Adaptive Vapor Ablation offers a safe, effective, and minimally invasive option for performing in-office endometrial ablation

AEGEA Medical, Inc., a privately held Silicon Valley company has developed a unique Adaptive Vapor Ablation technology for the in-office treatment of heavy menstrual bleeding. AEGEA Vapor System is unique because it does not require cervical dilatation, nor does the probe needs to reach the fundus like other conventional ablation systems.

Heavy menstrual bleeding (HMB) is a common entity nearly affecting 25% of the premenopausal female population and negatively impacts on the physical, emotional and social quality of life. 

Endometrial ablation became a popular non-surgical alternative for treatment of HMB with the advent of hysteroscopically guided techniques. Several devices that involve the delivery of heat, cold, radiofrequency, and microwave energy are in use for endometrial ablation, each with its limitation and downside.

AEGEA Vapor System harnesses the ability of water vapor to effectively reach every part of the endometrial cavity and ablate the endometrial lining. It is the only FDA approved device with the patented Smart Seal and IntegrityPro technology.

The slender, soft tip disposable vapor probe is gently inserted in the uterine cavity without the need for cervical dilatation. The cervical color of the probe holds it securely in place. The SmartSeal technology allows for real-time monitoring of the uterine and cervical seal while the IntegrityPro technology performs patented secondary safety check to ensure correct placement of the device. It is only after the secondary safety check that vapor is initiated. 

The total procedure time is 4 minutes with 2 minutes of vapor treatment, eliminating the need of any balloon, ice or other arrays. The vapor ablation can safely be performed in patients with a prior lower transverse cesarean scar, a particular type of fibroids and in the presence of Essure. It can also treat uterine cavities that are wider and up to 12 cm in length as opposed to conventional devices that can only treat cavities up to 10 cm length.

Recently, results of the 12-month prospective, multicenter, pivotal study of its AEGEA Vapor System™ were published in the peer-reviewed Journal of Minimally Invasive Gynecology. Conducted across 15 sites in the United States, Canada, Mexico, and the Netherlands, the prospective trial involved 155 perimenopausal women aged 30 to 50 years with heavy menstrual bleeding who received 120-sec vapor ablation to treat HMB.

At the end of 12 months study period, 90% of women had bleeding reduced by ≥50 percent and 99% reported an improvement in the quality of life. Additionally, 85% reported an improvement in physical intimacy after the treatment. No serious device or procedure related side effects reported.

AEGEA Vapor System also allows post-ablation uterine cavity access as shown by 11 patient data from the Pilot study. “This issue has never been addressed before and gives the vapor system a distinct advantage of the possibility of future uterine-related interventions,” said Maria Sainz, president, and CEO of AEGEA Medical in a press release.

AEGEA Medical, Inc. has announced the commencement of the Post-Ablation Cavity Access (PACE II) clinical study in women who previously underwent endometrial ablation as part of AEGEA’s pivotal trial of the company’s patented Adaptive Vapor Ablation technology. The multi-center observational study, which is being conducted at seven sites across the U.S. in up to 50 women, is designed to assess uterine cavity access as well as the feasibility of diagnostic and therapeutic interventions three to four years following treatment.

Here is an animation video about AEGEA Vapor Ablation procedure:

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Abstract 

News release about results of the pivotal study

News release about the launch of Post-Ablation Cavity Access (PACE II) clinical study

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EMA approves Ulipristal for Preop Treatment of Uterine Fibroids

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) grants marketing authorization for Ulipristal Acetate (Gedeon Richter) as pre-operative treatment for uterine fibroids.

Ulipristal is a selective progesterone receptor modulator used for intermittent treatment for moderate to severe symptoms of uterine fibroids in women of reproductive age. It is also used as a pre-operative treatment in women scheduled for a uterine fibroid surgery, where it helps reduce bleeding, anemia and fibroid size. It will be available as 5 mg tablet upon approval.

The application for ulipristal approval was an informed consent application, which means that reference is made to an already authorized medication upon obtaining consent to the use of their dossier in the application procedure. The reference product for Gedeon Richter Ulipristal was Esmya.

The approval further recommends that the drug should only be prescribed by physicians who are experienced in the treatment of fibroids. The common side effects of the drug include endometrial thickening, amenorrhea, and hot flushes.

However, European Union drug regulators have expressed concerns about the side effects on the liver by Esmya in the past. In December 2017, the EMA opened an investigation about liver injury by the drug, followed by a monthly recommendation of liver function test in women taking Esmya by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC).

Meanwhile, the United States FDA announced in February 2018 that it had extended the review of ulipristal new drug application (NDA) to August 2018.

  

Committee Statement

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Ulipristal Acetate effectively controls uterine bleeding in patients with symptomatic uterine leiomyomas

Nearly 50% of women with symptomatic uterine fibroid achieved amenorrhea with Ulipristal Acetate as compared to placebo, reports the results of small randomized control trial published in March issue of Journal of Obstetrics and Gynecology.

Leiomyomas are the most common indication for hysterectomy in the United States affecting nearly 70% of white women and more than 80% of black women of reproductive age. About a quarter or 50% of women experience symptoms, the most common being heavy and irregular uterine bleeding.

Many medical treatment options like nonsteroidal anti-inflammatory drugs (NSAIDs), levonorgestrel intrauterine devices, and oral and nonoral combination contraceptives are prescribed in the treatment of symptomatic fibroids but data about their efficacy is limited.

Other off-label drugs that are used for short-term management include gonadotropin-releasing hormone agonists and tranexamic acid.

This multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group phase 3, (NCT02147197) was conducted at 25 study centers across the United States.

Premenopausal women between 18-50 years of age with one or more discrete leiomyomas and uterine size 20 weeks of gestation with menorrhagia were included in the study. The researchers looked at the rate of and time to amenorrhea (no bleeding for the last 35 consecutive days of treatment) as the co-primary endpoints and Uterine Fibroid Symptoms and Quality of life (QoL) as the secondary endpoints.

Over a period of 2 years, 157 patients with similar demographics were randomized 1:1:1 to once-daily oral 5 mg ulipristal, 10 mg ulipristal, or placebo followed by a 12-week drug-free period.

Patients fared significantly better with both the doses of ulipristal, in terms of achieving amenorrhea 25 of 53 (47.2%) and 28 of 48 (58.3%) patients treated with 5 mg and 10 mg ulipristal, respectively achieved amenorrhea as compared with 1 of 56 (1.8%) of placebo-treated patients (both P <.001).

Patients on ulipristal also reported an improved quality of life and a decrease in the amount of blood loss. At the end of follow-up period decrease in volume of the leiomyomas was also observed in ulipristal treated groups as compared to placebo where an increase was noted.  

The small sample size and short duration of treatment were not enough to study the side effects but not a single patient discontinued the treatment because of side effects of the drug.

Other studies have shown that multiple 12-weeks courses of ulipristal (up to 8 coursed of 12 weeks duration each) is effective and well tolerated and maintains the efficacy and quality of life.

The authors concluded, “ulipristal may be useful for the medical management of abnormal uterine bleeding associated with uterine leiomyomas, especially for patients desiring uterine- and fertility-sparing treatment.”

Abstract

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Hologic, Inc launched MyoSure MANUAL, for in-office intrauterine tissue removal

Hologic, Inc today expanded its Myosure portfolio by adding the MyoSure MANUAL device which enables physicians to more easily resect and remove intrauterine polyps and fibroids in office settings when used along with the MyoSure hysteroscope.

The device comes with an ergonomically designed blade that can be rotated through 360 degrees, enabling wide range of smooth motion. The system does not require cauterization and have a transparent tissue trap that allows the physician to see the specimen and can holds up to 4gms of tissue.

The tissue trap can be detached, and the specimen can be sent for direct histopathological examination.

In addition, the system also comes with a built-in vacuum, eliminating the need of external suction and works with a one-liter saline bag. 

The complete MyoSure system is a minimally invasive hysteroscopic treatment for women with Abnormal Uterine Bleeding (AUB) due to polyps or fibroids and requires no cauterization, which preserves uterine form and function.

Edward Evantash, M.D., Medical Director and Vice President of Medical Affairs, Hologic said in a press release, “We recognize the increased demand for in-office procedures, and seek to develop innovative solutions to provide flexibility and convenience for both physicians and patients. The MyoSure MANUAL device was designed for in-office tissue removal procedures, requiring minimal setup and no vacuum or fluid management system, while offering direct visualization when used with the MyoSure hysteroscope."

