This document discusses endometriosis, a condition where tissue similar to the lining of the uterus grows outside the uterus. It defines endometriosis and discusses its prevalence, theories of pathogenesis, risk factors, clinical presentation, diagnosis, and treatment approaches. The key points are: - Endometriosis is an estrogen-dependent inflammatory condition characterized by ectopic endometrial tissue outside the uterus that can cause pelvic pain and infertility. - It has a prevalence of 10% in reproductive-aged women and 50% in women with subfertility. - Theories for its pathogenesis include retrograde menstruation and genetic/immunological factors. - It commonly presents as pelvic pain and infertility

1. Endometriosis
Dr Anuj Sharma
4/6/2022 Dr Anuj Sharma

2. Endometriosis- Mysterious disease
• Wide clinical spectrum
• Disease of theories
• Benign but it is locally invasive
• Cyclic hormones stimulate growth but
continuous hormones suppress it.
4/6/2022 Dr Anuj Sharma

3. References
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4. Definition
• Complex clinical syndrome
• Characterized by an Estrogen-dependent
chronic inflammatory process
• Due to ectopic functional endometrium
(glands and stroma) outside uterine cavity
• Presented commonly as chronic pelvic pain
and infertility.
4/6/2022 Dr Anuj Sharma

5. Prevalence
• 10% of reproductive-age women
• 21-30% among women with chronic pelvic
pain
• Up to 50% in women with subfertility.
• Highest rate of clinically diagnosed
endometriosis in women aged 25 – 34 yrs
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6. Disease of theories
• Retrograde Menstruation (Sampson’s theory)
• Coelomic metaplasia (Meyer and Ivanoff)
• Lymphatic theory (Halban)
• Direct Implantation
• Vascular Theory
• Genetic and immunological factors
• Environment theory
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7. Disease of theories
• Stem Cell theory
• Mullerian Duct remnant
• Inflammation theory
• Hormonal theory
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8. Pathogenesis
• Establishment of an endometriotic implant
–Presence of ectopic endometrium
• Attachment
• Invasion
• Survival
• Growth
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9. Attachment of endometrial cells to
peritoneum
• Matrix Metallo-proteinases (MMPs) - enzymes
which degrade structural components of the
Extra-cellular Matrix.
• Tissue Inhibitors of MMPs (TIMPs)- MMPs effects
are regulated by Tissue Inhibitors of MMPs
(TIMPs)
• MMPs degrade extra-cellular matrix, facilitating
adhesion to peritoneum and subsequent invasion
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10. Adhesion of endometrial cells to
peritoneum
• Endometriotic tissue has a higher proportion
of MMPs to TIMPs
• Severity & Extent of endometriosis has been
correlated with MMP expression
• Role of Inflammatory cytokines
• Role of cell adhesion molecules (Integrins & E-
cadherin )
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11. Survival & Growth
• Failed Immuno-surveillance prevents clearance of
ectopic endometrium
– ↓ T cell mediated cytotoxicity
– ↓ T cell dependant B cell proliferation
– ↓ NK cell activity
• Angiogenesis & neo-vascularization essential for
survival & growth of ectopic endometrium
• Estrogen enhances survival & persistence of ectopic
endometrium
– Ectopic endometrium expresses a complete set of
steroidogenic genes & aromatase activity enhancing locally
produced estradiol levels
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12. Role of VEGF
• Promotes angiogenesis
• Contributes to peritoneal adhesion formation
through formation of a fibrin matrix
• Induces expression of COX-2 enzyme and
prostaglandin production which play a key role
in pain & dysmennorrhoea
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13. Patho-physiology
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14. Predisposing factors
• Menstruation
– Early menarche
– HMB
– Outflow obstructiion
– Frequent cycle
• Pregnancy
– Delayed child birth
– Nulli/low parity
– Less Breast feeding
• Familial / high socio-economical status
• Lean and thin body habitus
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15. Other risk factors
• IUGR ↑ risk for subsequent development of
endometriosis by 30%
• In utero DES exposure
• Offspring of Multi-fetal gestation
• Affection of first degree relatives (Risk ↑ 4 – 8
times)
• Concurrent Immune disorders
• Red hair
• Diet high in fats / red meats
• Alcohol / Caffeine exposure
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16. Protective factors
• Greater parity
• Longer lifetime duration of lactation
• Current & Recent OC pill users (Oxford Family Planning Association
Study)
• ↑ BMI & WHR decrease risk (Every unit ↑ in BMI decreases risk
by 12 – 14%)
• Smoking & Tobacco exposure in utero
• Exercise
• Diet high in Fruits / Vegetables
• Progesterone
– Endometriosis related to ↓ progesterone responsiveness
– Progesterone required for production of local differentiating
factors necessary for regulation of gene expression
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17. Predisposing factors
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18. Pathology
• Superficial peritoneal endometriosis
• Deep infiltrative endometriosis
• Ovarian endometrioma
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19. Superficial peritoneal endometriosis
• Small black dots ‘powder burns’
• Red flame shaped areas
• Red polypoid areas
• Yellow brown patches
• White peritoneal areas
• Circular peritoneal defects
• Sub-ovarian adhesions
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20. Deep infiltrative endometriosis
• More than 5 mm deep infiltration
• Involve rectovaginal septum ,bowel,ureter,
bladder , rectum etc..
• Causes more symptoms, related to organ
involved
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21. Ovarian endometrioma
• Pseudocysts formed by the invagination of
endometriosis within the ovarian cortex
• Cyst diameter usually < 12 cm
• Adhesions to pelvic sidewall / Broad ligament
• Surface endometriosis
• Tarry thick chocolate coloured fluid content
• Histologic pattern of endometriosis
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22. Microscopic Appearance
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23.  DNA Micro-array analysis shows difference in gene
expression profiles
 Encoding pro-inflammatory cytokines & prostaglandins
 Activation of certain oncogenic pathways
 Ras, Wnt
 Altered estrogen metabolism
 Expression of aromatase activity and deficient expression
of 17 β hydroxysteroid dehydrogenase activity leads to
increased local levels of estrogens
 ↑expression of Nerve growth factors (NGF)
resulting in abnormal sprouting of nociceptors.
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24. Differences between Eutopic & Ectopic
endometrium
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25. Features of sub-clinical peritoneal
inflammation
• ↑ peritoneal fluid volume
• ↑ peritoneal fluid WBC
• ↑ peritoneal
– Inflammatory Cytokines
– Growth factors
– Angiogenesis promoting substances
• ↑ systemic markers of inflammation
– CRP, Serum Amyloid A, IL-6, TNFα, CCR1
4/6/2022 Dr Anuj Sharma

