1. MUSTAFA BAHÇECİ.M.D

2. Fibroids and Infertility Sperm migration Ovum transport Endometrial blood supply Implantation

3. Fibroids and Infertility Sperm migration Ovum transport Endometrial blood supply Implantation

4. Myomas and pregnancy outcomes Submucosal myomas: significantly reduce outcome Subserosal myomas: do not reduce outcome Intramural myomas: do these affect outcome?

5. What Is an Intramural Fibroid Not Impacting the Cavity?

6. What Is a 4 cm Intramural Fibroid?

7. Myomas and pregnancy outcomes Studies conflicting definations often not clear size, number, and location highly variable!

8. Do Fibroids That Impact the Cavity (SM or IM) Influence IVF Outcome? Two studies Meta-analysis relative risk 0.32 [0.13-0.70]

9. Objective:Establish the impact of any fibroid that impacts the cavity on IVF. Patients:46 women with fibroids (172 cycles) vs 50 without (127 cycles) 34 yo Up to 9 cycles per patient Size and location undefined Exclusion criteria:>12 wk size uterus on examination Randomization:None(observational) Intervention:None(observational) Farhi: Do Fibroids Impact IVF? Fibroids Impacting the Cavity FarhiJetal. Hum Reprod 1995;10:2576-8

10. Farhi: Do Fibroids Impact IVF? Fibroids Impacting the Cavity Pregnancy Rate*Delivery Rate*Loss Rate* Cavity Impacted9%(5/55)5%(3/55)40%(2/5) Normal Cavity29%(25/86)17%(15/86)40%(10/25) *=per transferx 2 =0.005x 2 =0,038x 2 =N.S. FarhiJetal. Hum Reprod 1995;10:2576-8

11. Eldar Geva Tet al. Fertil Steril l998;70:687-9l Eldar Geva: Do Fibroids Impact IVF? Fibroids Impacting Cavity Objective:Establish the impact of subserosal and intramural fibroids based on location on IVF. Patients:10 with fibroids impacting cavity, 318 controls35 yo>1 cycle per patientMean 2.67 fibroids/ptMean size of fibroid 4.5 cm Exclusion criteria:None stated Randomization:None(observational) Intervention:None(observational)

12. Eldar Geva: Do Fibroids Impact IVF? Fibroids Impacting the Cavity Pregnancy Rate*Delivery Rate*Loss Rate* Cavity Impacted10%(1/10)ND Normal Cavity30%(98/326)24%(78/326)20%(20/98) *=per transferx 2 SM:C=N.S.x 2 SS:C=N.D. Eldar Geva Tet al. Fertil Steril l998;70:687-9l

13. Vercellini P et al. Hum Reprod 1998;13:873-9 Do Patients Get Pregnant After Myomectomy?

14. Does Submucosal Myomectomy Improve Fertility? Retrospective: Patients post-myomectomy pregnancy rate = 53.9% (14 studies, 421 patients) Prospective: Patients post-myomectomy pregnancy rate = 43% (2 studies, 86 patients) Retrospective, case-controlled: Post-myomectomy vs. no fibroids = 61% vs. 53% (1 study, 31 patients vs. 896 patients)

15. Summary Presence of submucosal myomata decrease pregnancy rate in IVF Hysteroscopic myomectomy may return fecundability to control levels What about fibroids that do not impact the endometrial cavity?

16. Farhi: Do Fibroids Impact IVF? Fibroids Impacting the Cavity Pregnancy RateDelivery RateLoss Rate Fibroid29%(25/86)17%(15/86)40%(10/25) No Fibroid25%(32/127)19%(24/127)25%(8/32) x 2 =N.S. FarhiJetal. Hum Reprod 1995;10:2576-8

17. Bottom Line 28 patients with uterine leiomyoma (>12 week size) who undergo up to 9 IVF cycles (86 cycles) compared with 50 tubal factor patients (127 cycles) No difference Size and location (IM vs. SS) undefined More than 1 cycle/pt (not independe nt)

