Skip to main content


Log in

The Effect of Uterine Adenomyosis on IVF Outcomes: a Systematic Review and Meta-analysis

  • Review
  • Published:
Reproductive Sciences Aims and scope Submit manuscript


To investigate the impact of uterine adenomyosis on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) clinical outcomes and also to evaluate the impact of gonadotropin-releasing hormone agonist (GnRHa) and surgical treatments. Infertile women with adenomyosis undergoing conventional IVF or ICSI were compared with women without adenomyosis. Fertility outcomes were evaluated in two patients with adenomyosis untreated and treated surgically or medically therapy. The review protocol was registered in PROSPERO (CRD42020214586). We consider the live birth rate (LBR) as the primary outcome. The analysis showed that women with adenomyosis had lower LBR (OR 0.59, 95% CI 0.37–0.92, p = 0.02), clinical pregnancy rate (OR 0.66, 95% CI 0.48–0.90), and ongoing pregnancy rate (OR 0.43, 95% CI 0.21–0.88) compared to those without adenomyosis, and miscarriage rate was higher in women with adenomyosis (OR 2.11, 95% CI 1.33–3.33). Surgical treatment increases natural conception in women with adenomyosis although the paucity of data (only two studies), and conversely, treatment with GnRHa does not increase the IVF outcomes. Women with adenomyosis have decreased IVF clinical outcomes. Pretreatment with the use of long-term GnRHa could not be beneficial, even though only three studies were included in the meta-analysis. The major part of the studies has not divided focal and diffuse adenomyosis, and this represents a relevant source of bias: studies conducted with standardized diagnostic criteria for adenomyosis are still needed to determine if the different clinical presentations of such condition could compromise IVF outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Code Availability

PROSPERO registration CRD42020214586.



Gonadotropin-releasing hormone agonist


Assisted reproductive technology


Number of total oocytes


Clinical pregnancy rate


Integrin alpha-1


Integrin beta-1


Laminin subunit gamma-1


Live birth rate


Levonorgestrel-releasing intrauterine system


Miscarriage rate


Magnetic resonance imaging


Ongoing pregnancy rate




Transvaginal ultrasound scan


  1. Vercellini P, Viganò P, Somigliana E, Daguati R, Abbiati A, Fedele L. Adenomyosis: epidemiological factors. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):465–77.

    Article  PubMed  Google Scholar 

  2. Benagiano G, Habiba M, Brosens I. The pathophysiology of uterine adenomyosis: an update. Fertility and Sterility. 2012.

  3. Kobayashi H, Matsubara S. A classification proposal for adenomyosis based on magnetic resonance imaging. Gynecologic and Obstetric Investigation. 2020.

  4. Meredith SM, Sanchez-Ramos L, Kaunitz AM. Diagnostic accuracy of transvaginal sonography for the diagnosis of adenomyosis: systematic review and meta-analysis. Am J Obstet Gynecol. 2009

  5. Cecchino GN, Cozzolino M, Roque M, García-Velasco JA. Endometrioma and reproductive issues: a well-informed patient may be the driver for change. Minerva Ginecol. 2020;72(3):149–56.

    Article  PubMed  Google Scholar 

  6. Campo S, Campo V, Benagiano G. Infertility and adenomyosis. Obstet Gynecol Int. 2012

  7. Garavaglia E, Audrey S, Annalisa I, Stefano F, Iacopo T, Laura C, et al. Adenomyosis and its impact on women fertility. Iranian Journal of Reproductive Medicine. 2015.

  8. Taran FA, Stewart EA, Brucker S. Adenomyosis: epidemiology, risk factors, clinical phenotype and surgical and interventional alternatives to hysterectomy. Geburtshilfe Frauenheilkd. 2013

  9. Cozzolino M, Basile F, Pontrelli G. Effects of adenomyosis on obstetric outcomes. Minerva Ginecologica. 2019.

  10. Buggio L, Monti E, Gattei U, Dridi D, Vercellini P. Adenomyosis: fertility and obstetric outcome. A comprehensive literature review. Minerva Ginecologica. 2018.

  11. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update. 2019

  12. Nirgianakis K, Kalaitzopoulos DR, Schwartz ASK, Spaanderman M, Kramer BW, Mueller MD, et al. Fertility, pregnancy and neonatal outcomes of patients with adenomyosis: a systematic review and meta-analysis. Reprod Biomed Online [Internet]. 2020; Available from:

  13. Osada H. Uterine adenomyosis and adenomyoma: the surgical approach. Fertility and Sterility. 2018.

  14. Khan KN, Kitajima M, Hiraki K, Fujishita A, Nakashima M, Ishimaru T, et al. Cell proliferation effect of GnRH agonist on pathological lesions of women with endometriosis, adenomyosis and uterine myoma. Hum Reprod. 2010

  15. Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, Ishimaru T, et al. Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy. Hum Reprod. 2010

  16. Guo S, Li Z, Yan L, Sun Y, Feng Y. GnRH agonist improves pregnancy outcome in mice with induced adenomyosis by restoring endometrial receptivity. Drug Des Devel Ther. 2018

  17. Devlieger R, D’Hooghe T, Timmerman D. Uterine adenomyosis in the infertility clinic. Human Reproduction Update. 2003.

