Early Pregnancy Loss: Can It Be Attributed to IVF Laboratory Performance? 2 1 140254 2 In most IVF clinics worldwide, infertility specialists and embryologists often engage in discussions regarding the increased rate of early pregnancy loss (EPL) in women who have undergone embryo transfer during a defined period. They are always asked whether any modifications to IVF laboratory protocols, equipment, materials, or culture media have contributed to the rise in EPL. Indeed, the performance quality of the embryology laboratory, the type of protocols, materials, as well as the expertise and experience of the embryologists have critical role in both the success of an IVF center and the incidence of EPL. It is important to emphasize that EPL should not be predominantly attributed to deficiencies in IVF laboratory performance. Although the causes of EPL are not fully understood, the most likely proposed factors include the quality of transferred embryos in IVF/ICSI cycles or endometrial dysfunction. Both parental factors, particularly maternal ones, significantly influence the risk of EPL. Maternal age, induction ovulation protocols, oocyte and embryo quality, endometrial receptivity, and uterine abnormalities are key factors that affect the progression of early pregnancy. In addition, paternal factors such as age and sperm quality also play a role in EPL, although maternal factors are often the main focus of research into its causes. Several studies consistently identify advanced maternal age as a significant independent risk factor for EPL following IVF and embryo transfer (ET). Specifically, the risk of EPL is 1.35 times higher in women aged 35-39 compared to those under 35 years, and 3.88 times higher in women aged 40 years and older. This increased risk is often attributed to the higher rate of oocyte aneuploidy in older women, with the oocyte aneuploidy rate reaching up to 70% in women over 35 (1). Increased body mass index (BMI) is strongly associated with a higher likelihood of EPL even after singleton euploid embryo transfer. One study found that the miscarriage rate increased significantly with higher BMI (odds ratio 1.04). Non-chromosomal factors associated with obesity, such as metabolic, endocrine, inflammatory, and epigenetic mechanisms have been suggested as potential contributors. Weight loss before an IVF/ICSI cycle is proposed as a potential measure to reduce the risk of EPL (2). A history of miscarriage is another important factor in EPL. While some studies have found no association between the number of previous miscarriages and EPL, others have identified a history of spontaneous miscarriage as an important factor, particularly in younger women. Among women under 35 undergoing IVF/ICSI, a history of spontaneous miscarriage was identified as a significant risk factor for EPL. Additionally, recurrent pregnancy loss (RPL) is associated with increased rates of EPL in IVF/ICSI cycles (1). Endometrial thickness at the time of embryo transfer has been shown to be an independent protective factor for the development of EPL. One study found that the risk of EPL was 0.78 times higher in women with an endometrial thickness ≥8.5 mm compared with women with an endometrial thickness <8.5 mm. The overall trend suggests that thicker endometrium is associated with better clinical outcomes and a lower risk of EPL. However, some studies have shown inconsistency considering this association. Chronic endometritis increases the risk of EPL even after antibiotic treatment. Moreover, a history of induced abortions is considered as a potential risk factor for early miscarriage, possibly due to endometrial injury as its consequence (1). The type of controlled ovarian hyperstimulation (COH) protocol used during ovarian stimulation can also affect the risk of EPL. Studies have shown that GnRH antagonist and minimal stimulation protocols may be connected with a higher risk of EPL compared with a long GnRH agonist protocol. It is important to note that these factors can interact, and the risk of EPL is often multifactorial. In frozen-thawed embryo transfer (FET) cycles, the type of endometrial preparation protocol influences the risk of EPL. Natural cycle of embryo transfers was associated with a lower rate of EPL (0.73 times) compared with hormone replacement therapy (HRT) cycle. One study found that ovulation-induced FET cycles had a lower EPL rate than HRT cycles. The presence of a corpus luteum in natural or ovulation-induction cycles has been suggested as a possible explanation for these differences. The rate of EPL was significantly higher in HRT cycles compared with stimulated cycles (1, 3). Embryo quality, assessed by factors such as morphology or blastomere number, has been shown to be a predictor of EPL, particularly in fresh cycles. A higher number of high-quality embryos was an independent protective factor for early miscarriage. The number of good-quality embryos was identified as an important factor that could reduce the risk of EPL in younger women (<35). The risk of EPL was significantly decreased when the leading embryo had six to ten blastomeres compared with four to five blastomeres. Poor-quality embryos are more likely to have chromosomal abnormalities, metabolic defects, or mitochondrial dysfunction, leading to higher rates of early miscarriage. However, a study focusing on single euploid blastocyst transfer did not show any difference in clinical miscarriage rates between different embryo quality groups (high, normal, low, poor). This suggests that while embryo morphology predicts implantation, chromosomal composition (euploid status) may represent a more significant factor in the occurrence of EPL. The use of machine learning in time-lapse imaging to predict the risk of miscarriage based on early embryonic developmental features is currently being investigated. Some studies have shown that transferring more than one embryo (i.e., two embryos) is a protective factor with a lower risk of EPL compared with transferring a single embryo. Transferring two embryos was associated with a 29% reduced risk of EPL. In freeze-thaw cycles, the number of embryos transferred (i.e., more than one embryo) was a protective factor for early miscarriage. However, another study focusing on frozen-thawed embryo transfer of morphologically good, day 5 blastocysts found that double embryo transfer (DET) was associated with increased clinical pregnancy loss compared to single embryo transfer (SET). Other studies have found no significant relationship between the number of embryos transferred and early miscarriages. Despite the possible reduction in miscarriage rates with multiple embryos, limiting the number of embryos transferred is recommended due to the risks associated with multiple pregnancies (1, 4, 5). The technique used for oocyte fertilization, whether conventional IVF or intracytoplasmic sperm injection (ICSI), does not seem to be a relevant factor for EPL. Sperm DNA fragmentation (DFI) is frequently assessed in the laboratory and has been linked to pregnancy outcomes. Some studies indicate that increased DFI is linked to an increased risk of EPL, although findings from different studies on this association have varied. The risk of EPL has been found to be significantly higher in frozen-thawed embryo transfer cycles compared to fresh embryo transfer cycles. One study reported a 1.48 times higher risk in frozen cycles. This might be attributed to the embryo freezing and thawing process, affecting the developmental potential of embryos. Although vitrification is considered safe, but the skills and consistency of laboratory operators in performing cryopreservation can influence the survival and developmental competence of thawed embryos (1, 2, 4). Finally, EPL should not be absolutely attributed to factors related to the IVF laboratory performance. In fact, EPL is often multifactorial and some potential factors such as genetic factors (beyond aneuploidy), immune and systemic factors, environmental influences, and unhealthy lifestyle may not be fully identified or understood in retrospective studies due to their complexity. In addition, the results of most studies show variability or inconsistency, indicating the need for further large-scale prospective studies for validation. 01 3 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 140254.pdf Liying Zuo, Yuan Fan, Jiajia Ai, Li Tian. Analysis of factors related to early miscarriage after in vitro fertilization embryo transfer. Gynecol Obstet Clin Med. 2022;2(4):171-4.##del Carmen Nogales, Cruz M, de Frutos S, Martínez EM, Gaytán M, Ariza M, et al. Association between clinical and IVF laboratory parameters and miscarriage after single euploid embryo transfers. Reprod Biol Endocrinol. 2021;19(1):186.##Salame AA, Zhafal MJ, Peramo B. Early pregnancy loss in IVF: a literature review. Middle East Fertil Soci J. 2024;29(1):30. ##Hu L, Du J, Lv H, Zhao J, Chen M, Wang Y, et al. Influencing factors of pregnancy loss and survival probability of clinical pregnancies conceived through assisted reproductive technology. Reprod Biol Endocrinol. 2018;16(1):74.##Wang Y, Wan Q, Lu X, Li L, Wang H, Chen L, et al. The transfer of double morphologically good day 5 blastocysts increases the risk of clinical pregnancy loss in singleton pregnancies following frozen-thawed embryo transfer. Front Endocrinol (Lausanne). 2025;16:1508014.##

Time-Lapse Evaluation of Embryos in Non-Obstructive Azoospermia (NOA): High Rate of 1PN Fertilization and Rapid Embryo Development in TESE Compared to Ejaculated Sperm 2 1 140255 2 Background: Non-obstructive azoospermia (NOA), marked by impaired spermatogenesis, poses challenges in assisted reproduction. Limited data exist comparing chromosomal integrity of testicular versus ejaculated sperm. This study aimed to compare embryo morphokinetics, fertilization abnormalities, and PGT-A outcomes between embryos from ejaculated and testicular sperm in NOA cases. Subjects and Methods: This retrospective study analyzed 397 patients from two IVF centers (2015–2023), with 317 using ejaculated sperm and 80 using testicular sperm from NOA patients. Fertilization patterns (2PN, 1PN, ≥3PN), embryo morphokinetics, and aneuploidy rates were assessed. Logistic regression examined factors influencing aneuploidy including male and female age, recurrent implantation failure (RIF), hormone levels, and oocyte quality, while chi-square and t-tests compared groups, with significance at p<0.05. Results: Embryos derived from testicular sperm developed faster than those from ejaculated sperm (p<0.05). The 2PN fertilization rate was significantly lower, while the 1PN rate was higher in the testicular sperm group (10.1% vs. 16.4%, p=0.020). The rates of ≥3PN anomalies and embryo aneuploidy were similar between groups (p>0.05). Logistic regression identified male age (p=0.001), female age (p=0.007), and RIF (p=0.047) as significant predictors of aneuploidy. Conclusion: Our study identified advanced parental age and RIF as key predictors of embryo aneuploidy. PGT-A may improve outcomes, especially for older patients or those with RIF, regardless of sperm origin. Embryos from testicular sperm in NOA patients develop faster morphokinetically but show a higher rate of 1PN fertilization than those from ejaculated sperm. 