Master Class

 

Chronic pelvic pain continues not only to burden the individual, but society as well.

One in seven women between the ages of 18 and 50 endure chronic pelvic pain; with a lifetime incidence of as high as 33%, according to one Gallup poll. Interstitial cystitis/bladder pain syndrome (IC/BPS) has been estimated to have a prevalence of 850 in 100,000 women and 60 in 100,000 men in self-report studies. The RAND Interstitial Cystitis Epidemiology (RICE) study, a symptoms survey, showed that between 2.7% and 6.5% of women (3.3 to 7.9 million women) in the United States have symptoms consistent with a diagnosis of IC/BPS.

Unfortunately, there is little known about the etiology and pathogenesis of IC/PBS. Moreover, oftentimes, the diagnosis is one of exclusion.

To demystify interstitial cystitis/bladder pain syndrome, I have elicited the assistance of Dr. Kenneth Peters, a urologist on staff at William Beaumont Hospital, Royal Oak, Mich. Dr. Peters is the professor and chairman of urology at Oakland University, William Beaumont School of Medicine, and the chairman of urology at Beaumont Health, Royal Oak, Mich.

In his discussion, Dr. Peters will point out that interstitial cystitis actually consists of two different entities: a classic presentation featuring the pathognomonic Hunner’s lesion on cystoscopy and interstitial cystitis/painful bladder syndrome.

It must be acknowledged that Dr. Peters is a practicing urologist. Therefore, some of his recommendations, such as cauterizing Hunner’s lesions via a resectoscope, are beyond the scope of practicing gynecologists. However, it is important for us to realize what our potential referrals possess in their armamentarium. Moreover, it is obvious there is much that can be learned from this excellent diagnostician who professes the importance of physical examination.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He is an investigator on an interstitial cystitis study sponsored by Allergan.

 

Chronic pelvic pain continues not only to burden the individual, but society as well.

One in seven women between the ages of 18 and 50 endure chronic pelvic pain; with a lifetime incidence of as high as 33%, according to one Gallup poll. Interstitial cystitis/bladder pain syndrome (IC/BPS) has been estimated to have a prevalence of 850 in 100,000 women and 60 in 100,000 men in self-report studies. The RAND Interstitial Cystitis Epidemiology (RICE) study, a symptoms survey, showed that between 2.7% and 6.5% of women (3.3 to 7.9 million women) in the United States have symptoms consistent with a diagnosis of IC/BPS.

Unfortunately, there is little known about the etiology and pathogenesis of IC/PBS. Moreover, oftentimes, the diagnosis is one of exclusion.

To demystify interstitial cystitis/bladder pain syndrome, I have elicited the assistance of Dr. Kenneth Peters, a urologist on staff at William Beaumont Hospital, Royal Oak, Mich. Dr. Peters is the professor and chairman of urology at Oakland University, William Beaumont School of Medicine, and the chairman of urology at Beaumont Health, Royal Oak, Mich.

In his discussion, Dr. Peters will point out that interstitial cystitis actually consists of two different entities: a classic presentation featuring the pathognomonic Hunner’s lesion on cystoscopy and interstitial cystitis/painful bladder syndrome.

It must be acknowledged that Dr. Peters is a practicing urologist. Therefore, some of his recommendations, such as cauterizing Hunner’s lesions via a resectoscope, are beyond the scope of practicing gynecologists. However, it is important for us to realize what our potential referrals possess in their armamentarium. Moreover, it is obvious there is much that can be learned from this excellent diagnostician who professes the importance of physical examination.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He is an investigator on an interstitial cystitis study sponsored by Allergan.

 

Chronic pelvic pain continues not only to burden the individual, but society as well.

One in seven women between the ages of 18 and 50 endure chronic pelvic pain; with a lifetime incidence of as high as 33%, according to one Gallup poll. Interstitial cystitis/bladder pain syndrome (IC/BPS) has been estimated to have a prevalence of 850 in 100,000 women and 60 in 100,000 men in self-report studies. The RAND Interstitial Cystitis Epidemiology (RICE) study, a symptoms survey, showed that between 2.7% and 6.5% of women (3.3 to 7.9 million women) in the United States have symptoms consistent with a diagnosis of IC/BPS.

Unfortunately, there is little known about the etiology and pathogenesis of IC/PBS. Moreover, oftentimes, the diagnosis is one of exclusion.

To demystify interstitial cystitis/bladder pain syndrome, I have elicited the assistance of Dr. Kenneth Peters, a urologist on staff at William Beaumont Hospital, Royal Oak, Mich. Dr. Peters is the professor and chairman of urology at Oakland University, William Beaumont School of Medicine, and the chairman of urology at Beaumont Health, Royal Oak, Mich.

In his discussion, Dr. Peters will point out that interstitial cystitis actually consists of two different entities: a classic presentation featuring the pathognomonic Hunner’s lesion on cystoscopy and interstitial cystitis/painful bladder syndrome.

It must be acknowledged that Dr. Peters is a practicing urologist. Therefore, some of his recommendations, such as cauterizing Hunner’s lesions via a resectoscope, are beyond the scope of practicing gynecologists. However, it is important for us to realize what our potential referrals possess in their armamentarium. Moreover, it is obvious there is much that can be learned from this excellent diagnostician who professes the importance of physical examination.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He is an investigator on an interstitial cystitis study sponsored by Allergan.

 

Interstitial cystitis (IC) is a controversial diagnosis that has become muddied and oversimplified. It was originally described as a distinct ulcer (Hunner’s lesion) seen in the bladder on cystoscopy, the treatment of which often led to symptomatic relief. Hunner’s lesion IC is the “classic” form of IC and should be considered a separate disease; it is not a progression of nonulcerative interstitial cystitis/painful bladder syndrome (IC/BPS).

Only a fraction of patients with the key symptoms of IC/BPS – urinary frequency, urgency, and pelvic pain – have ulcers within the bladder. And many of the patients who are diagnosed with IC/BPS are found not to have bladder pathology as the name implies, but rather pelvic floor dysfunction. That the bladder is often an innocent bystander to a larger process means that, as clinicians, we must be thoughtful and astute about our diagnostic process.

Hunner’s lesions

Patients with Hunner’s lesions have a rapid onset of symptoms, typically are older, and have a visible lesion in their bladder that almost always is on the dome or lateral walls. The lesion is often erythematous with central vascularity and mucosal sloughing.

Courtesy Beaumont Urology

The bladder is a storage organ and urine is toxic. The exposed ulcer results in severe pain with bladder filling and also pain at the end of voiding as the bladder collapses, causing ulcerated tissue to come into contact with other sections of the bladder wall and sending a “jolt” of pain through the pelvis.

If the initial cystoscopy demonstrates inflammatory-appearing lesions or ulcerations suggestive of Hunner’s lesions, I will still do a hydrodistension. By stretching the bladder, the lesions typically expand, crack, and bleed. This helps define the entire diseased area and shows what areas of the bladder need to be cauterized to seal the ulcers and destroy the exposed nerve endings. If this is a new diagnosis, the lesion should be biopsied after the hydrodistension to rule out carcinoma.

Hunner’s lesions can lead to rapid disease progression due to chronic inflammation and subsequent collagen deposition and scarring. Even on initial diagnosis of Hunner’s lesions, a capacity of 350 cc or less (compared with 1,100 cc in a normal bladder) on hydrodistension under anesthesia is not uncommon. This markedly reduced bladder capacity may lead to end-stage bladder impacting the kidneys and requiring a urinary diversion.

Eradicating the ulcers with resection or cautery often results in marked and immediate improvement in bladder pain, albeit not long-lasting. I will typically place a resectoscope and use a roller ball at 25 watts of current. The entire ulcerated areas are cauterized by rapidly rolling the ball over the area of inflammation and avoiding a deep thermal burn. The goal is to seal the ulcer and destroy the exposed nerve endings so that urine can no longer act as an irritant. Recurrence in 6 months to 1 year is common and retreatment is almost always necessary. We have demonstrated, however, that recurrent cautery of ulcers does not lead to smaller anesthetic bladder capacities (Urology. 2015 Jan;85[1]:74-8).

Low-dose cyclosporine can be very effective at reducing Hunner’s lesion recurrence and improving storage symptoms (Exp Ther Med. 2016 Jul;12[1]:445-50). I use 100 mg twice a day for a month and then 1 pill a day thereafter. This is a relatively low dose, but hypertension can be a side effect and blood pressure should be monitored along with routine labs.

The broader picture

Hunner’s lesion IC is pretty straightforward and clearly a bladder disease. However, in recent years the term IC/BPS has been broadly used to describe women who have symptoms of pelvic pain, urinary urgency, and frequency, but no true bladder pathology to explain their symptoms. One problem: There is no definitive diagnostic test or evidence-based diagnostic process for IC/BPS. In fact, the diagnosis section of the American Urological Association guideline on diagnosis and treatment of IC/BPS, last updated in 2015, is almost entirely consensus-based (J Urol. 2015 May;193[5]:1545-53). It largely remains a diagnosis of exclusion.

As the AUA guidelines state, a careful history, physical examination, and laboratory assessment are all important for documenting symptoms and signs and ruling out significant causes of the symptoms. I frequently see patients who have been diagnosed with IC who have frequency and urgency but no pain (in which case overactive bladder should be considered) or who have pelvic pain but no bladder symptoms, again likely not IC. Pain that worsens with bladder filling and improves after bladder emptying is typical of IC/BPS. This finding in the absence of other confusing symptoms supports the diagnosis of IC/BPS.

It has become too easy for the average clinician to apply a label of IC/BPS to a patient complaining of pelvic pain; this often results in the patient undergoing invasive and nonhelpful therapies such as cystoscopy, hydrodistension, urodynamics, bladder instillations, and other bladder-directed therapies.

More than 20 years of research supported by the National Institutes of Health and industry have failed to show that bladder-directed therapy is superior to placebo. This fact suggests that the bladder may be an innocent bystander in a larger pelvic process. As clinicians, we must be willing to look beyond the bladder and examine for pelvic floor issues and other causes of patient’s symptoms and not be too quick to begin bladder-focused treatments.

A number of disease processes – such as recurrent urinary tract infection, urethral diverticulum, endometriosis, and pudendal neuropathy – can mimic the symptoms of IC/BPS. The most common missed diagnosis in the IC patient is pelvic floor dysfunction that results in a hypertonic contracted state of the levator muscles – a chronic spasm, in essence – that in turn leads to decreased muscle function, increased myofascial pain, and myofascial trigger points (Curr Urol Rep. 2006 Nov;7[6]:450-5).

