Assisted reproduction in endometriosis - Agui Online.ppt

ART e EndometriosiRoma 9 marzo 2009,Gianfranco Scarselli M.E.Coccia Departimento di Ginecologia,Perinatologia e Riproduzione UmanaUniversit di Firenze,Endometriosi,Auditorium del Ministero del lavoro della salute e delle politiche sociali,Endometriosis:Management Dilemma,Pain,Deep endometriosis,Recurrences and Sequelae,IS NOT THE SAME PATIENTChoosing a management,Ovarian cyst,Infertility,m.e.coccia 2006,Endometriosis Epidemiology,INCIDENCE histologically or surgically confirmed disease:1.6 per 1000/yr Pre-congress ESHRE 20041.3 per 1000/yr National Center for Healt Statistics2.372.49 per 1000/yr Vercellini,Maastricht 2005 PREVALENCE 610%in female population4060%women with pelvic pain 2030%women suffering from infertilityPrevalence has probably increased over the last 100 yrsModern women have many more menses than their predecessorsintroduction of laparoscopydelay in diagnosis averaging 8.3 yrs,endometriosis as a social disease,with the woman as the focal point,investigation by the Italian Senate,Barton-Smith 2006,INFERTILIT NELLE DONNE CON ENDOMETRIOSI,GRAVIDANZE SPONTANEE A 36 MESI,Collins JA,et al.1995,Endometriosis associated infertility,Women with minimal or mild endometriosis who undergo laparoscopy should be offered surgical ablation or resection of endometriosis plus laparoscopic adhesiolysis because this improves the chance of pregnancy it is widely accepted that minimal and mild endometriosis may be considered equivalent to unexplained infertility and managed accordingly,A,B,minimalmild endometriosis,moderatesevere endometriosis,EvidenceLevel 1b,Level 1a,No RCTs or metaanalyses are available to answer the question whether surgical excision of moderate to severe endometriosis enhances pregnancy rate.Based upon three studies(Adamson et al.,1993;Guzick et al.,1997;Osuga et al.,2002)there seems to be a negative correlation between the stage of endometriosis and the spontaneous cumulative pregnancy rate after surgical removal of endometriosis,but statistical significance was only reached in one study(Osuga et al.,2002).,Copyright restrictions may apply.,Vercellini,P.et al.Hum.Reprod.2009 24:254-269;doi:10.1093/humrep/den379,Overview of RCTs comparing laparoscopic ablation of lesions with no surgery in infertile women with minimal or mild endometriosis,Surgery for endometriosis-associatedinfertility:a pragmatic approach P.Vercellini Human Reproduction,2009,Copyright restrictions may apply.,Vercellini,P.et al.Hum.Reprod.2009 24:254-269;doi:10.1093/humrep/den379,Overview of RCTs comparing vaporization/coagulation with excision of ovarian endometriotic cysts,Surgery for endometriosis-associatedinfertility:a pragmatic approach Paolo Vercellin Human Reproduction,Vol.24,2009,Copyright restrictions may apply.,Vercellini,P.et al.Hum.Reprod.2009 24:254-269;doi:10.1093/humrep/den379,Results of studies comparing IVF-ET with second-line surgery in infertile women with recurrent moderate to severe endometriosis,Surgery for endometriosis-associatedinfertility:a pragmatic approach Paolo Vercellin Human Reproduction,2009,Conclusions only limitedThe absolute benefit increases in terms of enhancement of pregnancy rates seems lower than the previously suggested 38%(Adamson and Pasta,1994)being reasonably between 10 and 25%based on the results of observational or non-randomized trials and appears to be partly independent of specific lesion types.The practical impact of surgery for stage III disease,are greatly influenced by prevalence of the condition in the population undergoing laparoscopy.The effect of surgery for peritoneal disease is small.Excision of rectovaginal lesions is of doubtful value and associated with severe morbidity.First-line surgery for large ovarian endometriomas seems to be the procedure with the most favourable balance between benefits,harm and costs.A practical advantage of surgery is temporary pain relief in symptomatic patients.This may render feasible spontaneous attempts at conception in women who refuse or prefer to postpone IVF.Complete and detailed information on risks and benefits of treatment alternatives must be offered to patients,in order to allow unbiased choices between different possible options.,Paolo Vercellini Human Reproduction,2009,Objective is the baby,WHY NOT IVF?,Surgical management by the ablation of endometriotic lesions and the removal of endometriomas is an established approach but many women with endometriosis of all severities choose to have IVF treatment,Ovarian endometrioma,Laparoscopic ovarian surgery recommended if ovarian endometrioma 3 cm confirm the diagnosis histologicallyreduce the risk of infectionImprove access to follicles possibly improve ovarian responseDecision should be reconsidered if she has had previous ovarian surgery,GPP,A,Laparoscopic cystectomy for ovarian endometriomas 4 cm may offer better results vs drainage and coagulation-pain relief/PRCoagulation or laser vaporization of endometriomas without