[en] Background and Objectives: Adenomyosis (the presence of ectopic endometrial glands and stroma below the endometrial-myometrial junction) is a benign condition which is increasingly diagnosed in younger women suffering from infertility. The aim of this narrative review was to study the pathophysiology and prevalence of adenomyosis, the mechanisms causing infertility, treatment options, and reproductive outcomes in infertile women suffering from adenomyosis. Materials and Methods: A literature search for suitable articles published in the English language was performed using PubMed from January 1970 to July 2022. Results: The literature search retrieved 50 articles that met the purpose of this review and summarized the most recent findings regarding the accuracy of diagnostic methods, pathophysiology, and the prevalence of adenomyosis and optimal strategies for the treatment of infertile women with adenomyosis. Conclusions: Adenomyosis is a common gynecological disorder, affecting women of reproductive age. It negatively affects in vitro fertilization, pregnancy and the live birth rate, as well as increases the risk of miscarriage. With the advent of non-invasive diagnoses with MRI and TVUS, the role of adenomyosis in infertility has been better recognized. Overall, more randomized controlled trials (RCTs) are needed to provide strong data on the accuracy of diagnostic methods, the pathophysiology and the prevalence of adenomyosis, the fertility outcomes of patients and the optimal strategy for the treatment.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Pados, George; 1st Department of Obstetrics and Gynaecology, Papageorgiou General Hospital, School of Medicine, Aristotle University of Thessaloniki, 54643 Thessaloniki, Greece
Gordts, Stephan ; Life Expert Centre, 3000 Leuven, Belgium
Sorrentino, Felice ; Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, 71121 Foggia, Italy
Nisolle, Michelle ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Nappi, Luigi; Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, 71121 Foggia, Italy
Daniilidis, Angelos ; 1st Department of Obstetrics and Gynaecology, Papageorgiou General Hospital, School of Medicine, Aristotle University of Thessaloniki, 54643 Thessaloniki, Greece
Language :
English
Title :
Adenomyosis and Infertility: A Literature Review.
Publication date :
26 August 2023
Journal title :
Medicina
ISSN :
1010-660X
eISSN :
1648-9144
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Aleksandrovych V. Basta P. Gil K. Current facts constituting an understanding of the nature of adenomyosis Adv. Clin. Exp. Med. 2019 28 839 846 10.17219/acem/79176 30085434
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 haemorage and other obstetric complications Med. Hypotheses 2020 143 109833 10.1016/j.mehy.2020.109833
Ferenczy A. Pathophysiology of adenomyosis Hum. Reprod. Updat. 1998 4 312 322 10.1093/humupd/4.4.312
Zou Y. Liu F.-Y. Wang L.-Q. Guo J.-B. Yang B.-C. Wan X.-D. Wang F. He M. Huang O.-P. Downregulation of DNA methyltransferase 3 alpha promotes cell proliferation and invasion of ectopic endometrial stromal cells in adenomyosis Gene 2017 604 41 47 10.1016/j.gene.2016.12.011
Enatsu A. Harada T. Yoshida S. Iwabe T. Terakawa N. Adenomyosis in a patient with the Rokitansky-Kuster-Hauser syndrome Fertil. Steril. 2000 73 862 863 10.1016/S0015-0282(99)00643-3
Garcia L. Isaacson K. Adenomyosis: Review of the Literature J. Minim. Invasive Gynecol. 2011 18 428 437 10.1016/j.jmig.2011.04.004 21622029