We and others have reported that up to 85% of patients labeled with IC/BPS have been found on examination to have pelvic floor dysfunction or a diffuse pelvic floor hypersensitivity. The pelvic floor is important in maintaining healthy bladder, bowel, and sexual function. If the pelvic floor is in spasm, this can result in urinary frequency, hesitancy, and pelvic pain.

Many of these patients with contracted pelvic floor muscles report pain with sexual intercourse – often so severe as to cause abstention. In fact, when patients answer no to the question of whether they have pain with intercourse, I know it is unlikely that they have significant pelvic floor dysfunction. This is a key question for history taking.

Other key questions concern the impact of stress on symptoms and a history of any type of abuse. In a study we conducted about 10 years ago, we found that among 76 women who were diagnosed with IC and subsequently evaluated in our clinic, almost half (49%) reported abuse (emotional, physical, and/or sexual). The vast majority (85%) had levator pain (J Urol. 2007 Sep;178[3 Pt 1]:891-5).

Other types of stress – from past surgeries to traumatic life events – may similarly serve as triggers or precursors to pelvic floor dysfunction in some women. I often tell patients that people put stress in different areas of their bodies. While some get tension headaches or low-back aches, others get pelvic pain from contracting and guarding the levator muscles.

 

Pelvic floor dysfunction

The most important component of the physical exam in patients with the symptoms of frequency, urgency, and pelvic pain – and the most overlooked – is assessment of the levator muscles for tightness and tenderness. Levator pain and trigger points may be identified during the pelvic exam by pressing laterally on the levator complex in each quadrant of the vagina and at the ischial spines. The tension of the muscles and severity of pain should be assessed, and it is helpful to ask the patient if the pain reproduces her normal pelvic pain symptoms.

Courtesy Beaumont Urology

We’ve found that identifying and treating pelvic floor dysfunction with modalities such as pelvic floor physical therapy with intravaginal myofascial release, intravaginal valium, trigger point injections into the levator complex, pudendal nerve blocks, and neuromodulation can frequently resolve or significantly lessen the patient’s pain and bladder symptoms, suggesting that the diagnosis of IC/BPS was wrong.

Courtesy Beaumont Urology

Pelvic floor physical therapy works to stretch the contracted anterior pelvic muscles by releasing trigger points and connective tissue restrictions, and by decreasing periurethral tension; it also may decrease neurogenic triggers and central nervous system sensitivity. Kegel exercises will worsen pain in these patients and should be avoided.

When pelvic floor dysfunction is identified, such treatment by a therapist knowledgeable in intravaginal myofascial release is a next reasonable step before any medications or invasive testing, such as bladder hydrodistension, are used.

One of the only National Institutes of Health–funded studies to show benefit of a treatment in an IC population, in fact, was a multicenter randomized controlled trial comparing 10 sessions of myofascial pelvic floor physical therapy with “global therapeutic massage.” Myofascial physical therapy led to significant improvement, compared with the generalized spa-like massage (J Urol. 2012 Jun;187[6]:2113-8).

In our practice, we often use intravaginal valium, transvaginal trigger point injections, and pudendal nerve blocks as an adjunct to physical therapy. It is not uncommon for a therapist to report to us that progress in therapy is being stymied by pain in a particular area; in such cases a trigger point injection in the office with local anesthetic and sometimes corticosteroids will help the muscle relax enough and provide enough pain relief so that physical therapy can move forward successfully.

Our patients with IC/BPS symptoms and pelvic floor dysfunction require 1-2 visits weekly for an average of 12 weeks for tightness and tenderness to be significantly minimized or eliminated. Patients are also prescribed home stretching exercises and advised to use internal vaginal dilators. Most patients will report resolution of their pelvic pain, sexual pain, and bladder symptoms – especially with the combination of physical therapy and trigger point injections. In more severe cases, we may use sacral or pudendal neuromodulation to improve the frequency, urgency and pelvic pain.

Turning to the bladder

When urinary symptoms persist after the completion of pelvic floor therapy, or when pelvic floor dysfunction is not identified in the first place, we proceed with bladder-specific therapies. I will often suggest trials of amitriptyline or hydroxyzine, for instance, and/or changes in hydration and caffeine consumption. I am not a fan of pentosan polysulfate sodium (Elmiron) as it is a very expensive medication that has minimal benefit for the majority of patients.

When conservative therapies do not work, I move to cystoscopy with hydrodistension. The procedure can serve several purposes. It can be diagnostic, enabling us to rule out other potential symptom-causing pathologies, and it can be prognostic, helping us to understand when bladder capacity is severely reduced and to plan treatment. In some patients, it can even be therapeutic. Some of my patients have significant relief of symptoms from a hydrodistension of the bladder once or twice a year.

There is no standard method for performing a hydrodistension. I perform a complete cystoscopy to look for tumors, stones, diverticulum or Hunner’s lesions and, if the bladder is normal in appearance, I proceed with a 2-minute hydrodistension at 80-100 cm of water pressure under anesthesia. The bag is raised above the bladder, allowing the bladder to fill with the force of gravity and the pressures to equalize. The urethra must be compressed so that water doesn’t leak around the cystoscope. After 2 minutes of hydrodistension, the bladder is drained, volume is measured, and the procedure is repeated.

After the hydrodistension, the bladder is reinspected to be certain there is no bladder perforation and to evaluate for diffuse glomerulations (petechial hemorrhages) that are suggestive, but not diagnostic, of IC/BPS.

 

A holistic approach

Managing patients with voiding dysfunction and chronic pelvic pain can be a challenge, and a multidisciplinary approach is most effective. At Beaumont, we have a Women’s Urology Center that includes urologists, gynecologists, nurse practitioners, pelvic floor physical therapists, pain psychologists, colorectal specialists, sex therapists, and naturopathic and integrative medicine specialists who perform acupuncture, Reiki therapy, medical massage, and guided imagery.

The goal is to break out of our box of specialties and look at the whole patient – mind, body, and soul – while identifying pain triggers and directing therapy toward these triggers using a multidisciplinary, collaborative approach. For us, this approach has been very effective for managing complex pelvic pain issues (Transl Androl Urol. 2015 Dec;4[6]:611-9).

Ongoing studies

A number of research studies are ongoing to help treat the symptoms of IC/BPS. We currently have a Department of Defense grant to prospectively assess bladder-directed therapy (instillations) compared to pelvic floor physical therapy. Patients diagnosed with IC/BPS are being randomized into these two treatment arms and we hope to get a better understanding of the role of these modalities in managing IC/BPS.

Allergan is completing a phase II placebo-controlled trial using a lidocaine delivery device that is placed in the bladder and continuously releases lidocaine over 14 days. The LiNKA trial is designed to assess the impact of lidocaine on not only improving bladder symptoms, but also eradicating Hunner’s lesions through the anti-inflammatory effect of lidocaine. Early open-label data were very promising. In addition, a new medication for IC/BPS that modulates the SHIP1 pathway is being studied by Aquinox Pharmaceuticals. The agent, AQX-1125, is an activator of SHIP1, which controls the phosphoinositide 3-kinase (PI3K) cellular signaling pathway. If the PI3K pathway is overactive, immune cells can produce an abundance of proinflammatory signaling molecules and migrate to and concentrate in tissues, resulting in excessive or chronic inflammation. Early data in IC/BPS patients were supportive of the compound’s potential for reducing the pain associated with this condition.
 

A note from Charles E. Miller, MD, Master Class Medical Editor:

In a double-blind, placebo-controlled study by J.C. Nickel, et al., pentosan polysulfate sodium was shown to improve pain, urgency, and frequency over the control group (Urology. 2005 Apr;65[4]:654-8). Also, longer duration of treatment with pentosan polysulfate sodium was associated with greater response rates – 50% improved by 26 weeks (J Urol. 2005 Dec;174[6]:2235-8).
 

Dr. Peters is professor and chairman of urology at Oakland University William Beaumont School of Medicine, Royal Oak, Mich. He reported serving as a consultant for Taris, Medtronic, StimGuard, and Amphora Medical.

 

Interstitial cystitis (IC) is a controversial diagnosis that has become muddied and oversimplified. It was originally described as a distinct ulcer (Hunner’s lesion) seen in the bladder on cystoscopy, the treatment of which often led to symptomatic relief. Hunner’s lesion IC is the “classic” form of IC and should be considered a separate disease; it is not a progression of nonulcerative interstitial cystitis/painful bladder syndrome (IC/BPS).

Only a fraction of patients with the key symptoms of IC/BPS – urinary frequency, urgency, and pelvic pain – have ulcers within the bladder. And many of the patients who are diagnosed with IC/BPS are found not to have bladder pathology as the name implies, but rather pelvic floor dysfunction. That the bladder is often an innocent bystander to a larger process means that, as clinicians, we must be thoughtful and astute about our diagnostic process.

Hunner’s lesions

Patients with Hunner’s lesions have a rapid onset of symptoms, typically are older, and have a visible lesion in their bladder that almost always is on the dome or lateral walls. The lesion is often erythematous with central vascularity and mucosal sloughing.

Courtesy Beaumont Urology

The bladder is a storage organ and urine is toxic. The exposed ulcer results in severe pain with bladder filling and also pain at the end of voiding as the bladder collapses, causing ulcerated tissue to come into contact with other sections of the bladder wall and sending a “jolt” of pain through the pelvis.

If the initial cystoscopy demonstrates inflammatory-appearing lesions or ulcerations suggestive of Hunner’s lesions, I will still do a hydrodistension. By stretching the bladder, the lesions typically expand, crack, and bleed. This helps define the entire diseased area and shows what areas of the bladder need to be cauterized to seal the ulcers and destroy the exposed nerve endings. If this is a new diagnosis, the lesion should be biopsied after the hydrodistension to rule out carcinoma.

Hunner’s lesions can lead to rapid disease progression due to chronic inflammation and subsequent collagen deposition and scarring. Even on initial diagnosis of Hunner’s lesions, a capacity of 350 cc or less (compared with 1,100 cc in a normal bladder) on hydrodistension under anesthesia is not uncommon. This markedly reduced bladder capacity may lead to end-stage bladder impacting the kidneys and requiring a urinary diversion.

Eradicating the ulcers with resection or cautery often results in marked and immediate improvement in bladder pain, albeit not long-lasting. I will typically place a resectoscope and use a roller ball at 25 watts of current. The entire ulcerated areas are cauterized by rapidly rolling the ball over the area of inflammation and avoiding a deep thermal burn. The goal is to seal the ulcer and destroy the exposed nerve endings so that urine can no longer act as an irritant. Recurrence in 6 months to 1 year is common and retreatment is almost always necessary. We have demonstrated, however, that recurrent cautery of ulcers does not lead to smaller anesthetic bladder capacities (Urology. 2015 Jan;85[1]:74-8).

