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]

Achieving therapeutic balance in treatment of infertility associated with deep endometriosis!

 

From Getty Images

Endometriosis is a benign gynecologic disease diagnosed in 10%-15% of the general population and as many as one third of women with endometriosis are infertile.

picture courtesy: whisperedwordsforevercaptured.blogspot.com

Asymptomatic endometriosis does not need to be treated. For patients with recurrent or constant symptoms, medical or surgical treatments can be offered.

The management of endometriosis in infertile women is somewhat controversial.

Controversy exists surrounding the issue of surgical treatment of deep, infiltrating endometriosis in infertile women.

This opinion paper by Somigliana E and Garcia-Velasco JA from  Fertil Steril. 2015; 104:764-770 addresses this latter issue.

High-quality scientific evidence to support the treatment of deep endometriosis in the context of infertility is scant because in 50%-70% of affected women, superficial endometriosis can be found in addition to deep endometriosis.

Superficial endometriosis, compared with deeply buried, infiltrating lesions, is more likely to release inflammatory cytokines that can affect reproduction. Furthermore, a sizeable proportion of cases are complicated by the presence of adenomyosis, which interferes with successful implantation. Therefore, it is difficult to draw a definite conclusion about the management of women with deep endometriosis only.

According to a systemic review and meta-analysis by Hamdan M et al- Compared with women without endometriosis, women with endometriosis undertaking in vitro fertilization and intracytoplasmic sperm injection have a similar live birth rate per woman and a similar miscarriage rate per woman and lower clinical pregnancy rate per woman and a lower mean number of oocyte retrieved per cycle.

Women with more severe disease (American Society for Reproductive Medicine III-IV) have a lower live birth rate, clinical pregnancy rate, and mean number of oocytes retrieved when compared with women with no endometriosis.

They concluded that women with and without endometriosis have comparable ART outcomes in terms of live births, whereas those with severe endometriosis have inferior outcomes. There is insufficient evidence to recommend surgery routinely before undergoing ART.

Infact, Extensive surgery for intraperitoneal and deep endometriosis in infertile women does not modify global fertility outcome but is associated with a higher complication rate.

In vitro fertilization (IVF) can be offered as an option to treat infertility in women with deep endometriosis. Conflicting results have been published about the added benefit of pre-IVF surgical excision of deep endometriosis

The opinion statement concludes that the current evidence is confounded by the lack of pure studies on deep endometriosis that are free of the negative impact of superficial endometriosis and adenomyosis.

Women who are asymptomatic or whose symptoms can be managed by medical therapy should probably go straight to IVF without any surgery beforehand.

Women whose symptoms are refractory to medical therapy or those who need immediate surgery for ureteral or bowel stenosis should undergo operative treatment before IVF, however. Surgery can also be considered for asymptomatic patients with multiple failed assisted reproduction cycles.

References

1.      Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril. 1985;43:351-352. Abstract

2.      Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10:261-275. Abstract

3.      Dunselman GA, Vermeulen N, Becker C, et al; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29:400-412. Abstract

4.      http://www.fertstert.org/article/S0015-0282%2815%2901757-4/abstract

5.      http://www.fertstert.org/article/S0015-0282%2815%2901876-2/abstract

6.      Marcoux S, Maheux R, Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997;337:217-222. Abstract

7.      Vercellini P, Pietropaolo G, De Giorgi O, Daguati R, Pasin R, Crosignani PG. Reproductive performance in infertile women with rectovaginal endometriosis: is surgery worthwhile? Am J Obstet Gynecol. 2006;195:1303-1310. Abstract

8.      Douay-Hauser N, Yazbeck C, Walker F, Luton D, Madelenat P, Koskas M. Infertile women with deep and intraperitoneal endometriosis: comparison of fertility outcome according to the extent of surgery. J Minim Invasive Gynecol. 2011;18:622-628. Abstract

9.      http://whisperedwordsforevercaptured.blogspot.com/2015/03/what-is-endometriosis_1.html

Ondansetron Revisited: New and troubling data

Ondansetron

Ondansetron is a 5-HT₃ receptor antagonist manufactured by GlaxoSmithKline in US and is also available in its generic form, ondansetron.

The drug was approved by The U.S. Food and Drug Administration in 1991 for treating nausea and vomiting caused by cancer treatments such as chemotherapy.

However, doctors began using the drug off-label to treat women with morning sickness.

Presently, 97.7% of prescriptions for the treatment of nausea and vomiting in pregnancy in the United States are with medications not labeled for use in pregnancy, not indicated for nausea and vomiting in pregnancy, and not classified as safe in pregnancy by the Food and Drug Administration.

The use of ondansetron for nausea and vomiting in pregnancy has increased from 50,000 monthly prescriptions in 2008 to 110,000 at the end of 2013, despite unresolved issues regarding fetal safety and Food and Drug Administration warnings about serious dysrhythmias.

Sales of antiemetics for NVP in the US, 2008-2014

IMS National Prescription Audit from 2008 to 2014.

Estimates suggest one out of every four pregnant women receive a prescription for ondansetron.