  18. Younes G, Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis. Fertil Steril. 2017

  19. Liang Z, Yin M, Ma M, Wang Y, Kuang Y. Effect of pretreatment with a levonorgestrel-releasing intrauterine system on IVF and vitrified–warmed embryo transfer outcomes in women with adenomyosis. Reprod Biomed Online. 2019;39(1):111–8.

    Article  CAS  PubMed  Google Scholar 

  20. Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G, et al. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Medicine. 2009.

  21. Wang PH, Fuh JL, Chao HT, Liu WM, Cheng MH, Chao KC. Is the surgical approach beneficial to subfertile women with symptomatic extensive adenomyosis? J Obstet Gynaecol Res. 2009

  22. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. (Available from URL 2012

  23. Ballester M, Dargent EM, Morcel K, Belaisch-Allart J, Nisolle M, Daraí E. Cumulative pregnancy rate after ICSIIVF in patients with colorectal endometriosis: results of a multicentre study. Hum Reprod. 2012;27(4):1043–9.

    Article  PubMed  Google Scholar 

  24. Stanekova V, Woodman RJ, Tremellen K. The rate of euploid miscarriage is increased in the setting of adenomyosis. Hum Reprod Open. 2018

  25. Mijatovic V, Florijn E, Halim N, Schats R, Hompes P. Adenomyosis has no adverse effects on IVF/ICSI outcomes in women with endometriosis treated with long-term pituitary down-regulation before IVF/ICSI. Eur J Obstet Gynecol Reprod Biol. 2010;151(1):62–5.

    Article  CAS  PubMed  Google Scholar 

  26. Youm HS, Choi YS, Han HD. In vitro fertilization and embryo transfer outcomes in relation to myometrial thickness. In: Journal of Assisted Reproduction and Genetics. 2011.

  27. Chiang CH, Chang MY, Shiau CS, Hou HC, Hsieh TTA, Soong YK. Effect of a sonographically diffusely enlarged uterus without distinct uterine masses on the outcome of in vitro fertilization-embryo transfer. J Assist Reprod Genet. 1999;16(7):369–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Martínez-Conejero JA, Morgan M, Montesinos M, Fortuño S, Meseguer M, Simón C, et al. Adenomyosis does not affect implantation, but is associated with miscarriage in patients undergoing oocyte donation. Fertil Steril. 2011;96(4).

  29. Salim R, Riris S, Saab W, Abramov B, Khadum I, Serhal P. Adenomyosis reduces pregnancy rates in infertile women undergoing IVF. Reprod Biomed Online. 2012

  30. Sharma S, Bathwal S, Agarwal N, Chattopadhyay R, Saha I, Chakravarty B. Does presence of adenomyosis affect reproductive outcome in IVF cycles? A retrospective analysis of 973 patients. Reprod Biomed Online. 2019;38(1):13–21.

    Article  PubMed  Google Scholar 

  31. Al Jama FE. Management of adenomyosis in subfertile women and pregnancy outcome. Oman Med J. 2011;26(3):178–81.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Niu Z, Chen Q, Sun Y, Feng Y. Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis. Gynecol Endocrinol. 2013

  33. Park CW, Choi MH, Yang KM, Song IO. Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment. Clin Exp Reprod Med. 2016

  34. Chen M, Luo L, Wang Q, Gao J, Chen Y, Zhang Y, et al. Impact of gonadotropin-releasing hormone agonist pre-treatment on the cumulative live birth rate in infertile women with adenomyosis treated with IVF/ICSI: a retrospective cohort study. Front Endocrinol (Lausanne). 2020;11(May):1–9.

    Google Scholar 

  35. Benaglia L, Cardellicchio L, Leonardi M, Faulisi S, Vercellini P, Paffoni A, et al. Asymptomatic adenomyosis and embryo implantation in IVF cycles. Reprod Biomed Online. 2014

  36. Costello MF, Lindsay K, McNally G. The effect of adenomyosis on in vitro fertilisation and intra-cytoplasmic sperm injection treatment outcome. Eur J Obstet Gynecol Reprod Biol. 2011;158(2):229–34.

    Article  PubMed  Google Scholar 

  37. Hou X, Xing J, Shan H, Mei J, Sun Y, Yan G, et al. The effect of adenomyosis on IVF after long or ultra-long GnRH agonist treatment. Reprod Biomed Online. 2020;00:1–9.

    Google Scholar 

  38. Maubon A, Faury A, Kapella M, Pouquet M, Piver P. Uterine junctional zone at magnetic resonance imaging: a predictor of in vitro fertilization implantation failure. J Obstet Gynaecol Res. 2010

  39. Mavrelos D, Holland TK, O’Donovan O, Khalil M, Ploumpidis G, Jurkovic D, et al. The impact of adenomyosis on the outcome of IVF–embryo transfer. Reprod Biomed Online. 2017;35(5):549–54.

