Fertility in Fevered Planet, Hidden Costs of Global Warming 2 1 140272 2 The impact of climate change and global warming on human fertility is multifaceted. Its direct pathophysio-logical effects, such as heat stress and exposure to air pollution, affect men, women, adolescents, and pregnant individuals through different mechanisms and are often associated with impaired or reduced fertility, pregnancy complications, and miscarriage. In addition to the direct pathological effects, global warming has a tremendous impact on the social, economic, and environmental structures, which in turn indirectly influences the processes, goals, and outcomes of human reproduction (1). Global warming, particularly through extreme heat exposure, profoundly alters physiological and biological pathways involved in human fertility. In females, heat stress disrupts ovarian function, reduces ovarian reserve, and impairs folliculogenesis and oocyte development. This includes chromosomal abnormalities, increased follicular atresia, and apoptosis in granulosa cells. For example, an average of 1°C increase in maximum temperature for 90 days before ovarian reserve testing is associated with a 1.6% reduction in antral follicle count (AFC). At the molecular level, elevated temperatures increase the production of reactive oxygen species (ROS), deplete antioxidant defenses like reduced glutathione (GSH), and trigger ferroptosis, especially in granulosa cells. Hormonal imbalances, such as reduced estradiol levels, further compromise reproductive function. In males, high ambient temperatures interfere with testicular thermoregulation, reducing sperm con-centration and motility due to germ cell apoptosis and DNA damage during spermatogenesis. In a study published in the Journal of Demography, researchers found that days with average temperatures above 80°F (equal to 27°C) were associated with a large decline in birth rates eight to ten months later. This phenomenon is not caused by reduced sexual activity in high temperatures; it may even increase, but the effect is driven by the detrimental effect of heat on spermatogenesis and sperm functions. A 1°C increase in hot night excess (HNE) leads to a decline in both progressive and total sperm motility. The impact of heat excess was greatest on men who already had impaired sperm parameters, such as those with oligoasthenoteratozoospermia (OAT). Beyond individual reproductive systems, heat exposure is associated with poor pregnancy outcomes, including increased risks of miscarriage, stillbirth, preterm birth, low birth weight, and congenital anomalies like neural tube and heart defects (1-3). Climate change indirectly affects reproductive health through multiple interconnected pathways. Air pollu-tion and chemical contaminants, including fine particulate matter (PM2.5), nitrogen dioxide (NO₂), and pollutants from wildfire smoke such as polycyclic aromatic hydrocarbons (PAHs), are associated with reduced fertility in both genders, reduced IVF success rates, and increased risks of adverse pregnancy outcomes, such as preterm birth. These pollutants can also cause oxidative stress, DNA damage, chromosomal abnormality, and epigenetic alterations that potentially affect future generations. Climate change has a wide range of impacts on the socioeconomic and behavioral dimensions of communities, including reproductive outcomes. For example, climate-induced disruptions in agricultural production and income stability, particularly in low- and middle-income countries, can alter reproductive behaviors in these communities, increasing contraceptive use and preventing childbearing. In addition, rising global temperatures and the spread of climate-sensitive vector-borne diseases (e.g., dengue fever, malaria, Zika) significantly increase the risks during pregnancy, including stillbirth, low birth weight, and congenital anomalies. These impacts are disproportionately borne by vulnerable populations, particularly women, pregnant individuals, and those with lower socioeconomic status, due to their physiological susceptibility and unequal exposure to climate change as well as other environmental and social stressors (2, 4). Effective mitigation of further climate change and adaptation to unavoidable heat waves require integrated global policies, infrastructure transformation, and targeted public health strategies, particularly to protect vulnerable populations. Root cause analysis (RCA) focuses on limiting global warming to 1.5°C through sharp reductions in greenhouse gas emissions, large-scale replacement of fossil fuels with renewable green energy, and land-use changes including afforestation, sustainable agricultural practices, and decarbonization of transport through a shift to cleaner energy sources such as electricity, hydrogen, and biofuels (1, 2). Adaptation strategies aim to reduce vulnerability and encompass policy and governance measures, such as location-specific heat action plans (HAPs), early warning systems, emergency funding, legal recognition of heat waves as disasters, and adaptive social protections. Urban and infrastructure adaptations focus on minimizing urban heat islands through the development of green spaces, cool roofs, improved building design with passive ventilation and filtration, resilient water and electricity systems, and managed displacement in extreme cases. Health system preparedness requires strengthening access to health care, establishing cooling centers, providing hydration and heat protection kits, and targeted outreach to vulnerable groups, including pregnant women and the adolescents. Economic and behavioral interventions include workplace protection, empowering women with family planning education, and improving cooling technologies such as air conditioning, which have been shown to reduce heat-related reproductive impacts (5). Climate change and extreme heat pose a critical harm to reproductive health, manifesting as reduced fertility, diminished sperm quality, failure of ovarian function, and adverse pregnancy outcomes such as preterm birth and low birth weight. To mitigate the threads to reproductive health, the most important step is the urgent and sustainable reduction of climate change, particularly through rapid decarbonization and elimination of air-pollution by cutting greenhouse gas emissions to limit global warming to 1.5°C. At the same time, effective global plans must prioritize adaptation by empowering women, strengthening health care systems, and implementing targeted protection measures during critical reproductive periods. Based on the above evidence, climate change is a silent killer that intensifies inequality, poses enormous risks to vulnerable populations, and requires urgent action for adaptation and preparedness, particularly in the context of humanitarian responses. 142 144 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 140272.pdf Fernandez ACG, Pelnekar S, Robinson JF, Shaw GM, Padula AM, Woodruff TJ, et al. Climate change and reproductive health. Endocr Rev. 2025;4:bnaf026.##Papadiochou A, Diamanti A, Metallinou D, Georgakopoulou VE, Taskou C, Kagkouras I, et al. Impact of climate change on reproductive health and pregnancy outcomes: a systematic review. Cureus. 2024;16(8):e68221.##Kılavuz M, Ağralı C, Kanbay Y. As the planet warms, women pay the price: the climate change and reproductive health crisis. J Egypt Public Health Assoc. 2025;100(1):14.##Sergott RC, Grossman RI, Savino PJ, Bosley TM, Schatz NJ. Systematic review of climate change effects on reproductive health. Fertil Steril. 2022;118(2):215-23.##International federation of red cross and red crescent societies (IFRC), United nations office for the coordination of humanitarian affairs. Extreme heat: preparing for the heat waves of the future. Geneva: IFRC; 2022 Oct 10. Available from: https://www.ifrc.org/document/extreme-heat-preparing-heat-waves-future##

