Dr. Jaideep Malhotra is an IVF specialist based in Agra, India. He has over 50 published papers and 100 conference presentations. He is a fellow of many Indian and international obstetrics and gynecology organizations. He has received several awards for his work, including producing India's first IVF birth and test tube baby of Nepal. He practices at his nursing home in Agra and is a consulting IVF specialist at multiple other locations in Northern India and Nepal.

1. JAIDEEP MALHOTRA
M.D., F.I.C.O.G., F.I.C.M.C.H.
• Chairperson International Academic Exchange Committee FOGSI( 2002-2006)
• Member governing council ICOG
• Practising I.V.F. specialist at Agra (Special Interest in Infertility, Laparoscopy, Ultrasound and
Genetics)
• Member and Fellow of many Indian & International organization (IMA, FOGSI, ISAR, IFFS,
IAJAGO, IAGE, ISUOG, AIUM, NARCHI, ICMCH, IHAR, ISPAT, IFUMB, ICMU, AOFOG,
FIGO, FIS, IAFS)
• Indumati Zhaveri Award, Jagdeshwari Misra Award three times, Ethicon Fellowship,
Outstanding Achievement Award 1999, Chorion Award
• Over 50 published and 100 presented papers
• Co-editor of step by step series of books
• Co-editor of manual of operative obs gyn
• Editor of “Fetus Our Other Patient”
• Credited with producing firsts of U.P. : IVF birth, ICSI birth, IVF Twins, ICSI Twins, IVF
Triplets, TESA-ICSI Pregnancy etc.
• Credited for producing first Test Tube Baby of Nepal
• Awarded Corion Prize for best original research in “Improving endometrial receptivity and
blood flows.”
• Consultant IVF specialist at Ludhiana, Jalandhar, Ambala, Hissar, Panipat, Gorakhpur, Bariely,
Allahabad & Kathmandu
MALHOTRA NURSING & MATERNITY HOME PVT. LTD.
84, M.G. Road, Agra-282 010
Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98970-33335; Fax : 0562-2265194
E-mail : mnmhagra10@dataone.in / mnmhagra@gmail.com; Website : www.mnmhagra.com
Apollo Pankaj Hospitals, Agra
CHIEF I.V.F. UNIT

2. • Affects one in almost 15 women
• Reproductive age group
• Cause not yet known
• Not clear how it can be prevented
• Not known how to predict the
development of this disease
• No simple test except on surgery
• Even on operation the diagnosis is mostly
an educated guess
• There are at least 4 treatment options
none better

3. WELCOME TO THE WORLD
OF ENDOMETRIOSIS
20%
15%
25%
25%

4. ENDOMETRIOSIS
Presence of tissue outside the uterus
which is similar to endometrium.
invasive but non neoplastic growth
pattern.

5. ENDOMETRIOSIS
• EXTREMELY COMMON
• ACCOUNTS FOR 15% OF INFERTILITY
• CHALLENGING CONDITION BOTH FOR CLINICIAN
AND PATIENT
• CLASSIC SYMPTOMS :
• DYSMENORRHEA
• DYSPAREUNIA

6. PREVALANCE
• 20% in Asian women
• Asymptomatic: 5- 20%
• With pelvic pain: 15-45%
• With infertility: 20-50%
• Adolescents with chronic pelvic pain: 25%
• Premenopausal women: 50%

7. ECTOPIC ENDOMETRIUM
• COULD BE PRESENT :
• REPRODUCTIVE TRACT
• URINARY TRACT
• GIT
• SURGICAL SCAR/UMBILICUS
• LUNG
• RARELY PERICARDIUM,PLEURA,CNS,NOSE,EYE
• Ectopic endometrium responds to changes in
ovarian hormones
• Cyclical bleeding within & from deposits leads to
inflammation ,then fibrosis, peritoneal damage &
adhesions

8. Cause is unknown. However, the most widely
accepted explanation for endometriosis is that
viable cells from the lining of the womb pass
upwards into the Fallopian tube and out into the
pelvic cavity where they settle down.
In most women these cells will be destroyed by
the woman's immune system. However, in some
women, these cells implant and proliferate,
possibly due to a disorder of the woman’s
immune system.