Zhai J. Vannuccini S. Petraglia F. Giudice L.C. Adenomyosis: Mechanisms and Pathogenesis Semin. Reprod. Med. 2020 38 129 143 10.1055/s-0040-1716687
Tan J. Yong P. Bedaiwy M.A. A critical review of recent advances in the diagnosis, classification, and management of uterine adenomyosis Curr. Opin. Obstet. Gynecol. 2019 31 212 221 10.1097/GCO.0000000000000555
Vannuccini S. Petraglia F. Recent advances in understanding and managing adenomyosis F1000Research 2019 8 283 10.12688/f1000research.17242.1 30918629
Abu Hashim A. Elaraby S. Fouda A. El Rakhawy M.E. The prevalence of adenomyosis in an infertile population: A cross-sectional study Reprod. Biomed. Online 2020 40960 842 850 10.1016/j.rbmo.2020.02.011 32376315
Vercellini P. Parazzini F. Oldani S. Panazza S. Bramante T. Crosignani P.G. Surgery: Adenomyosis at hysterectomy: A study on frequency distribution and patient characteristics Hum. Reprod. 1995 10 1160 1162 10.1093/oxfordjournals.humrep.a136111
Levgur M. Abdai M.A. Tucker A. Adenomyosis: Symptoms, histology, and pregnancy terminations Obstet. Gynecol. 2000 95 688 691 10.1097/00006250-200005000-00011
Kobayashi H. Matsubara S. Imanaka S. Clinicopathological features of different subtypes in adenomyosis: Focus on early lesions PLoS ONE 2021 16 e0254147 10.1371/journal.pone.0254147
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 16 276 282 10.1002/rmb2.12036
Leyendecker G. Wildt L. Mall G. The pathophysiology of endometriosis and adenomyosis: Tissue injury and repair Arch. Gynecol. Obstet. 2009 280 529 538 10.1007/s00404-009-1191-0
Leyendecker G. Wildt L. A new concept of endometriosis and adenomyosis: Tissue injury and repair (TIAR) Horm. Mol. Biol. Clin. Investig. 2011 5 125 142 10.1515/HMBCI.2011.002 25961248
Leyendecker G. Bilgicyildirim A. Inacker M. Stalf T. Huppert P. Mall G. Böttcher B. Wildt L. Adenomyosis and endometriosis. Re-visiting their association and further insights into the mechanisms of auto-traumatisation. An MRI study Arch. Gynecol. Obstet. 2015 291 917 932 10.1007/s00404-014-3437-8 25241270
Leyendecker G. Wildt L. Laschke M.W. Mall G. Archimetrosis: The evolution of a disease and its extant presentation: Pathogenesis and pathophysiology of archimetrosis (uterine adenomyosis and endometriosis) Arch. Gynecol. Obstet. 2022 21 93 112 10.1007/s00404-022-06597-y 35596746
Koninckx P.R. Ussia A. Adamyan L. Wattiez A. Gomel V. Martin D.C. Pathogenesis of endometriosis: The genet-ic/epigenetic theory Fertil. Steril. 2019 111 327 340 10.1016/j.fertnstert.2018.10.013
Benagiano G. Brosens I. Adenomyosis and endometriosis have a common origin J. Obstet. Gynecol. India 2011 61 146 152 10.1007/s13224-011-0030-y
Vannuccini S. Tosti C. Carmona F. Huang S.J. Chapron C. Guo S.W. Petraglia F. Pathogenesis of adenomyosis: An update on molecular mechanisms Reprod Biomed Online 2017 35 592 601 10.1016/j.rbmo.2017.06.016
Bulun S.E. Yilmaz B.D. Sison C. Miyazaki K. Bernardi L. Liu S. Kohlmeier A. Yin P. Milad M. Wei J. Endometriosis Endocr. Rev. 2019 40 1048 1079 10.1210/er.2018-00242
Artymuk N. Zotova O. Gulyaeva L. Adenomyosis: Genetics of estrogen metabolism Horm. Mol. Biol. Clin. Investig. 2019 37 37 10.1515/hmbci-2018-0069
Tong X. Li Z. Wu Y. Fu X. Zhang Y. Fan H. COMT 158G/A and CYP1B1 432C/G polymorphisms increase the risk of endometriosis and adenomyosis: A meta-analysis Eur. J. Obstet. Gynecol. Reprod. Biol. 2014 179 17 21 10.1016/j.ejogrb.2014.04.039 24965973
Gordts S. Koninckx P. Brosens I. Pathogenesis of deep endometriosis Fertil. Steril. 2017 108 872 885.e1 10.1016/j.fertnstert.2017.08.036