 “The MyoSure MANUAL device is an exciting addition to Hologic's growing portfolio of gynecologic solutions, developed with the patient and physician in mind. This addition to the MyoSure product suite signals our ongoing commitment to providing effective surgical solutions that can be performed in office to address our customers' needs and improve the overall patient experience," added Sean Daugherty, President of GYN Surgical Solutions at Hologic.

Contraindications for the use of MyoSure MANUAL Tissue Removal Device includes  pregnancy or suspected pregnancy, has clinical evidence of an active pelvic infection or history of a recent pelvic infection, or has cervical malignancies or previously diagnosed uterine cancer.

Other devices in Myosure Portfolio include MyoSure^®, MyoSure^® REACH, MyoSure^® XL, and MyoSure^®LITE devices.

Complete MyoSure MANUAL device Instructions for use

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News from ASRM 2017: Uterine Artery Embolization is preferable over focused ultrasound for Uterine Fibroids

Women undergoing MR-guided focused ultrasound (MRgFUS) for symptomatic fibroids are twice as likely to undergo a second procedure as compared to women treated by Uterine Artery Embolization(UAE) reports results of study presented at ASRM 2017.

The study is also published in Fertility and Sterility September supplement.

The FIRSTT study (NCT00995878) enrolled 83 premenopausal women with symptomatic uterine fibroids and have completed their families, with an aim to compare the safety and effectiveness of two standard fibroid treatments approved by FDA: MRI guided ultrasound surgery (MRgFUS) and uterine artery embolization (UAE).

It also focused on better understanding of fibroid symptoms that bothered the women most, and how it affects the quality of life.

The study randomized the women to one of the treatment arms as well as observed the outcome for women who refused randomization but met the study criteria.

The average age of the study participant was 45 years with nearly 2/3 being obese (BMI > 25 kg/m²) and Caucasian. Nearly twice the number of women who underwent MRgFUS, required a second procedure at the end of two years as compared to women undergoing embolization (HR 2.8, 95% CI: 1.1, 7.8).

A significantly more number of women attained menopause in embolization arm (9%) vs MRgFUS(0%). Disease specific quality of life was also much better in women who had embolization, perhaps early menopause alleviated the symptoms of fibroid.

The authors concluded that, “Women undergoing MRgFUS were more likely to have a second procedure for fibroids compared with those undergoing UAE.”

More News from ASRM 2017

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Finally, an oral drug found effective in treatment of Uterine Fibroids following successful phase-3 trial

Relugolix successfully reduced heavy menstrual blood loss among Japanese women in a Multicenter, Randomized, Double-Blind, Parallel-Group, Phase 3 Study to Evaluate the Efficacy and Safety of Oral relugolix 40 mg as compared with injectable leuprolide  in the Treatment of Uterine Fibroids.

Relugolix is an oral, once-daily, small molecule GnRH receptor antagonist that has been evaluated in almost 1,600 study participants in Phase 1, Phase 2 and Phase 3 clinical trials. In these trials, it has shown to suppress estrogen and progesterone levels in women and testosterone levels in men. (It is also being evaluated in advanced prostate cancer via ongoing phase-3 HERO study).

The drug is being developed by Switzerland’s Myovant Sciences along with Japan’s Takeda. They said that these results will support the other ongoing global trials evaluating the drug in endometriosis and uterine fibroid patients.

"The positive results of decreased menstrual bleeding from Takeda's Phase 3 study of relugolix in Japanese women with uterine fibroids provides strong support for Myovant's ongoing Phase 3 studies with relugolix in North America, Europeand other regions," stated Lynn Seely, M.D., President and Chief Executive Officer of Myovant Sciences in a press release. 

"Uterine fibroids result in debilitating heavy menstrual bleeding and anemia in millions of women throughout the world, oftentimes requiring a hysterectomy to control the bleeding.  Myovant is working to develop relugolix, an oral, once-daily medication that can potentially provide women with an alternative option to major surgery for the treatment of uterine fibroids."

The study recruited 288 women with heavy menstrual bleeding associated with uterine fibroids. They were randomized to receive either relugolix 40 mg, administered orally once daily, or leuprolide acetate, an injectable GnRH agonist, administered by subcutaneous injection every four weeks, at a dose of 1.88 mg or 3.75 mg, for 24 weeks. 

The amount of blood loss was assessed by Pictorial Blood Loss Assessment Chart, or PBAC self-reported by patient themselves. At entry into study all patient had PBAC ≥ 120.

