Transcript Slayt 1

UTERINE CAVITY
FINDINGS BY
HYSTEROSCOPY IN IVF
FAILURE
Assoc. Prof. Dr. Rafael LEVİ
Ege University Family Planning And Infertility Research And
Treatment Center-İZMİR
2. Güncel Üreme Endokrinolojisi, Yardımcı Üreme Teknikleri
Kongresi
1. Üreme Tıbbı Derneği Kongresi
17-20 Nisan 2008 Çeşme- İzmir
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Objective: To determine current practice in the management of recurrent IVF
treatment failure in licenced UK infertility centers.
Human Fertilization And Embriyology Authority licenced centers in UK
(n=79)
How recurrent IVF treatment failure was defined?
Which investigations were initiated?
Which therapeutic options were subsuquently recommended?
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RESULTS:
The most common definition was three unseccessful IVF cycles (range 2-6)
Anticardiolipin antibodies and lupus anticoagulan antibodies
Hysteroscopy
Karyotype
Blastocyst culture
Assisted Hatching
The results of this survey suggest that there is considerable
variation in the approach to investigation and management of
recurrent IVF treatment failure in the UK.
Investigation and current management of recurrent IVF treatment failure in the UK.
Tan BK et all, BJOG, 112(6):773-80 2005
Definition of Repeated Implantation
Failure
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Failure to achieve a pregnancy following 2-6 IVF cycles, in which
more than 10 high-grade embryos were transferred to the uterus
was defined by various clinicians as ‘repeated implantation
failure’.
Tan et all, 2005
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Today with the tendency of transferring only one or two
embryos, the definition of repeated implantation failure is not
apparent.
After failure of two or three cycles in which reasonably
good embryos were transferred further investigation should be
initiated.
Margolioth EJ et all, 2006
The major determinant of the success of IVF treatment
is embryo quality.
Uterine receptivity and uterine integrity have also an
important impact for the achievement and continuation
of pregnancy.
It has been well established that implantation of fertilized
eggs is affected by intrauterine environment.
Shamma FN et all, Fertil Steril, 1992
Balmaceda JP, Obstet and Gynecol Clinicf of North America , 1995
The causes for repeated implantation failure may be
because of embrionic defects, reduced endometrial
receptivity or multifactorial effects.
Various uterine abnormalities, thin endometrium, altered
expression of adesive molecules and immunological
factors may decrease endometrial receptivity.
Genetic abnormalities of the male or female, sperm
deffects, embrionic aneuploidy, zona hardening are
among the embrionic reasons for failure of
implantation.
Endometriosis and hydrosalpinges may adversely
influence both.
Margalioth EJ et all, Hum Rerod 21(12):3036-43, 2006
The Uterine Abnormalities In
Infertile Women
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Uterine malformations
Myomas
Endometrial polyps
Intrauterine adhesions
Endometritis
Thin endrometrium
Endometrial Hyperplasia
Cervical adhesions
Lass A et all, Journal of Assisted Reproduction And Genetics, 16, 410-15,1999
Varasteh NN et all, Obstet Gynecol 94, 168-171, 1999
To diagnose intrauterine pathologies in infertil
women:
Transvaginal ultrasonography
 Saline infusion sonography
 Hysterosalpingography
 Hysteroscopy
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Hysteroscopy is superior to hysterosalpingography for
diagnosis of intrauterine pathology and it is not
suprising that anomalies might be overlooked when
relying on HSG alone.
Golan A et all, Acta Obstetrica et Gynecologyca Scandinavia, 75,654-56-1996
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Hysteroscopy demonstrates not only the location,
shape and size of adhesions, but also their nature
( mucosal, fibrous, myometrial).
