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Genital Tuberculosis: Is It All Circumstantial?

 
·         Why has this Q been asked?

·         In clinical practice we do not have an easy answer to lab diagnosis of genital TB

·         On most occasions we tend to make a presumptive diagnosis and start the treatment

·         TB is a classic case where the treatment is used to prove the diagnosis

My reply to the Q: Is It All Circumstantial is Yes and No!

·         This diagnostic dilemma arises because of varied clinical presentations, diverse results on imaging and endoscopy and a mixed bag of bacteriological and serological tests. Hence genital tuberculosis is a diagnosis based on the collective evidence from all these

Routine clinical scenario

·         Mrs A, 25 yrs nulligravida wants solution of her primary infertility of 4 years

·         Her M/H is regular

·         She has no past history of TB (in most cases this is true)

·         Her G/E is non contributory

·         Gyne Examination reveals normal size uterus with restricted mobility

Blood routine

·         Non-contributory except for the ESR being 56

·         Does this in any way lead you to genital tuberculosis?

ESR

·         Very non-specific investigation

·         Used previously for suspecting TB

·         Now used for prognostication and judging the treatment response

·         No other role

She is subjected to pelvic USG: Non-contributory

Pelvic ultrasound, a useful initial screening test, was able to identify In subjects with known genital tuberculosis:

·         Ascites/ loculated fluid (100%),

·         Adnexal mass (93%),

·         Peritoneal thickening(69%),

·         Omental thickening(61%), and

·         Endometrial involvement (83%)

If at this stage on any of these findings a genital pelvic TB is labeled: It is indeed Circumstantial

Review of her past investigations revealed an HSG plate

Chauhan reported genital TB in 7.5% of hysterosalpingography performed for infertility.

In their series, the most common feature was Isthmic-ampullary tubal occlusion in 81% cases With terminal hydrosalpinx in 16% cases and The uterus affected by scarring, irregular outline and intravasations in 27% cases,

HSG

·         This imaging technique became so over-hyped that orations were delivered on use of HSG in diagnosis of female genital tract TB

·         But we all know how circumstantial it was

·         We respect the practice at that time as competent modalities were limited or nonexistent 

X-ray chest

·         In view of this HSG picture she was subjected to X-ray chest which was normal

She was therefore taken up for endoscopy work-up

·         Endoscopy has the dual advantage of pelvic organ visualization and sample collection from inaccessible sites for laboratory diagnosis.

The fallopian tubes are almost universally affected, as evidenced by

·         Complete tubal block in            80%,

·         Adhesions and calcifications in 43%,

·         Adherent mass in                     35.8%,

·         Nodular sclerosis in                  11.7%, and

·         Miliary tubercles and ascites in 9.4% cases of genital TB

She was also subjected to hysteroscopy

Diagnostic hysteroscopy allows visualization of

·         Tubercles,

·         Microcaseation,

·         Distorted ostium,

·         Synechia, and

·         Outpouching in the endometrial cavity.

Biopsy may also be taken from suspicious sites.

Search for M. Tuberculosis continues

A saline wash matter was taken from the pelvic cavity for further investigations. The suspicious lesion was biopsied on hysteroscopy

How should the material be sent?

·         Material for laboratory diagnosis should be collected with two objectives, histology and culture, and the tissue should be divided into two equal parts. One part should be sent as per routine laboratory requirements in a fixative solution (formalin or Bouin’s fluid).

·         The other part for culture should be collected in a sterile container

·         Bacterial overgrowth should be prevented by storing it at a temperature of 40 to 80C.

·         Direct inoculation on the culture medium at the site of collection itself has also been described.

On staining for AFB two possibilities: AFB +ve or - ve

·         AFB +ve: Not definitive – could be Non Mycobacterial Tuberculosis organisms

·         AFB -ve: Doesn’t rule out, Number of the organisms may be very few, If so: GROW THEM (culture them!)

AFB Smear (Z.N. Stain)

·         It was negative

·         If it was positive it could have become nearly definitive and the circumstantial circuit would have ended

What about the good old HxP Histopathology

·         A histological diagnosis used to be made with traditional HE staining as well as with ZN staining with a basic fuschin dye.

·         The classic features are caseous necrosis,  giant cells, epithelial cell clusters and lymphocyte infiltration.

