Abandoned Cryopreserved Embryos: The Unresolved Challenge 2 1 2 Assisted reproductive technologies (ARTs) are the most wonderful advances in the field of obstetrics and gynecology in the last century. The advancements in embryo and gamete cryopreservation, especially the vitrification method, greatly helped infertile couples and IVF specialists in storage of surplus embryos following IVF cycles or delaying embryo transfer due to failure of the endometrial receptivity. The simplicity of this method and the lack of need for expensive equipment quickly spread its use in all IVF clinics around the world as an essential aspect of ART. The high survival rate of embryos after freezing with their ability to develop from cleavage to blastocyst stage, has prompted Reproductive and Endocrinology and Infertility (REI) physicians to expand the freeze-all strategy in ART cycles. Successful freezing of gametes and embryos maximized the cumulative pregnancy rate per oocyte retrieval and increased the safety and efficiency of IVF treatment which is beneficial in reducing the costs of IVF, particularly with the emphasis on elective single embryo transfer (eSET) (1). One of the main challenges of most IVF centers is the uncertainty over the fate and abundance of frozen gametes and embryos. Many couples abandon their stored embryos after a successful pregnancy and the birth of a healthy child or children without planning for another pregnancy. Also, some other couples leave their saved embryos due to other reasons such as despair after an unsuccessful IVF success, inability to afford the IVF costs, changes in their life plans, aging or separation of couples. Unfortunately, most of these couples never respond to repeated calls and follow-ups from IVF centers to determine the fate of their frozen embryos (2). There is technical complexity for long-term frozen storage of embryos in IVF centers. It is an expensive process and requires specific secure area under continuous temperature control and meticulous supervision. Since the frozen embryos are considered the property of couples, preserving their safety and preventing any harm has legal consequences for IVF centers. In many communities where there is a belief that life begins following conception, the legal and moral implications are even more serious regarding storage of frozen embryos. According to current practice in IVF centers, a limited number of frozen embryos will be birthed by their genetic mothers, yet thousands more belong to parents who are undecided about the destiny of their embryos. Therefore, millions of embryos have been stored and abandoned for decades, despite the fact that more frozen embryos are added to this abandoned population in all IVF centers worldwide every day. As a result, many clinics with long history in IVF are overwhelmed by the sheer numbers of nitrogen storage dewars that take up huge facility space (1, 2). Often, IVF centers produce more embryos than are needed for one cycle of embryo transfer. In some countries, due to lack of regulations and restrict guidelines for the precise control of the ovarian stimulation, sometimes 40 to 60 oocytes are retrieved in each cycle and the embryologist is forced to inseminate all of them. However, the satisfaction and the desire of the patient to retrieve this number of oocytes and fertilize them is not properly considered. The most important issue following production of surplus embryos is that there are numerous guidelines and protocols regarding the storage time of frozen gametes and embryos worldwide. For example, in the UK, frozen oocytes, sperm, and embryos can be stored for up to 55 years. Frozen embryos can be stored for up to 10 years in Sweden (before 2019, the storage period was limited to 5 years). In Australia, the duration of storage is 5 years. However, in the United States, gametes and embryos can be stored indefinitely. In the United States, the cost of storage is a disincentive for couples as they pursue frozen embryo destruction rather than preservation. In countries with the ability to store frozen embryos indefinitely, the practice contributes to the problem of embryo abandonment and the associated logistical and ethical dilemmas. Based on the available evidence, the longer storage of embryos is accompanied by the likelihood of their abundance and lack of response of owners in deciding the fate of the embryos (3). The abandoned embryos in storage dewars of IVF centers have several destinations. The most suitable outcome for the owner would be paying the cost of freezing and preserving the embryos for future pregnancies. Otherwise, they can be destroyed at the request of parents or they can be donated for biomedical research, although the number of research projects on human embryos and laboratories studying on abandoned embryos has been greatly reduced due to limited research funds in recent years. The frozen embryos can be donated to other couples who can have children only using donated embryos. Most of these couples turned to adoption due to impossibility of using embryo donation, but with the increase of surplus embryos in IVF centers and the development of NGOs to promote embryo donation as a cultural duty as well as encouragement of donor and recipient couples for embryo donation, these services are expanding in IVF centers. While embryo donation is beneficial for the couples in terms of affordability, nearly half the expense of an IVF cycle, and shorter waiting time to receive a donated embryo, child adoption has a longer history and its benefits and challenges are clearly defined. The basic problem for embryo donation in some countries and cultures is the direct connection of the donor and the recipient as well as their attitude towards donated embryos as a commercial item. Therefore, the development of these services in IVF centers requires proper standards, regulations, and ethical guidelines for donating and receiving embryos. If we believe that an embryo is potentially a human, it should not simply be traded as goods in social media without any protection. Stability and continuity of the recipient family foundation is another important issue. Currently, most of the organizations and IVF centers performing embryo donation prefer to provide services for heterosexual and legally married couples regardless of their ethnicity and race. Although most of the embryos donated in the United States are from Caucasian, Asian, or Hispanic families with few embryos available from African and American couples, the priority of IVF centers is the similar racial background of the recipient families and the donor’s embryos (4). Donation of abandoned embryos in IVF centers has its outspoken critics. They argue that the practice may be deemed immoral as it encourages production of more embryos than are needed for one or two transfer cycles. The critics state that the ideal scenario for a child is to grow up with their genetic parents. However, children resulting from embryo donation, like adopted children, will struggle with the story of their donation, acceptance of their parents, and searching for biological parents. On the other hand, there are parents who face a dilemma of whether accepting the donation program or consenting to the destruction of their abandoned embryos. Even supporters of embryo donation believe that the preferred solution would be to prevent the production of surplus frozen embryos. This would be achieved through strict regulations as well as increased awareness and education of infertile couples and professionals. A well-known example of these laws and regulations is found in Germany, where embryo freezing is prohibited except in rare cases; therefore, IVF centers and specialists avoid to produce additional embryos (3, 4). Finally, decision on the fate of abandoned frozen embryos is a complex and multifaceted issue, depending on views of different communities regarding the nature of the embryo. If IVF-produced embryos are considered as potential human beings, the issue of whether they can easily be destroyed becomes much more complex. Moreover, if we consider embryos stored by IVF centers as property, it becomes a challenge to decide which authority as an eligible entity would have the right to determine their fate in case that their owners abandon their property. 077 79 Mohammad Reza MR Sadeghi محمدرضا صادقی Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran sadeghi@avicenna.ac.ir No Keyword 140232.pdf Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, et al. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017;23(2):139-55.##Rinehart LA. Storage, transport, and disposition of gametes and embryos: legal issues and practical considerations. Fertil Steril. 2021;115(2):274-81.##Carvalho KB. Frozen embryos are the new orphan crisis. Christianity Today. Dec 2023. https://www. Christianitytoday.com/ct/2023/december/ivf-frozen-embryos-are-new-orphan-crisis.html.##Huele EH, Kool EM, Bos AME, Fauser BCJM, Bredenoord AL. The ethics of embryo donation: what are the moral similarities and differences of surplus embryo donation and double gamete donation? Hum Reprod. 2020;35(10): 2171-8.##

Modulatory Effects of Vitamin D: A Possible Approach to Mitigate Air Pollution Related Pregnancy Complications 2 1 2 Approximately 99% of people on the planet breathe air that exceeds the World Health Organization’s permitted threshold for pollution. South Asia is home to the world's most polluted cities. Population-based studies have suggested that women's reproductive health outcomes are worsening due to air pollution. Preeclampsia, miscarriage, gestational diabetes, high blood pressure, and unfavorable birth outcomes, including preterm birth, low birth weight, or even stillbirth are all linked to exposure to air pollution during pregnancy. It is estimated that 0.61 million deaths in India alone were related to indoor air pollution. Females frequently cook in the household using solid fuel as a primary combustion source. Women in the regions with the highest population density are disproportionately affected by high levels of poor-quality indoor air. Recently, it has been proposed that air pollution has a distinct role in the onset of vitamin D deficiency. Numerous studies have explored associations between low vitamin D level and various female reproductive health conditions since the discovery of the vitamin D receptor. It is worthy to note that some of these reproductive health conditions positively correlate with the severity of air pollution. In this study, the evidence has been synthesized on vitamin D's protective properties and dietary and pharmaceutical interventions have been discussed to show their beneficial effects in decreasing the long-term negative impacts of air pollution on women's health. 079 102 Bharti B Singhal Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India Sarthika S Chauhan Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India Nikita N Soni Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India Vikas V Gurjar Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India Vibhor V Joshi Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India Prasan P Kaur Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India Pooja P Ratre Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India Roshani R Kumari Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India Pradyumna PK Mishra Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH) India pkm_8bh@yahoo.co.uk Environmental healthMaternal-fetal medicineNano-engineered vitaminsParticulate matterTranslational research 140228.pdf Sicard P, Agathokleous E, Anenberg SC, De Marco A, Paoletti E, Calatayud V. Trends in urban air pollution over the last two decades: a global perspective. Sci Total Environ. 2023;858(Pt 2):160064.##Fuller R, Landrigan PJ, Balakrishnan K, Bathan G, Bose-O'Reilly S, Brauer M, et al. Pollution and health: a progress update. Lancet Planet Health. 2022;6(6):e535-e47. ##Zhao H, Zhang X, Wang W, Shi J, Lai W, Li Y, et al. Global, regional, and national burden of ambient and household PM2.5-related neonatal disorders, 1990-2019. Ecotoxicol Environ Saf. 2023;252:114560.##IQAir, World Air Quality Report. IQAir Rep; 2021. 41 p.##Olhoff A, Christensen JM. Emissions gap report. DTU Orbit; 2020.##Kumar K, Pande BP. Air pollution prediction with machine learning: a case study of Indian cities. Int J Environ Sci Technol (Tehran). 2023;20(5):5333-48.##Rehman A, Kumari R, Kamthan A, Tiwari R, Srivastava RK, van der Westhuizen FH, et al. Cell-free circulating mitochondrial DNA: an emerging biomarker for airborne particulate matter associated with cardiovascular diseases. Free Radic Biol Med. 2023;195:103-20.