Potentials for iatrogenic ovarian hyporresponse following endoscopic surgery Juan A Garcia-Velasco, MD IVI-Madrid, Rey Juan Carlos University Madrid, Spain
Transition from 1980 s to 2007 Old aforism in the operating rooms: When in doubt, cut it out! Both physicians and patients awareness towards a more conservative approach
Effects of the cyst Pain Infertility Cancer risk (age, markers ) Tissue damage (cyst & surgery) Tissue reduction Endometriosis itself Diameter Bilaterality Surgical technique
Risks of having a cyst Risk of torsion (endometrioma vs dermoid cyst) Cancer ART: reduced d ovarian response
Impact of technique Bipolar vs open surgery vs laser vs harmonic scalpel Reduced thermal injury Improved wound healing Harmonic Standard Harmonic Standard
Impact of technique Minimal i lateral l thermal tissue damage Minimal desiccation Reduces the need for ligatures Greater precision
Assesment of ovarian reserve Biochemical markers FSH Estradiol Inhibin B AMH FSH/LH ratio Morphometric markers Ovarian volume AFC Mean ovarian diameter LIMITATIONS cutoff level intercycle variability interlab variability Dynamic markers CCCT Exogenous FSH ovarian response test GnRH analogue stimulation test
Assesment of ovarian reserve Biochemical markers FSH Estradiol Inhibin B AMH FSH/LH ratio Morphometric markers Ovarian volume AFC Mean ovarian diameter Dynamic markers CCCT Exogenous FSH ovarian response test GnRH analogue stimulation test
Assesment of ovarian reserve Simple tool: individual ovarian dimensions (D1 + D2) / 2 Bowen et al 2007
How to evaluate success after surgery? menstrual period reduced follicular pool
Ovarian recovery after surgery Selection of patients t (usually, ART pts) How to evaluate ovarian recovery? Ovarian response to gonadotropins Serum hormonal evaluation Ultrasound examination (unethical) (compensation)
Left Ovary: BEFORE surgery Left Ovary: AFTER surgery Courtesy of Dra Cerrillo
Right Ovary: BEFORE surgery Right Ovary: AFTER surgery Courtesy of Dra Cerrillo
Ovarian recovery after surgery N=31 AFC and flow similar 3 months follow-up Candiani et al 2005
Ovarian recovery after surgery 25 ian volu me (cm3 3) 20 15 10 n.s. 0.001 0.05 62 dermoids + 67 endometriomas 14.7 months follow-up Ovar 5 0 Before After Dermoids Before After Endometriomas Exacoustos et al 2004
Ovarian recovery after surgery 12 Ovar ian volu me (cm3 3) 10 8 6 4 2 ns n.s. 0.001 46 dermoids 40 endometriomas 0 Operated Unoperated Dermoids Operated Unoperated Endometriomas Exacoustos et al 2004
Ovarian recovery after surgery Potential ti deleterious insults: Amount of ovarian tissue removed Damage inflicted both stroma and vascularization- Electrosurgical coagulation Local inflammation Damage by the cyst per se
Damage due to the presence of cyst Ovarian cortex surrounding benign neoplasms mature teratoma benign cyst endometrioma morphologic pattern 92% 77% 19% * similar to normal cortex regular vascular 84% 78% 22% * network (anti-vw) Maneschi et al 1993
All cysts are not created equal Well-defined ovarian capsule Ovarian tissue removed dermoids serous cystadenomas 6% mucinous cystadenomas Endometriomas (margin of ovarian tissue) 54-69% Muzii et al 2002
All cysts are not created equal Endometrioma cyst wall Primordial follicles Muzii et al 2002
All cysts are not created equal Risk of serious damage in bilateral endometrioma resection ovarian artery blood flow changes accidental removal of ovarian tissue severe local inflammation BUT Postsurgical - pain symptoms reduced - 66% pregnant in 24 months ovarian failure 24% 2.4% Busacca et al 2006
3D power doppler imaging after surgery 22 laparoscopic surgery for endometriomas > 6cm 26 tubal factor infertile women 3D power doppler US imaging decreased ovarian stromal blood flow (VI, FI, VFI) Wu et al. 2003
