2. SURGICAL TREATMENT OF PCOS SURGICAL TREATMENT OF PCOS Professor T C LI Professor of Reproductive Medicine & Surgery Sheffield

3. PCO : NON-SURGICAL TREATMENT OPTIONS WT REDUCTION CLOMIFENE CITRATE GONADOTROPHINS METFORMIN

4. 1. Is there still a role for surgical treatment ? 2. How should surgery be performed ?

5. The Evidence Does it work?

6. CUMULATIVE CONCEPTION RATE Li et al, 1998, BJOG

7. LAPAROSCOPIC OVARIAN DRILLING SUCCESS RATE, LITERATURE REVIEW

8. NICE Guidelines Ovarian diathermy Women with PCOS who have not responded to CC should be offered laparoscopic ovarian drilling because it is … effective …

9. The Evidence Is it better than gonadotrophins?

10. LOD vs GONADOTROPHIN COCHRANE DATABASE 3 RCTS Vegetti et al 1998 Farquhar et al 2002 Bayram et al 2004 CCR 6-12 month after LOD is similar to 3- 6 cycles of gonadotrophin therapy

11. LOD versus FSH: randomised controlled trial 29 Dutch hospitals 168 subjects with CC resistant PCO 83 LOD 85 rFSH Bayram et al, BMJ 2004

12. LOD versus FSH Bayram et al, 2004 Treatment Regimen No of women Pregnant(%)MiscarryMultipleLB(%) LOD strategy LOD LOD 83 (100) 31 (37) 3- 28 (34) LOD + CC LOD + CC 45 (54) 14 (31) 1- 13 (29) LOD + CC + FSH LOD + CC + FSH 23 (28) 18 (78) 31 12 (52) LOD strategy total 83 63 (76) 71 53 (64) FSH85 64 (75) 79 51 (60)

13. Conclusions of study An electrocautery strategy and ovulation induction with recombinant follicle stimulating hormone are similarly effective in inducing ovulation Multiple pregnancies can largely be avoided by electrocautery and clomifene citrate before rFSH

14. Multiple pregnancy Meta-analysis of 5 RCTs Multiple pregnancy with LOD is significantly lower (OR = 0.13, CI 0.17-0.98) than godadotrophin therapy Consensus on infertility treatment related to polycystic ovary syndrome. Human Reprod 2008, 23:462

15. NICE Guidelines Ovarian drilling Women with PCOS who have not responded to CC should be offered laparoscopic ovarian drilling because it is as effective as gonadotrophin treatment and is not associated with an increased risk of multiple pregnancy

16. LOD vs GONADOTROPHIN ECONOMIC CONSIDERATIONS Li et al 1998, BJOG

17. LOD vs GONADOTROPHIN ECONOMIC CONSIDERATIONS LODgonadotrophins Cost per live birth Farquhar et al, 2004 US $21095 US $28744 Cost per live birth + delivery Wely et al, 2004 Euro 11301 Euro 14489 Cost of term pregnancy : LOD 22-33% lower

18. ADVANTAGES OF LOD 1. Avoids risk of multiple pregnancy 2. Less costly 3. Long term beneficial effects including menstrual regularity, sustained reduction of FAI, sustained restoration of ovulation and further chances spontaneous conception in over 50% of subjects compared with subjects who did not undergo LOD (Amer et al, Human Reprod 2002, 17:2035; Amer et al, Human Reprod 2002, 17:2851)

19. 1. Is there still a role for surgical treatment ? 2. How should surgery be performed ?

20. SURGICAL TREATMENT Wedge resection via laparotomy Laparoscopic techniques – multiple punch biopsies, laser, diathermy Transvingal e.g.Fertiloscopic approach

21. SURGICAL TREATMENT Wedge resection via laparotomy Laparoscopic techniques – multiple punch biopsies, laser, diathermy Transvingal e.g.Fertiloscopic approach

22. How many punctures should one make?

23. The number of puncture is only one of several variables which determines the amount of electrical energy delivered to the ovary The amount of energy (J) used is calculated as: power (w) x duration (sec) x No of punctures

24. Laparoscopic Ovarian Diathermy How much electrical energy is required to produce optimal results?

25. The amount thermal energy used in LOD Gjonnaess (1984): 250 w x 3 sec x > 5 = > 3750 joules Armar et al (1990): 40 w x 4 sec x 4 = 640 joules Dabirashrafi (1989): Severe ovarian atrophy with 8 holes x 400w x 5 sec = 16,000 Joules

26. The Sheffield Prospective Dose Finding Study Amer, Li & Cooke, 2003 30 women divided into ten groups, each group with 3 women Dose in each group to be determined by the response of previous group Energy utilised for each puncture is standardised The modified Monte Carlo Up-and-Down design

