The Necessity to Retrieve Testicular Sperm in Infertile Non-Azoospermic Men with High Levels of SDF 2 1 2 Sperm cell’s shape and structure is different from other cells. The overall structure of the sperm has changed to suit its morphology to the main functions for transmission of biological information and paternal genome to the next generation. Therefore, most of the alterations during spermatogenesis and spermiogenesis include the loss of most of its organelles, cytoplasm, and chromatin compaction impair its defense mechanism and predispose sperm to damages by environmental factors. One of the most protected and critical part of sperm is its chromatin located in the head of spermatozoa. Sperm chromatin, despite being ten times more compact than other cells, is easily damaged by endogenous and external factors, leading to fragmentation of sperm DNA. For nearly one decade, sperm DNA fragmentation has been considered as one of the causes of male infertility and various methods have been proposed and used for evaluation and measurement of sperm DNA fragmentation (SDF) (1). In many infertile men, it is observed that despite performing various required interventions and medical treatments, the level of SDF remains high. There is adequate evidence that sperm DNA fragmentation is associated with poor ART results; therefore, SDF may exert negative effect on assisted reproduction and pregnancy outcome. Sperm chromatin integrity is essential for normal development of early embryo, successful pregnancy, and healthy live birth (2). The number of published articles in this field is continually growing. As of today, more than 2,000 articles on sperm DNA damage have been indexed by PubMed, half of which are published in the last 5 years. Also, a large number of them are concerned with the tests for selection of vital sperm with the lowest level of SDF for ART and many are focused on comparison of different SDF quantification methods. Analysis methods for SDF application determine the different features of DNA breakdown, while these characteristics relate to the properties of the DNA molecule. The ideal method for measuring SDF has not yet been introduced, so the limitations and potential benefits in clinical outcomes should be thoroughly investigated for selection of the effective analysis method in SDF application. It seems that such procedures to measure SDF level are not completely accurate and reliable until proposing a golden standard method for this purpose. Therefore, depending on the exigency of the circumstance, a reliable SDF measurement method with an appropriate threshold should be used (1, 3). One of the proposed interventions in infertile men with high levels of DNA fragmentation index (DFI) is to use retrieved testicular spermatozoa instead of ejaculated ones with reasonably lower SDF. The use of testicular sperm may be a suitable alternative to obtain a sample with less DNA fragmentation in couples who experienced recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) due to high levels of SDF. However, the SDF assays have been optimized to only measure the fragmentation of sperm DNA in ejaculate and their efficiency has not been approved for assessment of testicular sperm, making it difficult to interpret testicular SDF levels (1, 2). On the other hand, it has been well recognized that most of sperm DNA fragmentation is triggered by post-testicular sperm exposure to oxidative stress in the epididymis and vas deferens. Sperm DNA damages progressively increase from the seminiferous tubules to the epididymis and vas deferens with the highest level in ejaculation (4). Infertile men with increased level of SDF in semen can benefit from retrieved testicular spermatozoa for intracytoplasmic sperm injection (ICSI). However, testicular sperm appears to be desirable in ICSI when SDF level is low, yet elevated aneuploidy rates in testicular spermatozoa counteract such potential benefits. Testicular aneuploid sperm can fertilize an egg and lead to a successful pregnancy. In spite of its low risk, the rate of having a child with an aneuploidy is higher in such cases in comparison to other types of infertility (5). Literature review has shown that SDF has no significant impact on fertilization, cleavage and early pregnancy rate, but the rate of pregnancy loss is significantly higher in comparison to cases with lower SDF. The main problem in interpreting and applying the results of such studies is their retrospective nature and heterogeneous designs with different methods for evaluation of SDF. Recent international clinical guidelines recommend the use of testicular sperm in cases with a history of at least two recurrent pregnancy losses following ART and using ejaculated spermatozoa; however, before performing TESE-ICSI for these couples, it is necessary to receive thorough consultation and try all strategies to reduce SDF before performing this invasive and traumatic procedure. Clinical management of infertile men with high level of SDF should be considered as the first-line infertility treatment before performing invasive procedure of testis biopsy. Controlling the effect of all harmful factors on sperm chromatin, including treatment of underlying diseases such as obesity, diabetes, infection, smoking control, frequent ejaculation before ART, and the use of appropriate antioxidants can improve sperm chromatin integrity. Along with all these strategies, the selection of the sperm with intact chromatin using physiological ICSI (PICSI), IMSI, and MACS methods can reduce the effects of sperm chromatin damage on ART results (2, 3). Although many researches advocate the use of testicular sperm retrieval in normozoospermic men with RIF and RPL due to increased levels of SDF, most of their studies are categorized as small cohorts, case series, or case-control studies with unreliable evidence, inappropriate design, lack of proper control group, limited comprehensiveness, ignoring the role of female factor, ungeneralizable results, lacking statistical power which are solely confined to chemical and clinical pregnancy disregarding miscarriages and live birth rates. Therefore, prior to wide application of testis biopsy in these cases, a series of new and well-designed studies with detailed plan, inclusion of control groups, and appropriate outcome measures are essential to compensate for the drawbacks of previous studies and scientifically prove the priority of testicular sperm to ejaculate in cases with high SDF who are unresponsive to other first-line interventions. 225 226 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 120144.pdf Qiu Y, Yang H, Li C, Xu C. Progress in research on sperm DNA fragmentation. Med Sci Monit. 2020;26:e918746.##Ambar RF, Agarwal A, Majzoub A, Vij S, Tadros NN, Cho CL, et al. The use of testicular sperm for intracytoplasmic sperm injection in patients with high sperm DNA damage: a systematic review. World J Mens Health. 2021;39(3):391-8.##Esteves SC, Roque M, Garrido N. Use of testicular sperm for intracytoplasmic sperm injection in men with high sperm DNA fragmentation: a SWOT analysis. Asian J Androl. 2018;20(1):1-8.##Xie P, Keating D, Parrella A, Cheung S, Rosenwaks Z, Goldstein M, et al. Sperm genomic integrity by TUNEL varies throughout the male genital tract. J Urol. 2020;203(4):802-8.##Moskovtsev SI, Alladin N, Lo KC, Jarvi K, Mullen JB, Librach CL. A comparison of ejaculated and testicular spermatozoa aneuploidy rates in patients with high sperm DNA damage. Syst Biol Reprod Med. 2012;58(3):142-8.##

