DOI: 10.7860/JCDR/2017/22659.

9463
Review Article

Recent Advances in
Obstetrics and Gynaecology

the Management of Major

Section

Postpartum Haemorrhage -
A Review
P Reddi Rani1, JASMINA BEGUM2

ABSTRACT
Postpartum haemorrhage (PPH) is a leading cause of maternal mortality and morbidity worldwide and 75-90% of these haemorrhage
results from uterine atony. Delayed and substandard obstetrics care can kill a woman within hours of Major Obstetric Haemorrhage (MOH).
Prenatal identification of at risk women, prompt assessment of blood loss, effective management and involvement of multidisciplinary
teams is of utmost importance to save the lives of these women. However, even with the best prenatal care, PPH occurs, it can occur
without any risk factors. The first step in management is achieving haemodynamic stability, second being arrest of bleeding, both are
done simultaneously. Cases of refractory PPH is managed by postpartum hysterectomy which results in complete inability in hosting
a future pregnancy, a psychological impact and risk of intra operative surgical morbidities. This review discusses the current evidence
based management of PPH, existing controversies in transfusion of blood and blood products and newer advances in this field. It was
conducted by searching the English language medical literature using Medline (1994-2015). The current scenario in developing countries
mandates research on newer and practicable strategies to tackle PPH which can be implemented effectively and have an upper edge
over the existing practices in the management of PPH.

Keywords: Artery embolisation, Compression sutures, Fibrinogen,

Tranexamic acid, Transfusion protocols, Vascular ligation

INTRODUCTION Active management of third stage of labour is a feasible, low cost

PPH remains a major cause of both maternal mortality and morbidity measure to prevent 60-70% of atonic PPH [4]. Monitoring of pulse,
worldwide more so in developing countries with an estimated blood pressure, bleeding during fourth stage of labour and using
mortality rate of 140,000 per year or one maternal death every four bedside tool, Modified Early Obstetric Warning System (MEOWS)
minutes [1]. PPH occur in 5% of all deliveries, majorities of death in all obstetric inpatient will track maternal physiological parameters
occur within four hours of delivery indicating that it is a consequence which help in early recognition and treatment of the acutely ill patient,
of third stage of labour [2]. is important and crucial to prevent morbidity and mortality.
WHO estimates that of the 5,29,000 maternal death occurring every
year, 1,36,000 or 25.7% of death takes place in India and two third MATERIALS AND METHODS
of these maternal death occur after delivery, PPH being the most This review was conducted by searching Medline (1994-2015) and
commonly reported complication [3]. The unacceptably high maternal other online articles from Pubmed, Google scholar by using terms
death of 540 per 100,000 live births in India in last few decades remains like management of PPH/ haemorrhage, transfusion protocols in
a major challenge [3]. Hysterectomy is the traditional treatment for obstetric haemorrhage/ haemorrhage, recent advances in PPH/
cases of refractory PPH, when all other methods to arrest bleeding haemorrhage and it included 36 articles. No attempt was made
fails. Advances in interventional radiology and surgical techniques to analyze any specific aspect of PPH but an overview of effective
have provided safe and effective alternatives to hysterectomy in clinical management strategies and recent advances in treating
many cases. This review discusses the current evidence based major PPH was done. We have also highlighted community based
management of PPH, existing controversies in transfusion of blood emergency care in low resource settings thereby promoting and
and blood products and newer advances in this field. facilitating a more educated, systematic and effective physician
response.
Definition
The traditional definition of primary PPH, which is the most common Assessments of Blood Loss
of major obstetric haemorrhage is blood loses over 500 ml or more The important steps in the management of PPH are predicting
from the genital tract within 24 hours of the vaginal birth of a baby or PPH and assessment of blood loss during third stage of labour.
1000 ml or more after a cesarean delivery [4]. PPH can be minor (500 Visual estimation of blood loss after delivery is inaccurate, this
-1000 ml) or major (more than 1000 ml), major can be divided into was shown in a study after simulated vaginal delivery there was
moderate (1000 -2000 ml) and severe (more than 2000 ml) [4]. The a 16% underestimation at 300 ml loss, whereas, this increases to
four important causes of PPH are atony, trauma, retained placenta 41% underestimation at 2000 ml blood loss [6]. Massive obstetrics
or adherent placenta and coagulation abnormalities. Most common haemorrhage is variably defined as blood loss from uterus or genital
cause is uterine atony, which is episodic and unpredictable. Women tract >1500 ml or a decrease in haemoglobin of >4 gm/dl or acute
known to have risk factors for PPH, appropriate steps for prevention loss requiring transfusion of >4 units of packed cell transfusion,
should be incited during antenatal and intra partum periods to or any haemorrhage associated with haemodynamic instability
reduce this risk. PPH can also occur with no risk factors [5]. [7]. Accurate methods such as blood collection drapes for vaginal