·         Lesions are highly indicative of but not exclusive to TB unless tubercle bacilli are seen.

·         BUT a similar picture may also be seen in fungal or sarcoid disease

HP report showed caseous necrosis, giant cells, epithelial cell clusters and lymphocyte infiltration – Does this clinch the issue? Not necessarily!  Lesions are highly indicative of but not exclusive to TB unless tubercle bacilli are seen. A similar picture may also be seen in fungal or sarcoid disease. If AFB was positive and HP also positive then this would have ended the search: it is definitive. As in this patient AFB was negative and HP indicative it is still circumstantial and matter needs to be pursued

So the material was subjected to culture as the search for the illusive AFB continues because…

AFB – ve & HP + ve             Poor concentration of AFB in the sample of genital TB

OR

AFB – ve & HP + ve            fungal or sarcoid disease

AFB Culture

·         Higher sensitivity than AFB smears.

·         Culture methods are still the gold standard in the detection of genital TB.

·         Helps in exact identification of Mycobacterium and putting up drug sensitivity.

Culture

·         Culture is traditionally performed on solid egg or agar based media such as Lowenstein Jenson (LJ) or Middlebrook THIO and microinoculated at 37°C under 5% CO2.

·         Growth is detected after 4-5 weeks.  Colonies are seen if the bacillary count is more than 1000 bacilli. This improves the sensitivity as compared to ZN staining alone which requires 10,000 bacilli to be positive

·         However improvements in media have allowed colonies to grow even when the count is 100 bacilli

·         This is possible with the use of liquid based media radiometric growth detection such as BACTEC 460 or non-radiometric CO2 growth detection with BACTEC ALERT 3 D

·         This assay system is based on generation of radioactive carbon dioxide from substrate palmitic acid.

·         This method has been extensively used all over the world and Growth can be detected in 5-10 days in this system.

·         Inclusion of NAP (beta nitro alpha acetyl amine beta hydroxypropiophenone) can help in distinguishing M. TUBERCULOSIS (inhibited) from other mycobacteria.

·         This system has been widely used for drug susceptibility testing and is currently used as a comparative standard

·         BACTEC has a sensitivity of 80- 90%

·         LJ medium has a sensitivity of only 30- 35%.

·         This high sensitivity is particularly useful in cases of genital TB as traditional methods show poor recovery of acid fast bacilli

BACTEC report in this patient

·         Showed AFB organisms POSITIVE

·         Does this mean we are beyond circumstantial now

·         Yes, this is nearly definitive

·         The last frontier is to identify that these AFBs are M. TB

AFB Identification

·         Possible only after positive culture.

·         Very important to identify mycobacterium as it may or may not be pathogenic.

·         Identification by bacteriological method has about 60 – 70 % sensitivity

·         Identification by molecular methods has a sensitivity of >90 %

AFB identification by molecular methods

·         Two main methods.

o    TMA (Thermal Amplification)

o    PCR (Polymerase Chain reaction)

o    TMA is RNA based amplification.

o    PCR is DNA based amplification.

o    TMA is positive only if bacilli are viable while PCR is positive with both dead and viable mycobacterium.

PCR

o    The polymerase chain reaction is a technique that shows rapid detection and quantification of few DNA copies with high sensitivity and specificity.

o    Its sensitivity is VERY high

o    It requires only < 10 bacteria/ml of specimen 

o    Rapid method with results available within a day of the DNA being extracted from the sample.

o    It can also be applied to sterile fluids like peritoneal fluid where the culture is difficult due to a low bacterial load

Now the combinations

Culture  +ve  PCR +ve:

o    DEFINITIVE!

Culture  +ve  PCR - ve :

o    Culture remains the gold standard for diagnosis of TB

Culture  -  PCR - ve :

o    Not TB

Typical Clinician’s Question

Can the material could be subjected straight to molecular method of identification: PCR ?

o    The answer is may be!

o    But you must be ready to face a very small possibility of a false positive (lab contamination)

o    Fastest and most definitive solution

o    PCR in 24 hours and HP report confirming tuberculous lesion within 3 to 4 days will be a fair compromise

o    But none alone
 

 
 
 

ACTIVE PHASE ONSET: 3CM / 4 CM?