03 13 Tulay T Irez Department of Histology and Embryology, Faculty of Medicine, Istanbul Yeni Yuzyil University Department of Histology and Embryology, Faculty of Medicine, Istanbul Yeni Yuzyil University Turkey tulay.irez@yeniyuzyil.edu.tr Yagmur YAY Ozturk Health Science Institute, Istanbul Yeni Yuzyil University Health Science Institute, Istanbul Yeni Yuzyil University Turkey Fidan F Mammadova Health Science Institute, Istanbul Yeni Yuzyil University Health Science Institute, Istanbul Yeni Yuzyil University Turkey Sirin S Kinetli Health Science Institute, Istanbul Yeni Yuzyil University Health Science Institute, Istanbul Yeni Yuzyil University Turkey Mine M Erguven Department of Medical Biochemistry, Faculty of Medicine, Istanbul Aydin University Department of Medical Biochemistry, Faculty of Medicine, Istanbul Aydin University Turkey Nurten N Dayioglu Department of Medical Statistics, Faculty of Medicine, Istanbul Yeni Yuzyil University Department of Medical Statistics, Faculty of Medicine, Istanbul Yeni Yuzyil University Turkey Hakan H Ozornek Department of Obstetrics and Gynecology, Faculty of Medicine, Koç University Department of Obstetrics and Gynecology, Faculty of Medicine, Koç University Turkey 1PN fertilizationEmbryo developmentMicro-TESENon-obstructive azoospermiaPGT-ATime-lapse imaging 140255.pdf Practice committee of the American society for reproductive medicine. Management of nonobstructive azoospermia: a committee opinion. Fertil Steril. 2018;110(7):1239-45.##Tao Y. Endocrine aberrations of human nonobstructive azoospermia. Asian J Androl. 2022;24(3):274-86.##Chen X, Ma Y, Zou S, Wang S, Qiu J, Xiao Q, et al. Comparison and outcomes of nonobstructive azoospermia patients with different etiology undergoing microTESE and ICSI treatments. Transl Androl Urol. 2019;8(4):366-73.##Tharakan T, Luo R, Jayasena CN, Minhas S. Non-obstructive azoospermia: current and future perspectives. Fac Rev. 2021;10:7.##Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999;14(1):31-5. ##Bernie AM, Mata DA, Ramasamy R, Schlegel PN. Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: A systematic review and meta-analysis. Fertil Steril. 2015;104(5):1099-103.e1-3.##Caroppo E, Colpi EM, Gazzano G, Vaccalluzzo L, Scroppo FI, D’Amato G, et al. Testicular histology may predict the successful sperm retrieval in patients with non-obstructive azoospermia undergoing conventional TESE: a diagnostic accuracy study. J Assist Reprod Genet. 2017;34(1):149-54.##McLachlan RI, Rajpert-De Meyts E, Hoei-Hansen CE, de Kretser DM, Skakkebaek NE. Histological evaluation of the human testis--approaches to optimizing the clinical value of the assessment: mini review. Hum Reprod. 2007;22(1):2-16.##Deruyver Y, Vanderschueren D, van der Aa F. Outcome of microdissection TESE compared with conventional TESE in non-obstructive azoospermia: a systematic review. Andrology. 2014;2(1):20-4.##Alkandari MH, Zini A. Medical management of non-obstructive azoospermia: a systematic review. Arab J Urol. 2021;19(3):215-20.##Koşar PA, Özçelik N, Koşar A. Cytogenetic abnormalities detected in patients with non-obstructive azoospermia and severe oligozoospermia. J Assist Reprod Genet. 2010;27(1):17-21.##Peña VN, Kohn TP, Herati AS. Genetic mutations contributing to non-obstructive azoospermia. Best Pract Res Clin Endocrinol Metab. 2020;34(6):101479.##Cerván-Martín M, Castilla JA, Palomino-Morales RJ, Carmona FD. Genetic landscape of nonobstructive azoospermia and new perspectives for the clinic. J Clin Med. 2020;9(2):300.##Wang D, Chen R, Kong S, Pan QY, Zheng YH, Qiu WJ, et al. Cytogenic and molecular studies of male infertility in cases of Y chromosome balanced reciprocal translocation. Mol Med Rep. 2017;16(2):2051-4.##Cioppi F, Rosta V, Krausz C. Genetics of azoospermia. Int J Mol Sci. 2021;22(6):3264.##Buran A, Tulay P, Dayıoğlu N, Bakircioglu ME, Bahceci M, İrez T. Evaluation of the morphokinetic parameters and development of pre-implantation embryos obtained by testicular, epididymal and ejaculate spermatozoa using time-lapse imaging system. Andrologia. 51(4):e13217.##Palermo GD, Colombero LT, Hariprashad JJ, Schlegel PN, Rosenwaks Z. Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI. Hum Reprod. 2002;17(3):570-5.##Weng SP, Surrey MW, Danzer HC, Hill DL, Chen PC, Wu TC. Chromosome abnormalities in embryos derived from microsurgical epididymal sperm aspiration and testicular sperm extraction. Taiwan J Obstet Gynecol. 2014;53(2):202-5.##Scarselli F, Casciani V, Cursio E, Muzzì S, Colasante A, Gatti S, et al. Influence of human sperm origin, testicular or ejaculated, on embryo morphokinetic development. Andrologia. 2018;50(8):e13061.##Shah R. Surgical sperm retrieval: techniques and their indications. Indian J Urol. 2011;27(1):102-9.##Practice committee of the American society for reproductive medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015;103(3):e18-25.##Van Marion ES, Speksnijder JP, Hoek J, Boellaard WP, Dinkelman-Smit M, Chavli EA, et al. Time-lapse imaging of human embryos fertilized with testicular sperm reveals an impact on the first embryonic cell cycle. Biol Reprod. 2021;104(6):1218-27.##Desai N, Ploskonka S, Goodman LR, Austin C, Goldberg J, Falcone T. Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles. Reprod Biol Endocrinol. 2014;12:54.##Desai N, Gill P, Tadros NN, Goldberg JM, Sabanegh E, Falcone T. Azoospermia and embryo morphokinetics: testicular sperm-derived embryos exhibit delays in early cell cycle events and increased arrest prior to compaction. J Assist Reprod Genet. 2018;35(7):1339-48.##Lammers J, Reignier A, Splingart C, Catteau A, David L, Barriere P, et al. Does sperm origin affect embryo morphokinetic parameters? J Assist Reprod Genet. 2015;32(9):1325-32.##Kai Y, Moriwaki H, Yumoto K, Iwata K, Mio Y. Assessment of developmental potential of human single pronucleated zygotes derived from conventional in vitro fertilization. J Assist Reprod Genet. 2018;35(8):1377-84.##Dozortsev D, De Sutter P, Dhont M. Behaviour of spermatozoa in human oocytes displaying no or one pronucleus after intracytoplasmic sperm injection. Hum Reprod. 1994;9(11):2139-44.##Goud P, Goud A, Van Oostveldt P, Van der Elst J, Dhont M. Fertilization abnormalities and pronucleus size asynchrony after intracytoplasmic sperm injection are related to oocyte postmaturity. Fertil Steril. 1999;72(2):245-52.