The Management of Recurrent Endometriosis

The Management of Recurrent Endometriosis The Management of Recurrent Endometriosis

Prof. Cihat ÜNLÜ, M.D.Acibadem University Hospital, Department of Obstetrics & Gynecology, Istanbul/TURKEY

President of the Turkish-German Gynecology Association (TAJEV)Editor of the Journal of the Turkish-German Gynecology Association (JTGGA)

Disclosure

• No financial relationships to disclose.

Recu

rren

ce: D

efini

tions

• Reoperation because of reappearanceof symptoms• Ultrasonography• Second laparoscopy at the end of thesecond year• Ultrasonographic evidence and theneed for reoperation due to pains• Presence of clinical and/orbiopsy-proven endometriosis atlaparoscopy or as the presence of

anendometriotic cyst on ultrasound withcytological confirmation• Recurrence of 1 symptom (urgency,frequency and pain at micturition) ofmoderate-to-severe

intensity• Clinical examinationUltrasonographic exam during theproliferative phase of the menstrualCycle• Evaluation of symptoms, pelvicexamination, transvaginalultrasonography and renal ultrasound• Detection of cysts 2 cm byUltrasonography• Presence of endometrioma 2 cm asdetected by ultrasonography• Exacerbated symptoms 3 monthsafter surgery plus at least one of: (i)reappearance of

disappeared positivepelvic characteristics followingsurgery; (ii) ultrasonography and (iii)arise of serum CA125 following fall

• The presence of ovarian cysts morethan 3 cm in diameter with a typicalaspect detected by ultrasonography

• For two consecutive menstrual cycles• Not clearly defined• Either pain or ultrasonographicEvidence• Pain: evaluated by visual analog scale(VAS)• Symptom recurrence• Clinical exam, ultrasound, CA-125,second look laparoscopy based onclinical finding• The sum of pain score (total pelvicsymptom score) 7• Four-point grading of dysmenorrhea,• Non-menstrual pain and deep• Dyspareunia, and the total score 5

36 month cumulative recurrence rates according to disease stage

From Vercellini et al. Human Reprod 2006

From Vercellini et al. RBM Online 2010

• Impaired ovarian reserve

• Recurrence

Endo

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Endometrioma recurrence

• More common when the endometrioma is removed piecemeal and the tissue planes are scarred

• More common when the ovarian reserve is better

From Somigliana et al. AJOG 2011

The reported recurrence rate was high, estimated as 21.5% at 2 years and 40-50% at 5 years.

(23 years follow up)

Risk factors for Recurrence

Predictive factors for recurrence of endometriotic lesions and pain

Recurrence & Problems

1. Impaired QoL (Pain)2. Infertility3. Asymptomatic Endometrioma

Impaired QoLPain

1. Second Surgery2. Medical Supression3. Expectant Management

Impaired QoLSecond Surgery

• Re-Excision• Pelvic Denervations

– Presacral Neurectomy– LUNA

• Hysterectomy

Re-Excision • Pain symptoms (42 women )

– StageIV in 14– Stage III in 25– Stage I in 3

• Follow-up of 42 months • Dysmenorrhea and deep dyspareunia reappeared in 8

women• Non-cyclical pelvic pain in 7 women• A third operation was necessary in 6 women (14%)• The symptoms recurrence rate when repeat laparotomy was

performed specifically for pain is 25%

Candiani GB, Fedele L, Vercellini P, Bianchi S, Di Nola G. Repetitive conservativesurgery for recurrence of endometriosis.

Obstet Gynecol 1991;77:421–4.

Repetetive Surgery for Pelvic Pain

Berlando N, Curr Opin Obstet Gynecol 2010,

2nd Surgery 3rd Surgery

Re-Excision • 81 women re-operated, 60 months Laparotomy (n = 41) Laparoscopy(n = 40)

Stage IV………………..14………………………………….. 11 Stage III ………………..25………………………………….. 21 Stage II…………………..0……………………………………...2 Stage I…………………… 2……………………………………...6 Dysmenorrhea……..22%(7/32)………………………29%(10/35) Deep dyspareunia.. 30%(7/23)…………………….25%(4/16) Pelvic pain............... 35%(9/26)..................... 32%(7/22)

Busacca M, Fedele L, Bianchi S, et al. Surgical treatment of recurrent endometriosis:laparotomy versus laparoscopy.

Hum Reprod 1998;13:2271–4.

Re-Excision

Recurrence rate (5-year cumulative pain)

After the first surgical procedure 20%

After the second procedure 17%

Fedele L, Bianchi S, Zanconato G, et al. Laparoscopic excision of recurrent endometriomas: long-term outcome and comparison with primary surgery.

Fertil Steril 2006;85:694–9.

The effect of repetitive laparoscopic surgery on pain is similar to that observed after first-line surgery.

Re-Excision

Ovarian surgery for bilateral endometriomas influences age at menopause

Patients who had been operated on for bilateral endometriomas have an increased risk of POF.