 

·         Are we splitting hairs? Not really

Clarification is sought as improper diagnosis of commencement of active labour can lead to

·         Prolongation of latent phase or

·         Dangers of late intervention

Blix E, Kumle M, Øian P. Tidsskr Nor Laegeforen. 2008 Mar 13;128(6):686-9.
Institutt for klinisk medisin, Universitetet i Tromsø, 9038 Tromsø

·         Consensus on features of active labour lacks scientific agreement

·         As many women are assessed to have slow progress of labour, the duration of labour should be systematically recorded.

·         Prospective studies are needed on labour duration, the consequences of prolonged labour and the appropriate timing for intervention

Prolongation of latent phase
 (Obstet Gynecol. 2005 Apr;105(4):705-9)

·         A longer latent phase was associated with a greater rate of cesarean delivery, although only after 18 hours did a majority of induced labors result in cesarean.

·         Chorioamnionitis and postpartum hemorrhage were more frequent with latent phases of labor greater than 18 hours (16% and 26%, respectively), although these diagnoses did not translate into greater risk of transfusion, hysterectomy, or prolonged hospitalization.

The crux of the debate: 3 or 4?

·         However there is no disagreement to the fact that women in active phase of labor are at least 4 cm dilated

·         Many women will demonstrate some dilatation (1-3 cm) for weeks or months prior to the onset of true labor

·         Therefore the crux of the debate: 3 or 4?

A comprehensive view becomes necessary

·         Is it accompanied by contractions atleast 5 minutes apart or less, 60 seconds or longer, radiating in nature, may have back pain

·         Accompanying other signs like a small bag of water

·         Mother becoming focused, losing hunger, decreasing talkativeness, having deliberate movements

In that case active phase has begun

·         If these features are found at 3 cms. for this mother 3cms is the commencement of active phase for her

However there is no debate after 4 cms:

·         In all subjects at 4 cms and beyond active phase has begun

·         If these features are not found at 4 cms it means there is inefficient uterine action or there is some passenger problem

·         Review the findings again and take remedial measures

Research Horizons

Chen DC, Yuan SS, Su HY, Lo SC, Ren SS, Wu GJ; Urinary cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate changes in spontaneous and induced onset active labor Acta Obstet Gynecol Scand. 2005 Nov;84(11):1081-6

·         Our results suggest that U cGMP/Cr and U cAMP/Cr can serve as easily obtained secondary messenger markers of myometrial contractility and cervical ripening at the onset of active labor.

·         The NO-cGMP system and the G-protein alpha-cAMP system in the human uterus may concomitantly contribute to uterine quiescence during pregnancy and show downregulation in U cGMP/Cr and U cAMP/Cr at the initiation of active labor

·         Urinary cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate changes can herald the onset of active labour

·         Urocortin dysfunction?
 Shang T, Cheng ZX, Jin F, Zhang L: Level of urocortin mRNA during labor and effect of urocortin on myometrial contractility in vitro Zhonghua Fu Chan Ke Za Zhi 2006 Apr;41(4):249-52

·         The expression level of urocortin mRNA in placenta and myometrium after the onset of labor were higher than before labor

·         Urocortin itself did not affect myometrial tension development at all concentrations tested, but it markedly increased PG-induced labour related events

Future

·         It is possible that in future it may simply suffice to measure Urinary cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate and/or urocortin levels and diagnose whether active labour has begun

·         There may not be any need to assess it through the amount of dilatation of cervix

Blame it on the genes
 (Bukowski R, Hankins GD, Saade GR, Anderson GD, Thornton S. Labor-associated gene expression in the human uterine fundus, lower segment, and cervix. PLoS Med. 2006 Jun;3(6):e276)

·         Our results provide support for many of the established processes of parturition and also describe novel-to-labor genes not previously associated with this process.

