Is Male Reproductive System More Vulnerable to SARS-CoV-2 Than Female’s? 2 1 2 Coronaviruses are the largest family of viruses with RNA genome and more than 30 identified members. Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 was initially identified with extensive respiratory symptoms such as chest pain, pulmonary edema, dyspnea, heavy breathing, shortness of breath, and dry cough. Following spreading of the pandemic worldwide and increasing the number of patients with severe disease, multiorgan failures including fever, fatigue and myalgia, sore throat, diarrhea, nausea, dizziness, headache, rhinorrhea and vomiting in addition to respiratory manifestations were reported. At the same time, ACE2 was identified as a receptor for spike protein (S) of SARS-CoV-2, which facilitates virus entry into target cells. ACE2 was known to be expressed in more than 30 organs, such as the kidneys, testes, heart, gallbladder, small intestine, colon, thyroid, and adipose tissue, etc. which are potentially targets of SARS-CoV-2 and may be the cause of several organ failures following COVID-19 infection (1). Notwithstanding the persistent increase of our knowledge about pathogenesis, clinical manifestations and complications of the disease, there are still many unresolved questions, especially about the effects of COVID-19 on the reproductive system and fertility, including probability of its existence in semen, cervical mucus, vaginal discharge, follicular fluid and also its transmission through sexual contact; moreover, it is not clear whether the susceptibility to fertility failure after COVID-19 infection is the same among males and females or not. According to preliminary data, there is a significant difference between men and women in terms of prevalence and severity of COVID-19. Therefore, susceptibility and vulnerability of men is much higher than women of the same age. In addition, severe respiratory symptoms with a relatively high probability of death are more frequent among men who need intensive care unit services (2). ACE2 expression is higher in testis and male genital tract in comparison to ovaries and female genital tract, reflecting the fact that male fertility is much more vulnerable than fertility of females in COVID-19. However, in human tissues, co-expression of TMPRSS2 as an essential metalloprotease with ACE2 is essential for SARS-CoV-2 infection. ACE2 is highly expressed in spermatogonia, spermatids, Sertoli, and Leydig cells, although co-expression of TMPRSS2 in all of these cells has not been confirmed with ACE2. For example, Sertoli cells have high levels of ACE2 expression and low levels of TMPRSS2, while spermatogonia have high levels of TMPRSS2 and low levels of ACE2 expression. Leydig and Sertoli cells have ACE2 at the protein level, but no overlapping of expression for these two target viral molecules has been reported in these cells. Thus, the inconsistent findings cannot confirm the direct effects of the virus on spermatogenesis and testicular damage following SARS-CoV-2 infection (3). In addition, most clinical studies did not detect SARS-CoV-2 RNA in seminal fluid or testicular biopsy in cured or acute positive cases of COVID-19. In addition, there is no evidence of virus existence in the testes of adult men who have died from COVID-19. However, inconvenience in testicles is one of the complaints of patients after COVID-19 recovery, even in the absence of the virus genome in testicular biopsy. Semen is composed of several components and secretion by seminiferous tubules provides less than 10% of semen and seminal vesicle and prostate secretions make up more than 90% of semen. This evidence leads to the hypothesis that semen could not be a route of SARSCoV-2 transmission and there is low risk of viral transmission through assisted reproductive techniques (ARTs) during COVID-19 outbreak. Eventually, severe destruction of the testicular tissue is quite evident in histopathological examinations despite the above finding (1, 4). So, it seems another mechanism is at work for indirect involvement of virus in testicular damages and male fertility. The most probable mechanism is the systemic effects of the virus on other organs, which has a wide variety of consequences on the reproductive system in different individuals. Male fertility problems, at first glance, could be induced by immune system. The testis is an immune privileged organ with blood-testis barrier (BTB) that protects spermatogenic cells against a wide range of pathogens, but BTB is not a complete barrier for protection of spermatogenic cells under systemic or local inflammation with cytokine storm due to SARS-CoV-2 virus infection. Inflammatory cytokines can provoke leukocytes infiltration into testicular tissue, which is characteristic of orchitis. It has also been shown that high levels of IL-6 disrupt the integrity of BTB, which facilitates virus infiltration and probably direct damages to spermatogenic cells. In fact, this may be the reason for the various reports on orchitis-like syndrome in COVID-19 patients (1, 5). Immunohistochemical examination on slides of testicular tissue of dead men from COVID-19 showed orchitis-like syndrome with a large amount of IgG deposition in the seminiferous epithelium and also destroyed spermatogenic and Sertoli cells. This may be a key factor for secondary autoimmune response to SARS-CoV-2 virus, thereby leading to exacerbation of testicular damage with autoimmune orchitis (1). SARS-CoV-2 may directly affect the hypothalamic-pituitary- gonadal axis and subsequently impair Leydig cells’ functions, testosterone production, and significantly increase serum LH and prolactin. Based on the available data, cells of the nervous system extensively express ACE2 receptors, which may be a possible explanation for the neurological symptoms of COVID-19 and consequent SARS-CoV-2 damage on the hypothalamic-pituitary-testis axis. Thus, the production of pituitary and testicular hormones and male fertility are affected. In addition, elevated ROS production, oxidative stress and sperm DNA fragmentation due to long-term fever are another mechanism for destruction of male fertility by SARS-CoV-2 virus (3, 4). The SARS-CoV-2 pandemic has raised concerns about male fertility over the past 10 months, and a comprehensive review of studies with controversial evidence necessitates more investigations on the relationship between COVID-19 and fertility. Despite the lack of conclusive findings for preventing its effects on the reproductive system, this is a starting point for further research into the effects of COVID-19 disease on male fertility. There has always been concern about a gradual decline in sperm quantity and quality and thus male fertility over time, with some studies reporting a 50% reduction in semen quality over less than half a century. Though the causative factors have not been identified yet, lifestyle and environmental factors seem to be the fundamental influences. Due to above clinical features of COVID-19, the SARS-CoV-2 may also exacerbate this process; therefore, assessing the effects of the virus on spermatogenesis and male fertility is an exigency which requires serious attention and further studies in future. 01 3 Mohammad Reza MR Sadeghi محمدرضا صادقی Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran sadeghi@ari.ir No Keyword 120094.pdf Huang C, Ji X, Zhou W, Huang Z, Peng X, Fan L, et al. Coronavirus: a possible cause of reduced male fertility. Andrology. 2020 Sep 22;10.1111/andr.12907.##Khalili MA, Leisegang K, Majzoub A, Finelli R, Panner Selvam MK, Henkel R, et al. Male fertility and the COVID-19 pandemic: systematic review of the literature. World J Mens Health. 2020;38(4):506-20.##Khan RIN, Malla WA. Does SARS-CoV-2 have influence on male reproductive system? Hum Reprod. 2020;35(11):2626-7.##Navarra A, Albani E, Castellano S, Arruzzolo L, Levi-Setti PE. Coronavirus disease-19 infection: implications on male fertility and reproduction. Front Physiol. 2020;11:574761.##Li H, Xiao X, Zhang J, Zafar MI, Wu C, Long Y, et al. Impaired spermatogenesis in COVID-19 patients. EClinical Medicine. 2020;28:100604.##

