Surgery and Infertility Dr Phill McChesney BHB MBChB FRANZCOG MRMed CREI
Laparoscopy Prior to Considering IVF Diagnostic Tubal Surgery Treatment of peritubal adhesions Reconstructive surgery Sterilization reversal Treatment of endometriosis Treatment of fibroids
Laparoscopy Prior to Commencing IVF Treatment of endometriosis Treatment of fibroids Treatment of hydrosalpinges
Diagnostic Laparoscopy Value of diagnostic laparoscopy debated for years Poor quality studies Most retrospective Most don t include pregnancy data Unexplained infertility with normal HSG 21-80% have abnormalities found at laparoscopy (Cundiff et al 1995, Belisle et al 1996, Badawi et al 1999, Corson et al 2000, Tsuji et al 2009 ) Proposed that abnormalities may: be treated to improve natural fecundity alter future management No RCT that looks at pregnancy outcomes in these women
Diagnostic Laparoscopy Comparison of HSG and Laparoscopy in Predicting fertility outcome Prospective cohort study, Mol et al; 1999 5% with normal HSG had bilateral occlusion at laparoscopy Treatment independent pregnancy virtually zero 42% with bilateral HSG abnormality had no abnormality at laparoscopy Fertility prospects only slightly impaired Conclusions: Diagnostic Laparoscopy very useful after bilateral occlusion at HSG Laparoscopy can be delayed after normal HSG for at least 10 months
Diagnostic Laparoscopy The role of laparoscopy in IUI (with normal HSG) Prospective randomised allocation study, Tanahatoe et al; 2005 Laparoscopy first + up to 6 IUI vs 6 IUI then laparoscopy No difference in abnormalities found (48% vs 56%) No difference in ongoing pregnancy rate (44% vs 49%) NB: high natural pregnancy rate in both groups (12/77 and 16/77) Conclusions: The impact of detection and treatment of pelvic pathology prior to IUI seems negligible
Diagnostic Laparoscopy Laparoscopic evaluation after failure to achieve pregnancy after ovulation induction with clomiphene citrate Retrospective review, Ochoa Capelo et al; 2003 All had normal HSG 35.9% Normal findings 29.3% Stage I-II Endometriosis 34.8% positive laparoscopy No pregnancy outcome data after operative laparoscopy Conclusion: More than 1/3 rd of patients failing to conceive after 4 cycles have significant pelvic pathology
Diagnostic Laparoscopy Accuracy of diagnostic laparoscopy in the infertility work-up before IUI Retrospective review, Tanahatoe et al; 2003 495 patients, all had normal HSG 65% Normal Laparoscopic findings 35% Pathologic abnormalities 25% of patients had a change in initial treatment decision 20.8% laparoscopic surgical treatment 2.6% laparotomy 1.6% IVF No data on pregnancy outcome Conclusion: Laparoscopy may be of considerable value
Diagnostic Laparoscopy Benefit of diagnostic laparoscopy for patients with unexplained infertility and normal HSG findings Retrospective analysis (57 cases), Tsuji et al; 2009 46 patients (80.7%) had pathologic abnormalities 36 (63.2%) Endometriosis 6 (10.5%) fibroids 5 (8.8%) peritubal adhesions 3 (5.3%) bilateral tubal occlusion 8 patients (14%) had management plan changed to IVF due to adhesions or bilateral tubal occlusion Others had treatment of endometriosis/fibroids and conservative treatment, cc or IUI 29 pregnancies achieved (most within 12 months, 6 with IVF) Conclusion: Results illustrate the high success rate of laparoscopic treatment BUT NO CONTROL GROUP
Diagnostic Laparoscopy Diagnostic laparoscopy is needed after abnormal HSG to prevent overtreatment with IVF Retrospective review, Tanahatoe et al; 2008, (252 cases) Laparoscopy normal in 35% of cases Stage 1-2 Endometriosis in 14% Stage 3-4 Endometriosis in 4% Similar results in only 27% IVF final treatment decision in only 29% IUI used 121 patients (48%) with normal findings or unilateral abnormalities IUI used in 57 patients (23%) after laparoscopic treatment of endometriosis or unilateral adhesions Estimated that omitting laparoscopy would increase cost per pregnancy No data on pregnancy outcome
Diagnostic Laparoscopy Summary Paucity of good quality evidence Most retrospective Most do not include pregnancy data High proportion of patients have abnormalities found Still considered gold standard investigation Considerations: Diagnostic versus prognostic approach Availability of resources Cost-effectiveness Patient preference Risks Complications, General anaesthesia Benefits Diagnosis and therapeutic intervention Potentially avoiding future fertility treatments (cost, multiple pregnancy) Avoiding treatments that are unlikely to be beneficial
