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Endometriosis & Adenomyosis
Infertility Treatment
Levent M. SENTURK, M.D.,
Professor in Ob&Gyn
Istanbul University Cerrahpasa School of Medicine
Dept. of Ob&Gyn, Division of Reproductive Endocrinology, IVF Unit
Endometriosis-associated infertility: a
decade’s trend study of women from
the Estrie Region of Quebec, Canada
N: 6845
INF
ENDO
EAI
KRYSTEL PARIS & AZIZ ARIS, 2010
Effects of endometriosis on human reproduction
Dominique de Ziegler, 2010
Pathophysiology of Pain and Infertility Associated
with Endometriosis
Linda C. Giudice, 2010
Eijkemans et al., 2008
Cumulative conception rates with untreated
endometriosis related to disease grading,
compared with normal conception rate
N
Minor
Moderate Severe
Kevin D. Jones, 2002
Fertility in women with minimal endometriosis compared
with normal women was assessed by means of a
donor insemination program in unstimulated cycles
N: 51
N: 24
Roberto Matorras 2010
Endometriosis
COH + 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 COH+IUI for moderate-severe
endometriosis.
• COH+IUI should be limited to 3-4 cycles
ESHRE Guidelines, Recommedation grade A ,
evidence level 1b
2010
To develop a clinical tool that predicts pregnancy
rates (PRs) in patients with surgically documented
endometriosis who attempt non-IVF conception.
Decreased anti-Mullerian hormone and
altered ovarian follicular cohort in infertile
patients with minimal/mild endometriosis
N:17
EE
p:0.004
N:17
CC
Nadiane Albuquerque Lemos, 2009
Anti mullerian hormone serum levels in
women with endometriosis:
A case–control 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 (2.75+2.0 ng/ml vs.
3.46+2.30 ng/ml, p 0.001).
• In women with mild endometriosis (rAFS I-II), the mean
AMH level was almost equal to the control group
(3.28+1.93 ng/ml vs. 3.44+2.06 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 (2.38+1.83 ng/ml vs.
3.58+2.46 ng/ml; p 0.0001).
OMAR SHEBL, 2009
A comparison of histopathologic findings of ovarian
tissue inadvertently excised with endometrioma and
other kinds of benign ovarian cyst in patients
undergoing 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
The impact of electrocoagulation on ovarian
reserve after laparoscopic excision of ovarian
cysts: a prospective clinical study of 191 patients
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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 12month follow-up evaluations and in unilateral-cyst patients at the 1month 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
Analysis of risk factors for the removal
of 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
IVF-ICSI outcome in women operated
for bilateral endometriomas
• 68 cases (bilat. cystectomy) - 136 controls
• the number of follicles (p=0.006), oocytes
retrieved (p=0.024) and embryos obtained
(p=0.024) were significantly lower.
• The clinical pregnancy rate per started cycle in
cases and controls was 7% and 19% (p=0.037)
• CONCLUSIONS: IVF outcome is significantly
impaired in women operated on for bilateral
ovarian endometriomas.
Edgardo Somigliana1, 2008
P¨ aivi H¨arkki, 2010
Effects of (unilateral) ovarian endometrioma
on the number of oocytes retrieved for IVF
81 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
Spontaneous Pregnancy After 1 surgery
Spontaneous Pregnancy After 2 surgery
236/577
28/124
(41%)
(23%)
Sp. Pregnancy following L/T
Sp. Pregnancy following L/S
12 – 47% (27%)
22 – 42% (25%)
Results of studies comparing IVF-ET with
second-line surgery in infertile women with
recurrent moderate to severe endometriosis
P. Vercellini , 2009
Endometrioma and IVF
GPP
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.
30 June 2007
http://guidelines.endometriosis.org
Endometriosis-associated infertility: surgery and
IVF, a comprehensive therapeutic approach
825 patients, 2001-2008,
observational study
Pedro N Barri, 2010
Does Controlled Ovarian Hyperstimulation
in Women with a History of Endometriosis
Influence Recurrence Rate?
• Retrospective cohort study of 592 patients submitted to
laparoscopy for endometriosis, 177 with infertility-related
endometriosis who underwent a periodic ultrasound followup after laparoscopy were selected.
• Women who started ART after laparoscopy (n=90) were
compared with the control group, who did not undergo ART
(28.6% vs. 37.9%, p=0.471)
(n=87).
• Recurrence of endometriosis was defined as the presence
of endometriotic lesions observed through TV-US.
• During a long-term TV-US follow-up (1–15 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, p=0.471)
Maria Elisabetta Coccia, 2010
SART-2005
SART-2006
SART-2007
Endometriosis-GnRHa
• Pain
• After operation for the prevention
• Before IVF
• Empirical
Pathophysiology of Pain and Infertility Associated
with Endometriosis
Linda C. Giudice, 2010
Three randomised controlled trials (with 165 women) were
included
GnRH agonist vs no agonist before IVF
(Clinical pregnancy rate per woman)
Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006
N=165
Live birth rate
Clinical pregnancy rate
OR 9.19, (95% CI 1.08 to 78.22)
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.
Use of oral contraceptives in women with
endometriosis 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
Endometrioma and oocyte retrieval–induced
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, 0.0–
1.7%).
• 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
Preterm birth, ovarian endometriomata, and
assisted reproduction technologies
Shavi Fernando, 2009
Adenomyosis
• A benign disorder,
characterized with
the presence of
glandular and
stromal endometrial
tissue in
myometrium
Adenomyosis
Myometrial location
• Diffuse
• Focal
• Adenomyotic cyst
• Adenomyoma
Adenomyosis
Epidemiology
• ≈ %20 of women.
(J Minim Invasive Gynecol 2009; 16:622–625)
• More frequently seen in women with
endometriosis.
• More frequently seen in women with low BMI.
(Hum Reprod 2010; 25:1325–1334)
Adenomyosis
Symptoms
• Dysmenorrhea (66% vs 42%)
• Chronic pelvic pain (53% vs 21+)
•Menorrhagia
•Infertility
Fertil Steril 2010;94:1223–8
Adenomyosis
Diagnosis - US
• Globular uterus
• Asymmetric thickening of anterior and/or posterior
uterus wall
• Difficulty in distunguishing the endometrialmyometrial junction
• Focal or diffuse heterogenous myometrial
echogenity
• Myometrial cyst
• Increased vascularity
3D TV-US: Normal Uterus
•Minimum JZ
•Maximum JZ
•Total myometrial
thickness
3D TV-US: Adenomyosis
3D TV-US: Adenomyosis
Adenomyosis
Diagnosis - MRI
T2
T1
Adenomyosis
Diagnosis - MRI
Adenomyoma
Diagnosis - MRI
• 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.
Algorithm for management of infertility
associated with endometriosis
Dominique de Ziegler, 2010
Endometriosis - Infertility
Q&A
• 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
Endometriosis - Infertility
Q&A
• Does endometriosis decrease IVF success?
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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
Endometriosis - Infertility
Q&A
• GnRHa use before IVF in endometriosis?
•
May be helpful, more studies are needed
• Management of recurrent endometrioma (IVF vs
surgery)?
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IVF
• Which protocol?
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No difference
• Adenomyosis – ART?
•
Had no adverse effect on IVF/ICSI outcomes