Endometriosis

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Endometriosis AdenomyosisInfertility Treatment

• Levent M. SENTURK, M.D.,
• Professor in ObGyn
• Istanbul University Cerrahpasa School of Medicine
• Dept. of ObGyn, Division of Reproductive
  Endocrinology, IVF Unit

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BRANDI S. MCLEOD, and MATTHEW G. RETZLOFF, 2010
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Prevalence of endometriosis according to stage
of disease in infertile and fertile women
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Deep Endometriosis Symptoms
Pandis GK, 2010
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Diagnosis of Endometriosis

• History (The most important)
• Symptoms
• Physical Examination (not much help)
• Serum Markers (Lacks sensitivity)
• Ultrasound (of little value except endometrioma)
• Magnetic Resonance Imaging (MRI) (a good guess!)
• Other Imaging Modalities
• immunoscintigraphy and positron emission
  tomography
• Transvaginal Hydrolaparoscopy
• Laparoscopic Visualization of the Pelvis (The
  gold standard)
• Biopsy Preferable Over Visual Inspection
• Novel Diagnostic Test

Rule out other Causes of Symptoms (The next most
important)
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Endometriosis-associated infertility a decades
trend study of women from the Estrie Region of
Quebec, Canada
N 6845
INF
ENDO
EAI
KRYSTEL PARIS AZIZ ARIS, 2010
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Effects of endometriosis on human reproduction
Dominique de Ziegler, 2010
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Pathophysiology of Pain and Infertility
Associated with Endometriosis
Linda C. Giudice, 2010
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Eijkemans et al., 2008
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Collins JA , 1995
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Cumulative conception rates with untreated
endometriosis related to disease grading,
compared with normal conception rate
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Minor
Moderate Severe
Kevin D. Jones, 2002
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Fertility in women with minimal endometriosis
comparedwith normal women was assessed by means
of a donor insemination program in unstimulated
cycles
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N 24
Roberto Matorras 2010
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Success in intrauterine insemination the role of
etiology

• A total of 1,171 cycles among 532 infertile
  couples were retrospectively studied and the
  impact of different prognostic factors on
  pregnancy rate in five different etiology
  subgroups was analyzed.
• Results. The pregnancy rate/cycle was highest
  (19.2) among women with anovulatory infertility
  and lowest (11.9) in endometriosis based
  infertility.

Katja Ahinko-Hakamaa 2007
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EndometriosisCOH IUI

• Treatment with intra-uterine insemination (IUI)
  improves fertility in minimal-mild endometriosis
  IUI with ovarian stimulation is effective but the
  role of unstimulated IUI is uncertain (Tummon et
  al., 1997).
• Evidence A, Level 1b 
• No RCTs exist for COHIUI for moderate-severe
  endometriosis.
• ?COHIUI should be limited to 3-4 cycles
• ESHRE Guidelines, Recommedation grade A ,
  evidence level 1b

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2010
To develop a clinical tool that predicts
pregnancy rates (PRs) in patients with surgically
documented endometriosis who attempt non-IVF
conception.
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Decreased anti-Mullerian hormone and altered
ovarian follicular cohort in infertile patients
with minimal/mild endometriosis
p0.004
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N17
EE
CC
Nadiane Albuquerque Lemos, 2009
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Anti mullerian hormone serum levels in women with
endometriosisA casecontrol study

• 909 patients undergoing in vitro fertilisation/
  intracytoplasmic sperm injection (IVF/ICSI)
  treatment or consulting our specific
  endometriosis unit.
• Mean AMH serum level was significantly lower in
  the study than in the control group (2.752.0
  ng/ml vs. 3.462.30 ng/ml, p 0.001).
• In women with mild endometriosis (rAFS I-II), the
  mean AMH level was almost equal to the control
  group (3.281.93 ng/ml vs. 3.442.06 ng/ml p
  0.61).
• A significant difference in mean AMH serum level
  was found between women with severe endometriosis
  (rAFS III-IV) and the control group (2.381.83
  ng/ml vs. 3.582.46 ng/ml p 0.0001).