##Van der Heijden GW, Van den Berg IM, Baart EB, Derijck AA, Martini E, De Boer P. Parental origin of chromatin in human monopronuclear zygotes revealed by asymmetric histone methylation patterns, differs between IVF and ICSI. Mol Reprod Dev. 2009;76(1):101-8.##Liao Q, Zhang Q, Feng X, Huang H, Xu H, Tian B, et al. 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Investigating the Relationship Between Semen Paraoxonase-3 Concentration, Sperm Parameters, and DNA Fragmentation in Fresh or Post-Thaw Semen of Normozoospermic Men 2 1 140258 2 Background: PON3 is associated with high-density lipoprotein (HDL) and plays a protective role against oxidative damage to low-density lipoprotein (LDL). The purpose of the current study was to investigate the effect of semen paraoxonase-3 (PON3) concentration on sperm parameters and DNA fragmentation in both fresh or post-thaw semen. Methods: This study analyzed PON3 levels in 30 normospermic semen samples obtained from men who attended Dezful Infertility Center and provided informed consent. The samples were analyzed before and after cryopreservation for sperm motility, DNA fragmentation, and seminal PON3 levels. Data analysis was performed using SPSS software and statistical differences were evaluated using ANOVA. A p≤0.05 was considered statistically significant. Results: There was no significant difference in sperm morphology (p=0.37) and count (p=0.25) before and after freezing at different levels of PON3. The highest levels of progressive motility were observed in samples with the highest PON3 concentrations both before (p=0.01) and after freezing (p=0.02), whereas non-progressive motility was significantly greater in samples with the lowest PON3 concentrations at both time points (p=0.01). Sperm DNA fragmentation significantly decreased before or after freezing as PON3 levels increased (p=0.03). Conclusion: This study suggests that PON3 levels may serve as an indicator for both sperm motility and DNA fragmentation pre- or post-cryopreservation, potentially contributing to future clinical research. 13 19 Sima S Janati Department of Obstetrics and Gynecology, School of Medicine, Research and Clinical Center for Infertility, Dezful University of Medical Sciences Department of Obstetrics and Gynecology, School of Medicine, Research and Clinical Center for Infertility, Dezful University of Medical Sciences Iran Mohammad Amin MA Behmanesh Department of Histology, School of Medicine, Dezful University of Medical Sciences Department of Histology, School of Medicine, Dezful University of Medical Sciences Iran Ehsan E Biabani Student Research Committee, Dezful University of Medical Sciences Student Research Committee, Dezful University of Medical Sciences Iran Seyedeh Mahsa SM Poormoosavi Department of Histology, School of Medicine, Dezful University of Medical Sciences Department of Histology, School of Medicine, Dezful University of Medical Sciences Iran m.poormoosavi@ymail.com DNA fragmentationParaoxonaseParaoxonaseSemen analysisSemen 140258.pdf Verit FF, Verit A, Ciftci H, Erel O, Celik H. Paraoxonase‐1 activity in subfertile men and relationship to sperm parameters. J Androl. 2009;30(2):183-9.##Marsillach J, Mackness B, Mackness M, Riu F, Beltrán R, Joven J, et al. Immunohistochemical analysis of paraoxonases-1, 2, and 3 expression in normal mouse tissues. Free Radic Biol Med. 2008;45(2):146-57.##Lazaros LA, Xita NV, Hatzi EG, Kaponis AI, Stefos TJ, Plachouras NI, et al. Association of paraoxonase gene polymorphisms with sperm parameters. J Androl. 2011;32(4):394-401.##Colás C, Junquera C, Pérez‐Pé R, Cebrián‐Pérez JA, Muiño‐Blanco T. Ultrastructural study of the ability of seminal plasma proteins to protect ram spermatozoa against cold‐shock. Microsc Res Tech. 2009;72(8):566-72.##Said TM, Gaglani A, Agarwal A. Implication of apoptosis in sperm cryoinjury. Reprod Biomed Online. 2010;21(4):456-62.##Amidi F, Pazhohan A, Shabani Nashtaei M, Khodarahmian M, Nekoonam S. The role of antioxidants in sperm freezing: a review. Cell Tissue Bank. 2016;17(4):745-56.##Ball BA. Oxidative stress, osmotic stress and apoptosis: impacts on sperm function and preservation in the horse. Anim Reprod Sci. 2008;107(3-4):257-67.##Gadea J, Molla M, Selles E, Marco M, Garcia-Vazquez F, Gardon J. Reduced glutathione content in human sperm is decreased after cryopreservation: Effect of the addition of reduced glutathione to the freezing and thawing extenders. Cryobiology. 2011;62(1):40-6.##Taylor K, Roberts P, Sanders K, Burton P. Effect of antioxidant supplementation of cryopreservation medium on post-thaw integrity of human spermatozoa. Reprod Biomed Online. 2009;18(2):184-9.##Li P, Li ZH, Dzyuba B, Hulak M, Rodina M, Linhart O. Evaluating the impacts of osmotic and oxidative stress on common carp (Cyprinus carpio, L.) sperm caused by cryopreservation techniques. Biol Reprod. 2010;83(5):852-8.##Silva SV, Soares AT, Batista AM, Almeida FC, Nunes JF, Peixoto CA, et al. In vitro and in vivo evaluation of ram sperm frozen in tris egg‐yolk and supplemented with superoxide dismutase and reduced glutathione. Reprod Domest Anim. 2011;46(5):874-81.##Lanzafame FM, La Vignera S, Vicari E, Calogero AE. Oxidative stress and medical antioxidant treatment in male infertility. Reprod Biomed Online. 2009;19(5):638-59.##Mostafa T, Anis T, Imam H, El‐Nashar A, Osman I. Seminal reactive oxygen species‐antioxidant relationship in fertile males with and without varicocele. Andrologia. 2009;41(2):125-9.##Kelly CD, Jennions MD. Sexual selection and sperm quantity: meta‐analyses of strategic ejaculation. Biol Rev Camb Philos Soc. 2011;86(4):863-84.##Kanannejad Z, Gharesi‐Fard B. Difference in the seminal plasma protein expression in unexplained infertile men with successful and unsuccessful in vitro fertilisation outcome. Andrologia. 2019;51(1):e13158.##Aitken RJ, Flanagan HM, Connaughton H, Whiting S, Hedges A, Baker MA. Involvement of homocysteine, homocysteine thiolactone, and paraoxonase type 1 (PON‐1) in the etiology of defective human sperm function. Andrology. 2016;4(2):345-60.##Efrat M, Stein A, Pinkas H, Breitbart H, Unger R, Birk R. Paraoxonase 1 (PON1) attenuates sperm hyperactivity and spontaneous acrosome reaction. Andrology. 2019;7(1):24-30.##Gong D, Li Z, Zhuang X, Zhang X, Kang M, Liao Y. [Clinical value of seminal paraoxonase-1 activity evaluation in the diagnosis of male infertility]. Nan Fang Yi Ke Da Xue Xue Bao. 2012;32(9):1355-7. Chinese.##Catalán J, Yánez-Ortiz I, Torres-Garrido M, Ribas-Maynou J, Llavanera M, Barranco I, et al. Impact of seminal plasma antioxidants on DNA fragmentation and lipid peroxidation of frozen–thawed horse sperm. Antioxidants (Basel). 2024;13(3):322.##Efrat M, Stein A, Pinkas H, Unger R, Birk R. Dietary patterns are positively associated with semen quality. Fertil Steril. 2018;109(5):809-16.##

