What is the most effective uterotonic agent to prevent PPH?

Postpartum hemorrhage (PPH) is responsible for more than 25% of all maternal death around the world and is the leading cause of maternal mortality in low resource settings. It affects 5% of all women during labor and leads to substantial morbidity because of compromised maternal blood volume. 

Use of uterotonics during the third stage of labor could avoid a majority of complications due to PPH. WHO recently published updated guidance on uterotonics for the prevention of PPH, after which the Cochrane Review published the results of a network meta‐analysis to identify the most effective uterotonic agent.

The network meta‐analysis included 196 trials involving 135,559 women, with the majority of women having vaginal births (71.5%, 140/196) in a hospital setting (95.4%, 187/196). 

The WHO recommendations and results of the Cochrane analysis suggest:

To effectively prevent PPH, only one of the following uterotonics should be used: Oxytocin, Carbetocin, Misoprostol, Ergometrine/methylergometrine, Oxytocin, and ergometrine fixed-dose combination.

Oxytocin (10 IU, IM/IV) is the standard recommended drug of choice for prevention of PPH in all cases. The drug has minimum side effects and is cost effective too. The main problem with Oxytocin is it requires refrigeration and rapidly loses its potency if stored at room temperature.

The use of carbetocin (100 µg, IM/IV) is also recommended for the prevention of PPH for all births if cost is not the limiting factor. It is also not readily available everywhere.

Misoprostol, injectable prostaglandins, and ergometrine have no additional benefits compared with oxytocin. Misoprostol causes more undesirable effects than oxytocin (including nausea, vomiting, shivering, fever, and diarrhea).

Combination therapy involving ergometrine plus oxytocin combination (Syntometrine ®), misoprostol plus oxytocin combination and carbetocin have the additional desirable effects compared with oxytocin and can be used if oxytocin is unavailable. However, there is always a risk of undesirable side effects as compared to oxytocin. Injectable prostaglandins (carboprost or sulprostone) are not recommended for the prevention of PPH.

Misoprostol and oxytocin are not available in fixed-dose combination and require different routes of administration so its use in routine clinical settings may not be very feasible as compared to using them alone.

If using ergometrine (alone or in combination), it is important to rule out hypertensive disorders and cardiovascular diseases.

In low resource settings and non-availability of skilled healthcare personnel, misoprostol (400 µg or 600 µg) can be administered orally by the community or lay health workers.

WHO recommendations Uterotonics for the prevention of postpartum haemorrhage

Uterotonic agents for preventing postpartum haemorrhage: a network meta‐analysis

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Intrauterine balloon tamponade for PPH significantly reduces the need for invasive procedures

Using Intrauterine balloon tamponade to control bleeding in postpartum hemorrhage lowers the use of invasive procedures by 84% in women with vaginal delivery reports the results of a large population-based retrospective cohort study published in January issue of Obstetrics and Gynecology Journal.

However, the same intervention did not lower the use of invasive procedures in women delivered by cesarean section.

This large, multicenter center study included 72,529 women delivered across 19 maternity units belonging to two perinatal networks in France.

The two networks either used Intrauterine balloon tamponade (pilot network) or used other methods for management of PPH.

Total .4% of women (298) had to undergo either pelvic vessel ligation, arterial embolization or hysterectomy.

A significant less number of women in the balloon tamponade group had to undergo invasive procedure as compared to the control group (3.0/1,000 vs 5.1/1,000, P<.01).

Similarly, the incidence of arterial embolization was significantly less in women in whom balloon was used to arrest PPH, for both vaginal (0.2/1,000 vs 3.7/1,000, P<.01) and operative mode of delivery (1.3/1,000 vs 5.7/1,000, P<.01).

After considering the confounding variables, it was seen that the risk of women undergoing an invasive procedure for PPH was 84% lower in women who underwent Intrauterine balloon tamponade as compared to other procedures used for control of PPH.   

Abstract

Media courtesy: slideshare.net

WHO updates its guidance on Tranexamic Acid for the Treatment of Postpartum Hemorrhage

WHO has recently updated their guidelines for use of Tranexamic acid for treatment of Postpartum Hemorrhage: TXA should now be included in the treatment regimen for PPH along with other drugs, irrespective of the cause of hemorrhage.  

In 2012, WHO recommended Use of TXA  for the treatment of PPH if oxytocin and other uterotonics fail to stop the bleeding or if it is thought that the bleeding may be partly due to trauma.