9. Signs and symptoms
• Endometriosis should be suspected in presence
of triad of symptoms-
• Subfertility
• Dysmenorhoea
• Dyspareunia.
• Chocolate cysts may be present as tender adnexal
masses
• Extragenital endometriosis may present as
hematuria.
• It may be asymptomatic even in advanced disease
( ovarian or rectovaginal endometriosis)
• Risk factors include short cycles, heavy menstruation
and longer flow duration.

10. • Endometriosis is also
associated with abdominal
symptoms like nausea,
vomiting, early satiety,
bloating and altered bowel
habits.
• Extra pelvic endometriosis
is usually asymptomatic
and should be suspected
when symptom of pain or
palpable mass occurs
outside pelvis in a cyclic
manner.

11. Diagnosis
Points to include:
• History (risk factors and clinical
presentation)
• Examination (preferably during
menstruation): retrograde uterus, tender
nodules, tenderness in fornices can be
appreciated on palpation.

12. DIAGNOSIS
3 categories of techniques;
• Serum immunoassay
• Imaging techniques
• Laparoscopic examination.

13. LAB MARKERS
Tumour markers: CA-125, CA-19-9,
SICAM-1, Glycodelin A, AromataseP450,
Cytokeratins, Hormone receptors.
Immunological markers: Cytokines:IL-1,
TNF, Auto-antibodies, anti-endometrial auto
antibodies, leptin, adiponectin
Genetic markers: placental protein ,
Early growth response-1 gene P450
aromatase.

14. • CA-125 : there are no blood tests available for
endometriosis. Levels of CA-125 , a marker
found on derivatives of coelomic epithelium is
significantly higher in 60% women with
moderate to severe endometriosis.
• Serial CA-125 determinations maybe useful to
predict recurrence of endometriosis.
• Compared with laparoscopy, measurement
of CA-125 has no value as a diagnostic tool.

15. IMAGING
• ULTRASONOGRAPHY
• COMPUTED TOMOGRAPHY
• MAGNETIC RESONANCE IMAGING

16. ULTRASONOGRAPHY
• TVS IS A USEFUL TOOL TO
DIAGNOSE OVARIAN
ENDOMETRIOMAS ESP
LARGER THAN 10MM.
• CHARACTERISTIC FEATURES
• presence of diffuse low level
internal echoes and hyperechoic
foci in the walls (classic chocolate
cyst)

17. DIAGNOSIS
• TVS HELPS IN DETERMINING:
• TYPE- CYSTIC
• MIXED
• SOLID
• SHAPE
• LOCATION

18. •CYSTIC LESIONS 30%-62%
•(seen as irregular cysts with septation)

19. MIXED TYPE (compatible with
pelvic inflammatory disease)

20. •SOLID (may mimic ovarian malignancy)

21. staging

22. REVISED AMERICAN FERTILITY STAGING

23. COMPUTED TOMOGRAPHY
• Gathers anatomical
information from cross-
sectional planes
• Rarely used as diagnostic
method owing to high cost
and differing appearances
of lesions
• Differential diagnosis of
endometriosis and
peritoneal carcinomatosis
can be difficult

24. MAGNETIC RESONANCE IMAGING
• Non invasive
• Does not involve ionising radiation
• Consistently demonstrates
anatomic tissue planes
• More valuable than CT
• Can detect haemorrhagic nature
of masses
• MRI cannot be used to detect
extra-ovarian endometrial
adhesions and intraperitoneal
implants, nor can co relate with
surgical assessment of severity
• Cannot substitute laparoscopy for
diagnosis or staging

25. LAPROSCOPY is the gold standard
for diagnosis and treatment with
histological confirmation.

26. Superficial lesions
• Are not detected by TVS
• MRI also fails to detect
lesions <5mm
• Laparoscopy is diagnostic
•Characteristic findings include
typical powder-burn or gunshot
lesions on serosal surface of
peritoneum.

27. Endometriosis
Allen masters syndrome.
bluish nodules, haemorrhagic spots,
blebs,
fibrosis and presence of dense adhesions.

