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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Analysis of the Growth and Development of Children Born with ICSI of Epididymal and Testicular Spermatozoa: A Propensity Matching Study

Author(s): Chunmei Yu, Chao Zhou, Feng Lin, Wanchao Zhang, Xiaoyu Wang, Lingmin Hu* and Renjie Lu*

Volume 29, Issue 33, 2023

Published on: 31 October, 2023

Page: [2668 - 2678] Pages: 11

DOI: 10.2174/0113816128264448231022201641

Price: $65

Abstract

Objective: The study aimed to evaluate whether singleton live births (at 0, 1, 6, 12, and 24 months) following intracytoplasmic sperm injection (ICSI) using sperm of different origins (ejaculated or non-ejaculated sperm) are associated with the growth and development of children born.

Methods: This was a retrospective cohort study conducted at a single center from January 2016 to December 2019. Follow-up data of the children were obtained from the Jiangsu Province Maternal and Child database. A total of 350 singleton live births after fresh embryo transfer (ET) with ICSI were included. Based on the origin of the sperm, the patients were divided into two groups: the ejaculated group (n = 310) and the non-ejaculated group (n = 40). Propensity score matching was used to control for multiple baseline covariates, resulting in 80 singleton live births (ejaculated sperm) matched to 40 singleton live births (non-ejaculated). The non-ejaculated group was further divided into two subgroups: the PESA group (n = 23) and the TESA group (n = 17). The primary outcome of the study was the growth and development of children. Secondary outcomes included the 2PN rate, high-cleavage embryo rate, blastocyst formation rate, and others.

Results: After matching parental age, BMI, occupation, and maternal serum AMH level, there was no significant difference found in the growth and development of children between the non-ejaculated and ejaculated group or the PESA group and TESA group, respectively. However, the 2PN rate and the blastocyst formation rate were higher in the ejaculated group compared to the non-ejaculated group (91.02 and 85.45, P = 0.002) and (67.37 and 56.06, P = 0.019), respectively. The high-quality cleavage embryo rate was also higher in the TESA group compared to the PESA group (85.06 and 65.63, P = 0.001).

Conclusion: This study suggests that there are no significant differences in the growth and development of children born following ICSI using sperm of different origins (ejaculated or non-ejaculated). For nonobstructive azoospermia (OA) patients, sperm derived from the testis may be more effective than derived from the epididymis. However, due to the limited sample size of the non-ejaculated group in this study, further investigations with larger sample sizes are needed to validate these findings.