27. Conception rates after LOD Sheffield Prospective Study 1 puncture 234

28. ELECTRICAL ENERGY Rockett of London diathermy needle needle 8 mm long, 2 mm diameter monopolar coagulation power - 30 W puncture –number 4 –duration 5 seconds

29. COMPLICATIONS OF LOD Compromised ovarian function Ovarian adhesions

30. LAPAROSCOPIC OVARIAN DIATHERMY Basic technique three portal entry grasp ovarian ligament stabilise ovary avoid the hilum irrigation

31. With the use of proper techniques, laparoscopic ovarian diathermy is very safe Sheffield series : Adhesions – often minimal ovarian failure – 0/250cases

32. OVARIAN DIATHERMY

33. PATIENT SELECTION PATIENT SELECTION Everything in medicine is patient selection – the chief determinant of results

34. LH (iu/l) LH and Pregnancy rates in LOD * <10 >10 Pregnancy rate 60% 40% 20%

35. Free Androgen Index and the outcome of LOD FAI % *** ** * P < 0.05 ** P < 0.01 *** P < 0.001

36. BMI and the outcome of LOD % BMI (kg/m 2 ) * ** * P < 0.05 ** P < 0.01 *** P < 0.001

37. With proper patient selection, the pregnancy rate after laparoscopic ovarian diathermy is up to 80 %

38. Is repeat surgery effective?

39. Repeat LOD: Ovulation rates Amer et al, Fertil Steril (2003)

40. Repeat LOD: Conception rates Amer et al, Fertil Steril (2003 )

41. What’s new?

42. The value of measuring AMH in women with anovulatory polycystic ovary syndrome undergoing laparoscopic ovarian diathermy Human Reproduction 2009 Amer, Li, and Ledger Amer, Li, and Ledger High AMH (>7.7ng/ml) predicts poor response

43. AMH < 7.7AMH > 7.7 P value ovulation18/19 (95%)6/10 (60%)0.036 pregnancy12/19 (63%)3/10 (30%)0.095

44. Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome Amer, Li, Metwally, Emarh & Ledger Human Reproduction 2009

45. LOD group (n=33) Clomiphene group (n=32) Ovulation64%76% Conception after first treatment 27%44% Conception after second treatment ( at 12m) 53%63% miscarriage12%10% Live Birth46%56%

46. SUMMARY 1 Laparoscopic ovarian diathermy, a very simple form of surgery, has a high success rate and has a definite, useful role in the management of anovulatory infertility in women with PCOS.

47. SUMMARY 2 Laparoscopic ovarian diathermy is an excellent example to illustrate that the key to success of endoscopic surgery depends very much on 1. careful patient selection 2. the use of proper techniques

48. THANKYOU

50. PCO : TREATMENT OPTIONS WT REDUCTIONCLOMIFENE CITRATE LOD GONADOTROPHINS

51. PCO : TREATMENT OPTIONS WT REDUCTIONCLOMIFENE CITRATE LOD GONADOTROPHINS METFORMIN ?

52. LOD v METFORMIN Two studies Malkawi et al 2003 J Obstet Gynaecol 23:289-293 - no difference Palomba et al 2004 JCEM 89:4801-9

53. LOD v METFORMIN Palomba et al, 2004 JCEM RCT 120 clomifene citrate resistant anovulatory infertile women with PCOS BMI 25-30 Metformin 850mg bd for six months LOD : 240-720 Joules to each ovary

54. LOD v METFORMIN Palomba et al, 2004 JCEM CCR, 6 months ** Metformin 39 / 54 ( 72.2% ) LOD 31 / 55 ( 56.4% ) ** p=0.1

55. LOD v METFORMIN Palomba et al, 2004 JCEM CCR, 6 months ** Metformin 39 / 54 ( 72.2% ) LOD 31 / 55 ( 56.4% ) ** p=0.1

56. TREATMENT OPTIONS: SUMMARY WT REDUCTION CLOMIFENE CITRATE LOD GONADOTROPHINS METFORMIN

57. PCO : TREATMENT OPTIONS WT REDUCTIONCLOMIFENE CITRATE

58. PCO : TREATMENT OPTIONS WT REDUCTION CLOMIFENE CITRATE LOD GONADOTROPHINS METFORMIN ?

59. WHAT IS THE ROLE OF LAPAROSCOPIC OVARIAN DIATHERMY ?

60. 100 PATIENTS WITH PCO 40 will conceive with clomifene Of the remaining 60, laparoscopic ovarian diathermy should be considered and 30+ should conceive afterwards