‘President’s Medal’ for best medical graduate 1970-75.
‘Dr. B.C Roy’s award’ in 1999 for outstanding contribution towards
...
Pelvic tuberculosis and
infertility
Prof. Dr. Abha Majumdar
Director and Head
Center of IVF and Human Reproduction
Sir Gan...
2 types of tuberculosis infection
in humans
 Latent TB: Exposure to tuberculosis but
organism is dormant or inactive. Onl...
Latent tuberculosis
 Latent TB is a clinical condition defined
by a positive mantoux’s test in people
who have no clinica...
Differences in latent and active
tuberculosis
Latent tuberculosis
 TB bacteria enter humans
and stimulates immune
system ...
 Genital tuberculosis is mostly secondary
to a primary infection in the lungs
 Rarely primary infection can be through
a...
 Hematogenous (most common)
 Lymphatic spread (from hilar LNs to
intestinal LNs to pelvic LNs)
 Direct spread from adja...
How does tuberculosis infection
cause infertility?
TB infection actively affects genital organs, starts
tissue destruction...
Tests to suspect genital
tuberculosis
Pelvic Ultrasound
HSG
Laparoscopy and hysteroscopy
Pelvic ultrasound
Hydrosalpinx, T-O masses, encysted fluid in
pelvis
Thin endometrium or poor, unclear
endometrium, flui...
HSG findings in genital
tuberculosis
 Hydrosalpinges with fimbrial blocks
 Blocked or lead pipe tubes
 Scarring leading...
HSG findings in genital
tuberculosis
Laparoscopy and Hysteroscopy
(closest to confirmatory tests)
Direct visualization of tuberculous
lesion and its sequele in...
Advanced endometrial
tuberculosis on hysteroscopy
Normal uterine cavity
Advanced pelvic tuberculosis
on laparoscopy
Fitz hugh curtis or
abdominal tuberculosis
Direct test or confirmatory
tests for active disease
Histopathology
Visualization of bacteria
Epitheloid and langhans giant
cells & lyphocytes
Reliable & specific method of diagnosis of TB
with sensitivity of 70-100%...
Direct visualization of
mycobacterium
 Demonstration of AFB in tissue:
(>10,000 org/ml)
 Ziel Nelson staining
 Fluoresc...
Categories and Rx of Genital TB
Category Description Initial phase
(daily or thrice
weekly)
Continuation
phase (daily or
t...
 Convenient commercial combipacks of
AKT-4 to be taken for 2 months daily.
 One capsule of Rifampicin- 450mg
 Two table...
Why INDIA is different when the
question of treating latent
tuberculosis arises?
Why can’t we follow western
countries in ...
Prevalence of Tuberculosis
 High prevalence countries :
 INDIA =40% (800:2000)of population has
been exposed to TB that ...
Pitfalls in treatment of Latent
TB in India
 Due to constant exposure to Mycobacterium
tuberculosis in high prevalence ar...
Treatment of tuberculosis in
India
 The priority of TB control program in India
(RNTCP) is treatment of active TB
 Testi...
 In developed countries- where prevalence of TB
is minimal, most new cases are only due to
activation of latent TB infect...
Indirect Tests used to detect
tuberculosis
(cannot detect between latent and active
tuberculosis)
 Mantoux Test skin test...
Prevalence of tuberculosis in
India
 Latent tuberculosis 40%
 Active pulmonary tuberculosis 8-10%
 Genital tuberculosis...
Changing epidemiology of TB in
INDIA by treatment of L-TB
Urban MDR 51% vs rural MDR 2%
Clin Infect Dis 2003 Jun 15;36(12...
Some scary facts
 Indiscriminate use of ATT - XDR (extreme) and
TDR (total)
 Need of sanatoriums may re-emerge to
preven...
TOI
Finally, tuberculosis declared a notifiable disease TOI 09 May
2012, 06:27 IST ...They finally land up in government t...
All the TB-PCR positive women were administered standard 6-
month anti-tubercular chemotherapy only….. There were no
stati...
Indian publications advocating
favorable fertility outcome following
ATT for endometrial PCR positivity
 None of the stud...
Facts about tuberculosis
treatment in Northern India
 500 to 600 laparoscopies done under my care
of urban infertile wome...
Some facts in my experience
 Centre of IVF SGRH
 1200 IVF cycles/year with a pregnancy rate
of 42% in last 1 year
 2400...