OMAR SHEBL, 2009
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A comparison of histopathologic findings of
ovariantissue inadvertently excised with
endometrioma andother kinds of benign ovarian
cyst in patientsundergoing laparoscopy versus
laparotomy
The surgical approach had no statistically
significant impact on conservation of ovarian
reserves. The nature of the ovarian cyst played a
greater role in the quality and quantity of the
excised ovarian tissue
Saeed Alborzi, 2009
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Excision of endometriotic cyst wall may cause
lossof functional ovarian tissue
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Umut Dilek, 2006
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The impact of electrocoagulation on ovarian
reserve after laparoscopic excision of ovarian
cysts a prospective clinical study of 191
patients

• 191 patients with benign ovarian cysts undergoing
  ovarian cystectomy.
• When comparing the bipolar group and ultrasonic
  scalpel group (L/S) with the suture (L/T) group,
  a statistically significant increase of the mean
  FSH value was found in bilateral-cyst patients at
  1-, 3-, 6-, and 12-month follow-up evaluations
  and in unilateral-cyst patients at the 1-month
  follow-up evaluation.
• Statistically significant decreases of basal
  antral follicle number and mean ovarian diameter
  were found during the 3-, 6-, 12-month follow-up
  evaluations as well as statistically significant
  decreases of peak systolic velocity at all of the
  follow-up evaluations.
• Conclusion(s) Bi-polar electrocoagulation after
  laparoscopic excision of ovarian cysts is
  associated with a statistically significant
  reduction in ovarian reserve, which is partly a
  consequence of the damage to the ovarian vascular
  system.

Chang-Zhong Li, 2009
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Analysis of risk factors for the removalof
normal ovarian tissue during laparoscopic
cystectomy for ovarian endometriosis

• A total of 121 patients who had histologically
  confirmed ovarian endometriosis and 56 control
  patients who had other histologically confirmed
  benign cysts were included
• Normal ovarian tissue adjacent to the cyst wall
  was detected in 71 patients (58.7) with
  endometriosis, whereas normal ovarian tissue was
  removed from only three patients (5.4) with
  other benign cysts.
• A significant factor that was independently
  associated with the removal of normal ovarian
  tissue with ovarian endometriosis was
  pre-operative medical treatment

Sachiko Matsuzak,2009
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IVF-ICSI outcome in women operatedfor bilateral
endometriomas

• 68 cases (bilat. cystectomy) - 136 controls
• the number of follicles (p0.006), oocytes
  retrieved (p0.024) and embryos obtained
  (p0.024) were significantly lower.
• The clinical pregnancy rate per started cycle in
  cases and controls was 7 and 19 (p0.037)
• CONCLUSIONS IVF outcome is significantly
  impaired in women operated on for bilateral
  ovarian endometriomas.

Edgardo Somigliana1, 2008
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NS
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P aivi Harkki, 2010
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Effects of (unilateral) ovarian endometrioma on
the number of oocytes retrieved for IVF81 women
with unilateral endometrioma who underwent their
first IVF cycle
Benny Almog, 2010
Conclusion(s) The presence of ovarian
endometrioma in a controlled ovarian
hyperstimulation cycle for IVF treatment is not
associated with a reduced number of oocytes
retrieved from the affected ovary
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Spontaneous Pregnancy After 1? surgery
236/577 (41) Spontaneous Pregnancy After 2?
surgery 28/124 (23)
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Sp. Pregnancy following L/T 12 47 (27) Sp.
Pregnancy following L/S 22 42 (25)
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Results of studies comparing IVF-ET with
second-line surgery in infertile women with
recurrent moderate to severe endometriosis
P. Vercellini , 2009
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Endometrioma and IVF
Laparoscopic ovarian cystectomy is recommended if an ovarian endometrioma 4 cm in diameter, is present to confirm the diagnosis histologically reduce the risk of infection improve access to follicles and possibly improve ovarian response. The woman should be counselled regarding the risks of reduced ovarian function after surgery and the loss of the ovary. The decision should be reconsidered if she has had previous ovarian surgery.
GPP
http//guidelines.endometriosis.org
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Endometriosis-associated infertility surgery
andIVF, a comprehensive therapeutic approach
825 patients, 2001-2008, observational study
Pedro N Barri, 2010
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Does Controlled Ovarian Hyperstimulationin Women
with a History of EndometriosisInfluence
Recurrence Rate?

