Coming Soon: Disclosing the Identity of Donors by Genealogical Tests of Donor Offspring 2 1 2 Globally, more than 7 million live births now result from IVF cycles so that more than 6% of the European births and especially in Denmark about 10% of children are conceived through ART. Compliant with this increment, the infertility treatment using third-party and its success rate are increasing during the past decades. At present, more than 16% of the total IVF cycles, more than 20% of all live births result from oocytes, sperm, embryo donation and gestational carriers in US, so that the third-party IVF cycles are the main infertility treatment for aged couples and the success rate of ART cycles is 39.7% in live birth for third-party compared to 29.6% for autologous cycles (1). The first sperm donation was performed in 1884 and the first donation of the oocyte was done almost one century later in 1983. Since that time, the most important aspects of third-party reproduction have always been the confidentiality in procedure and anonymity of donors. In that era, IVF clinics refused to disclose identity of donor and recommended to recipient couples not to disclose the usage of embryo or gamete donation to their children. Over the centuries, the same tendency and practice were common for adoption. Few parents left a child for adoption namelessly–so that the child and her/his adoptive couple had no data and background about abandoned child (2). Anonymity is a multifaceted concept which is rarely continual and absolute. Anonymity expresses the rights and privacy of both donors and recipients. However, every child has a right to identify their biological parents and it should be regarded that these children never submit a consent form for their everlasting anonymity, and most of them will try to find their genetic parent in the future. But the rights, interests and privacy of other players of this scene (parents and donors) should not be ignored. The widespread expansion of genetic databases is generally accompanied with the risk of identification of formerly anonymous donors. Voluntary DNA testing has been entirely common in recent years and so several huge genetic databases covering millions of genetic profiles are available worldwide. Although about 10 companies and websites collect biological samples and offer genealogy services, there is over 100 online DNA databases on medical DNA testing that most of them are available to community (3). The ease of access to DNA ancestry and genealogical tests will change the concept of anonymity so that even the privacy of people who did not register may be threatened through searching in these accessible genetic databases. It is obvious that adoption facilities and IVF clinics active in donation should urgently change their guidelines, procedures, documents and counseling with donors and recipients to remove the word "anonymous" and substitute it with phrases and content that precisely describe the new situation for possible identification of anonymous donors and donor-conceived children in the future more easily and rapidly. Accordingly, several countries such as Sweden as the pioneer and subsequently Austria, Finland, Iceland, Netherlands, Switzerland, UK, New Zealand and Australia removed donor anonymity. Following this change of approach, donation fee increased and the tendency to donation was slightly reduced and also the demography of donors has now shifted from young students to older men (2, 4). This legislation allowed donor-conceived children to apply for identification of their donor through the court at legal age. Although the goal of anonymity is to protect the right of the donor, but donors should understand the possible short and long-term consequences of their donated gift. Although IVF clinics can still claim to keep secret the information of their donors from recipients and donor-conceived offspring, but the clinics have no authority on future facilities and technologies that allow us to search for genetics identity of individuals (4). In this regard, the first DNA registry (UK donor link, UKDL) for all parties of donation (donor and donor offspring) was established in UK in 2004 for identification of each other through voluntary sharing of their complete data (5). In the current situation, without DNA testing, they can be identified through DNA matching of their relatives who had DNA testing. At present, age, sex, and contact information of everybody are enough to find their DNA data in genetic databases. This availability of DNA databases and genealogical tests enhances the risk to the accidental disclosure of donor or donor conceived children. Therefore, disclosure of biological heritage of donor conceived children is now considered a right in most countries. So many active groups support parents for disclosing the origin of donor conceived children at an early age to decrease the risk of accidental identification (2). Finally, the duty of IVF clinics is very significant in counseling and advising infertile couples and donors about the future potential risks and right of conceived donor children in confronting with biological and legal parents. They should be correctly advised on privacy violation of all parties in the era of DNA ancestry and genealogical testing. Therefore, the donors who cannot accept the potential risk in the future should not be the donors whatsoever. 119 121 Mohammad Reza MR Sadeghi محمدرضا صادقی Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran sadeghi@avicenna.ac.ir No Keyword 60053.pdf Kushnir VA, Darmon SK, Shapiro AJ, Albertini DF, Barad DH, Gleicher N. Utilization of third-party in vitro fertilization in the United States. Am J Obstet Gynecol. 2017;216(3):266.e1-266.e10.##Harper JC, Kennett D, Reisel D. The end of donor anonymity: how genetic testing is likely to drive nonymous gamete donation out of business. Hum Reprod. 2016:31(6):1135-40.##Forman I. Security risks of DNA testing. Comp 116: Security, December 12, 2018.##Borry P, Rusu O, Dondorp W, De Wert G Knoppers, BM, Howard HC. Anonymity 2.0: direct-to-consumer genetic testing and donor conception. Fertil Steril. 2014;101(3):630-2.##Van den Akker OB, Crawshaw MA, Blyth ED, Frith LJ. Expectations and experiences of gamete donors and donor-conceived adults searching for genetic relatives using DNA linking through a voluntary register. Hum Reprod. 2015;30 (1):111-21.##

Association of Sperm Aneuploidy Frequency and DNA Fragmentation Index in Infertile Men 2 1 2 Background: For improving the evaluation of male infertility, many parameters were studied and reported in earlier literature. The aim of this study was to estimate the frequency of sperm aneuploidy and DNA fragmentation in infertile men and to assess the correlation between sperm aneuploidy and DNA fragmentation. Methods: In this study 100 infertile men were included, cases with azoospermia were 68%, oligospermia 18%, severe oligospermia 6%, and oligoasthenoteratospermia (OAT) 8%. Ten normozoospermic men who had two normal children were included as a control. The sperm aneuploidy test by Fluorescence In Situ Hybridization (FISH) and sperm DNA fragmentation index by TdT (Terminal deoxynucleotidyl transferase)-mediated dUTP nick end labelling (TUNEL) were carried out. To determine the aneuploidy status and DNA fragmentation index, frequency was used. The correlation between sperm aneuploidy and sperm DNA fragmentation along with age was assessed by using Spearman's correlation coefficient. The p<0.05 was considered significant. Results: The age of 100 subjects ranged between 22-48 years (35.5±5.1). Sperm aneuploidy frequency and DNA fragmentation rate were found to be higher in infertile men compared to control men (n=10). There was a significant relationship between age and sex chromosomal aneuploidy (p<0.05) and significant difference between sperm aneuploidy and damaged DNA (p<0.05). Conclusion: FISH and TUNEL assay results showed increased sperm aneuploidy frequency, and DNA fragmentation index in infertile men compared with the fertile men. There is significant relationship observed between sperm aneuploidy and DNA fragmentation. These two parameters are important and they must be investigated for clinical practice. 121 127 Meenakshi M Arumugam KSHEMA Centre for Genetic Services, K. S. Hegde Medical Academy, Nitte University, Mangalore KSHEMA Centre for Genetic Services, K. S. Hegde Medical Academy, Nitte University, Mangalore India Deyyanthody DP Shetty KSHEMA Centre for Genetic Services, K. S. Hegde Medical Academy, Nitte University, Mangalore KSHEMA Centre for Genetic Services, K. S. Hegde Medical Academy, Nitte University, Mangalore India dprashanthshetty@gmail.com Jayarama JS Kadandale KSHEMA Centre for Genetic Services, K. S. Hegde Medical Academy, Nitte University, Mangalore KSHEMA Centre for Genetic Services, K. S. Hegde Medical Academy, Nitte University, Mangalore India Suchetha SN Nalilu KSHEMA Centre for Genetic Services, K. S. Hegde Medical Academy, Nitte University, Mangalore KSHEMA Centre for Genetic Services, K. S. Hegde Medical Academy, Nitte University, Mangalore India DNA fragmentationMale infertilitySperm aneuploidyTUNEL assay 60050.pdf Harton GL, Tempest HG. Chromosomal disorders and male infertility. Asian J Androl. 2012;14(1):32-9.##Di Santo M, Tarozzi N, Nadalini M, Borini A. Analysis of sperm DNA fragmentation and aneuploidy in 109 infertile patients: are the two parameters correlated? Gynecol Obstet Case Rep. 2016;2:2.##Rosalia Sa, Sousa M. Sperm aneuploidy and DNA integrity: a review. EMJ Repro Health. 2015;1(1):65-73.##Templado C, Uroz L, Estop A. New insights on the origin and relevance of aneuploidy in human spermatozoa. Mol Hum Reprod. 2013;19(10):634-43.##Carrell DT, Emery BR, Wilcox AL, Campbell B, Erickson L, Hatasaka HH, et al. Sperm chromosome aneuploidy as related to male factor infertility and some ultrastructure defects. Arch Androl. 2004;50 (3):181-5.##Muriel L, Goyanes V, Segrelles E, Gosalvez J, Alvarez J, Fernandez JL. Increased aneuploidy rate in sperm with fragmented DNA as determined by the sperm chromatin dispersion (SCD) test and FISH analysis. J Androl. 