uterine cavity findings by hysteroscopy in ivf failure assoc. prof. dr. rafael levİ ege university...

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UTERINE CAVITY UTERINE CAVITY FINDINGS BY FINDINGS BY HYSTEROSCOPY IN IVF HYSTEROSCOPY IN IVF FAILURE FAILURE Assoc. Prof. Dr. Rafael LEVİ Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Ege University Family Planning And Infertility Research And Treatment Center- Infertility Research And Treatment Center- İZMİR İZMİR 2. Güncel Üreme Endokrinolojisi, 2. Güncel Üreme Endokrinolojisi, Yardımcı Üreme Teknikleri Kongresi Yardımcı Üreme Teknikleri Kongresi 1. Üreme Tıbbı Derneği Kongresi 1. Üreme Tıbbı Derneği Kongresi 17-20 Nisan 2008 Çeşme- İzmir 17-20 Nisan 2008 Çeşme- İzmir

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Page 1: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

UTERINE CAVITY UTERINE CAVITY FINDINGS BY FINDINGS BY

HYSTEROSCOPY IN IVF HYSTEROSCOPY IN IVF FAILUREFAILURE

Assoc. Prof. Dr. Rafael LEVİAssoc. Prof. Dr. Rafael LEVİ

Ege University Family Planning And Infertility Ege University Family Planning And Infertility Research And Treatment Center-İZMİRResearch And Treatment Center-İZMİR

2. Güncel Üreme Endokrinolojisi, Yardımcı 2. Güncel Üreme Endokrinolojisi, Yardımcı Üreme Teknikleri KongresiÜreme Teknikleri Kongresi

1. Üreme Tıbbı Derneği Kongresi1. Üreme Tıbbı Derneği Kongresi17-20 Nisan 2008 Çeşme- İzmir17-20 Nisan 2008 Çeşme- İzmir

Page 2: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Investigation and current management of recurrent IVF treatment failure in Investigation and current management of recurrent IVF treatment failure in the UK.the UK.

Tan BK et all, BJOG, 112(6):773-80 2005Tan BK et all, BJOG, 112(6):773-80 2005

Objective: To determine current practice in the management of Objective: To determine current practice in the management of recurrent IVF treatment failure in licenced UK infertility recurrent IVF treatment failure in licenced UK infertility centers.centers.

Human Fertilization And Embriyology Authority licenced Human Fertilization And Embriyology Authority licenced centers in UK (n=79)centers in UK (n=79)

How recurrent IVF treatment failure was defined? How recurrent IVF treatment failure was defined?

Which investigations were initiated?Which investigations were initiated?Which therapeutic options were subsuquently Which therapeutic options were subsuquently recommended?recommended?RESULTS:RESULTS:

The most common definition was three unseccessful IVF cycles The most common definition was three unseccessful IVF cycles (range 2-6)(range 2-6)

Anticardiolipin antibodies and lupus anticoagulan antibodiesAnticardiolipin antibodies and lupus anticoagulan antibodies HysteroscopyHysteroscopy KaryotypeKaryotype Blastocyst cultureBlastocyst culture Assisted HatchingAssisted Hatching

The results of this survey suggest that there is considerableThe results of this survey suggest that there is considerablevariation in the approach to investigation and management variation in the approach to investigation and management

ofofrecurrent IVF treatment failure in the UK.recurrent IVF treatment failure in the UK.

Page 3: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Definition of Repeated Definition of Repeated Implantation FailureImplantation Failure

Failure to achieve a pregnancy following 2-6 IVF Failure to achieve a pregnancy following 2-6 IVF cycles, in which more than 10 high-grade cycles, in which more than 10 high-grade embryos were transferred to the uterus was embryos were transferred to the uterus was defined by various clinicians as ‘repeated defined by various clinicians as ‘repeated implantation failure’.implantation failure’.

Tan et all, 2005Tan et all, 2005

Today with the tendency of transferring only one Today with the tendency of transferring only one or two embryos, the definition of repeated or two embryos, the definition of repeated implantation failure is not apparent.implantation failure is not apparent.

After failure of two or three cycles in which After failure of two or three cycles in which reasonably good embryos were transferred reasonably good embryos were transferred further investigation should be initiated.further investigation should be initiated.

Margolioth EJ et all, 2006Margolioth EJ et all, 2006

Page 4: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Shamma FN et all, Fertil Steril, 1992Shamma FN et all, Fertil Steril, 1992Balmaceda JP, Obstet and Gynecol Clinicf of North America , 1995Balmaceda JP, Obstet and Gynecol Clinicf of North America , 1995

The major determinant of the success of IVF The major determinant of the success of IVF treatment is embryo quality.treatment is embryo quality.

Uterine receptivity and uterine integrity have Uterine receptivity and uterine integrity have also an important impact for the also an important impact for the achievement and continuation of pregnancy.achievement and continuation of pregnancy.

It has been well established that implantation It has been well established that implantation of fertilized eggs is affected by intrauterine of fertilized eggs is affected by intrauterine environment.environment.

