D). The maternal outcomes include gestational diabetes mellitus, pregnancy-induced hypertension, premature rupture of membranes, preterm labor, small-for-gestational age birth, intrauterine growth restriction, intrauterine mortality, preeclampsia, abortion, amniotic fluid disorders, delivery method, and cause of cesarean section were studied between groups. Additionally, neonatal outcomes such as neonatal weight, neonatal recovery, 5-min Apgar score, neonatal icter, the need for NICU admission, the cause of hospitalization, and infant mortality rate were investigated and compared among the groups. Results: According to the results, phenotype D (37%) was the most common phenotype among the participants. The risk of gestational diabetes was more common in phenotype A than in the other phenotypes, whereas pregnancy-induced hypertension was most common in phenotype B. No significant differences were observed in the neonatal complications among the PCOS phenotypes. Conclusion: Considering the higher risk of gestational diabetes mellitus and pregnancy-induced hypertension in PCOS phenotypes A and B, women with these phenotypes need more precise prenatal care. 339 346 2019/05/122019/06/182019/07/6 1398/4/15 2019/11/102019/11/192019/10/26 1398/8/4 Akramsadat Dehghani Firoozabadi Akramsadat Dehghani Firoozabadi Shahid Sadougui Hospital, Shahid Sadougui University of Medical Sciences, and Health Services, Yazd, Iran. ایران akramsadatdehghani@gmail.com Razieh Dehghani Firoozabadi Razieh Dehghani Firoozabadi Research and Clinical Centre for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadougui University of Medical Sciences and Health Services, Yazd, Iran. ایران dr.firouz@yahoo.com Maryam Eftekhar Maryam Eftekhar Research and Clinical Centre for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadougui University of Medical Sciences and Health Services, Yazd, Iran. Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران eftekharmaryam@yahoo.com Afsar Sadat Tabatabaei Bafghi Afsar Sadat Tabatabaei Bafghi Shahid Sadougui Hospital, Shahid Sadougui University of Medical Sciences, and Health Services, Yazd, Iran. ایران afsar_taba@yahoo.com Farimah Shamsi Farimah Shamsi Shahid Sadougui Hospital, Shahid Sadougui University of Medical Sciences, and Health Services, Yazd, Iran. ایران farimah.shamsi1982@gmail.com Pregnancy outcome Polycystic ovary syndrome Phenotype Pregnancy. عوارض نوزادی عوارض مادری سندروم تخمدان پلی کیستیک فنوتیپ بارداری. Homburg R. Pregnancy complications in PCOS. Best Practice & Research Clinical Endocrinology & Metabolism 2006; 20: 281-292.##Ghazeeri GS, Nassar AH, Younes Z, Awwad JT. Pregnancy outcomes and the effect of metformin treatment in women with polycystic ovary syndrome: an overview. Acta Obstet Gynecol Scand 2012; 91: 658-678.##Carmina E, Lobo RA. Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab 1999; 84: 1897-1899.##Bruce-Jones W, Zolese G, White P. Polycystic ovary syndrome and psychiatric morbidity. J Psychosom Obstet Gynecol 1993; 14: 111-116.##Bagegni N, Blaine J, Van Voorhis BJ, Dokras A. Risk of early & late obstetric complications in women with IVF-conceived pregnancies and polycystic ovary syndrome (PCOS). Proceed Obstet Gynecol 2010; 1:1-10.##Galazis N, Docheva N, Nicolaides KH, Atiomo W. Proteomic biomarkers of preterm birth risk in women with polycystic ovary syndrome (PCOS): a systematic review and biomarker database integration. PloS One 2013; 8: e53801.##Nikbakht R, Zargar M, Barekati Z, Mohammad Jafari R, Shahbazian N, Barati M. Adverse pregnancy and neonatal outcomes in polycystic ovary syndrome women. Tehran Univ Med J 2016; 73: 827-831.##Wang JX, Davies MJ, Norman RJ. Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment. Hum Reprod 2001; 16: 2606-2609.##Elting MW, Korsen TJ, Rekers-Mombarg LT, Schoemaker J. Women with polycystic ovary syndrome gain regular menstrual cycles when ageing. Hum Reprod 2000; 15: 24-28.##Moran LJ, Norman RJ, Teede HJ. Metabolic risk in PCOS: phenotype and adiposity impact. Trends in Endocrinology and Metabolism 2015; 26: 136-143.##Vaggopoulos V, Trakakis E, Chrelias C, Panagopoulos P, Basios G, Makridima S, et al. Comparing classic and newer phenotypes in Greek PCOS women: the prevalence of metabolic syndrome and their association with insulin resistance. J Endocrinol Invest 2013; 36: 478-484.##Baldani DP, Škrgatić L, Goldštajn MS, Vrčić H, Čanić T, Strelec M. Clinical, hormonal and metabolic characteristics of polycystic ovary syndrome among obese and nonobese women in the Croatian population. Coll Antropol 2013; 37: 465-470.