Tubal Surgery: Adhesiolysis No studies comparing natural fecundity after laparoscopic adhesiolysis with no treatment In 1990, 1 non-randomised study comparing open adhesiolysis with no treatment (Tulandi et al) Cummulative pregnancy rate at 12 months 32 vs 11% Cummulative pregnancy rate at 24 months 45 vs 16% Laparoscopic treatment is likely to have similar outcomes
Reconstructive Tubal Surgery No RCT comparing with IVF Laparoscopic salpingostomy in the treatment of hydrosalpinx Taylor et al; Prospective study, 2001 Intra-uterine pregnancy rate 24.5% Mean time to conception 17.7 months (range 0.5-86.4) Ectopic pregnancy rate 16.5% Other similar studies IUP rates 0-44%, EP rates 0-14%
Tubal Surgery: Sterilisation Reversal No RCT comparing IVF with tubal reanastomosis Laparoscopic tubal reanastomosis Prospective cohort, Bissonnette et al 1999 Intrauterine pregnancy rate 65.3% Cummulative pregnancy rate at 6 months = 50% Ectopic rate 7.2% Other studies show: Pregnancy rates similar to microsurgery (40-80%), monthly fecundability 8-10%, ectopic <10% Operating time longer Ectopic risk may be increased
Tubal Surgery Summary No RCT comparing with IVF Laparoscopic adhesiolysis probably improves natural fecundity Laparoscopic tubal reconstruction is of limited use Patient objects to IVF Laparoscopic tubal reanastomosis is useful in selected patients
Fibroids and Fertility Effect of intramural fibroids on pregnancy rate (spont & IVF) Pritts et al 2009: RR 0.81 (0.696 0.941) Klastky et al 2008: OR 0.84 (0.74 0.95) Effect of fibroids on IVF Somigliana et al 2007 Fibroids have a detrimental effect on IVF pregnancy Submucous: OR conception = 0.3 (0.1-0.7) Intramural: OR conception = 0.8 (0.6 0.9) Sunkara et al 2010 Non cavity distorting, intramural fibroids have a detrimental effect on IVF pregnancy RR pregnancy = 0.85 (0.77 0.94)
Laparoscopic Myomectomy There is insufficient evidence! Pritts et al 2009 (systematic review includes Spont and IVF pregnancies) Myomectomy for Intramural fibroids No significant effect: RR clinical pregnancy 3.765 (0.470 30.136) Myomectomy for submucous fibroids RR clinical pregnancy = 2.034 (1.081 3.826) Some large myomas classified as submucous may be better approached abdominally rather than hysteroscopically
Laparoscopic Treatment of Endometriosis Up to 50% of subfertile women have endometriosis (c.f. 5-10% fertile) 2 different questions Treatment prior to considering IVF Treatment prior to commencing IVF And perhaps Treatment after failed IVF
Excision vs Ablation
Spontaneous pregnancy after operative laparoscopy for endometriosis Stage I-II 1 st 6/12 = 27% 2 nd 6/12 = 17% (not signif) Total 57.7% Stage III-IV 1 st 6/12 = 23% 2 nd 6/12 = 5% (p<0.05) Total 31% (p<0.05)
Summary: Treatment of Endometriosis and Natural Fecundity Meta-analysis of operative laparoscopy for stage I-II disease suggests a benefit Maximising pre-test probability will maximise benefit of laparoscopy No RCT for stage III-IV ovarian disease Observational data suggest a possible benefit of laparoscopic treatment No RCT for stage III-IV rectovaginal disease Observational data suggest a possible benefit of laparoscopic treatment May be related to treatment of coexistent peritoneal and ovarian endometriosis Important to consider a woman s other symptoms when considering surgery
Summary: Treatment of endometriosis prior to IVF cycle Stage I-II disease No RCT Deep Infiltrating Endometriosis No RCT Non-randomised May benefit Bianchi et al, 2009 (Prospective cohort study) PR for Laparoscopic surgery before IVF = 41% vs 24% direct to IVF
Surgery for endometriomas before commencing IVF Non RCT Garcia-Velasco et al 2004 (retrospective, matched case-control) Surgery before IVF pregnancy rate 25.4% Endometrioma present, Direct to IVF (no prev surgery) pregnancy rate 22.7% (not signif) Wong et al 2004 (retrospective, cohort study) Surgery before IVF pregnancy rate 47% Direct to IVF pregnancy rate 34% (not signif) Suganuma et al 2002 (?retrospective, cohort) Surgery before IVF pregnancy rate 37% Direct to IVF (no prev surgery) pregnancy rate 29% (not signif) Tinkanen and Kujansuu 2000 (retrospective, cohort study) Endometrioma surgery before IVF pregnancy rate 22% Endometrioma present @ IVF pregnancy rate 38% Both groups contain patients with multiple previous ovarian surgery 3 different clinical scenarios Endometriomas without prior ovarian surgery Prior surgery, currently disease free Recurrent endometriomas RCT Demirol et al 2006 Surgery before IVF pregnancy rate 34% Direct to IVF pregnancy rate 38% No significant difference