Controlling Semi-Invasive Activity of Human Endometrial Stromal Cells by Inhibiting NF-kB Signaling Pathway Using Aloe-emodin and Aspirin 2 1 2 Background: Inflammation and its master regulator, Nuclear Factor-kB (NF-kB), have been implicated in the development of endometriosis. Inhibition of NF-kB pathway using small molecules ameliorated disease progression and reduced the lesion size; nevertheless, the underlying mechanism is not fully understood. Therefore, this study, is an attempt to assess whether inhibiting NF-kB signaling by aloe-emodin (AE) or aspirin (Asp), as anti-inflammatory compounds, can suppresses the invasive activity of human endometrial stromal cells at stage IV endometriosis. Methods: The eutopic and healthy endometrial biopsies from a total of 8 infertile women with confirmed endometriosis and 8 women without endometriosis were digested and the single cells were cultured. Gene and protein markers of proliferation, migration, adhesion, and invasion of eutopic endometrial stromal cells (EuESCs) with and without treatment with AE or Asp, as well as control endometrial stromal cells (CESCs) was analyzed using q-PCR and immunofluorescence staining, respectively. Comparison between groups was performed using one-way ANOVA and the Bonferroni post hoc and p≤0.5 was considered statistically significant. Results: There was an association between NF-kB overexpression and higher proliferation/adhesion capacity in EuESCs. EuESCs (at stage IV endometriosis) displayed no invasive and migratory behaviors. Pre-treatment of EuESCs with AE or Asp significantly attenuated NF-kB expression and reduced proliferative, adhesive, invasive, and migratory activity of endometrial cells (p≤0.5). Conclusion: Eutopic endometrial stromal cells seem to have a semi-invasive activity which is largely suppressed by AE or Asp. It can be suggested that both Asp and AE (as potent NF-kB inhibitors) can be used as a supplement in conventional endometriosis treatments. 227 241 Nahid N Nasiri 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 Sara S Babaei Department of Developmental Biology, Factually of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture Department of Developmental Biology, Factually of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture Iran Ashraf A Moin 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 Poopak P Eftekhari-Yazdi Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR Iran eftekhari@royaninstitute.org AdhesionAspirinCell proliferationEndometrial biopsy 120116.pdf Alimi Y, Iwanaga J, Loukas M, Tubbs RS. 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Ovarian Stem Cells Differentiation into Primary Oocytes Using Follicle Stimulating Hormone, Basic Fibroblast Growth Factor, and Neurotrophin 3 2 1 2 Background: In vitro obtaining oocytes can be an appropriate alternative for patients with gonadal insufficiency or cancer survivors. The purpose of the current research was isolating stem cells from ovarian cortical tissue as well as evaluating the effectiveness of follicle stimulating hormone (FSH), basic fibroblast growth factor (bFGF), and neurotrophin 3 (NT3) in differentiating to oocyte-like cells. Methods: A human ovary was dissected and cortical tissue pieces were cultured for cell isolation. Isolated cells were divided into 8 groups (3 cases in each group) of control, FSH, NT3, bFGF, FSH+NT3, FSH+bFGF, NT3+bFGF, and FSH+NT3+ bFGF. Pluripotency specific gene (OCT4-A and Nanog), initial germ cells (c-KIT and VASA) and PF growth initiators (GDF-9 and Lhx-8) were evaluated by qRT-PCR. Experiments were performed in triplicate and there were 3 samples in each group. The results were analyzed using one-way ANOVA and p-value less than 0.05 was considered statistically significant. Results: Flow cytometry results showed that cells isolated from the ovarian cortex expressed markers of pluripotency. The results showed that the expression of Nanog, OCT4, GDF-9 and VASA was significantly increased in FSH+NT3 group, while treatment with bFGF caused significant expression of c-KIT and Lhx-8 (p<0.05). Also, according to the results, isolated cells treated with NT3 significantly increased c-KIT expression. Conclusion: According to our results, the ovarian cortex cells could be differentiated into primordial follicles if treated with the proper combination of FSH, bFGF, and NT3. These findings provided a new perspective for the future of in vitro gamete proudest. 241 251 Sara S Tanbakooei Cellular and Molecular Research Center, Iran University of Medical Sciences Cellular and Molecular Research Center, Iran University of Medical Sciences Iran Seyed Mohammad Amin SMA Haramshahi Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences Iran Gelareh G Vahabzadeh Department of Pharmacology, School of Medicine, Iran University of Medical Sciences Department of Pharmacology, School of Medicine, Iran University of Medical Sciences Iran Mahmood M Barati Department of Biotechnology, School of Allied Medicine, Iran University of Medical Sciences Department of Biotechnology, School of Allied Medicine, Iran University of Medical Sciences Iran Majid M Katebi Department of Anatomy, Hormozgan University of Medical Sciences Department of Anatomy, Hormozgan University of Medical Sciences Iran Fereshteh F Golab Cellular and Molecular Research Center, Iran University of Medical Sciences Cellular and Molecular Research Center, Iran University of Medical Sciences Iran fgolab520@gmail.com Qazal Q Shetbi Department of Biology, Islamic Azad University, Science and Research Branch Department of Biology, Islamic Azad University, Science and Research Branch Iran Narges N Niknam Department of Biology, Islamic Azad University, Science and Research Branch Department of Biology, Islamic Azad University, Science and Research Branch Iran Leila L Roudbari Cellular and Molecular Research Center, Iran University of Medical Sciences Cellular and Molecular Research Center, Iran University of Medical Sciences Iran Motahareh M Rajabi Fomeshi Cellular and Molecular Research Center, Iran University of Medical Sciences Cellular and Molecular Research Center, Iran University of Medical Sciences Iran Soheila S Amini Moghadam Department of Gynecology, Firoozgar Hospital, Iran University of Medical Sciences Department of Gynecology, Firoozgar Hospital, Iran University of Medical Sciences Iran Cell differentiationGrowth factorsOogenesisOvarian tissueStem cells 120133.pdf Feigin E, Freud E, Fisch B, Orvieto R, Kravarusic D, Avrahami G, et al. 