Al-Inany H. Acte Obstetrica et Gynecologyca Scandinavia, 80, 986-93, 2001
Sonographic findings of 879 infertile patients.
n
%
Normal Uterine
Cavity
793
90,22
Intrauterine
Abnormalities
86
9,78
Endometrial Polyp
9
1,02
Submucous Myoma
59
6,71
Mullerian defect
18
2,05
Hysteroscopy
Abnormal
U
S
G
Normal
Sensitivity of USG
20%
Specificity of USG
95%
Positive predictive value 64%
Negative predictive value 74%
Total
Abnormal
55
31
86
Normal
207
586
793
Total
262
617
879
Ege University IVF Center
Hysterosalpingographyc findings of 585 infertile patients.
n
%
Normal Uterine
Cavity
255
43,58
Intrauterine
Abnormalities
330
56,41
Filling defect
224
38,29
Intrauterine adhesion
20
3,42
Mullerian defect
55
9,46
Tubal pathologies
31
5,30
Sensitivity of HSG
Specificity of HSG
Positive predictive value
Negative predictive value
Hysteroscopy
Abnormal
H
S
G
Normal
Total
Abnormal
153
177
330
Normal
27
228
255
Total
180
405
585
85%
56%
46%
89%
Ege University IVF Center
Hysteroscopic findings of 879 infertile patients.
n
%
Normal Uterine
Cavity
617
70,19
Intrauterine
Abnormalities
262
29,81
Cervical polyp
30
3,42
Endometrial polyp
54
6,14
Submucous myoma
16
1,82
Intrauterine adhesion
49
5,58
Mullerian defect
102
11,60
Cervical stenosis
11
1,25
Ege University IVF Center
Hysteroscopic findings of 98 patients who had 2 unsuccessful IVF cycles.
n
%
Normal Uterine
Cavity
73
74,49
Intrauterine
Abnormalities
25
25,51
Cervical polyp
7
7,14
Endometrial polyp
2
2,04
Submucous myoma
3
3,06
Intrauterine adhesion
5
5,01
Mullerian defect
9
9,17
Ege University IVF Center
360 patients underwent hysteroscopy before entering the IVF
program (247-%70- was obstructive tubal disease).
 148 showed uterine abnormalities (44,5%)
 Endometrial polyps
 Adhesions
 Hypoplasie
 Malforrnations
 Cervical stenosis
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114 of these patients had normal hysterographic findings.
In an IVF programme hysteroscopic evaluation can reduce the
failure rate due to intrauterine abnormalities.
Hysteroscopy in on IVF-ET programme. Clinicial experience with 360 infertile patients.
Senera P et all, Acte Obstet Gynecol Scand 67(2): 135-137,1988
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50 patients who had undergone 2 or more failed
IVF cycles or failed GIFT cycles.
Fertilization have been demostrated.
Hysteroscopy
RESULTS: 28 % were found to have intrauterine abnormalities.
Patients with an abnormality found at hysteroscopy 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.
The role of hysteroscopy in patients having failed IVF/GIFT transfer cycles.
Kirsop R. et all, Aust NZJ Obstet Gynecol 31(3):263-4,1991
Objective: To study the medicine of unsuspected endouterine
abnormalities in patients for whom IVF-ET repeatedly fails
 100 patients
 2 IVF cycles failed (2≥good quality embryos)
RESULTS: In 18 patients hysteroscopy showed endouterine abnormality.
6 endometrial polyps
3 submucous myoma
7 intrauterine adhesions
1 endometritis
1 tuberculous endrometritis
Conclusion: Diagnostic hysteroscopy should be performed on all patients
before they undergo IVF-ET.
The role of diagnostic hysteroscopy and endometrial, biopsy in ART
La Sala GB et all,Fertil Steril, 70(2), 378-80,1998
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110 women with normal initial hysteroscopy
3 or more repeated implantation failure with IVF.
RESULTS: 20 patients (18,2%) with uterine abnormalities.
Hyperplasia
Polyps
Endometritis
Synechiae
Our results indicate that repeat hysteroscopic evaluation in cases of recurrent IVF-ET failure is
an important adjunctive method for further avaluating and posibly optimizing the IVF-ET
procedure.
The value of repeat hysteroscopic evaluation in patients with failed IVF transfer cycles.
Dicker D et all, 58(4):833-5, Fertil Steril, 1992
Objective: To determine the usefulness of uterine reassessment by hysteroscopy in women with 2 unsuccessful
IVF-ET.