Low-dose cyclosporine can be very effective at reducing Hunner’s lesion recurrence and improving storage symptoms (Exp Ther Med. 2016 Jul;12[1]:445-50). I use 100 mg twice a day for a month and then 1 pill a day thereafter. This is a relatively low dose, but hypertension can be a side effect and blood pressure should be monitored along with routine labs.

The broader picture

Hunner’s lesion IC is pretty straightforward and clearly a bladder disease. However, in recent years the term IC/BPS has been broadly used to describe women who have symptoms of pelvic pain, urinary urgency, and frequency, but no true bladder pathology to explain their symptoms. One problem: There is no definitive diagnostic test or evidence-based diagnostic process for IC/BPS. In fact, the diagnosis section of the American Urological Association guideline on diagnosis and treatment of IC/BPS, last updated in 2015, is almost entirely consensus-based (J Urol. 2015 May;193[5]:1545-53). It largely remains a diagnosis of exclusion.

As the AUA guidelines state, a careful history, physical examination, and laboratory assessment are all important for documenting symptoms and signs and ruling out significant causes of the symptoms. I frequently see patients who have been diagnosed with IC who have frequency and urgency but no pain (in which case overactive bladder should be considered) or who have pelvic pain but no bladder symptoms, again likely not IC. Pain that worsens with bladder filling and improves after bladder emptying is typical of IC/BPS. This finding in the absence of other confusing symptoms supports the diagnosis of IC/BPS.

It has become too easy for the average clinician to apply a label of IC/BPS to a patient complaining of pelvic pain; this often results in the patient undergoing invasive and nonhelpful therapies such as cystoscopy, hydrodistension, urodynamics, bladder instillations, and other bladder-directed therapies.

More than 20 years of research supported by the National Institutes of Health and industry have failed to show that bladder-directed therapy is superior to placebo. This fact suggests that the bladder may be an innocent bystander in a larger pelvic process. As clinicians, we must be willing to look beyond the bladder and examine for pelvic floor issues and other causes of patient’s symptoms and not be too quick to begin bladder-focused treatments.

A number of disease processes – such as recurrent urinary tract infection, urethral diverticulum, endometriosis, and pudendal neuropathy – can mimic the symptoms of IC/BPS. The most common missed diagnosis in the IC patient is pelvic floor dysfunction that results in a hypertonic contracted state of the levator muscles – a chronic spasm, in essence – that in turn leads to decreased muscle function, increased myofascial pain, and myofascial trigger points (Curr Urol Rep. 2006 Nov;7[6]:450-5).

We and others have reported that up to 85% of patients labeled with IC/BPS have been found on examination to have pelvic floor dysfunction or a diffuse pelvic floor hypersensitivity. The pelvic floor is important in maintaining healthy bladder, bowel, and sexual function. If the pelvic floor is in spasm, this can result in urinary frequency, hesitancy, and pelvic pain.

Many of these patients with contracted pelvic floor muscles report pain with sexual intercourse – often so severe as to cause abstention. In fact, when patients answer no to the question of whether they have pain with intercourse, I know it is unlikely that they have significant pelvic floor dysfunction. This is a key question for history taking.

Other key questions concern the impact of stress on symptoms and a history of any type of abuse. In a study we conducted about 10 years ago, we found that among 76 women who were diagnosed with IC and subsequently evaluated in our clinic, almost half (49%) reported abuse (emotional, physical, and/or sexual). The vast majority (85%) had levator pain (J Urol. 2007 Sep;178[3 Pt 1]:891-5).

Other types of stress – from past surgeries to traumatic life events – may similarly serve as triggers or precursors to pelvic floor dysfunction in some women. I often tell patients that people put stress in different areas of their bodies. While some get tension headaches or low-back aches, others get pelvic pain from contracting and guarding the levator muscles.

 

Pelvic floor dysfunction

The most important component of the physical exam in patients with the symptoms of frequency, urgency, and pelvic pain – and the most overlooked – is assessment of the levator muscles for tightness and tenderness. Levator pain and trigger points may be identified during the pelvic exam by pressing laterally on the levator complex in each quadrant of the vagina and at the ischial spines. The tension of the muscles and severity of pain should be assessed, and it is helpful to ask the patient if the pain reproduces her normal pelvic pain symptoms.

Courtesy Beaumont Urology

We’ve found that identifying and treating pelvic floor dysfunction with modalities such as pelvic floor physical therapy with intravaginal myofascial release, intravaginal valium, trigger point injections into the levator complex, pudendal nerve blocks, and neuromodulation can frequently resolve or significantly lessen the patient’s pain and bladder symptoms, suggesting that the diagnosis of IC/BPS was wrong.

Courtesy Beaumont Urology

Pelvic floor physical therapy works to stretch the contracted anterior pelvic muscles by releasing trigger points and connective tissue restrictions, and by decreasing periurethral tension; it also may decrease neurogenic triggers and central nervous system sensitivity. Kegel exercises will worsen pain in these patients and should be avoided.

When pelvic floor dysfunction is identified, such treatment by a therapist knowledgeable in intravaginal myofascial release is a next reasonable step before any medications or invasive testing, such as bladder hydrodistension, are used.

One of the only National Institutes of Health–funded studies to show benefit of a treatment in an IC population, in fact, was a multicenter randomized controlled trial comparing 10 sessions of myofascial pelvic floor physical therapy with “global therapeutic massage.” Myofascial physical therapy led to significant improvement, compared with the generalized spa-like massage (J Urol. 2012 Jun;187[6]:2113-8).

In our practice, we often use intravaginal valium, transvaginal trigger point injections, and pudendal nerve blocks as an adjunct to physical therapy. It is not uncommon for a therapist to report to us that progress in therapy is being stymied by pain in a particular area; in such cases a trigger point injection in the office with local anesthetic and sometimes corticosteroids will help the muscle relax enough and provide enough pain relief so that physical therapy can move forward successfully.

Our patients with IC/BPS symptoms and pelvic floor dysfunction require 1-2 visits weekly for an average of 12 weeks for tightness and tenderness to be significantly minimized or eliminated. Patients are also prescribed home stretching exercises and advised to use internal vaginal dilators. Most patients will report resolution of their pelvic pain, sexual pain, and bladder symptoms – especially with the combination of physical therapy and trigger point injections. In more severe cases, we may use sacral or pudendal neuromodulation to improve the frequency, urgency and pelvic pain.

Turning to the bladder

When urinary symptoms persist after the completion of pelvic floor therapy, or when pelvic floor dysfunction is not identified in the first place, we proceed with bladder-specific therapies. I will often suggest trials of amitriptyline or hydroxyzine, for instance, and/or changes in hydration and caffeine consumption. I am not a fan of pentosan polysulfate sodium (Elmiron) as it is a very expensive medication that has minimal benefit for the majority of patients.

When conservative therapies do not work, I move to cystoscopy with hydrodistension. The procedure can serve several purposes. It can be diagnostic, enabling us to rule out other potential symptom-causing pathologies, and it can be prognostic, helping us to understand when bladder capacity is severely reduced and to plan treatment. In some patients, it can even be therapeutic. Some of my patients have significant relief of symptoms from a hydrodistension of the bladder once or twice a year.

There is no standard method for performing a hydrodistension. I perform a complete cystoscopy to look for tumors, stones, diverticulum or Hunner’s lesions and, if the bladder is normal in appearance, I proceed with a 2-minute hydrodistension at 80-100 cm of water pressure under anesthesia. The bag is raised above the bladder, allowing the bladder to fill with the force of gravity and the pressures to equalize. The urethra must be compressed so that water doesn’t leak around the cystoscope. After 2 minutes of hydrodistension, the bladder is drained, volume is measured, and the procedure is repeated.

After the hydrodistension, the bladder is reinspected to be certain there is no bladder perforation and to evaluate for diffuse glomerulations (petechial hemorrhages) that are suggestive, but not diagnostic, of IC/BPS.

 

A holistic approach

Managing patients with voiding dysfunction and chronic pelvic pain can be a challenge, and a multidisciplinary approach is most effective. At Beaumont, we have a Women’s Urology Center that includes urologists, gynecologists, nurse practitioners, pelvic floor physical therapists, pain psychologists, colorectal specialists, sex therapists, and naturopathic and integrative medicine specialists who perform acupuncture, Reiki therapy, medical massage, and guided imagery.

The goal is to break out of our box of specialties and look at the whole patient – mind, body, and soul – while identifying pain triggers and directing therapy toward these triggers using a multidisciplinary, collaborative approach. For us, this approach has been very effective for managing complex pelvic pain issues (Transl Androl Urol. 2015 Dec;4[6]:611-9).

Ongoing studies

A number of research studies are ongoing to help treat the symptoms of IC/BPS. We currently have a Department of Defense grant to prospectively assess bladder-directed therapy (instillations) compared to pelvic floor physical therapy. Patients diagnosed with IC/BPS are being randomized into these two treatment arms and we hope to get a better understanding of the role of these modalities in managing IC/BPS.

Allergan is completing a phase II placebo-controlled trial using a lidocaine delivery device that is placed in the bladder and continuously releases lidocaine over 14 days. The LiNKA trial is designed to assess the impact of lidocaine on not only improving bladder symptoms, but also eradicating Hunner’s lesions through the anti-inflammatory effect of lidocaine. Early open-label data were very promising. In addition, a new medication for IC/BPS that modulates the SHIP1 pathway is being studied by Aquinox Pharmaceuticals. The agent, AQX-1125, is an activator of SHIP1, which controls the phosphoinositide 3-kinase (PI3K) cellular signaling pathway. If the PI3K pathway is overactive, immune cells can produce an abundance of proinflammatory signaling molecules and migrate to and concentrate in tissues, resulting in excessive or chronic inflammation. Early data in IC/BPS patients were supportive of the compound’s potential for reducing the pain associated with this condition.
 

A note from Charles E. Miller, MD, Master Class Medical Editor:

In a double-blind, placebo-controlled study by J.C. Nickel, et al., pentosan polysulfate sodium was shown to improve pain, urgency, and frequency over the control group (Urology. 2005 Apr;65[4]:654-8). Also, longer duration of treatment with pentosan polysulfate sodium was associated with greater response rates – 50% improved by 26 weeks (J Urol. 2005 Dec;174[6]:2235-8).
 

Dr. Peters is professor and chairman of urology at Oakland University William Beaumont School of Medicine, Royal Oak, Mich. He reported serving as a consultant for Taris, Medtronic, StimGuard, and Amphora Medical.

