Does Lack of Vertical Transmission of COVID-19 Guarantee the Health of the Fetus or Neonate in Infected Mothers? 2 1 2 Although in SARS-CoV-2 infection, the aged people as a high-risk group are exposed to respiratory and related systemic diseases, pregnant women should also be regarded as a high-risk population. This issue should be placed at the core of public health strategies focusing on prevention and treatment of SARS-CoV-2 infection. In COVID-19 outbreak, infected pregnant women appear to have fewer maternal and neonatal complications than those pregnant women infected with other respiratory viruses, such as H1N1 influenza and SARS-CoV and MERS-CoV. Infection of pregnant women with H1N1, SARS and MERS has been reported to be the cause of severe dysfunction of some organs and eventually death of mother and fetus. Having COVID-19 infection during the first or second trimester can lead to miscarriage, premature birth, birth defects and other congenital infections (1). Pregnant women need more attention due to physiological changes and their susceptibility to disease during the outbreak of COVID-19. Changes in the immune system, increased metabolism and oxygen consumption, cardiovascular changes and increased ACE2 expression during pregnancy are physiological causes making pregnant women susceptible to viral diseases (2). The placenta is a complex and unique organ with a critical function in proper growth and development of the fetus during pregnancy. The placenta acts like a heart, lung, liver and kidney for the fetus, and is a part of the innate immune system; its main role is to prevent the transmission of pathogens from mother to fetus. Syncytiotrophoblast cells, viz placental epithelial cells, act as a physical barrier against viruses and other infectious agents. SARS-CoV-2 infection causes inflammatory and vascular changes in the placenta including decidual arteriopathy, fibrinoid necrosis, and amniotic membrane arteriole hypertrophy (3). Altogether, the outcomes on fetus and neonates of infected mothers are largely unclear. However, SARS-CoV-2 is unlikely to be transmitted across the placenta but vertical transmission of some pathogens from mother to fetus can lead to serious complications and damage. Vertical infection can occur prenatal, per-partum or postnatal. Prenatal transfer has different consequences depending on the gestational age. The severity of fetal injuries is very high in the first trimester, while sometimes maternal infections in the second and third trimesters manifest with immunological symptoms or preterm labor. SARSCoV-2 is a highly pro-inflammatory infection that may cause similar changes in neonatal inflammation and immunity. The presence of IgM in fetus or umbilical cord is indicative of vertical transmission and subsequent intrauterine infection. Nevertheless, detection methods for IgM are prone to inaccuracies due to cross-reactivity with rheumatoid factors or non-specific IgM antibodies (4). There is always the possibility of the indirect negative effects of COVID-19 on the fetus of the infected mother through the maternal immune system. Maternal infection produces a broad immune response that is related to an inflammatory response associated with excessive secretion of cytokines (Cytokine storms) and severe activation of cellular immunity. Cytokine storm increases the levels of humoral proinflammatory compounds such as interleukin-6 (IL-6), interferon gamma (IFN-Y), MCP-1/CCL2, IL-1, IL-12, IL-8, TNFα, and CXCL 10 activates the maternal immune system and increases the pathogenesis of COVID-19. In addition, some of these cytokines can cross the placental barrier and stimulate inflammatory responses in the fetus, which may lead to damage of multiorgan system with negative effects on fetal development (5). According to one study, pregnant women with SARS-CoV-2 infection have higher levels of IL-6 than non-pregnant women; this increase in IL-6 levels subsequently activates a cascade of proinflammatory reactions that reduces synthesis of growth hormone and IGF-1 in the placenta. IGF-1 deficiency during uterine growth or after childbirth can cause autistic brain damage in the neonate. However, it is suggested that the role of IL-6 is determining in the pathogenesis of neurodevelopmental disorders. IL-6 has been considered as an indicator of maternal systemic inflammation with the potential to affect placental and fetal interactions, subsequent fetal brain development, and risk of psychiatric disorders. Therefore, it seems that maternal inflammation provides intrauterine conditions that are associated with potential psychiatric and neurological disorders (6). SARS-CoV-2 may indirectly lead to long term side effects on fetal neurodevelopment by affecting maternal immune activation (MIA). MIA and inflammation show a wide range of short-term and long-term adverse outcomes in neonates. In addition, the association between maternal immune activation-induced autism and schizophrenia has been well established through epidemiological studies and animal models (3). Therefore, the effect of this virus on people in different age, sex and ethnic groups and even on different organs of an infected person is unknown and every day new symptoms and complications of this disease are reported. Due to the lack of knowledge about its effects on the fetus, neonates, and infected mothers, pregnancy should be delayed as much as possible. At the same time, by conducting more studies, our knowledge can be consolidated regarding the short and long-term effects of this virus on both mother and fetus during pregnancy. Currently, published studies with small sample size are often performed on infected women at late phases of pregnancy (Third trimester). Therefore, special attention should be paid to early stages of pregnancy, during which the virus affects the placental functions with subsequent risks for the fetus. In addition, further research on the inflammatory disorders in pregnant women with SARS-CoV-2 and longitudinal studies on newborns, exposed to the virus directly or indirectly, are required to ensure proper care of infected pregnant women and their newborns. It seems the coronavirus will be with us for many years to come, and we need to know more about living with this unknown virus with maximum protection and suppress its harmful effects. 229 231 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 120088.pdf Qiancheng X, Jian S, Lingling P, Lei H, Xiaogan J, Weihua L, et al. Coronavirus disease 2019 in pregnancy. Int J Infect Dis. 2020;95:376-83.##Zhao X, Jiang Y, Zhao Y, Xi H, Liu C, Qu F, et al. Analysis of the susceptibility to COVID-19 in pregnancy and re-commendations on potential drug screening. Eur J Clin Microbiol Infect Dis. 2020;39(7):1209-20.##Prochaska E, Jang M, Burd I. COVID-19 in pregnancy: placental and neonatal involvement. Am J Reprod Immunol. 2020:e13306.##Lamouroux A, Attie-Bitach T, Martinovic J, Leruez-Ville M, Ville Y. Evidencenfor and against vertical transmission for severe acute respiratory syndrome Coronavirus 2. Am J Obstet Gynecol. 2020;223(1):91.e1-91.e4.##Stafstrom CE, Jantzie LL. COVID-19: neurological considerations in neonates and children. Children (Basel). 2020;7(9):E133.##Martins-Filho PR, Tanajura DM, Santos HP, Santos VS. COVID-19 during pregnancy: potential risk for neurodevelop-mental disorders in neonates? Eur J Obstet Gynecol Reprod Biol. 2020;250:255-6.##

Detailed Investigation of Downstream TLR Signaling in the Follicular Cells of Women with Endometriosis 2 1 2 Background: Inflammatory responses within the peritoneal cavity may result in endometrial dysfunction in women with endometriosis. The true causes of this disease remain poorly understood. It is hypothesized that downstream toll-like receptors (TLRs) inflammatory cytokines in response to pathogens may be associated with endometriosis. So, this study was aimed at evaluating the expression of TLRs signaling and endometriosis-associated inflammatory responses. Methods: Totally, 20 infertile endometriosis patients and 20 normal women undergoing controlled ovarian stimulation were enrolled. The cellular pellet and supernatant were obtained by centrifugation of follicular fluid (FF). Evaluation of TLRs and their signaling pathway gene expression was performed on cellular pellets using quantitative-PCR. The supernatant was used for determination of cytokine protein expression by ELISA. The results are expressed as mean±SEM and a p<0.05 was considered statistically significant. Results: Quantitative-PCR analysis suggested that TLR1, 5, 6, 7, 8, 10, MYD88, NF-ĸB, IL-10 and TGF-β genes expression significantly increased in patients compared to the control group (p<0.05). TLR3, 9, INF-β genes expression was significantly lower in endometriosis than control group (p<0.05). There was no significant difference in the expression of TLR2, TLR4, TIRAP, TRIF, TRAM, and IRF3 between two groups. Also, significant increase in the levels of IL-6, IL-8 and MIF protein in FF of endometriosis group was detected in comparison with normal women (p<0.05). Conclusion: The expression of TLR downstream signaling in the follicular cells can initiate inflammatory responses and changes in the FF cytokine profile which in turn may induce endometriosis and infertility disorder. 