Liu X. Guo S.-W. Aberrant immunoreactivity of deoxyribonucleic acid methyltransferases in adenomyosis Gynecol. Obstet. Investig. 2012 74 100 108 10.1159/000337718 22572543
Nie J. Liu X. Guo S.-W. Promoter Hypermethylation of Progesterone Receptor Isoform B (PR-B) in Adenomyosis and Its Rectification by a Histone Deacetylase Inhibitor and a Demethylation Agent Reprod. Sci. 2010 17 995 1005 10.1177/1933719110377118
Xiang Y. Sun Y. Yang B. Yang Y. Zhang Y. Yu T. Huang H. Zhang J. Xu H. Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology J. Cell. Mol. Med. 2019 23 8381 8391 10.1111/jcmm.14718
Liu X. Guo S.-W. Valproic acid alleviates generalized hyperalgesia in mice with induced adenomyosis J. Obstet. Gynaecol. Res. 2011 37 696 708 10.1111/j.1447-0756.2011.01655.x
Bird C.C. McElin T.W. Manalo-Estrella P. The elusive adenomyosis of the uterus—Revisited Am. J. Obstet. Gynecol. 1972 112 583 593 10.1016/0002-9378(72)90781-8 5059589
Hulka C.A. Hall D.A. McCarthy K. Simeone J. Sonographic Findings in Patients with Adenomyosis: Can Sonography Assist in Predicting Extent of Disease? Am. J. Roentgenol. 2002 179 379 383 10.2214/ajr.179.2.1790379
Sammour A. Pirwany I. Usubutun A. Arseneau J. Tulandi T. Correlations between Extent and Spread of Adenomyosis and Clinical Symptoms Gynecol. Obstet. Investig. 2002 54 213 216 10.1159/000068385 12592064
Vercellini P. Viganò P. Somigliana E. Daguati R. Abbiati A. Fedele L. Adenomyosis: Epidemiological factors Best Pract. Res. Clin. Obstet. Gynaecol. 2006 20 465 477 10.1016/j.bpobgyn.2006.01.017
Harmen M.J. Van den Bosch T. De Leeuw R.A. Dueholm M. Exacoustos C. Valentin L. Hehenkamp W.J.K. Groenman F. Uyn C.D.E. Rasmussen C. et al. Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: Results of modified Delphi procedure Ultrasound Obstet. Gynecol. 2022 60 118 131 10.1002/uog.24786
Marques A.L.S. Andres M.P. Mattos L.A. Gonçalves M.O. Baracat E.C. Abrão M.S. Association of 2D and 3D transvaginal ultrasound findings with adenomyosis in symptomatic women of reproductive age: A prospective study Clinics 2021 76 e2981 10.6061/clinics/2021/e2981 34406269
Tellum T. Nygaard S. Lieng M. Noninvasive Diagnosis of Adenomyosis: A Structured Review and Meta-analysis of Diagnostic Accuracy in Imaging J. Minim. Invasive Gynecol. 2020 27 408 418.e3 10.1016/j.jmig.2019.11.001
Gordts S. Brosens J.J. Fusi L. Benagiano G. Brosens I. Uterine adenomyosis: A need for uniform terminology and consensus classification Reprod. Biomed. Online 2008 17 244 248 10.1016/S1472-6483(10)60201-5
Kishi Y. Suginami H. Kuramori R. Yabuta M. Suginami R. Taniguchi F. Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification Am. J. Obstet. Gynecol. 2012 207 114.e1 114.e7 10.1016/j.ajog.2012.06.027
Grimbizis G.F. Mikos T. Tarlatzis B. Uterus-sparing operative treatment for adenomyosis Fertil. Steril. 2014 101 472 487.e8 10.1016/j.fertnstert.2013.10.025
Bazot M. Daraï E. Role of transvaginal sonography and magnetic resonance imaging in the diagnosis of uterine adenomyosis Fertil. Steril. 2018 109 389 397 10.1016/j.fertnstert.2018.01.024
Lazzeri L. Morosetti G. Centini G. Monti G. Zupi E. Piccione E. Exacoustos C. A sonographic classification of adenomyosis: Interobserver reproducibility in the evaluation of type and degree of the myometrial involvement Fertil. Steril. 2018 110 1154 1161.e3 10.1016/j.fertnstert.2018.06.031 30396560
