1. ENDOMETRIOSIS

2. INTRODUCTION It was first described by Von Rokitansky in 1860. Definition: Presence of tissue resembling functioning endometrial glands and stroma outside the uterine cavity. These ectopic implants can be located throughout the pelvic cavity.

3. Most common sites are:-  Ovaries  Uterine ligaments  Rectovaginal sepum  Parietal peritoneum  Intestinal serosa  Appendix Less common sites are:  Cervix  Hernial sacs  Laparotomy scar  Episiotomy scar  Pleural Cavity  Pericardial Cavity

4. Prevalence It is a disease of reproductive age. Incidence: 3-10% But endometriotic implants have also been found in teenagers who underwent diagnostic laparoscopy for chronic pelvic pain. (incidence 69.6%) Incidence of endometriosis is 40-60% in woman with Dysmenorrhoea. It is 20-40% in infertile woman. Infertile woman are 7-10 times more likely to have endometriosis than fertile women. Occurrence rate in 1 st degree female relatives is 6- 9%

5. HISTOGENESIS The mechanism by which endometriosis develops is unknown, although there are several possible theories like: 1. Transtubal regurgitation / retrograde menstruation 2. Direct implantation of endometrial cells 3. Metaplasia of coelomic Epithelium 4. Lymphatic dissemination 5. Hematogenous spread 6. Activation of embryonic cell rests 7. Activation of wolffian rests 8. Metaplaisa of urothelium 9. Hereditary factor 10. Immunologic factor

6. REFLUX AND DIRECT IMPLANTATION THEORY (RETROGRADE MENSTRUATION OR SAMPSON’S THEORY) There is a retrograde flow of menstrual blood through the uterine tubes during menstruation. Endometrial fragments get implanted in the peritoneal surface of the pelvic organs The anatomic distribution of endometriosis is noted at laparoscopy is consistent with a reflux pattern of development; like the common sites of disease in the pelvis are the ovary, uterosacral ligament, posterior cul-de-sac and posterior broad ligament.

7. Basic anatomy of Retrograde menstruation

8. Endometrium desquamated at the time of menstruation is viable tissue and capable of growth after implantation Endometriosis is a common finding in woman with stenosis of external cervical os and obstruction of the outflow tract.

9. COELOMIC METAPLASIA THEORY (MEYER AND IVANOFF) The germinal epithelia of the ovary, endometrium and peritoneum all originate from the same totipotential coelomic epithelium These totipotential cells could undergo metaplasia and transformed into endometrium in the presence of repeated exposure to hormonal or infectious stimuli This theory can explain endometriosis of the abdominal viscera, the rectovaginal septum and the umbilicus.

10. VASCULAR DISSEMINATION THEORY Endometrial cells can be transported to extrauterine sites by blood vessels or the lymphatic system or by contamination of the pelvis or abdominal wall incision if the uterine cavity is surgically entered Retroperitoneal endometriosis is thought to arise from lymph vascular spread In 29% of patients with pelvic endometriosis documented on autopsy had pelvic lymphnodes endometriosis. These theories explain endometriosis at different sites such as lung, pericardium etc.

11. AUTOIMMUNE DISEASE Peritoneal macrophages normally remove the menstrual debris by phagocytosis The peritoneal fluid of affected women contains increased numbers of immune cells Instead of acting to efficiently remove refluxed endometrial cells from the peritoneal cavity, these immune cells appear to promote the disease by secreting a variety of cytokines and growth factors which stimulate attachment and proliferation of ectopic endometrium and local angiogenesis. Although it is not yet clear whether these abnormalities are the cause or the consequence of the disease, which almost certainly play an important role in the pathogenesis of endometriosis.

12. GENETIC FACTORS Genes are differentially expressed in the endometrium of women with endometriosis. There is increased expression of MCP – 1 gene.

