Surgical Management of Endometriosis associated Infertility Dr. Ingrid Lok Specialist in Obstetrics and Gynaecology (Honorary Clinical Associate Professor, CUHK) HA commission training 24.2.2014
Endometriosis Presence of endometrial glands or stroma outside the uterus Pain Infertility Etiology Egnima Multifactorial
Endometriosis and Infertility Higher Prevalence in Infertile population - 6 to 8 times higher prevalence in infertile vs fertile controls Verkauf J Lam Med Assoc 1987-5-10% in fertile vs up to 50% in infertile women D Hooghe et al Semin Reprod Med 2003-20-30% in infertile women Farquhar et al 2007 Lower Fecundity in women with endometriosis - normal couple 0.15-0.20 - untreated women with endometriosis/infertility 0.02-0.10 Schwartz et al N Engl J Med 1982 - fecundity in patients with endometriosis nearly half of patients with unexplained infertility Association Cause and effect Johnson et al Hum Reprod 2004
Possible Mechanisms Distorted Pelvic Anatomy Altered Hormonal and Cellmediated Function Altered Peritoneal Function Endocrine and ovulatory abnormalities Impaired ovarian reserve Impaired Implantation de Ziegler et al Lancet 2010
Diagnosis and Staging Diagnosis: Laparoscopy ASRM staging - Arbitrary assignment of point score - Does not correlate well with outcome - Heterogeneous disease - Anatomical not Biological assessment
Management options Expectant Medical Surgical ART
Percent couples Expectant Management 100 Minor 1-4 Moderate, ovarian 4 0 Months 24 Severe 5,6 Cumulative conception rates with untreated endometriosis related to disease grading, compared with normal. (From: 1, Portuondo et al., 1983; 2, Hull et al., 1987; 3, Badawy et al., 1988; 4, Hull, 1990; 5, Garcia and David, 1977; 6, Olive et al., 1985.) 36
Management options Expectant Medical Surgical ART
Surgery - principles Removal of macroscopic endometriosis Restoration of normal pelvic anatomy May NOT be able to completely reverse the inflammatory state or repair severe anatomical distortion
Surgical management and outcome Staging: Minimal/Mild disease (I/II) Moderate/severe diease (III/IV) Deep/infiltrating (rectovaginal) Endometrioma Outcomes: Spontaneous pregnancy ART outcomes
Minimal/Mild Endometriosis (I/II)
Minimal/Mild Endometriosis (Spontaneous pregnancy) Jacobson et al Cochrane Database Syst Rev 2002 Issue 4 update 2010 Laparoscopic surgery for subfertility associated with endometriosis - 2 RCTs: Absolute difference 9.7%; Number need to treat: 12 (20%) (22%) (29%) (17%) (26.9%) (18.2%)
Minimal/Mild Endometriosis (surgical techniques) Ablation vs Excision No RCTs Excision: - Histological diagnosis - Complete resection of disease - Reduction in residual nonviable tissue and hence potential reduction in adhesion formation - Possible lower recurrence rates
Minimal/Mild Endometriosis (surgical techniques) Ablative techniques Chang et al J Am Assoc Gynecol Laparosc 1997 Prospective controlled cohort study Post-op cumulative pregnancy rate over 36 mo 87% (CO2 vaporization) vs 71% (monopolar coagulation) vs 65% (diagnostic laparoscopy) vs 63% (diagnostic laparoscopy + 3 mo danazole)
Minimal/Mild Endometriosis (ART outcome) No RCTs Opoien et al Reprod Biomed Online 2011 - retrospective study: - Rx: 399 (with surgical diathermy) vs 262 (diagnostic laparoscopy) Results: - Improved IVF pregnancy rate (40.1% vs 29.4% P = 0.004) - Improved cumulative pregnancy rate
Moderate/severe (III/IV)
Percent couples Moderate/severe endometriosis (spontaneous pregnancy) 100 Normal 50 Laparoscopic 1,2 laser Microsurgery 3,4 Macrosurgery 5 0 0 12 Months 24 36 Cumulative conception rates in severe endometriosis related to type of surgical treatment, compared with normal. (From: 1, Olive and Martin, 1987; 2, Nezhat et al., 1989; 3, Donnez et al., 1987; 4, Badawy et al., 1988; 5, Guzick et al., 1982.)