The Impact of L-Arginine on Uterine Artery Resistance and Pregnancy Outcomes in Frozen Embryo Transfer for IVF Candidates with Recurrent Implantation Failure: A Clinical Trial 2 1 140253 2 Background: Recurrent implantation failure (RIF) refers to the inability to achieve pregnancy after two or three high-quality embryo transfers, representing a significant challenge in in vitro fertilization (IVF). In these women, endometrial perfusion is diminished, and uterine artery resistance is increased. The purpose of this study was to investigate the effect of oral L-arginine on uterine artery resistance and the results of IVF in infertile women with RIF. Methods: This clinical trial was conducted on 72 infertile women, candidates for frozen embryo transfer, with a history of two previous transfer failures, who were referred to Fatemieh Infertility Center. Patients were randomly divided into two groups of control and intervention. In addition to standard drug treatment and protocol, the intervention group received oral L-arginine supplementation (3 gr daily for 20 days), beginning from the luteal phase. Uterine artery resistance index (RI) and pulsatility index (PI) were measured using two-dimensional Doppler ultrasound. Statistical analysis was performed using SPSS software, version 26, with a significance level set at less than 5%. Results: Statistical analysis revealed a significant difference in the right uterine artery RI (p<0.05), left uterine artery RI (p<0.05), clinical pregnancy rate (p<0.05), and chemical pregnancy rate (p<0.05) between the two groups. Conclusion: This study demonstrates that the daily administration of 3 grams of oral L-arginine for 20 days in women with RIF effectively reduces uterine resistance and increases both clinical and biochemical pregnancy rates. 19 38 Faezeh F Fazli Fertility and Infertility Research Center, Hamadan University of Medical Sciences Fertility and Infertility Research Center, Hamadan University of Medical Sciences Iran Elham E Khanlarzadeh Department of Community Medicine, School of Medicine, Hamadan University of Medical Sciences Department of Community Medicine, School of Medicine, Hamadan University of Medical Sciences Iran Shamim Sh Pilehvari Fertility and Infertility Research Center, Hamadan University of Medical Sciences Fertility and Infertility Research Center, Hamadan University of Medical Sciences Iran sh.pilehvari@yahoo.com Embryo transferFemale infertilityPulsatility indexRecurrent implantation failureResistance index 140253.pdf Sirait BI, Reviani N, Udjung GI. 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Proportion and Pregnancy Outcomes of Rescued Frozen-Thawed Cycles with Low Serum Progesterone Levels: A Cross-Sectional Study 2 1 140256 2 Background: Low serum progesterone concentration on the day of frozen embryo transfer (FET) has been associated with adverse pregnancy outcomes. Progesterone supplementation has been shown to improve the outcomes in these cycles. The purpose of the current study was to investigate the prevalence, pregnancy outcomes, and factors associated with rescued FET cycles involving low serum progesterone concentrations. Methods: A cross-sectional study was conducted on 367 FET cycles with hormonal endometrium preparation (oral estradiol+vaginal progesterone) at Hung Vuong Hospital, Vietnam, from October 2022 to February 2023. Serum progesterone concentrations were measured on the day of FET. All cycles with serum progesterone <10 ng/ml were supplemented with intramuscular progesterone according to the hospital protocol, and outcomes were subsequently observed. Results: The prevalence of cycles with low serum progesterone concentration was 71.66% (263/367). Factors associated with low serum progesterone were female body weight (ORadj=1.04; 95%CI: 1.0006–1.07) and duration from the last progesterone dose to blood sampling (ORadj=1.11; 95%CI: 1.03–1.19). Despite being rescued with progesterone supplementation, cycles with serum progesterone <10 ng/ml had significantly lower chemical (ORadj=0.52; 95%CI: 0.31–0.89), clinical (ORadj=0.54; 95%CI: 0.31–0.93) and ongoing (ORadj=0.54; 95%CI: 0.31–0.94) pregnancy rates. Conclusion: A high prevalence of frozen-thawed cycles with low serum progesterone concentrations was observed in this study, which was associated with female body weight and duration from the last progesterone dose to blood sampling. Despite progesterone rescue, lower pregnancy rates were detected in cycles with serum progesterone <10 ng/ml. 28 36 Minh MPK Huynh Department of Infertility, Hung Vuong Hospital Department of Infertility, Hung Vuong Hospital Vietnam huynhminh1504@gmail.com Lan LN Vuong Department of Obstetrics and Gyncecology, University of Medicine and Pharmacy at Ho Chi Minh City Department of Obstetrics and Gyncecology, University of Medicine and Pharmacy at Ho Chi Minh City Vietnam Artificial cycleFrozen embryo transferRescueSerum progesterone 140256.pdf Pouget O, Zemmache Z, Kabani S, Alsawaf M, Zuna I, Bonneau M, et al. Comparison of serum progesterone levels on the day of frozen embryo transfers according to type of endometrial preparation: a single centre, retrospective study. Zygote. 