231 240 Reza R Jafari School of Medicine, Shahroud University of Medical Sciences School of Medicine, Shahroud University of Medical Sciences Iran Seyed Abdolvahab SA Taghavi Department of Gynecology and Obstetrics, School of Medicine, Yasuj University of Medical Sciences Department of Gynecology and Obstetrics, School of Medicine, Yasuj University of Medical Sciences Iran Elham E Amirchaghmaghi الهام امیرچقماقی Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran Reza R Salman Yazdi Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran Leili L Karimian 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 Mahnaz M Ashrafi مهناز اشرفی Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran Reza R Aflatoonian Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran r.aflatoonian@gmail.com EndometriosisFollicular cellsInfertilityInflammationTLR 100085.pdf Jones R. Bisphenol A and Bisphenol AF potentiate endometriosis differently based on hormonal status in female mice and disrupt normal ovarian function [dissertation]: [USA]: University of Cincinnati; 2018. 54 p.##Stilley JAW, Birt JA, Sharpe-Timms KL. Cellular and molecular basis for endometriosis-associated infertility. Cell Tissue Res. 2012;349(3):849-62.##Kajihara H, Yamada Y, Kanayama S, Furukawa N, Noguchi T, Haruta S, et al. New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal. Gynecol Endocrinol. 2011;27(2):73-9.##Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511-9.##Sidell N, Han SW, Parthasarathy S. Regulation and modulation of abnormal immune responses in endometriosis. Ann N Y Acad Sci. 2002;955:159-73.##Berbic M, Fraser I. Regulatory T cells and other leukocytes in the pathogenesis of endometriosis. J Reprod Immunol. 2011;88(2):149-55.##Ahn SH, Monsanto SP, Miller C, Singh SS, Thomas R, Tayade C. Pathophysiology and immune dysfunction in endometriosis. Biomed Res Int. 2015;2015:795976.##Latha M, Vaidya S, Movva S, Chava S, Govindan S, Govatati S, et al. Molecular pathogenesis of endometriosis; Toll-like receptor-4 A896G (D299G) polymorphism: a novel explanation. Genet Test Mol Biomarkers. 2011;15(3):181-4.##Khan KN, Kitajima M, Fujishita A, Nakashima M, Masuzaki H. Toll‐like receptor system and endometriosis. J Obstet Gynaecol Res. 2013;39(8):1281-92.##Redegeld FA, Yu Y, Kumari S, Charles N, Blank U. Non‐IgE mediated mast cell activation. Immunol Rev. 2018;282(1):87-113.##Amirchaghmaghi E, Taghavi SA, Shapouri F, Saeidi S, Rezaei A, Aflatoonian R. The role of toll like receptors in Pregnancy. Int J Fertil Steril. 2013;7(3):147-54.##McKernan DP. Toll-like receptors and immune cell crosstalk in the intestinal epithelium. AIMS Allergy Immunol. 2019;3(1):13.##Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003;21:335-76.##Jafari R, Aflatoonian R, Falak R, Pourmand G, Dehghani S, Mortazavi M, et al. Down-regulation of inflammatory signaling pathways despite up-regulation of Toll-like receptors; the effects of corticosteroid therapy in brain-dead kidney donors, a double-blind, randomized, controlled trial. Mol Immunol. 2018;94:36-44.##Kawai T, Akira S. TLR signaling. Semin Immunol. 2007;19(1):24-32.##Fazeli A, Bruce C, Anumba DO. Characterization of Toll-like receptors in the female reproductive tract in humans. Hum Reprod. 2005;20(5):1372-8.##Aflatoonian R, Tuckerman E, Elliott SL, Bruce C, Aflatoonian A, Li TC, et al. Menstrual cycle-dependent changes of Toll-like receptors in endometrium. Hum Reprod. 2007;22(2):586-93.##Aboussahoud W, Aflatoonian R, Bruce C, Elliott S, Ward J, Newton S, et al. Expression and function of Toll-like receptors in human endometrial epithelial cell lines. J Reprod Immunol. 2010;84(1):41-51.##Taghavi SA, Ashrafi M, Mehdizadeh M, Karimian L, Joghataie MT, Aflatoonian R. Toll-like receptors expression in follicular cells of patients with poor ovarian response. Int J Fertil Steril. 2013;8(2):183-92.##Gholamnezhadjafari R, Tajik N, Falak R, Aflatoonian R, Dehghan S, Rezaei A. Innate inflammatory gene expression profiling in potential brain-dead donors: detailed investigation of the effect of common corticosteroid therapy. Innate Immun. 2017;23(5):440-8.##Agic A, Xu H, Finas D, Banz C, Diedrich K, Hornung D. Is endometriosis associated with systemic subclinical inflammation? Gynecol Obstet Invest. 2006;62(3):139-47.##Zarmakoupis PN, Rier SE, Maroulis GB, Becker JL. Uterus and endometrium: inhibition of human endometrial stromal cell proliferation by interleukin 6. Hum Reprod. 1995;10(9):2395-9.##Rier SE, Zarmakoupis PN, Hu X, Becker JL. Dysregulation of interleukin-6 responses in ectopic endometrial stromal cells: correlation with decreased soluble receptor levels in peritoneal fluid of women with endometriosis. J Clin Endocrinol Metabol. 1995;80(4):1431-7.##[No authors listed]. Revised American society for reproductive medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817-21.##Rezazadeh Valojerdi M, Eftekhari-Yazd P, Karimian L, Hassani F, Movaghar B. Vitrification versus slow freezing gives excellent survival, post warming embryo morphology and pregnancy outcomes for human cleaved embryos. J Assist Reprod Genet. 2009;26(6):347-54.##Mönkkönen KS, Aflatoonian R, Lee KF, Yeung WS, Tsao SW, Laitinen JT, et al. Localization and variable expression of G alpha(i2) in human endometrium and fallopian tubes. Hum Reprod. 2007;22(5):1224-30.##Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.##Herreros-Villanueva M, Chen CC, Tsai EM, Er TK. Endometriosis-associated ovarian cancer: What have we learned so far? Clin Chim Acta. 2019;493:63-72.##Allhorn S, Böing C, Koch AA, Kimmig R, Gashaw I. TLR3 and TLR4 expression in healthy and diseased human endometrium. Reprod Biol Endocrinol. 2008;6:40.##Kyama CM, Overbergh L, Mihalyi A, Meuleman C, Mwenda JM, Mathieu C, et al. Endometrial and peritoneal expression of aromatase, cytokines, and adhesion factors in women with endometriosis. Fertil Steril. 2008;89(2):301-10.##Xu H, Schultze-Mosgau A, Agic A, Diedrich K, Taylor RN, Hornung D. Regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 in follicular fluid accumulate differentially in patients with and without endometriosis undergoing in vitro fertilization. Fertil Steril. 2006;86(6):1616-20.##Bedaiwy M, Shahin AY, AbulHassan AM, Goldberg JM, Sharma RK, Agarwal A, et al. Differential expression of follicular fluid cytokines: relationship to subsequent pregnancy in IVF cycles. Reprod Biomed Online. 2007;15(3):321-5.##Kats R, Collette T, Metz CN, Akoum A. Marked elevation of macrophage migration inhibitory factor in the peritoneal fluid of women with endometriosis. Fertil Steril. 2002;78(1):69-76.##Morin M, Bellehumeur C, Therriault MJ, Metz C, Maheux R, Akoum A. Elevated levels of macrophage migration inhibitory factor in the peripheral blood of women with endometriosis. Fertil Steril. 2005;83(4):865-72.##Carli C, Leclerc P, Metz CN, Akoum A. Direct effect of macrophage migration inhibitory factor on sperm function: possible involvement in endometriosis-associated infertility. Fertil Steril. 2007;88(4 Suppl):1240-7.##Xu X, Wang B, Ye C, Yao C, Lin Y, Huang X, et al. Overexpression of macrophage migration inhibitory factor induces angiogenesis in human breast cancer. Cancer Lett. 2008;261(2):147-57.##Beswick EJ, Reyes VE. Macrophage migration inhibitory factor and interleukin-8 produced by gastric epithelial cells during Helicobacter pylori exposure induce expression and activation of the epidermal growth factor receptor. Infect Immun. 2008;76(7):3233-40.##Soni UK, Chadchan SB, Kumar V, Ubba V, Khan MTA, Vinod BSV, et al. A high level of TGF-B1 promotes endometriosis development via cell migration, adhesiveness, colonization, and invasiveness. Biol Reprod. 2018;100(4):917-38.##Yang HL, Zhou WJ, Chang KK, Mei J, Huang LQ, Wang MY, et al. The crosstalk between endometrial stromal cells and macrophages impairs cytotoxicity of NK cells in endometriosis by secreting IL-10 and TGF-β. Reproduction. 2017;154(6):815-25.##Young VJ, Brown JK, Saunders PT, Duncan WC, Horne AW. The peritoneum is both a source and target of TGF-β in women with endometriosis. PloS one. 2014;9(9):e106773.##Young VJ, Ahmad S, Duncan WC, Horne AW. The role of TGF-β in the pathophysiology of peritoneal endometriosis. Hum Reprod Update. 2017;23(5):548-59.##da Silveira JC, Winger QA, Bouma GJ, Carnevale EM. Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-β signalling during follicle development in the mare. Reprod Fertil Dev. 2015;27(6):897-905.##

Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia 2 1 2 Background: Soluble fms-like tyrosine kinase 1 (sFlt-1) is believed to be a prominent component in the pathogenesis of pre-eclampsia, although the precise etiology has remained elusive. In this study, the etiological role of FLT1 variant was further validated in pre-eclampsia by examining this association in a Japanese sample population. Methods: The genotypes of three variants (rs4769613, rs12050029 and rs149427560) were examined in the upstream region of the FLT1 gene in placentas from pre-eclamptic (n=47) or normotensive control (n=49) pregnancy samples. Additionally, FLT1 mRNA levels in placenta were determined by qRT-PCR. ELISA was further used to detect circulating sFlt-1 levels in maternal sera. The intergroup comparisons were made using the Mann-Whitney U test or one way analysis of variance and P values of less than 0.05 were considered statistically significant. Results: First, the rs4769613 (C>T) and rs12050029 (G>A) genotypes were examined in placentas but no significant differences were found in the genotype or allele-type frequencies. Next, nearby short tandem repeat, rs149427560, was examined which manifested four size variants. In the genotypewise analysis, the frequency of the 474/476 heterozygote was significantly lower in pre-eclampsia (p<0.05). As expected, the FLT1 mRNA levels were significantly elevated in the pre-eclamptic placentas and sFlt-1 was higher in pre-eclamptic maternal sera. However, the genotype of these variants did not affect the FLT1 mRNA or serum sFlt-1 levels. Conclusion: Our findings did not support the hypothesis that genetic variations around the FLT1 gene affect the subtle expression changes underlying the etiologic pathway of pre-eclampsia. The hypothesis deserves further investigation through a larger sample size. 240 247 Akiko A Ohwaki Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Haruki H Nishizawa Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan nharuki@fujitahu.ac.jp Asuka A Kato Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Takema T Kato Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University Japan Jun J Miyazaki Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Hikari H Yoshizawa Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Yoshiteru Y Noda Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Yoshiko Y Sakabe Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Ryoko R Ichikawa Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Takao T Sekiya Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Takuma T Fujii Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Department of Obstetrics and Gynecology, Fujita Health University School of Medicine Japan Hiroki H Kurahashi Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University Japan FLT1PlacentaPre-eclampsiaShort tandem repeatSingle nucleotide variant 90089.pdf Lenfant C, National education program working group on high blood pressure in pregnancy. Working group report on high blood pressure in pregnancy. J Clin Hypertens (Greenwich). 2001;3(2):75-88.##Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension. 2005;46(6):1243-9.##Van Dijk M, Mulders J, Poutsma A, Könst AA, Lachmeijer AM, Dekker GA, et al. Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family. Nat Genet. 2005;37(5):514-9. ##Roten LT, Johnson MP, Forsmo S, Fitzpatrick E, Dyer TD, Brennecke SP, et al. Association between the candidate susceptibility gene ACVR2A on chromosome 2q22 and pre-eclampsia in a large Norwegian population-based study (the HUNT study). Eur J Hum Genet. 2009;17(2):250-7.##Yong HEJ, Murthi P, Brennecke SP, Moses EK. Genetic approaches in preeclampsia. Methods Mol Biol. 2018;1710:53-72.##McGinnis R, Steinthorsdottir V, Williams NO, Thorleifsson G, Shooter S, Hjartardottir S, et al. Variants in the fetal genome near FLT1 are associated with risk of preeclampsia. Nat Genet. 2017;49(8):1255-60.##Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649-58.##Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672-83.##Nishizawa H, Pryor-Koishi K, Kato T, Kowa H, Kurahashi H, Udagawa Y. Microarray analysis of differentially expressed fetal genes in placental tissue derived from early and late onset severe pre-eclampsia. Placenta. 2007;28(5-6):487-97.##Dixon JR, Jung I, Selvaraj S, Shen Y, Antosiewicz-Bourget JE, Lee AY, et al. Chromatin architecture reorganization during stem cell differentiation. Nature. 2015;518(7539):331-6.##Golkaram M, Jang J, Hellander S, Kosik KS, Petzold LR. The role of chromatin density in cell population heterogeneity during stem cell differentiation. Sci Rep. 2017;7(1):13307.##Patel P, Boyd CA, Johnston DG, Williamson C. Analysis of GAPDH as a standard for gene expression quantification in human placenta. Placenta. 2002;23(8-9):697-8.##Nishizawa H, Ota S, Suzuki M, Kato T, Sekiya T, Kurahashi H, et al. Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction. Reprod Biol Endocrinol. 2011;9:107.##Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001;357(9249):53-6.##Cross JC. The genetics of pre-eclampsia: a feto-placental or maternal problem? Clin Genet. 2003;64(2):96-103.##Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365(9461):785-99.##Medica I, Kastrin A, Peterlin B. Genetic polymorphisms in vasoactive genes and preeclampsia: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2007;131(2):115-26.##Kaartokallio T, Wang J, Heinonen S, Kajantie E, Kivinen K, Pouta A, et al. Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants. Sci Rep. 2016;6:29085.##Ota S, Miyamura H, Nishizawa H, Inagaki H, Inagaki A, Inuzuka H, et al. Contribution of fetal ANXA5 gene promoter polymorphisms to the onset of pre-eclampsia. Placenta. 2013;34(12):1202-10.##Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642-9.##Giannakou K, Evangelou E, Papatheodorou SI. Genetic and non-genetic risk factors for pre-eclampsia: umbrella review of systematic reviews and meta-analyses of observational studies. Ultrasound Obstet Gynecol. 2018;51(6):720-30.##Gray KJ, Saxena R, Karumanchi SA. Genetic predisposition to preeclampsia is conferred by fetal DNA variants near FLT1, a gene involved in the regulation of angiogenesis. 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Estrogenic Effect of Scoparia dulcis (Linn) Extract in Mice Uterus and In Silico Molecular Docking Studies of Certain Compounds with Human Estrogen Receptors 2 1 2 Background: Scoparia dulcis Linn. is reported to be used by women of Assam and Arunachal Pradesh in northeast India for treating menstrual disorders. Scoparia dulcis contains compounds that bind with estrogen receptors (ERα and ERβ) evidenced by increased PCNA in endometrial epithelium. Methods: Crude extract was orally administered at the dose of 500 mg/kg body weight/day to the female mice (60–70 days old) in five different groups. Each group containing six females included: (I) cyclic control, (II) cyclic extract treated, (III) Ovariectomized (OVX)-vehicle treated (Control), (IV) OVX-E2 treated (V) OVX- extract treated. Extract was administered for eight days to the cyclic groups and three days to the OVX groups. PCNA was detected immunohistochemically in uterine tiss ues and signals were analyzed by Image J software (NIH, USA). Compounds were separated by GC-MS and identified using NIST. In silico molecular docking studies was performed with human estrogen receptors (ERα and ERβ). Molecular dynamics (MD) simulations of the best interacting compound was done using gromacs. Results: The results showed cell proliferation in the uterine endometrium evidenced by PCNA. Two phytocompounds, Octadecanoic acid and methyl stearate showed binding affinity with ERα and ERβ. Conclusion: Scoparia dulcis contains compounds having binding affinity with ERα and ERβ. The present study is the first report on compounds from Scoparia dulcis showing binding affinity with human estrogen receptors which may have biological effect on female reproduction. 247 259 Khamhee K Wangsa Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar India Indira I Sarma Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar India isarma14@gmail. com Purbajyoti P Saikia Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar India Dhanabalan D Ananthakrishnan Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus India Hirendra HN Sarma Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar Department of Zoology, Rajiv Gandhi University, Rono Hills, Itanagar India Devadasan D Velmurugan Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus India EndometriumEstrogen receptorsIn silicoMenstrual disordersMolecular dockingPhytoestrogenScoparia dulcis (Linn) 120087.pdf Mishra MR, Mishra A, Pradhan DK, Behera RK, Jha S, Panda AK, et al. 