13. Metabolic Factors 1. BMI Endometriosis is associated with low BMI 2. NO(Nitric Oxide) level Higher levels of NO are found both in serum and peritoneal fluid associated with endometriosis 3. Leptin Leptin receptor expression may be deregulated during late implantation phase in endometriosis 4. Anti Oxidants Anti Oxidants like Vit-E, C & RU-486 reduces endometriosis related pelvic pain and also slows down the generation of MCP-1

14. PATHOPHYSIOLOGY GROSS APPEARANCE : In pelvis, three different forms of endometriosis are : Peritoneal endometriosis, Ovarian endometriosis and Rectovaginal Septum endometriosis. There may be extensive adhesions in the posterior cul-de- sac and posterior surface of uterus, obliterating its lower portion and uniting the cervix or the lower portion of the uterus to the rectum; with adenoma of the endometrial type invading the rectovaginal septum, which is infact an ‘Adenomyotic nodule’ Scarring in the peritoneum appears as puckered lesions to red polypoid material to clear vesicles.

15. LAPAROSCOPIC APPEARNCES : Area to be focussed are : Anterior and Posterior cul-de-sac Ovaries Posterior broad ligaments Uterosacral ligaments - Panoramic view provides general assesment of pelvis and upper abdomen including paracolic gutter, liver, gall bladder and appendix.

16. A) PERITONEAL LESIONS I) SUBTLE LESIONS/ ATYPICAL ENDOMETRIOSIS Non pigmented lesions originating from microscopic glands Represent early stage of development of disease Appears as blebs on peritoneal surface With progressive fibrosis convert to classic pigmented inactive white disease.

17. Histopathology of clear lesion Peritoneal fibrosis

18. II)WHITE LESIONS Contain sparse glands and stroma embedded in fibromuscular scared tissues Must be differentiated from postoperative scarring and fibrotic adhesions resulting from inflammatory disease. III) RED LESIONS Polypoid- biologically active appearing glands and stroma Strawberry like red – dish lesions : represents extension of deeper invasive lesions Flame like flat lesions- hypervascular

19. Red flashy lesion of Yellow macules broad ligament

20. Endometriotic implants on peritoneal surface – Varied appearances

21. Iv) Brown / Black puckered lesions/ Typical Endometriosis / ‘Powder burn’ Comprised of stroma, glands, fibromuscular scarring and intraluminal debris Intensity of coloration depends on intraluminal hemosiderin deposition Consequence of cyclic growth and regression of lesion

22. V ) Peritoneal defects : Commonly found in posterior cul-de-sac and broad ligaments, in the areas of pelvis that overlie loose connective tissue Approximately 80% of the peritoneal defects are associated with endometriosis

23. B) OVARIAN ENDOMETRIOSIS Ovaries are frequently involved bilaterally ENDOMETRIOMA : Due to metaplasia of invaginated mesothelium in proximity to the hilus of ovary Vary in size from 3.5 – 5 cm to cysts of 12 cms in size Regular borders, thick walled with internal echoes

24. Chocolate Cyst : The endometrial cyst enlarges with cyclical bleeding The serum gets absorbed in between the periods and the content inside becomes chocolate coloured. Hence, it is called chocolate cyst. Chocolate cyst may also be due to haemorrhagic follicular or corpus luteum cyst or bleeding in to the cyst adenoma. Sub-ovarian adhesions : Common to fossa ovarica and posterior leaf of broad ligament

25. C) INFILTRATING ENDOMETRIOSIS Localised to posterior cul-de-sec and uterosacral ligaments Better diagnosed by palpation with blunt probe TYPE I : Large pelvic areas of subtle or typical lesion with white sclerotic tissue During excision, disease becomes obvious TYPE II : Retraction of bowel, induration associated with retraction Excision reveals nodule

26. TYPE III : Rectovaginal Septum Adenomyotic Nodule Clinically suspected if nodularity of the septum is felt during rectovaginal examination or if dark blue lesions are seen at the vaginal fornix at the time of speculum examination Small typical lesions at laparoscopy Most severe form; may involve ureter Cul-de-sac obliteration : I) Partial – some normal peritoneum visible below uterosacral ligaments II) Complete – No peritoneum visible Endometriotic lesions become easily visible during premenstrual and menstrual phase of cycle. The fallopian tube is usually non obstructed although peritubal adhesions can extend to other adjacent structures

27. MICROSCOPIC APPEARANCE Histologically, there is presence of endometrial tissue – both glands and stroma Because of the presence of the retained blood in the cyst cavities of endometriomas, a large concentration of endothelial leucocytes heavily laden with hemosiderin may be found,and the glandular lining may be nearly absent or replaced by connective tissue Endometriotic implants contains lower concentrations of progesterone and estrogen receptors than those corresponding normal endometrium, so the histological response to progesterone is less profound

