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Endometriosis and art


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ART and endometriosis

Endometriosis and art

  1. 1. NARENDRA MALHOTRA M.D., F.I.C.O.G., F.I.C.M.C.H• Prof .DIU, Croatia• President FOGSI (2008)• Dean of I.C.M.U. (2008)• Director Ian Donald School of Ultrasound• National Tech. Advisor for FOGSI-G.O.I.—Mc Arthur Foundation EOC Course• Hon Prof Ob Gyn at DMIMS,Sawangi,Advisor ART unit at MAMC & SMS Jaipur• Practicing Obstetrician Gynecologist at Agra. Special Interest in High Risk Obs., Ultrasound, Laparoscopy and Infertility, ART & Genetics• Member and Fellow of many Indian and international organisations• FOGSI Imaging Science Chairman (1996-2000)• Awarded best paper and best poster at FOGSI : 5 times, Ethicon fellowship, AOFOG young gyn. award, Corion award, Man of the year award, Best Citizens of India award• Over 30 published and 100 presented papers• Over 50 guest lectures given in India & Abroad.Presented 15 orations.• Organised many workshops, training programmes, travel seminars and conferences• Editor 8 books, many chapters, on editorial board of many journals• Editor SAFOG journal• Editor of series of STEP by STEP books• Revising editor for Jeatcoate’s Textbook of Gynaecology (2007)• Very active Sports man, Rotarian and Social worker MALHOTRA HOSPITALS 84, M.G. Road, Agra-282 010 Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98370-33335; Fax : 0562-2265194 E-mail : / Website : Apollo Pankaj Hospitals, Agra Consultant for IVF at jalandhar,ludhiana,ambala,bhiwani,gwalior,allahabad,gorakhpur,udaipur,bariely,jaipur,delhi Neapal & Bangladesh
  2. 2. ENDOMETRIOSIS AND ASSISTED REPRODUCTION OUR EXPERIENCE jaideep malhotra narendra malhotra neharika malhotra
  3. 3. ENDOMETRIOSIS• Endometriosis is a challenging disease observed in 20-40% subfertile women• Alteration of immunologic milieu in the peritoneal cavity creates an “hostile enviornment” for gamete interaction and early embryo development.• Treatments available are: medical,surgical,expectant and COH with ART
  4. 4. ENDOMETRIOSISPresence of tissue outside the uteruswhich is similar to endometrium.invasive but non neoplastic growthpattern.
  5. 5. WHERE ALL CAN ECTOPIC ENDOMETRIUM BE ?• COULD BE PRESENT :• REPRODUCTIVE TRACT• URINARY TRACT• GIT• SURGICAL SCAR/UMBILICUS• LUNG• RARELY PERICARDIUM,PLEURA,CNS,NOSE,EYE• Ectopic endometrium responds to changes in ovarian hormones• Cyclical bleeding within & from deposits leads to inflammation ,then fibrosis, peritoneal damage & adhesions
  6. 6. “ He who knows Endometriosis, knows Gynecology ” Sir William OslerEndometriosis is a Benign ,Estrogen dependantProgressive GynecologicalDisease in women ofReproductive Age ,which is extremely commonYet however , there is much that is still notunderstood and the condition still arousesInterest and Controversies Robert W. Shaw
  7. 7. DIAGNOSIS & TREATMENT• Laparoscopy is the gold standard, as far as diagnosis and therapy.
  8. 8. In our practice ,on diagnostic laparoscopy, even small implants seen are fulgurated, and case is managed aggressively.
  9. 9. Generally we try to do laparoscopy for endometriomas of more than 3cm in size ,with H/O infertility, however ,small endometriomas withshort period of infertility, medical management with ovarian stimulation and IUI is tried for 3-4 cycles ,before taking the patient up for laparoscopy
  10. 10. For endometriotic cysts ,most preferred is cystectomy, but wheneverthis is not possible then removal of the cyst lining as much as possible is done, along with fulguration of the rest .
  11. 11. Larger endometriomas, with long standing infertility, laparoscopic cystectomy is the first choice and immediately the patient is put on GnRH analogues and taken up for IVF. This has proved to be very successful .
  12. 12. ASSISTED REPRODUCTION• Definitely referred for ART little earlier• IUI improves fertility in minimal –mild endometriosis• IUI with ovarian stimulation is more effective• IVF appropriate where IUI fails or tubal function compromised.
  13. 13. Indications for IVF - ICSI Tubal Infertility 30 % Male Infertility 20 % Endometriosis 10 % PCOS 5 % Unexplained Infertility 15 % 3rd Party Reproduction 20 % Egg Donation Sperm Donation Embryo Donation Surrogacy
  14. 14. Endometriosis Fertility IndexThe New Validated Endometriosis Staging System
  15. 15. Endometriosis Fertility IndexThe New Validated Endometriosis Staging System• Objective: To develop a clinical tool that predicts pregnancy rates (PRs) in patients with surgically documented endometriosis who attempt non-IVF conception• Design: Prospective data collection on 579 patients and comprehensive statistical analysis to derive a new staging system— the endometriosis fertility index (EFI)—from data rather than a priori assumptions, followed by testing the EFI prospectively on 222 additional patients for correlation of predicted and actual outcomes• Setting: Private reproductive endocrinology practice• Patient(s): A total of 801 consecutively diagnosed and treated infertile patients with endometriosis.
  16. 16. Descriptions of Least Function Terms
  17. 17. Endometriosis Fertility Index (EFI) Surgery FormLeast Function (LF) Score at Conclusion of Surgery
  18. 18. Endometriosis Fertility Index (EFI)
  19. 19. Estimated Percent Pregnant by EFI Score
  20. 20. MINIMAL & MILD ENDOMETRIOSIS ( Stage I & II ) Pregnancy RateSuper Ovulation + IUI 10 - 15 % Per CycleClomipheneFSH / HMG + HCG 3-4 CyclesTreatment with Intrauterine Insemination ( IUI )Improves Fertility in MINIMAL & MILD ENDOMETRIOSIS .IUI with Super Ovulation is effective but theRole of Unstimulated IUI is Uncertain. Tummon et. al, 1997ESHRE GuidelineRecommendation Grade A , Evidence Level 1b
  21. 21. MINIMAL & MILD ENDOMETRIOSIS ( Stage I & II ) SUPEROVULATION ( HMG / FSH ) + IUI To be considered for 3 – 4 Cycles Super Ovulation & Intrauterine Insemination in EndometriosisENDOMETRIOSIS No. of PREGNANCIES / CYCLE FECUNDITY (%)STAGE No. of CYCLESMINIMAL 45/280 16MILD 14/143 10MODERATE 9/51 18SEVERE 0/14 0TOTAL 68/488 14 Data from Haney et al , 1997‘ Endometriosis ’ has Decreased per Cycle Conception Rate in Comparison with Male Factor & Unexplained Infertility Hughes et al , 1997Repetitive Super Ovulation + IUI Cycles have a Plateau effectAfter 3 – 4 Cycles Deaton et al , 1990
  22. 22. MODERATE ( Stage III ) &SEVERE ENDOMETRIOSIS ( Stage IV ) ENDOMETRIOMA Cyst Wall Excision Deep Infiltrating Recto - Vaginal ENDOMETRIOSIS
  23. 23. AFTER LAPAROSCOPIC SURGERY WHAT NEXT ? Aggressive Treatment of ENDOMETRIOMAS is associated with CUMULATIVE PREGNANCY RATE of 60 % over 12 Months Koninck PR & Martin D ( 1994 ), Treatment of deeply infiltrating endometriosis , ( review ) Curr Opin Obstet Gynecol , 6 : 231 - 241 No RCTs or Meta - analyses are available to answer the question whether Surgical Excision of Moderate to Severe Endometriosis Enhances Pregnancy Rate. Based upon 3 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 ) ESHRE Guideline Recommendation Grade B , Evidence Level 3
  24. 24. When is IVF - ICSIIndicated in Endometriosis ? Failed Super Ovulation + IUI in Minimal - Mild Endometriosis Failed Super Ovulation + IUI in Moderate - SevereEndometriosis in Women < 35 years Moderate to Severe Endometriosis in Women > 35 years Associated Tubal Factor Associated Male Factor ESHRE 2005 Guidelines for Diagnosis & Treatment of Endometriosis
  25. 25. ART: IVF-ICSI IVF may improve the conception rates Several studies say that preg rates are lower Some studies have reported equal preg rates Lower fertilization rates Decreased no of oocytes retrieved Oocyte development Negative effect on embryogenesis Negative effect on implantation
  26. 26. Indications of IVF in endometriosis• stage III/IV• Tubal block secondary to endometriosis• Associated male factor
  27. 27. ART procedures in endometriosis• COH + IUI in stage I/II when atleast one tube is patent(live birth rate 11% vs. 2%)• IVF in stage III/IV
  28. 28. Issues to be considered• GnRH analogs requirement?• Prolonged downregulation with depo or daily injection long protocol?• Cyst aspiration pre IVF• Effect of stage of disease• Agonist vs. Antagonist
  29. 29. Our experiences
  30. 30. Table1: Characteristics of patientsNo. of patients 1258Age year (mean ± ) 31.2 ±4.6Infertile 1006 (80%)Stage I 201 (20%)Stage II 231 (23%)Stage III 322 (32%)Stage IV 252 (25%)
  31. 31. Table2: Pregnancy outcome after one year of surgery without IVFLaparoscopy 1006 (100%)Pregnancy in I&II stage 402 (40%)Pregnancy in III stage 41(4%)Pregnancy in IV stage 10 (1%)
  32. 32. Table 3 : IVF outcomeCharacteristic n (%)No. of patients starting IVF 115No. of patients retrieved oocytes 110 (95.65%)No. of patients performed ET 107 (93.04%)No. of patients achieved pregnancy 37 (32.17%)No. of patients with live birth 29(25%)
  33. 33. Table 4: Recurrence of endometriosis after one year stage III-IV n =572Recurrence 178 (31.1%)
  35. 35. Issues to be considered• GnRH analogs requirement?• Prolonged downregulation with depo or daily injection long protocol?• Cyst aspiration pre IVF• Effect of stage of disease• Agonist vs. Antagonist
  36. 36. Cochrane database 2006• Three randomised controlled trials (with 165 women) were included.• The live birth rate per woman was significantly higher in women receiving the GnRH agonist compared to the control group (OR 9.19, 95% CI 1.08 to 78.22).• The clinical pregnancy rate per woman was also significantly higher (three studies: OR 4.28, 95% CI 2.00 to 9.15).
  37. 37. Cochrane database 2006• AUTHORS CONCLUSIONS: The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold.(khurd/malhotra/ISAR/others)
  38. 38. Cochrane database 2007,issue 4 • Six studies, with a total of 552 women • No statistically significant difference between the use of depot GnRHa or daily GnRHa in clinical pregnancy rates per woman (OR 0.94, 95% CI 0.65 to 1.37). • However, the use of depot GnRHa for pituitary desensitization in IVF cycles increased the number of gonadotrophins ampoules (WMD 3.30, 95% CI 1.27 to 5.34) and the duration of the ovarian stimulation (WMD 0.56, 95% CI 0.31 to 0.81), as compared with daily GnRHa.
  39. 39. Cochrane database 2007,issue 4 • Long-acting GnRHa instead of a daily dose in IVF cycles increases costs, without improving pregnancy rates or other outcomes
  40. 40. Stage of disease• No difference in the IVF outcome was found between patients with AFS stage I-II or AFS stage III-IV disease.• No evidence of an increased incidence of miscarriage.Human Reproduction, Vol. 10, No. 6, pp. 1507-1511, 1995 ESHRE
  41. 41. Ovarian Endometrioma• Ovarian response was reduced during IVF-ET cycles in patients with history of severe endometriosis and laparoscopic excision of endometriomas compared to women with mild or minimal endometriosis without ovarian surgery.Gynecol Obstet Fertil. 2006 Sep;34(9):808-12
  42. 42. Agonist vs.Antagonist• Considering the implantation and clinical pregnancy rates, COH with both GnRH antagonist and GnRH-a protocols may be equally effective in patients with mild-to-moderate endometriosis and endometrioma who did and did not undergo ovarian surgery. Fertil Steril. 2007 Oct;88(4):832-9
  43. 43. U/L vs. B/L endometrioma• A higher amount of FSH is needed to achieve an acceptable IVF outcome after unilateral endometrioma surgery. Indications for surgical treatment of patients having larger and bilateral cysts with an expectation for future fertility should be cautiously reviewed J Reprod Med. 2007 Sep;52(9):805-9
  44. 44. Does SurgeryPrior to IVFImproveIVF Success
  45. 45. Retrospective Matched Case - Control StudyEndometrioma <3 Cms Laparoscopic No Surgery Ovarian Cystectomy Gonadotropins More Requirement E 2 Peak Levels Lower Levels Implantation Rate Same Same Clinical Pregnancy Rate Same Same Miscarriage Rate Same Same Conclusion : In Asymptomatic Patients with Endometriomas, Not Larger than 4 Cms , offer IVF treatment directly, because - Shorter ‘ Time to Pregnancy ’ - Avoidance of Risk - Decreased Cost Garcia – Velasco JA et al Removal of Endometriomas before IVF does not improve fertility outcomes : a matched case - control study Fertil Steril 2004 ; 81 :1194-97
  46. 46. Large Randomized Trials are needed to solve the issue ofSurgical Removal of Endometriomas ,Prior to or After IVF CycleConsiderations – Pregnancy SuccessEndometriomas > 4 Cms # Difficulties in Oocyte Retrieval # Added Risk of Cyst Puncture during Ovum Pickup • Risk of Rupture • Infection • Follicular Fluid Contamination Somigliana E, Vercellini P, Vigano P, Ragni G, Corsignani P Should Endometriomas be Treated before IVF – ICSI Cycles ? Hum Reprod 2006;12:57-64
  47. 47. Endometrioma Excision Large Endometrioma > 4 cms Oocyte Retrieval may be Difficult with possibility of Infection and Follicular Fluid Contamination Symptomatic Women should undergo Excision Possibility of Occult Malignancy to be kept in mind POST – SURGERY COUNSELING • Chances of Successful IVF Outcome - Not Decreased • No Difference in Implantation Rate, Pregnancy Rate & Miscarriage Rate ASRM Guidelines • 20 – 30 % Recurrence Rate • < 3 % Chances of Premature Ovarian Failure
  49. 49. ENDOMETRIOMAPRE - IVF SURGICAL TREATMENTLARGE ENDOMETRIOMA > 4 cmsLAPAROSCOPIC ? Aspiration OnlySURGERY ? Incision - Drainage & Vaporize Implants Lining The Cyst Wall + * Incision - Drainage & Excision Of Cyst Wall RCOG Guidelines , 2006MEDICAL TREATMENT GnRH Agonist 3 – 6 MonthsIMMEDIATELY AFTER MEDICAL TREATMENT IVF - ICSI to be Done
  52. 52. Stimulation protocols for endometriosis• Stimulation response for patients with endometriosis/ endometriomas, generally does not seem to be compromised, however, after the surgery, we do get smaller number of follicles, though pregnancy rates are comparable.INDIVIDUALISED IVF PROTOCOLS ACCORDING TO VARIOUS STAGES ONENDOMETRIOMASNO PROSPECTIVE STUDY COMAPRING AGONIST/ANTAGONIST PROTOCOL
  53. 53. Endometriosis & IVF - ICSIGnRH Agonist3 RCTs of 165 patients OR 4.28 95 % CI 2.00 – 9.15 3 – 6 Cycles of GnRH Agonist before IVF - ICSI  Improves the Outcome of Pregnancy and  Reduces Miscarriage GnRH Agonist Modulates NK Cells of Uterus Normalises the Endometrial Aromatase expression Sallam et al, 2006
  54. 54. Endometrioma & IVF - ICSI Controlled Ovarian Stimulation Post - Surgical Patients Need More Gonadotropins Reduced E 2 Levels Oocyte Retrieval Decreased Oocyte yield due to Poor Folliculogenesis Decreased Ovarian Reserve in Post - Surgical Cases Technical Difficulty
  55. 55. Agonist vs Antagonist protocol• We prefer to do long agonist protocol, for all our endometriosis patients, however of late, we have done quite a few cycles with antagonist protocol and have got comparable results in mild to moderate endometriosis. AGONIST PROTOCOLS IN GRD 1 AND 2 DISEASE GIVES SAME RESULTS AS IN TUBAL FACTOR ANTAGONIST MAY BE USED AS A REASONABLE CHOICE FOR POOR RESPONDERSTHE RESULTS OF IVF IN ADVANCED ENDOMETRIOSIS IS 36% REDUCED AS COMPARED TO OTHER INDICATIONS(IMPAIRED FERTILIZATION AND IMPLANTATION)
  56. 56. Deeply Infiltrating Endometriosis & ARTProspective study of 169 Patients, < 38 years of AGE withSymptomatic Deeply Infiltrating EndometriosisPregnancy Rate achieved with IVF wasSignificantly Higher in Women who chosePreliminary Surgical Treatment Bianchi PH, Pareira RM, Zanatta A, Alegretti JR, Motta EL, Serafini PC, Extensive excision of deep infiltrating endometriosis before in vitro fertilization significantly improves pregnancy rates J Minim Invasive Gynecol 16:174, 2009,
