Will Artificial Intelligence Change the Future of IVF? 2 1 2 "Nothing is lost, nothing is created, everything changes," says the famous chemist, Antoine Lavoisier. The same is true for Artificial intelligence (AI); everything touched by AI undergoes transformation. Therefore, this question arises whether AI is effective in assisted reproductive technologies (ART) as in other industries or not (1). The global industry of IVF is predictable to grow by about 10% annually from $638 million in 2021 to $987 million in 2026. Increased age of first pregnancy, decline in fertility rates, prevalence of male infertility, obesity, alcohol consumption, public awareness of infertility, and development of several new treatment options are important factors in the growth of this market (2). While most studies on humans and animals have been conducted with the aim of improving ART success, the rate remained almost constant at 30% with no noticeable change for a decade. AI as one of the greatest human discoveries of the present century can be used to improve IVF success rate. AI mimics human in-telligence in medicine such as managing medical records and other data, performing repetitive tasks, designing treatments, providing digital counseling, virtual nursing, administration of medicine, designing drugs, utilizing precision medicine, and health monitoring and analysis of health care system. AI has the potential to overtake physicians and help them in prognosis and diagnosis of diseases more effectively, more accurately and more quickly (3, 4). Artificial intelligence is the interface between humans and computers, while reproductive medicine is a combination of clinical medicine and embryology lab. The application of AI has the potential to create a distance between physicians and patients through computer algorithms. The term of Repro-AI is defined as the interdisciplinary technology between reproductive medicine and mathematical sciences to advance the appli-cations of AI in the diagnosis and treatment of infertility. In many areas of research, especially in the field of physics, a long time has elapsed before discovering the benefits of the new technologies and application of them in people's daily lives. However, the advantages of Repro-AI are perceptible in a shorter period of time. The efficiency of Repro-AI relies on continuous develop-ment and the use of powerful technologies such as automated time-lapse imaging, single-step culture, inte-grated digital and laboratory health data, and monitoring of environmental systems. Hopefully, some of these technologies are attainable in the near future, such as " laboratory on a chip" (IVF, ICSI, biopsy and freezing of embryo on fine chamber) and "DIY"(do-it-yourself) IVF cycles (1, 2). The expansion of AI in reproductive sciences is so fast that it covers a wide range of procedures in IVF clinics, from assessment of couples' fertility to the success rate of IVF cycles. High-resolution image pro-cessing has been developed to interpret and analyze the quality of embryos for their correct grading and best selection. Therefore, the rate of implantation potential, ongoing pregnancy, and endometrial receptivity would be the highest for a synchronized dialogue between uterus and embryo (5). In an IVF clinic, several obstacles should be overcome including managing large volumes of treatment data, tests, equipment and consumables used in various departments such as clinics, laboratories, operation rooms, consultation rooms, etc. AI and machine learning (ML) are much more effective in comparison to human power in intelligent management of all necessary information without the need for paper (1, 4). Automation is one of the most important benefits of AI, which leads to increased productivity and efficacy. AI in embryology lab potentially helps to increase safety of gametes, embryos, patients, and staff. Moreover, infertility treatment can be standardized through automation and elimination of dreary, mental, manual, and time-consuming tasks such as embryo grading, semen analysis, embryo and oocyte cryopreservation, quality control, and quality assurance. The use of microfluidic systems and artificial intelligence-based robots can greatly contribute to embryo culture systems and the optimal use of culture media, chemicals, and plasticware (1, 2). At present, embryologists spend a great deal of their time on the heavy and time-consuming work of the embryology lab, which prevents them from focusing on more important tasks such as intracytoplasmic sperm injection (ICSI), embryo biopsy, and training new embryologists and young staff. Unfortunately, there is a shortage of skilled and experienced embryologists worldwide, and their appropriate training requires a lot of time and effort under supervision of seasoned senior embryologists or lab supervisors (1, 2). Despite significant advances in the IVF industry over the past 40 years, adoption of a common approach by inventers and users of Repro-AI technologies, universities, regulators, and professional groups will make incredible development in the infertility treatment industry. The Repro-AI will eventually provide quick and safe benefits to infertile patients (2, 4). Though the applications of AI in the embryology lab is more widespread in comparison to other areas, its use is likely to be expanded into other aspects of reproductive medicine in the near future. Extensive use of AI for correct assessment of infertile couples' characteristics such as their ovarian reserve, status of spermatogenesis and sperm parameters, age, endocrine status and diagnostic tests will undoubtedly increase the efficiency and speed of diagnosis and subsequent treatment of all reproductive dis-orders (5). Despite huge reports regarding the bright and growing future of AI in all aspects of human life, AI has opponents and critics, such as the leading physicist Stephen Hawking, who warned of AI: "The develop-ment of full artificial intelligence could spell the end of the human race…. It would take off on its own, and re-design itself at an ever increasing rate. Humans, who are limited by slow biological evolution, couldn't com-pete, and would be superseded" (1). All in all, notwithstanding the entire benefits and criticisms of AI, there is great hope that AI can reform and improve all aspects of our life, including medicine and particularly IVF-related issues. The current challenge of AI is its different methods and algorithms on different platforms. Therefore, the generalizability of AI algorithms is currently limited to the population or clinic for which the platform is designed. In other words, the minimum necessary standards for its application have not yet been prepared to apply the technology to the whole community. Accordingly, despite the current satisfactory results of AI, it is necessary to be cautious about using the technology and wait for its development in the future. Perhaps the future will prove us that it was another creation of technology developers which is released ahead of time, and maybe it would be more advisable that human beings exert their best efforts to improve their intelligence instead of AI. 139 141 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 130158.pdf Trolice MP, Curchoe C, Quaas AM. Artificial intelligence-the future is now. J Assist Reprod Genet. 2021;38(7):1607-12.##Medical Product Outsourcing. Online exclusive: AI-Based platforms are shaping the IVF industry [Internet]. New Jersey: Medical Product Outsourcing; 2003. [cited 2022 Jul 2]; [about 4 screens]. Available from: https://www.mpo-mag.com/contents/view_online-exclusives/2021-12-09/ai-based-platforms-are-shaping-the-ivf-industry##Chow DJ, Wijesinghe Ph, Dholakia K, Dunning KR. Does artificial intelligence have a role in the IVF clinic? Reprod Fertil. 2021;2(3):C29-C34.##Wang R, Pan W, Jin L, Li Y, Geng Y, Gao Ch, et al. Artificial intelligence in reproductive medicine. Reproduction. 2019;158(4):R139-R54.##Zaninovic N, Rosenwaks Z. Artificial intelligence in human in vitro fertilization and embryology. Fertil Steril. 2020; 114(5):914-20.##

Sperm Retrieval in Non-azoospermic Patients with Persistent Ejaculation Dysfunction 2 1 2 Infertility is a common disease that affects 15 to 20% of couples at some point in their lives. Among infertile couples, male factor accounts for 50% of infertile cases. Assisted reproductive techniques are the gold standard approach in case of failure in medical or surgical treatments. Moreover, the role of the urologist in these approaches is to provide appropriate sperm on the day of oocyte pick-up. However, sperm retrieval procedure is quite different in azoospermic and non-azoospermic men. Although most cases of infertile patients are not azoospermic, their ejaculation disorder prevents obtaining sperm for assisted reproductive techniques. This review article explains common problems of sperm retrieval in non-azoospermic patients with persistent ejaculatory dysfunction and introduces some management strategies. In fact, it is possible to design a classic approach for managing such patients, which definitely reduces the problems faced by clinicians as well. 141 148 Hamed H Akhavizadegan Urology Department, Tehran University of Medical Sciences Urology Department, Tehran University of Medical Sciences Iran Mohammad Ali MA Sadighi Gilani Urology Department, Tehran University of Medical Sciences Urology Department, Tehran University of Medical Sciences Iran Naser N Amirjannati Department of Andrology and Embryology, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Department of Andrology and Embryology, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran namirjannati@yahoo.com Mahnaz M Heidari مهناز حیدری Department of Andrology and Embryology, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Department of Andrology and Embryology, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran AzoospermiaEjaculationInfertilitySemen analysisSperm retrieval 120155.pdf Qi L, Liu YP, Zhang NN, Su YC. Predictors of testicular sperm retrieval in patients with non-obstructive azoospermia: a review. J Int Med Res. 2021;49(4):3000605211002703.