Globally, PPH accounts for 25% of all maternal deaths and in most low-income countries it is the leading cause of maternal deaths. And minutes count when treating postpartum hemorrhage with tranexamic acid: for every 15-min delay, there's a 10% reduction in effect.

The key recommendations from WHO are:

• The World Health Organization (WHO) recommends early use of intravenous tranexamic acid (TXA) within 3 hours of birth in addition to standard care for women with clinically diagnosed postpartum hemorrhage (PPH) following vaginal birth or caesarean section.
• Administration of TXA should be considered as part of the standard PPH treatment package and be administered as soon as possible after onset of bleeding and within 3 hours of birth. TXA for PPH treatment should not be initiated more than 3 hours after birth.
• TXA should be used in all cases of PPH, regardless of whether the bleeding is due to genital tract trauma or other causes.
• TXA should be administered at a fixed dose of 1 g in 10 mL (100 mg/mL) IV at 1 mL per minute (i.e., administered over 10 minutes), with a second dose of 1 g IV if bleeding continues after 30 minutes.
• TXA should be administered via an IV route only for treatment of PPH. Research on other routes of TXA administration is a priority.

ACOG also has recently updated its practice bulletin on Postpartum Hemorrhage, based on the results of The WOMAN (World Maternal Antifibrinolytic) trial published in May 2017, in The Lancet.

The researchers concluded that “Tranexamic acid reduces death due to bleeding in women with post-partum hemorrhage with no adverse effects. When used as a treatment for postpartum hemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.”

ACOG says, “Although the generalizability of the WOMAN trial and the degree of effect in the United States is uncertain, given the mortality reduction findings, tranexamic acid should be considered in the setting of obstetric hemorrhage when initial medical therapy fails.” (Level B evidence)

WHO Update

WOMAN trial full text in Lancet

ACOG practice bulletin postpartum hemorrhage abstract

ACOG resources on obstetric hemorrhage

AWHONN video on Quantification of Blood Loss

Midpelvic forceps and vacuum deliveries are more traumatic than cesarean section

Taking a decision in favor of cesarean section is considerably safer than attempting midpelvic operative vaginal delivery in terms of reducing severe birth trauma and obstetric trauma reports a study finding published June 5, 2017 in Canadian Medical Association Journal (CMAJ).

Midpelvic arrest in second stage of labor and operative interventions are a test of obstetrician’s skills and experience. In recent year, there has been a shift towards cesarean section, increasing the rates of cesarean section worldwide.

In 2014, a consensus statement by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine supported operative vaginal delivery over cesarean delivery to bring down the cesarean rate and improve maternal and neonatal outcome. Although, ACOG statement was not specific for midpelvic operative vaginal delivery but included it in more general sense.

Studies on the risk and benefits of these two procedures are lacking and not stratified by the station of fetal head in pelvis, which is an important decisive factor for maternal and fetal outcome.

The researcher team involved in the current study looked at data across a span of 10 years including 187,234 singleton births which included all mid pelvic live or stillbirths via forceps or vacuum and C-section deliveries between 37 and 41 weeks of gestation that resulted in a singleton live birth or stillbirth.

In all the cases, the head was engaged and the leading point of fetal head was as above station +2 cm but below 0 station.

It was seen that infants born by midpelvic operative vaginal delivery in women having dystocia, with prolonged second stage of labor has 81% more chances of severe morbidity and mortality as compared to when they were delivered by cesarean section. It included higher rates of birth asphyxia, meconium aspiration syndrome and intracranial hemorrhage.

Forceps delivery and vacuum delivery exposed the neonate to nearly 5 times the risk of birth trauma, but the rates were considerably high (9.5 times ) in sequential application.

Rates of obstetric trauma were also quite higher using forceps (5 times the risk), vacuum (2.7 times the risk) and sequential instruments (3 times the risk) as compared to delivery by cesarean section. In addition, significant more third and fourth degree perineal tear occurred in women who had midpelvic forceps (19%), midpelvic vacuum (12%), and 20% among women who delivered using a combination of midpelvic vacuum and forceps.

Rates of maternal morbidity and mortality did not differ much in the two groups, but midpelvic forceps and vacuum use was associated with significantly higher rates of post-partum hemorrhage.