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 P Reddi Rani and Jasmina Begum, Recent Advances in the Management of Major Postpartum Hemorrhage www.jcdr.net

deliveries, weighing of soaked swabs, active periodic estimation, a MEDICAL TREATMENT (Uterotonics)
written and pictorial guide to aid visual estimation in labour wards
may improve the accuracy of the estimation of blood loss [8]. Contraindications Side effects/
Medications Dose
Or cautions Comments

Protocol for the Management of Major Pph 5 IU slow IV X 2

Overdose or prolonged
Management involves four components all of which must be (may have repeat dose)
use can cause water
Or
taken simultaneously, communication, resuscitation, monitoring Oxytocin
40 IU /500 ml
intoxication. Rare
IV push dosing may
investigation and arresting the bleeding. Main therapeutic goals of Hartmann’s solution at
cause hypotension
125 ml/hour
management of massive haemorrhage is to maintain haemoglobin
>8 gm/dl, platelet count >75 x 109/l, prothrombin <1.5 x mean Hypertension/ toxemia,
patients with HIV taking Nausea,
control, activated prothrombin time <1.5 x mean control, fibrinogen protease inhibitors, vomiting and
Ergometrine 0.5 mg slow IV/IM
>1.0 gm/l [8]. The cornerstones of resuscitation during PPH are patient with vascular increased
restoration of both blood volume and oxygen carrying capacity, disease, hepatic or renal B/P
or sepis
which includes establishing two 14 gauge intravenous lines, 20
250 µg IM every 15 Active or history of
ml blood sample for diagnostic tests includes full blood count, Nausea,
minutes up to 8 times pulmonary disease
coagulation screen including fibrinogen, urea and electrolytes and Carboprost vomiting, and
Direct Intra myometrial (asthma), renal hepatic or
diarrhea
cross matching minimum of 4 units blood. 0.5 µg cardiac disease

A high concentration of oxygen (15l/minute) should be Nausea,

vomiting,
administrated. Pulse rate, blood pressure, oxygen saturation Mispoprostol 1000 µg rectally Cardiovascular disease diarrhea,
using oximeter, electrocardiogram and automated blood pressure pyrexia,
recording, considering central and arterial lines, Foley’s catheter shivering