excision of the pseudocapsule sign risk of cyst recurrenceFenestration followed by GnRHa where no cyst wall present may prove beneficial,Before ART.,2008,2006,Does endometriosis affect chances of success using ART?US-CDC 2006;Canada 2006 Metanalysis 2002Does the presence of endometriosis affect the success rate of ART?effect of surgically treated endometriosis on the outcome of ARTOUR DATA,ENDOMETRIOSIS&ARTObjective,Does endometriosis affect the chances of success using ART?,I,What are the causes of infertilityamong couples who use ART?,ART Success Rayes 2008US Department of Healt and Human ServicesCDC centers for disease Control and Prevention,2005,Does the cause of infertility affectthe chances of success using ART?,National average success rate slightly 28%success rates varied somewhat depending on diagnosis,US Department of Healt and Human ServicesCDC centers for disease Control and Prevention,2008,had above-average success ratestubal factor,ovulatory dysfunction,endometriosis,male factor,unexplained infertility,low success rates,Survellainces Summaries,ART-USA 2001/April 30,2004,Effect of endometriosis on IVF Kurt Barnhart,2002,Unadjusted meta-analysis of odds of pregnancy in endometriosis patients vs.tubal factor controls,I-II stages vs tubal factor:Significative differences in all comparisonsPR no statistical significance(OR,0.79;CI,0.60-1.03)III-IV stages vs tubal factor:PR large reduction(OR,0.46;CI,0.28-0.74)FR higher in with severe endometriosis(OR,1.54;CI,1.39-1.70),Kurt Barnhart,Fertility and Sterility,June 2002,Meta-analysisKurt Barnhart,Fertility and Sterility,June 2002,Our considerations none of the studies RCT and very old study much more improvement of embryo-lab during last 5 yearsthe studies did not report which patients were treatedPrevious treated endometriosis?Endometriosis present at the time of IVF?not determinated presence or absence of hydrosalpinxWere women with tubal infertility submitted to diagnostic laparoscopy before IVF to assess the presence of minimal-mild endometriosis?,available studies have rarely distinguished between previously surgery endometriomas endometriomas not previous ovarian surgery both endometriomas+previous ovarian surgery with endometriosis no cystat the time of the IVF-ET cycle,not possible to discern whether observed effects are consequent to the presence of the endometrioma and/or to surgical treatment,Although there are indications to support surgery-mediated damage the possibility that injury may,at least in part,also precede surgery cannot be excluded,Consequently,Somigliana 2006,Literature review of the last 5 yrs:endometriosis and IVF outcome,*P 0.05,Does the presence of endometrioma affect the success rate of ART?,II,The impact of ovarian endometriomas on the outcome of ART is controversialOngoing debate on how to manage endometriomas,especially for those larger than 3 cm in,before ART The presence of an ovarian endometriotic cyst might impair oocyte quality in the ipsilateral ovary response to COHfertilization,implantation rates,Removal of endometriomas before IVF does not improve fertility outcomes,ART cycle outcomes in women treated by laparoscopic cystectomy for an endometrioma 3 cm with an ovarian endometriotic cyst of similar size who had not previously undergone conservative ovarian surgery,Garcia-Velasco 2004,Laparoscopic cystectomy Does not compromise number or quality of oocytes obtained with COH Does not offer any additional benefit in term of fertility outcomeGarcia-Velasco 2004The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins Somigliana 2006,EFFECT OF SURGICALLY TREATED ENDOMETRIOSIS ON THE OUTCOME OF ART,III,ENDOMETRIOSIS STAGES III-IV,women with severe endometriosis who had had previous surgical treatmentsignificantly higher withdrawal rate than tubal infertilitydiscontinued because of poor ovarian response:29.7%with endometriosis 1.1%with tubal infertility Avoid surgery in infertile patients?Aboulghar et al.(2003)vaporization of the internal cyst wall of endometriomas did not impair ovarian functionno in ovarian response to stimulation between and with tubal infertility Donnez et al.(2001),Surgical treatment prior to in-vitro fertilization,Surrey ES 2003:retrospective study study group:with endometriosis,excluded with persistent or recurrent endometriomas 3 cm at the time of IVF divided into 2 groups based on the interval between the most recent surgical intervention and oocyte aspiration(more or less than 6 months)No significant(ovarian stimulation,number of oocytes retrieved,ongoing PR)possibly the pregnancy-enhancing effect of surgery on spontaneous conception is overcome by the inherently greater impact of IVF-embryo transfer on implantation and pregnancyGarcia-Velasco JA 2004:retrospective casecontrol study removal of endometriomas prior to IVF does not improve fertility outcomesThe study was recently criticized by Littman E,2005 since diagnosis of endometriomas in the control group was only based on US complete resection