• Alexandra S. Kohl SchwartzEmail author
  • Sara Imboden
  • Michael von Wolff


In advanced endometriosis, there is a substantial risk of a reduction of the ovarian reserve. Both the endometriosis itself and the required surgery can affect ovarian function and fertility. For fertility preservation medical treatment to slow down the progression of the disease and ovary conserving surgery by specialised surgeons are essential. If a substantial decrease in fertility is expected as in young women with deep infiltrating endometriosis or in women with endometrioma of both ovaries or of one remaining ovary, ovarian stimulation and freezing of oocytes can be an option. The stimulation regime needs to be adapted to avoid complications and ovarian surgery should not be performed directly after follicle aspiration.


Adenomyosis Endometriosis Endometrioma Endometriosis Fertility Index (EFI) FertiPROTEKT Letrozole Oocyte freezing Ovarian stimulation Ovarian surgery 


  1. 1.
    Viganò P, Parazzini F, Somigliana E, Vercellini P. Endometriosis: epidemiology and aetiological factors. Best Pract Res Clin Obstet Gynaecol. 2004;18:177–200.PubMedGoogle Scholar
  2. 2.
    de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376:730–8.PubMedGoogle Scholar
  3. 3.
    Brosens I, Gordts S, Benagiano G. Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion. Hum Reprod. 2013;28:2026–31.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Benagiano G, Guo S-W, Puttemans P, Gordts S, Brosens I. Progress in the diagnosis and management of adolescent endometriosis: an opinion. Reprod Biomed Online. 2018;36:102–14.PubMedGoogle Scholar
  5. 5.
    Vercellini P, Trespidi L, De Giorgi O, Cortesi I, Parazzini F, Crosignani PG. Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril. 1996;65:299–304.PubMedGoogle Scholar
  6. 6.
    Guzick DS, Silliman NP, Adamson GD, Buttram VC, Canis M, Malinak LR, Schenken R. Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicine’s revised classification of endometriosis. Fertil Steril. 1997;67:822–9.PubMedGoogle Scholar
  7. 7.
    American Society for Reproductive. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817–21.Google Scholar
  8. 8.
    Haas D, Chvatal R, Habelsberger A, Wurm P, Schimetta W, Oppelt P. Comparison of revised American Fertility Society and ENZIAN staging: a critical evaluation of classifications of endometriosis on the basis of our patient population. Fertil Steril. 2011;95:1574–8.PubMedGoogle Scholar
  9. 9.
    Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75:1–10.PubMedGoogle Scholar
  10. 10.
    Wu G, Bersinger NA, Mueller MD, von Wolff M. Intrafollicular inflammatory cytokines but not steroid hormone concentrations are increased in naturally matured follicles of women with proven endometriosis. J Assist Reprod Genet. 2017;34:357–64.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Oral E, Seli E, Bahtiyar MO, Olive DL, Arici A. Growth-regulated alpha expression in the peritoneal environment with endometriosis. Obstet Gynecol. 1996;88:1050–6.PubMedGoogle Scholar
  12. 12.
    Lyons RA, Djahanbakhch O, Saridogan E, Naftalin AA, Mahmood T, Weekes A, Chenoy R. Peritoneal fluid, endometriosis, and ciliary beat frequency in the human fallopian tube. Lancet. 2002;360:1221–2.PubMedGoogle Scholar
  13. 13.
    Ota H, Igarashi S, Sato N, Tanaka H, Tanaka T. Involvement of catalase in the endometrium of patients with endometriosis and adenomyosis. Fertil Steril. 2002;78:804–9.PubMedGoogle Scholar
  14. 14.
    Grandi G, Mueller MD, Bersinger NA, Facchinetti F, McKinnon BD. The association between progestins, nuclear receptors expression and inflammation in endometrial stromal cells from women with endometriosis. Gynecol Endocrinol. 2017;33:712–5.PubMedGoogle Scholar
  15. 15.
    McKinnon BD, Kocbek V, Nirgianakis K, Bersinger NA, Mueller MD. Kinase signalling pathways in endometriosis: potential targets for non-hormonal therapeutics. Hum Reprod Update. 2016;22:382–403.PubMedGoogle Scholar
  16. 16.
    Patel BG, Rudnicki M, Yu J, Shu Y, Taylor RN. Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet Gynecol Scand. 2017;96:623–32.PubMedGoogle Scholar
  17. 17.