Reactive Oxygen Species in Follicular Fluid as a Potential Biomarker of Oocyte Developmental Competence 2 1 140280 2 ckground: Reactive oxygen species (ROS) are critical factors for oocyte maturation and early embryogenesis; however, excessive ROS can induce oxidative stress, impairing mitochondrial function, DNA integrity, and embryo competence. The role of oxidative status in buffalo follicular fluid (FF) remains underexplored. This study assessed the relationship between total oxidant status (TOS) in buffalo FF and the developmental competence of oocytes retrieved by ovum pick-up (OPU) for subsequent in vitro fertilization (OPU-IVF). Methods: Follicular fluid and cumulus–oocyte complexes (COCs) were collected from 62 healthy buffaloes. Oocytes were matured and fertilized in vitro, and the animals were classified based on blastocyst yield: G1 (no blastocysts), G2 (≥2 blastocysts), and G3 (>3 blastocysts). TOS was measured spectrophotometrically. The relationship between TOS and oocyte competence was analyzed by ROC (G1 vs. G3) and Spearman correlation (G1 vs. G2), with p<0.05 considered statistically significant. Results: G2 group with >2 blastocyst exhibited lower TOS levels (1.10±0.51 µmol H₂O₂ Eq/L) than G1 (2.15±0.92; p=0.004), with higher follicle counts, oocyte yield, cleavage rate, and blastocyst production (p<0.05). ROC analysis identified a TOS threshold of 1.12 µmol H₂O₂ Eq/L (area under the curve [AUC]=0.851), and TOS inversely correlated with the proportion of high-quality blastocysts (r=-0.553, p=0.021). Conclusion: Elevated oxidative stress in FF compromises oocyte developmental competence and embryo quality. TOS may serve as a predictive biomarker, supporting antioxidant-based optimization of assisted reproductive technology (ART) in buffalo. 144 152 Sara S Borjian-Boroujeni Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University Iran Naser N Shams-Esfandabadi Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University Iran drn_shams@yahoo.com Abolfazl A Shirazi ابوالفضل شیرازی Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran a.shirazi2023@gmail.com Ebrahim E Ahmadi ابراهیم احمدی Research Institute of Animal Embryo Technology, Shahrekord University Research Institute of Animal Embryo Technology, Shahrekord University Iran Kambiz K Gilany کامبیز گیلانی Department of Integrative Oncology, Breast Cancer Research Center, Motamed Cancer Institute, ACECR Department of Integrative Oncology, Breast Cancer Research Center, Motamed Cancer Institute, ACECR Iran BiomarkerBuffaloFollicular fluidIVFOocyte competenceTotal oxidant status 140280.pdf Deluao JC, Winstanley Y, Robker RL, Pacella-Ince L, Gonzalez MB, McPherson NO. Oxidative stress and reproductive function: reactive oxygen species in the mammalian pre-implantation embryo. Repro-duction. 2022;164(6):F95-108.##Das S, Chattopadhyay R, Ghosh S, Ghosh S, Goswami S, Chakravarty B, et al. Reactive oxygen species level in follicular fluid—embryo quality marker in IVF? Hum Reprod. 2006;21(9):2403-7.##Siristatidis C, Vogiatzi P, Varounis C, Askoxylaki M, Chrelias C, Papantoniou N. The effect of reactive oxygen species on embryo quality in IVF. In Vivo. 2016;30(2):149-53.##Dalvit GC, Cetica P, Pintos L, Beconi M. Reactive oxygen species in bovine embryo in vitro production. Biocell. 2005;29(2):209-12.##Chen Y, Yang J, Zhang L. The impact of follicular fluid oxidative stress levels on the outcomes of assisted reproductive therapy. Antioxidants (Basel). 2023;12(12):2117.##Chiariotti A, Borghese A, Boselli C, Barile VL. Water Buffalo’s adaptability to different environments and farming systems: a review. Animals (Basel). 2025;15(11):1538.##Pournourali M, Tarang A, Mashayekhi F. Chromosomal analysis of two buffalo breeds of Mazani and Azeri from Iran. Iran J Veterin Sci Technol. 2015;7(1):22-31.##Srirattana K, Hufana-Duran D, Atabay EP, Duran PG, Atabay EC, Lu K, et al. Current status of assisted reproductive technologies in buffaloes. Anim Sci J. 2022;93(1):e13767.##Baruselli PS, Soares JG, Bayeux BM, Silva JC, Mingoti RD, Carvalho NA. Assisted reproductive technologies (ART) in water buffaloes. Anim Reprod. 2018;15(Suppl 1):971-83.##Guerin P, El Mouatassim S, Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001;7(2):175-89.##Sarvari A, Niasari-Naslaji A, Shirazi A, Heidari B, Boroujeni SB, Moradi MH, et al. Effect of intraovarian injection of mesenchymal stem cells or its conditioned media on repeated OPU-IVEP out-comes in jersey heifers and its relationship with follicular fluid inflammatory markers. Avicenna J Med Biotechnol. 2024;16(1):16-28.##Naderi MM, Boroujeni SB, Sarvari A, Heidari B, Akhondi MM, Zarnani AH, et al. The effect of angiotensin on the quality of in vitro produced (IVP) sheep embryos and expression of Na /K / ATPase. Avicenna J Med Biotechnol. 2016;8(1):9-15.##Amini MS, Naderi MM, Shirazi A, Aminafshar M, Boroujeni SB, Pournourali M, et al. Bioactive materials derived from menstrual blood stem cells enhance the quality of in vitro bovine embryos. Avicenna J Med Biotechnol. 2022;14(4):287-93.##Farahavar A, Shirazi A, Kohram H, Sarvari A, Borjian-Boroujeni S, Naderi MM, et al. Improving the quality of ovine embryo produced in vitro by culturing zygote in isolated mouse oviduct. Small Ruminant Res. 2018;161:1-6.## Khazani H, Kondori BJ, Sahraei H, Meftahi GH. Terminalia chebula attenuates restraint stress-in-duced memory impairment and synaptic loss in the dentate gyrus of the hippocampus and the basolateral and central nuclei of the amygdala by inhibiting oxidative damage. Brain Res Bull. 2024; 213:110975.##Sasaki H, Hamatani T, Kamijo S, Iwai M, Kobanawa M, Ogawa S, et al. Impact of oxidative stress on age-associated decline in oocyte developmental competence. Front Endocrinol (Lausanne). 2019;10:811.##Martin JH, Nixon B, Cafe SL, Aitken RJ, Bromfield EG, Lord T. Oxidative stress and reproductive function: oxidative stress and in vitro ageing of the post-ovulatory oocyte: an update on recent advances in the field. Reproduction. 2022; 164(6):F109-24.##Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012;10:49.##Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2018;16(1):80.##Da Broi M, Giorgi V, Wang F, Keefe D, Albertini D, Navarro P. Influence of follicular fluid and cumulus cells on oocyte quality: clinical implications. J Assist Reprod Genet. 2018;35(5):735-51.##Behera B, Sharma C, Singh S, Kumar H, Chaudhari R, Mahla A, et al. Relationship between endometritis and oxidative stress in the follicular fluid and luteal function in the buffalo. Reprod Domest Anim. 2016;51(5):844-7.##Kosior MA, Esposito R, Cocchia N, Piscopo F, Longobardi V, Cacciola NA, et al. Seasonal variations in the metabolomic profile of the ovarian follicle in Italian mediterranean Buffaloes. Theriogenology. 2023;202:42-50.##Oyawoye O, Abdel Gadir A, Garner A, Constantinovici N, Perrett C, Hardiman P. Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome. Hum Reprod. 2003;18(11):2270-4.##Liu B, Otoi T, Namula Z, Widodo OS, Hirata M, Nakai A, et al. Oxidative stress index of porcine follicular fluid influences meiotic maturation and embryo development duringin vitro culture. Vet World. 2025;18(7):2078-86.##Mauchart P, Vass RA, Nagy B, Sulyok E, Bódis J, Kovács K. Oxidative stress in assisted reproductive techniques, with a focus on an underestimated risk factor. Curr Issues Mol Biol. 2023;45(2):1272-86.##Li Y, Wei Y, Yang M, Sun M, Yan L, Yang Y, et al. Metabolomics of follicular fluid reveals the impact of heat stress on OPU-IVP efficiency in dairy cows. J Anim Sci. 2025;103:skaf216.##Mora MB, Kosior M, Damiano S, Longobardi V, Presicce G, Di Vuolo G, et al. Dietary supplementation with green tea extract improves the anti-oxidant status and oocyte developmental competence in Italian Mediterranean buffaloes. Theriogenology. 2024;215:50-7.##Wang F, Tian X, Zhou Y, Tan D, Zhu S, Dai Y, et al. Melatonin improves the quality of in vitro produced (IVP) bovine embryos: implications for blastocyst development, cryotolerance, and modifications of relevant gene expression. PloS One. 2014;9(4):e93641.##Piras AR, Menéndez-Blanco I, Soto-Heras S, Català MG, Izquierdo D, Bogliolo L, et al. Resveratrol supplementation during in vitro maturation improves embryo development of prepubertal goat oocytes selected by brilliant cresyl blue staining. J Reprod Dev. 2019;65(2):113-20.##Mukunoki A, Takeo T, Nakagata N. N-acetyl cysteine restores the fertility of vitrified–warmed mouse oocytes derived through ultrasuperovulation. PLoS One. 2019;14(10):e0224087.##Ren J, Hao Y, Liu Z, Li S, Wang C, Wang B, et al. Effect of exogenous glutathione supplementation on the in vitro developmental competence of ovine oocytes. Theriogenology. 2021;173:144-55.##Maleki-Hajiagha A, Shafie A, Maajani K, Amidi F. Effect of astaxanthin supplementation on female fertility and reproductive outcomes: a systematic review and meta-analysis of clinical and animal studies. J Ovarian Res. 2024;17(1):163.##Chen Y, Xie M, Wu S, Deng Z, Tang Y, Guan Y, et al. Multi-omics approach to reveal follicular metabolic changes and their effects on oocyte competence in PCOS patients. Front Endocrinol (Lausanne). 2024;15:1426517.##

