Endometriosis is a disease where endometrial tissue grows outside the uterus, most commonly on the ovaries, fallopian tubes, and peritoneum. It typically affects women during their reproductive years and some of the main symptoms include painful periods, pain with intercourse, and infertility. Diagnosis involves a combination of clinical examination, imaging like ultrasound, and laparoscopy which remains the gold standard for direct visualization and biopsy of suspicious lesions. Common signs seen at laparoscopy include powder burn-like black or blue lesions on the pelvic organs and peritoneum.

1. PRESENTOR-DR.JOYDEEP
CHAKRABORTY
MODERATOR-DR.JL BAIDYA
AGMC & GBP HOSPITAL,AGARTALA

2. 
 Endometriosis is defined as the presence of
endometrial tissue (glands and stroma) outside the
uterus.
 This tissue is not only morphologically similar to
normal endometrium ,but is also functional.
 It typically a disease of reproductive years.
 It is estimated to occur in 7%-10% of reproductive
age women
Introduction

3. 
Site of endometriosis
 PELVIC
ENDOMETRIOSIS-
 Tubes & ovaries
 Uterus-adenomyosis
 Peritoneum
 Uterovesical fold
 Posterior cul de sac
 Pelvic side wall
 EXTRA PELVIC
ENDOMETRIOSIS
 Gynecologic sites-vulva,
vagina, cervix.
 Non gynecologic sites-
 Bowel
 lungs and pleural cavity
 skin (episiotomy or other
surgical scars, lymph
glands, nerves, and brain

4. 

5. 
 Although signs and symptoms of endometriosis
have been described since the 1800s, its widespread
occurrence was acknowledged only during this
century.
 Endometriosis is an estrogen-dependent disease.
 Three theories have been proposed to explain the
histogenesis of endometriosis:
 1. Ectopic transplantation of endometrial tissue
 2. Coelomic metaplasia
 3. The induction theory
 No single theory can account for the location of
endometriosis in all cases.
Etiology

6. 
 The transplantation theory, originally proposed by
Sampson in the mid-1920s, is based on the assumption
that endometriosis is caused by the seeding or
implantation of endometrial cells by transtubal
regurgitation during menstruation
Transplantation Theory

7. 
 The transformation (metaplasia) of coelomic
epithelium into endometrial tissue has been
proposed as a mechanism for the origin of
endometriosis.
 This theory proposed by Meyer could explain
endometriosis in nearly all ectopic sites.
 This theory has not been supported by either strong
clinical or experimental data.
Coelomic Metaplasia
Theory

8. 
 The induction theory is, in principle, an extension of the
coelomic metaplasia theory.
 It proposes that an endogenous (undefined) biochemical
factor can induce undifferentiated peritoneal cells to
develop into endometrial tissue.
 This theory has been supported by experiments in
rabbits but has not been substantiated in women
and primates.
Induction Theory

9. 
 Halban suggest that endometriosis could result from
lymphatic & haematogenous dissemination of
endometrial cells.
 There is extensive communication of lymphatic
between the uterus ,tubes,ovaries,pelvic & vaginal
lymph nodes,kidneys & umbilicus.
 This explain disease effecting remote sites like-
lungs,muscle,skin etc.
Lymphatic & vascular
metastases theory

10. 
 The risk or endometriosis is 7 times greater if a first-
degree relative has been affected by endometriosis .
 Multifactorial inheritance has been postulated.
 Monozygotic twins are markedly concordant for
endometriosis.
 A worldwide collaborative project (The Oxford
Endometriosis Gene Study) has been organized to
identify a genetic basis for endometriosis
Genetic Factors

11. 
 Steroid Receptor Genetics
 An association of estrogen receptor gene
polymorphisms (two-allele and multiallele
polymorphism) with endometriosis has been
reported .

12. 
 Aneuploidy
 Epithelial cells of endometriotic cysts are monoclonal
, but normal endometrial glands are polyclonal.
 Recent studies using comparative genomic
hybridization or multicolor in situ hybridization
showed aneuploidy for chromosomes 11, 16, and 17 ,
increased.