18. İntramural myomas and pregnancy outcomes 434 patients IVF/ICSI Prospective intramural =<5cm Hart et. Al. Hum Reprod 2001;16:2411-7

19. İntramural myomas and pregnancy outcomes myomaNo myomaP PR23%34%0.016 IR12%20%0.018 OPR15%28%0.003 Age(years)36.434.6<0.01 Hart et. Al. Hum Reprod 2001;16:2411-7

20. İntramural myomas and pregnancy outcomes Hart et. Al. Hum Reprod 2001;16:2411-7 434 patients IVF/ICSI Prospective intramural =<5cm Logistic regression OPR OR 0.46(95%CI,0.24-0.88) Logistic regression OPR OR 0.46(95%CI,0.24-0.88)

21. İntramural myomas and pregnancy outcomes retrospective cohort analysis; Surrey et. Al. Fertil Steril 2001;75:405-10

22. İntramural myomas and pregnancy outcomes Retrospective analysis * P<0.01 Eldar-Gave et. Al. Fertil Steril 1998;70:687-91 Subserosal N=33 Intramural N=46 No myoma N=318 PR34%16%*30% IR15%6%*16%

23. İntramural myomas and pregnancy outcomes Retrospective analysis of 3 IVF cycles Khalaf et. Al. Hum Reprod2006;21:2640-4 Myoma =<5cm No myomaP OPR19%29%<0.05 LB15%24%<0.05

24. İntramural myomas and pregnancy outcomes Retrospective analysis Oliveira et. al. Fertil Steril 2004;81:582-7 Intramural myoma >4cm Sinificantly lower PR

25. İntramural myomas and pregnancy outcomes Myoma presentNo myomaP CPR47%54%NS IR36%38%NS Donor egg-recipients subserosal and intramural myomas No effect: location, number, and size Klatsky et. al. Hum Reprod 2007;22:521-6

26. Objective:Establish the impact of intramural intramural orsubserosai fibroids on IVF and ZlFT outcome. Patients:91 patients with fibroids vs 91 matched controls 36 yo1 cycleMean 1.8 fibroids/pt Mean size of largest fibroid 2.9cm 94.5% with intramural, 5.5%subserosal Exclusion criteria:Submucosal fibroid Prior myomectomy or polypectomy Randomization:None(observational) Intervention:None(observational) Stovall: Do Fibroids Impact IVF? IM or SS Detected at Baseline Stovall DW et al. Hum Reprod 1998;13:192-7

27. Stovall: Do Fibroids Impact IVF? IM or SS Detected at Baseline Pregnancy RateDelivery RateLoss Rate Fibroid37%(34/91)33%(30/91)12%(4/34) No Fibroid53%(48/91)48%(44/91)8%(4/48) x 2 =0.037x 2 =0.035x 2 =N.S. Stovall DW et al. Hum Reprod 1998;13:192-7

28. Bottom Line Retrospective analysis of 91 first-cycle IVF patients with leiomyomata not impacting the cavity by HSG/ultrasound compared with 91 first-cycle IVF patients without Decreased pregnancy/live-birth rate *95% intramural

29. Objective:Establish the impact of subserosal and irtramural fibroids not impacting the cavity on IVF Patients:39 patients with fibroids vs 367 controls34 yo72.7% subserosal, 27.3% intramuralMean 1.8 fibroids/ptMean size of fibroid 3.5 cm Exclusion criteria:Submucosal fibroid Fibroid impacting endometrial cavity Fibroid > 7 cm Randomization:None(observational) Intervention:None(observational) Ramzy: Do Fibroids Impact IVF? Not Impacting the Cavity Ramzy AM et al. Hum Reprod 1998;13:198-202

30. Ramzy: Do Fibroids Impact IVF? Not Impacting the Cavity Pregnancy RateDelivery RateLoss Rate Fibroid38%(15/39)23%(9/39)40%(6/15) No Fibroid34%(123/367)26%(95/367)23%(28/123) x 2 =N.S. x 2 =0.14 Ramzy AM et al. Hum Reprod 1998;13:198-202