##Winter E, Wang J, Davies MJ, Norman R. Early pregnancy loss following assisted reproductive technology treatment. Hum Reprod 2002; 17: 3220-3223.##Palomba S, Falbo A, Orio FJr, Zullo F. Effect of preconceptional metformin on abortion risk in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 2009; 92: 1646-1658.##Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts KA, Nestler JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 524-529.##Kollmann M, Klaritsch P, Martins WP, Guenther F, Schneider V, Herzog SA, et al. Maternal and neonatal outcomes in pregnant women with PCOS: comparison of different diagnostic definitions. Hum Reprod 2015; 30: 2396-2403.##Palomba S, Falbo A, Russo T, Tolino A, Orio F, Zullo F. Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes. Fertil Steril 2010; 94: 1805-1811.##Roos N, Kieler H, Sahlin L, Ekman-Ordeberg G, Falconer H, Stephansson O. Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study. BMJ 2011; 343: d6309.##Qin JZ, Pang LH, Li MJ, Fan XJ, Huang RD, Chen HY. Obstetric complications in women with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol 2013; 11: 56.##Palomba S, De Wilde MA, Falbo A, Koster MP, La Sala GB, Fauser BC. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update 2015; 21: 575-592.## ##

Expression levels of circulatory mir-185-5p, vascular endothelial growth factor, and platelet-derived growth factor target genes in endometriosis بررسی میزان میکرو ریبونوکلئیک اسید-185 (miRNA-185) و اهداف مولکولی VEGA و PDGF در بیماران مبتلا به آندومتریوزیس 2 1 مقدمه: استفاده از نشانگرهای زیستی در خون از قبیل میکروریبونوکلئیک اسیدها، امکان تشخیص و درمان غیرتهاجمی با بازدهی بالای بیماری آندومتریوزیس را فراهم نموده است. هدف: در این پژوهش، میزان کمّی بیان مولکول miRNA-185 گردش خون و اهداف مولکولی VEGA و PDGF در بیماران مبتلا به آندومتریوزیس در مقایسه با افراد سالم مورد بررسی و مقایسه قرار گرفته است. مواد و روش ها: 25 خانم با تاریخچه تشخیصی آندومتریوزیس (درجه 3-4) با لاپاراسکوپی به عنوان گروه بیمار و 25 خانم که به منظور بررسی کیستهای تخمدانی یا درد لگنی تحت لاپاراسکوپی قرار گرفته و غیرمبتلا تشخیص داده شده بودند، به عنوان گروه سالم و کنترل در نظر گرفته شدند پس از جمعآوری نمونههای خون از گروههای مورد مطالعه، RNA کل از آنها استخراج و توالییابی مبتنی بر RNA بر روی آنها انجام شده و میزان بیان miRNA-185 و ژنهای هدف به روش Q-RT-PCR مورد ارزیابی قرار گرفت. نتایج: پروفایل بیانی توالییابی RNA های غیرکدکننده نشان داد که سطح بیان miRNA-185 در خون کامل بیماران نسبت به افراد سالم کاهش یافته است. همچنین، نتایج Q-RT-PCR نشان داد که میزان بیان miRNA-185 در پلاسمای خون بیماران نیز کاهش معناداری داشته است. آنالیز منحنی ROC، سطح زیر نمودار (AUC) به میزان 919/0 را نشان داد که نشان از ارزش تشخیصی miRNA-185 مذکور بود (001/0p< ). همچنین، نتایج RT-PCR نیز نشان داد که هیچ افزایش یا کاهش معنادار در میزان رونوشتهای VEGF و PDGF در خون کامل بیماران و گروه کنترل مشاهده نشده است (3608/0 = VEGF ,pو 0976/0 =.(PDGF, p نتیجه گیری: نتایج به دست آمده از مطالعه نشان میدهد که کاهش بیان miRNA-185 در پلاسمای خون بیماران مبتلا به آندومتریوزیس در مقایسه با افراد کنترل میتواند به عنوان یک بیومارکر غیرتهاجمی در تشخیص زود هنگام و غربالگری سرطان تخمدان با استفاده از نمونههای خونی استفاده نمود. 2 Background: Using blood-based biomarkers such as microRNAs (miRNAs) may allow particularly effective and minimally invasive diagnosis and treatment of endometriosis. Objective: We evaluated the differential expression of circulating miRNA-185-5p (miR-185-5p), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) target genes between endometriosis and healthy women. Materials and Methods: 25 women with a history of endometriosis (grad III-IV) diagnosed by laparoscopy as the case group and 25 women without endometriosis underwent laparoscopy for ovarian cysts or pelvic pain as the control group were enrolled in this case-control study. Blood samples were obtained, and total RNA was used for high-throughput small RNA sequencing, and this was confirmed by means of quantitative real-time polymerase chain reaction (qRT-PCR). Results: miRNA expression profiling using non-coding RNA sequencing revealed that one miRNA including miR-185-5p was significantly down-regulated in the case group compared with the controls. The qRT-PCR results showed significant downregulation of the expression level of miR-185-5p (p < 0.01) in the plasma of the case group. Receiver operating characteristic (ROC) curve analysis showed the area of miR-185-5p under the ROC curve for endometriosis diagnosis was 0.919 (p < 0.001). The RT-PCR results demonstrated that there was no significant difference in the expression of VEGF and PDGF mRNA of blood samples in the cases compared to the control group (PDGF, p = 0.09 and VEGF, p = 0.36). Conclusion: The low expression of miR-185-5p in the plasma of women with endometriosis could be employed as an important non-invasive biomarker for early detection and screening of endometriosis by blood samples. 