Van den Bosch T. De Bruin A.M. De Leeuw R.A. Dueholm M. Exacoustos C. Valentin L. Bourne T. Timmerman D. Huirne J.A.F. Sonographic classification and reporting system for diagnosing adenomyosis Ultrasound Obstet Gynecol. 2019 53 576 582
Exacoustos C. Morosetti G. Conway F. Camilli S. Martire F.G. Lazzeri L. Piccione E. Zupi E. New Sonographic Classification of Adenomyosis: Do Type and Degree of Adenomyosis Correlate to Severity of Symptoms? J. Minim. Invasive Gynecol. 2020 27 1308 1315 10.1016/j.jmig.2019.09.788
Günther V. Allahqoli L. Gitas G. Maass N. Tesch K. Ackermann J. Rosam P. Mettler L. von Otte S. Alkatout I. Impact of Adenomyosis on Infertile Patients—Therapy Options and Reproductive Outcomes Biomedicines 2022 10 3245 10.3390/biomedicines10123245 36552001
Brosens J. Verhoeven H. Campo R. Gianaroli L. Gordts S. Hazekamp J. Hägglund L. Mardesic T. Varila E. Zech J. et al. High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome Hum. Reprod. 2004 19 352 356 10.1093/humrep/deh075
Xiao Y. Sun X. Yang X. Zhang J. Xue Q. Cai B. Zhou Y. Leukemia inhibitory factor is dysregulated in the endometrium and uterine flushing fluid of patients with adenomyosis during implantation window Fertil. Steril. 2010 94 85 89 10.1016/j.fertnstert.2009.03.012 19361790
Vercellini P. Consonni D. Dridi D. Bracco B. Frattaruolo M.P. Somigliana E. Uterine adenomyosis and in vitro fertilization outcome: A systematic review and meta-analysis Hum. Reprod. 2014 29 964 977 10.1093/humrep/deu041
Mavrelos D. Holland T.K. O’Donovan O. Khalil M. Ploumpidis G. Jurkovic D. Khalaf Y. The impact of adenomyosis on the outcome of IVF–embryo transfer Reprod. Biomed. Online 2017 35 549 554 10.1016/j.rbmo.2017.06.026
Younes G. Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: A meta-analysis Fertil. Steril. 2017 108 483 490.e3 10.1016/j.fertnstert.2017.06.025
Dueholm M. Aagaard J. Adenomyosis and IVF/ICSI treatment: Clinical considerations and recommendations Expert Rev. Endocrinol. Metab. 2018 13 177 179 10.1080/17446651.2018.1493923 30063420
Nirgianakis K. Kalaitzopoulos D.R. Schwartz A.S.K. Spaanderman M. Kramer B.W. Mueller M.D. Mueller M. Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: A systematic review and meta-analysis Reprod. Biomed. Online 2021 42 185 206 10.1016/j.rbmo.2020.09.023 33191131
Zhang X.-P. Zhang Y.-F. Shi R. Zhang Y.-J. Zhang X.-L. Hu X.-M. Hu X.-Y. Hu Y.-J. Pregnancy outcomes of infertile women with ultrasound-diagnosed adenomyosis for in vitro fertilization and frozen–thawed embryo transfer Arch. Gynecol. Obstet. 2021 304 1089 1096 10.1007/s00404-021-06011-z
Liang T. Zhang W. Pan N. Han B. Li R. Ma C. Reproductive Outcomes of In Vitro Fertilization and Fresh Embryo Transfer in Infertile Women With Adenomyosis: A Retrospective Cohort Study Front. Endocrinol. 2022 13 865358 10.3389/fendo.2022.865358 35966061
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 29 3177 3193 10.1007/s43032-021-00818-6
Bourdon M. Santulli P. Oliveira J. Marcellin L. Maignien C. Melka L. Bordonne C. Millisher A.E. Plu-Bureau G. Cormier J. et al. Focal adenomyosis is associated with primary infertility Fertil. Steril. 2020 114 1271 1277 10.1016/j.fertnstert.2020.06.018
Osada H. Uterine adenomyosis and adenomyoma: The surgical approach Fertil. Steril. 2018 109 406 417 10.1016/j.fertnstert.2018.01.032
Pacheco L.A. Laganà A.S. Garzon S. Garrido A.P. Gornés A.F. Ghezzi F. Hysteroscopic outpatient metroplasty for T-shaped uterus in women with reproductive failure: Results from a large prospective cohort study Eur. J. Obstet. Gynecol. Reprod. Biol. 2019 243 173 178 10.1016/j.ejogrb.2019.09.023 31570176
