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Role of Reproductive Surgery Prior ART’s

Role of Reproductive Surgery Prior ART’s. Timur Gürgan , MD Professor, Hacettepe University , Dept of Ob & Gyn , Division of Reproductive Endocrinology and Infertility ,Ankara, Turkey Scientific Director of Gurgan Clinic IVF Center Ankara/ Turkey.

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Role of Reproductive Surgery Prior ART’s

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  1. Role of Reproductive Surgery Prior ART’s Timur Gürgan, MD Professor, Hacettepe University, Dept of Ob&Gyn, Division of ReproductiveEndocrinology and Infertility,Ankara,Turkey ScientificDirector of Gurgan Clinic IVF Center Ankara/Turkey

  2. Surgery Before Assisted Reproduction • Uterine pathologies • Endometriomas • Tubal diseases • To achieve pregnancy • To increase the success of the IVF/ICSI

  3. Surgery Before ART’s / ART • Cost • Complication(s) • Increase the sucess rate ? Which patients ? Which operation ? Which technique? Timing ?

  4. Surgery Before Assisted Reproduction Endometriomas : Remove or not to Remove ? Mechanical ,biochemical,adhessions,surgical effects !

  5. Before IVF Should be removed endometriomas? *P < 0.001 Somigliana E , Hum Reprod, 2003 Thenumber of dominant follicles is reduced in theoperatedovaries.

  6. Before IVF Should be removed endometriomas? L/S cystecyomy for endometriomas before commencing an IVF cycles does not improve fertility outcome Garcia-Velasco JA. Fertil Steril 2004

  7. ENDOMETRİOMAS Comparison of in the operated and contralateral intact ovaries In the operated ovaries; • The number of follicles %60  • The number of oocytes %53  • The number of embryo %55  • The number of high quality embryo %52 ? Ragni et al., Esiner et al.,2006

  8. Endometriomas and Ovarian Reserve: Insigths from IVF-ICSI Cycles in Women with Endometriomas • Contralateral gonad may adequately compansate for the reduced function of the affected gonad • The number of follicles developed in the cystectomized ovary significantly reduced when compared to the contralateral intact gonad! • Bilateral cysts may elevated risk of ovarian function impairement (19%-28% bilaterality) Prefumo et al.,2002;Al-Fozan and Tulandi,2003,Demirol,2006,Esiner et al.2006,Ragni,2006

  9. Endometriomas and IVF/ICSI Individualized treatment plan can be developed ,executed and modified as necessary based on : • Bilaterality • Number of endometriomas • Size of the endometrioma • Surgical technic • Previous ovarian surgery • Ovarian reserve • Other factor(s) which contribute(s) to infertility

  10. Surgery should be envisaged in specific circumstances

  11. Hydrosalpinx / Infertility • Mechanicalfactors • Embryotoxicfactors / gametetoxicity • Lowosmolarityand protein • cytokines, prostoglandin, locotrien, endotoksin • Endometrialreceptivity • integrinexpresion • ebfdysregulation (TGF b) • LIF  • Abnormalendometrium : Glandular-stromaldissencronization Chronicendometritis

  12. Hydrosalpinx and IVFZeyneloglu H,. 1998/Meta-Analisis CPR/ET IR Abortus

  13. Unilateral Salpingectomy Patients with unilateral hydrosalpenx in whose contralateral tube are normal can concieve spontanously after unilateral salpengectomy or proximal occlusion procedure where no IVF treatment is required. n=22/25 pregnancy Time interval for pregnancy=5.6 months Sagoskin AW, Hum Reprod, 2003

  14. Salpingectomy ovarian reserve? • Ovarianreserveevaluation, number of follicules and number of oocytesretrieved is significantlylower in Group A whencomparedwithgroup B and C • PR and abortusratesaresimilar Gelbaya T, Fertil Steril, 2006

  15. Hysteroscopic Occlussion • Microinsert / Essure • IVF pregnacy (Rosenfield RB et al., 2005) • IVF pregnancies (Mijatovic J et al., 2009)

  16. Surgical treatment for tubal disease in women due to undergo IVF • Laparoscopic salpingectomy increases clinical and ongoing pregnancy rates • Tubal occlussion shown to improve clinical pregnancy rate showing the comparable efficacy with salpingectomy • The beneficial effect of the aspiration needs to be shown wth more trials • Currently,no conclussion can be made regarding the adverse effects of the interventions Neil Johnson et al,Cochrane Datebase of Systemic Reviews 2010

  17. Surgical treatment for tubal disease in women due to undergo IVF • Tubal disease,and particularly hydrosalpinx,has detrimental effect on the outcome of in-vitro fertilisation. Performing a surgical intervention such as salpingectomy,tubal occlussion,aspiration of the hydrosalpinx fluid prior to the IVF procedure in women with hydrosalpinges is thought improve the likelihood of successful outcome • Author’s Conclussion • Diseases of the fallopian tube,such as hydrosalpinx can severely reduce the chance of pregnancy from IVF. Removing or occluding blocked or diseased fallopian tubes before IVF can increase pregnancy and live birth rates for women on the IVF program. Neil Johnson et al,Cochrane Datebase of Systemic Reviews 2010

  18. Intracavitary pathologies that might effect embryo implantation • Intrauterine adhesions • Submucous myomas • Endometrial polyps • Uterine septum • 10-62% infertile couples are effected one or more of these pathologies • Gold standart : Office Hysteroscopy !