Our ongoing study at SGRH
 This is the first study of its kind being
conducted in the country as prevalence of TB
PCR has...
Pelvic tuberculosis and infertility trivandrum 31.8.13
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Pelvic tuberculosis and infertility trivandrum 31.8.13

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Pelvic tuberculosis and infertility trivandrum 31.8.13

  1. 1. ‘President’s Medal’ for best medical graduate 1970-75. ‘Dr. B.C Roy’s award’ in 1999 for outstanding contribution towards medicine and field of specialty, ‘Vikas Ratan Award’Nations economic development & growth society 2002 ‘Chiktsa Ratan Award’ International Study Circle , 2007 Felicitated by Agra medical college for ‘Outstanding contribution towards field of specialty. 2008 Appointed by National Board of Examination as course director to award post doctoral Fellowship in Reproductive Medicine since 2007, and by FOGSI for basic as well as advanced infertility training since 2008 Member of Editorial board of ‘Worldwide IVF’ and peer reviewer for ‘Journal of Human Reproductive Sciences’ Over 15 publications in indexed journals and 20 chapters in textbooks for ob/gyn and reproductive medicine Over 150 guest lectures and orations in national /international conferences. Prof. Dr. Abha Majumdar Director and Head Center of IVF and Human Reproduction Sir Ganga Ram Hospital, New Delhi, INDIA
  2. 2. Pelvic tuberculosis and infertility Prof. Dr. Abha Majumdar Director and Head Center of IVF and Human Reproduction Sir Ganga Ram Hospital New Delhi
  3. 3. 2 types of tuberculosis infection in humans  Latent TB: Exposure to tuberculosis but organism is dormant or inactive. Only 5- 10 % of latent TB will progress to active disease in ones life time  Active TB: occurs by active multiplication of the bacteria to cause disease and tissue destruction in the body
  4. 4. Latent tuberculosis  Latent TB is a clinical condition defined by a positive mantoux’s test in people who have no clinical evidence of active disease. (CDC definition) According to an estimate performed in 1999, 1.86 billion, or almost 1/3 of the world’s population has exposure to TB.
  5. 5. Differences in latent and active tuberculosis Latent tuberculosis  TB bacteria enter humans and stimulates immune system to stimulate cell mediated immunity after which it remains dormant as bacteria or its DNA or antibodies. Active tuberculosis  Big pellet of myco- bacteria enters body to surpass ones immunity OR  Dormant bacteria in body start multiplying due to lowered immunity to start active disease damaging the cells and tissue BCG vaccinePrimary infection (TB bacteria enters from environment but remains dormant due to good immunity Treated tuberculosis
  6. 6.  Genital tuberculosis is mostly secondary to a primary infection in the lungs  Rarely primary infection can be through abraded skin, GIT or genitalia.  Focus of genital tuberculosis is fallopian tubes which are almost always affected bilaterally but not symmetrically. This spreads to endometrium in approx half the cases Genital tuberculosis
  7. 7.  Hematogenous (most common)  Lymphatic spread (from hilar LNs to intestinal LNs to pelvic LNs)  Direct spread from adjacent abdominal organs (rare)  Venereal transmission (very rare) The routes of spread for genital tuberculosis
  8. 8. How does tuberculosis infection cause infertility? TB infection actively affects genital organs, starts tissue destruction-tubal damage/ blockage-leads to increased risk of ectopic pregnancy or infertility due to tubal blockage. Further involvement of endometrium can lead to destruction of implantation surface and further infertility. Women with pulmonary tuberculosis or of other organs with no genital involvement get pregnant with ease
  9. 9. Tests to suspect genital tuberculosis Pelvic Ultrasound HSG Laparoscopy and hysteroscopy
  10. 10. Pelvic ultrasound Hydrosalpinx, T-O masses, encysted fluid in pelvis Thin endometrium or poor, unclear endometrium, fluid filled spaces or synechia Thick endometrium with haphazard endometrial lining
  11. 11. HSG findings in genital tuberculosis  Hydrosalpinges with fimbrial blocks  Blocked or lead pipe tubes  Scarring leading to irregular uterine margins, distorted uterine contour, pseudo-unicornuate uterus, or T shaped uteri  Synechia as filling defects, calcification  Venous and lymphatic intra-vasation of dye
  12. 12. HSG findings in genital tuberculosis
