{"paper_id":"0e84f1e3-e333-44a2-9405-d878b426c261","body_text":"Adenomyosis and it's impact of female infertility\nDOI:\nhttps://doi.org/10.12775/JEHS.2025.80.59352Keywords\nAdenomyosis, Infertility, Fertility, Reproductive outcome, TreatmentAbstract\nIntroduction: The aim of this review is to explore the relationship between adenomyosis and infertility. The issue of adenomyosis and infertility is the subject of numerous scientific studies due to the mechanisms that may establish a correlation between them. These mechanisms present a dilemma for many researchers, and efforts to address it lead to increasingly innovative solutions for treating infertility and improving the reproductive health of women diagnosed with adenomyosis.\nMaterial and methods: We have gathered the available materials and scientific reports, analyzing and summarizing them in a single study. An English-language literature review was conducted. We analysed studies from PubMed up to October 2024 regarding the correlation between adenomyosis and infertility.\nAim of study: We aimed to summarize the studies conducted so far by analyzing the available scientific reports to answer the question about adenomyosis correlation in infertility and understand it.\nConclusion: The article examines the relationship between adenomyosis and infertility, emphasizing its negative impact on the reproductive potential of women of reproductive age. Adenomyosis reduces pregnancy rates, increases the risk of miscarriages, and hinders embryo implantation, particularly in patients undergoing assisted reproductive techniques. Long protocols with GnRH analogs can improve treatment outcomes in both medical procedures and natural conception attempts. Surgical treatment may enhance fertility but carries risks of complications, and the effectiveness of surgery remains a topic of debate. Accurate diagnosis, appropriate therapy, and improved prenatal care for patients with adenomyosis are essential. Further research, including randomized controlled trials (RCTs), is needed to better understand the impact of adenomyosis on fertility and to develop effective treatment methods.\nReferences\n1. Aleksandrovych V, Basta P, Gil K. Current facts constituting an understanding of the nature of adenomyosis. Adv Clin Exp Med. 2019 Jun;28(6):839-846. https://doi.org/10.17219/acem/79176\n2. Donnez J, Donnez O, Dolmans MM. Introduction: Uterine adenomyosis, another enigmatic disease of our time. Fertil Steril. 2018 Mar;109(3):369-370. https://doi.org/10.1016/j.fertnstert.2018.01.035\n3. Garcia L, Isaacson K. Adenomyosis: review of the literature. J Minim Invasive Gynecol. 2011 Jul-Aug;18(4):428-37. https://doi.org/10.1016/j.jmig.2011.04.004\n4. Vercellini P, Viganò P, Somigliana E, Daguati R, Abbiati A, Fedele L. Adenomyosis: epidemiological factors. Best Pract Res Clin Obstet Gynaecol. 2006 Aug;20(4):465-77. https://doi.org/10.1016/j.bpobgyn.2006.01.017\n5. Tan J, Yong P, Bedaiwy MA. A critical review of recent advances in the diagnosis, classification, and management of uterine adenomyosis. Curr Opin Obstet Gynecol. 2019 Aug;31(4):212-221. https://doi.org/10.1097/gco.0000000000000555\n6. Yeniel O, Cirpan T, Ulukus M, Ozbal A, Gundem G, Ozsener S, Zekioglu O, Yilmaz H. Adenomyosis: prevalence, risk factors, symptoms and clinical findings. Clin Exp Obstet Gynecol. 2007;34(3):163-7.\n7. Martone S, Centini G, Exacoustos C, Zupi E, Afors K, Zullo F, Maneschi F, Habib N, Lazzeri L. Pathophysiologic mechanisms by which adenomyosis predisposes to postpartum haemorrhage and other obstetric complications. Med Hypotheses. 2020 Oct;143:109833. https://doi.org/10.1016/j.mehy.2020.109833\n8. Vannuccini S, Petraglia F. Recent advances in understanding and managing adenomyosis. F1000Res. 2019 Mar 13;8:F1000 Faculty Rev-283. https://doi.org/10.12688/f1000research.17242.1\n9. Abu Hashim H, Elaraby S, Fouda AA, Rakhawy ME. The prevalence of adenomyosis in an infertile population: a cross-sectional study. Reprod Biomed Online. 