28. Histopathological appearance

29. Malignant transformation Approximately, 0.7 to 1% of patients undergo malignant transformation Endometriod Adenocacinomas account for 69% of the reported lesions with ovary being the primary site Risk of malignant transformation in ovarian endometriosis is 2.5% Some tumors especially endometrioid & clear cell CA can arise from endometriosis Endometriosis associated ovarian CA represents a distinct clinical entity with a more favourable biological behaviour, given a lower stage distribution and better survival than non-endometriosis associated ovarian CA Histological differentiation in endometriosis(hyperplasia & atypia) and several studies of molecular biology supports the theory of Genetic Alterations interfering with malignant transformation of endometriosis

30. HISTOLOGY OF TUMOURS HISTOLOGY INCIDENCE(%) Endometriod Ca Adenocarcinoma 46.4 Adenoacanthoma 20.8 Adenosquamous Ca 1.9 Clear cell carcinoma 13.5 Sarcoma 11.6 Serous cystadenocarcinoma 2.9 Squamous cell Ca 1.4 Mucinous cystadenocarcinoma 1.0 Mixed germ cell tumour 0.5

31. CLINICAL FEATURES : Symptoms vary according to – - location of implants -presence of adhesions -distortion of ovarian anatomy -ability to respond to hormones -involvment of other organs Depth of infilteration is also important, endometrial lesions greater than 1 cm in depth are associated with severe discomfort

32. SYMPTOMS ASSOCIATED WITH ENDOMETRIOSIS PELVIC Dysmenorrhoea Dyspareunia Chronic Pelvic Pain Sciatica Premenstrual spotting URINARY Flank pain Abdominal pain Urgency, frequency,hematuria GIT Constipation Diarrhoea Dyschezia Tenesmus Hematochezia PULMONARY Hemoptysis Catamenial chest pain Pnuemothorax Others : Painful scars

33. Progressively increasing dysmenorrhoea,dyspareunia and infertility – described as classical triad of the disease DYSMENORRHOEA ( 40 – 60%) Usually develops after age of 20 years Spasmodic pain beginning before the onset of menstruation and is not well relieved by NSAIDS or oral contraceptives When the rectovaginal septum or uterosacral region is involved, the pain is reffered to rectum, lower sacral and coccygeal region because of premenstrual and menstrual implants leading to chronic pelvic pain

34. Increasing secretion of PGF2@, cytokines, thromboxaneB2, growth factors from endomeriotic tissue is the cause of pain Premenstrual spotting can occur for 3-7 days before the onset of menses An endometrial cyst can cause considerable pain or it can rupture and produce clinical picture like that seen in ruptured ectopic in 10% of patients DYSPAREUNIA Due to stimulation of pain fibres by stretching of the structures in the pouch of douglas or direct pressure on the tender nodules present in the rectovaginal septum or pouch of douglas or with fixed retroverted uterus

35. INFERTILITY ( 20 – 40%) Mechanisms by which endometriosis causes infertility 1) Mechanical interference -Pelvic adhesions -Chronic Salpingitis -Altered tubal motility -Distortion of tubo-ovarian relation -Impaired oocyte pick up, despite normal process of oocyte maturation and ovulation

36. Mechanisms influencing symptoms Increased Macrophage proliferation Increased prostaglandins production Interleukins 6 Fibroblast proliferation Collagen deposition fibrinogen formation Fibrosis & adhesions Decreased plasminogen activator activity Increased leucocytes macrophages helper T Cell, lymphocyte Decreased sperm motility Decreased fimbrial ovum capture Decreased sperm oocyte interaction Decreased embryo growth Implantation Failure Infertility Increased sperm phagocytosis

37. 2) HORMONAL OR OVULATORY DYSFUNCTION Defective folliculogenesis In endometriosis, there is an abnormal follicular growth which may affect oocyte maturation and ovulation and also preovulaory estradiol levels at the time of LH surge Lutenized unruptured follicle syndrome (28- 49%) Luteal Phase deficiency In endometriosis luteal phase is shortened and there is delayed increase in progesterone secretion after ovulation