Ovarian surgery diminishes # eggs Surgical # cycles control operated P technique Nargund 1996 Not reported 90 8.9 6.3 0.001 Loh 1999 Donnez 2001 Ho 2002 Somigliana 2003 Esinler 2006 Cyst enucleation Cyst wall vaporization Cyst enucleation Cyst enucleation Cyst enucleation 12 3.6 4.6 ns 87 6.6 5.2 ns 38 3.3 1.9 0.001 46 4.2 2.0 0.001 34 6.6 4.5 0.05
Ovarian surgery diminishes # eggs Nargund et al. 1995
Ovarian surgery diminishes # eggs Ovarian response after endometriotic cystectomy in 132 cycles Loh et al. 1999
Ovarian surgery diminishes # eggs Laparoscopic endometriotic cystectomy: insights from IVF Somigiliana et al. 2003
Ovarian surgery diminishes # eggs Laparoscopic endometriotic cystectomy: insights from IVF 3cm >3cm n 18 20 # folls >15mm control 4.2 4.4 operated 2.1 1.9 p 0.003003 0.001001 Basal volume (cm 3 ) control 8.8 11 operated 6.9 8.3 p 0.20 0.12 Somigiliana et al. 2003
Does endometrioma affect IVF? Unproven gold standard any endometrioma in an infertile woman undergoing IVF should be removed lower ovarian response after cystectomy Pagidas 1996; Loh 1999; Al-Azemi 2000; Tinkanen 2000 cystectomy t vs tubal similar ovarian response and cycle outcome Donnez 2001; Canis 2001; Marconi 2002
Does endometrioma affect IVF? Removal of endometriomas prior to IVF Garcia-Velasco et al. 2004
Does endometrioma affect IVF? Removal of endometriomas prior to IVF Garcia-Velasco et al. 2004
Damage due to the presence of cyst Unilateral endometrioma w/o surgery # co-dominant follicles intact ovary endometrioma # cysts 1 3.9 3.2 # cysts 2 5.1 2.0 * < 20mm >20mm 3.7 4.5 3.0 3.2 * # eggs < 5 3.6 2.9 > 5 45 4.5 32* 3.2 Somigliana et al 2006
Unilateral endometrioma w/o surgery Impact on ovarian response Effect depends on size & number of cysts
Non endometriotic ovarian cysts OR Ctr Sx Mean reduction Dominant follicles basal volumen (cm3) 4.6 2.7 42% (10-74%) 5.7 3.4 39% (12-66%) n = 17 Somigliana et al. 2006
Effect of salpinguectomy on ovarian function Kamina. 1974
Effect of salpinguectomy on ovarian function Nº of oocytes Ipsi vs contra-lateral Overall (two ovaries) Verhulst 1994 Not studied 11.2 vs 11.2 Lass 1998 3.8 vs 6 9.9 vs 9.1 Bredkjaer 1999 Not studied 9.3 vs 9.1 Dar 2000 6.1 vs 5.3 11.1 vs 9.7 Stadtmauer 2000 Not studied 14 vs 12.9 Strandell 2001 Not studied 9.4 vs 8.7 Surrey 2001 Not studied 16.2 vs 17.5 Tal 2002 6.3 vs 6.2 8.6 vs 8.4 Gelbaya 2006 Not studied 10.2 vs 12.9
Effect of salpinguectomy on ovarian function No consensus Risk of impaired ovarian function after surgery No unnecessary excision of mesosalpinx Avoid damage to medial tubal artery L ti f dh t t b th th Leave a portion of an adherent tube rather than unnecessary radical salpinguectomy
And what about the risk of cancer? Most ovarian cysts are benign Ovarian cancer: 17 cases / 100.000000 women Malignant potential of endometriosis is VERY LOW US (transvaginal scan + color flow doppler) High false positive rate serum ovarian markers CA 125 (CA 19.9, β-hcg, αfp,.) proteomics? Age / family history (x12 fold increase from 29 to 69 years)
And what about the risk of cancer? Swedish Register (2006) SIR 1.43 (95% CI 1.19-1.71).ovarian cancer If relative risk is low, absolute risk increase is even lower Endometrioma a precursor? Common predisposing factors to both diseases? Jiang et al. 1998
Conclusions Ovarian cysts are common and the majority are benign Surgery mediated damage to OR not fertility potential- is NOT an argument AGAINST surgical treatments Surgery is an effective treatment for infertile women Surgery is an effective treatment for infertile women with severe endometriosis
Conclusions Removal of endometrioma causes more damage to the ovaries than the removal of simple cysts Ovarian surgery should be carefully evaluated in those women who wish to conceive in the future Reduction in OV may represent a quantitative not qualitative- injury to OR
Thank you! jgvelasco@ivi.es