13. 
 Loss of Heterozygosity
 Microsatellite DNA assays reveal an allelic
imbalance (loss of heterozygosity) in p16 (Ink4),
GALT, p53, and APOA2 loci in patients with
endometriosis.

14. 
 Although retrograde menstruation appears to be a
common event in women, not all women who have
retrograde menstruation develop endometriosis.
 It has been hypothesized that the disease may
develop as a result of reduced immunologic
clearance of viable endometrial cells from the pelvic
cavity
Immunologic Factors

15. 
 Decreased clearance of peritoneal fluid endometrial
cells due to-
 Reduced natural killer (NK) cell activity, or
decreased macrophage activity.
 Decreased cell-mediated cytotoxicity toward
autologous endometrial cells.

 There is no clinical evidence, however, that
the prevalence of endometriosis is increased in
immunosuppressed patients.

16. 
 Substantial evidence suggests that endometriosis is
associated with a state of subclinical peritoneal
inflammation, marked by
↑ peritoneal fluid volume,
↑ peritoneal fluid white blood cell concentration
↑ inflammatory cytokines, growth factors, and
angiogenesis-promoting substances
 Macrophages or other cells may promote the growth of
endometrial cells by secretion of growth and angiogenic
factors such as epidermal growth factor (EGF)
Inflamation

17. 
 There is increasing evidence that local inflammation
and secretion of prostaglandins (PG) is related to
differences in endometrial aromatase activity
between women with and without endometriosis

18. 
 Endometriosis should be suspected in women with
subfertility, dysmenorrhea, dyspareunia, or chronic
pelvic pain.
 However, endometriosis may be asymptomatic.
Clinical Presentation

19. 
 In adult women, dysmenorrhea may be especially
suggestive of endometriosis if it begins after years
of pain-free menses.
 Dysmenorrhea often starts before the onset of
menstrual bleeding and continues throughout the
menstrual period.
 In adolescents, the pain may be present after
menarche without an interval of pain-free menses.
The distribution of pain is variable but most often is
bilateral.
Pain

20. 
 A common observation is that some women with
extensive endometriosis have little or no pain, whereas
others with only minimal endometriosis complain of
severe pain.
 Very severe pain, however, is associated with deeply
infiltrating endometriosis.
 Local symptoms can arise from rectal, ureteral, and
bladder involvement.
 Lower back pain can occur.
 Dyspareunia may be associated with deep infiltrating
subperitoneal endometriosis

21. 
 An association between endometriosis and subfertility is
generally accepted.
 Although numerous mechanisms have been proposed-
 ovulatory dysfunction,
 luteal insufficiency,
 luteinized unruptured follicle syndrome,
 recurrent abortion,
 altered immunity, and
 intraperitoneal inflammation.
The association between fertility and minimal or mild
endometriosis remains controversial.
Subfertility

22. 
 Endometriosis has been associated with-
 Anovulation,
 abnormal follicular development with impaired follicle
growth,
 reduced circulating E 2 levels during the preovulatory
phase,
 disturbed luteinizing hormone (LH) surge patterns,
 premenstrual spotting,
 the luteinized unruptured follicle syndrome, and
 galactorrhea and hyperprolactinemia.
Endocrinologic
Abnormalities

23. 
 Extrapelvic endometriosis, although often
asymptomatic, should be suspected when symptoms
of pain or a palpable mass occur outside the pelvis in
a cyclic pattern.
 Intestinal Tract (especially colon and rectum) is the
most common site of extrapelvic disease and may
cause abdominal and back pain.
 abdominal distention, cyclic rectal bleeding,
constipation, and obstruction.
Extrapelvic Endometriosis

24. 
 Ureteral -involvement can lead to obstruction and
result in cyclic pain, dysuria, and hematuria.
 Pulmonary endometriosis can manifest as
pneumothorax, hemothorax, or hemoptysis during
menses.
 Umbilical endometriosis should be suspected when
a patient has a palpable mass and cyclic pain in the
umbilical area
 Scar Endometriosis may present with cyclical pain
&swelling.