38. 3) ABNORMAL SYSTEMIC IMMUNE SYSTEM RESPONSE Increased cell-mediated gamete injury Increased prevalance of autoantibodies -positive antinuclear antibody titres -positive lupus anticoagulant titres -IgM and IgG antibodies -IgG antiphospholipid and antihistone antibodies Antiendometrial antibody production 4) EARLY SPONTANEOUS ABORTION

39. BIMANUAL EXAMINATION : Findings suggestive of endometriosis are: Tender uterosacral ligaments Cul-de-sac nodularity Induration of rectovaginal septum Fixed retroverted uterus Adenexal masses Perceptible painful swelling of implant during menses is a reliable sign of the disease

40. Diagnosis Difficult to diagnose clinically as symptoms are non-specific. More often diagnosed accidentally on laparoscopy. BIO-CHEMICAL MARKERS: 1. CA-125 levels: Significantly elevated in advanced stages of the disease with adhesions to peritoneum, omentum, fallopian tubes and cul-de-sac. Pre-op levels >35U/ml – sensitivity 88%, specificity 40% >65U/ml – sensitivity 76%, specificity 71% However, serial monitoring may help in evaluating response to therapy.

41. 2. Placental protein – 14 Elevated in presence of endometriotic cysts and deep endometriosis. Not routinely performed. 3. PAPP-A(Pregnancy associated plasma protein –A) Levels are significantly increased in women with endometriosis Degree of elevation corresponds to extent of disease 4. Aromatase Presence in human eutopic endometrium is a valuable screening marker to predict endometriosis 5. IL-18 Elevated levels of IL-18 in the peritoneal fluid are found in minimal to mild stage endometriosis

42. ULTRASONOGRAPHY Not much useful to diagnose, classify the extent or severity of disease. Features of the disease are: -Higher echogenicity around uterus and ovaries -Diffuse hypoechoic areas surrounded by strong echogenic tissue. -Hypoechoic or mixed pattern cysts. -Cul-de-sac abnormal effusions. -Ovarian enlargement – Typical endometriotic cyst is 5 – 10cm in diameter, thick walled, having unilocular or multilocular cystic areas with ground glass appearance called as ENDOMETRIOMA.

43. Newer approach of Transrectal sonography is under study to diagnose endometriosis grown deeply into the rectovaginal septum which may be missed at surgical exploration or during transabdominal/transvaginal sonography. Has a sensitivity of 97% and specificity of 96%. Endovaginal ultrasound (US) and magnetic resonance imaging (MRI) play crucial roles in the diagnosis, staging, and follow-up of the disease. The specific features of endometriosis of the rectovaginal septum on MRI and transvaginal US enable a noninvasive diagnosis, thereby reduce diagnostic delay and avoid unnecessary invasive procedures. Sonovaginography diagnoses rectovaginal endometriosis more accurately than transvaginal ultrasonography, with a sensitivity and specificity of 90.6% and 85.7%, respectively, whereas the transvaginal ultrasonography has a sensitivity and specificity of 43.7% and 50%, respectively.

44. LAPAROSCOPY

45. Gold standard investigation. Areas to be focussed are-Anterior and posterior cul-de-sac -Ovaries -posterior broad ligaments -Uterosacral ligaments Near contact laparoscopy is used for analysis of peritoneum for subtle lesions. Excision of peritoneal lesion or representative biopsy may be taken in uncertain visual diagnosis.

46. CLASSIFICATION (American fertility society) Endometriosis<1cm1-3 cm>3 cm Peritoneum Superficial deep 1212 2424 4646 Ovary Rt superficial Rt deep Lt superficial Lt deep 14141414 2 16 2 16 4 20 4 20 Posterior cul-de- sac obliteration Partial 4 Complete 40

47. Adhesions<1/3 enclosure1/3-2/3 enclosure >2/3 enclosure Ovary Rt filmy124 Rt dense4816 Lt filmy124 Lt dense4816 Tube Rt filmy124 Rt dense4816 Lt filmy124 Lt dense4816

48. Stage I(minimal disease)- 1-5, Stage II(mild disease)- 6-1 Stage III(moderate disease)- 16-40,Stage IV(severe disease) - >40 If the fimbrial end of the tube is completely enclosed, point assignment is directly changed to 16. Limitations of AFS classification: Laparoscopy or laparotomy has to be done. Evaluation of extent may be limited due to lack of recognition of atypical implants. No parameters to indicate present activity and state of evolution of disease. No correlation between extent of disease and degree of symptoms.