In that subset of women in which the midpelvic forceps application was done for fetal distress, the composite maternal morbidity and mortality was 48% lower in vacuum group, but nearly 3 times higher rates of obstetric trauma and higher rates of PPH was observed.

The association between midpelvic operative vaginal delivery and composite severe perinatal morbidity and mortality were significantly stronger in those women who had dystocia but not prolonged second stage of labor. Similar outcomes were seen in women who had fetal distress but not prolonged second stage of labor. Midpelvic forceps and vacuum deliveries are more traumatic than cesarean section.

The study showed that encouraging higher rates of operative vaginal delivery to reduce the rate of cesarean delivery comes at the cost of increase in severe perinatal and maternal morbidity and mortality, especially neonatal birth trauma, severe postpartum hemorrhage and obstetric trauma.

"It is important to understand that similar to cesarean deliveries, midpelvic forceps and vacuum deliveries are invasive procedures with their own risks -- risks that we have now quantified and that should be communicated to women who may encounter them, especially when the risk is as high as one in five," says lead author, Giulia Muraca, a doctoral researcher at the School of Population and Public Health, University of British Columbia (UBC). "Women who are delivered by midpelvic forceps or midpelvic vacuum should be afforded the same standard of informed consent as women who consent to cesarean delivery. Ideally, this should take place prior to labour when women are considering their birth plans."

The full text of the journal article can be accessed here.

An inexpensive intervention reduces maternal mortality due to Post-partum hemorrhage.

An inexpensive intervention like Tranexamic acid (TXA) has the potential to significantly reduce maternal death due to Post-Partum hemorrhage(PPH) when used in timely manner, report the results of large randomized control trial.

The WOMAN (World Maternal Antifibrinolytic) Trial results along with an accompanying editorial were published online April 26, 2017 in Lancet.

Primary Post-partum hemorrhage is responsible for about 100 000 deaths every year primarily in developing countries and in low resource settings.

Before the WOMAN trial, tranexamic acid was shown to be effective in surgical blood loss and trauma cases but a review of literature failed to document any research in use of tranexamic acid in postpartum hemorrhage. Interestingly, the drug was originally developed for controlling hemorrhage in obstetrics and gynecology.

Further, WHO guideline in 2012 recommended “tranexamic acid should be used for the treatment of post-partum hemorrhage when uterotonics fail to control the bleeding or when the bleeding is thought to be due to trauma,” but the results were extrapolated from surgery or trauma cases.

Comprising of 20,060 patients with a clinical diagnosis of PPH during normal or cesarean delivery, the WOMAN trial spanned across 193 hospitals in 21 countries.

All patients received normal obstetric care and were randomized to receive 1 g tranexamic acid or placebo by slow intravenous injection. If bleeding persisted after 30 minutes or restarted after once controlled within 24 hours, a dose of TXA was repeated.  

Trial results were evaluated in terms of number of deaths from all causes or hysterectomy within 42 days of drug administration. Deaths due to bleeding was also looked at as main secondary outcome.

The results showed that treatment with TXA reduces the chances of death due to bleeding by almost 20% as compared to placebo (risk ratio [RR], 0.81; P = .045). The effect was maximum when TXA was used within 3 hours of delivery (RR, 0.69; P = .008).

When the drug was used after 3 hours, there was no significant reduction in risk of death due to bleeding (RR, 1.07; P = .70).

The risk of death due to hysterectomy and all causes or hysterectomy including pulmonary embolism, organ failure, sepsis, and eclampsia were similar between the study and control group.

TXA did not increase the risk of thromboembolic events as compared to placebo.

An accompanying editorial writes that “Hemorrhage accounts for 18% of these deaths, and is a particularly important cause of maternal mortality in Africa and Asia. Discovering new ways to prevent maternal death, especially from bleeding, therefore continues to be a high priority, and WOMAN trial is an important milestone in that quest.”

The authors recognize that most deaths due to PPH occur in developing or low resource setting countries, where administering IV TXA may not be feasible.  So, studies investigating alternate routes of TXA administration should be planned.

The trial also supported the WHO recommendation of inclusion of tranexamic acid in treatment guidelines for primary postpartum hemorrhage but with a caveat that it should be given as soon as possible.

Full text of the article can be accessed here.

Full text of the editorial can be accessed here.

                                          Woman Trial: Tranexamic acid for the treatment of PPH

Vaginal delivery in twins increases risk of maternal morbidity as compared to elective C-section.