Page 5: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Margalioth EJ et all, Hum Rerod 21(12):3036-43, 2006Margalioth EJ et all, Hum Rerod 21(12):3036-43, 2006

The causes for repeated implantation failure The causes for repeated implantation failure may be because of embrionic defects, reduced may be because of embrionic defects, reduced endometrial receptivity or multifactorial endometrial receptivity or multifactorial effects.effects.

Various uterine abnormalities, thin Various uterine abnormalities, thin endometrium, altered expression of adesive endometrium, altered expression of adesive molecules and immunological factors may molecules and immunological factors may decrease endometrial receptivity.decrease endometrial receptivity.

Genetic abnormalities of the male or female, Genetic abnormalities of the male or female, sperm deffects, embrionic aneuploidy, zona sperm deffects, embrionic aneuploidy, zona hardening are among the embrionic reasons hardening are among the embrionic reasons for failure of implantation.for failure of implantation.

Endometriosis and hydrosalpinges may Endometriosis and hydrosalpinges may adversely influence both. adversely influence both.

Page 6: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

The Uterine Abnormalities The Uterine Abnormalities In Infertile WomenIn Infertile Women

Uterine malformations Uterine malformations MyomasMyomas Endometrial polypsEndometrial polyps Intrauterine adhesions Intrauterine adhesions EndometritisEndometritis Thin endrometrium Thin endrometrium Endometrial HyperplasiaEndometrial Hyperplasia Cervical adhesionsCervical adhesions

Lass A et all, Journal of Assisted Reproduction And Genetics, Lass A et all, Journal of Assisted Reproduction And Genetics, 16, 410-15,199916, 410-15,1999

Varasteh NN et all, Obstet Gynecol 94, 168-171, 1999Varasteh NN et all, Obstet Gynecol 94, 168-171, 1999

Page 7: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

To diagnose intrauterine pathologies To diagnose intrauterine pathologies in infertil women:in infertil women:

Transvaginal ultrasonographyTransvaginal ultrasonography Saline infusion sonographySaline infusion sonography HysterosalpingographyHysterosalpingography HysteroscopyHysteroscopy

Page 8: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Hysteroscopy is superior to Hysteroscopy is superior to hysterosalpingography for diagnosis of hysterosalpingography for diagnosis of intrauterine pathology and it is not suprising intrauterine pathology and it is not suprising that anomalies might be overlooked when that anomalies might be overlooked when relying on HSG alone.relying on HSG alone.

Golan A et all, Acta Obstetrica et Gynecologyca Scandinavia, 75,654-56-Golan A et all, Acta Obstetrica et Gynecologyca Scandinavia, 75,654-56-19961996

Hysteroscopy demonstrates not only the Hysteroscopy demonstrates not only the location, shape and size of adhesions, but also location, shape and size of adhesions, but also their nature ( mucosal, fibrous, their nature ( mucosal, fibrous, myometrial).myometrial).

Al-Inany H. Acte Obstetrica et Gynecologyca Scandinavia, 80, 986-93, 2001Al-Inany H. Acte Obstetrica et Gynecologyca Scandinavia, 80, 986-93, 2001

Page 9: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

nn %%

Normal Uterine Normal Uterine CavityCavity

793793 90,2290,22

Intrauterine Intrauterine AbnormalitiesAbnormalities

8686 9,789,78

Endometrial Endometrial PolypPolyp

99 1,021,02

Submucous Submucous MyomaMyoma

5959 6,716,71

Mullerian Mullerian defectdefect

1818 2,052,05

Sonographic findings of 879 infertile Sonographic findings of 879 infertile patients.patients.

HysteroscopyHysteroscopy

UUSSGG

AbnormalAbnormal NormalNormal TotalTotal

AbnormAbnormalal

5555 3131 8686

NormalNormal 207207 586586 793793

TotalTotal 262262 617617 879879

Sensitivity of USG Sensitivity of USG 20%20%

Specificity of USG Specificity of USG 95%95%

Positive predictive value Positive predictive value 64%64%Negative predictive value Negative predictive value 74%74%Ege University IVF CenterEge University IVF Center

Page 10: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Hysterosalpingographyc findings of 585 infertile patients.Hysterosalpingographyc findings of 585 infertile patients.

nn %%

Normal Uterine Normal Uterine CavityCavity

255255 43,5843,58

Intrauterine Intrauterine AbnormalitiesAbnormalities

330330 56,4156,41

Filling defect Filling defect 224224 38,2938,29

Intrauterine Intrauterine adhesionadhesion

2020 3,423,42

Mullerian defectMullerian defect 5555 9,469,46

Tubal pathologiesTubal pathologies 3131 5,305,30

HysteroscopyHysteroscopy

HHSSGG

AbnormalAbnormal NormalNormal TotalTotal

AbnormAbnormalal

153153 177177 330330

NormalNormal 2727 228228 255255

TotalTotal 180180 405405 585585

Sensitivity of HSG Sensitivity of HSG 85% 85%

Specificity of HSGSpecificity of HSG 56% 56%

Positive predictive value Positive predictive value 46% 46%Negative predictive Negative predictive value 89%value 89%Ege University IVF CenterEge University IVF Center