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The Effect of Preincubation Time and Myo-inositol Supplementation on the Quality of Mouse MII Oocytes 2 1 2 Background: It is demonstrated that optimal preincubation time improves oocyte quality, fertilization potential and developmental rate. This study aimed to evaluate the effect of preincubation time in the simple and myo-inositol supplemented medium on the oocyte quality regarding oxidative stress and mitochondrial alteration. Methods: Cumulus oocyte complexes (COCs) retrieved from superovulated NMRI mice were divided in groups of 0, 4 and 8 hr preincubation time in the simple and 20 mmol/L myo-inositol supplemented media. Intracellular reactive oxygen species (H2O2), glutathione (GSH), mitochondrial membrane potential (MMP), ATP content, and mitochondrial amount were measured and analyzed in experimental groups. One-way ANOVA and Kruskal-Wallis were respectively used for parametric and nonparametric variables. Statistical significance was defined as p<0.05. Results: In comparison to control group, variables including ROS, GSH, mitochondrial amount, fertilization and developmental rates were significantly changed after 4 hr of preincubation in the simple medium, while MMP decreased following 8 hr of preincubation in the simple medium (p˂0.001). Preincubation of oocytes up to 8 hr in the simple medium could not decrease ATP content. For both 4 and 8 hr preincubation times, myo-inositole could decrease H2O2 and increase GSH and MMP levels and consequently could improve fertilization rate compared to oocytes preincubated in the simple culture. Conclusion: It seems that 4 hr or more preincubation time can decrease the oocyte quality and lead to reduced oocyte fertilization and developmental potential. Howevere, myo-inositol may prevent oocyte quality reduction and improve fertilization potential in comparision to the equivalent simple groups. 259 269 Fatemeh F Mohammadi Student Research Committee, School of Medicine, Iran University of Medical Sciences (IUMS) Student Research Committee, School of Medicine, Iran University of Medical Sciences (IUMS) Iran Mahnaz M Ashrafi مهناز اشرفی Shahid Akbar Abadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences (IUMS) Shahid Akbar Abadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences (IUMS) Iran Ashrafi.m@iums.ac.ir Zahra Z Zandieh Shahid Akbar Abadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences (IUMS) Shahid Akbar Abadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences (IUMS) Iran Zandieh.z@iums.ac.ir Mohammad M Najafi Biochemistry Department, School of Medicine, Iran University of Medical Sciences (IUMS) Biochemistry Department, School of Medicine, Iran University of Medical Sciences (IUMS) Iran Behrooz B Niknafs Anatomy Department, School of Medicine, Tabriz University of Medical Sciences Anatomy Department, School of Medicine, Tabriz University of Medical Sciences Iran Fatemeh Sadat FS Amjadi Anatomy Department, School of Medicine, Iran University of Medical Sciences (IUMS) Anatomy Department, School of Medicine, Iran University of Medical Sciences (IUMS) Iran Maryam M Haghighi Student Research Committee, School of Medicine, Iran University of Medical Sciences (IUMS) Student Research Committee, School of Medicine, Iran University of Medical Sciences (IUMS) Iran Developmental rateFertilization potentialMitochondrial alterationMyo-inositol supplementOocyte preincubation timeOocyte qualityOxidative stress 120086.pdf Irit G, Dekel N. 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Chromosomal Abnormalities in Couples with Primary and Secondary Infertility: Genetic Counseling for Assisted Reproductive Techniques (ART) 2 1 2 Background: World Health Organization estimates that 60-80 million couple worldwide currently suffer from infertility. Recurrent pregnancy loss (RPL) is also another major concern. Chromosomal rearrangements play a crucial role in primary and secondary infertility and RPL. Underlying genetic abnormalities like chromosomal abnormalities contribute to 5-10% of the reproductive failures. The aim of the study was to evaluate the chromosomal abnormalities in infertility and RPL cases to help obstetrician/fertility experts carry out risk assessment and provide appropriate assisted reproductive techniques for better management of the problem. Methods: Karyotyping was performed for 414 cases with the history of infertility and RPL over a period of one year. Samples were processed according to procedures of AGT cytogenetic laboratory manual. Results: Chromosomal abnormalities were observed in 15% of cases. Robertsonian translocation, reciprocal translocation, inversion, derivatives, marker chromosomes, mosaics, aneuploidy and polymorphic variants each contributed 2%, 3%, 3%, 13%, 2%, 10%, 6% and 61%, respectively. Conclusion: Evaluation of chromosomal abnormalities in couple is warranted prior to planning pregnancy especially for assisted reproductive management cases. Chromosomal analysis can be used as one of the diagnostic tools by OBG/IVF specialists in association with geneticist/genetic counselor for proper reproductive counseling and management. 269 275 Subhadra S Poornima Department of Genetics and Molecular Medicine, Kamineni Life Sciences, Moulali Department of Genetics and Molecular Medicine, Kamineni Life Sciences, Moulali India Subhadrapoornima1@gmail.com Swarnalatha S Daram Department of Genetics and Molecular Medicine, Kamineni Life Sciences, Moulali Department of Genetics and Molecular Medicine, Kamineni Life Sciences, Moulali India Rama RK Devaki Department of Biochemistry, Kamineni Academy of Medical Sciences and Research Centre Department of Biochemistry, Kamineni Academy of Medical Sciences and Research Centre India Hasan H Qurratulain Department of Genetics and Molecular Medicine, Kamineni Hospitals Department of Genetics and Molecular Medicine, Kamineni Hospitals India BandingCulturingHeterochromatinInfertilityInversionPolymorphismTranslocation 80080.pdf Vander Borght M, Wyns C. 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Cytogenetic abnormalities in 1162 couples with recurrent miscarriages in southern region of India: report and review. J Assist Reprod Genet. 2011;28(2):145-9.##Hanson B, Johnstone E, Dorais J, Silver B, Peterson CM, Hotaling J. Female infertility, infertility-associated diagnoses, and comorbidities: a review. J Assist Reprod Genet. 2017;34(2):167-77.##Arsham MS, Barch MJ, Lawce HJ, editors. The AGT cytogenetics laboratory manual. USA: John Wiley & Sons; 2017. 1103 p.##Patki A, Chauhan N. An epidemiology study to determine the prevalence and risk factors associated with recurrent spontaneous miscarriage in India. J Obstet Gynecol India. 2016;66(5):310-5.##Seidahmed MZ, Abdelbasit OB, Shaheed MM, Alhussein KA, Miqdad AM, Samadi AS, et al. Genetic, chromosomal, and syndromic causes of neural tube defects. Saudi Med J. 2014;35(Suppl 1):S49-56.##Hu Q, Chai H, Shu W, Li P. Human ring chromosome registry for cases in the Chinese population: re-emphasizing cytogenomic and clinical heterogeneity and reviewing diagnostic and treatment strategies. Mol Cytogenet. 2018;11(1):19.##Ghazaey S, Keify F, Mirzaei F, Maleki M, Tootian S, Ahadian M, et al. Chromosomal analysis of couples with repeated spontaneous abortions in northeastern iran. Int J Fertil Steril. 2015;9(1):47-54.##Kate UV, Pokale YS, Jadhav AM, Gangane SD. Chromosomal aberrations and polymorphic evaluation in males with primary infertility from Indian population. J Clin Diagn Res. 2014;8(10):SC01-6.##Mathur A, Stekol L, Schatz D, MacLaren NK, Scott ML, Lippe B. The parental origin of the single X chromosome in Turner syndrome: lack of correlation with parental age or clinical phenotype. Am J Hum Genet. 1991;48(4):682-6.##Skuse DH, James RS, Bishop DV, Coppin B, Dalton P, Aamodt-Leeper G, et al. Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function. 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Reproductive endocrinology and infertility. New York: Springer; 2010. p. 325-42.##Gardner RM, Sutherland GR, Shaffer LG. Chromosome abnormalities and genetic counseling. 4th ed. USA: Oxford university press; 2011. 511 p.##Li P, Pomianowski P, DiMaio MS, Florio JR, Rossi MR, Xiang B, et al. Genomic characterization of prenatally detected chromosomal structural abnormalities using oligonucleotide array comparative genomic hybridization. Am J Med Genet A. 2011;155A(7):1605-15.##Settin A, Abu-Saif IS, El-Baz R, Dowaidar M, Kasim RA, Shabana S. Diagnosis of sex chromosome disorders and prenatal diagnosis of down syndrome using interphase fluorescent in-situ hyperidization technique. Int J Health Sci (Qassim). 2007;1(2):203-9.##Kovaleva NV, Cotter PD. Somatic/gonadal mosaicism for structural autosomal rearrangements: female predominance among carriers of gonadal mosaicism for unbalanced rearrangements. Mol Cytogenet. 2016;9(1):8.##Baghbani F, Mirzaee S, Hassanzadeh-Nazarabadi M. Association of heteromorphism of chromosome 9 and recurrent abortion (ultrasound diagnosed blighted ovum): a case report. Iran J Reprod Med. 2014;12(5):357-60.##Sheth FJ, Liehr T, Kumari P, Akinde R, Sheth HJ, Sheth JJ. Chromosomal abnormalities in couples with repeated fetal loss: An Indian retrospective study. Indian J Hum Genet. 2013;19(4):415-22.##Sípek Jr A, Mihalová R, Panczak A, Hrčková L, Janashia M, Kaspříková N, et al. Heterochromatin variants in human karyotypes: a possible association with reproductive failure. Reprod Biomed Online. 2014;29(2):245-50.##Sahin FI, Yilmaz Z, Yuregir OO, Bulakbasi T, Ozer O, Zeyneloglu HB. Chromosome heteromorphisms: an impact on infertility. J Assist Reprod Genet. 2008;25(5):191-5.##