##Ghosh R, Causey K, Burkart K, Wozniak S, Cohen A, Brauer M. Ambient and household PM2.5 pollution and adverse perinatal outcomes: a meta-regression and analysis of attributable global burden for 204 countries and territories. PLoS Med. 2021;18(9):e1003718.##Sofia D, Gioiella F, Lotrecchiano N, Giuliano A. Mitigation strategies for reducing air pollution. Environ Sci Pollut Res Int. 2020;27(16):19226-35.##Rajagopalan S, Brauer M, Bhatnagar A, Bhatt DL, Brook JR, Huang W, et al. Personal-level protective actions against particulate matter air pollution exposure: a scientific statement from the American heart association. Circulation. 2020;142(23):e411-e31.##Ratre P, Chauhan P, Bhargava A, Tiwari R, Thareja S, Srivastava RK, et al. Nano-engineered vitamins as a potential epigenetic modifier against environmental air pollutants. Rev Environ Health. 2022;38(3):547-64.##Qin Y, Zhang H, Jiang B, Chen J, Zhang T. Food bioactives lowering risks of chronic diseases induced by fine particulate air pollution: a comprehensive review. Crit Rev Food Sci Nutr. 2023;63(25):7811-36.##Hennig B, Petriello MC, Gamble MV, Surh YJ, Kresty LA, Frank N, et al. The role of nutrition in influencing mechanisms involved in environmentally mediated diseases. Rev Environ Health. 2018;33(1):87-97.##Almetwally AA, Bin-Jumah M, Allam AA. Ambient air pollution and its influence on human health and welfare: an overview. Environ Sci Pollut Res Int. 2020;27(20):24815-30. ##Chatkin J, Correa L, Santos U. External environmental pollution as a risk factor for Asthma. Clin Rev Allergy Immunol. 2022;62(1):72-89.##Brumberg HL, Karr CJ, Council on environmental health. Ambient air pollution: health hazards to children. Pediatrics. 2021;147(6):e2021051484.##Yang W, Omaye ST. Air pollutants, oxidative stress and human health. Mutat Res. 2009;674(1-2):45-54.##Agrawal D, Kumari R, Ratre P, Rehman A, Srivastava RK, Reszka E, et al. Cell-free circulating miRNAs-lncRNAs-mRNAs as predictive markers for breast cancer risk assessment in women exposed to indoor air pollution. Case Stud Chem Environ Eng. 2022;1(6):100267.##World Health Organization. WHO global air quality guidelines: Particulate matter (PM2.5 and PM10), ozone, nitrogen dioxide, sulfur dioxide and carbon monoxide. Geneva: World Health Organization; 2021. 290 p.##Keel J, Walker K, Pant P. Air Pollution and its impacts on health in Africa-insights from the State of Global Air 2020. Clean Air J. 2020;30(2):1-2.##Duan X, Wang B, Zhao X, Shen G, Xia Z, Huang N, et al. Personal inhalation exposure to polycyclic aromatic hydrocarbons in urban and rural residents in a typical northern city in China. Indoor Air. 2014;24(5):464-73.##Shukla A, Bunkar N, Kumar R, Bhargava A, Tiwari R, Chaudhury K, et al. Air pollution associated epigenetic modifications: Transgenerational inheritance and underlying molecular mechanisms. Sci Total Environ. 2019;656:760-77.##Bhargava A, Bunkar N, Aglawe A, Pandey KC, Tiwari R, Chaudhury K, et al. Epigenetic biomarkers for risk assessment of particulate matter associated lung cancer. Curr Drug Targets. 2018;19(10):1127-47.##Mishra PK, Bunkar N, Singh RD, Kumar R, Gupta PK, Tiwari R, et al. Comparative profiling of epigenetic modifications among individuals living in different high and low air pollution zones: a pilot study from India. Environ Adv. 2021(1):4:100052.##Bhargava A, Shukla A, Bunkar N, Shandilya R, Lodhi L, Kumari R, et al. Exposure to ultrafine particulate matter induces NF-κβ mediated epigenetic modifications. Environ Pollut. 2019;252(Pt A):39-50.##Bhargava A, Khare NK, Bunkar N, Chaudhury K, Pandey KC, Jain SK, et al. Cell-free circulating epigenomic signatures: non-invasive biomarker for cardiovascular and other age-related chronic diseases. Curr Pharm Des. 2017;23(8):1175-87.##Bhargava A, Tamrakar S, Aglawe A, Lad H, Srivastava RK, Mishra DK, et al. Ultrafine particulate matter impairs mitochondrial redox homeostasis and activates phosphatidylinositol 3-kinase mediated DNA damage responses in lymphocytes. Environ Pollut. 2018;234:406-19.##Sharma J, Parsai K, Raghuwanshi P, Ali SA, Tiwari V, Bhargava A, et al. Emerging role of mitochondria in airborne particulate matter-induced immunotoxicity. Environ Pollut. 2021;270:116242.##Kumari R, Kaur P, Verma SK, Ratre P, Mishra PK. Omics-based cutting-edge technologies for identifying predictive biomarkers to measure the impact of air borne particulate matter exposure on male reproductive health. J Reprod Healthc Med. 2024;5(2):1-14.##International Panel on Climate Change. Climate Change 2022: Impacts, Adaptation, and Vulnera-bility. Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change. Geneva: International Panel on Climate Change; 2022. 3056 p.##Mishra PK, Bhargava A, Kumari R, Bunkar N, Chauhan P, Mukherjee S, et al. Integrated mitoepigenetic signalling mechanisms associated with airborne particulate matter exposure: A cross-sectional pilot study. Atmos Pollut Res. 2022;13(5):101399.##Glencross DA, Ho TR, Camiña N, Hawrylowicz CM, Pfeffer PE. Air pollution and its effects on the immune system. Free Radic Biol Med. 2020;151:56-68.##Brunekreef B, Holgate ST. Air pollution and health. Lancet. 2002;360(9341):1233-42.##Bromberg PA. Mechanisms of the acute effects of inhaled ozone in humans. Biochim Biophys Acta. 2016;1860(12):2771-81.##Raz-Maman C, Carel RS, Borochov-Greenberg N, Zack O, Portnov BA. The exposure assessment period to air pollutants which affects lung function: analysis of recent studies and an explanatory model. Air Qual Atmos Health. 2021;15:393-402.##Mishra PK, Kumari R, Shandilya R, Ratre P, Bhargava A, Pathak N, et al. Reproductomics: An impending driver for exposome research. J Reprod Healthc Med. 2022;3(10):1-6.##Uauy R, Kain J, Corvalan C. How can the developmental origins of health and disease (DOHaD) hypothesis contribute to improving health in developing countries? Am J Clin Nutr. 2011;94(6 Suppl):1759S-64S.##Barker DJ. The fetal and infant origins of adult disease. BMJ. 1990;301(6761):1111.##Blanc AK, Wardlaw T. Monitoring low birth weight: an evaluation of international estimates and an updated estimation procedure. Bull World Health Organ. 2005;83(3):178-85.##Carlsten C, Salvi S, Wong GWK, Chung KF. Personal strategies to minimise effects of air pollution on respiratory health: advice for providers, patients and the public. Eur Respir J. 2020;55(6):1902056.##Leshem A, Liwinski T, Elinav E. Immune-microbiota interplay and colonization resistance in infection. Mol Cell. 2020;78(4):597-613.##Hennig B, Ormsbee L, McClain CJ, Watkins BA, Blumberg B, Bachas LG, et al. Nutrition can modulate the toxicity of environmental pollutants: implications in risk assessment and human health. Environ Health Perspect. 2012;120(6):771-4. ##Mousa A, Naqash A, Lim S. Macronutrient and micronutrient intake during pregnancy: an overview of recent evidence. Nutrients. 2019;11(2):443.##Calkins K, Devaskar SU. Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care. 2011;41(6):158-76.##Li S, Chen M, Li Y, Tollefsbol TO. Prenatal epigenetics diets play protective roles against environmental pollution. Clin Epigenetics. 2019;11(1):82.##Mishra PK, Kumari R, Bhargava A, Bunkar N, Chauhan P, Tiwari R, et al. Prenatal exposure to environmental pro-oxidants induces mitochondria-mediated epigenetic changes: a cross-sectional pilot study. Environ Sci Pollut Res Int. 2022;29(49):74133-49.##Alavi N, Ebrahimi M, Akbari-Asbagh F. The effect of vitamin D status on ovarian reserve markers in infertile women: a prospective cross-sectional study. Int J Reprod Biomed. 2020;18(2):85-92.##Péter S, Holguin F, Wood LG, Clougherty JE, Raederstorff D, Antal M, et al. Nutritional solutions to reduce risks of negative health impacts of air pollution. Nutrients. 2015;7(12):10398-416.##Barrea L, Savastano S, Di Somma C, Savanelli MC, Nappi F, Albanese L, et al. Low serum vitamin D-status, air pollution and obesity: a dangerous liaison. Rev Endocr Metab Disord. 2017;18(2):207-14.##Arshad R, Gulshad L, Haq IU, Farooq MA, Al-Farga A, Siddique R, et al. Nanotechnology: a novel tool to enhance the bioavailability of micronutrients. Food Sci Nutr. 2021;9(6):3354-61.##Crintea A, Dutu AG, Sovrea A, Constantin AM, Samasca G, Masalar AL, et al. Nanocarriers for drug delivery: an overview with emphasis on vitamin D and K transportation. Nanomaterials (Basel). 2022;12(8):1376.##Bertozzi S, Corradetti B, Seriau L, Diaz Ñañez JA, Cedolini C, Fruscalzo A, et al. Nanotechnologies in obstetrics and cancer during pregnancy: a narrative review. J Pers Med. 2022;12(8):1324.##Ashley B, Simner C, Manousopoulou A, Jenkinson C, Hey F, Frost JM, et al. Placental uptake and metabolism of 25(OH)vitamin D determine its activity within the fetoplacental unit. Elife. 2022;11:e71094. ##Shin JS, Choi MY, Longtine MS, Nelson DM. Vitamin D effects on pregnancy and the placenta. Placenta. 2010;31(12):1027-34.##Wagner CL, Taylor SN, Johnson DD, Hollis BW. The role of vitamin D in pregnancy and lactation: emerging concepts. Womens Health (Lond). 2012;8(3):323-40. ##Sahay M, Sahay R. Rickets-vitamin D deficiency and dependency. Indian J Endocrinol Metab. 2012;16(2):164-76.##De-Regil LM, Palacios C, Lombardo LK, PeñaRosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2016(1):CD008873. ##Bikle DD. Vitamin D: Production, metabolism and mechanisms of action. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al, editors. Endotext (Internet). South Dart-mouth (MA): MDText.com, Inc.; 2000##Kiely ME, Wagner CL, Roth DE. Vitamin D in pregnancy: where we are and where we should go. J Steroid Biochem Mol Biol. 2020;201:105669. ##Lapillonne A. Vitamin D deficiency during pregnancy may impair maternal and fetal outcomes. Med Hypotheses. 2010;74(1):71-5.##Battistini C, Ballan R, Herkenhoff ME, Saad SMI, Sun J. Vitamin D modulates intestinal microbiota in inflammatory bowel diseases. Int J Mol Sci. 2020;22(1):362. ##Pagnini C, Di Paolo MC, Graziani MG, Delle Fave G. Probiotics and vitamin D/vitamin D receptor pathway interaction: potential therapeutic implications in inflammatory bowel disease. Front Pharmacol. 2021;12:747856.##Mishra PK, Kaur P. Mitochondrial biomarkers for airborne particulate matter–associated cardiovascular diseases. Curr Opin Environ Sci Health. 2023;35:100494.##Fetahu IS, Höbaus J, Kállay E. Vitamin D and the epigenome. Front Physiol. 2014;5:164. ##Schröder-Heurich B, Springer CJP, von Versen-Höynck F. Vitamin D effects on the immune system from periconception through pregnancy. Nutrients. 2020;12(5):1432. ##Kaushal M, Magon N. Vitamin D in pregnancy: a metabolic outlook. Indian J Endocrinol Metab. 2013;17(1):76-82.##Zhao H, Wong RJ, Stevenson DK. The impact of hypoxia in early pregnancy on placental cells. Int J Mol Sci. 2021;22(18):9675.##Liu Y, Li L, Xie J, Jiao X, Hu H, Zhang Y, et al. Foetal 25-hydroxyvitamin D moderates the association of prenatal air pollution exposure with foetal glucolipid metabolism disorder and systemic inflammatory responses. Environ Int. 2021;151:106460. ##Yang D, Chen L, Yang Y, Shi J, Huang Z, Li M, et al. Effect of PM2.5 exposure on vitamin D status among pregnant women: a distributed lag analysis. Ecotoxicol Environ Saf. 2022;239:113642.##Olsson D, Ekström M, Forsberg B. Temporal variation in air pollution concentrations and preterm birth-a population based epidemiological study. Int J Environ Res Public Health. 2012;9(1):272-85.##Lyall K, Schmidt RJ, Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. Int J Epidemiol. 2014;43(2):443-64.##Baïz N, Dargent-Molina P, Wark JD, Souberbielle JC, Slama R, Annesi-Maesano I, et al. Gestational exposure to urban air pollution related to a decrease in cord blood vitamin d levels. J Clin Endocrinol Metab. 2012;97(11):4087-95. ##Tingskov Pedersen CE, Eliasen AU, Ketzel M, Brandt J, Loft S, Frohn LM, et al. Prenatal exposure to ambient air pollution is associated with early life immune perturbations. J Allergy Clin Immunol. 2023;151(1):212-21.##Sordillo JE, Rifas-Shiman SL, Switkowski K, Coull B, Gibson H, Rice M, et al. Prenatal oxidative balance and risk of asthma and allergic disease in adolescence. J Allergy Clin Immunol. 2019;144(6):1534-41.e5. ##Zhao W, Zhao Y, Wang P, Zhou Y, Meng X, Ma W, et al. PM2.5 exposure associated with prenatal anxiety and depression in pregnant women. Ecotoxicol Environ Saf. 2022;248:114284.##Li C, Gong YQ, Xia YY, Wang XC, Chen L, Yan SJ, et al. Particulate matter may have a limited influence on maternal vitamin D levels. Sci Rep. 2022;12(1):16807.##Li J, Xiao X, Wang P, Meng X, Zhou Y, Shi H, et al. PM2.5 exposure and maternal glucose metabolism in early pregnancy: Associations and potential mediation of 25-hydroxyvitamin D. Ecotoxicol Environ Saf. 2021;224:112645. ##Wang P, Yin WJ, Zhang Y, Jiang XM, Yin XG, Ma YB, et al. Maternal 25(OH)D attenuates the relationship between ambient air pollution during pregnancy and fetal hyperinsulinism. Chemosphere. 