2007;28(1):38-49.##Perrin A, Louanjli N, Ziane Y, Louanjli T, Le Roy C, Gueganic N, et al. Study of aneuploidy and DNA fragmentation in gametes of patients with severe teratozoospermia. Reprod Biomed Online. 2011;22 (2):148-54.##Bernardini L, Borini A, Preti S, Conte N, Flamigni C, Capitanio GL, et al. Study of aneuploidy in normal and abnormal germ cells from semen of fertile and infertile men. Hum Reprod. 1998;13(12):3406-13.##Sarrate Z, Vidal F, Blanco J. Role of sperm fluorescent in situ hybridization studies in infertile patients: indications, study approach, and clinical relevance. Fertil Steril. 2010;93(6):1892-902.##Borini A, Tarozzi N, Bizzaro D, Bonu MA, Fava L, Flamigni C, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006;21(11):2876-81.##Wyrobek AJ, Eskenazi B, Young S, Arnheim N, Tiemann-Boege I, Jabs EW, et al. Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl Acad Sci USA. 2006;103(25): 9601-6.##Martin RH, Spriggs E, KO E, Rademaker AW. The relationship between paternal age, sex ratios, and aneuploidy frequencies in human sperm, as assessed by multicolor FISH. Am J Hum Genet. 1995;57(6):1395-9.##Ramasamy R, Scovell JM, Kovac JR, Cook PJ, Lamb DJ, Lipshultz LI. Fluorescence in situ hybridization detects increased sperm aneuploidy in men with recurrent pregnancy loss. Fertil Steril. 2015;103(4):906-9.##Aran B, Blanco J, Vidal F, Vendrell JM, Egozcue S, Barri PN, et al. Screening for abnormalities of chromosomes X, Y, and 18 and for diploidy in spermatozoa from infertile men participating in an in vitro fertilization intra cytoplasmic sperm injection program. Fertil Steril. 1999;72(4):696-701.##Moosani N, Pattinson HA, Carter MD, Cox DM, Rademaker AW, Martin RH. Chromosomal analysis of sperm from men with idiopathic infertility using sperm karyotyping and fluorescence in situ hybridization. Fertil Steril. 1995;64(4):811-7.##Singh NP, Muller CH, Berger RE. Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril. 2003;80(6):1420-30.##Sergerie M, Laforest G, Bujan L, Bissonnette F, Bleau G. Sperm DNA fragmentation: threshold value in male fertility. Hum Reprod. 2005;20(12):3446-51.##Brahem S, Mehdi M, Elghezal H, Saad A. Study of aneuploidy rate and sperm DNA fragmentation in large-headed, multiple-tailed spermatozoa. Andrologia. 2012;44(2):130-5.##Enciso M, Alfarawati S, Wells D. Increased numbers of DNA-damaged spermatozoa in samples presenting an elevated rate of numerical chromosome abnormalities. Hum Reprod. 2013;28(6):1707-15.##Balasuriya A, Speyer B, Serhal P, Doshi A, Harper JC. Sperm chromatin dispersion test in the assessment of DNA fragmentation and aneuploidy in human spermatozoa. Reprod Biomed Online. 2011;22(5):428-36.##

The Frequency of Chromosomal Euploidy Among 3PN Embryos 2 1 2 Background: The evaluation of embryo morphology is one of the most important parameters used to evaluate developmental timing, also providing an indication of chromosomal failure or degeneration. The first step in the evaluation of a fertilization event is determining the number and shape of the pronuclei (PN). Normally fertilized eggs possess two even PN. However, some embryos which develop from abnormally fertilized zygotes may be tri-pronuclear zygotes (3PN). Methods: Thirty embryos were collected from 12 women who underwent in vitro fertilization (IVF) at Dr. Cipto Mangunkusumo General Hospital in Jakarta, Indonesia. Embryos were cultured until the blastocyst stage on days 5-6. The blastomere biopsy was performed by piercing the zona pellucida with a laser under a microscope. Chromosomal numerical abnormalities were analyzed using Next Generation Sequencing (NGS). Results: Among the 30 embryos with 3PN zygotes, 33.3% had a normal chromosomal array, with 22 pairs of autosomes and 2 pairs of sex chromosomes. While the rest of sample population detected as abnormal chromosome (66.7%), with the highest percentage of abnormality was triploidy 43.3%, followed by mosaicism 13.4% and aneuploidy 10%. Conclusion: This was a preliminary study revealed not all morphologically 3PN embryos are genetically abnormal. 127 132 Kresna K Mutia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Indonesia Budi B Wiweko Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Indonesia budiwiweko@gmail.com Pritta PA Iffanolida Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Indonesia Ririn RR Febri Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Indonesia Naylah N Muna Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Indonesia Oki O Riayati Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Indonesia Shanty SO Jasirwan Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Indonesia Tita T Yuningsih Yasmin IVF Clinic, Dr. Cipto Mangunkusumo General Hospital Yasmin IVF Clinic, Dr. Cipto Mangunkusumo General Hospital Indonesia Eliza E Mansyur Yasmin IVF Clinic, Dr. Cipto Mangunkusumo General Hospital Yasmin IVF Clinic, Dr. Cipto Mangunkusumo General Hospital Indonesia Andon A Hestiantoro Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Human Reproductive, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia Indonesia AneuploidyEmbryoIVFMosaisicmPronucleus 60052.pdf Porter R, Han T, Tucker MJ, Graham J, Liebermann J, Sills ES. Estimation of second polar body retention rate after conventional insemination and intracytoplasmic sperm injection: in vitro observations from more than 5000 human oocytes. J Assist Reprod Genet. 2003;20(9):371-6.##Staessen C, Van Steirteghem AC. The chromosomal constitution of embryos developing from abnormally fertilized oocytes after intracytoplasmic sperm injection and conventional in-vitro fertilization. Hum Reprod. 1997;12(2):321-7.##Munne S, Cohen J. Chromosome abnormalities in human embryos. Hum Reprod Update. 1998;4(6):842-55.##Li M, Zhao W, Xue X, Zhang S, Shi W, Shi J. Three pro-nuclei (3PN) incidence factors and clinical outcomes: a retrospective study from the fresh embryo transfer of in vitro fertilization with donor sperm (IVF-D). Int J Clin Exp Med. 2015;8(8):13997-4003.##Grau N, Escrich L, Martin J, Rubio C, Pellicer A, Escriba MJ. Self-correction in tripronucleated human embryos. Fertil Steril. 2011;96(4):951-6.##Sachs AR, Politch JA, Jackson KV, Racowsky C, Hornstein MD, Ginsburg ES. Factors associated with the formation of triploid zygotes after intracytoplasmic sperm injection. Fertil Steril. 2000;73(6):1109-14.##Rosen MP, Shen S, Dobson AT, Fujimoto VY, McCulloch CE, Cedars MI. Triploidy formation after intracytoplasmic sperm injection may be a surrogate marker for implantation. Fertil Steril. 2006;85(2):384-90.##Montag M, Toth B, Strowitzki T. New approaches to embryo selection. Reprod Biomed Online. 2013;27(5):539-46.##Sallam HN, Sallam NH, Sallam SH. Non-invasive methods for embryo selection. Facts Views Vis Obgyn. 2016;8(2):87-100.##Rienzi L, Ubaldi F, Iacobelli M, Romano S, Minasi MG, Ferrero S, et al. Significance of morphological attributes of the early embryo. Reprod Biomed Online. 2005;10(5):669-81.##Kola I, Trounson A, Dawson G, Rogers P. Tripronuclear human oocytes: altered cleavage patterns and subsequent karyotypic analysis of embryos. Biol Reprod. 1987;37(2):395-401.##Chen Z, Yan J, Feng HL. Aneuploid analysis of tripronuclear zygotes derived from in vitro fertilization and intracytoplasmic sperm injection in humans. Fertil Steril. 2005;83(6):1845-8.##Macas E, Imthurn B, Rosselli M, Keller PJ. The chromosomal complements of multipronuclear human zygotes resulting from intracytoplasmic sperm injection. Hum Reprod. 1996;11(11):2496-501.##Dale B, DeFelice L. Polyspermy prevention: facts and artifacts? J Assist Reprod Genet. 2011;28(3):199-207.##Bianchi E, Wright GJ. Izumo meets Juno: preventing polyspermy in fertilization. Cell Cycle. 2014;13(13):2019-20.##Magli MC, Jones GM, Gras L, Gianaroli L, Korman I, Trounson AO. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Hum Reprod. 2000;15(8):1781-6.##Kaufman RA, Menezo Y, Hazout A, Nicollet B, DuMont M, Servy EJ. Cocultured blastocyst cryopreservation: experience of more than 500 transfer cycles. Fertil Steril. 1995;64(6):1125-9.##Janny L, Menezo YJ. Maternal age effect on early human embryonic development and blastocyst formation. Mol Reprod Dev. 1996;45(1):31-7.##Itoi F, Asano Y, Shimizu M, Honnma H, Murata Y. Birth of nine normal healthy babies following transfer of blastocysts derived from human single-pronucleate zygotes. J Assist Reprod Genet. 2015;32(9):1401-7.##Mateo S, Vidal F, Parriego M, Rodriguez I, Montalvo V, Veiga A, et al. Could monopronucleated ICSI zygotes be considered for transfer? Analysis through time-lapse monitoring and PGS. J Assist Reprod Genet. 2017;34(7):905-11.##Bradley CK, Traversa MV, Hobson N, Gee AJ, McArthur SJ. Clinical use of monopronucleated zygotes following blastocyst culture and preimplantation genetic screening, including verification of biparental chromosome inheritance. Reprod Biomed Online. 2017;34(6):567-74.##Feng H, Hershlag A. Fertilization abnormalities following human in vitro fertilization and intracytoplasmic sperm injection. Microsc Res Tech. 2003;61(4):358-61.##Feenan K, Herbert M. Can 'abnormally' fertilized zygotes give rise to viable embryos? Hum Fertil (Camb). 2006;9(3):157-69.##Yalcinkaya E, Ozay A, Ergin EG, Oztel Z, Ozornek H. Live birth after transfer of a tripronuclear embryo: An intracytoplasmic sperm injection as a combination of microarray and time-lapse technology. Turk J Obstet Gynecol. 2016;13(2):95-8.##