·         The elucidation of these mechanisms likely to be fundamental for controlling labor is an important prerequisite to the development of effective treatments for major obstetric problems

Back To Clinical Practice

·         Many variables step-in

o    Thickness of the examining finger

o    It is important to note that not every mother will respond in the same way or with the same behaviors and signs

o    Cervical dilatation may not be the only determining factor

To conclude

·         At 4 cms and beyond: Active labour is on

·         If associated signs of active labour (contractions atleast 5 minutes apart or less, 60 seconds or longer, radiating in nature, may have back pain, accompanying other signs like a small bag of water, mother becoming focused, losing hunger, decreasing talkativeness, having deliberate movements) have appeared even at 3 cms then for this mother active phase has begun
 

REDUCING SYSTEMS

IN

PRE-ECLAMPSIA

The etiology of preeclampsia is still unknown. The 4 hypotheses currently accepted are the placental ischemia hypothesis, genetic hypothesis, the immune maladaption and hypothesis of the imbalance between free oxygen radicals and scavengers in favor of oxidants. At the present is most popular the theory of oxidative stress, that lead to increased production of lipid peroxides, thromboxane A2 and decreased level of prostacyclin. This imbalance triggers endothelial dysfunction and its clinical manifestation. Scavenging reducing systems have protective effect in this process. This chapter reviews these oxidative stress and the current status of reducing systems like Vit. C and E in pre-eclampsia.

 

 

OXIDANT-ANTIOXIDANT INTERACTIONS:

 

Free Radicals And Reactive Oxygen Species:

 

     A free radical is any molecular species capable of independent, albeit brief, existence that contains one or more unpaired electrons.

     There are comprehensive reviews on interactions between reactive oxygen species and reducing systems in human health and disease.  Tissue ischemia/hypoxia followed by reperfusion is one established generator of reactive oxygen species and lipid peroxidation in vivo. Postischemic reperfusion generation of reactive oxygen species could be one source of oxidative injury in placentae of women with preeclampsia.

 

     Recently decreased expression of reducing systems thioredoxin and glutaredoxin in placentae from pregnancies with pre-eclampsia and intrauterine growth restriction have been documented. Placental tissue from normal pregnancies (NC), severe pre-eclampsia with fetuses small for gestational age (SPE), mild pre-eclampsia with fetuses small for gestational age (MPE) and pregnancies with small fetuses for gestational age without any sign of pre-eclampsia (IUGR) was collected immediately after delivery. The levels of these proteins were increased approximately 2- to 3-fold in the pre-eclamptic placentae compared to the normal placentae. These results indicated that the pre-eclamptic placentae were exposed to oxidative stress and that the protein thiol/disulphide oxidoreductases were adaptively induced in pre-eclamptic placentae, suggesting possible roles for thioredoxin, glutaredoxin, and protein disulphide isomerase in protecting placental functions against oxidative stress caused by pre-eclampsia.

 

 

     A diverse array of cellular and extra cellular fluid reducing systems has evolved to control and compartmentalize, but not necessarily eliminate, the production of reactive oxygen species; Reducing systems MPSTahomarmal and pre-eclamptic pregnancies include the enzymatic reducing systems (super oxide dismutases (SOD), catalasMPSMPSMPSTahomaidase), and transition metal binding proteins (transferrin, ceruloplasmin, aMPSTahMPSTahoma

 

Lipid Peroxidation:

 

     Lipid peroxidation has received a great deal of attention in preeclampsia. The primary products of lipid peroxidation, lipid hydroperoxides, function in normal physiology. Reactive oxygen species/ reducing system imbalances can lead to uncontrolled lipid peroxidation.

 

Oxidative Stress And The Vascular Endothelium:

 

Circulating lipids have diverse effects upon endothelial cell function, and dyslipidemia is associated with endothelial cell dysfunction. Continued oxidation is facilitated (primed) by “ feed-forward” interaction of lipid hydroperoxides in the LDL particle with cell-derived oxidants. Also, the “oxidative stress theory” of preeclampsia finds indirect support in that many of the endothelial abnormalities described in preeclampsia can be reproduced by lipid peroxidation in experimental system. 

 

PLACENTAL OXIDATIVE STRESS:

 

 

Placental Nitrotyrosine, Xanthine Oxidase, And The Issue Of Reperfusion Damage:

 

     Tissue hypoxia/ ischemia followed by reoxygenation can generate reactive oxygen species and lipid peroxidation in vivo. If conjoined with vascular reperfusion, placental hypoxia /ischemia could result in oxidative damage and elaboration of cytotoxic reactive oxygen products into the circulation. However, it is unclear whether placental postischemic reoxygenation damage occurs in preeclampsia.