2023;325:138427. ##Guxens M, Aguilera I, Ballester F, Estarlich M, Fernández-Somoano A, Lertxundi A, et al. Prenatal exposure to residential air pollution and infant mental development: modulation by antioxidants and detoxification factors. Environ Health Perspect. 2012;120(1):144-9. ##Amegah AK, Sewor C, Obeng AA, Coker ES, Eliason S. Vitamin D intake modifies the association of household air pollution exposure with maternal disorders of pregnancy. Indoor Air. 2022;32(1):e12963.##Sordillo JE, Switkowski KM, Coull BA, Schwartz J, Kloog I, Gibson H, et al. Relation of prenatal air pollutant and nutritional exposures with biomarkers of allergic disease in adolescence. Sci Rep. 2018;8(1):10578.##Ren Z, Yuan J, Luo Y, Wang J, Li Y. Association of air pollution and fine particulate matter (PM2.5) exposure with gestational diabetes: a systematic review and meta-analysis. Ann Transl Med. 2023;11(1):23.##Gruzieva O, Xu CJ, Yousefi P, Relton C, Merid SK, Breton CV, et al. Prenatal particulate sir pollution and DNA methylation in newborns: sn epigenome-wide meta-snalysis. Environ Health Perspect. 2019;127(5):57012.##Bai W, Li Y, Niu Y, Ding Y, Yu X, Zhu B, et al. Association between ambient air pollution and pregnancy complications: a systematic review and meta-analysis of cohort studies. Environ Res. 2020;185:109471.##Agrawal S, Yamamoto S. Effect of indoor air pollution from biomass and solid fuel combustion on symptoms of preeclampsia/eclampsia in Indian women. Indoor Air. 2015;25(3):341-52.##Pope DP, Mishra V, Thompson L, Siddiqui AR, Rehfuess EA, Weber M, et al. Risk of low birth weight and stillbirth associated with indoor air pollution from solid fuel use in developing countries. Epidemiol Rev. 2010;32:70-81.##Yang YL, Yang HL, Shiao SPK. Meta-prediction of MTHFR gene polymorphisms and air pollution on the risk of hypertensive disorders in pregnancy worldwide. Int J Environ Res Public Health. 2018;15(2):326.##Liu C, Sun J, Liu Y, Liang H, Wang M, Wang C, et al. Different exposure levels of fine particulate matter and preterm birth: a meta-analysis based on cohort studies. Environ Sci Pollut Res Int. 2017;24(22):17976-84.##Yu H, Yin Y, Zhang J, Zhou R. The impact of particulate matter 2.5 on the risk of preeclampsia: an updated systematic review and meta-analysis. Environ Sci Pollut Res Int. 2020;27(30):37527-39.##Pedersen M, Stayner L, Slama R, Sørensen M, Figueras F, Nieuwenhuijsen MJ, et al. Ambient air pollution and pregnancy-induced hypertensive disorders: a systematic review and meta-analysis. Hypertension. 2014;64(3):494-500. ##Zhou X, Li C, Cheng H, Xie J, Li F, Wang L, et al. Association between ambient air pollution exposure during pregnancy and gestational diabetes mellitus: a meta-analysis of cohort studies. Environ Sci Pollut Res Int. 2022;29(45):68615-35.##Stieb DM, Chen L, Eshoul M, Judek S. Ambient air pollution, birth weight and preterm birth: a systematic review and meta-analysis. Environ Res. 2012;117:100-11.##Amegah AK, Quansah R, Jaakkola JJ. Household air pollution from solid fuel use and risk of adverse pregnancy outcomes: a systematic review and meta-analysis of the empirical evidence. PLoS One. 2014;9(12):e113920. ##Liang W, Zhu H, Xu J, Zhao Z, Zhou L, Zhu Q, et al. Ambient air pollution and gestational diabetes mellitus: An updated systematic review and meta-analysis. Ecotoxicol Environ Saf. 2023;255:114802.##Chen EK, Zmirou-Navier D, Padilla C, Deguen S. Effects of air pollution on the risk of congenital anomalies: a systematic review and meta-analysis. Int J Environ Res Public Health. 2014;11(8):7642-68.##Chun H, Leung C, Wen SW, McDonald J, Shin HH. Maternal exposure to air pollution and risk of autism in children: A systematic review and meta-analysis. Environ Pollut. 2020;256:113307.##Rappazzo KM, Nichols JL, Rice RB, Luben TJ. Ozone exposure during early pregnancy and preterm birth: A systematic review and meta-analysis. Environ Res. 2021;198:111317.##Li SS, Zhang R, Lan X, Qu PF, Dang SN, Chen FY, et al. [Prenatal exposure to ambient air pollution and congenital heart disease: a Meta-analysis]. Zhonghua Liu Xing Bing Xue Za Zhi. 2017;38(8):1121-6. Chinese.##Xie G, Sun L, Yang W, Wang R, Shang L, Yang L, et al. Maternal exposure to PM2.5 was linked to elevated risk of stillbirth. Chemosphere. 2021;283:131169.##Ju L, Hua L, Xu H, Li C, Sun S, Zhang Q, et al. Maternal atmospheric particulate matter exposure and risk of adverse pregnancy outcomes: a meta-analysis of cohort studies. Environ Pollut. 2023;317:120704.##Zhao B, Wang M, Song W, Ma H, Meng H, Qi M, et al. Increasing risk of gestational diabetes and preeclampsia associated with long-term exposure effects of air pollution. Air Qual Atmos Health. 2022;15(6):917-28.##Martens PJ, Gysemans C, Verstuyf A, Mathieu AC. Vitamin D's effect on immune function. Nutrients. 2020;12(5):1248.##Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023.##Zeng Q, Zou D, Wei Y, Ouyang Y, Lao Z, Guo R. Association of vitamin D receptor gene rs739837 polymorphism with type 2 diabetes and gestational diabetes mellitus susceptibility: a systematic review and meta-analysis. Eur J Med Res. 2022;27(1):65. ##Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. 2016;24(5):547-553. ##Karras SN, Wagner CL, Castracane VD. Understanding vitamin D metabolism in pregnancy: From physiology to pathophysiology and clinical outcomes. Metabolism. 2018;86:112-23. ##Sergeev IN. 1,25-Dihydroxyvitamin D3 and type 2 diabetes: Ca2 -dependent molecular mechanisms and the role of vitamin D status. Horm Mol Biol Clin Investig. 2016;26(1):61-5.##Sergeev IN. Vitamin D status and vitamin D-dependent apoptosis in obesity. Nutrients. 2020;12(5):1392.##Wimalawansa SJ. Vitamin D deficiency: effects on oxidative stress, epigenetics, gene regulation, and aging. Biology (Basel). 2019;8(2):30. ##Szymczak-Pajor I, Śliwińska A. Analysis of association between vitamin D deficiency and insulin resistance. Nutrients. 2019;11(4):794.##Tamblyn JA, Pilarski NSP, Markland AD, Marson EJ, Devall A, Hewison M, et al. Vitamin D and miscarriage: a systematic review and meta-analysis. Fertil Steril. 2022;118(1):111-22.##Gallo S, McDermid JM, Al-Nimr RI, Hakeem R, Moreschi JM, Pari-Keener M, et al. Vitamin D supplementation during pregnancy: an evidence analysis center systematic review and meta-analysis. J Acad Nutr Diet. 2020;120(5):898-924.e4.##Khaing W, Vallibhakara SA, Tantrakul V, Vallibhakara O, Rattanasiri S, McEvoy M, et al. Calcium and vitamin D supplementation for prevention of preeclampsia: a systematic review and network meta-analysis. Nutrients. 2017;9(10):1141. ##Fogacci S, Fogacci F, Banach M, Michos ED, Hernandez AV, Lip GYH, et al. Vitamin D supplementation and incident preeclampsia: a systematic review and meta-analysis of randomized clinical trials. Clin Nutr. 2020;39(6):1742-52.##Hu KL, Zhang CX, Chen P, Zhang D, Hunt S. Vitamin D levels in early and middle pregnancy and preeclampsia, a systematic review and meta-analysis. Nutrients. 2022;14(5):999. ##Rodrigues MRK, Lima SAM, Mazeto GMFDS, Calderon IMP, Magalhães CG, Ferraz GAR, et al. Efficacy of vitamin D supplementation in gestational diabetes mellitus: Systematic review and meta-analysis of randomized trials. PLoS One. 2019;14(3):e0213006.##Poel YHM, Hummel P, Lips P, Stam F, van der Ploeg T, Simsek S. Vitamin D and gestational diabetes: a systematic review and meta-analysis. Eur J Intern Med. 2012;23(5):465-9. ##Zhang MX, Pan GT, Guo JF, Li BY, Qin LQ, Zhang ZL. Vitamin D deficiency increases the risk of gestational diabetes mellitus: a meta-snalysis of observational studies. Nutrients. 2015;7(10):8366-75.##Palacios C, De-Regil LM, Lombardo LK, Peña-Rosas JP. Vitamin D supplementation during pregnancy: Updated meta-analysis on maternal outcomes. J Steroid Biochem Mol Biol. 2016;164:148-55.##Milajerdi A, Abbasi F, Mousavi SM, Esmaillzadeh A. Maternal vitamin D status and risk of gestational diabetes mellitus: A systematic review and meta-analysis of prospective cohort studies. Clin Nutr. 2021;40(5):2576-86.##Fang K, He Y, Mu M, Liu K. Maternal vitamin D deficiency during pregnancy and low birth weight: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2021;34(7):1167-73.##Luo T, Lin Y, Lu J, Lian X, Guo Y, Han L, et al. Effects of vitamin D supplementation during pregnancy on bone health and offspring growth: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2022;17(10):e0276016.##Wei Z, Zhang J, Yu X. Maternal vitamin D status and childhood asthma, wheeze, and eczema: a systematic review and meta-analysis. Pediatr Allergy Immunol. 2016;27(6):612-9. ##Sharafi SM, Yazdi M, Goodarzi-Khoigani M, Kelishadi R. Effect of vitamin D supplementation on serum 25-Hydroxyvitamin D and homeostatic model of insulin resistance levels in healthy pregnancy: a systematic review and meta-analysis. Iran J Med Sci. 2023;48(1):4-12. ##Guo Y, Zhang Y, Tang X, Liu X, Xu H. Association between vitamin D receptor (VDR) gene polymorphisms and hypertensive disorders of pregnancy: a systematic review and meta-analysis. Peer J. 2023;11:e15181.##Tan Q, Liu S, Chen D. Poor vitamin D status and the risk of maternal depression: a dose-response meta-analysis of observational studies. Public Health Nutr. 2021;24(8):2161-70. ##Siddiqee MH, Bhattacharjee B, Siddiqi UR, Rahman MM. High prevalence of vitamin D insufficiency among South Asian pregnant women: a systematic review and meta-analysis. Br J Nutr. 2022;128(6):1118-29.##Sadeghian M, Asadi M, Rahmani S, Akhavan Zanjani M, Sadeghi O, Hosseini SA, et al. Circulating vitamin D and the risk of gestational diabetes: a systematic review and dose-response meta-analysis. Endocrine. 2020;70(1):36-47.##Wang M, Chen Z, Hu Y, Wang Y, Wu Y, Lian F, et al. The effects of vitamin D supplementation on glycemic control and maternal-neonatal outcomes in women with established gestational diabetes mellitus: a systematic review and meta-analysis. Clin Nutr. 2021;40(5):3148-57.##Akbari S, Khodadadi B, Ahmadi SAY, Abbaszadeh S, Shahsavar F. Association of vitamin D level and vitamin D deficiency with risk of preeclampsia: a systematic review and updated meta-analysis. Taiwan J Obstet Gynecol. 2018;57(2):241-7.##Yuan Y, Tai W, Xu P, Fu Z, Wang X, Long W, et al. Association of maternal serum 25-hydroxyvitamin D concentrations with risk of preeclampsia: a nested case-control study and meta-analysis. J Matern Fetal Neonatal Med. 2021;34(10):1576-85.##Wang L, Lv S, Li F, Yu X, Bai E, Yang X. Vitamin D deficiency is associated with metabolic risk factors in women with polycystic ovary syndrome: a cross-sectional study in Shaanxi China. Front Endocrinol (Lausanne). 2020;11:171. ##European society for human reproduction and embryology (ESHRE) guideline group on POI, Webber L, Davies M, Anderson R, Bartlett J, Braat D, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926-37.##Pan W, Ye X, Yin S, Ma X, Li C, Zhou J, et al. Selected persistent organic pollutants associated with the risk of primary ovarian insufficiency in women. Environ Int. 2019;129:51-8.##Shirasuna K, Karasawa T, Takahashi M. Role of the NLRP3 inflammasome in preeclampsia. Front Endocrinol (Lausanne). 2020;11:80.##Fleisch AF, Kloog I, Luttmann-Gibson H, Gold DR, Oken E, Schwartz JD. Air pollution exposure and gestational diabetes mellitus among pregnant women in Massachusetts: a cohort study. Environ Health. 2016;15:40.##Rizzo G, Garzon S, Fichera M, Panella MM, Catena U, Schiattarella A, et al. Vitamin D and gestational diabetes mellitus: is there a link? Antioxidants (Basel). 2019;8(11):511. ##