Association Between Sex Steroids and Oxidative Status with Vitamin D Levels in Follicular Fluid of Non-obese PCOS and Healthy Women 2 1 2 Background: Human follicular fluid (FF) is rich in hormones and antioxidants. Many components of FF differ in follicles of patients with polycystic ovary syndrome (PCOS). Regarding vitamin D effects on gene expression, 25(OH)D level of FF and its association with oxidative status and sex steroids dysregulation in PCOS group was evaluated and compared to controls of Non-obese healthy women. Methods: FF of 50 non-obese healthy women and 50 women with PCOS (18-36 years old) who were candidates for IVF/ICSI was aspirated on the oocyte retrieval day. Sex steroids and 25(OH)D levels were measured by ELISA. Reactive oxygen species (ROS) levels, total antioxidant capacity (TAC), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were assessed by chemiluminescence and spectrophotometric methods. Data were analyzed by unpaired t-test or Mann-Whitney test, and Pearson correlation coefficient. The p<0.05 was considered statistically significant. Results: Estradiol, progesterone, 25(OH)D, TAC, and activities of SOD, GPx, and CAT in FF of women with PCOS were significantly lower, whilst their free and total testosterone and ROS levels were significantly higher than controls. There were significant positive correlations between FF levels of 25(OH)D with TAC, estradiol and progesterone concentrations, SOD, GPx, and CAT activities. Negative correlations were found between 25(OH)D with free and total testosterone, and ROS levels. Conclusion: Despite different hormonal and antioxidant levels in FF of normal and cystic follicles, the correlation between 25(OH)D levels with sex steroids and oxidative stress markers showed a possible role of 25(OH)D in regulating sex hormones secretion and enhancement of antioxidant defense. 132 143 Fatemeh F Masjedi Department of Physiology, School of Medicine, Shiraz University of Medical Sciences Department of Physiology, School of Medicine, Shiraz University of Medical Sciences Iran Sara S Keshtgar Department of Physiology, School of Medicine, Shiraz University of Medical Sciences Department of Physiology, School of Medicine, Shiraz University of Medical Sciences Iran keshtgar@sums.ac.ir, keshtgars@yahoo.com Fatemeh F Agah Department of Physiology, School of Medicine, Shiraz University of Medical Sciences Department of Physiology, School of Medicine, Shiraz University of Medical Sciences Iran Narges N Karbalaei Department of Physiology, School of Medicine, Shiraz University of Medical Sciences Department of Physiology, School of Medicine, Shiraz University of Medical Sciences Iran Oxidative stressPolycystic ovarian syndromeSex steroid hormonesVitamin D 60047.pdf Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E, et al. 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Association between hypoadiponectinemia and low serum concentrations of calcium and vitamin D in women with polycystic ovary syndrome. ISRN Endocrinol. 2012;2012:949427.##Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR, Obermayer-Pietsch B. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol. 2011;164(5):741-9.##Ngo DT, Chan WP, Rajendran S, Heresztyn T, Amarasekera A, Sverdlov AL, et al. Determinants of insulin responsiveness in young women: impact of polycystic ovarian syndrome, nitric oxide, and vitamin D. Nitric Oxide. 2011;25(3):326-30.##Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, et al. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol. 2009;161(4):575-82.##Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S, et al. 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Lower limit of antioxidant activity in follicular fluid: relationship to embryo quality in IVF cycle. Int J Clin Exp Med. 2016;9(8):16346-52.##Bianchi L, Gagliardi A, Landi C, Focarelli R, De Leo V, Luddi A, et al. Protein pathways working in human follicular fluid: the future for tailored IVF? Expert Rev Mol Med. 2016;18:e9.##Ozkan S, Jindal S, Greenseid K, Shu J, Zeitlian G, Hickmon C, et al. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril. 2010;94(4):1314-9.##Velija-Asimi Z. Evaluation of the association of vitamin D deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome. Med Glas (Zenica). 2014;11(1):170-6.##Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7.##Lin H, Li Y, Li L, Wang W, Yang D, Zhang Q. Is a GnRH antagonist protocol better in PCOS patients? a meta-analysis of RCTs. PLoS One. 2014;9(3):e91796.##Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V. Method for the measurement of antioxidant activity in human fluids. J Clini Pathol. 2001;54(5):356-61.##Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247(10):3170-5.##Fecondo JV, Augusteyn RC. Superoxide dismutase, catalase and glutathione peroxidase in the human cataractous lens. Exp Eye Res. 1983;36(1):15-23.##Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-6.##Balen AH, Conway GS, Kaltsas G, Techatrasak K, Manning PJ, West C, et al. Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod. 1995;10(8):2107-11.##Goldzieher JW, Axelrod LR. Clinical and biochemical features of polycystic ovarian disease. Fertil Steril. 1963;14:631-53.##Voulgaris N, Papanastasiou L, Piaditis G, Angelousi A, Kaltsas G, Mastorakos G, et al. Vitamin D and aspects of female fertility. Hormones (Athens). 2017;16(1):5-21.##Irani M, Merhi Z. Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertil Steril. 2014;102(2):460-8.e3.##Teegarden D, Donkin SS. Vitamin D: emerging new roles in insulin sensitivity. Nutr Res Rev. 2009;22(1):82-92.##Fishel SB, Edwards RG, Walters DE. Follicular steroids as a prognosticator of successful fertilization of human oocytes in vitro. J Endocrinol. 1983;99(2):335-44.##Pellicer A, Valbuena D, Bauset C, Albert C, Bonilla-Musoles F, Remohi J, et al. The follicular endocrine environment in stimulated cycles of women with endometriosis: steroid levels and embryo quality. Fertil Steril. 1998;69(6):1135-41.##Eden JA, Jones J, Carter GD, Alaghband-Zadeh J. Follicular fluid concentrations of insulin-like growth factor 1, epidermal growth factor, transforming growth factor-alpha and sex-steroids in volume matched normal and polycystic human follicles. Clin Endocrinol (Oxf). 1990;32(4):395-405.##Naessen T, Kushnir MM, Chaika A, Nosenko J, Mogilevkina I, Rockwood AL, et al. Steroid profiles in ovarian follicular fluid in women with and without polycystic ovary syndrome, analyzed by liquid chromatography-tandem mass spectrometry. Fertil Steril. 2010;94(6):2228-33.##de Resende LO, dos Reis RM, Ferriani RA, Vireque AA, Santana LF, de Sa Rosa e Silva AC, et al. [Concentration of steroid hormones in the follicular fluid of mature and immature ovarian follicles of patients with polycystic ovary syndrome submitted to in vitro fertilization]. Rev Bras Ginecol Obstet. 2010;32(9):447-53. Portuguese.##Farzadi L, Khayatzadeh Bidgoli H, Ghojazadeh M, Bahrami Z, Fattahi A, Latifi Z, et al. Correlation between follicular fluid 25-OH vitamin D and assisted reproductive outcomes. Iran J Reprod Med. 2015;13(6):361-6.##Ganie MA, Marwaha RK, Nisar S, Farooqi KJ, Jan RA, Wani SA, et al. Impact of hypovitaminosis D on clinical, hormonal and insulin sensitivity parameters in normal body mass index polycystic ovary syndrome women. J Obstet Gynaecol. 2016;36(4):508-12.##Sadhir M, Kansra AR, Menon S. Vitamin D deficiency among adolescent females with polycystic ovary syndrome. J Pediatr Adolesc Gynecol. 2015;28(5):378-81.##Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-9.##Mishra S, Das AK, Das S. Hypovitaminosis D and associated cardiometabolic risk in women with PCOS. J Clin Diagn Res. 2016;10(5):Bc01-4.##Bedaiwy MA, Elnashar SA, Goldberg JM, Sharma R, Mascha EJ, Arrigain S, et al. Effect of follicular fluid oxidative stress parameters on intracytoplasmic sperm injection outcome. Gynecol Endocrinol. 2012;28(1):51-5.##Ambekar AS, Kelkar DS, Pinto SM, Sharma R, Hinduja I, Zaveri K, et al. Proteomics of follicular fluid from women with polycystic ovary syndrome suggests molecular defects in follicular development. J Clin Endocrinol Metab. 2015;100(2):744-53.##Pekel A, Gonenc A, Turhan NO, Kafali H. Changes of sFas and sFasL, oxidative stress markers in serum and follicular fluid of patients undergoing IVF. J Assist Reprod Genet. 2015;32(2):233-41.##Appasamy M, Jauniaux E, Serhal P, Al-Qahtani A, Groome NP, Muttukrishna S. Evaluation of the relationship between follicular fluid oxidative stress, ovarian hormones, and response to gonadotropin stimulation. Fertil Steril. 2008;89(4):912-21.##Yilmaz N, Inal HA, Gorkem U, Sargin Oruc A, Yilmaz S, Turkkani A. Follicular fluid total antioxidant capacity levels in PCOS. J Obstet Gynaecol. 2016;36(5):654-7.##Oyawoye OA, Abdel-Gadir A, Garner A, Leonard AJ, Perrett C, Hardiman P. The interaction between follicular fluid total antioxidant capacity, infertility and early reproductive outcomes during in vitro fertilization. Redox Rep. 2009;14(5):205-13.##Garg D, Grazi R, Lambert-Messerlian GM, Merhi Z. Correlation between follicular fluid levels of sRAGE and vitamin D in women with PCOS. J Assist Reprod Genet. 2017;34(11):1507-13.##Luddi A, Capaldo A, Focarelli R, Gori M, Morgante G, Piomboni P, et al. Antioxidants reduce oxidative stress in follicular fluid of aged women undergoing IVF. Reprod Biol Endocrinol. 2016;14(1):57.##Moy V, Fisher T, Neal-Perry G. Chronic vitamin d deficiency increases intra-ovarian oxidative stress. Fertil Steril. 2014;102(3):e138.##

