1. Endometriosis

2. Definition
“Presence of endometrial tissue outside the lining of the uterine cavity” or
“Proliferation of endometrium in any site other than the uterine mucosa”

3. Epidemiology Age: common in reproductive period
True Incidence Unknown: ? 1-5% & 30 – 50 % infertility.
Does NOT Discriminate by Race.
Histology: Endometrial Glands with Stroma +/- Inflammatory Reaction.
Herdietary (↑↑ among sisters).

4. - Pelvic - Extra pelvic Sites Umbilicus. Scars (Lap.). Lungs & plura.
Others.

5. Pelvic Endometriosis Uterine= Adenomyosis (50%). Extraut: - Ovary 30%
- Pelvic peritoneum 10%.
- F. tube.
- Vagina.
-Bladder & rectum.
- Pelvic colon.
- Ligaments.

10. Theories of histiogenesis
Endometrial implantation theory
Retrograde
Vascular and lymphatic
Mechanical
Immunological and genetic theory
Composite theory

11. Theories Of Histiogenesis
continue
In situ development
Coelomic metaplasia theory
Induction theory
Embryonic cell nest
Wolffian ducts
Mullerian ducts
Germinal epithelium of ovary

12. Predisposing Factors 1. Hyperoestrinism:
a) Fibroid & metropathia hemorrhagica.
b) Delayed marriage, infertility.
c) Oestrogen secreting tumours of the ovary e.g. granulosa & theca cell tumours, or with prolonged oestrogen therapy.
2. Cervical Stenosis.
3. Insufflation.
4. Curettage.

13. CMI fault
The endometrium in an ectopic site escapes immune surveillance and continues to grow, probably there is a deficiency in CMI, or the amount of regurgitated endometrium exceeds the capacity of cytotoxic cells. TSG may be deleted and or inactivated.
The percentages of Tc and NKC in the peripheral blood in endometriosis is not different from control, however their cytotoxicity is so diminished to allow growth of endometriotic implants.
Peritoneal fluid macrophages increase in number and activity. IL-1/TNF-, PGE2, IL-8, MCP-1, and C3 increase being macrophage products

14. Cytokines and endometriosis
Peritoneal fluid macrophages are in excess and active.
TH/Ts ratio decreases in pregnancy, malignancy, and endometriosis.
Peritoneal fluid E2 is high and support the growth of endometriotic implants via EGF/TGF-.
Peritoneal fluid chemokines are high and correlate with the stage of the disease.

15. CD4 cell is the master of immune orchestra
Macrophages
NKCs
TC-cells
NKCs
B-cells
IL2
IFN-
IL4
CD4 (T-Helper)
TGF-
IL10 Ts
Th/Ts ratio:
Increases in autoimmune diseases
Decreases in pregnancy, malignancy endometriosis and AIDS

16. Is endometriosis an autoimmune disease?
Endometriosis shares SLE
More in females
Run in families
Autoantibodies
Response to danazol
Both can be combined
Endometriosis differs from SLE
HLA-unassociated
Does not satisfy Witebsky postulate

18. Diagnosis Delay in diagnosis: Progression of symptoms.
Endometriosis is often misdiagnosed leading to delays in treatment sometimes for several years.
Delay in diagnosis:
Progression of symptoms.
Increasing infertility till completed reproductive failure.

19. Diagnosis
Cont…
Symptoms (history).
Signs (Exam).
Investigations.
DD.

20. Symptoms Asymptomatic. Pain (DYS…….):
- Dysmenorrhea (crescendo = progessive)
- Dyspareunia.
- Dyschesia.
- Dysuria.
Backache.
Acute abdomen.
premenst. Tension syndrome.

21. Symptoms cont… Bleeding: - Menorrhagia.
- Cyclic hematuria during menstruation.
- Cyclic bleeding per rectum during menstruation.
- Vicarious menstruation.
Infertility.
Mass
Intermittent pyrexia.

22. Signs Pelvic examination may reveal: 1. Pelvic tenderness.
2. Fixed retroverted uterus.
3. Nodularity of the Douglas pouch and uterosacral ligaments.
4. Ovaries may be enlarged and tender . Ovarian cyst may be detected.

23. Investigations 1. Laparoscopy . 2. Cystoscopy and proctosigmoidoscopy.
3. Histopathological examination.
4. Imaging.
5. Serum CA
6. ? IL-8 & CEA.

25. Laparoscopy
Value:
It permits a “see and treat” approach, although its effectiveness may be limited by the nature of the disease and the surgeon's skill.

26. Laparoscopy cont…. Appearance: Endometriosis May Appear
Brown
Black (“Powderburn”)
Clear (“Atypical”)
Endometriosis May Be Associated with Peritoneal Windows

31. Differential diagnosis
1. Ovarian cysts.
2. Pelvic inflammatory disease .
3. Other causes of nodularity in Douglas pouch as tuberculous peritoni­tis and metastases of ovarian cancer.
4. Causes of haematuria , bleeding per rectum and acute abdominal pain if the patient is presented by one of these symptoms.
5. Asymmetrical enlarged uterus.

32. Ovarian Endometriosis (Endometrioma)
Formed by invagination of the ovarian cortex after accumulation of menstrual debris from bleeding of endometriotic implants.

34. Chocolate cyst of the ovary Endometrioma

35. Rectovaginal Septum Endometriosis
Nodules are formed by hyperplasia of smooth muscles and fibrous tissue surrounding the infiltrated tissue.
No cyclical bleeding as the endometriotic tissue are enclosed in nodules.

36. Classification / Staging
Several Proposed Schemes.
Revised AFS System: Most Often Used.
Ranges from Stage I (Minimal) to Stage IV (Severe).
Staging Involves Location and Depth of Disease, Extent of Adhesions.