• Retrospective cohort study of 592 patients
  submitted to laparoscopy for endometriosis, 177
  with infertility-related endometriosis who
  underwent a periodic ultrasound follow-up after
  laparoscopy were selected.
• Women who started ART after laparoscopy (n90)
  were compared with the control group, who did not
  undergo ART (n87).
• Recurrence of endometriosis was defined as the
  presence of endometriotic lesions observed
  through TV-US.
• During a long-term TV-US follow-up (115 years),
  40 (22.6) recurrences were observed.
• Patients submitted to ART showed a cumulative
  recurrence rate similar to that of the control
  group (28.6 and 37.9 respectively, p0.471)

(28.6 vs. 37.9, p0.471)
Maria Elisabetta Coccia, 2010
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SART-2005
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SART-2006
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SART-2007
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Endometriosis-GnRHa

• Pain
• After operation for the prevention
• Before IVF
• Empirical

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Pathophysiology of Pain and Infertility
Associated with Endometriosis
Linda C. Giudice, 2010
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Three randomised controlled trials (with 165
women) were included
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GnRH agonist vs no agonist before IVF(Clinical
pregnancy rate per woman)
Sallam et al, Cochrane Database Syst Rev
25(1)CD004635, 2006
N165
Live birth rate OR 9.19, (95 CI 1.08 to
78.22) Clinical pregnancy rate OR 4.28, (95 CI
2.00 to 9.15) CONCLUSIONS The administration of
GnRH agonists for a period of three to six months
prior to IVF or ICSI in women with endometriosis
increases the odds of clinical pregnancy by
fourfold. Data regarding adverse effects of this
therapy on the mother or fetus are not available
at present.
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Use of oral contraceptives in women
withendometriosis before assisted reproduction
treatment improves outcomes

• In women with endometriosis, including those with
  endometriomas, 6 to 8 weeks of continuous use of
  oral contraception (OC) before assisted
  reproduction treatment (ART) maintains ART
  outcomes comparable with the outcomes of
  age-matched controls without endometriosis.
• In contrast, ART outcomes are markedly
  compromised in endometriosis patients who are not
  pretreated with OC.
• Ovarian responsiveness to stimulation was not
  altered by 6 to 8 weeks use of pre-ART OC,
  including in poor responders with endometriomas
• Our data indicate that 6 to 8 weeks of continuous
  OC use before ART not only improves outcomes in
  endometriosis but possibly is as effective as 3
  months of GnRH-agonist treatment before ART

Dominique de Ziegler, 2010
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Deep Endometriosis Symptoms
Pandis GK, 2010
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Deep endometriosis Excisional surgeryPregnancy
rates
Vercellini et al., Hum Reprod (2009)
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Fertility and clinical outcome after bowel
resection in infertile women with endometriosis

• 62 infertile women who underwent laparoscopic
  excision of endometriosis with segmental bowel
  resection performed for severe intestinal
  symptoms.
• Among women younger than 30 years trying to
  conceive spontaneously, the cumulative pregnancy
  rate was 58 and the cumulative pregnancy rate
  was 45 in those aged 3034 years.

Anna Stepniewska, 2010
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Results of first in vitro fertilization cyclein
women with colorectal endometriosiscompared with
those with tubal or malefactor infertility
Emmanuelle Mathieu dArgent, 2010
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Deep endometrisois Complications
Vercellini et al., Hum Reprod (2009)
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Endometrioma ve oosit toplanmasi

• Hacim artmasi
• Enfeksiyon, abse
• Akut abdomen
• Toksik etki
• Malignite

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Endometrioma and oocyte retrievalinduced pelvic
abscess a clinical concern or an exceptional
complication

• The authors evaluated the risk of developing a
  pelvic abscess in a series of 214 in vitro
  fertilization cycles that were performed in women
  with endometriomas. This complication was never
  recorded, indicating that its risk is very low
  (0.0 95 confidence interval, 0.01.7).
• Literature
• nine cases were described. Prophylactic
  antibiotics have been administered in at least
  eight cases. The endometrioma was punctured at
  the time of oocyte retrieval in at least six
  cases.