  57. 57. Endometrioma & IVF - ICSI Controlled Ovarian Stimulation Post - Surgical Patients Need More Gonadotropins Reduced E 2 Levels Oocyte Retrieval Decreased Oocyte yield due to Poor Folliculogenesis Decreased Ovarian Reserve in Post - Surgical Cases Technical Difficulty
  58. 58. Endometriosis ManagementIVF or ICSIWhich is better ?Barnhart et al 2002 , reported Less Fertilization in IVF in Womenwith Endometriosis Improved Ovarian Stimulation and TVS Oocyte Reterival Techniques have Increased Oocyte yield which Compensates for Reduced Fertilization Rate in IVF ICSI is always Better than IVF Endometriosis - “ ICSI for ALL ”
  59. 59. Our strategy• Laparoscopy for all unexplained infertility• Any endometriotic implant visualised during laparoscopy is taken care of.• Short history of infertilty ,with endometriomas , <3cms,ovarian stimulation and IUI if required.• Endometriomas >3cms,laparoscopy, followed by, ovarian stimulation and IUI• If longstanding infertility with endometriomas,surgery followed by IVF immediately.Bigger and recurrent cysts are drained before stimulation cycle.• Recurrence is quite common, so proper couselling is required.
  60. 60. Problem with refferal for ART• Infertile women with endometriosis do not systamatically undego early ART• Attitude of women towards ART• Possible benefits of second line surgery• IVF as an emotional and physical burden• Gynaecs not involved in ART are still hesitant for early refferal even with grd 3-4 disease(lack of awareness)
  61. 61. ENDOMETRIOSIS SUMMARY ENDOMETRIOSIS at ALL STAGES has a NEGATIVE IMPACT on FERTILITY Causes SUBFERTILITY More Severe the Disease Lesser is the Fecundity H / O PAIN, Clinical Exam, USG, Doppler, MRI & CA 125help in Provisional Diagnosis LAPAROSCOPY is the GOLD STANDARD to make a Correct & Confirmed Diagnosis TREATMENT – INDIVIDUALIZED LAPAROSCOPIC SURGERY is the GOLD STANDARD for Management of ENDOMETRIOSIS 1st Line of Treatment for ALL STAGES EXCISE or DESTROY LESIONS Surgery Enhances Pregnancy Success & brings Pain Relief
  62. 62. ENDOMETRIOSIS SUMMARYENDOMETRIOMA Considerations LOSS of OVARIAN RESERVE Vs RECURRENCE Aspiration & Drainage Incision & Drainage & Vaporization  Incision & Drainage & Excision CUMULATIVE PREGNANCY RATE 43 % - 60 % following Laparoscopic SurgeryASSISTED REPRODUCTIVE TECHNOLOGY SUPER – OVULATION + IUI 4 – 6 Cycles Enhances Lowered Fecundity IVF – ICSI 30 - 40 % per Cycle Live Birth • Reduced with Severity of Endometriosis • Reduced in Comparison with Tubal Infertility, Ovulatory Dysfunction, Male Factor, Unexplained Infertility
  63. 63. PRE IVF – ICSI TREATMENTS Laparoscopic Surgery  Endometrioma > 4 Cms  Endometrioma with Symptoms  Symptomatic Deeply Infiltrating Endometriosis Inj. GnRH (lupride) 3 – 6 Months before IVF – ICSIICSI Preferred over IVF toImprove Reduced Fertilization Rate inENDOMETRIOSIS
  64. 64. conclusion• ART-IUI/IVF/ICSI is currently an effective treatment in women with endometriosis.• There is a general consensus that IVF should be recommended in infertile women who fail to get pregnant after surgical treatment.• In grd d 3-4 disease early reference to IVF/ICSI
  65. 65. CONCLUSION• Endometriosis is an example – the more treatments there are for a disease ,the more likely it is that none is ideal• Albert Yuzpe
  66. 66. endometriosis remains an enigma shrouded in mysteryis this chronic,enigmatic and incurable ??Chronic ..YES,potentially curable and preventable with surgery,but the surgery must Be complete and performed by a qualified gynaec surgeon withexperience in Dealing with endometriosis
  68. 68. THANKYOU