28. Endometriomas
• Caused by recurrent shedding of
endometrial tissue that lines the wall of
cyst
• 90% of endometriomas are pseudocysts
formed by invagination of ovarian cortex
• Recent endometriomas have marble like
cortical surface
• Older ones have pigmented,fibrotic,&
poorly vascularised
• Preferential site is left ovary

29. Endometriosis

30. Chocolate cysts are cysts containing dark
brown, thick fluid.( ovarian endometriosis)

31. LAPAROSCOPY
• Optimal tool for
diagnosis
• Resulting in 90% correct
diagnosis and staging.
• Visualisation may be difficult or
inaccurate, in minimal lesions,
adhesions that obscure
visualisation.
• Invasive
• Repeat exam to monitor
therapy , or recurrence not
feasible

32. • Rectal USG(6.5 mHz): recto vaginal
endometriosis and uterosacral
infiltration.
• Endoscopic rectal USG:
circumferential imaging of rectum
and surrounding areas.
• MRI: small lesions, implants,
uterosacral ligament, bladder and
cul-de-sac.
• CT-scan: brain and pleura
• Barium enema: bowel infiltration
• IVP, Cystoscopy, ureteroscopy:
bladder and ureteral infiltration

33. Deep retroperitoneal
endometriomas
• Represent nodular,
myoproliferative lesion
characterised by presence of
microendometriomas and sparse
amount of glandular & stromal
tissue.
• OCCURS PREFERENTIALLY IN
RECTOVAGINAL AND
VESICOUTERINE AND UTERINE
LIGAMENTS
• PELVIC ENDOMETRIOSIS CAN
AFFECT RECTOSIGMOID COLON,
APPENDIX,AND ILEUM

34. RECTOVAGINAL
Transrectal USG considered as valid diagnostic tool for rectovaginal endometriosis
FEDELE,BIANCHI

35. BLADDER ENDOMETRIOSIS
• TYPICALLY FOUND IN PTS WITH
DYSMENORRHOEA WITH
URINARY SYMPTOMS
• TVS MAY SHOW SOLID NODULE
WITHIN POSTERIOR BLADDER
WALL
• COLOR DOPPLER MAY SHOW
LOW TO MODERATE
VASCULARITY

36. D/D
• HAEMORRHAGIC CYSTS
• DERMOID CYSTS
• EPITHELIAL OV. TUMORS.

37. TVS WITH DOPPLER
• DIAGNOSTIC EFFICIENCY IN EARLY DISEASE
UNCERTAIN
• ALEEM 95 CONCLUDED SCATTERED VASCULARITY TYPICAL OF
OVARIAN ENDOMETRIOMAS AND DISTINCT FROM DENSE
VASCULARIZATION OF CORPUS LUTEUM CYSTS & OV NEOPLASMS
• Fairly accurate diagnosis of endometriomas,and
posterior endometriosis 93%as first line .

38. Advantage of TVS
• Non invasive
• Reproducible
• Exploration of the whole pelvis,including
bladder,uterus,ligaments,pouch of
douglas,ovaries,rectvaginal septum and
colorectum at the same time
LIMITATIONS ; VIRGINITY,
DIFFICULT TO DISTINGUISH,BETWEEN BORDERS,MARGINS DEPTH
OF INVOLVEMENT
VESICOUTERINE LESIONS
SMALL SUPERFICIAL LESIONS

39. VASCULARITY
• Doppler evaluation :
• Vascular location
• Type of vascularization
• Vascular quality
Vascular location typically is pericystic.
Type of vascularization can be regularly
separated vessels or no vessels.
Vascular quality is doppler waveform
signals

40. Guerriero reported endometriomas are poorly
vascularised

41. DOPPLER
• SHOW MODERATE VASCULAR
IMPEDANCE
• IF INFLAMMATORY CHANGES ARE
PRESENT THEN THERE IS MARKED
REDUCTION IN BLOOD FLOW
RESISTANCE (DIFF. TO DIFFERENTIATE
FROM MALIGNANCY)

42. • Vascularity is important in determining
the mode of treatment and its efficacy.
• Medical treatment of endometriomas with
fibrous plaques is not going to be
successful
• Injection of GnRh analogues could be
successful with optimal vascular pattern
• An avascular lesion must be removed
surgically

43. ENOMETRIOSIS IN
ADOLESCENTS
• Was considered disease of
women over 20
• Higher incidence in teenagers
• Being reported even before
menarche
• Reported that adolescents
with endometriosis have
uterine contractions with
higher frequency,amplitude
and basal pressure tone.