Surgery plus PSN vs Surgery Alone

Berlando N, Curr Opin Obstet Gynecol 2010,

Presacral Neurectomy Conservative surgery Conservative plus PSN surgery (n:63) (n:63)Dysmenorrhea cure rate

– 6-month follow-up …………………………87% ……………………………….57%– 12-month follow-up ………………………60%....................................86%– 24-month follow-up ……………………….83%...................................53%

At the end of the study period, the frequency and severity of deep dyspareunia and non-menstrual pain were also significantly lower in women from the PSN those in conservative.

11 women who underwent PSN referred long-term complaints such as de-novo constipation (n = 9,15%) and urinary urgency (n = 3, 5%).

Zullo F, Palomba S, Zupi E, et al. Am J Obstet Gynecol 2003;189:5–10. Zullo F, Palomba S, Zupi E, et al. J AmAssoc Gynecol Laparosc 2004;11:23–8.

Presacral neurectomy

From Berlanda et al. Curr Opin Obstet Gynecol 2010

Addition of pelvic denervation

• PSN has been reported as an effective procedure in reducing pain recurrences in women undergoing first-line surgical treatment of endometriosis

• Although no data are available in women with recurrent endometriosis, it might be argued that women with recurrent pain are those in whom the greatest surgical effort should be made in order to cure the disease, including therefore PSN

Limitations of PSN

• Effective in reducing midline pain only, whereas lateral, adnexal pain is not influenced

• Denervation of bowel and bladder might cause constipation and urinary dysfunction

• It must be performed by an experienced surgeon because it is carried out in a complex anatomic area and great care must be taken to avoid damaging the right ureter as well as major and midsacral vessels

LUNA Conservative surgery Conservative plus LUNA surgery (n:78) (n:78)Dysmenorrhea recurrence rate

– 12-month follow-up ………………………29% ………………………………..27%– 24-month follow-up ………………………36%....................................32%

•68 of 90 (75%) patients in the LUNA group and •67 of 90 (75%) patients in the conservative surgery only group were satisfied at 1 year.

Vercellini P et alFertil Steril 2003;80:310–9.

Hysterectomy• Young patients?????????????????• Ovaries???????????????????????

Symptomatic endometriosis in 29 women Ovarian tissue was preserved Both ovaries removed n: 29 n:109 Recurrent pain…………… 18 (62%)……………………........11 (10%) Required reoperation……. 9 (31%)…………………………...4 (3.7%)

Patients who underwent hysterectomy with ovarian conservation had •6.1 times greater risk of developing recurrent pain and •8.1 times greater risk of re-operation.

Namnoum AB et al. Fertil Steril1995;64:898–902.

Removal of the ovaries at definitive surgery

Reoperation rates-definitive vs conservative surgery

Surgery Reoperation rateDefinitive with removal of the ovariesDefinitive with ovarian conservation 2.89Conservative surgery 6.16

Impaired QoLMedical Suppression

Recurrent EndometriosisAromatase Inhibitors

• Good case reports

• No randomized controlled studies

Lall Seal S, Kamilya G, Mukherji J, De A, Ghosh D, Majhi AK. Aromatase inhibitors in recurrent ovarian endometriomas: report of five cases with literature review.

Fertil Steril. 2011 Jan;95(1):291.e15-8.

Recurrent EndometriosisGnRH Analogues

Sesti F, Capozzolo T, Pietropolli A, Marziali M, Bollea MR, Piccione E. Recurrence rate of endometrioma after laparoscopic cystectomy: a comparative randomized trial between post-operative

hormonal suppression treatment or dietary therapy vs. placebo. Eur J Obstet Gynecol Reprod Biol. 2009 Nov;147(1):72-7.

• A 6-month course of hormonal suppression treatment or dietary therapy after laparoscopic cystectomy had no significant effect on the recurrence rate of ovarian endometriosis when compared with surgery plus placebo.

• So, treatment of endometrioma can be carried out exclusively by laparoscopic cystectomy without post-operative therapy, if a complete excision of ovarian endometriosis has been assured.

Sesti F, Capozzolo T, Pietropolli A, Marziali M, Bollea MR, Piccione E. Recurrence rate of endometrioma after laparoscopic cystectomy: a comparative randomized trial between post-operative

hormonal suppression treatment or dietary therapy vs. placebo. Eur J Obstet Gynecol Reprod Biol. 2009 Nov;147(1):72-7.

Recurrent EndometriosisGnRH Analogues


• Impaired QoL-Pain• Infertility• Asymptomatic Endometrioma

Recurrent EndometriosisInfertility

• 2nd Surgery• Medical Therapy• Medical Therapy + ART• ART

– KOH

– KOH +IUI– ICSI-ET

Pregnancy rates after second-line surgical treatment for infertility in women with recurrent endometriosis

The mean conception rate among women undergoing repetitive surgery for recurrent endometriosis associated with infertility was 26%, whereas the overall crude pregnancy rate after a primary procedure was 41%.