The Effect of hCG Supplementation on Embryo Quality after Rescue In Vitro Maturation (r-IVM) 2 1 140273 2 Background: The supplementation of human chorionic gonadotropin (hCG) into culture medium in rescue in vitro maturation (r-IVM) has been reported to improve the maturation rates of immature oocytes derived from stimulated cycles. However, the impact of this enrichment on embryo quality is yet to be understood. The purpose of the current study was to investigate the effect of hCG on the embryo quality following r-IVM. Methods: A total of 152 immature oocytes consisting of germinal vesicles (GV) and metaphase I (MI) were collected and classified into 1) control group (n=73; GV=22, MI=51) cultured in culture medium only, and 2) experimental group (n=79; GV= 23, MI=56) cultured in culture medium supplemented with 0.5 IU hCG. Study parameters were analyzed using Student’s T-test or Kruskal Wallis and chi-square at a 95% confidence level. Results: After 24 hr, the maturation rate of the control and experimental groups was comparable (57% vs. 70%, p=0.58). Following intracytoplasmic sperm injection (ICSI), the fertilization rate was significantly higher in the experimental group than in the control group (49% vs. 36%; p=0.03). However, the number of good-quality embryos was similar in the groups (16% vs. 6%). Conclusion: Our study suggests that hCG supplementation into the culture medium during r-IVM does not affect embryo quality but improves the fertilization rate. Further research is needed to scrutinize the role of hCG in fertilization. 152 159 Novita N Prasetiawati Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia Indonesia Ayu AM Sundari 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 Agus A Supriyadi Melati Clinic, Harapan Kita Women and Children Hospital Melati Clinic, Harapan Kita Women and Children Hospital Indonesia Hadi H Sjarbaini Melati Clinic, Harapan Kita Women and Children Hospital Melati Clinic, Harapan Kita Women and Children Hospital Indonesia Sudirmanto S Tarigan Melati Clinic, Harapan Kita Women and Children Hospital Melati Clinic, Harapan Kita Women and Children Hospital Indonesia Gde G Suardana Melati Clinic, Harapan Kita Women and Children Hospital Melati Clinic, Harapan Kita Women and Children Hospital Indonesia Mohammad M Haekal Melati Clinic, Harapan Kita Women and Children Hospital Melati Clinic, Harapan Kita Women and Children Hospital Indonesia Gangsar G Pariyanti Melati Clinic, Harapan Kita Women and Children Hospital Melati Clinic, Harapan Kita Women and Children Hospital Indonesia Deana DR Indah Melati Clinic, Harapan Kita Women and Children Hospital Melati Clinic, Harapan Kita Women and Children Hospital Indonesia Mulyoto M Pangestu Department of Obstetrics and Gynecology, School of Clinical Sciences, Monash University Department of Obstetrics and Gynecology, School of Clinical Sciences, Monash University Australia Anom A Bowolaks Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia Indonesia alaksono@sci.ui.ac.id EmbryoHuman chorionic gonadotropinOocytesRescue IVM 140273.pdf Handayani N, Sundari AM, Aprilliana T, Boediono A, Polim AA, Wiweko B, et al. Immature oocyte proportion in a cohort led to poor embryo development but did not reduce clinical pregnancy rate. Middle East Fertil Soc J. 2024;29(1):23.##Lee HJ, Jee BC, Suh CS, Kim SH, Moon SY. Oocyte maturity in relation to woman’s age in in vitro fertilization cycles stimulated by single regimen. Yonsei Med J. 2012;53(1):181-5.##Rienzi L, Ubaldi F, Anniballo R, Cerulo G, Greco E. Preincubation of human oocytes may improve fertilization and embryo quality after intracytoplasmic sperm injection. Hum Reprod. 1998;13(4): 1014-9.##Astbury P, Subramanian GN, Greaney J, Roling C, Irving J, Homer HA. The presence of immature GV−stage oocytes during IVF/ICSI is a marker of poor oocyte quality: a pilot study. Med Sci (Basel). 2020;8(1):4.##Teramoto S, Osada H, Sato Y, Shozu M. Non-dominant small follicles are a promising source of mature oocytes in modified natural cycle in vitro fertilization and embryo transfer. Fertil Steril. 2016; 106(1):113-8. ##Kok JD, Looman CWN, Weima SM, Te Velde ER. A high number of oocytes obtained after ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection is not associated with decreased pregnancy outcome. Fertil Steril. 2006;85 (4):918-24.##Coticchio G, Dal Canto M, Guglielmo MC, Albertini DF, Mignini Renzini M, Merola M, et al. Double-strand DNA breaks and repair response in human immature oocytes and their relevance to meiotic resumption. J Assist Reprod Genet. 2015;32 (10):1509-16.##Wei J, Luo Z, Dong X, Jin H, Zhu L, Ai J. Cut-off point of mature oocyte for routine clinical application of rescue IVM: a retrospective cohort study. J Ovarian Res. 2023;16(1):226.##Shani AK, Haham LM, Balakier H, Kuznyetsova I, Bashar S, Day EN, et al. The developmental potential of mature oocytes derived from rescue in vitro maturation. Fertil Steril. 2023;120(4):860-9.##Ahmad MF, Mohd Nor NY, Mohammad Ramadneh MM, Roseli NI, Elias MH, Mat Jin N, et al. Comparative analysis of rescue-in vitro-maturation (r-IVM) outcomes in women with diminished ovarian reserve (DOR) versus normal ovarian reserve (NOR). Biomedicines. 2025;13(5):1084.##Tantitham C, Panunumpa S, Satirapod C. The effect of human chorionic gonadotropin on the in vitro development of immature to mature human oocytes: a randomized controlled study. J Hum Reprod Sci. 2020;13(2):133-7.##De Los Reyes M, De Lange J, Miranda P, Palominos J, Barros C. Effect of human chorionic gonadotrophin supplementation during different culture periods on in vitro maturation of canine oocytes. Theriogenology. 2005;64(1):1-11. ##Son WY, Yoon SH, Lim JH. Effect of gonadotrophin priming on in-vitro maturation of oocytes collected from women at risk of OHSS. Reprod Biomed Online. 2006;13(3):340-8.##Zheng X, Wang L, Zhen X, Lian Y, Liu P, Qiao J. Effect of hCG priming on embryonic development of immature oocytes collected from unstimulated women with polycystic ovarian syndrome. Reprod Biol Endocrinol. 2012;10:40.##Skvirsky S, Blais I, Lahav-Baratz S, Koifman M, Wiener-Megnazi Z, Dirnfeld M. Time interval between hCG administration and oocyte pick up: analysis of oocyte maturation, embryonic morphology, morphokinetics, and IVF outcome. Clin Exp Obstet Gynecol. 2021;48(2):402-9.##Son WY, Chung JT, Chian RC, Herrero B, Demirtas E, Elizur S, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008;23(9):2010-6.##Arroyo A, Kim B, Yeh J. Luteinizing hormone action in human oocyte maturation and quality: signaling pathways, regulation, and clinical impact. Reprod Sci. 2020;27(6):1223-52.##Abbara A, Clarke SA, Dhillo WS. Novel concepts for inducing final oocyte maturation in in vitro fertilization treatment. Endocr Rev. 2018;39(5):593-628.##European IVF-monitoring consortium (EIM); European society of human reproduction and embryology (ESHRE), Kupka MS, D’hooghe T, Ferraretti AP, de Mouzon J, et al. Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE. Hum Reprod. 2016;31(2):233-48.##Casarini L, Lispi M, Longobardi S, Milosa F, la Marca A, Tagliasacchi D, et al. LH and hCG action on the same receptor results in quantitatively and qualitatively different intracellular signalling. PLoS One. 2012;7(10):e46682.##Castillo JC, Humaidan P, Bernabéu R. Pharmaceutical options for triggering of final oocyte maturation in ART. Biomed Res Int. 2014;2014:580171.##Ge HS, Huang XF, Zhang W, Zhao JZ, Lin JJ, Zhou W. Exposure to human chorionic gonadotropin during in vitro maturation does not improve the maturation rate and developmental potential of immature oocytes from patients with polycystic ovary syndrome. Fertil Steril. 2008;89(1):98-103.##Alpha scientists in reproductive medicine and ESHRE special interest group of embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270-83.##Das M, Son WY. In vitro maturation (IVM) of human immature oocytes: is it still relevant? Reprod Biol Endocrinol. 2023;21(1):110.##Soler N, Cimadomo D, Escrich L, Grau N, Gal An A, Alam P, et al. Rescue in vitro maturation of germinal vesicle oocytes after ovarian stimulation: the importance of the culture media. Hum Reprod. 2025;40(8):1504-15.##Coticchio G, Cimadomo D, De Vos M, Ebner T, Esbert M, Escribá MJ, et al. To rescue or not to rescue immature oocytes: prospects and challenges. Fertil Steril. 2025;123(5):749-58.##Procházka R, Bartková A, Němcová L, Murín M, Gad A, Marcollová K, et al. The role of MAPK3/1 and AKT in the acquisition of high meiotic and developmental competence of porcine oocytes cultured in vitro in FLI medium. Int J Mol Sci. 2021;22(20):11148.##Choi J, Smitz J. Luteinizing hormone and human chorionic gonadotropin: origins of difference. Mol Cell Endocrinol. 2014;383(1-2):203-13. ##Nwabuobi C, Arlier S, Schatz F, Guzeloglu-Kayisli O, Lockwood CJ, Kayisli UA. hCG: biological functions and clinical applications. Int J Mol Sci. 2017;18(10):2037.##Maman E, Yung Y, Kedem A, Yerushalmi GM, Konopnicki S, Cohen B, et al. High expression of luteinizing hormone receptors messenger RNA by human cumulus granulosa cells is in correlation with decreased fertilization. Fertil Steri. 2025;97(3):592-8.##Drakakis P, Loutradis D, Beloukas A, Sypsa V, Anastasiadou V, Kalofolias G, et al. Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation. Reprod Biol Endocrinol. 2009;7:110.##Siu KK, Serrão VHB, Ziyyat A, Lee JE. The cell biology of fertilization: Gamete attachment and fusion. J Cell Biol. 2021;220(10):e202102146.##Riccetti L, De Pascali F, Gilioli L, Potì F, Giva LB, Marino M, et al. Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse leydig cells in vitro. Reprod Biol Endocrinol. 2017;15(1):2.##Tesarik J, Mendoza-Tesarik R. Cyclic adenosine monophosphate: a central player in gamete development and fertilization, and possible target for infertility therapies. Int J Mol Sci. 2022;23(23):15068.##Ramu S, Acacio B, Adamowicz M, Parrett S, Jeyendran RS. Human chorionic gonadotropin from day 2 spent embryo culture media and its relationship to embryo development. Fertil Steril. 2011;96(3):615-7.##