 73 infertile women
 Repeat hysteroscopy after 2 implantation failure in IVF
RESULTS:
50% of the cases an abnormality was diagnosed.
Cervical synechiae
polyp
false passage
Hormono-dependent abnormalities
polyp
hyperplasia
submucous myoma
22% of these patients →pregnant
It seems legitimate to perform hysteroscopy in women who have had 2 IVFET failure before attempting a third procedure.
The value of hysteroscopy after repeated implantation failures with IVF
Sciano A et all. Contracept Fertil sex 27(2):129-132,1999
Objective: The study was conducted to evaluate if the
diagnosis and treatment of intrauterine lesions with office
hysteroscopy is of value in improving the pregnancy
outcome in patients with recurrent IVF failure.
 421 patients who had undergone 2 or more falled IVF
cycles (prospectively randomized)
Group I: (n=211) did not have office hysteroscopic
evaluation
Group II: (n=210) had office hysteroscopy
Group IIa: (n=154) normal hysteroscopic findings
Group IIb: (n=56) abnormal hysteroscopic
findings(corrected at the same time )
 No difference existed in the mean number of oocyte
retrived, fertilization rate, number of embrios transferred
or first trimester abortion rates among the groups.
Effect of treatment of intrauterine pathologies with office histeroscopy inpatients with recurrent IVF failure
Demirol A, Gürgan T, Reprod Biomed Online 8(5): 590-42004
Results: Clinicial pregnancy rates:
Group I: 21,6%
Group IIa: 32,5% p=0,044
Group IIb: 30,4% p=0,044
Patients with normal hysterosalpingography but
recurrent IVF failure should be evaluated by
hysteroscopy.
Effect of treatment of intrauterine pathologies with office histeroscopy inpatients with recurrent IVF
failure
Demirol A, Gürgan T, Reprod Biomed Online 8(5): 590-42004
Objective: To evaluate if the diagnosis and treatment of the
uterine cavity abnormalities by hysteroscopy in IVF is of any
value in improving clinical pregnancy outcome
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520 patients who had undergone 2 or more falled IVF cycle
Group I(n=265) without office hysteroscopy
Group II(n=255) had office hysteroscopy
Group II a (n=160)had normal findings
Group IIb (n=95) had abnormal findings
(corrected at the same time)
No difference in the mean number of oocytes retrieved,
fertilization rate, number of embryos transferred
Rama-Raju GA et al., Archieves of Gynocology and Obstetrics 274(3):460-462, 2006
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Result:
clinical pregnancy rates
Group I
26,2 %
Group IIa
44,44 % (p<0,05)
Group IIb
39,55 % (p<0,05)
Patients with recurrent IVF failure after normal
HSG should also be reevaluated using
hysteroscopy
Rama-Raju GA et al., Archieves of Gynocology and Obstetrics 274(3):460-462, 2006
The value of hysteroscopy in elderly women prior to IVF-ET:
a comparative study
Dicker D.et al., J In Vitro Fert Embryo Transf. 1990
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284 hysteroscopies were performed in 312(91%)
candidates for IVF who were divided into 2 groups;
Group I; elderly women over 40 years (n=66)
Group II; below 40 years (n=218)
All of which failed in 1 to 3 cycles previously
Results;
Uterine abnormalities in all patients 29,9%
Abnormal findings were significantly increased in
group I (p<0,001)
The value of hysteroscopy in elderly women prior to IVF-ET:
a comparative study
Dicker D.et al., J In Vitro Fert Embryo Transf. 1990
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In elderly women age related uterine pathology such as
submucos myoma, endometrial hyperplasia and polips
were more prominent. In younger patients adhesions
and tubal ostia occlusion were more common.
