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Treatment of endometriosis associated
infertility
An evidence based approach
ABOUBAKR ELNASHAR
Benha university, Egypt
EB Guidelines
1. RCOG: Evidence-based Clinical, 1999
2. Endometriosis and infertility. ASRM, 2004.
3. ACOG. Endometriosis in adolescents, 2005.
4. ESHRE guideline for the diagnosis and
treatment of endometriosis, 2005.
5. Endometriosis and infertility. ASRM, 2006 .
6. Endometriosis: diagnosis and management.
SOGC, 2010
7. Fertility: Assessment and Treatment for People
with Fertility Problems. NICE, 2013.
8. ESHRE guideline: management of women
with endometriosis, 2014
ABOUBAKR ELNASHAR
OBJECTIVES
Review
ESRH: 2014 EB guideline
Literature: 2015 and 2016
Diagnosis
 Treatment
1. Hormonal
2. Nutritional supplements, complementary and
alternative treatments
3. Surgery
4. IUI and COS
5. ART
 Conclusion
ABOUBAKR ELNASHAR
ESRH 2014 EB guideline
Grade of recommendations based on
A:
Meta-analysis or multiple RCT (of high quality)
B:
Meta-analysis or multiple RCT (of moderate quality)
Single RCT, large non-RCT(s) or case control/cohort studies
(of high quality)
C
Single RCT, large non-RCT(s) or
case control/cohort studies (of moderate quality)
D
Non-analytic studies or case reports / case series (of high or
moderate quality)
GPP
Good practice point, based on experts’ opinionABOUBAKR ELNASHAR
I. DIAGNOSIS
Laparoscopy
with biopsy and histology: gold standard for diagnosis
Negative diagnostic laparoscopy: highly
accurate for excluding endometriosis
Positive laparoscopy:
less informative
of limited value when used without taking biopsies
(Wykes et al., 2004).
To obtain tissue for histology in women undergoing
surgery for
endometrioma and/or
deep infiltrating disease
{exclude rare instances of malignancy}
{GPP}
ABOUBAKR ELNASHAR
Histopathologic confirmation
necessary for the diagnosis of endometriosis
{Definition: ectopic endometrial stroma and glands}
(Berker, Seval, 2015)
ABOUBAKR ELNASHAR
II. TREATMENT
1. Hormonal therapies
No need
For suppression of ovarian function to improve
fertility
(Hughes et al., 2007).{A}
hormonal contraceptives,
Progestagens
GnRH analogues or
Danazol
to improve fertility in minimal to mild endometriosis is not
effective and should not be offered for this indication alone.
The published evidence does not comment on more severe
disease
(Hughes et al., 2007).
ABOUBAKR ELNASHAR
2. Nutritional supplements,
complementary and alternative
treatments
No evidence for a beneficial effect
(GPP)
ABOUBAKR ELNASHAR
3. Surgery
Stage I/II:
•Operative laparoscopy:
excision or
ablation of the endometriosis lesions
adhesiolysis
rather than
•Diagnostic laparoscopy only, to increase PR
(Nowroozi et al., 1987; Jacobson et al., 2010).{A}
ABOUBAKR ELNASHAR
CO2 laser vaporization of endometriosis, instead
of monopolar electrocoagulation
{higher cumulative spontaneous PR }
(Chang et al., 1997).{C}
ABOUBAKR ELNASHAR
Endometrioma
Excision of the capsule, instead of drainage and
electrocoagulation of the endometrioma wall
{increase spontaneous PR}
(Hart et al., 2008).{A}
Counseling:
Risks of reduced ovarian function after surgery
and the possible loss of the ovary.
The decision to proceed with surgery should be
considered carefully if the woman has had previous
ovarian surgery.
{GPP}
ABOUBAKR ELNASHAR
Stage III/IV
Operative laparoscopy, instead of expectant
management: increase spontaneous PR
(Nezhat et al., 1989; Vercellini et al.,2006). {B}
Crude spontaneous pregnancy rates of
(Olive et al., 1985; Nezhat et al., 1989; Vercellini et al., 2006).
After expectant
management
After operative
laparoscopy
Stage
33%52-68%III
0%57-69%IV
ABOUBAKR ELNASHAR
Operative Laparoscopy
(Jozwiak et al, 2015)
an efficient method
most effective particularly at stage III.
The period for expectant management after a
surgical procedure should last 6 months.
ABOUBAKR ELNASHAR
Hormonal treatment
Before surgery to improve spontaneous PR:
No
{evidence is lacking}
(GPP)
For pain
Yes
(GPP)
After surgery to improve spontaneous PR
No
(Furness et al., 2004).{A}
ABOUBAKR ELNASHAR
4. IUI WITH COS
instead of expectant management
In Stage I/II
{increases LBR}
(Tummon et al., 1997).{C}
In Stage I/II within 6 months after surgical TT
{PR are similar to those achieved in unexplained
infertility }
(Werbrouck et al., 2006). {C}
ABOUBAKR ELNASHAR
5. ART
Indications
tubal function is compromised
male factor infertility
other treatments have failed.