    McKinnon B, Mueller M, Montgomery G. Progesterone resistance in endometriosis: an acquired property? Trends Endocrinol Metab. 2018;29:535–48.PubMedGoogle Scholar
  18. 18.
    Giudice LC. Endometriosis. N Engl J Med. 2010;362:2389–98.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Santamaria X, Massasa EE, Taylor HS. Migration of cells from experimental endometriosis to the uterine endometrium. Endocrinology. 2012;153:5566–74.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Vallvé-Juanico J, Houshdaran S, Giudice LC. The endometrial immune environment of women with endometriosis. Hum Reprod Update. 2019;25:565–92.Google Scholar
  21. 21.
    Sanchez AM, Papaleo E, Corti L, Santambrogio P, Levi S, Vigano P, Candiani M, Panina-Bordignon P. Iron availability is increased in individual human ovarian follicles in close proximity to an endometrioma compared with distal ones. Hum Reprod. 2014;29:577–83.PubMedGoogle Scholar
  22. 22.
    Kitajima M, Defrère S, Dolmans M-M, Colette S, Squifflet J, Van Langendonckt A, Donnez J. Endometriomas as a possible cause of reduced ovarian reserve in women with endometriosis. Fertil Steril. 2011;96:685–91.PubMedGoogle Scholar
  23. 23.
    Kohl Schwartz AS, Wölfler MM, Mitter V, Rauchfuss M, Haeberlin F, Eberhard M, von Orelli S, Imthurn B, Imesch P, Fink D, Leeners B. Endometriosis, especially mild disease: a risk factor for miscarriages. Fertil Steril. 2017;108:806–14.PubMedGoogle Scholar
  24. 24.
    Somigliana E, Marchese MA, Frattaruolo MP, Berlanda N, Fedele L, Vercellini P. Serum anti-mullerian hormone in reproductive aged women with benign ovarian cysts. Eur J Obstet Gynecol Reprod Biol. 2014;180:142–7.PubMedGoogle Scholar
  25. 25.
    Bourdon M, Raad J, Dahan Y, Marcellin L, Maignien C, Even M, Pocate-Cheriet K, Lamau M, Santulli P, Chapron C. Endometriosis and ART: A prior history of surgery for OMA is associated with a poor ovarian response to hyperstimulation. PLoS One. 2018;13:e0202399.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Benaglia L, Bermejo A, Somigliana E, Faulisi S, Ragni G, Fedele L, Garcia-Velasco J. In vitro fertilization outcome in women with unoperated bioateral endometriomas. Fertil Steril. 2013;99:1714–9.PubMedGoogle Scholar
  27. 27.
    Benaglia L, Somigliana E, Vercellini P, Abbiati A, Ragni G, Fedele L. Endometriotic ovarian cysts negatively affect the rate of spontaneous ovulation. Hum Reprod. 2009;24:2183–6.PubMedGoogle Scholar
  28. 28.
    Raffi F, Metwally M, Amer S. The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012;97:3146–54.PubMedGoogle Scholar
  29. 29.
    Hirokawa W, Iwase A, Goto M, Takikawa S, Nagatomo Y, Nakahara T, Bayasula B, Nakamura T, Manabe S, Kikkawa F. The post-operative decline in serum anti-Müllerian hormone correlates with the bilaterality and severity of endometriosis. Hum Reprod. 2011;26:904–10.PubMedGoogle Scholar
  30. 30.
    Hamdan M, Dunselman G, Li TC, Cheong Y. The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis. Hum Reprod Update. 2015;21:809–25.PubMedGoogle Scholar
  31. 31.
    Adamson GD, Pasta DJ. Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril. 2010;94:1609–15.PubMedGoogle Scholar
  32. 32.
    Tomassetti C, Geysenbergh B, Meuleman C, Timmerman D, Fieuws S, D’Hooghe T. External validation of the endometriosis fertility index (EFI) staging system for predicting non-ART pregnancy after endometriosis surgery. Hum Reprod. 2013;28:1280–8.PubMedGoogle Scholar
  33. 33.
    Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, Heikinheimo O, Horne AW, Kiesel L, Nap A, Prentice A, Saridogan E, Soriano D, Nelen W, European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29:400–12.PubMedGoogle Scholar
  34. 34.
    Muzii L, Di Tucci C, Di Feliciantonio M, Marchetti C, Perniola G, Panici PB. The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis. Hum Reprod. 2014;29:2190–8.PubMedGoogle Scholar
  35. 35.