7 clinical pregnancies (8,9%) in Group I
41 clinical pregnancies (19,9%) in Group II (treatment
prior to IVF)
All of which failed in one or three cycles previously
It seems that hysteroscopic evaluation may reduce the
IVF-ET failure rate due to intrauterine abnormalities in
elderly as well as young patients
The Association Between Uterine Septum and Infertility
Abuzeid M. Et al. Fertil Steril, 2005
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Objective: To report the incidence of short uterine
septum in infertility patients based on hysteroscopic
findings
1011 patients who underwent laparoscopic and
hysteroscopic surgery for treatment of infertility
Group I: 661 patients with endometriosis
Group II: 350 patients who had no endometriosis
If a uterine septum was detected the type was
determined : short <2cm
long>2 cm
Hysteroscopic division was performed
Following surgery 33 patients underwent ART
Results;
The mean age of the women with septum 31,0±5,1
Duration of infertility, 3,6 ±3,4 years
Uterine septum in Group I
117( 17,7%)
in Group II 61 (17,4%)
Short type
in Group I
15,6 %
in Group II
14,3 %
 33 patients who attended ART pregnancy rate 51,9%
Conclusion;
The incidence of short uterine septum in infertile patients is much higher
than what has previously been reported
After hysteroscopic surgical correction high pregnancy rates can be achieved
after assisted conception
Abuzeid M. Et al. Fertil Steril, 2005
Is hysteroscopic correction of an incomplete uterine septum
justified prior to IVF
Özgür K et al. Reprod Biomed Online 2007
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Objective: To examine the effect of hystreroscopic correction of an
incomplete uterine septum on IVF outcome
Mesurement of fundal myometrial thicness (Fm)
cornual myometrial thicness (Cm)
By sonohysteroscopy
Incomplete septum criteria: Fm> 11 mm and Fm-Cm> 5 mm
Group I ( n=119) patients with incomplete septum
Grup II (n=116) control patients; age matched with normal cavity who
underwent IVF with in the same time period
Result: Group I had a hystory of more spontaneus abortions (14,20 vs 6,03 %
p=0,04)
Group I higher previous IVF failure (32,7 vs 20,6 % p=0,04)
After surgical correction of the septum in Group I; IVF pregnancy outcome
was similar in both groups clinical pregnancy rates 47,8% vs 46,5%
pregnancy loss 10,52% vs 20,3%
Hysteroscopic findings in women with a history of very thin
endometrium during assisted conception treatment:
Marikinti K. Fertil Steril 84(1); 364-65, 2005
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Objective: To study the value of hysteroscopy in ‘thin endometrium’ on
transvaginal sonography
A thin endometrium on transvaginal sonography is the most vidaly used
screening test for endometrial inadequency
34 women with thin endometrium (≤6 mm prior to embryo transfer)
underwent both a repeat TV sonography and hysteroscopy either during and
abondoned treatment cycle or in a naturalş cycle after the failed attempt
Results: All 34 cases gave a hystory of uterine interventions :
18 uterine evacuations
8 assisted conception related procedures
3 caesarean sections
2 endometritis
2 peritonitis
2 myomectomy
The hysteroscopic findings:
Group A (n=14): narrow glandular openings, thin blood vessels mal
distributed, fragile Em. 8 samples out of phase em, 13 non homogeneus
and/or non trilaminar em
Group B (n=12): moderately developed glandular openings, blood vessels
uniformly distributed, healthy Em, 1 sample out of phase
Group C (n=8): Intra uterine synechie, obliteration of the uterine cavity. 3
samples out of phase Em. 4 non homogeneus and/or non trilaminer
Em
34 womens subsequently underwent 6 cycles of high dose estrogen therapy,
aspirin or empirical antibiotics
Follow-up TV sonography;
21 cases: 7,2 mm endometrial thicness
13 cases: ≤ 6 mm endometrial thicness
Group A (6/14)
Group B (11/12)
Group C (4/8)
attempted to conceive following hysteroscopy 2 singleton livebirth
1 singleton livebirth
1 singleton livebirth
4 pregnancies were complicated by recurrent bleeding and preterm delivery
and 1 required a caesarean hysterectomy for placenta accreata
Marikinti K. Fertil Steril 84(1); 364-65, 2005
Hysteroscopic findings in women with a history of very thin
endometrium during assisted conception treatment:
Marikinti K. Fertil Steril 84(1); 364-65, 2005
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Conclusion:
The hysteroscopic findings of atrophic Em, correlated
well with poor grade Em on trans vaginal USG and out
of phase histology which may have led to the low
uptake of further treatments.