The Effect of Progesterone Elevation on the Day of Trigger Administration: A Review of the Literature 2 1 2 Since the advent of assisted reproductive technology, different variables have been shown to affect pregnancy outcomes. One of the most prevalent studied events is the premature rise in serum progesterone concentrations on the day of trigger administration during cycles of ovarian stimulation. This phenomenon, classically known as premature luteinization, has been observed significantly for decades and has been linked to adverse pregnancy outcomes and lower live birth rates. Ultimately, a quest to find a precise serum progesterone concentration cut-off value that can be effectively used to predict pregnancy outcomes prior to trigger administration is still underway. The purpose of the current research was to study the available literature on the relationship between serum progesterone on the day of trigger administration in controlled ovarian stimulation cycles used for IVF in an attempt to identify a cut-off serum progesterone concentration that can be used to effectively predict future pregnancy outcomes in fresh transfers. This study is a review of the literature and is based on information and data gathered from 36 published articles. The majority of the literature shows that a serum progesterone concentration cut-off of 1.5 ng/ml (4.77 nmol/L) can be used prior to trigger administration to effectively predict pregnancy outcomes. Premature progesterone elevation on the day or prior to the trigger administration is associated with adverse pregnancy outcomes in IVF cycles. Other factors such as follicle number, serum concentration of other hormones, and ovarian response to ovarian stimulation should also be considered to predict the success of IVF protocols. 102 110 Chris Ch Jreij Faculty of Medicine, University of Balamand Faculty of Medicine, University of Balamand Lebanon Rawad R Halimeh Clinical Department, The Centre for Reproductive and Genetic Health Clinical Department, The Centre for Reproductive and Genetic Health United Kingdom Rawad.halimeh@gmail.com Doha D Fadel Faculty of Medicine, University of Balamand Faculty of Medicine, University of Balamand Lebanon Perla P Chamoun Faculty of Medicine, University of Balamand Faculty of Medicine, University of Balamand Lebanon Jean J Nassar Faculty of Medicine, University of Balamand Faculty of Medicine, University of Balamand Lebanon Wael W Saab Clinical Department, The Centre for Reproductive and Genetic Health Clinical Department, The Centre for Reproductive and Genetic Health United Kingdom Srividya S Seshadri Clinical Department, The Centre for Reproductive and Genetic Health Clinical Department, The Centre for Reproductive and Genetic Health United Kingdom Marianne M Bersaoui Faculty of Medicine, University of Balamand Faculty of Medicine, University of Balamand Lebanon Embryo implantationEmbryo transferEndometriumIn vitro fertilizationOocyte collectionOvarian hyperstimulation syndromeOvarian stimulation Endometrium 140225.pdf Pelinck MJ, Hoek A, Simons AHM, Heineman MJ. Efficacy of natural cycle IVF: a review of the literature. Hum Reprod Update. 2002;8(2):129-39.##Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2011;18(1):73-91.##Alper MM, Fauser BC. Ovarian stimulation protocols for IVF: is more better than less? Reprod Biomed Online. 2017;34(4):345-53.##Leão R de, Esteves SC. Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech. Clinics (Sao Paulo). 2014;69(4):279-93.##Gonadotropin preparations: past, present, and future perspectives. Fertil Steril. 2008;90(5 Suppl):S13-20.##Fatemi HM, Popovic-Todorovic B, Humaidan P, Kol S, Banker M, Devroey P, et al. Severe ovarian hyperstimulation syndrome after gonadotropin-releasing hormone (GnRH) agonist trigger and “freeze-all” approach in Gnrh antagonist protocol. Fertil Steril. 2014;101(4):1008-11.##Humaidan P, Polyzos NP, Alsbjerg B, Erb K, Mikkelsen AL, Elbaek HO, et al. GnRHa trigger and individualized luteal phase hcg support according to ovarian response to stimulation: Two prospective randomized controlled multi-centre studies in IVF patients. Hum Reprod. 2013;28(9):2511-21.##Graham JD, Clarke CL. Physiological action of progesterone in target tissues. Endocr Rev. 1997;18(4):502-19.##Di Renzo GC, Mattei A, Gojnic M, Gerli S. Progesterone and pregnancy. Curr Opin Obstet Gynecol. 2005;17(6):598-600.##Drakopoulos P, Racca A, Errázuriz J, De Vos M, Tournaye H, Blockeel C, et al. The role of progesterone elevation in IVF. Reprod Biol. 2019;19(1):1-5.##Kyrou D, Al-Azemi M, Papanikolaou EG, Donoso P, Tziomalos K, Devroey P, et al. The relationship of premature progesterone rise with serum estradiol levels and number of follicles in GnRH antagonist/recombinant FSH-stimulated cycles. Eur J Obstet Gynecol Reprod Biol. 2012;162(2):165-8.##Hoff JD, Quigley ME, Yen SS. Hormonal dynamics at midcycle: a reevaluation. J Clin Endocrinol Metab. 1983;57(4):792-6.##Ashmita J, Vikas S, Swati G. The impact of progesterone level on day of hCG injection in IVF cycles on clinical pregnancy rate. J Hum Reprod Sci. 2017;10(4):265-70.##Schoolcraft W, Sinton E, Schlenker T, Huynh D, Hamilton F, Meldrum DR. Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate. Fertil Steril. 1991;55(3):563-6.##Lawrenz B, Beligotti F, Engelmann N, Gates D, Fatemi HM. Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles. Hum Reprod. 2016;31(11):2554-60.##Wu Z, Dong Y, Ma Y, Li Y, Li L, Lin N, et al. Progesterone elevation on the day of hCG trigger has detrimental effect on live birth rate in low and intermediate ovarian responders, but not in high responders. Sci Rep. 2019;9(1):5127.##Al-Azemi M, Kyrou D, Kolibianakis EM, Humaidan P, Van Vaerenbergh I, Devroey P, et al. Elevated progesterone during ovarian stimulation for IVF. Reprod Biomed Online. 2012;24(4):381-8.##Labarta E, Martinez-Conejero JA, Alama P, Horcajadas JA, Pellicer A, Simon C, et al. Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: A functional genomics analysis. Hum Reprod. 2011;26(7):1813-25.##Simón C, Martı́n JC, Pellicer A. Paracrine regulators of implantation. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14(5):815-26.##Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Embryo cryopreservation rescues cycles with premature luteinization. Fertil Steril. 2010;93(2):636-41.##Bourgain C, Ubaldi F, Tavaniotou A, Smitz J, Van Steirteghem AC, Devroey P. Endometrial hormone receptors and proliferation index in the periovulatory phase of stimulated embryo transfer cycles in comparison with natural cycles and relation to clinical pregnancy outcome. Fertil Steril. 2002;78(2):237-44.##Feldberg D, Goldman GA, Ashkenazi J, Dicker D, Shelef M, Goldman JA. The impact of high progesterone levels in the follicular phase of in vitro fertilization (IVF) cycles: a comparative study. J In Vitro Fertil Embryo Transfer. 1989;6(1):11-4.##Schoolcraft W, Sinton E, Schlenker T, Huynh D, Hamilton F, Meldrum DR. Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate. Fertil Steril. 1991;55(3):563-6.##Özçakir HT, Levi R, Tavmergen E, Göker ENT. Premature luteinization defined as progesterone estradiol ratio >1 on hCG administration day seems to adversely affect clinical outcome in long gonadotropin‐releasing hormone agonist cycles. J Obstet Gynaecol Res. 2004;30(2):100-4.##Park JH, Jee BC, Kim SH. Factors influencing serum progesterone level on triggering day in stimulated in vitro fertilization cycles. Clin Expe Reprod Med. 2015;42(2):67-71.##Lawrenz B, Fatemi HM. Effect of progesterone elevation in follicular phase of IVF-cycles on the endometrial receptivity. Reprod Biomed Online. 2017;34(4):422-8.##Ibrahim Y, Haviland MJ, Hacker MR, Penzias AS, Thornton KL, Sakkas D. Elevated progesterone and its impact on birth weight after fresh embryo transfers. J Assist Reprod Genet. 2017;34(6):759-64.##Kiliçdag EB, Haydardedeoglu B, Cok T, Hacivelioglu SO, Bagis T. Premature progesterone elevation impairs implantation and live birth rates in GnRH-agonist IVF/ICSI cycles. Arch Gynecol Obstet. 2010;281(4):747-52.##Lee CI, Chen HH, Huang CC, Lin PY, Lee TH, Lee MS. Early progesterone change associated with pregnancy outcome after fresh embryo transfer in assisted reproduction technology cycles with progesterone level of >1.5 ng/ML on human chorionic gonadotropin trigger day. Front Endocrinol (Lausanne). 2020;11:653.##Elnashar AM. Progesterone rise on the day of HCG administration (premature luteinization) in IVF: an overdue update. J Assist Reprod Genet. 2010;27(4):149-55.##Esteves SC, Khastgir G, Shah J, Murdia K, Gupta SM, Rao DG, et al. Association between progesterone elevation on the day of human chronic gonadotropin trigger and pregnancy outcomes after fresh embryo transfer in in vitro fertilization/intracytoplasmic sperm injection cycles. Front Endocrinol (Lausanne). 2018;9:201.##Vanni VS, Somigliana E, Reschini M, Pagliardini L, Marotta E, Faulisi S, et al. Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles. Pose One. 2017;12(5):e0176482.##Vanni VS, Viganò P, Quaranta L, Pagliardini L, Giardina P, Molgora M, et al. Are extremely high progesterone levels still an issue in IVF? J Endocrinol Invest. 2017;40(1):69-75.##Amin KV, Nadkarni P, Singh PN, Singh P. Serum progesterone levels on the day of hCG trigger and ICSI outcome: a retrospective observational cohort study. Int J Reprod Contracept Obstet Gynecol. 2018;7(8):3194-8.##Xu B, Li Z, Zhang H, Jin L, Li Y, Ai J, et al. Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles. Fertil Steril. 2012;97(6):1321-7.e1-4.##

Improving Deep Learning-Based Algorithm for Ploidy Status Prediction Through Combined U-NET Blastocyst Segmentation and Sequential Time-Lapse Blastocysts Images 2 1 2 Background: Several approaches have been proposed to optimize the construction of an artificial intelligence-based model for assessing ploidy status. These encompass the investigation of algorithms, refining image segmentation techniques, and discerning essential patterns throughout embryonic development. The purpose of the current study was to evaluate the effectiveness of using U-NET architecture for embryo segmentation and time-lapse embryo image sequence extraction, three and ten hr before biopsy to improve model accuracy for prediction of embryonic ploidy status. Methods: A total of 1.020 time-lapse videos of blastocysts with known ploidy status were used to construct a convolutional neural network (CNN)-based model for ploidy detection. Sequential images of each blastocyst were extracted from the time-lapse videos over a period of three and ten hr prior to the biopsy, generating 31.642 and 99.324 blastocyst images, respectively. U-NET architecture was applied for blastocyst image segmentation before its implementation in CNN-based model development. Results: The accuracy of ploidy prediction model without applying the U-NET segmented sequential embryo images was 0.59 and 0.63 over a period of three and ten hr before biopsy, respectively. Improved model accuracy of 0.61 and 0.66 was achieved, respectively with the implementation of U-NET architecture for embryo segmentation on the current model. Extracting blastocyst images over a 10 hr period yields higher accuracy compared to a three-hr extraction period prior to biopsy. Conclusion: Combined implementation of U-NET architecture for blastocyst image segmentation and the sequential compilation of ten hr of time-lapse blastocyst images could yield a CNN-based model with improved accuracy in predicting ploidy status. 110 120 Nining N Handayan Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia Indonesia Gunawan GB Danardono IRSI Research and Training Centre IRSI Research and Training Centre Indonesia Arief A Boediono IRSI Research and Training Centre IRSI Research and Training Centre Indonesia Budi B Wiweko Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia Indonesia Ivan IR Sini IRSI Research and Training Centre IRSI Research and Training Centre Indonesia Batara B Sirait IRSI Research and Training Centre IRSI Research and Training Centre Indonesia Arie AA Polim Department of Obstetrics and Gynecology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia Department of Obstetrics and Gynecology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia Indonesia Irham I Suheimi IRSI Research and Training Centre IRSI Research and Training Centre Indonesia Anom A Bowolaks Cellular and Molecular Mechanisms in Biological System (CEMBIOS) Research Group, Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia Cellular and Molecular Mechanisms in Biological System (CEMBIOS) Research Group, Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia Indonesia alaksono@sci.ui.ac.id Artificial intelligenceImage processingNeural networksPloidy measurement 140230.pdf Huang L, Bogale B, Tang Y, Lu S, Xie XS, Racowsky C. Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy. Proc Natl Acad Sci USA. 2019;116(28):14105-12.##Rubio C, Navarro-Sánchez L, García-Pascual CM, Ocali O, Cimadomo D, Venier W, et al. Multicenter prospective study of concordance between embryonic cell-free DNA and trophectoderm biopsies from 1301 human blastocysts. Am J Obstet Gynecol. 2020;223(5):751.e1-751.e13.##Feichtinger M, Vaccari E, Carli L, Wallner E, Mädel U, Figl K, et al. Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: a proof-of-concept pilot study. Reprod Biomed Online. 2017;34 (6):583-9.##Fishel S, Campbell A, Montgomery S, Smith R, Nice L, Duffy S, et al. Time-lapse imaging algorithms rank human preimplantation embryos according to the probability of live birth. Reprod Biomed Online. 2018;37(3):304-13.##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.##Reignier A, Lammers J, Barriere P, Freour T. Can time-lapse parameters predict embryo ploidy? A systematic review. Reprod Biomed Online. 2018;36(4):380-7.##Pennetta F, Lagalla C, Borini A. Embryo morphokinetic characteristics and euploidy. Curr Opin Obstet Gynecol. 2018;30(3):185-96.##Kramer YG, Kofinas JD, Melzer K, Noyes N, McCaffrey C, Buldo-Licciardi J, et al. Assessing morphokinetic parameters via time lapse microscopy (TLM) to predict euploidy: are aneuploidy risk classification models universal? J Assist Reprod Genet. 