Skip to main content

Advertisement

Log in

Uterine Fibroids in the Setting of Infertility: When to Treat, How to Treat?

  • Reproductive Endocrinology and Infertility (REI) (R Anchan, Section Editor)
  • Published:
Current Obstetrics and Gynecology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

We aim to provide insight on the treatment of fibroids in the infertile patient. Specifically, we discuss which fibroids, based on size and location within the uterine wall, have the most impact on fertility outcomes. In addition, we demonstrate which methods are best for treatment of fibroids in the infertile patient, focusing on minimally invasive techniques.

Recent Findings

Current research demonstrates that, in addition to submucosal fibroids, also intramural fibroids can have a negative impact on fertility via molecular and mechanical disruption of the endometrium and of normal uterine peristalsis. Certain intramural fibroids should be considered for removal or treatment in the infertile patient, depending on size and patient history. We also provide a large body of evidence demonstrating the safety and clinical advantages of minimally invasive techniques, such as hysteroscopy, laparoscopy, and robot-assisted laparoscopy in the treatment of uterine fibroids.

Summary

All submucosal and many intramural fibroids interfere with uterine function. In the evaluation of the infertile patient, accurate fibroid mapping within the uterus is essential to identify those submucosal and intramural fibroids that are likely to have the most impact of fertility outcomes. The mainstay of treatment is surgery for those fibroids with the most detrimental impact. Nonsurgical alternatives such as magnetic resonance-guided focused ultrasound (MRgFUS) and radiofrequency volumetric thermal ablation (RFVTA) need further validation before their widespread adoption in infertile patients.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • of importance

  1. Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Myomas and reproductive function. Fertil Steril. 2008;90(Suppl):S125–30.

    Google Scholar 

  2. • Silbersweig JE, Powell DK, Matsumoto AH, Spies JB. Management of uterine fibroids: a focus on uterine-sparing interventional techniques. Radiology. 2016;280:675–92. Comprehensive review of non-surgical treatment of fibroids.

    Article  Google Scholar 

  3. Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188:100–7.

    Article  PubMed  Google Scholar 

  4. Buttram Jr VC, Reiter RC. Uterine leiomyomata: etiology, symptomatology, and management. Fertil Steril. 1981;36:433–5.

    Article  PubMed  Google Scholar 

  5. Klatsky PC, Tran ND, Caughey AB, Fujimoto VY. Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. Am J Obstet Gynecol. 2008;198:357–66.

    Article  PubMed  Google Scholar 

  6. Martin JA, Hamilton BE, Osterman MJ. Births in the United States, 2015. NCHS Data Brief. 2016;258:1–8.

    Google Scholar 

  7. • Munro MG, Critchley HO, Broder MS, Fraser IS, FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113:3–13. Watershed article allowing classification of different types of fibroids based on location.

    Article  PubMed  Google Scholar 

  8. Du H, Taylor HS. The role of hox genes in female reproductive tract development, adult function, and fertility. Cold Spring Harb Perspect Med. 2015;6:1–14.

    Google Scholar 

  9. Rackow BW, Taylor HS. Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertil Steril. 2010;93:2027–34.

    Article  CAS  PubMed  Google Scholar 

  10. Makker A, Goel MM, Nigam D, Bhatia V, Mahdi AA, Das V, Pandey A. Endometrial expression of homeobox genes and cell adhesion molecules in infertile women with intramural fibroids during window of implantation. Reprod Sci 2016 Jul 12. pii:1933719116657196. [Epub ahead of print].

  11. Unlu C, Celik O, Celik N, Otlu B. Expression of endometrial receptivity genes increase after myomectomy of intramural leiomyomas not distorting the endometrial cavity. Reprod Sci. 2016;23:31–41.

    Article  CAS  PubMed  Google Scholar 

  12. Sinclair DC, Mastroyannis A, Taylor HS. Leiomyoma simultaneously impair endometrial BMP-2 mediated decidualization and anticoagulant expression through secretion of TGF-β. J Clin Endocrinol Metab. 2011;96:412–21.

    Article  CAS  PubMed  Google Scholar 

  13. Moon JW, Kim CH, Kim SH, Chae HD, Kang BM. Alterations in uterine hemodynamics caused by uterine fibroids and their impact on in vitro fertilization outcomes. Clin Exp Reprod Med. 2015;42:163–8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Fanchin R, Avoubi JM. Uterine dynamics: impact on the human reproduction process. Reprod BioMed Online. 2009;18(Suppl 2):57–62.

