26 year old Indian 26 year old Indian female with infertility female with infertility

and pelvic painand pelvic pain

Wednesday ID case Wednesday ID case conferenceconference

David Fitzgerald, MDDavid Fitzgerald, MD

March 19March 19thth, 2008, 2008

HPIHPI

► 26 yo Indian female being evaluated for 26 yo Indian female being evaluated for infertility and found to have tubal scarring on infertility and found to have tubal scarring on hysterosalpingogram. She presented hysterosalpingogram. She presented originally to her infertility specialist with originally to her infertility specialist with several years of inability to conceive and several years of inability to conceive and underwent initial fertility work up. underwent initial fertility work up.

► Was being considered for IVF when she Was being considered for IVF when she developed gradual onset of pelvic and developed gradual onset of pelvic and abdominal pain. Described abd/pelvic as abdominal pain. Described abd/pelvic as constant and sharp. No N/V/diarrhea. No constant and sharp. No N/V/diarrhea. No vaginal discharge or dysuria. vaginal discharge or dysuria.

► At that time denied fevers, chill, NS, wt loss At that time denied fevers, chill, NS, wt loss or other systemic symptoms.or other systemic symptoms.

PMHPMH

►Significant for a tuberculoma in her Significant for a tuberculoma in her brain at 10 years of age. brain at 10 years of age. Presented with seizures and headaches. Presented with seizures and headaches.

She was treated with what she recalls as She was treated with what she recalls as 2-3 months of multiple antibiotics and 2-3 months of multiple antibiotics and repeat CT scan of her brain showed the repeat CT scan of her brain showed the tuberculoma was no longer there. tuberculoma was no longer there.

►History of positive PPD at admission to History of positive PPD at admission to US US

Social historySocial history

►She has been married for five years. She has been married for five years. ►Works as an independent contractor in Works as an independent contractor in

the information technology industry. the information technology industry. ►She does not drink, smoke, take drugs She does not drink, smoke, take drugs

or use herbal medications. or use herbal medications. ►No petsNo pets►Last travel to India 2 years agoLast travel to India 2 years ago

► MedicationsMedications► Prenatal vitaminsPrenatal vitamins

► AllergyAllergy► NKDANKDA

ROSROS

► Gen: No wt loss, fevers, Gen: No wt loss, fevers, chills, fatiguechills, fatigue

► HEENT – no visual HEENT – no visual complaints, oral complaints, oral lesions, dysphagia or lesions, dysphagia or odynophagiaodynophagia

► Lymph – no Lymph – no lymphadenopathylymphadenopathy

► CV – no CP, SOBCV – no CP, SOB► Pulm – no sob, cough, Pulm – no sob, cough,

hemoptysishemoptysis

► GI – no N/V/diarrheaGI – no N/V/diarrhea► GU – no dysuria, GU – no dysuria,

hematuria, normal hematuria, normal menustral periodsmenustral periods

► Skin – no rashSkin – no rash► Neuro – No HA, focal Neuro – No HA, focal

weaknessweakness

PEPE

► T 98.7, Pulse 79, blood T 98.7, Pulse 79, blood pressure 99/65, R 16, Sat pressure 99/65, R 16, Sat 99% on RA, weight is 54.5 99% on RA, weight is 54.5 kg or 120.1 lbs. kg or 120.1 lbs.

► HEENT: Pupils are equal, HEENT: Pupils are equal, round, reactive to light and round, reactive to light and accommodation. accommodation. Extraocular movements are Extraocular movements are intact. Sclerae are anicteric. intact. Sclerae are anicteric. Oropharynx is clear. Oropharynx is clear.

► NECK: Supple. NECK: Supple. ► Lymph – no cervical, SC, Lymph – no cervical, SC,

axillary or inguinal LANaxillary or inguinal LAN► HEART: Regular rate and HEART: Regular rate and

rhythm. rhythm.

► LUNGS: Clear to LUNGS: Clear to auscultation. auscultation.

► ABDOMEN: Soft, nontender, ABDOMEN: Soft, nontender, nondistended, no nondistended, no hepatosplenomegaly, no hepatosplenomegaly, no pelvic pain and no masses pelvic pain and no masses felt. felt.

► EXTREMITIES: No clubbing, EXTREMITIES: No clubbing, cyanosis or edema. cyanosis or edema.

► NEUROLOGIC: The patient is NEUROLOGIC: The patient is alert and oriented x3 with a alert and oriented x3 with a grossly nonfocal neuro grossly nonfocal neuro exam. exam.

DataData

►WBC 7.7WBC 7.7►HGB 14.3HGB 14.3►Plt 335Plt 335►Basic panel WNLBasic panel WNL►LFTs WNLLFTs WNL►UA negative LE/Nit, no WBC or RBCUA negative LE/Nit, no WBC or RBC►UCX NEGUCX NEG

HysterosalpingogramHysterosalpingogram

Scarred Fallopian tube

Scarred Fallopian tube“T-shaped”

uterus

ImagingImaging► There is a large, multicystic There is a large, multicystic

mass in the pelvis which mass in the pelvis which abuts and surrounds the abuts and surrounds the uterus and abuts the dome of uterus and abuts the dome of the bladder. the bladder.