« Previous
[1]
Moutel G, Hervé C, Tritto J, Boucaya V, Le Roux N. [Intracytoplasmic injection of spermatozoa (ICSI). Ethical requirements and assessment]. Presse Med 1996; 25(21): 989-93.
[PMID: 8692778]
[2]
Westlander G. Utility of micro-TESE in the most severe cases of non-obstructive azoospermia. Ups J Med Sci 2020; 125(2): 99-103.
[http://dx.doi.org/10.1080/03009734.2020.1737600] [PMID: 32233715]
[3]
Mansour R. Intracytoplasmic sperm injection: A state of the art technique. Hum Reprod Update 1998; 4(1): 43-56.
[http://dx.doi.org/10.1093/humupd/4.1.43] [PMID: 9622412]
[4]
Platteau P, Staessen C, Michiels A, et al. Comparison of the aneuploidy frequency in embryos derived from testicular sperm extraction in obstructive and non-obstructive azoospermic men. Hum Reprod 2004; 19(7): 1570-4.
[http://dx.doi.org/10.1093/humrep/deh306] [PMID: 15142999]
[5]
Sciorio R, Esteves SC. Contemporary use of ICSI and epigenetic risks to future generations. J Clin Med 2022; 11(8): 2135.
[http://dx.doi.org/10.3390/jcm11082135] [PMID: 35456226]
[6]
Staessen C, Tournaye H, Van Assche E, et al. PGD in 47,XXY Klinefelter’s syndrome patients. Hum Reprod Update 2003; 9(4): 319-30.
[http://dx.doi.org/10.1093/humupd/dmg029] [PMID: 12926526]
[7]
Zhang XY, Li HJ. [Medicinal treatment of idiopathic male infertility]. Zhonghua Nan Ke Xue 2008; 14(10): 939-42.
[PMID: 19157110]
[8]
Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 1992; 340(8810): 17-8.
[http://dx.doi.org/10.1016/0140-6736(92)92425-F] [PMID: 1351601]
[9]
Ald M, Niederberger CS, Ross LS. Surgical sperm retrieval for assisted reproduction. Minerva Ginecol 2004; 56(3): 217-22.
[PMID: 15258533]
[10]
Practice Committee of the American Society for Reproductive Medicine in Collaboration with the Society for Male Reproduction and Urology. Electronic address: asrm@asrm.org. The management of obstructive azoospermia: A committee opinion. Fertil Steril 2019; 111(5): 873-80.
[http://dx.doi.org/10.1016/j.fertnstert.2019.02.013] [PMID: 31029241]
[11]
Iammarrone E, Balet R, Lower AM, Gillott C, Grudzinskas JG. Male infertility. Best Pract Res Clin Obstet Gynaecol 2003; 17(2): 211-29.
[http://dx.doi.org/10.1016/S1521-6934(02)00147-5] [PMID: 12758096]
[12]
Brant A, Schlegel PN. Modern surgical treatment of azoospermia. Curr Opin Urol 2023; 33(1): 39-44.
[http://dx.doi.org/10.1097/MOU.0000000000001055] [PMID: 36301052]
[13]
Esteves S. Clinical management of infertile men with nonobstructive azoospermia. Asian J Androl 2015; 17(3): 459-70.
[http://dx.doi.org/10.4103/1008-682X.148719] [PMID: 25677138]
[14]
Minhas S, Bettocchi C, Boeri L, et al. European association of urology guidelines on male sexual and reproductive health: 2021 update on male infertility. Eur Urol 2021; 80(5): 603-20.
[http://dx.doi.org/10.1016/j.eururo.2021.08.014] [PMID: 34511305]
[15]
Borges E Jr, Souza A, Braga DPAF, Iaconelli A Jr. Successful twin pregnancy with intracytoplasmic sperm injection using surgical sperm retrieval after 25 years of vasectomy: A case report. JBRA Assist Reprod 2020; 24(1): 87-8.
[PMID: 31589390]
[16]
Tournaye H, Camus M, Vandervorst M, et al. Surgical sperm retrieval for intracytoplasmic sperm injection. Int J Androl 1997; 20(S3): 69-73.
[PMID: 9466189]
[17]
Esteves SC. An update on sperm retrieval techniques for azoospermic males. Clinics 2013; 68(S1): 99-110.
[http://dx.doi.org/10.6061/clinics/2013(Sup01)11]
[18]
Cioppi F, Rosta V, Krausz C. Genetics of azoospermia. Int J Mol Sci 2021; 22(6): 3264.
[http://dx.doi.org/10.3390/ijms22063264] [PMID: 33806855]
[19]