##Eslamian G, Amirjannati N, Rashidkhani B, Sadeghi MR, Baghestani AR, Hekmatdoost A. Adherence to the western pattern is potentially an unfavorable indicator of asthenozoospermia risk: a case-control study. J Am Coll Nutr. 2016;35(1):50-8.##Shin DH, Turek PJ. Sperm retrieval techniques. Nat Rev Urol. 2013;10(12):723-30.##Akhavizadegan H. Benefit of sperm freezing before radical orchiectomy. Clin Transl Oncol. 2009;11 (12):849-50.##Eslamian G, Amirjannati N, Rashidkhani B, Sadeghi MR, Baghestani AR, Hekmatdoost A. Dietary fatty acid intakes and asthenozoospermia: a case-control study. Fertil Steril. 2015;103(1):190-8.##Phillips E, Carpenter C, Oates RD. Ejaculatory dysfunction. Urol Clin North Am. 2014;41(1):115-28.##Mostafa T, Abdel-Hamid IA. Ejaculatory dysfunction in men with diabetes mellitus. World J Diabetes. 2021;12(7):954-74.##Eslamian G, Amirjannati N, Rashidkhani B, Sadeghi MR, Hekmatdoost A. Nutrient patterns and asthenozoospermia: a case-control study. Andrologia. 2017;49(3).##Pizzol D, Trott M, Grabovac I, Yang L, Barnett Y, Parris C, et al. Ejaculation disorders in male patients with cancer: a systematic review and meta-analysis of prevalence. J Urol. 2021;206(6):1361-72.##Trinchieri M, Trinchieri M, Perletti G, Magri V, Stamatiou K, Cai T, et al. Erectile and ejaculatory dysfunction associated with use of psychotropic drugs: a systematic review. J Sex Med. 2021;18(8):1354-63.##Salonia A, Bettocchi C, Boeri L, Capogrosso P, Carvalho J, Cilesiz NC, et al. European association of urology guidelines on sexual and reproductive health-2021 update: male sexual dysfunction. Eur Urol. 2021;80(3):333-57.##Ebner T, Shebl O, Mayer RB, Moser M, Costamoling W, Oppelt P. Healthy live birth using theophylline in a case of retrograde ejaculation and absolute asthenozoospermia. Fertil Steril. 2014;101(2):340-3.##Marmar JL, Praiss DE, DeBenedictis TJ. Postcoital-voiding insemination: technique for patients with retrograde ejaculation and infertility. Urology. 1977;9(3):288-90.##Hsiao W, Deveci S, Mulhall JP. Outcomes of the management of postchemotherapy retroperitoneal lymph node dissection–associated anejaculation. BJU Int. 2012;110(8):1196-200.##Revenig L, Leung A, Hsiao W. Ejaculatory physiology and pathophysiology: assessment and treatment in male infertility. Transl Androl Urol. 2014;3(1):41-9.##Ibrahim E, Brackett NL, Lynne CM. Advances in the management of infertility in men with spinal cord injury. Asian J Androl. 2016;18(3):382-90.##Perrin J, Saïas-Magnan J, Lanteaume A, Thiry-Escudié I, Serment G, Bladou F, et al. [Initial results of a novel technique for sperm retrieval in male infertility due to refractory retrograde ejaculation]. Prog Urol. 2011;21(2):134-8. French.##Lu S, Cui Y, Li X, Zhang H, Hu J, Liu J, et al. Sperm retrieval in anejaculatory diabetic men who failed in drug treatment and penile vibratory stimulation during blood sugar under control. Andrologia. 2014;46(4):370-3.##Kondoh N. Ejaculatory dysfunction as a cause of infertility. Reprod Med Biol. 2012;11(1):59-64. ##Mehta A, Sigman M. Management of the dry ejaculate: a systematic review of aspermia and retrograde ejaculation. Fertil Steril. 2015;104(5):1074-81.##Marina S, Marina F, Alcolea R, Nada J, Pons MC, Grossmann M, et al. Triplet pregnancy achieved through intracytoplasmic sperm injection with spermatozoa obtained by prostatic massage of a paraplegic patient. Hum Reprod. 1999;14(6):1546-8.##Hadiji N, Benbouzid R, Previnaire JG, Leblond C, Mieusset R, Enjalbert M, et al. [Evaluation of treatment of erectile and ejaculatory dysfunction in a series of 90 spinal cord injured]. Prog Urol. 2013;23(17):1489-93. French.##Arafa MM, Zohdy WA, Shamloul R. Prostatic massage: a simple method of semen retrieval in men with spinal cord injury. Int J Androl. 2007;30(3):170-3.##Ohl DA, Sonksen J, Menge AC, McCabe M, Keller LM. Electroejaculation versus vibratory stimulation in spinal cord injured men: sperm quality and patient preference. J Urol. 1997;157(6):2147-9.##Engin-Üstün Y, Korkmaz C, Duru NK, Başer İ. Comparison of three sperm retrieval techniques in spinal cord-injured men: pregnancy outcome. Gynecol Endocrinol. 2006;22(5):252-5. ##Qiu Y, Wang LG, Zhang LH, Zhang AD, Wang ZE. Quality of sperm obtained by penile vibratory stimulation and percutaneous vasal sperm aspiration in men with spinal cord injury. J Androl. 2012;33(5):1036-46.##Fode M, Ohl DA, Sønksen J. A step-wise approach to sperm retrieval in men with neurogenic anejaculation. Nat Rev Urol. 2015;12(11):607-16.##Leduc BE. Treatment of infertility in 31 men with spinal cord injury. Can J Urol. 2012;19(5):6432-6.##Sonksen J, Ohl DA. Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction. Int J Androl. 2002;25(6):324-32. ##Soler JM, Previnaire JG, Plante P, Denys P, Chartier-Kastler E. Midodrine improves orgasm in spinal cord-injured men: the effects of autonomic stimulation. J Sex Med. 2008;5(12):2935-41.##Nancy LB. Infertility in men with spinal cord injury: research and treatment. Scientifica (Cairo). 2012;2012:578257.##Brackett NL, Kafetsoulis A, Ibrahim E, Aballa TC, Lynne CM. Application of 2 vibrators salvages ejaculatory failures to 1 vibrator during penile vibratory stimulation in men with spinal cord injuries. J Urol. 2007;177(2):660-3. ##Sonksen J, Fode M, Löchner-Ernst D, Ohl DA. Vibratory ejaculation in 140 spinal cord injured men and home insemination of their partners. Spinal Cord. 2012;50(1):63-6. ##Goetz LL, Stiens SA. Abdominal electric stimulation facilitates penile vibratory stimulation for ejaculation after spinal cord injury: a single-subject trial. Arch Physical Med Rehabil. 2005;86(9): 1879-83.##Trofimenko V, Hotaling JM. Fertility treatment in spinal cord injury and other neurologic disease. Transl Androl Urol. 2016;5(1):102-16.##Reignier A, Lammers J, Splingart C, Redhead D, Labat JJ, Mirallié S, et al. Sperm cryopreservation and assisted reproductive technology outcome in patients with spinal cord injury. Andrologia. 2018;50(1).##Iwahata T, Shin T, Shimomura Y, Suzuki K, Kobayashi T, Miyata A, et al. Testicular sperm extraction for patients with spinal cord injury related anejaculation: a single-center experience. Int J Urol. 2016;23(12):1024-7.##

The Association of Mitochondrial Translocator Protein and Voltage-Dependent Anion Channel-1 in Granulosa Cells with Estradiol Levels and Presence of Immature Follicles in Polycystic Ovary Syndrome 2 1 2 Background: Granulosa cells (GCs) play key roles in oocyte maturation by providing required estradiol (E2). Since the presence of immature oocytes has been reported in cases with polycystic ovary syndrome (PCOS), in this study, the levels of mitochondrial membrane transporter proteins involved in E2 synthesis were determined. E2 concentration and parameters of oxidative status were also measured in follicular fluids of PCOS women. Methods: Forty-three women with PCOS and 43 healthy women who were candidates for IVF procedure due to their husbands' infertility were enrolled in this case-control study. The gene expression and protein levels of mitochondrial translocator protein (TSPO) and voltage-dependent anion channel 1 (VDAC1) were determined in GCs using RT-qPCR and immunocytochemistry assay, respectively. E2 level was measured with electrochemiluminescence, whereas total cholesterol, total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) were determined using colorimetric methods in follicular fluids. Data were analyzed using unpaired t-test or Mann-Whitney U test, and Spearman’s correlation coefficient. Results: VDAC1 and TSPO were significantly lower in mRNA (p<0.05) and protein levels (p<0.001) of PCOS patients. PCOS patients had lower cholesterol, estradiol, and TAC levels, and higher TOS and MDA contents. E2 level had direct correlation with VDAC1, TSPO, and TAC while it was negatively correlated with TOS, oxidative stress index (OSI), and MDA (p<0.001). Higher E2 levels were associated with higher numbers of high-quality oocytes and conceived embryos (p<0.001). Conclusion: Decreased E2 levels and increased oxidative stress in the follicular fluid may be the cause of immature oocytes in PCOS cases. 148 160 Sahar S Mazloomi Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Iran Marzieh M Sanoeei Farimani Fertility Research Centre, Fatemieh Hospital, Hamadan University of Medical Sciences Fertility Research Centre, Fatemieh Hospital, Hamadan University of Medical Sciences Iran Heidar H Tayebinia Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Iran Jamshid J Karimi Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Iran Iraj I Amiri ایرج امیری Fertility Research Centre, Fatemieh Hospital, Hamadan University of Medical Sciences Fertility Research Centre, Fatemieh Hospital, Hamadan University of Medical Sciences Iran Ebrahim E Abbasi Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Iran Iraj I Khodadadi Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences Iran khodadadi@umsha.ac.ir EstradiolGranulosa cellOxidative stressPolycystic ovary syndromeTSPO proteinVoltage-dependent anion channel 1 130156.pdf Fainberg J, Kashanian JA. Recent advances in understanding and managing male infertility. F1000Res. 2019;8:F1000 Faculty Rev-670.##Sarhan D, El Mazny A, Taha T, Aziz A, Azmy O, Fakhry D, et al. Estradiol and luteinizing hormone concentrations in the follicular aspirate during ovum pickup as predictors of in vitro fertilization (IVF) outcome. Middle East Fertil Soci J. 2017;22(1):27-32.##Crespo RP, Bachega TA, Mendonça BB, Gomes LG. An update of genetic basis of PCOS pathogenesis. Arch Endocrinol Metab. 2018;62(3):352-61.##Balen AH, Morley LC, Misso M, Franks S, Legro RS, Wijeyaratne CN, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016;22(6):687-708.##Masjedi F, Keshtgar S, Agah F, Karbalaei N. Association between sex steroids and oxidative status with vitamin D levels in follicular fluid of non-obese PCOS and healthy women. J Reprod Infertil. 2019;20(3):132-42.##Li J, Ma XJ, Wu X, Si SJ, Li C, Yang PK, et al. Adiponectin modulates steroid hormone secretion, granulosa cell proliferation and apoptosis via binding its receptors during hens’ high laying period. Poult Sci. 2021;100(7):101197.