MUSTAFA BAHÇECİ.M.D

Fibroids and Infertility

• Sperm migration

• Ovum transport

• Endometrial blood supply

• Implantation

Fibroids and Infertility

• Sperm migration

• Ovum transport

• Endometrial blood supply

• Implantation

Myomas and pregnancy outcomes

• Submucosal myomas: significantly reduce outcome

• Subserosal myomas: do not reduce outcome

• Intramural myomas: do these affect outcome?

What Is an Intramural Fibroid Not Impacting the Cavity?

What Is a 4 cm Intramural Fibroid?

Myomas and pregnancy outcomes

Studies conflicting definations often not clear size, number, and location highly variable!

Do Fibroids That Impact the Cavity (SM or IM) Influence IVF Outcome?

• Two studies

• Meta-analysis relative risk 0.32 [0.13-0.70]

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 yoUp to 9 cycles per patientSize 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

Farhi: Do Fibroids Impact IVF? Fibroids Impacting the Cavity

Pregnancy Rate*

Delivery Rate* Loss Rate*

Cavity Impacted

9%(5/55) 5%(3/55) 40%(2/5)

Normal Cavity 29%(25/86) 17%(15/86) 40%(10/25)

*=per transfer x2=0.005 x2=0,038 x2=N.S.

FarhiJetal. Hum Reprod 1995;10:2576-8

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)

Eldar Geva: Do Fibroids Impact IVF? Fibroids Impacting the Cavity

Pregnancy Rate*

Delivery Rate* Loss Rate*

Cavity Impacted

10%(1/10) ND ND

Normal Cavity 30%(98/326) 24%(78/326) 20%(20/98)

*=per transfer x2SM:C=N.S. x2SS:C=N.D. x2SS:C=N.D.

Eldar Geva Tet al. Fertil Steril l998;70:687-9l

Vercellini P et al. Hum Reprod 1998;13:873-9

Do Patients Get Pregnant After Myomectomy?

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)

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?

Farhi: Do Fibroids Impact IVF? Fibroids Impacting the Cavity

Pregnancy Rate Delivery Rate Loss Rate

Fibroid 29%(25/86) 17%(15/86) 40%(10/25)

No Fibroid 25%(32/127) 19%(24/127) 25%(8/32)

x2=N.S. x2=N.S. x2=N.S.

FarhiJetal. Hum Reprod 1995;10:2576-8

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 independent)

İntramural myomas and pregnancy outcomes

434 patients IVF/ICSI Prospective intramural =<5cm

Hart et. Al. Hum Reprod 2001;16:2411-7

İntramural myomas and pregnancy outcomes

myoma No myoma P

PR 23% 34% 0.016

IR 12% 20% 0.018

OPR 15% 28% 0.003

Age(years) 36.4 34.6 <0.01

Hart et. Al. Hum Reprod 2001;16:2411-7

İntramural myomas and pregnancy outcomes

Hart et. Al. Hum Reprod 2001;16:2411-7

434 patients IVF/ICSI Prospective intramural =<5cm 434 patients IVF/ICSI Prospective intramural =<5cm

Logistic regression OPROR 0.46(95%CI,0.24-0.88)

Logistic regression OPROR 0.46(95%CI,0.24-0.88)

İntramural myomas and pregnancy outcomes

retrospective cohort analysis;Surrey et. Al. Fertil Steril 2001;75:405-10

İntramural myomas and pregnancy outcomes

Retrospective analysis

*P<0.01 Eldar-Gave et. Al. Fertil Steril 1998;70:687-91

SubserosalN=33

IntramuralN=46

No myomaN=318

PR 34% 16%* 30%

IR 15% 6%* 16%

İntramural myomas and pregnancy outcomes

Retrospective analysis of 3 IVF cycles

Khalaf et. Al. Hum Reprod2006;21:2640-4

Myoma=<5cm

No myoma P

OPR 19% 29% <0.05

LB 15% 24% <0.05

İntramural myomas and pregnancy outcomes

Retrospective analysis

Oliveira et. al. Fertil Steril 2004;81:582-7

Intramural myoma >4cm

Intramural myoma >4cm

Sinificantly lower PR

Sinificantly lower PR

İntramural myomas and pregnancy outcomes

Myoma present No myoma P

CPR 47% 54% NS

IR 36% 38% NS

Donor egg-recipients subserosal and

intramural myomas

Donor egg-recipients subserosal and

intramural myomas

No effect: location, number, and size

Klatsky et. al. Hum Reprod 2007;22:521-6

Objective: Establish the impact of intramural intramural orsubserosai fibroids on IVF and ZlFT outcome.

