1. Endometriosis is a chronic disease where endometrial tissue grows outside the uterus, causing pain and infertility. While surgery can help improve fertility for mild or minimal disease, evidence is lacking on its effectiveness for moderate or severe disease including deep infiltrating endometriosis. 2. Laparoscopic excision of endometriosis lesions is preferred to ablation techniques like laser or electrocoagulation, especially for deep infiltrating endometriosis where pain is an issue. Cystectomy for endometriomas over 4cm improves fertility more than drainage and coagulation. 3. IVF is recommended as first-line treatment for more severe endometriosis, advanced maternal age, or

1. Dr Kokila Das
Fertility Consultant & Trainer
Keya FERTILITY & Embryoedu
Bhubaneswar, India
Member , Neoindia Fertility Society (NIFS)
Member , ISAR , ESHRE,ISMAAR

3. Endometriosis and fertility
How and when to treat…

4. Introduction
• Endometriosis is an enigmatic disease that could start at birth.
• yet- unknown origin and pathogenesis
• Pathogenesis is supported by different theories.
• Accumulating facts relate it to a multigenic disorder.
• Incidence : 20-25% of reproductive age group
• Three main variants: superficial peritoneal disease,
deep infiltrating endometriosis
ovarian endometriomas

5. Introduction
• Endometriosis is defined as the presence of endometrial-like tissue
(glands or stroma) outside the uterus, which induces a chronic
inflammatory reaction.
• Although endometriosis impairs fertility, it does not usually completely
prevent conception.
• The question of evidence based-medicine guidelines in endometriosis-
associated infertility is weak in many situations.
• Therefore, we will highlight in this issue where the challenges are.

6. Etiology
• Sampson’s Implantation theory
• Coelomic metaplasia theory- embryonic cells persist in
ectopic location
• Nyholt et al. -- endometriosis is a “heritable, hormone-
dependent gynecological disorder”.
• Recently, Brosens and Benagiano suggested that it starts
with neonatal hormonal deprivation bleeding that many
newborn girls express in a retrograde fashion. Implants
would remain until puberty.
• Immunological causes
• Inflammatory causes
• Genetic & epigenetic modulators

9. Diagnosis
• ANAMNESIA -to recall history of chronic pain & infertility
• Bimanual examination
INVESTIGATION
No definite serum marker - ?CA 125(>30u/ml)
• Ultrasound
• MRI & CT Scan
• Laparoscopy

10. Ultrasound
• TVS is most specific
• First line of imaging technique
• Cheap n non invasive
• Sensitivity and specificty
• sonolucent lakes
• Cytic spaces
• TO mass
• Endometriotic cysts

11. Endometrioma by TVS
Retrospective observational study by Italian group )
o Mean endometriomas detected 40mm
o Bilateral disease in 25.5% ,
o Posterior rectal DIE in 21.5%,
o One uterosacral ligament in 35.4%.
o 73% of the patients showed adhesion signs,
o 53% had concurrent uterine adenomyosis.
o Only 15% of the studied population presented a single
isolated endometrioma with a mobile ovary
o Sensitivity 83%,specificity: 85%, DIE : 53%-83%

12. • The International Deep Endometriosis Analysis
group proposes some basic steps that should be followed at
the time of examination: TVS
• 1.Routine evaluation of uterus and adnexa (search for
adenomyosis and presence, or absence, of endometriomas)
• 2.Evaluation of transvaginal sonographic soft markers such
as specific tenderness and ovarian mobility
• 3.Assessment of the Douglas pouch status (sliding sign)
• 4.Assessment for DIE nodules at the anterior and posterior
compartments.
• Transvaginal US is the first option for the imaging diagnosis
of ovarian endometriomas.

13. CT & MRI
• Computerized axial tomography. “Computed tomography
has no role in the routine evaluation of endometriosis
except in very few particular scenarios”
• The authors propose that the association of both
techniques improves the accuracy of preoperative
assessment of colorectal DIE.
• “MRI findings did not correlate with the surgically
determined severity of the disease”
• MRI could not be used as the first study to detect
endometriosis, laparoscopy was the procedure of choice.
Pelvic endometriosis: MR imaging.Arrivé L, Hricak H, Martin
MCRadiology. 1989 Jun; 171(3):687-92.