26. Clinical presentation
• Asymptomatic
• Subfertility
• Dysmenorrhoea
• Dyspareunia
• Chronic Pelvic / Abdominal pain
• Menstrual abnormalities
• Acute abdominal pain
• GI symptoms (Pain, Nausea, Early satiety, Bloating /
distention, Altered bowel habits)
Delay in onset of symptoms to confirmation of diagnosis
varies between 3yrs (Infertile patients) to 6yrs (Chr. Pain)
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27. Quality of Life (QOL) Issues in
Endometriosis
• Pain
– Dysmenorrhoea
– Chronic abdomino-pelvic pain
– Dyspareunia
• Subfertility / Infertility
• Long term medical therapy with its related
side effects
• Repeated surgeries
• Disease recurrence
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28. Why Pain ?
• Peritoneal inflammation
• Tissue infiltration
• Presence of adhesions
– Painful traction with physiologic movement of the tissues
• Collection of shed menstrual blood in implants
• Nerve entrapment in fibrotic components
• Abnormal sprouting of nociceptors in endometriotic
lesions in response to ↑expression of Nerve growth
factors (NGF)
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29. Why Sub-fertility ?
• Hormonal & Ovulatory dysfunction
– Defective folliculogenesis
– Luteal phase insufficiency
– Luteinized unruptured follicle
– Gametotoxicity due to alterations in peritoneal
fluid
• ↑ pro-inflammatory cytokines (IL-1β, IL-6, TNFα)
• ↑ prostaglandins and other mediators of inflammation
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30. Why Sub-fertility ?
• Mechanical interference
– Adhesions disrupting
• Tubo-ovarian relationship
• Tubal motility
• Ovum pickup
• Altered Immune responses
– Presence of activated macrophages
• Increased sperm phagocytosis
• Decreased sperm motility
• Interference with fertilization
• Hostile endometrium- implantation failure
• Dyspareunia
• Spontaneous miscarriage
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31. Clinical examination
• Abd exam – tenderness, pelvic mass
• PSV
• Visible lesions vagina/cervix
• Fixed/retroverted uterus
• Nodularity / tenderness POD and US Ligament
• PR
• Tenderness and nodules POD
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32. Differential diagnosis
• Chronic PID
• Ectopic Pregnancy
• pelvic congestion syndrome
• Ovarian Ca
• Inflammatory bowel syndrome
• post operative adhesion
• Chronic appendicitis
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33. Investigations
• Blood tests
– BhCG
– TLC / DLC
– ESR
– CA-125
• Urine analysis C/S
• Cervical swab C/S
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34. Investigations
• Imaging
– TVS
• Endometrioma
• Doppler blood flow
– MRI
• Higher accuracy
• Smaller lesions
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35. Laparoscopy
• Small black dots ‘powder burns’
• Red flame shaped areas
• Red polypoid areas
• Yellow brown patches
• White peritoneal areas
• Circular peritoneal defects
• Sub-ovarian adhesions
• Infiltrative lesions
• endometrioma
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36. Laparoscopy
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37. Laparoscopy
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40. Staging of Endometriosis
(ASRM 1997)
• Peritoneal & Ovarian implants
– Appearance
– Size
– Depth
• Adnexal adhesions
– Presence
– Extent
– Type
• Degree of Cul de sac obliteration
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41. Staging of Endometriosis
ASRM 1997
Stage Grade Score
I Minimal 1 - 5
II Mild 6 -15
III Moderate 16 – 40
IV Severe > 40
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42. Treatment principles
• Address concerns of the patient (individualized
treatment)
• Address the clinical problem in its entirety
• Address QOL issues including impact on QOL
of treatment options
• Consider referral to centres with appropriate
expertise
• Prevent sequelae / recurrence
• Produce Pseudo Pregnancy / Pseudo
menopause state
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43. NSAIDs
• First line therapy
• COX inhibitor
– Mephenemic acid
– Ibuprophen
• Long-term administration of a selective COX2
inhibitor
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44. Hormonal therapy
• Suppression of ovarian function for 6 months
reduces endometriosis-associated pain
• Various preparation
– COCs
– Progestogens
– SPRM/SERM
– GnRH Analogues
– LNG IUS
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45. Medical management
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46. Progestogens
• Progestins induce
– a hypogonadotropic hypogonadal state
– a pseudo-decidual endometrial response
• Results in a hypo-estrogenic environment and
atrophy of endometriotic implants
• Preparations
– Tab MPA
– Tab Norethisterone
– Inj DMPA
– Tab Dinogest- Drug of choice
– LNG-IUS
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47. GnRH analogues
• GnRH Agonist
– Treatment for 3 months with a GnRH agonist
may be as effective as 6 months in terms of
pain relief .
– Treatment for up to 2 years with combined E &
P‘add-back’
• GnRH Antagonist
– Recently introduced
– Inj Cetrorelix 3 mg weekly
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49. • SPRM
– Mifepristone
– ullipristal
• Androgens
– Tab Danazol
– Tab gestrinone
• Dopamin agonist
– cabargoline
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50. Recent Innovations in Management
• Oral GnRH antagonists(e.g., elagolix,relugolix)
• Aromatase inhibitors in combination with an oral
contraceptive
• SPRM
– mifepristone ,asoprisnil,
• Selective COX2 inhibitor
• GnRH antagonists
– Inj Cetrorelix 3 mg weekly
• MMP inhibitors
4/6/2022 Dr Anuj Sharma