Page 11: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Hysteroscopic findings of 879 infertile patients.Hysteroscopic findings of 879 infertile patients.

nn %%

Normal Uterine Normal Uterine CavityCavity

617617 70,1970,19

Intrauterine Intrauterine AbnormalitiesAbnormalities

262262 29,8129,81

Cervical polypCervical polyp 3030 3,423,42

Endometrial Endometrial polyppolyp

5454 6,146,14

Submucous Submucous myomamyoma

1616 1,821,82

Intrauterine Intrauterine adhesionadhesion

4949 5,585,58

Mullerian Mullerian defectdefect

102102 11,6011,60

Cervical Cervical stenosisstenosis

1111 1,251,25Ege University IVF CenterEge University IVF Center

Page 12: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Hysteroscopic findings of 98 patients who had 2 unsuccessful IVF cycles.Hysteroscopic findings of 98 patients who had 2 unsuccessful IVF cycles.

nn %%

Normal Uterine Normal Uterine CavityCavity

7373 74,4974,49

Intrauterine Intrauterine AbnormalitiesAbnormalities

2525 25,5125,51

Cervical polypCervical polyp 77 7,147,14

Endometrial Endometrial polyppolyp

22 2,042,04

Submucous Submucous myomamyoma

33 3,063,06

Intrauterine Intrauterine adhesionadhesion

55 5,015,01

Mullerian Mullerian defectdefect

99 9,179,17

Ege University IVF CenterEge University IVF Center

Page 13: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Hysteroscopy in on IVF-ET programme. Clinicial experience with 360 infertile Hysteroscopy in on IVF-ET programme. Clinicial experience with 360 infertile patients.patients.Senera P et all, Acte Obstet Gynecol Scand 67(2): 135-137,1988Senera P et all, Acte Obstet Gynecol Scand 67(2): 135-137,1988

360 patients underwent hysteroscopy before entering 360 patients underwent hysteroscopy before entering the IVF program (247-%70- was obstructive tubal the IVF program (247-%70- was obstructive tubal disease).disease).

148 showed uterine abnormalities (44,5%)148 showed uterine abnormalities (44,5%) Endometrial polypsEndometrial polyps AdhesionsAdhesions HypoplasieHypoplasie Malforrnations Malforrnations Cervical stenosisCervical stenosis

114 of these patients had normal hysterographic 114 of these patients had normal hysterographic findings.findings.

In an IVF programme hysteroscopic evaluation can In an IVF programme hysteroscopic evaluation can reduce the failure rate due to intrauterine reduce the failure rate due to intrauterine abnormalities.abnormalities.

Page 14: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

The role of hysteroscopy in patients having failed IVF/GIFT transfer cycles.The role of hysteroscopy in patients having failed IVF/GIFT transfer cycles.Kirsop R. et all, Aust NZJ Obstet Gynecol 31(3):263-4,1991Kirsop R. et all, Aust NZJ Obstet Gynecol 31(3):263-4,1991

50 patients who had undergone 2 or 50 patients who had undergone 2 or more failed IVF cycles or failed GIFT more failed IVF cycles or failed GIFT cycles.cycles.

Fertilization have been demostrated.Fertilization have been demostrated.HysteroscHysteroscopyopyRESULTS: 28 % were found to have intrauterine RESULTS: 28 % were found to have intrauterine

abnormalities.abnormalities.Patients with an abnormality found at Patients with an abnormality found at

hysteroscopyhysteroscopy had undergone a significantly higher mean number of transfer cycles.

These results suggest that intrauterine abnormalities may be cause for failure of IVF-ET or GIFT.

Hysteroscopy should be part of the infertility work-up of all patients prior to undergoing IVF treatment.

Page 15: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

The role of diagnostic hysteroscopy and endometrial, biopsy in ART The role of diagnostic hysteroscopy and endometrial, biopsy in ART La Sala GB et all,Fertil Steril, 70(2), 378-80,1998La Sala GB et all,Fertil Steril, 70(2), 378-80,1998

Objective: To study the medicine of Objective: To study the medicine of unsuspected endouterine abnormalities in unsuspected endouterine abnormalities in patients for whom IVF-ET repeatedly failspatients for whom IVF-ET repeatedly fails

100 patients100 patients 2 IVF cycles failed (2≥good quality 2 IVF cycles failed (2≥good quality

embryos)embryos)

RESULTS: In 18 patients hysteroscopy showed endouterine RESULTS: In 18 patients hysteroscopy showed endouterine abnormality.abnormality.

6 endometrial polyps3 submucous myoma7 intrauterine adhesions1 endometritis1 tuberculous endrometritis

Conclusion: Diagnostic hysteroscopy should be performed Conclusion: Diagnostic hysteroscopy should be performed on all patients before they undergo IVF-ET.on all patients before they undergo IVF-ET.