49. Management of Endometriosis

50. Expectant Medical Surgical-Conservative- Laparoscopic -Laparotomy -Radical Combined medical & surgical Assisted reproductive techniques

51. Expectant Case selection: Minimal endometriosis with no other abnormal pelvic finding Unmarried Young married who are ready to start family Approaching menopause Observation Pain relief: Non-steroidal anti inflammatory, Prostaglandin synthetase inhibitors

52. Medical management AIM: To induce atrophy of the endometriotic implants To suppress ovarian function offers the best chance for clinical remission of endometriosis Suppressive rather than curative; endometriosis is a chronic disease with high rate of recurrence of symptoms after medical treatment Mechanism of atrophy is either by producing pseudo- pregnancy or by pseudo-menopause or by medical castration Drugs used are : -Combined Oestrogen and progesterone pills -Progestogens -Danazol -Gestrinone -GnRH analogues -Anti-Progestins -Aromatase inhibitors

53. Combined Pills Limited role Low dose contraceptive pills in young patients with mild disease who want to defer pregnancy 1 – 2 tablets per day for 6 -9 months produces pseudo-pregnancy Councelling with the couple regarding early conception Adverse effects limits its use; weight gain, mastalgia, nausea, headaches, irregular- bleeding

54. Progestogens Different preparations: Natural progestogens: Medroxy progesterone acetate Dydrogesterone Derivatives of C-19 nor testosterone Nor-ethisterone Lynestrenol Desogestrel Levonorgestrel

55. Mechanism of action: Secretory transformation of estrogen primed uterine endometrium for which different dosages are necessary because of their different biological activities Progestines reduces the frequency and increase the amplitude of the GnRH release which results in a reduction of FSH and LH secretion Continuous application leads to suppression of ovarian steroidogenesis with anovulation and low serum levels of ovarian steroids; so, break-through bleeding is a common event Promotes secretory changes in the glandular epithelium and decidualization of endometrial stroma Mode of action on the target tissue, the endometriotic implant, is a matter of debate

56. Endometriotic foci contain either very low concentrations of progesterone receptors or are deficient in them Progestins reduces further synthesis of their own receptors, resulting in a diminished sensitivity of the implants during long term therapy Eliminates cyclical bleeding and suppress uterine contractility; prevent reflux menstruation Progesterones opposes the growth promoting effects of estrogens on the endometrial tissues by altering clearance of the nuclear estrogen receptor and inducing 17-B-hydroxysteroid- Dehydrogenase

57. Oral: Medroxy progesterone acetate 10 mg thrice daily x 6 – 9 months Dydrogesterone 10-20 mg daily x 6 – 9 months Norethisterone acetate 10-30 mg daily x 6 – 9 months IM: Medroxy progesterone acetate 100 mg two weekly x 4 doses or 200 mg every month x 4 doses

58. Subcutaneous Progestin implant Interesting option for endometriosis related pain Dose: 150 to 400 mcg SC 2 – 4 implants for 7 months Adv: No significant changes in the HDL,LDL & total cholesterol levels LNG Intra uterine system A hormonal option effective for mild to moderate endometriosis Adv: Improved compliance, better tolerance, less systemic side effects compared to oral progesterones

59. Danazol Synthetic derivative of 17-  ethinyl testosterone Androgenic action ; anti-progestational M/A: Inhibits GnRH secretion, mid cycle LH surge is altered; although basal gonadotropin concentrations are maintained Interact with endometrial androgen and progesterone receptors Displaces androgens from sex hormone binding globulin, enhancing androgenic action on endometrial receptors in SHBG estradiol binding estradiol clearance promotes fall in circulating level of estradiol

60. Thus direct androgenic and antiprogestational action on endometrial implants leads to hypoestrogenic ; hypo progestational environment Produces amenorrhea and prevents peritoneal seeding of refluxed endometrial tissue Reduces immunoglobulin and autoantibody levels in women with endometriosis Elevated free testosterone levels ; alteration in HDL-LDL ratio ADRs: - Androgenic -Antiestrogenic -Dose related weight gain, acne, deepening of voice, muscle cramps, decreased breast size, vasomotor symptoms