Zhao L, Yao C, Xing X, et al. Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells. Nat Commun 2020; 11(1): 5683.
[http://dx.doi.org/10.1038/s41467-020-19414-4] [PMID: 33173058]
[20]
Fedder J, Carlsen E, Jørgensen N, Jensen CFS. Treatment of male infertility. Ugeskr Laeger 2021; 183(48): V05210402.
[PMID: 34852902]
[21]
Krausz C, Riera-Escamilla A, Moreno-Mendoza D, et al. Genetic dissection of spermatogenic arrest through exome analysis: Clinical implications for the management of azoospermic men. Genet Med 2020; 22(12): 1956-66.
[http://dx.doi.org/10.1038/s41436-020-0907-1] [PMID: 32741963]
[22]
Caroppo E, Colpi GM. Update on the management of non-obstructive azoospermia: Current evidence and unmet needs. J Clin Med 2021; 11(1): 62.
[http://dx.doi.org/10.3390/jcm11010062] [PMID: 35011799]
[23]
Cao DH, Rong WL, Liu LR, Wei Q. Advances in the study of vasovasostomy under the microscope. Zhonghua Nan Ke Xue 2022; 28(3): 239-42.
[PMID: 37462963]
[24]
Ørstavik KH. Genetic causes of male infertility. Tidsskr Nor Laegeforen 2008; 128(3): 324-6.
[PMID: 18264159]
[25]
Wosnitzer M, Goldstein M, Hardy MP. Review of azoospermia. Spermatogenesis 2014; 4(1): e28218.
[http://dx.doi.org/10.4161/spmg.28218] [PMID: 25105055]
[26]
Zhankina R, Baghban N, Askarov M, et al. Mesenchymal stromal/stem cells and their exosomes for restoration of spermatogenesis in non-obstructive azoospermia: A systemic review. Stem Cell Res Ther 2021; 12(1): 229.
[http://dx.doi.org/10.1186/s13287-021-02295-9] [PMID: 33823925]
[27]
Sharma M, Leslie SW. Disclosure: Stephen Leslie declares no relevant financial relationships with ineligible companies. Azoospermia. Treasure Island: StatPearls 2023.
[28]
Robin G, Boitrelle F, Leroy X, et al. [Assessment of azoospermia and histological evaluation of spermatogenesis]. Ann Pathol 2010; 30(3): 182-95.
[http://dx.doi.org/10.1016/j.annpat.2010.03.015] [PMID: 20621595]
[29]
Coward RM, Mills JN. A step-by-step guide to office-based sperm retrieval for obstructive azoospermia. Transl Androl Urol 2017; 6(4): 730-44.
[http://dx.doi.org/10.21037/tau.2017.07.15] [PMID: 28904906]
[30]
Miyaoka R, Orosz JE, Achermann AP, Esteves SC. Methods of surgical sperm extraction and implications for assisted reproductive technology success. Panminerva Med 2019; 61(2): 164-77.
[http://dx.doi.org/10.23736/S0031-0808.18.03508-5] [PMID: 29962187]
[31]
Ou L, Guo YH, Sun YP, Su YC. Outcomes of ICSI with microamount frozen-thawed sperm obtained by PESA or TESA in the treatment of azoospermia. Zhonghua Nan Ke Xue 2010; 16(4): 328-32.
[PMID: 20626161]
[32]
de Cássia Savio Figueira R, Madaschi C, Nichi M, et al. A comparison of post-thaw results between embryos arising from intracytoplasmic sperm injection using surgically retrieved or ejaculated spermatozoa. Fertil Steril 2009; 91(3): 727-32.
[http://dx.doi.org/10.1016/j.fertnstert.2007.12.063] [PMID: 18281039]
[33]
Lisek EW, Levine LA. Percutaneous technique for aspiration of sperm from the epididymis and testicle. Tech Urol 1997; 3(2): 81-5.
[PMID: 9297767]
[34]
Sullivan R, Mieusset R. The human epididymis: Its function in sperm maturation. Hum Reprod Update 2016; 22(5): 574-87.
[http://dx.doi.org/10.1093/humupd/dmw015] [PMID: 27307387]
[35]
Ozkocer SE, Konac E. The current perspective on genetic and epigenetic factors in sperm maturation in the epididymis. Andrologia 2021; 53(3): e13989.
[http://dx.doi.org/10.1111/and.13989] [PMID: 33491190]
[36]
Barrachina F, Battistone MA, Castillo J, et al. Sperm acquire epididymis-derived proteins through epididymosomes. Hum Reprod 2022; 37(4): 651-68.