2023;31(4):373-9.##Cédrin-Durnerin I, Isnard T, Mahdjoub S, Sonigo C, Seroka A, Comtet M, et al. Serum progesterone concentration and live birth rate in frozen-thawed embryo transfers with hormonally prepared endometrium. Reprod Biomed Online. 2019;38(3):472-80.##Labarta E, Mariani G, Paolelli S, Rodriguez-Varela C, Vidal C, Giles J, et al. Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone. Hum Reprod. 2020;36(3):683-92.##Stavridis K, Kastora SL, Triantafyllidou O, Mavrelos D, Vlahos N. Effectiveness of progesterone rescue in women presenting low circulating progesterone levels around the day of embryo transfer: a systematic review and meta-analysis. Fertil Steril. 2023;119(6):954-63.##Vuong LN, Pham TD, Le KTQ, Ly TT, Le HL, Nguyen DTN, et al. Micronized P plus dydrogesterone versus micronized P alone for luteal phase support in frozen-thawed cycles (MIDRONE): a prospective cohort study. Hum Reprod. 2021;36(7):1821-31.##Archer DF, Fahy GE, Viniegra-Sibal A, Anderson FD, Snipes W, Foldesy RG. Initial and steady-state pharmacokinetics of a vaginally administered formulation of Progesterone. Am J Obstet Gynecol. 1995;173(2):471-7.##von Eye Corleta H, Capp E, Cardoso Ferreira MB. Pharmacokinetics of natural Progesterone vaginal suppository. Gynecol Obstet Invest. 2004;58(2):105-8.##Levy T, Gurevitch S, Bar-Hava I, Ashkenazi J, Magazanik A, Homburg R, et al. Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet. Hum Reprod. 1999;14(3):606-10.##González-Foruria I, Gaggiotti-Marre S, Álvarez M, Martínez F, García S, Rodríguez I, et al. Factors associated with serum progesterone concentrations the day before cryopreserved embryo transfer in artificial cycles. Reprod Biomed Online. 2020;40(6):797-804.##Brady PC, Kaser DJ, Ginsburg ES, Ashby RK, Missmer SA, Correia KF, et al. Serum progesterone concentration on day of embryo transfer in donor oocyte cycles. J Assist Reprod Genet. 2014;31(5):569-75.##Basnayake SK, Volovsky M, Rombauts L, Osianlis T, Vollenhoven B, Healey M. Progesterone concentrations and dosage with frozen embryo transfers-what's best? Aust NZJ Obstet Gynaecol. 2018;58(5):533-8.##

The Synergistic Effect of Autophagy and Apoptosis in Iraqi Women with Polycystic Ovary Syndrome 2 1 140259 2 Background: Apoptosis and autophagy play important roles in the development and maturation of the ovaries in women. Any abnormalities in these processes may lead to conditions such as polycystic ovary syndrome (PCOS); therefore, evaluating the synergistic effects of apoptosis and autophagy in PCOS patients may explain the complexity of this disease. Methods: This study included 68 patients diagnosed with PCOS and 66 non-PCOS women as control subjects, with ages ranging from 20 to 45 years. The serum levels and gene expression of Beclin-1 and programmed cell death 1 (PD-1) were assessed using ELISA and RT-PCR, respectively. Results: Serum Beclin-1 and PD-1 levels were considerably higher in women with PCOS compared to the control group (p<0.0001). Significant overexpression of Beclin-1 and PD-1 genes was observed in PCOS patients compared to the control group (p=0.019 and <0.0001). Higher Beclin-1 and PD-1 gene expression was observed in PCOS patients over 25 compared to controls over and under 25 (p<0.05) years of age. In obese PCOS patients (waist-hip ratio >0.8), gene expression of Beclin-1 and PD-1 was significantly higher than in controls (p<0.01). Beclin-1 gene overexpression was detected in PCOS patients with a family history of PCOS compared to those without such history (p<0.05). The statistical analysis demonstrated a positive association between hormonal profile, autophagy, and apoptosis in PCOS patients. Conclusion: These findings suggest that Beclin-1 and PD-1 may have a significant role in the development of PCOS. 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Serum Levels of Angiopoietin-Like Protein 6 (ANGPTL6) in Iranian Women with Polycystic Ovary Syndrome 2 1 140260 2 Background: Infertility and miscarriage are common complications in women with PCOS, and may be linked with metabolic status and thyroid function. However, the role of ANGPTL6 in PCOS-related infertility and miscarriage remains underexplored. Study assessed serum ANGPTL6 levels in Iranian PCOS patients and its association with miscarriage, infertility, and thyroid dysfunction. Methods: This case-control study included 116 PCOS women (58 with infertility, 58 with a history of miscarriage) and 58 non-PCOS controls. The measurement of ANGPTL6, adiponectin, fasting insulin, and other hormonal parameters were measured using ELISA. Parametric data were analyzed with t-tests and ANOVA, and non-parametric data with Mann-Whitney and Kruskal-Wallis tests. Correlations were assessed using Pearson and Spearman tests. Logistic regression was used predicted PCOS risk. A p<0.05 was considered statistically significant. Results: ANGPTL6 levels were significantly higher in the PCOS group (48.72± 21.41 ng/ml) and the PCOS-miscarriage subgroup (50.16±19.57 ng/ml) compared to the non-PCOS group (41.56±14.74 ng/ml). T4 levels were significantly lower in the PCOS group (2.5±1.9 μg/dl) compared to controls (3.9±4.6 μg/dl, p<0.001). No significant correlation was found between ANGPTL6 and thyroid function tests. A positive correlation was observed between ANGPTL6 and adiponectin in the PCOS group (p<0.01). Logistic regression showed a significant association between ANGPTL6 and the risk of PCOS (OR: 1.02, 95%CI: 1.002-1.038), even after adjusting for age, body mass index (BMI), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Conclusion: Elevated ANGPTL6 levels were correlated with PCOS. Future research is needed to explore the molecular pathways linking ANGPTL6 to PCOS and its interaction with metabolic biomarkers. 