to measure urinary output and commencing record chart for fluid Intra uterine balloon tamponade
Consider Interventional Radiology
balance, blood, blood product and procedures. Using appropriate MECHANICAL METHODS
(Selective arterial Embolisation / Balloon
measures, patient should be kept warm in a flat position. Blood Occlusion)
should be transfuse as soon as available, till then, 3.5 liters of Brace Suture
warmed crystalloid Hartmann’s solution (2 liters) and/or colloid (1-2 SURGICAL TREATMENT
Bilateral uterine artery ligation
liters) infused. Recombinant factor VII, a therapy should be based Bilateral Internal iliac ligation
Hysterectomy (Second consultant)
on the results of coagulation. Compatible blood is the best fluid
[Table/Fig-1]: Summary of management of major PPH.
to replace and should be transfused as soon as available, if fully
crossmatched blood is not available then uncrossmatched group Radiological management: Uterine artery embolisation is useful
specific blood or ‘O’ Rh-D negative blood may be safest to give in in situations in which preservation of fertility is desired when surgical
an acute emergency [5]. options have been exhausted in controlling PPH both atonic and
traumatic.
Arrest of Bleeding Major drawback is 24 hour availability of interventional radiologist with
There may be one or more causes for PPH related to four Ts’, Tone, appropriate facilities and team, patient should be haemodynamically
Tissue, Trauma, Thrombin. The most common cause of primary stable enough to be transferred to a radiology suite.
PPH is uterine atony, clinical examination should be done to exclude
Complications include local hematoma formation at the site of
other or additional causes. Regardless of the cause of MOH, uterine
injection site, infection, ischemic phenomenon including uterine
massage, bimanual uterine compression to stimulate contraction,
necrosis though rarely. It can be done as elective or emergency
administration of uterotonic drugs should be instituted, until the
intervention [11]. Emergency indications are persistent atonic PPH
bleeding stops.
and surgical complications, uterine tears at the time of cesarean
If the pharmacological method fails to control bleeding in case of section, bleeding following hysterectomy. Access to the anterior
atonic PPH, exclude other or additional causes by undertaking division of internal iliac artery is via a femoral artery approach and is
clinical examination in theatre and the next intervention mechanical done by injecting gelatin particles. Use of polyvinyl alcohol particles
method of control by balloon catheter tamponade is instituted is however, permanent. It usually offer very high success rate of 75
before considering surgical procedures [5] [Table/Fig-1]. -100%.
Elective can be done in known or suspected cases of placenta
Mechanical Methods accrete such as placenta previa or previous cesarean section scar
Balloon tamponade: The various types of balloons used are Foley’s diagnosed by Ultrasonography (USG) or Magnetic Resonance
catheter, Rusch balloon, Bakri balloon, Sengstaken-Blackmore Imaging (MRI). The strategy used for elective cases in minimizing
oesophageal catheter or sterile glove and condom. Akhter et blood loss, number of blood transfusion and ICU admission usually
al., described the use of condom catheter to tamponade uterine incorporates placement of balloon catheters within internal iliac artery
bleeding in women with PPH in Bangladesh [9]. or uterine artery, which works with balloon inflation and if it doesn’t
This was a prospective study involving 152 cases of PPH, 23 of then it can be a route for embolisation as well [12]. Intravascular
which were managed using condom catheter. It was successful in Aortic Balloon Occlusion (IABO) has emerged as prophylactic,
all cases with no further intervention. It was kept for 24-48 hours simple, safe and minimally invasive method in management of life
(mean 36 hour) before removal [9]. Balloon tamponade was effective threatening PPH and in the conservative management of abnormal
in 91.5% of cases and recommended that, this is a relatively placentation. It has similar results in terms of blood loss and
simple technology and should be a part of existing protocol in the absence of need of blood products as internal lilac artery occlusion
management of PPH [10]. This intervention as tamponade test but requires further research by using control group before regarding
serves as first line surgical management. A positive test controls this method, as an ancillary procedure of choice during scheduled
PPH following inflation and a negative test where bleeding does cesarean hysterectomy in known or suspected cases of abnormal
not stop with inflation, it is likely to be coming from a genital organ placentation [12].
laceration. Cases with negative balloon tamponade test and failure Hysterectomy was avoided in 10 out of 14 cases of major PPH by
to arrest bleeding by intra uterine balloon tamponade in uterine arterial embolisation, this was reported by Penney et al., in Scottish
atony requires immediate surgical interventions. confidential audit [13].