44. Management
• Medical
• Surgical

45. MEDICAL
• NSAIDS
• OCPs
• ANDROGENIC AGENTS
• PROGESTOGENS
• GnRH ANALOGUES
• ANTIPROGESTOGENS
• ? LEVONORGESTREL IUCD

46. OCPs
• COC
• 0.02 to 0.03mg ethinyl estradiol and
0.15mg desogestrel daily cyclically for 6
months
• Endometriosis can remain active despite
OCPs, some pts continue to complain .if
no relief in symptoms in 3 months than
,more aggressive tt is warranted

47. PROGESTOGENS
• 100-150 mg depot medroxyprogesterone
acetate given intramuscularly every two
weeks
• 30-100mg MDPA orally daily.
• 5mg norethindrone acetate daily x 6months
• 40mg megestrol acetate daily
• S/E wt gain, fluid retention, headaches,and
depression.
• Recurrence rate 42% after 2 yrs of therapy

48. GnRH analogues
• 3.6mg goserelin
• 3.75 mg leuprolide
• 3.75 triptorelin
• Given subcutaneously every 4 weeks
• Three monthly depot injections also
available
• S/E vaginal dryness, hot flushes ,insomnia
,depression, libido changes,
headache,fatigue ,bone mineral density
changes.
• Add back with conjugated equine estrogen
with medroxy progesterone acetate ,or
bisphosphonates or norethindrone.

49. Danazol
• 200-800mg daily divided doses 3-6
months
• S/E acne, hirsuitism, wt gain, hot flushes,
hoarseness of voice, muscle cramps,
decrease in breast size.
• Recurrence rate 50% within 4-12 months
of therapy

50. Antiprogestogens
Gestrinone is a synthetic hormone that effects the
production of estrogen by the ovaries.
2.5 mg given twice weekly .
Side effects of Gestrinone include:
weight gain, acne depression, mood swings, hot
flushes and loss of libido.
Gestrinone is a treatment used more commonly in
Europe.
It works in much the same way as danazol with
similar, but milder, side effects. g

51. • There is no evidence that progestins
and GnRH analogs are less safe than
OCs for endometriosis therapy in teens
• The ACOG Committee Opinion does a
disservice in promoting laparoscopy as
superior to drug therapy for
endometriosis in young women

52. • Suppression of ovarian function for 6 months
reduces endometriosis associated pain. The
hormonal drugs investigated - COCs, danazol,
gestrinone, medroxyprogesterone, acetate and
GnRH agonists - are equally effective but their
side-effect and cost profiles differ (Davis et al.,
2007 ; Prentice et al., 1999; Prentice et al., 2000;
Selak et al., 2007).
• Evidence
level 1a

53. Pain-Medical therapy
(Comparative Trials)
• GnRHa vs. Danazol
• 15 Trials No difference
• GnRHa vs. Progestins
• 2 Trials, No difference
• GnRHa vs. OCP
• 1 Trial, No difference for pelvic pain,
GnRH more effective for
dysmenorrhea and dyspareunia

54. Chronic Pelvic Pain-Treatment vs.
Placebo
• 1976-1998, 6 RCT, n:381
• L/S surgery, MPA, Danazol, GnRHa effective
than placebo (40-70% )
• No one is better after six months
• Medical treatment after surgery----NO
difference
Howard FM, 2000

55. Pain-Surgery vs. Medical
• Initial surgery superior with more severe
disease
• No difference
• Stage I-II endometriosis
• Chronic Pelvic Pain
• Previous surgery

56. Suggested approach to
endometriosis-associated pain
• 1st line: continuous low-dose monophasic oral
contraceptive with NSAIDs as needed
• 2nd line: progestins (start with oral dosing,
consider switching to levonorgestrel intrauterine
device or depo if well tolerated)
• 3rd line: GnRH agonist with immediate add-back
therapy
• 4th line: repeat surgery, followed by 1, 2, or 3a
• a May consider low-dose (100–200 mg every day)
danazol if other therapies poorly tolerated.
Mahutte and Arici, 2003

