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Patient Management and Outcome of IVF/ICSI in Patients with Peritoneal Endometriosis and Endometriomas

Patient Management and Outcome of IVF/ICSI in Patients with Peritoneal Endometriosis and Endometriomas. Timur G ü rgan , MD Head and Professor Division of Reproductive Medicine and Infertility Faculty of Medicine , Hacettepe University Ankara , Turkey. pelvic factors.

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Patient Management and Outcome of IVF/ICSI in Patients with Peritoneal Endometriosis and Endometriomas

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  1. PatientManagementandOutcome of IVF/ICSI in PatientswithPeritonealEndometriosisandEndometriomas Timur Gürgan, MD HeadandProfessor Division of ReproductiveMedicineandInfertility Faculty of Medicine,Hacettepe University Ankara,Turkey

  2. pelvic factors Pelvic inflammation (microphages producing cytokines): interferes w/ sperm-oocyte interaction. Affect in-vivo fertility

  3. pelvic factors Pelvic inflammation (microphages producing cytokines): interferes w/ sperm-oocyte interaction. Affect in-vivo fertility ovarian factors endometriomas and Sx. for OMAS: affects ovarian reserve and (?) oocyte quality.

  4. pelvic factors uterine factors Pelvic inflammation (microphages producing cytokines): interferes w/ sperm-oocyte interaction. Affect in-vivo fertility Increase E2 prod and P4 resistance Medical treatment: favors IVF outcome (endom. Receptivity) ovarian factors endometriomas and Sx. for OMAS: affects ovarian reserve and (?) oocyte quality.

  5. pelvic factors uterine factors Pelvic inflammation (microphages producing cytokines): interferes w/ sperm-oocyte interaction. Affect in-vivo fertility Increase E2 prod and P4 resistance Medical treatment: favors IVF outcome (endom. Receptivity) Sx med TT ovarian factors endometriomas and Sx. for OMAS: affects ovarian reserve and (?) oocyte quality. ov. Res.

  6. Treatment options • Expectant management • Analgesia • Hormonal medical therapy • Combined oral contraceptive pills, cyclic or continuous • Gonadotropin-releasing hormone (GnRH) agonists • Progestins, given by an oral, parenteral, or intrauterine route • Danazol • Aromatase inhibitors • Surgical intervention, which may be • conservative (retain uterus and ovarian tissue) • definitive (removal of the uterus and possibly the ovaries) • Combination therapy in which medical therapy is given before and/or after surgery

  7. Expectant management for infertility Cumulative probability of a pregnancy carried beyond 20 weeksin the 36 weeks after the diagnostic laparoscopy of infertile women with minimal or mild endometriosis is not significantly lower than that of women with unexplained infertility. Berube et al,Fertil Steril 1998;69:1034-41.

  8. Resection or ablation of visible endometriosis or diagnostic laparoscopy only p<0.05 N Engl J Med 1997;337:217-22.

  9. Thebeneficaleffect of Laparoscopicsurgery on pregnancy rate

  10. Resection or ablation of visible endometriosis or diagnostic laparoscopy only N Engl J Med 1997;337:217-22.

  11. a Marcoux S et al.NEJM 1997;337:217-22. Consider Sx + 6-18 Mo in vivo b Akande VA, et al.Hum Reprod. 2004;19:96-103. c Vercellini P, et al. Hum Reprod. 2009;24:254-69. Vercellini et al. Human Reprod 2009;24:254-69.

  12. a Marcoux S et al.NEJM 1997;337:217-22. Consider Sx + 6-18 Mo in vivo b Akande VA, et al.Hum Reprod. 2004;19:96-103. c Vercellini P, et al. Hum Reprod. 2009;24:254-69. 50% Overall weighted mean Vercellini et al. Human Reprod 2009;24:254-69.

  13. Fertil Steril 2006;86:566–71

  14. IUI success after surgically untreated minimal to mild endometriosis than in women with unexplained infertility. Fertil Steril 2006;86:566–71.

  15. ESHRE guidelines-infertility

  16. ESHRE guidelines-infertility

  17. ESHRE guidelines-infertility

  18. ESHRE guidelines-infertility

  19. Med Efficacy No benefit med treatment is contraceptive Conclusion Medical treatment of endometriosis is contraceptive. No rebound-effect on fertility upon stopping. Is not indicated after Sx. Diagnosis infertility time

  20. Sx Efficacy COH-IUI not indicated in case of endometriosis Conclusion In early and late stage endometriosis, surgery facilitates in vivo pregnancies. Indication for surgery implies: Sperm characteristics permit in vivo pregnancy. Ovarian reserve authorizes a 12-month waiting Diagnosis infertility time

  21. Endometriomas • Adnexeal mass (14%-44%) • Pelvic pain • Infertility Treatment Options • Expectant management • Surgery Aspiration Fenestration Ablation,coagulation Cystectomy Recurrence of the endometriomas is an important issue ! (18%-30%)

  22. Treatment of Endometriomas • Medical therapy alone has a limited role • Operative laparoscopy represents the first-line treatment Chapron et al.,2002; Jones and Sutton,2002 • Better PR and a lower rate of recurrences after laparoscopic ovarian cystectomy • PR after surgey vary between 23%-67% Elsheikh et al.,2003;Alborzi et al.,2004 • PR significantly influenced by patients charasteristics,length of follow – up, selection criteria, adhesion score and surgical technics (40%-50%) • USG guided aspiration associated with high rate of recurrances

  23. There was a significantly lower pregnancy rate per fresh embryo transfer after pooled cycles (1–4) among women with stage III/IV endometriosis (22.6%) compared to stage I/II group (40.0%) or tubal infertility (36.6%). After 1–4 IVF/ICSI treatments, including frozen embryo transfer, 56.7% of the women with stage III/IV endometriosis were pregnant and 40.3% gave birth. Kuivasaari et al, Hum Reprod, 2005

  24. EndometriomaCystectomyand IVF/ICSI The average time between laparoscopic cystectomy and IVF cycle (6-24 m)

  25. EndometriomasandOvarianReserve • Mechanical streching Meneschi et al.,1993 May cyst per se damage the the surrounding ovarian tissue? Yes ! Maneschi et al.,1993- Using pathological sections of the ovarian cortex found reduced number of follicles Need for clinical studies in human comparing follicular growth in the affected and contralateral intact gonad ! • Biochemical negative influence Khamsi et al.,2001 • Adhesions which typically surround affected ovaries.In a rabbit model of endometriosis endometrial implants in the gonads decreased ovulation points Kaplan et al.,1989

  26. Damage Machanisms • Surgery-mediateddamage Negativeeffect of SURGERY !? Presence of healthyovariantissueadjacenttoremovedthecystwall Muzzi et al.,2002;HachisugaandKawarabayashi,2002 Excissionof healthyovariancortexwithfollicles Brosens et al.,2004 Surgeryrelatedlocalinflamationandelectrocoagulationduringhaemostasis La Torre et al.,1998;Marconi et al.,2002;Fedele et al.,2004

  27. EndometriomaCystectomy • Recognizable ovarian tissue inadvertently removed 54% of the cases • Close to the ovarian hilus ovarian tissue remove by endometriomas consisted of mostly primary and secondary follicles GREAT CAUTION SHOULD BE UNDERTAKEN TO AVOID OVARIAN DAMAGE WHİLE STRIPPING THE CYST CAPSULE AND HEMOSTASIS NEAR THE HILUS ! Muzzi et al. Fertil Steril 2002;Human Reprod,2005

  28. Endometriomas >3 cm

  29. Influance of EndometriomaCytectomy on Ovarianreserve • Low peak E2 levels and higher gonadotropin requrements were documented in the operated patients • Number of oocytes retrieved, number of embryos obtained and pregnancy rates were similar in both groups !!

  30. Surgery prior to IVF bilateral endometrioma 1 Somigliana et al. Human Reprod 2009;23:1526-1530.

  31. Surgery prior to IVF bilateral endometrioma 1 Casesn= 68 Controlsn= 136 Somigliana et al. Human Reprod 2009;23:1526-1530.

  32. Surgery prior to IVF bilateral endometrioma Casesn= 68 Controlsn= 136 * PR/ sarting cycle P=0.037 Somigliana et al. Human Reprod 2009;23:1526-1530.

  33. AMH? Ovaries Decreased ovarian response to COH: * More FSH/hMG needed * Less oocytes obtained

  34. 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.Esiner et al.2006

  35. OvarianEndometriomas • Ovarian endometriosis is unilateral in the vast majority of the cases- 72%-82% • The contralateral intact ovary adequately compansate the ovarian function ! • Overall, studies suggest that surgery does not benefit asymptomatic women preparing to undergo IVF-ICSI who are found to have endometrioma

  36. Ovarian suppression before COH 2006 meta-analysis

  37. Ovarian suppression before COH results Effects of GnRH-aIVF outcome The 3 trials retained for study indicate that the administration of GnRH-a for 3-6 months prior to IVF/ICSI in women w/ endometriosis increases the odd of pregnancy >4fold. 1

  38. Ovarian suppression before COH results Effects of GnRH-aIVF outcome The 3 trials retained for study indicate that the administration of GnRH-a for 3-6 months prior to IVF/ICSI in women w/ endometriosis increases the odd of pregnancy >4fold. 1 Effects on ovarian response There were no differences between the amounts of FSH/hMG needed in women who received ovarian suppression or not. 2 The mechanism of action Corrects effects of endmetriosis on etopic endometrium? 3

  39. ESHRE guidelines-infertility

  40. 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

  41. Infertility pre ART Work up

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