347 358 2019/05/122019/06/182019/07/62019/07/12 1398/4/21 2019/11/102019/11/192019/10/262019/11/30 1398/9/9 Mohammad Hossein Razi Mohammad Hossein Razi Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران raziir@yahoo.com Maryam Eftekhar Maryam Eftekhar Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران eftekharmaryam@yahoo.com Nasrin Ghasemi Nasrin Ghasemi Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران n479g@yahoo.co.uk Mohammad Hasan Sheikhha Mohammad Hasan Sheikhha Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران Sheikhha@yahoo.com Ali Dehghani Firoozabadi Ali Dehghani Firoozabadi Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران ali.dehghani.molmed@gmail.com Biomarker miRNA Diagnosis Endometriosis Angiogenesis بیومارکر میکروریبونوکلئیک اسید تشخیص آندومتریوزیس رگ زایی Panina YA, Yakimov AS, Komleva YK, Morgun AV, Lopatina OL, Malinovskaya NA, et al. Plasticity of adipose tissue-derived stem cells and regulation of angiogenesis. Front Physiol 2018; 9: 1656-1668.##Zetter BR. Angiogenesis and tumor metastasis. Annual Review of Medicine 1998; 49: 407-424.##Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002: 29 (suupl.); 15-18.##Ribatti D, Vacca A, Presta M. The discovery of angiogenic factors: A historical review. Gen Pharmacol 2000; 35: 227-231.##Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003; 9: 677-684.##Ucuzian AA, Gassman AA, East AT, Greisler HP. Molecular mediators of angiogenesis. J Burn Care Res 2010; 31: 158-175.##Mustonen T, Alitalo K. Endothelial receptor tyrosine kinases involved in angiogenesis. J Cell Biol 1995; 129: 895-898.##Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 1995; 376: 70-74.##Raica M, Cimpean AM. Platelet-derived growth factor (PDGF)/PDGF receptors (PDGFR) axis as target for antitumor and antiangiogenic therapy. Pharmaceuticals 2010; 3: 572-599.##Lindblom P, Gerhardt H, Liebner S, Abramsson A, Enge M, Hellstrom M, et al. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev 2003; 17: 1835-1840.##Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res 2005; 97: 512-523.##Presta M, Foglio E, Churruca Schuind A, Ronca R. Long Pentraxin-3 modulates the angiogenic activity of fibroblast growth factor-2. Front Immunol 2018; 9: 2327-2335.##Yoshiji H, Harris SR, Thorgeirsson UP. Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. Cancer Res 1997; 57: 3924-3928.##Guzick DS, Silliman NP, Adamson GD, Buttram VC Jr, Canis M, Malinak LR, et al. Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicine's revised classification of endometriosis. Fertil Steril 1997; 67: 822-829.##Pösel C, Möller K, Fröhlich W, Schulz I, Boltze J, Wagner DC. Density gradient centrifugation compromises bone marrow mononuclear cell yield. PloS One 2012; 7: e50293.##Ling G, Waxman DJ. DNase I digestion of isolated nulcei for genome-wide mapping of DNase hypersensitivity sites in chromatin. Methods Mol Biol 2013; 977: 21-33.##McAlexander MA, Phillips MJ, Witwer KW. Comparison of methods for mirna extraction from plasma and quantitative recovery of RNA from cerebrospinal fluid. Front Genet 2013; 4: 83-90.##Alamro RA, Mustafa M, Al-Asmari AK. Inflammatory gene mRna expression in human peripheral blood and its association with colorectal cancer. J Inflamm Res 2018; 11: 351-357.##Agrawal S, Tapmeier T, Rahmioglu N, Kirtley S, Zondervan K, Becker C. The miRNA mirage: how close are we to finding a non-invasive diagnostic biomarker in endometriosis? A systematic review. Int J Mol Sci 2018; 19: e599-e624.##Laschke MW, Menger MD. Basic mechanisms of vascularization in endometriosis and their clinical implications. Hum Reprod Update 2018; 24: 207-224.##Gagne D, Page M, Robitaille G, Hugo P, Gosselin D. Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis. Hum Reprod 2003; 18: 1674-1680.##Liu XJ, Bai XG, Teng YL, Song L, Lu N, Yang RQ. miRNA-15a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis. Eur Rev Med Pharmacol Sci 2016; 20: 3319-3326.##Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 1998; 70: 425-431.##Acimovic M, Vidakovic S, Milic N, Jeremic K, Markovic M, Milosevic-Djeric A, et al. Survivin and vegf as novel biomarkers in diagnosis of endometriosis/survivin i vegf kao novi biomarkeri u dijagnostici endometrioze. J Med Biochem 2016; 35: 63-68.