The Effects of In Vitro Incubation of Asthenoteratozoospermic Semen after Density Gradient Centrifugation at Room Temperature and 37oC on Sperm Parameters, Chromatin Quality and DNA Fragmentation in a Short Time Period 2 1 2 Background: Sperm quality is an important factor in assisted reproductive technology (ART) that affects the success rate of infertile couples treatment. In vitro incubation of sperm can influence its parameters and DNA integrity. The present study focused on the effect of different incubation temperatures sperm parameters on asthenoteratozoospermia semen prepared with density gradient centrifugation at different times. Methods: Twenty-seven samples were collected and prepared. Then, the suspension was divided into two parts. One part was incubated at room temperature (RT), and another was incubated at 37oC. Immediately and after 2 hr (2H) and 4 hr (4H), spermatozoa were evaluated regarding motility, viability, morphology, sperm protamine deficiency, chromatin and DNA fragmentation. Statistical analysis was performed using paired t-test and repeated measures. The p<0.05 was considered statistically significant. Results: Our results showed that following 2 and 4 hr of incubation at RT, sperm progressive motility and viability decreased significantly. Sperm DNA fragmentation increased significantly following 2 and 4 hr of incubation at RT and 37oC. The Trend analysis confirmed that there were no significant differences between sperm parameters and DNA fragmentation after different times at RT and 37oC. Conclusion: Incubation of sperm at RT in comparison to 37oC didn’t preserve sperm parameters and DNA efficiently. Therefore, IVF, ICSI and IUI procedure should be performed in the soonest possible time after sperm preparation. 275 283 Motahareh M Karimi Zarchi Department of Biology, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University Department of Biology, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University Iran Behnam B Maleki Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Iran Mahmood M Dehghani Ashkezari Department of Biology, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University Department of Biology, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University Iran Leila L Motamed Zadeh Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Iran Azam A Agha-Rahimi اعظم آقارحیمی Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Iran 63rahimi@gmail.com AsthenoteratozoospermiaDNA fragmentationIn vitro incubationRoom temperature 120085.pdf Elder K, Dale B. In-vitro fertilization. 3rd ed. Cambridge: Cambridge University Press; 2010. 252 p.##World health organization, department of reproductive health and research. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World health organization; 2010. 287 p.##Holmes E, Björndahl L, Kvist U. Post‐ejaculatory increase in human semen osmolality in vitro. Andrologia. 2019;51(7):e13311.##Ahmed I, Abdelateef S, Laqqan M, Amor H, Abdel‐Lah MA, Hammadeh ME, et al. Influence of extended incubation time on Human sperm chromatin condensation, sperm DNA strand breaks and their effect on fertilisation rate. Andrologia. 2018;50(4)e12960.##Çok T, Aytaç PÇ, Şimşek E, Haydardedeoğlu B, Kalaycı H, Özdemir H, et al. The effect of preserving prepared sperm samples at room temperature or at 37oC before intrauterine insemination (IUI) on clinical pregnancy rate. Turk J Obstet Gynecol. 2015;12(1):6-10.##Thijssen A, Klerkx E, Huyser C, Bosmans E, Campo R, Ombelet W, et al. Influence of temperature and sperm preparation on the quality of spermatozoa. Reprod Biomed Online. 2014;28(4):436-42.##Nabi A, Khalili MA, Halvaei I, Roodbari F. Prolonged incubation of processed human spermatozoa will increase DNA fragmentation. Andrologia. 2014;46(4):374-9.##Rougier N, Uriondo H, Papier S, Checa MA, Sueldo C, Sedó CA, et al. Changes in DNA fragmentation during sperm preparation for intracytoplasmic sperm injection over time. Fertil Stril. 2013;100(1):69-74.##Nagy ZP, Varghese AC, Agarwal A. In Vitro Fertilization: a textbook of current and emerging methods and devices. 2nd ed. switzerland: Springer; 2019. 947 p.##Bourne H, Archer J, Edgar DH, Gordon Baker HW. Sperm preparation techniques. In: Textbook of assisted reproductive techniques. US: CRC Press; 2012. p. 61-74.##Schuffner A, Morshedi M, Vaamonde D, Duran EH, Oehninger S. Effect of different incubation conditions on phosphatidylserine externalization and motion parameters of purified fractions of highly motile human spermatozoa. J Androl. 2002;23(2):194-201.##Chen MJ, Bongso A. Comparative evaluation of two density gradient preparations for sperm separation for medically assisted conception. Hum Reprod. 1999;14(3):759-64.##Talebi AR, Sarcheshmeh AA, Khalili MA, Tabibnejad N. Effects of ethanol consumption on chromatin condensation and DNA integrity of epididymal spermatozoa in rat. Alcohol. 2011;45(4):403-9.##Mangoli E, Talebi AR, Anvari M, Pourentezari M. Effects of experimentally-induced diabetes on sperm parameters and chromatin quality in mice. Iran J Reprod Med. 2013;11(1):53-60.##Gosálvez J, Rodríguez‐Predreira M, Mosquera A, López‐Fernández C, Esteves SC, Agarwal A, et al. Characterisation of a subpopulation of sperm with massive nuclear damage, as recognised with the sperm chromatin dispersion test. Andrologia. 2014;46(6):602-9.##Gallup Jr GG, Finn MM, Sammis B. On the origin of descended scrotal testicles: the activation hypothesis. Evolutionary psychology. 2009;7(4):147470490900700402.##Matsuura R, Takeuchi T, Yoshida A. Preparation and incubation conditions affect the DNA integrity of ejaculated human spermatozoa. Asian J Androl. 2010;12(5):753-9.##Guthrie HD, Welch GR. Effects of reactive oxygen species on sperm function. Theriogenology. 2012;78(8):1700-8.##Peer S, Eltes F, Berkovitz A, Yehuda R, Itsykson P, Bartoov B. Is fine morphology of the human sperm nuclei affected by in vitro incubation at 37° C? Fertil Steril. 2007;88(6):1589-94.##Agarwal A, Sharma R, Ahmad G. Sperm chromatin assessment. In: Textbook of assisted reproductive techniques. 5th ed. US: CRC Press; 2017. p. 65-87.##Irez T, Dayioglu N, Alagöz M, Karatas S, Güralp O. The use of aniline blue chromatin condensation test on prediction of pregnancy in mild male factor and unexplained male infertility. Andrologia. 2018;50(10):e13111.##Dadoune JP, Mayaux MJ, Guihard‐Moscato ML. Correlation between defects in chromatin condensation of human spermatozoa stained by aniline blue and semen characteristics: Beziehungen zwischen Defekten der chromatinkondensation menschlicher spermatozoen, die mittels anilinblau gefärbt wurden und spermacharakteristika. Andrologia. 1988;20(3):211-7.##Hassanen E, Elqusi K, Zaki H, Henkel R, Agarwal A. TUNEL assay: Establishing a sperm DNA fragmentation cut‐off value for Egyptian infertile men. Andrologia. 2019;51(10):e13375.##Liffner S, Pehrson I, García‐Calvo L, Nedstrand E, Zalavary S, Hammar M, et al. Diagnostics of DNA fragmentation in human spermatozoa: Are sperm chromatin structure analysis and sperm chromatin dispersion tests (SCD‐HaloSpermG2®) comparable? Andrologia. 2019;51(8):e13316.##Kumar D, Kalthur G, Mascarenhas C, Kumar P, Adiga SK. Ejaculate fractions of asthenozoospermic and teratozoospermic patients have differences in the sperm DNA integrity. Andrologia. 2011;43(6):416-21.##Delbès G, Herrero MB, Troeung ET, Chan PT. The use of complimentary assays to evaluate the enrichment of human sperm quality in asthenoteratozoospermic and teratozoospermic samples processed with Annexin‐V magnetic activated cell sorting. Andrology. 2013;1(5):698-706.##Pujol A, García D, Obradors A, Rodríguez A, Vassena R. Is there a relation between the time to ICSI and the reproductive outcomes? Hum Reprod. 2018;33(5):797-806.##