61. Precaution: Barrier contraception for entire course of treatment to eliminate the possibilities of conception ; although high doses of Danazol usually cause anovulation Recurrence of symptoms within 4 to 12 months of discontinuation of therapy Pregnancy rate: mild endometriosis 30.9 to 52.6% Moderate endometriosis 23.1 to 50 % Severe endometriosis 0 to 100 %

62. Gestrinone Same mechanism of action like Danazol Side effects are less Costlier than Danazol Administration is simple, twice a week

63. Gonadotropin Releasing Hormone Agonists Continued administration of GnRH agonists leads to a desensitization of the pituitary gonadotrope receptors and a reversible down regulation of the pituitary-ovarian axis -- reduction of ovarian estrogen secretion Initial response to GnRH agonist administration leads to markedly increased secretion of pituitary stores of FSH & LH If GnRH given in follicular phase: The developing follicle may respond to the flare in circulating gonadotropin levels with a rapid rise in estradiol production ; Estradiiol production may remain elevated for 3 weeks before declining

64. GnRH agonist started in luteal phase : more rapid decline in estrogen secretion, although FSH & LH levels remain elevated for 1 & 4 weeks respectively Advantages: Improvement in symtoms; pelvic pain, discomfort;Dysmenorrhoea;Dyspareunia;Pelvic tenderness Response to therapy depends on route of administration ; Buserelin: administered by long acdting subcutaneous implant gives better results than intranasal route ; because of a greater consistency in hormonal release by the injeced preperation

65. Symptoms recures after stopage of the drug within 6 months-1 year in 40-60% of patients Pregnancy rate: 0-60% Side effects: are related to hypoestrogenism Hot flushes Vaginal dryness Sleep disturbances Superficial dyspareunia Chronic fatigue Headaches, Depression Osteoporosis: decrease in bone density & rise in urinary calcium excretion to menopausal levels- on long term therapy Side effects are better tolerated than Danazol No undesirable changes in HDL,LDL or total cholesterol levels unlike Danazol

66. Drugs used are: Naferelin 200-400 mcg intranasally twice daily x 6 months Goserelin 3.6 mg depot monthly x 6 months Buserelin 200-400 mcg intranasally twice daily x 6 months Leuprolide acetate 3.6 mg depot monthly x 6 months

67. GnRH agonist with Add back therapy Concomittent administration of progesterons leads to diminuation of side effects induced by GnRH agonists GnRH agonist combined with estrogen and progesterone have been shown to be protective of bone mineral density

68. Anti Progestogens Mefiprestone 50 mg once a day Aromatase inhibitors Letrozol Anestrozol Anti angiogenic agents Under trial

69. Conservative surgeries Laparoscopic Laparotomy

70. Laparoscopic conservative surgeries Electroexcision Thermal endocoagulation Laser vaporization Monopolar electroexcision Laser excision of endometriosis

71. Monopolar electroexcision of endometriosis Advantages of monopolar electroexcision over medical therapy: Medical therapy is suppressive rather then curative Recurrences of lesions occurs after discontinuation of therapy Electroexcision is the surgical removal of the disease- curative

72. Laser vaporization, electro-coagulation, endo-coagulation destroys the lesion superficially; they may not burn deeply enough to destroy invasive disease Laparoscopic excision of lesions provides a pathology report and allows treatment of deeply invasive disease which can be done by laparoscopic monopolar electroexcision, laser excision or sharp dissection Advantages of monopolar electroexcision over Laser excision, Laser vaporization,Electro-coagulation & Endocoagulation:

73. Technical principles of monopolar electroexcision Consists of 80% blunt dissection to prepare the surgical field and 20% electrosurgery to sever abnormal tissue from healthy tissue When electrosurgery is used, coagulation current is more versatile than pure cutting current, so it is more frequently used. Non polar electrosurgery is used in short bursts after the plane of separation between diseased tissue and healthy tissue has been developed. While coagulating bleeding vessels, the vessel is superficially grasped first with the scissors, and then 50 w of coagulation current is applied to stop the bleeding.