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Surgical treatment: For surgical management multiple surgical increta, acreta and percreta, rupture uterus where repair not
options are available, to include a variety of uterine compression possible, persistant atonic PPH. Incidence of hysterectomy varies
sutures, vascular ligations and Peripartum Hysterectomy. from 1 in 331 to 1 in 6978 deliveries [22]. It should not be delayed
Uterine compression sutures: In severe PPH not responding to too long till the women is moribund. Subtotal hysterectomy is the
pharmacological and mechanical methods, the treatment used was choice unless there is a trauma to cervix or lower uterine segment.
peripartum hysterectomy to prevent maternal deaths even in primi The maneuver of aortic compression is at times useful for control of
and in young women. With the increasing rates of cesarean section, bleeding in the surgical field for severe cases.
complications like placenta previa, placenta accreta, rupture
uterus contributes to severe PPH apart from atony. Introduction of Transfusion Protocols
compression sutures made a revolution in decreasing the incidence Massive transfusion protocol is essential in institutional management
of hysterectomy for severe PPH. Credit goes to Christopher B- of major obstetric haemorrhage. It should be recommended when
Lynch who in 1997 introduced compression sutures to control there is uncontrolled haemorrhage or when use of more than 10
bleeding avoiding peripartum hysterectomy. These compression unit packed cells is anticipated [23]. Early use of blood products is
sutures exert a mechanical compression of the uterine vascular generally required in MOH to avoid dilutional coagulopathy.
sinuses without occluding either uterine arteries or uterine cavity There is no consensus on the use of components of the transfusion in
[14]. Several modifications of this technique developed mainly women suffering from PPH or in obstetrics. Research in transfusion
aiming at greater simplicity and applicability with equivalent efficacy medicine has pointed towards use of packed blood cell and FFP in a
like Chi-Square sutures, Hayman sutures, Pereira suture, Cervico ratio of 1:1 and 1:2 and targeted use of platelets in an effort to avoid
Isthumic Compression sutures etc [15]. dilutional coagulopathy with regular measurement of haemoglobin
Uterine compression sutures related complications like pyometra, and clotting by conventional tests [24]. Transfusion protocols have
uterine inflammation leading to chronic endometritis, systemic advantages in decreasing mortality, multiorgan failure and increase
sepsis, ischemic uterine necrosis, uterine suture erosion, uterine ventilator free days. It also have some disadvantages of transfusion
synechiae have been reported by several studies [16,17]. We have related lung injury, circulatory overload, immunomodulation and
a similar experience of a case treated with B-Lynch suture, followed iron overload which can be avoided by regular measurements of
by bilateral uterine and hypogastric artery ligation for severe PPH; haemoglobin and clotting to guide transfusion.
however, we faced a difficult situation, when the patient developed In most cases, transfusion therapy is not based on the actual
synechia, and extensive pelvic adhesions jeopardizing any further coagulation state because conventional laboratory test usually
scope of pregnancy [18]. takes 45-60 minutes and conventional test on plasma ends
Fertility after application of uterine compression sutures: Vast with the formation of fibrin strands. Viscoelastic test like,
majority of cases do not show any serious complications in future Thromboelastography (TEG) and Thromboelastometry (ROTEM)
pregnancies and no higher rates of infertility. Ovahba et al., reported can test whole blood coagulation, clot strength, stability and
eight pregnancies out of 20 women who underwent uterine lysis with a particular reference range, which can be used for
compression sutures; six had term delivery with four cases of management of obstetric cases seen amongst the recent trends
cesarean section and two cases of uncomplicated vaginal delivery in PPH management [25]. At present transfusion monitoring still
[19]. require a combination of conventional test of Hb and coagulation,
perhaps there will be wide practice of point of care testing alone in
The risk of potential complication appears to be higher when
future based on further studies.
non absorbable sutures are used. Uterine compression sutures
irrespective of its type should not prevent the blood drainage from The best marker for developing coagulopathy and blood loss is
the uterine cavity and it should not affect the uterine vascularity. well correlated by fibrinogen levels, whereas, prothrombin time and
Monofilament sutures with an absorption time of 90–120 days partial thromboplastin time somehow are not very useful, this has
can decrease this complications and subsequent hysteroscopic been revealed by a survey. It is also an early predictor of severity of
assessment should be done especially after putting stepwise PPH, a level of < 2 gm/l has a 100% Positive Predictive Value (PPV)
devascularization and compression sutures [20]. for severe PPH [26].
Vascular ligations [21]: The objective is to decrease blood flow to Cryoprecipitate contain approximately 10 times the concentration
the uterus, in order to arrest life threatening PPH before hysterectomy of fibrinogen as FFP, in order to raise the fibrinogen level by 1
when medical therapy is unsuccessful. gm/l, 30 ml/kg of FFP needs to be given compared with 3 ml/kg
of cryoprecipitate. So, FFP is not the product of choice to restore
1. Bilateral uterine artery ligation: 90% of the uterus blood
fibrinogen levels. Upto 1 litre of FFP and 10 units of cryoprecipitate
supply in pregnancy comes from these vessels. If this
may be given empirically in face of relevant bleeding while waiting
measure fails to control bleeding, the next step is ovarian
for coagulation studies [27].
artery ligation.
Fibrinogen concentrate, a virally inactivated lyophilized powder that
2. Bilateral ovarian artery ligation: it arises from abdominal
can be stored at room temperature, no thawing or blood typing is
aorta and forms utero-ovarian vascular anastomosis. A
required, it restores fibrinogen levels rapidly. The results of fibrinogen
suture is placed on the ovarian artery through a vascular
concentrate in initial treatment for severe PPH, (FIB-PPH) trail in
area in mesoovarium. If this also fails to control then the
order to reduce the requirement of blood transfusion stated that
next step is internal iliac artery ligation.
pre-emptive treatment with fibrinogen concentrate for severe PPH
3. Internal iliac artery ligation: it causes almost 85% reduction in patients with normofibrinogenaemia is not justified but the role of
in pulse pressure in those arteries distal to ligation thereby, fibrinogen substitution in severe PPH with hypofibrinogenaemia is
causing arterial pressure system into one with pressure yet to be studied [28].
approaching those in venous circulation and provides
haemostasis via clot formation. It needs expertise in
Intra Operative Cell Salvage in Obstetrics
doing this and avoids complication of injury to vessels
It is an option in women who refuse traditional blood transfusion as
and ureter.
well as in MOH situations. It may not be substituted for allogenic
Hysterectomy: Peripartum hysterectomy can be a total or subtotal, blood transfusion but is an adjunct to acute resuscitation in PPH and
it is done as a last resort when all other methods to control PPH fail. also can reduce the exposure to allogenic blood transfusion and its
The common indications are abnormal placentation with placenta associated risks and is cost effective. It contains only red cells with
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 P Reddi Rani and Jasmina Begum, Recent Advances in the Management of Major Postpartum Hemorrhage www.jcdr.net