     Placental trophoblasts produce nitric oxide. Preeclampsia and intrauterine growth restriction are associated with increased expression of the endothelial isoform of nitric oxide synthase (eNOS) in the villous vessel endothelium. The role of nitric oxide (NO) in normal pregnancy and pregnancy complicated with preeclampsia (PE) and/or intrauterine growth restriction (IUGR) is under investigations.

 

Placental Lipid Peroxidation:

 

     The lipid peroxidation degradation product, malondialdehyde, is reportedly increased in placental tissue along with decreases in SOD activity in preeclampsia. In pre-eclampsia, increased levels of lipid peroxide and decreased SOD activity have been described in the placenta. Chemical inhibition of placental glutathione peroxides resulted in increased production of lipid hydroperoxides and an increase in the placental thromboxane to prostacyclin output ratio. The consequences of this altered ratio might include vasospasm with exacerbation of placental ischemia, increased cell damage, and increased lipid peroxidation (amplification loop)

 

DYSLIPIDEMIA AND OXIDATIVE STRESS IN PREECLAMPSIA:

 

     The dyslipidemia of preeclampsia is best understood in the context of lipid changes during normal pregnancy.

 

Lipid Metabolism In Normal Pregnancy:

 

     Circulating lipids are carried primarily in lipoproteins, which are composed MPSTahomaee and esterified lipids, proteins (apolipoprotein), and phospholipids. The two main cholesterol- carrying lipoproteins are LDL and high-density lipoproteins (HDL). The triglyceride-enrichment of LDL and HDL contributing to hyper- triglyceridemia may be due to increased cholesteryl ester transfer protein (CETP) activity during normal   pregnancy.

 

Dyslipidemia In Preeclampsia:

Super-normal increases in serum triglyceride and free fatty acids develop as early as 10 weeks’ gestation in women destined to develop preeclampsia. Nearly 50% of women with preeclampsia have triglyceride concentrations > 400 mg/ dL. Total cholesterol 12,14,101 and LDL – cholesterol concentrations are usually not different whereas HDL2 cholesterol is decreased in clinically evident preeclampsia.

 

POTENTIAL IMPACT OF DYSLIPIDEMIA ON OXIDATIVE STRESS:

 

     Free fatty acid increases might contribute to endothelial dysfunction in preeclampsia by several means. The pathogenic significance of small, dense LDL, and the formation of small, dense LDL, during normal and preeclamptic pregnancy are summarized in the next two sections,

 

Small Dense LDL Phenotype And Its Vascular Consequences: 

 

Metabolic changes producing hypertriglyceridemia generally shift the spectrum of LDL sub fractions toward a proportional increase of smaller, denser LDL. Small, dense LDL particles are relatively depleted of cholesteryl esters, and enriched in protein. Proportional increases in small, dense LDL with heightened susceptibility to oxidative modification may account for part of the increased cardiovascular risk in individuals with the small, dense LDL phenotype.  The reasons for increased oxidation susceptibility with decreasing particle size may include proportional polyunsaturated fatty acid increases  and decreased reducing systems (ubiquinol-10 and/or vitamin) per particle.

Small, Dense LDL In Normal And Pre-eclamptic Pregnancy:

 

     The normal pregnancy rise in plasma triglyceride is associated with a shift from predominantly large and buoyant LDL (no pregnancy) to intermediate and small, dense LDL (36 week’s gestation), with partial reversal by 6 weeks postpartum. LDL size correlated negatively with triglycerides (R= -0.61, P<0.01).

 

     Some studies measured the mass of three LDL sub fractions (LDL –I, II, and III) isolated on the basis of increasing density from plasma of women with preeclampsia and normal pregnancy. Preheparin hepatic lipase activity was increased in preeclampsia plasma that, by hydrolysis of LDL triglycerides, could partially explain predominance of small, dense LDL in the syndrome.

 

     It is evident that not all women with preeclampsia exhibit smaller, denser LDL relative to normal pregnancy. Apart from size differences one component of pathophysiology in preeclampsia might be abnormal maternal or placental response to (or handling of) the small, dense LDL may impart substantial increases in LDL oxidation susceptibility. The intrinsic susceptibility of isolated LDL to Cu2+ mediated oxidation is increased in preeclampsia. Whether this is a function of LDL size shift or some unrelated LDL difference is presently unclear.