[http://dx.doi.org/10.1093/humrep/deac015] [PMID: 35137089]
[37]
Chen H, Alves MBR, Belleannée C. Contribution of epididymal epithelial cell functions to sperm epigenetic changes and the health of progeny. Hum Reprod Update 2021; 28(1): 51-66.
[http://dx.doi.org/10.1093/humupd/dmab029] [PMID: 34618012]
[38]
Shum W, Zhang BL, Cao AS, et al. Calcium homeostasis in the epididymal microenvironment: Is extracellular calcium a cofactor for matrix gla protein-dependent scavenging regulated by vitamins. Front Cell Dev Biol 2022; 10: 827940.
[http://dx.doi.org/10.3389/fcell.2022.827940] [PMID: 35252193]
[39]
Hinton BT. The epididymal microenvironment: A site of attack for a male contraceptive? Invest Urol 1980; 18(1): 1-10.
[PMID: 6773905]
[40]
Rompala GR, Ferguson C, Homanics GE. Coincubation of sperm with epididymal extracellular vesicle preparations from chronic intermittent ethanol-treated mice is sufficient to impart anxiety-like and ethanol-induced behaviors to adult progeny. Alcohol 2020; 87: 111-20.
[http://dx.doi.org/10.1016/j.alcohol.2020.05.001] [PMID: 32445808]
[41]
Cheung S, Schlegel PN, Rosenwaks Z, Palermo GD. Revisiting aneuploidy profile of surgically retrieved spermatozoa by whole exome sequencing molecular karyotype. PLoS One 2019; 14(1): e0210079.
[http://dx.doi.org/10.1371/journal.pone.0210079] [PMID: 30608972]
[42]
Lee JY, Dada R, Sabanegh E, Carpi A, Agarwal A. Role of genetics in azoospermia. Urology 2011; 77(3): 598-601.
[http://dx.doi.org/10.1016/j.urology.2010.10.001] [PMID: 21195467]
[43]
Esteves SC, Roque M, Bedoschi G, Haahr T, Humaidan P. Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nat Rev Urol 2018; 15(9): 535-62.
[http://dx.doi.org/10.1038/s41585-018-0051-8] [PMID: 29967387]
[44]
Wu X, Lin D, Sun F, Cheng CY. Male infertility in humans: An update on non-obstructive azoospermia (noa) and obstructive azoospermia (OA). Adv Exp Med Biol 2021; 1381: 161-73.
[http://dx.doi.org/10.1007/978-3-030-77779-1_8] [PMID: 34453736]
[45]
Wosnitzer MS. Genetic evaluation of male infertility. Transl Androl Urol 2014; 3(1): 17-26.
[PMID: 26813518]
[46]
Legoff L, D’Cruz SC, Tevosian S, Primig M, Smagulova F. Transgenerational inheritance of environmentally induced epigenetic alterations during mammalian development. Cells 2019; 8(12): 1559.
[http://dx.doi.org/10.3390/cells8121559] [PMID: 31816913]
[47]
Guo YH, Dong RN, Su YC, Li J, Zhang YJ, Sun YP. Follow-up of children born after intracytoplasmic sperm injection with epididymal and testicular spermatozoa. Chin Med J 2013; 126(11): 2129-33.
[PMID: 23769571]
[48]
Fedder J, Loft A, Parner ET, Rasmussen S, Pinborg A. Neonatal outcome and congenital malformations in children born after ICSI with testicular or epididymal sperm: A controlled national cohort study. Hum Reprod 2013; 28(1): 230-40.
[http://dx.doi.org/10.1093/humrep/des377] [PMID: 23154066]
[49]
Woldringh GH, Besselink DE, Tillema AHJ, Hendriks JCM, Kremer JAM. Karyotyping, congenital anomalies and follow-up of children after intracytoplasmic sperm injection with non-ejaculated sperm: A systematic review. Hum Reprod Update 2010; 16(1): 12-9.
[http://dx.doi.org/10.1093/humupd/dmp030] [PMID: 19700489]
[50]
Halliday J. Outcomes for offspring of men having ICSI for male factor infertility. Asian J Androl 2012; 14(1): 116-20.
[http://dx.doi.org/10.1038/aja.2011.71] [PMID: 22157986]
[51]
Belva F, De Schrijver F, Tournaye H, et al. Neonatal outcome of 724 children born after ICSI using non-ejaculated sperm. Hum Reprod 2011; 26(7): 1752-8.
[http://dx.doi.org/10.1093/humrep/der121] [PMID: 21511713]