► This is a multi-lobulated mass This is a multi-lobulated mass with the largest portions of with the largest portions of the mass measuring up to the mass measuring up to approximately 10 by 10.2 cm. approximately 10 by 10.2 cm.

► There are multiple defined There are multiple defined cystic areas within the mass. cystic areas within the mass. Some of these cystic Some of these cystic components have thin components have thin enhancing walls.enhancing walls.

► The uterus appears The uterus appears unremarkable. unremarkable.

► The normal ovaries are not The normal ovaries are not identified. identified.

DiscussionDiscussion

Further work upFurther work up

►Pt had already had an endometrial Pt had already had an endometrial biopsy done by fertility specialist and biopsy done by fertility specialist and this revealed:this revealed:

Uterus, endometrium, biopsy- Focally necrotizing granulomatous endometritis.- AFB and GMS stains negative for AFB and fungal organisms respectively.- No hyperplasia or malignancy identified.

Further work upFurther work up

►Had also had repeat endometrial Had also had repeat endometrial biopsy and a sample of menustral biopsy and a sample of menustral blood sent for AFB cultureblood sent for AFB culture Mycobacterium tuberculosis complex Mycobacterium tuberculosis complex 

This isolate was identified by sequencing the 16s This isolate was identified by sequencing the 16s rRNA gene.rRNA gene.

►ETHAMBUTOL 5.0 S ETHAMBUTOL 5.0 S ►ISONIAZID 0.1 S ISONIAZID 0.1 S ►RIFAMPIN 1.0 S RIFAMPIN 1.0 S ►PYRAZINAMIDE 100.0 S PYRAZINAMIDE 100.0 S

Female Genital tuberculosisFemale Genital tuberculosis

►Manifests as infertility, menstrual Manifests as infertility, menstrual irregularities, and chronic pelvic or irregularities, and chronic pelvic or lower abdominal painlower abdominal pain

►Fallopian tubes are most common Fallopian tubes are most common infected organ followed by the infected organ followed by the endometrium (50-60%), ovary (20-30%) endometrium (50-60%), ovary (20-30%) and cervix (5-15%)and cervix (5-15%)

►Many pts have a history of TB Many pts have a history of TB elsewhere or prior Tb treatmentelsewhere or prior Tb treatment

EpidemiologyEpidemiology

► Represents 1-2% of all diagnosed TB cases in Represents 1-2% of all diagnosed TB cases in most seriesmost series Although estimated that 5-13% of pulmonary TB Although estimated that 5-13% of pulmonary TB

patients develop genital TBpatients develop genital TB

► 5-10 percent among infertile patients 5-10 percent among infertile patients worldwideworldwide Less than 1% in US, closer to 20% in IndiaLess than 1% in US, closer to 20% in India

► Median age 28 (usually 20-40 years of age)Median age 28 (usually 20-40 years of age)

See: Namavar Jahromi,B, Parsanezhad,ME,Ghane,Ghane-Shirazi R. (2001). See: Namavar Jahromi,B, Parsanezhad,ME,Ghane,Ghane-Shirazi R. (2001). Female genital tuberculosis and infertilityFemale genital tuberculosis and infertility. International Journal of Gynecology . International Journal of Gynecology and Obstetrics (75). 269-272.and Obstetrics (75). 269-272.

PathogenesisPathogenesis

►Almost always secondary to TB Almost always secondary to TB elsewhere in bodyelsewhere in body

►Primary genital Tb is very rare but has Primary genital Tb is very rare but has been described in partners of male been described in partners of male patients with genitourinary TBpatients with genitourinary TB

Sites of female genital TBSites of female genital TB

► Fallopian Tube TuberculosisFallopian Tube Tuberculosis Tends to be bilateralTends to be bilateral Tubes become congested with flimsy adhesions that then Tubes become congested with flimsy adhesions that then

progress to dense adhesionsprogress to dense adhesions► Endometrial involvementEndometrial involvement

Is secondary to Fallopian infectionIs secondary to Fallopian infection Usually grossly normal appearing however in advanced disease Usually grossly normal appearing however in advanced disease

may be atrophic or have an obliterated endometrial cavitymay be atrophic or have an obliterated endometrial cavity► OvarianOvarian

Ovary may be surrounded by dense adhesions or may be site of Ovary may be surrounded by dense adhesions or may be site of tubo-ovarian cysts or abscesstubo-ovarian cysts or abscess

► OtherOther Cervical TB as well as vaginal and vulva TB have been reportedCervical TB as well as vaginal and vulva TB have been reported

Clinical presentationClinical presentation

► Infertility – Infertility – 40-80% incidence of infertility in patients with 40-80% incidence of infertility in patients with

female genital TBfemale genital TB►Chronic lower abd or pelvic pain – 20-50%Chronic lower abd or pelvic pain – 20-50%

Pain is non-characteristic, chronic, dull, with Pain is non-characteristic, chronic, dull, with possible episodes of acute painpossible episodes of acute pain

►Alterations in menstrual pattern – 10-50%, Alterations in menstrual pattern – 10-50%, amenorrhea, menorrhagia or postmenopausal amenorrhea, menorrhagia or postmenopausal

bleedingbleeding

►Comparative presence of symptoms Comparative presence of symptoms and signs in groups of women and signs in groups of women suffering from infertility and suffering from infertility and gynaecological problems.gynaecological problems.