50 58 Amir A Azadi Department of Anatomy, School of Medicine, Tehran University of Medical Sciences Department of Anatomy, School of Medicine, Tehran University of Medical Sciences Iran Asma A Kheirollahi Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran Iran Fardin F Amidi Department of Anatomy, School of Medicine, Tehran University of Medical Sciences Department of Anatomy, School of Medicine, Tehran University of Medical Sciences Iran Masoome M Jabarpour Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences Iran Akram A Vatannejad Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran Iran vatannejad@ut.ac.ir Maryam M Shabani Nashtaei Department of Anatomy, School of Medicine, Tehran University of Medical Sciences Department of Anatomy, School of Medicine, Tehran University of Medical Sciences Iran maryam.shabani.n@gmail.com Nariman N Moradi Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences Iran Soheila S Ansaripour Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Angiopoietin-like protein 6InfertilityMiscarriagePolycystic ovarian syndrome 140260.pdf Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. 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Severe Immune Thrombocytopenic Purpura in a Patient at 33 Weeks of Gestation: A Case Report 2 1 140261 2 Background: Immune thrombocytopenia (ITP) is an autoimmune condition that affects individuals of all ages, leading to a heightened risk of bleeding. ITP accounts for 5% of all pregnancy-related thrombocytopenia cases with an incidence of 1 in every 1,000 pregnant women. Several conditions can cause thrombocytopenia during pregnancy, making the diagnosis challenging. Current treatment of patients with ITP focuses on maintaining a safe platelet count rather than correcting it to normal levels. Case Presentation: This article presents a case of a 26-year-old patient at 33 weeks of gestation with severe symptoms of thrombocytopenia, evidenced by a platelet count of 1000/mm3. The patient experienced self-resolving episodes of gingival bleeding, vaginal bleeding, and petechiae on her abdomen, as well as on both upper and lower extremities, over a duration of three days. She was successfully managed with prednisolone and intravenous immunoglobulin (IVIG), resulting in favorable maternal and neonatal outcomes. Conclusion: While there are currently no universally accepted guidelines for the treatment of ITP, expert consensus recommendations are available. Therefore, treatment should be individualized and closely monitored. A multidisciplinary team approach is essential for the effective management of ITP during pregnancy. 58 64 Rawad R Halimeh The Centre for Reproductive and Genetic Health (CRGH) The Centre for Reproductive and Genetic Health (CRGH) UK rawad.halimeh@gmail.com Joseph J Klim Faculty of Medicine and Medical Sciences, University of Balamand Faculty of Medicine and Medical Sciences, University of Balamand Lebanon Lea L Aoude Faculty of Medicine and Medical Sciences, University of Balamand Faculty of Medicine and Medical Sciences, University of Balamand Lebanon Marianne M Bersaoui Department of Obstetrics and Gynecology, Saint George Hospital University Medical Center Department of Obstetrics and Gynecology, Saint George Hospital University Medical Center Lebanon Bernard B Najib Centre Antoine Lacassagne Centre Antoine Lacassagne France Saab S Wiam Department of Obstetrics and Gynecology, American University of Beirut Medical Center Department of Obstetrics and Gynecology, American University of Beirut Medical Center Lebanon Fadi F Fakhoury Department of Anesthesia, Montreuil Intercommunal Hospital Center Department of Anesthesia, Montreuil Intercommunal Hospital Center France Rana R Skaf Department of Obstetrics and Gynecology, Saint George Hospital University Medical Center Department of Obstetrics and Gynecology, Saint George Hospital University Medical Center Lebanon BleedingImmune thrombocytopeniaImmunoglobulinsPlatelet countPrednisolonePregnancyPurpura 140261.pdf Cooper N, Bussel J. The pathogenesis of immune thrombocytopaenic purpura. Br J Haematol. 2006; 133(4):364-74. ##Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-93. ##Amorim JG de, Abecasis MR, Rodrigues FMNL. Refractory severe thrombocytopenia during pregnancy: how to manage. Rev Bras Ginecol Obstet. 2018;40(12):803-7. ##Stavrou E, McCrae KR. Immune thrombocytopenia in pregnancy. Hematol Oncol Clin North Am. 2009; 23(6):1299-316. ##Webert KE, Mittal R, Sigouin C, Heddle NM, Kelton JG. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood. 2003;102(13):4306-11. ##British committee for standards in haematology general haematology task force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120(4):574-96. ##Godeau B, Provan D, Bussel J. Immune thrombocytopenic purpura in adults. Curr Opin Hematol. 2007; 14(5):535-56. ##Cortelazzo S, Finazzi G, Buelli M, Molteni A, Viero P, Barbui T. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood. 1991;77(1):31-3. ##Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med. 2000;160(11):1630-8. ##George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American society of hematology. Blood. 1996;88(1):3-40. ##Ferreira IJMCF, Sousa F, Vasco EM, Areia ALF de A, Moura JPAS, Carda J, et al. Severe immune thrombocytopenia in pregnancy treated with Eltrombopaga case report. J Gynecol Obstet Hum Reprod. 2018;47(8):405-8. ##Sieunarine K, Shapiro S, Al Obaidi MJ, Girling J. Intravenous anti-D immunoglobulin in the treatment of resistant immune thrombocytopenic purpura in pregnancy. BJOG. 2007;114(4):505-7. ##Veneri D, Franchini M, Raffaelli R, Musola M, Memmo A, Franchi M, et al. Idiopathic thrombocytopenic purpura in pregnancy: analysis of 43 consecutive cases followed at a single Italian institution. Ann Hematol. 2006;85(8):552-4. ##Gilmore KS, McLintock C. Maternal and fetal outcomes of primary immune thrombocytopenia during pregnancy: a retrospective study. Obstet Med. 2018;11(1):12-6.