Patients: 91 patients with fibroids vs 91 matched controls36 yo1 cycleMean 1.8 fibroids/ptMean size of largest fibroid 2.9cm94.5% with intramural, 5.5%subserosal

Exclusion criteria: Submucosal fibroidPrior 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

Stovall: Do Fibroids Impact IVF? IM or SS Detected at Baseline

Pregnancy Rate Delivery Rate Loss Rate

Fibroid 37%(34/91) 33%(30/91) 12%(4/34)

No Fibroid 53%(48/91) 48%(44/91) 8%(4/48)

x2=0.037 x2=0.035 x2=N.S.

Stovall DW et al. Hum Reprod 1998;13:192-7

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

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 fibroidFibroid impacting endometrial cavityFibroid > 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

Ramzy: Do Fibroids Impact IVF? Not Impacting the Cavity

Pregnancy Rate Delivery Rate Loss Rate

Fibroid 38%(15/39) 23%(9/39) 40%(6/15)

No Fibroid 34%(123/367) 26%(95/367) 23%(28/123)

x2=N.S. x2=N.S. x2=0.14

Ramzy AM et al. Hum Reprod 1998;13:198-202

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

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 patientMean size of fibroid 2cm (range 1.1-2.6cm)

Exclusion criteria: Fibroids impacting the cavityPrior pregnancy through their practiceHistory of prior myomectomy< 36yoPrior uterine surgery or abnormalitiesPatients 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

Dietterich: Do Fibroids Impact IVF? Fibroids Not Impacting Cavity

Pregnancy Rate Delivery Rate Loss Rate

Fibroid 56%(5/9) N.D. N.D.

No Fibroid 64%(7/11) N.D. N.D.

x2=N.S.

Dietterich C et al. Clin Exp Obst & Gyn 2000;27:168-21

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.)

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

Effect of inner myometrium fibroid onreproductive outcome after IVF

Effect of inner myometrium fibroid onreproductive outcome after IVF

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

Do uterine fibroids affect IVF outcomes?

Do uterine fibroids affect IVF outcomes?

Do uterine fibroids affect IVF outcomes?

Summary: Leiomyoma Not Impacting Cavity "Meta-Analysis"

ALL STUDIES:

Pregnancy Rate

Delivery Rate Loss Rate

Fibroid37%(534/1447

)24%(343/1438) 28%(122/431)

No Fibroid35%(1156/328

3)30%(992/3273) 16%(157/1007)

x2=N.S. x2<0.001 x2<0.001

Summary: Leiomyoma Not Impacting Cavity Structured Review

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

Post-myomectomy

No myomasNo myomas

Smilar outcomes 1-2Smilar outcomes 1-2

FERTILITY AND STERILITY VOL. 83, NO. 5, MAY 2005

Effect of myomectomy on the outcome of assistedreproductive technologies

Eric S. Surrey, M.D., Debra A. Minjarez, M.D., John M. Stevens, B.S., andWilliam B. Schoolcraft, M.D. Colorado Center for Reproductive Medicine, Englewood, Colorado

Effect of myomectomy on the outcome of assistedreproductive technologies

Effect of myomectomy on the outcome of assistedreproductive technologies

Effect of myomectomy on the outcome of assistedreproductive technologies

Effect of myomectomy on the outcome of assistedreproductive technologies

Conclusions• Submucosal => remove

• Impacting cavity => remove

• Intramural, not impacting cavity => weight of data supports removal

• Subserosal => remove if symptomatic