The Association Between Elevated Progesterone Level on Day of hCG Trigger and Live Birth Rates in ART Cycles: A Single Centre Observational Study 2 1 2 Background: The advent of ovarian stimulation within an in vitro fertilization (IVF) cycle has resulted in modifying the physiology of stimulated cycles and has helped optimize pregnancy outcomes. In this regard, the importance of progesterone (P4) elevation at time of human chorionic gonadotrophin (hCG) administration within an IVF cycle has been studied over several decades. Our study aimed to evaluate the association of P4 levels at time of hCG trigger with live birth rate (LBR), clinical pregnancy rate (CPR) and miscarriage rate (MR) in fresh IVF or IVF-ICSI cycles. Methods: This was a retrospective cohort study (n=170) involving patients attending the Centre for Reproductive and Genetic Health (CRGH) in London. The study cohort consisted of women undergoing controlled ovarian stimulation using GnRH antagonist or GnRH agonist protocols. Univariate and multiple logistic regression analyses were used to evaluate the association of clinical outcomes. Differences were considered statistically significant if p<0.05. Results: As serum progesterone increased, a decrease in LBR was observed. Following multivariate logistical analyses, LBR significantly decreased with P4 thresholds of 4.0 ng/ml (OR 0.42, 95% CI:0.17-1.0) and 4.5 ng/ml (OR 0.35, 95% CI:0.12-0.96). Conclusion: P4 levels are important in specific groups and the findings were statistically significant with a P4 threshold value between 4.0-4.5 ng/ml. Therefore, it seems logical to selectively measure serum P4 levels for patients who have ovarian dysfunction or an ovulatory cycles and accordingly prepare the individualized management packages for such patients. 283 291 Shahin Sh Robati Institute for Women’s Health, Faculty of Population Health Sciences, University College London Institute for Women’s Health, Faculty of Population Health Sciences, University College London United Kingdom s.robati.11@ucl.ac.uk Saab S Wiam Department of Obstetrics and Gynaecology, The American University of Beirut Medical Centre Department of Obstetrics and Gynaecology, The American University of Beirut Medical Centre Lebanon Montserrat M Durán-Retamal Institute for Women’s Health, Faculty of Population Health Sciences, University College London Institute for Women’s Health, Faculty of Population Health Sciences, University College London United Kingdom Wael W Saab Institute for Women’s Health, Faculty of Population Health Sciences, University College London Institute for Women’s Health, Faculty of Population Health Sciences, University College London United Kingdom Efstathios E Theodorou Institute for Women’s Health, Faculty of Population Health Sciences, University College London Institute for Women’s Health, Faculty of Population Health Sciences, University College London United Kingdom Suzanne S Cawood Institute for Women’s Health, Faculty of Population Health Sciences, University College London Institute for Women’s Health, Faculty of Population Health Sciences, University College London United Kingdom Paul P Serhal Institute for Women’s Health, Faculty of Population Health Sciences, University College London Institute for Women’s Health, Faculty of Population Health Sciences, University College London United Kingdom Srividya S Seshadri Institute for Women’s Health, Faculty of Population Health Sciences, University College London Institute for Women’s Health, Faculty of Population Health Sciences, University College London United Kingdom ARThCG triggerIn vitro fertilization (IVF)Live birth rate (LBR)Ovarian stimulationProgesterone elevation 110085.pdf Human fertility and embryology authority (HFEA). Fertility treatment 2014-2016 trends and figures. UK: Human fertility and embryology authority. 2018 Mar. 60 p.##Ecochard R, Bouchard T, Leiva R, Abdulla S, Dupuis O, Duterque O, et al. Characterization of hormonal profiles during the luteal phase in regularly menstruating women. Fertil Steril. 2017;108(1):175-82.e1.##Schoolcraft W, Sinton E, Schlenker T, Huynh D, Hamilton F, Meldrum DR. Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate. Fertil Steril. 1991;55(3):563-6.##Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone evaluation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60000 cycles. Hum Reprod. 2013;19(5):433-57.##Venetis CA, Kolibianakis EM, Bosdou JK, Lainas GT, Sfontouris IA, Tarlatzis BC, et al. Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles. Hum Reprod. 2015;30(3):684-91.##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(6):e100011.##Venetis CA, Kolibianakis EM, Papanikolaou E, Bontis J, Devroey P, Tarlatzis BC. Is progesterone elevation on the day of human chorionic gonadotrophin administration associated with the probability of pregnancy in in vitro fertilization? A systematic review and meta-analysis. Hum Reprod. 2007;13(4):343-55.##Kolibianakis EM, Venetis CA, Bontis J, Tarlatzis BC. Significantly lower pregnancy rates in the presence of progesterone elevation in patients treated with GnRH antagonists and gonadotrophins: a systematic review and meta-analysis. Curr Pharm Biotechnol. 2012;13(3):464-70.##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(8):1698-705.##Tsai YR, Huang FJ, Lin PY, Kung FT, Lin YJ, Lin YC, et al. Progesterone elevation on the day of human chorionic gonadotropin administration is not the only factor determining outcomes of in vitro fertilization. Fertil Steril. 2015;103(1):106-11.##Lawrenz B, Beligotti F, Engelmann N, Gates D, Fatemi HM. Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles. Hum Reprod. 2016;31 (11):2554-60.##Venetis CA, Kolibianakis EM, Bosdou JK, Lainas GT, Sfontouris IA, Tarlatzis BC, et al. Basal serum progesterone and history of elevated progesterone on the day of hCG administration are significant predictors of late follicular progesterone elevation in GnRH antagonist IVF cycles. Hum Reprod. 2016;31(8):1859-65.##Harbottle S, Hughes C, Cutting R, Roberts S, Brison D, Association of clinical embryologists & the (ACE) British fertility society (BFS). Elective single embryo transfer: an update to UK best practice guidelines. Hum Fertil (Camb). 2015;18(3):165-83.##Xiao J, Su C, Zeng X. Comparisons of GnRH antagonist versus GnRH agonist protocol in supposed normal ovarian responders undergoing IVF: a systematic review and meta-analysis. PLoS One. 2014;9(9):e106854.##Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016;4:CD001750.##Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod. 1992;7(10):1342-6.##Faddy MJ, Gosden RG. A model conforming the decline in follicle numbers to the age of menopause in women. Hum Reprod. 1996;11(7):1484-6.##Malizia BA, Hacker MR, Penzias AS. Cumulative live-birth rates after in vitro fertilisation. N Engl J Med. 2009;360(3):236-43.##Loendersloot LLV, Wely MV, Limpens J, Bossuyt PMM, Repping S, Veen FVD. Predictive factors in in vitro fertilisation (IVF): a systematic review and meta-analysis. Hum Reprod Upadate. 2010;16(6):577-89.##Vaegter KK, Lakic TG; Olovsson M, Berglund L, Brodin T, Holte J. Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers. Fertil Steril. 2017;107(3):641-8.e2.##Sunkara SK, Coomarasamy A, Faris R, Braude P, Khalaf Y. Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilisation: a randomized controlled trial. Fertil Steril. 2014;101(1):147-53.##