[52]
Chinta P, Deepti MK, Reka K, Karthikeyan M, Kunjummen A, Kamath M. Perinatal outcomes using ejaculate versus surgical sperm retrieval in patients undergoing intracytoplasmic sperm injection for male infertility – A retrospective analysis of 628 cycles. J Hum Reprod Sci 2021; 14(1): 49-55.
[http://dx.doi.org/10.4103/jhrs.jhrs_197_20] [PMID: 34083992]
[53]
Oldereid NB, Hanevik HI, Bakkevig I, et al. Pregnancy outcome according to male diagnosis after ICSI with non-ejaculated sperm compared with ejaculated sperm controls. Reprod Biomed Online 2014; 29(4): 417-23.
[http://dx.doi.org/10.1016/j.rbmo.2014.06.009] [PMID: 25131554]
[54]
Woldringh GH, Horvers M, Janssen AJWM, et al. Follow-up of children born after ICSI with epididymal spermatozoa. Hum Reprod 2011; 26(7): 1759-67.
[http://dx.doi.org/10.1093/humrep/der136] [PMID: 21531993]
[55]
Alkandari MH, Moryousef J, Phillips S, Zini A. Testicular sperm aspiration (TESA) or microdissection testicular sperm extraction (Micro–tese): Which approach is better in men with cryptozoospermia and severe oligozoospermia? Urology 2021; 154: 164-9.
[http://dx.doi.org/10.1016/j.urology.2021.04.037] [PMID: 33991573]
[56]
Wu Y, Ying Y, Cao M, Liu J, Liu H. Trophectoderm biopsy of blastocysts for a preimplantation genetic test does not affect serum β-hCG levels in early pregnancy: A study using propensity score matching. J Ovarian Res 2021; 14(1): 78.
[http://dx.doi.org/10.1186/s13048-021-00824-x] [PMID: 34116694]
[57]
Tsai CC, Huang FJ, Wang LJ, et al. Clinical outcomes and development of children born after intracytoplasmic sperm injection (ICSI) using extracted testicular sperm or ejaculated extreme severe oligo-astheno-teratozoospermia sperm: a comparative study. Fertil Steril 2011; 96(3): 567-71.
[http://dx.doi.org/10.1016/j.fertnstert.2011.06.080] [PMID: 21880275]
[58]
Hafhouf E, Taar JP, Demouzon J, Tibi C, Lévy R. ICSI with non-ejaculated sperm: What about children?. Gynécol Obstét Fertil 2009; 37(11-12): 873-83.
[http://dx.doi.org/10.1016/j.gyobfe.2009.09.007] [PMID: 19818669]
[59]
Jin L, Li Z, Gu L, Huang B. Neonatal outcome of children born after ICSI with epididymal or testicular sperm: A 10-year study in China. Sci Rep 2020; 10(1): 5145.
[http://dx.doi.org/10.1038/s41598-020-62102-y] [PMID: 32198466]
[60]
Sadeghi N, Boissonneault G, Tavalaee M, Nasr-Esfahani MH. Oxidative versus reductive stress: A delicate balance for sperm integrity. Syst Biol Reprod Med 2023; 69(1): 20-31.
[http://dx.doi.org/10.1080/19396368.2022.2119181] [PMID: 36215401]
[61]
Moubasher AE, Taha EA, Younis A, Fakhry ME, Morsy H. Testicular tissue oxidative stress in azoospermic patients: Effect of cryopreservation. Andrologia 2020; 52(11): e13817.
[http://dx.doi.org/10.1111/and.13817] [PMID: 32920894]
[62]
Cito G, Becatti M, Natali A, et al. Redox status assessment in infertile patients with non-obstructive azoospermia undergoing testicular sperm extraction: A prospective study. Andrology 2020; 8(2): 364-71.
[http://dx.doi.org/10.1111/andr.12721] [PMID: 31654557]
[63]
Suganuma R, Yanagimachi R, Meistrich ML. Decline in fertility of mouse sperm with abnormal chromatin during epididymal passage as revealed by ICSI. Hum Reprod 2005; 20(11): 3101-8.
[http://dx.doi.org/10.1093/humrep/dei169] [PMID: 16037114]
[64]
Zhang J, Xue H, Qiu F, Zhong J, Su J. Testicular spermatozoon is superior to ejaculated spermatozoon for intracytoplasmic sperm injection to achieve pregnancy in infertile males with high sperm DNA damage. Andrologia 2019; 51(2): e13175.