2014;31(9):1231-42.##Liang B, Gao Y, Xu J, Song Y, Xuan L, Shi T, et al. Raman profiling of embryo culture medium to identify aneuploid and euploid embryos. Fertil Steril. 2019;111(4):753-62.e1.##Bori L, Dominguez F, Fernandez EI, Del Gallego R, Alegre L, Hickman C, et al. An artificial intelligence model based on the proteomic profile of euploid embryos and blastocyst morphology: a preliminary study. Reprod Biomed Online. 2021;42 (2):340-50.##Chavez-Badiola A, Flores-Saiffe-Farías A, Mendizabal-Ruiz G, Drakeley AJ, Cohen J. Embryo ran-king intelligent classification algorithm (ERICA): artificial intelligence clinical assistant predicting embryo ploidy and implantation. Reprod Biomed Online. 2020;41(4):585-93.##Lee CI, Su YR, Chen CH, Chang TA, Kuo EES, Zheng WL, et al. End-to-end deep learning for recognition of ploidy status using time-lapse videos. J Assist Reprod Genet. 2021;38(7):1655-63.##Diakiw SM, Hall JMM, VerMilyea MD, Amin J, Aizpurua J, Giardini L, et al. Development of an artificial intelligence model for predicting the likelihood of human embryo euploidy based on blastocyst images from multiple imaging systems during IVF. Hum Reprod. 2022;37(8):1746-59.##Huang TT, Huang DH, Ahn HJ, Arnett C, Huang CT. Early blastocyst expansion in euploid and aneuploid human embryos: evidence for a non-invasive and quantitative marker for embryo selection. Reprod Biomed Online. 2019;39(1):27-39.##Louis CM, Handayani N, Aprilliana T, Polim AA, Boediono A, Sini I. Genetic algorithm–assisted machine learning for clinical pregnancy prediction in in vitro fertilization. AJOG Glob Rep. 2023;3(1):100133.##VerMilyea M, Hall JMM, Diakiw SM, Johnston A, Nguyen T, Perugini D, et al. Development of an artificial intelligence-based assessment model for prediction of embryo viability using static images captured by optical light microscopy during IVF. Hum Reprod. 2020;35(4):770-84.##Huang TTF, Kosasa T, Walker B, Arnett C, Huang CTF, Yin C, et al. Deep learning neural network analysis of human blastocyst expansion from time-lapse image files. Reprod Biomed Online. 2021;42 (6):1075-85.##Danardono GB, Handayani N, Louis CM, Polim AA, Sirait B, Periastiningrum G, et al. Embryo ploidy status classification through computer-assisted morphology assessment. AJOG Glob Rep. 2023;3(3):100209.##Tran D, Cooke S, Illingworth PJ, Gardner DK. Deep learning as a predictive tool for fetal heart pregnancy following time-lapse incubation and blastocyst transfer. Hum Reprod. 2019;34(6):1011-8.##Louis CM, Handayani N, Aprilliana T, Polim AA, Boediono A, Sini I. Genetic algorithm–assisted machine learning for clinical pregnancy prediction in in vitro fertilization. AJOG Glob Rep. 2022;3 (1):100133.##Boediono A, Handayani N, Sari HN, Yusup N, Indrasari W, Polim AA, et al. Morphokinetics of embryos after IMSI versus ICSI in couples with sub-optimal sperm quality: a time-lapse study. Andrologia. 2021;53(4):e14002.##Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155-8.##Polim AA, Handayani N, Nurputra DK, Lubis AM, Sirait B, Jakobus D, et al. Birth of spinal muscular atrophy unaffected baby from genetically at-risk parents following a pre-implantation genetic screening: a case report. Int J Reprod Biomed. 2022;20 (9):779-86.##García-Pascual CM, Navarro-Sánchez L, Navarro R, Martínez L, Jiménez J, Rodrigo L, et al. Optimized NGS approach for detection of aneuploidies and mosaicism in PGT-A and imbalances in PGT-SR. Genes (Basel). 2020;11(7):724.##Leigh D, Cram DS, Rechitsky S, Handyside A, Wells D, Munne S, et al. PGDIS position statement on the transfer of mosaic embryos 2021. Reprod Biomed Online. 2022;45(1):19-25.##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.##Mumusoglu S, Yarali I, Bozdag G, Ozdemir P, Polat M, Sokmensuer LK, et al. Time-lapse morphokinetic assessment has low to moderate ability to predict euploidy when patient- and ovarian stimulation–related factors are taken into account with the use of clustered data analysis. Fertil Steril. 2017;107(2):413-21.e4.##Abadi M, Barham P, Chen J, Chen Z, Davis A, Dean J, et al. TensorFlow: a system for largescale machine learning. Proceedings of the 12th USENIX symposium on operating systems design and implementation (OSDI). Savannah, GA, USA, 2016. 265 p.##Ronneberger O, Fischer P, Brox T. U-net: Convolutional networks for biomedical image segmentation. In proceedings of the 18th international conference on medical image computing and computer-assisted intervention–MICCAI. Munich, Germany, 5–9 October 2015; Springer: Cham, Switzerland, 2015. 234 p.##Handayani N, Louis CM, Erwin A, Aprilliana T, Polim AA, Sirait B, et al. Machine learning approach to predict clinical pregnancy potential in women undergoing IVF program. Fertil Reprod. 2022;04(02):77-87.##K. He, X. Zhang, S. Ren and J. Sun. Deep residual learning for image recognition. Proceedings of the IEEE conference on computer vision and pattern recognition (CVPR). Las Vegas, NV, USA, 2016. 770 p.##Szegedy C, Vanhoucke V, Ioffe S, Shlens J, Wojna Z. Rethinking the inception architecture for computer vision. Proceedings of the IEEE conference on computer vision and pattern recognition (CVPR). Las Vegas, NV, USA, 2016. 2818 p.##Tan M, Le QV. Efficientnet: rethinking model scaling for convolutional neural networks. Proceeding of the 36th international conference on machine learning (ICML). Rovira I Virgilly University, Tarragona, Spain, 2019. 10691 p.##Thirumalaraju P, Kanakasabapathy MK, Bormann CL, Gupta R, Pooniwala R, Kandula H, et al. Evaluation of deep convolutional neural networks in classifying human embryo images based on their morphological quality. Heliyon. 2021;7(2):e06298.##Chen TJ, Zheng WL, Liu CH, Huang I, Lai HH, Liu M. Using deep learning with large dataset of microscope images to develop an automated embryo grading system. Fertil Reprod. 2019;1(01):51-6.##Danardono GB, Erwin A, Purnama J, Handayani N, Polim AA, Sini I, et al. A Homogeneous ensem-ble of robust pre-defined neural network enables automated annotation of human embryo morphokinetics. J Reprod Infertil. 2022;23(4):250-6.##Abadi M, Barham P, Chen J, Chen Z, Davis A, Dean J, et al. TensorFlow: a system for largescale machine learning. Proceedings of the 12th USENIX symposium on operating systems design and implementation (OSDI). Savannah, GA, USA, 2016. 265 p. ##Fernandez EI, Ferreira AS, Cecílio MHM, Chéles DS, de Souza RCM, Nogueira MFG, et al. Artificial intelligence in the IVF laboratory: overview through the application of different types of algorithms for the classification of reproductive data. J Assist Reprod Genet. 2020;37(10):2359-76.##Khan A, Sohail A, Zahoora U, Qureshi AS. A survey of the recent architectures of deep convolutional neural networks. Artif Intell Rev. 2020; 53:5455-516.##Huang B, Tan W, Li Z, Jin L. An artificial intelligence model (euploid prediction algorithm) can predict embryo ploidy status based on time-lapse data. Reprod Biol Endocrinol. 2021;19(1):185.##Kragh MF, Karstoft H. Embryo selection with artificial intelligence: how to evaluate and compare methods? J Assist Reprod Genet. 2021;38(7):1675-89.##

Comparison of the Effect of Fenugreek and Metformin on Clinical and Metabolic Status of Cases with Polycystic Ovary Syndrome: A Randomized Trial 2 1 2 Background: It is hypothesized that fenugreek seeds are a rich source of fiber with anti-diabetic effects, which can help to lower blood glucose in patients with polycystic ovary syndrome (PCOS). In this study, the clinical and metabolic effects of fenugreek were compared to those of metformin in women with PCOS aged 16-40 years. Methods: In a randomized, triple-blind, parallel clinical trial, the efficacy of fenugreek 333 mg (n=55) was compared with metformin 500 mg (n=55), both administered three times a day in women with PCOS of reproductive age. Changes in some clinical outcomes and metabolic laboratory profile outcomes were evaluated at baseline and two months after the study. Results: By the end of the intervention period, all investigated factors improved significantly in patients of both groups (p<0.05). Reduction in biometric indices (body mass index and waist–hip ratio), fasting blood sugar (FBS), and insulin resistance was significantly higher after metformin consumption (p<0.001). Metformin also significantly improved irregular menstruation (p=0.02). In contrast, fenugreek significantly improved patients' lipid profiles, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) compared to metformin (p<0.001). Both interventions improved the patient's hair loss and hirsutism. Conclusion: Fenugreek cannot substitute metformin in PCOS treatment. However, regarding its lipid-lowering ability and low frequency of adverse effects, it can be used as an adjuvant treatment in PCOS, especially in PCOS patients with hyperlipidemia and severe hair loss. 120 133 Shahla Sh Mirgalobayat Endometriosis Research Center, School of Medicine, Iran University of Medical Sciences Endometriosis Research Center, School of Medicine, Iran University of Medical Sciences Iran Azadeh A Akbari Sene Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), School of Medicine, Iran University of Medical Sciences Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), School of Medicine, Iran University of Medical Sciences Iran Fatemeh F Jayervand Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), School of Medicine, Iran University of Medical Sciences Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), School of Medicine, Iran University of Medical Sciences Iran Mahdi M Vazirian Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences Iran Arash A Mohazzab Epidemiology Department, School of Public Health, Iran University of Medical Sciences Epidemiology Department, School of Public Health, Iran University of Medical Sciences Iran Mitra M Kazerooni Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), School of Medicine, Iran University of Medical Sciences Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), School of Medicine, Iran University of Medical Sciences Iran mitrakazerooni.md@gmail.com CholesterolFenugreekHerbal medicinePolycystic ovary syndromeRandomized clinical trialTriglycerideTrigonella 140231.pdf Galluzzo A, Amato MC, Giordano C. Insulin resistance and polycystic ovary syndrome. Nutr Metab Cardiovasc Dis. 2008;18(7):511-8.##Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab. 2006;91(11):4237-45.##Bond R, Nachef A, Adam C, Couturier M, Kadoc I, Lapensée L, et al. Obesity and Infertility: A Metabolic Assessment Strategy to Improve Pregnancy Rate. J Reprod Infertil. 2020;21(1):34-42.##Eisenhardt S, Schwarzmann N, Henschel V, Germeyer A, von Wolff M, Hamann A, et al. Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2006;91(3):946-52.##Valsamakis G, Lois K, Kumar S, Mastorakos G. Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS). Hormones (Athens). 2013;12(3):363-78.##Cho LW, Kilpatrick ES, Keevil BG, Coady AM, Atkin SL. Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome. Clin Endocrinol (Oxf). 2009;70(2):233-7.##Sharma N, Siriesha, Lugani Y, Kaur A, Ahuja VK. Effect of metformin on insulin levels, blood sugar, and body mass index in polycystic ovarian syndrome cases. J Family Med Prim Care. 2019;8(8):2691-5.##Spritzer PM, Motta AB, Sir-Petermann T, Diamanti-Kandarakis E. Novel strategies in the management of polycystic ovary syndrome. Minerva Endocrinol. 2015;40(3):195-212.##Nagulapalli Venkata KC, Swaroop A, Bagchi D, Bishayee A. A small plant with big benefits: Fenugreek (Trigonella foenum-graecum Linn.) for disease prevention and health promotion. Mol Nutr Food Res. 2017;61(6).##Vijayakumar MV, Singh S, Chhipa RR, Bhat MK. The hypoglycaemic activity of fenugreek seed extract is mediated through the stimulation of an insulin signalling pathway. Br J Pharmacol. 2005;146(1):41-8.##Sharma RD, Sarkar A, Hazra DK, Misra B, Singh JB, Maheshwari BB, et al. Hypolipidaemic effect of fenugreek seeds: a chronic study in non-insulin dependent diabetic patients. Phytother Res. 1996;10(4):332-4.##Kumar P, Bhandari U, Jamadagni S. Fenugreek seed extract inhibit fat accumulation and ameliorates dyslipidemia in high fat diet-induced obese rats. Biomed Res Int. 2014;2014:606021.##Pandey A, Tripathi P, Pandey R, Srivatava R, Goswami S. Alternative therapies useful in the management of diabetes: a systematic review. J Pharm Bioallied Sci. 2011;3(4):504-12.##Neelakantan N, Narayanan M, de Souza RJ, van Dam RM. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;13:7.##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.##Geller DH, Pacaud D, Gordon CM, Misra M. State of the art review: emerging therapies: the use of insulin sensitizers in the treatment of adolescents with polycystic ovary syndrome (PCOS). Int J Pediatr Endocrinol. 