November 17, 2015

Study Suggests Decline in Ovarian Reserve After Surgery

Cleveland Clinic investigators report preliminary results

Endometrioma-690×380

By Linnea R. Goodman, MD, and Tommaso Falcone, MD

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Preliminary results of a prospective evaluation suggest that surgical resection of ovarian endometriomas may precipitate a substantial, persistent decline in ovarian reserve.

Endometriosis, affecting up to 2 percent of women of reproductive age 1,2, can be asymptomatic but often causes pain and/or infertility. Researchers hypothesize that the mere presence of endometriomas — cysts that form when the ovaries are involved — may have a detrimental effect on ovarian reserve3.

Resection to improve fertility controversial

While surgery offers definitive treatment, removal of endometrioma(s) for fertility purposes remains controversial due to concerns that cyst removal may damage healthy ovarian tissue, further decreasing ovarian reserve4,5.

Anti-Mullerian hormone (AMH) has proven to be a reliable surrogate marker of ovarian reserve 6, 7. Despite extensive scientific exploration, however, the relationship between pelvic endometriosis and AMH levels remains uncertain8,9.

Studies on the impact of endometrioma excision on ovarian reserve over time have also had mixed results. However, most studies of AMH levels after endometrioma removal report a decrease in ovarian reserve, particularly with bilaterality.

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No studies to date have looked at ovarian reserve, before and after surgery, in women with ovarian endometriomas versus a similar subfertile population whose complaints are consistent with suspected pelvic endometriosis.

Comparing AMH levels in cohorts over time

The goals of our prospective cohort trial were to determine whether baseline ovarian reserve was lower in women with ovarian endometriomas than in women with only pelvic endometriotic lesions, as compared to those with negative laparoscopies; and to assess the impact of laparoscopic surgical excision of endometriomas on long-term ovarian reserve.

We recruited 116 patients from our reproductive endocrinology and infertility clinic. Half the women had radiological evidence of endometrioma(s). The other half had complaints (pain and/or infertility) consistent with pelvic endometriosis but no evidence of ovarian involvement on imaging.

We further segregated the control group into subjects with pathological confirmation of pelvic endometriosis on surgical exploration and subjects with no evidence of endometriosis. There were no significant differences in age, body mass index or presenting complaints between the groups.

Patients underwent AMH testing preoperatively for a baseline value; at four to six weeks after surgery; and then six months postoperatively. AMH values were compared longitudinally and between groups.

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Early findings recommend cautious approach

Overall, based on preliminary results, baseline AMH values were lower in subjects with endometriomas than in those without endometriomas. AMH levels remained stable after surgery in subjects with only pelvic endometriosis or with negative laparoscopies. However, evidence suggested a substantial, persistent decline in ovarian reserve over the six-month follow-up period for those undergoing endometrioma resection.

These preliminary results support the need for conservative surgical management in the subfertile population as ovarian endometrioma surgery may have persistent, deleterious effects on ovarian reserve.

Dr. Falcone is Professor and Chair of Cleveland Clinic’s Ob/Gyn & Women’s Health Institute and may be reached at 216.444.1758 or falcont@ccf.org.

Dr. Goodman is a fellow in the Department of Reproductive Endocrinology and Infertility, and may be reached at 216.839.3150 or goodmal3@ccf.org.

References

  1. Abbas S, Ihle P, Koster I, Schubert I. Prevalence and incidence of diagnosed endometriosis and risk of endometriosis in patients with endometriosis-related symptoms: findings from a statutory health insurance-based cohort in Germany. Eur J Obstet Gynecol Reprod Biol 2012;160:79-83.
  2. Gylfason JT, Kristjansson KA, Sverrisdottir G, Jonsdottir K, Rafnsson V, Geirsson RT. Pelvic endometriosis diagnosed in an entire nation over 20 years. Am J Epidemiol 2010;172:237-243.
  3. Uncu G, Kasapoglu I, Ozerkan K, Seyhan A, Oral Yilmaztepe A, Ata B. Prospective assessment of the impact of endometriomas and their removal on ovarian reserve and determinants of the rate of decline in ovarian reserve. Hum Reprod. 2013 Aug;28(8):2140-5.
  4. Muzii L, Bianchi A, Crocè C, Manci N, Panici PB. Laparoscopic excision of ovarian cysts: is the stripping technique a tissue-sparing procedure? Fertil Steril, 77 (2002), pp. 609–614.
  5. Hachisuga T, Kawarabayashi T. Histopathological analysis of laparoscopically treated ovarian endometriotic cysts with special reference to loss of follicles. Hum Reprod, 17 (2002), pp. 432–435.
  6. Fanchin R, Schonäuer LM, Righini C, Guibourdenche J, Frydman R, Taieb J. Serum anti-Mullerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod 2003; 18:323–327.
  7. Van Rooij IA, Broekmans FJ, Scheffer GJ, Looman CW, Habbema JD, de Jong FH, Fauser BJ, Themmen AP, te Velde ER. Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertil Steril 2005; 83:979–987.
  8. Shebl O, Ebner T, Sommergruber M, Sir A, Tews G. Anti Muellerian hormone serum levels in women with endometriosis: a case-control study. Gynecol Endocrinol 2009;25:713-716.
  9. Streuli I, de Ziegler D, Gayet V, Santulli P, Bijaoui G, de Mouzon J, Chapron C. In women with endometriosis anti-Müllerian hormone levels are decreased only in those with previous endometrioma surgery. Hum Reprod. 2012 Nov;27(11):3294-303.
  10. Chang HJ, Han SH, Lee JR, Jee BC, Lee BI, Suh CS et al. Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-Müllerian hormone levels Fertil Steril, 94 (2010), pp. 343–349.
  11. Ercan CM, Sakinci M, Duru NK, Alanbay I, Karasahin KE, Baser I. Antimullerian hormone levels after laparoscopic endometrioma stripping surgery Gynecol Endocrinol, 26 (2010), pp. 468–472.
  12. Iwase A, Hirokawa W, Goto M, Takikawa S, Nagatomo Y, Nakahara T et al. Serum anti-Müllerian hormone level is a useful marker for evaluating the impact of laparoscopic cystectomy on ovarian reserve. Fertil Steril, 94 (2010), pp. 2846–2849.
  13. Hirokawa W, Iwase A, Goto M, Takikawa S, Nagatomo Y, Nakahara T et al. The post-operative decline in serum anti-Mullerian hormone correlates with the bilaterality and severity of endometriosis. Hum Reprod, 26 (2011), pp. 904–910.
  14. Hwu YM, Wu FS, Li SH, Sun FJ, Lin MH, Lee RK. The impact of endometrioma and laparoscopic cystectomy on serum anti-Müllerian hormone levels. Reprod Biol Endocrinol, 9 (2011), p. 80.
  15. 15. Celik HG, Dogan E, Okyay E, Ulukus C, Saatli B, Uysal S, Koyuncuoglu M. Effect of laparoscopic excision of endometriomas on ovarian reserve: serial changes in the serum antimüllerian hormone levels. Fertil Steril, 97 (2012), pp. 1472–1478.

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