  19. 1000 office-based hysteroscopies prior to in vitro fertilization: feasibility and findings. • Conclusıon: When hysteroscopy is routinely performed prior to in vitro fertilization, a significant percentage of patients have uterine pathology that may impair the success of fertility treatment. Patient tolerance, safety, and the feasibility of simultaneous operative correction make office hysteroscopy an ideal procedure. Hinckley et al.JSLS,2004

  20. Office Hysteroscopy after Recurrent IVF/ICSI Failure(Bozdağ G et al., RBM Online, 2008)

  21. Updated Meta-analysis: CPR

  22. Inconclussion,thissystematicreview and meta-analysis of publishedcontrolledstudiesshowedthatofficehysteroscopymigth be associatedwithimprove IVF outcomewhenperformingimmediatelybefore IVF treatment Outpatienthysteroscopy and subsequent IVF cycleoutcome: a systematicreview and meta-analysis. Tarek El-Toukhy, RBM Online,2009

  23. Intrauterine adhesions • Pregnancy rate ranges between 30-50% • Live birth rates range between 10-35% • Poor prognostic indicators:- Adhesions obliterating both ostia- Age >35 years- Persistence of amenorrhea- Reformation of adhesions at 2nd look Thompson et al,2009; Pabuccu et al, 2008; Yu et al, 2008

  24. Endometrial polyps >15mm

  25. Surgery before assisted reproduction Uterineanomalies Recurrentpregnancyloss %3.5 Obstetricscomplications II. Trimestrloss Pretermbirth Fetalmalpresentation IUGR Reproductivefailure • Poorseptalvascularity • Implantationfailure • Defects in embryonaldevelopment Relativecervicalincompetence • Homer et al., FS, 2000,Pace S et al,. 2006,Hollett-Caines et al., 2006

  26. Uterine septum resection Mollo et al, 2009 Fertil Steril • Controlled study showed higher live birth rate after septal resection (n=44) compared to controls (n=132) 34% vs 19% (P<0.01)

  27. The effect of Hysteroscopic Metroplasty on Pregnancy Outcome

  28. EndometrialInjury: Biological explanation • Release of cytokines and growth factors(LIF, IL-6 and 11, EGF) promoting endometrial development • Alternation in endometrial gene expression(Laminin œ 4, Integrin œ 6, MMP1), which play key roles in implantation • Delay endometrial maturation, thus promoting synchronisation with embryo stage backward development

  29. Endometrial injury: CPR,LBR and RIF

  30. TROPHY Trial Protocol

  31. Surgery before assisted reproduction Thecentralquestion in thisdebate; 1.Do womenwithmyomassufferfromdecreasedfertility,increasedmiscarriegerates? 2.Can wehope to improvefertilitybyremovingthemyoma? 3. Howabouttheincreasedobstetricscomplications ? • Dysfunctionaluterinecontractility • Interferewith sperm migration • Interferewithovum transport ornidation • Implantationfailure • Gestationdiscontinuationdue to focalendometrialvasculardisturbance • Endometrialinflamation • Secretion of vasoactivesubstancesor an enhancedendometrialandrogenenvironment

  32. 1. Not distortingthecavity Uterine Myomas/Adenomyosis 2. Distortingcavity

  33. Classification • Type 0 European Society for Gynaecological Endoscopy (ESGE) Type 0 Type I Type II

  34. Myomas and ART Success • Menstrual disorders/bleeding pattern • Location • Number • Size • Previous history (surgery,miscarriage,premature labor etc.) • Age • Male factor • Previous IVF/ICSI attemps

  35. Myomas and IVF 1. Decreased Pregnancy rates 2. Increased abortus rates

  36. Myomasdistortingcavity Meta- analysis of Six trial results Pregnancy rate Uterine cavity deformation  %9 Uterin cavity normal  %30 No fibroid  %40 Donnez, Hum Reprod, 2002

  37. HYSTEROSCOPIC MYOMECTOMY • Hysteroscopic resection of submucousmyomas is now well established and is the preferred approach

  38. Submucous fibroids <4cm Submucous fibroid

  39. Larger submucous fibroids 204 women with unexplained infertility and submucous fibroids randomised to either 101 hysteroscopic myomectomy 103 diagnostic hysteroscopy Follow up for 1 year CPR 63.4% CPR 28.2% RR-2.1, 95%CI 1.5-2.9 Shokeir et al, 2010 Fertil Steril

  40. Myomas and in-vitro fertilization: which comes first • Reproductive outcomes before and after myomectomy, and IVF outcomes based on fibroid size and location.. • Conclussion: Fibroid location, followed by size, is the most important factor determining the impact of fibroids on IVF outcomes. Any distortion of the endometrial cavity seriously affects IVF outcomes, and myomectomy is indicated in this situation. Myomectomy should also be considered for patients with large fibroids, and for patients with unexplained unsuccessful IVF cycles. Rackow BW, Arıcı A. Curr Opin Obstet gynecol 2005

  41. Impact of subserosal and intramural uterine fibroids that do not distort the endometrial cavity on the outcome of IVF-ICSI • Conclussion: Patients having subserosal or intramural leiomyomas of <4 cm not encroaching on the uterine cavity have IVF-ICSI outcomes comparable to those of patients without such leiomyomas. Therefore, they might not require myomectomy before being scheduled for assisted reproduction cycles. However, we recommend caution for patients with fibroids >4 cm /7 cm and that such patients be submitted to treatment before they are enrolled in IVF-ICSI cycles. Whether or not women with fibroids > 4 cm would benefit from fibroid treatment remains to be determined. Oliveira FG, Fertil Steril, 2004

  42. The challenges and controversies to ART’s can not be underestimated BUT the reward is also great: What reward can be better than a happy mother,a proud father, a healty child and a harmonious family for a loving successful group of medical professionals !!

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