Laura Benaglia, 2008
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Preterm birth, ovarian endometriomata, and
assisted reproduction technologies
Shavi Fernando, 2009
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Adenomyosis

• A benign disorder, characterized with the
  presence of glandular and stromal endometrial
  tissue in myometrium

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Adenomyosis

• Myometrial location
• Diffuse
• Focal
• Adenomyotic cyst
• Adenomyoma

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AdenomyosisEpidemiology

• 20 of women.
• (J Minim Invasive Gynecol 2009 16622625)
• More frequently seen in women with endometriosis.
• More frequently seen in women with low BMI.
• (Hum Reprod 2010 2513251334)

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AdenomyosisSymptoms

• Dysmenorrhea (66 vs 42)
• Chronic pelvic pain (53 vs 21)

• Menorrhagia
• Infertility

Fertil Steril 20109412238
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AdenomyosisDiagnosis - US

• Globular uterus
• Asymmetric thickening of anterior and/or
  posterior uterus wall
• Difficulty in distunguishing the
  endometrial-myometrial junction
• Focal or diffuse heterogenous myometrial
  echogenity
• Myometrial cyst
• Increased vascularity

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3D TV-US Normal Uterus

• Minimum JZ
• Maximum JZ
• Total myometrial thickness

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3D TV-US Adenomyosis
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3D TV-US Adenomyosis
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AdenomyosisDiagnosis - MRI
T2
T1
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AdenomyosisDiagnosis - MRI
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AdenomyomaDiagnosis - MRI
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• Retrospective study in 74 infertile patients with
  surgically proven endometriosis
• The diagnosis of adenomyosis was based on
  transvaginal ultrasound criteria
• All patients were pretreated with long-term (?3
  months) GnRH-agonist prior to IVF/ICSI.
• Endometriosis rASRM stages III-IV adenomyosis

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• mean dosage of FSH used was 208IU
• the mean number of oocytes retrieved was 8.73
• the mean number of embryos obtained was 3.86
• the mean number of embryos transferred was 1.6
• a mean fertilization rate of 43.6
• a mean implantation rate of 26.3
• a mean miscarriage rate of 24.3
• and a clinical pregnancy rate (?12 gw) of 31.7

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• No significant differences were found for any of
  the IVF/ICSI outcomes between women with and
  without adenomyosis.
• CONCLUSIONS Adenomyosis had no adverse effects
  on IVF/ICSI outcomes in infertile women with
  proven endometriosis who were pretreated with
  long-term GnRH-agonist.

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Algorithm for management of infertility
associated with endometriosis
Dominique de Ziegler, 2010
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Endometriosis - InfertilityQA

• Does stage I-II endometriosis cause infertility
  ?
• Yes
• Is COH IUI effective in EA infertility?
• Yes in I-II / Data is not sufficient for III-IV
• Does endometriosis decrease ovarian reserve?
• Yes
• Does deep endometriosis cause infertility?
• Yes, probably
• Does endometriosis cause pregnancy loss?
• No

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Endometriosis - InfertilityQA

• Does endometriosis decrease IVF success?
• No (???for St IV ? ovarian reserve)
• Endometrioma and infertility?
• Not related
• Surgery for endometrioma before IVF?
• Not effective (May decrease ovarian reserve)
• Does IVF treatment increase endometriosis
  recurrence rate?
• No
• Role of surgery after an unsuccessful IVF cycle
• Not effective except few cases

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Endometriosis - InfertilityQA

• GnRHa use before IVF in endometriosis?
• May be helpful, more studies are needed
• Management of recurrent endometrioma (IVF vs
  surgery)?
• IVF
• Which protocol?
• No difference
• Adenomyosis ART?
• Had no adverse effect on IVF/ICSI outcomes