74. Procedures Superficial peritoneal resection Deep peritoneal resection Resection of the uterosacral ligament Ureterolysis, angiolysis and neurolysis

75. Superficial peritoneal resection Since most patients do not have severely invasive disease, this technique is very commonly used. For superficial lesions on peritoneum which slides easily over retroperitoneal vessels.

76. Deep peritoneal resection Used for deeper and larger lesions, has fibrosis, or retroperitoneal invasion is suspected Resection of the uterosacral ligament Indication: Involvement by invasive endometriosis with a volume of 15 cc. Fibrotic extension down to the sacrum

77. Ureterolysis, angiolysis and neurolysis Indication: Retroperitoneal fibrosis associated with invasive endometriosis will commonly invade the ureters; occasionally internal iliac vessels and branches; rarely major pelvic nerves.

78. Ovarian endometriosis Small areas of superficial ovarian endometriosis can be excised by cutting the cortex around the lesion with pure cutting current or sharp dissection and then undermining the cortex with the scissors. Disadvantage:Removal of more normal ovarian tissues Laproscopic laser fulguration or vaporisation of larger superficial lesion Advantages:Preservation of more ovarian normal tissue

79. . Probe the interior of ovary with needle to search for underlying choclate cysts. Endometriotic cysts are frequently adherent to pelvic side walls, uterus or sigmoid colon at points of previous rupture and contagious endometriosis Therefore an ovary adherent to pelvic side wall should bring to mind the possible presence of an underlying endometriotic cyst Endometriotic cysts usually rupture during surgical treatment. After irrigation and suction of the cyst fluid from the peritoneal cavity, the edge of the cyst wall is grasped and the scissors are used bluntly to dissect away the normal ovarian cortex

80. Rectovaginal endometriosis In case of rectovaginal endometriosis sufficient radical surgery is the preferred treatment. It is necessary to remove all nodules completely and preoperative medical treatment with GnRH-Agonists seems to reduce the recurrence rates Operative laparoscopy is efficient for the treatment of patients presenting painful symptoms related to deep endometriotic infiltrating the RVS.

81. Endometriosis of large bowel Most common sites of involvement in descending order; sigmoid, rectum, ilium, cecum and appendix Invasive bowel lesions have a yellowish fibrotic appearance which blends well with the bowel wall. Other type of lesions are haemorrhagic.

82. Obliteration of cul-de-sac -Highly predictive of the presence of disease invading the anterior wall of the rectum and uterosacral ligaments. -Surgical treatment of obliterated cul-de-sac involves en-bloc resection of the uterosacral ligaments, posterior cervix and cul- de-sac as well as the rectal nodule

83. Partial oblitration of Cul-de-sac

84. Extrapelvic endometriosis Diaphragmatic endometriosis Produces ipsilateral chest pain, shoulder pain which can intensify with menses For partial thickness involvement of diaphragm; laproscopic resection is possible. For full thickness involvement laparotomy is ideal route; also for invasive procedure of posterior diaphragm adjacent to the liver.

85. Adjuvant medical therapy Preoperative: Medical therapy given before surgery can make endometriosis less visible. Increasing the chances of incomplete identification Surgery seems easier only because it is incomplete Postoperative: May delay the return of symptoms which may obscure the results of surgery.

86. Key points of laparoscopic approach Regardless of the hormonal status of the patient at operation; the surgeon must be aware that any abnormality of peritoneum must be considered as endometriosis unless proved otherwise by biopsy.

87. Results of laparoscopic surgical Mx Pregnancy rates, 60% cases with moderate, 35% cases with severe form of disease Laparoscopic excision of endometriosis results in prompt durable relief of pain due to the disease. Recurrence of disease is not as common as was formerly thought, and usually minimal when it occurs Adhesion formation more likely to occur following surgery on or around the ovaries, or adhesions already existed at the time of the surgery

88. Complications of advanced laparoscopic surgery Injury caused by trocar insertion insufflation of co 2 Haemorrhage Injuries to vessels and nerves Injuries to vital organs, bladder, bowel, ureters requiring laparotomy.