of the endometriotic cyst was impossible in some case the authors did not mention if peritoneal endometriosis,known to be copresent with ovarian endometriomas,was surgically excised at the same timeThe simple truth is that we do not know and thatrandomized trials are desperately needed to solve this issue,De Hondt,2006,surgical ablation or resection performed in the 6 months prior to IVF-ET did not have a beneficial effect on cycle outcome in the absence of large endometriomas,International guidelines on surgical treatment of endometriosis-associated infertility in asymptomatic women,Surgery for endometriosis-associatedinfertility:a pragmatic approach Paolo Vercellini,Human Reproduction,2009,Our dataENDOMETRIOSIS AND IVF OUTCOME,IV,Retrospective cohort study IVF cycles 1999-2004;40 yrs144with endometriosis48 previous ovarian cystectomy for endometriomas22 previous ovarian cystectomy for endometriomas and the presence of endometrioma during TV-US examination 11 presence of endometrioma during TV-US examination without previous cystectomy63 who had endometriosis but not endometriomas70 tubal factor,to evaluate effect Of endometriosis or surgery for endometriosis vs tubal factor on“IVF-ET cycles”,AIM:,Materials and Methods,Coccia et al Pelvic Pain Milan2006,Clinical Pregnancy rate(gestational sac on US),Primary outcome,Peak serum estradiol levelsTotal number of mature oocytes Fertilization rateNumber of embryos that were obtained and transferredImplantation rateOverall Pregnancy rate,Secondary outcomes,*P 0.05,P=0.052,r45gtf,Results Pregnancy Rate,ss in the clinical PR between tubal factor and previously submitted to cystectomy without recurrences(28.6%vs 10.4%;P0.05)The direction towards a higher clinical PR among with tubal factor and no past or current diagnosis of endometriomas(Wong 2004)with hystory of endometriomas higher PR were observed among those who were never submitted to ovarian surgery(18.2%)compared with submitted to cystectomy(10.4%)and submitted to cystectomy and with recurrences(9%),Characteristics IVFICSI cycles in pt operated bilateral endometriomas and controls,Somigliana Hum.Reprod 2008,Results,Tubal factor the most responsiveness to ovarian stimulation while women with hystory of cystectomy and recurrences required higher dosage of gonadotropins OVARIAN RESERVE:in never submitted to surgery with endometrioma during IVF comparable to endometriosis with no hystory of endometrioma and tubal factor(Estradiol levels,num follicles,num oocytes retrieved)Surgery for ovarian endometrioma reduces ovarian reserve Loh 1999,Canis 2001;Marconi 2002;Wong 2004 Various techniques?Nature of endometriomas?Different Surgeons?,Muzii et al.,2002 stripping procedure pathological analysis of endometriotic cyst wall ovarian tissue inadvertently excised in 54%of casesin no case this tissue show a normal follicular pattern as the one present in healthy ovaries,Risk of reduced ovarian reserve,removal of a thin layer of ovarian tissue,if any,may not represent an overtreatment,Muzii et al.,2005 strip of ovarian tissue,0.10.3mm thick in the whole specimen thicker near the hilus,0.8 mm,most of specimens:devoid of follicles,or scanty primordial folliclesapproaching the hilus:70%of specimens,functional stages of follicular development,Stripping procedure is a tissue-preserving procedure Great caution while stripping and hemostasis near the hilus,Infertile submitted to endometrioma cystectomy,Our Study,stage I-II endometriosis or tubal factor infertilitynever undergone ovarian surgery,VS,Coccia et al.2006“World pelvic pain Milan”,Younger patients(35 years):mean follicular response of postcystectomy ovaries significantly Older patients(35 years):Even the normal ovaries showed poor responseno SSD between the ovarian responses of postcystectomy and controls.mean follicular response of controls and mean number of follicle of 15mm were reduced significantly when compared to control ovaries in women 35 yrs(4.13.5 vs 8.74.4;1.91.8 versus 5.12.7;),while post-surgery ovaries showed a similar reduced response in both age groups.,Coccia et al.2006,LA QUALIT DELLOVOCITA ALTERATA NELLE DONNE CON ENDOMETRIOSI DI STADIO III-IV,Simon,et al.1994,Aim of the studyTo assess whether IVFET can significantly increase the overall pregnancy rate in infertile patients with endometriosis who failed to conceive spontaneously after laparoscopic surgeryStudy on a cohort of women with endometriosis who were infertile at the time of laparoscopy,47 additional infertility factors,154 infertility-related-endometriosis at least 1 years duration,440 laparoscopy endometriosis,107 women withEndometriosis-related-infertility,Retrospective StudyMarch 1995 and December 2003 Endometriosis staged according to the r-ASRM,Characteristics of infertile women,ENDOMETRIOSIS&INFERTILITY.SURGERY AND ART AN INTEGRATED APPROACH FOR A SUCCESSFUL MANAGEMENT,Coccia,2008,Pregnancy rates after laparoscopy and IVF-ET,Cumulative fecundity rates analysed according to the stage of endome