##Yu L, Liu M, Wang Z, Liu T, Liu S, Wang B, et al. Correlation between steroid levels in follicular fluid and hormone synthesis related substances in its exosomes and embryo quality in patients with polycystic ovary syndrome. Reprod Biol Endocrinol. 2021;19(1):74.##Wen X, Li D, Tozer AJ, Docherty SM, Iles RK. Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles. Reprod Biol Endocrinol. 2010;8:117.##Miller WL. Steroid hormone synthesis in mitochondria. Mol Cell Endocrinol. 2013;379(1-2):62-73.##Sreerangaraja Urs DB, Wu WH, Komrskova K, Postlerova P, Lin YF, Tzeng CR, et al. Mitochondrial function in modulating human granulosa cell steroidogenesis and female fertility. Int J Mol Sci. 2020;21(10):3592.##Rone MB, Midzak AS, Issop L, Rammouz G, Jagannathan S, Fan J, et al. Identification of a dynamic mitochondrial protein complex driving cholesterol import, trafficking, and metabolism to steroid hormones. Mol Endocrinol. 2012;26(11):1868-82.##Veenman L, Shandalov Y, Gavish M. VDAC activation by the 18 kDa translocator protein (TSPO), implications for apoptosis. J Bioenerg Biomembr. 2008;40(3):199-205.##Gatliff J, Campanella M. TSPO is a REDOX regulator of cell mitophagy. Biochem Soc Trans. 2015;43(4):543-52.##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.##Liu Y, Yu Z, Zhao S, Cheng L, Man Y, Gao X, et al. Oxidative stress markers in the follicular fluid of patients with polycystic ovary syndrome correlate with a decrease in embryo quality. J Assist Reprod Genet. 2021;38(2):471-7.##Artimani T, Karimi J, Mehdizadeh M, Yavangi M, Khanlarzadeh E, Ghorbani M, et al. Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2018;34(2):148-52.##Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.##Tan IF, Lim AJ, Indran IR, Kramer MS, Yong EL. Reproductive outcomes of women with polycystic ovarian syndrome following in-Vitro fertilization—a meta-analysis and systematic review. Fertil Reprod. 2019;1(4):193-201.##Pellicer A, Valbuena D, Bauset C, Albert C, Bonilla-Musoles F, Remohı́ 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.##Masjedi F, Keshtgar S, Zal F, Talaei-Khozani T, Sameti S, Fallahi S, et al. Effects of vitamin D on steroidogenesis, reactive oxygen species production, and enzymatic antioxidant defense in human granulosa cells of normal and polycystic ovaries. J Steroid Biochem Mol Biol. 2020;197:105521.##Joo HK, Lee YR, Lim SY, Lee EJ, Choi S, Cho EJ, et al. Peripheral benzodiazepine receptor regulates vascular endothelial activations via suppression of the voltage-dependent anion channel-1. FEBS Lett. 2012;586(9):1349-55.##Fan J, Wang K, Zirkin B, Papadopoulos V. CRISPR/Cas9‒mediated Tspo gene mutations lead to reduced mitochondrial membrane potential and steroid formation in MA-10 mouse tumor Leydig cells. Endocrinology. 2018;159(2):1130-46.##Owen DR, Fan J, Campioli E, Venugopal S, Midzak A, Daly E, et al. TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis. Biochem J. 2017;474(23):3985-99.##Zhang J, Bao Y, Zhou X, Zheng L. Polycystic ovary syndrome and mitochondrial dysfunction. Reprod Biol Endocrinol. 2019;17(1):67.##Sulaiman MA, Al-Farsi YM, Al-Khaduri MM, Saleh J, Waly MI. Polycystic ovarian syndrome is linked to increased oxidative stress in Omani women. Int J Womens Health. 2018;10:763-71.##Moti M, Amini L, Ardakani SSM, Kamalzadeh S, Masoomikarimi M. Oxidative stress and anti-oxidant defense system in Iranian women with polycystic ovary syndrome. Iran J Reprod Med. 2015;13(6):373-8.##Mazloomi S, Sheikh N, Sanoee Farimani M, Pilehvari S. Association of Prx4, total Oxidant status, and inflammatory factors with insulin resistance in polycystic ovary syndrome. Int J Endocrinol. 2021;2021:9949753.##Ilkan Z, Akar FG. The mitochondrial translocator protein and the emerging link between oxidative stress and arrhythmias in the diabetic heart. Front Physiol. 2018;9:1518.##Jamilian M, Modarres SZ, Siavashani MA, Karimi M, Mafi A, Ostadmohammadi V, et al. The influences of chromium supplementation on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome women candidate for in vitro fertilization: a randomized, double-blind, placebo-controlled trial. Biol Trace Element Res. 2018;185(1):48-55.##Adeoye O, Olawumi J, Opeyemi A, Christiania O. Review on the role of glutathione on oxidative stress and infertility. JBRA Assist Reprod. 2018;22(1):61-6.##Nasiri N, Moini A, Eftekhari-Yazdi P, Karimian L, Salman-Yazdi R, Zolfaghari Z, et al. Abdominal obesity can induce both systemic and follicular fluid oxidative stress independent from polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2015;184:112-6.##Lai Q, Xiang W, Li Q, Zhang H, Li Y, Zhu G, et al. Oxidative stress in granulosa cells contributes to poor oocyte quality and IVF-ET outcomes in women with polycystic ovary syndrome. Front Med. 2018;12(5):518-24.##

Nesfatin-1, Dopamine, and NADPH levels in Infertile Women with Polycystic Ovary Syndrome: Is There a Relationship Between Their Levels and Metabolic and Hormonal Variables 2 1 2 Background: Polycystic ovary syndrome (PCOS) is commonest endocrine disease occurring in women of reproductive age. This study conducted to clarify altered concentrations of Nesfatin-1, nicotinamide adenine dinucleotide phosphate (NADPH), and dopamine in PCOS women and controls. Also, to assess their role in PCOS pathophysiology and their correlation with measured biochemical parameters. Methods: In this observational study, 60 PCOS patients and 24 controls included. Medical history was recorded and full examinations were done. Serum concentrations of lipid profile, fasting blood glucose (FBG), fasting insulin (FSI), luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone, progesterone, estradiol, Nesfatin-1, dopamine, and NADPH were measured by ELISA kits. Values were analyzed using unpaired t-test and Pearson Chi-square test. The p<0.05 was considered statistically significant. Results: In this study, there was significantly elevated waist hip ratio (WHR) and body mass index (BMI) in PCOS patients versus controls (p<0.0001 and p=0.014). There was significant increase in FSH, LH, prolactin, estradiol, testosterone, Nesfatin-1, and dopamine (p=0.021, p=0.015, p<0.0001, p<0.0001, p=0.006, p=0.017, p<0.0001) and decrease of NADPH (p<0.0001) in PCOS patients. There were significant positive correlations between Nesfatin-1, prolactin, and dopamine levels. Also, there was significant positive correlation between dopamine and BMI, FSI, FSH, LH, estradiol, and prolactin levels; however, significant negative correlations observed between NADPH and BMI, FSI, estradiol, and prolactin levels. Conclusion: Elevated serum Nesfatin-1 concentrations and their association with hyperprolactinemia indicate that they have a role in PCOS pathophysiology. Moreover, elevated dopamine and decreased NADPH concentrations could play role in PCOS pathogenesis. 160 169 Enas Ahmed EA Hamed Department of Medical Physiology, Faculty of Medicine, Assiut University Department of Medical Physiology, Faculty of Medicine, Assiut University Egypt eah3a2010@yahoo.com Hayam Gaber HG Sayyed Department of Medical Physiology, Faculty of Medicine, Assiut University Department of Medical Physiology, Faculty of Medicine, Assiut University Egypt Ahmed Mohamed AM Abbas Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University Egypt Mohamed Maher MM Abdel Gaber Department of Clinical Pathology, Faculty of Medicine, Assiut University Department of Clinical Pathology, Faculty of Medicine, Assiut University Egypt Hassnaa Mahmoud HA Abd El Aleem Department of Medical Physiology, Faculty of Medicine, Assiut University Department of Medical Physiology, Faculty of Medicine, Assiut University Egypt DopamineInfertilityNesfatin-1Nicotinamide adenine dinucleotide phosphatePolycystic ovarian syndromeProlactin 120152.pdf Regidor PA, Mueller A, Sailer M, Gonzalez Santos F, Rizo JM, Egea FM. Chronic inflammation in PCOS: the potential benefits of specialized proresolving lipid mediators (SPMs) in the improvement of the resolutive response. Int J Mol Sci. 2021;22(1):384.##Daghestani MH. Rs1799817 in INSR associates with susceptibility to polycystic ovary syndrome. J Med Biochem. 2020;39(2):149-59.##Prinz P, Goebel-Stengel M, Teuffel P, Rose M, Klapp BF, Stengel A. Peripheral and central localization of the nesfatin-1 receptor using autoradiography in rats. Biochem Biophysic Res Commun. 2016;470(3):521-7.##Gao X, Zhang K, Song M, Li X, Luo L, Tian Y, et al. Role of nesfatin-1 in the reproductive axis of male rat. Sci Rep. 2016;6:32877.##Kim J, Yang H. Nesfatin-1 as a new potent regulator in reproductive system. Dev Reprod. 2012;16(4):253-64.##Dore R, Levata L, Lehnert H, Schulz C. Nesfatin-1: functions and physiology of a novel regulatory peptide. J Endocrinol. 2017;232(1):R45-R65.##Nakata M, Manaka K, Yamamoto S, Mori M, Yada T. 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Does Embryonic Culture Environment Affect Ploidy Rates in ART Cycles: A Single Center Study in UK 2 1 2 Background: The purpose of the current study was to assess whether embryonic culture conditions has an impact on embryo ploidy in a preimplantation genetic testing for aneuploidy (PGT-A) cycle. Methods: In this retrospective single center cohort study, a total of 1099 blastocysts from 278 PGT-A cycles were analyzed. The generated blastocysts were biopsied on days 5 and 6. Inseminated oocytes were allocated in different incubators (benchtop and time lapse) and assisted zona hatching was performed on day 3 of embryo development to facilitate the biopsy process which was performed on days 5 and 6 (blastocyst stage). Results: The average age across the groups was 38.7±3.6 years and the total number of mature eggs was 2912 which were randomly distributed across both incubators. The euploidy rate obtained from both groups showed a higher proportion of euploid embryos in the TLM incubator (37.03%, 95% CI 31.9-42.1) compared to those cultured in the BT incubator (30.4%, 95% CI 23.1-37.7). Regression analysis showed that female age remains to be the key variable driving euploidy rates (0.85, 95% CI 0.82-0.88) although incubator type could be an important covariable (0.54, 95% CI 0.45-0.59). A subgroup analysis of 74 single euploid embryo transfers showed comparable pregnancy and live birth rates. Conclusion: This large cohort study demonstrates that uninterrupted controlled culture environment provides increased probability to develop euploid embryo in a PGT-A cycle. However, further evaluation is required to assess how environmental culture conditions at a cellular level could affect epigenetic mechanisms in embryo development and higher aneuploidy rate. 169 177 Rabi R Odia The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health UK rabiodia@yahoo.co.uk Vinals-Gonzalez VG Xavier The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health UK Carleen C Heath The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health UK Wael W Saab The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health UK Ozkan O Ozturk The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health UK Srividya S Seshadri The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health UK Paul P Serha The Centre for Reproductive and Genetic Health The Centre for Reproductive and Genetic Health UK Benchtop incubatorBlastocystEuploiTime lapse incubato 120157.pdf Hughes C, Association of clinical Embryologists. Association of clinical embryologists-guidelines on good laboratory practice in clinical embryology laboratories 2012. Hum Fertil (Camb). 