{GPP}
after surgery
{cumulative endometriosis recurrence rates are not
increased after COS for IVF/ICSI}
(D’Hooghe et al., 2006; Benaglia et al., 2010;Coccia et al., 2010;
Benaglia et al., 2011). {C}
ABOUBAKR ELNASHAR
Going straight to IVF.
(Polat et al, 2015)
Age ≥38 y
infertility is long lasting.
Semen characteristics
tubal status that is incompatible with natural conception
IVF
bypasses the distortion of pelvic anatomy
removes gametes from a hostile peritoneal
environment.
ABOUBAKR ELNASHAR
Surgery before ART
In Stage I/II
laparoscopy for complete removal of endometriosis
to improve LBR, although the benefit is not well
established
(Opoien et al., 2011). {C}
ABOUBAKR ELNASHAR
In I/II
surgical excision or ablation of endometriosis is
recommended as first line with doubling PR
(Rizk et al, 2015)
In patients who failed to conceive spontaneously
after surgery: ART is more effective than repeat
surgery.
ABOUBAKR ELNASHAR
Surgical resection of nonovarian disease has not
been consistently shown to improve outcomes with
the possible exception of resection of deeply invasive
disease, although the data is limited.
(Surrey, 2015)
ABOUBAKR ELNASHAR
Endometrioma
Counsel women regarding the risks of reduced
ovarian function after surgery and the possible loss
of the ovary.
{A}
The decision to proceed with surgery should be
considered carefully if the woman has had previous
ovarian surgery.
Cystectomy to
improve endometriosis-associated pain or
accessibility of follicles.
{GPP}
Cystectomy for endometrioma larger than 3 cm:
no evidence for improvement PR
(Donnez et al., 2001; Hart et al., 2008; Benschop et al.,2010).{A}
ABOUBAKR ELNASHAR
Endometriomas > 4 cm should be removed
(Rizk et al, 2015)
Precycle resection of endometriomas:
does not have benefit
should only be performed for gynecologic
indications.
deleterious impact on ovarian reserve and
response.
(Surrey, 2015)
ABOUBAKR ELNASHAR
Although endometriomas can be detrimental to
the ovarian reserve, surgical therapy may further
lower a woman's ovarian reserve.
(Keyhan et al, 2015)
Presence of an endometrioma does not appear
to adversely affect IVF outcomes
Surgical excision of endometriomas does not
improve IVF outcomes.
(Kaponis et al, 2015; Keyhan et al, 2015)
ABOUBAKR ELNASHAR
o Surgery or expectant management.
(Keyhan et al, 2015)
Symptoms
age
ovarian reserve
size and laterality of the cyst
prior surgical treatment
level of suspicion for malignancy.
Proceeding directly to in IVF
≥38
diminished ovarian reserve
bilateral endometriomas
 prior surgical treatment.
ABOUBAKR ELNASHAR
Indications for Resection of a Suspected
Endometrioma prior to IVF
(Surrey et al, 2015)
(i) Rapid growth,
(ii) Suspicious features noted on ultrasound,
(iii) Painful symptoms that can be attributed to the
mass
(iv) Potential for rupture in pregnancy,
(v) Inability to access follicles in normal ovarian
tissue.
ABOUBAKR ELNASHAR
Deep endometriosis
The effectiveness of surgical excision is
not well established with regard to reproductive
outcome
(Bianchi et al.,2009; Papaleo et al., 2011).{C}
laparoscopic excision of deep endometriosis
enhances PR, by both spontaneous conception and
ART.
(Surrey, 2015 ; Centeni et al, 2016)
ABOUBAKR ELNASHAR
The therapeutic decision should be based on
clinical history
instrumental findings
pain symptoms
risks of pregnancy complications
woman's wishes.
(Somigliana et al, 2015)
ABOUBAKR ELNASHAR
GnRHa for a period of 3–6 months prior to
treatment with ART: improve PR
(Sallam et al., 2006). {B}
A benefit (which did not reach clinical significance)
only when fresh and cryopreserved embryo
transfers were combined.