The Impact of Third Party Reproduction on Family and Kinship 2 1 2 The development of in vitro fertilization (IVF) in the UK, in 1978, proved a major breakthrough in the process of human reproduction, which had remained constant in human history. The impact of IVF and the ensuing assisted reproductive technologies (ARTs) has not been limited in revolutionizing the "natural" practice of biological reproduction, but has reached out to and affected almost every institution in society. Family and kinship, as the social expression of reproduction and the institutions which are the most transparently structured realm of human life are those most profoundly affected by ARTs. Although literature on the implications of ARTs is in general abundant, this article presents new insights on their impact on family and kinship in Iran, which remains a unique case in the Muslim world. It explores the particular way ARTs, especially third-party donation, have been endorsed and practiced in Iran, and their consequences for the family, the infertile individuals, and their position vis-à-vis their kin and social group. The conclusion points to the lack of clarity concerning the initial rulings by the Islamic jurists, who allowed the practice of ARTs, and which has led to a number of unintended consequences regarding the legal, religious, cultural, and ethical issues, affecting the family, its structure and the relationship between the kin group. These consequences range, inter alia, from the question of the anonymity of third-party donor, to the permissibility of gamete donation between blood relatives, and to the absence of enforceable legislation. 03 16 Zohreh Z Behjati Ardakani Department of Sociology, Central Tehran Branch, Islamic Azad University Department of Sociology, Central Tehran Branch, Islamic Azad University Iran Mehrdad M Navabakhsh Faculty of Humanistic and Social Sciences, Science and Research Branch, Islamic Azad University Faculty of Humanistic and Social Sciences, Science and Research Branch, Islamic Azad University Iran navabakhsh@srbiau.ac.ir Soraya S Tremayne Fertility and Reproductive Studies Group (FRSG), Institute of Social and Cultural Anthropology Fertility and Reproductive Studies Group (FRSG), Institute of Social and Cultural Anthropology UK Mohammad Mehdi MM Akhondi محمدمهدی آخوندی Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Fahimeh F Ranjbar Nursing Care Research Center, School of Nursing and Midwifery, Iran University of Medical Sciences Nursing Care Research Center, School of Nursing and Midwifery, Iran University of Medical Sciences Iran Alireza AR Mohseni Tabrizi Department of Sociology, University of Tehran Department of Sociology, University of Tehran Iran FamilyInfertilityKinshipThird party reproduction 120093.pdf Bamford SC. The Cambridge Handbook of kinship. 1st ed. Cambridge: Cambridge university press; 2019. 750 p.##Behjati-Ardakani Z, Navabakhsh M, Hosseini SH. Sociological study on the transformation of fertility and childbearing concept in Iran. J Reprod Infertil. 2017;18(1):153-61.##Ginsburg F. Conceiving the new world order: The global politics of reproduction. 1st ed. California: University of California Press; 1995. 421 p.##Robertson AF. Beyond the family: the social organization of human reproduction. 1st ed. California: Univ of California Press; 1991. 199 p.##Kligman G. The politics of duplicity: Controlling reproduction in Ceausescu’s Romania. 1st ed. California: Univ of California Press; 1998. 341 p.##Unnithan-Kumar M. Female selective abortion–beyond ‘culture’: family making and gender inequality in a globalising India. Cult Health Sex. 2010;12(2):153-66.##Inhorn M, Van Balen F. Infertility around the globe: new thinking on childlessness, gender, and reproductive technologies. California: University of California Press; 2002. 315 p.##Hampshire K, Simpson B. Assisted reproductive technologies in the third phase: global encounters and emerging moral worlds. 1st ed. New York: Berghahn Books; 2015. 284 p.##Ginsburg F, Rapp R. The politics of reproduction. Annu Rev Anthropol. 1991;20(1):311-43.##Strathern M. After nature: English kinship in the late twentieth century. 1st ed. Cambridge: Cambridge University Press; 1992. 218 p.##Strathern M. Reproducing the future: essays on anthropology, kinship and the new reproductive technologies. Manchester: Manchester University Press; 1992. 183 p.##Franklin S. Embodied progress: a cultural account of assisted conception. 1st ed. London: Routledge. 1997. 252 p.##Ragoné H. Surrogate motherhood: conception in the heart. 1st ed. Oxford: Westview Press; 1994. 215 p.##Edwards J, Franklin S, Strathern M, Hirsch E, Price F. Technologies of procreation: Kinship in the age of assisted conception. 2nd ed. London: Routledge; 1999. 256 p.##Carsten J. Cultures of relatedness: new approaches to the study of kinship. 1st ed. Cambridge: Cambridge University Press; 2000. 191 p.##Carsten J. After kinship. 1st ed. Cambridge: Cambridge University Press; 2004. 191 p.##Parkin R, Stone L. Kinship and family: an anthropological reader. 1st ed. US: Blackwell Pub; 2004. 496 p.##Inhorn MC. Making muslim babies: IVF and gamete donation in Sunni versus Shi’a Islam. Cult Med Psychiatry. 2006;30(4):427-50.##Kahn SM, Farquhar J, Appadurai A. Reproducing Jews: a cultural account of assisted conception in Israel. 1st ed. Durham: Duke University Press; 2000. 217 p.##Clarke M. Islam and new kinship: reproductive technology and the Shariah in Lebanon. New York: Berghahn Books; 2009. 220 p.##Eich T. Constructing kinship in Sunni Islamic legal texts. Islam and assisted reproductive technologies: Sunni and Shia perspectives. New York: Berghahn Books; 2012. 285 p.##Houlot S. Islamic Jurisprudence (Figh) and assisted reproduction: establishing limits to avoid social disorders. In: Inhorn MC, Tremayne S, editors. Islam and assisted reproductive technologies: Sunni and Shia perspectives. New York: Berghahn Books; 2012. p. 53-70.##Inhorn MC, Tremayne S. Islam and assisted reproductive technologies. 1st ed. New York: Berghahn Books; 2012. 285 p.##Ardekani ZB, Akhondi MM, Kamali K, Khalaf ZF, Eskandari S, Ghorbani B. Mental health status of patients attending avicenna infertility clinic. J Reprod Infertil. 2010;11(4):319-24.##Tremayne S, Akhondi MM. Conceiving IVF in Iran. Reprod Biomed Soc Online. 2016;2:62-70.##Tremayne S. The “down side” of gamete donation: challenging “happy family” rhetoric in Iran. Islam and assisted reproductive technologies: Sunni and Shia perspectives. 1st ed. New York: Berghahn. 2012. chapter 5. p. 130-56.##Hendriks S, Dondorp W, de Wert G, Hamer G, Repping S, Dancet EA. Potential consequences of clinical application of artificial gametes: a systematic review of stakeholder views. Hum Reprod Update. 2015;21(3):297-309.##Hermann BP, Sukhwani M, Winkler F, Pascarella JN, Peters KA, Sheng Y, et al. Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm. Cell Stem Cell. 2012;11(5):715-26.##Rafati M, Akhondi MM, Sadeghi MR, Tara SZ, Ghaffari SR. Preimplantation high-resolution HLA sequencing using next generation sequencing. Biol Blood Marrow Transplant. 2018;24(8):1575-80.##Brännström M, Johannesson L, Bokström H, Kvarnström N, Mölne J, Dahm-Kähler P, et al. Livebirth after uterus transplantation. Lancet. 2015;385(9968):607-16.##Donnez J, Dolmans MM, Pellicer A, Diaz-Garcia C, Serrano MS, Schmidt KT, et al. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation. Fertil Steril. 2013;99(6):1503-13.##Sadri-Ardekani H, Akhondi MA, van der Veen F, Repping S, van Pelt AM. In vitro propagation of human prepubertal spermatogonial stem cells. JAMA. 2011;305(23):2416-8.##Marina S, Marina D, Marina F, Fosas N, Galiana N, Jové I. Sharing motherhood: biological lesbian co-mothers, a new IVF indication. Hum Reprod. 2010;25(4):938-41.##Franssen MT, Musters AM, van der Veen F, Repping S, Leschot NJ, Bossuyt PM, et al. Reproductive outcome after PGD in couples with recurrent miscarriage carrying a structural chromosome abnormality: a systematic review. Hum Reprod Update. 2011;17(4):467-75.##Ardekani ZB, Akhondi MM, Sadeghi MR, Sadri-Ardekani H. The necessity of a comprehensive study on abortion in Iran. J Reprod Infertil. 2005;6(4):299-320.##Golombok S. Parenting in new family forms. Curr Opin Psychol. 2017;15:76-80.##Purewal S, van den Akker OB. Systematic review of oocyte donation: investigating attitudes, motivations and experiences. Hum Reprod Update. 