2012;15(4):174-89.##Magli MC, Gianaroli L, Ferraretti AP, Lappi M, Ruberti A, Farfalli V. Embryo morphology and development are dependent on the chromosomal complement. Fertil Steril. 2007;87(3):534-41.##Munne S, Magli C, Adler A, Wright G, De Boer K, Mortimer D, et al. Treatment related chromosome abnormalities in human embryos. Hum Reprod. 1997;12(4):780-4.##Gardner DK, Balaban B. Assessment of human embryo development using morphological criteria in an era of time-lapse, algorithms and ‘OMICS’: is looking good still important? Mol Hum Reprod. 2016;22(10):704-18. ##Munne S, Alikani M, Ribustello L, Colls P, Martinez-Ortiz P, McCulloh DH, Referring Physician Group. Euploid rates in donor egg cycles significantly differ between fertility centres. Hum Reprod. 2017;32(4):743-9.##Munne S. Status of preimplantation genetic testing and embryo selection. Reprod Biomed Online. 2019;37(4):393-6.##Mumusoglu S, Ozbek IY, Sokmensuer LK, Polat M, Bozdag G, Papanikolaou E, et al. Duration of blastulation may be associated with ongoing pregnancy rate in single euploid blastocyst transfer cycles. Reprod Biomed Online. 2017;35(6):633-9.##Almedia PA, Bolton VN. The effect of temperature fluctuations on the cytoskeletal organisation and chromosomal constitution of the human oocyte. 1995;3(4):357-65.##Hong KH, Lee H, Forman EJ, Upham KM, Scott Jr RT. Examining the temperature of embryo culture in in vitro fertilizaton: a randomized controlled trial comparing traditional core temperature (37C) to a more physiologic, cooler temperature (36C). Fertil Steril. 2014;102(3):767-73.##Wells D, Kaur K, Grifo J, Glassner M, Taylor JC, Fragouli E, et al Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation. J Med Genet. 2014;51(8):553-62.##Alhelou Y, Adenan NA, Ali J. Embryo culture conditions are significantly improved during uninterrupted incubation: a randomised control trial. Reprod Biol. 2017;18(1):40-5.##Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Thornton S. Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived from time-lapse imaging without PGS. Reprod Biomed Online. 2013;27(2):140-6.##Coticchio G, Mignini Renzini M, Novara PV, Lain M, De Ponti E, Turchi D, et al. Focused time-lapse analysis reveals novel aspects of human fertilisation and suggests new parameters of embryo viability. Hum Reprod. 2018;33(1):23-31.##Desai N, Goldberg J, Austin C, Falcone T. Are cleavage anomolises, multinucleation, or specific cell cycle kinetics observed with time-lapse imaging predictive of embryo development capacity or ploidy? Fertil Steril. 2018;109(4):665-74. ##Mantikou E, Wong KM, Repping S, Mastenbroek S. Molecular origin of mitotic aneuplodies in preimplantation embryos. Biochim Biophys Acta. 1822(12):1921-30.##Bean CJ, Hassold TJ, Judis L, Hunt PA. Fertilisation in vitro increases non-disjunction during early cleavge division in a mouse model system. Hum Reprod. 2002;17(9):2362-7. ##Sunde A, Brison D, Dumoulin J, Harper J, Lundin K, Magli MC, et al. Time to take human embryo culture seriously. Hum Reprod. 2016;31(10):2174-82.##

Effect of Administrating Coenzyme Q10 with Clomiphene Citrate on Ovulation Induction in Polycystic Ovary Syndrome Cases with Resistance to Clomiphene Citrate: A Randomized Controlled Trial 2 1 2 Background: The purpose of this study was to assess the effect of combining low dose of Coenzyme Q10 with clomiphene citrate on ovulation induction in polycystic ovary syndrome (PCOS) women with clomiphene resistance. Methods: A total of 149 women with clomiphene resistant PCOS who needed ovulation induction were randomly allocated to oral clomiphene citrate and Coenzyme Q10 group and oral clomiphene citrate only group using a computer generated allocation sequence. The study was conducted at Aziz Medical Center, Karachi, Pakistan from 1st July 2020 to 1st October 2020. Polycystic ovary syndrome was diagnosed according to Rotterdam criteria. The primary outcome was ovulation and conception rate per cycle. Chi square test and Fischer’s exact test were used to compare these variables at p<0.05 level of significance. Results: Of the 133 women assessed, the proportion of women who ovulated with combination (70% vs., 19%, p=0.001) was greater and the combination group had greater conception rate per cycle than those who received only clomiphene (48.6% vs. 6.3%, p˂0.001). When stratified according to obesity, 85.3% of non-obese women who received combination ovulated whereas only 55.6% of obese women ovulated (p=0.002). Moreover, 48.6% of non-obese women conceived in the combination group as compared to 6.3% of obese women (p=0.007). Women who received combination were six times more likely to conceive than women who only received clomiphene citrate (AOR=6.344, 95% CI: 1.452-27.71, p=0.014). Conclusion: Coenzyme Q10 is a valuable adjunct in women with PCOS undergoing ovulation induction. It improves ovulation and conception in women with clomiphene resistance. 177 184 Rubina R Izhar Department of Gynaecology and Obstetrics, Aziz Medical Center Department of Gynaecology and Obstetrics, Aziz Medical Center Pakistan Samia S Husain Department of Gynaecology and Obstetrics, Aziz Medical Center Department of Gynaecology and Obstetrics, Aziz Medical Center Pakistan samiahusain_scorpio@hotmail.com Muhammad Ahmad MA Tahir Department of Gynaecology and Obstetrics, Aziz Medical Center Department of Gynaecology and Obstetrics, Aziz Medical Center Pakistan Samia S Husain Department of Gynaecology and Obstetrics, Aziz Medical Center Department of Gynaecology and Obstetrics, Aziz Medical Center Pakistan Clomiphene citrateCoenzyme Q10Polycystic ovary syndrome 120151.pdf Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (polycystic ovarian syndrome): a systematic review and meta-analysis. Hum Reprod Update. 2013;19(3):268-88.##Mohammadi M. Oxidative stress and polycystic ovary syndrome: a brief review. Int J Prev Med. 2019;10:86.##Ilie IR. Advances in polycystic ovarian syndrome pathogenesis and progression-mitochondrial mutations and dysfunction. Adv Clin Chem. 2018;86:127-55.##O’Flynn N. Assessment and treatment for people with fertility problems: NICE guideline. Br J Gen Pract. 2014;64(618):50-1.##Raizner AE. Coenzyme Q10. Methodist Debakey Cardiovasc J. 2019;15(3):185-91.##Boots CE, Boudoures A, Zhang W, Drury A, Moley KH. Obesity-induced oocyte mitochondrial defects are partially prevented and rescued by supplementation with co-enzyme Q10 in a mouse model. Hum Reprod. 2016;31(9):2090-7.##El Refaeey A, Selem A, Badawy A. Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome. Reprod Biomed Online. 2014;29 (1):119-24.##Roman R, Mussarat N, Detti L. Ovarian stimulation in poor responders: have we made progress? Curr Pharm Biotechnol. 2017;18(8):614-8.##Tiseo BC, Gaskins AJ, Hauser R, Chavarro JE, Tanrikut C; EARTH Study Team. Coenzyme Q10 intake from food and semen parameters in a subfertile population. Urology. 2017;102:100-5.##Rotterdam ESHRE/ASRM-Sponsored polycystic ovarian syndrome Consensus Workshop Group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.##Rocha AL, Oliveira FR, Azevedo RC, Silva VA, Peres TM, Candido AL, et al. Recent advances in the understanding and management of polycystic ovary syndrome. F1000Res. 2019;8:F1000 Faculty Rev-565.##Ben-Meir A, Burstein E, Borrego-Alvarez A, Chong J, Wong E, Yavorska T, et al. Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell. 2015;14(5):887-95.##Xu Y, Nisenblat V, Lu C, Li R, Qiao J, Zhen X, et al. Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. Reprod Biol Endo-crinol. 2018;16(1):29.##Chou CH, Chen SU, Chen CD, Shun CT, Wen WF, Tu YA, et al. Mitochondrial dysfunction induced by high estradiol concentrations in endometrial epithelial cells. J Clin Endocrinol Metab. 2020;105(1):dgz015.##Van Blerkom J, Davis PW, Lee J. ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo transfer. Hum Reprod. 1995;10(2):415-24.##Rhee JS, Saben JL, Mayer AL, Schulte MB, Asghar Z, Stephens C, et al. Diet-induced obesity impairs endometrial stromal cell decidualization: a potential role for impaired autophagy. Hum Reprod. 2016;31(6):1315-26.##Florou P, Anagnostis P, Theocharis P, Chourdakis M, Goulis DG. Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials. J Assist Reprod Genet. 2020;37(10):2377-87.##