2020 Jun;40(6):842-850. https://doi.org/10.1016/j.rbmo.2020.02.011\n10. García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018 Mar;109(3):371-379. https://doi.org/10.1016/j.fertnstert.2017.12.030\n11. Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G. Adenomyosis in endometriosis--prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod. 2005 Aug;20(8):2309-16. https://doi.org/10.1093/humrep/dei021\n12. Peric H, Fraser IS. The symptomatology of adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006 Aug;20(4):547-55. https://doi.org/10.1016/j.bpobgyn.2006.01.006\n13. Ferenczy A. Pathophysiology of adenomyosis. Hum Reprod Update. 1998 Jul-Aug;4(4):312-22. https://doi.org/10.1093/humupd/4.4.312\n14. Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, Somigliana E. Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis. Hum Reprod. 2014 May;29(5):964-77. https://doi.org/10.1093/humrep/deu041\n15. Younes G, Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis. Fertil Steril. 2017 Sep;108(3):483-490.e3. https://doi.org/10.1016/j.fertnstert.2017.06.025\n16. Zhang XP, Zhang YF, Shi R, Zhang YJ, Zhang XL, Hu XM, Hu XY, Hu YJ. Pregnancy outcomes of infertile women with ultrasound-diagnosed adenomyosis for in vitro fertilization and frozen-thawed embryo transfer. Arch Gynecol Obstet. 2021 Oct;304(4):1089-1096. https://doi.org/10.1007/s00404-021-06011-z\n17. Cozzolino M, Tartaglia S, Pellegrini L, Troiano G, Rizzo G, Petraglia F. The Effect of Uterine Adenomyosis on IVF Outcomes: a Systematic Review and Meta-analysis. Reprod Sci. 2022 Nov;29(11):3177-3193. https://doi.org/10.1007/s43032-021-00818-6\n18. Mehasseb MK, Bell SC, Pringle JH, Habiba MA. Uterine adenomyosis is associated with ultrastructural features of altered contractility in the inner myometrium. Fertil Steril. 2010 May 1;93(7):2130-6. https://doi.org/10.1016/j.fertnstert.2009.01.097\n19. Kissler S, Hamscho N, Zangos S, Wiegratz I, Schlichter S, Menzel C, Doebert N, Gruenwald F, Vogl TJ, Gaetje R, Rody A, Siebzehnruebl E, Kunz G, Leyendecker G, Kaufmann M. Uterotubal transport disorder in adenomyosis and endometriosis--a cause for infertility. BJOG. 2006 Aug;113(8):902-8. https://doi.org/10.1111/j.1471-0528.2006.00970.x\n20. Ota H, Igarashi S, Hatazawa J, Tanaka T. Immunohistochemical assessment of superoxide dismutase expression in the endometrium in endometriosis and adenomyosis. Fertil Steril. 1999 Jul;72(1):129-34. https://doi.org/10.1016/s0015-0282(99)00152-1\n21. Brosens J, Verhoeven H, Campo R, Gianaroli L, Gordts S, Hazekamp J, Hägglund L, Mardesic T, Varila E, Zech J, Brosens I. High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome. Hum Reprod. 2004 Feb;19(2):352-6. https://doi.org/10.1093/humrep/deh075\n22. Kitawaki J, Noguchi T, Amatsu T, Maeda K, Tsukamoto K, Yamamoto T, Fushiki S, Osawa Y, Honjo H. Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium. Biol Reprod. 1997 Sep;57(3):514-9. https://doi.org/10.1095/biolreprod57.3.514\n23. Goteri G, Lucarini G, Montik N, Zizzi A, Stramazzotti D, Fabris G, Tranquilli AL, Ciavattini A. Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1alpha (HIF-1alpha), and microvessel density in endometrial tissue in women with adenomyosis. Int J Gynecol Pathol. 2009 Mar;28(2):157-63. https://doi.org/10.1097/pgp.0b013e318182c2be\n24. Li T, Li YG, Pu DM. Matrix metalloproteinase-2 and -9 expression correlated with angiogenesis in human adenomyosis. Gynecol Obstet Invest. 2006;62(4):229-35. https://doi.org/10.1159/000094426\n25. Tremellen KP, Russell P. The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. II: adenomyosis and macrophages. J Reprod Immunol. 2012 Jan;93(1):58-63. https://doi.org/10.1016/j.jri.2011.12.001\n26. Kunz G, Beil D, Deininger H, Wildt L, Leyendecker G. The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum Reprod. 1996 Mar;11(3):627-32. https://doi.org/10.1093/humrep/11.3.627\n27. Kunz G, Beil D, Huppert P, Leyendecker G. Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging. Hum Reprod. 2000 Jan;15(1):76-82. https://doi.org/10.1093/humrep/15.1.76\n28. IJland MM, Evers JL, Dunselman GA, Volovics L, Hoogland HJ. Relation between endometrial wavelike activity and fecundability in spontaneous cycles. Fertil Steril. 1997 Mar;67(3):492-6. https://doi.org/10.1016/s0015-0282(97)80075-1\n29. Zhu L, Che HS, Xiao L, Li YP. Uterine peristalsis before embryo transfer affects the chance of clinical pregnancy in fresh and frozen-thawed embryo transfer cycles. Hum Reprod. 2014 Jun;29(6):1238-43. https://doi.org/10.1093/humrep/deu058\n30. Pirtea P, Cicinelli E, De Nola R, de Ziegler D, Ayoubi JM. Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis. Fertil Steril. 2021 Mar;115(3):546-560. https://doi.org/10.1016/j.fertnstert.2020.12.010\n31. Noda Y, Matsumoto H, Umaoka Y, Tatsumi K, Kishi J, Mori T. Involvement of superoxide radicals in the mouse two-cell block. Mol Reprod Dev. 1991 Apr;28(4):356-60. https://doi.org/10.1002/mrd.1080280408\n32. Telfer JF, Lyall F, Norman JE, Cameron IT. Identification of nitric oxide synthase in human uterus. Hum Reprod. 1995 Jan;10(1):19-23. https://doi.org/10.1093/humrep/10.1.19\n33. Kaga N, Katsuki Y, Obata M, Shibutani Y. Repeated administration of low-dose lipopolysaccharide induces preterm delivery in mice: a model for human preterm parturition and for assessment of the therapeutic ability of drugs against preterm delivery. Am J Obstet Gynecol. 1996 Feb;174(2):754-9. https://doi.org/10.1016/s0002-9378(96)70460-x\n34. Jenkinson PC, Anderson D, Gangolli SD. Malformations induced in cultured rat embryos by enzymically generated active oxygen species. Teratog Carcinog Mutagen. 1986;6(6):547-54. https://doi.org/10.1002/tcm.1770060608\n35. Yamamoto T, Noguchi T, Tamura T, Kitawaki J, Okada H. Evidence for estrogen synthesis in adenomyotic tissues. Am J Obstet Gynecol. 1993 Sep;169(3):734-8. https://doi.org/10.1016/0002-9378(93)90654-2\n36. Kitawaki J, Noguchi T, Amatsu T, Maeda K, Tsukamoto K, Yamamoto T, Fushiki S, Osawa Y, Honjo H. Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium. Biol Reprod. 1997 Sep;57(3):514-9. https://doi.org/10.1095/biolreprod57.3.514\n37. Takahashi K, Nagata H, Kitao M. Clinical usefulness of determination of estradiol level in the menstrual blood for patients with endometriosis. Nihon Sanka Fujinka Gakkai Zasshi. 1989 Nov;41(11):1849-50.\n38. Lessey BA, Palomino WA, Apparao KB, Young SL, Lininger RA. Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006;4 Suppl 1(Suppl 1):S9. https://doi.org/10.1186/1477-7827-4-s1-s9\n39. Brosens J, Verhoeven H, Campo R, Gianaroli L, Gordts S, Hazekamp J, Hägglund L, Mardesic T, Varila E, Zech J, Brosens I. High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome. Hum Reprod. 2004 Feb;19(2):352-6. https://doi.org/10.1093/humrep/deh075\n40. Brosens I, Derwig I, Brosens J, Fusi L, Benagiano G, Pijnenborg R. The enigmatic uterine junctional zone: the missing link between reproductive disorders and major obstetrical disorders? Hum Reprod. 2010 Mar;25(3):569-74. https://doi.org/10.1093/humrep/dep474\n41. Cullinan-Bove K, Koos RD. Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth. Endocrinology. 1993 Aug;133(2):829-37. https://doi.org/10.1210/endo.133.2.8344219\n42. Carrarelli P, Yen CF, Arcuri F, Funghi L, Tosti C, Wang TH, Huang JS, Petraglia F. Myostatin, follistatin and activin type II receptors are highly expressed in adenomyosis. Fertil Steril. 2015 Sep;104(3):744-52.e1. https://doi.org/10.1016/j.fertnstert.2015.05.032\n43. Zhou S, Yi T, Liu R, Bian C, Qi X, He X, Wang K, Li J, Zhao X, Huang C, Wei Y. Proteomics identification of annexin A2 as a key mediator in the metastasis and proangiogenesis of endometrial cells in human adenomyosis. Mol Cell Proteomics. 2012 Jul;11(7):M112.017988. https://doi.org/10.1074/mcp.m112.017988\n44. Huang TS, Chen YJ, Chou TY, Chen CY, Li HY, Huang BS, Tsai HW, Lan HY, Chang CH, Twu NF, Yen MS, Wang PH, Chao KC, Lee CC, Yang MH. Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells. J Cell Mol Med. 2014 Jul;18(7):1358-71. https://doi.org/10.1111/jcmm.12300\n45. Liu X, Shen M, Qi Q, Zhang H, Guo SW. Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis. Hum Reprod. 2016 Apr;31(4):734-49. https://doi.org/10.1093/humrep/dew018\n46. Wang F, Wen Z, Li H, Yang Z, Zhao X, Yao X. Human leukocyte antigen-G is expressed by the eutopic and ectopic endometrium of adenomyosis. Fertil Steril. 2008 Nov;90(5):1599-604. https://doi.org/10.1016/j.fertnstert.2007.06.073\n47. Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005 Jul 14;3:28. https://doi.org/10.1186/1477-7827-3-28\n48. Tremellen KP, Russell P. The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. II: adenomyosis and macrophages. J Reprod Immunol. 2012 Jan;93(1):58-63. https://doi.org/10.1016/j.jri.2011.12.001\n49. Ota H, Igarashi S, Hatazawa J, Tanaka T. Is adenomyosis an immune disease? Hum Reprod Update. 1998 Jul-Aug;4(4):360-7. https://doi.org/10.1093/humupd/4.4.360\n50. Ota H, Igarashi S, Tanaka T. Xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. Fertil Steril. 2001 Apr;75(4):785-90. https://doi.org/10.1016/s0015-0282(01)01670-3\n51. Ota H, Igarashi S, Kato N, Tanaka T. Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. Fertil Steril. 2000 Aug;74(2):313-8. https://doi.org/10.1016/s0015-0282(00)00638-5\n52. Aleksandrovych V, Basta P, Gil K. Current facts constituting an understanding of the nature of adenomyosis. Adv Clin Exp Med. 2019 Jun;28(6):839-846. https://doi.org/10.17219/acem/79176\n53. Vannuccini S, Luisi S, Tosti C, Sorbi F, Petraglia F. Role of medical therapy in the management of uterine adenomyosis. Fertil Steril. 2018 Mar;109(3):398-405. https://doi.org/10.1016/j.fertnstert.2018.01.013\n54. Garcia L, Isaacson K. Adenomyosis: review of the literature. J Minim Invasive Gynecol. 2011 Jul-Aug;18(4):428-37. https://doi.org/10.1016/j.jmig.2011.04.004\n55. Grimbizis GF, Mikos T, Tarlatzis B. Uterus-sparing operative treatment for adenomyosis. Fertil Steril. 2014 Feb;101(2):472-87. https://doi.org/10.1016/j.fertnstert.2013.10.025\n56. Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Hum Reprod Update. 2012 Jul;18(4):374-92. https://doi.org/10.1093/humupd/dms006\n57. Lan J, Wu Y, Wu Z, Wu Y, Yang R, Liu Y, Lin H, Jiao X, Zhang Q. Ultra-Long GnRH Agonist Protocol During IVF/ICSI Improves Pregnancy Outcomes in Women With Adenomyosis: A Retrospective Cohort Study. Front Endocrinol (Lausanne). 2021 May 31;12:609771. https://doi.org/10.3389/fendo.2021.609771\n58. Rocha TP, Andres MP, Borrelli GM, Abrão MS. Fertility-Sparing Treatment of Adenomyosis in Patients With Infertility: A Systematic Review of Current Options. Reprod Sci. 2018 Apr;25(4):480-486. https://doi.org/10.1177/1933719118756754\n59. Wu Y, Huang J, Zhong G, Lan J, Lin H, Zhang Q. Long-term GnRH agonist pretreatment before frozen embryo transfer improves pregnancy outcomes in women with adenomyosis. Reprod Biomed Online. 2022 Feb;44(2):380-388. https://doi.org/10.1016/j.rbmo.2021.10.014\n60. Osada H. Uterine adenomyosis and adenomyoma: the surgical approach. Fertil Steril. 2018 Mar;109(3):406-417. https://doi.org/10.1016/j.fertnstert.2018.01.032\n61. Tamura H, Kishi H, Kitade M, Asai-Sato M, Tanaka A, Murakami T, Minegishi T, Sugino N. Clinical outcomes of infertility treatment for women with adenomyosis in Japan. Reprod Med Biol. 2017 May 16;16(3):276-282. https://doi.org/10.1002/rmb2.12036\nDownloads\nPublished\nHow to Cite\nIssue\nSection\nLicense\nCopyright (c) 2025 Mateusz Paniak, Paweł Maciej Rycąbel, Oliwia Brygida Woszczyńska, Agnieszka Ewelina Wojciechowska, Marta Szymura, Marek Jarosław Molenda, Maria Wachowska, Mateusz Romaniuk, Wojciech Jan Sowiński, Michał Brunon Krawczyk\nThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.\nThe periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0\nStats\nNumber of views and downloads: 547\nNumber of citations: 0","source_license":"CC0","license_restricted":false}