    Article  PubMed  Google Scholar 

  15. Kido A, Ascher SM, Hahn W, Kishimoto K, Kashitani N, Jha RC, et al. 3 T MRI uterine peristalsis: comparison of symptomatic fibroid patients versus controls. Clin Radio. 2014;69:468–72.

    Article  CAS  Google Scholar 

  16. Orisaka M, Kurokawa T, Shukunami K, Orisaka S, Fukuda MT, Shinagawa A, et al. A comparison of uterine peristalsis in women with normal uteri and uterine leiomyoma by cine magnetic resonance imaging. Eur J Obstet Gynecol Reprod Biol. 2007;135:111–5.

    Article  PubMed  Google Scholar 

  17. Yoshino O, Nishil O, Osuga Y, Asada H, Okuda S, Orisaka M, et al. Myomectomy decreases abnormal uterine peristalsis and increases pregnancy rate. J Minim Invasive Gynecol. 2012;19:63–7.

    Article  PubMed  Google Scholar 

  18. • Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril. 2009;91:1215–23. Largest meta-analysis on the role of fibroids on infertility.

    Article  PubMed  Google Scholar 

  19. Somigliani E, De Benedictis S, Vercellini P, Nicolosi AE, Benaglia L, Scarduelli C, et al. Fibroids not encroaching the endometrial cavity and IVF success rate: a prospective study. Hum Reprod. 2011;26:834–9.

    Article  Google Scholar 

  20. Retracted article. Shokeir T, El-Shafei M, Yousef H, Allam AF, Sadek E. Submucous myomas and their implications in the pregnancy rates of patients with otherwise unexplained primary infertility undergoing hysteroscopic myomectomy: a randomized matched control study. Fertil Steril 2010;94:724–9.

  21. Pritts EA. Fibroids and infertility: a systematic review of the evidence. Obstet Gynecol Surv. 2001;56:483–91.

    Article  CAS  PubMed  Google Scholar 

  22. Somigliana E, Vercellini P, Daguati R, Pasin R, De Giorgi O, Crosignani PG. Fibroids and female reproduction: a critical analysis of the evidence. Hum Reprod Update. 2007;13:465–76.

    Article  CAS  PubMed  Google Scholar 

  23. Sunkara SK, Khair M, El-Toukhy T, Khalaf Y, Coomarasamy A. The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta-analysis. Human Reprod. 2010;25:418–29.

    Article  Google Scholar 

  24. Oliveira FG, Abdelmassih VG, Diamond MP, Dozortsev D, Melo NR, Abdelmassih R. Impact of subserosal and intramural uterine fibroids that do not distort the endometrial cavity on the outcome of in vitro fertilization-intracytoplasmic sperm injection. Fertil Steril. 2004;81:582–7.

    Article  PubMed  Google Scholar 

  25. Guven S, Kart C, Unsal MA, Odaci E. Intramural leiomyoma without endometrial cavity distortion may negatively affect the ICSI-ET outcome. Reprod Biol Endocrinol. 2013;11:1–7.

    Article  Google Scholar 

  26. Yan L, Ding L, Li C, Wang Y, Tang R, Chen ZJ. Effect of fibroids not distorting the endometrial cavity on the outcome of in vitro fertilization treatment: a retrospective cohort study. Fertil Steril. 2014;101:716–21.

    Article  PubMed  Google Scholar 

  27. Shavell VI, Thakur M, Sawant A, Kruger ML, Jones TB, Singh M. Adverse obstetric outcomes associated with sonographically identified large uterine fibroids. Fertil Steril. 2012;97:107–10.

    Article  PubMed  Google Scholar 

  28. Metwally M, Cheong YC, Horne AW. Surgical treatment of fibroids for subfertility. Cochrane Database Syst Rev 2012;CD003857.

  29. Bosteels J, Kasius J, Weyers S, Broekmans FJ, Mol BW, D’Hooghe TM. Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities. Cochrane Database Syst Rev 2015;(2):CD009461.

  30. Bulletti C, De Ziegler D, Polli V, Flamigni C. The role of leiomyomas in infertility. J Am Assoc Gynecol Laparosc. 1999;6:441–5.