Comparison of Long-Term and Stimulated Cycle Protocols in Frozen Embryo Transfer Cycles in Women with Polycystic Ovary Syndrome: A Non-Randomized Clinical Trial 2 1 140281 2 Background: In women with polycystic ovary syndrome (PCOS), the optimal endometrial preparation strategy for frozen embryo transfer (FET) remains unclear. This clinical trial aimed to compare a long-term protocol with a stimulated cycle protocol in FET cycles of PCOS women, with clinical pregnancy rate per embryo transfer as the primary outcome. Methods: This non-randomized, open-label, two-arm clinical trial was conducted at Fatemieh Hamedan Hospital, Iran, involving 340 women with PCOS. Participants were allocated to the long-term or stimulated cycle protocols based on clinical scheduling and physician decision. The long-term protocol included low-dose combined oral contraceptives for 14 days, GnRH agonist downregulation, estradiol valerate (4–6 mg/day for ≥10 days), and progesterone before embryo transfer. The stimulated cycle protocol involved recombinant FSH with ultrasound monitoring, hCG trigger for oocyte maturation, and intramuscular progesterone (50 mg/day) for luteal phase support. For each participant one FET cycle was analyzed. Results: Baseline characteristics were similar between groups (n=170 each). The long-term protocol showed higher clinical pregnancy rates (35.9%) compared to the stimulated cycle (22.9%) (OR=1.92; 95%CI: 1.15–3.19; p=0.011). Chemical pregnancy rates also favored the long-term protocol (34.7% vs. 21.8%) (OR=1.91; 95%CI: 1.17–3.09; p=0.008). Endometrial thickness was significantly greater in the long-term protocol (8.7±0.9 mm vs. 8.4±0.8 mm; p=0.004). Conclusion: Although the long-term protocol showed higher clinical pregnancy rates in unadjusted analyses, after adjusting for confounders, protocol type was not independently associated with clinical pregnancy. Larger randomized trials are needed to confirm these findings, and adverse outcomes should be assessed in future studies. 159 165 Shamim Sh Pilevari Clinical Research Development Unit, Fatemieh Hamedan Hospital, Hamadan University of Medical Sciences Clinical Research Development Unit, Fatemieh Hamedan Hospital, Hamadan University of Medical Sciences Iran Mahnaz M Yavangi Clinical Research Development Unit, Fatemieh Hamedan Hospital, Hamadan University of Medical Sciences Clinical Research Development Unit, Fatemieh Hamedan Hospital, Hamadan University of Medical Sciences Iran Zakieh Z Yarahmadi Clinical Research Development Unit, Fatemieh Hamedan Hospital, Hamadan University of Medical Sciences Clinical Research Development Unit, Fatemieh Hamedan Hospital, Hamadan University of Medical Sciences Iran zakiyehyarahmadi@gmail.com Elahe E Talebi Ghane Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences Iran Embryo transferEndometriumGonadotropin-releasing hormoneOvulation inductionPolycystic ovarian syndrome 140281.pdf Suturina L. The epidemiology of polycystic ovary syndrome. In: Kovacs GT, Fauser BC, Legro RS, editors. Polycystic ovary syndrome. 3rd ed. Cabridge (Uk): Cambridg university press; 2022. P. 21-8.##Sharmeen S, Nomani H, Taub E, Carlson H, Yao Q. Polycystic ovary syndrome: epidemiologic assessment of prevalence of systemic rheumatic and autoimmune diseases. Clin Rheumatol. 2021;40(12):4837-43.##Sun B, Ma Y, Li L, Hu L, Wang F, Zhang Y, et al. Factors associated with ovarian hyperstimulation syndrome (OHSS) severity in women with polycystic ovary syndrome undergoing IVF/ICSI. Front Endocrinol (Lausanne). 2021;11:615957.##Yang Y, Zhu D, Wang Q, Ma C, Li D, Wang J, et al. Frozen embryo transfer in the menstrual cycle after moderate-severe ovarian hyperstimulation syndrome: a retrospective analysis. BMC Pregnancy Childbirth. 2022;22(1):907.##Xie Y, Deng M, Deng W, Fan Q, Shi Y. Letrozole ovulation regimen for frozen-thawed embryo transfer in women with polycystic ovary syndrome: study protocol for a randomized controlled trial. Trials. 2024;25(1):364.##Palomba S, de Wilde MA, Falbo A, Koster MP, La Sala GB, Fauser BC. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21(5):575-92.##Wang P, Yang H, Chen Z, Chen Y, Jin C, Yu R, et al. Agonist long protocol improves outcomes of vitrified-warmed embryo transfer in repeatedly thin endometrium. Reprod Biomed Online. 2023;46(3):527-35.##Pilehvari S, Yavangi M, Salemi L, Charaghi Z. A comparative study of the effects of two different treatment periods with estradiol in endometrial preparation on the pregnancy outcome of frozen embryos. Iran J Obstet Gynecol Infertil. 2023;26(1):25-32.##Tsai HW, Wang PH, Lin LT, Chen SN, Tsui KH. Using gonadotropin-releasing hormone agonist before frozen embryo transfer may improve ongoing pregnancy rates in hyperandrogenic polycystic ovary syndrome women. Gynecol Endocrinol. 2017;33(9):686-9.##Man Y, Bian Y, Zhao S, Zhao R, Xu X, Wei D, et al. The effect of different endometrial preparations on women with polycystic ovary syndrome undergoing initial frozen embryo transfer: a historical cohort analysis. Acta Obstet Gynecol Scand. 2021;100(6):1116-23.##Hu KL, Zheng X, Hunt S, Li X, Li R, Mol BW. Blastocyst and perinatal outcome in women undergoing single blastocyst transfar in forzen cycles. Hum Reprod Open. 2021;2021(4):hoab036.##Siristatidis C, Arkoulis T, Christoforidis N, Salamalekis G, Koutlaki N, Karageorgiou V, et al. Investigating the impact of different strategies for endometrial preparation in frozen cycles considering normal responders undergoing IVF/ICSI cycles: a multicenter retrospective cohort study. Syst Biol Reprod Med. 2021;67(3):201-8.##Zeng MF, Zhou X, Duan JL. Stimulated cycle versus artificial cycle for frozen embryo transfer in patients with polycystic ovary syndrome: a meta-analysis. Gynecol Endocrinol. 2021;37(4):294-9.##Rabiei S, Fallah M, Jamshidi F. Comparison of pregnancy rate of frozen embryos by two methods: long with GnRH agonist and OCP with estradiol only. Avicenna J Clin Med. 2020;27(1):5-12.##Zhang J, Li Z, Sun L, Guan Y, Du M. Comparison of pregnancy and neonatal outcomes of single frozen blastocyst transfer between letrozole-induction and HRT cycles in patients with abnormal ovulation. Front Endocrinol (Lausanne). 2021;12:664072.##Zhu X, Ye H, Ye J, Fu Y. Progesterone protocol versus gonadotropin-releasing hormone antagonist protocol in women with polycystic ovarian syndrome undergoing in vitro fertilization treatments with frozen-thawed embryo transfer: a prospective randomized controlled trial. Ann Transl Med. 2021;9(5):387.##

The Effect of Aspirin Administration on Fetal Cardiovascular Function Between 18 to 24 Weeks of Gestation: A New Perspective on ASA Indication in Obstetrics 2 1 140279 2 Background: Low-dose aspirin (ASA) is used in obstetrics for different indications, mainly to prevent preeclampsia. This study investigated the underlying mechanism of ASA’s effect on the fetus’s cardiovascular functions. Methods: 42 pregnant women at 18-24 weeks of gestation, identified as high-risk for preeclampsia, received 160 mg of ASA daily. Fetal Doppler ultrasound was performed before and three weeks after ASA treatment, assessing ductus venosus, middle cerebral, umbilical, and uterine arteries pulsatility indices as well as pulmonary, aorta, and superior vena cava (SVC) diameters in the three-vessel view, including pulmonary/aorta and SVC/aorta ratios. All analyses were performed using SPSS software version 27, with a significance threshold set at p<0.05. A paired t-test was used to assess differences in means. The Chi-square and Fisher’s exact test analyzed nominal variables. Results: Post-intervention analysis revealed significant improvements in abnormal uterine artery resistance (p<0.001) and abnormal pulsatility index of the umbilical artery, middle cerebral artery, and ductus venosus (p<0.001 for all). Moreover, 160 mg/day aspirin administration significantly increased mitral E/A (early filling velocity/atrial contraction velocity: 0.397±0.029; p<0.001), diameters of aorta (4.390±0.852; p<0.001), pulmonary artery (4.895±1.087; p<0.001), and SVC (2.511±0.535; p<0.001), while significantly decreasing left ventricular myocardial performance index (p<0.05). Conclusion: Daily administration of 160 mg of aspirin enhances fetal vascular and cardiac function. Evaluating fetal cardiovascular parameters beyond routine uterine artery Doppler, especially in high-risk pregnancies, and initiating ASA therapy in cases of insidious abnormalities, may help delay or prevent fetal complications such as intrauterine growth restriction (IUGR) by improving cardiovascular function. 165 172 Behrokh B Sahebdel Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Iran Mohammad Nasir MN Hematian Department of Perinatology and Fetal Cardiology, Yas Hospital complex, Tehran University of Medical Sciences Department of Perinatology and Fetal Cardiology, Yas Hospital complex, Tehran University of Medical Sciences Iran Zohreh Z Heidary Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences Iran Fatemeh F Golshahi Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Iran Nafiseh N Saedi Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Iran Fatemeh F Rahimi-Sharbaf Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Iran Mahboobeh M Shirazi Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Iran Arian A Tavasol Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences Iran Gita G Manzari Tavakoli Pediatric Urology and Regenerative Medicine Research Center (PURMRC), Gene, Cell and Tissue Research Institute, Tehran University of Medical Sciences Pediatric Urology and Regenerative Medicine Research Center (PURMRC), Gene, Cell and Tissue Research Institute, Tehran University of Medical Sciences Iran Mohammad Hossein MH Golezar Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences Iran Hamed H Ghorani Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences Iran Elham E Feizabad Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Iran Soudabeh S Rezaei Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Department of Obstetrics and Gynecology, Yas Hospital complex, Tehran University of Medical Sciences Iran sodabe.rezaei80@gmail.com AspirinCardiovascular functionsUltrasound imagingObstetrics 140279.pdf Salafia CM, Minior VK, Pezzullo JC, Popek EJ, Rosenkrantz TS, Vintzileos AM. Intrauterine growth restriction in infants of less than thirty-two weeks' gestation: associated placental pathologic features. Am J Obstet Gynecol. 1995;173(4):1049-57.##Sekielska-Domanowska MI, Myszkowski B, Czuba B, Pietryga M, Cnota W, Dubiel M. The role of individual blood flow parameters through ductus venosus in the first and second trimesters of pregnancy in predicting the condition of the fetus and newborn. Ginekol Pol. 2022;93(7):558-63.##Wallenburg HC, Rotmans N. Prevention of recurrent idiopathic fetal growth retardation by low-dose aspirin and dipyridamole. Am J Obstet Gynecol. 1987;157(5):1230-5. ##Wertaschnigg D, Reddy M, Mol BWJ, da Silva Costa F, Rolnik DL. Evidence-based prevention of preeclampsia: commonly asked questions in clinical practice. J Pregnancy. 2019;2019:2675101.##Wallenburg HC, Rotmans N. Prevention of recurrent idiopathic fetal growth retardation by low-dose aspirin and dipyridamole. Am J Obstet Gynecol. 1987;157(5):1230-5. ##Uzan S, Beaufils M, Bazin B, Danays T. Idiopathic recurrent fetal growth retardation and aspirin-dipyridamole therapy. Am J Obstet Gynecol. 1989;160(3):763-4.##Lazzarin N, Vaquero E, Exacoustos C, Bertonotti E, Romanini ME, Arduini D. Low-dose aspirin and omega-3 fatty acids improve uterine artery blood flow velocity in women with recurrent miscarriage due to impaired uterine perfusion. Fertil Steril. 2009;92(1):296-300.##Alsolai AA, Bligh LN, Greer RM, Kumar S. Correlation between fetoplacental Doppler indices and measurements of cardiac function in term fetuses. Ultrasound Obstet Gynecol. 2019;53(3):358-66.##Akolekar R, Sarno L, Wright A, Wright D, Nicolaides KH. Fetal middle cerebral artery and umbilical artery pulsatility index: effects of maternal charac-teristics and medical history. Ultrasound Obstet Gynecol. 2015;45(4):402-8.##Link G, Clark KE, Lang U. Umbilical blood flow during pregnancy: evidence for decreasing placental perfusion. Am J Obstet Gynecol. 2007;196(5):489.e1-7.##Bower SJ, Harrington KF, Schuchter K, McGirr C, Campbell S. Prediction of pre‐eclampsia by abnormal uterine Doppler ultrasound and modification by aspirin. Br J Obstet Gynaecol. 1996;103(7):625-9.##Veille JC, Hanson R, Sivakoff M, Swain M, Henderson L. Effects of maternal ingestion of low-dose aspirin on the fetal cardiovascular system. Am J Obstet Gynecol. 1993;168(5):1430-7.##Grab D, Paulus WE, Erdmann M, Terinde R, Oberhoffer R, Lang D, et al. Effects of low-dose aspirin on uterine and fetal blood flow during pregnancy: results of a randomized, placebo-controlled. Ultrasound Obstet Gynecol. 2000;15(1):19-27.##Bamfo JEAK, Odibo AO. Diagnosis and management of fetal growth restriction. J Pregnancy. 2011;2011:640715.##Dall’Asta A, Brunelli V, Prefumo F, Frusca T, Lees CC. Early onset fetal growth restriction. Matern Health Neonatol Perinatol. 2017;3:2.##Matsumoto‐Runser J, Ando K, Yoda H. EP04.06: High SVC/Ao ratio in 3-vessel view can be one of the indicators for the placental insufficiency. Ultrasound Obstet Gynecol. 2017;50(S1):270.##

Fetal Brain Midline Structure Measurements: Cavum Septi Pellucidi and Corpus Callosum Indices in Multiple Views at Late Gestation 2 1 140274 2 Background: Few studies evaluated cavum septum pellucidum (CSP) and cor-pus callosum (CC) indices in late gestation. This study assessed CSP and CC indices, along with frontal lobe measurements, and examined correlations among parameters. Methods: A cross-sectional study was conducted at Imam Khomeini Hospital Complex on 150 fetuses at ≥36 weeks’ gestation. Transabdominal ultrasound was used to measure CSP length, width, trace length, and area in the axial view; frontal lobe thickness from anterior and posterior CSP margins in horizontal and vertical directions; and CC lengths and thicknesses. CSP trace length and area were also obtained in the midsagittal view. Data were analyzed using SPSS 23. Results: Mean gestational age, biparietal diameter (BPD), head circumference (HC), and estimated fetal weight (EFW) were 37.56±1.08 weeks, 90.73±3.20 mm, 326.58± 10.59 mm, and 2987.82±333.68 gr. In the trans-thalamic view, median CSP length, width, trace length, and area were 8.92 mm, 6.05 mm, 2.81 mm, and 0.49 mm². Median CSP height in the coronal view was 5.85 mm. In the midsagittal view, mean CC outer-to-outer length, inner-to-inner length, CSP trace length, and CSP area were 41.31±4.81 mm, 29.73±4.17 mm, 2.56±0.63 mm, and 0.36±0.19 mm². All CC and CSP indices correlated significantly with HC (p<0.05). Frontal bone–to–CSP anterior and posterior distances in axial and near-field views also correlated with HC (p=0.0001). Conclusion: This study provides normative measurements for CC, CSP, and frontal lobe indices at ≥36 weeks’ gestation. These values support late-gestation brain assessment and early identification of newborns potentially at risk for neurodevelopmental concerns. 172 180 Sedigheh S Borna Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences Iran Azadeh A Shabani Preventative Gynecology Research Center, Taleghani Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences Preventative Gynecology Research Center, Taleghani Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences Iran Seyedeh Noushin SN Ghalandarpoor-Attar Obstetrics and Gynecology Department, Baqiyatallah Hospital, Baqiyatallah University of Medical Sciences Obstetrics and Gynecology Department, Baqiyatallah Hospital, Baqiyatallah University of Medical Sciences Iran Seyedeh Mojgan SM Ghalandarpoor-Attar Maternal, Fetal, and Neonatal Research Center, Family Health Research Institute, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Maternal, Fetal, and Neonatal Research Center, Family Health Research Institute, Vali-E-Asr Hospital, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Iran mojganghalandarpour@gmail.com Asghar A Ghorbani Department of Pediatrics, Baharloo Hospital, Tehran University of Medical Sciences Department of Pediatrics, Baharloo Hospital, Tehran University of Medical Sciences Iran Ghornabiasghar414@gmail.com Corpus callosumFetal brainFetal organ maturityPregnancyPrenatal careSeptum pellucidumUltrasonography 140274.pdf Winter TC, Kennedy AM, Byrne J, Woodward PJ. The cavum septi pellucidi: why is it important? J Ultrasound Med. 2010;29(3):427-44.##Zeng Q, Wen H, Yuan Y, Ding Y, Liao Y, Luo D, et al. A novel technique to assess fetal corpus callosum by two-dimensional axial plane. Eur Radiol. 2020; 30(11):5871-80.##Fantasia I, Ciardo C, Bracalente G, Filippi E, Murru FM, Spezzacatene A, Bin M, Mendez Quintero O, Montaguti E, Lees C. Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance. Acta Obstet Gynecol Scan-dinavica. 2023;102(6):744-50.##Pylypjuk CL, Memon SF, Chodirker BN. Utility of measuring fetal cavum septum pellucidum (CSP) width during routine obstetrical ultrasound for improving diagnosis of 22q11. 2 deletion syndrome: a case-control study. Appl Clin Genet. 2022;15:87-95.##Wu Y, Shen K, Chen Z, Wu J, editors. Automatic measurement of fetal cavum septum pellucidum from ultrasound images using deep attention network. In: 2020 IEEE International Conference on Image Processing (ICIP); 2020. IEEE.##Kertes I, Hoffman D, Yahal O, Berknstadt M, BarYosef O, Ezra O, et al. The normal fetal cavum septum pellucidum in MR imaging–new biometric data. Eur J Radiol. 2021;135:109470.##Achiron R, Achiron A. Development of the human fetal corpus callosum: a high‐resolution, cross‐sectional sonographic study. Ultrasound Obstet Gynecol. 2001;18(4):343-7.##Pashaj S, Merz E, Wellek S. Biometry of the fetal corpus callosum by three‐dimensional ultrasound. Ultrasound Obstet Gynecol. 2013;42(6):691-8.##Youssef A, Ghi T, Pilu G. How to image the fetal corpus callosum. Ultrasound Obstet Gynecol. 2013;42(6):718-20.##Kyriakopoulou V, Gray L, Allsop J, McGuinness A, Ederies A, Rutherford M. ‘Watch this space’: the cavum septum pellucidum during development. Archiv Dis Childhood Fetal Neon Ed. 2011;96 (Suppl 1):Fa60-Fa.##Jarvis D, Griffiths PD. Normal appearances and dimensions of the foetal cavum septi pellucidi and vergae on in utero MR imaging. Neuroradiology. 2020;62(5):617-27.##Nagaraj UD, Calvo-Garcia MA, Kline-Fath BM. Abnormalities associated with the cavum septi pellucidi on fetal MRI: what radiologists need to know. AJR Am J Roentgenol. 2018;210(5):989-97.##Pilu G, Segata M, Ghi T, Carletti A, Perolo A, Santini D, et al. Diagnosis of midline anomalies of the fetal brain with the three‐dimensional median view. Ultrasound Obstet Gynecol. 2006;27(5):522-9.##Jou HJ, Shyu MK, Wu SC, Chen SM, Su CH, Hsieh FJ. Ultrasound measurement of the fetal cavum septi pellucidi. Ultrasound Obstet Gynecol. 1998;12(6):419-21.##Falco P, Gabrielli S, Visentin A, Perolo A, Pilu G, Bovicelli L. Transabdominal sonography of the cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy. Ultrasound Obstet Gynecol. 2000;16(6):549-53.##Serhatlioglu S, Kocakoc E, Kiris A, Sapmaz E, Boztosun Y, Bozgeyik Z. Sonographic measurement of the fetal cerebellum, cisterna magna, and cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy. J Clin Ultrasound. 2003;31(4):194-200.##

A Comparative Analysis of Oxidative Stress and Inflammatory Biomarkers in Different Stages of Endometriosis 2 1 140275 2 Background: The fundamental mechanisms behind the causes and development of endometriosis are still poorly understood. Therefore, identifying biomarkers that can help with early detection and targeted treatment is crucial for effective management of this disease. This study aimed to compare total antioxidant capacity (TAC), the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the concentrations of interleukin-6 (IL-6) and phenylalanine (Phe) across different stages of endometriosis. Methods: The plasma samples were collected from women with endometriosis who had undergone laparoscopic surgery. The stages were confirmed by a gynecologist, with 30 plasma samples from stages I-II (mild) and 30 from stages III-IV (severe). The obtained measurement data were first normalized and tested for normality, followed by analysis using the t-test and Mann-Whitney U test. The p-value below 0.05 was considered statistically significant. The sample size was determined based on Cohen's guideline of 30. Biomarker levels were assessed using ELISA and colorimetric techniques. Results: TAC levels, GPx, and SOD activities, as well as Phe concentration significantly differed between endometriosis stages I-II and III-IV (p<0.05). These measured biomarkers were higher in stage I-II. On the other hand, although IL-6 levels were higher in stages III–IV, the differences between stages were not statistically significant. Conclusion: The potential of TAC, SOD, GPx, and Phe as biomarkers for the early diagnosis and treatment of endometriosis underscore the roles of inflammation and oxidative stress in the pathogenesis of the disease, providing insights that may aid in developing more targeted diagnostic and therapeutic strategies. 180 186 Ghazaleh Gh Bigdeli Department of Converging Science and Technologies (NBIC), Science and Research Branch, Islamic Azad University Department of Converging Science and Technologies (NBIC), Science and Research Branch, Islamic Azad University Iran Maryam M Ghobeh Department of Converging Science and Technologies (NBIC), Science and Research Branch, Islamic Azad University Department of Converging Science and Technologies (NBIC), Science and Research Branch, Islamic Azad University Iran Roya R Padmehr Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Iran Simin S Zafardoust Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Nanobiotechnology Research Center, Avicenna Research Institute, ACECR Iran Zahra Z Sheikhi Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR Iran Negin N AmirJannati Department of Veterinary Medicine, Science and Research Branch, Islamic Azad University Department of Veterinary Medicine, Science and Research Branch, Islamic Azad University Iran Mohammad Reza MR Mahdavi Amiri Thalassemia Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences Thalassemia Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences Iran Kambiz K Gilany کامبیز گیلانی Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran gilani@acecr BiomarkersEndometriosisGPxIL-6PhenylalanineSODTAC 140275.pdf Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397(10276):839-52.##Shafrir AL, Vitonis AF, Wallace B, DiVasta AD, Sadler Gallagher J, Sasamoto N, et al. Cohort profile: the endometriosis pain quality after surgical treatment (EndoQUEST) study. PLoS One. 2022;17(6):e0269858.##Santulli P, Chouzenoux S, Fiorese M, Marcellin L, Lemarechal H, Millischer AE, et al. Protein oxidative stress markers in peritoneal fluids of women with deep infiltrating endometriosis are increased. Hum Reprod. 2015;30(1):49-60.##Lambrinoudaki IV, Augoulea A, Christodoulakos GE, Economou EV, Kaparos G, Kontoravdis A, et al. Measurable serum markers of oxidative stress response in women with endometriosis. Fertil Steril. 2009;91(1):46-50.##Wang F, Wang H, Jin D, Zhang Y. Serum miR-17, IL-4, and IL-6 levels for diagnosis of endometriosis. Medicine (Baltimore). 2018;97(24):e10853.##Luporini RL, Pott-Junior H, Di Medeiros Leal MCB, Castro A, Ferreira AG, Cominetti MR, et al. Phenylalanine and COVID-19: tracking disease severity markers. Int Immunopharmacol. 2021;101(Pt A):108313.##Ortiz CN, Torres-Reverón A, Appleyard CB. Metabolomics in endometriosis: challenges and perspectives for future studies. Reprod Fertil. 2021;2(2):R35-50.##Cacciottola L, Donnez J, Dolmans MM. Can endometriosis-related oxidative stress pave the way for new treatment targets? Int J Mol Sci. 2021;22(13):7138.##Anastasiu CV, Moga MA, Elena Neculau A, Bălan A, Scârneciu I, Dragomir RM, et al. Biomarkers for the noninvasive diagnosis of endometriosis: state of the art and future perspectives. Int J Mol Sci. 2020;21(5):1750.##Tian Z, Chang XH, Zhao Y, Zhu HL. Current biomarkers for the detection of endometriosis. Chin Med J (Engl). 2020;133(19):2346-52.##Wickiewicz D, Chrobak A, Gmyrek GB, Halbersztadt A, Gabryś MS, Goluda M, et al. Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis. Arch Gynecol Obstet. 2013;288(4):805-14.##Amreen S, Kumar P, Gupta P, Rao P. Evaluation of oxidative stress and severity of endometriosis. J Hum Reprod Sci. 2019;12(1):40-6.##Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2):hoac009.##Gao Y, Shen M, Ma X, Li J, Wang B, Wang J, et al. Seven hormonal biomarkers for diagnosing endometriosis: meta-analysis and adjusted indirect comparison of diagnostic test accuracy. J Minim Invasive Gynecol. 2019;26(6):1026-35.e4.##Kovács Z, Glover L, Reidy F, MacSharry J, Saldova R. Novel diagnostic options for endometriosis–Based on the glycome and microbiome. J Adv Res. 2021;33:167-81.