89. Laparotomy and radical surgery Large ovarian endometrioma is often associated with extensive adhesion to other pelvic structures requiring laparotomy. Cases of severe endometriosis who have completed family: abdominal hysterectomy with bilateral salpingo-oopherectomy along with resection of endometrial lesion as complete as possible.

90. LASER LAPAROSCOPY Principle : Debulking of endometriotic implants is performed by using continous firing mode. Visualisation of three-dimensional boundaries of lesions permits complete removal. Lesions overlying vital structures are vaporised by single or repeat pulse modes or lower power continous modes. Lasers with long wavelength are more effective for vaporisation while those with shorter wavelength are better coagulators.

91. SELECTION OF LASER CO 2 Laser: wavelength 10,600 nm Advantages: i) most precise. ii) better cutting properties. iii) shallow depth of penetration. iv) greater safety while working around vital structures. v) minimal fibrosis or scar tissue formation. Disadvantages: i) poor coagulating property. ii) high smoke production. iii) continous evacuation required.

92. KTP laser: i) wavelength-532 nm ii) works well in haemorrhagic field with 0.5- 2mm penetration. iii) Delivered through flexible fibre. Nd YAG laser: wavelength-1064 Advantages: i)better coagulation. ii)deeper tissue penetration. iii)seals vessels upto 5mm diameter – good hemostasis. Disadvantages: i)not preferred for vaporisation or cutting. ii)back scatter – 40%, protective eyeware necessary.

93. PROCEDURES A)Peritoneal endometriosis: For lesions >3mm in depth, therapy extended down upto healthy tissue. Excision preferred over vaporisation for deeply infiltrating lesions(>5mm) and crowded lesions. Aquadissection technique is preferred while vaporising lesions on vital structures thus achieving aquaprotection.

94. B)Bladder and bowel lesions: Superficial lesions involving serosa vaporised with CO 2 superpulse laser beam. Biodegradable cellulose may be used to prevent adhesions between bladder and uterus. C)Cul-de-sac lesions: CO 2 laser with aquadissection frees anterior rectum from loose areolar tissue of rectovaginal septum. Visible endometriotic lesions are then excised and vaporised with 0.5mm disease free margin.

95. D)Ovarian endometriosis: <1cm implants are vaporised until follicles containing fluid are encountered. Large deposits- 3mm portion of cyst excised – inner wall of cyst is vaporised with CO 2 laser at 25-30 W continous mode – irrigation is performed – incision is left open or closed. Results: Statistically significant pain relief as compared to expectant treatment after six months has been seen. Significantly better fecundity rates after laser treatment of stage I and stage II disease have been proved in studies.

96. Advantages over conventional laparoscopy: Precise destruction of disease. Minimal bleeding. Minimal thermal damage to normal tissue. No increase in tissue reaction. No increase in adhesion formation. Complications: Burn injuries to vital structures. Thermal injury is always a risk. Protective eyeware required.

97. LAPAROSCOPIC UTERINE NERVE ABLATION Principle: Destruction of both sensory fibres and ganglia lying in, under and around the attachments of uterosacral ligaments by vaporising close to posterior cervix and creating crater of 1 cm wide and 5 mm deep. Effective in resolving pain related to endometriosis. Haemorrhage is controlled by direct pressure,coagulating with defocussed laser beam or bipolar coagulation.

98. ENDOMETRIOSIS AND ASSISTED REPRODUCTIVE TECHNOLOGIES Techniques in assisted reproduction have been widely used during the past decade for the management of endometriosis associated infertility unresponsive to cytoreductive surgical or hormonal therapy Endometriosis is the sole identifiable cause of infertility in 25% to 35% of women undegoing in vitro fertilization/ embyro transfer ( IVF/ET) The necessity of initial medical or surgical therapy before use of ART remains controversial

99. Gonadotropin or GIFT (GAMETE INTRA FALLOPIAN TRANSFER) may overcome impairment of sperm transport,failed ovum capture, or abnormalities in the peritoneal environment associated with endometriosis COH (CONTROLLED OVARIAN HYPERSTIMULATION with Human Menopausal pure FSH together with IUI can be used as a method to increase cycle fecundity of patients with endometriosis By increasing the number of oocytes at the time of ovulation and introducing a high concentration of spermatozoa into the female reproductive tract the chance of conception is improved because of larger number of gametes available for fertilization

100. THANK YOU