 

Interstitial cystitis (IC) is a controversial diagnosis that has become muddied and oversimplified. It was originally described as a distinct ulcer (Hunner’s lesion) seen in the bladder on cystoscopy, the treatment of which often led to symptomatic relief. Hunner’s lesion IC is the “classic” form of IC and should be considered a separate disease; it is not a progression of nonulcerative interstitial cystitis/painful bladder syndrome (IC/BPS).

Only a fraction of patients with the key symptoms of IC/BPS – urinary frequency, urgency, and pelvic pain – have ulcers within the bladder. And many of the patients who are diagnosed with IC/BPS are found not to have bladder pathology as the name implies, but rather pelvic floor dysfunction. That the bladder is often an innocent bystander to a larger process means that, as clinicians, we must be thoughtful and astute about our diagnostic process.

Hunner’s lesions

Patients with Hunner’s lesions have a rapid onset of symptoms, typically are older, and have a visible lesion in their bladder that almost always is on the dome or lateral walls. The lesion is often erythematous with central vascularity and mucosal sloughing.

Courtesy Beaumont Urology

The bladder is a storage organ and urine is toxic. The exposed ulcer results in severe pain with bladder filling and also pain at the end of voiding as the bladder collapses, causing ulcerated tissue to come into contact with other sections of the bladder wall and sending a “jolt” of pain through the pelvis.

If the initial cystoscopy demonstrates inflammatory-appearing lesions or ulcerations suggestive of Hunner’s lesions, I will still do a hydrodistension. By stretching the bladder, the lesions typically expand, crack, and bleed. This helps define the entire diseased area and shows what areas of the bladder need to be cauterized to seal the ulcers and destroy the exposed nerve endings. If this is a new diagnosis, the lesion should be biopsied after the hydrodistension to rule out carcinoma.

Hunner’s lesions can lead to rapid disease progression due to chronic inflammation and subsequent collagen deposition and scarring. Even on initial diagnosis of Hunner’s lesions, a capacity of 350 cc or less (compared with 1,100 cc in a normal bladder) on hydrodistension under anesthesia is not uncommon. This markedly reduced bladder capacity may lead to end-stage bladder impacting the kidneys and requiring a urinary diversion.

Eradicating the ulcers with resection or cautery often results in marked and immediate improvement in bladder pain, albeit not long-lasting. I will typically place a resectoscope and use a roller ball at 25 watts of current. The entire ulcerated areas are cauterized by rapidly rolling the ball over the area of inflammation and avoiding a deep thermal burn. The goal is to seal the ulcer and destroy the exposed nerve endings so that urine can no longer act as an irritant. Recurrence in 6 months to 1 year is common and retreatment is almost always necessary. We have demonstrated, however, that recurrent cautery of ulcers does not lead to smaller anesthetic bladder capacities (Urology. 2015 Jan;85[1]:74-8).

Low-dose cyclosporine can be very effective at reducing Hunner’s lesion recurrence and improving storage symptoms (Exp Ther Med. 2016 Jul;12[1]:445-50). I use 100 mg twice a day for a month and then 1 pill a day thereafter. This is a relatively low dose, but hypertension can be a side effect and blood pressure should be monitored along with routine labs.

The broader picture

Hunner’s lesion IC is pretty straightforward and clearly a bladder disease. However, in recent years the term IC/BPS has been broadly used to describe women who have symptoms of pelvic pain, urinary urgency, and frequency, but no true bladder pathology to explain their symptoms. One problem: There is no definitive diagnostic test or evidence-based diagnostic process for IC/BPS. In fact, the diagnosis section of the American Urological Association guideline on diagnosis and treatment of IC/BPS, last updated in 2015, is almost entirely consensus-based (J Urol. 2015 May;193[5]:1545-53). It largely remains a diagnosis of exclusion.

As the AUA guidelines state, a careful history, physical examination, and laboratory assessment are all important for documenting symptoms and signs and ruling out significant causes of the symptoms. I frequently see patients who have been diagnosed with IC who have frequency and urgency but no pain (in which case overactive bladder should be considered) or who have pelvic pain but no bladder symptoms, again likely not IC. Pain that worsens with bladder filling and improves after bladder emptying is typical of IC/BPS. This finding in the absence of other confusing symptoms supports the diagnosis of IC/BPS.

It has become too easy for the average clinician to apply a label of IC/BPS to a patient complaining of pelvic pain; this often results in the patient undergoing invasive and nonhelpful therapies such as cystoscopy, hydrodistension, urodynamics, bladder instillations, and other bladder-directed therapies.

More than 20 years of research supported by the National Institutes of Health and industry have failed to show that bladder-directed therapy is superior to placebo. This fact suggests that the bladder may be an innocent bystander in a larger pelvic process. As clinicians, we must be willing to look beyond the bladder and examine for pelvic floor issues and other causes of patient’s symptoms and not be too quick to begin bladder-focused treatments.

A number of disease processes – such as recurrent urinary tract infection, urethral diverticulum, endometriosis, and pudendal neuropathy – can mimic the symptoms of IC/BPS. The most common missed diagnosis in the IC patient is pelvic floor dysfunction that results in a hypertonic contracted state of the levator muscles – a chronic spasm, in essence – that in turn leads to decreased muscle function, increased myofascial pain, and myofascial trigger points (Curr Urol Rep. 2006 Nov;7[6]:450-5).

We and others have reported that up to 85% of patients labeled with IC/BPS have been found on examination to have pelvic floor dysfunction or a diffuse pelvic floor hypersensitivity. The pelvic floor is important in maintaining healthy bladder, bowel, and sexual function. If the pelvic floor is in spasm, this can result in urinary frequency, hesitancy, and pelvic pain.

Many of these patients with contracted pelvic floor muscles report pain with sexual intercourse – often so severe as to cause abstention. In fact, when patients answer no to the question of whether they have pain with intercourse, I know it is unlikely that they have significant pelvic floor dysfunction. This is a key question for history taking.

Other key questions concern the impact of stress on symptoms and a history of any type of abuse. In a study we conducted about 10 years ago, we found that among 76 women who were diagnosed with IC and subsequently evaluated in our clinic, almost half (49%) reported abuse (emotional, physical, and/or sexual). The vast majority (85%) had levator pain (J Urol. 2007 Sep;178[3 Pt 1]:891-5).

Other types of stress – from past surgeries to traumatic life events – may similarly serve as triggers or precursors to pelvic floor dysfunction in some women. I often tell patients that people put stress in different areas of their bodies. While some get tension headaches or low-back aches, others get pelvic pain from contracting and guarding the levator muscles.

 

Pelvic floor dysfunction

The most important component of the physical exam in patients with the symptoms of frequency, urgency, and pelvic pain – and the most overlooked – is assessment of the levator muscles for tightness and tenderness. Levator pain and trigger points may be identified during the pelvic exam by pressing laterally on the levator complex in each quadrant of the vagina and at the ischial spines. The tension of the muscles and severity of pain should be assessed, and it is helpful to ask the patient if the pain reproduces her normal pelvic pain symptoms.

Courtesy Beaumont Urology

We’ve found that identifying and treating pelvic floor dysfunction with modalities such as pelvic floor physical therapy with intravaginal myofascial release, intravaginal valium, trigger point injections into the levator complex, pudendal nerve blocks, and neuromodulation can frequently resolve or significantly lessen the patient’s pain and bladder symptoms, suggesting that the diagnosis of IC/BPS was wrong.

Courtesy Beaumont Urology

Pelvic floor physical therapy works to stretch the contracted anterior pelvic muscles by releasing trigger points and connective tissue restrictions, and by decreasing periurethral tension; it also may decrease neurogenic triggers and central nervous system sensitivity. Kegel exercises will worsen pain in these patients and should be avoided.

When pelvic floor dysfunction is identified, such treatment by a therapist knowledgeable in intravaginal myofascial release is a next reasonable step before any medications or invasive testing, such as bladder hydrodistension, are used.

One of the only National Institutes of Health–funded studies to show benefit of a treatment in an IC population, in fact, was a multicenter randomized controlled trial comparing 10 sessions of myofascial pelvic floor physical therapy with “global therapeutic massage.” Myofascial physical therapy led to significant improvement, compared with the generalized spa-like massage (J Urol. 2012 Jun;187[6]:2113-8).

In our practice, we often use intravaginal valium, transvaginal trigger point injections, and pudendal nerve blocks as an adjunct to physical therapy. It is not uncommon for a therapist to report to us that progress in therapy is being stymied by pain in a particular area; in such cases a trigger point injection in the office with local anesthetic and sometimes corticosteroids will help the muscle relax enough and provide enough pain relief so that physical therapy can move forward successfully.

Our patients with IC/BPS symptoms and pelvic floor dysfunction require 1-2 visits weekly for an average of 12 weeks for tightness and tenderness to be significantly minimized or eliminated. Patients are also prescribed home stretching exercises and advised to use internal vaginal dilators. Most patients will report resolution of their pelvic pain, sexual pain, and bladder symptoms – especially with the combination of physical therapy and trigger point injections. In more severe cases, we may use sacral or pudendal neuromodulation to improve the frequency, urgency and pelvic pain.

Turning to the bladder

When urinary symptoms persist after the completion of pelvic floor therapy, or when pelvic floor dysfunction is not identified in the first place, we proceed with bladder-specific therapies. I will often suggest trials of amitriptyline or hydroxyzine, for instance, and/or changes in hydration and caffeine consumption. I am not a fan of pentosan polysulfate sodium (Elmiron) as it is a very expensive medication that has minimal benefit for the majority of patients.

When conservative therapies do not work, I move to cystoscopy with hydrodistension. The procedure can serve several purposes. It can be diagnostic, enabling us to rule out other potential symptom-causing pathologies, and it can be prognostic, helping us to understand when bladder capacity is severely reduced and to plan treatment. In some patients, it can even be therapeutic. Some of my patients have significant relief of symptoms from a hydrodistension of the bladder once or twice a year.

There is no standard method for performing a hydrodistension. I perform a complete cystoscopy to look for tumors, stones, diverticulum or Hunner’s lesions and, if the bladder is normal in appearance, I proceed with a 2-minute hydrodistension at 80-100 cm of water pressure under anesthesia. The bag is raised above the bladder, allowing the bladder to fill with the force of gravity and the pressures to equalize. The urethra must be compressed so that water doesn’t leak around the cystoscope. After 2 minutes of hydrodistension, the bladder is drained, volume is measured, and the procedure is repeated.

After the hydrodistension, the bladder is reinspected to be certain there is no bladder perforation and to evaluate for diffuse glomerulations (petechial hemorrhages) that are suggestive, but not diagnostic, of IC/BPS.