    Ferrero S, Venturini PL, Gillott DJ, Remorgida V, Leone Roberti Maggiore U. Hemostasis by bipolar coagulation versus suture after surgical stripping of bilateral ovarian endometriomas: a randomized controlled trial. J Minim Invasive Gynecol. 2012;19:722–30.PubMedGoogle Scholar
  36. 36.
    Muzii L, Achilli C, Bergamini V, Candiani M, Garavaglia E, Lazzeri L, Lecce F, Maiorana A, Maneschi F, Marana R, Perandini A, Porpora M, Seracchioli R, Spangolo E, Vignali M, Benedetti PP. Comparison between the stripping technique and the combined excisional/ablative technique for the treatment of bilateral ovarian endometriomas: a multicentre RCT. Hum Reprod. 2016;31:339–44.PubMedGoogle Scholar
  37. 37.
    Elizur SE, Chian R-C, Holzer HEG, Gidoni Y, Tulandi T, Tan SL. Cryopreservation of oocytes in a young woman with severe and symptomatic endometriosis: a new indication for fertility preservation. Fertil Steril. 2009;91:293.e1–3.Google Scholar
  38. 38.
    Raad J, Sonigo C, Tran C, Sifer C, Cedrin Durnerin I, Grynberg M. Oocyte vitrification for preserving fertility in patients with endometriosis: first observational cohort study and many unresolved questions. Eur J Obstet Gynecol Reprod Biol. 2018;220:140–1.PubMedGoogle Scholar
  39. 39.
    Cobo A, García-Velasco JA. Why all women should freeze their eggs. Curr Opin Obstet Gynecol. 2016;28:206–10.PubMedGoogle Scholar
  40. 40.
    Seyhan A, Urman B, Turkgeldi E, Ata B. Do endometriomas grow during ovarian stimulation for assisted reproduction? A three-dimensional volume analysis before and after ovarian stimulation. Reprod Biomed Online. 2018;36:239–44.PubMedGoogle Scholar
  41. 41.
    Kim SJ, Choo CW, Kim SK, Lee JR, Jee BC, Suh CS, Lee W, Kim S. The effects of letrozole on women with endometriosis undergoing ovarian stimulation for in vitro fertilization. Gynecol Endocrinol. 2019;36:257–60.PubMedGoogle Scholar
  42. 42.
    Chen M-J, Yang J-H, Yang Y-S, Ho H-N. Increased occurrence of tubo-ovarian abscesses in women with stage III and IV endometriosis. Fertil Steril. 2004;82:498–9.PubMedGoogle Scholar
  43. 43.
    Yaron Y, Peyser MR, Samuel D, Amit A, Lessing JB. Infected endometriotic cysts secondary to oocyte aspiration for in-vitro fertilization. Hum Reprod. 1994;9:1759–60.PubMedGoogle Scholar
  44. 44.
    Benaglia L, Somigliana E, Iemmello R, Colpi E, Nicolosi AE, Ragni G. Endometrioma and oocyte retrieval–induced pelvic abscess: a clinical concern or an exceptional complication? Fertil Steril. 2008;89:1263–6.PubMedGoogle Scholar
  45. 45.
    von Wolff M, Stute P. Hormonelle Substanzklassen. Gynäkologische Endokrinologie und Reproduktionsmedizin. Schattauer 1. Ausgabe, 2013:5-18.Google Scholar
  46. 46.
    Xue Cao, Hong-yang Chang, Jun-yan Xu, Yi Zheng, Yun-gai Xiang, Bing Xiao, Xu-jing Geng, Li-li Ni, Xi-ying Chu, Shi-bo Tao, Yan He, Gen-hong Mao. The effectiveness of different down-regulating protocols on in vitro fertilization-embryo transfer in endometriosis: a meta-analysis. Reprod Biol and Endocrinol. 2020;18:1.Google Scholar
  47. 47.
    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;29:1026–30.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Alexandra S. Kohl Schwartz
    • 1
    Email author
  • Sara Imboden
    • 2
  • Michael von Wolff
    • 1
  1. 1.Division of Gynecological Endocrinology and Reproductive MedicineUniversity Women’s Hospital, University of BernBernSwitzerland
  2. 2.Department of Obstetrics and GynecologyUniversity Women’s Hospital, University of BernBernSwitzerland

Personalised recommendations