In the study, relugolix successfully demonstrated that it was as good as leuprolide acetate with 82.2% of patients achieving a score of less than 10 on the PBAC, compared with 83.1% of patients treated with leuprolide acetate (p = 0.0013).

The incidence of adverse effects was nearly similar and varied according to the drug. Another phase 3 trial with relugolix is currently ongoing in Japan with 70 patients who also complained of pain because of fibroids.

Two more trials (LIBERTY 1 and LIBERTY 2) are ongoing and were initiated by Myovant in January 2017.  These trials are looking at reducing heavy menstrual blood loss by relugolix alone followed by leuprolide  as monotherapy, relugolix combined with low dose leuprolide  or placebo for 24 weeks. 

These two trials are looking at reduction in blood loss by at least 50%, decrease in pain and size of fibroid and safety of the drug, as evident by bone -mineral density.

Myovant is solely responsible for obtaining Food and Drug Administration (FDA) approval for relugolix in the United States and the results of Takeda study will definitely reinforce its application. 

The drug is also currently tested by two phase-3 ongoing trials for relieving endometriosis associated pain, named as SPIRIT 1 and SPIRIT 2. These two trials are still recruiting patients and will run through 2020. The trials will evaluate relugolix with and without low-dose hormonal add-back therapy, to avoid the iatrogenic menopausal side effects.

Twelve important risk factors for Uterine Fibroid identified: A systematic review

First and only systematic review conducted so far to know the prevalence and risk factors for developing Uterine Fibroid (UF), identified race and ovarian hormone exposure as the most important determinants of fibroid development. The review was published recently in BJOG.

Uterine fibroids are most common benign neoplasm in women and nearly affect 2/3 of women before menopause, but largely remain undetected as only 25% cause symptoms that warrant treatment.

They are also the number one cause of gynecological hospital admissions and also an important indication for hysterectomy.

A literature search identified 60 studies that were eligible to be included in the review. There was considerable variations in type of studies, some reported single center experience while mostly were registry based studies. Studies included cohort and case control studies with international or local population with women from different race and ethnicity.

Fibroids were diagnosed by pelvic examination, Ultrasound or at the time of surgery.

There was a wide range in incidence of UF, and varied between 217–3745 cases per 100 000 women-years while the prevalence was between 4.5% to 68.6%.

After analysis of data, broadly 30 factors were identified that increased a woman’s risk of developing UF, of which  12 were of considerable magnitude.

Risk Factors:

Demographically, black race is important risk  factor and increases the risk by 2-3-fold as compared to  whites, followed  by age. 

Age increases the risk by nearly 10 folds,  for women between age the  40 -60 years as compared to women in their 20s. 

A positive family history also predisposes the women to higher risk for UF.

More than 5 years since child birth puts you at higher risk as compared to woman who has recently given birth.

Premenopausal women have 3-5 times increased risk as compared to postmenopausal women.

Women who are diagnosed with hypertension are 5 times the risk as compared to their normotensive counterparts.

Consuming food with additives and Soyabean increases the risk by 2.5times.

Protective Factors:

Increased parity (more than 3 children) is protective against UF and lowers the risk by 80% as compared to Nulliparous woman.

Smoking was found to be protective, but only in women with low BMI

Oral and injectable contraceptives protect against UF and reduces the risk by nearly 20-50%.

This study supports the view that genetic and ovarian hormones are two important risk factors for development of UF. The genetic aspect cannot be modified, but life style and hormonal modification can reduce the risk of fibroid development.

In an accompanying commentary, Vercellini P and Frattaruolo MP stress the importance of therapies using selective progesterone receptor modulators (SPRMs) as an alternative to invasive treatments for fibroid associated menorrhagia and volume symptoms.

This study has identified important risk factors that can be used by physicians in clinical settings and researchers for further drug and treatment development.

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Commentary 

An effective, minimal invasive but “vastly underutilized” treatment option for fibroids: Uterine Fibroid Embolization

Statistics by National Institute of Health (NIH) indicate that nearly 3 in 4 women will develop fibroid by the time they reach age 50, but more than half of these women have never heard of Uterine Fibroid Embolization and 11% think that hysterectomy is the only treatment option available to them says the results of a Nationwide survey conducted by Harris Poll between June 23 and 27, 2017.