38. Revised AFS 1985 Stage I (minimal) 1 – 5. Stage II (mild) 6 – 15.
Stage III (moderate) – 40.
Stage IV (severe) > 40.

39. Management goals Control of pain Control of bleeding
Restoration of fertility
Reduction of implant volume
CA125
Second look laparoscopy
Improvement of the score

40. Treatment : Consideration
Age.
Symptoms.
Stage.
Infertility.

41. Endometriosis & IVF
The presence of endometriosis does not generally impair the results of IVF but it increases the risk of infection.
It is preferable not to cauterize ovarian endometrioma if IVF or ICSI is indicated for fear of destruction of ovarian tissues.

42. Lines of treatment Lines are Expectant treatment Medical treatment
Hormonal treatment
Conservative surgery
Extirpative surgery
Combined treatment
Choice depends
Patient
Age
Need for children
Disease
Extent
Manifestations
Association
Other pathology
Systemic illness

43. Expectant treatment
Young , asymptomatic infertile patient with mild endometriosis.
If pregnancy is not achieved within months of observation:
- hormonal or surgical treatment is indicated .

44. (II) Medical Treatment
Symptomatizing patients with minimal or mild lesions:
1. Analgesics : for pain.
2. Prostaglandin inhibitors.
3. Pregnancy.
4. Opoids.
5. NSAID.

45. (Ill) Hormonal treatment
Oestrogen.
Combined oestrogen-progestogen Pills.
Progestins.
Danazol.
GnRH agonists.

46. Indications of Hormonal ttt
1. Small endometriotic; lesions.
2. Recurrence after conservative surgery.
3. Preoperative for 6-12 weeks to decrease size.
4. Postoperative for residual lesions.
5. When operation is contraindicated or refused by the patient.

47. Aim of the hormonal therapy
(A) Pseudopregnancy :
1. Combined low - dose contraceptive pills( months to inhibit ovulation and menstruation and induce decidualization to endometriotic tissues). or
2. Progestins (to avoid oestrogen's side effects medroxy progesterone acetate Depo medroxy progesterone acetate (DMPA) can be given in a dose of 150 mg IM every I - 3 months .

48. Aim of the hormonal therapy cont….
(B) Pseudomenopause (induction of amenorrhoea) by:
1. Danazol.
2. Gn RH analogues.
3. Gestrinone.
4. Gossypol.

49. Danazol
Weak Androgen (isoxazole derivative of 16 – alpha ethinyl testosterone).
Suppresses LH / FSH.
Causes Endometrial Regression, Atrophy.
Expensive.
Dose 400 – 800 mgm orally /day/ 6 – 9 months.
Side-Effects: Weight Gain, Masculinization, Occ. Permanent Vocal Changes

50. GnRH-a Initially Stimulate FSH / LH Release.
Down-Regulates GnRH Receptors–”Pseudomenopause”.
Long-Term Success Varies.
Expensive.
Use Limited by Hypoestrogenic Effects.
May be Combined with Add-Back (? >1 Year ), using E2/progesterone preparation.

51. GnRH-a Addback (E2/progesterone preparation) :
Reduce effect on bone mineral density.
Relieve hot flushes.

52. Gossypol
Is a phenolic compound extracted from the seed , stem and root of the cotton plant.
It is a sup­pressor of FSH and LH , producing endomelrial atrophy in about 50% of patients after 3 months .
Dose : 20 mg daily for 2 months then 25 mg twice weekly for main­tenance .
Side effects : include electrolyte disturbance especially hypokalaemia and alteration of hepatic and renal functions .

53. Gestrinone
It is a synthetic 19 Nor steroid exhibits marked and - progcs-terogenic and anti - oestrogenic as well as mild androgenic and anti -gonadotrophic properties .
The endocrine effects of Gestrinone are similar to those of Danazol which leads mainly to inhibition of ovari­an steroidogenesis .
The dose is mg orally twice weekly .

54. Hormonal treatment Danazol (Danol) Gestrinone (Dimetriose) Goserelin
(Zoladex)
Dose
200 mg bid
2.5 mg biw
3.6 mg /mo
Suppression
Hypothalamus
Immunity
Ovary
Pituitary
Pain relief
60%
40%
50%
Side effects
Hirsutism
Bleeding
Hot flush
Osteopenia
Cost
Low
Moderate
High
Add-back
Danazol inhibits IL1/TNF, CA125, IL-8, C3 and autoantibodies
Not only is it used in endometriosis but also it is useful in SLE, AIHA, and ITP

55. Hormonal therapy Disadvantages Does not dissolve adhesion
Does not relive obstruction
Does not eliminate large foci
Side effects
Recurrence
Costs

56. Surgical Treatment (Laparoscopy / Laparotomy)
Excision sí / Fulgeration no!
Resection of Endometrioma.
Lysis of Adhesions, Cul-de-sac Reconstruction.
Uterosacral Nerve Ablation.
Presacral Neurectomy.
Appendectomy.
Uterine Suspension (? Efficacy).
Hysterectomy +/- BSO.

57. Conservative surgery Route Goals Laparoscopy Destruction of implants
Laparotomy
Nature
Conventional
Laser
Goals
Destruction of implants
Drainage of a cyst
Excision of a cyst
Lysis of adhesion
LUNA for pain relief

58. Conservative surgery 1. Large adnexal masses .
2. Failure of medical and hormonal treatment.
3. Severe endometriosis (follow principles of microsurgery).

59. Conclusion
Endometriosis is a mystery tour as it requires decision making at every stage by the physician and the patient.
Endometriosis still stand as one of the most-investigated disorders in gynecology. SO is one of the highest priorities for research.