    Article  CAS  PubMed  Google Scholar 

  31. Purohit P, Vigneswaran K. Fibroids and infertility. Curr Obstet Gynecol Rep. 2016;5:81–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Carranza-Mamane B, Havelock J, Hemmings R, Cheung A, Sierra S, Reproductive Endocrinology and Infertility Committee, et al. The management of uterine fibroids in women with otherwise unexplained infertility. J Obstet Gynaecol Can. 2015;37:277–88.

    Article  PubMed  Google Scholar 

  33. Tsuji I, Fujinami N, Kotani Y, Tobiume T, Aoki M, Murakami K, et al. Reproductive outcome of infertile patients with fibroids based on patient and fibroid characteristics; optimal and personalized management. Gynecol Obstet Investig. 2016;81:325–32.

    Article  Google Scholar 

  34. • Lewis EI, Gargiulo AR. The role of hysteroscopic and robot-assisted laparoscopic myomectomy in the setting of infertility. Clin Obstet Gynecol. 2016;59:53–65. Recently published review of minimally invasive techniques for myomectomy in the setting of infertility.

    Article  PubMed  Google Scholar 

  35. Gargiulo AR. Fertility preservation and the role of robotics. Clin Obstet Gynecol. 2011;54:531–48.

    Article  Google Scholar 

  36. Groszmann YS, Benacerraf BR. Complete evaluation of anatomy and morphology of the infertile patient in a single visit; the modern infertility pelvic ultrasound examination. Fertil Steril 2016;105:1381–93.

  37. Dueholm M, Hjorth IM. Structured imaging technique in the gynecologic office for diagnosis of abnormal uterine bleeding. Best Pract res Clin Obstet Gynaecol 2016 Oct 1. pii: S1521-6934(16)30087-6. [Epub ahead of print]

  38. Dueholm M, Lundorf E, Hansen E, et al. Evaluation of the uterine cavity with magnetic resonance imaging, transvaginal sonography, hysterosonographic examination, and diagnostic hysteroscopy. Fertil Steril. 2001;76:350–7.

    Article  CAS  PubMed  Google Scholar 

  39. Levens E, Wesley R, Premkumar A, et al. Magnetic resonance imaging and transvaginal ultrasound for determining fibroid burden: implications for research and clinical care. Am J Obstet Gynecol. 2009;200:537.e1–7.

    Article  Google Scholar 

  40. • Falcone T, Parker WH. Surgical management of leiomyomas for fertility or uterine preservation. Obstet Gynecol. 2013;121:856–68. Methodical review of every surgical technique for fibroid removal.

    Article  PubMed  Google Scholar 

  41. Emanuel MH, Wamsteker K. The intra uterine morcellator: a new hysteroscopic operating technique to remove intrauterine polyps and myomas. J Minim Invasive Gynecol. 2005;12:62–6.

    Article  PubMed  Google Scholar 

  42. Shazly SA, Laughlin-Tommaso SK, Breitkopf DM, Jopkins MR, Burnett TL, Green IC, et al. Hysteroscopic morcellation versus resection for the treatment of uterine cavitary lesions: a systematic review and meta-analysis. J Minim Invasive Gynecol. 2016;23:867–77.

    Article  PubMed  Google Scholar 

  43. Yang JH, Chen MJ, Wu MY, et al. Office hysteroscopic early lysis of intrauterine adhesions after transcervical resection of multiple apposing submucous myomas. Fertil Steril. 2008;89:1254–9.

    Article  PubMed  Google Scholar 

  44. Taskin O, Sadik S, Onoglu A, et al. Role of endometrial suppression on frequency of intrauterine adhesions after resectoscopic surgery. J Am Gynecol Laparosc. 2000;7:351–4.

    Article  CAS  Google Scholar 

  45. Mazzon I, Favilli A, Cocco P, et al. Does cold loop hysteroscopic myomectomy reduce intrauterine adhesions? A retrospective study. Fertil Steril. 2013;101:294–8.

    Article  PubMed  Google Scholar 

  46. Di Spiezio SA, Calagna G, Scognamiglio M, O’Donovan P, Campo R, De Wilde RL. Prevention of intrauterine post-surgical adhesions in hysteroscopy. A systematic review. Eur J Obstet Gynecol Reprod Biol. 2016;203:182–92.

    Article  Google Scholar 

  47. Bhave Chittawar P, Franik S, Pouwer AW, Farquhar C. Minimally invasive surgical techniques versus open myomectomy for uterine fibroids. Cochrane Database Syst Rev. 2014;10:CD004638.

    Google Scholar 

  48. • Palomba S, Zupi E, Falbo A, Russo T, Marconi D, Tolino A, et al. A multicenter randomized, controlled study comparing laparoscopic versus minilaparotomic myomectomy: reproductive outcomes. Fertil Steril. 2007;88:933–41. Randomized controlled study comparing laparoscopic to mini-laparotomy myomectomy and their respective pregnancy rates after surgery.

    Article  PubMed  Google Scholar 

  49. Seracchioli R, Manuzzi L, Vianello F, Gualerzi B, Savelli L, Paradisi R, et al. Obstetric and delivery outcome of pregnancies achieved after laparoscopic myomectomy. Fertil Steril. 2006;86:159–65.

    Article  PubMed  Google Scholar 

  50. Sizzi O, Rossetti A, Malzoni M, Minelli L, La Grotta F, Soranna L, et al. Italian multicenter study on complications of laparoscopic myomectomy. J Minim Invasive Gynecol. 2007;14:453–62.

    Article  PubMed  Google Scholar 

  51. Parker WH, Einarsson J, Istre O, Dubuisson JB. Risk factors for uterine rupture after laparoscopic myomectomy. J Minim Invasive Gynecol. 2010;17:551–4.

    Article  PubMed  Google Scholar 

  52. Lui G, Zolis L, Kung R, et al. The laparoscopic myomectomy: a survey of Canadian gynaecologists. J Obstet Gynaecol Can. 2010;32:139–48.

    Article  Google Scholar 

  53. Lenihan JP Jr, Kovando C, Seshadi-Kreadon U. What is the learning curve for robotic assisted gynecologic surgery? J Minim Invas Gyncol. 2008;589–94.

  54. Lonnerfors C, Persson J. Pregnancy following robot-assisted laparoscopic myomectomy in women with deep intramural myomas. Acta Obstet Gynecol Scand. 2011;90:972–7.

    Article  PubMed  Google Scholar 

  55. Tinelli A, Mynbaev OA, Sparic R, Vergara D, Di Tommaso S, Salzet M, et al. Angiogenesis and vascularization of uterine leiomyoma: clinical value of pseudocapsule containing peptides and neurotransmitters. Curr Prot Pep Sci. 2017;18:1–11.

    Google Scholar 

  56. • Pitter MC, Srouji SS, Gargiulo AR, Kardos L, Seshadri-Kreaden U, Hubert HB, et al. Fertility and symptom relief following robot-assisted laparoscopic myomectomy. Obstet Gynecol Int. 2015;2015:967568. Largest review to date of reproductive and symptomatic outcomes following robot-assisted laparoscopic myomectomy.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Muzzi L, Boni T, Bellati F, et al. GnRH analogue treatment before hysteroscopic resection of submucous fibroids: a prospective, randomized, multicenter study. Fertil Steril. 2010;94:1496–9.

    Article  Google Scholar 

  58. Mavrelos D, Ben Nagi J, Davies A, et al. The value of pre-operative treatment with GnRH analogues in women with submucous fibroids: a double-blind, placebo controlled randomized trial. Hum Reprod. 2010;25:2264–9.

    Article  CAS  PubMed  Google Scholar 

  59. Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012;366:409–20.

    Article  CAS  PubMed  Google Scholar 

  60. Sancho JM, Delgado VS, Valero MJ, Soteras MG, Amate VP, Carrascosa AA. Hysteroscopic myomectomy outcomes after 3-month treatment with either ulipristal acetate or GnRH analogues: a retrospective comparative study. Eur J Obstet Gynecol Reprod Biol. 2016;198:127–30.

    Article  CAS  PubMed  Google Scholar 

  61. Ferrero S, Alessandri F, Vellone VG, Venturini PL, Maggiore LR. Three month treatment with ulipristal acetate prior to laparoscopic myomectomy of large uterine myomas: a retrospective study. Eur J Obstet Gynecol Reprod Bio. 2016;205:43–7.