31. Bottom Line Retrospective analysis of 39 patients with leiomyomata <7 cm vs. age-matched control group with normal uteri No difference 72% subserosal, 28% intramural

32. Objective:Establish the impact of intramural fibroids not impacting the cavity on IVF. Patients:61 women with fibroids vs. 61 matched controls 41-44 yo (older patients in fibroid group) 1 cycle per patient Mean size of fibroid 2cm (range 1.1-2.6cm) Exclusion criteria:Fibroids impacting the cavity Prior pregnancy through their practice History of prior myomectomy < 36yoPrior uterine surgery or abnormalities Patients monitored outside of their practice Randomization:None(observational) Intervention:None(observational) Dietterich: Do Fibroids Impact IVF? Fibroids Not Impacting Cavity Dietterich C et al. Clin Exp Obst & Gyn 2000;27:168-21

33. Dietterich: Do Fibroids Impact IVF? Fibroids Not Impacting Cavity Pregnancy RateDelivery RateLoss Rate Fibroid56%(5/9)N.D. No Fibroid64%(7/11)N.D. x 2 =N.S. Dietterich C et al. Clin Exp Obst & Gyn 2000;27:168-21

34. Bottom Line Retrospective study of 9 patients with at least one IM leiomyoma (somewith SS; smallest 1.2 cm, largest 2cm), compared with 11 patients without leiomyomata No difference Location (IM vs. SS) undefined High pregnancy rate for age (see Check et al.)

35. Effect of inner myometrium fibroid on reproductive outcome after IVF Luca Gianaroli1,4, Stephan Gordts2, Arianna D’Angelo1, M Cristina Magli1, Ivo Brosens2, Carlo Cetera3, Rudi Campo2, Anna Pia Ferraretti1 Vol 10. No 4. 2005 473–477 Reproductive BioMedicine Online; www.rbmonline.com/Article/1662 on web 18 February 2005

36. Effect of inner myometrium fibroid on reproductive outcome after IVF

38. Do uterine fibroids affect IVF outcomes? Antonella Vimercati, Marco Scioscia1, Filomenamila Lorusso, Anna Franca Laera, Giuseppina Lamanna, Alfredo Coluccia, Stefano Bettocchi, Luigi Selvaggi, Raffaella Depalo Department of Gynaecology, Obstetrics and Neonatology, University of Medical Science of Bari, Policlinico of Bari Vol 15. No 6. 2007 686-691 Reproductive BioMedicine Online; www.rbmonline.com/Article/2775 on web 3 October 2007 686 2007

39. Do uterine fibroids affect IVF outcomes?

42. Summary: Leiomyoma Not Impacting Cavity "Meta-Analysis" ALL STUDIES: Pregnancy RateDelivery RateLoss Rate Fibroid37%(534/1447)24%(343/1438)28%(122/431) No Fibroid35%(1156/3283)30%(992/3273)16%(157/1007) x 2 =N.S.x 2 <0.001

43. Summary: Leiomyoma Not Impacting Cavity Structured Review

45. Myomectomy and pregnancy outcomes in IVF 1-Surrey et. al. Fertil Steril 2005;83:1473-9 2-Seoud et. al. J Assist Reprod Genet 1992;9:217-21 Post- myomectomy No myomas Smilar outcomes 1-2

46. FERTILITY AND STERILITY VOL. 83, NO. 5, MAY 2005 Effect of myomectomy on the outcome of assisted reproductive technologies Eric S. Surrey, M.D., Debra A. Minjarez, M.D., John M. Stevens, B.S., and William B. Schoolcraft, M.D. Colorado Center for Reproductive Medicine, Englewood, Colorado

47. Effect of myomectomy on the outcome of assisted reproductive technologies

51. Conclusions Submucosal => remove Impacting cavity => remove Intramural, not impacting cavity => weight of data supports removal Subserosal => remove if symptomatic