Prediction of Responsiveness to Clomiphene Citrate in Infertile Women with PCOS 2 1 2 Background: The purpose of the study was to evaluate the role of clinical, metabolic, hormonal and ultrasound features of women with PCOS in predicting the response to clomiphene citrate in treatment of infertility. Methods: A prospective observational study was done over a period of one year. A total of 164 women with PCOS related infertility were enrolled. They were treated with an incremental dose of clomiphene citrate starting with 50 mg/day to a maximum of 150 mg over 3 cycles. The response was recorded as either presence or absence of ovulation. Multiple logistic regression was used to analyze various clinical, metabolic, hormonal and ultrasound features in these women. Sensitivity and specificity of each of these parameters in predicting non-responsiveness (failure to ovulate with 150 mg clomiphene) were calculated. Results: Ferriman-Gallwey score, androstenedione levels, HDL, and cholesterol were found to be the independent predictors of non-responsiveness to clomiphene citrate. The overall best predictor of non-responsiveness to clomiphene citrate is Ferriman- Gallwey score (FG). FG score, with a cut off value of 15, had 73.9% sensitivity and 86.8% specificity in predicting non-responsiveness to clomiphene. BMI was the best anthropometric predictor of the non-responsiveness to clomiphene. Fasting insulin was the best metabolic predictor of the non-responsiveness to clomiphene. AFC was the best ovarian reserve marker as the predictor of the non-responsiveness to clomiphene (cut-off value of 11.75 with 73.9% sensitivity and 73.7% specificity). Conclusion: Ferriman-Gallwey score, androstenedione levels, and lipid profile are clinically useful parameters to predict which groups of PCOS women are unlikely to respond to clomiphene. 143 151 Garima G Sachdeva Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research India gsachdeva25@gmail.com Shalini Sh Gainder Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research India Vanita V Suri Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research India Naresh N Sachdeva Department of Endocrinology, Post Graduate Institute of Medical Education and Research Department of Endocrinology, Post Graduate Institute of Medical Education and Research India Aronieh A Chopra آرونیه چوپرا Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research India Anti- mullerian hormoneBody Mass IndexClomipheneHyperandrogenismPolycystic ovarian syndrome 60049.pdf Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370(9588):685-97.##Broekmans F, Knauff EA, Valkenburg O, Laven JS, Eijkemans MJ, Fauser B. PCOS according to the Rotterdam consensus criteria: change in prevalence among WHO‐II anovulation and association with metabolic factors. BJOG. 2006;113(10):1210-7.##Hughes E, Collins J, Vandekerckhove P. Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea. Cochrane Database Syst Rev. 2000;(2):CD000056.##Radosh L. Drug treatments for polycystic ovary syndrome. Am Fam Physician. 2009;79(8):671-6.##Wang L, Qi H, Baker PN, Zhen Q, Zeng Q, Shi R, et al. Altered circulating inflammatory cytokines are associated with anovulatory polycystic ovary syndrome (PCOS) women resistant to clomiphene citrate treatment. Med Sci Monit. 2017;23:1083-9.##Parsanezhad ME, Alborzi S, Zarei A, Dehbashi S, Omrani G. Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin. Int J Gynaecol Obstet. 2001;75(1):43-50.##Xi W, Yang Y, Mao H, Zhao X, Liu M, Fu S. Circulating anti-mullerian hormone as predictor of ovarian response to clomiphene citrate in women with polycystic ovary syndrome. J Ovarian Res. 2016;9:3.##Ellakwa HE, Sanad ZF, Hamza HA, Emara MA, Elsayed MA. Predictors of patient responses to ovulation induction with clomiphene citrate in patients with polycystic ovary syndrome experiencing infertility. Int J Gynaecol Obstet. 2016;133(1):59-63.##Johnson NP, Bontekoe S, Stewart AW. Analysis of factors predicting success of metformin and clomiphene treatment for women with infertility owing to PCOS‐related ovulation dysfunction in a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2011;51(3):252-6.##Rotterdam ESHRE/ASRM-Sponspred PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 200419(1):41-7.##WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157-63.##Nishida C, Ko GT, Kumanyika S. Body fat distribution and noncommunicable diseases in populations: overview of the 2008 WHO expert consultation on waist circumference and waist-hip ratio. Eur J Clin Nutr. 2010;64(1):2-5.##Wild RA, Vesely S, Beebe L, Whitsett T, Owen W. Ferriman gallwey self-scoring I: performance assessment in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(7):4112-4.##Ray S, Bairagi AK, Guha S, Ganguly S, Ray D, Basu AK, et al. A simple way to identify insulin resistance in non-diabetic acute coronary syndrome patients with impaired fasting glucose. Indian J Endocrinol Metab. 2012;16(Suppl 2):S460-4.##Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab. 1998;83(7):2361-5.##Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37(5):467-520.##Nardo LG, Gelbaya TA, Wilkinson H, Roberts SA, Yates A, Pemberton P, et al. Circulating basal anti-Mullerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization. Fertil Steril. 2009;92(5):1586-93.##Jayaprakasan K, Campbell B, Hopkisson J, Johnson I, Raine-Fenning N. A prospective, comparative analysis of anti-Mullerian hormone, inhibin-B, and three-dimensional ultrasound determinants of ovarian reserve in the prediction of poor response to controlled ovarian stimulation. Fertil Steril. 2010;93(3):855-64.##Mahran A, Abdelmeged A, El-Adawy AR, Eissa MK, Shaw RW, Amer SA. The predictive value of circulating anti-Mullerian hormone in women with polycystic ovarian syndrome receiving clomiphene citrate: a prospective observational study. J Clin Endocrinol Metab. 2013;98(10):4170-5.##La Marca A, Broekmans F, Volpe A, Fauser B, Macklon N. Anti-Müllerian hormone (AMH): what do we still need to know? Hum Reprod. 2009;24 (9):2264-75.##Akpinar F, Dilbaz B, Cirik DA, Yilmaz S, Kiykac S, Karahanoglu E, et al. The significance of anthropometric and endocrine parameters in ovulation induction with clomiphene citrate in women with polycystic ovary syndrome. Saudi Med J. 2016;37(11):1272-5.##Baptiste CG, Battista MC, Trottier A, Baillargeon JP. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2010;122(1-3):42-52.##

Impact of Genetic Variants in Estrogen Receptor-β Gene in the Etiology of Uterine Leiomyomas 2 1 2 Background: Uterine leiomyomas are steroid hormone dependent myometrial neoplasms of female genital tract which appear after menarche and regress at menopause. The present study evaluated the role of ER-β gene polymorphisms (rs3020449 C/T, rs3020450 G/A, rs1271572 G/T, rs1256049 G/Aand rs4986938 G/A) in the etiology of disease. Methods: A total of 150 clinically, ultrasonographically evaluated uterine leiomyoma patients and an equal number of individuals as controls were considered for the present study. Genotype analysis was carried out by TETRA Primer Amplification Refractory Mutation System–PCR for promoter polymorphisms and PCR- RFLP method was done for exonic polymorphisms followed by agarose gel electrophoresis. The strength of the association of ER-β gene polymorphisms between controls and patients were measured by appropriate statistical methods. Results: An increased frequency of T/T genotype and T allele of rs3020449, AA genotype and A allele of rs3020450, T/T genotype and T allele of rs1271572, AA genotype and A allele of rs1256049 and A/A genotype and A allele of rs4986938 was observed in cases when compared with controls. Conclusion: The study indicates that the ER-β gene polymorphisms may act as a major genetic regulator in the etiology of uterine leiomyomas. 151 161 Chitroju Ch Bharathi Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet India Desamala D Anupama Department of Gynaecology, Modern Government Maternity Hospital Department of Gynaecology, Modern Government Maternity Hospital India Nallari N Pratibha نالاری پراتیبها Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet India Anantapur A Venkateshwari Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet India venkateshwari@yahoo.com Cell proliferationEstrogensLeiomyomaMyometriumNeoplasmsTranscription factorsUterus 60051.pdf Litovkin KV, Ivanova OV, Bauer A, Hoheisel JD, Bubnov VV, Zaporozhan, VN. Microarray study of gene expression in uterine leiomyoma. Exp oncol. 2008;30(2):106-11.##Makinen N, Heinonen HR, Moore S, Tomlinson IP, van der Spuy ZM, Aaltonen LA. MED12 exon 2 mutations are common in uterine leiomyomas from South African patients. Oncotarget. 2011;2(12):966-9.##Villanova FE, Andrade PM, Otsuka AY, Gomes MT, Leal ES, Castro RA, et al. Estrogen receptor alpha polymorphism and susceptibility to uterine leiomyoma. Steroids. 2006;71(11-12):960-5.##Wei CD, Zheng HY, Wu W, Dai W, Tong YQ, Wang M, et al. Meta-analysis of the association of the rs2234693 and rs9340799 polymorphisms of estrogen receptor alpha gene with coronary heart disease risk in Chinese Han population. Int J Med Sci. 2013;10(4):457-66.##Zhai XD, Ye Y, Yang Y, Wang Z, Mo YN. No association between estrogen receptor beta polymorphisms and uterine leiomyoma. DNA Cell Biol. 2009;28(12):633-6.##Burns KA, Korach KS. Estrogen receptors and human disease: an update. Arch Toxicol. 2012;86(10):1491-504.##Figtree GA, Noonan JE, Bhindi R, Collins P. Estrogen receptor polymorphisms: significance to human physiology, disease and therapy. Recent Pat DNA Gene Seq. 2009;3(3):164-71.##Gennari L, Merlotti D, De Paola V, Calabro A, Becherini L, Martini G, et al. Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol. 2005;15;161(4):307-20.##Rivadeneira F, Van Meurs JB, Kant J, Zillikens MC, Stolk L, Beck TJ, et al. Estrogen receptor beta (ESR2) polymorphisms in interaction with estrogen receptor (ESR1) and insulin-like growth factor I (IGF1) variants influence the risk of fracture in postmenopausal women. J Bone Miner Res. 2006;21(9):1443-56.##Wu H, Xu L, Chen J, Hu J, Yu S, Hu G, et al. Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study. BMC Cancer. 2012;12:276.##Tang L, Li J, Bao M, Xiang J, Chen Y, Wang Y. Genetic association between HER2 and ESR2 polymorphisms and ovarian cancer: a meta-analysis. Onco Targets Ther. 2018;11:1055-66.##Chen L, Liang Y, Qiu J, Zhang L, Chen X, Luo X, et al. Significance of rs1271572 in the estrogenreceptor beta gene promoter and its correlation with breast cancer in a southwestern Chinese population. J Biomed Sci. 2013;20:32.##Lahiri DK, Nurnberger JI Jr. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991;19(19):5444.##Medikare V, Kandukuri LR, Ananthapur V, Deenadayal M, Nallari P. The genetic bases of uterine fibroids; a review. J Reprod Infertil. 2011;12(3):181-91.##Ciavattini A, Di Giuseppe J, Stortoni P, Montik N, Giannubilo SR, Litta P, et al. Uterine fibroids: pathogenesis and interactions with endometrium and endomyometrial junction. Obstet Gynecol Int. 2013;2013:173184.##Flake GP, Andersen J, Dixon D. Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect. 2003;111(8):1037-54.