##Wegnelius G, Bremme K, Lindqvist PG, on the behalf of Hem-ARG, a reference, working group of obstetricians regarding hematological issues in Obstetrics, gynecology under the auspices of the Swedish society of obstetrics, gynecology. Efficacy of treatment immune thrombocytopenic purpura in pregnancy with corticosteroids and intravenous immunoglobulin: a prospective follow-up of suggested practice. Blood Coagul Fibrinolysis. 2018; 29(2):141-7. ##Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood. 2013;121 (1):38-47. ##Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytepenia. Blood. 2010;115(2):168-86. ##Bussel J. Intravenous immune serum globulin in immune thrombocytopenia: clinical results and biochemical evaluation. Vox Sang. 1985;49 Suppl 1:44-50. ##Spahr JE, Rodgers GM. Treatment of immune-mediated thrombocytopenia purpura with con-current intravenous immunoglobulin and platelet transfusion: a retrospective review of 40 patients. Am J Hematol. 2008;83(2):122-5.##Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA, et al. 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Management of Recurrent Large Bilateral Benign Mucinous Cystadenomas of the Ovary: A Case Report 2 1 140257 2 Background: The recurrence of benign ovarian mucinous cystadenomas is rare, and the presence of these cysts bilaterally is even more uncommon. Overall, 11 cases in our literature review were identified. Of these recurrences, only two cases were bilateral. The management of ovarian cysts in young patients is challenging, especially if they recur. Laparoscopic surgery is the most common intervention for ovarian cysts and a conservative approach using ovarian cystectomy is preferred in women in the reproductive age group. Case Presentation: A 16-year-old nulliparous female was admitted with persistent lower abdominal pain and bloating. A pelvic magnetic resonance imaging showed large bilateral cystic and multiloculated adnexal masses arising from her ovaries. Her tumor markers were normal. The patient underwent three seperate ovarian cystectomies over a seven-year period from the age of sixteen due to recurrent large bilateral benign ovarian mucinous cystadenomas. Repeated histological examinations were the same after each case. Given her age and the history of multiple ovarian surgeries, she was referred to the fertility clinic to explore options for oocyte cryopreservation. Conclusion: This unusual case of bilateral recurrent benign ovarian mucinous cystadenomas underscores the importance of early laparoscopy and cystectomy as a recommended approach. Postoperative transvaginal ultrasound scans during follow-up may assist in the early detection of recurrence cases. Clinicians should strongly consider referring young patients with a history of repeated adnexal surgeries to infertility treatment centers for fertility preservation. 64 69 Miyuki M Omura Barnsley Hospital NHS Foundation Trust, Obstetrics and Gynaecology Department, Barnsley Hospital Barnsley Hospital NHS Foundation Trust, Obstetrics and Gynaecology Department, Barnsley Hospital UK miyukiomura@gmail.com Rupak RK Sarkar Barnsley Hospital NHS Foundation Trust, Obstetrics and Gynaecology Department, Barnsley Hospital Barnsley Hospital NHS Foundation Trust, Obstetrics and Gynaecology Department, Barnsley Hospital UK Ajesh A Sankar Barnsley Hospital NHS Foundation Trust, Obstetrics and Gynaecology Department, Barnsley Hospital Barnsley Hospital NHS Foundation Trust, Obstetrics and Gynaecology Department, Barnsley Hospital UK FertilityGynaecologyOvarian mucinous cystadenomaReproductive medicine 140257.pdf El-Agwany AS. Recurrent bilateral mucinous cystadenoma: laparoscopic ovarian cystectomy with review of literature. Indian J Surg Oncol. 2018;9(2):146-9. ##Brown J, Frumovitz M. Mucinous tumors of the ovary: current thoughts on diagnosis and management. Curr Oncol Rep. 2014;16(6):389.##Gotoh T, Hayashi N, Takeda S, Itoyama S, Takano M, Kikuchi Y. Synchronous mucinous adenocarcinoma of the endometrium and mucinous cystadenoma of bilateral ovaries presenting during fertility therapy. Int J Gynecol Cancer. 2004;14(1):169-71. ##Marko J, Marko KI, Pachigolla SL, Crothers BA, Mattu R, Wolfman DJ. Mucinous neoplasms of the ovary: radiologic-pathologic correlation. Radio-graphics. 2019;39(4):982-97. ##Ben-Ami I, Smorgick N, Tovbin J, Fuchs N, Halperin R, Pansky M. Does intraoperative spillage of benign ovarian mucinous cystadenoma increase its recurrence rate? Am J Obstet Gynecol. 2010;202(2):142.e1-5.##Olesen H EAK. [Recurrent mucineous cystadenoma in an 11-year-old premenarchal girl]. Ugeskr Laeger. 2001;163(47):6001-2. Danish.##Baksu B, Akyol A, Davas I, Yazgan A, Ozgul J, Tanik C. Recurrent mucinous cystadenoma in a 20-year-old woman: Was hysterectomy inevitable? J Obstet Gynaecol Res. 2006;32(6):615-8. ##Mittal S, Gupta N, Sharma AK, Dadhwal V. Laparoscopic management of a large recurrent benign mucinous cystadenoma of the ovary. Arch Gynecol Obstet. 2008;277(4):379-80.##Turkyilmaz E, Korucuoglu U, Kutlusoy F, Efeturk T, Dogan HT, Onan A, et al. Recurrent mucinous cystadenoma: a laparoscopic approach. Arch Gynecol Obstet. 2009;279(3):387-9. ##Fujishima A, Kumazawa Y, Togashi K, Shirasawa H, Sato W, Terada Y. A case of ovarian mucinous cystadenoma in a child that recurred 1 year after surgery. Int J Surg Case Rep. 2021;83:106006. ##Mizrachi Y, Weiner E, Keidar R, Kerner R, Golan A, Sagiv R. Intraoperative rupture of benign mucinous cystadenoma does not increase its recurrence rate. Arch Gynecol Obstet. 2015;291(5):1135-9. ##Salat-Baroux J, Merviel PH, Kuttenn F. Management of ovarian cysts. BMJ. 1996;313(7065):1098. ##Alobaid A, Memon A, Alobaid S, Aldakhil L. Laparoscopic management of huge ovarian cysts. Obstet Gynecol Int. 2013;2013:380854. ##Royal college of obstetricians and gynaecologists. Management of suspected ovarian masses in premenopausal women: green-top guideline no. 62. London: RCOG Press; 2011.##