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Clinical Outcomes of Rescue Intracytoplasmic Sperm Injection at Different Timings Following In Vitro Fertilization 2 1 2 Background: Although rescue intracytoplasmic sperm injection (r-ICSI) is extensively used worldwide, the indication of r-ICSI and its optimal timing remains obscure. This study aimed to assess the outcomes of r-ICSI following in vitro fertilization in different timings when fertilization is confirmed. Methods: This study included 5,156 cycles (47,785 eggs). Fertilization was confirmed by polar body analysis after 4 and 6 hr of coincubation of the sperm and oocyte. Oocytes that underwent IVF were divided into two groups based on the time when a second polar body was detected in more than 30% of all oocytes (Four-hr group and six-hr group). If the second polar body was not detected or was present in less than 30% of all oocytes after six hr of coincubation, rescue-ICSI (r-ICSI) was performed for oocytes without a second polar body (r-ICSI group). Results: The fertilization rates of two pronuclear (2PN) oocytes in the three groups (Four-hr group, six-hr group, and r-ICSI group) were 70.7%, 51.3%, and 58.0%, respectively. The blastocyst formation rates were 62.8%, 53.4%, and 42.9%, respectively. Conclusion: Performing r-ICSI after six hr of coincubation can salvage cases with fertilization failure in IVF. The higher fertilization rate of r-ICSI indicates that all oocytes without signs of fertilization after six hr of coincubation should undergo r-ICSI. 251 258 Yuki Y Shiraiwa Hanabusa Women’s Clinic Hanabusa Women’s Clinic Japan Noritoshi N Enatsu Hanabusa Women’s Clinic Hanabusa Women’s Clinic Japan enatsunoritoshi@hanabusaclinic.com Kazuki K Yamagami Hanabusa Women’s Clinic Hanabusa Women’s Clinic Japan Koyu K Furuhashi Hanabusa Women’s Clinic Hanabusa Women’s Clinic Japan Toshiroh T Iwasaki Hanabusa Women’s Clinic Hanabusa Women’s Clinic Japan Junko J Otsuki Hanabusa Women’s Clinic Hanabusa Women’s Clinic Japan Masahide M Shiotani Hanabusa Women’s Clinic Hanabusa Women’s Clinic Japan Assisted reproductive techniquesFertilization failureIn vitro fertilizationInfertilityIntracytoplasmic sperm injection 120137.pdf Barlow P, Englert Y, Puissant F, Lejeune B, Delvigne A, Van Rysselberge M, et al. Fertilization failure in IVF: why and what next? Hum Reprod. 1990;5(4):451-6.##Molloy D, Harrison K, Breen T, Hennessey J. The predictive value of idiopathic failure to fertilize on the first in vitro fertilization attempt. Fertil Steril. 1991;56(2):285-9.##Bell H, Garcia RB. ICSI of unfertilized oocytes after IVF insemination: are the traditional markers of fertilization adequate? Hum Reprod. 1995;10(3):491-3.##Nagy ZP, Joris H, Liu J, Staessen C, Devroey P, Van Steirteghem AC. Intracytoplasmic single sperm injection of 1-day-old unfertilized human oocytes. Hum Reprod. 1993;8(12):2180-4.##Chen C, Kattera S. Rescue ICSI of oocytes that failed to extrude the second polar body 6 h post-insemination in conventional IVF. Hum Reprod. 2003;18(10):2118-21.##Kuczyński W, Dhont M, Grygoruk C, Pietrewicz P, Redzko S, Szamatowicz M. Rescue ICSI of unfertilized oocytes after IVF. Hum Reprodu. 2002;17(9):2423-7.##Zhu Lx, Ren Xl, Wu L, Hu J, Li Yf, Zhang Hw, et al. Rescue ICSI: Choose the Optimal Rescue Window before Oocyte Aging. 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Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015;313(3):255-63.##Li Z, Wang A, Bowman M, Hammarberg K, Farquhar C, Johnson L, et al. ICSI does not increase the cumulative live birth rate in non-male factor infertility. Hum Reprod. 2018;33(7):1322-30.##Chen W, Bai H, Li M, Xue X, Shi J. Effects of three pro-nuclei (3PN) incidence on laboratory and clinical outcomes after early rescue intracytoplasmic sperm injection (rescue-ICSI): an analysis of a 5-year period. Gynecol Endocrinol. 2021;37(2):137-40.##Xia P. Biology of polyspermy in IVF and its clinical indication. Curr Obstet Gynecol Rep. 2013;2(4):226-31.##Beck-Fruchter R, Lavee M, Weiss A, Geslevich Y, Shalev E. Rescue intracytoplasmic sperm injection: a systematic review. Fertil Steril. 2014;101(3):690-8.##Cao S, Wu X, Zhao C, Zhou L, Zhang J, Ling X. 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Association of Novel Single Nucleotide Polymorphisms of Genes Involved in Cell Functions with Male Infertility: A Study of Male Cases in Northwest Iran 2 1 2 Background: Infertility is a global health problem caused by various environmental and genetic factors. Male infertility accounts for 40–50% of all cases of infertility and approximately half of them are grouped as idiopathic with no definitive causes. Previous studies have suggested an association between some SNPs and infertility in men. In this study, an attempt was made to investigate the association of 7 different SNPs of 4 genes involved in common cell functions with male infertility. Methods: MTHFR rs1801131 (T>G), MTHFR rs2274976 (G>A), FASLG rs80358238 (A>G), FASLG rs12079514 (A>C), GSTM1 rs1192077068 (G>A), BRCA2 rs4987117(C>T), and BRCA2 rs11571833 (A>T) were genotyped in 120 infertile men with idiopathic azoospermia or severe oligospermia and 120 proven fertile controls using ARMS-PCR methods. Next, 30% of SNPs were regenotyped to confirm the results. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using SPSS statistical software to evaluate the strength of association. The p˂0.05 were considered statistically significant. Results: Statistical analysis revealed significant association between MTHFR rs2274976 AA variant (OR: 10.00, CI: 3.203-31.225), FASLG rs12079514 AC variant (OR: 0.412, CI: 0.212-0.800), and BRCA2 rs11571833 TT variant OR: 6.233, CI: 3.211-12.101) with male infertility, but there was no significant difference between case and control groups in MTHFR rs1801131 (p= 0.111), GSTM1 rs1192077068 (p=0.272), BRCA2 rs4987117 (p=0.221), and FASLG rs80358238 (p=0.161). Conclusion: Our findings suggested that some novel polymorphisms including MTHFR rs2274976, FASLG rs12079514, and BRCA2 rs11571833 might be the possible predisposing risk factors for male infertility in cases with idiopathic azoospermia. 258 267 Elham E Ghadirkhomi Department of Genetics, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University Department of Genetics, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University Iran Abdolhamid A Angaji Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University Iran angaji@khu.ac.ir Maryam M Khosravi Biology Department, Faculty of Bio Sciences, North Tehran Branch, Islamic Azad University Biology Department, Faculty of Bio Sciences, North Tehran Branch, Islamic Azad University Iran Mohammad Reza MR Mashayekhi Department of Genetics, Faculty of Biological Sciences, Tabriz Branch, Islamic Azad University Department of Genetics, Faculty of Biological Sciences, Tabriz Branch, Islamic Azad University Iran BRCA2FASLGGenetic variationGSTM1Male infertilityMTHFR 120117.pdf Tirumala Vani G, Mukesh N, Siva Prasad B, Rama Devi P, Hema Prasad M, Usha Rani P, et al. 