(Houwen et al, 2014)
Significant benefit was noted only among patients
stages III and IV
(Rickes et al, 2002)
ABOUBAKR ELNASHAR
At Oocyte retriveal
Antibiotic prophylaxis
although the risk of ovarian abscess following
follicle aspiration is low
(Benaglia et al., 2008).{D}
ABOUBAKR ELNASHAR
Conclusion
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
1.Aboubakr
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Treatment of endometriosis associated infertility An evidence based approach

  • 1. Treatment of endometriosis associated infertility An evidence based approach ABOUBAKR ELNASHAR Benha university, Egypt
  • 2. EB Guidelines 1. RCOG: Evidence-based Clinical, 1999 2. Endometriosis and infertility. ASRM, 2004. 3. ACOG. Endometriosis in adolescents, 2005. 4. ESHRE guideline for the diagnosis and treatment of endometriosis, 2005. 5. Endometriosis and infertility. ASRM, 2006 . 6. Endometriosis: diagnosis and management. SOGC, 2010 7. Fertility: Assessment and Treatment for People with Fertility Problems. NICE, 2013. 8. ESHRE guideline: management of women with endometriosis, 2014 ABOUBAKR ELNASHAR
  • 3. OBJECTIVES Review ESRH: 2014 EB guideline Literature: 2015 and 2016 Diagnosis  Treatment 1. Hormonal 2. Nutritional supplements, complementary and alternative treatments 3. Surgery 4. IUI and COS 5. ART  Conclusion ABOUBAKR ELNASHAR
  • 4. ESRH 2014 EB guideline Grade of recommendations based on A: Meta-analysis or multiple RCT (of high quality) B: Meta-analysis or multiple RCT (of moderate quality) Single RCT, large non-RCT(s) or case control/cohort studies (of high quality) C Single RCT, large non-RCT(s) or case control/cohort studies (of moderate quality) D Non-analytic studies or case reports / case series (of high or moderate quality) GPP Good practice point, based on experts’ opinionABOUBAKR ELNASHAR
  • 5. I. DIAGNOSIS Laparoscopy with biopsy and histology: gold standard for diagnosis Negative diagnostic laparoscopy: highly accurate for excluding endometriosis Positive laparoscopy: less informative of limited value when used without taking biopsies (Wykes et al., 2004). To obtain tissue for histology in women undergoing surgery for endometrioma and/or deep infiltrating disease {exclude rare instances of malignancy} {GPP} ABOUBAKR ELNASHAR
  • 6. Histopathologic confirmation necessary for the diagnosis of endometriosis {Definition: ectopic endometrial stroma and glands} (Berker, Seval, 2015) ABOUBAKR ELNASHAR
  • 7. II. TREATMENT 1. Hormonal therapies No need For suppression of ovarian function to improve fertility (Hughes et al., 2007).{A} hormonal contraceptives, Progestagens GnRH analogues or Danazol to improve fertility in minimal to mild endometriosis is not effective and should not be offered for this indication alone. The published evidence does not comment on more severe disease (Hughes et al., 2007). ABOUBAKR ELNASHAR
  • 8. 2. Nutritional supplements, complementary and alternative treatments No evidence for a beneficial effect (GPP) ABOUBAKR ELNASHAR
  • 9. 3. Surgery Stage I/II: •Operative laparoscopy: excision or ablation of the endometriosis lesions adhesiolysis rather than •Diagnostic laparoscopy only, to increase PR (Nowroozi et al., 1987; Jacobson et al., 2010).{A} ABOUBAKR ELNASHAR
  • 10. CO2 laser vaporization of endometriosis, instead of monopolar electrocoagulation {higher cumulative spontaneous PR } (Chang et al., 1997).{C} ABOUBAKR ELNASHAR
  • 11. Endometrioma Excision of the capsule, instead of drainage and electrocoagulation of the endometrioma wall {increase spontaneous PR} (Hart et al., 2008).{A} Counseling: Risks of reduced ovarian function after surgery and the possible loss of the ovary. The decision to proceed with surgery should be considered carefully if the woman has had previous ovarian surgery. {GPP} ABOUBAKR ELNASHAR
  • 12. Stage III/IV Operative laparoscopy, instead of expectant management: increase spontaneous PR (Nezhat et al., 1989; Vercellini et al.,2006). {B} Crude spontaneous pregnancy rates of (Olive et al., 1985; Nezhat et al., 1989; Vercellini et al., 2006). After expectant management After operative laparoscopy Stage 33%52-68%III 0%57-69%IV ABOUBAKR ELNASHAR
  • 13. Operative Laparoscopy (Jozwiak et al, 2015) an efficient method most effective particularly at stage III. The period for expectant management after a surgical procedure should last 6 months. ABOUBAKR ELNASHAR
  • 14. Hormonal treatment Before surgery to improve spontaneous PR: No {evidence is lacking} (GPP) For pain Yes (GPP) After surgery to improve spontaneous PR No (Furness et al., 2004).{A} ABOUBAKR ELNASHAR