2011;2011(1):9.##Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Assessment of insulin sensitivity/resistance. Indian J Endocrinol Metab. 2015;19(1):160-4.##Borai A, Livingstone C, Kaddam I, Ferns G. Selection of the appropriate method for the assessment of insulin resistance. BMC Med Res Methodol. 2011;11:158.##Aswini R, Jayapalan S. Modified ferriman-gallwey score in hirsutism and its association with metabolic syndrome. Int J Trichology. 2017;9(1):7-13.##Naderpoor N, Shorakae S, de Courten B, Misso ML, Moran LJ, Teede HJ. Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis. Hum Reprod Update. 2015;21(5):560-74.##He C, Lin Z, Robb SW, Ezeamama AE. Serum vitamin D levels and polycystic ovary syndrome: a systematic review and meta-analysis. Nutrients. 2015;7(6):4555-77.##Han Y, Wu H, Sun S, Zhao R, Deng Y, Zeng S, et al. Effect of high fat diet on disease development of polycystic ovary syndrome and lifestyle intervention strategies. Nutrients. 2023;15(9):2230.##Sarray S, Madan S, Saleh LR, Mahmoud N, Almawi WY. Validity of adiponectin-to-leptin and adiponectin-to-resistin ratios as predictors of polycystic ovary syndrome. Fertil Steril. 2015;104(2):460-6.##Ezeh U, Pall M, Mathur R, Azziz R. Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome. Hum Reprod. 2014;29(7):1508-17.##Ranasinha S, Joham AE, Norman RJ, Shaw JE, Zoungas S, Boyle J, et al. The association between polycystic ovary syndrome (PCOS) and metabolic syndrome: a statistical modelling approach. Clin Endocrinol (Oxf). 2015;83(6):879-87.##Al-Habori M, Raman A. Antidiabetic and hypocholesterolaemic effects of fenugreek. Phytother Res. 1998;12(4):233-42.##Gupta A, Gupta R, Lal B. Effect of trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India. 2001;49:1057-61.##Puri D, Prabhu KM, Murthy PS. Mechanism of action of a hypoglycemic principle isolated from fenugreek seeds. Indian J Physiol Pharmacol. 2002;46(4):457-62.##Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek. Altern Med Rev. 2003;8(1):20-7.##Ghaneei A, Jowkar A, Hasani Ghavam MR, Ghaneei ME. Cabergoline plus metformin therapy effects on menstrual irregularity and androgen system in polycystic ovary syndrome women with hyperprolactinemia. Iran J Reprod Med. 2015;13(2):93-100.##Franik S, Kremer JA, Nelen WL, Farquhar C, Marjoribanks J. Aromatase inhibitors for subfertile women with polycystic ovary syndrome: summary of a Cochrane review. Fertil Steril. 2015;103(2):353-5.##Caserta D, Ralli E, Matteucci E, Bordi G, Mallozzi M, Moscarini M. Combined oral contraceptives: health benefits beyond contraception. Panminerva Med. 2014;56(3):233-44.##Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, et al. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002;77(6):1128-35.##Kolodziejczyk B, Duleba AJ, Spaczynski RZ, Pawelczyk L. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome. Fertil Steril. 2000;73(6):1149-54.##Kashyap S, Wells GA, Rosenwaks Z. Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome. Hum Reprod. 2004;19(11):2474-83.##Lakshmi JN, Babu AN, Kiran SSM, Nori LP, Hassan N, Ashames A, et al. Herbs as a source for the treatment of polycystic ovarian syndrome: a systematic review. Biotech (Basel). 2023;12(1):4.##Budani MC, Tiboni GM. Novel insights on the role of nitric oxide in the ovary: a review of the literature. Int J Environ Res Public Health. 2021;18(3):980.##Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol. 1998;138(3):269-74.##Harborne L, Fleming R, Lyall H, Sattar N, Norman J. Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(9):4116-23.##Tharaheswari M, Kumar JSP, Reddy NJ, Subhashree S, Rani SS. Fenugreek seed extract stabilize plasma lipid levels in type 2 diabetes by modulating PPARs and GLUT4 in insulin target tissues. Am J Phytomed Clin Ther. 2014;2:587-602.##Swaroop A, Jaipuriar AS, Gupta SK, Bagchi M, Kumar P, Preuss HG, et al. Efficacy of a novel fenugreek seed extract (trigonella foenum-graecum, furocyst) in polycystic ovary syndrome (PCOS). Int J Med Sci. 2015;12(10):825-31.##

Exploring the Therapeutic Potential of Sodium Hydrosulfide in Alleviating Oxidative Stress and Ovarian Dysfunction in a Rat Model of Polycystic Ovary Syndrome 2 1 2 Background: Oxidative stress is known to play a key role in the occurrence of polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility. The purpose of the current study was to investigate whether diminished activity of ovarian enzymes responsible for hydrogen sulfide (H2S) production, cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) contributes to oxidative stress in PCOS. The study also explored whether administration of sodium hydrosulfide (NaSH), an H2S donor, could ameliorate PCOS symptoms by reducing oxidative stress. Methods: The rats were randomly assigned into three groups (n=6): control, PCOS, and PCOS+NaSH. PCOS was induced by intramuscular injection of estradiol valerate in the PCOS and PCOS+NaSH groups. The PCOS+NaSH group received 30 μmol/L/day of NaSH in drinking water for 27 days after PCOS induction. Ovarian tissue samples were analyzed for oxidative stress indices including malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Additional analyses measured H2S levels, CBS, and CSE activity. Results: PCOS induction led to a significant decrease in SOD activity, H2S levels, and CBS and CSE activity, accompanied by a significant increase in MDA levels (p<0.0001). Furthermore, PCOS caused severe histological alterations in the ovaries. However, administration of NaSH effectively restored all measured parameters to pre-PCOS induction levels (p<0.0001). Conclusion: This study showed that the decrease in the activity of H2S-producing enzymes and H2S levels may contribute to oxidative stress in PCOS. Therefore, administration of H2S donor NaSH can be considered as a potential therapeutic strategy for PCOS patients. 133 140 Maryam M Vaziripour Department of Physiology, School of Medicine, Tehran University of Medical Sciences Department of Physiology, School of Medicine, Tehran University of Medical Sciences Iran Mahdieh M Faghihi Department of Physiology, School of Medicine, Tehran University of Medical Sciences Department of Physiology, School of Medicine, Tehran University of Medical Sciences Iran Mina M Ranjbaran Department of Physiology, School of Medicine, Tehran University of Medical Sciences Department of Physiology, School of Medicine, Tehran University of Medical Sciences Iran Bahareh B Asadi Department of Physiology, School of Medicine, Tehran University of Medical Sciences Department of Physiology, School of Medicine, Tehran University of Medical Sciences Iran Arash A Abdi Department of Physiology, School of Medicine, Tehran University of Medical Sciences Department of Physiology, School of Medicine, Tehran University of Medical Sciences Iran Farzaneh F Kianian Department of Physiology, School of Medicine, Tehran University of Medical Sciences Department of Physiology, School of Medicine, Tehran University of Medical Sciences Iran Mahdi M Hajiaqaei Department of Physiology, School of Medicine, Tehran University of Medical Sciences Department of Physiology, School of Medicine, Tehran University of Medical Sciences Iran Behjat B Seiﬁ Department of Physiology, School of Medicine, Tehran University of Medical Sciences Department of Physiology, School of Medicine, Tehran University of Medical Sciences Iran Cystathionine β-synthaseCystathionine γ-lyaseHydrogen sulfideInfertilityOvaryOxidative stressPCOS 140222.pdf Singh S, Pal N, Shubham S, Sarma DK, Verma V, Marotta F, et al. Polycystic ovary syndrome: etiology, current management, and future therapeutics. J Clin Med. 2023;12(4):1454.##Joham AE, Norman RJ, Stener-Victorin E, Legro RS, Franks S, Moran LJ, et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022;10(9):668-80.##Kim CH, Lee SH. Effectiveness of lifestyle modification in polycystic ovary syndrome patients with obesity: a systematic review and meta-analysis. Life (Basel). 2022;12(2):308.##Bednarska S, Siejka A. The pathogenesis and treatment of polycystic ovary syndrome: what's new? Adv Clin Exp Med. 2017;26(2):359-67.##Bargiota A, Diamanti-Kandarakis E. The effects of old, new and emerging medicines on metabolic aberrations in PCOS. Ther Adv Endocrinol Metab. 2012;3(1):27-47.##Dubey P, Reddy S, Boyd S, Bracamontes C, Sanchez S, Chattopadhyay M, et al. Effect of nutritional supplementation on oxidative stress and hormonal and lipid profiles in PCOS-affected females. Nutrients. 2021;13(9):2938.##Mancini A, Bruno C, Vergani E, d’Abate C, Giacchi E, Silvestrini A. Oxidative stress and low-grade inflammation in polycystic ovary syndrome: controversies and new insights. Int J Mol Sci. 2021;22(4):1667.##Shan H, Luo R, Guo X, Li R, Ye Z, Peng T, et al. Abnormal endometrial receptivity and oxidative stress in polycystic ovary syndrome. Front Pharmacol. 2022;13:904942.##Liu X, Hussain R, Mehmood K, Tang Z, Zhang H, Li Y. Mitochondrial-Endoplasmic Reticulum Communication-Mediated Oxidative Stress and Autophagy. Biomed Res Int. 2022;2022:6459585.##Hao Y, Wang H, Fang L, Bian J, Gao Y, Li C. H2S donor and bone metabolism. Front Pharmacol. 2021;12:661601.##Cirino G, Szabo C, Papapetropoulos A. Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs. Physiol Rev. 2023;103(1):31-276.##Gao L, Wu TW, Ni X. Gas transmitters in female reproductive system. Sheng Li Xue Bao. 2016;68(5):611-20.##Mitidieri E, Vanacore D, Turnaturi C, Sorrentino R, d’Emmanuele di Villa Bianca R. Uterine dysfunction in diabetic mice: the role of hydrogen sulfide. Antioxidants (Basel). 2020;9(10):917.##Murphy B, Bhattacharya R, Mukherjee P. Hydrogen sulfide signaling in mitochondria and disease. FASEB J. 2019;33(12):13098-125.##Daneasa A, Cucolas C, Lenghel LM, Olteanu D, Orasan R, Filip GA. Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment. Reproduction. 2016;151(4):401-9.##Lorian K, Kadkhodaee M, Kianian F, Abdi A, Ranjbaran M, Ashabi G, et al. Long‐term NaHS administration reduces oxidative stress and apoptosis in a rat model of left‐side varicocele. Andrologia. 2020;52(2):e13496.##Ramadoss M, Vijayaraman M, Jessica A. Estradiol valerate dose determination for PCOS induction. Int J Pharm Biol Sci. 2019;9(2):1131-6.##Kianian F, Seifi B, Kadkhodaee M, Sadeghipour HR, Ranjbaran M. Nephroprotection through modifying the apoptotic tnf-α/erk1/2/bax signaling pathway and oxidative stress by long-term sodium hydrosulfide administration in ovalbumin-induced chronic asthma. Immunol Invest. 2022;51(3):602-18.##Pourmirzaei F, Ranjbaran M, Kadkhodaee M, Kianian F, Lorian K, Abdi A, et al. Sperm and testicular dysfunction during cecal ligation and puncture-induced sepsis in male rats and effects of tannic acid through reducing testicular oxidative stress and inflammation. Iran J Basic Med Sci. 2021;24(11):1554-60.##Shafie A, Kianian F, Ashabi G, Kadkhodaee M, Ranjbaran M, Hajiaqaei M, et al. Beneficial effects of combination therapy with testosterone and hydrogen sulfide by reducing oxidative stress and apoptosis: Rat experimental varicocele model. Int J Reprod Biomed. 2022;20(11):941-54.##Chinwe GS, Azuka OI, Adaeze NC. Resveratrol supplementation rescues pool of growing follicles and ovarian stroma from Cisplatin-induced toxicity on the ovary in sprague-dawley rats: an experimental study. Int J Reprod Biomed. 2018;16(1):19-30.##Ighodaro O, Akinloye O. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2018;54(4):287-93.##Bandariyan E, Mogheiseh A, Ahmadi A. The effect of lutein and Urtica dioica extract on in vitro production of embryo and oxidative status in polycystic ovary syndrome in a model of mice. BMC Complement Med Ther. 2021;21(1):55.##Nawrocka-Rutkowska J, Szydłowska I, Jakubowska K, Olszewska M, Chlubek D, Rył A, et al. Assessment of the parameters of oxidative stress depending on the metabolic and anthropometric status indicators in women with PCOS. Life (Basel). 2022;12(2):225.##Zeber-Lubecka N, Ciebiera M, Hennig EE. Polycystic ovary syndrome and oxidative stress-from bench to bedside. Int J Mol Sci. 2023;24(18):14126.##Scammahorn JJ, Nguyen IT, Bos EM, Van Goor H, Joles JA. Fighting oxidative stress with sulfur: Hydrogen sulfide in the renal and cardiovascular systems. Antioxidants (Basel). 2021;10(3):373.##Bries AE, Webb JL, Vogel B, Carrillo C, Keating AF, Pritchard SK, et al. Letrozole-induced polycystic ovary syndrome attenuates cystathionine-β synthase mRNA and protein abundance in the ovaries of female sprague dawley rats. J Nutr. 2021;151(6):1407-15.##Li D, Liu HX, Fang YY, Huo JN, Wu QJ, Wang TR, et al. Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine β-synthase-mediated homocysteine metabolism. Reprod Biomed Online. 2018;37(2):234-41.##Novera W, Lee ZW, Nin DS, Dai MZY, Binte Idres S, Wu H, et al. Cysteine deprivation targets ovarian clear cell carcinoma via oxidative stress and iron-sulfur cluster biogenesis deficit. Antioxid Redox Signal. 2020;33(17):1191-208.##Areloegbe SE, Peter MU, Oyeleke MB, Olaniyi KS. Low-dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole-induced PCOS rat model. BMC Endocr Disord. 2022;22(1):224.##Pruett JE, Everman SJ, Hoang NH, Salau F, Taylor LC, Edwards KS, et al. Mitochondrial function and oxidative stress in white adipose tissue in a rat model of PCOS: effect of SGLT2 inhibition. Biol Sex Differ. 2022;13(1):45.##Witchel SF, Oberfield SE, Peña AS. Polycystic ovary syndrome: pathophysiology, presentation, and treatment with emphasis on adolescent girls. J Endocr Soc. 2019;3(8):1545-73.##Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a sys-tematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023;21 (1):10.##deOliveira TA, Marchesan LB, Spritzer PM. Potas-sium levels in women with polycystic ovary syn-drome using spironolactone for long‐term. Clin Endocrinol (Oxf). 2024;100(3):278-83.##