Page 16: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

The value of repeat hysteroscopic evaluation in patients with failed IVF transfer The value of repeat hysteroscopic evaluation in patients with failed IVF transfer cycles.cycles.Dicker D et all, 58(4):833-5, Fertil Steril, 1992Dicker D et all, 58(4):833-5, Fertil Steril, 1992

110 women with normal initial hysteroscopy110 women with normal initial hysteroscopy 3 or more repeated implantation failure 3 or more repeated implantation failure

with IVF.with IVF.

RESULTS: 20 patients (18,2%) with uterine RESULTS: 20 patients (18,2%) with uterine abnormalities.abnormalities.

HyperplasiaPolypsEndometritisSynechiaeOur results indicate that repeat hysteroscopic evaluation in cases of Our results indicate that repeat hysteroscopic evaluation in cases of

recurrent IVF-ET failure is an important adjunctive method for further recurrent IVF-ET failure is an important adjunctive method for further avaluating and posibly optimizing the IVF-ET procedure.avaluating and posibly optimizing the IVF-ET procedure.

Page 17: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

TheThe value of hysteroscopy after repeated implantation failures with IVF value of hysteroscopy after repeated implantation failures with IVFSciano A et all. Contracept Fertil sex 27(2):129-132,1999Sciano A et all. Contracept Fertil sex 27(2):129-132,1999

Objective: To determine the usefulness of uterine re-Objective: To determine the usefulness of uterine re-assessment by hysteroscopy in women with 2 assessment by hysteroscopy in women with 2 unsuccessful IVF-ET.unsuccessful IVF-ET.

73 infertile women73 infertile women Repeat hysteroscopy after 2 implantation failure in Repeat hysteroscopy after 2 implantation failure in

IVFIVFRESULTS: RESULTS:

50% of the cases an abnormality was diagnosed.50% of the cases an abnormality was diagnosed.Cervical synechiaeCervical synechiae polyppolyp false passagefalse passageHormono-dependent abnormalitiesHormono-dependent abnormalities polyp polyp hyperplasiahyperplasia submucous myomasubmucous myoma

22% of these patients →pregnant22% of these patients →pregnantIt seems legitimate to perform hysteroscopy in women who It seems legitimate to perform hysteroscopy in women who

have had 2 IVF-ET failure before attempting a third procedure.have had 2 IVF-ET failure before attempting a third procedure.

Page 18: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Effect of treatment of intrauterine pathologies with office histeroscopy inpatients with Effect of treatment of intrauterine pathologies with office histeroscopy inpatients with recurrent IVF failurerecurrent IVF failureDemirol A, Gürgan T, Reprod Biomed Online 8(5): 590-42004Demirol A, Gürgan T, Reprod Biomed Online 8(5): 590-42004

Objective: The study was conducted to evaluate if Objective: The study was conducted to evaluate if the diagnosis and treatment of intrauterine lesions the diagnosis and treatment of intrauterine lesions with office hysteroscopy is of value in improving with office hysteroscopy is of value in improving the pregnancy outcome in patients with recurrent the pregnancy outcome in patients with recurrent IVF failure.IVF failure.

421 patients who had undergone 2 or more falled 421 patients who had undergone 2 or more falled IVF cycles (prospectively randomized)IVF cycles (prospectively randomized)

Group I: (n=211) did not have office hysteroscopic Group I: (n=211) did not have office hysteroscopic evaluation evaluation

Group II: (n=210) had office hysteroscopy Group II: (n=210) had office hysteroscopy

Group IIa: (n=154) normal Group IIa: (n=154) normal hysteroscopic findings hysteroscopic findings

Group IIb: (n=56) abnormal Group IIb: (n=56) abnormal hysteroscopic findings(corrected at the same time )hysteroscopic findings(corrected at the same time )

No difference existed in the mean number of oocyte No difference existed in the mean number of oocyte retrived, fertilization rate, number of embrios retrived, fertilization rate, number of embrios transferred or first trimester abortion rates among transferred or first trimester abortion rates among the groups.the groups.

Page 19: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Effect of treatment of intrauterine pathologies with office histeroscopy Effect of treatment of intrauterine pathologies with office histeroscopy inpatients with recurrent IVF failureinpatients with recurrent IVF failureDemirol A, Gürgan T, Reprod Biomed Online 8(5): 590-42004Demirol A, Gürgan T, Reprod Biomed Online 8(5): 590-42004

Results: Clinicial pregnancy rates: Results: Clinicial pregnancy rates:

Group I: 21,6%Group I: 21,6%

Group IIa: 32,5% p=0,044Group IIa: 32,5% p=0,044

Group IIb: 30,4% p=0,044Group IIb: 30,4% p=0,044

Patients with normal hysterosalpingography Patients with normal hysterosalpingography but recurrent IVF failure should be but recurrent IVF failure should be evaluated by hysteroscopy.evaluated by hysteroscopy.

Page 20: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Objective: To evaluate if the diagnosis and Objective: To evaluate if the diagnosis and treatment of the uterine cavity abnormalities treatment of the uterine cavity abnormalities

by hysteroscopy in IVF is of any value in by hysteroscopy in IVF is of any value in improving clinical pregnancy outcomeimproving clinical pregnancy outcome

520 patients who had undergone 2 or more falled 520 patients who had undergone 2 or more falled IVF cycleIVF cycle

Group I(n=265) without office hysteroscopy Group I(n=265) without office hysteroscopy Group II(n=255) had office hysteroscopy Group II(n=255) had office hysteroscopy Group II a (n=160)had normal Group II a (n=160)had normal findings findings Group IIb (n=95) had Group IIb (n=95) had abnormal findings abnormal findings (corrected at the same time)(corrected at the same time)

No difference in the mean number of oocytes No difference in the mean number of oocytes retrieved, fertilization rate, number of embryos retrieved, fertilization rate, number of embryos transferred transferred

Rama-Raju GA et al., Archieves of Gynocology and Obstetrics 274(3):460-462, 2006

Page 21: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Result: Result: clinical pregnancy ratesclinical pregnancy rates

Group I 26,2 %Group I 26,2 %

Group IIa 44,44 % Group IIa 44,44 % ((pp<0,05) <0,05)

Group IIb 39,55 % Group IIb 39,55 % ((pp<0,05)<0,05)

Patients with recurrent IVF failure Patients with recurrent IVF failure after normal HSG should also be after normal HSG should also be reevaluated using hysteroscopyreevaluated using hysteroscopyRama-Raju GA et al., Archieves of Gynocology and Obstetrics 274(3):460-462, 2006

Page 22: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

The value of hysteroscopy in elderly women The value of hysteroscopy in elderly women prior to IVF-ET: a comparative study prior to IVF-ET: a comparative study

Dicker D.et al., J In Vitro Fert Embryo Transf. Dicker D.et al., J In Vitro Fert Embryo Transf. 19901990

284 hysteroscopies were performed in 284 hysteroscopies were performed in 312(91%) candidates for IVF who were divided 312(91%) candidates for IVF who were divided into 2 groups; into 2 groups;

Group I; elderly women over 40 years (n=66)Group I; elderly women over 40 years (n=66) Group II; below 40 years (n=218)Group II; below 40 years (n=218) All of which failed in 1 to 3 cycles previouslyAll of which failed in 1 to 3 cycles previously Results; Results;

Uterine abnormalities in all patients 29,9%Uterine abnormalities in all patients 29,9%

Abnormal findings were significantly Abnormal findings were significantly increased in group I (increased in group I (pp<0,001) <0,001)

Page 23: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

The value of hysteroscopy in elderly women The value of hysteroscopy in elderly women prior to IVF-ET: a comparative studyprior to IVF-ET: a comparative study

Dicker D.et al., J In Vitro Fert Embryo Transf. Dicker D.et al., J In Vitro Fert Embryo Transf. 19901990

In elderly women age related uterine pathology In elderly women age related uterine pathology such as submucos myoma, endometrial such as submucos myoma, endometrial hyperplasia and polips were more prominent. hyperplasia and polips were more prominent. In younger patients adhesions and tubal ostia In younger patients adhesions and tubal ostia occlusion were more common. occlusion were more common.

7 clinical pregnancies (8,9%) in Group I7 clinical pregnancies (8,9%) in Group I 41 clinical pregnancies (19,9%) in Group II 41 clinical pregnancies (19,9%) in Group II

(treatment prior to IVF)(treatment prior to IVF) All of which failed in one or three cycles All of which failed in one or three cycles

previously previously It seems that hysteroscopic evaluation may It seems that hysteroscopic evaluation may

reduce the IVF-ET failure rate due to reduce the IVF-ET failure rate due to intrauterine abnormalities in elderly as well as intrauterine abnormalities in elderly as well as young patients young patients

Page 24: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

The Association Between Uterine Septum and The Association Between Uterine Septum and Infertility Abuzeid M. Et al. Fertil Steril, 2005Infertility Abuzeid M. Et al. Fertil Steril, 2005

Objective: To report the incidence of short Objective: To report the incidence of short uterine septum in infertility patients based on uterine septum in infertility patients based on hysteroscopic findingshysteroscopic findings

1011 patients who underwent laparoscopic and 1011 patients who underwent laparoscopic and hysteroscopic surgery for treatment of hysteroscopic surgery for treatment of infertilityinfertility

Group I: 661 patients with endometriosisGroup I: 661 patients with endometriosis Group II: 350 patients who had no Group II: 350 patients who had no

endometriosisendometriosis If a uterine septum was detected the type was If a uterine septum was detected the type was

determined : short <2cm long>2 cmdetermined : short <2cm long>2 cm Hysteroscopic division was performedHysteroscopic division was performed Following surgery 33 patients underwent ARTFollowing surgery 33 patients underwent ART

Page 25: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Results;Results; The mean age of the women with septum 31,0The mean age of the women with septum 31,0±±5,15,1Duration of infertility, 3,6 Duration of infertility, 3,6 ±±3,4 years3,4 yearsUterine septum in Group I 117( 17,7%)Uterine septum in Group I 117( 17,7%) in Group II 61 (17,4%)in Group II 61 (17,4%)Short type in Group I 15,6 % Short type in Group I 15,6 % in Group II 14,3 %in Group II 14,3 % 33 patients who attended ART pregnancy rate 51,9%33 patients who attended ART pregnancy rate 51,9%Conclusion;Conclusion; The incidence of short uterine septum in infertile patients The incidence of short uterine septum in infertile patients

is much higher than what has previously been reportedis much higher than what has previously been reported After hysteroscopic surgical correction high pregnancy After hysteroscopic surgical correction high pregnancy

rates can be achieved after assisted conceptionrates can be achieved after assisted conception

Abuzeid M. Et al. Fertil Steril, 2005Abuzeid M. Et al. Fertil Steril, 2005

Page 26: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Is hysteroscopic correction of an incomplete Is hysteroscopic correction of an incomplete uterine septum justified prior to IVF uterine septum justified prior to IVF

Özgür K et al. Reprod Biomed Online 2007Özgür K et al. Reprod Biomed Online 2007 Objective: To examine the effect of hystreroscopic correction of Objective: To examine the effect of hystreroscopic correction of

an incomplete uterine septum on IVF outcomean incomplete uterine septum on IVF outcome Mesurement of fundal myometrial thicness (Fm) Mesurement of fundal myometrial thicness (Fm) cornual myometrial thicness (Cm) cornual myometrial thicness (Cm) By sonohysteroscopyBy sonohysteroscopy Incomplete septum criteria: Fm> 11 mm and Fm-Cm> 5 mm Incomplete septum criteria: Fm> 11 mm and Fm-Cm> 5 mm Group I ( n=119) patients with incomplete septumGroup I ( n=119) patients with incomplete septum Grup II (n=116) control patients; age matched with normal Grup II (n=116) control patients; age matched with normal

cavity who underwent IVF with in the same time periodcavity who underwent IVF with in the same time period Result: Group I had a hystory of more spontaneus abortions Result: Group I had a hystory of more spontaneus abortions

(14,20 vs 6,03 % p=0,04)(14,20 vs 6,03 % p=0,04) Group I higher previous IVF failure (32,7 vs 20,6 % Group I higher previous IVF failure (32,7 vs 20,6 %

p=0,04)p=0,04) After surgical correction of the septum in Group I; IVF pregnancy After surgical correction of the septum in Group I; IVF pregnancy

outcome was similar in both groups clinical pregnancy rates outcome was similar in both groups clinical pregnancy rates 47,8% vs 46,5% 47,8% vs 46,5%

pregnancy loss 10,52% vs pregnancy loss 10,52% vs 20,3%20,3%

Page 27: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Hysteroscopic findings in women with a Hysteroscopic findings in women with a history of very thin endometrium during history of very thin endometrium during

assisted conception treatment:assisted conception treatment:Marikinti K. Fertil Steril 84(1); 364-65, 2005Marikinti K. Fertil Steril 84(1); 364-65, 2005

Objective: To study the value of hysteroscopy in ‘thin Objective: To study the value of hysteroscopy in ‘thin endometrium’ on transvaginal sonographyendometrium’ on transvaginal sonography

A thin endometrium on transvaginal sonography is the most A thin endometrium on transvaginal sonography is the most vidaly used screening test for endometrial inadequencyvidaly used screening test for endometrial inadequency

34 women with thin endometrium (≤6 mm prior to embryo 34 women with thin endometrium (≤6 mm prior to embryo transfer) underwent both a repeat TV sonography and transfer) underwent both a repeat TV sonography and hysteroscopy either during and abondoned treatment cycle or hysteroscopy either during and abondoned treatment cycle or in a naturalş cycle after the failed attemptin a naturalş cycle after the failed attempt

Results: All 34 cases gave a hystory of uterine interventions :Results: All 34 cases gave a hystory of uterine interventions : 18 uterine evacuations18 uterine evacuations 8 assisted conception related procedures 8 assisted conception related procedures 3 caesarean sections3 caesarean sections 2 endometritis2 endometritis 2 peritonitis2 peritonitis 2 myomectomy 2 myomectomy

Page 28: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

The hysteroscopic findings:The hysteroscopic findings:Group A (n=14): narrow glandular openings, thin blood Group A (n=14): narrow glandular openings, thin blood vessels mal distributed, fragile Em. 8 samples out of vessels mal distributed, fragile Em. 8 samples out of phase em, 13 non homogeneus and/or non trilaminar phase em, 13 non homogeneus and/or non trilaminar ememGroup B (n=12): moderately developed glandular openings, blood Group B (n=12): moderately developed glandular openings, blood

vessels uniformly distributed, healthy Em, 1 sample out of vessels uniformly distributed, healthy Em, 1 sample out of phasephase

Group C (n=8): Intra uterine synechie, obliteration of the uterine Group C (n=8): Intra uterine synechie, obliteration of the uterine cavity. 3 samples out of phase Em. 4 non homogeneus and/or cavity. 3 samples out of phase Em. 4 non homogeneus and/or non trilaminer Emnon trilaminer Em

34 womens subsequently underwent 6 cycles of high dose estrogen 34 womens subsequently underwent 6 cycles of high dose estrogen therapy, aspirin or empirical antibioticstherapy, aspirin or empirical antibiotics

Follow-up TV sonography;Follow-up TV sonography; 21 cases: 7,2 mm endometrial thicness21 cases: 7,2 mm endometrial thicness 13 cases: ≤ 6 mm endometrial thicness13 cases: ≤ 6 mm endometrial thicnessGroup A Group A (6/14) (6/14) attempted to conceive following hysteroscopy attempted to conceive following hysteroscopy 2 singleton 2 singleton

livebirthlivebirthGroup BGroup B (11/12) (11/12) 1 singleton 1 singleton

livebirthlivebirth Group CGroup C (4/8) (4/8) 1 singleton livebirth1 singleton livebirth

4 pregnancies were complicated by recurrent bleeding and preterm 4 pregnancies were complicated by recurrent bleeding and preterm delivery and 1 required a caesarean hysterectomy for placenta delivery and 1 required a caesarean hysterectomy for placenta accreataaccreata

Marikinti K. Fertil Steril 84(1); Marikinti K. Fertil Steril 84(1); 364-65, 2005364-65, 2005

Page 29: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Hysteroscopic findings in women with a Hysteroscopic findings in women with a history of very thin endometrium during history of very thin endometrium during

assisted conception treatment:assisted conception treatment:Marikinti K. Fertil Steril 84(1); 364-65, 2005Marikinti K. Fertil Steril 84(1); 364-65, 2005

Conclusion:Conclusion: The hysteroscopic findings of atrophic Em, The hysteroscopic findings of atrophic Em,

correlated well with poor grade Em on trans correlated well with poor grade Em on trans vaginal USG and out of phase histology which vaginal USG and out of phase histology which may have led to the low uptake of further may have led to the low uptake of further treatments.treatments.

The presence of thin but healthy Em at The presence of thin but healthy Em at hysteroscopy correlated well with a good grade hysteroscopy correlated well with a good grade of Em on TV-USG and in phase histology, which of Em on TV-USG and in phase histology, which probably led to the high uptake rate of further probably led to the high uptake rate of further treatments. But the pregnancy rate remained treatments. But the pregnancy rate remained low.low.

In group C, selected cases of treatable In group C, selected cases of treatable Asherman’s Syndrome achieved pregnancies that Asherman’s Syndrome achieved pregnancies that were high risk .were high risk .

Page 30: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Chromo-hysteroscopy for evaluation of Chromo-hysteroscopy for evaluation of endometrium in recurrent IVF failure endometrium in recurrent IVF failure

Küçük T, Safali MKüçük T, Safali MAssit Reprod Genet 25(2-3); 79-82, 2008Assit Reprod Genet 25(2-3); 79-82, 2008

Objective: To assess the efficacy of chromo-Objective: To assess the efficacy of chromo-hysteroscopy in detecting endometrial pathologies in hysteroscopy in detecting endometrial pathologies in recurrent IVF failurerecurrent IVF failure

64 patients in whom conventional hysteroscopy did 64 patients in whom conventional hysteroscopy did not show any apparent endometrial pathology.not show any apparent endometrial pathology.

5 ml. of 1 %methylene blue dye was introduced 5 ml. of 1 %methylene blue dye was introduced through the hysteroscopıc inlet.through the hysteroscopıc inlet.

Biopsies were obtained both from dark stained and Biopsies were obtained both from dark stained and light stained areas.light stained areas.

Group I :22 patients with focal dark stainingGroup I :22 patients with focal dark staining Group II:41 patients with light blue stainingGroup II:41 patients with light blue staining No significant difference between two groups in No significant difference between two groups in

age,smoking,BMI,number of IVF failure.age,smoking,BMI,number of IVF failure.

Page 31: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Result: There was a statistically significant Result: There was a statistically significant difference in the incidance of endometritis difference in the incidance of endometritis between two groups (between two groups (pp=0,007)=0,007)

The power of dark staining for detection of The power of dark staining for detection of endometritis was calculated as follows: endometritis was calculated as follows: sensitivity 69,2 % sensitivity 69,2 %

specificity 74 %specificity 74 % positive predictive value 40,9 %positive predictive value 40,9 % negative predictive value 90,2 % negative predictive value 90,2 %

Chromo-hysteroscopy improves the efficacy of Chromo-hysteroscopy improves the efficacy of hysteroscopy in recurrent IVF failure. hysteroscopy in recurrent IVF failure.