Deep/ infiltrating endometriosis (spontaneous pregnancy) Vercellini et al. Am J Obstet Gynecol 2006 - Retrospective study with 105 women - Rectovaginal endometriosis - 12-month probability of conception (20.5% in surgical group and 34.7% in expectant P = 0.12) - Surgical benefits: pain control and recurrence LB one yr (20%) (22%) Pregnancy 36 wks (29%) (17%) (26.9%) (18.2%)
Deep/ infiltrating endometriosis (spontaneous pregnancy) Stepinewska et al. Hum Reprod 2009 Nonrandomised severe pain/bowel endometriosis Rx: excision of endometriosis with or without segmental bowel resection Results: higher MFR (2.3% vs 0.84% P = 0.03) Complications: 3.2% anastomotic fistula, 1.6% ureteral lesion, 12.8% severe blood loss, 25% urinary retention LB one yr (20%) requiring catheterisation (22%) Pregnancy 36 wks (29%) (17%) (26.9%) (18.2%)
Deep/ infiltrating endometriosis (spontaneous pregnancy) Donnez J and Squifflet J. Hum Reprod 2010 Prospective - 500 women Rx: laparoscopic rectal shaving of endometriotic lesions 51% women wished to conceive conceived naturally over 3.1 years Complications: 1.4% rectal perforation, 0.8% ureteral injury LB one yr (20%) (22%) Pregnancy 36 wks (29%) (17%) (26.9%) (18.2%)
Deep/ infiltrating endometriosis (ART outcome) Bianchi et al J Min Inv Gynecol 2009 Non-randomized prospective cohort 179 women Rx: Extensive excision of infiltrating endometriosis before IVF vs IVF alone Results: Pregnancy rate 41% (surgery group) vs 24% (no surgery) P = 0.004; more gonadotrophins and few oocytes No reported major complications except one pudendal LB one yr (20%) (22%) nerve injury Pregnancy 36 wks (29%) (17%) (26.9%) (18.2%)
Endometrioma
Endometrioma Endometrioma: Pseudocyst Endometriosis tissue penetrate the cyst wall <2mm >50% endometrioma contains primordial follicles Hachisuga&Kawarabayashi Hum Reprod 2002 Muzii et al Fertil Steril 2002 Deprived ovarian function - before operation LB one yr (20%) (22%) - after operation Pregnancy 36 wks (29%) (17%) (17%) (26.9%)
Endometrioma (reduced ovarian reserve pre-op) Maneschi et al Am J Obstet Gynecol 1993 - When compared with other benign cysts; ovarian cortex surrounding endometrioma with reduced follicle number and activity Matsuzaki et al Fertil Steril 2010 - Oxidative stress in normal ovarian cortex surrounding endometriosis Donnez J et al Fertil Steril 2011 LB one yr (20%) (22%) - Biopsies of normal cortex from ovary affected by endometrioma vs Pregnancy 36 wks (29%) (17%) contralateral ovary without cysts (17%) (26.9%) 55% showed fibrosis/ loss in cortex specific stroma Significantly lower in follicular density
Endometrioma (reduced ovarian reserve post-op) Raffi et al The Impact of Excision of Ovarian Endometrioma on Ovarian Reserve: A Systematic Review and Meta-Analysis J Clin Endocrinol Metab 2012 Prospective cohort studies 8 studies 237 patients with unilateral or bilateral endometrioma Busacca et al AJOG 2006 2.4% POF in bilateral cyst excision
Endometrioma Surgical considerations Complete resection and prevent recurrence vs Minimize damage of surrouding ovarian tissues Surgical procedures: - Cystectomy vs Aspiration/fenestration LB one yr (20%) (22%) - Cystecotmy vs ablation Pregnancy 36 wks (29%) (17%) - Coagulation: diathermy (26.9%) (18.2%) vs suture vs haemostatic matrix - Combined technique
Endometrioma (spontaneous pregnancy rate) Beretta et al Fertil Steril 1998 - RCT (endometrioma >3cm) - Lap ovarian cystectomy vs drainage/coagulation (N= 32 vs 32) cystectomy LB one yr (20%) (22%) drainage Pregnancy 36 wks (29%) (17%) (17%) (26.9%) (18.2%) drainage cystectomy