    Article  PubMed  Google Scholar 

  40. Neal S, Morin S, Werner M, Gueye NA, Pirtea P, Patounakis G, et al. Three-dimensional ultrasound diagnosis of adenomyosis is not associated with adverse pregnancy outcome following single thawed euploid blastocyst transfer: prospective cohort study. Ultrasound Obstet Gynecol. 2020;56(4):611–7.

    Article  CAS  PubMed  Google Scholar 

  41. Thalluri V, Tremellen KP. Ultrasound diagnosed adenomyosis has a negative impact on successful implantation following GnRH antagonist IVF treatment. Hum Reprod. 2012;27(12):3487–92.

    Article  CAS  PubMed  Google Scholar 

  42. Yan L, Ding L, Tang R, Chen ZJ. Effect of adenomyosis on in vitro fertilization/intracytoplasmic sperm injection outcomes in infertile women: a retrospective cohort study. Gynecol Obstet Invest. 2014

  43. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ WV. Cochrane handbook for systematic reviews of interventions version 6.0 (updated July 2019). Cochrane, 2019. Handbook. 2019

  44. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. British Medical Journal. 2003.

  45. Deeks JJ, Hopewell S, Moher D, Higgins JP, Moons KG, Chandler J, et al. Doug Altman’s legacy to Cochrane and evidence synthesis. Cochrane database Syst Rev. 2018

  46. Tanos V, Lingwood L, Balami S. The importance of the junctional zone of the endometrium in human reproduction. Human Fertility. 2020.

  47. Shen M, Liu X, Zhang H, Guo SW. Transforming growth factor β1 signaling coincides with epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis in mice. Hum Reprod. 2016

  48. Ota H, Igarashi S, Sasaki M, Tanaka T. Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Hum Reprod. 2001

  49. Kitawaki J, Kusuki I, Koshiba H, Tsukamoto K, Honjo H. Expression of aromatase cytochrome P450 in eutopic endometrium and its application as a diagnostic test for endometriosis. In: Gynecologic and Obstetric Investigation. 1999.

  50. Li Y, Zhang D, Jin B, Xia L, Zhang A. Proteomic analysis of uterine tissues during peri-implantation period in mice with experimentally induced adenomyosis that treated with anti-Ngf: implications for cell-cell adhesion and metabolic processes. Reprod Sci. 2020

  51. Kay N, Huang CY, Shiu LY, Yu YC, Chang Y, Schatz F, et al. TGF-β1 neutralization improves pregnancy outcomes by restoring endometrial receptivity in mice with adenomyosis. Reprod Sci. 2020

  52. Xiao Y, Sun X, Yang X, Zhang J, Xue Q, Cai B, et al. Leukemia inhibitory factor is dysregulated in the endometrium and uterine flushing fluid of patients with adenomyosis during implantation window. Fertil Steril. 2010

  53. Wang J, Huang C, Jiang R, Du Y, Zhou J, Jiang Y, et al. Decreased endometrial IL-10 impairs endometrial receptivity by downregulating HOXA10 expression in women with adenomyosis. Biomed Res Int. 2018

  54. Bourdon M, Santulli P, Jeljeli M, Vannuccini S, Marcellin L, Doridot L, et al. Immunological changes associated with adenomyosis: a systematic review. Hum Reprod Update. 2020;1–22.

  55. Puente JM, Fabris A, Patel J, Patel A, Cerrillo M, Requena A, et al. Adenomyosis in infertile women: prevalence and the role of 3D ultrasound as a marker of severity of the disease. Reprod Biol Endocrinol. 2016

  56. Garcia-Velasco JA. Is there a link between focal adenomyosis and infertility? Fertility and Sterility. 2020.

  57. Bourdon M, Santulli P, Oliveira J, Marcellin L, Maignien C, Melka L, et al. Focal adenomyosis is associated with primary infertility. Fertil Steril. 2020;8–10.

  58. Chapron C, Vannuccini S, Santulli P, Abrão MS, Carmona F, Fraser IS, et al. Diagnosing adenomyosis: an integrated clinical and imaging approach. Hum Reprod Update. 2020

  59. 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

  60. Van Den Bosch T, Dueholm M, Leone FPG, Valentin L, Rasmussen CK, Votino A, et al. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol. 2015

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Mauro Cozzolino.

Ethics declarations

Ethics Approval and Consent to Participate

All the procedures performed in the studies that involved human participants were made under the ethical standards of the Institutional and National Research Committee, and also with the 1964 Declaration of Helsinki as well as its later amendments, or comparable ethical standards. Consent to participate is not required.

Consent for Publication

Not required.

Conflict of Interest

The authors declare no competing interests.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cozzolino, M., Tartaglia, S., Pellegrini, L. et al. The Effect of Uterine Adenomyosis on IVF Outcomes: a Systematic Review and Meta-analysis. Reprod. Sci. 29, 3177–3193 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: