Fertility-related considerations in endometriosis

  • Zaraq KhanEmail author
Special Section: The pelvic floor


Endometriosis and infertility often present together but the exact cause–effect mechanism of this association is unknown. Though there are several proposed mechanisms regarding the pathophysiology of endometriosis-related infertility, no one theory is universally accepted. Surgical exploration is gold standard for diagnosis but imaging modalities especially specialized ultrasonography and magnetic resonance imaging can highlight disease burden and aid in planning for surgical excision. Overall, medical therapy is ineffective for endometriosis-related infertility; however, surgery may be fertility enhancing in women with minimal stage disease and in women with large endometriomas. Assisted reproductive technology may be required with endometriosis-related infertility. Medically induced superovulation with intrauterine insemination is typically the first line; however, women with advanced disease may need a more aggressive form of treatment with in vitro fertilization.


Endometriosis Infertility Pregnancy ART IVF Endometrioma Deep infiltrating endometriosis (DIE) 



  1. 1.
    Endometriosis and infertility: a committee opinion. Fertility and Sterility. 2012;98(3):591-8.CrossRefGoogle Scholar
  2. 2.
    Balasch J, Creus M, Fabregues F, Carmona F, Ordi J, Martinez-Román S, et al. Visible and non-visible endometriosis at laparoscopy in fertile and infertile women and in patients with chronic pelvic pain: a prospective study. Human Reproduction. 1996;11(2):387-91.CrossRefGoogle Scholar
  3. 3.
    Carter JE. Combined hysteroscopic and laparoscopic findings in patients with chronic pelvic pain. J Am Assoc Gynecol Laparosc. 1994;2(1):43-7.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Simoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Human Reproduction. 2012;27(5):1292-9.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chandra A MW. The demography of infertility and the use of medical care for infertility. Infertil Reprod Med Clin North Am 1994;5:283-96.Google Scholar
  6. 6.
    Schwartz D, Mayaux MJ. Female Fecundity as a Function of Age. New England Journal of Medicine. 1982;306(7):404-6.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hughes EG, Fedorkow DM, Collins JA. A quantitative overview of controlled trials in endometriosis-associated infertility. Fertil Steril. 1993;59(5):963-70.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Akande VA, Hunt LP, Cahill DJ, Jenkins JM. Differences in time to natural conception between women with unexplained infertility and infertile women with minor endometriosis. Hum Reprod. 2004;19(1):96-103.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Brosens I. Endometriosis and the outcome of in vitro fertilization. Fertil Steril. 2004;81(5):1198-200.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Olivennes F. [Results of IVF in women with endometriosis]. J Gynecol Obstet Biol Reprod (Paris). 2003;32(8 Pt 2):S45-7.Google Scholar
  11. 11.
    Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268-79.CrossRefPubMedGoogle Scholar
  12. 12.
    Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362(25):2389-98.CrossRefPubMedGoogle Scholar
  13. 13.
    Schenken RS, Asch RH, Williams RF, Hodgen GD. Etiology of infertility in monkeys with endometriosis: luteinized unruptured follicles, luteal phase defects, pelvic adhesions, and spontaneous abortions. Fertil Steril. 1984;41(1):122-30.CrossRefPubMedGoogle Scholar
  14. 14.
    Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, et al. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod. 2002;17(2):426-31.CrossRefPubMedGoogle Scholar
  15. 15.
    Pizzo A SF, Ardita FV, Sofo V, Tripepi M, Marsico S. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2003;54:82-7.CrossRefGoogle Scholar
  16. 16.
    Opoien HK, Fedorcsak P, Polec A, Stensen MH, Abyholm T, Tanbo T. Do endometriomas induce an inflammatory reaction in nearby follicles? Hum Reprod. 2013;28(7):1837-45.CrossRefPubMedGoogle Scholar
  17. 17.
    Punnonen J, Teisala K, Ranta H, Bennett B, Punnonen R. Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis. Am J Obstet Gynecol. 1996;174(5):1522-6.CrossRefPubMedGoogle Scholar
  18. 18.
    Yoshida S, Harada T, Iwabe T, Taniguchi F, Mitsunari M, Yamauchi N, et al. A combination of interleukin-6 and its soluble receptor impairs sperm motility: implications in infertility associated with endometriosis. Hum Reprod. 2004;19(8):1821-5.CrossRefPubMedGoogle Scholar
  19. 19.
    Mansour G, Aziz N, Sharma R, Falcone T, Goldberg J, Agarwal A. The impact of peritoneal fluid from healthy women and from women with endometriosis on sperm DNA and its relationship to the sperm deformity index. Fertil Steril. 2009;92(1):61-7.CrossRefPubMedGoogle Scholar
  20. 20.
    Pellicer A, Oliveira N, Ruiz A, Remohi J, Simon C. Exploring the mechanism(s) of endometriosis-related infertility: an analysis of embryo development and implantation in assisted reproduction. Hum Reprod. 1995;10 Suppl 2:91-7.CrossRefPubMedGoogle Scholar
  21. 21.
    Dmowski WP, Rao R, Scommegna A. The luteinized unruptured follicle syndrome and endometriosis. Fertil Steril. 1980;33(1):30-4.CrossRefPubMedGoogle Scholar
  22. 22.
    Cahill DJ, Hull MG. Pituitary-ovarian dysfunction and endometriosis. Hum Reprod Update. 2000;6(1):56-66.CrossRefPubMedGoogle Scholar
  23. 23.
    Kitajima M, Dolmans MM, Donnez O, Masuzaki H, Soares M, Donnez J. Enhanced follicular recruitment and atresia in cortex derived from ovaries with endometriomas. Fertil Steril. 2014;101(4):1031-7.CrossRefPubMedGoogle Scholar
  24. 24.
    Garrido N, Navarro J, Garcia-Velasco J, Remoh J, Pellice A, Simon C. The endometrium versus embryonic quality in endometriosis-related infertility. Hum Reprod Update. 2002;8(1):95-103.CrossRefPubMedGoogle Scholar
  25. 25.
    Matorras R, Corcostegui B, Esteban J, Ramon O, Prieto B, Exposito A, et al. Fertility in women with minimal endometriosis compared with normal women was assessed by means of a donor insemination program in unstimulated cycles. Am J Obstet Gynecol. 2010;203(4):345 e1-6.CrossRefGoogle Scholar
  26. 26.
    Lessey BA, Castelbaum AJ, Sawin SW, Buck CA, Schinnar R, Bilker W, et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab. 1994;79(2):643-9.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Bulun SE, Cheng YH, Yin P, Imir G, Utsunomiya H, Attar E, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006;248(1-2):94-103.CrossRefPubMedGoogle Scholar
  28. 28.
    Taylor HS, Bagot C, Kardana A, Olive D, Arici A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328-31.CrossRefPubMedGoogle Scholar
  29. 29.
    Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1-10.CrossRefPubMedGoogle Scholar
  30. 30.
    Leyendecker G, Kunz G, Wildt L, Beil D, Deininger H. Uterine hyperperistalsis and dysperistalsis as dysfunctions of the mechanism of rapid sperm transport in patients with endometriosis and infertility. Hum Reprod. 1996;11(7):1542-51.CrossRefGoogle Scholar
  31. 31.
    Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68(4):585-96.CrossRefGoogle Scholar
  32. 32.
    Bazot M, Darai E. Diagnosis of deep endometriosis: clinical examination, ultrasonography, magnetic resonance imaging, and other techniques. Fertil Steril. 2017;108(6):886-94.CrossRefGoogle Scholar
  33. 33.
    Falcone T, Flyckt R. Clinical Management of Endometriosis. Obstet Gynecol. 2018;131(3):557-71.CrossRefGoogle Scholar
  34. 34.
    Guerriero S, Condous G, van den Bosch T, Valentin L, Leone FP, Van Schoubroeck D, et al. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group. Ultrasound Obstet Gynecol. 2016;48(3):318-32.CrossRefGoogle Scholar
  35. 35.
    Abrao MS, Goncalves MO, Dias JA, Jr., Podgaec S, Chamie LP, Blasbalg R. Comparison between clinical examination, transvaginal sonography and magnetic resonance imaging for the diagnosis of deep endometriosis. Hum Reprod. 2007;22(12):3092-7.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Bazot M, Malzy P, Cortez A, Roseau G, Amouyal P, Darai E. Accuracy of transvaginal sonography and rectal endoscopic sonography in the diagnosis of deep infiltrating endometriosis. Ultrasound Obstet Gynecol. 2007;30(7):994-1001.CrossRefGoogle Scholar
  37. 37.
    Bazot M, Bharwani N, Huchon C, Kinkel K, Cunha TM, Guerra A, et al. European society of urogenital radiology (ESUR) guidelines: MR imaging of pelvic endometriosis. Eur Radiol. 2017;27(7):2765-75.CrossRefGoogle Scholar
  38. 38.
    Nisenblat V, Bossuyt PM, Farquhar C, Johnson N, Hull ML. Imaging modalities for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016;2:CD009591.Google Scholar
  39. 39.
    Ozkan S, Murk W, Arici A. Endometriosis and infertility: epidemiology and evidence-based treatments. Ann N Y Acad Sci. 2008;1127:92-100.CrossRefGoogle Scholar
  40. 40.
    Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997;337(4):217-22.CrossRefPubMedGoogle Scholar
  41. 41.
    Berube S, Marcoux S, Langevin M, Maheux R. Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. The Canadian Collaborative Group on Endometriosis. Fertil Steril. 1998;69(6):1034-41.CrossRefPubMedGoogle Scholar
  42. 42.
    Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst Rev. 2007(3):CD000155.Google Scholar
  43. 43.
    Guo YH, Lu N, Zhang Y, Su YC, Wang Y, Zhang YL, et al. Comparative study on the pregnancy outcomes of in vitro fertilization-embryo transfer between long-acting gonadotropin-releasing hormone agonist combined with transvaginal ultrasound-guided cyst aspiration and long-acting gonadotropin-releasing hormone agonist alone. Contemp Clin Trials. 2012;33(6):1206-10.CrossRefPubMedGoogle Scholar
  44. 44.
    Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril. 2002;78(4):699-704.CrossRefPubMedGoogle Scholar
  45. 45.
    Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006(1):CD004635.Google Scholar
  46. 46.
    Busacca M, Fedele L, Bianchi S, Candiani M, Agnoli B, Raffaelli R, et al. Surgical treatment of recurrent endometriosis: laparotomy versus laparoscopy. Hum Reprod. 1998;13(8):2271-4.CrossRefPubMedGoogle Scholar
  47. 47.
    Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535-49.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Pundir J, Omanwa K, Kovoor E, Pundir V, Lancaster G, Barton-Smith P. Laparoscopic Excision Versus Ablation for Endometriosis-associated Pain: An Updated Systematic Review and Meta-analysis. J Minim Invasive Gynecol. 2017;24(5):747-56.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Parazzini F. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell’Endometriosi. Hum Reprod. 1999;14(5):1332-4.Google Scholar
  50. 50.
    Jacobson TZ, Duffy JM, Barlow D, Farquhar C, Koninckx PR, Olive D. Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database Syst Rev. 2010(1):CD001398.Google Scholar
  51. 51.
    Flyckt R, Kim S, Falcone T. Surgical Management of Endometriosis in Patients with Chronic Pelvic Pain. Semin Reprod Med. 2017;35(1):54-64.CrossRefPubMedGoogle Scholar
  52. 52.
    Camus E, Poncelet C, Goffinet F, Wainer B, Merlet F, Nisand I, et al. Pregnancy rates after in vitro fertilization in cases of tubal infertility with and without hydrosalpinx: a meta-analysis of published comparative studies. Hum Reprod. 1999;14(5):1243-9.CrossRefPubMedGoogle Scholar
  53. 53.
    Zeyneloglu HB, Arici A, Olive DL. Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization-embryo transfer. Fertil Steril. 1998;70(3):492-9.CrossRefPubMedGoogle Scholar
  54. 54.
    Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane Database Syst Rev. 2008(2):CD004992.Google Scholar
  55. 55.
    Goodman LR, Goldberg JM, Flyckt RL, Gupta M, Harwalker J, Falcone T. Effect of surgery on ovarian reserve in women with endometriomas, endometriosis and controls. Am J Obstet Gynecol. 2016;215(5):589 e1- e6.CrossRefPubMedGoogle Scholar
  56. 56.
    Chapron C, Vercellini P, Barakat H, Vieira M, Dubuisson JB. Management of ovarian endometriomas. Hum Reprod Update. 2002;8(6):591-7.CrossRefPubMedGoogle Scholar
  57. 57.
    Deaton JL, Gibson M, Blackmer KM, Nakajima ST, Badger GJ, Brumsted JR. A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertil Steril. 1990;54(6):1083-8.CrossRefPubMedGoogle Scholar
  58. 58.
    Fedele L, Bianchi S, Marchini M, Villa L, Brioschi D, Parazzini F. Superovulation with human menopausal gonadotropins in the treatment of infertility associated with minimal or mild endometriosis: a controlled randomized study. Fertil Steril. 1992;58(1):28-31.CrossRefPubMedGoogle Scholar
  59. 59.
    Kemmann E, Ghazi D, Corsan G, Bohrer MK. Does ovulation stimulation improve fertility in women with minimal/mild endometriosis after laser laparoscopy? Int J Fertil Menopausal Stud. 1993;38(1):16-21.PubMedGoogle Scholar
  60. 60.
    Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77(6):1148-55.CrossRefPubMedGoogle Scholar
  61. 61.
    Stephansson O, Kieler H, Granath F, Falconer H. Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome. Hum Reprod. 2009;24(9):2341-7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Reproductive Endocrinology & Infertility and Minimally Invasive, Gynecologic Surgery, Department of Obstetrics & GynecologyMayo ClinicRochesterUSA

Personalised recommendations