51. Recent Innovations in Management
• Leukotriene receptor antagonists /
Immunomodulators
– Pentoxifylline 800 mg / day
• Cytokine modulators (TNFα blockers)
– Recombinant human TNFα binding protein – Inhibits development of
endometriosis
– Results with Infliximab have been disappointing
• PPAR-γ Ligands
– PPAR-γ is a nuclear transcription factor which controls the
transcription of cytokines
– Thiazolidenediones have been considered for use in endometriosis.
Advantage is non interference with fertility
• Anti- angiogenic agents
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52. Surgical treatment
• Ablation of endometriotic lesions
• laparoscopic uterine nerve ablation (LUNA)
• Adhesiolysis followed by ART
• Cyst excision
• Pre sacral neurectomy
• Hysterectomy + BSO
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53. Endometriosis with infertility
• Adhesiolysis followed by ART
• Laparoscopic ovarian cystectomy can be considered if an
ovarian endometrioma > 3 cm in diameter is present
– To confirm the diagnosis histologically
– Improve access to follicles
– Possibly improve ovarian response.
• The woman should be counseled regarding the risks of
reduced ovarian function
• A prolonged treatment with a GnRH agonist
before IVF
4/6/2022 Dr Anuj Sharma

54. न हि धनं विद्या-वििीनः पशः
4/6/2022 Dr Anuj Sharma