2009;15(5):499-515.##Indekeu A, Dierickx K, Schotsmans P, Daniels K, Rober P, D'Hooghe T. Factors contributing to parental decision-making in disclosing donor conception: a systematic review. Hum Reprod Update. 2013;19(6):714-33.##Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21(4):411-26.##Behjati-Ardakani Z, Karoubi MT, Milanifar A, Masrouri R, Akhondi MM. Embryo donation in Iranian legal system: a critical review. J Reprod Infertil. 2015;16(3):130-7.##Al-Hasani S. Islamic consideration (in Suni school) regarding bioethics and ART (especially oocyte and embryo donation) and the law in Germany. Payesh. 2007;6(4):379-84.##Sadeghi Fasaei S, Erfanmanesh I. Methodological foundations of documentary research in the social sciences: a study of the impacts of modernization on the Iranian family. Strategy Culture. 2015;8(29):61-91.##Altorki S. Milk-kinship in Arab society: an unexplored problem in the ethnography of marriage. Ethnology. 1980;19(2):233-44.##Rahbari L. Milk kinship and the maternal body in Shia Islam. De Gruyter. 2020;6:4353.##Castells M. The rise of the network society. USA: John wiley & sons; 2011. 1990 p.##Behjati Ardakani Z, Akhondi MM, Milanifar AR, Modaberi Y, Chamani Tabriz L, Moeeni M, et al. Counseling, evaluation and screening of donor and recipient in third party reproduction and the mat-ching process. Payesh. 2007;6(4):443-51.##Behjati Ardakani Z, Abbasi Shavazi MJ, Shidfar F, Moeini M, Akhondi MM. The effect of ageing on natural and artificial reproduction. Payesh. 2007;6(4):331-45.##Abma JC. Fertility, family planning, and women's health: new data from the 1995 national survey of family growth. US: CDC; 1997. 101 p.##Braverman AM. Defining, understanding, and managing the complex psychological aspects of third-party reproduction. In: Saure MV, editor. Principles of oocyte and embryo donation. 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Inhibition of Fatty Acid Binding Protein 4 in Obese Male Mice Adversely Affects Reproductive Parameters 2 1 2 Background: As obesity is increasing worldwide, obese people use various methods to get rid of excess weight. BMS309403 (A drug) is a specific inhibitor of fatty acid binding protein 4. In this study, the effects of the BMS309403 on serum biochemical markers, testis tissue spermatogenesis and apoptotic markers were investigated in male mice. Methods: Balb/c mice (total=56, each group n=14) were divided into control, obese control, obese solvent and obese drug groups. The obese control, obese solvent and obese drug groups were fed on the high sucrose diet to lead to obesity. After the development of obesity, BMS309403 was orally administered to the obese drug group for six weeks. It was performed in testicular tissues (Johnson Score and apoptosis markers) and biochemical tests (total testosterone, sex hormone binding globulin, inhibin-B tests and free androgen index) were used to evaluate reproductive parameters. The p<0.05 was considered to indicate a statistical significance. Results: Serum fatty acid binding protein 4 levels were higher in obese control group and obese solvent group, compared to control (p<0.05) and obese drug groups (p<0.001). Serum total testosterone, free androgen index, inhibin-B, sex hormone binding globulin levels, testicular tissue B-cell lymphoma-2 expression level and Johnson Score parameters were lower in all obese groups compared with the control group. Inhibin-B levels and Johnson Score results were lower in obese drug group compared to other two obese groups (p<0.05). Conclusion: Contrary to expectations, the use of BMS309403 negatively affected male reproductive parameters. Negative changes in reproductive parameters may be a result of the increased lee index of obesity. 16 23 Tevfik T Balci Osmaniye Provincial Health Directorate, Public Health Laboratories Osmaniye Provincial Health Directorate, Public Health Laboratories Turkey balcitevfik86@gmail.com Rahim R Kocabas Department of KONUDAM Experimental Medicine Application and Research, Necmettin Erbakan University, Meram Department of KONUDAM Experimental Medicine Application and Research, Necmettin Erbakan University, Meram Turkey Gokhan G Cuce Department of Histology and Embryology, Faculty of Meram Medicine, Necmettin Erbakan University Department of Histology and Embryology, Faculty of Meram Medicine, Necmettin Erbakan University Turkey Mehmet M Akoz Department of Biochemistry, Faculty of Meram Medicine, Necmettin Erbakan University Department of Biochemistry, Faculty of Meram Medicine, Necmettin Erbakan University Turkey BMS309403Experimental obesityFatty acid binding proteinMale fertility impairmentMiceSide-effect 120097.pdf Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the global burden of disease study. Lancet. 2014;384(9945):766-81.##Palmer NO, Bakos HW, Fullston T, Lane M. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis. 2012;2(4):253-63.##Youngson NA, Whitelaw E. The effects of acquired paternal obesity on the next generation. Asian J Androl. 2011;13(2):195-6.##Kralisch S, Fasshauer M. Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease? Diabetologia. 2013;56(1):10-21.##Okada T, Hiromura M, Otsuka M, Enomoto S, Miyachi H. Synthesis of BMS-309403-related compounds, including [14C]BMS-309403, a radioligand for adipocyte fatty acid binding protein. Chem Pharm Bull (Tokyo). 2012;60(1):164-8.##Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007;447(7147):959-65.##Suhre K, Römisch-Margl W, De Angelis MH, Adamski J, Luippold G, Augustin R. Identification of a potential biomarker for FABP4 inhibition: The power of lipidomics in preclinical drug testing. J Biomol Screen. 2011;16(5):467-75.##Plocher TA, Powley TL. Maintenance of obesity following hypophysectomy in the obese hyperglycemic mouse (ob/ob). Yale J Biol Med. 1997;50(3):291-300.##Hilwani IN, Nasibah R, Nurdiana S, Norashirene MJ. Gonadotoxic and cytotoxic effect of induced obesity via monosodium glutamate on mus musculus testis cytoarchitecture and sperm parameter. Int J Agric Biosyst Eng. 2014;8(9):1000-3.##Lee CG, Da Silva CA, Dela Cruz CS, Ahangari F, Ma B, Kang MJ, et al. Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annu Rev Physiol. 2011;73:479-501.##Novelli EL, Diniz YS, Galhardi CM, Ebaid GM, Rodrigues HG, Mani F, et al. Anthropometrical parameters and markers of obesity in rats. Lab Anim. 2007;41(1):111-9.##Ritze Y, Bárdos G, D'Haese JG, Ernst B, Thurnheer M, Schultes B, et al. Effect of high sugar intake on glucose transporter and weight regulating hormones in mice and humans. PLoS One. 2014;9(7):e101702.##Al Kindi MK, Al Essry FS, Al Essry FS, Mula-Abed WA. Validity of serum testosterone, free androgen index, and calculated free testosterone in women with suspected hyperandrogenism. Oman Med J. 2012;27(6):471-4.##Cai WJ, Huang JH, Zhang SQ, Wu B, Kapahi P, Zhang XM, et al. Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans. PLoS One. 2011;6(12):e28835.##Yang R, Castriota G, Chen Y, Cleary MA, Ellsworth K, Shin MK, et al. RNAi-mediated germline knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice. Int J Obes (Lond). 2011;35(2):217-25. ##Hotamisligil GS, Bernlohr DA. Metabolic functions of FABPs - mechanisms and therapeutic implications. Nat Rev Endocrinol. 2015;11(10):592-605.##Makowski L, Brittingham KC, Reynolds JM, Suttles J, Hotamisligil GS. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity: Macrophage expression of aP2 impacts peroxisome proliferator-activated receptor γ and IκB kinase activities. J Biol Chem. 2005;280(13):12888-95.##Bourlier V, Bouloumie A. Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes Metab. 2009;35(4):251-60. ##Baar RA, Dingfelder CS, Smith LA, Bernlohr DA, Wu C, Lange AJ, et al. Investigation of in vivo fatty acid metabolism in AFABP/aP2(-/-) mice. Am J Physiol Endocrinol Metab. 2005;288(1): E187-93.##Uysal KT, Scheja L, Wiesbrock SM, Bonner-Weir S, Hotamisligil GS. Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology. 2000;141(9):3388-96.##Kasturi SS, Tannir J, Brannigan RE. The metabolic syndrome and male infertility. J Androl. 2009;29(3):251-9.##Pinilla L, Seoane LM, Gonzalez L, Carro E, Aguilar E, Casanueva FF, et al. Regulation of serum leptin levels by gonadal function in rats. Eur J Endocrinol. 1999;140(5):468-73.##Wang C, McDonald V, Leung A, Superlano L, Berman N, Hull L, et al. Effect of increased scrotal temperature on sperm production in normal men. Fertil Steril. 1997;68(2):334-9.##Chambers TJ, Richard RA. The impact of obesity on male fertility. Hormones (Athens). 2015;14(4): 563-8.##