25. 
 Recommended that pelvic examination be performed
at the time of menses when tenderness is easier to
detect.
 The vulva, vagina, and cervix should be inspected
for any signs of endometriosis, although the
occurrence of endometriosis in these areas is rare
(e.g., episiotomy scar).
 The uterus is often in fixed retroversion, and the
mobility of the ovaries and fallopian tubes is
reduced.
CLINICAL
EXAMINATIONS

26. 
 Other possible signs of endometriosis include
uterosacral or cul-de-sac nodularity, cervical
displacement due to uterosacral scarring , painful
swelling of the rectovaginal septum, and unilateral
ovarian (cystic) enlargement.

27. 
 The classic chocolate cyst of the ovary is the result of
a blood-filled cavity within an endometrioma.
 Ultrasonography and magnetic resonance imaging
can be helpfulin diagnosing endometriomas.
 However, neither can diagnose small peritoneal
implants or adhesions.
 Although transvaginal ultrasonography is highly
accurate in diagnosing ovarian endometriomas,
hemorrhagic cysts account for a significant false
positive rate
IMAGING STUDY

28. 
Ultrasound pictures of endometriotic cyst
which shows fine stippling inside ovary
(ground glass appearance)

29. 
 Serum CA-125 levels are often elevated in patients
with endometriosis and correlate with both the
degree of disease and the response to treatment.
 Serum CA-125 determinations may be able to
differentiate endometriotic from nonendometriotic
benign adnexal cysts, especially when combined
with transvaginal ultrasonography
The CA-125 Assay

30. 
 During diagnostic laparoscopy, the pelvic and
abdominal cavity should be systematically
investigated for the presence of endometriosis.
 This examination should include a complete
inspection and palpation in a clockwise or
counterclockwise fashion with a blunt probe of the
bowel, bladder, uterus, tubes, ovaries, cul-de-sac,
and broad ligament.
Laparoscopic Findings-
GOLD STANDARD

31. 
 Characteristic findings include typical (“powder-burn,”
“gunshot”) lesions on the serosal surfaces of the
peritoneum.
 These are black, dark brown, or bluish nodules or small
cysts containing old hemorrhage surrounded by a
variable degree of fibrosis.
 Scarring of perotoneum causes adhesions
 Endometriosis can appear as subtle lesions ,including red
implants (petechial, vesicular, polypoid, hemorrhagic,
red flamelike), serous or clear vesicles, white plaques or
scarring, yellow-brown discoloration of the peritoneum,
and subovarian adhesions.
Laparoscopic view of
peritoneal lesion

32. 

35. 

36. 
36
Upon closer view, these five small areas of
endometriosis have a reddish-brown to bluish
appearance.

37. 
EXTENSIVE PELVIC ENDOMETRIOSIS

38. 
DENSE ADHESIONS

39. 
 The diagnosis of ovarian endometriosis is facilitated by careful
inspection of all sides of both ovaries, which may be difficult
when adhesions are present in more advanced stages of
disease.
 With superficial ovarian endometriosis, lesions can be both
typical and subtle.
 Larger ovarian endometriotic cysts (endometrioma) are
usually located on the anterior surface of the ovary and are
associated with retraction, pigmentation, and adhesions to the
posterior peritoneum.
 These ovarian endometriotic cysts often contain a thick, viscous
dark brown fluid (“chocolate fluid”) composed of hemosiderin
derived from previous intraovarian hemorrhage.
Ovarian endomeriosis

40. 

41. 
41
This is a section through an enlarnged 12 cm ovary
to demonstrate a cystic cavity filled with old blood
typical for endometriosis with formation of an
endometriotic, or "chocolate", cyst.

42. 
 Histologic confirmation is essential in the
diagnosis of endometriosis.
 Microscopically, endometriotic implants consist of
endometrial glands and stroma with or without
hemosiderin-laden macrophages
Histologic Confirmation

43. 