14. Laparoscopy
• Final recommendation: “Laparoscopy remains the gold standard
for the diagnosis of endometriosis and using any non-invasive
tests should only be undertaken in a research setting”
Nisenblat V, Prentice L, Bossuyt PMM, et al. : Combination of
different types of tests for the non-invasive diagnosis of
endometriosis. Cochrane Evidence. 2016.
• Gold standard with biopsy and histology
• Sensitivity – 97% & Specificity – 95%
• Type of lesion
• Grading of disease
• Extent of endometriosis
• Operablity
• Biopsy with histopathological examination

15. Classification
• rAFS scoring most commonly used
• Several schemes proposed
• Stage 1 to stage 4 depending on the extent ,depth and
location
• Helps in treatment
• Operablity

16. Classification
• WES consensus on the Classification of Endometriosis
XII World Congress on Endometriosis in São Paulo, Brazil, in 2014.
• Says: “until better classification systems are developed, we propose a
classification toolbox”.
• revised American Society for Reproductive Medicine (rASRM) classification,
• the Enzian classification, and the endometriosis fertility index (EFI).
World Endometriosis Society consensus on the classification of
endometriosis.Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS,
Abrao MS, Bush D, Kiesel L, Tamimi R, Sharpe-Timms KL, Rombauts L, Giudice LC,
World Endometriosis Society Sao Paulo Consortium .
Hum Reprod. 2017 Feb; 32(2):315-324.

17. Classification
• ASRM classification(1997) -- exludes DIE and useful in infertility
• Enzian classification(2013) – includes DIE
• Endometriosis fertility index by (2010)– Adamson & Pasta
CRITICISM CONTINUES …
poor correlation with disease symptoms
lack of predictive prognosis
unclear pathways of treating pelvic pain and infertility based on
them till date

20. A B C
compartment
A: rectovaginal space
vagina
B : sacrouterine
cardinal
pelvic sidewall
external uretral
compession
C : rectum
F : uterine & DIE

21. EFI : endometriosis
fertility index
1.better diagnosis for endometriosis
associated with fertility
2.Incldes lap findings, period of infertilty
,age of patient, previous pregnancy history
DRAWBACK: NO CLASSIFICATION
CORRELATES WITH THE SEVERITY OF THE
PAIN

22. Koninckx and Wattiez et
al.(DIE) proposal
• includes adenomyosis, peritoneal pocket lesions, and
subtle endometriosis plus the three traditionally
recorded lesions (peritoneal, cystic, and deep).
• It considers the size of each lesion and includes pain as
an issue.
• For them, subtle lesions and DIE (any lesion deeper
than 5 mm under the peritoneal surface) should be
classified apart.
• In regard to pain, they cite authors who link pelvic pain
with lymph node involvement in the case of DIE.
• That is, lymph compromise is a marker of more intense
pain.
classification proposal, which is not yet validated

23. Treatment consideration
• Age
• Symptoms
• Stage
• Infertility

24. Goal of the treatment
Recognize Goals:
– Pain Management
– Preservation / Restoration of Fertility
Discuss/counselling the Patient:
– Disease may be Chronic and Not Curable
– Optimal Treatment Unproven or Nonexistent

25. Gynecologists dilemma ..
• Diagnostic dilemma
• Debilitating disease
• Progressive disease
• Disease with no cure

26. Even today endometriosis remains an enigma full of mystery?
“There is much , that is still not understood and the condition
continues to arise interest and controversies”.
Robert W. Shaw
““He who knows endometriosis knows Gynaecology ”knows
Gynaecology ”
Sir William Osler

27. PAIN MANAGEMENT
• Common reason for the consultation
• Infertility patients also present with CPP
• Arrest of pain is always a priority
• Management :
NSAIDS
Oc pills
progstogens
aromatse inhibitors
Danazol
GnRh agonist & antgonist
Non hormonal : antiangigenic and immunomodulatory (research)