The Effects of Ovarian Encapsulation on Morphology and Expression of Apoptosis-Related Genes in Vitrified Mouse Ovary 2 1 2 Background: The purpose of this study was to determine the effects of alginate hydrogel as a capsule to protect the ovary against possible detrimental effects of vitrification and warming on morphology and expression of apoptosis-related genes in the mouse ovary. Methods: In this experimental study, the ovaries from twenty-five female 8-week-old mice were divided into five groups of non-vitrified ovaries, vitrified ovaries, ovaries that were encapsulated with concentrations of 0.5, 0.75 and 1% of alginate hydrogel. The morphological study was performed using hematoxylin and eosin staining. Expression levels of apoptosis-associated genes were quantified in each group by real-time RT-PCR. The one-way ANOVA and post hoc test were used to analyze the data and values of p<0.05 were considered statistically significant. Results: The results of follicle count showed that the mean of total follicles in all groups was not significantly different. The average number of atretic follicles in vitrified and experimental groups significantly increased in comparison with the non-vitrified group (p=0.001). The results of the evaluation of apoptosis-related genes showed that the ratio of Bax/Bcl-2 in experimental groups 1 and 2 was significantly higher than the vitrified group and experimental group 3 (p=0.000). The expression level of caspase 3 gene was not significantly different among all groups. Conclusion: Ovarian encapsulation with used concentrations of alginate hydrogel failed to improve the morphology and molecular aspects of follicles and it was not able to better preserve the intact follicles of vitrified ovaries. However, morphological and molecular findings appear to improve with increasing alginate hydrogel concentration. 23 32 Atefeh A Shirazi Tehrani Gametogenesis Research Center, Kashan University of Medical Sciences Gametogenesis Research Center, Kashan University of Medical Sciences Iran Tahereh T Mazoochi Gametogenesis Research Center, Kashan University of Medical Sciences Gametogenesis Research Center, Kashan University of Medical Sciences Iran taherehmazoochi@gmail.com Maryam M Akhavan Taheri Anatomical Sciences Research Center, Kashan University of Medical Sciences Anatomical Sciences Research Center, Kashan University of Medical Sciences Iran Esmat E Aghadavood Department of Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences Department of Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences Iran Mojdeh M Salehnia مژده صالح نیا Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University Iran Alginate hydrogelMouseOvaryVitrification 120096.pdf Dittrich R, Maltaris T, Hoffmann I, Oppelt PG, Beckmann MW, Mueller A. Fertility preservation in cancer patients. Minerva Ginecol. 2010;62(1):63-80.##Fathi R, Rezazadeh Valojerdi M, Salehnia M, Ebrahimi B, SalmanYazdi R. Ovarian tissue transplantation: advantages, disadvantages and upcoming challenges (A review article). J Mazandaran Univ Med Sci. 2014;24(113):253-65.##Donnez J. Introduction: fertility preservation, from cancer to benign disease to social reasons: the challenge of the present decade. Fertil Steril. 2013;99(6):1467-8.##Abdollahi M, Salehnia M, Salehpour S, Ghorbanmehr N. Human ovarian tissue vitrification/warming has minor effect on the expression of apoptosis-related genes. Iran Biomed J. 2013;17(4):179-86.##Zhou XH, Wu YJ, Shi J, Xia YX, Zheng SS. Cryopreservation of human ovarian tissue: comparison of novel direct cover vitrification and conventional vitrification. Cryobiology. 2010;60(2):101-5.##Choi J, Lee B, Lee E, Yoon BK, Bae D, Choi D. Cryopreservation of ovarian tissues temporarily suppresses the proliferation of granulosa cells in mouse preantral follicles. Cryobiology. 2008;56(1):36-42.##Gandolfi F, Paffoni A, Brambilla EP, Bonetti S, Brevini TA, Ragni G. Efficiency of equilibrium cooling and vitrification procedures for the cryopreservation of ovarian tissue: comparative analysis between human and animal models. Fertil Steril. 2006;85 Suppl 1:1150-6.##Keros V, Xella S, Hultenby K, Pettersson K, Sheikhi M, Volpe A, et al. Vitrification versus controlled-rate freezing in cryopreservation of human ovarian tissue. Hum Reprod. 2009;24(7):1670-83.##Lee D, Ouhibi N, Battaglia D. Cryopreservation of ovarian tissue: banking reproductive potential for the future. Curr womens Health Rep. 2001;1(2):152-6.##Mazoochi T, Salehnia M, Valojerdi MR, Mowla SJ. Morphologic, ultrastructural, and biochemical identification of apoptosis in vitrified-warmed mouse ovarian tissue. Fertil Steril. 2008;90(4 Suppl):1480-6. ##Mazoochi T, Khamechian T, Ehteram M, Kashani HH. The effect of melatonin on expression of p53 and ovarian preantral follicle development isolated from vitrified ovary. Comp Clin Path. 2018;27(1):83-8.##Posillico S, Kader A, Falcone T, Agarwal A. Ovarian tissue vitrification: Modalities, challenges and potentials. Curr Womens Health Rev. 2010;6(4):352-66.##Huang H, Choi JK, Rao W, Zhao S, Agarwal P, Zhao G, et al. Alginate hydrogel microencapsulation inhibits devitrification and enables large‐volume low‐CPA cell vitrification. Adv Funct Mater. 2015;25(44):6839-50.##Abdi S, Salehnia M, Hosseinkhani S. Comparison of Survival and Developmental rates of Mouse Ovarian Follicles after Two- and Three-Dimensional Cultures. Pathobiol Res. 2013;16(2):51-63.##Brito IR, Lima IM, Xu M, Shea LD, Woodruff TK, Figueiredo JR. Three-dimensional systems for in vitro follicular culture: overview of alginate-based matrices. Reprod Fertil Dev. 2014;26(7):915-30.##Shikanov A, Zhang Z, Xu M, Smith RM, Rajan A, Woodruff TK, et al. Fibrin encapsulation and vascular endothelial growth factor delivery promotes ovarian graft survival in mice. Tissue Eng Part A. 2011;17(23-24):3095-104.##Akhavan Taheri M, Rezazadeh Valojerdi M, Ebrahimi B. Intramuscular autotransplantation of vitrified rat ovary encapsulated with hyaluronic acid hydrogel. Biopreserv Biobank. 2016;14(2):114-21.##Gao JM, Yan J, Li R, Li M, Yan LY, Wang TR, et al. Improvement in the quality of heterotopic allotransplanted mouse ovarian tissues with basic fibroblast growth factor and fibrin hydrogel. Hum Reprod. 2013;28(10):2784-93.##Caligioni CS. Assessing reproductive status/stages in mice. Curr Protoc Neurosci. 2009;48(1):A-4I.##Mofarahe ZS, Novin MG, Jafarabadi M, Salehnia M, Noroozian M, Ghorbanmehr N. Effect of human ovarian tissue vitrification/warming on the expression of genes related to folliculogenesis. 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Relationship Between Polycystic Ovarian Morphology and Ectopic Pregnancy 2 1 2 Background: The purpose of the current study was to investigate the presence of polycystic ovarian morphology (PCOM) in patients with ectopic pregnancy (EP) and to find out the value of sonographic appearance of ovaries on the earlier diagnosis of EP. Methods: In the current case-control study, thirty five patients with EP were recruited to evaluate ovarian sonographic morphology whereas 35 gestational age-matched women with healthy intrauterine pregnancy (IUP) were the controls. After ovarian sonography, ultrasound images were analyzed offline for ovarian area, ovarian volume, follicle number per cross section, and follicle distribution pattern. A questionnaire about the presence of hirsutism and menstrual irregularity prepared as well. Student's t-test or Mann-Whitney U test were used to compare continuous variables between 2 groups and categorical data were evaluated by using Chi-square or Fisher’s exact test, where appropriate. Multiple logistic regression was used to find out the risk factors for EP. Results: Mean gravidity and parity were significantly higher in the EP group compared to IUP group (p<0.05). PCOM was found to be significantly higher in the study group (51.4% vs. 20%, p=0.006). Logistic regression analysis showed that multiparity (OR=8.635; 95% CI, 1.653-45.104) and PCOM image on ultrasound (OR=19.081; 95% CI, 1.139-319.560) were found to be significantly associated with EP. Conclusion: PCOM is more prevalent among women diagnosed with EP. This study demonstrates that PCOM assessed by transvaginal ultrasound may reflect EP in women with EP suspicion and may therefore serve as a clinical marker to assess EP. 32 38 Sule S Ozel Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Turkey Mihriban M Alkan Department of Radiology, Zekai Tahir Burak Women's Health Education and Research Hospital Department of Radiology, Zekai Tahir Burak Women's Health Education and Research Hospital Turkey Aytekin A Tokmak Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Turkey aytekintokmak@gmail.com Aysegul A Oksuzoglu Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Turkey Melike M Kaya Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Turkey Yaprak Y Engin-Ustun Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital Turkey Ectopic pregnancyEstrogensHormonesParityPolycystic ovarian syndromeProgesterone 120098.pdf Park JE, Yuk JS, Cho IA, Baek JC, Lee JH, Park JK. Ectopic pregnancy incidence in the Republic of Korea in 2009-2015: a population-based cross-sectional study. Sci Rep. 2018;8(1):17308.##Marion LL, Meeks GR. Ectopic pregnancy: history, incidence, epidemiology, and risk factors. Clin Obstet Gynecol. 2012;55(2):376-86.##Jauniaux E, Jurkovic D. Ectopic pregnancy: 130 years of medical diagnostic challenges. BJOG. 2018;125(13):1672.##San Lazaro Campillo IS, Meaney S, O'Donoghue K, Corcoran P. Ectopic pregnancy hospitalisations: A national population-based study of rates, management and outcomes. Eur J Obstet Gynecol Reprod Biol. 2018;231:174-9.##Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12):2841-55.##Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 2012;97(1):28-38.e25.##Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.##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(5):575-92.##Pedersen T, Peters H. Follicle growth and cell dynamics in the mouse ovary during pregnancy. Fertil Steril. 1971;22(1):42-52.##Glanc P, Brofman N, Kornecki A, Abrams J, Farine D, Salem S. Visualization of the ovaries in early pregnancy by transvaginal sonography. J Obstet Gynaecol Can. 2007;29(3):228-31.##Parashi S, Moukhah S, Ashrafi M. Main risk factors for ectopic pregnancy: a case-control study in a sample of Iranian women. Int J Fertil Steril. 2014;8(2):147-54.##Wang J, Wei Y, Diao F, Cui Y, Mao Y, Wang W, et al. The association between polycystic ovary syndrome and ectopic pregnancy after in vitro fertilization and embryo transfer. Am J Obstet Gynecol. 2013;209(2):139.e1-9.##Murphy MK, Hall JE, Adams JM, Lee H, Welt CK. Polycystic ovarian morphology in normal women does not predict the development of polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(10):3878-84.##Nahuis MJ, Kose N, Bayram N, Van Dessel HJ, Braat DD, Hamilton CJ, et al. Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins. Hum Reprod. 2011;26(7):1899-904.##Zhang S, Lin H, Kong S, Wang S, Wang H, Wang H, et al. Physiological and molecular determinants of embryo implantation. Mol Aspects Med. 2013;34(5):939-80.##Horne AW, King AE, Shaw E, McDonald SE, Williams AR, Saunders PT, et al. Attenuated sex steroid receptor expression in fallopian tube of women with ectopic pregnancy. J Clin Endocrinol Metab. 2009;94(12):5146-54.##Daan NM, Koster MP, de Wilde MA, Dalmeijer GW, Evelein AM, Fauser BC, et al. Biomarker profiles in women with PCOS and PCOS offspring; a pilot study. PLoS One. 2016;11(11):e0165033.##Shao R, Feng Y, Zou S, Weijdegård B, Wu G, Brännström M, et al. The role of estrogen in the pathophysiology of tubal ectopic pregnancy. Am J Transl Res. 2012;4(3):269-78.##Hewitt SC, Li Y, Li L, Korach KS. Estrogen-mediated regulation of Igf1 transcription and uterine growth involves direct binding of estrogen receptor alpha to estrogen-responsive elements. J Biol Chem. 2010;285(4):2676-85.##Sindos M, Togia A, Sergentanis TN, Kabagiannis A, Malamas F, Farfaras A, et al. Ruptured ectopic pregnancy: risk factors for a life-threatening condition. Arch Gynecol Obstet. 2009;279(5):621-3.##Majhi AK, Roy N, Karmakar KS, Banerjee PK. Ectopic pregnancy--an analysis of 180 cases. J Indian Med Assoc. 2007;105(6):308-12.##

Exploring the Genetic Diversity of Isolated Hypogonadotropic Hypogonadism and Its Phenotypic Spectrum: A Case Series 2 1 2 Background: Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder being classified as Kallmann syndrome (KS). The present study was conducted to study the genotype and relative proportion of different genetic mutations in IHH and to assess its correlation with phenotype. Methods: Eleven consecutive subjects presenting to the Department of Endocrinology were retrospectively analyzed during May 2017 to December 2018 with IHH. Phenotypic features and hormonal studies were analyzed along with clinical exome by targeted gene sequencing (Next generation sequencing). Thirty-nine relevant genes were tested in the analysis. Results: Of the 11 patients studied, five had KS and six had nIHH. At diagnosis, mean chronological age was 25 years. There were associated anomalies in KS group including bimanual synkinesia (n=2), unilateral renal agenesis (n=1) and submucosal cleft palate (n=1). Absence or hypoplasia of the olfactory bulb/sulci was found in 4/5 patients with KS. Genetic mutations in KAL1, CHD7, FGFR1, GNRHR, PROKR2, HS6ST1 genes were found in nine of the eleven subjects. Of the five subjects with KS, two had mutations in KAL1 gene. Two siblings who had bimanual synkinesia had CHD7 mutation. The genotype of nIHH subjects (n=6) was more heterogeneous. Conclusion: This study analyzed the clinical, endocrinological, and genetic features in IHH patients. Detectable genetic mutations were seen in a large proportion of cases. A considerable heterogeneity was seen in the genotype with new variants detected. A definite correlation of phenotype-genotype was not possible, and significant overlap was seen between CHD7 and KAl1, and FGFR1 phenotypes. 38 47 Vijay VSR Danda Department of Endocrinology, Gandhi Medical College, Hospital Department of Endocrinology, Gandhi Medical College, Hospital India drdvsreddyendo@yahoo.com Srinivas SR Paidipelly Department of Endocrinology, Gandhi Medical College, Hospital Department of Endocrinology, Gandhi Medical College, Hospital India Madhavi M Verepula Department of Endocrinology, Gandhi Medical College, Hospital Department of Endocrinology, Gandhi Medical College, Hospital India Piyush P Lodha Department of Endocrinology, Gandhi Medical College, Hospital Department of Endocrinology, Gandhi Medical College, Hospital India Krishna KR Thaduri Department of Endocrinology, Gandhi Medical College, Hospital Department of Endocrinology, Gandhi Medical College, Hospital India Chaitanya C Konda Department of Endocrinology, Gandhi Medical College, Hospital Department of Endocrinology, Gandhi Medical College, Hospital India Apsia A Ruhi Department of Endocrinology, Gandhi Medical College, Hospital Department of Endocrinology, Gandhi Medical College, Hospital India AnosmiaGenetic mutationsHypogonadotropic hypogonadismKallmann syndromePhenotype-genotype 120095.pdf Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L, et al. Expert consensus document: European consensus statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11(9):547-64.##Lewkowitz-Shpuntoff HM, Hughes VA, Plummer L, Au MG, Doty RL, Seminara SB, et al. Olfactory phenotypic spectrum in idiopathic hypogonadotropic hypogonadism: pathophysiological and genetic implications. J Clin Endocrinol Metab. 2012;97(1):E136-44.##Sykiotis GP, Plummer L, Hughes VA, Au M, Durrani S, Nayak-Young S, et al. Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. Proc Natl Acad Sci USA. 2010;107(34):15140-4.##Dodé C, Levilliers J, Dupont JM, De Paepe A, Le Dû N, Soussi-Yanicostas N, et al. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003;33(4):463-5.##Costa-Barbosa FA, Balasubramanian R, Keefe KW, Shaw ND, Al-Tassan N, Plummer L, et al. Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes. J Clin Endocrinol Metab. 2013;98:E943-53.