44. 
 Stage I (Minimal) 1-5
 Stage II (Mild) 6-15
 Stage III (Moderate) 16-40
 Stage IV (Severe) >40
American society for reproductive medicine revised
classification of endometriosis

45. 

46. 

47. 
 In most cases, preservation of reproductive function is desirable.
 The least invasive and least expensive approach that is effective
should be used.
 GOAL- is to excise or coagulate all visible endometriotic lesions and
associated adhesions
 -and to restore normal anatomy.
 Laparoscopy can be used in most women, and this technique
decreases cost, morbidity, and the possibility of recurrence of
adhesions postoperatively.
 Laparotomy should be reserved for patients with advanced-stage
disease who cannot undergo a laparoscopic procedure and for those
in whom fertility conservation is not necessary.
SURGICAL
TREATMENT

48. 
 Endometriosis lesions can be removed during laparoscopy
by surgical excision with scissors, bipolar coagulation, or
laser methods (CO 2 laser, potassium-titany-phosphate
laser, or argon laser).
Peritoneal
Endometriosis

49. 

50. 
LAPAROSCOPIC EXCISION

51.  Superficial ovarian lesions can be vaporized.
 Small ovarian endometrioma (<3 cm in diameter) can be
aspirated, irrigated, and inspected with ovarian
cystoscopy for intracystic lesions; their interior wall can
be vaporized to destroy the mucosal lining of the cyst.
 Large (>3 cm in diameter) ovarian endometrioma
should be aspirated, followed by incision and removal
of the cyst wall from the ovarian cortex.
 To prevent recurrence, the cyst wall of the
endometrioma must be removed, and normal ovarian
tissue must be preserved.
OVARIAN
ENDOMETRIOSIS

52. 
 The removal of endometriosis-related adhesions
(adhesiolysis) should be performed carefully .
 Routine use of pharmacologic or liquid agents to
prevent postoperative adhesions after fertility
surgery cannot be recommended based on evidence
from randomized controlled trials.
Adhesiolysis

53. 
 Deep Rectovaginal and Rectosigmoidal Endometriosis
 The surgical excision of deep rectovaginal and rectosigmoidal
endometriosis is difficult and can be associated with major
complications. Postoperative bowel perforations with
peritonitis have been reported in 2% to 3% of cases .
 LUNA(Laparoscopic uterosacral nerve ablation)
 Extrapelvic endometrios-surgical excision may be
difficult.
 Scar endometriosis may need excision.
OTHERS

54. 
 In patients with severe endometriosis, it has been
recommended that surgical treatment be preceded by a 3-
month course of medical treatment to reduce
vascularization and nodular size.
 However, a recent randomized study comparing 3
months of preoperative treatment with GnRH and
no treatment in 75 women with moderate to severe
endometriosis failed to show a significant difference
in ease of surgery between the two groups .
Preoperative Hormonal
Treatment

55. 
 Postoperative medical therapy may be required in
patients with incomplete surgical resection and
persistent pain.
 Treatment should last at least 3 to 6 months, and
pain relief may be of short duration, presumably
because endometriosis recurs
Postoperative medical
therapy

56. 
 Although hormonal therapy of infertility associated
with endometriosis is not of proven value, medical
therapy for dysmenorrhea, dyspareunia, and pelvic
pain associated with endometriosis is very successful
(although relief may be short-term).
Medical Treatment

57. 
 Implants of endometriosis react to steroid hormones in a
manner somewhat, but not exactly,similar to normally
stimulated endometrium.
 Because estrogen is known to stimulate the growth of
endometriosis, hormonal therapy has been designed to
suppress estrogen synthesis, thereby inducing atrophy of
ectopic endometrial implants or interrupting the cycle of
stimulation and bleeding.
 Manipulation of the endogenous hormonal milieu is the
basis for the medical management of endometriosis.
Basis For The Medical
Management

