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  Table of Contents    
BRIEF COMMUNICATION  
Year : 2013  |  Volume : 56  |  Issue : 2  |  Page : 155-157
Role of newer methods of diagnosing genital tuberculosis in infertile women


1 Department of Obstetrics and Gynaecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India
2 Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India
3 Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India

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Date of Web Publication23-Sep-2013
 

   Abstract 

Genital tuberculosis is an important under-diagnosed factor of infertility. A vast majority of cases are asymptomatic and diagnosing them will help in treating such patients. We conducted a retrospective study in a tertiary care hospital of Delhi with an aim to compare different methods i.e., histopathological examination (HPE), acid-fast bacilli (AFB) smears, Lowenstein-Jensen (LJ) culture, BACTEC culture and polymerase chain reaction deoxyribonucleic acid (PCR-DNA) for diagnosing endometrial tuberculosis in infertile women. The data from 546 samples of endometrial biopsy histopathology, AFB smears and LJ culture was collected and then analyzed. Of these, HPE for tuberculosis was positive in 13, LJ culture in 10, AFB smear was positive in one case. BACTEC and PCR-DNA were feasible for 90 patients and PCR-DNA was positive in 20 and BACTEC in eight patients. Out of 20 patients with PCR positive results, 15 were only PCR positive and were subjected to hyster-laparoscopy and five had evidence of tuberculosis. Thus, none of the available tests can pick up all cases of genital tuberculosis, but conventional methods i.e., histopathology and LJ culture still has an important role in the diagnosis of endometrial tuberculosis in government setups where BACTEC and PCR are not performed routinely due to lack of resources.

Keywords: Genital tuberculosis, histopathology, mycobacterium tuberculosis culture, polymerase chain reaction

How to cite this article:
Goel G, Khatuja R, Radhakrishnan G, Agarwal R, Agarwal S, Kaur I. Role of newer methods of diagnosing genital tuberculosis in infertile women. Indian J Pathol Microbiol 2013;56:155-7

How to cite this URL:
Goel G, Khatuja R, Radhakrishnan G, Agarwal R, Agarwal S, Kaur I. Role of newer methods of diagnosing genital tuberculosis in infertile women. Indian J Pathol Microbiol [serial online] 2013 [cited 2019 Sep 18];56:155-7. Available from: http://www.ijpmonline.org/text.asp?2013/56/2/155/118670



   Introduction Top


Infertility is the most common symptom in patients with genital tuberculosis. Its prevalence among the infertile in developing countries range between 5% and 20% and it is reported to be 39-41% in patients with tubal factor infertility. The  Fallopian tube More Detailss along with the endometrium are the prime areas of involvement in genital tuberculosis. These patients may present with infertility or some may have menstrual disturbances, pelvic pain or discharge per vaginum. [1] Due to its high prevalence, especially in developing countries, work-up of an infertile couple should include evaluation for tuberculosis irrespective of history or exposure, but a diagnostic dilemma arises because of varied presentations and different modalities of diagnosis. In this light, we carried out this study in order to compare the different methods, i.e., histopathological examination (HPE), acid-fast bacilli (AFB) smear, Lowenstein-Jensen (LJ) culture, BACTEC culture ( Bactenecin) and polymerase chain reaction (PCR) in diagnosing endometrial tuberculosis.


   Methodology Top


Study setting

It was a retrospective study conducted from January 2011 to October 2011 in the Department of Obstetrics and Gynecology, Pathology and Microbiology of a tertiary care hospital with an aim of comparing different diagnostic modalities of genital tuberculosis.

Participant recruitment

The present study consisted of 546 women attending gynecological out-patient department for the evaluation of infertility (defined as the inability to conceive despite regular unprotected intercourse for 1 year), of which there were 360 women who presented with primary and 186 women with secondary infertility. These patients underwent premenstrual endometrial biopsy as a routine institutional protocol for evaluation of infertility. All samples were subjected to HPE, AFB smear, LJ culture and wherever feasible (n = 90) BACTEC culture (radiometric growth detection or non-radiometric carbon dioxide growth detection with BACTEC alert 3D) and PCR method of deoxyribonucleic acid (DNA) amplification of 165 bp region in 65 kDa gene of mycobacterium tuberculosis were performed. Patients with only PCR positivity underwent hystero-laparoscopy for evidence of tuberculosis. The data was collected and then analyzed.


   Results Top


The average age of patients presenting with infertility was 26.95 years.