57. Experimental Treatments
• RU486 (mifepristone) and SPRMs
• GnRH antagonists
• TNF-a Inhibitors
• Angiogenesis Inhibitors
• MMP Inhibitors
• Immunomodulators
• Estrogen Receptor-b Agonists
• Aromatase Inhibitors

58. MIFEPRISTONE
• Intractable pain of extensive endometriosis
Mifepristone is useful
• 50 mg daily x 6 months effective in
improving symptoms and causing
regression
• S/E hot flashes,fatigue ,nausea,liver
enzyme changes

59. Aromatase inhibitors
• Still in research stage
• Prescribed especially in women who do
not respond to, or can not take other
treatments.
AIs: complete inhibition in estrogen synthesis
Attar E and S.E. Bulun, Hum Reprod
Update.2005; 0: 341

60. Pain relief
Acupuncture for pain relief
Up to 70% of these patients whose pain is unresponsive
to first-line therapy have endometriosis.
Surgical treatment with laparoscopy frequently fails to
resolve adolescent endometriosis-related pelvic pain.
Medical treatments with Gonadotrophin releasing
hormones
(GnRH) analogues are not approved for use in
adolescents under the age of 16 and elicit menopause-
related side effects that some young adults find
distressing.

61. LEVONORGESTREL IUCD
• increasingly being used
• Few studies right now
• May have a potential for long
term treatment in women not
desiring pregnancy
• S/E irregular bleeding

62. Simultaneous use of
levonorgestrel IUCD and
etonorgestrel subdermal implants
for debilitating adolescent disease

63. Assistant dependent
• Laparoscopy should be considered if
adolescents with chronic pelvic pain who do not
respond to medical treatment (NSAIDs, OCPs)
since endometriosis is very common under
these circumstances (Goldstein et al., 1980;
Vercellini et al., 1989; Reese et al, 1996; Laufer
et al., 1997; Emmert et al., 1998; Hassan et al.,
1999; Kontoravdis et al., 1999; Shin et al., 2005;
Stavroulis et al., 2006).
Evidence Level 3

64. Surgical
CONSERVATIVE
• Ablation of endometriotic deposits
• Cyst drainage excision of lesion
• Laser vaporisation
• Cystectomy
• Nerve ablation
CURATIVE
• Oopherectomy
• Hysterectomy with b/l salpingo-oopherectomy

65. Pregnancy rates 50% over 3 years

67. Follow up
• Recurrences are common
• Rate of recurrence increases with duration
• Post op OCs reduce recurrence after one
year but not 3 yrs
2nd look laparoscopy for extensive pelvic
endometriosis.
TVS for endometriomas
Tumor markers for severe disease

68. ASSISTED REPRODUCTION
• Definitely referred for ART little earlier
• IUI improves fertility in minimal –mild
endometriosis
• IUI with ovarian stimulation is more
effective
• IVF appropriate where IUI fails or tubal
function compromised.

69. SUMMARY OF MANAGEMENT OPTIONS
• Female age, duration of infertility ,family history ,pelvic
pain and stage of endometriosis should be always
considered before planning treatment
• On laparoscopy treat grade1/2 endometriosis
• Younger patients with grade1/2 disease expectant
management or COH-IUI can be offered
• Older patients i.e.>35yrs can be treated with COH-IUI or
IVF-ET
• In women with grade ¾ disease conservative
laparoscopic surgery should be offered
• Women with grade ¾ disease who fail to conceive after
surgical therapy or because of advancing reproductive
age group ,IVF-ET should be offered

70. CONCLUSION
• Endometriosis is an example – the more
treatments there are for a disease ,the
more likely it is that none is ideal
• Albert Yuzpe

71. THANKYOU

73. CONCLUSIONS
• AS IT STANDS TODAY WE HAVE TO
ADMIT THAT WE HAVE GOT MUCH OF
ENDOMETRIOSIS WRONG
• DESPITE MUCH RESEARCH IN THE LAST
30 YEARS WE HAVE BEEN ASKING ALL
THE WRONG QUESTIONS
• WE MUST ASK OUR PATIENTS TO
FORGIVE US AND LET US DO IT ALL
OVER AGAIN

74. Aspiration of endometrioma is not an effective treatment,
but may be helpful in pts who had prior surgery & recurrence

77. • In a study conducted by Ayers et al , abnormal
luteolysis, as a second factor of luteal dysfunction,
was assessed in 13 women with endometriosis
and 25 control patients by measurement of ovarian
vein estradiol (E2) and P during the follicular
phase. The results reveal that women with
endometriosis have
• (1) significantly lower ovarian vein E2,
• (2) significantly higher both peripheral and
ovarian vein P
• (3) threefold higher P/E2 ratios than controls
during the follicular phase.