##Baranov VS, Ivaschenko TE, Liehr T, Yarmolinskaya MI. Systems genetics view of endometriosis: a common complex disorder. Eur J Obstet Gynecol Reprod Biol 2015; 185: 59-65.##Matalliotakis IM, Goumenou AG, Koumantakis GE, Neonaki MA, Koumantakis EE, Dionyssopoulou E, et al. Serum concentrations of growth factors in women with and without endometriosis: the action of anti-endometriosis medicines. Int Immunopharmacol 2003; 3: 81-89.##McLaren J, Prentice A, Charnock-Jones DS, Smith SK. Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis. Hum Reprod 1996; 11: 220-223.##Pupo‐Nogueira A, de Oliveira RM, Petta CA, Podgaec S, Dias Jr Jr, Abrao MS. Vascular endothelial growth factor concentrations in the serum and peritoneal fluid of women with endometriosis. Int J Gynecol Obstet 2007; 99: 33-37.##Malhotra N, Karmakar D, Tripathi V, Luthra K, Kumar S. Correlation of angiogenic cytokines-leptin and IL-8 in stage, type and presentation of endometriosis. Gynecol Endocrinol 2012; 28: 224-227.##Lange S, Heger J, Euler G, Wartenberg M, Piper HM, Sauer H. 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Hum Reprod 2005; 21: 262-268.## ##

Frequency of the rs 14035 polymorphism of RAN gen in Recurrent pregnancy loss: A case-control study بررسی فراوانی و ارتباط پلی مورفیسم rs 14035 ژن RAN با سقط مکرر با علت ناشناخته: یک مقاله مورد-شاهدی 2 1 مقدمه: عوامل ژنتیکی میتوانند باعث سقط مکرر ایدیوپاتیک شوند. ژن RAN عضو "خانواده بزرگ RAS" و یک GTPase کوچک است که برای انتقال RNA و پروتئینها از طریق منافذ هستهای ضروری است. جهش در ژن سازنده RAN میتواند سنتز DNA را متوقف کند، و بیان ژنها در رحم را تغییر دهد، احتمال میرود که در سقط مکرر نقش داشته باشد. هدف: هدف از این مطالعه بررسی فراوانی پلیمورفیسم (RAN (rs 14035 در زنان مبتلا به سقط مکرر با علت ناشناخته در مقایسه با زنان بدون سابقه سقط جنین است. مواد و روش ها: در این مطالعه مورد شاهدی، 100 زن 20 تا 40 ساله با حداقل دو مورد سقط جنین پیاپی قبل از هفته 20 بارداری و داشتن همسران با کاریوتایپ و پارامترهای نرمال اسپرم به عنوان گروه مورد و 100 زن بدون سابقه سقط جنین و داشتن حداقل یک بارداری موفق و زایمان طبیعی به عنوان گروه کنترل انتخاب شد. پلیمورفیسم rs 14035 ژن RAN با استفاده از تکنیک (PCR-RFLP) بررسی و فراوانی آن در دو گروه مقایسه گردید. نتایج: فراوانی ژنوتیپهایTT ، TC و CC پلیمورفیسم ژن RAN در گروه مورد به ترتیب 9% ، 40% و 51% بود و فراوانی در گروه شاهد به ترتیب 11%، 38% و 51% بود. بین گروه مورد و شاهد اختلاف معنیداری از نظر ژنوتیپها وجود نداشت. (882/0 =p). نتیجه گیری: با توجه به نتایج مطالعه حاضر به نظر میرسد پلیمورفیسم ژن (rs 14035) RAN با خطر سقط مکرر خودبهخودی در جمعیت مورد مطالعه مرتبط نیست. 2 Background: Genetic factors could account for Recurrent pregnancy loss (RPL). The RAN gene is a member of the "large RAS family" and a small GTPase that is essential for the translocation of Ribonucleic acid (RNA) and proteins through the nuclear pore. Mutation in the RAN constitutive gene could stop DNA synthesis and alter the expression of genes in the uterus, likely playing a role in recurrent miscarriage. Objective: The aim was to investigate the frequency of RAN (rs 14035) polymorphism in women with RPL compared with women without abortion history. Materials and Methods: In this case-control study, 100 women with at least two consecutive miscarriages before the 20th wk of gestation and having spouses with karyotype and normal sperm parameters as the case group and 100 women with no history of abortion and having at least one successful pregnancy and normal delivery as the control group. The groups were age matched (20-40 yr). The rs 14035 polymorphism of RAN gene was investigated by Polymerase Chain Reaction-Restriction Fragment Length poly morphism technique and the frequency of which was compared between the two groups. Results: The frequency of TT, TC, and CC genotypes of RAN gene polymorphism in the case group were 9%, 40%, and 51%, respectively, and in the control group were 11%, 38%, and 51%, respectively. There was no significant difference in the genotypes between two groups (p = 0.882). Conclusion: According to our results, it seems that RAN polymorphism (rs 14035) is not associated with the risk of RPL in this study population. 