 

In preeclampsia, however, evidence for the interaction of plasma lipids, reactive   oxygen species, and endothelial cell dysfunction is largely indirect, In contrast to arteriosclerosis, for example, there are currently no positive or negative reports on isolation of oxidized lipids from vascular tissues in preeclampsia.

 

LESSONS FROM EXTRACELLULAR REDUCING SYSTEMS:

 

For example, µ-tocopherol (µ-TOH) slows lipid peroxidation by scavenging lipid peroxyl radicals (LOO·). Ascorbate is thus a supreme reducing system nutrient. 133

 

Reducing System Hazards and Clinical Trials:

 

     There has been increasing interest in clinical trials of reducing systems for prevention or treatment or preeclampsia. The heterorganic function of reducing systems is exemplified by two different reducing system bioassays used to study preeclampsia. A substantial deficit in this serum reducing system activity is observed in preeclampsia relative to normal pregnancy because serum-transferring iron binding reserve (apotransferrin) is decreased.  In contrast, reducing system activity measured as the ability of plasma to scavenge water-soluble peroxyl radicals is increased in preeclampsia and this is largely a function of increased uric acid concentrations. Xanthine oxidase produces uric acid (an reducing system) but can also be a major source of local reactive oxygen species, such as hydMPSMPSTahomas (OH), can generate uric acid radicals that are themselves capable of causing cell damage. It would not be surprising if the effects of a xanthine-oxidase inhibitor, such as allopurinol, were complex in preeclampsia.

 

     In one trial vitamin E supplementation failed to have a salutary effect on the course of already established preeclampsia, but as noted, plasma vitamin E deficiency is not a characteristic of the disorder. In another report, a randomized control trial in which a combination of reducing systems were given orally for 1-2 weeks) to women with established early-onset preeclampsia (usually severe), no changes in maternal placental thiobarbituric acid- reactive substances (an index of lipid peroxidation) and no alterations in glutathione concentration were noted. There was, however, a tendency for the treated group to deliver later. Also, decreased concentration of uric acid and increased concentrations of vitamin E, but no differences in thiobarbituric acid-reactive substance, were noted in the sera of these treated subjects.

 

     In essence, although the potential for administering reducing systems to prevent or treat preeclampsia is appealing, we suggest that their incorporation into clinical care be deferred until (1) appropriate reducing systems can be established and (2) clinical trials demonstrate safety and efficacy for both mother and baby.

 

EXERCISE: AN EFFECTIVE REDUCING SYSTEM FOR PREVENTION OF PRE-ECLAMPSIA?

 

     It is reported that regular exercise increases beneficial reducing systems in pregnant women, which in turn reduces oxidative stress.

 
 
 

Exploding the Myths in Obstetrics and Gynecology: Evidence based solutions

 

I Trimester

·         Routine USG in I trimester? Yes or No?

Routine ultrasound scanning in early pregnancy is useful for determining gestational age, but benefits in terms of improved pregnancy outcome have not been established. Hence, routine use of ultrasound scanning in early pregnancy would not be warranted.

·         Do you still measure SFH?

The review found no evidence of any benefit or harm associated with the routine measurement of symphysis-fundal height (SFH) in pregnant women. However, available literature indicates that routine SFH measurement is a sound method for detecting small-for-gestational-age babies in developing countries. Hence, it should still be recommended as standard practice for antenatal care.

·         Bed rest during pregnancy for preventing miscarriage?

There is insufficient evidence of high quality that supports a policy of bed rest in order to prevent miscarriage in women with confirmed fetal viability and vaginal bleeding in first half of pregnancy.

Antenatal Care

·         Name the most effective iron with no gastric side-effects

An iron without gastric side-effects is incompetent

·         How important is dietary advice in pregnancy?

 Dietary advice is unlikely to yield any major benefits for either the infant or the mother.

·         Calcium supplementation for hypertensive disorders and related problems: How effective?

Calcium supplementation is probably beneficial for women at high risk of hypertension in pregnancy and those living in communities with low dietary intake of calcium

·         Antihypertensives When?

DP > 100 is an indication for starting Anti-hypertensives. However The benefits and harms of the use of antihypertensive agents to treat mild-to-moderate hypertension states that the practice of using these drugs, particularly in under-resourced regions, should not be abandoned until firm evidence becomes available.