Berlando N, Current Opinion in Obstetrics and Gynecology 2010, 22:320–

325

Recurrent EndometriosisInfertility/2nd Surgery

LAPAROTOMY LAPAROSCOPY

Acta Obstet Gynecol Scand 2009

Spontaneous Pregnancy After 1 surgery 236/577 (41%)(41%)Spontaneous Pregnancy After 2 surgery 28/124 (23%)(23%)


Vercellini P, Somigliana E, Viganò P, De Matteis S, Barbara G, Fedele L. The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: a systematic review.

Acta Obstet Gynecol Scand. 2009;88(10):1074-82.

Sp. Pregnancy following L/TSp. Pregnancy following L/T 12 – 47% (27%)(27%)Sp. Pregnancy following L/SSp. Pregnancy following L/S 22 – 42% (25%)(25%)


Vercellini P, Somigliana E, Viganò P, De Matteis S, Barbara G, Fedele L. The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: a systematic review.

Acta Obstet Gynecol Scand. 2009;88(10):1074-82.

TVUSG Guided Aspiration

• Agostini A et al, Eur J Obstet Gynecol Rep Biol, 2007

Repeat surgery for infertility

• Repeat surgery for infertility is associated with low pregnancy rates

• This is mainly due to affected ovarian reserve• When there is no risk of malignancy and no

pain IVF should be preferred over surgery in these patients

Is it possible to avoid repeat surgery for endometriosis?

• Refrain from operating early in the asymptomatic patient• Operation should be done by surgeons with expertise and

training in endometriosis surgery-to preserve the ovarian reserve; to remove DIE

• Complete excision or destruction of all endometriosis lesions should be carried out although there is no randomized study showing the effectiveness of this approach

• Postoperative suppressive treatment with OCPs or insertion of LNG IUD

• Removal of the ovaries in women who have completed their family

Alternatives to surgery in recurrent endometriosis

• Long term BCPs• Long term GnRHa with add back• LNG IUD• Aromatase inhibitors

• There is no evidence to support the use of ovarian suppression agents in the treatment of endometriosis-associated infertility.

• More harm than good can be done by treatment, because of side-effects and the lost opportunity to conceive

The RCOG Guidelines N.24, 2000

ESHRE Guidelines 2005

Recurrent EndometriosisInfertility/Medical Supressive Therapy

P. Vercellini , 2009


NO DIFFERENCES

• In patients with endometriosis-associated infertility, surgery followed by IVF–ET is more effective than surgery alone.

• When patients fail to conceive spontaneously, after a maximum of 1 year from laparoscopic surgery, IVF should be suggested.

• When reoperation is being considered with the specific aim of achieving conception, and not because severe symptoms or large cysts are present, the caring gynecologist should warn the patient that

– the chances of pregnancy may be substantially lower than after the primary procedure and the role of IVF should be considered adequately as an alternative to repetitive surgery

Recurrent EndometriosisInfertility/2nd Surgery or ART

Meta-analysis of Surgery vs No Surgery for endometriomas before IVF

Tsoumpou et al, FS 2009

Who have previously had one or more infertility operations

• IVF-ET is often a better therapeutic option than another surgical intervention, though this is another question that has not been addressed in any randomized trial.

• If initial surgery fails to restore fertility in patients with moderate to severe endometriosis, IVF-ET is an effective alternative.

• Current data are insufficient to estimate the effect of surgical treatment in addition to IVF-ET on the outcome of pregnancy in endometriosis associated infertility.

DECISIONS AMONG INFERTILE WOMEN WITHENDOMETRIOSIS


• Impaired QoL-Pain• Infertility• Asymptomatic Endometrioma

Endometriosis and ovarian cancer

• There may be a link between endometriosis and ovarian cancer– x2 risk in women with endometriosis– x4 risk in women with endometriosis and infertility

• The etiology of both diseases appears to be multifactorial with hormonal, genetic, and immunologic factors potentially playing a role

From the Ovarian Cancer Association Consortium Lancet Oncology 2012

• Recommendation: –Surgery+ Long term suppression

Only supression is not effective Definitive surgery—based on patients requirements LUNA—Not effective for pain PSN – Effective but creates new long term problems

Conclusion-1Recurrent Endometrioma and Pain

• Recommendation: –Long term suppression

OCP can be used AI or GnRH Analogs can be used, need RCT If there is DIE, first surgery then long term suppression

Conclusion-2No Endometrioma and Pain

• Recommendation: –ART

ART has the same effect in comparison with re-surgery But

Every surgery increase the complications Every surgery impaired the ovarian reserve It seems that ART can be first recommendation

Conclusion-3Recurrent Endometrioma and Infertility

• Recommendation: –Expectant Management

If there are strong evidence for malignancy then surgery can be recommended

Conclusion-4Asymptomatic Endometrioma

The Management of Recurrent Endometriosis

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