359 366 2019/05/122019/06/182019/07/62019/07/122019/12/5 1398/9/14 2019/11/102019/11/192019/10/262019/11/302020/06/7 1399/3/18 zahrasadat Mortazavifar zahrasadat Mortazavifar Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran. ایران nazanin_m2004@yahoo.com Hamidreza Ashrafzadeh Hamidreza Ashrafzadeh Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران hr_ashrafzadeh@yahoo.com Sayed Morteza Seifati Sayed Morteza Seifati Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran. ایران seifati@gmail.com Nasrin Ghasemi Nasrin Ghasemi Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. ایران n479g@yahoo.co.uk RAN gene Repeated abortion Polymorphism PCR-RFLP. ژن RAN سقط مکرر پلی مورفیسم PCR-RFLP. Sierra S, Stephenson M. Genetics of recurrent pregnancy loss. Semin Reprod Med 2006; 24: 17-24.##Meka A, Reddy BM. Recurrent spontaneous abortions: an overview of genetic and non-genetic backgrounds. Int J Hum Genet 2006; 6: 109-117.##Moore MS, Blobel G. A G protein involved in nucleocytoplasmic transport: the role of Ran. Trends Biochem Sci 1994; 19: 211-216.##Sazer S, Dasso M. The ran decathlon: multiple roles of Ran. J Cell Sci 2000; 113: 1111-1118.##Fotoohi M, Ghasemi N, Mirghanizadeh SA, Vakili M, Samadi M. Association between HLA-E gene polymorphism and unexplained recurrent spontaneous abortion (RSA) in Iranian women. Int J Reprod Biomed 2016; 14: 477-482.##Arjmand F, Ghasemi N, Mirghanizadeh SA, Samadi M. The balance of the immune system between HLA-G and NK cells in unexplained recurrent spontaneous abortion and polymorphisms analysis. Immunol Res 2016; 64: 785-790.##Abdollahi E, Tavasolian F, Ghasemi N, Mirghanizadeh SA, Azizi M, Ghoryani M, et al. Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA). J Immunotoxicol 2015; 12: 317-321.##Zahraei M, Sheikhha MH, Kalantar SM, Ghasemi N, Jahaninejad T, Rajabi S, et al. The association of arylendosulfatase 1 (SULF1) gene polymorphism with recurrent miscarriage. J Assist Reprod Genet 2014; 31: 157-161.##Teremmahi Ardestani M, Nodushan HH, Aflatoonian A, Ghasemi N, Sheikhha MH. Case control study of the factor V Leiden and factor II G20210A mutation frequency in women with recurrent pregnancy loss. Iran J Reprod Med 2013; 11: 61-64.##O'Toole AS, Miller S, Haines N, Zink MC, Serra MJ. Comprehensive thermodynamic analysis of 3′ double-nucleotide overhangs neighboring Watson-Crick terminal base pairs. Nucleic Acids Res 2006; 34: 3338-33344.##Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120: 15-20.##Tohidi N, Ghorbian S. [Investigating the association of RAN (rs 14035) and XPO5 (rs 2257082) genes polymorphisms with the recurrent pregnancy loss in women referred to Imam Khomeini Hospital of Ardabil During 2015-2017 years.] J Rafsanjan Univ Med Sci 2018; 17: 201-212. (in Persian)##Jung YW, Jeon YJ, Rah H, Kim JH, Shin JE, Choi DH, et al. Genetic variants in microRNA machinery genes are associate with idiopathic recurrent pregnancy loss risk. PloS One 2014; 9: e95803-e95811.##Fallah-Sohy A, Zaker Bostanabad S, Mirza Ahmadi S. [Investigation of relationship between MicroRNA Machinery Genes polymorphism (RAN rs14035, DICER rs3742330) and recurrent spontaneous abortion in city of Tehran.] New Cell Mol Biotech J 2018; 8: 23-30. (in Persian).##Tabibnejad N, Sheikhha MH, Ghasemi N, Fesahat F, Soleimani M, Aflatoonian A. Association between early embryo morphokinetics plus cumulus cell gene expression and assisted reproduction outcomes in polycystic ovary syndrome women. Reprod Biomed Online 2019; 38: 139-151.##Rah H, Jeon YJ, Lee BE, Kim JO, Shim SH, Lee WS, et al. Association of polymorphisms in microRNA machinery genes (DROSHA, DICER1, RAN, and XPO5) with risk of idiopathic primary ovarian insufficiency in Korean women. Menopause 2013; 20: 1067-1073.##Jeon YJ, Choi YS, Rah H, Kim SY, Choi DH, Cha SH, et al. Association study of microRNA polymorphisms with risk of idiopathic recurrent spontaneous abortion in Korean women. Gene 2012; 494: 168-173.##Fu M, Xu WM, Qin TZ, Xu KH. The association between the polymorphisms of mirna biogenesis related genes (DICER, DROSHA and RAN) and unexplained recurrent spontaneous abortion in chinese women. Sichuan Da Xue Xue Bao Yi Xue Ban 2017; 48: 880-885.##Kotlabova K, Doucha J, Hromadnikova I. Placental-specific microRNA in maternal circulation-identification of appropriate pregnancy-associated microRNAs with diagnostic potential. J Reprod Immunol 2011; 89: 185-191.##Chakrabarty A, Tranguch S, Daikoku T, Jensen K, Furneaux H, Dey SK. MicroRNA regulation of cyclooxygenase-2 during embryo implantation. Proc Nati Acad Sci USA 2007; 104: 15144-15149.##Enquobahrie DA, Abetew DF, Sorensen TK, Willoughby D, Chidambaram K, Williams MA. Placental microRNA expression in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 2011; 204: 178. e12-e21.##Choi YS, Kwon H, Kim JH, Shin JE, Choi Y, Yoon TK, et al. Haplotype-based association of ACE I/D, AT1R 1166A> C, and AGT M235T polymorphisms in renin-angiotensin-aldosterone system genes in Korean women with idiopathic recurrent spontaneous abortions. Eur J Obstet Gynecol Reprod Biol 2011; 158: 225-228.##Donker RB, Mouillet JF, Nelson DM, Sadovsky Y. The expression of Argonaute2 and related microRNA biogenesis proteins in normal and hypoxic trophoblasts. Mol Hum Reprod 2007; 13: 273-279.## ##