30. Dienogest
• Launched in 2014
• Dienogest is a synthetic oral progestogen-only hormone
preparation for the treatment of endometriosis.
• Suppresses oestradiol production and preventing the growth
of the endometrium.
Pharmacological effects
• • Excellent anti-proliferative and anti-inflammatory
• • Considerable anti-androgenic properties
• • No glucocorticoid and no anti-mineralocorticoid activity
• • No anti-estrogenic activity
• • No effect on metabolic and cardiovascular systems

31. Dienogest and fertility
• Prolonged use can cause anovulation and amenorrhea
• Resumption of periods occur within 2 months
• Minimal effects on BMD
• Can be used as long as 52 weeks
• Decreases the endometriosis associated pelvic pain
• Reduces symptoms, signs and severity
• As effective as GnRH agonists
• More safer side effects profile
• Not associated with clinically relevant androgenic A/Es
No changes in BMD No alterations in lipid, metabolic or
hematic parameters
Restores fertility post cessation (1 – 43 days)

32. • New Clinical applications
• Adenomyosis
• Extragenital endometriosis (bladder, colon etc)
• Post-operative therapy
• Pretreatment for hysteroscopy
• Long term effect after discontinuation
• Low-dose therapy (2mg/day to 1mg/day)
• Infertility treatment Pre IVF

33. • Dienogest: Cyclic administration
• • It has been seen that cyclic administration of Dienogest
may relieve the intermittent uterine bleeding,
• • Equally reduce the associated menstrual pain in patients
post surgery
Yanase T et al,
2014
• • Showed disappearance of intestinal endometriosis
• • Marked reduction in lower abdominal pain
• • Significant reduction in endometriotic cyst size
• • Disappearance of endometriotic lesions (endoscopy)

34. Newer drugs
• New oral medication
• In 2018, the U.S. Food and Drug Administration (FDA) approved the
first oral gonadotropin-releasing hormone
• (GnRH) antagonist to help women with moderate to
severe pain from endometriosis.
• Elagolix is a daily pill, It works by stopping the production of
estrogen.
• Proellx : progesterone receptor modulator
progesterone antagonist property
increases liver enzymes so FDA ? Its use.

35. • Ulipristal ( esmya)
• Clinical improvement in 56%
• Endometrial malignancies and liver damage changes seen
• FDA banned this drug in 2018
• Resveratral
• Derived from grape wine
• Apptosis of endometrial cells
• Under research

36. Impact on fertility ?
Endometriosis of all stages have negative
impact on fertility
More severe is the disease, lesser the
fecundity

37. Important facts about fertility
• 25-50% of infertile women have
endometriosis
• 30-50% of women with endometriosis are
infertile
• Infertile women are 6-8 times more likely
to have endometriosis than fertile women

38. Treatment on evidence based guidelines
Hormonal therapies
1. No need
2. For suppression of ovarian function to improve fertility
3. hormonal contraceptives:no
4. 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)

39. Indications: Surgical management of endometriosis.
• Severe incapacitating pain symptoms with significant functional
impairment
• Severe and advanced disease with significant anatomic impairment
(distortion of pelvic organs and/or endometriomas)
• Failure of expectant or medical management Noncompliance with or
intolerance to medical treatment
• Endometriosis emergencies: Rupture or torsion of endometrioma,
obstructive uropathy, or bowel obstruction
Adapted from Bedaiwy and Liu Pathophysiology, diagnosis, and surgical management
of endometriosis: A chronic disease, SRM, Vol. 8, No. 3/ August 2010.

40. Surgery
BIG TUSSLE BETWEEN LAP SURGEONS & IVF CONSULTANTS?
STAGE 1 / STAGE 2
Infertile women with Stage I/II endometriosis Evidence recommends
that clinicians should perform operative laparoscopy (excision and
adhesiolysis ) rather than performing diagnostic laparoscopy only to
increase pregnancy rates
(Nowroozi , 1987; Jacobson , 2010).