A 7-year assembled retrospective cohort study of women with vertex presenting twin who underwent vaginal delivery have higher incidence of maternal morbidity as compared to women delivered by C-section.

The findings of this study was published on-line on January 9,2017 in Obstetrics andGynecology Journal.[1]

Guidelines suggest an attempt at vaginal birth if first twin is vertex with no uterine scar or other contraindication exits. Many  studies have compared neonatal mortality and morbidity but not much information is available on maternal morbidities based on route of delivery in twins.

 Dr. Sarah Rae Easter of Brigham and Women's Hospital and Harvard Medical School in Boston is the lead author of the study. She and her colleagues carried out the study from 2007-2014. Out of 2,272 twin pregnancies beyond 32 weeks of gestation, 1,140 (50%) met inclusion criteria of no uterine scar and no other contraindication for vaginal birth.  571 (50%) women chose to have elective cesarean delivery and 569 (50%) underwent a trial of labor to attempt vaginal birth. 

In the trial of vaginal birth group, 74% had an uneventful vaginal delivery, while others required operative assistance or breech extraction.

After adjusting for confounders, trial of labor group  had higher rate of maternal morbidity (12.3%) as compared to elective C-section group (9.1%). The rates of Postpartum hemorrhage were nearly twice in women having vaginal births.3% of women had major lacerations of genital tract.

An earlier RCT published in BJOG by Hutton EK et al did not show any difference in maternal morbidities in elective C-section vs Vaginal delivery group. [2]

Dr. Easter did not advice against trial of labor in twins, but wanted the clinicians to be more cautious while counselling the patients. She quoted. "Though our findings suggest a trend towards increased maternal morbidity in those who labor, we do not see this as a deterrent to twin vaginal delivery, we feel the immediate increased risk of postpartum hemorrhage should be balanced with the benefits of a vaginal birth. We hope clinicians will thoughtfully incorporate our findings into counseling while keeping in mind the known long-term consequences of Cesarean delivery and its impact on future pregnancies."

“Delivery in hospitals equipped to manage postpartum hemorrhage is of equal importance for mothers attempting vaginal birth of twins” she further added.

The authors concluded “In pragmatic terms, the tradeoff for a 74% chance of vaginal delivery is a 4% absolute increase in the rate of serious postpartum hemorrhage.”

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[1] http://journals.lww.com/greenjournal/Abstract/publishahead/Association_of_Intended_Route_of_Delivery_and.98512.aspx

[2] https://www.ncbi.nlm.nih.gov/pubmed/26328526

Misoprostol as an add on to Oxytocin does not further reduce Postpartum hemorrhage in active management or treatment of PPH.

Clinical Pearls:

• Prophylactic misoprostol at a dose of 400 micrograms, added to oxytocin for active management of the third stage of labor, did not reduce the rate of postpartum hemorrhage, severe postpartum hemorrhage, or second-line procedures.
• Misoprostol will produce no further uterotonic effects after a prophylactic infusion of 10 international units of oxytocin.
• Findings of this trial do not support the use of misoprostol in addition to oxytocin for the prevention of postpartum hemorrhage. 
• Misoprostol may be useful in countries with poor health resources where facilities for refrigeration and skilled birth attendants are not freely available.
• Oxytocin should be used as prophylaxis and as the first line of treatment in active management of labor, especially in high income countries or countries with good healthcare facilities.

Postpartum hemorrhage remains the leading cause of maternal morbidity and mortality worldwide with a prevalence of 6% worldwide with Africa topping the list with 10.5% prevalence. It accounts for 30% of maternal deaths in Africa and Asia.[1]

Deaths due to PPH are preventable and considerable variation exist between developed and developing countries. Uterine Atony is the most common cause of PPH and active management of labor is promoted in developing countries to bring down the maternal mortality.

Oxytocin is the agent of choice because of high efficacy and low adverse effects.[2]

Misoprostol is a prostaglandin E1 analog often used off label in active management of labor because of cost, multiple route of administration and storage advantage.[3] An earlier large randomized multicentric trial compared the efficacy of oxytocin and misoprostol and showed that oxytocin was always the first agent of choice.[4]

After that another study suggested that they both could have synergist effect and reduce PPH further.