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Combined effect of GSTM1 gene deletion, GSTT1 gene deletion and MTHFR C677T mutation in male infertility. Arch Biol Sci Belgrade. 2010;62(3):525-30.##Krausz C, Escamilla AR, Chianese C. Genetics of male infertility: from research to clinic. Reproduction. 2015;150(5):R159-74.##Hotaling JM. Genetics of male infertility. Urol Clin North Am. 2014;41(1):1-17.##Aston KI, Conrad DF. A review of genome-wide approaches to study the genetic basis for spermatogenic defects. Methods Mol Biol. 2013;927:397-410.##Agarwal A, Prabakaran S, Allamaneni S. What an andrologist/urologist should know about free radicals and why. Urology. 2006;67(1):2-8.##Tremellen K. Oxidative stress and male infertility--a clinical perspective. Hum Reprod Update. 2008;14(3):243-58.##Iwasaki A, Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril. 1992;57(2):409-16.##Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. 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Unusual Cases of Pure Malignant Germ Cell Tumors of the Ovary: A Case Series on 10 Years Experience at a Tertiary Care Center 2 1 2 Background: Malignant ovarian germ cell tumors (MOGCTs) are rare female cancers, constituting up to 10% of ovarian cancers. Dysgerminoma is the most common histological variant. Surgical removal of the tumor with optimal debulking is the treatment of choice. Multidrug chemotherapy following surgery offers high remission rates. Considering the prevalence of these tumors in adolescent and young females, fertility-sparing treatment is of paramount importance. Methods: The data of all patients with ovarian malignancy admitted at a tertiary-care-teaching hospital from September 2009-March 2019 were analyzed. Ten patients of MOGCTs were treated in this period. The clinical features, radiological and biochemical findings, and management and treatment outcome were evaluated. Results: The median age of patients was 23 years. Histological subtypes included immature teratoma (n=3), endodermal sinus tumor (n=4), and dysgerminoma (n=3). Tumor markers namely AFP, βHCG, and LDH increased in all except the patients with immature teratoma. Two patients with dysgerminoma were in the second trimester of pregnancy. All patients except one underwent surgery followed by BEP chemotherapy. Two patients had developed metastasis within six months of treatment and died. In seven patients, no evidence of disease was reported till date. Conclusion: Management of antenatal patients with dysgerminoma by surgery followed by BEP chemotherapy has favorable prognosis. Fertility-sparing surgery with adjuvant chemotherapy offers great advantage in young girls. However, risk stratification based on prognostic factors should be implemented in order to individualize the treatment for achieving higher survival rates. The option for oocyte-cryopreservation prior to surgery must be discussed with patients desiring future fertlity. 267 274 Lajya LD Goyal Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences India Balpreet B Kaur Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences India bdhaliwal199@gmail.com Gitanjali G Goyal Department of Biochemistry, Guru Gobind Singh Medical College and Hospital Department of Biochemistry, Guru Gobind Singh Medical College and Hospital India Parveen P Rajora Department of Obstetrics and Gynaecology, Guru Gobind Singh Medical College and Hospital, Faridkot Department of Obstetrics and Gynaecology, Guru Gobind Singh Medical College and Hospital, Faridkot India DysgerminomaPlatinum-based chemotherapyYolk sac tumor 120125.pdf Zhang Y, Luo G, Li M, Guo P, Xiao Y, Ji H, et al. 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Comparison of Tamoxifen and Clomiphene Citrate for Ovulation Induction in Women with Polycystic Ovarian Syndrome: A Prospective Study 2 1 2 Background: The purpose of this study was to compare the efficacy of tamoxifen and clomiphene citrate in induction of ovulation in women with PCOS and anovulation. Methods: In this prospective cohort study, 104 women with PCOS and primary infertility were enrolled after fulfilling the inclusion and exclusion criteria. The patients were allocated in two groups; group A (n=54) received tamoxifen 40 mg once daily (Days 3-7) and group B (n=50) received clomiphene citrate 100 mg once daily (Days 3-7). Serial ultrasounds were done till the administration of human chorionic gonadotropin (hCG). The ovulation and pregnancy rates in both groups were compared. The number of dominant follicles, estradiol levels, and endometrial thickness were also studied. Comparison was done using chi-square and student’s t-test and a p-value of less than 0.05 was considered statistically significant. Results: The number of dominant follicles and serum estradiol levels were significantly higher in group B (p<0.05), whereas the endometrial thickness was significantly more in group A (p<0.05). The ovulation rates were similar in both groups (66.6% vs. 70%, p=0.715). Pregnancy rate per treatment cycle and per ovulatory cycle was marginally higher in group A (14.81% and 22.22%, respectively), as compared to group B (14% and 20%, respectively), but the difference was not statistically significant (p>0.05). Conclusion: Tamoxifen and clomiphene citrate are both equally effective in induction of ovulation and achieving a pregnancy in women with PCOS. 274 282 Sangita S Sharma Department of Reproductive Medicine, Mahatma Gandhi University of Medical Science and Technology Department of Reproductive Medicine, Mahatma Gandhi University of Medical Science and Technology India sangi237@yahoo.com Manisha M Choudhary Department of Reproductive Medicine, Mahatma Gandhi University of Medical Science and Technology Department of Reproductive Medicine, Mahatma Gandhi University of Medical Science and Technology India Vikas V Swarankar Department of Reproductive Medicine, Mahatma Gandhi University of Medical Science and Technology Department of Reproductive Medicine, Mahatma Gandhi University of Medical Science and Technology India Vaibhav V Vaishnav Manipal Hospital Jaipur Manipal Hospital Jaipur India AnovulationClomipheneInfertilityOvulation inductionPolycystic ovary syndromePregnancy ratesTamoxifen 120126.pdf Hamilton-Fairley D, Kiddy D, Watson H, Paterson C, Franks S. Association of moderate obesity with poor pregnancy outcome in women with polycystic ovary syndrome. Br J Obstet Gynaecol. 1999;99(2):128-31.##Berek JS. Novak's textbook of gynecology. 13th ed. US: Williams & Wilkins; 2002. 1432 p.##NICE guidelines. Fertility problems: assessment and treatment (CG156); 2013. 51 p.##Greenblatt RB, Barfield WE, Jungck EC, Ray AW. Induction of ovulation with MRL/41, preliminary report. JAMA. 1961;178:101-4.##Wolf LJ. Ovulation induction. Clin Obstet Gynecol. 2000;43(4):902-15.##Gorlitsky GA, Kase NG, Speroff L. Ovulation and pregnancy rates with clomiphene citrate. Obstet Gynecol. 1978;51(3):265-9.##Gysler M, March CM, Mishell DR Jr, Bailey EJ. A decade’s experience with an individualized clomiphene treatment regimen including its effect on the postcoital test. Fertil Steril. 