41. SURGERY
• CO2 laser vaporization of endometriosis, instead of monopolar
electrocoagulation {higher cumulative spontaneous PR }
(Chang et al., 1997).{C}
• Endometrioma
Excision of the capsule, instead of drainage and electrocoagulation of
the endometrioma wall {increase spontaneous PR}
(Hart et al., 2008).{A}

42. STAGE 3/4
• 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).
STAGE AFTER SURGERY AFTER
EXPECTANT
STAGE 3 52-68% 33%
STAGE 4 57-69% 0

43. The World Consensus for the Current
Management of Endometriosis
1.Principles of laparoscopic surgery for infertility are similar to those for other
symptoms.
2.Surgical training and expertise are the keys for the best outcomes.
3.Ovarian reserve should be considered prior to surgery.
4.There is growing evidence that surgery of endometriomas affects ovarian
reserve.
5.Pain is to be considered at the time to decide whether to proceed to surgery.

44. 6.Surgery and ART should be considered complementary strategies.
7.Laparoscopic removal of endometriosis is effective to improve fertility in
minimal and mild cases.
8.Lesion excision is preferred to thermal or laser destruction, especially in DIE
where pain is an issue.
9.There is no high-grade evidence to assess whether surgery improves
fertility in moderate and severe disease, including DIE.
10.Functional appearance of the tubes and ovaries at the end of surgery is
related to the chances of natural conception afterwards.

45. 11.Cystectomy for endometriomas larger than 4 cm in diameter, if
possible, improves fertility more than simple ablation (drainage and
coagulation).
12.Cystectomy should be performed with expertise and care,
identifying tissue planes and carrying out careful dissection and
avoiding the removal of surrounding ovarian tissue.
13.Suturing versus coagulation for hemostasis is better in order not to
affect ovarian reserve.

46. 14.Young patients should be counselled about oocyte cryopreservation
prior to ovarian surgeries.
15.Observational studies suggest good fertility results after surgery for DIE.
16.Surgery for DIE should be considered as a second-line treatment after
failed IVF.
17.Pregnancy rates after repeat surgery are low.
18.Two cycles of IVF might be more effective than second surgeries.
19.Surgery should be considered if pain is present or there are enlarging
endometriomas as well as for those with repeated IVF failure or difficult
access to such procedures.

47. 20.Postoperative medical (hormonal) therapies delay and do not
enhance pregnanc, eExcept in the case of severe endometriosis
before IVF.
21.Intrauterine insemination combined with ovarian stimulation is an
effective option provided that tubes are patent.
22.The use of gonadotrophins appears to be more effective versus
clomid.

48. 23.IVF is first-line in preference in more severe cases, advanced
female age, or reduced sperm quality.
24.Endometriosis may have a negative impact on IVF success rates.
25.It is mandatory if tubes are compromised.
26.IVF does not appear to increase the risk of recurrence of
endometriosis.

49. MOST IMPORTANT !!!!
Surgery must be complete & performed
by a qualified gynae surgeon with
experience in dealing with
endometriosis.

50. ART needed in women with Endometriosis ???
ART…. Not complementary but needed
• Objective is the baby
• Dictum is to send the patient for ART earlier
than late

51. IUI IN ENDOMETRIOSIS
Live Birth Rate is 5.6 times higher in couples with minimal to mild
endometriosis after COS with gonadotrophins and IUI as compared to couples
after expectant management .
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).

52. 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}

53. Going straight to IVF
(Polat et al, 2015)
• infertility is long lasting.
• Age ≥38 yrs
• Semen characteristics, tubal status that is incompatible with
natural conception
• bypasses the distortion of pelvic anatomy
• removes gametes from a hostile peritoneal environment.

56. 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}

57. • 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)

58. Surgery Vs Expectant management
(Keyhan et al, 2015)
• Symptom
• 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.

59. Treatment
• 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)

60. At Oocyte retrieval
“ Antibiotic prophylaxis although the risk of ovarian abscess
following follicle aspiration is low “
(Benaglia et al., 2008).

61. To conclude…

62. To conclude…
• ART improves pregnancy rates as compared with no
treatment, but
the pregnancy rates remain lower than that of endometriosis-
free women.
• Medical, surgical, and ART treatments do not need to occur
separately and many women may benefit from a combination
of
these three approaches.

63. Thank you