The impact of late follicular progesterone level on in vitro fertilization-intracytoplasmic sperm injection outcome: Case-control study اثر سطح پروژسترون آخر فولیکولار بر نتایج باروری آزمایشگاهی با تزریق داخل سیتوپلاسمی اسپرم: مطالعه مورد شاهدی 2 1 مقدمه: مطالعات زیادی جهت بهبود نتایج باروری آزمایشگاهی (IVF) و تزریق داخل سیتوپلاسمی اسپرم (ICSI) انجام شده است.در سالهای اخیر تمرکز پژوهشگران بر یافتن اثر سطح بالای پروژسترون بر روی گیرندگی آندومتر بوده است. با این حال اطلاعات در مورد اینکه آیا سطح پروژسترون بر روی کیفیت امبریو نیز تاثیر میگذارد، محدود است. هدف: هدف این مطالعه بررسی تاثیر سطح پروژسترون آخر فولیکولار بر نتایج باروری آزمایشگاهی با تزریق داخل سیتوپلاسمی (IVF-ICSI) است. مواد و روش ها: این یک مطالعه مورد شاهدی است که بر روی 245 زن که در مرکز ناباروری حلیم در اندونزی تحت درمان باروری آزمایشگاهی قرار گرفتند انجام شد. نتایج مورد بررسی قرار گرفته شامل تعداد تخمکهای بدست آمده، میزان بلوغ آنها، میزان باروری، تعداد امبریوهای خوب، تعداد امبریوهای نسبتا خوب و تعداد امبریوهای ضعیف میباشد. سطح پروژسترون و استرادیول در روز تزریق گونادوتروپین جفتی انسانی اندازهگیری شد. سطج پروژسترون سرم به سه گروه تقسیم شد: 1/ پروژسترون پایین (ng/ml 50/0 ≥) 2/0 پروژسترون نرمال (ng/ml 05/1-51/0) و 3/ پروژسترون بالا (ng/ml 50/1 <). تمام نتایج بدست آمده بین گروههای مختلف مقایسه شد. نتایج: تغیرات معنیداری در سطح پروژسترون در روز تزریق گونادوتروپین جفتی انسانی مشاهده شد. تعداد تخمکهای بدست آمده در گروههای 1 و 2 و3 به ترتیب 88/5±41/8 و 51/8±99/12 و 52/9±58/17 بود. نتیجه گیری: سطح پروژسترون در روز تزریق گونادوتروپین جفتی انسانی ممکن است که بر روی نتایج IVF-ICSI تاثیر داشته باشد. 2 Background: Studies have been conducted to improve the pregnancy rate through the in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) program. In recent years, researchers have been focusing on finding impact of high progesterone level on endometrial receptivity. However, data on whether progesterone level also affects the quality of the embryo is still limited. Objective: The aim is to assess the effect of late follicular progesterone level on the outcome of in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI). Materials and Methods: This was a case-control of 245 women who underwent in vitro fertilization cycle at Halim Fertility Center, Indonesia. The outcomes assessed were number of oocytes retrieved (OR), maturation rate (MR), fertilization rate (FR), number of good embryos (GE), number of fair embryos (FE), and number of poor embryos (PE). The progesterone (P4) and estradiol (E2) levels were analyzed on the day of human chorionic gonadotropin injection. Serum progesterone level was divided into three groups: 1. low progesterone (≤ 0.50 ng/ml), 2. normal progesterone (0.51-1.50 ng/ml), and 3. high progesterone (> 1.50 ng/ml). All outcomes were compared amongst the groups. Results: Significant differences occurred between progesterone level on the day of human chorionic gonadotropin administration. The number of OR in group 1, 2, and 3 were 8.41 ± 5.88 vs. 12.99 ± 8.51 vs. 17.58 ± 9.52, respectively. Conclusion: Progesterone level on the day of human chorionic gonadotropin injection may have an impact on the outcome of IVF-ICSI. 367 374 2019/05/122019/06/182019/07/62019/07/122019/12/52019/04/8 1398/1/19 2019/11/102019/11/192019/10/262019/11/302020/06/72019/12/2 1398/9/11 Diana Novia Diana Novia Department of Biology, Faculty of Mathematics and Science, University of Indonesia, Depok, Indonesia. Halim Fertility Center, Stella Maris Women and Children Hospital, Medan, Indonesia. اندونزی diana.novia@yahoo.com Hilma Putri Lubis Hilma Putri Lubis Halim Fertility Center, Stella Maris Women and Children Hospital, Medan, Indonesia. Faculty of Medicine University of Sumatera Utara, Haji Adam Malik General Hospital, Medan, Indonesia. اندونزی hilmaputrilubis@gmail.com Binarwan Halim Binarwan Halim Halim Fertility Center, Stella Maris Women and Children Hospital, Medan, Indonesia. Faculty of Medicine University of Sumatera Utara, Haji Adam Malik General Hospital, Medan, Indonesia. اندونزی binarwan2002@yahoo.com Anantya Pustimbara Anantya Pustimbara Department of Biology, Faculty of Mathematics and Science, University of Indonesia, Depok, Indonesia. اندونزی anantya_1996@yahoo.com Retno Lestari Retno Lestari Department of Biology, Faculty of Mathematics and Science, University of Indonesia, Depok, Indonesia. اندونزی retno.lestari.budiman@gmail.com Abinawanto Abinawanto Abinawanto Abinawanto Department of Biology, Faculty of Mathematics and Science, University of Indonesia, Depok, Indonesia. اندونزی abinawanto@gmail.com Anom Bowolaksono Anom Bowolaksono Department of Biology, Faculty of Mathematics and Science, University of Indonesia, Depok, Indonesia. اندونزی alaksono@sci.ui.ac.id Intracytoplasmic sperm injection Embryo Progesterone In vitro fertilization. تزریق داخل رحمی اسپرم جنین پروژسترون لقاح آزمایشگاهی. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glosarry on infertility and fertility care, 2017. Fertil Steril 2017; 108: 393-406.##Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem 2018; 62: 2-10.##Persson J. The ART of assisted reproductive technology. Aust Fam Physician 2005; 34: 119-122.##Lestari L, Pratama G, Maidarti M, Harzif AK, B. Wiweko. Characteristic and pregnancy rate of IVF patient: A retrospective analysis from two centres. ASPIRE conference proceedings, the 6th congress of the asia pacific initiative on reproduction, KnE Medicine 2016: 43-48.##Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril 2015; 103: 44-50.##Santos-Ribeiro S, Polyzos NP, Haentjens P, Smitz J, Camus M, Tournaye H, et al. Live birth rates after IVF are reduced by both low and high progesterone levels on the day of human chorionic gonadotrophin administration. Hum Reprod 2014; 29: 1698-1705.##Lawrenz B, Fatemi HM. Effect of progesterone elevation in follicular phase of IVF-cycles on the endometrial receptivity. Reprod Biomed Online 2017; 34: 422-428.##Segal S, Glatstein I, McShane P, Hotamisligil S, Ezcurra D, Carson R. Premature luteinization and in vitro fertilization outcome in gonadotropin/gonadotropin-releasing hormone antagonist cycles in women with polycystic ovary syndrome. Fertil Steril 2009; 91: 1755-1759.##Huang B, Li Z, Zhu L, Hu D, Liu Q, Zhu G, et al. Progesterone elevation on the day of HCG administration may affect rescue ICSI. Reprod Biomed Online 2014; 29: 88-93.##M. Choudhary, Sharma S, Swarankar M L, Bhardwaj S L. Risk of premature luteinization in IVF cycles and its impact on clinical pregnancy rate. Int J Res Med Sci 2016; 4: 139-143.##Lawrenz B, Labarta E, Fatemi H, Bosch E. Premature progesterone elevation: targets and rescue strategies. Fertil Steril 2018; 109: 577-582.##Liu Y, Copeland C, Chapple V, Roberts P, Feenan K, Matson P. The relationship between embryo quality assessed using routine embryology or time-lapse videography and serum progesterone concentration on the day of ovulatory trigger in in vitro fertilization cycles. Asian Pacific Journal of Reproduction 2015; 4: 140-146.##Sonigo C, Dray G, Roche C, Cédrin-Durnerin I, Hugues JN. Impact of high serum progesterone during the late follicular phase on IVF outcome. Reprod Biomed Online 2014; 29: 177-186.##Alpha scientists in reproductive medicine and ESHRE special interest group of embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011; 26: 1270-1283.##Trounson A, Gosden R, Eichenlaub-Ritter U. Second edition biology and pathology of the oocyte role in fertility, medicine, and nuclear reprogramming. Cambridge University Press, New York; 2013.##Abbara A, Clarke SA, Dhillo WS. Novel concepts for inducing final oocyte maturation in in vitro fertilization treatment. Endocr Rev 2018; 39: 593-628.##Rehman R, Khan R, Baig M, Hussain M, Fatima SS. Estradiol progesterone ratio on ovulation induction day: a determinant of successful pregnancy outcome after intra cytoplasmic sperm injection. Iran J Reprod Med 2014; 12: 633-640.##Bu Z, Zhao F, Wang K, Guo Y, Su Y, Zhai J, et al. Serum progesterone elevation adversely affects cumulative live birth rate in different ovarian responders during in vitro fertilization and embryo transfer: a large retrospective study. PloS One 2014; 9: e100011.##Hoshino Y. Updating the markers for oocyte quality evaluation: intracellular temperature as a new index. Reprod Med Biol 2018; 17: 434-441.##Huang B, Ren X, Wu L, Zhu L, Xu B, Li Y, et al. Elevated progesterone levels on the day of oocyte maturation may affect top quality embryo IVF cycles. PLoS One 2016; 11: e0145895.##Huang PC, Chen MJ, Guu HF, Yi YC, Ho JY, Chen YF, et al. Effect of premature serum progesterone rise on embryo transfer outcomes and the role of blastocyst culture and transfer in assisted reproductive technology cycles with premature progesterone rise. Taiwan J Obstet Gynecol 2015; 54: 641-646.##Huang Y, Wang EY, Du QY, Xiong YJ, Guo XY, Yu YP, et al. Progesterone elevation on the day of human chorionic gonadotropin administration adversely affects the outcome of IVF with transferred embryos at different developmental stages. Reprod Biol Endocrinol 2015; 13: 82-91.## ##