  ·         Which antihypertensive? Nifedipine ?  Methyldopa ? Labetalol ? Hydralazine ? Message

No anti-hypertensive is superior to the other except parenteral Hydralazine

Pre-term Labour

·         Tocolytics for preterm labour: How effective? Which is the best?

Success in the management of preterm labour is very much related to the initiation of treatment as soon as possible and administration of corticosteroids for fetal lung maturity. Calcium channel blockers are preferred to other agents for stopping labour contractions

·         Do you routinely administer prophylactic antibiotics for inhibiting preterm labour with intact membranes?

Prophylactic antibiotic treatment for preterm labour with intact membranes has no overall benefit for in terms of neonatal outcomes. On the contrary, it increases the risk of neonatal mortality. This treatment is not recommended for routine practice. 

Beyond Term Pregnancy

·         Labour induction in post-term pregnancy: When?

Compared to waiting indefinitely or at least one week for labour to occur spontaneously, labour induction after 41 weeks of gestation is associated with fewer perinatal deaths.

Labour

·         Amnioinfusion for umbilical cord compression in labour: How much helpful?

 Trans-cervical amnioinfusion reduces the frequency of variable fetal heart rate decelerations and reduces the risk of caesarean section. 

·         Amnioinfusion for meconium-stained liquor in labour?

Amnioinfusion decreases the risk of meconium aspiration syndrome, caesarean section and neonatal morbidity. Available evidence supports its use in women with meconium-stained amniotic fluid, even in under-resourced settings, as relatively inexpensive instruments for amnioinfusion are available.

·         Mrs. A, young primi gravida comes to you in advanced labour. She has a deeply engaged head in second stage of labour. There is a thick meconium stained liquor. F.H.S: Bradycardia. What will you decide?

If speed of delivery is important, use of forceps results in a quicker birth than use of the ventouse, without any compromise to the condition of the baby at delivery, and with similar rates of perineal trauma.

·         Mrs. B, 23 yrs, G2P1, has a previous live child weighing 2.75 kg. She had an LSCS for an arrest of descent in the second stage. There was a failed forceps after which LSCS was done. At present she has a cephalic presentation with an EBW of 2.7 Kg. Will you decide for a vaginal trial this time?

In women with a cephalic presentation who had an arrest of descent in the second stage of labour during their first delivery, the chances of vaginal delivery in their next pregnancy are high, even after a failed instrumented vaginal delivery, and a trial of labour can usually be pursued

Post delivery

·         Oral fluids and food after caesarean section: early versus delayed initiation

Early initiation of feeding was associated with reduced time to return of bowel sounds, reduced postoperative hospital stay and with suggestion of reduced abdominal distention. There is no evidence to justify a policy of restricting oral fluids or food after uncomplicated caesarean section.

·         Topical umbilical cord antiseptics at birth yes or no?

 No differences were found in umbilical cord infection rates when use of a topical antiseptic was compared with dry cord care or placebo.

·         Does your neonatologist routinely intubate a vigorous term new-born with meconium stained liquor at birth?

Routine endotracheal intubation at birth in vigorous, term, meconium-stained babies has not been shown to be superior to routine resuscitation, including oro-pharyngeal suction.  

·         Prophylactic Anticonvulsants for babies with perinatal asphyxia?

The use of anticonvulsants prior to development of seizures in asphyxiated term newborns to prevent death, seizures or subsequent severe neurodevelopment disabilities was unsuccessful. Hence, routine use of anticonvulsants in asphyxiated term infants, in the absence of seizures, cannot be recommended.

Gynecology

·         You only need a Pap smear if you’re sexually active: True?

Not true. Even though most cervical cancer is associated with HPV, which is a sexually transmitted infection, there are reports of women who have never had sexual intercourse who have had cervical cancer. We don’t have an explanation for this . . . yet!

·         Are menopausal women more depressed? Are they less sexually active?

Contemporary epidemiologic and clinical studies show a decline in the prevalence of depression among women in this age group. Studies on sexual activity fail to demonstrate a consistent and predictable decline. The presence of a suitable male partner appears to play a more important role than age per se

Surgical aspects:

·         Non-closure of peritoneum gives better results instead of causing complications

·         Single dose antibiotics give equally good results compared to traditional 7 days course

·         For uncomplicated gynec surgeries, intra-op catheterization is not essential.

·         Bladder catheterization for 7 days is sufficient in cases of bladder injury and repair.

