The abuse, misuse and overuse of TB PCR testing of the endometrium is causing confused gynecologists to overtreat infertile women with ant TB drugs

2. Dr Aniruddha Malpani, MD
www.drmalpani.com

3. Gynecologists seem to be diagnosing
endometrial TB at the drop of a hat
for all infertile women.

4.  Tuberculosis is endemic in India
 Genital TB can cause infertility
 Can cause symptoms ( amenorrhea, pelvic
pain, abnormal uterine bleeding)
 Is often silent
 Hard to confirm this diagnosis in the lab,
because it's very difficult to grow the TB
bacillus in vitro.

5.  HPE
 AFB microscopy
 Culture in L-J media
 Bactec
 Guinea pig inoculation

6.  Lots of false negatives
 Pauci-bacillary TB
 Empiric TB treatment based on clinical
findings. If patient improves clinically,
diagnosis is confirmed

17.  Clinical impression
 “Suspect” tuberculosis on clinical grounds
 “Doughy feel”
 Thin endometrium on scans
 Adhesions on laparoscopy
 Repeated failed IVF cycles

19.  While in the past the diagnosis was often
missed, today the problem is exactly the
opposite !
 Gynecologists are overdiagnosing genital TB,
based on a positive endometrial TB PCR
( polymerase chain reaction) test result.

20.  Detection is based on multiplication not of
whole bacilli, as in culture, but of their
genetic material, chromosomal DNA or
ribosomal RNA
 In principle, from one target sequence, of
one bacillus, the reaction can produce
millions of copies and thus yield a positive
result
20

21.  Simple , Rapid and Sensitive
Amplifies a DNA sequence which is unique to
mycobacteria.
 Positive test = Presence of mycobacterial
DNA is present in the endometrium.
 If TB PCR of endometrium is positive =
patient has endometrial TB
 Extremely logical , but very flawed. Let's see
why by starting from first principles.

22.  It does NOT mean the patient has genital TB !
 All it tells us that a few molecules of
mycobacterial DNA was found in the sample
processed in the lab.

23.  The type of mycobacteria
 The DNA sequence amplified is not specific only
to M tuberculosis - it is found in many other
mycobacterial species as well.
 Are the mycobacteria alive or dead?
 Where did the mycobacteria came from ?
(contaminant from the OT or the lab)

24.  Not just Mycobacterium tuberculosis or
Mycobacterium leprae
 Mycobacteria are a diverse group of rod-
shaped bacteria that include more than 100
different species. The others which are far
commoner, are called Nontuberculous
mycobacteria (NTM), environmental
mycobacteria, atypical mycobacteria and
mycobacteria other than tuberculosis (MOTT).

25.  Environmental mycobacteria are found
practically everywhere - even in the water in
the lab which is used to clean the instruments

26.  Fools both pathologists and gynecologists
 Pathologists are forced to report what they
see – do not provide any clinical
interpretation
 Gynecologists – knee jerk reflex ! Positive test
result = disease = treat !

28.  Fail to realize that a positive PCR report is
very non specific
 It’s because it so sensitive that it gives rise to
so many false positives, which mislead both
doctors and patients.

29.  With a positive TB PCR, the odds are that a
positive result ( in an asymptomatic patient)
means that there is something wrong with
the test, not with the patient .
 These mycobacteria have created iatrogenic
harm - Non pathogenic Ubiquitous
Mycobacteria - NUM !

30.  When the TB PCR test is positive,
gynecologists then rely on even more
unreliable tests ( such as Quantiferon Gold,
TB PAMP testing, and TB IgG and IgM
antibody tests) to "confirm" their diagnosis ,
even though the Government of India has
banned many of these tests because they are
so unreliable !

31.  New class of in vitro
assay that measure
interferon (IFN-γ)
released by sensitized T
cells after stimulation by
M. tuberculosis
antigens.
 Measures immune
reactivity to M.tb.
31

35.  What happens if they give conflicting
results ?
 For example, one test may be positive and
the other is negative !
 Which should you trust ?

36.  Clinical suspicion confirmed !
 Patient is happy that the doctor has finally
found out why the endometrium is thin; or
why the IVF cycles have failed .
 Few patients may get pregnant after starting
the antiTB medicines, this doesn't mean that
there was a cause and effect relationship
between the treatment and the pregnancy.

37.  Tragic ! Most of these patients don't have TB
at all
 Overdiagnosis causes havoc in the life of
infertile couples
 Unnecessarily exposed to nine months of
toxic drugs
 Time wasted , during which her ovarian
reserve and fertility will go down.
 Divorce

38.  Harming the country's TB control program
 The misuse of antiTB drugs leads to drug-
resistant TB ( MDR and XDR) , which is the
man-made result of interrupted, erratic, or
inadequate TB therapy.

39.  Can’t hurt !
 Why take a chance ?
 Patients want you to do something !
 It’s expected that doctors will always
prescribe medicines !
 Doctors are scared that if they “do nothing”
they will lose their patient

40.  Mindless overdiagnosis
 Overtreatment
 TORCH tests
 NK cells
 Pressure to test and treat – from both patient
and doctor !
 Marketing pressures