##Oliveira LM, Seminara SB, Beranova M, Hayes FJ, Valkenburgh SB, Schipani E, et al. The importance of autosomal genes in Kallmann syndrome: genotype- phenotype correlations and neuroendocrine characteristics. J Clin Endocrinol Metab. 2001;86(4):1532-8.##Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 2015;17(5):405-24.##Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 2016;44(D1):D862-8.##Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA. Online mendelian inheritance in man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 2005;33(Database issue):D514-7.##Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, et al. The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 2014;42(Database issue):D1001-6.##Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, et al. Human gene mutation database (HGMDR): 2003 update. Hum Mutat. 2003;21(6):577-81.##Mottaz A, David FP, Veuthey AL, Yip YL. Easy retrieval of single amino-acid polymorphisms and phenotype information using SwissVar. Bioinformatics. 2010;26(6):851-2.##1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68-74.##Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536(7616):285-91.##Nagasaki M, Yasuda J, Katsuoka F, Nariai N, Kojima K, Kawai Y, et al. Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals. Nat Commun. 2015;6:8018.##Ayers KL, Bouty A, Robevska G, van den Bergen JA, Juniarto AZ, Listyasari NA, et al. Variants in congenital hypogonadotrophic hypogonadism genes identified in an Indonesian cohort of 46, XYunder-virilised boys. Hum Genomics. 2017;11(1):1.##Bianco SD, Kaiser UB. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol. 2009;5(10):569-76.##Vizeneux A, Hilfiger A, Bouligand J, Pouillot M, Brailly-Tabard S, Bashamboo A, et al. Congenital hypogonadotropic hypogonadism during childhood: presentation and genetic analyses in 46 boys. PLoS One. 2013;8(10):e77827.##Abujbara MA, Hamamy HA, Jarrah NS, Shegem NS, Ajlouni KM. Clinical and inheritance profiles of Kallmann syndrome in Jordan. Reprod Health. 2004;1(1):5.##Quinton R, Duke V, de Zoysa P, Platts A, Valentine A, Kendall B, et al. 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Causes and Grounds of Childbirth Fear and Coping Strategies Used by Kurdish Adolescent Pregnant Women in Iran: A Qualitative Study 2 1 2 Background: Fear of childbirth is one of the most common problems among pregnant women that can threaten their and their baby’s health. Therefore, the purpose of this study was to explore the causes and grounds of childbirth fear and the strategies used by pregnant adolescent women in Iran to overcome such fears. Methods: In this study, which was conducted among primiparous Kurdish women in Iran, conventional qualitative content analysis was used. Data were selected through purposive sampling and semi-structured interviews. Data saturation was reached with 15 participants. The Lincoln and Guba criteria were used to strengthen the research. Results: After analyzing the data, two main categories were resulted. The first category was fear of childbirth with subcategories of fear of child health, fear of childbirth process, fears about inappropriate medical staff performance, fears about hospital environment, and postpartum fears. The second category was strategies to reduce childbirth fear with subcategories of choosing appropriate medical centers, increasing information on childbirth, avoiding stressful sources, improving self-care, getting prepared for delivery day in advance, and resorting to spirituality. Conclusion: Pregnancy in adult age is better than adolescent age. The women’s fear can be reduced by increasing their assurance about child health, providing appropriate training during pregnancy, explaining the whole process of childbirth and making it easier, improving the hospital environment and medical staff specialization, as well as providing appropriate conditions for further care and support after birth. 47 57 Javad J Yoosefi Lebni Department of Education and Health Promotion, School of Health, Iran University of Medical Sciences Department of Education and Health Promotion, School of Health, Iran University of Medical Sciences Iran Farideh F Khalajabadi Farahani Department of Population and Health, National Population Studies and Comprehensive Management Institute Department of Population and Health, National Population Studies and Comprehensive Management Institute Iran Mahnaz M Solhi Department of Education and Health Promotion, School of Health, Iran University of Medical Sciences Department of Education and Health Promotion, School of Health, Iran University of Medical Sciences Iran solhi.m@iums.ac.ir Farbod F Ebadifar Azar فربد عبادی‌فرآذر Department of Education and Health Promotion, School of Health, Iran University of Medical Sciences Department of Education and Health Promotion, School of Health, Iran University of Medical Sciences Iran f-ebadi@iums.ac.ir Adolescent pregnancyChildbirthFearQualitative study 120089.pdf Nour NM. 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Frequency of Sperm Aneuploidy in Oligoasthenoteratozoospermic (OAT) Patients by Comprehensive Chromosome Screening: A Proof of Concept 2 1 2 Background: Embryonic aneuploidy usually results in implantation failure and miscarriage. Considering significantly high frequency of sperm aneuploidy reported in oligoasthenoteratozoospermia (OAT) using fluorescence in situ hybridization (FISH) in limited number of chromosomes and lack of comprehensive chromosome screening (CCS) in OAT, the aim of this study was applying CCS in OAT sperm and comparison of the results with FISH findings. Methods: Five OAT patients with normal blood karyotypes and history of implantation failure were included. The successfully amplified samples, each containing two sperm, were analyzed by array comparative genomic hybridization (aCGH). FISH was utilized mainly depending on the aneuploidies found by aCGH to assess their frequencies in total sperm population. Results: In aCGH for 30 sperm, aneuploidy was found in 66% of samples. Following the study of 4300 sperm by FISH, an average of 55.46% aneuploidy was observed. No pregnancy was resulted with normal partners. Conclusion: Using aCGH, some abnormalities were observed that are not typically considered in sperm FISH studies. Despite small sample size of the comprehensive study, like other similar studies, the frequency of aneuploidies was considerable and similar to FISH. Aneuploidies revealed by aCGH at single sperm resolution were different from sperm population detected by FISH. Considering high frequency of aneuploidy in OATs sperm, preimplantation genetic testing for aneuploidy (PGT-A) can be used for in transfer of chromosomally normal embryos. 57 66 Parishad P Saei Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran Masood M Bazrgar Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran mbazrgar@royaninstitute.org Hamid H Gourabi Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran Roxana R Kariminejad Kariminejad-Najmabadi Pathology and Genetics Center Kariminejad-Najmabadi Pathology and Genetics Center Iran Poopak P Eftekhari-Yazdi Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran Mostafa M Fakhri Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran AneuploidyArray comparative genomic hybridizationFluorescenceIn situ hybridizationOligospermiaSpermatozoa 120090.pdf Singh R, Singh K. Male infertility: understanding, causes and treatment. 1st ed. Singapore: Springer; 2017. 497 p.##Martin RH, Ko E, Chan K. Detection of aneuploidy in human interphase spermatozoa by fluorescence in situ hybridization (FISH). Cytogenet Cell Genet. 1993;64(1):23-6.##Munné S, Chen S, Colls P, Garrisi J, Zheng X, Cekleniak N, et al, Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos. Reprod Biomed Online. 2007;14(5):628-34.##Templado C, Vidal F, Estop A. Aneuploidy in human spermatozoa. Cytogenet Genome Res. 2011;133(2-4):91-9.##Calogero AE, Burrello N, De Palma A, Barone N, D'Agata R, Vicari E. Sperm aneuploidy in infertile men. Reprod Biomed Online. 2003;6(3):310-7.##Piomboni, Paola, Anita Stendardi, and Laura Gambera. Chromosomal aberrations and aneuploidies of spermatozoa. In: Genetic damage in human spermatozoa. New York: Springer; 2014. p. 27-52.##Harton GL, Tempest HG. Chromosomal disorders and male infertility. Asian J Androl. 