Evaluation of Sexual Function Among Infertile Women and Their Sexual Self-Concept 2 1 2 Background: The present study was designed to assess the association between sexual self-concept and sexual function in infertile women. Methods: A study with a convenience sample of women attending a referral infertility center (Royan Institute) was conducted in Tehran, Iran, in 2017. The Multidimensional Sexual Self-Concept Questionnaire (MSSCQ) and the Female Sexual Function Index (FSFI) were used to collect data. Chi-Square, t-test, Mann-Whitney U test and logistic regression were applied to analyze the data. The significance level was set at p<0.05. Results: The mean age of participants was 29.7±5.2 years. Overall, 152 women (60.8%) reported that they were experiencing sexual dysfunction. Comparing women with and without sexual dysfunction, there were significant differences between two groups on most measures such as sexual anxiety, sexual motivation, sexual satisfaction, and sexual depression (p<0.05). However, the results obtained from logistic regression indicated that women’s and husband’s age (OR for women’s age=1.26, 95% CI=1.10-1.44, p<0.001; OR for husband’s age=0.86, 95% CI=0.77-0.97, p=0.014), cause of infertility (OR for female factor=9.17, 95% CI=2.26-37.2, p=0.002; OR for male factor=3.90, 95% CI=1.26-12.1, p=0.018; OR for male and female factor=3.57, 95% CI=1.12-11.4, p=0.032), sexual motivation (OR=0.35, 95% CI=0.16-0.75, p=0.007) and sexual satisfaction (OR=0.23, 95% CI=0.09-0.56, p=0.001) were significantly associated with sexual dysfunction. Conclusion: The findings suggest that sexual motivation and sexual satisfaction are important dimensions of sexual self-concept in infertile women. Indeed, it is essential to inform policy makers and stakeholders to provide more sexual health support for this population in the process of treatment. 291 298 Hedyeh H Riazi Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences Iran Hajar H Lotfollahi Students Research Office, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences Students Research Office, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences Iran Reza R Omani-Samani Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine Iran Saman S Maroufizadeh Department of Biostatistics, School of Nursing and Midwifery, Guilan University of Medical Sciences Department of Biostatistics, School of Nursing and Midwifery, Guilan University of Medical Sciences Iran Ali A Montazeri Population Health Research Group, Health Metrics Research Center, Iranian Institute for Health Sciences Research, ACECR Population Health Research Group, Health Metrics Research Center, Iranian Institute for Health Sciences Research, ACECR Iran InfertilitySexual dysfunctionSexual healthSexual self-concept 90088.pdf Thomas HN, Thurston RC. 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Psychosocial aspects of infertility and its treatment. Ginekol Pol. 2016;87(7):527-31.##Akhondi MM, Kamali K, Ranjbar F, Shirzad M, Shafeghati S, Behjati Ardakani Z, et al. Prevalence of primary infertility in Iran in 2010. Iran J Public Health. 2013;42(12):1398-404.##Tayebi N, Yassini Ardakani SM. The prevalence of sexual dysfunctions in infertile women. Middle East Fertil Soc J. 2007;12(3):184-7.##Snell WE. The multidimensional sexual self-con-cept questionnaire. In: Davis CM, Yarber WL, Baurermen R, Schreer G, Davis SL, editors. Sexua-lity-related measures: A compendium. California: Sage Pub; 1998. p. 507-8.##Ramezani MA, Ghaemmaghami A, Talakar M, Saadat SH, Zamani E, Shams J, et al. Validity and reliability assessment of multi-dimensional sexual self-concept questionnaire for Iranian population. Iran J Mil Med. 2013;14(4):1-8.##Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, et al. 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Intra-individual Genomic Variation in Tissues (Blood vs. Testis) Through SNP Microarray: A Case report of Two Patients with Idiopathic Sertoli Cell Only Syndrome (SCOS) 2 1 2 Background: Sertoli cell only syndrome (SCOS) or germ cell aplasia is characterized by the existence of only sertoli cells in the seminiferous tubule without any germ cells. SCOS is a multifactorial disorder but genetic factors play a major role in pathogenesis of idiopathic SCOS. Case Presentation: Two cases of idiopathic SCOS had been reported with no non-genetic factor in their medical history that could play a role in aetiology of SCOS. Also, two normal fertile males were recruited as controls in this study. For evaluation of genomic imbalance, karyotyping (G-banding), FISH, STS-PCR and SNP microarray were carried out. SNP microarray was carried out in DNA of peripheral blood for cases as well as controls. However, for cases, SNP microarray was conducted in DNA of testicular Fine needle aspiration cytology (FNAC). Conclusion: No chromosome abnormality and Yq microdeletion was found in cases as well as in controls. Microarray detected many CNVs and LOH that cover genes with spermatogenesis related function and PAR CNVs in both cases. Differential genomic variations were found in blood and testis for cases. Therefore, the evaluation of pathogenesis of idiopathic SCOS might be dependent on both tissue samples. The evaluation of genomic imbalances at both tissue levels should be done for a large cohort of patients. 298 308 Aiyush A Sharma Department of Reproductive Biology, All India Institute of Medical Sciences Department of Reproductive Biology, All India Institute of Medical Sciences India Ashutosh A Halder Department of Reproductive Biology, All India Institute of Medical Sciences Department of Reproductive Biology, All India Institute of Medical Sciences India Seema S Kaushal Department of Pathology, All India Institute of Medical Sciences Department of Pathology, All India Institute of Medical Sciences India Manish M Jain Department of Reproductive Biology, All India Institute of Medical Sciences Department of Reproductive Biology, All India Institute of Medical Sciences India om_704@yahoo.co.in Copy number variationsLoss of heterozygositySertoli cell only syndromeSingle nucleotide polymorphisms 90087.pdf Del Castillo EB, Trabucco A, DE la Balze FA. 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A Novel De Novo Chromosomal Insertion, 46 XX, ins(7:13)(p14; q14.2q21.1) is Related to the Embryo Development Arrest Following Assisted Reproductive Technique 2 1 2 Background: Infertility is a problem affecting a large number of couples in the world. One of the causes of infertility can be chromosomal rearrangements such as insertions. In this case report study, the outcome of two intra-cytoplasmic sperm injection (ICSI) cycles of an infertile woman with de novo chromosomal insertion is explained. Case Presentation: A couple with a 10-year history of infertility referred to our infertility clinic. The husband had a daughter in his first previous marriage. The wife had a 7 and a 10 year history of infertility in the first and second marriages, respectively. In the first marriage, she reported a history of 2 failed intra-uterine insemination (IUI) cycles. In the second marriage, she had a history of 1 spontaneous abortion at 12 weeks of pregnancy, 4 failed IUI cycles, and 1 failed ICSI cycle. The couple was subjected to ICSI cycles twice and failed due to embryo development arrest. The couple referred for karyotyping. The husband showed a normal male karyotype. In comparison, the wife revealed an abnormal female karyotype with two rearrangements: chromosome 13 with an interstitial deletion between bands q14.2 and q21.1, and a derivative chromosome 7 containing this segment of chromosome 7 as an insertion onto short arm at the p14 position. Conclusion: To the best of our knowledge, this is the first report of insertion 46 XX, ins(7:13)(p14; q14.2q21.1) which is associated with the embryo development arrest following assisted reproductive technique. 308 312 Azam A Azargoon Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences Iran Nahid N Azad Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences Iran nazad1390@gmail.com Assisted reproductive techniqueChromosomal rearrangementCytogenetic analysisInfertility womanIVF failure 90085.pdf Shakoori AR, Aftab S, Al-Ghanim K. Structural Changes in Chromosomes. In: Bhat T, Wani A, editors. Chromosome Structure and Aberrations. New Delhi: Springer; 2017. p. 245-74.##Kurahashi H, Bolor H, Kato T, Kogo H, Tsutsumi M, Inagaki H, et al. Recent advance in our understanding of the molecular nature of chromosomal abnormalities. J Hum Genet. 2009;54(5):253-60.##Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kajita M, et al. Genomic characterization of chromosomal insertions: insights into the mechanisms underlying chromothripsis. Cytogenet Genome Res. 2017;53(1):1-9.##Mau-Holzmann UA. Somatic chromosomal abnormalities in infertile men and women. Cytogenet Genome Res. 2005;111(3-4):317-36.##Mierla D, Malageanu M, Tulin R, Albu D. Prevalence of chromosomal abnormalities in infertile couples in Romania. Balkan J Med Genet. 2015;18(1):23-30.##Setti AS, Figueira RC, de Almeida Ferreira Braga DP, Azevedo MC, Iaconelli A Jr, Borges E Jr. Oocytes with smooth endoplasmic reticulum clusters originate blastocysts with impaired implantation potential. Fertil Steril. 2016;106(7):1718-24.##Shaw-Jackson C, Thomas AL, Van Beirs N, Ameye L, Colin J, Bertrand E, et al. Oocytes affected by smooth endoplasmic reticulum aggregates: to discard or not to discard? Arch Gynecol Obstet. 2016;294(1):175-84.##Jansz N, Torres-Padilla ME. Genome activation and architecture in the early mammalian embryo. Curr Opin Genet Dev. 2019;55:52-8.‏##Wamaith SE, Niakan KK. Human pre-gastrulation development. Curr Top Dev Biol. 2018;128:295-338.##Carbone L, Chavez SL. Mammalian pre-implantation chromosomal instability: species comparison, evolutionary considerations, and pathological correlations. Syst Biol Reprod Med. 2015;61(6):321-35. ##Doheny KF, Rasmussen SA, Rutberg J, Semenza GL, Stamberg J, Schwartz M, et al. Segregation of a familial balanced (12; 10) insertion resulting in Dup(10)(q21. 