 

A holistic approach

Managing patients with voiding dysfunction and chronic pelvic pain can be a challenge, and a multidisciplinary approach is most effective. At Beaumont, we have a Women’s Urology Center that includes urologists, gynecologists, nurse practitioners, pelvic floor physical therapists, pain psychologists, colorectal specialists, sex therapists, and naturopathic and integrative medicine specialists who perform acupuncture, Reiki therapy, medical massage, and guided imagery.

The goal is to break out of our box of specialties and look at the whole patient – mind, body, and soul – while identifying pain triggers and directing therapy toward these triggers using a multidisciplinary, collaborative approach. For us, this approach has been very effective for managing complex pelvic pain issues (Transl Androl Urol. 2015 Dec;4[6]:611-9).

Ongoing studies

A number of research studies are ongoing to help treat the symptoms of IC/BPS. We currently have a Department of Defense grant to prospectively assess bladder-directed therapy (instillations) compared to pelvic floor physical therapy. Patients diagnosed with IC/BPS are being randomized into these two treatment arms and we hope to get a better understanding of the role of these modalities in managing IC/BPS.

Allergan is completing a phase II placebo-controlled trial using a lidocaine delivery device that is placed in the bladder and continuously releases lidocaine over 14 days. The LiNKA trial is designed to assess the impact of lidocaine on not only improving bladder symptoms, but also eradicating Hunner’s lesions through the anti-inflammatory effect of lidocaine. Early open-label data were very promising. In addition, a new medication for IC/BPS that modulates the SHIP1 pathway is being studied by Aquinox Pharmaceuticals. The agent, AQX-1125, is an activator of SHIP1, which controls the phosphoinositide 3-kinase (PI3K) cellular signaling pathway. If the PI3K pathway is overactive, immune cells can produce an abundance of proinflammatory signaling molecules and migrate to and concentrate in tissues, resulting in excessive or chronic inflammation. Early data in IC/BPS patients were supportive of the compound’s potential for reducing the pain associated with this condition.
 

A note from Charles E. Miller, MD, Master Class Medical Editor:

In a double-blind, placebo-controlled study by J.C. Nickel, et al., pentosan polysulfate sodium was shown to improve pain, urgency, and frequency over the control group (Urology. 2005 Apr;65[4]:654-8). Also, longer duration of treatment with pentosan polysulfate sodium was associated with greater response rates – 50% improved by 26 weeks (J Urol. 2005 Dec;174[6]:2235-8).
 

Dr. Peters is professor and chairman of urology at Oakland University William Beaumont School of Medicine, Royal Oak, Mich. He reported serving as a consultant for Taris, Medtronic, StimGuard, and Amphora Medical.

 

Electronic fetal monitoring (EFM) is the most commonly used instrument in obstetrics and is the perceived standard of care. However, the U.S. Preventive Services Task Force recommended against its use in low-risk women in 1996 (a “D” rating) – signifying the lack of evidence for benefit and the potential for harm – and said there was insufficient evidence to recommend for or against its use in high-risk women (a “C” rating).

Today, available data still suggest that EFM does not reduce overall perinatal mortality or the risk of cerebral palsy. Moreover, its use is associated with increased operative vaginal deliveries and cesarean deliveries.

Given the near-zero positive predictive value of EFM for stillbirth or cerebral palsy, some have called EFM “useless” and a “failure.” However, I see potential in the technology. I believe that we are beginning to see evidence emerge that – if confirmed and expanded – will enable us to quantify and interpret indeterminate EFM patterns in new ways that positively impact clinical outcomes.

Despite EFM’s routine use and our specialty’s well-ingrained clinical habits, we should critically and meaningfully examine new science and new data on category II fetal heart rate tracings as they come to light. In the meantime, there is more we can do to resolve concerning elements of these tracings – without using supplemental oxygen – or to provide reassurance of fetal well-being so that cesarean deliveries are not unnecessarily performed.

Emerging research

An abnormal or indeterminate fetal heart rate tracing is the second most common indication for primary cesarean, after labor arrest, according to a study published in 2011 of more than 32,000 live births. Given the rarity of category III tracings (“abnormal”), it is likely that category II tracings (“indeterminate”) account for most of the cesarean deliveries performed out of concern for fetal acidemia (Obstet Gynecol. 2011 Jul;118[1]:29-38).

Until recently, we’ve known very little about the patterns contained within category II of our current three-tier system for categorizing fetal heart rate patterns. The system was defined by the 2008 consensus workshop sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine (Obstet Gynecol. 2008 Sep;112[3]:661-6).

We have reasonable data to know that the vast majority of patients with category I fetal heart rate tracings will have a normal pH. We also have reasonable data showing us that patients with category III tracings have a high risk of acidemia and morbidity. However, the majority of tracings we see during labor at term fall into category II, with no clear indication of risk and characterized most often by the presence of decelerations.

As we’ve delved more deeply into the highly variable and complex category II tracings defined in 2008, we’ve begun to demonstrate that tracings can have different meanings for different patients, and that particular clinical factors can make EFM patterns more informative and predictive. In other words, EFM patterns may require different interpretations based on a priori risk and clinical factors.

One of these factors may be the presence of meconium. In a prospective cohort of more than 3,000 women with category II tracings, the presence of meconium – especially thick meconium – was associated with a higher risk of acidemia and neonatal morbidity than when meconium was absent. Interestingly, the negative predictive value was higher than the overall predictive ability in this cohort, which suggests that the absence of meconium in the setting of a category II tracing can be considered a reassuring feature (Am J Obstet Gynecol. 2014;211:644.e1-8).

We have also found through retrospective cohort studies that magnesium sulfate can impact fetal heart rate tracings, causing a transient decrease in variability (Obstet Gynecol. 2012 Jun;119[6]:1129-36 and Am J Perinatol. 2014 Nov;31[10]:869-74). In addition, intrauterine growth restricted fetuses have a higher risk of decelerations without a commensurate higher risk of morbidity (Am J Perinatol. 2015 Jul;32[9]:873-8).

Such findings need to be reproduced, expanded, and further analyzed to show us how the risk of acidemia can be better predicted. For now, just as we increasingly appreciate that tracings have a transient nature and should be considered with two lenses – one looking back in time and one looking forward – we have a growing sense that EFM should not be interpreted without consideration of clinical factors.

Research at our institution and others has shown that acidemia is more significantly associated with non-NICHD measures of fetal heart rate deceleration than with each of the main deceleration types defined by the 2008 NICHD system (i.e., repetitive variable, repetitive late, and repetitive prolonged).

For instance, Emily Hamilton, MD, and her colleagues at PeriGen, a perinatal software company, found that only prolonged decelerations, in addition to the variability within the deceleration and a depth below 60 beats per minute for more than 60 seconds, could discriminate between cases of metabolic acidosis and those with normal umbilical artery gases (J Matern Fetal Neonatal Med. 2012 Jun;25[6]:648-53).

In a 4-year retrospective cohort study of nearly 5,340 consecutive singleton, term, nonanomalous gestations, we found acidemia was most significantly associated with a calculation of the “total deceleration area” – the sum of the estimates of area within all the decelerations. This measure accounted for the frequency, depth, and duration of all decelerations in the final 30 minutes of EFM.

Each of the NICHD deceleration types was associated in our study with acidemia after adjustment for fever, obesity, prolonged first stage, and nulliparity. However, total deceleration area had superior predictive ability. After the same adjustments were made, an abnormal total deceleration area (greater than the 95th percentile) was significantly associated with an increased risk for acidemia (odds ratio, 3.79) (Am J Obstet Gynecol. 2012 Sep;207[3]:206.e1-8).

Pathophysiologically, it seems logical that the total area is most predictive, as it captures both the temporal and dose effect of decelerations. At this point, however, we can only apply this concept crudely at the bedside. There is more work to do to translate such findings into software-driven bedside tools.

 

Gaining reassurance

Although efforts to manage intrapartum fetal heart rate tracings focus largely on attempting to better predict who is at greatest risk for acidemia, it is important and worthwhile that we also attempt to determine whether a fetus with a category II tracing is not acidotic.

Research has consistently shown that the presence of accelerations, whether spontaneous or stimulated, is a highly reliable indicator of normal neonatal umbilical cord pH. It is therefore reasonable, when faced with indeterminate tracings (e.g., minimal variability), to consider scalp stimulation to elicit fetal heart rate acceleration. Scalp stimulation is the easiest noninvasive tool to employ to quickly secure clinical reassurance – within a couple of minutes – that the fetus is not acidotic.

For guidance on managing repetitive variable decelerations, amnioinfusion with normal saline is similarly worthy of consideration. It has been demonstrated (Level A evidence) to resolve variable fetal heart rate decelerations and reduce the incidence of cesarean delivery for nonreassuring fetal heart rate patterns. Both amnioinfusion and scalp stimulation are recommended in the 2014 ACOG/SMFM consensus statement on “Safe Prevention of the Primary Cesarean Delivery” (Obstet Gynecol. 2014 Mar;123[3]:693-711).

Oxygen administration, on the other hand, is ingrained in practice and is included in the American College of Obstetricians and Gynecologists’ practice bulletin on managing intrapartum fetal rate tracings. It is listed as a possible resuscitative measure for category II or III tracings, despite the fact that there are extremely limited data for its effectiveness or safety in labor.

Maureen S. Hamel, MD, and her colleagues at the Warren Albert Medical School at Brown University reviewed the literature and concluded that the only two randomized trials investigating the use of maternal oxygen supplementation in laboring women do not support the idea that supplementation may benefit the fetus. Moreover, they contended that oxygen supplementation may even be harmful (Am J Obstet Gynecol. 2014 Aug;211[2]:124-7).

If supplemental oxygen were a medication, we would want to know the dose, as well as the length and duration of administration before fetal heart rate tracing improved. We don’t know the answers to these questions.

There is research ongoing, both observational studies and at least one registered randomized clinical trial, that should provide more information and guidance on the impact of supplemental oxygen in the setting of category II fetal heart rate patterns. I do not expect these findings to resolve all the questions. We’re going to need a thorough body of work to provide us with definitive answers.
 

Dr. Cahill is the chief of the division of maternal-fetal medicine at Washington University in St. Louis. She reported having no financial disclosures relevant to this Master Class.

 

Electronic fetal monitoring (EFM) is the most commonly used instrument in obstetrics and is the perceived standard of care. However, the U.S. Preventive Services Task Force recommended against its use in low-risk women in 1996 (a “D” rating) – signifying the lack of evidence for benefit and the potential for harm – and said there was insufficient evidence to recommend for or against its use in high-risk women (a “C” rating).