A large multicentric, double-blind, randomized, placebo-controlled trial recruited women across three French University hospitals from April 2010 to September 2013. The study subjects consist of women 18 years and older,36-42 weeks of pregnancy, in first stage of labor and under epidural anesthesia. The study was published on September 8 in Obstetrics& Gynecology.[5]

Women who met the inclusion criteria were randomized to receive two tablets of 200 micrograms misoprostol (ie, a total dose of 400 micrograms) or two tablets of placebo orally immediately after delivery of the newborn. Women in both the arm had active management of labor and received prophylactic intravenous injection of 10 international units’ oxytocin after delivery of the fetal anterior shoulder, early clamping of the umbilical cord, and controlled cord traction. 

If patient continued hemorrhaging after the treatment, they received treatment according to the standard protocol of PPH, but misoprostol was not repeated.   

There was not significant difference in both the groups in terms of primary outcome of postpartum hemorrhage greater than 500 mL within 2 hours of birth. (8.4% [68/806] in the misoprostol vs 8.3% [66/797] in the placebo group; P = .98).

After the analysis was performed on 1,721 patients enrolled in study, the trial was discontinued because the combination of misoprostol and oxytocin did nothing to reduce the PPH. Misoprostol when added to prophylactic Oxytocin did not further reduced Postpartum hemorrhage, but rather increased incidence of adverse events in mother. Misoprostol was associated with high rates of adverse effects like fever greater than 38°C (P<.001) and shivering (P<.001), diarrhea and vomiting.

"All in all, the findings of this trial do not support the use of misoprostol in addition to oxytocin for the prevention of postpartum hemorrhage," the authors write. "[D]espite misoprostol's ready availability, easy use, and utility for other pregnancy indications, oxytocin should remain the mainstay of prophylaxis of postpartum hemorrhage in high-income countries, and misoprostol should be used infrequently for this indication."

Misoprostol may be useful in countries with poor health resources where facilities for refrigeration and skilled birth attendants are not freely available.

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[1] http://apps.who.int/rhl/archives/guideline_pphprevention_fawoleb/en/

[2] Westhoff G, Cotter AM, Tolosa JE. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage

[3] Tunçalp Ö, Hofmeyr GJ, Gülmezoglu AM. Prostaglandins for preventing postpartum haemorrhage.

[4] Gülmezoglu AM, Villar J, Ngoc NT, Piaggio G, Carroli G, Adetoro L, et al. WHO multicentre randomised trial of misoprostol in the management of the third stage of labour. Lancet 2001;358:689–95.

[5] http://journals.lww.com/greenjournal/Fulltext/2016/10000/Active_Management_of_the_Third_Stage_of_Labor_With.17.aspx#P70

Abnormally invasive placenta---Can we predict and do better?

Clinical Pearls:

• Previous cesarean section or uterine surgery is the single most important predisposing factors for Abnormally Invasive placenta.
• One cesarean section increases the risk of AIP seven fold in subsequent pregnancy.
• History of post-partum hemorrhage is also a risk factor for AIP and increases the risk 6 fold in current pregnancy.
• In 70% of cases, the diagnosis of AIP was missed during antenatal period.
• Increasing clinician awareness for incidence of AIP in the high risk patients leads to increased diagnosis in antenatal period.
• Avoiding unnecessary cesarean section is the only way to decrease the incidence of AIP.  

Lowering the Cesarean section rate in the population is the only most effective way in reducing the incidence of Abnormally invasive placenta(AIP) is the conclusion of a large, population based cohort study from the Nordic countries.

The Nordic Obstetric Surveillance Study (NOSS) required obstetricians’ collaboration in reporting AIP, uterine rupture, excessive blood loss and peripartum hysterectomy from 2009-2012. Due to paucity of cases at a single hospital the data was pooled and validated by National Health Registries. 

The data was analyzed and identified 205 cases of AIP amounting to an incidence of 3.4 per 10,000 deliveries.

The study was published in the current issue of British Journal of Obstetrics and Gynecology(BJOG).[1]

The study goal was to gauge the prevalence, risk prediction, predisposing factors, antenatal suspicion, maternal morbidity and birth complications in cases of AIP.

The study confirmed the association between AIP and previous cesarean section or any other previous uterine surgeries like endometrial ablation, and in vitro fertilization. The risk of AIP in subsequent pregnancy is seven fold with one prior Cesarean section to 56-fold after three or more CS.

Placenta previa was the single most important risk factor identified in nearly half of the pregnancies.