Out of total 546, 52 samples were inadequate for opinion and 13 (2.63%) had their endometrial biopsy report positive for evidence of tuberculosis such as chronic inflammation or granuloma [Table 1].
Table 1: Distributi on of pati ents according to HPE

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All samples (n = 546) were sent for AFB smear and LJ culture in the Department of Microbiology. Out of these, AFB smear and LJ culture were positive in only one case though that the sample was inadequate for histopathological opinion. Only LJ culture was positive in three samples. HPE and LJ culture were positive in one case. Out of 90 samples analyzed by BACTEC and PCR, LJ culture along with BACTEC or PCR positivity was seen in five patients (n = 90) [Table 2].
Table 2: Distributi on of pati ents according to LJ culture

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Of the 90 samples sent, BACTEC culture was positive in eight of them (8.8%). BACTEC and LJ culture was positive in four samples, BACTEC with HPE for two and only BACTEC was positive in two patients [Table 3].
Table 3: Distributi on of pati ents according to BACTEC and PCR

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A total of 20 patients had their PCR report as positive out of 90 samples sent (22.2%) [Table 4]. PCR and other parameters like HPE or culture were positive for tuberculosis in five cases. Those (n = 15) with only PCR positivity were subjected to hystero-laparoscopy and targeted biopsies were taken. As shown in [Table 5], the evidence of tuberculosis such as tubercles, thickened tubes, hydrosalpinx and peritubal adhesions was seen in only five and the rest 10 had no signs of the disease.
Table 4: Distributi on of pati ents according to PCR

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Table 5: Laparoscopy results

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Thus, by using conventional methods i.e., HPE or LJ culture, we could diagnose 21 cases out of 546 (3.8%). These newer methods such as BACTEC and PCR could detect 18 cases of tuberculosis out of 90 (20%).


   Discussion Top


Female genital tuberculosis poses a diagnostic dilemma because of its varied presentations and lack of sensitive and specific methods of diagnosis. Culture though remains the gold standard of diagnosis; PCR method of DNA amplification gives rapid results and it requires <10 bacilli/ml for diagnosis. PCR test has also shown to be reasonably sensitive (78.5%) in diagnosis of extra pulmonary tuberculosis. [2],[3]

In the present study, 2.6% of patients had their endometrial histopatholgical slides suggestive of tuberculosis, which is less as compare to study by Thangappah et al. on 72 infertile women with tubal factor infertility, adnexal mass on ultrasound, recurrent refractory pelvic inflammatory disease and those with unexplained infertility, where they found 6.9% of endometrial samples positive for tuberculosis. [4] A study of 100 infertile women by Kohli et al. showed 4% positive results on HPE. [5] Mani et al. reported tubercular endometritis from the samples obtained from 110 infertile women in 3.6% on histology. [6] Kumar et al. studied on association of tubercular endometritis with infertility and other gynecological complaints of women in India and revealed endometrial tuberculosis in 3.2% (n = 220). [7] However, the results of our study were greater than what is reported by Khanna and Aggarwal where they had 2% positivity by HPE on premenstrual endometrial biopsy obtained from 100 patients for the evaluation of infertility. [8] In the study by Prasad et al. where they studied 150 infertile women suspected to have genital tuberculosis and subjected them to diagnostic endoscopy, microscopy, histopathology, BACTEC and PCR found 0.66% positive results on HPE. [9]

In the present study, LJ culture was positive in 1.83%, whereas it was 5.6%, 13.6%, 4.6% and 4% as reported in studies by Thangappah et al. Mani et al. Kumar et al. and Khanna and Aggarwal respectively. [4],[6],[7],[8] Kohli et al. could not diagnose any patient on LJ culture. [5]

With the use of BACTEC culture, we could diagnose tuberculosis in 8.8% (n = 90), whereas it was 3.3% in the study by Prasad et al. on 150 infertile women. [9]

PCR positive patients in our study were 22.2%. These were comparable with the results by Khanna and Aggarwal, Gupta et al. (26% and 22.5%). [8],[10] Compared to Thangappah et al. (36.7%), Kumar et al. (38.9%), Baxi et al. (32.1%) and Bhanu et al. (53.3%) the positive results were lower in this study. [4],[7],[11],[12] The study by Kohli et al. (13%) and Prasad et al. (14.6%) showed low positivity as compared with the present study. [5],[9]

The patients having positive results on HPE, AFB smear or culture were treated with anti-tubercular drugs (ATT). The patients with only PCR positive results (n = 15) revealed evidence of disease in 33.3% on laparoscopy were treated, but 66.7% cases who didn't show any evidence of tuberculosis were not given ATT as PCR cannot distinguish between live and dead bacilli. Various studies could find evidence of tuberculosis in 59.7% and 12.6% in all patients of their study group. [4],[9] As reported earlier, our study had normal laparoscopy with PCR positive in 66.7%, but it was 14.28% and 25% in the study by Baxi et al. and Bhanu et al. [11],[12] In the study by Khanna and Aggarwal only 26.3% of patients who were PCR positive had laparoscopy suggestive of tuberculosis. [8]

Starting ATT on the basis of PCR positivity alone was not done where there was no endoscopic or other laboratory evidence of genital tuberculosis seen and hence treatment on the basis of sole PCR positive results may not be advisable. Favorable infertility outcomes following ATT prescribed on the sole basis of a positive PCR for endometrial tuberculosis was shown by Jindal et al. [13] in their study on 443 infertile women, but it has been criticized by Malpani and Malpani. [14]

In the present study, HPE revealed caseation necrosis, suggestive of tuberculosis even when all the other diagnostic modalities for the disease were negative making it a very useful tool in the diagnosis of tuberculosis.