Today, available data still suggest that EFM does not reduce overall perinatal mortality or the risk of cerebral palsy. Moreover, its use is associated with increased operative vaginal deliveries and cesarean deliveries.

Given the near-zero positive predictive value of EFM for stillbirth or cerebral palsy, some have called EFM “useless” and a “failure.” However, I see potential in the technology. I believe that we are beginning to see evidence emerge that – if confirmed and expanded – will enable us to quantify and interpret indeterminate EFM patterns in new ways that positively impact clinical outcomes.

Despite EFM’s routine use and our specialty’s well-ingrained clinical habits, we should critically and meaningfully examine new science and new data on category II fetal heart rate tracings as they come to light. In the meantime, there is more we can do to resolve concerning elements of these tracings – without using supplemental oxygen – or to provide reassurance of fetal well-being so that cesarean deliveries are not unnecessarily performed.

Emerging research

An abnormal or indeterminate fetal heart rate tracing is the second most common indication for primary cesarean, after labor arrest, according to a study published in 2011 of more than 32,000 live births. Given the rarity of category III tracings (“abnormal”), it is likely that category II tracings (“indeterminate”) account for most of the cesarean deliveries performed out of concern for fetal acidemia (Obstet Gynecol. 2011 Jul;118[1]:29-38).

Until recently, we’ve known very little about the patterns contained within category II of our current three-tier system for categorizing fetal heart rate patterns. The system was defined by the 2008 consensus workshop sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine (Obstet Gynecol. 2008 Sep;112[3]:661-6).

We have reasonable data to know that the vast majority of patients with category I fetal heart rate tracings will have a normal pH. We also have reasonable data showing us that patients with category III tracings have a high risk of acidemia and morbidity. However, the majority of tracings we see during labor at term fall into category II, with no clear indication of risk and characterized most often by the presence of decelerations.

As we’ve delved more deeply into the highly variable and complex category II tracings defined in 2008, we’ve begun to demonstrate that tracings can have different meanings for different patients, and that particular clinical factors can make EFM patterns more informative and predictive. In other words, EFM patterns may require different interpretations based on a priori risk and clinical factors.

One of these factors may be the presence of meconium. In a prospective cohort of more than 3,000 women with category II tracings, the presence of meconium – especially thick meconium – was associated with a higher risk of acidemia and neonatal morbidity than when meconium was absent. Interestingly, the negative predictive value was higher than the overall predictive ability in this cohort, which suggests that the absence of meconium in the setting of a category II tracing can be considered a reassuring feature (Am J Obstet Gynecol. 2014;211:644.e1-8).

We have also found through retrospective cohort studies that magnesium sulfate can impact fetal heart rate tracings, causing a transient decrease in variability (Obstet Gynecol. 2012 Jun;119[6]:1129-36 and Am J Perinatol. 2014 Nov;31[10]:869-74). In addition, intrauterine growth restricted fetuses have a higher risk of decelerations without a commensurate higher risk of morbidity (Am J Perinatol. 2015 Jul;32[9]:873-8).

Such findings need to be reproduced, expanded, and further analyzed to show us how the risk of acidemia can be better predicted. For now, just as we increasingly appreciate that tracings have a transient nature and should be considered with two lenses – one looking back in time and one looking forward – we have a growing sense that EFM should not be interpreted without consideration of clinical factors.

Research at our institution and others has shown that acidemia is more significantly associated with non-NICHD measures of fetal heart rate deceleration than with each of the main deceleration types defined by the 2008 NICHD system (i.e., repetitive variable, repetitive late, and repetitive prolonged).

For instance, Emily Hamilton, MD, and her colleagues at PeriGen, a perinatal software company, found that only prolonged decelerations, in addition to the variability within the deceleration and a depth below 60 beats per minute for more than 60 seconds, could discriminate between cases of metabolic acidosis and those with normal umbilical artery gases (J Matern Fetal Neonatal Med. 2012 Jun;25[6]:648-53).

In a 4-year retrospective cohort study of nearly 5,340 consecutive singleton, term, nonanomalous gestations, we found acidemia was most significantly associated with a calculation of the “total deceleration area” – the sum of the estimates of area within all the decelerations. This measure accounted for the frequency, depth, and duration of all decelerations in the final 30 minutes of EFM.

Each of the NICHD deceleration types was associated in our study with acidemia after adjustment for fever, obesity, prolonged first stage, and nulliparity. However, total deceleration area had superior predictive ability. After the same adjustments were made, an abnormal total deceleration area (greater than the 95th percentile) was significantly associated with an increased risk for acidemia (odds ratio, 3.79) (Am J Obstet Gynecol. 2012 Sep;207[3]:206.e1-8).

Pathophysiologically, it seems logical that the total area is most predictive, as it captures both the temporal and dose effect of decelerations. At this point, however, we can only apply this concept crudely at the bedside. There is more work to do to translate such findings into software-driven bedside tools.

 

Gaining reassurance

Although efforts to manage intrapartum fetal heart rate tracings focus largely on attempting to better predict who is at greatest risk for acidemia, it is important and worthwhile that we also attempt to determine whether a fetus with a category II tracing is not acidotic.

Research has consistently shown that the presence of accelerations, whether spontaneous or stimulated, is a highly reliable indicator of normal neonatal umbilical cord pH. It is therefore reasonable, when faced with indeterminate tracings (e.g., minimal variability), to consider scalp stimulation to elicit fetal heart rate acceleration. Scalp stimulation is the easiest noninvasive tool to employ to quickly secure clinical reassurance – within a couple of minutes – that the fetus is not acidotic.

For guidance on managing repetitive variable decelerations, amnioinfusion with normal saline is similarly worthy of consideration. It has been demonstrated (Level A evidence) to resolve variable fetal heart rate decelerations and reduce the incidence of cesarean delivery for nonreassuring fetal heart rate patterns. Both amnioinfusion and scalp stimulation are recommended in the 2014 ACOG/SMFM consensus statement on “Safe Prevention of the Primary Cesarean Delivery” (Obstet Gynecol. 2014 Mar;123[3]:693-711).

Oxygen administration, on the other hand, is ingrained in practice and is included in the American College of Obstetricians and Gynecologists’ practice bulletin on managing intrapartum fetal rate tracings. It is listed as a possible resuscitative measure for category II or III tracings, despite the fact that there are extremely limited data for its effectiveness or safety in labor.

Maureen S. Hamel, MD, and her colleagues at the Warren Albert Medical School at Brown University reviewed the literature and concluded that the only two randomized trials investigating the use of maternal oxygen supplementation in laboring women do not support the idea that supplementation may benefit the fetus. Moreover, they contended that oxygen supplementation may even be harmful (Am J Obstet Gynecol. 2014 Aug;211[2]:124-7).

If supplemental oxygen were a medication, we would want to know the dose, as well as the length and duration of administration before fetal heart rate tracing improved. We don’t know the answers to these questions.

There is research ongoing, both observational studies and at least one registered randomized clinical trial, that should provide more information and guidance on the impact of supplemental oxygen in the setting of category II fetal heart rate patterns. I do not expect these findings to resolve all the questions. We’re going to need a thorough body of work to provide us with definitive answers.
 

Dr. Cahill is the chief of the division of maternal-fetal medicine at Washington University in St. Louis. She reported having no financial disclosures relevant to this Master Class.

 

Electronic fetal monitoring (EFM) is the most commonly used instrument in obstetrics and is the perceived standard of care. However, the U.S. Preventive Services Task Force recommended against its use in low-risk women in 1996 (a “D” rating) – signifying the lack of evidence for benefit and the potential for harm – and said there was insufficient evidence to recommend for or against its use in high-risk women (a “C” rating).

Today, available data still suggest that EFM does not reduce overall perinatal mortality or the risk of cerebral palsy. Moreover, its use is associated with increased operative vaginal deliveries and cesarean deliveries.

Given the near-zero positive predictive value of EFM for stillbirth or cerebral palsy, some have called EFM “useless” and a “failure.” However, I see potential in the technology. I believe that we are beginning to see evidence emerge that – if confirmed and expanded – will enable us to quantify and interpret indeterminate EFM patterns in new ways that positively impact clinical outcomes.

Despite EFM’s routine use and our specialty’s well-ingrained clinical habits, we should critically and meaningfully examine new science and new data on category II fetal heart rate tracings as they come to light. In the meantime, there is more we can do to resolve concerning elements of these tracings – without using supplemental oxygen – or to provide reassurance of fetal well-being so that cesarean deliveries are not unnecessarily performed.

Emerging research

An abnormal or indeterminate fetal heart rate tracing is the second most common indication for primary cesarean, after labor arrest, according to a study published in 2011 of more than 32,000 live births. Given the rarity of category III tracings (“abnormal”), it is likely that category II tracings (“indeterminate”) account for most of the cesarean deliveries performed out of concern for fetal acidemia (Obstet Gynecol. 2011 Jul;118[1]:29-38).

Until recently, we’ve known very little about the patterns contained within category II of our current three-tier system for categorizing fetal heart rate patterns. The system was defined by the 2008 consensus workshop sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine (Obstet Gynecol. 2008 Sep;112[3]:661-6).

We have reasonable data to know that the vast majority of patients with category I fetal heart rate tracings will have a normal pH. We also have reasonable data showing us that patients with category III tracings have a high risk of acidemia and morbidity. However, the majority of tracings we see during labor at term fall into category II, with no clear indication of risk and characterized most often by the presence of decelerations.

As we’ve delved more deeply into the highly variable and complex category II tracings defined in 2008, we’ve begun to demonstrate that tracings can have different meanings for different patients, and that particular clinical factors can make EFM patterns more informative and predictive. In other words, EFM patterns may require different interpretations based on a priori risk and clinical factors.

One of these factors may be the presence of meconium. In a prospective cohort of more than 3,000 women with category II tracings, the presence of meconium – especially thick meconium – was associated with a higher risk of acidemia and neonatal morbidity than when meconium was absent. Interestingly, the negative predictive value was higher than the overall predictive ability in this cohort, which suggests that the absence of meconium in the setting of a category II tracing can be considered a reassuring feature (Am J Obstet Gynecol. 2014;211:644.e1-8).

We have also found through retrospective cohort studies that magnesium sulfate can impact fetal heart rate tracings, causing a transient decrease in variability (Obstet Gynecol. 2012 Jun;119[6]:1129-36 and Am J Perinatol. 2014 Nov;31[10]:869-74). In addition, intrauterine growth restricted fetuses have a higher risk of decelerations without a commensurate higher risk of morbidity (Am J Perinatol. 2015 Jul;32[9]:873-8).