The survey was conducted on behalf of the Society of Interventional Radiology (SIR) and results were presented at the Society of Interventional Radiology’s 2017 Annual Scientific Meeting.

The survey of almost 1,200 women found that about one third of women did not know what fibroids are, 37% did not know anybody else with the diagnosis of fibroid, and nearly 60% did not think that they are at risk of developing fibroid.

Courtesy: Linkedin.com 

One in 5 women thought fibroids are cancerous and surgery is the only treatment option they have.

A majority of women (62%)have never heard of Uterine Fibroid Embolization, and 73% of women who knew about UFE reported that they got the information elsewhere, other than their Ob/Gyn.

As per National Uterine Foundation, nearly 600,000 hysterectomies performed annually in the United States out of which ~170,000 - ~300,000 are due to uterine fibroids. A review of published studies has shown that nearly 1 in 5 hysterectomy is unindicated and 40% of patient who have hysterectomy do not receive full information about other medical or less invasive procedures available to them. It appears that it was presented to them as the best treatment option available, says the SIR report.

James Spies, MD, MPH, a professor of radiology at Georgetown University Medical Center, Washington, DC, and the president-elect of SIR said, "Misperceptions about uterine fibroids and the treatments available often lead women to undergo invasive and potentially unnecessary surgery for their fibroids, despite more than 20 years of clinical use supporting uterine fibroid embolization.”

"Unfortunately, still many health care professionals start and end with hysterectomy as the recommendation for patients," he further added.

An NIH study showed that 165,000 more hysterectomies were performed than UFEs (167,650 vs. 2,470) nationwide, a difference of whopping 67% between the two procedures.

The study also reported that nine out of 10 women who have uterine fibroid embolization have significant improvement. Many women report their symptoms disappear completely.

UFE also helps women in getting back to normal lives quickly after the procedure, with no residual effects of early menopause and sexual dysfunction, as often experienced after hysterectomies.

It is also minimally invasive with a hospital stay of one day or less, cost effective, low rate of complications and few women require follow up treatment. If the fibroids recur, they can be again be treated: A second UFE is not contraindicated, said Dr Spies.

It’s also a great option for women desiring future pregnancies.  A study published in Radiology Journal showed a 41.5 percent pregnancy rate after an average follow-up of almost six years.

The ACOG has included UAE in its FAQs on Uterine Fibroids. The procedure was included as one of the treatment option in its 2008 bulletin, reaffirmed again in 2016. The bulletin concludes, "Based on long- and short-term outcomes, uterine artery embolization is a safe and effective option for appropriately selected women who wish to retain their uteri." 

Courtesy: SIR

UFE is performed by an interventional radiologist who inserts a thin catheter into the artery at the groin or wrist. The doctor guides the catheter to the fibroid’s blood supply where small particles, about the size of grains of sand, are released to float downstream and block the small blood vessels and deprive the fibroid of nutrients. This results in the fibroid softening, bleeding less, and shrinking in size.

Does  the push to promote UFE by SIR means promoting self-interest? No, it only means that women diagnosed with fibroids deserve to know about all the options they have and the clinicians should be able to inform them about it. 

Executive summary of survey, Full PDF, SIR news release
RCOG recommendations for UAE for Fibroids

Endocrine Disruptors linked to Endometriosis, Fibroids and rising healthcare costs!

 European Union data revealed that Women are facing a potential risk of several reproductive disorders being exposed common chemicals in the household and incurring huge public health cost.

Endocrine-disrupting compounds (EDCs) act as covert bombers of environmental toxins on human body. They are ubiquitous in our environment, entering our bodies without our knowledge-plastic linings in cans, water bottles, toys and most recently in the thermal paper used in cash register and gas pump receipts.

The recent study led by Patricia Hunt, PhD, at Washington State University was published online March 22, 2016 in the Journal of Clinical Endocrinology & Metabolism. The researchers found that exposure to controversial chemicals, like phthalates and diphenyldichlorethene (DDE), increase a woman’s likelihood of developing endometriosis and fibroids, causing reproductive health problems and incurring a whopping sum of  estimated €1.4 billion ($1.5 billion) a year in health care expenditures and lost earning potential to European Union.

Senior author Leonardo Trasande, MD, MPP, associate professor of pediatrics, environmental medicine & population health at NYU Langone Medical Center, New York, opines that this is just the tip of the iceberg of the entire female reproductive disease burden due to EDC.