In January 2012, a study from the Center for Birth Defects Research and Prevention identified a twofold increased risk for cleft palate associated with ondansetron exposure used for Nausea Vomiting in Pregnancy (NVP) in the first trimester. The study used data from the National Birth Defects Prevention Study, looking at the association between NVP and treatments for NVP and cleft palate, and other noncardiac birth detects.

In 2013, a Danish study by Pasternak B et al compared pregnancy outcomes among almost 2,000 women exposed to ondansetron in pregnancy, and women not exposed to the drug between 2004 and 2011. Exposure to ondansetron was not associated with an increased rate of major malformations (at about 3%), or other adverse fetal outcomes, including stillbirth, preterm delivery, and low birth weight, compared with the unexposed pregnancies

Following this in August 2013, at the International Society of Pharmacoepidemiology meeting in Montreal, the results of a different group of Danish researchers using data from the same national registries employed in the study published in February, but with more pregnancies (almost 900,000) over a longer period (1997 to 2010), detected a twofold increase in congenital heart defects associated with ondansetron during the first trimester of pregnancy.

Overall, the risks associated with ondansetron exposure during the first trimester of pregnancy remain unclear. Most observational research suggests that ondansetron is unlikely to increase the risk for miscarriage, stillbirth, or major birth defects. The few studies evaluating the effect of ondansetron on specific birth defects associate ondansetron exposure early in pregnancy with a small but significant risk for cleft palate and heart defects.

There are also potential maternal risks associated with taking Ondansetron  especially in pregnant women with electrolyte imbalance due to severe nausea and vomiting. These risks include the Serotonin Syndrome which is a triad of cognitive or behavioral changes including confusion, agitation, autonomic instability, and neuromuscular changes.

With these recent studies, we are left with contradictory results regarding the risk of birth defects associated with ondansetron exposure in the first trimester, and more studies may be needed.

Prescribing ondansetron as a first line option is not consistent with American Professors in Gynecology and Obstetrics and American College of Obstetricians and Gynecologists evidence-based recommendations for the management of NVP.

Ondansetron is not recommended by current guidelines as a first-line option for nausea and vomiting in pregnancy. Initial treatments are lifestyle and dietary modifications. If drug therapy is required, doxylamine/pyridoxine is FDA-approved and guideline-endorsed for the treatment of nausea and vomiting in pregnancy. 

In conclusion, with the availability of a safe and effective FDA-approved drug for NVP, there is no reason for women to be exposed to a drug of unproven maternal and fetal safety, which has not been labeled for NVP. 

Given the current evidence, ondansetron should be avoided in the first trimester of pregnancy unless other treatments are ineffective.

Several families filed lawsuits after their children suffered a number of defects, including: mental problems, vision issues, heart defects, cleft palate and lip, clubbed foot and skull deformities.

One of the suits, filed in July 2015 by Angela and Brian Kutzer, claims Glaxo paid doctors to promote and prescribe Zofran and made “false representations about the safety and efficacy” of the drug.

As of October 2015, these lawsuits were consolidated into a multidistrict legislation in the Eastern District of Pennsylvania.

References:

• http://www.drugwatch.com/2015/11/24/study-links-zofran-to-birth-defects/ Accessed December 08, 2015.
• Treating morning sickness in the United States - Changes in prescribing are needed. Koren G. (2014) American Journal of Obstetrics and Gynecology, 211 (6), pp. 602-606.
• http://www.obgynnews.com/single-view/ondansetron-new-and-troubling-data/00595b8bf7a0ec96a0d280e28af9edd6.html Accessed December 15, 2015.
• Mayhall EA, Gray R, Lopes V, Matteson KA. Comparison of antiemetics for nausea and vomiting of pregnancy in an emergency department setting. Am J Emerg Med. 2015;33:882-886. Abstract
• American College of Obstetricians and Gynecologists. ACOG (American College of Obstetrics and Gynecology) Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004; 103:803-814. Abstract
• American Professors in Gynecology and Obstetrics (APGO) Educational Series on Women's Health. Nausea and vomiting of pregnancy. American Professors in Gynecology and Obstetrics. 2015.
• https://www.apgo.org/images/nvp/nvp_monograph_040215_final.pdf Accessed December 08, 2015.

·        Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G. The safety of ondansetron for nausea and vomiting of pregnancy: A prospective comparative study. BJOG. 2004;111:940-943. Abstract

·        Colvin L, Gill AW, Slack-Smith L, Stanley FJ, Bower C. Off-label use of ondansetron in pregnancy in Western Australia. Biomed Res Int. 2013;2013:909860.

·        Pasternak B, Svanstrom H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med. 2013;368:814-823. Abstract

·        http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm351864.htm

• Anderka, M., Mitchell, A.A., Louik, C., Werler, M.M., Hernández-Diaz, S., and Rasmussen, S.A. National Birth Defects Prevention Study. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth Defects Res A Clin Mol Teratol. 2012; 94: 22–30
• http://www.utswmedicine.org/stories/articles/year-2015/zofran-pregnancy.html Accessd December 08, 2015.
• http://www.fertilitycenter.com/fertility_cares_blog/fda-warns-against-zofran-use-in-pregnancy/ Accessd December 08, 2015