Such findings need to be reproduced, expanded, and further analyzed to show us how the risk of acidemia can be better predicted. For now, just as we increasingly appreciate that tracings have a transient nature and should be considered with two lenses – one looking back in time and one looking forward – we have a growing sense that EFM should not be interpreted without consideration of clinical factors.

Research at our institution and others has shown that acidemia is more significantly associated with non-NICHD measures of fetal heart rate deceleration than with each of the main deceleration types defined by the 2008 NICHD system (i.e., repetitive variable, repetitive late, and repetitive prolonged).

For instance, Emily Hamilton, MD, and her colleagues at PeriGen, a perinatal software company, found that only prolonged decelerations, in addition to the variability within the deceleration and a depth below 60 beats per minute for more than 60 seconds, could discriminate between cases of metabolic acidosis and those with normal umbilical artery gases (J Matern Fetal Neonatal Med. 2012 Jun;25[6]:648-53).

In a 4-year retrospective cohort study of nearly 5,340 consecutive singleton, term, nonanomalous gestations, we found acidemia was most significantly associated with a calculation of the “total deceleration area” – the sum of the estimates of area within all the decelerations. This measure accounted for the frequency, depth, and duration of all decelerations in the final 30 minutes of EFM.

Each of the NICHD deceleration types was associated in our study with acidemia after adjustment for fever, obesity, prolonged first stage, and nulliparity. However, total deceleration area had superior predictive ability. After the same adjustments were made, an abnormal total deceleration area (greater than the 95th percentile) was significantly associated with an increased risk for acidemia (odds ratio, 3.79) (Am J Obstet Gynecol. 2012 Sep;207[3]:206.e1-8).

Pathophysiologically, it seems logical that the total area is most predictive, as it captures both the temporal and dose effect of decelerations. At this point, however, we can only apply this concept crudely at the bedside. There is more work to do to translate such findings into software-driven bedside tools.

 

Gaining reassurance

Although efforts to manage intrapartum fetal heart rate tracings focus largely on attempting to better predict who is at greatest risk for acidemia, it is important and worthwhile that we also attempt to determine whether a fetus with a category II tracing is not acidotic.

Research has consistently shown that the presence of accelerations, whether spontaneous or stimulated, is a highly reliable indicator of normal neonatal umbilical cord pH. It is therefore reasonable, when faced with indeterminate tracings (e.g., minimal variability), to consider scalp stimulation to elicit fetal heart rate acceleration. Scalp stimulation is the easiest noninvasive tool to employ to quickly secure clinical reassurance – within a couple of minutes – that the fetus is not acidotic.

For guidance on managing repetitive variable decelerations, amnioinfusion with normal saline is similarly worthy of consideration. It has been demonstrated (Level A evidence) to resolve variable fetal heart rate decelerations and reduce the incidence of cesarean delivery for nonreassuring fetal heart rate patterns. Both amnioinfusion and scalp stimulation are recommended in the 2014 ACOG/SMFM consensus statement on “Safe Prevention of the Primary Cesarean Delivery” (Obstet Gynecol. 2014 Mar;123[3]:693-711).

Oxygen administration, on the other hand, is ingrained in practice and is included in the American College of Obstetricians and Gynecologists’ practice bulletin on managing intrapartum fetal rate tracings. It is listed as a possible resuscitative measure for category II or III tracings, despite the fact that there are extremely limited data for its effectiveness or safety in labor.

Maureen S. Hamel, MD, and her colleagues at the Warren Albert Medical School at Brown University reviewed the literature and concluded that the only two randomized trials investigating the use of maternal oxygen supplementation in laboring women do not support the idea that supplementation may benefit the fetus. Moreover, they contended that oxygen supplementation may even be harmful (Am J Obstet Gynecol. 2014 Aug;211[2]:124-7).

If supplemental oxygen were a medication, we would want to know the dose, as well as the length and duration of administration before fetal heart rate tracing improved. We don’t know the answers to these questions.

There is research ongoing, both observational studies and at least one registered randomized clinical trial, that should provide more information and guidance on the impact of supplemental oxygen in the setting of category II fetal heart rate patterns. I do not expect these findings to resolve all the questions. We’re going to need a thorough body of work to provide us with definitive answers.
 

Dr. Cahill is the chief of the division of maternal-fetal medicine at Washington University in St. Louis. She reported having no financial disclosures relevant to this Master Class.

 

There is no question that we are living in the information age where “big data” isn’t just reserved for scientists but is accessible to everyone. Wearable devices have revolutionized when and how often we exercise. Smartphones have changed the way in which we consume news, watch television, take photographs, and record home movies. Online video chatting has allowed people who live miles – or even countries – away to connect on a whole new level. Today’s 7-year-olds have never lived in a world without iPhones and don’t know what life is like without iPads. Technology has improved our daily lives in countless ways. However, is “too much of a good thing” ever just too much?

Last year, we looked back over the preceding 5 decades of ob.gyn. practice. This retrospective analysis demonstrated that today’s practitioners have infinitely more tools at their disposal than many of their mentors did to ensure the best pregnancy outcomes. From prenatal diagnostic approaches, such as ultrasonography and genetic screening, to in utero surgical interventions, our discipline has advanced in leaps and bounds, all over the course of one person’s lifetime.

As technology continues to change and, in many ways, enhance the patient experience, the question we should continually ask is, “just because we can do something, should we do it?” Just because we can perform a chorionic villus sampling, should we perform one? Perhaps not. Just because we can schedule a planned cesarean section, should we? Probably not. The same line of questioning applies to the tools we employ to assist us in labor and delivery, including one of the most ubiquitous ones – the electronic fetal monitor.

The electronic fetal heart rate monitor was developed in the late 1950s to continuously record the fetal heart rate during delivery and to help ob.gyns. identify patterns that might indicate fetal distress. Although the monitors have improved over time, the interpretation of the data obtained, and what measures to employ based on these data, can be unclear. Just because the electronic fetal monitor can detect an abnormal heart rate pattern, should we intervene, and what approaches should we employ?

To help answer these questions, I have invited Dr. Alison G. Cahill, associate professor in the department of obstetrics and gynecology at Washington University, St. Louis, and chief of the division of maternal-fetal medicine, to explore the use, utility, and interpretation of data obtained by electronic fetal monitors.
 

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

 

There is no question that we are living in the information age where “big data” isn’t just reserved for scientists but is accessible to everyone. Wearable devices have revolutionized when and how often we exercise. Smartphones have changed the way in which we consume news, watch television, take photographs, and record home movies. Online video chatting has allowed people who live miles – or even countries – away to connect on a whole new level. Today’s 7-year-olds have never lived in a world without iPhones and don’t know what life is like without iPads. Technology has improved our daily lives in countless ways. However, is “too much of a good thing” ever just too much?

Last year, we looked back over the preceding 5 decades of ob.gyn. practice. This retrospective analysis demonstrated that today’s practitioners have infinitely more tools at their disposal than many of their mentors did to ensure the best pregnancy outcomes. From prenatal diagnostic approaches, such as ultrasonography and genetic screening, to in utero surgical interventions, our discipline has advanced in leaps and bounds, all over the course of one person’s lifetime.

As technology continues to change and, in many ways, enhance the patient experience, the question we should continually ask is, “just because we can do something, should we do it?” Just because we can perform a chorionic villus sampling, should we perform one? Perhaps not. Just because we can schedule a planned cesarean section, should we? Probably not. The same line of questioning applies to the tools we employ to assist us in labor and delivery, including one of the most ubiquitous ones – the electronic fetal monitor.

The electronic fetal heart rate monitor was developed in the late 1950s to continuously record the fetal heart rate during delivery and to help ob.gyns. identify patterns that might indicate fetal distress. Although the monitors have improved over time, the interpretation of the data obtained, and what measures to employ based on these data, can be unclear. Just because the electronic fetal monitor can detect an abnormal heart rate pattern, should we intervene, and what approaches should we employ?

To help answer these questions, I have invited Dr. Alison G. Cahill, associate professor in the department of obstetrics and gynecology at Washington University, St. Louis, and chief of the division of maternal-fetal medicine, to explore the use, utility, and interpretation of data obtained by electronic fetal monitors.
 

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

 

There is no question that we are living in the information age where “big data” isn’t just reserved for scientists but is accessible to everyone. Wearable devices have revolutionized when and how often we exercise. Smartphones have changed the way in which we consume news, watch television, take photographs, and record home movies. Online video chatting has allowed people who live miles – or even countries – away to connect on a whole new level. Today’s 7-year-olds have never lived in a world without iPhones and don’t know what life is like without iPads. Technology has improved our daily lives in countless ways. However, is “too much of a good thing” ever just too much?

Last year, we looked back over the preceding 5 decades of ob.gyn. practice. This retrospective analysis demonstrated that today’s practitioners have infinitely more tools at their disposal than many of their mentors did to ensure the best pregnancy outcomes. From prenatal diagnostic approaches, such as ultrasonography and genetic screening, to in utero surgical interventions, our discipline has advanced in leaps and bounds, all over the course of one person’s lifetime.

As technology continues to change and, in many ways, enhance the patient experience, the question we should continually ask is, “just because we can do something, should we do it?” Just because we can perform a chorionic villus sampling, should we perform one? Perhaps not. Just because we can schedule a planned cesarean section, should we? Probably not. The same line of questioning applies to the tools we employ to assist us in labor and delivery, including one of the most ubiquitous ones – the electronic fetal monitor.

The electronic fetal heart rate monitor was developed in the late 1950s to continuously record the fetal heart rate during delivery and to help ob.gyns. identify patterns that might indicate fetal distress. Although the monitors have improved over time, the interpretation of the data obtained, and what measures to employ based on these data, can be unclear. Just because the electronic fetal monitor can detect an abnormal heart rate pattern, should we intervene, and what approaches should we employ?

To help answer these questions, I have invited Dr. Alison G. Cahill, associate professor in the department of obstetrics and gynecology at Washington University, St. Louis, and chief of the division of maternal-fetal medicine, to explore the use, utility, and interpretation of data obtained by electronic fetal monitors.
 

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

For minimally invasive surgeons throughout the world, particularly in the United States, as well as the patients we treat, April 17, 2014, is our day of infamy. It was on this day that the Food and Drug Administration recommended against the use of the electronic power morcellator. The basis of the agency’s decision was the concern about inadvertent spread of sarcomatous tissue. Many hospitals, medical centers, and hospital systems subsequently banned the use of power morcellation. With such bans, a subsequent study by Wright et al. noted a decrease in the percentage of both laparoscopic and vaginal hysterectomy (JAMA. 2016 Aug 23-30;316[8]:877-8). This is concerning when you consider that the complication rate for abdominal hysterectomy is around 17%, compared with about 4% for the minimally invasive procedure.