Strategies for whole-exome sequencing analysis in a case series study of familial male infertility استراتژی های تجزیه و تحلیل توالی یابی اگزوم در خانواده هایی با مردان نابارور 2 1 مقدمه: ناباروری یکی از مسائل بهداشت عمومی در سراسر جهان است. شیوع ناباروری در زوجین حدود 30 تا 35 درصد است. در میان فاکتورهای متعددی که منجر به ناباروری مردان می شوند، 15% موارد منشاء ژنتیکی دارند. توالییابی کل اگزونها (اگزوم) یکی از کارآمدترین روشها در تشخیصهای بالینی است. با استفاده از این روش به طور چشمگیری روندشناسایی ژنهای دخیل در ناباروری به طور چشمگیری افزایش یافته است. در میان استراتژیها متعدد آنالیز دادههای اگزوم، رویکردهای مبتنی بر خانواده دقت بالاتری در شناسایی ژنهای کاندید دارند. با این حال در مطالعات ناباروری انتخاب نمونه مناسب برای توالییابی یکی از چالشهای اصلی میباشد. هدف: هدف از این مطالعه شناسایی جهشهای عامل ناباروری مردان در بیماران مبتلا به آستنوزواسپرمیا است. مواد و روش ها: دو خانواده با چندین مرد نابارور مبتلا به آستنوزواسپرمیا فراخوانده شدند. در این مطالعه از روش توالییابی اگزوم به منظور تولید داده در دو فرد نابارور و والدینشان در خانواد I و سه فرد نابارور در خانواده II استفاده شد. به منظور شناسایی ژنهای کاندید دو نرم افزار مختلف SAMtools و GATK در دو استتراتژی SSCS و MSCS به کار برده شدند. نتایج: در این تحقیق بدون توالییابی برادران بارور در شجرهنامهها، نتایج الویتبندی دادههای WES با استفاده از دو استراتژی هموزیگوسیتی و آنایز پیوستگی ارائه شده است. نتیجه گیری: از طریق استراتژیهای ذکر شده لیست کوتاهی از واریتههای کاندید در هر دو شجرهنامه بدست آمد. 2 Background: Infertility is one of the common health issues around the world. The prevalence of male factor infertility among infertile couples is approximately 30%-35%, of which genetic factors account for 15%. The family-based whole-exome sequencing (WES) approach can accurately detect novel variants. However, selecting an appropriate sample for data generation using WES has proven to be challenging in familial male infertility studies. The aim of this study was to identify types of pathogenic male infertility in cases of familial asthenozoospermia. Case: Two families with multiple cases were recruited for the purpose of WES. The study population included two affected cases in pedigree I and three affected cases in pedigree II. Two different variant callers (SAMtools and GATK) with a single-sample calling strategy (SSCS) and a multiple-sample calling strategy (MSCS), were applied to identify variant sites. Conclusion: In this study, we represented the results for variant prioritization of WES data without sequencing fertile siblings in the same pedigree by applying two different pipelines (homozygosity and linkage-based strategy). Using the aforementioned strategies, we prioritized annotated variants and generated a logical shortlist of private variants for each pedigree. 375 384 2019/05/122019/06/182019/07/62019/07/122019/12/52019/04/82018/12/31 1397/10/10 2019/11/102019/11/192019/10/262019/11/302020/06/72019/12/22019/10/28 1398/8/6 Masomeh Askari Masomeh Askari Department of Biology, Sistan and Baluchestan University, Zahedan, Iran. ایران masomeasgari89@gmail.com Dor Mohammad Kordi Tamandani Dor Mohammad Kordi Tamandani Department of Biology, Sistan and Baluchestan University, Zahedan, Iran. ایران dor_kordi@science.usb.ac.ir Navid almadani Navid almadani Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. ایران navidalmadani@yahoo.com Mehdi Totonchi Mehdi Totonchi Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. ایران m.totonchi@royaninstitute.org Male infertility Whole-exome sequencing GATK SAMtools. ناباروری مردان توالی یابی اگزوم GATK SAMtools. Jungwirth A, Diemer T, Dohle GR, Giwercman A, Kopa Z, Krausz C, et al. Guidelines on male infertility. Eur Urol 2015; 62: 324-332.##Shi X, Chan CPS, Waters T, Chi L, Chan DYL, Li TC. Lifestyle and demographic factors associated with human semen quality and sperm function. Syst Biol Reprod Med 2018; 64: 358-367.##O'Flynn O'Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: A review. Fertil Steril 2010; 93: 1-12.##Theisen A, Shaffer LG. Disorders caused by chromosome abnormalities. Appl Clin Genet 2010; 3: 159-174.##Hamada AJ, Esteves SC, Agarwal A. A comprehensive review of genetics and genetic testing in azoospermia. 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