Endometrioma (spontaneous pregnancy rate) Alborzi et al Fertil Steril 1998 - RCT (endometrioma >3cm) - Lap cystectomy vs fenestration (N= 52 vs 48) - Mean age 28.4 vs 28.5 LB one yr - One year CPRs: (20%) (22%) Pregnancy 36 wks (29%) (17%) (26.9%) (18.2%) 19/32 (59.4%) vs 7/30 (23.3%), p<0.009 cystectomy fenestration
Endometrioma (spontaneous pregnancy rate) Hart et al Cochrane Database Syst Rev 2008 update 2011 Excisional surgery versus ablative surgery for ovarian endometriomata LB one yr (20%) (22%) Pregnancy 36 wks (29%) (17%) (17%) (26.9%) (18.2%)
Endometrioma impact on ART To treat or Not to treat? To treat: - for pathological examination - to prevent possible cyst associated complications -? Adverse impact of endometrioma on ovarian response - difficulty in oocyte retrieval Not to treat: - potential in depriving ovarian function/response - risks associated with surgery
Impact on endometrioma on IVF outcome Opoien et al Fertil Steril 2012 Retrospective cohort study (1996-2011) 2245 women with endometriosis (1074) vs control (1171)
Impact on endometrioma on IVF outcome Benaglia et al Fertil Steril 2012 Retrospective cohort study 39 cases with bilateral unoperated endometriomata vs 78 control
Impact on endometrioma on IVF outcome Benaglia et al Fertil Steril 2012
Impact on endometrioma on IVF outcome Benaglia et al Fertil Steril 2012
Endometrioma (ART outcome) Tsoumpou et al Fertil Steril 2009 Studies included: 1 RCT, 2 prospective, 17 retrospective case controlled studies Treated ovary vs normal non-operated contra-lateral ovary less number of oocytes retrieved Meta-analysis: treated endometrioma vs non-treated endometrioma NO significant difference in outcome measures: ovarian stimulation, ovarian response, pregnancy rate - 4 retrospective studies, 1 prospective study - size of endometrioma not documented in 3 - lack of documentation of surgery to IVF interval
Endometrioma (ART outcome) Tsoumpou et al Fertil Steril 2009 The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis
Endometrioma (ART outcome) Demirol et al Reprod Biomed Online 2006 Effect of endometrioma cystectomy on IVF outcome: a prospective randomized study
Surgery Endometrioma (ART outcome) Benschop L et al Cochrane Database Syst Rev 2010 Interventions for women with endometrioma prior to assisted reproductive technology
Surgical treatment - summary Minimal/mild endometriosis Impact on spontaneous pregnancy - RCTs and meta-analysis Ablation of endometriosis/adhesiolysis improve spontaneous pregnancy rate Impact on ART outcome - no RCT - retrospective study: improvement on IVF outcome
Surgical treatment - summary Moderate/severe endometriosis Impact on spontaneous pregnancy - no RCT - observational studies: improvement over time Impact on ART outcome - No RCT - Prospective cohort study: extensive excision of infiltrating endometriosis may improve IVF outcome Beware of inherent surgical risks Operation in cases for pain in experienced hands
Surgical treatment - summary Endometrioma Impact on spontaneous pregnancy rate - RCTs and meta-analysis for endometrioma >3cm excision improves fertility compared to drainage/fenestration and coagulation Impact on ART outcome - RCTs and meta-analysis no difference on IVF pregnancy outcome
ESHRE 2013
Thank you Acknowledgement: Dr Jacqueline Cheung Dr LP Cheung