Evaluation of the Effect of Embryo Transfer Methods on Pregnancy Outcomes: A Retrospective Study and Future Perspectives 2 1 2 Background: Trans-abdominal ultrasound (TAUS) and transvaginal ultrasound (TVUS) are used for embryo transfer. However, few studies were conducted to compare the methods and assess their effect on pregnancy outcomes. Methods: A retrospective cohort study was conducted at Mahdieh Hospital in Tehran, analyzing 506 ICSI cycles with fresh embryo transfer. The study period was from April 2019 to March 2022. Following the evaluation of patients’ profile, they were divided into two groups of TAUS (n=250) and TVUS (n=256). The pregnancy outcomes included positive test of β-HCG, history of miscarriage, ectopic pregnancy (EP), clinical pregnancy, and the duration of the embryo transfer were compared between two groups. Mann-Whitney U test, Pearson Chi-Square test, Fisher's exact test, and logistic regression were used for data analysis. Results: The rate of chemical and clinical pregnancy in the TAUS group was higher compared to the TVUS group, which was statistically significant (p<0.05). The rate of live term birth and live preterm birth was higher in the TAUS group compared to the TVUS group, though the difference was insignificant. Moreover, EP and abortion rates were higher in TVUS group compared to the TAUS group, but the differences were not statistically significant. The odds ratio of achieving pregnancy was higher with TAUS compared to TVUS, but this was only statistically significant for the age variable. Conclusion: The use of TAUS method appears to be associated with improved pregnancy outcome, including higher rates of chemical and clinical pregnancy, compared to TVUS. Yet, further research is needed to confirm these findings and elucidate underlying mechanisms. 140 148 Samira S Azimi Clinical Research Development Center, Mahdieh Hospital, Shahid Beheshti University of Medical Science Clinical Research Development Center, Mahdieh Hospital, Shahid Beheshti University of Medical Science Iran Shahrzad Sh Zadeh Modarres Department of Obstetrics and Gynecology, School of Medicine, Mahdieh Hospital, Shahid Beheshti University of Medical Sciences Department of Obstetrics and Gynecology, School of Medicine, Mahdieh Hospital, Shahid Beheshti University of Medical Sciences Iran Mahsa M Esgandari Department of Obstetrics and Gynecology, Medical Faculty, Shahid Beheshti University of Medical Sciences Department of Obstetrics and Gynecology, Medical Faculty, Shahid Beheshti University of Medical Sciences Iran Saba S Abdollahzadeh Fahimi Department of Obstetrics and Gynecology, Medical Faculty, Shahid Beheshti University of Medical Sciences Department of Obstetrics and Gynecology, Medical Faculty, Shahid Beheshti University of Medical Sciences Iran Ramina R Fazeli Student Research Committee, School of Medicine, Alborz University of Medical Sciences Student Research Committee, School of Medicine, Alborz University of Medical Sciences Iran Abdominal ultrasoundEmbryo transferInfertilityPregnancy outcomesVaginal ultrasound 140221.pdf Carson SA, Kallen AN. Diagnosis and management of infertility: a review. JAMA. 2021;326(1):65-76.##Seivani MK, Modabber N, Shadpirouz M, Amiri BS, Bahoorzahi P, Bahraminia S. Evaluation of genes and molecular pathway related pathogenesis of endometriosis: a bioinformatics approach. Inform Med Unlocked. 2023;41:101324.##Walker Z, Gunn D. Review of infertility diagnosis and evaluation. Curr Obst Gynecol Rep. 2021;10 (4):77-82##Andrus M. Exhibition and film about miscarriage, infertility, and stillbirth: art therapy implications. Art ther. 2020;37(4):169-76.##Lehmann P, Vélez MP, Saumet J, Lapensée L, Jamal W, Bissonnette F, et al. Anti-Müllerian hormone (AMH): a reliable biomarker of oocyte quality in IVF. J Assist Reprod Genet. 2014;31(4):493-8.##Feizollahi N, Zayeri ZD, Moradi N, Zargar M, Rezaeeyan H. The effect of coagulation factors polymorphisms on abortion. Front Biol. 2018;13:190-6.##Sigalos G, Triantafyllidou O, Vlahos N. How do laboratory embryo transfer techniques affect IVF outcomes? a review of current literature. Hum Fertil (Camb). 2017;20(1):3-13.##Masroor MJ, Asl LY, Sarchami N. The effect of uterine contractions on fertility outcomes in frozen embryo transfer cycles: a cohort study. J Reprod Infertil. 2023;24(2):132-8.##Saravelos SH, Wong AW, Kong GW, Huang J, Klitzman R, Li TC. Pain during embryo transfer is independently associated with clinical pregnancy in fresh/frozen assisted reproductive technology cycles. J Obstet Gynaecol Res. 2016;42(6):684-93.##Ghaemi M, Hantoushzadeh S, Shafiee A, Gargari OK, Fathi H, Eshraghi N, et al. The effect of COVID‐19 and COVID‐19 vaccination on serum anti‐Mullerian hormone: a systematic review and meta‐analysis. Immun Inflamm Dis. 2024;12(1): e1136.##Larue L, Keromnes G, Massari A, Roche C, Moulin J, Gronier H, et al. Transvaginal ultrasound-guided embryo transfer in IVF. J Gynecol Obstet Hum Reprod. 2017;46(5):411-6.##Tran HP, Tran TT, Le LT, Pham BT, Vu SNT, Ly LT, et al. The impact of an endometrial receptivity array on personalizing embryo transfer for patients with infertility: a meta-analysis. FS Rev. 2022;3(3):157-73.##Khanjani S, Farahbod F, Zarean E, Tarrahi MJ, Mohammadi B. Evaluation of the relation between cerebroplacental ratio, umbilical-cerebral ratio, and cerebro-placental-uterine ratio with the occurrence of adverse perinatal outcomes in pregnancies complicated by fetal growth restriction. Immunopathol Persa. 2023;X(X):e39503.##Farahbod F, Zarean E, Khanjani S, Moezzi M, Mohammadizadeh F, Shabanian S. Relationship between placental thickness, grading, and heterogeneity in fetal growth restriction in the third trimester of pregnancy by ultrasonography and pathology tests and their relationship with estimated fetal weight and neonatal outcome. Immunopathol Persa. 2023;X(X):e39471.##Porat N, Boehnlein LM, Schouweiler CM, Kang J, Lindheim SR. Interim analysis of a randomized clinical trial comparing abdominal versus transvaginal ultrasound‐guided embryo transfer. J Obstet Gynaecol Res. 2010;36(2):384-92.##Barton SE, Politch JA, Benson CB, Ginsburg ES, Gargiulo AR. Transabdominal follicular aspiration for oocyte retrieval in patients with ovaries inaccessible by transvaginal ultrasound. Fertil Steril. 2011;95(5):1773-6.##Wageh A, Abdelhafez MS, Shams M. Transvaginal sonography (TVS) guided versus transabdominal sonography (TAS) guided embryo transfer: A retrospective analysis. Middle East Fertil Soci J. 2018;23(4):431-4.##Karavani G, Ben-Meir A, Shufaro Y, Hyman JH, Revel A. Transvaginal ultrasound to guide embryo transfer: a randomized controlled trial. Fertil Steril. 2017;107(5):1159-65.##Mohamed Hassan S, Ramadan W, Elsharkawy M, Ali Bayoumi Y. The role of transvaginal ultrasound guided embryo transfer to improve pregnancy rate in obese patients undergoing Intracytoplasmic sperm injection. Int J Womens Health. 2021;13:861-7.##Malekkheili PG, Zadehmodarres S, Heidar Z. A comparative study of transabdominal and transvaginal ultrasound guidance on consequences of embryo transfer at Mahdiyeh hospital of Tehran in 2020: An RCT. Int J Reprod Biomed. 2022;20(3):169-76..##Medhat Mohamed A, Mahmoud El Khyat A, El Shahat El Gergawy A, El Sayed El Halwagy A, Salah El Deen Hamouda M. Trans vaginal versus Trans abdominal ultrasound guided embryo transfer in in vitro fertilization and intra cytoplasmic sperm injection (IVF–ICSI). J Adv Med Med Res. 2021;33(23):145-52.##Samy AA, El-Kassar YS, Gaafar SS, Hamza HA, Menshawi SS. Comparison between transvaginal and transabdominal ultrasound-guided embryo transfer: a randomized, prospective trial. Menoufia Med J. 2020;33(2):419.##Tiras B, Polat M, Korucuoglu U, Zeyneloglu HB, Yarali H. Impact of embryo replacement depth on in vitro fertilization and embryo transfer outcomes. Fertil Steril. 2010;94(4):1341-5.##Zhu W, Yeung Q, Chan D, Chi L, Huang J, Wang Q, et al. Maternal β-HCG concentrations in early IVF pregnancy: association with the embryo development stage of blastocysts. Reprod Biomed Online. 2019;38(5):683-90.##Nasri H. Renal effects of hydatiform mole and choriocarcinoma. J Ren Endocrinol. 2023;9:e25097.##

Comparative Analysis of the Effects of Magnesium Oxide Nanoparticles on Sperm Parameters in Fresh and Frozen Samples 2 1 2 Background: Freezing is a crucial technique in reproductive science utilized for the preservation of sperm samples. However, the process of freezing and thawing sperm can result in detrimental effects on sperm quality. One of the major mechanisms underlying this decline in sperm quality is the generation of reactive oxygen species during the freeze process. The purpose of the current study was to investigate the effects of magnesium oxide nanoparticles on frozen sperm parameters. Methods: Semen samples were collected from 8 fertile men, aged 30 to 42 years, with normozoospermia, following 3 to 5 days of abstinence. The samples were divided into fresh (n=3), freeze (n=3), and control (n=2) groups. Three fresh experimental groups were only exposed to MgO NPs with concentrations of 5, 25, and 50 μg/ml and three freezing experimental groups were frozen after being treated with MgO NPs, thawed, and analyzed after 30 min. Results: Our findings revealed that the progressive movement and vitality of sperm experienced a significant decline, while non-progressive and immotile sperm showed a notable increase in both fresh and frozen experimental groups exposed to MgO NPs. However, the application of MgO NPs during fresh and freezing processes demonstrated an effective preservation of pH, morphology, and DNA fragmentation in sperm cells. Conclusion: The analysis revealed that MgO NPs negatively impact sperm motility and viability in both fresh and freeze analysis. Also, the use of MgO NPs in fresh and frozen processes effectively maintains the pH, morphology, and fragmentation of DNA in sperm cells. 148 157 Sheida Sh Mirgalooye Bayat Department of Biology, Islamic Azad University Science and Research Branch Department of Biology, Islamic Azad University Science and Research Branch Iran sheidabayat777@yahoo.com Farahnaz F Farzaneh Department of Obstetrics and Gynecology, School of Medicine, Iran University of Medical Sciences Department of Obstetrics and Gynecology, School of Medicine, Iran University of Medical Sciences Iran f.farzaneh2019@gmail.com Shahla Sh Mirgalobayat Department of Obstetrics and Gynecology, School of Medicine, Iran University of Medical Sciences Department of Obstetrics and Gynecology, School of Medicine, Iran University of Medical Sciences Iran Human seminal fluidMgO NPsSperm cryopreservationSperm Parameters 140223.pdf Torki-Boldaji B, Azadi L, Tavalaee M, Nasr-Esfa-hani MH. [Human sperm cryopreservation update in treatment of infertility: a review study]. Cell Tissue J. 2017;8(4):332-53. In Persian.##Cai L, Chen J, Liu Z, Wang H, Yang H, Ding W. Magnesium oxide nanoparticles: effective agricul-tural antibacterial agent against Ralstonia solana-cearum. Front Microbiol. 2018;9:790.##Nilsson PM, Viigimaa M, Giwercman A, Cifkova R. Hypertension and reproduction. Curr Hypertens Rep. 2020;22(4):29.##Sharma R, Kattoor AJ, Ghulmiyyah J, Agarwal A. Effect of sperm storage and selection techniques on sperm parameters. Syst Biol Reprod Med. 2015;61(1):1-12.##Wang R, Song B, Wu J, Zhang Y, Chen A, Shao L. Potential adverse effects of nanoparticles on the re-productive system. Int J Nanomedicine. 2018;13:8487-506.##Mangalampalli B, Dumala N, Grover P. Acute oral toxicity study of magnesium oxide nanoparticles and microparticles in female albino Wistar rats. Regul Toxicol Pharmacol. 2017;90:170-84.##Iftikhar M, Noureen A, Uzair M, Jabeen F, Abdel Daim M, Cappello T. Perspectives of nanoparticles in male infertility: evidence for induced abnormali-ties in sperm production. Int J Environ Res Public Health. 