 
 
 

Case studies in Immunology of Recurrent Pregnancy Loss

 

?  Case study in Immunology of Recurrent Pregnancy Loss

?  Case Study: Mrs. M.A., 35 yrs female, G5 P0, had history of four missed abortions. All these were at or around 8 to10 weeks. On all four instances cardiac activity was documented and then there was a fetal demise. She presented to us with H/O amenorrhea 5 weeks. On examination she had an intrauterine pregnancy which was confirmed on USG. There was a distinct fetal pole, faint cardiac activity. On investigations she tested negative for APA. In view of her clinching history she was grouped as Alloimmune loss and treated for immunological losses. She was put on Tab Aspirin 1.2 mg/kg every day and Tab. Progesterone vaginal tablet 200 mgms twice a day

?  Why Progesterone? Ever-green debate. However the areas that are catching interest of scientists that are working in this field includes the immune-modulation role for progesterones.

?  Pinopodes: The endometrium generates on itself finger like projections, which are designed to physically trap the blastocyst and bring about changes at the blastocyst endometrial interface in such a way that successful nidation results. These are pinopodes. Today, the most sensitive marker indicating the receptivity of the endometrium is the pinopodes. The only known agent that has some bearing on the generation of pinopodes is progesterone.

?  At 6 weeks she had bleeding P/V. Her USG picture showed a huge sub chorionic bleed obviously more than fifty percent of the chorionic plate. At this stage she was put on Inj. Heparin 5000 I.U. subcutaneously. Aspirin and progesterone were continued.

?  WHEN DO WE USE HEPARIN? [+ ASPIRIN]

?  Her repeat USG showed a persistent sub-chorionic collection for three weeks. The fetus was growing in size matching point to point with the duration. Why did she have a SCH? What is the prognosis of SCH?    

?  At 10 weeks she spotted again. The hematoma had reduced in size indicating a resorption process supervening. Pregnancy continued satisfactorily.

?  How do pregnancies of immunological cause of failure behave after fourteen weeks? Is she out of woods?

?  OBSTETRIC OUTCOME IN PATIENTS WITH H/O SPONTANEOUS ABORTIONS

?  Patients with H/o immunological abortions were more likely to have Threatened abortions, APH, Pre-term Labour, Depressed APGAR at 1 minute and IUGR

?  She continued to be on high-risk pregnancy list of our hospital and therefore close monitoring. Heparin was discontinued at 28 weeks as the Umbilical flow notch disappeared by 20 weeks. Aspirin was discontinued one week before intervention. Disappeared notch: Satisfactory II wave of trophoblastic invasion. Her B.P. showed a rise at 34 weeks. She was subjected to USG for decision making for intervention. Satisfactory USG picture Pregnancy was continued.

?  At 37 weeks she was subjected to colour doppler study for deciding the route of delivery. Her NST was reactive As per the policy of the hospital, in view of

�  Adequate liquor,

�  Reactive NST

�  Normal flow in vessels and

�  Term pregnancy with adequate pelvis for this baby

?  She was offered a vaginal delivery. She refused a vaginal trial and insisted on a CS. She delivered abdominally a 3.3 kgms full-term normal child with  an normal APGAR

?  We use the following protocol:

�  In interval period :
® For low and moderate positive: Aspirin in a dose of 1.2 mg/kg./day till conception – Allow a conception – continue aspirin from interval period upto 36 weeks.
®For High positive: Aspirin in a dose of 1.2 mg/kg./day till conception in the interval period. Allow conception- continue aspirin from interval period upto 36 weeks. ADD Heparin in a dose of 5000 IU/ day.

�  In Pregnancy:
® For these cases we give only the post-conception protocol of aspirin or aspirin + heparin as specified

?  Immune factors: Evidence?

�  A

�  Immunotherapy, including paternal cell immunization, third-party donor leucocytes, trophoblast membranes and intravenous immunoglobulin (IVIG), in women with previous unexplained recurrent miscarriage does not improve the live birth rate.

?  B

?  Primary antiphospholipid syndrome (APS) refers to the association between antiphospholipid antibodies (APL) and adverse pregnancy outcome or vascular thrombosis.

?  Adverse pregnancy outcomes include

�  three or more consecutive miscarriages before ten weeks of gestation,