Comparison of the Efficiency of Magnetic-Activated Cell Sorting (MACS) and Physiological Intracytoplasmic Sperm Injection (PICSI) for Sperm Selection in Cases with Unexplained Infertility 2 1 2 Background: The cases with unexplained infertility may have an abnormality in their sperm chromatin structure. Sperm selection methods can be used to separate sperm with low DNA fragmentation. The purpose of this study was to compare the efficacy of physiological intracytoplasmic sperm injection (PICSI) with magnetic-activated cell sorting (MACS) in assisted reproductive techniques in cases with unexplained infertility. Methods: The semen samples were collected from couples with unexplained infertility. After semen analysis and sperm DNA fragmentation (SDF) evaluations, samples were prepared with swim-up method. The rates of SDF in different fractions including raw semen (n=20), swim-up (n=20), only motile sperm after swim-up (swim-up selection) (n=20), MACS sperm selection (n=20), only motile sperm after MACS (MACS selection) (n=20), and PICSI sperm selection (n=16) were evaluated. Also, the main sperm characteristics and fine morphology of sperm suspension after MACS were assessed. Statistical analysis was performed using GraphPad Prism. The p<0.05 was considered statistically significant. Results: DNA fragmentation index (DFI) values in PICSI and MACS groups were significantly reduced as compared to the swim-up group. The rate of this reduction was more pronounced in MACS (58.20±13.02) than PICSI (36.57±15.52) group. Also, our results showed that MACS resulted in decreased sperm motility, with no alteration in their fine morphology. Conclusion: MACS was found to be more efficient in reduction of SDF rates than PICSI. However, none of the sperm selection techniques can not totally eliminated the spermatozoa with DNA fragmentation in the final sperm sample. 184 192 Alireza A Ahmadi علیرضا احمدی Department of Anatomy, School of Medicine, Tehran University of Medical Sciences Department of Anatomy, School of Medicine, Tehran University of Medical Sciences Iran Aligholi A Sobhani Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Iran sobhania@tums.ac.ir Mohammad Ali MA Khalili محمد علی خلیلی Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Iran Azam A Agha-Rahimi اعظم آقارحیمی Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Iran Ali A Nabi Andrology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Andrology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences Iran Necati N Findikli Bahceci Fulya Assisted Reproduction Center Bahceci Fulya Assisted Reproduction Center Iran MACSPICSISDFSpermatozoa 120153.pdf Pierik FH, Van Ginneken AM, Dohle GR, Vreeburg JT, Weber RF. The advantages of standardized evaluation of male infertility. Int J Androl. 2000;23(6):340-6.##Santos R, Palos-Ladeiro M, Besnard A, Reggio J, Vulliet E, Porcher JM, et al. Parental exposure to methyl methane sulfonate of three-spined stickleback: contribution of DNA damage in male and female germ cells to further development impairment in progeny. Ecotoxicology. 2013;22(5):815-24.##Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: diagnosis and management. Int Braz J Urol. 2012;38(5):576-94.##Bibancos M, Vaz RM, Mega PF, Borges E Jr, Ribeiro M, Buttros D, et al. Sperm selection for micro TESE-ICSI in Non-Obstructive azoospermia, a case report. JBRA Assist Reprod. 2021;25(4):653-6.##Duarte C, Núñez V, Wong Y, Vivar C, Benites E, Rodriguez U, et al. Impact of the Z potential technique on reducing the sperm DNA fragmentation index, fertilization rate and embryo development. JBRA Assist Reprod. 2017;21(4):351-5.##Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, et al. Molecular biology of the cell: USA: W.W. Norton & Company; 2014. 1464 p.##Gil M, Sar-Shalom V, Melendez Sivira Y, Carreras R, Checa MA. Sperm selection using magnetic activated cell sorting (MACS) in assisted reproduction: a systematic review and meta-analysis. J Assist Reprod Genet. 2013;30(4):479-85.##Chung MK, Chiu PC, Lee CL, Pang RT, Ng EH, Lee KF, et al. Cumulus-associated alpha2-macroglobulin derivative retains proconceptive glycodelin-C in the human cumulus matrix. Hum Reprod. 2009;24(11):2856-67.##Kızılay F, Altay B. Sperm function tests in clinical practice. Turk J Urol. 2017;43(4):393-400.##Jakab A, Sakkas D, Delpiano E, Cayli S, Kovanci E, Ward D, et al. Intracytoplasmic sperm injection: a novel selection method for sperm with normal frequency of chromosomal aneuploidies. Fertil Steril. 2005;84(6):1665-73.##Cayli S, Sakkas D, Vigue L, Demir R, Huszar G. Cellular maturity and apoptosis in human sperm: creatine kinase, caspase-3 and Bcl-XL levels in mature and diminished maturity sperm. Mol Hum Reprod. 2004;10(5):365-72.##Omidi M, Faramarzi A, Agharahimi A, Khalili MA. Noninvasive imaging systems for gametes and embryo selection in IVF programs: a review. J Microsc. 2017;267(3):253-64.##Mangoli E, Khalili MA, Talebi AR, Kalantar SM, Montazeri F, Agharahimi A, et al. Association between early embryo morphokinetics plus transcript levels of sperm apoptotic genes and clinical outcomes in IMSI and ICSI cycles of male factor patients. J Assist Reprod Genet. 2020;37(10):2555-67.##Mangoli E, Khalili MA, Talebi AR, Agha‐Rahimi A, Soleimani M, Faramarzi A, et al. IMSI procedure improves clinical outcomes and embryo morphokinetics in patients with different aetiologies of male infertility. Andrologia. 2019;51(8):e13340.##Hasanen E, Elqusi K, ElTanbouly S, AlKhadr H, Zaki H, Henkel R, et al. PICSI vs. MACS for abnormal sperm DNA fragmentation ICSI cases: a prospective randomized trial. J Assist Reprod Genet. 2020;37(10):2605-13.##WHO. WHO laboratory manual for the examin-ation and processing of human semen. 5th ed. Geneva: World Health Organization; 2010. 271 p.##Cassuto NG, Bouret D, Plouchart JM, Jellad S, Vanderzwalmen P, Balet R, et al. A new real-time morphology classification for human spermatozoa: a link for fertilization and improved embryo quality. Fertil Steril. 2009;92(5):1616-25.##Anbari F, Khalili MA, Agha-Rahimi A, Maleki B, Nabi A, Esfandiari N. Does sperm DNA fragmentation have negative impact on embryo morphology and morphokinetics in IVF programme? Andrologia. 2020;52(11):e13798.##Neri QV, Tanaka N, Wang A, Katagiri Y, Takeuchi T, Rosenwaks Z, et al. Intracytoplasmic sperm injection. Minerva Ginecol. 2004;56:189-96.##World Health Organization. World health statistics 2010. 1st ed. Geneva: World Health Organization; 2010. 168 p.##Esbert M, Pacheco A, Soares S, Amorós D, Florensa M, Ballesteros A, et al. High sperm DNA fragmentation delays human embryo kinetics when oocytes from young and healthy donors are microinjected. Andrology. 2018;6(5):697-706.##Borges Jr E, Zanetti BF, Setti AS, Braga DPdAF, Provenza RR, Iaconelli Jr A. Sperm DNA fragmentation is correlated with poor embryo development, lower implantation rate, and higher miscarriage rate in reproductive cycles of non–male factor infertility. Fertil Steril. 2019;112(3):483-90.##Kim SM, Kim SK, Jee BC, Kim SH. Effect of sperm DNA fragmentation on embryo quality in normal responder women in in vitro fertilization and intracytoplasmic sperm injection. Yonsei Med J. 2019;60(5):461-6.##Yang H, Li G, Jin H, Guo Y, Sun Y. The effect of sperm DNA fragmentation index on assisted reproductive technology outcomes and its relationship with semen parameters and lifestyle. Transl Androl Urol. 2019;8(4):356-65.##Ten J, Guerrero J, Linares Á, Rodríguez-Arnedo A, Morales R, Lledó B, et al. Sperm DNA fragmentation on the day of fertilisation is not associated with assisted reproductive technique outcome independently of gamete quality. Hum Fertil (Camb). 2021:1-17.##Ribas‐Maynou J, Yeste M, Becerra‐Tomás N, Aston KI, James ER, Salas‐Huetos A. Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta‐analysis. Biol Rev Camb Philos. 2021;96(4):1284-300.##Feijó CM, Esteves SC. Diagnostic accuracy of sperm chromatin dispersion test to evaluate sperm deoxyribonucleic acid damage in men with unexplained infertility. Fertil Steril. 2014;101(1):58-63.e3.##McDowell S, Kroon B, Ford E, Hook Y, Glujovsky D, Yazdani A. Advanced sperm selection techniques for assisted reproduction. Cochrane Database Syst Rev. 2014;(10):CD010461.##Xue X, Wang WS, Shi JZ, Zhang SL, Zhao WQ, Shi WH, et al. Efficacy of swim-up versus density gradient centrifugation in improving sperm deformity rate and DNA fragmentation index in semen samples from teratozoospermic patients. J Assist Reprod Genet. 2014;31(9):1161-6.##Parmegiani L, Cognigni GE, Bernardi S, Troilo E, Ciampaglia W, Filicori M. "Physiologic ICSI": hyaluronic acid (HA) favors selection of spermatozoa without DNA fragmentation and with normal nucleus, resulting in improvement of embryo quality. Fertil Steril. 2010;93(2):598-604.##Miller D, Pavitt S, Sharma V, Forbes G, Hooper R, Bhattacharya S, et al. Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect): a parallel, two-group, randomised trial. Lancet. 2019;393(10170):416-22.##Lee TH, Liu CH, Shih YT, Tsao HM, Huang CC, Chen HH, et al. Magnetic-activated cell sorting for sperm preparation reduces spermatozoa with apoptotic markers and improves the acrosome reaction in couples with unexplained infertility. Hum Reprod. 2010;25(4):839-46.##Bucar S, Gonçalves A, Rocha E, Barros A, Sousa M, Sá R. DNA fragmentation in human sperm after magnetic-activated cell sorting. J Assist Reprod Genet. 2015;32(1):147-54.##Cakar Z, Cetinkaya B, Aras D, Koca B, Ozkavukcu S, Kaplanoglu İ, et al. Does combining magnetic-activated cell sorting with density gradient or swim-up improve sperm selection? J Assist Reprod Genet. 2016;33(8):1059-65.##Horta F, Crosby J, Mackenna A, Huidobro C. Male factor infertility outcomes using magnetic activated cell sorting in intra citoplasmatic sperm injection cycles. Andrology (Los Angel). 2016;5(1):1-6.##Dirican EK, Ozgün OD, Akarsu S, Akin KO, Ercan O, Uğurlu M, et al. Clinical outcome of magnetic activated cell sorting of non-apoptotic spermatozoa before density gradient centrifugation for assisted reproduction. J Assist Reprod Genet. 2008;25(8):375-81.##Delbes G, Herrero MB, Troeung ET, Chan PT. The use of complimentary assays to evaluate the enrichment of human sperm quality in asthenoteratozoospermic and teratozoospermic samples processed with Annexin-V magnetic activated cell sorting. Andrology. 2013;1(5):698-706.##Esteves SC, Agarwal A, Majzoub A. Comparison of strategies to reduce sperm DNA fragmentation in couples undergoing ICSI. Transl Androl Urol. 2017;6(Suppl 4):S570-3.##Lepine S, McDowell S, Searle LM, Kroon B, Glujovsky D, Yazdani A. Advanced sperm selection techniques for assisted reproduction. Cochrane Database Syst Rev. 2019:7(7): CD010461.##