The presence of thin but healthy Em at hysteroscopy
correlated well with a good grade of Em on TV-USG
and in phase histology, which probably led to the high
uptake rate of further treatments. But the pregnancy
rate remained low.
In group C, selected cases of treatable Asherman’s
Syndrome achieved pregnancies that were high risk .
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Chromo-hysteroscopy for evaluation of endometrium in
recurrent IVF failure
Küçük T, Safali M
Assit Reprod Genet 25(2-3); 79-82, 2008
Objective: To assess the efficacy of chromo-hysteroscopy in
detecting endometrial pathologies in recurrent IVF failure
64 patients in whom conventional hysteroscopy did not show
any apparent endometrial pathology.
5 ml. of 1 %methylene blue dye was introduced through the
hysteroscopıc inlet.
Biopsies were obtained both from dark stained and light stained
areas.
Group I :22 patients with focal dark staining
Group II:41 patients with light blue staining
No significant difference between two groups in
age,smoking,BMI,number of IVF failure.
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Result: There was a statistically significant difference in the
incidance of endometritis between two groups (p=0,007)
The power of dark staining for detection of endometritis was
calculated as follows:
sensitivity 69,2 %
specificity 74 %
positive predictive value 40,9 %
negative predictive value 90,2 %
Chromo-hysteroscopy improves the efficacy of hysteroscopy in
recurrent IVF failure.
Küçük T, Safali M
Assit Reprod Genet 25(2-3); 79-82, 2008
Polypoid appearance of the endometrium on office
hysteroscopy a significant predictor of miscarriage after
IVF-ET
Zeyneloglu HB et al., Fertil Steril 2007
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Objective: To assess the impact of polypoid appearance
detected by office hysteroscopy on clinical pregnancy
and abortion rates in IVF cycles
Patients in whom office hysteroscopy was performed in
between days 17-20 of their menstruel cycle prior to
their IVF-ET
Polypoid structures were biopsied using grasper or
scissors or pipelle
Group I: (n=41) polipoid endometrium
Group II: (n=48) no abnormalities
No statistically significant differences in between the groups with
respect to age, basal FSH levels, basal E2 levels, BAF count, BMI,
the number of embryos transferred and causes of infertility
Results:
implantation rates
Group I 69%
Group II 52%
p=0,43 (NS)
abortion rates
Group I 25,6%
Group II 6,5 % p=0,01
Conclusion:
A polypoid appearance of the endometrium may
negatively affect the IVF result by increasing the
abortion rates rather than directly influencing the
pregnancy rates.
Zeyneloglu HB et al., Fertil Steril 2007
Pregnancy rates after hysteroscopic polypectomy and
myomectomy in infertile women.
Varasteh NN, Neuwirth RS et al., Obstet Gynecol, 1999
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78 patients with bilateral tubal occlusion;
36 patients hysteroscopic myomectomy
23 patients hysteroscopic polypectomy
19 patients normal
Following surgery 78 patients underwent ART
No significant difference in age, type of infertility and length of infertility
Results: Polypectomy subjects had significantly higher pregnancy and LBR
than women with normal cavities (RR 2.42, p=0,06)
Women who had myomectomies larger than 2 cm. had significantly higher
pregnancy and LBR, achieving statistical significance at a myoma size of ≥3
cm (3,15 cm versus 2,5 cm p=0,05)
Spontaneus abortion rates among first pregnancies after myomectomy,
polypectomy or normal cases were similar
Both hysteroscopic polypectomy and hysteroscopic myomectomy appear to
enhance fertility.
Conclusion
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Hysteroscopy is the gold standard in infertile
patients for determining uterine cavity and
should be performed especially in women with
≥2 unsuccessful IVF cycles.
Repeat hysteroscopic evaluation in cases of
recurrent IVF-ET failure is an important
adjunctive method for further evaluating and
possibly optimizing the IVF-ET procedure.