##Zulli K, Bianco B, Mafra FA, Teles JS, Christofolini DM, Barbosa CP. Polymorphism of the estrogen receptor β gene is related to infertility and infertility-associated endometriosis. Arq Bras Endocrinol Metabol. 2010;54(6):567-71.##Borahay MA, Al-Hendy A, Kilic GS, Boehning D. Signaling pathways in Leiomyoma: understanding pathobiology and implications for therapy. Mol Med. 2015;21:242-56.##Salimi S, Khodamian M, Narooie-Nejad M, Hajizadeh A, Fazeli K, Namazi L, et al. Association of polymorphisms and haplotypes in the cytochrome P450 1B1 gene with uterine leiomyoma: a case control study. Biomed Rep. 2015;3(2):201-6.##Sarais V, Cermisoni G, Schimberni M, Alteri A, Papaleo E, Somigliana E, et al. Human chorionic gonadotrophin as a possible mediator of leiomyoma growth during pregnancy: molecular mechanisms. Int J Mol Sci. 2017;18(9). pii: E2014.##Fischer C, Juhasz-Boess I, Lattrich C, Ortmann O, Treeck O. Estrogen receptor beta gene polymorphisms and susceptibility to uterine fibroids. Gynecol Endocrinol. 2010;26(1):4-9.##Strissel PL, Swiatek J, Oppelt P, Renner SP, Beckmann MW, Strick R. Transcriptional analysis of steroid hormone receptors in smooth muscle uterine leiomyoma tumors of postmenopausal patients. J Steroid Biochem Mol Biol. 2007;107(1-2):42-7.##Lecomte S, Demay F, Ferrière F, Pakdel F. Phytochemicals targeting estrogen receptors: beneficial rather than adverse effects? Int J Mol Sci. 2017;18(7). pii: E1381.##Sareddy GR, Vadlamudi RK. Cancer therapy using natural ligands that target estrogen receptor beta. Chin J Nat Med. 2015;13(11):801-7.##Massart F, Becherini L, Marini F, Noci I, Piciocchi L, Del Monte F, et al. Analysis of estrogen receptor (ERalpha and ERbeta) and progesterone receptor (PR) polymorphisms in uterine leiomyomas. Med Sci Monit. 2003;9(1):BR25-30.##Wang Z, Yoshida S, Negoro K, Kennedy S, Barlow D, Maruo T. Polymorphisms in the estrogen receptor beta gene but not estrogen receptor alpha gene affect the risk of developing endometriosis in a Japanese population. Fertil Steril. 2004;81(6):1650-6.##Seleem AK, Aziz AA, Sayd EH, el Dahtory F, Basha EA. The progins progesterone receptor gene polymorphism and polymorphism of the estrogen receptor β gene in endometriosis. J Pharmd Biol Sci. 2014;9(3):16-22.##Sundarrajan C, Liao WX, Roy AC, Ng SC. Association between estrogen receptor-beta gene polymorphisms and ovulatory dysfunctions in patients with menstrual disorders. J Clin Endocrinol Metab. 2001;86(1):135-9.##Abbas S, Beckmann L, Chang-Claude J, Hein R, Kropp S, Parthimos M, et al. Polymorphisms in genes of the steroid receptor superfamily modify postmenopausal breast cancer risk associated with menopausal hormone therapy. Int J Cancer. 2010;126(12):2935-46.##Ghosh J, Joshi G, Pradhan S, Mittal B. Potential role of aromatase over estrogen receptor gene polymorphisms in migraine susceptibility: a case control study from north India. PLoS One. 2012;7(4):e34828.##Lattrich C, Häring J, Schüler S, Skrzypczak M, Ortmann O, Treeck O. Polymorphisms in the promoter region of estrogen receptor b gene in endometrial cancer. Arch Gynecol Obstet. 2014;289(3):631-5.##Treeck O, Elemenler E, Kriener C, Horn F, Springwald A, Hartmann A, et al. Polymorphisms in the promoter region of ESR2 gene and breast cancer susceptibility. J Steroid Biochem Mol Biol. 2009;114(3-5):207-11.##

Nutrient Patterns and Risk of Polycystic Ovary Syndrome 2 1 2 Background: There are limited data on the role of nutrient patterns in development of polycystic ovary syndrome (PCOS). The aim of the study is to document the relationship between nutrient patterns and PCOS. Methods: In this study, 281 incident PCOS women and 472 controls were interviewed through the endocrine clinics between February 2013 and March 2015 in Tehran, Iran. Usual dietary intakes were obtained using a validated semi-quantitative food frequency questionnaire. Factor analysis was conducted on the basis of 32 nutrients. Unconditional logistic regression was performed to ascertain odds ratios. The p<0.05 was considered for significance level. Results: In principal component analysis two nutrient patterns emerged. Factor 1 had high loadings for riboflavin, niacin, pyridoxine, thiamin, magnesium, pantothenic acid, cobalamin, vitamin C, folate, vitamin D, total fiber, selenium, phosphorus, vitamin E, manganese, vitamin K, monounsaturated fatty acids, polyunsaturated fatty acids, potassium and vegetable protein. Factor 2 characterized by high loadings for carbohydrate, animal protein, fat, cholesterol, saturated fatty acid, sodium, biotin, copper, iron, fluoride, zinc, and calcium. After adjusting for potential confounders, the risk of PCOS was significantly higher in the highest tertile of factor 2 (OR: 2.38, 95% CI: 1.69-3.21). Conversely, being in the highest tertile of factor 1 was associated with a lower risk of PCOS (OR: 0.48, 95% CI: 0.21-0.82). Conclusion: Our results provide a possible new insight into the interactions between nutrient intakes and PCOS. 161 169 Ghazaleh Gh Eslamian Student Research Committee, Shahid Beheshti University of Medical Sciences Student Research Committee, Shahid Beheshti University of Medical Sciences Iran Azita A Hekmatdoost Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences Iran a_hekmat2000@yahoo.com MacronutrientsMicronutrientsNutrient patternsPolycystic ovarian syndromePrincipal component analysis 60046.pdf Moran LJ, Brinkworth G, Noakes M, Norman RJ. Effects of lifestyle modification in polycystic ovarian syndrome. Reprod Biomed Online. 2006;12(5):569-78.##Glueck CJ, Goldenberg N. Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics. Metabolism. 2019;92:108-20.##Neven ACH, Laven J, Teede HJ, Boyle JA. A summary on polycystic ovary syndrome: diagnostic criteria, prevalence, clinical manifestations, and management according to the latest international guidelines. Semin Reprod Med. 2018;36(1):5-12.##Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-9.##Turner-McGrievy G, Davidson CR, Billings DL. Dietary intake, eating behaviors, and quality of life in women with polycystic ovary syndrome who are trying to conceive. Hum Fertil (Camb). 2015;18(1):16-21.##Ujvari D, Hulchiy M, Calaby A, Nybacka A, Bystrom B, Hirschberg AL. Lifestyle intervention up-regulates gene and protein levels of molecules involved in insulin signaling in the endometrium of overweight/obese women with polycystic ovary syndrome. Hum Reprod. 2014;29(7):526-35.##Rodrigues AM, Martins LB, Franklin AM, Candido AL, Santos LC, Ferreira AV. Poor quality diet is associated with overweight status and obesity in patients with polycystic ovary syndrome. J Hum Nutr Dietet. 2015;28 Suppl 2:94-101.##Douglas CC, Norris LE, Oster RA, Darnell BE, Azziz R, Gower BA. Difference in dietary intake between women with polycystic ovary syndrome and healthy controls. Fertil Steril. 2006;86(2):411-7.##Marsh K, Brand-Miller J. The optimal diet for women with polycystic ovary syndrome? Br J Nutr. 2005;94(2):154-65.##Moran LJ, Ko H, Misso M, Marsh K, Noakes M, Talbot M, et al. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet. 2013;113(4):520-45.##Kasim-Karakas SE, Cunningham WM, Tsodikov A. Relation of nutrients and hormones in polycystic ovary syndrome. Am J Clin Nutr. 2007;85(3):688-94.##Marsh KA, Steinbeck KS, Atkinson FS, Petocz P, Brand-Miller JC. Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am J Clin Nutr. 2010;92(1):83-92.##Nadjarzadeh A, Dehghani Firouzabadi R, Vaziri N, Daneshbodi H, Lotfi MH, Mozaffari-Khosravi H. The effect of omega-3 supplementation on androgen profile and menstrual status in women with polycystic ovary syndrome: A randomized clinical trial. Iran J Reprod Med. 2013;11(8):665-72.##Mehrabani HH, Salehpour S, Amiri Z, Farahani SJ, Meyer BJ, Tahbaz F. Beneficial effects of a high-protein, low-glycemic-load hypocaloric diet in overweight and obese women with polycystic ovary syndrome: a randomized controlled intervention study. J Am Coll Nutr. 2012;31(2):117-25.##Eslamian G, Baghestani AR, Eghtesad S, Hekmatdoost A. Dietary carbohydrate composition is associated with polycystic ovary syndrome: a case-control study. 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Effects of Group Counseling on Stress and Gender-Role Attitudes in Infertile Women: A Clinical Trial 2 1 2 Background: Infertility stress can have a devastating impact on the lives of couples and influence their physical and psychological health. The purpose of this study was to investigate the effects of group counseling on female stress and gender-role attitudes in infertile women. Methods: The present study is a randomized clinical trial conducted on 90 infertile women referred to Rooyesh Infertility Treatment Center in the city of Karaj, Iran. The convenience sampling method was used. Samples were divided into intervention and control groups through four-block random allocations. Accordingly, the intervention group received five-session group counselling and the control group only received routine care. Newton’s fertility problem inventory (FPI) and gender role questionnaire (GRQ) were used for collecting data before, after, and one month after the intervention. The significance level was set at 0.05. Results: The result showed a significant relationship between gender role attitude and stress in infertile women (p=0.03) and indirect association between of them (r=0.13). And also repeated measures test indicated that length of time had affected the total scores of infertility stress (p<0.001) and gender role attitude scores (p=0.001) and there was a significant difference between the two groups in infertility stress scores (p<0.001) and gender role attitude scores (p=0.001). Discussion: Group counseling can be used in stress reduction and also improved gender role attitude of infertile women. 