  13. 13. Laparoscopy and Hysteroscopy (closest to confirmatory tests) Direct visualization of tuberculous lesion and its sequele in pelvis and endometrium If endometrium is involved tubes will be involved in almost 100% cases
  14. 14. Advanced endometrial tuberculosis on hysteroscopy Normal uterine cavity
  15. 15. Advanced pelvic tuberculosis on laparoscopy Fitz hugh curtis or abdominal tuberculosis
  16. 16. Direct test or confirmatory tests for active disease Histopathology Visualization of bacteria
  17. 17. Epitheloid and langhans giant cells & lyphocytes Reliable & specific method of diagnosis of TB with sensitivity of 70-100% & high specificity Histopathology
  18. 18. Direct visualization of mycobacterium  Demonstration of AFB in tissue: (>10,000 org/ml)  Ziel Nelson staining  Fluorescent staining with Auramine Rhodamine  Culture (>100 org/ml in sample  Lowenstein Jenson Media- 6 wks  Bactec 460 TB system (radiometric test)-1-3 wks
  19. 19. Categories and Rx of Genital TB Category Description Initial phase (daily or thrice weekly) Continuation phase (daily or thrice weekly) I Severe forms of Extrapulm TB- Genital TB 2 HRZE 4 HR II Relapse /defaulter/ t/t failure 2 HRZES/ f/b 1 HRZE 5 HRE III Less sev forms of Extrapulm TB 2 HRZ 4 HR IV Chronic and MDR-TB cases Standard drug regimen daily- 6-9 months intensive phase 18 months continuation phase
  20. 20.  Convenient commercial combipacks of AKT-4 to be taken for 2 months daily.  One capsule of Rifampicin- 450mg  Two tablets of Pyrazinamide- 750mg each  One tablet of Ethambutol – 800mg  One tablet of Isoniazid 300mg  Followed by Rifampicin (450mg - 600mg) and Isoniazid 300mg- for another 4 months. American Thoracic Society/British thoracic Society/ UK National Institute for Health & Clinical Excellence (NICE-2006)
  21. 21. Why INDIA is different when the question of treating latent tuberculosis arises? Why can’t we follow western countries in treating latent tuberculosis? Because the prevalence of latent tuberculosis is different within these 2 areas
  22. 22. Prevalence of Tuberculosis  High prevalence countries :  INDIA =40% (800:2000)of population has been exposed to TB that is 500 million individuals have latent TB India TB 2006 RNTCP status report, N. Delhi D.G.H.S, Ministry of Health & Family Welfare  Low prevalence countries  USA < 0.5%(1:2000) of population, 2 lac individuals in country of 330 million have latent TB
  23. 23. Pitfalls in treatment of Latent TB in India  Due to constant exposure to Mycobacterium tuberculosis in high prevalence areas like India, even after treating Latent TB, the person may again get infected and this would mean repeated courses of chemoprophylaxis  Treatment of Latent TBI would only increase the logistic and financial burden on the health care system of the country
  24. 24. Treatment of tuberculosis in India  The priority of TB control program in India (RNTCP) is treatment of active TB  Testing and treating of Latent TB is not recommended in INDIA as it is a high prevalence zone, unless individual leaves the country for living in a low prevalence zone India TB 2006 RNTCP status report, N. Delhi D.G.H.S, Ministry of Health & Family Welfare
  25. 25.  In developed countries- where prevalence of TB is minimal, most new cases are only due to activation of latent TB infection  In such low prevalence countries, treatment of latent TB is a major component of TB control, by which 80-90% of active TB in community can be reduced. Latent TB in developed countries with low prevalence
  26. 26. Indirect Tests used to detect tuberculosis (cannot detect between latent and active tuberculosis)  Mantoux Test skin test  Quantiferon Gold (QFT-G) humoral test (immunological response to antigen exposure)  Antibody Detection Test: ELISA  Antigen Detection Tests such as TB PCR (Nucleic Acid Amplification Tests)
  27. 27. Prevalence of tuberculosis in India  Latent tuberculosis 40%  Active pulmonary tuberculosis 8-10%  Genital tuberculosis 3-4% of pul tub LOGISTICS: due to higher prevalence of TB in India - percentage of pulmonary TB cases will increase but ratio of pulmonary TB to genital TB will remain same (numbers will be more due to higher population and prevalence percentage of genital TB cannot exceed that of pulmonary TB)
  28. 28. Changing epidemiology of TB in INDIA by treatment of L-TB Urban MDR 51% vs rural MDR 2% Clin Infect Dis 2003 Jun 15;36(12) Second line ATT now required for neonates and infants due to emerging MDR (SGRH pub) Long term as well as fatal toxicity of ATT Epigenetic changes in progeny of Indian immigrants to US (reduction in bone marrow mass) Boston university US unpub data