►See Table 1 in: Jindal, UN. See Table 1 in: Jindal, UN. An algorithmic approach to female genAn algorithmic approach to female genital tuberculosis causing infertility.ital tuberculosis causing infertility. Int J Tuberc Lung Dis. 2006 Int J Tuberc Lung Dis. 2006 Sep;10(9):1045-50. Sep;10(9):1045-50.

DiagnosisDiagnosis

► Female genital Tb is a pauci-bacillary disease Female genital Tb is a pauci-bacillary disease ► Endometrial biopsy for path and culture is Endometrial biopsy for path and culture is

most common diagnostic toolmost common diagnostic tool► Best time to perform is shortly before Best time to perform is shortly before

menustration as lesions are likely to be close menustration as lesions are likely to be close to surface of endometrium during this phaseto surface of endometrium during this phase

► Histopath positive in 50-60%Histopath positive in 50-60% often granulomas, and caseation necrosisoften granulomas, and caseation necrosis

► Culture of bxp, menustrual blood, tubal bxp Culture of bxp, menustrual blood, tubal bxp material or peritoneal fluid may all be positivematerial or peritoneal fluid may all be positive

►Results of diagnostic tests for TBResults of diagnostic tests for TB

►See Table 2 in: Jindal, UN. An See Table 2 in: Jindal, UN. An algorithmic approach to female genital algorithmic approach to female genital tuberculosis causing infertility. Int J tuberculosis causing infertility. Int J Tuberc Lung Dis. 2006 Tuberc Lung Dis. 2006 Sep;10(9):1045-50. Sep;10(9):1045-50.

HysterosalpinogographyHysterosalpinogography

►Visualization of uterine cavity, and Visualization of uterine cavity, and fallopian tubes by injection of fallopian tubes by injection of radioopaque contrast in the uterus radioopaque contrast in the uterus through the cervixthrough the cervix

► If performed during acute disease may If performed during acute disease may lead to worseninglead to worsening

►Multiple findingsMultiple findings

LaparoscopyLaparoscopy

► Findings depend on the Findings depend on the stage of disease and stage of disease and include, miliary include, miliary granulations, plaques, granulations, plaques, adhesions, congestionadhesions, congestion

► Findings on Findings on laparoscopy/laparotomy in 70 laparoscopy/laparotomy in 70 Group I patients with Group I patients with infertilityinfertility

► See Table 3 in:See Table 3 in:

Jindal, UN. An Jindal, UN. An algorithmic approach to algorithmic approach to female genital female genital tuberculosis causing tuberculosis causing infertility. Int J Tuberc infertility. Int J Tuberc Lung Dis. 2006 Lung Dis. 2006 Sep;10(9):1045-50. Sep;10(9):1045-50.

TreatmentTreatment

► Medical treatment is main mode of therapyMedical treatment is main mode of therapy► Similar to treatment elsewhere in bodySimilar to treatment elsewhere in body► Much less need for surgical interventionMuch less need for surgical intervention► 4 drug therapy with INH, Rif, Ethambutol, 4 drug therapy with INH, Rif, Ethambutol,

PZA, followed by 2 drug therapy PZA, followed by 2 drug therapy ► 6 month course followed by repeat 6 month course followed by repeat

endometrial samplingendometrial sampling► Results generally successful – 97% in one Results generally successful – 97% in one

studystudy

Pregnancy following Female Pregnancy following Female genital TBgenital TB

►Full term pregnancy is uncommon Full term pregnancy is uncommon following genital TB – 10%following genital TB – 10%

►Pregnancy is more likely to result in Pregnancy is more likely to result in ectopic pregnancy or miscarriageectopic pregnancy or miscarriage

► IVF – unclear success rate but may be IVF – unclear success rate but may be as high as 20%as high as 20%

Infertility outcomeInfertility outcome

►Outcome of infertility group (Group I) Outcome of infertility group (Group I) following ATT and specific ARTfollowing ATT and specific ART

►See Table 5 in: Jindal, UN. An See Table 5 in: Jindal, UN. An algorithmic approach to female genital algorithmic approach to female genital tuberculosis causing infertility. Int J tuberculosis causing infertility. Int J Tuberc Lung Dis. 2006 Tuberc Lung Dis. 2006 Sep;10(9):1045-50. Sep;10(9):1045-50.

Search PubMedSearch PubMed

►Female Genital TuberculosisFemale Genital Tuberculosis Case ReportsCase Reports ReviewReview Differential DiagnosisDifferential Diagnosis TherapyTherapy

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