1982;37(2):161-7.##Eden JA, Place J, Carter GD, Jones J, Alaghband-Zadeh J, Pawson ME. The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume. Fertil Steril. 1989;73(2):187-90.##Williamson JG, Ellis JD. The induction of ovulation by tamoxifen. J Obstet Gynecol Br Commonw. 1973;80(9):844-7.##Borenstein R, Shoham Z, Yemini M, Barash A, Fienstein M, Rozenman D. Tamoxifen treatment in women with failure of clomiphene citrate therapy. Aust N Z J Obstet Gynaecol. 1989;29(2):173-5.##Gulekli B, Ozaksit G, Turhan NO, Senoz S, Oral H, Gokman O. Tamoxifen: an alternative approach in clomiphene resistant polycystic ovarian syndrome patients. J Pak Med Assoc. 1993;43(5):89-90.##Nicholas S, Macklon. Optimizing protocols for ovulation induction. Female infertility therapy. London: Martin Dunitz; 2000. p. 75-83.##Fox R, Corrigan E, Thomas PA, Hull MGR. The diagnosis of polycystic ovarian in women with menstrual disorder. Fertil Steril. 2000;66:761-4.##Roumen FJ, Doesburg HW, Rolland R. Treatment of infertile women with a deficient postcoital test with two antiestrogens: clomiphene and tamoxifen. Fertil Steril. 1984;41(2):237-43.##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.##World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010. 271 p.##Boostanfar R, Jain JK, Mishell DR Jr, Paulson RJ. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertil Steril. 2001;75(5):1024-6.##Nardo LG. Management of anovulatory infertility associated with polycystic ovary syndrome: tamoxifen citrate an effective alternative compound to clomiphene citrate. Gynecol Endocrinol. 2004;19(50:235-8.##Seyedoshohadaei F, Zandvakily F, Shahgeibi S. Comparison of the effectiveness of clomiphene citrate, tamoxifen and letrozole in ovulation induction in infertility due to isolated unovulation. Iran J Reprod Med. 2012;10(6):531-6.##Badawy A, Gibreal A. Clomiphene citrate versus tamoxifen for ovulation induction in women with PCOS: a prospective randomized trial. Eur J Obstet Gynecol Reprod Biol. 2011;159(1):151-4.##Chunfeng Sun, Musen Wang. Comparative study on the curative effect of clomifene and tamoxifen in infertile patients with polycystic ovary syndrome. China Health Stand Manage. 2016;13:121-3.##Daqing Xiang, Ling Chen, Ling Zeng. Clinical efficacy of clomiphene and tamoxifen on infertility patients with polycystic ovary syndrome. Iran J Reprod Med. 2016;2:284-7.##Narayanan M, Jahaan U, Gupta N. Comparative evaluation of different cost effective ovulation induction drugs and their effect on follicular growth, endometrial thickness and pregnancy outcome. Int J Reprod Contracept Obstet Gynecol. 2019;8(11):4549-53.##Steiner AZ, Terplan M, Paulson RJ. Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod. 2005;20(6):1511-5.##Jie L, Li D, Yang C, Haiying Z. Tamoxifen versus clomiphene citrate for ovulation induction in infertile women. Eur J Obstet Gynecol Reprod Biol. 2018;228:57-64.##Sattar MM, El-Halaby AE, El-Shamy ES, Taha SN. Effect of clomiphene citrate, tamoxifen, and letrozole on endometrial thickness in cycles of ovulation induction: a randomized controlled trial. Menoufia Med J. 2020;33(2):405.##Huang Xuekun Shang, Huiling Zhang, Siyou. Different stimulate ovulation drugs influence of early pregnancy outcome in patients with polycystic ovary syndrome. Pract Med J. 2011;27:3760-2. ##Yu Li, Dong-zi Yang. Letrozole, tamoxifen or clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome after pretreatment: a prospective randomized trial. 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Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome. Cochrane Database Syst Rev. 2016;12(12):CD002249.##Cook LS, Weiss NS, Schwartz SM, White E, McKnight B, Moore DE, et al. Population-based study of tamoxifen therapy and subsequent ovarian, endometrial and breast cancers. J Natl Cancer Inst. 1995;87(18):1359-64.##

The Relationship Between Infertility, Stress, and Quality of Life with Posttraumatic Stress Disorder in Infertile Women 2 1 2 Background: The infertility experience and its treatment are accompanied by the symptoms of posttraumatic stress disorder (PTSD). The aim of this study was determining the relationship between posttraumatic stress disorder and quality of life and the infertile women’s stress. Methods: In this descriptive-analytic study, 172 infertile women were divided in four groups. Convenience sampling was done and eligible infertile women referred to Qafqaz Infertility Center in Iran were included in the study. The data was collected between January and March 2019 through posttraumatic stress disorder checklist, The Fertility Quality of Life (FertiQoL) questionnaire, and Newton's infertility stress questionnaire. Pearson correlation, linear regression analysis, and two-way analysis of variance (ANOVA) were applied for data analysis with a significance level of 0.05. Results: The results of two-way analysis of variance (ANOVA) revealed that there was no significant relationship between the type of treatment (p=0.548) and the reception of psychological intervention (p=0.450). In addition, the results of Pearson correlation showed that there was an inverse significant relationship between the total score of posttraumatic stress disorder and quality of life (r=-0.91, p<0.001) and a direct relationship between the total score of posttraumatic stress disorder and level of stress (r=0.56, p<0.001). Conclusion: The results of this study showed that 41.3% of the infertile women had the symptoms of posttraumatic stress disorder. Due to the relationships of posttraumatic stress disorder with the quality of life and infertility stress, providing regular designed psychological interventions is recommended for infertile individuals. 282 289 Sahar S Roozitalab 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 Mitra M Rahimzadeh Social Determinants of Health Research Center, School of Public Health, Alborz University of Medical Sciences Social Determinants of Health Research Center, School of Public Health, Alborz University of Medical Sciences Iran Seyed Roghieh SR Mirmajidi Obstetrics and Gynecology Department, Alborz University of Medical Sciences Obstetrics and Gynecology Department, Alborz University of Medical Sciences Iran Mina M Ataee Obstetrics and Gynecology Department, Alborz University of Medical Sciences Obstetrics and Gynecology Department, Alborz University of Medical Sciences Iran Sara S Esmaelzadeh-Saeieh Social Determinants of Health Research Center, School of Public Health, Alborz University of Medical Sciences Social Determinants of Health Research Center, School of Public Health, Alborz University of Medical Sciences Iran Esmaelzadeh1360@gmail.com FemaleInfertility Posttraumatic stress disordersPsychologyQuality of life 675.pdf Wdowiak A, Wdowiak A, Moroz E, Bojar I. Comparison of selected sperm parameters between 6,278 males in Poland and Ukraine. Ann Agric Environ Med. 2016;23(1):174-81.