2q22. 1) and Del (10)(q21. 2q22. 1) in first cousins. Am J Med Genet. 1997;69(2):188-93.##Kang SH, Shaw C, Ou Z, Eng PA, Cooper ML, Pursley AN, et al. Insertional translocation detected using FISH confirmation of array‐comparative genomic hybridization (aCGH) results. 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Infertility Distress Management in Couples Treated with Assisted Reproductive Techniques (ART) in COVID-19 Pandemic 2 1 2 The respiratory disease caused by a new coronavirus was first observed in Wuhan, Hubei Province, China in December 2019. The coronavirus disease (Covid-19) spread rapidly with human-to-human transmission around the world and raised global concerns, and it caused the World Health Organization (WHO) to consider it as a pandemic. Currently, the lives of many people around the world are affected by the crisis caused by the outbreak of Covid-19 disease, which despite efforts in many countries to reduce the risk and negative effects of this crisis, the damage and the resulting costs are increasing (1). This crisis may affect infertile couples, and it may have a negative impact on the mental health and all aspects of an individual’s life (2). Infertility is a disease of the genital tract that is characterized by a lack of pregnancy after twelve months or more of having a regular unprotected sex (3). The World Health Organization estimates that one in six couples will experience a delay in pregnancy, and that an increasing number will require treatment with assisted reproductive techniques. Statistically about 9% of couples all around the world will experience infertility during their lifetime (4). Infertility is one of the most stressful and sensitive experiences that threatens the stability of the individual, family, marriage and society, which will be more threatening in crisis situations (5). Assisted reproductive techniques (ARTs) are a common treatment of choice for many infertile couples due to male or female or idiopathic factors (6). There are various methods of mental disorders management in pregnant women such as CBT, acupuncture, and food supplements (7). For overcoming the stress during the outbreak of such diseases such as influenza and SARS, there are ways to manage such anxiety such as psychological intervention by using therapeutic dialogues, inducing hope, listening and support, social support and face-to-face counseling which should be offered by the health-care workers such as the nursing and medical staff (8). Due to the lack of information about the new coronavirus and its behaviors, various methods are used by infertility treatment centers. Some health centers recommend that patients who are undergoing a new IVF cycle or recently have started taking their relevant medications should continue their treatments. On the other hand, some associations in American, British and European societies all emphasize that due to the unknown effects of coronavirus on the fetus and pregnancy and considering emergency conditions for public health service providers, no fertility treatment cycle should be started at present. This means that no ovulation, IUI, fresh IVF or frozen embryo transfer cycles should be performed. Due to the decrease in number of visits and counseling with infertile couples in clinics, the mental health issues and the strategies for reducing distresses of infertile couples are of paramount importance. Since infertile couples are also more vulnerable to disease, it is important to pay attention to their health. Delays in fertility treatment during the Covid-19 pandemic can cause stress and anxiety and it’s completely understandable. Stress and anxiety can alter the balance of hormones needed for pregnancy. It can also affect the success of a couple's pregnancy in other ways (9-11). A review of literatures shows that currently couples are getting help by using a variety of methods, such as online counseling through social networks like Skype to receive virtual counseling, support, and assistance. Couples can also sign a consent form and, if necessary, receive their treatment protocol online at the patient's portal. If Covid-19 worries people about their treatment, talking to a fertility counselor, fertility coach and health care provider can help couples feel more in control of their life during this confusing period. Telemedicine and psychological support have established a good tool for ART specialists. Most fertility organizations recommended the use of such tools during the pandemic (9, 12). Lack of preparedness, stress, anxiety and failing to cope with this kind of crisis cause a lot of psychological damage to infertile couples, which is irreparable. Therefore, for distress management, health care providers can use a variety of safe methods such as online counseling, online supports, social networks, peer supports, thereby continuing treatment with a full explanation of the existing conditions and giving the right of choice to couples, especially for infertile couples who are being treated with assisted reproductive techniques (ARTs) in Covid-19 pandemic. Conflict of Interest Authors declare no conflict of interest. 312 314 Fatemeh F Hamidi M.Sc., Student of Midwifery Counseling, Student Research Committee, Department of Midwifery, Nasibeh School of Nursing and Midwifery, Mazandaran University of Medical Sciences M.Sc., Student of Midwifery Counseling, Student Research Committee, Department of Midwifery, Nasibeh School of Nursing and Midwifery, Mazandaran University of Medical Sciences Iran Farzaneh F Babapour M.Sc., Student of Midwifery Counseling, Student Research Committee, Department of Midwifery, Nasibeh School of Nursing and Midwifery, Mazandaran University of Medical Sciences M.Sc., Student of Midwifery Counseling, Student Research Committee, Department of Midwifery, Nasibeh School of Nursing and Midwifery, Mazandaran University of Medical Sciences Iran Zeinab Z Hamzehgardeshi Sexual and Reproductive Health Research Center, Department of Reproductive Health and Midwifery, School of Nursing and Midwifery, Mazandaran University of Medical Sciences Sexual and Reproductive Health Research Center, Department of Reproductive Health and Midwifery, School of Nursing and Midwifery, Mazandaran University of Medical Sciences Iran Z.hamzehgardeshi@mazums.ac.ir No Keyword 90086.pdf World Health Organization‎. Clinical management of COVID-19: interim guidance. Geneva: World Health Organization; 2020. 62 p.##Hamzehgardeshi Z, Yazdani F, Elyasi F, Moosazadeh M, Peyvandi S, Samadaee Galekolaee K, et al. Investigating the mental health status of infertile women. Int J Reprod Biomed (Yazd). 2019;17(4):293-4.##Trinchant RM, Cruz M, Marqueta J, Requena A. Infertility and reproductive rights after COVID-19 pandemic. Reprod Biomed Online. 2020;41(2):151-3.##Allot L, Payne D, Dann L. Midwifery and assisted reproductive technologies. N Zealand Coll Midwives J. 2013;47:10-3.##Hamzehgardeshi Z, Yazdani F, Elyasi F, Moosazadeh M, Peyvandi S, Gelehkolaee KS, et a;. The efficacy of groupcounselling on perceived stress among infertile women undergoing in vitro fertilization treatment: an RCT. Int J Reprod Biomed. 2019;17(1):57-66.##Vaiarelli A, Bulletti C, Cimadomo D, Borini A, Alviggi C, Ajossa S, et al. COVID-19 and ART: the view of the Italian society of fertility and sterility and reproductive medicine. Reprod Biomed Online. 2020;40(6):755-9.##van Ravesteyn LM, Lambregtse-van den Berg MP, Hoogendijk WJ, Kamperman AM. Interventions to treat mental disorders during pregnancy: A systematic review and multiple treatment meta-analysis. PLoS One. 2017;12(3):e0173397.##Cheng SK, Wong CW. Psychological intervention with sufferers from severe acute respiratory syndrome (SARS): lessons learnt from empirical findings. Clin Psychol Psychother. 2005;12(1):80-6.##de Souza MCB, Nakagawa H, Taitson PF, Cordts EB, Antunes RA. Management of ART and COVID-19: infertility in times of pandemic. What now? JBRA Assist Reprod. 2020;24(3):231-2. ##Vaiarelli A, Bulletti C, Cimadomo D, Borini A, Alviggi C, Ajossa S, et al. COVID-19 and ART: the view of the Italian society of fertility and sterility and reproductive medicine. Reprod Biomed Online. 2020;40(6):755-9. ##Rodriguez‐Wallberg KA, Wikander I. A global recommendation for restrictive provision of fertility treatments during the COVID‐19 pandemic. Acta Obstet Gynecol Scand. 2020;99(5):569-70.##World Health Organization. WHO consolidated guideline on self-care interventions for health: sexual and reproductive health and rights. Geneva: World Health Organization; 2019. 180 p.##