2012;14(1):32-9.##Rubio C, Gil-Salom M, Simon C, Vidal F, Rodrigo L, Minguez Y, et al. Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod. 2001;16(10):2084-92.##Pang MG, Hoegerman SF, Cuticchia AJ, Moon SY, Doncel GF, Acosta AA, et al. Detection of aneuploidy for chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 13, 17, 18, 21, X and Y by fluorescence in-situ hybridization in spermatozoa from nine patients with oligoasthenoteratozoospermia undergoing intracytoplasmic sperm injection. Hum Reprod. 1999;14(5):1266-73.##Pfeffer J, Pang MG, Hoegerman SF, Osgood CJ, Stacey MW, Mayer J, et al. Aneuploidy frequencies in semen fractions from ten oligoasthenoteratozoospermic patients donating sperm for intracytoplasmic sperm injection. Fertil Steril. 1999;72(3):472-8.##Patassini C, Garolla A, Bottacin A, Menegazzo M, Speltra E, Foresta C, et al. Molecular karyotyping of human single sperm by array-comparative genomic hybridization. PLoS One. 2013;8(4):e60922.##Garolla A, Sartini B, Cosci I, Pizzol D, Ghezzi M, Bertoldo A, et al. Molecular karyotyping of single sperm with nuclear vacuoles identifies more chromosomal abnormalities in patients with testiculopathy than fertile controls: implications for ICSI. Hum Reprod. 2015;30(11):2493-500.##Ghoraeian P, Mozdarani H, Aleyasin A, Alizadeh-Nili H. Frequency of sex chromosomal disomy in spermatozoa of normal and oligozoospermic Iranian patients and its effects on fertilisation and implantation rates after ICSI. Andrologia. 2013;45(1):46-55.##Mihajlović AI, FitzHarris G. Segregating chromosomes in the mammalian oocyte. Curr Biol. 2018;28(16):R895-907.##Nakhuda G, Jing C, Butler R, Guimond C, Hitkari J, Taylor E, et al. Frequencies of chromosome-specific mosaicisms in trophoectoderm biopsies detected by next-generation sequencing. Fertil Steril. 2018;109(5):857-65.##Fishel S, Craig A, Lynch C, Dowell K, Ndukwe G, Jenner L, et al. Assessment of 19,803 paired chromosomes and clinical outcome from first 150 cycles using array CGH of the first polar body for embryo selection and transfer. J Fertil In Vitro. 2011;1(1):1-8.##Vicari E, de Palma A, Burrello N, Longo G, Grazioso C, Barone N, et al. Absolute polymorphic teratozoospermia in patients with oligo‐asthenozoospermia is associated with an elevated sperm aneuploidy rate. J Androl. 2003;24(4):598-603.##Ferlin A, Garolla A, Foresta C. Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities. Cytogenet Genome Res. 2005;111(3-4):310-6.##Moemen MN, Mostafa T, Gadalla AM, Abbas M, Ismail HF, Abd El‐Hamid MF, et al. Sperm disomy in idiopathic severely oligoasthenoteratozoospermic males. Andrologia. 2008;40(6):381-6.##Burrello N, Arcidiacono G, Vicari E, Asero P, Di Benedetto D, De Palma A, et al. Morphologically normal spermatozoa of patients with secretory oligo-astheno-teratozoospermia have an increased aneuploidy rate. Hum Reprod. 2004;19(10):2298-302.##Tran QT, Jatsenko T, Poolamets O, Tšuiko O, Lubenets D, Reimand T, et al. Chromosomal scan of single sperm cells by combining fluorescence-activated cell sorting and next-generation sequencing. J Assist Reprod Genet. 2019;36(1):91-7.##Sha Y, Sha Y, Ji Z, Ding L, Zhang Q, Ouyang H, et al. Comprehensive genome profiling of single sperm cells by multiple annealing and looping‐based amplification cycles and next‐generation sequencing from carriers of robertsonian translocation. Ann Hum Genet. 2017;81(2):91-7.##Magli MC, Gianaroli L, Ferraretti AP, Gordts S, Fredericks V, Crippa A. Paternal contribution to aneuploidy in preimplantation embryos. Reprod Biomed Online. 2009;18(4):536-42.##Coates A, Hesla JS, Hurliman A, Coate B, Holmes E, Matthews R, et al. Use of suboptimal sperm increases the risk of aneuploidy of the sex chromosomes in preimplantation blastocyst embryos. Fertil Steril. 2015;104(4):866-72.##Rodrigo L, Meseguer M, Mateu E, Mercader A, Peinado V, Bori L et al, Sperm chromosomal abnormalities and their contribution to human embryo aneuploidy. Biol Reprod. 2019;101(6):1091-101.##

Successful Targeted Testicular Sperm Extraction Using Microsurgical Technique (microTESE) Following Fine Needle Aspiration (FNA) Mapping in a Non-Obstructive Azoospermia (NOA) Patient: A Case Report 2 1 2 Background: Management for male infertility can be difficult for some cases. Surgical intervention has long been thought as the last resort to help married couples to conceive. The current guideline recommends testicular sperm extraction with microsurgery technique (microTESE) in severe cases of male infertility. However, the success rate still varies. Thus, a new strategy was needed to further increase the sperm retrieval success rate. Case Presentation: A 39-year-old male with a history of failed sperm extraction, non-obstructive azoospermia (NOA) and Y-chromosomal microdeletion came to the fertility center to undergo sperm retrieval. Fine needle aspiration (FNA) Mapping was performed prior to microTESE to increase the accuracy of sperm retrieval. After further examination with laser assisted immotile sperm selection (LAISS), five spermatozoa were found. Conclusion: The combination of FNA Mapping and microTESE increases the chance of a successful sperm extraction. 65 70 Ponco P Birowo Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia Indonesia ponco.birowo@gmail.com William W Tendi Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia Indonesia Nur N Rasyid Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia Indonesia Paul PJ Turek The Turek Clinic The Turek Clinic USA Ivan I Sini Indonesian Reproductive Science Institute, Bunda General Hospital Indonesian Reproductive Science Institute, Bunda General Hospital Indonesia Muhammad M Rizal Indonesian Reproductive Science Institute, Bunda General Hospital Indonesian Reproductive Science Institute, Bunda General Hospital Indonesia FNA MappingLAISSmicroTESENOAY-chromosomal microdeletion 120091.pdf Jungwirth A, Diemer T, Kopa Z, Krausz C, Minhas S, Tournaye H. EAU guidelines on male infertility. 1st ed. The Netherlands: EAU Guidelines Office; 2018. 48 p.##Wein AJ, Kavoussi LR, Partin AW, Peters CA. Campbell-Walsh Urology. 11th ed. Philadelphia PA: Elsevier, Inc.; 2016. 596 p.##Salehi P, Derakhshan-Horeh M, Nadeali Z, Hosseinzadeh M, Sadeghi E, Izadpanahi MH, et al. Factors influencing sperm retrieval following testicular sperm extraction in nonobstructive azoospermia patients. Clin Exp Reprod Med. 2017;44(1):22-7.##Shah R, Gupta C. Advances in sperm retrieval techniques in azoospermic men: a systematic review. Arab J Urol. 2017;16(1):125-31.##Liu T, Song YX, Jiang YM. Early detection of Y chromosome microdeletions in infertile men is helpful to guide clinical reproductive treatments in southwest of China. Medicine (Baltimore). 2019;98(5):e14350.##Birowo P, Putra DE, Dewi M, Rasyid N, Taher A. Y-chromosomal microdeletion in idiopathic azoospermic and severe oligozoospermic Indonesian men. Acta Med Indones. 2017;49(1):17-23.##Jarvis S, Yee HK, Thomas N, Cha I, Prasad KC, Ramsay JW, et al. Sperm fine-needle aspiration (FNA) mapping after failed microdissection testicular sperm extraction (TESE): location and patterns of found sperm. Asian J Androl. 2018;21(1):50-5.##Ma Y, Li F, Wang L, Zhao W, Li D, Xian Y, et al. A risk prediction model of sperm retrieval failure with fine needle aspiration in males with non-obstructive azoospermia. Hum Reprod. 2019;34(2):200-8.##Verheyen G, Todorovic BP, Tournaye H. Processing and selection of surgical-retrieved sperm for ICSI: a review. Basic Clin Androl. 2017;27:6.##Beliveau ME, Turek PJ. The value of testicular ‘mapping’ in men with non-obstructive azoospermia. Asian J Androl. 2011;13(2):225-30.##Sabbaghian M, Meybodi AM, Rafaee A, Saba S, Zamanian M, Gilani MAS. Sperm retrieval rate and reproductive outcome of infertile men with azoospermia factor c deletion. Andrologia. 2018;50(7):e13052.##Aktan TM, Montag M, Duman S, Gorkemli H, Rink K, Yurdakul T. Use of a laser to detect viable but immotile spermatozoa. Andrologia. 2004;36(6):366-9.##