58. 
 The treatment of endometriosis with continuous low-dose
monophasic combination contraceptives ( for 6 to 12months)
was originally used to induce pseudopregnancy caused by
the resultant amenorrhea and decidualization of
endometrial tissue.
 In addition, the subsequent amenorrhea induced by oral
contraceptives could potentially reduce the amount of
retrograde menstruation (one of the many risk factors
proposed in the etiology of endometriosis).
Oral Contraceptives

59. 
 Pathologically, oral contraceptive use is associated with
decidualization of endometrial tissue, necrobiosis, and
possibly absorption of the endometrial tissue .
 Unfortunately, there is no convincing evidence that
medical therapy with oral contraceptives offers definitive
therapy.
 Instead, the endometrial implants survive the induced
atrophy and, in most patients, reactivate after termination
of treatment.
 Any low-dose combination oral contraceptive
containing 30 to 35 mg of ethinyl estradiol used
continuously can be effective in the management of
endometriosis

60. 
 Progestins may exert an anti endometriotic effect by
causing initial decidualization of endometrial tissue
followed by atrophy.
 They can be considered as the first choice for the
treatment of endometriosis because they are as
effective as danazol or GnRH analogues and have a lower
cost and a lower incidence of side effects than these
agents.
Progestins

61.  Medroxyprogesterone acetate (150 mg) given intramuscularly
every 3 months is effective for the treatment of pain associated
with endometriosis.
 Megestrol acetate has been administered in a dose of 40 mg/d
with good results .
 Other treatment strategies have included
 dydrogesterone (20 to 30 mg/d, either continuously or on days
5 to 25) and lynestrenol (10 mg/d).

62. 
 Local progesterone treatment with a levonorgestrel-
releasing intrauterine system for 12 months has resulted
in a significant reduction in dysmenorrhea, pelvic
pain, and dyspareunia.

63. 
 Progesterone antagonists and progesterone receptor
modulators may suppress endometriosis based on
their antiproliferative effects on the endometrium,
without the risk for hypo-estrogenism or bone loss
that occurs with GnRH treatment
Progesterone Antagonists

64. 
 Mifepristone Mifepristone (RU-486) is a potent
antiprogestagen with a direct inhibitory effect on
human endometrial cells and, in high doses, an
antiglucocorticoid action .
 The recommended dose for endometriosis is 25 to
100 mg/d.
 mifepristone, 50 to 100 mg/d, reduced pelvic pain and
induced 55% regression of the lesions without
significant side effects .

65. 
 Gestrinone
 Gestrinone is a 19-nortestosterone derivative with androgenic,
antiprogestagenic, antiestrogenic, and antigonadotropic
properties.
 It acts centrally and peripherally to
 ↑ free testosterone and ↓ sex hormone–binding globulin levels
(androgenic effect),
 ↓ serum estradiol values to early follicular phase
levels(antiestrogenic effect),
 ↓ mean LH levels, and obliterate the LH and follicle-stimulating
hormone (FSH) surge (antigonadotropic effect).
 Gestrinone causes cellular inactivation and degeneration of
endometriotic implants but not their disappearance .
 The standard dose has been 2.5 mg twice a week 6-9 months.

66. 
Pharmacologic properties of danazol include suppression
of GnRHor gonadotropin secretion, direct inhibition
of steroidogenesis, increased metabolic clearance of
estradiol and progesterone .
 The multiple effects of danazol produce a high-
androgen, low-estrogen environment that does not
support the growth of endometriosis, and the
amenorrhea that is produced prevents new seeding
of implants from the uterus into the peritoneal cavity
Danazol

67. 
 start treatment with 400 mg daily (200 mg twice a
day) and increase the dose, if necessary, to achieve
amenorrhea and relieve symptoms .
 local danazol treatment using a vaginal danazol ring
(1,500 mg) has been shown to be effective for pain relief in
deeply infiltrative endometriosis without the classic
danazol sideeffects, or detectable serum danazol levels,
while allowing ovulation and conception