169 178 Zeinab Z Ehsan Student Research Committee, School of Medical Sciences, Alborz University of Medical Sciences Student Research Committee, School of Medical Sciences, Alborz University of Medical Sciences Iran Mansooreh M Yazdkhasti Non-communicable Diseases Research Center, Alborz University of Medical Sciences Non-communicable Diseases Research Center, Alborz University of Medical Sciences Iran Mitra M Rahimzadeh Social Determinants of Health Research Center, Alborz University of Medical Sciences Social Determinants of Health Research Center, Alborz University of Medical Sciences Iran Mina M Ataee Department of Obstetrics and Gynecology, Clinical Research Development Center of Kamali Hospital, School of Medical Sciences, Alborz University of Medical Sciences Department of Obstetrics and Gynecology, Clinical Research Development Center of Kamali Hospital, School of Medical Sciences, Alborz University of Medical Sciences Iran Sara S Esmaelzadeh-Saeieh Non-communicable Diseases Research Center, Alborz University of Medical Sciences Non-communicable Diseases Research Center, Alborz University of Medical Sciences Iran Esmaelzadeh1360@gmail. com CounselingGender roleInfertilityStress 30042.pdf Karaca A, Unsal G. Psychosocial problems and coping strategies among Turkish women with infertility. Asian Nurs Res (Korean Soc Nurs Sci). 2015;9(3):243-50.##Begum BN, Hasan S. Psychological problems among women with infertility problem: a comparative study. J Pak Med Assoc. 2014;64(11):1287-91.##Kazemijaliseh H, Ramezani Tehrani F, Behboudi-Gandevani S, Hosseinpanah F, Khalili D, Azizi F. The prevalence and causes of primary infertility in Iran: a population-based study. Global J Health Sci. 2015;7(6):226-32.##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.##Parsanezhad ME, Jahromi BN, Zare N, Keramati P, Khalili A, Parsa-Nezhad M. Epidemiology and etiology of infertility in Iran, systematic review and meta-analysis. J Womens Health Issues Care. 2013;2(6):2-6.##Chandra A, Copen CE, Stephen EH. Infertility and impaired fecundity in the United States, 1982-2010: data from the National survey of family growth. USA: National Center for Health Statistics; 2013. 18 p.##Sehhati SF, Mirghafourvand M, Rahimi M. Perceived stress and its social-individual predicors among infertile couples referring to infertility center of Alzahra hospital in Tabriz in 2013. Int J Womens Health Reprod Sci. 2014;2(5):291-6.##Sexton MB, Byrd MR, von Kluge S. Measuring resilience in women experiencing infertility using the CD-RISC: Examining infertility-related stress, general distress, and coping styles. J Psychiatric Res. 2010;44(4):236-41.##Pouragha B, Khabiri R, Pourreza A, Zarei E. Behavior of under the Iranian social security organization-insured persons on utilization of laboratory and imaging services. J Mazandaran Univ Med Sci. 2013;23(106):38-47.##Peterson BD, Gold L, Feingold T. The experience and influence of Infertility: considerations for couple counselors. Fam J. 2007;15(3):251-7.##Cotter D, Hermsen JM, Vanneman R. The end of the gender revolution? gender role attitudes from 1977 to 2008. AJS. 2011;117(1):259-89.##Hedaya NK. Attribution style and gender role attitudes as predictors of infertility distress in women coping with infertility diagnoses [dissertation]: Alliant International University; 2015. 24 p.##Inhorn MC. Local babies, global science: gender, religion and in vitro fertilization in Egypt: 1st ed. New York: Routledge; 2012. 320 p.##Huckert T, Krampen G. Empirical test of an integrative model explaining higher prevalence of subclinical depression in women: a normative sex‐role orientation approach. J Appl Biobehav Res. 2010;15(3):144-60.##Ranjbar F, Akhondi MM, Borimnejad L, Ghaffari SR, Behboodi-Moghadam Z. Paradox of modern pregnancy: a phenomenological study of women’s lived experiences from assisted pregnancy. J Pregnancy. 2015;2015:543210.##Martins MV, Peterson BD, Costa P, Costa ME, Lund R, Schmidt L. Interactive effects of social support and disclosure on fertility-related stress. J Soc Pers Relat. 2013;30(4):371-88.##Van den Broeck U, Emery M, Wischmann T, Thorn P. Counselling in infertility: individual, couple and group interventions. Patient Educ Couns. 2010;81(3):422-8.##Frederiksen Y, Farver-Vestergaard I, Skovgård NG, Ingerslev HJ, Zachariae R. Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: a systematic review and meta-analysis. BMJ Open. 2015;5(1):e006592.##Faramarzi M, Pasha H, Esmailzadeh S, Kheirkhah F, Heidary S, Afshar Z. The effect of the cognitive behavioral therapy and pharmacotherapy on infertility stress: a randomized controlled trial. Int J Fertil Steril. 2013;7(3):199-206.##Covington SN, Burns LH. Infertility counseling: a comprehensive handbook for clinicians. 2nd ed. UK: Cambridge University Press; 2006. 521 p.##Boivin J, Appleton TC, Baetens P, Baron J, Bitzer J, Corrigan E, et al. Guidelines for counselling in infertility: outline version. Hum Reprod. 2001;16(6):1301-4.##Ranjbar F, Behboodi-Moghadam Z, Borimnejad L, Ghaffari SR, Akhondi MM. Experiences of infertile women seeking assisted pregnancy in Iran: a qualitative study. J Reprod Infertil. 2015;16(4):221-8.##Rabeipour S, Arefi M, Ordoni Avval Z, Behroozilak T. The effectiveness of group counseling by collaborative approaches on specific stress in infertile women. J Urmia Nurs Midwifery Fac. 2016;14(1):56-65.##Crawshaw M, Hunt J, Monach J, Pike S, Wilde R. British infertility counselling association-guidelines for good practice in infertility counselling. Third edition 2012. Hum Fertil (Camb). 2013;16(1):73-88.##Newton CR, Sherrard W, Glavac I. The fertility problem inventory: measuring perceived infertility-related stress. Fertil Steril. 1999;72(1):54-62.##Samani RO, Almasi-Hashiani A, Shokri F, Maroufizadeh S, Vesali S, Sepidarkish M. Validation study of the fertility problem inventory in Iranian infertile patients. Middle East Fertil Soc J. 2017;22(1):48-53.##De Berardis D, Mazza M, Marini S, Del Nibletto L, Serroni N, Pino M, et al. Psychopathology, emotional aspects and psychological counselling in infertility: a review. Clin Ter. 2014;165(3):163-9.##Peterson B, Boivin J, Norré J, Smith C, Thorn P, Wischmann T. An introduction to infertility counseling: a guide for mental health and medical professionals. J Assisted Reprod Genet. 2012;29(3):243-8.##Klemetti R, Raitanen J, Sihvo S, Saarni S, Koponen P. Infertility, mental disorders and well-being–a nationwide survey. Acta Obstet Gynecol Scand. 2010;89(5):677-82.##Chachamovich JR, Chachamovich E, Ezer H, Fleck MP, Knauth D, Passos EP. Investigating quality of life and health-related quality of life in infertility: a systematic review. J Psychosom Obstet Gynecol. 2010;31(2):101-10.##Greil AL, Slauson‐Blevins K, McQuillan J. The experience of infertility: a review of recent literature. Sociol Health Illn. 2010;32(1):140-62.##Wischmann TH. Couples sexual dysfunctions: sexual disorders in infertile couples. J Sex Med. 2010;7(5):1868-76.##Wischmann T, Korge K, Scherg H, Strowitzki T, Verres R. A 10-year follow-up study of psychosocial factors affecting couples after infertility treatment. Hum Reprod. 2012;27(11):3226-32.##Soleimani AA, Najafi M, Ahmadi K, Javidi N, Kamkar EH, Mahboubi M. The effectiveness of emotionally focused couples therapy on sexual satisfaction and marital adjustment of infertile couples with marital conflicts. Int J Fertil Steril. 2015;9(3):393-402.##Latifnejad Roudsari R, Rasolzadeh Bidgoly M, Mousavifar N, Modarres Gharavi M. The effect of collaborative counseling on perceived infertility-related stress in infertile women undergoing IVF. Iran J Obstet Gynecol Infertil. 2011;14(4):22-31.##Greil AL. Infertility and psychological distress: a critical review of the literature. 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The Social Construction of Infertility Among Iranian Infertile Women: A Qualitative Study 2 1 2 Background: Infertility is considered an important phenomenon in couples’ life. Infertility and its treatment process influence all aspects of the individual’s life. This study aimed to explain the psycho-social process of social construction of infertility among Iranian infertile women. Methods: This was a qualitative study using a grounded theory approach. The study setting was the Vali-e-Asr Fertility Health Research Center and Avicenna Fertility clinic in Tehran. The sampling started purposefully and it was continued theoretically. The data collection was performed by using 36 semi-structured interviews, observation and field notes with 27 women who suffered from primary and secondary infertility having no living child. The method suggested by Strauss and Corbin was used for data analysis. Results: Results indicate that "Concerns over life instability" and "being judged by others" were the participants’ most important preoccupation. Attempts to stabilize life and get rid of being judged by others were key aspects of the social construction of infertility and the main strategies for resolving their preoccupation. This core concept explained the basic psychological-social process of infertility in relation to axial codes. Conclusion: The results of the study show that various interactive factors affect the social construction of infertility among infertile women who focus on the central concept of attempts to stabilize life and get rid of being judged by others. Therefore, in order to achieve this goal, infertile women should be empowered by effective coping strategies. 178 191 Syedeh Batool SB Hasanpoor-Azghady Department of Reproductive Health and Midwifery, Nursing Care Research Center (NCRC), School of Nursing and Midwifery, Iran University of Medical Science Department of Reproductive Health and Midwifery, Nursing Care Research Center (NCRC), School of Nursing and Midwifery, Iran University of Medical Science Iran Masumeh M Simbar معصومه سیمبر Midwifery and Reproductive Health Research Center (MRHRC), Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences Midwifery and Reproductive Health Research Center (MRHRC), Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences Iran msimbar@yahoo.com, msimbar@sbmu.ac.ir Abu Ali AA Vedadhir ابوعلی ودادهیر Department of Anthropology, Faculty of Social Sciences, University of Tehran Department of Anthropology, Faculty of Social Sciences, University of Tehran Iran Seyed Ali SA Azin Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Leila L Amiri-Farahani Department of Reproductive Health and Midwifery, Nursing Care Research Center (NCRC), School of Nursing and Midwifery, Iran University of Medical Science Department of Reproductive Health and Midwifery, Nursing Care Research Center (NCRC), School of Nursing and Midwifery, Iran University of Medical Science Iran Grounded theoryInfertile womenInfertilitySocial construction 60045.pdf Romeiro J, Caldeira S, Brady V, Timmins F, Hall J. Spiritual aspects of living with infertility: Synthesis of qualita-tive studies. J Clin Nurs. 2017;26(23-24):3917-35.