The limitation of this study was that BACTEC and PCR were performed only in 90 cases out of total 546. PCR negative cases were not subjected to laparoscopy, which would have been helpful to detect the disease in them.


   Conclusion Top


Conventional methods of diagnosing tuberculosis, i.e., HPE and LJ culture also have a place, especially in government setups where BACTEC and PCR are not done routinely due to lack of resources. Though, culture remains the gold standard for the diagnosis of tuberculosis, PCR should be collaborated with histopathology or culture or laparoscopy before starting treatment. A larger case-control studies are required to suggest the most appropriate and cost-effective test for the diagnosis of genital tuberculosis. Until date, none of the available tests can pick up all cases of genital tuberculosis.

 
   References Top

1.Botha MH, Vander Merwe FH. Female genital tuberculosis. S Afr Fam Pract 2008;50:12-6.  Back to cited text no. 1
    
2.Singh KK, Muralidhar M, Kumar A, Chattopadhyaya TK, Kapila K, Singh MK, et al. Comparison of in house polymerase chain reaction with conventional techniques for the detection of Mycobacterium tuberculosis DNA in granulomatous lymphadenopathy. J Clin Pathol 2000;53:355-61.  Back to cited text no. 2
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3.Rimek D, Tyagi S, Kappe R. Performance of an IS6110-based PCR assay and the COBAS AMPLICOR MTB PCR system for detection of Mycobacterium tuberculosis complex DNA in human lymph node samples. J Clin Microbiol 2002;40:3089-92.  Back to cited text no. 3
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4.Thangappah RB, Paramasivan CN, Narayanan S. Evaluating PCR, culture and histopathology in the diagnosis of female genital tuberculosis. Indian J Med Res 2011;134:40-6.  Back to cited text no. 4
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5.Kohli MD, Nambam B, Trivedi SS, Sherwal BL, Arora S, Jain A. PCR based evaluation of tubercular endometritis in infertile women of North India. J Reprod Infertil 2011;12:9-14.  Back to cited text no. 5
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6.Mani R, Nayak S, Kagal A, Deshpande S, Dandge N, Bharadwaj R. Tubercular endometritis in infertility: A bacteriological and histopathological study. Indian J Tuberc 2003;50:161.  Back to cited text no. 6
    
7.Kumar P, Shah NP, Singhal A, Chauhan DS, Katoch VM, Mittal S, et al. Association of tuberculous endometritis with infertility and other gynecological complaints of women in India. J Clin Microbiol 2008;46:4068-70.  Back to cited text no. 7
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8.Khanna A, Agrawal A. Markers of genital tuberculosis in infertility. Singapore Med J 2011;52:864-7.  Back to cited text no. 8
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9.Prasad S, Singhal M, Negi SS, Gupta S, Singh S, Rawat DS, et al. Targeted detection of 65 kDa heat shock protein gene in endometrial biopsies for reliable diagnosis of genital tuberculosis. Eur J Obstet Gynecol Reprod Biol 2012;160:215-8.  Back to cited text no. 9
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10.Gupta N, Sharma JB, Mittal S, Singh N, Misra R, Kukreja M. Genital tuberculosis in Indian infertility patients. Int J Gynaecol Obstet 2007;97:135-8.  Back to cited text no. 10
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11.Baxi A, Hansali N, Manila K, Priti S, Dhawal B. Genital tuberculosis in infertile women: Assessment of endometrial TB PCR results with laparoscopic and hysteroscopic features. J Obstet Gynaecol India 2011;61:301-6.  Back to cited text no. 11
    
12.Bhanu NV, Singh UB, Chakraborty M, Suresh N, Arora J, Rana T, et al. Improved diagnostic value of PCR in the diagnosis of female genital tuberculosis leading to infertility. J Med Microbiol 2005;54:927-31.  Back to cited text no. 12
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13.Jindal UN, Verma S, Bala Y. Favorable infertility outcomes following anti-tubercular treatment prescribed on the sole basis of a positive polymerase chain reaction test for endometrial tuberculosis. Hum Reprod 2012;27:1368-74.  Back to cited text no. 13
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14.Malpani A, Malpani A. Anti-tubercular treatment, genital TB and infertility. Hum Reprod 2012;27:3120.  Back to cited text no. 14
[PUBMED]    

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Correspondence Address:
Geetika Goel
D-1/5, Rana Pratap Bagh, New Delhi - 110 007
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.118670

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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