2021;18(4):1758.##Fernandes M, RB Singh K, Sarkar T, Singh P, Pratap Singh R. Recent applications of magnesium oxide (MgO) nanoparticles in various domains. Adv Mater Lett. 2020;11(8):1-10.##Taurian O, Springborg M, Christensen NE. Self-consistent electronic structures of MgO and SrO. Solid State Commun. 1985;55(4):351-5.##Heidari M, Darbandi S, Darbandi M, Akhondi MM, Sadeghi MR. Fibronectin as a new biomarker for human sperm selection in assisted reproductive technology. Turk J Urol. 2019;45(2):83-90.##Fanaei H, Azizi Y, Khayat S. A review: role of oxidative stress in male infertility. J Adv Biomed Sci. 2013;3(2):93-103.##Ren C, Hu X, Zhou Q. Graphene oxide quantum dots reduce oxidative stress and inhibit neuro-toxicity in vitro and in vivo through catalase‐like activity and metabolic regulation. Adv Sci (Weinh). 2018;5(5):1700595.##Han JW, Jeong JK, Gurunathan S, Choi YJ, Das J, Kwon DN, et al. Male-and female-derived somatic and germ cell-specific toxicity of silver nano-particles in mouse. Nanotoxicology. 2016;10(3):361-73.##Samrot AV, Noel Richard Prakash LX. Nano-particles induced oxidative damage in reproductive system and role of antioxidants on the induced toxicity. Life (Basel). 2023;13(3):767.##Pugazhendhi A, Prabhu R, Muruganantham K, Shanmuganathan R, Natarajan S. Anticancer, antimicrobial and photocatalytic activities of green synthesized magnesium oxide nanoparticles (MgONPs) using aqueous extract of Sargassum wightii. J Photochem Photobiol B. 2019;190:86-97.##Pinho AR, Rebelo S, Pereira MdL. The impact of zinc oxide nanoparticles on male (in) fertility. Materials (Basel). 2020;13(4):849.##Fraser L, Wasilewska-Sakowska K, Zasiadczyk L, Piątkowska E, Karpiesiuk K. Fractionated seminal plasma of boar ejaculates analyzed by LC–MS/MS: its effects on post-thaw semen quality. Genes (Basel). 2021;12(10):1574.##Kalinin RE, Igor’A S, Klimentova ЕA, Egorov AA, Povarov VO. Apoptosis in vascular pathology: present and future. IP pavlov Russian medical biological Herald. 2020;28(1):79-87.##Fatahian Dehkordi RA, Heidarnejad MS, Mohebbi A, Mosayebi F. [The histopathological and bio-chemical effects of thiamine on mice liver ex-posure by the copper oxide and copper oxide nano-partic]. J Anim Res. 2017;30(2):161-77. In Persian.##Ajdary M, Keyhanfar F, Moosavi MA, Shabani R, Mehdizadeh M, Varma RS. Potential toxicity of nanoparticles on the reproductive system animal models: a review. J Reprod Immunol. 2021;148:103384.##Mehrparavar B, Minai-Tehrani A, Arjmand B, Gilany K. Metabolomics of male infertility: a new tool for diagnostic tests. J Reprod Infertil. 2019;20(2):64-9.##

A Bizarre Case of Periovarian Hematoma in a Patient Undergoing Controlled Ovarian Stimulation Managed Conservatively 2 1 2 Background: The occurrence of ovarian hematoma during controlled ovarian stimulation (COS) is very rare. Until now, there is no such case reported in the literature. In this study, an attempt was made to discuss the possible mechanisms for the development of hematoma in such patients, the clinical presentation, monitoring, and management of these cases. Case Presentation: A rare case of periovarian hematoma was reported in a patient with a history of endometriosis undergoing ovarian stimulation for in vitro fertilization. On the seventh day of stimulation, the patient complained of severe pain in the abdomen. Her vitals and blood investigations were within normal limits. On abdominal examination, mild tenderness was noted in the left iliac fossa. On vaginal examination, fullness and tenderness were noted in the left fornix. On ultrasound, probe tenderness was present and a left ovarian hematoma measuring 2.0x1.81x1.55 cm was observed. She was managed conservatively. The hematoma exhibited a gradual reduction following the pick-up procedure and eventually resolved completely within a month. Conclusion: Underlying endometriosis could be one of the possible causes of this periovarian hematoma. A conservative approach with close monitoring forms the first-line management in hemodynamically stable patients. 157 163 Garima G Sachdeva Department of Reproductive Medicine, Milann Indiranagar Centre Department of Reproductive Medicine, Milann Indiranagar Centre India Devi D Ravikumar Department of Reproductive Medicine, Milann Indiranagar Centre Department of Reproductive Medicine, Milann Indiranagar Centre India Viqat V Ara Department of Reproductive Medicine, Milann Indiranagar Centre Department of Reproductive Medicine, Milann Indiranagar Centre India HematomaIn vitro fertilizationOocyte retrievalOvarian stimulationUltrasonography 140226.pdf Gautam A. Complications of IVF. J Obstet Gynecol India. 2010;60(4):297-8.##Levi-Setti PE, Cirillo F, Scolaro V, Morenghi E, Heilbron F, Girardello D, et al. Appraisal of clinical complications after 23,827 oocyte retrievals in a large assisted reproductive technology program. Fertil Steril. 2018;109(6):1038-1043.e1.##Liberty G, Hyman JH, Eldar-Geva T, Latinsky B, Gal M, Margalioth EJ. Ovarian hemorrhage after transvaginal ultrasonographically guided oocyte aspiration: a potentially catastrophic and not so rare complication among lean patients with polycystic ovary syndrome. Fertil Steril. 2010;93(3):874-9.##Aziz U, Kulkarni A, Lazic D, Cullimore JE. Spontaneous rupture of the uterine vessels in pregnancy. Obstet Gynecol. 2004;103(5 Pt 2):1089-91.##Katorza E, Soriano D, Stockheim D, Mashiach R, Zolti M, Seidman DS, et al. Severe intraabdominal bleeding caused by endometriotic lesions during the third trimester of pregnancy. Am J Obstet Gynecol. 2007;197(5):501.e1-4.##Patterson JW, Kashyap S, Dominique E. Acute abdomen [internet]. In: Treasure Island, (FL): StatPearls Publishing; 2021. StatPearls [cited May 20 2021]. Available from: http://www.ncbi.nlm.nih. gov/books/NBK459328/.##Holesh JE, Bass AN, Lord M. Physiology, ovulation [internet]. In: Treasure Island, (FL): StatPearls Publishing; 2021. StatPearls [cited May 20 2021]. Available from: http://www.ncbi.nlm.nih.gov/ books/NBK441996/.##Niringiyumukiza JD, Cai H, Xiang W. Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation. Reprod Biol Endocrinol. 2018;16(1):43.##Gaytán M, Morales C, Bellido C, Sánchez-Criado JE, Gaytán F. Non-steroidal anti-inflammatory drugs (NSAIDs) and ovulation: lessons from morphology. Histol Histopathol. 2006;21(5):541-56.##Sehgal N. Efficacy of color doppler ultrasonography in differentiation of ovarian masses. J Midlife Health. 2019;10(1):22-8.##Sanchez AM, Vanni VS, Bartiromo L, Papaleo E, Zilberberg E, Candiani M, et al. Is the oocyte quality affected by endometriosis? a review of the literature. J Ovarian Res. 2017;10(1):43.##ESHRE special interest group of embryology and alpha scientists in reproductive medicine. The vienna consensus: report of an expert meeting on the development of ART laboratory performance indicators. Reprod Biomed Online. 2017;35(5):494-510.##

Simultaneous Endometrial Cancer with Extensive Pelvic and Vulvar Endometriosis: A Case Report 2 1 2 Background: Endometrial cancer represents the most prevalent malignant genital tract neoplasm in high-income countries and is the second most common cancer worldwide following cervical cancer. Endometriosis is a benign condition wherein endometrial glands and stroma are found outside the uterine cavity. Case Presentation: During a routine care and ultrasound examination of the uterus and adnexa of a 64-year-old woman, an increased endometrial thickness (22 mm) was noted. In 2023, according to ultrasound report, the patient underwent diagnostic curettage with immunohistochemistry, revealing a pathological diagnosis of endometrial cancer (endometrioid adenocarcinoma) with positive staining for p16, estrogen receptor (ER), and vimentin. Subsequently, after one week, she underwent complete surgical staging. Extensive superficial endometriosis disseminated in the pelvis and vulva was noted during surgery and preoperative examinations. Final pathology confirmed a well-differentiated typical endometrioid carcinoma (grade 1) with 40% myometrial invasion and positive lymphovascular invasion. The patient was considered to be at stage 1A. Conclusion: Despite some studies suggesting an unclear association between endometriosis and endometrioid or clear-cell ovarian cancers, the correlation between endometriosis and endometrial cancer and its prognosis remains ambiguous. Additionally, although infertility has been linked to both endometrial cancer and endometriosis in various studies, the presented case exhibited no signs of infertility. Extensive pelvic endometriosis with vulvar involvement was present, yet the patient did not exhibit any symptoms. This is in contrast to the typical initial manifestation of endometrial cancer, which is abnormal uterine bleeding. The patient's condition was incidentally detected through routine care due to an abnormal increase in endometrial thickness, prompting this presentation. 163 169 Soheila S Aminimoghaddam Department of Gynecologic Oncology, School of Medicine, Iran University of Medical Sciences, Firoozgar Hospital Department of Gynecologic Oncology, School of Medicine, Iran University of Medical Sciences, Firoozgar Hospital Iran Nastaran N Abolghasem Department of Gynecologic Oncology, School of Medicine, Iran University of Medical Sciences, Firoozgar Hospital Department of Gynecologic Oncology, School of Medicine, Iran University of Medical Sciences, Firoozgar Hospital Iran nastaran_a3014@yahoo.com Niousha N Jamshidnezhad Department of Gynecologic Oncology, School of Medicine, Iran University of Medical Sciences, Firoozgar Hospital Department of Gynecologic Oncology, School of Medicine, Iran University of Medical Sciences, Firoozgar Hospital Iran Endometrial cancerEndometrioid adenocarcinomaEndometriosisUterine bleedingVulva 140229.pdf Felix AS, Weissfeld JL, Stone RA, Bowser R, Chivukula M, Edwards RP, et al. Factors associated with type I and type II endometrial cancer. Cancer Causes Control. 2010;21(11):1851-6.##Rock CL, Thomson CA, Sullivan KR, Howe CL, Kushi LH, Caan BJ, et al. American cancer society nutrition and physical activity guideline for cancer survivors. CA Cancer J Clin. 2022;72(3):230-62.##Afrooz N, Nasiri S, Aminimoghaddam S. Comparison of PFS-OS between two treatment methods (surgery and then chemotherapy compared with neoadjuvant and then surgery) in patients with endometrial cancer: a retrospective study. Iran J Obstet Gynecol Infertil. 2022;25(11):fa26-fa33 ref. 22 ref.##Hickey M, Ballard K, Farquhar C. Endometriosis. BMJ. 2014;348:g1752.##Rashidi BH, Sarhangi N, Aminimoghaddam S, Haghollahi F, Naji T, Amoli MM, et al. Association of vascular endothelial growth factor (VEGF) gene polymorphisms and expression with the risk of endometriosis: a case–control study. Mol Biol Rep. 2019;46(3):3445-50.##Berek JS, Matias‐Guiu X, Creutzberg C, Fotopoulou C, Gaffney D, Kehoe S, et al. FIGO staging of endometrial cancer: 2023. Int J Gynecol Obstet. 2023;162(2):383-94.##American college of obstetricians and gynecologists. ACOG practice bulletin, clinical management guidelines for obstetrician‐gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol. 2005;106(2):413-25.##Burghaus S, Häberle L, Schrauder MG, Heusinger K, Thiel FC, Hein A, et al. Endometriosis as a risk factor for ovarian or endometrial cancer-results of a hospital-based case-control study. BMC Cancer. 2015;15:751.##Johnatty SE, Stewart CJ, Smith D, Nguyen A, O’Dwyer J, O’Mara TA, et al. Co-existence of leiomyomas, adenomyosis and endometriosis in women with endometrial cancer. Sci Rep. 2020;10(1):3621.##Ye J, Peng H, Huang X, Qi X. The association between endometriosis and risk of endometrial cancer and breast cancer: a meta-analysis. BMC Womens Health. 2022;22(1):455.##Terzic M, Aimagambetova G, Kunz J, Bapayeva G, Aitbayeva B, Terzic S, et al. Molecular basis of endometriosis and endometrial cancer: current knowledge and future perspectives. Int J Mol Sci. 2021;22(17):9274.##Poole EM, Lin WT, Kvaskoff M, De Vivo I, Terry KL, Missmer SA. Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of US nurses. Cancer Causes Control. 2017;28(5):437-45.##Kvaskoff M, Mahamat-Saleh Y, Farland LV, Shigesi N, Terry KL, Harris HR, et al. Endometriosis and cancer: a systematic review and meta-analysis. Hum Reprod Update. 2021;27(2):393-420.##Guidozzi F. Endometriosis-associated cancer. Climacteric. 2021;24(6):587-92.##Hermens M, van Altena AM, Velthuis I, van de Laar DC, Bulten J, van Vliet HA, et al. Endometrial cancer incidence in endometriosis and adenomyosis. Cancers (Basel). 2021;13(18):4592.##Painter JN, O'mara TA, Morris AP, Cheng TH, Gorman M, Martin L, et al. Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses. Cancer Med. 2018;7(5):1978-87.##