  29. 29. Some scary facts  Indiscriminate use of ATT - XDR (extreme) and TDR (total)  Need of sanatoriums may re-emerge to prevent spread of infection with these resistant strains  Travel to western world may need to be quarantined  TB recently has been declared as notifiable disease like dengu plague and swine flue
  30. 30. TOI Finally, tuberculosis declared a notifiable disease TOI 09 May 2012, 06:27 IST ...They finally land up in government treatment programme," said a senior official of the revised national TB control programme (RNTCP). Multi-drug resistant TB has become a menace in India. Every year, the country reports 15 lakh new cases of TB. WHO says around... In two months, 63 new MDR-TB cases in district TOI 24 Apr 2012, 06:33 IST ... Paediatric TB a major concern in state TOI 22 Apr 2012, 02:57 IST…. Finally, tuberculosis declared a notifiable disease Kounteya Sinha, TNN May 9, 2012, 06.27AM IST NEW DELHI: India has finally declared tuberculosis (TB) a notifiable disease. The announcement signifies that with immediate effect, all private doctors, caregivers and clinics treating a patient suffering from TB will have to report every single case of the air-borne disease to the government. The notification was sent to all states on May 7. Till now, doctors in the private sector were free to treat TB patients, and weren't required to keep a record. India
  31. 31. All the TB-PCR positive women were administered standard 6- month anti-tubercular chemotherapy only….. There were no statistical differences in the two groups in the overall pregnancy rate. …-4 to 5 ml menstrual blood was collected from the remaining 60 women and subjected to PCR against M.tuberculosis. Sterilized collection tubes were provided to the patients to collect menstrual blood. Type I: suggestive of GTB on all cases of lap visual inspection 1 Confirmatory: clear evidence of GTB in the form of multiple granulomas, exudates, loculated fluid, adhesions, hydrosalpinges and beaded blocked tubes 2 Suspicious: subtle signs of chronic inflammation, e.g., patent tubes with pelvic congestion, only a few scattered small granulomas, fimbrial agglutination and phimosis, tubal sacculation, mild adhesions and straw-coloured fluid in POD.... Some quotes from our publications
  32. 32. Indian publications advocating favorable fertility outcome following ATT for endometrial PCR positivity  None of the studies are RCT’s with 2 arms in PCR positive group: one with and the other without treatment to compare the benefit of treatment  The criteria to diagnose TB PCR positivity has been menstrual blood collection by patient herself  Any pelvic finding of slightest adhesion also has been taken as indicator of TB. Apparently all other pathogens causing tubal factor infertility such as poly microbes, chlamydia, gonococci etc prevalent all over the world appear to have been abolished from Indian women…….
  33. 33. Facts about tuberculosis treatment in Northern India  500 to 600 laparoscopies done under my care of urban infertile women attending SGRH  Evidence of TB seen on laparo/hysteroscopy is only 3% to 4%  Young healthy women on ATT on indirect test approximately 30% to 40% (latent tuberculosis prevalence in the country is same 40%)  Popular indirect test done to start ATT  TB-PCR menstrual blood/endometrium  ELISA TB  Montoux and quantiferon gold  No tests
  34. 34. Some facts in my experience  Centre of IVF SGRH  1200 IVF cycles/year with a pregnancy rate of 42% in last 1 year  2400 IUI cycles/year with pregnancy rate of >24% in unexplained infertility in the last 1 year  5000 approximate new and 25000 old infertility consultations/year ATT is used in not more than 10 patients per year
  35. 35. Our ongoing study at SGRH  This is the first study of its kind being conducted in the country as prevalence of TB PCR has never been validated in fertile population.  It is a RCT where endometrial TB PCR is being done to evaluate its prevalence in infertile women with clear pelvis undergoing laparoscopic evaluation vs fertile women undergoing laparoscopic sterilization with clear pelvis  Results indicate so far the same prevalence of TB PCR positivity in the 2 groups (18.18% infertile 16% fertile women)

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