##Akhondi MM, Ranjbar F, Shirzad M, Ardakani ZB, Kamali K, Mohammad K. Practical difficulties in estimating the prevalence of primary infertility in Iran. Int J Fertil Steril. 2019;13(2):113-7.##Ghasemi Gojani M, Kordi M, Asgharipur N, Amirian M, Esmaeli H, Eskandarnia E. Comparing the effect of positive reappraisal coping intervention on anxiety of waiting period in IUI treatment using problem-solving skills training. J Mazandaran Univ Med Sci. 2017;27(149):111-23.##Hasanpoor-Azghady SB, Simbar M, Vedadhir AA, Azin SA, Amiri-Farahani L. The social construction of infertility among Iranian infertile women: a qualitative study. J Reprod Infertil. 2019;20(3):178-90.##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.##Haelyon H. The psychological needs of women undergoing IVF treatment. J Reprod Stem Cell Biotechnol. 2010;1(2):212-8.##Hesam AA, Taghipour L, Rasekhi S, Fallahi S, Hesam Z. Investigating the multiple aspects of mental health in infertile women. Int J Mental Health Addict. 2017;15(4):928-32.##Morshed-Behbahani B, Mossalanejad L, Shahsavari S, Dastpak M. The experiences of infertile women on assistant reproductive treatments: a phenomenological study. Iran Red Crescent Med J. 2012;14(6):382-3.##Luk BH, Loke AY. A review of supportive interventions targeting individuals or couples undergoing infertility treatment: directions for the development of interventions. J Sex Marital Ther. 2016;42(6):515-33.##Mains L, Zimmerman M, Blaine J, Stegmann B, Sparks A, Ansley T, et al. Achievement test performance in children conceived by IVF. Hum Reprod. 2010;25(10):2605-11.##Huang JP. The unique challenges in counseling infertile individuals and couples [dissertation]. [US]: University of Minnesota; 2013. 174 p.##Edmondson D, Chaudoir SR, Mills MA, Park CL, Holub J, Bartkowiak JM. From shattered assumptions to weakened worldviews: trauma symptoms signal anxiety buffer disruption. J Loss Trauma. 2011;16(4):358-85.##Karimi FZ, Taghipour A, Latifnejad Roudsari R, Kimiaee SA, Mazloum SR, Amirian M. Psycho-social effects of male infertility in Iranian women: a qualitative study. Iran J Obstet Gynecol Infertil. 2016;19(10):20-32.##Jaffe J. Reproductive trauma: psychotherapy for pregnancy loss and infertility clients from a reproductive story perspective. Psychotherapy (Chic). 2017;54(4):380-5.##Öztürk R, Herbell K, Morton J, Bloom T. "The worst time of my life": treatment‐related stress and unmet needs of women living with infertility. J Community Psychol. 2021;49(5):1121-33.##Corley-Newman A. The relationship between infertility, infertility treatment, therapeutic interventions, and posttraumatic stress disorder [dissertation]: [US]: Walden University; 2017. 149 p.##Weathers FW, Litz BT, Herman DS, Huska JA, Keane TM, editors. The PTSD Checklist (PCL): Reliability, validity, and diagnostic utility. annual convention of the international society for traumatic stress studies, San Antonio, TX; 1993: San Antonio, TX.##Mirzamani MS, Mahmoudi-Gharaei J, Mohammadi MR, Mirzamani SM. Validity of the PTSD symptoms scale self report (PSS-SR) in Iran. Iran J Psychiatry. 2007;2(3):120-3.##Boivin J, Takefman J, Braverman A. The fertility quality of life (FertiQoL) tool: development and general psychometric properties. Hum Reprod. 2011;26(8):2084-91.##Keramat A, Masoomi SZ, Mousavi SA, Poorolajal J, Shobeiri F, Hazavhei SMM. Quality of life and its related factors in infertile couples. J Res Health Sci. 2014;14(1):57-64.##Newton CR, Sherrard W, Glavac I. The fertility problem inventory: measuring perceived infertility-related stress. Fertil Steril. 1999;72(1):54-62.##Alizadeh T, Farahani MN, Shahraray M, Alizadegan S. The relationship between self esteem and locus of control with infertility related stress of no related infertile men and women. J Reprod Infertil. 2005;6(2):194-204.##Van der Kolk BA, McFarlane AC, Weisaeth L. Traumatic stress: The effects of overwhelming ex-perience on mind, body, and society. 1st ed. New York: Guilford. 1996. 559 p.##Bradow A. Primary and secondary infertility and post traumatic stress disorder: experiential differences between type of infertility and symptom characteristics [dissertation]. [Louisville]: Spalding University; 2011. 405 p.##Ranjbar F, Warmelink JC, Gharacheh M. Prenatal attachment in pregnancy following assisted reproductive technology: a literature review. J Reprod Infant Psychol. 2020;38(1):86-108.##Huppelschoten AG, van Duijnhoven NT, Hermens RP, Verhaak C, Kremer JA, Nelen WL. Improving patient-centeredness of fertility care using a multifaceted approach: study protocol for a randomized controlled trial. Trials. 2012;13:175.##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.##Zaig I, Azem F, Schreiber S, Gottlieb-Litvin Y, Meiboom H, Bloch M. Women's psychological profile and psychiatric diagnoses and the outcome of in vitro fertilization: is there an association? Arch Women's Mental Health. 2012;15(5):353-9.##Rooney KL, Domar AD. The relationship between stress and infertility. Dialogues Clin Neurosci. 2018;20(1):41-7.##Huppelschoten AG, Van Dongen A, Verhaak C, Smeenk J, Kremer J, Nelen W. Differences in quality of life and emotional status between infertile women and their partners. Hum Reprod. 2013;28(8):2168-76.##Péloquin K, Brassard A, Arpin V, Sabourin S, Wright J. Whose fault is it? blame predicting psychological adjustment and couple satisfaction in couples seeking fertility treatment. J Psychosomatic Obstet Gynecol. 2018;39(1):64-72.##Farzadi L, Ghasemzadeh A, Bahrami Asl Z, Mahinib M, Shirdel H. Intimate partner violence against infertile women. J Clin Res Gov. 2014;3(2):147-51.##Luk BHK, Loke AY. The impact of infertility on the psychological well-being, marital relationships, sexual relationships, and quality of life of couples: a systematic review. J Sex Marital Ther. 2015;41(6):610-25.##Ying L, Wu LH, Loke AY. The effects of psychosocial interventions on the mental health, pregnancy rates, and marital function of infertile couples undergoing in vitro fertilization: a systematic review. J Assist Reprod Genet. 2016;33(6):689-701.##