essentially no platelets or clotting factors. The risk of amniotic fluid of PPH resulting due to uterine atony. If bleeding persist
embolism is very low if leucocytes depletion filter are used. Infection after the administration of uterotonics the immediate life
is also uncommon [29]. saving measures are bimanual compression. Bimanual
compression is done by placing one hand in the vagina
Recombinant Activated Factor VII and clenched into a fist and other hand on the fundus
There is lot of controversy regarding its usage and it is very of uterus. Squeezing the uterus between two hands by
expensive. Current recommendation is that, it should be used applying pressure to stop or slow the bleeding, uterus
after failure of conventional methods. Major concern is, it causes has to keep compressed till next medical support.
thrombin burst, promoting clotting in open vessels and there is a 3. Aortic Compression: It is a life saving measure when there
potiential for thrombotic complication. Women with severe PPH are is heavy PPH whatever the cause. It does not prevent or
particularly susceptible to severe hypofibrinogenaemia and these delay any of the steps in management of PPH. Circulating
are cases where factor VIIa is considered. blood volume is restricted to the upper part of the body
It should be given only when hematocrit is adequate, platelet count and thereby to the vital organs, blood pressure is kept
is >50x109/l, fibrinogen >1 gm/l, pH>7.2 and temperature >340C. higher, blood is prevented from reaching bleeding area
Dose is 90 µg/Kg IV over 3-5 minutes, repeated only if necessary. in pelvis and volume is conserved. By cutting off the
Franchiniet et al., reported 65 women treated with rFVIIa for PPH blood supply to pelvis via compression, patient can be
and observed reduced bleeding and 30 of the 65 women underwent prepared to shift higher center, simultaneously doing
peripartum hysterectomy [30]. other measures.
4. Non Pneumatic Anti Shock Garment (NASG): Use of
Role of Tranexamic Acid antishock garment for the treatment of hypovolumic
It is being tried both prophylactically and also for treatment of PPH shock for transfer to higher center. NASG reverses the
in cases of continued bleeding due to uterine atony, uterine ruptures shock by compressing the lower body vessels. So that
and lower genital tract trauma. Gungorduk et al., used prophylactic circulating blood is directed mainly to the core organs
tranexamic acid administration in a prospective randomized placebo heart, lungs, brains, adrenals.
controlled trial in 660 women who underwent elective Lower This device with its pneumatic action effectively prevents obstetric
Segment Caesarean Section (LSCS). They have observed reduced haemorrhage, maternal mortality and morbidity by impending the
mean estimated blood loss and need of additional uterotonic agents blood flow to the uterus through its vascular compression [35].
following to LSCS in the treatment group. It can decrease the bleeding
Obstetric haemorrhage is the result of uterine atony, but other
and reduce the need for further transfusion without any major side
entities may also cause or contribute to acute bleeding. Sibai et al.,
effects [31]. Initial dose is a slow IV bolus of 1gm followed by further
in his article has summarized 10 evidence based recommendations
1 gm four hours later. Sentilhes et al., in his review with various RCT’s
on the management of severe postpartum haemorrhage that may
dealing with prevention and treatment of PPH with tranexamic acid
help in reducing acute and long term maternal complications [36]
use, concludes that, the benefits definitely overscores the side effects
[Table/Fig-2].
for both vaginal and caesarean delivery. The current level of evidence
is however, lacking and the use is yet to be established in the given
1. Plan and rehearse a step by step Early recognition of haemorrhage,
context [32]. Perhaps the outcome of the largest trial sponsored approach Identifying cause of bleeding,
by WHO (WOMAN trial) for determining the effect of the early quick and effective evaluation and
administration of TXA on death, hysterectomy, and other morbidity management of bleeding
(surgical intervention, blood transfusion and risk of non fatal vascular 2. Know the symptoms and signs of Symptoms: anxiety, restlessness,
events) will throw some light on this debatable issue [33]. severe PPH tachypnea, hunger to air, confusion.
Signs : tachycardia, hypotension, cold
clamminess, pale, oliguria or anuria
Prevention and Treatment in Low Resource Settings
3.  Call for help Within 10 minutes after making the
PPH is the major cause of direct maternal death in low resource diagnosis of PPH
settings where there are no birth attendants or they lack skills or
equipment to manage PPH and shock. 4. Identify women at very high risk Cases like placenta previa, placenta
of hysterectomy and end organ accreta, uterine rupture, number of
The vices like poverty, discrimination, limited health accessibility, dysfunction previous cesarean section
continue to haunt women living in low socio economic status apart 5. Perform uterine compression sutures Within one hour of delivery.
from their vulnerability to concurrent disease. This attributes further
6. Diagnosed cases of placenta previa or Plan delivery by a multidisciplinary
to maternal deaths despite having safe motherhood activities. accrete team
Even with major advances in prevention of PPH women are
7. Conservative management of placenta Considered only in carefully selected
still dying. What is needed in these women is community based accrete and placenta percreta women who desire future fertility
emergency care/ home base life saving skills. Community workers Planned cesarean hysterectomy is the
treatment of choice for multiparous
can be taught with techniques such as uterine massage and women.
emergency preparedness as the key to effectiveness of treatment is
early identification of haemorrhage and prompt action [34]. 8.  Exclude Von willebrand disease Requires multidisciplinary approach