Küçük T, Safali MKüçük T, Safali M Assit Reprod Genet 25(2-3); 79-82, 2008 Assit Reprod Genet 25(2-3); 79-82, 2008

Page 32: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Polypoid appearance of the endometrium on Polypoid appearance of the endometrium on office hysteroscopy a significant predictor of office hysteroscopy a significant predictor of

miscarriage after miscarriage after IVF-ETIVF-ET

Zeyneloglu HB et al., Fertil Steril 2007Zeyneloglu HB et al., Fertil Steril 2007 Objective: To assess the impact of Objective: To assess the impact of

polypoid appearance detected by office polypoid appearance detected by office hysteroscopy on clinical pregnancy and hysteroscopy on clinical pregnancy and abortion rates in IVF cyclesabortion rates in IVF cycles

Patients in whom office hysteroscopy was Patients in whom office hysteroscopy was performed in between days 17-20 of their performed in between days 17-20 of their menstruel cycle prior to their IVF-ETmenstruel cycle prior to their IVF-ET

Polypoid structures were biopsied using Polypoid structures were biopsied using grasper or scissors or pipellegrasper or scissors or pipelle

Group I: (n=41) polipoid endometriumGroup I: (n=41) polipoid endometrium Group II: (n=48) no abnormalitiesGroup II: (n=48) no abnormalities

Page 33: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

No statistically significant differences in between No statistically significant differences in between the groups with respect to age, basal FSH levels, the groups with respect to age, basal FSH levels, basal E2 levels, BAF count, BMI, the number of basal E2 levels, BAF count, BMI, the number of

embryos transferred and causes of infertilityembryos transferred and causes of infertilityResults: Results: implantation ratesimplantation rates Group I 69% Group I 69% Group II 52% p=0,43 (NS)Group II 52% p=0,43 (NS) abortion ratesabortion rates Group I 25,6%Group I 25,6% Group II 6,5 % p=0,01 Group II 6,5 % p=0,01 Conclusion:Conclusion: A polypoid appearance of the endometrium A polypoid appearance of the endometrium

may negatively affect the IVF result by may negatively affect the IVF result by increasing the abortion rates rather than increasing the abortion rates rather than directly influencing the pregnancy rates.directly influencing the pregnancy rates.

Zeyneloglu HB et al., Fertil Steril Zeyneloglu HB et al., Fertil Steril 20072007

Page 34: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

Pregnancy rates after hysteroscopic Pregnancy rates after hysteroscopic polypectomy and myomectomy in infertile polypectomy and myomectomy in infertile

women.women.Varasteh NN, Neuwirth RS et al., Obstet Varasteh NN, Neuwirth RS et al., Obstet

Gynecol, 1999Gynecol, 1999 78 patients with bilateral tubal occlusion;78 patients with bilateral tubal occlusion; 36 patients hysteroscopic myomectomy 36 patients hysteroscopic myomectomy 23 patients hysteroscopic polypectomy 23 patients hysteroscopic polypectomy 19 patients normal 19 patients normal Following surgery 78 patients underwent ART Following surgery 78 patients underwent ART No significant difference in age, type of infertility and length of No significant difference in age, type of infertility and length of

infertilityinfertility Results: Polypectomy subjects had significantly higher Results: Polypectomy subjects had significantly higher

pregnancy and LBR than women with normal cavities (RR 2.42, pregnancy and LBR than women with normal cavities (RR 2.42, p=0,06)p=0,06)

Women who had myomectomies larger than 2 cm. had Women who had myomectomies larger than 2 cm. had significantly higher pregnancy and LBR, achieving statistical significantly higher pregnancy and LBR, achieving statistical significance at a myoma size of ≥3 cm (3,15 cm versus 2,5 cm significance at a myoma size of ≥3 cm (3,15 cm versus 2,5 cm p=0,05)p=0,05)

Spontaneus abortion rates among first pregnancies after Spontaneus abortion rates among first pregnancies after myomectomy, polypectomy or normal cases were similarmyomectomy, polypectomy or normal cases were similar

Both hysteroscopic polypectomy and hysteroscopic Both hysteroscopic polypectomy and hysteroscopic myomectomy appear to enhance fertility.myomectomy appear to enhance fertility.

Page 35: UTERINE CAVITY FINDINGS BY HYSTEROSCOPY IN IVF FAILURE Assoc. Prof. Dr. Rafael LEVİ Ege University Family Planning And Infertility Research And Treatment

ConclusionConclusion

Hysteroscopy is the gold standard in Hysteroscopy is the gold standard in infertile patients for determining uterine infertile patients for determining uterine cavity and should be performed cavity and should be performed especially in women with ≥2 especially in women with ≥2 unsuccessful IVF cycles.unsuccessful IVF cycles.

Repeat hysteroscopic evaluation in Repeat hysteroscopic evaluation in cases of recurrent IVF-ET failure is an cases of recurrent IVF-ET failure is an important adjunctive method for further important adjunctive method for further evaluating and possibly optimizing the evaluating and possibly optimizing the IVF-ET procedure.IVF-ET procedure.