Depression Among Infertile Men in the Gaza Strip, Palestine: The Neglected Aspect of Fertility Care 2 1 2 Background: Infertility is a worldwide public health problem and affects psychological aspects of males’ and females’ life. However, the problem has not been well investigated in Palestine. Therefore, the purpose of this study was to determine prevalence and predictors of depression among infertile men in the Gaza strip. Methods: A cross-sectional study was carried out among three hundred eighty five infertile males from January to December 2019. Participants were selected from three main in-vitro fertilization (IVF) centers following simple random sampling. The Arabic version of Beck Depression Inventory was used. Descriptive and inferential analyses were performed using the SPSS V22. Binary analysis was done to determine independent variables and t-test and one-way ANOVA were conducted afterwards. Logistic regression was performed to determine independent factors associated with depression symptoms. The p-value of 0.05 or less was considered statistically significant. Results: Findings showed that 42.6% (164/385) of infertile men had at least one type of depression. Severe depression was presented in 16.6% (64/164) of participants, while 13.2% (51/164) and 12.7% (49/164) showed moderate and mild depression, respectively. Predictors for depression were duration of marriage (>8 years) (CI 95%: 1.099-2.615) and at least one IVF attempt (CI 95%: 0.373-0.873). Conclusion: It has been revealed that depression is prevalent among infertile men. Marriage of long duration and several failures in IVF attempts are predictors for depressions. Psychological counseling besides medical interventions seems to be an optimal strategy to alleviate psychological distress associated with infertility. 289 295 Suha S Baloushah Reproductive Health Department, Nursing and Midwifery School, Tehran University of Medical Science Reproductive Health Department, Nursing and Midwifery School, Tehran University of Medical Science Iran sbaloushah@gmail.com Aymen A Elsous Faculty of Medical Sciences, Israa University-Gaza Faculty of Medical Sciences, Israa University-Gaza Palestine Soha S Abu Eid Shifa Medical Compound, Palestinian Ministry of Health Shifa Medical Compound, Palestinian Ministry of Health Palestine Hanan H Zaqou Directorate General of Primary Healthcare, Ministry of Health Directorate General of Primary Healthcare, Ministry of Health Palestine Fatima FM Ibrahim Reproductive Health Department, Nursing and Midwifery School, Tehran University of Medical Science Reproductive Health Department, Nursing and Midwifery School, Tehran University of Medical Science Iran Mohammed M Abu Shawish Directorate General of Mental Health, Ministry of Health Directorate General of Mental Health, Ministry of Health Palestine DepressionInfertilityIVFMenPalestine 120123.pdf Pozzilli P, Lenzi A, Clarke L, Young WF. 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Anxiety, depression and anger suppression in infertile couples: a controlled study. Hum Reprod. 2002;17(11):2986-94.##Péloquin K, Brassard A, Arpin V, Sabourin S, Wright J. Whose fault is it? blame predicting psychological adjustment and couple satisfaction in couples seeking fertility treatment. J Psychosom Obstet Gynaecol. 2018;39(1):64-72.##El Kissi Y, Romdhane AB, Hidar S, Bannour S, Idrissi KA, Khairi H, et al. General psychopathology, anxiety, depression and self-esteem in couples undergoing infertility treatment: a comparative study between men and women. Eur J Obstet Gynecol Reprod Biol. 2013;167(2):185-9.##Gourounti K, Anagnostopoulos F, Vaslamatzis G. Primary appraisal of infertility: evaluation of the psychometric properties of a Greek version of the appraisal of life events scale (ALE) in a sample of infertile women undergoing fertility treatment. Women Health. 2010;50(7):688-704.##Boivin J, Griffiths E, Venetis CA. Emotional distress in infertile women and failure of assisted reproductive technologies: meta-analysis of prospective psychosocial studies. BMJ. 2011;342:d223.##Jongbloed-Pereboom M, Middelburg K, Heineman M, Bos A, Haadsma M, Hadders-Algra M. The impact of IVF/ICSI on parental well-being and anxiety 1 year after childbirth. Hum Reprod. 2012;27(8):2389-95.##Yang B, Zhang J, Qi Y, Wang P, Jiang R, Li H. Assessment on occurrences of depression and anxiety and associated risk factors in the infertile Chinese men. Am J Mens Health. 2017;11(3):767-74.##Chiaffarino F, Baldini MP, Scarduelli C, Bommarito F, Ambrosio S, D'Orsi C, et al. Prevalence and incidence of depressive and anxious symptoms in couples undergoing assisted reproductive treatment in an Italian infertility department. Eur J Obstet Gynecol Reprod Biol. 2011;158(2):235-41.##Drosdzol A, Skrzypulec V. Depression and anxiety among Polish infertile couples--an evaluative prevalence study. 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Identification of Novel Nucleotide Changes in INHBB Gene by Mutation Screening in Females with Ovarian Dysgenesis: A Case Report 2 1 2 Background: Inhibin and activin regulate the follicle stimulating hormone level by their antagonistic actions and thus have been considered as strong candidate genes in the etiology of ovarian dysgenesis. In the present study, two cases of primary amenorrhea with poorly developed secondary sexual characteristics were reported. The purpose of the study was to identify mutations in candidate gene. Case Presentation: In this paper, clinical, genetic, biochemical, and molecular findings in female patients with primary amenorrhea were reported. Whole blood culture and G-banding for karyotyping, sequencing, and in silico analysis were performed following the standard protocol. Both cases were cytogenetically characterized as normal females with 46,XX, chromosome constitution. Hormonal assay revealed high level of follicle stimulating hormone and luteinizing hormone. DNA sequence analysis of inhibin identified two novel heterozygous missense mutations of c.975T>A and c.1156G>A which were translated into p.I310N and p.D386N, respectively. These identified positions were highly conserved across species during evolution. In silico prediction tools, intramolecular hydrogen bonding pattern and hydrophobicity analysis, revealed deleterious effect of p.I310N and neutral effect of p.D386N mutation. Conclusion: Our observation suggested that identified novel mutation in the first case might be the reason for ovarian dysgenesis and provides additional support to the previously reported genotype-phenotype correlations. 295 302 Pooja P Chauhan Centre for Genetic Disorders, Institute of Science, Banaras Hindu University Centre for Genetic Disorders, Institute of Science, Banaras Hindu University India Anjali A Rani Department of Obstetrics and Gynaecology, Institute of Medical Science, Banaras Hindu University Department of Obstetrics and Gynaecology, Institute of Medical Science, Banaras Hindu University India Amit AK Rai Centre for Genetic Disorders, Institute of Science, Banaras Hindu University Centre for Genetic Disorders, Institute of Science, Banaras Hindu University India akrai10@gmail.com AmenorrheaFollicle stimulating hormoneGonadal dysgenesisInhibinsLuteinizing hormoneMutation 120118.pdf MacNaughton J, Banah M, McCloud P, Hee J, Burger H. Age related changes in follicle stimulating hormone, luteinizing hormone, oestradiol and immunoreactive inhibin in women of reproductive age. Clin Endocrinol (Oxf). 1998;36(4):339-45.##Burger HG, Cahir N, Robertson DM, Groome NP, Dudley E, Green A, et al. Serum inhibins A and B fall differentially as FSH rises in perimenopausal women. Clin Endocrinol (Oxf). 1998;48(6):809-13.##Reame NE, Wyman TL, Phillips DJ, de Kretser DM, Padmanabhan V. Net increase in stimulatory input resulting from a decrease in inhibin B and an increase in activin A may contribute in part to the rise in follicular phase follicle-stimulating hormone of aging cycling women. J Clin Endocrinol Metab. 1998;83(9):3302-7.