  • 15. 4. IUI WITH COS instead of expectant management In Stage I/II {increases LBR} (Tummon et al., 1997).{C} In Stage I/II within 6 months after surgical TT {PR are similar to those achieved in unexplained infertility } (Werbrouck et al., 2006). {C} ABOUBAKR ELNASHAR
  • 16. 5. ART Indications tubal function is compromised male factor infertility other treatments have failed. {GPP} after surgery {cumulative endometriosis recurrence rates are not increased after COS for IVF/ICSI} (D’Hooghe et al., 2006; Benaglia et al., 2010;Coccia et al., 2010; Benaglia et al., 2011). {C} ABOUBAKR ELNASHAR
  • 17. Going straight to IVF. (Polat et al, 2015) Age ≥38 y infertility is long lasting. Semen characteristics tubal status that is incompatible with natural conception IVF bypasses the distortion of pelvic anatomy removes gametes from a hostile peritoneal environment. ABOUBAKR ELNASHAR
  • 18. Surgery before ART In Stage I/II laparoscopy for complete removal of endometriosis to improve LBR, although the benefit is not well established (Opoien et al., 2011). {C} ABOUBAKR ELNASHAR
  • 19. In I/II surgical excision or ablation of endometriosis is recommended as first line with doubling PR (Rizk et al, 2015) In patients who failed to conceive spontaneously after surgery: ART is more effective than repeat surgery. ABOUBAKR ELNASHAR
  • 20. Surgical resection of nonovarian disease has not been consistently shown to improve outcomes with the possible exception of resection of deeply invasive disease, although the data is limited. (Surrey, 2015) ABOUBAKR ELNASHAR
  • 21. Endometrioma Counsel women regarding the risks of reduced ovarian function after surgery and the possible loss of the ovary. {A} The decision to proceed with surgery should be considered carefully if the woman has had previous ovarian surgery. Cystectomy to improve endometriosis-associated pain or accessibility of follicles. {GPP} Cystectomy for endometrioma larger than 3 cm: no evidence for improvement PR (Donnez et al., 2001; Hart et al., 2008; Benschop et al.,2010).{A} ABOUBAKR ELNASHAR
  • 22. Endometriomas > 4 cm should be removed (Rizk et al, 2015) Precycle resection of endometriomas: does not have benefit should only be performed for gynecologic indications. deleterious impact on ovarian reserve and response. (Surrey, 2015) ABOUBAKR ELNASHAR
  • 23. Although endometriomas can be detrimental to the ovarian reserve, surgical therapy may further lower a woman's ovarian reserve. (Keyhan et al, 2015) Presence of an endometrioma does not appear to adversely affect IVF outcomes Surgical excision of endometriomas does not improve IVF outcomes. (Kaponis et al, 2015; Keyhan et al, 2015) ABOUBAKR ELNASHAR
  • 24. o Surgery or expectant management. (Keyhan et al, 2015) Symptoms age ovarian reserve size and laterality of the cyst prior surgical treatment level of suspicion for malignancy. Proceeding directly to in IVF ≥38 diminished ovarian reserve bilateral endometriomas  prior surgical treatment. ABOUBAKR ELNASHAR
  • 25. Indications for Resection of a Suspected Endometrioma prior to IVF (Surrey et al, 2015) (i) Rapid growth, (ii) Suspicious features noted on ultrasound, (iii) Painful symptoms that can be attributed to the mass (iv) Potential for rupture in pregnancy, (v) Inability to access follicles in normal ovarian tissue. ABOUBAKR ELNASHAR
  • 26. Deep endometriosis The effectiveness of surgical excision is not well established with regard to reproductive outcome (Bianchi et al.,2009; Papaleo et al., 2011).{C} laparoscopic excision of deep endometriosis enhances PR, by both spontaneous conception and ART. (Surrey, 2015 ; Centeni et al, 2016) ABOUBAKR ELNASHAR
  • 27. The therapeutic decision should be based on clinical history instrumental findings pain symptoms risks of pregnancy complications woman's wishes. (Somigliana et al, 2015) ABOUBAKR ELNASHAR
  • 28. GnRHa for a period of 3–6 months prior to treatment with ART: improve PR (Sallam et al., 2006). {B} A benefit (which did not reach clinical significance) only when fresh and cryopreserved embryo transfers were combined. (Houwen et al, 2014) Significant benefit was noted only among patients stages III and IV (Rickes et al, 2002) ABOUBAKR ELNASHAR
  • 29. At Oocyte retriveal Antibiotic prophylaxis although the risk of ovarian abscess following follicle aspiration is low (Benaglia et al., 2008).{D} ABOUBAKR ELNASHAR
  • 32. ABOUBAKR ELNASHAR 1.Aboubakr elnashar lectures: 270 lectures 3702 members 2. Slide share 270 lectures 1271 followers