 In addition, patient who had postpartum hemorrhage in previous pregnancy have 6 times the risk of AIP in current pregnancy as compared to patients who did not have PPH.

An antenatal diagnosis of AIP can strikingly reduce the complication rate but in nearly two-third of patients (70%) of patients the diagnosis was missed. Of these, 39% had prior CS and 33% had placenta praevia.

Increased awareness about the risk factors among clinicians can raise the index of suspicion and led to more and more patients being diagnosed in prenatal period. Clinicians performing Ultrasound(USG) should have high index of suspicion in high risk women with previous uterine surgery or a placenta over uterine scar. These women should be offered additional sonography.

Nordic countries have lower rates of AIP than US, perhaps due to lower rate of cesarean section and high order cesarean births or better obstetrics facilities. 

But, the only sure way to decrease the incidence of AIP is to avoid unnecessary cesarean delivery, especially the first cesarean section.

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[1] Thurn L, Lindqvist PG, Jakobsson M, Colmorn LB, Klungsoyr K, Bjarnadóttir RI, Tapper AM, Børdahl PE, Gottvall K, Petersen KB, Krebs L, Gissler M, Langhoff-Roos J, Källen K. Abnormally invasive placenta—prevalence, risk factors and antenatal suspicion: results from a large population-based pregnancy cohort study in the Nordic countries. BJOG 2015; DOI: 10.1111/1471-0528.13547.

Acute Ovarian Insufficiency and Uterine Infarction Following Uterine Artery Embolization for Postpartum Hemorrhage-- A case report

Acute Ovarian Insufficiency and Uterine Infarction Following Uterine Artery Embolization for Postpartum Hemorrhage.

An interesting case reported by Elsarrag SZ et al in Clinical medical reviews and case reports. 2015;2(2):040.

This paper reports a case of acute ovarian insufficiency occurring within two weeks of UAE for PPH, most likely due to anomalous pelvic vasculature with large uterineovarian arteries anastomosis.

UAE is a life-saving procedure and complications are usually minimal.

There is, however, a possibility of uterine infarction and subsequent ovarian insufficiency in patients with significant ovarian to uterine artery anastomoses

A primparous patient underwent bilateral internal hypogastric artery embolization to control severe postpartum hemorrhage following primary cesarean section.

The bleeding continued, and a repeat aortogram demonstrated significant filling of the uterus from an anomalous proximal take off of the right uterine artery and from the left ovarian artery.

Further embolization was required to control the bleeding. The patient developed acute primary ovarian insufficiency within two weeks of the procedure and subsequently presented with uterine infarction necessitating hysterectomy.

 This case demonstrates the increased risk of acute ovarian insufficiency and uterine infarction following uterine artery embolization for postpartum hemorrhage in the settings of aberrant pelvic vasculature.

Uterine infarction has typically been reported with high injection of small-size polyvinyl alcohol particles (150-300μm), as these can migrate and block fine branches in the arterial tree, leading to ischemia

Avoiding uterine infarction may be facilitated by utilizing large size (>500μm) particles and particles with a shorter life span to allow sooner recanalization and collateral blood vessel formation.

Additionally, finer micro-catheterization techniques of select collateral vessels, where the catheter tip is meticulously placed as distal as possible and reflux of embolization material is minimized, is also warranted to prevent uterine infarction.

A total of seven cases of uterine infarction necessitating hysterectomy have also been described; two of these cases occurred following UAE for PPH, while five cases occurred following UAE for uterine fibroids.

Image courtesy-South Florida Fibroid Center

References: 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623578/

Elsarrag SZ, Forss AR, Richman S, Salih SM. Acute Ovarian Insufficiency and Uterine Infarction Following Uterine Artery Embolization for Postpartum Hemorrhage. Clinical medical reviews and case reports. 2015;2(2):040.

Vashisht A, Studd J, Carey A, Burn P. Fatal septicaemia after fibroid embolisation. Lancet. 1999;354:307–308. [PubMed]

Vedantham S, Goodwin SC, McLucas B, Mohr G. Uterine artery embolization: an underused method of controlling pelvic hemorrhage. Am J Obstet Gynecol. 1997;176:938–948. [PubMed]

Razavi MK, Wolanske KA, Hwang GL, Sze DY, Kee ST, et al. Angiographic classification of ovarian artery-to-uterine artery anastomoses: initial observations in uterine fibroid embolization. Radiology. 2002;224:707–712. [PubMed]