##Zaha I, Muresan M, Tulcan C, Huniadi A, Naghi P, Sandor M, et al. The role of oxidative stress in infertility. 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Trends of Multiple Births in Iran from 2014 to 2023 2 1 140277 2 Background: The aim of this study was to analyze the trends of multiple births at both national and provincial levels in Iran from 2014 to 2023. Methods: Data on the number of live births and multiple births from 2014 to 2023 at national and provincial levels were obtained from the Iran’s Bureau of Vital Statistics. The multiple birth rate (MBR), defined as the number of live births from multiple births per 1,000 live births, was calculated annually. To examine temporal trends and detect significant changes in MBR over the study period, joinpoint regression analysis was performed. Annual percent change (APC) and average annual percent change (AAPC) were calculated for the entire period. Result: The national AAPC in the MBR was estimated at 2.38% (95%CI: 1.95 to 2.76) over the entire study period. A significant shift in trend was identified in 2020. Specifically, the APC from 2014 to 2020 was 0.24%. However, from 2020 to 2023, the APC markedly increased to 6.8%, reflecting a substantial rise in MBR during this latter period. Furthermore, the study findings demonstrated that nearly all provinces across the country have exhibited an upward trend in MBR in recent years. Conclusion: The increasing trend of multiple births in Iran aligns with global patterns. Several factors may have contributed to this rise, including increased maternal age at childbirth, higher prevalence of infertility, expanded use of assisted reproductive technologies (ARTs), and shifts in population policies. 186 193 Milad M Ahmadi Gohari Modeling in Health Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences Modeling in Health Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences Iran Maryam M Chegeni Molecular and Medicine Research Center, Khomein University of Medical Sciences Molecular and Medicine Research Center, Khomein University of Medical Sciences Iran Firoozeh F Mirzaee Reproductive and Family Health Research Center, Kerman University of Medical Sciences Reproductive and Family Health Research Center, Kerman University of Medical Sciences Iran Yunes Y Jahani Medical Informatics Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences Medical Informatics Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences Iran yonesjahani@yahoo.com IranJoinpoint regressionMultiple birth 140277.pdf Choi SH, Park YS, Shim KS, Choi YS, Chang JY, Hahn WH, et al. Recent trends in the incidence of multiple births and its consequences on perinatal problems in Korea. J Korean Med Sci. 2010;25(8):1191-6.##Vlachadis N, Vrachnis D, Loukas N, Fotiou A, Maroudias G, Antonakopoulos N, et al. Temporal trends in multiple births in Greece: the evolution of an epidemic. Cureus. 2023;15(2):w35414.##Wenstrom KD, Gall SA. Incidence, morbidity and mortality, and diagnosis of twin gestations. Clin Perinatol. 1988;15(1):1-11.##Loos RJF, Derom C, Derom R, Vlietinck R. Determinants of birthweight and intrauterine growth in liveborn twins. paediatr Perinat Epidemiol. 2005;19 Suppl 1:15-22.##Kim NO, Choi SJ, Han KH, Hyung HS, Shin SR. Birth weight distribution of twins according to gestational age. Korean J Obstet Gynecol. 2004;47:1860-4.##Lee KH, Hwang SJ, Kim SH, Lee SH, Yu DK, Hwang JH, et al. Comparison of mortality and morbidity in multiple versus singleton very low birth weight infants in a neonatal intensive care unit. 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Optimizing Reproductive Autonomy in Cystic Fibrosis: The Role of Oocyte Cryopreservation 2 1 140278 2 Cystic fibrosis (CF), an inherited genetic disorder compromising the body’s viscera, is a major contributor to infertility in women of reproductive age. Because of dysfunctional activity of cystic fibrosis transmembrane conductance regulator (CFTR), women with CF may have thicker cervical mucus. A thicker mucus can prolong the time to get pregnant by making it more difficult for sperm to pass through the cervix. Delayed conception or female infertility may result from changes in uterine pH balance, protracted puberty, and irregular menstruation (1). The establishment of patient registries, CF care centers, as well as the implementation of early diagnostic and screening programs have culminated in substantial advancements in CF prognosis, with life expectancy now extending into to the late 40s and 50s. Oocyte cryopreservation (OC), particularly through vitrification, can substantially enhance the fertilization and later productive outcomes in either surrogacy or assisted reproduction. Oocyte cryopreservation may provide a suitable alternative to increase fertility by 34-35%. However, it remains a largely neglected technique in CF, despite its widespread use in oncology, mainly due to technical challenges associated with the mature ovum including its large size, low surface area to volume ratio, and limited cell number (2). The success rates have reached unprecedented levels by using ultra-rapid vitrification techniques and intracytoplasmic sperm injection (ICSI). Advances such as artificial intelligence–based image analysis and spindle visualization using polscope technology are expected to further enhance the ac-curacy and reliability of this technique. In women with CF, more than 50% can conceive without the use of assisted reproductive approaches, although the overall fertility remains reduced (3). Compared to women of similar age, estimates of subfertility and infertility are higher among those with CF. This issue is exacerbated by factors such as the presence of thickened cervical mucus, which can impede sperm motility and alter the bicarbonate (HCO3) and pH balance in the uterus, therefore affecting sperm capacitation. Some women with CF may experience irregular menstruation, delayed puberty, or amenorrhea, all of which can significantly impair normal ovulation and fertility. Moreover, women with CF may also experience cystic fibrosis-related diabetes (CFRD) and inflammation, which can also play an important role in decreased ovarian reserves due to low anti-Müllerian hormone (AMH) levels. A study conducted in 2021 found that the number of ovarian follicles decreases with age, with the rate of decline being steeper in women with CF (3). Couples affected by CF require comprehensive counseling when planning to start a family. Women with CF require support to make informed, patient-centered reproductive decisions for themselves as they plan for their future family by consulting a doctor or a health professional (4). This can be achieved by educating them about advances in the technique, such as assisted reproductive technology (ART). Although some CF–specific guidelines exist, they are not widely disseminated; these include the use of ovulation-inducing medications, intrauterine sperm insemination, in vitro fertilization (IVF), and cryopreservation techniques. Cryopreservation is a technique used to freeze biological materials like cells or tissues, although OC is mostly used in fertility treatments. When using frozen oocytes, there are no significant differences in fertilization or pregnancy rates, and the clinical outcomes are generally favorable (5). OC, which is age-dependent with respect to oocyte quality, is most affected when performed in the early stages of reproductive life, ideally in the early to mid-20s. According to the study in 2024, among women who underwent planned OC, those aged 40 and older had lower birth rate compared to the women under 35, with an overall oocyte survival rate of 78.5%. The whole method is highly safe and effective as a result of advancements made in cryotechnology and research on oocyte structure and integrity. In another study, 748 oocytes were cryopreserved, with a survival rate of 76.1%, a fertilization rate of 66.2%, and 39.1% reaching the blastocyst stage (6). Planned OC provides social revolution and reproductive autonomy for women, particularly prior to lung transplantation or long-term therapies that compromise fertility, thereby increasing the potential for successful reproduction. With the progress in CF care, it continues to improve the life expectancy of women living with CF; hence, their reproductive futures must not be overlooked. OC represents a feasible alternative in fertility preservation, and opportunities for child-bearing are increasing in a healthier context (6). Integrating personalized conception planning with early OC is a primary consideration in reproductive care counseling and routine assessment of oocyte reserve, aimed at safeguarding reproductive autonomy, and optimizing the likelihood of healthy live births in women with OC. Multidisciplinary collaboration is crucial, as each specialist contributes to the effectiveness of patient care. For instance, genetic counselors provide guidance on the hereditary nature of CF, while reproductive endocrinologists analyze ovarian reserve and overall reproductive potential. Given the reproductive challenges faced by women with CF, there is an urgent need for CF-specific reproductive guidance, including information on fertility preservation options such as OC, the impact of CFTR modulators, and the use of medications to address these complications (7). Addressing the aforementioned barriers is essential to uphold reproductive autonomy and enable women with CF to overcome fertility limitations. Conflict of Interest Authors declare no conflict of interest. 