Hunt and her colleagues identified other chemicals namely dioxins and polychlorinated biphenyls (PCBs), among others -- but decided to focus on phthalates and diphenyldichlorethene (DDE) as most robust set of data existed for these chemicals. 

DDE is a breakdown product of the insecticide DDT that, although banned in the United States in 1972 and in Europe starting in the 1970s still lingers in the environment and enters our body through food. The main exposure to phthalates is through eating food and drink stored in plastic containers that have phthalates.

In both cases, the epidemiological evidence was low and toxicological evidence was moderate but of all the total cases 20%–39% cases were attributed to these chemicals.

The researchers determined that 145,000 cases of endometriosis among women aged 20 to 44 years and 56,700 cases of uterine fibroids in Europe could be attributed to exposure to endocrine-disrupting chemicals.

In women 15-54 of age, the exposure to DDE was measured in 12 studies by taking a sample of cord blood. They then adapted an Intergovernmental Panel on Climate Change (IPCC) model for determining the probability of causation. The women were separated into groups according to degree of exposure, with the lowest level used as the base and than the odds ratio for developing fibroid was calculated.

The process for phthalate attributable endometriosis was similar, but the investigators relied on data from a large biomonitoring study called as DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale (DEMOCOPHES). Human biomonitoring (HBM) involves collecting samples from human volunteers – blood, hair, saliva or urine – and measuring the levels of indicators of chemicals uptake (known as biomarkers) that are of interest.

The authors further added that "Although it is highly appropriate to focus on these extremely important uterine tract health deficits, [polycystic ovary syndrome], infertility, and pregnancy complications also affect a considerable number of women, have major cost implications, and are increasingly linked to EDC exposures." For instance, phthalate exposure has a 40% to 69% likelihood of causing 618,000 additional assisted reproductive technology procedures each year, and a 20% to 69% likelihood of causing 42,400 new cases of childhood obesity each year.

The director of the National Institute of Environmental Health Sciences and the National Toxicology Program Linda S. Birnbaum said “Some of these chemicals, including PCBs and dioxins, have already been restricted through a treaty called the Stockholm Convention on Persistent Organic Pollutants, which went into effect in 2004.”

The current study is important because it focused on chemicals that have not been restricted, and in the case of DDE -- which persists in the environment -- are not able to be restricted.

"This study is kind of a wake-up to say endocrine disruptors impact the female reproductive system, and we have some evidence they are associated with an increase in endometriosis and fibroids and it costs a lot of money," Birnbaum said.

Not all researchers are convinced by the methodology. They say that to imply causation based on current data is highly speculative because most of the data is based on observational study and trials is human are hard to do.

Even with all the questions that remain, and few regulations in place, "there are safe and simple steps that families and women can take to reduce exposure to endocrine-disrupting chemicals," Trasande said.

"They can eat organic, reduce canned food consumption, which reduces exposure to BPA, and avoid packaged or highly processed food, which is a major route for phthalates to enter food. They can also open windows to allow chemical dust, which accumulates on the carpet and electronics, to circulate out of homes."

Although the study had several limitations: it focused on adult EDC exposure only; it relies on assumption of causation; and it focuses only on two reproductive disorders and two EDCs, it does draws attention on urgent need of  further research , government regulations and public awareness on the issue of toxic chemicals in the environment.

References:

http://press.endocrine.org/doi/10.1210/jc.2015-2873

http://saferchemicals.org/health-report/chemicals-and-our-health/reproduction/

http://www.aboutlawsuits.com/endocrine-disruptor-women-study-97423/

http://www.medpagetoday.com/OBGYN/GeneralOBGYN/56864

http://www.eu-hbm.info/democophes

http://www.thedoctorwillseeyounow.com/content/womens_health/art4602.html

https://www.endocrine.org/news-room/current-press-releases/womens-health-endocrine-disruptors-diabetes-research-will-be-in-spotlight-at-endo-2016

Abnormal Uterine Bleeding (AUB)

Abnormal Uterine Bleeding (AUB) also called as dysfunctional uterine bleeding is a common problem especially at the beginning and end of the reproductive years affecting 14–25% of women.

An orderly approach using the International Federation of Gynecology and Obstetrics

(FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification helps in arriving at accurate diagnosis and well informed management options for the patient.

Fibroids are the most common cause in women presenting with AUB especially by the age of 50, According to a paper by Baird  DD et al the estimated cumulative incidence at this age is almost 70% of white women and >80% of black women will have developed at least one fibroid.