78. Dysmenorrhea
OCP vs. Placebo
Proctor et al 2002
50 mcg monophasic
GPRG 1968
Nakano 1971
Cullberg 1972
Subtotal
80 mcg biphasic
Buttram 1968
Common OR
OR for reduction in dysmenorrhea N = 320
Placebo OCP

79. SCORING SYSTEM
REPRODUCTIVE AGE 2
CHRONIC PAIN 1
INFERTILITY 1
ULTRASOUND
POSITION(MID R.V.) 2
BILATERAL 1
SERIAL SONO POSITIVE 2
THICK WALLS 2
HOMOGENOUS ECHOGENICITY 2
CLEAR DEMARCATION FROM OV 1

80. SCORING (CONT)
TRANSVAGINAL COLOR DOPPLER
VASCULARISATION 2
PERICYSTIC/HILAR LOCATION 2
REGULAR SEPARATED VESSELS 2
EXISTENCE OF NOTCHING 1

81. SCORING (CONT)
RI <0.40 (MENSTRUAL
PHASE)
2
RI=0.41T0 0.60 (LATE
FOLLICULAR /CORPUS
LUTEUM)
2
CA 125 >35 IU/ml 2
Discrimination between endometriosis & others
is score of 20

82. ACCURACY OF SCORING
MORPH SC HISTOPATH.
TRUE
POSITIVE(73)
73 ENDOMETRIOMA 73 ENDOMETRIOMA
FALSE
NEGATIVE(14)
7 HAEMO
5 DERMOID
2CYSTADENOMA
7 ENDOMETRIOM
5 ENDOMETRIOM
2 ENDOMETIROM
FALSE
POSITIVE(15)
7 ENDOM
6 ENDOM
2 ENDOM
7 HAEMORRAG
6 DERMOIDS
2 CYSTADENOM
TRUE
NEGATIVE(553)

83. COMBINED SCORING
SYSTEMS
COMBINED HISTOPATH
TRUE
POSITIVE(102)
102 ENDOM 102 ENDOM
FALSE
NEGATIVE(1)
1 HAEMORRAG 1 ENDOMT
FALSE
POSITIVE(2)
1 ENDOM 1 HAEMORR
TRUE NEGATIVE
(551) Sensitivity 99%
Specificity 99.64%

84. Conclusion
• AIs administered in combination with an ovarian
suppressant represent promising and novel treatments
• Patients with endometriosis who do not respond to existing
treatments appear to obtain significant pain relief from AIs
• Most of the AI regimens are fairly simple, consisting of
taking one or two tablets a day.
• Finally, the side-effect profiles of the AI regimens
(including a progestin or OC add-back) are more favorable
compared with treatments using GnRH-a or danazol.
• Some of these regimens may potentially be administered
over prolonged periods of time.

85. Recurrence rate is 8%

86. DIAGNOSIS
• KURJAK AND KUPESIC FIRST TO
REPORT USE OF TVS COLOR DOPPLER
AND CA 125 LEVELS IN
ENDOMETRIOMAS.
• A SCORING SYSTEM WAS DEVELOPED
BASED ON THESE TO IMPROVE
SENSITVITY AND SPECIFICITY OF
DIAGNOSIS.

87. • OKARO 1999 REPORTED
COMBINATION OF
• SOFT MARKERS
• SITE SPECIFIC TENDERNESS
• PRESENCE OR ABSENCE OF FREE
FLUID
• OVARIAN MOBILITY
• HARD MARKERS
• PELVIC PATHOLOGY WAS DETECTED
IN 78% OF PTS WITH ABNORMAL SCAN
USING THESE MARKERS