##Farnworth PG, Robertson DM, de Kretser DM, Burger HG. Effects of 31 kDa bovine inhibin on FSH and LH in rat pituitary cells in vitro: antagonism of gonadotrophin-releasing hormone agonists. J Endocrinol. 1988;119(2):233-41.##Harris SE, Chand AL, Winship IM, Gersak K, Nishi Y, Yanase T, et al. INHA promoter polymorphisms are associated with premature ovarian failure. Mol Hum Reprod. 2005;11(11):779-84.##Stenvers KL, Findlay JK. Inhibins: from reproductive hormones to tumor suppressors. Trends Endocrinol Metab. 2009;21(3):174-80.##Cho BN, McMullen ML, Pei L, Yates CJ, Mayo KE. Reproductive deficiencies in transgenic mice expressing the rat inhibin alpha-subunit gene. Endocrinology. 2001;142(11):4994-5004.##Shelling AN, Burton KA, Chand AL, Van Ee CC, France JT, Farquhar CM, et al. Inhibin: a candidate gene for premature ovarian failure. Hum Reprod. 2000;15(12):2644-9.##Chand AL, Harrison CA, Shelling AN. Inhibin and premature ovarian failure. Hum Reprod Update. 2010;16(1):39-50.##Dixit H, Rao KL, Padmalatha V, Kanakavalli M, Deenadayal M, Gupta N, et al. Expansion of the germline analysis for the INHA gene in Indian women with ovarian failure. Hum Reprod. 2006;21(6):1643-4.##Prakash GJ, Ravi Kanth VV, Shelling AN, Rozati R, Sujatha M. Mutational analysis of inhibin alpha gene revealed three novel variations in Indian women with premature ovarian failure. Fertil Steril. 2010;94(1):90-8.##Lopes AM, Aston KI, Thompson E, Carvalho F, Goncalves J, Huang N, et al. Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1. PLoS Genet. 2013;9(3):e1003349.##Hagen CP, Main KM, Kjaergaard S, Juul A. FSH, LH, inhibin B and estradiol levels in Turner syndrome depend on age and karyotype: longitudinal study of 70 Turner girls with or without spontaneous puberty. Hum Reprod, 2010;25(12):3134-41.##Gravholt CH, Naeraa RW, Andersson AM, Christiansen JS, Skakkebaek NE. Inhibin A and B in adolescents and young adults with Turner’s syndrome and no sign of spontaneous puberty. Hum Reprod. 2002;17(8):2049-53.##Chand AL, Ooi GT, Harrison CA, Shelling AN, Robertson DM. Functional analysis of the human inhibin a subunit variant A257T and its potential role in premature ovarian failure. Hum Reprod. 2007;22(12):3241-8.##Dixit H, Deendayal M, Singh L. Mutational analysis of the mature peptide region of inhibin genes in Indian women with ovarian failure. Hum Reprod. 2004;19(8):1760-4.##Marozzi A, Porta C, Vegetti W, Crosignani PG, Tibiletti MG, Dalprà L, et al. Mutation analysis of the inhibin alpha gene in a cohort of Italian women affected by ovarian failure. Hum Reprod. 2002;17(7):1741-5.##

Kallmann Syndrome and X-linked Ichthyosis Caused by Translocation Between Chromosomes X and Y: A Case Report 2 1 2 Background: Xp22.3 region is characterized by low frequency of interspersed repeats and low GC content. Several clinically important genes including ANOS1 (KAL1) reside in this region. This gene was first identified due to translocation between chromosomes X and Y in a patient with Kallmann syndrome. Case Presentation: A 20 year old male presented with complaints of delayed secondary sexual characteristics, impaired sense of smell, and poor scholastic performance. On examination, he had short stature (151 cm; <3rd centile). His sexual maturity corresponded to Tanner stage 3. Stretched penile length was 3.6 cm (<3rd centile). Right testis was undescended with low left testicular volume (12 ml). There was mild ichthyosis over abdomen and back. He had hyposmia, hoarse voice, and synkinesia. Investigations were suggestive of hypogonadotrophic hypogonadism. Karyotype revealed an extra chromosomal material on p arm of chromosome X (46,Xp+,Y). On cytogenetic microarray, deletion of 8.3 Mb on Xp22.33 region and duplication of 12.8 Mb on Yq11.22 region were identified. The breakpoint on X chromosome resulted in deletion of exons 7-14 of ANOS1 gene and complete STS, NLGN4X, ARSL (ARSE), SHOX, and VCX genes. Conclusion: Patients diagnosed with Kallmann syndrome should receive careful clinical evaluation to detect presence of a contiguous gene syndrome. 302 307 Haseena H Sait Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences India Priyanka P Srivastava Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences India Preeti P Dabadghao Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences India Shubha R SR Phadke Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences India drshubharaophadke@gmail.com HypogonadismHyposmiaIchthyosisKallmann syndromeStunting 120124.pdf Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, et al. The DNA sequence of the human X chromosome. Nature. 2005;434(7031):325-37.##Guioli S, Incerti B, Zanaria E, Bardoni B, Franco B, Taylor K, et al. Kallmann syndrome due to a translocation resulting in an X/Y fusion gene. Nat Genet. 1992;1(5):337-40.##Khudr G, Benirschke K, Judd HL, Strauss J. Y to X translocation in a woman with reproductive failure. a new rearrangement. JAMA. 1973;226(5):544-9.##Bernstein R, Wagner J, Isdale J, Nurse GT, Lane AB, Jenkins T. X-Y translocation in a retarded phenotypic male. Clinical, cytogenetic, biochemical, and serogenetic studies. J Med Genet. 1978;15(6):466-74.##Ballabio A, Bardoni B, Carrozzo R, Andria G, Bick D, Campbell L, et al. Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome. Proc Natl Acad Sci USA. 1989;86(24):10001-5.##Meindl A, Hosenfeld D, Bruckl W, Schuffenhauer S, Jenderny J, Backsulin, et al. Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism. J Med Genet. 1993;30(10):838-42.##Klink A, Meindl A, Hellbrand H, Rappold GA. A patient with an interstitial deletion in Xp22.3 locates the gene for X linked recessive chondrodysplasia punctata to within a one megabase interval. Hum Genet. 1994;93(4):463-6.##Parenti G, Rizzolo MG, Ghezzi M, Di Maio S, Sperandeo MP, Incerti B, et al. Variable penetrance of hypogonadism in a sibship with Kallmann syndrome due to a deletion of the KAL1 gene. Am J Med Genet. 1995;57(3):476-8.##Maya-Núñez G, Cuevas-Covarrubias S, Carlos Zenteno J, Ulloa-Aguirre A, Kofman-Alfaro S, Pablo Méndez JP. Contiguous gene syndrome due to deletion of the first three exons of the Kallmann gene and complete deletion of the steroid sulphatase gene. Clin Endocrinol (Oxf). 1998;48(6):713-8.##Lonardo F, Parenti G, Luquetti DV, Annunziata I, Monica MD, Perone L, et al. Contigous gene syndrome due to an interstitial deletion in Xp22.3 in a boy with ichthyosis, chondrodysplasia punctate, mental retardation and ADHD. Eur J Med Genet. 2007;50(4):301-8.##Cho EH, Kim SY, Kim JK. A case of 9.7 Mb terminal Xp deletion including OA1 locus associated with contiguous gene syndrome. J Korean Med Sci. 2012;27(10):1273-7.##Berges-Raso I, Giménez-Palop O, Gabau E, Capel I, Caixàs A, Rigla M. Kallmann syndrome and ichthyosis: a case of contiguous gene deletion syndrome. Endocrinol Diabetes Metab Case Rep. 2017;2017:EDM170083.##Nagai K, Shima H, Kamimura M, Kanno J, Suzuki E, Ishiguro A, et al. Xp22.31 microdeletion due to microhomology-mediated break-induced replication in a boy with contiguous gene deletion syndrome. Cytogenet Genome Res. 2017;151(1):1-4.##