Comparison of Follicular Fluid Paraoxonase 3 Level, Ovarian Hormones and Oocyte Quality between Fertile and Infertile Women 2 1 2 Background: The purpose of the current study was to evaluate the possible effect of follicular fluid paraoxonase 3 (PON 3) on oocyte quality and sex hormones. Methods: This descriptive-analytical study was performed on totally 90 enrolled women including fifty infertile women presenting with polycystic ovaries and unilateral tubal factor and forty fertile women with male factor infertility referring to Umm-al-Banin Infertility Clinic in Dezful, Iran for in vitro fertilization during October 2018 to November 2019. Oocyte removal was carried out under transvaginal ultrasound guidance, and follicular fluid (FF) was removed and preserved to detect PON3, estrogen, and progesterone levels. In addition, oocyte number and quality were assessed and its association with PON3 activity in the FF was evaluated. One-way ANOVA and Fisher's least significant difference (LSD) were used for data analysis and p≤0.05 were considered statistically significant. Results: A significant increase was observed in the total number of the oocytes and mature metaphase II oocytes with ≥20 pg/ml of PON3 concentration in the FF (p≤0.05). Moreover, a positive relationship was shown between the increased estradiol level in follicular fluid and PON3, so that the highest estradiol level was observed in the amount of 31-40 pg/ml of PON3 (p≤0.05). Conclusion: According to the results, as the number of the mature oocytes increased, the amount of PON3 as well as estradiol levels in the FF increased. This research displays an increase in the level of PON3 with mature oocytes, thus supporting the indirect evidence for the function of PON3 in follicle development. 192 199 Sima S Janati Department of Obstetrics and Gynecology, School of Medicine, Research and Clinical Center for Infertility, Dezful University of Medical Sciences Department of Obstetrics and Gynecology, School of Medicine, Research and Clinical Center for Infertility, Dezful University of Medical Sciences Iran Mohammad Amin MA Behmanesh Department of Histology, School of Medicine, Dezful University of Medical Sciences Department of Histology, School of Medicine, Dezful University of Medical Sciences Iran Hosein H Najafzadehvarzi Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences Iran Boshra B Nezami Department of Histology, School of Medicine, Dezful University of Medical Sciences Department of Histology, School of Medicine, Dezful University of Medical Sciences Iran Seyedeh Mahsa SM Poormoosavi Department of Obstetrics and Gynecology, School of Medicine, Research and Clinical Center for Infertility, Dezful University of Medical Sciences Department of Obstetrics and Gynecology, School of Medicine, Research and Clinical Center for Infertility, Dezful University of Medical Sciences Iran m.poormoosavi@ymail.com OocyteParaoxonase 3Follicular fluidAntioxidantsAssisted reproduction 130155.pdf Kormi Nouri R. Psycho-social aspects of infertility. J Reprod Infertil. 2000;1(2):57-68.##Eftekhar M, Janati S, Rahsepar M, Aflatoonian A. Effect of oocyte activation with calcium ionophore on ICSI outcomes in teratospermia: A randomized clinical trial. Iran J Reprod Med. 2013;11(11):875-82.##Poormoosavi SM, Behmanesh MA, Varzi HN, Mansouri S, Janati S. The effect of follicular fluid selenium concentration on oocyte maturation in women with polycystic ovary syndrome undergoing in vitro fertilization/Intracytoplasmic sperm injection: a cross-sectional study. Int J Reprod Biomed. 2021;19(8):689-98.##Eppig JJ. Coordination of nuclear and cytoplasmic oocyte maturation in eutherian mammals. Reprod Fertil Deve. 1996;8(4):485-9.##Pasqualotto EB, Agarwal A, Sharma RK, Izzo VM, Pinotti JA, Joshi NJ, et al. Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril. 2004;81(4):973-6.##Agarwal A, Sekhon LH. The role of antioxidant therapy in the treatment of male infertility. Hum Fertil. 2010;13(4):217-25.##Ishikawa M. [Oxygen radicals-superoxide dismutase system and reproduction medicine]. Nihon Sanka Fujinka Gakkai Zasshi. 1993;45(8):842-8. Japanese.##Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN. The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics. 1996;33(3):498-507.##Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN. Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005;46(6):1239-47.##Angelucci S, Ciavardelli D, Di Giuseppe F, Eleuterio E, Sulpizio M, Tiboni GM, et al. Proteome analysis of human follicular fluid. Biochim Biophys Acta. 2006;1764(11):1775-85.##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.##Scott L, Alvero R, Leondires M, Miller B. The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Hum Reprod. 2000;15(11):2394-403.##Draganov D, La Du BN. Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(1):78-88.##Opuwari CS, Henkel RR. An update on oxidative damage to spermatozoa and oocytes. Biomed Res Int. 2016;2016:9540142.##Fernandez H. [Oocyte and embryo quality in polycystic ovary syndrome. Gynécol Obstét Fertil 2003; 31: 350-354]. Gynecol Obstet Fertil. 2003;31(11):988-9. French.##Meijide S, Pérez-Ruiz I, Hernández ML, Navarro R, Ferrando M, Larreategui Z, et al. Paraoxonase activities in human follicular fluid: role in follicular maturation. Reprod Biomed Online. 2017;35(4):351-62.##Bacchetti T, Morresi C, Vignini A, Tiano L, Orlando P, Montik N, et al. HDL functionality in follicular fluid in normal-weight and obese women undergoing assisted reproductive treatment. J Assist Reprod Genet. 2019;36(8):1657-64.##Rashidi MR, Eisa-Khaje J, Farzadi L, Darabi M, Gasemzadeh A, Shahnazi V, et al. Paraoxonase 3 activity and the ratio of antioxidant to peroxidation in the follicular fluid of infertile women. Int J Fertil Steril. 2014;8(1):51-8.##Closshey W, Browne R, Huddleston H, Sandler J, Schisterman E, Fujimoto V. High activity of paraoxonase 3 (PON3), a known potent antioxidant, identified in follicular fluid. Fertil Steril. 2007;88:S304-S5.##Giordano G, Tait L, Furlong C, Cole T, Kavanagh T, Costa L. Gender differences in brain susceptibility to oxidative stress are mediated by levels of paraoxonase-2 expression. Free Radic Biol Med. 2013;58:98-108.##Pizarro BM, Cordeiro A, Reginatto MW, Campos SP, Mancebo ACA, Areas PC, et al. Estradiol and progesterone levels are related to redox status in the follicular fluid during in vitro fertilization. J Endocr Soc. 2020;4(7):bvaa064.##Sutherland WH, Manning PJ, de Jong SA, Allum AR, Jones SD, Williams SM. Hormone-replacement therapy increases serum paraoxonase arylesterase activity in diabetic postmenopausal women. Metabolism. 2001;50(3):319-24.##

Alterations in Human Semen After Infection with SARS-CoV-2: A Meta-analysis 2 1 2 Background: The purpose of the current study was to assess pooled prevalence (PP) of SARS-CoV-2 in semen and pooled estimates including weighted mean difference (WMD) and risk ratio (RR) of semen characteristics in infected cases as compared with healthy controls. Methods: Major databases were searched by two authors. SARS-CoV-2-positive cases were assigned to the exposed arm (group A), whereas the controls to the unexposed (group B). Risk of bias was assessed with Newcastle-Ottawa Scale and PRISMA guidelines were followed. Random-effects model was employed for analyzing the heterogeneity and fixed-effects model for homogeneity of studies. Results: Of 170 studies, 14 studies were eligible involving 507 subjects (316 in group A, 191 in group B). The risk of bias was the highest for "comparability" domain. SARS-CoV-2 RNA was found in only two studies among 7 subjects (PP= 2.10%, 95%CI 0.58–4.42). There was a significant decrease in sperm concentration (WMD= -15.29, 95%CI -24.70 – -5.88) and total sperm in ejaculate (WMD= -47.58, 95%CI -86.40 – -8.75) in group A. The effect of COVID-19 upon progressive motility, ejaculate volume, and leukocyte presence in semen was not significant. Conclusion: Prevalence of SARS-CoV-2 in semen among the infected cases is low. Sexual transmission through semen is improbable and of little concern for public health. Sperm concentration and total sperm in ejaculate are significantly reduced as compared with controls. Due to limited information of the current research, longer follow-up is needed to identify delayed or progressive impact. 199 207 Marta M Klepinowska Pomeranian Medical University Pomeranian Medical University Poland Tomasz T Klepinowsk Pomeranian Medical University Pomeranian Medical University Poland sapos93@gmail.com CoronavirusCOVID-19Meta-analysisPandemicsSARS-CoV-2Semen 130157.pdf Cipriano M, Giacalone A, Ruberti E. Sexual behaviors during COVID-19: the potential risk of transmission. Arch Sex Behav. 2020;49(5):1431-2.##Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020;323(18):1843-4.##Karia R, Gupta I, Khandait H, Yadav A, Yadav A. COVID-19 and its Modes of Transmission. SN Compr Clin Med. 2020:1-4. Online ahead of print.##Li W, Moore MJ, Vasllieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-4.##Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HWG, Behre HM, et al. World health organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231-45.##Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical characteristics and results of semen tests among men with Coronavirus disease 2019. JAMA Netw Open. 2020;3(5):e208292.##Temiz MZ, Dincer MM, Hacibey I, Yazar RO, Celik C, Kucuk SH, et al. Investigation of SARS-CoV-2 in semen samples and the effects of COVID-19 on male sexual health by using semen analysis and serum male hormone profile: a cross-sectional, pilot study. Andrologia. 2021;53(2):e13912.##Guo L, Zhao S, Li W, Wang Y, Li L, Jiang S, et al. Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort. Andrology. 2021;9(1):42-7.##Song C, Wang Y, Li W, Hu B, Chen G, Xia P, et al. Absence of 2019 novel coronavirus in semen and testes of COVID-19 patients. Biol Reprod. 2020;103(1):4-6.##Machado B, Barra GB, Scherzer N, Massey J, dos Santos Luz H, Jacomo RH, et al. Presence of SARS-CoV-2 RNA in semen-cohort study in the United States COVID-19 positive patients. Infect Dis Rep. 2021;13(1):96-101.##Burke CA, Skytte A, Kasiri S, Howell D, Patel ZP, Trolice MP, et al. A cohort study of men infected with COVID-19 for presence of SARS-CoV-2 virus in their semen. J Assist Reprod Genet. 2021;38(4):785-9.##Li H, Xiao X, Zhang J, Zafar MI, Wu C, Long Y, et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine. 2020;28:100604.