68. 
 GnRH agonists bind to pituitary GnRH receptors and stimulate
LH and FSH synthesis and release.
 However, the agonists have a much longer biologic half-life (3
to 8 hours) than endogenous GnRH (3.5 minutes), resulting in
the continuous exposure of GnRH receptors to GnRH agonist
activity.
 This causes a loss of pituitary receptors and downregulation of
GnRH activity, resulting in low FSH and LH levels.
 Consequently, ovarian steroid production is suppressed,
providing a medically induced and reversible state of
pseudomenopause.
 A direct effect of GnRH agonists on ectopic endometrium is
also possible because expression of the GnRH receptor gene has
been documented in ectopic endometrium and because direct
inhibition of endometriosis cells has been demonstrated in vitro.
Gonadotropin-releasing
Hormone Agonists

69. 
 These agents include leuprolide(leuporide 3.75 mg im
monthly), buserelin, nafarelin, histrelin, goserelin, deslorelin,
and triptorelin.
 These drugs are inactive orally and must be administered
intramuscularly, subcutaneously, or by intranasal absorption.
 The best therapeutic effect is often associated with an
estradiol dose of 20 to 40 pg/mL (75 to 150 pmol/L).
 These so-called depot formulations are attractive because of the
reduced frequency of administration and because nasal
administration can be complicated by variations in
absorption rates and problems with patient compliance

70. 
 Aromatase Inhibitors-anastrozole, 1 mg/d,
 Selective Estrogen Receptor Modulators-Raloxifen
OTHER

71. 
 Modulation of Cytokines-
 1recombinant human TNF-a–binding protein
effectively inhibits the development of endometriosis
and endometriosis-related adhesions
 2.immune-enhancing modulators loxoribine and
levamisole
Nonhormonal Medical
Therapy

72. 
 Antiinflammation-
 leukotriene receptor antagonists
 oral pentoxifylline,

73. 
 Based on published studies, medroxyprogesterone
acetate, danazol, gestrinone,and GnRH agonists have
similar efficacy in resolution of the laparoscopically
documented disease and in pain alleviation
 .
 Disadvantages of medical therapy over surgical
therapy include the high cost of hormone
preparations, the high prevalence of side effects, and
the higher recurrence rate of endometriosis
Efficacy of Medical
Treatment

74. 
 Conception is either impossible or contraindicated
during medical treatment of endometriosis.
 There is no evidence that medical treatment of
minimal to mild endometriosis leads to better
chances of pregnancy than expectant management

75. 
 Recurrence
 Endometriosis tends to recur unless definitive surgery
is performed. The recurrence rate is about 5% to 20% per
year, reaching a cumulative rate of 40%
 after 5 years. The rate of recurrence increases with the
stage of disease, the duration of follow-up, and the
occurrence of previous surgery .
 The likelihood of recurrence appears to be lower when
endometriosis is located only on the right side of the
pelvis than when the left side is involved

76. 
 The treatment of endometriosis-related infertility is
dependent on the age of the woman, the duration of
infertility, the stage of endometriosis, the involvement of
ovaries, tubes, or both in the endometriosis process,
previous therapy, associated pain symptoms, and the
priorities of the patient, taking into account her attitude
toward the disease, the cost of treatment, her financial
means, and the expected results.
 Assisted reproduction, including controlled ovarian
hyperstimulation with intrauterine insemination, IVF, and
GIFT, may be options for infertility treatment in addition
to surgical reconstruction and expectantmanagement.
 IVF is the method of choice when distortion of the
tuboovarian anatomy contraindicates the use of
superovulation with intrauterine insemination or GIFT.
Assisted Reproduction
and Endometriosis

77. 
Conclusion
Endometriosis is a chronic, costly disease
requiring long-term, multidisciplinary treatment
Profound personal and economic impact
underscores urgent need for continued research
and improvement in diagnostic and treatment
modalities
Timely intervention and appropriate,
multifactorial treatments may restore quality of
life, preserve or improve fertility, and lead to
long-term effective management in absence of
permanent cure