1. Uterine massage: Massage of fundus of uterus through 9.  Have Fibrinogen concentrate on hand For cases of intrauterine death of fetus,
abruption, amniotic fluid embolism etc.
the abdomen after placenta delivery until uterus is
contracted. It was repeated at every 15 minutes during 10. Implement a protocol for massive By administration of adequate blood
transfusion and blood products, oxygen delivery
first two hours to keep the uterus contracted. and correction of DIC.
2. Misoprostol: Though, oxytocin is ideal due to its [Table/Fig-2]: Ten practical evidence based recommendations for managing severe
effectiveness in 2-3 minutes with minimal side effects and PPH.
can be used by all women but it needs refrigeration and
administered in injectable route. If oxytocin is not available Conclusion
or administration is not feasible, single dose of 800 µg Globally PPH is the leading cause of maternal mortality and
of misoprostol, sublingually, is a safe effective treatment morbidity. Prevention plays a very important role by identifying

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www.jcdr.net P Reddi Rani and Jasmina Begum, Recent Advances in the Management of Major Postpartum Hemorrhage

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PARTICULARS OF CONTRIBUTORS:
1. Professor, Department of Obstetrics and Gynaecology, Mahatama Gandhi Medical College and Research, Pillaiyarkuppam, Puducherry, India.
2. Associate Professor, Department of Obstetrics and Gynaecology, Mahatama Gandhi Medical College and Research, Pillaiyarkuppam, Puducherry, India.

NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR:

Dr. Jasmina Begum,
Associate Professor, Department of Obstetrics and Gynecology, Mahatama Gandhi Medical College and Research,
Pillaiyarkuppam-607402, Puducherry, India. Date of Submission: Jul 09, 2016
E-mail: [email protected] Date of Peer Review: Aug 02, 2016
Date of Acceptance: Oct 25, 2016
Financial OR OTHER COMPETING INTERESTS: None. Date of Publishing: Feb 01, 2017

Journal of Clinical and Diagnostic Research. 2017 Feb, Vol-11(2): QE01-QE05 5