##Latifnejad R. How religious faiths and spiritual be-liefs affect the experiences of infertile women seek-ing infertility treatments: A feminist grounded theo-ry approach [dissertation]. [Guildford]: University of Surrey; 2008. 384 p.##Ombelet W, Van Blerkom J, Klerkx E, Janssen M, Dhont N, Mestdagh G, et al. The (t)WE lab simplified IVF procedure: first births after freezing/thawing. Facts Views Vis Obgyn. 2014;6(1):45-9.##Akhondi MM, Kamali K, Ranjbar F, Shirzad M, Shafeghati S, Ardakani ZB, et al. Prevalence of primary infertility in Iran in 2010. Iran J Public Health. 2013;42(12):1398-404.##Greil A, McQuillan J, Slauson‐Blevins K. The social construction of infertility. Sociol Compass. 2011;5(8):736-46.##Kim JH, Shin HS. Validation of a Korean version of fertility problem inventory. Asian Nurs Res. 2014;8 (3):207-12.##Jonaidy E, Sadodin SN, Mokhber N, Shakeri MT. Comparing the marital satisfaction in infertile and fertile women referred to the public clinics in Mashhad in 2006-07. Iran J Obstet Gynecol Infertil. 2009;12(1):7-16.##World Health Organization, United Nations Population Fund, Key Centre for Women's Health in Society. Mental health aspects of women's reproductive health: a global review of the literature. Geneva: World Health Organiza-tion; 2009. 167 p.##Cousineau TM, Domar AD. Psychological impact of infertility. Best Pract Res Clin Obstet Gynaecol. 2007;21(2):293-308.##Serour GI. Medical and socio-cultural aspects of infertility in the Middle East. Eshre Monographs. 2008;(1):34-41.##Karaca A, Unsal G. Psychosocial problems and coping strategies among Turkish women with infertility. Asian Nurs Res (Korean Soc Nurs Sci). 2015;9(3):243-50.##Greil AL, Slauson‐Blevins K, McQuillan J. The experience of infertility: a review of recent literature. Sociol Health Illn. 2010;32(1):140-62.##Berger R, Paul MS, Henshaw LA. Women's experience of infertility: a multi-systemic perspective. J Int Womens Stud. 2013;14(1):54-68.##Abbasi SM, Asgari KA, Razeghi NH. [Women and infertility experience a case study in Tehran]. Womens Res. 2005;3(3):91-114. Persian.##Fahami F, Hoseini Quchani S, Ehsanpour S, Zargham A. [Women’s lived experiences of female infertility]. Iran J Obstet Gynecol Infertil. 2010;13(4):45-53. Persian.##Bos H, van Balen F, Visser A. Social and cultural factors in infertility and childlessness. Patient Educ Couns. 2005;59(3):223-5.##Corbin JM, Strauss AL. Basics of qualitative research: techniques and procedures for developing grounded theory. Washington, DC: Sage Publications, Inc; 2008. 456 p.##Dyer SJ, Abrahams N, Hoffman M, van der Spuy ZM. Men leave me as I cannot have children': women's experi-ences with involuntary childlessness. Hum Reprod. 2002;17(6):1663-8.##Ried K, Alfred A. Quality of life, coping strategies and support needs of women seeking traditional Chinese med-icine for infertility and viable pregnancy in Australia: a mixed methods approach. BMC Womens Health. 2013;13:17.##Savadzadeh S, Madadzadeh N. [Explanation of emotional feelings of women with infertility: a qualitative study]. J Ilam Univ Med Sci. 2013;21(1):16-24. Persian.##Omoaregba JO, James BO, Lawani AO, Morakinyo O, Olotu OS. Psychosocial characteristics of female infertility in a tertiary health institution in Nigeria. Ann Afr Med. 2011;10(1):19-24.##Khodakarami N, Hashemi S, Saddigh S, Hamdiyeh M, Taheripanah R. [Life experience with infertility; a phenomenological study]. J Reprod Infertil. 2009;10(4):287-97. Persian.##Wiersema NJ, Drukker AJ, Dung MB, Nhu GH, Nhu NT, Lambalk CB. Consequences of infertility in developing countries: results of a questionnaire and interview survey in the South of Vietnam. J Transl Med. 2006;4:54.##Nilforoshan P, Ahmadi SA, Abedi MR, Ahmadi SM. [Attitude toward infertility and its relationship with depres-sion and anxiety in infertile people]. J Reprod Infertil. 2006;6(5):546-52. Persian.##Pacheco Palha A, Lourenço MF. Psychological and cross-cultural aspects of infertility and human sexuality. Adv Psychosom Med. 2011;31:164-83.##Sultan S, Tahir A. Psychological Consequences of Infertility. Hell J Psychol. 2011;8(2):229-47.##Adewunmi AA, Etti EA, Tayo AO, Rabiu KA, Akindele RA, Ottun TA, et al. Factors associated with acceptability of child adoption as a management option for infertility among women in a developing country. Int J Womens Health. 2012;4:365-72.##Rahim ME, Zarezadeh Mehrizi E. [The study of gender differences in the psycho-social consequences of infertility among clients referring to the Yazd infertility center]. Womens Strateg Stud. 2012;14(56):155-210. Persian.##Drosdzol A, Skrzypulec V. Quality of life and sexual functioning of Polish infertile couples. 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Infertility, psychological distress, and coping strategies among women in Mali, West Africa: a mixed-methods study. Afr J Reprod Health. 2018;22(1):60-72.‏##Bailey A, Ellis-Caird H, Croft C. Living through unsuccessful conception attempts: a grounded theory of resilience among women undergoing fertility treatment. J Reprod Infant Psychol. 2017;35(4):324-33.‏##Bokaie M, Farajkhoda T, Enjezab B, Heidari P, Karimi Zarchi M. Barriers of child adoption in infertile couples: Iranian’s views. Iran J Reprod Med. 2012;10(5):429-34.##

Patient with Disorders of Sex Development (DSD): A Case Report from a Tertiary Care Hospital in Thiruvananthapuram, India 2 1 2 Background: 46 XX male syndrome, a rare case of infertility was first reported by de la Chapelle in 1964. In newborn males, the incidence rate of the syndrome varies from 1/9000 to 1/20000. Here, a case of 46 XX male syndrome is reported with clinical, biochemical and genetic changes of the patient and normal masculine features. Case Presentation: A 29 year old male with infertility registered at the Sree Avittom Thirunal Hospital of Government Medical College, Thiruvananthapuram for fertility treatment. He was diagnosed with non obstructive azoospermia in repeated semen analysis. Chromosomal analysis on peripheral blood lymphocytes has revealed 46 XX male syndrome and the result was confirmed with Fluorescent In situ Hybridization (FISH). Real time polymerase chain reaction failed to detect genes on azoospermia factor regions, AZFa, AZFb and AZFc of Y chromosome, but detected SRY gene positivity. Masculine features of patient were normal except small sized testis, ejaculatory dysfunction and azoospermia. Conclusion: Appearance of the external genitalia will be generally normal in 46 XX with SRY positive males and generally difficult to identify before puberty because there will not be any significant clinical indication. The present case report demonstrates that mere physical or clinical examination may not disclose the genetic defects. Therefore, in addition to general examination, it is essential to perform genetic analysis on men with infertility. 191 195 Pongillyathundiyil PS Sreejith Multi Disciplinary Research Unit, Government Medical College Multi Disciplinary Research Unit, Government Medical College India Sheila Sh Balakrishnan Department of Reproductive Medicine and Surgery, Sree Avittom Thirunal Hospital, Government Medical College Department of Reproductive Medicine and Surgery, Sree Avittom Thirunal Hospital, Government Medical College India Vaikom VH Sankar Department of Pediatrics, Sree Avittom Thirunal Hospital, Government Medical College Department of Pediatrics, Sree Avittom Thirunal Hospital, Government Medical College India Remya R Syamala Child Development Centre, Government Medical College Child Development Centre, Government Medical College India Reji R Mohan Department of Reproductive Medicine and Surgery, Sree Avittom Thirunal Hospital, Government Medical College Department of Reproductive Medicine and Surgery, Sree Avittom Thirunal Hospital, Government Medical College India Sankar S Sundaram Department of Pathology, Government Medical College, Kottayam Department of Pathology, Government Medical College, Kottayam India Krishna K Govindan Multi Disciplinary Research Unit, Government Medical College Multi Disciplinary Research Unit, Government Medical College India Kaleeluvilayil KR Chandramohanan Nair Department of Anatomy, Government Medical College Department of Anatomy, Government Medical College India chandramohan1964@yahoo.co.in 46 XX male syndromeAzoospermiaSRY geneY chromosome microdeletion 60048.pdf DelaChapelle A, Hortling H, Niemi M, Wennstroem J. XX sex chromosomes in a human male. first case. Acta Med Scand. 1964;175: Suppl 412:25-8.##de la Chapelle A. Analytic review: nature and origin of males with XX sex chromosomes. Am J Hum Genet. 1972;24(1):71-105.##Nielsen J, Sillesen I. Incidence of chromosome aberrations among 11148 newborn children. Humangenetik. 1975;30(1):1-12.##Anık A, Çatlı G, Abacı A, Böber E. 46, XX male disorder of sexual development: a case report. J Clin Res Pediatr Endocrinol. 2013;5(4):258-60.##Fechner PY, Marcantonio SM, Jaswaney V, Stetten G, Goodfellow PN, Migeon CJ, et al. The role of the sex-determining region Y gene in the etiology of 46, XX maleness. J Clin Endocrinol Metab. 1993;76:690-5.##Boucekkine C, Toublanc JE, Abbas N, Chaabouni S, Ouahid S, Semrouni M, et al. Clinical and anatomical spectrum in XX sex reversed patients. Relationship to the presence of Y specific DNA-sequences. Clin Endocrinol (Oxf). 1994;40(6):733-42.##Lopez M, Torres L, Mendez JP, Cervantes A, Alfaro G, Perez-Palacios G, et al. SRY alone can induce normal male sexual differentiation. Am J Med Genet. 1995;55(3):356-8.##McElreavey K, Vilain E, Abbas N, Herskowitz I, Fellous M. A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. Proc Natl Acad Sci. 1993;90(8):3368-72.##Zenteno-Ruiz JC, Kofman-Alfaro S, Mendez JP. 46,XX sex reversal. Arch Med Res. 2001;32(6):559-66.##Ferguson-Smith MA, Cooke A, Affara NA, Boyd E, Tolmie JL. Genotype-phenotype correlations in XX males and their bearing on current theories of sex determination. Hum Genet. 1990;84(2):198-202.##Krausz C, Hoefsloot L, Simoni M, Tüttelmann F; European academy of andrology; European molecular genetics quality network. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: state-of-the-art 2013. Andrology. 2014;2(1):5-19.##Rajender S, Rajani V, Gupta NJ, Chakravarty B, Singh L, Thangaraj K. SRY-negative 46, XX male with normal genitals, complete masculinization and infertility. Mol Hum Reprod. 2006;12(5):341-6.##