193 195 Saim S Mahmood Khan Department of Medicine, Karachi Medical and Dental College, Karachi Metropolitan University Department of Medicine, Karachi Medical and Dental College, Karachi Metropolitan University Pakistan saimmahmoodkhanrajput@gmail.com Rashmeen R Khan Department of Medicine, Karachi Medical and Dental College, Karachi Metropolitan University Department of Medicine, Karachi Medical and Dental College, Karachi Metropolitan University Pakistan Safiyullah S Bashir Department of Medicine, Karachi Medical and Dental College, Karachi Metropolitan University Department of Medicine, Karachi Medical and Dental College, Karachi Metropolitan University Pakistan Mehak M Rani Department of Medicine, Dow University of Health Sciences Department of Medicine, Dow University of Health Sciences Pakistan Surraiya S RiazMahmood Khan Department of Medicine, Sohail University Department of Medicine, Sohail University Pakistan No Keyword 140278.pdf Cystic Fibrosis Foundation. Fertility in women with CF [Internet]. [cited 2025 Nov 12]. Available from: https://www.cff.org/managing-cf/fertility-women-cf.##Pai HD, Baid R, Palshetkar NP, Pai A, Pai RD, Palshetkar R. Oocyte cryopreservation: current scen-ario and future perspectives: a narrative review. J Hum Reprod Sci. 2021;14(4):340-9. ##Cohen-Cymberknoh M, Garber KM, Reiter J, Shte-inberg M, Stolovas A, Barghouti I, et al. Ovarian reserve in women with cystic fibrosis: is this a cause of sub-fertility? J Ovarian Res. 2023;16(1):148.##Rafeeq MM, Murad HAS. Cystic fibrosis: current therapeutic targets and future approaches. J Transl Med. 2017;15(1):84.##Han E, Seifer DB. Oocyte cryopreservation for medical and planned indications: a practical guide and overview. J Clin Med. 2023;12(10):3542.##Hughan KS, Daley T, Rayas MS, Kelly A, Roe A. Female reproductive health in cystic fibrosis. J Cyst Fibros. 2019;18 Suppl 2:S95-104.##Shteinberg M, Taylor-Cousar JL, Durieu I, Cohen-Cymberknoh M. Fertility and pregnancy in cystic fibrosis. Chest. 2021;160(6):2051-60.##

Management of Recurrent Intrahepatic Cholestasis of Pregnancy: A Case Report 2 1 140276 2 Background: Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent hepatic disorder exclusive to pregnancy, associated with significant maternal morbidity and increased risk of adverse perinatal outcomes. Recurrence in subsequent pregnancies and comorbidities such as gestational diabetes and hypertensive disorders further complicate clinical management. This case presentation, an attempted to describe the diagnostic and therapeutic challenges in managing recurrent ICP, especially in the context of overlapping maternal comorbidities and limited diagnostic resources. Case Presentation: A case of a 32-year-old Iranian woman, gravida 3 para 2, with a history of one intrauterine fetal death and one neonatal death, was ultimately diagnosed with recurrent ICP. In her third pregnancy, elevated bile acid levels were confirmed by routine monitoring from 20 weeks’ gestation, peaking at 333 µmol/L by 32 weeks. Despite intensive medical therapy including ursodeoxycholic acid, hydroxychloroquine, corticosteroids, and low-molecular-weight heparin, her pruritus worsened and bile acid levels escalated, prompting preterm cesarean delivery. The neonate experienced complications, including respiratory distress, suspected Hirschsprung’s disease, sepsis, and hyperbilirubinemia. Management included continuous positive airway pressure (CPAP), broad-spectrum antibiotics, surgery, phototherapy, and parenteral nutrition. Multidisciplinary intervention enabled neonatal recovery, and maternal symptoms resolved postpartum. Conclusion: This case underscores the complexities of managing recurrent ICP, particularly in resource-limited settings. It highlights the critical need for early diagnosis, vigilant monitoring, and a multidisciplinary approach to mitigate the risk of stillbirth and improve perinatal outcomes. Additionally, it suggests that recurrent ICP may present earlier or with greater intensity in subsequent pregnancies, necessitating more comprehensive surveillance and tailored management strategies for affected mothers. 195 201 Mohadese M Dashtkoohi Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Iran Mohammad Sadeq MS Najafi Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences Iran Zohreh Z Heidary Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Iran Afsaneh A Alimadad-Tafreshi Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Iran Seyedeh Mojgan SM Ghalandarpoor-Attar Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Iran Sedigheh S Hantoushzadeh صدیقه حنطوش‌زاده Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences Iran hantoushzadeh@tums.ac.ir Bile acidsFetal distressIntrahepatic cholestasis of pregnancyIntrauterine fetal deathMultidisciplinary managementPruritus 140276.pdf Goel A, Jamwal KD, Ramachandran A, Balasubramanian KA, Eapen CE. Pregnancy-related liver disorders. J Clin Exp Hepatol. 2014;4(2):151-62.##Tang M, Xiong L, Cai J, Fu J, Liu H, Ye Y, et al. Intrahepatic cholestasis of pregnancy: insights into pathogenesis and advances in omics studies. Hepatol Int. 2024;18(1):50-62.##Girling J, Knight CL, Chappell L. Intrahepatic cholestasis of pregnancy: green‐top guideline No. 43 June 2022. BJOG. 2022;129(13):e95-114.##Beuers U, Wolters F, Oude Elferink RP. Mechanisms of pruritus in cholestasis: understanding and treating the itch. Nat Rev Gastroenterol Hepatol. 2023;20(1):26-36.##Parsaei M, Dashtkoohi M, Haddadi M, Rashidian P, Mansouri Z, Hantoushzadeh S. The association of serum total bile acid levels with gestational diabetes mellitus: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2024;24(1):744.##Arrese M, Macias RI, Briz O, Perez MJ, Marin JJ. Molecular pathogenesis of intrahepatic cholestasis of pregnancy. Expert Rev Mol Med. 2008;10:e9.##Xiao J, Li Z, Song Y, Sun Y, Shi H, Chen D, et al. Molecular pathogenesis of intrahepatic cholestasis of pregnancy. Can J Gastroenterol Hepatol. 2021;2021:6679322.##Jamshidi Kerachi A, Shahlaee MA, Habibi P, Dehdari Ebrahimi N, Ala M, Sadeghi A. Global and regional incidence of intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis. BMC Med. 2025;23(1):129.##Hobson SR, Cohen ER, Gandhi S, Jain V, Niles KM, Roy-Lacroix MÈ, et al. Guideline No. 452: diagnosis and management of intrahepatic cholesta-sis of pregnancy. J Obstet Gynaecol Can. 2024;46(8):102618.##Odutola PO, Olorunyomi PO, Olatawura OO, Olorunyomi I, Madojutimi O, Fatunsin AO, et al. Intrahepatic cholestasis of pregnancy is associated with increased risk of hepatobiliary disease and adverse fetal outcomes: a systematic review and meta-analysis. ILIVER. 2023;2(4):219-26.##Lyutakov I, Ursini F, Penchev P, Caio G, Carroccio A, Volta U, et al. Methods for diagnosing bile acid malabsorption: a systematic review. 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A multicentre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset intrahepatic cholestasis of pregnancy: the TURRIFIC randomised trial. BMC Pregnancy Childbirth. 2021;21(1):51.##Li C, Yang J, Wang Y, Qi Y, Yang W, Li Y. Farnesoid X receptor agonists as therapeutic target for cardiometabolic diseases. Front Pharmacol. 2020;11:1247.##Wasmuth HE, Glantz A, Keppeler H, Simon E, Bartz C, Rath W, et al. Intrahepatic cholestasis of pregnancy: the severe form is associated with common variants of the hepatobiliary phospholipid transporter ABCB4 gene. Gut. 2007;56(2):265-70.##Anzivino C, Odoardi MR, Meschiari E, Baldelli E, Facchinetti F, Neri I, et al. ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population. Dig Liver Dis. 2013;45(3): 226-32.##Dixon PH, Sambrotta M, Chambers J, Taylor-Harris P, Syngelaki A, Nicolaides K, et al. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahe-patic cholestasis of pregnancy. Sci Rep. 2017;7(1):11823.##