##Rawlings SA, Ignacio C, Porrachia M, Du P, Smith DM, Chaillon A. No evidence of SARS-CoV-2 seminal shedding despite SARS-CoV-2 persistence in the upper respiratory tract. Open Forum Infect Dis. 2020;7(8):ofaa325.##Pavone C, Giammanco GM, Baiamonte D, Pinelli M, Bonura C, Montalbano M, et al. Italian males recovering from mild COVID-19 show no evidence of SARS-CoV-2 in semen despite prolonged nasopharyngeal swab positivity. Int J Impot Res. 2020;32(5):560-2.##Ruan Y, Hu B, Liu Z, Liu K, Jiang H, Li H, et al. No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: a perspective and urogenital evaluation. Andrology. 2021;9(1):99-106.##Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, et al. No evidence of severe acute respiratory syndrome–coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020;113(6):1135-9.##Ma L, Xie W, Li D, Shi L, Ye G, Mao Y, et al. Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients. J Med Virol 2021;93(1):456-62.##Kayaaslan B, Korukluoglu G, Hasanoglu I, Kalem AK, Eser F, Akinci E, et al. Investigation of SARS-CoV-2 in semen of patients in the acute stage of COVID-19 infection. Urol Int. 2020;104(9-10):678-83.##Holtmann N, Edimiris P, Andree M, Doehmen C, Baston-Buest D, Adams O, et al. Assessment of SARS-CoV-2 in human semen-a cohort study. Fertil Steril. 2020;114(2):233-38.##Schrader C, Schielke A, Ellerbroek L, Johne R. PCR inhibitors - occurrence, properties and removal. J Appl Microbiol. 2012;113(5):1014-26.##Tobe SS, Swaran YC, Dennany L, Sibbing U, Schulze Johann K, Welch L, et al. A proof of principal study on the use of direct PCR of semen and spermatozoa and development of a differential isolation protocol for use in cases of alleged sexual assault. Int J Legal Med. 2017;131(1):87-94.##Carlsen E, Andersson AM, Petersen JH, Skakkebæk NE. History of febrile illness and variation in semen quality. Hum Reprod 2003;18(10):2089-92.##

Brain Derived Neurotrophic Factor as a Non-invasive Biomarker for Detection of Endometriosis 2 1 2 Background: Endometriosis is an estrogen-dependent chronic progressive gynecological disease that affects around 10% of women of reproductive age. A recent study shows that brain-derived neurotrophic factor (BDNF) has the potential as a clinical marker in the diagnosis of endometriosis. We aimed to determine whether BDNF levels are correlated with pain scores associated with endometriosis. Methods: Fifty women who underwent laparoscopy surgery at Dr. Soetomo General Hospital and Dr. Ramelan Navy Hospital were prospectively recruited from October 2017 until August 2018. A blood sample was obtained before surgery and BDNF was measured using the Human BDNF Quantakine®️ kit. The relationship of BDNF levels in serum with the diseases's level of pain and stages was compared between cases and controls. BDNF validity as an endometriosis diagnosis biomarker was assessed using receiver operating characteristic (ROC) analysis. Results: Serum concentrations of BDNF were significantly greater in women with endometriosis (30.42±7.41 pg/ml), compared to controls (25.66±3.30 pg/ml). Serum concentrations of BDNF were moderately correlated with the patient’s reported pain scores (r=0.44, p=0.01). Receiver operating characteristic curve analysis confirmed the potential of BDNF in the diagnosis of endometriosis. Using a cut-off value of 27.06 pg/ml, the sensitivity and specificity were reported to be 66.7% and 64.3%, respectively. Conclusion: BDNF serum levels in endometriosis women are significantly higher than in women without the disorder. BDNF serum level seems to have low accuracy and predictive value as a diagnostic marker for endometriosis. However, there was a moderate relationship between BDNF serum level and the degree of pain. 207 213 Sri Ratna SR Dwiningsih Department of Obstetrics and Gynaecology, Faculty of Medicine, Airlangga University Department of Obstetrics and Gynaecology, Faculty of Medicine, Airlangga University Indonesia sri-r-d@fk.unair.ac.id Christina Ch Meilani Department of Obstetrics and Gynaecology, Faculty of Medicine, Airlangga University Department of Obstetrics and Gynaecology, Faculty of Medicine, Airlangga University Indonesia Samsul S Hadi Department of Obstetrics and Gynaecology, Faculty of Medicine, Airlangga University Department of Obstetrics and Gynaecology, Faculty of Medicine, Airlangga University Indonesia Brain derived neurotrophic factorEndometriosis 120150.pdf Garcia-Velasco JA, Somigliana E. Management of endometriomas in women requiring IVF: To touch or not to touch. Hum Reprod. 2009;24(3):496-501##Fritz M, Speroff L. Clinical gynecologic endocrinology and infertility. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2011. 938 p.##Russo N, Russo M, Daino D, Freschi L, Fiore L, Merlini S, et al. Evaluation of brain-derived neurotrophic factor in menstrual blood and its identification in human endometrium. Gynecol Endocrinol. 2012;28(6):492-5.##Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, et al. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging. 2005;26(1):115-23.##Browne AS, Yu J, Huang RP, Francisco AM, Sidell N, Taylor RN. Proteomic identification of neurotrophins in the eutopic endometrium of women with endometriosis. Fertil Steril. 2012;98(3):713-9.##Wessels JM, Kay VR, Leyland NA, Agarwal SK, Foster WG. Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis. Fertil Steril. 2016;105(1):119-28.e1-5.##Davies A. Neurotrophins: Neurotrophins: Neurotrophic modulation of neurite growth. Curr Biol. 2000;10(5):R198-R200.##Seifer DB, Feng B, Shelden RM, Chen S, Dreyfus CF. Brain-derived neurotrophic factor: a novel human ovarian follicular protein. J Clin Endocrinol Metab. 2002;87(2):655-9.##Dissen GA, Garcia-Rudaz C, Ojeda SR. Role of neurotrophic factors in early ovarian development. Semin Reprod Med. 2009;27(1):24-31.##Seifer DB, Feng B, Shelden RM. Immunocytochemical evidence for the presence and location of the neurotrophin-Trk receptor family in adult human preovulatory ovarian follicles. Am J Obstet Gynecol. 2006;194(4):1129-34; discussion 1134-1126.##Ding S, Zhu T, Tian Y, Xu P, Chen Z, Huang X, et al. Role of brain-derived neurotrophic factor in endometriosis pain. Reprod Sci. 2017;25(7):1045-57.##Begliuomini S, Casarosa E, Pluchino N, Lenzi E, Centofanti M, Freschi L, et al. Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor. Hum Reprod. 2007;22(4):995-1002.##Giannini A, Bucci F, Luisi S, Cela V, Pluchino N, Merlini S, et al. Brain-derived neurotrophic factor in plasma of women with endometriosis. J of Endometriosis. 2010;2(3):144-150.##Rocha AL, Vieira EL, Ferreira MC, Maia LM, Teixeira AL, Reis FM. Plasma brain-derived neurotrophic factor in women with pelvic pain: a potential biomarker for endometriosis? Biomark Med. 2017; 11(4):313-7.##Sohrabji F, Miranda R, Toran-Allerand D. Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor. Proc Natl Acad Sci USA. 1995;92(24):11110-4.##Anger DL, Zhang B, Boutross-Tadross O, Foster WG. Tyrosine receptor kinase B (TrkB) protein expression in the human endometrium. Endocrine. 2007;31(2):167-73.##Dong F, Zhang Q, Kong W, Chen J, Ma J, Wang L, et al. Regulation of endometrial cell proliferation by estrogen-induced BDNF signaling pathway. Gynecol Endocrinol. 2017;33(6):485-9.##Ballard K, Lowton K, Wright J. What’s the delay? a qualitative study of women’s experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006;86(5):1296-301.##Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(8):441-7.##Howard FM. Endometriosis and mechanisms of pelvic pain. J Minim Invasive Gynecol. 2009;16 (5):540-50.##de Arellano ML, Mechsner S. The peritoneum--an important factor for pathogenesis and pain generation in endometriosis. J Mol Med (Berl). 2014;92(6):595-602.##Tokushige N, Russell P, Black K, Barrera H, Dubinovsky S, Markham R, et al. Nerve fibers in ovarian endometriomas. Fertil Steril. 2010;94(5):1944-7.##Anaf V, Simon P, El Nakadi I, Fayt I, Simonart T, Buxant F, et al. Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod. 2002;17(7):1895-900.##Wang G, Tokushige N, Markham R, Fraser IS. Rich innervation of deep infiltrating endometriosis. Hum Reprod. 2009;24(4):827-34.##Obata K, Noguchi K. BDNF in sensory neurons and chronic pain. Neurosci Res. 2006;55(1):1-10.##Lentz SI, Knudson CM, Korsmeyer SJ, Snider WD. Neurotrophins support the development of diverse sensory axon morphologies. J Neurosci. 1999;19(3):1038-48.##Guo JQ, Deng HH, Bo X, Yang XS. Involvement of BDNF/TrkB and ERK/CREB axes in nitroglycerin-induced rat migraine and effects of estrogen on these signals in the migraine. Biol Open. 2017;6(1):8-16.##Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmaco-logy. 1998;37(12):1553-61.##