The First Livebirth Using Warmed Oocytes by a Semi-Automated Vitrification Procedure 2 1 2 Background: The first successful livebirth using warmed oocytes (vitrified by the GAVITM system) is reported in this paper. Embryologists throughout the world have vitrified oocytes using a manual technique which is susceptible to error and variation. In this era of automated laboratory procedures, vitrification was made semi-automatic by using the GAVITM system. Case presentation: Donor oocytes were initially vitrified using the GAVITM system. They remained in the clinic’s oocyte bank until they were allocated to the patient. Donor oocytes were warmed as per Genea BIOMEDX protocol and inseminated to create embryos. Resulting embryos for the 42-year-old patient were cultured to the blastocyst stage, biopsied to perform PGT-A, using next generation sequencing and subsequently vitrified. The patient underwent a single euploid transfer in a frozen embryo transfer cycle which resulted in a healthy livebirth. Conclusion: The introduction of a semi-automated system should minimize the risk to the oocytes, standardize the procedure worldwide and potentially reduce the laboratory time taken by the embryologists. This case report demonstrates the safety of the technology used for vitrification, but larger randomized studies need to be performed to demonstrate the safety and efficacy of newer technologies like the GAVITM system before adopting it as a standard laboratory procedure. 70 73 Xavier XO Brunetti The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health United Kingdom Suzanne S Cawood The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health United Kingdom Matthew M Gaunt The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health United Kingdom Wael W Saab The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health United Kingdom Paul P Serhal The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health United Kingdom Srividya S Seshadri The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health United Kingdom CryopreservationGAVITMOocytesPGT-ASemi-automated vitrification systemVitrification 120092.pdf Ho J, Woo I, Louie K, Salem W, Jabara S, Bendikson K, et al. A comparison of live birth rates and perinatal outcomes between cryopreserved oocytes and cryopreserved embryos. J Assist Reprod Genet. 2017;34(10):1359-66.##Smith GD, Serafini PC, Fioravanti J, Yadid I, Coslovsky M, Hassun P, et al. Prospective randomized comparison of human oocyte cryopreservation with slow-rate freezing or vitrification. Fertil Steril. 2010;94:2088-95.##Dyer C. Human error and systems failure caused IVF mix up. BMJ. 2004;328(7455):1518.##Thornhill A, Brunetti X, Bird S, Bennett K, Rios L, Taylor J. Reducing human error in IVF with electronic witnessing. Fertil Steril. 2011;96(3):S179.##Roy T, Brandi S, Tappe N, Bradley C, Vom E, Henderson C, et al. Embryo vitrification using a novel semi-automated closed system yields in vitro outcomes equivalent to the manual Cryotop method. Hum Reprod. 2014;29(11):2431-8.##Kuwayama M. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. Theriogenology. 2007;67(1):73-80.##Kuwayama M, Vajta G, Kato O, Leibo S. Highly efficient vitrification method for cryopreservation of human oocytes. Reprod Biomed Online. 2005;11(3):300-8.##

Obesity and Infertility: Persian Medicine Perspective 2 1 2 Dear Editor, We read enthusiastically the paper written by Bond et al. (1). In this retrospective cohort study, the efficacy of metabolic global approach has been evaluated in 127 obese (BMI ≥30 kg/m2) women. This investigation showed that lower BMI significantly improves the rate of pregnancy in obese women. Another recent study not only revealed that higher levels of physical activity are associated with reduced risk of fertility problems in women but also, once again, emphasized the negative impact of higher body mass index (BMI) on fertility (2). In this survey, which included 6130 women participated in The Australian Longitudinal Study on Women’s Health (ALSWH), those who were overweight had the hazard ratios (HR) of 1.18 (95% CI: 0.99-1.39) while this index was 1.36 (95% CI 1.14-1.63) in obese women. It is worth mentioning that about a millennium ago, Avicenna (980-1037 AD) has pointed out such associations in his feat, "The Canon of Medicine". In the third volume of his book, this Iranian physician addresses the causes of infertility in both sexes in details in "sexuality weakness" section. Avicenna mentions that the decrease in the quantity and quality of sperm/ovule which could happen due to various causes plays a crucial role in the male/female fertility (3). According to the Persian medicine which is one of the oldest comprehensive medical schools relying on humoral medicine and theory of temperaments (4), the process of reproductive cell production requires a normal temperament of the body organs (Especially vital organs, i.e., brain, heart, liver, and gonads). When there is excessive wet humor or wetness increase (The situation which is associated with increased BMI), the quantity and quality of sperm/ovule are negatively affected. Consequently, assisted reproduction techniques could be virtually ineffective, too (5, 6). In addition, this increase in wet humor negatively affects the digestive system of the patient, impairs the normal production of reproductive cells, and ultimately disrupts the sperm production in the testicles and the same happens in the female reproductive system (7-9). On the other hand, it should be kept in mind that the increase in wet humor or BMI could have a harmful effect on the vital body organs including heart which is also involved in blood and nutrients supply of the reproductive process (10, 11). Considering the holistic experiences in use of complementary and alternative medicines, applying Persian medicine as an integrative evidence-based approach could provide new promising horizons in the treatment of infertility. Conflict of Interest Authors declare no conflict of interest. 73 75 Mehdi M Pasalar Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences Iran Maryam M Mosaffa-Jahromi Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences Iran Sedigheh S Amooee Infertility Research Center, Shiraz University of Medical Sciences Infertility Research Center, Shiraz University of Medical Sciences Iran Babak B Daneshfard Traditional Medicine Clinical Trial Research Center, Shahed University Traditional Medicine Clinical Trial Research Center, Shahed University Iran babakdaneshfard@gmail.com No Keyword 60068.pdf Bond RT, Nachef A, Adam C, Couturier M, Kadoch IJ, Lapensée L, Bleau G, Godbout A. Obesity and Infertility: A Metabolic Assessment Strategy to Improve Pregnancy Rate. J Reprod Infertil. 2020;21(1):34-41.##Mena GP, Mielke GI, Brown WJ. Do physical activity, sitting time and body mass index affect fertility over a 15-year period in women? Data from a large population-based cohort study. Hum Reprod. 2020;35(3):676-83.##Avicenna. Al-Qanun fi al-Tibb (The Canon of Med-icine). 3rd ed. Tehran, Iran: Soroush Press; 2005. p. 228-35.##Atarzadeh F, Daneshfard B, Dastgheib L, Jaladat AM, Amin G. Early Description of Diet-Induced Blistering Skin Diseases in Medieval Persia: Avicenna's Point of View. Skinmed. 2016;14(5):367-70.##Parvizi MM, Salehi A, Nimroozi M, Hajimonfarednejad M, Amini F, Parvizi Z. The Relationship between Body Mass Index and Temperament, Based on the Knowledge of Traditional Persian Medicine. Iran J Med Sci. 2016;41(3 Suppl):S14.##Sohrabvand F, Mahroozade S, Bioos S, Nazari SM, Dabaghian FH. Improvement in Sperm Parameters With Traditional Iranian Remedy: A Case Report. J Evid Based Complementary Altern Med. 2017;22(2):223-6.##Daneshfard B, Jaladat AM. Male infertility and diet: a perspective of traditional persian medicine. Galen Med J. 2016;5(2):103-4.##Pasalar M, Nimrouzi M, Choopani R, Mosaddegh M, Kamalinejad M, Mohagheghzadeh A, Bagheri Lankarani K. Functional dyspepsia: A new approach from traditional Persian medicine. Avicenna J Phytomed. 2016;6(2):165-74.##Tahvilzadeh M, Hajimahmoodi M, Toliyat T, Karimi M, Rahimi R. An evidence-based approach to medicinal plants for the treatment of sperm abnormalities in traditional Persian medicine. Andrologia. 2016;48(8):860-79.##Daneshfard B, Jaladat AM, Sanaye MR, Dalfardi B. Cardiac Infertility in Persian Medicine: Avicenna’s View. Galen Med J. 2017;6(4):356-7.##Zohalinezhad ME, Zarshenas MM. Cardiovascular aspects of erectile dysfunction as outlined by Avicenna. Int J Cardiol. 2014;175(2):e33-4.##