Summary: Treatment of endometriomas prior to IVF cycle Endometriomas RCT and cohort studies do not support a benefit Consideration must be given to potential harm to ovarian reserve Other considerations: Symptoms Natural fecundity Risk of cancer in an undiagnosed complex cyst Endometriomas >4cm May create difficulty with oocyte retrieval Puncture, rupture, infection, follicular contamination
Laparoscopic Salpingectomy for Hydrosalpinges Hydrosalpinges 50% reduction in IVF implantation rates and twofold increase in miscarriage Meta-analysis; Zeyneloglu et al, F&S 1998 Salpingectomy improves clinical and ongoing pregnancy OR 2.31 (1.48 3.62) Tubal Occlusion improves clinical pregnancy OR 4.66 (2.47 10.01) No difference between salpingectomy and occlusion Cochrane Review; Johnson et al, 2010
Caesarean Scar Niche (Isthmocoele) Becoming increasingly common Associated with: Secondary infertility Post menstrual spotting Dysmenorrhea and chronic pelvic pain Intrauterine fluid accumulation Treatment options Laparoscopic niche repair Hysteroscopic niche repair Best if not desiring fertility and overlying myometrium >3mm
Hysteroscopy Prior to IVF Diagnostic Polypectomy Myomectomy Metroplasty Synechiolysis
Diagnostic Hysteroscopy 11-33% of women with normal TVS will have abnormal hysteroscopy findings Pundir et al 2014 Systematic review and meta-analysis of hysteroscopy prior to 1 st IVF 1 RCT and 5 non-rct OR LBR 1.3 (1.00-1.67) Smit et al 2016 Large RCT in women prior to first IVF and normal TVS No difference in LBR (57% vs 54%) Cao et al 2018 Systematic review and meta-analysis of hysteroscopy in women with RIF OR LBR 1.29 (1.03-1.62) El-Toukhy et al 2016 Large RCT in women with 2-4 unsuccessful IVF cycles and normal TVS No difference in LBR (29% in each group) No data on pregnancy
Hysteroscopic Polypectomy No RCT on polypectomy before IVF RCT on polypectomy before IUI Perez-Medina et al, 2005 Polyp detected by TVS prior to IUI cycle Clinical pregnancy rate after 4 IUI cycles 63% in polypectomy group 28% in control group (diagnostic hysteroscopy and biopsy) RR = 2.3 (1.6-3.2) NNT = 3 65% of pregnancies in polypectomy group occurred spontaneously before the 1 st IUI Mean diameter of polyp = 16mm (range 3-24mm)
Hysteroscopic Myomectomy Effect of submucous fibroids on pregnancy Pritts et al 2009: RR 0.363 (0.170 0.737) Klatsky et al 2008: OR 0.44 (0.28 0.70) Somigliana et al 2007: OR 0.3 (0.1 0.7) IVF pregnancy only Hysteroscopic resection improves pregnancy rate Pritts et al 2009: RR 2.034 (1.081 3.826) Shokeir et al 2009 (pseudo-randomised study) Resection pregnancy rate 63.4% No surgery pregnancy rate 28.2% RR = 2.1 (1.5 2.9)
Hysteroscopic Metroplasty Many observational studies suggest an improved fecundity rate in subfertile women self-control design Many believe it is not reasonable to perform a RCT of treatment vs expectant management Prospective case-control trial Mollo et al, 2009 Case = septate uterus + otherwise unexplained infertility (n=44) Controls = unexplained infertility (n=132) 12 month cumulative spontaneous pregnancy rate Cases = 38.6% Controls = 20.4% (p<0.05) Live birth rate Cases = 34.1% Controls = 18.9% (p<0.05)
Hysteroscopic Synechiolysis No RCT or controlled trials Many poor quality non-controlled studies Difficult to compare results Use different, non-validated classification of disease severity Capella-Allouc et al, 1999 Retrospective review (31 patients) Pregnancy rate 42.8% Live birth rate 32.1% 2 1 st trimester losses, 3 2 nd trimester losses 2 haemorrhages due to placenta accreta in the 9 live births Roy et al, 2009 Retrospective review (89 patients) Pregnancy rate 40.4% 12.5% (4/32) of live births had adherent placenta
Hysteroscopy Summary There is a lack of good quality evidence There is insufficient evidence to support routine diagnostic hysteroscopy Hysteroscopy may improve pregnancy rate after failed IVF cycle Hysteroscopic myomectomy for submucous fibroids appears likely to improve fertility outcomes Scarce evidence suggests a potential benefit of; Hysteroscopic Polypectomy Hysteroscopic Metroplasty Hysteroscopic Synechiolysis
The Evidence There is insufficient evidence for most surgery we do! Exceptions Removing / occluding hydrosalpinges prior to IVF Hysteroscopic resection of submucous fibroids Possible Exceptions Treatment of Stage I-II endometriosis
The Reality IVF will often be the best treatment when age, ovarian reserve and ideal family size is taken into account A good history and examination will identify most women likely to have endometriosis (and therefore benefit from laparoscopy) Be afraid of operating on endometriomas in women desiring fertility If performing a diagnostic laparoscopy, do it properly. It is NOT a race May change eligibility for publically funded fertility treatment