As women postpone motherhood in favor of better career choices, fertility preservation and newer medical options becomes genuine choices as treatment options.

This review by Whitaker L and Critchley H.O.D published in forthcoming issue of Best Practice & Research Clinical Obstetrics & Gynecology considers the FIGO classification of   AUB and addresses the general principles of managing it in premenopausal women.

FIGO in 2009 defined chronic AUB as ‘bleeding from the uterine corpus that is abnormal in volume, regularity and/or timing that has been present for the majority of the last 6 months’.

With regard to volume, however, both the Royal College of Obstetricians and Gynaecologists (RCOG) and American College of Obstetricians and Gynecologists (ACOG) prefer the patient-centered definition of HMB, ‘excessive menstrual blood loss which interferes with a woman's physical, social, emotional and/or material quality of life’ as an indication for investigation and treatment options.

FIGO classification of cause: ‘PALM-COEIN’ is now being increasingly used for categorising causes: Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified The ‘PALM’ are assessed visually (imaging and histopathology) and the ‘COEIN’ are non-structural.

Adapted from Best Practice & Research Clinical Obstetrics & Gynecology March 2016 issue.

Assessment of the patient presenting with AUB and fibroids

Adapted from Best Practice & Research Clinical Obstetrics & Gynecology March 2016 issue.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 Structured history for coagulopathy screen. Adapted from Koudies et al. .

Criteria
1. Heavy bleeding since the menarche
2. One of the following: Postpartum haemorrhage •Surgical-related bleeding •Bleeding associated with dental work
3. Two or more of the following: Bruising 1–2 times/month Epistaxis 1–2 times per/month Frequent gum bleeding Family history of bleeding problems

Endometrial sampling

Endometrial sampling: In the UK, NICE recommend endometrial sampling in women with persistent inter-menstrual bleeding or aged ≥45 years with treatment failure .This has been highlighted in the RCOG guidelines with an exception of reducing the age of sampling in the context of treatment failure to 40 . With the marked increase in endometrial cancer, the authors would encourage all gynaecologists to continue to excise their clinical judgement for those women aged <40 years with HMB who have risk factors for premalignant change such as obesity and PCOS.

Approach to management

In those patients where the cause of AUB is fibroid, the treatment should be tailored based on individual symptoms and requirements.  It should be based upon fertility desire, age of the patient, and associated co morbidities.

Specific treatment options for individual PALM-COEIN causes of AUB.

AUB  Sub-classification	Specific treatment
Polyp	Resection
Adenomyosis	Surgery: hysterectomy; adenomyomectomy (not frequently performed)
Malignancy	Surgery +/− adjuvant treatment High-dose progestogens (if surgery not possible)  Palliation (including radiotherapy)
Coagulopathy	Tranexamic acid  DDVAP
Ovulation	Lifestyle modification Cabergoline (if hyperprolactinaemia)  Levothyroxine (if hypothyroid)
Endometrial	Specific therapies await further delineation of underlying mechanisms
Iatrogenic	Refer to FSRH CEU guidance on problematic bleeding with hormonal contraception
Not otherwise classified	Antibiotics for endometritis  Embolisation of AV malformation

Some salient features in  the management are:

• Fully non hormonal medical options are Tranexamic acid and NSAIDs (e.g. mefenamic acid)
• While the risk for expulsion due to distortion of the cavity does exist, (LNG–IUS) are still efficacious in controlling the bleeding.
• The current Cochrane review only includes mifepristone, and a future review that includes other medical options is awaited. Although  PEARL II study has documented the efficacy of SPRM ulipristal acetate (UPA) particularly in short term use before surgery.
• With regards to interventional radiological procedures like uterine artery embolism and it’s comparison to myomectomy, the authors are awaiting the result of FEMME trial to provide robust evidence.
• Hysterectomy will remain the definitive treatment, especially in context of HMB in patients who have completed the families, until alternative treatment strategies are developed and well documented.

References:

http://www.bestpracticeobgyn.com/article/S1521-6934%2815%2900226-6/fulltext

Fraser, I.S., Langham, S., and Uhl-Hochgraeber, K. Health-related quality of life and economic burden of abnormal uterine bleeding. Expert Rev Obstet Gynecol. 2009; 4: 179–189

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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.

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