Preimplantation Genetic Testing for Couples with Balanced Chromosomal Rearrangements 2 1 2 Background: Chromosomal rearrangements play an important role in infertility. Carriers of chromosomal rearrangements have a lower chance of producing normal or balanced gametes due to abnormal segregation of chromosomes at meiosis, which leads to recurrent spontaneous abortions and infertility. Preimplantation genetic testing for structural chromosome rearrangements (PGT-SR) is offered to couples who have balanced chromosomal rearrangements in order to select embryos with a balanced karyotype prior to implantation, thereby increasing the chances of pregnancy. The purpose of the current study was to assess the outcomes of PGT-SR in patients carrying various balanced chromosomal rearrangements and to assess their clinical pregnancy outcome after in vitro fertilization (IVF). Methods: In this study, infertile couples with balanced chromosomal abnormalities undergoing PGT-SR were retrospectively analyzed at a single fertility center from January 2016 to December 2019. Results: PGT-SR was performed on 87 embryos from 22 couples in whom one partner carried a balanced translocation or an inversion. Fifty-seven (65.5%) of these embryos had unbalanced or sporadic aneuploidies, 30 (34.5%) embryos were normal or chromosomally balanced, which were then transferred in 18 couples. A higher rate of unbalanced translocations in comparison to sporadic aneuploidies was observed in couples with reciprocal translocation. The live birth rate per embryo transfer was found to be 66.6% (12/18). Conclusion: PGT-SR is a useful tool in selecting normal or balanced embryos for transfer in IVF, which could lead to a pregnancy by reducing the chance of miscarriages due to chromosome aneuploidy in couples with balanced chromosomal rearrangements. 213 224 Sachin S Shetty Tattvagene Pvt. Ltd Tattvagene Pvt. Ltd India Jiny J Nair Tattvagene Pvt. Ltd Tattvagene Pvt. Ltd India Jnapti J Johnson Tattvagene Pvt. Ltd Tattvagene Pvt. Ltd India Navya N Shetty Tattvagene Pvt. Ltd Tattvagene Pvt. Ltd India Ajay A Kumar J Tattvagene Pvt. Ltd Tattvagene Pvt. Ltd India Nirmala N Thondehalmath Gunasheela Surgical and Maternity Hospital Gunasheela Surgical and Maternity Hospital India Deepanjali D Ganesh Gunasheela Surgical and Maternity Hospital Gunasheela Surgical and Maternity Hospital India Vidyalakshmi R VR Bhat Gunasheela Surgical and Maternity Hospital Gunasheela Surgical and Maternity Hospital India Sajana S M Gunasheela Surgical and Maternity Hospital Gunasheela Surgical and Maternity Hospital India Anjana A R Gunasheela Surgical and Maternity Hospital Gunasheela Surgical and Maternity Hospital India Rajsekhar R Nayak Tattvagene Pvt. Ltd Tattvagene Pvt. Ltd India Devika D Gunasheela Tattvagene Pvt. Ltd Tattvagene Pvt. Ltd India Jayarama JS Kadandale Gunasheela Surgical and Maternity Hospital Gunasheela Surgical and Maternity Hospital India Swathi S Shetty Gunasheela Surgical and Maternity Hospital Gunasheela Surgical and Maternity Hospital India swathi@chg.res.in AneuploidyBalanced chromosomal rearrangementsIn vitro fertilizationInversionPreimplantation genetic testingReciprocal translocationRecurrent miscarriagesRobertsonian translocation 694.pdf Zorrilla M, Yatsenko AN. The genetics of infertility: current status of the field. Curr Genet Med Rep. 2013;1(4):1-22.##Pylyp LY, Spinenko LO, Verhoglyad NV, Kashevarova OO, Zukin VD. [Chromosomal abnormalities in patients with infertility]. Tsitol Genet. 2015;49(3):33-9. Russian.##Liu Y, Kong XD, Wu QH, Li G, Song L, Sun YP. Karyotype analysis in large-sample infertile couples living in Central China: a study of 14965 couples. J Assist Reprod Genet. 2013;30(4):547-53.##Kayed HF, Mansour RT, Aboulghar MA, Serour GI, Amer AE, Abdrazik A. Screening for chromosomal abnormalities in 2650 infertile couples undergoing ICSI. Reprod Biomed Online. 2006;12(3):359-70.##Madan K, Nieuwint AW, van Bever Y. Recombination in a balanced complex translocation of a mother leading to a balanced reciprocal translocation in the child. Review of 60 cases of balanced complex translocations. Hum Genet. 1997;99(6):806-15.##Foresta C, Ferlin A, Gianaroli L, Dallapiccola B. Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet. 2002;10(5):303-12.##Zhang YP, Xu JZ, Yin M, Chen MF, Ren DL. [Pregnancy outcomes of 194 couples with balanced translocations]. Zhonghua Fu Chan Ke Za Zhi. 2006;41(9):592-6. Chinese.##Priya PK, Mishra VV, Roy P, Patel H. A study on balanced chromosomal translocations in couples with recurrent pregnancy loss. J Hum Reprod Sci. 2018;11(4):337-42.##ESHRE PGT-SR/PGT-A Working Group, Coonen E, Rubio C, Christopikou D, Dimitriadou E, Gontar J, et al. ESHRE PGT Consortium good practice recommendations for the detection of structural and numerical chromosomal aberrations. Hum Reprod Open. 2020;2020(3):hoaa017.##Martín J, Cervero A, Mir P, Martinez-Conejero JA, Pellicer A, Simón C. The impact of next-generation sequencing technology on preimplantation genetic diagnosis and screening. Fertil Steril. 2013;99(4):1054-61.##Yang Z, Lin J, Zhang J, Fong WI, Li P, Zhao R, et al. Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study. BMC Med Genom. 2015;8:30.##Rooney DE, Czepulkowski. Human Cytogenetics. a practical approach. 1st ed. Oxford: IRL Press;1992. 260 p.##Shaffer LG, McGowan J, Schmid M. ISCN 2013 An international system for human cytogenetic nomenclature. Published in collaboration with cytogenetic and genome research. Switzerland: Karger; 2013. 141 p.##Merrion K, Maisenbacher M. Pericentric inversion (Inv) 9 variant-reproductive risk factor or benign finding? J Assist Reprod Genet. 2019;36(12):2557-61.##Jungheim ES, Meyer MF, Broughton DE. Best practices for controlled ovarian stimulation in in vitro fertilization. Semin Reprod Med. 2015;33(2):77-82.##Stephenson MD, Sierra S. Reproductive outcomes in recurrent pregnancy loss associated with a parental carrier of a structural chromosome rearrangement. Hum Reprod. 2006;21(4):1076-82.##Munné S. Analysis of chromosome segregation during preimplantation genetic diagnosis in both male and female translocation heterozygotes. Cytogenet Genome Res. 2005;111(3-4):305-9.##Vozdova M, Kasikova K, Oracova E, Prinosilova P, Rybar R, Horinova V, et al. The effect of the swim-up and hyaluronan-binding methods on the frequency of abnormal spermatozoa detected by FISH and SCSA in carriers of balanced chromosomal translocations. Hum Reprod. 2012;27(3):930-7.##Ishikawa T, Shiotani M, Izumi Y, Hashimoto H, Kokeguchi S, Goto S, et al. Fertilization and pregnancy using cryopreserved testicular sperm for intracytoplasmic sperm injection with azoospermia. Fertil Steril. 2009;92(1):174‑9.##Lledo B, Ortiz JA, Morales R, Ten J, de la Fuente PE, Garcia-Ochoa C, et al. The paternal effect of chromosome translocation carriers observed from meiotic segregation in embryos. Hum Reprod. 2010;25(7):1843-8.##Morin SJ, Eccles J, Iturriaga A, Zimmerman RS. Translocations, inversions and other chromosome rearrangements. Fertil Steril. 2017;107(1):19-26.##Alfarawati S, Fragouli E, Colls P, Wells D. Embryos of robertsonian rranslocation carriers exhibit a mitotic interchromosomal effect that enhances genetic instability during early development. PLoS Genet. 2012;8(10):e1003025. ##Simon A, Laufer N. Assessment and treatment of repeated implantation failure (RIF). J Assist Reprod Genet. 2012;29(11):1227-39.##Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril. 2004;81(2):367-73.##Bono S, Biricik A, Spizzichino L, Nuccitelli A, Minasi MG, Greco E, et al. Validation of a semiconductor next-generation sequencing based protocol for preimplantation genetic diagnosis of Reciprocal translocations. Prenat Diagn. 2015;35(10):938-44.##Zhang W, Liu Y, Wang L, Wang H, Ma M, Xu M, et al. Clinical application of next-generation sequencing in preimplantation genetic diagnosis cycles for Robertsonian and reciprocal translocations. J Assist Reprod Genet. 2016;33(7):899-906.##Idowu D, Merrion K, Wemmer N, Mash JG, Pettersen B, Kijacic D, et al. Pregnancy outcomes following 24-chromosome preimplantation genetic diagnosis in couples with balanced Reciprocal or Robertsonian translocations. 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PEComa-A Rare Uterine Neoplasm: A Case Report 2 1 2 Background: Perivascular Epithelioid Cell Tumors (PEComas) are rare mesenchymal tumors originating from perivascular epithelioid cells. The second common affected organ is uterine. Most of PEComas are benign and patients have good prognosis. At the present time, surgery is the main treatment and adjuvant chemotherapy is used in malignant cases, although the best diagnostic and management method is yet to be discovered considering the rarity of this neoplasm. Case Presentation: The patient was a 53 year old lady with a history of two vaginal deliveries and no previous surgery. She had severe pelvic pain and underwent MRI with the primary impression of sarcoma. In MRI, she had a 7 cm mass in lower segment of uterus. The patient underwent laparoscopic hysterectomy, bilateral oophorectomy, lymphadenectomy, and omental biopsy in Jam Hospital. Pathologic report of the patient revealed malignant PEComa without lymph node and omentum involvement. Conclusion: Diagnosis of PEComa before surgery is difficult and its differential diagnoses form uterine leiomyoma or leiomyosarcoma. Final diagnosis can be made after surgical biopsy and immunohistochemistry evaluation. Surgery is still the main treatment and adjuvant therapy is used in high risk patients. 224 228 Roya R Padmehr Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Saeid S Arasteh Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Soheila S Aminimoghaddam Department of Gynecology Oncology, School of Medicine, Iran University of Medical Sciences Department of Gynecology Oncology, School of Medicine, Iran University of Medical Sciences Iran Ali A Rahbari Assistance Professor of Pathology, Arak University of Medical Sciences Assistance Professor of Pathology, Arak University of Medical Sciences Iran Mehrdad M Bohloli Department of Surgery, Jam General Hospital Department of Surgery, Jam General Hospital Iran Seyed Mohammad SM Mir Eskandari Assistance Professor of Anesthesiology and Intensive Care, Tehran University of Medical Sciences Assistance Professor of Anesthesiology and Intensive Care, Tehran University of Medical Sciences Iran Hamid H Mohabbat Dar Shahid Beheshti University of Medical Sciences Shahid Beheshti University of Medical Sciences Iran Morvarid M Ahmad Beigi Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran padmehrroya@gmail.com Negin N Talebi Biderouni Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Case reportPathologyPEComaPerivascular epithelioid cell tumor 120156.pdf Pea M, Bonetti F, Zamboni G, Martignoni G, Riva M, et al. 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Primary malignant perivascular epithelioid cell neoplasm (PEComa) of the bone mimicking granular cell tumor in core biopsy: a case report and literature review. Oncol Lett. 2018;15(3):2946-52.##Conlon N, Soslow RA, Murali R. Perivascular epithelioid tumours (PEComas) of the gynaecological tract. J Clin Pathol. 2015;68(6):418-26.##Sanfilippo R, Jones RL, Blay JY, Le Cesne A, Provenzano S, Antoniou G, et al. Role of chemotherapy, VEGFR inhibitors, and mTOR inhibitors in advanced perivascular epithelioid cell tumors (PEComas). Clin Cancer Res. 2019;25(17): 5295-300.##Pan CC, Chung MY, Ng KF, Liu CY, Wang JS, Chai CY, et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol. 2008;214(3):387-93.##Prasad SR, Sahani DV, Mino-Kenudson M, Narra VR, Humphrey PA, Menias CO, et al. 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