Exposure to Environmental Organic Mercury and Impairments in Human Fertility 2 1 2 It is widely known that mercury (Hg) is highly toxic to humans. Environmental Hg pollution still represents a huge health concern worldwide (1). Human industrial activities have led to raised levels of Hg in the air, soil, and fresh and sea waters, and to bioaccumulation along the food chain. Humans easily absorb Hg through fish consumption. Also, it is a major toxicant because it has adverse effects on human reproductive health (2). Mercury, particularly in its organic forms, methyl-Hg and ethyl-Hg, is toxic even when individuals are exposed to relatively low Hg levels (3). Toxic effects of Hg can easily be observed in the nervous, digestive, and immune systems, in addition to lungs, kidneys, skin, and eyes, as reported by the World Health Organization (4). Many of these effects are mediated by the host’s immune response via its limited detoxification and metal excretion capabilities. Genetic polymorphism of scavenging Hg-complexed proteins are factors that can induce stressor effects, which also depend on the capability of enzymatic detoxification systems, aside from the dose of the toxicant (5). The evidence that organic Hg easily crosses the placental barrier and reaches the fetus represents another great concern. Thereby, Hg is a major cause of neural developmental defects including delayed postnatal development (6). Both elemental Hg0 and methyl-Hg easily cross the placenta, and it should be emphasized that the developing fetal brain is the most sensitive organ. However, the more recent debate about the toxicity of dietary Hg in fetal or prenatal toxicology (7) has revealed controversies about Hg effects on fetal development, particularly because it is difficult to establish a reliable Hg-pharmacokinetics in adult women undergoing pregnancy. The pharmacokinetics and threshold of plasma Hg-acceptable levels in pregnancy are still matters of debate, and updated evidence-based official guidelines are generally lacking (8). Recent reports together with the previous information from the Minimata and Iraq disasters have reignited this debate (9). Mercury exposure may explain cases of idiopathic infertility in males as well as in females (10). Moreover, it affects chromosomes or embryonic cell DNA, presumably by its interference with one-carbon transfer since a methionine carrier transports it across membranes (11). Recent evidence has reported that Hg inhibits the energy metabolism of spermatozoa, thus preventing their normal functioning (12). Methyl-Hg causes reproductive organ damage in women (13). Furthermore, menstrual disorders, sterility, and spontaneous abortion following abnormal Hg toxicology have been reported (14). Spontaneous abortion can occur when the pregnant woman is exposed to organic Hg or other toxic agents (15). Many spontaneous abortions do not have a known cause, but reports indicate that Hg exposure might be a triggering factor in several cases (16). Paternal exposure to Hg, and to other industrial chemicals, and pesticides are also presumed to play a role 17). Studies on a Chinese population revealed that neural tube defects were associated with exposure to methyl-Hg in pregnancy and higher placental deposition of the compound (18). Based on the current knowledge, great concerns have been raised regarding Romanian districts with remarkably high Hg pollution (19). Regarding pre-and postnatal risks of Hg exposure, it is relevant that the concentrations of Hg in the nervous system and other target organs of children may be higher than in the mothers, in part due to the small weight of a newborn child associated with a high rate of gastrointestinal absorption and low renal excretion, implying that hazardous Hg exposure may continue after birth (20). Taken together, the comments presented here illustrate that the relationship between Hg toxicology and fertility has still been scarcely addressed in the literature, despite previous lessons from Minimata and some few reports in recent years. Apparently, Hg exposure may have a considerable impact on multiple stages of reproduction, from before conception to the maturation of organs and endocrine systems and further to the healthy development of the child. Therefore, a continued systematic investigation and assessment of the current state of knowledge about congenital and developmental anomalies with possible associations to environmental pollutants are of particular importance. Conflict of Interest The authors declare no conflict of interest. 195 198 Geir G Bjørklund Council for Nutritional and Environmental Medicine Council for Nutritional and Environmental Medicine Norway bjorklund@conem.org Jan J Aaseth Research Department, Innlandet Hospital Trust Research Department, Innlandet Hospital Trust Norway Maryam M Dadar Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO) Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO) Iran Monica M Butnariu Banat’s University of Agricultural Sciences and Veterinary Medicine "King Michael I of Romania" from Timisoara Banat’s University of Agricultural Sciences and Veterinary Medicine "King Michael I of Romania" from Timisoara Romania Salvatore S Chirumbolo Department of Neurological and Movement Sciences, University of Verona Department of Neurological and Movement Sciences, University of Verona Italy No Keyword 60054.pdf Rana MN, Tangpong J, Rahman MM. Toxicodynamics of Lead, Cadmium, Mercury and Arsenic-induced kidney toxicity and treatment strategy: a mini review. Toxicol Rep. 2018;5:704-13.##Rahmani AM, Gia TN, Negash B, Anzanpour A, Azimi I, Jiang M, et al. Exploiting smart e-health gateways at the edge of healthcare Internet-of-things: a fog computing approach. Future Gener Comput Syst. 2018;78(2):641-58.##Bjørklund G, Dadar M, Mutter J, Aaseth J. The toxicology of mercury: current research and emerging trends. Environ Res. 2017;159:545-54.##World Health Organization. Mercury and health [Internet]. Geneva: World Health Organization; 2017 Mar 31. Available from: https://www.who.int/news-room/fact-sheets/detail/mercury-and-health##Llop S, Ballester F, Broberg K. Effect of gene-mercury interactions on mercury toxicokinetics and neurotoxicity. Curr Environ Health Rep. 2015;2(2):179-94.##Carocci A, Rovito N, Sinicropi MS, Genchi G. Mercury toxicity and neurodegenerative effects. Rev Environ Contam Toxicol. 2014;229:1-18.##Taylor CM, Emond AM, Lingam R, Golding J. Prenatal lead, cadmium and mercury exposure and associations with motor skills at age 7 years in a UK observational birth cohort. Environ Int. 2018;117:40-7.##Golding J, Gregory S, Iles-Caven Y, Hibbeln J, Emond A, Taylor CM. Associations between prenatal mercury exposure and early child development in the ALSPAC study. Neurotoxicology. 2016;53:215-22.##Syversen T, Kaur P. The toxicology of mercury and its compounds. J Trace Elem Med Biol. 2012;26(4):215-26.##Choy CM, Lam CW, Cheung LT, Briton‐Jones CM, Cheung LP, Haines CJ. Infertility, blood mercury concentrations and dietary seafood consumption: a case-control study. BJOG. 2002;109(10):1121-5.##Simmons-Willis TA, Koh AS, Clarjson TW, Ballatori N. Transport of a neurotoxicant by molecular mimicry: the methylmercury–L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. Biochem J. 2002;367(Pt 1):239-46.##Altunkaynak ME, Akgül N, Yahyazadeh A, Altunkaynak BZ, Türkmen AP, Akgül HM, et al. A stereological and histopathological study of the effects of exposure of male rat testes to mercury vapor. Biotech Histochem. 2015;90(7):529-34.##Wright DL, Afeiche MC, Ehrlich S, Smith K, Williams PL, Chavarro JE, et al. Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic. Reprod Toxicol. 2015;51:125-32.##García-Fortea P, Cohen-Corcia I, Córdoba-Doña JA, Reche-Rosado A, González-Mesa E. Toxic elements in hair and in vitro fertilization outcomes: a prospective cohort study. Reprod Toxicol. 2018;77:43-52.##Yu E, Sim C, Park D, Koh Y, Heo J, Choe S, et al. Relationship between heavy metal concentration and number of spontaneous abortion experiences in Korean women: a retrospective study of the 6th Korean national health and nutrition examination survey. Fertil Steril. 2017;108(3):e320.##Anttila A, Sallmén M. Effects of parental occupational exposure to lead and other metals on spontaneous abortion. J Occup Environ Med. 1995;37(8):915-21.##Mínguez-Alarcón L, Afeiche MC, Williams PL, Arvizu M, Tanrikut C, Amarasiriwardena CJ, et al. Hair mercury (Hg) levels, fish consumption and semen parameters among men attending a fertility center. Int J Hyg Environ Health. 2018;221(2):174-82.##Jin L, Liu M, Zhang L, Li Z, Yu J, Liu J, et al. Exposure of methyl mercury in utero and the risk of neural tube defects in a Chinese population. Reprod Toxicol. 2016;61:131-5.##Neamtiu IA, Al-Abed SR, McKernan JL, Baciu CL, Gurzau ES, Pogacean AO, et al. Metal contamination in environmental media in residential areas around Romanian mining sites. Rev Environ Health. 2017;32(1-2):215-20.##Berlin M, Zalups RK, Fowler BA. Mercury. In: Nordberg GF, Fowler BA, Nordberg M, editors. Handbook on the toxicology of metals. Amsterdam: Elsevier; 2015. p. 1013-69.##