[http://dx.doi.org/10.1111/and.13175] [PMID: 30474187]
[65]
Bradley CK, McArthur SJ, Gee AJ, Weiss KA, Schmidt U, Toogood L. Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: A retrospective analysis. Andrology 2016; 4(5): 903-10.
[http://dx.doi.org/10.1111/andr.12215] [PMID: 27231097]
[66]
Hervas I, Gil Julia M, Rivera-Egea R, Navarro-Gomezlechon A, Mossetti L, Garrido N. Switching to testicular sperm after a previous ICSI failure with ejaculated sperm significantly improves blastocyst quality without increasing aneuploidy risk. J Assist Reprod Genet 2022; 39(10): 2275-85.
[http://dx.doi.org/10.1007/s10815-022-02595-w] [PMID: 35972585]
[67]
Esteves SC, Roque M, Bradley CK, Garrido N. Reproductive outcomes of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with high levels of DNA fragmentation in semen: Systematic review and meta-analysis. Fertil Steril 2017; 108(3): 456-467.e1.
[http://dx.doi.org/10.1016/j.fertnstert.2017.06.018] [PMID: 28865546]
[68]
Arafa M, AlMalki A, AlBadr M, et al. ICSI outcome in patients with high DNA fragmentation: Testicular versus ejaculated spermatozoa. Andrologia 2018; 50(1): e12835.
[http://dx.doi.org/10.1111/and.12835] [PMID: 28497461]
[69]
Esteves SC, Sánchez-Martín F, Sánchez-Martín P, Schneider DT, Gosálvez J. Comparison of reproductive outcome in oligozoospermic men with high sperm DNA fragmentation undergoing intracytoplasmic sperm injection with ejaculated and testicular sperm. Fertil Steril 2015; 104(6): 1398-405.
[http://dx.doi.org/10.1016/j.fertnstert.2015.08.028] [PMID: 26428305]
[70]
O’Connell M, McClure N, Lewis SEM. Mitochondrial DNA deletions and nuclear DNA fragmentation in testicular and epididymal human sperm. Hum Reprod 2002; 17(6): 1565-70.
[http://dx.doi.org/10.1093/humrep/17.6.1565] [PMID: 12042279]
[71]
O’Connell M, McClure N, Lewis SEM. A comparison of mitochondrial and nuclear DNA status in testicular sperm from fertile men and those with obstructive azoospermia. Hum Reprod 2002; 17(6): 1571-7.
[http://dx.doi.org/10.1093/humrep/17.6.1571] [PMID: 12042280]
[72]
Dozortsev D, Neme R, Diamond MP, et al. Embryos generated using testicular spermatozoa have higher developmental potential than those obtained using epididymal spermatozoa in men with obstructive azoospermia. Fertil Steril 2006; 86(3): 606-11.
[http://dx.doi.org/10.1016/j.fertnstert.2006.01.036] [PMID: 16952508]
[73]
Ben-Ami I, Raziel A, Strassburger D, Komarovsky D, Ron-El R, Friedler S. Intracytoplasmic sperm injection outcome of ejaculated versus extracted testicular spermatozoa in cryptozoospermic men. Fertil Steril 2013; 99(7): 1867-71.
[http://dx.doi.org/10.1016/j.fertnstert.2013.02.025] [PMID: 23490166]
[74]
Gilman AR, Younes G, Tannus S, Son WY, Chan P, Buckett W. Does using testicular sperm retrieval rather than ejaculated spermatozoa improve reproductive outcomes in couples with previous ART failure and poor ovarian response? A case-controlled study. Andrology 2018; 6(1): 142-5.
[http://dx.doi.org/10.1111/andr.12447] [PMID: 29195015]
[75]
Fedder J, Gabrielsen A, Humaidan P, Erb K, Ernst E, Loft A. Malformation rate and sex ratio in 412 children conceived with epididymal or testicular sperm. Hum Reprod 2007; 22(4): 1080-5.
[http://dx.doi.org/10.1093/humrep/del488] [PMID: 17224411]
[76]
Huang B, Qian K, Li Z, et al. Neonatal outcomes after early rescue intracytoplasmic sperm injection: An analysis of a 5-year period. Fertil Steril 2015; 103(6): 1432-1437.e1.
[http://dx.doi.org/10.1016/j.fertnstert.2015.02.026] [PMID: 25813286]

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