    Article  CAS  Google Scholar 

  62. Chang WC, Chu LH, Huang PS, et al. Comparison of laparoscopic myomectomy in large myomas with and without leuprolide acetate. J Minim Invasive Gynecol. 2015;22:992–6.

    Article  PubMed  Google Scholar 

  63. Campbell J, Rajan DK, Kachura JR, Jaskolka J, Beecroft JR, Sniderman KW, et al. Efficacy of ovarian artery embolization for uterine fibroids: clinical and magnetic resonance imaging evaluation. Can Assoc Radiol J. 2015;66:164–70.

    Article  PubMed  Google Scholar 

  64. Gupta JK, Sinha A, Lumsden MA, Hickey M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev 2013: CD005073.

  65. Walker WJ, MvFoerll DJ. Pregnancy subsequent to uterine artery embolization. Fertil Steril. 2010;75:1246–8.

    Google Scholar 

  66. Torre A, Paillusson B, Fain V, Labauge P, Pelage JP, Fauconnier A. Uterine artery embolization for severe symptomatic fibroids: effects on fertility and symptoms. Hum Reprod. 2014;29:490–501.

    Article  CAS  PubMed  Google Scholar 

  67. Mara M, Maskova J, Fucikova Z, Kuzel D, Belsan T, Sosna O. Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy. Cardiovasc Intervent Radiol. 2008;31:73–85.

    Article  PubMed  Google Scholar 

  68. Spies JB. Current role of uterine arty embolization in the management of uterine fibroids. Spies JB Clin Obstet Gynecol. 2016;59:93–102.

    Article  PubMed  Google Scholar 

  69. Park MK, Kim YS, Rhim H, Lim HK. Safety and therapeutic efficacy of complete or near-complete ablation of symptomatic uterine fibroid tumors by MR imaging-guided high-intensity focused US therapy. J Vasc Interv Radiol. 2014;25:231–9.

    Article  PubMed  Google Scholar 

  70. Rabinovici J, David M, Fukunishi H, Morita Y, Gostout BS, Stewart EA, MRgFUS Study Group. Pregnancy outcomes after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for conservative treatment of uteirne fibroids. Fertil Steril. 2010;93:199–209.

    Article  PubMed  Google Scholar 

  71. Stewart EQ, Gostout B, Rabinovici J, Kim HS, Regan L, Tempany CM. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gyencol. 2007;110:279–87.

    Article  Google Scholar 

  72. Laughlin-Tommaso SK. Alternative to hysterectomy: management of uterine fibroids. Obstet Gynecol Clin N Am. 2016;43:397–413.

    Article  Google Scholar 

  73. Berman JM, Guido RS, Garza Leal JG, Pemueller RR, Whaley FS, Chudnoff SG, Halt Study Group. Three-year outcome of the Halt trial: a prospective analysis of radiofrequency volumetric thermal ablation of myomas. J Minim Invasive Gynecol. 2014;21:767–74.

    Article  PubMed  Google Scholar 

  74. Kramer B, Hahn M, Taran FA, Kraemer D, Isaacson KB, Brucker SY. Interim analysis of a randomized controlled trial comparing laparoscopic radiofrequency volumetric thermal ablation of uterine fibroids with laparoscopic myomectomy. Int J Gynaecol Obstet. 2016;133:206–11.

    Article  PubMed  Google Scholar 

  75. Berman JM, Thiel J, Brucker SY. Reproductive outcomes in subjects following radiofrequency volumetric thermal ablation (RFVTA) of their symptomatic myomas: a retrospective case series. J Minim Invasive Gynecol. 2015;22:S237.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio R. Gargiulo.

Ethics declarations

Conflict of Interest

Erin I. Lewis declares no conflicts of interest.

Antonio R. Gargiulo is a consultant for Medicaroid, which builds robotic equipment for medical use, and a consultant for OmniGuide Holdings, which builds laser and ferromagnetic energy tools for medical use.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Reproductive Endocrinology and Infertility (REI)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lewis, E.I., Gargiulo, A.R. Uterine Fibroids in the Setting of Infertility: When to Treat, How to Treat?. Curr Obstet Gynecol Rep 6, 1–10 (2017). https://doi.org/10.1007/s13669-017-0192-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13669-017-0192-4

Keywords

Navigation