Despite a call for improved diagnostics, over the past 3 years, there has been virtually no change in our ability to diagnose a sarcomatous mass. Thus, the ability to minimize the spread of tissue is of paramount importance.

For this edition of the Master Class in Gynecologic Surgery, I have asked Tony Shibley, MD, to describe the PneumoLiner, the first FDA-approved bag for the purpose of contained laparoscopic morcellation. Dr. Shibley, who is in private practice in the Minneapolis area, first came to national attention because of his expertise in single-port surgery. He has been performing power morcellation in a contained system for 5 years and is the thought leader behind the design and creation of the PneumoLiner.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported receiving research funds from Espiner Medical Inc., and being a consultant to Olympus, which manufacturers the PneumoLiner.

For minimally invasive surgeons throughout the world, particularly in the United States, as well as the patients we treat, April 17, 2014, is our day of infamy. It was on this day that the Food and Drug Administration recommended against the use of the electronic power morcellator. The basis of the agency’s decision was the concern about inadvertent spread of sarcomatous tissue. Many hospitals, medical centers, and hospital systems subsequently banned the use of power morcellation. With such bans, a subsequent study by Wright et al. noted a decrease in the percentage of both laparoscopic and vaginal hysterectomy (JAMA. 2016 Aug 23-30;316[8]:877-8). This is concerning when you consider that the complication rate for abdominal hysterectomy is around 17%, compared with about 4% for the minimally invasive procedure.

Despite a call for improved diagnostics, over the past 3 years, there has been virtually no change in our ability to diagnose a sarcomatous mass. Thus, the ability to minimize the spread of tissue is of paramount importance.

For this edition of the Master Class in Gynecologic Surgery, I have asked Tony Shibley, MD, to describe the PneumoLiner, the first FDA-approved bag for the purpose of contained laparoscopic morcellation. Dr. Shibley, who is in private practice in the Minneapolis area, first came to national attention because of his expertise in single-port surgery. He has been performing power morcellation in a contained system for 5 years and is the thought leader behind the design and creation of the PneumoLiner.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported receiving research funds from Espiner Medical Inc., and being a consultant to Olympus, which manufacturers the PneumoLiner.

For minimally invasive surgeons throughout the world, particularly in the United States, as well as the patients we treat, April 17, 2014, is our day of infamy. It was on this day that the Food and Drug Administration recommended against the use of the electronic power morcellator. The basis of the agency’s decision was the concern about inadvertent spread of sarcomatous tissue. Many hospitals, medical centers, and hospital systems subsequently banned the use of power morcellation. With such bans, a subsequent study by Wright et al. noted a decrease in the percentage of both laparoscopic and vaginal hysterectomy (JAMA. 2016 Aug 23-30;316[8]:877-8). This is concerning when you consider that the complication rate for abdominal hysterectomy is around 17%, compared with about 4% for the minimally invasive procedure.

Despite a call for improved diagnostics, over the past 3 years, there has been virtually no change in our ability to diagnose a sarcomatous mass. Thus, the ability to minimize the spread of tissue is of paramount importance.

For this edition of the Master Class in Gynecologic Surgery, I have asked Tony Shibley, MD, to describe the PneumoLiner, the first FDA-approved bag for the purpose of contained laparoscopic morcellation. Dr. Shibley, who is in private practice in the Minneapolis area, first came to national attention because of his expertise in single-port surgery. He has been performing power morcellation in a contained system for 5 years and is the thought leader behind the design and creation of the PneumoLiner.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported receiving research funds from Espiner Medical Inc., and being a consultant to Olympus, which manufacturers the PneumoLiner.

Experience with electromechanical power morcellation in a bag has advanced in the last several years in an effort to achieve safe tissue removal for minimally invasive procedures such as myomectomy, laparoscopic supracervical hysterectomy, or total hysterectomy of a large uterus.

Tissue extraction using contained power morcellation has become favored over contained morcellation using a scalpel – not only because the latter approach is cumbersome but because of the risk of bag puncture and subsequent organ injury. Surgeons have experimented with various sizes and types of retrieval bags and with various techniques for contained power morcellation.

When I stopped performing uncontained power morcellation about 5 years ago, I developed an approach for enclosed morcellation that involves the creation of an artificial pneumoperitoneum inside a bag (J Minim Invasive Gynecol. 2012;19[6]:[Suppl] S75). This technique provides direct vision and a good, safe working space. In essence, for morcellation, the laparoscopic procedure moves from an inflated abdomen into an inflated bag.

Courtesy Dr. Tony Shibley

To standardize this approach and make it more efficient, I subsequently collaborated with Advanced Surgical Concepts to design a morcellation containment device consisting of a specialized bag that opens automatically and assists in capturing the specimen. The PneumoLiner device was approved by the Food and Drug Administration in April 2016.

Courtesy Olympus

The PneumoLiner carries the same restrictions as do other laparoscopic power morcellation systems – namely that it should not be used in surgery in which the tissue to be morcellated is known or suspected to contain malignancy, and that it should not be used in women who are peri- or postmenopausal. Moreover, to further enhance safety, physicians must have successfully completed the FDA-required validated training program run by Advanced Surgical Concepts and Olympus in order to use the device.

The FDA reviewed the PneumoLiner through a regulatory process known as the de novo classification process. This regulatory process is for first of its kind, low- to moderate-risk medical devices. The PneumoLiner was tested in laboratory conditions to ensure that it could withstand stress force in excess of the normal forces of surgery, and was found to be impervious to substances similar in molecular size to tissues, cells, and body fluids. There could be no cellular migration or leakage.

As surgeons were advancing the idea of inflated bag morcellation, one promising adaptation was to puncture the inflated bag to place accessory ports. However, recent research has shown that contained morcellation involving intentional bag puncture with a trocar may result in tissue or fluid leakage.

Spillage was noted in 7 of 76 cases (9.2%) in a multicenter prospective cohort of women who underwent hysterectomy or myomectomy using a contained power morcellation technique that involved perforation of the containment bag with a balloon-tipped lateral trocar. Investigators had injected blue dye into the bag prior to morcellation and examined the abdomen and pelvis after removing the bag for signs of spillage of dye, fluid, or tissue. In all cases, the containment bags were intact (Am J Obstet Gynecol. 2016 Feb;214[2]:257.e1-6).

The authors prematurely closed this study and recommended against this puncture technique. For complete containment, it appears to be important that we morcellate using a bag that has a single opening and is not punctured with accessory trocars.

Courtesy Dr. Tony Shibley

My partners and I have successfully used my technique in hundreds cases since 2011. The PneumoLiner is specifically designed for this procedure and should provide a solid platform for improving safety and preserving, for our patients, the advantages of minimally invasive surgery. Further studies may broaden the indications for use within and outside of gynecology.

The technique

The PneumoLiner comes loaded in an insertion tube for placement. It has a plunger to deploy the device and a retrieval lanyard that closes the bag around the specimen, enabling retrieval of the neck of the bag outside the abdomen.

Courtesy Olympus

Included with the PneumoLiner is a multi-instrument port that can be used during the laparoscopic procedure and then converted to the active port for morcellation. The port has an opening for the laparoscope (either a 5-mm 30-degree straight or a 5-mm articulating laparoscope) and an opening for the morcellator, as well as two small openings for insufflation and for smoke exhaustion.

Surgery may be performed using this single-port or a multiport laparoscopic or robotic approach. For morcellation, the approach converts to a single-site technique that involves only one entry point for all instruments and no perforation of the bag.

At the beginning of the procedure (or at the end of the case if preferred), a 25-mm incision is made in the umbilicus and the system’s port is inserted and trimmed. The port cap is placed, the abdomen is insufflated, and the laparoscope is inserted. If placed at the beginning of the case, this port can be used as a camera or accessory port.

Before deployment of the PneumoLiner, the uterus or target tissue is placed out of the way; I recommend the upper right quadrant. The PneumoLiner is then inserted with its directional tab pointing upward, and the system’s plunger is depressed while the sleeve is pulled back. In essence, the PneumoLiner is advanced while the sleeve is simultaneously withdrawn, laying it flat in the pelvis.
 

With an atraumatic grasper, the uterus is placed within the opening of the bag, and the bag is grasped at the collar and elevated up and around the specimen. When full containment of the specimen is visualized, the retrieval lanyard is withdrawn until an opening ring partially protrudes outside the port. All lateral trocars must have been withdrawn prior to inflation of the bag to prevent it from being damaged.

At this point, the port cap is removed and the PneumoLiner neck is withdrawn until a black grid pattern on the bag is visible. The surgeon should then ensure there are no twists in the bag before replacing the port cap and insufflating the bag to a pressure of 15 mm Hg.*

The bag must be correctly in place and fully insufflated before the laparoscope is inserted. The laparoscope must be inserted prior to the morcellator. When the morcellator is inserted, care must be taken to ensure that the morcellator probe is in place.

Once the morcellator is placed, the probe is withdrawn and a closed tenaculum is placed. With the closed tenaculum, the surgeon can manipulate tissue and gauge depth and bearings without inadvertently grabbing the bag. The black grid pattern on the bag assists with estimation of tissue fragment size; morcellation proceeds under direct vision until the tissue fragments are smaller than four printed grids.

Instrumentation is removed in a set order, with the morcellator first and the laparoscope last. The port cap is detached and the PneumoLiner is removed while allowing fumes to escape. The morcellator, camera, tenaculum, and port cap are considered contaminated at this point and should not re-enter the field.

 

Pearls for morcellation

• The single-site nature of the procedure can sometimes be challenging. If you’ve placed your laparoscope and are having difficulty locating the morcellator, bring your laparoscope and morcellator shaft in parallel to each other, and you’ll be able to better orient yourself.
• To enlarge your field of view after you’ve inflated the PneumoLiner and captured the tissue within the bag, level the patient a bit and move the tissue further away from the laparoscope.
• If the morcellator tube is limiting visualization of the tenaculum tip, slide the morcellator back while leaving the tenaculum in a fixed position.

  The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

Courtesy Dr. Tony Shibley and Olympus

Dr. Shibley is an ob.gyn. in private practice in the Minneapolis area. He receives royalties from Advanced Surgical Concepts and serves as a consultant for Olympus.

*Correction 3/8/17: An earlier version of this article misstated the name of the Pneumoliner device in a photo caption. The pressure of the morcellation bag also was misstated.

Experience with electromechanical power morcellation in a bag has advanced in the last several years in an effort to achieve safe tissue removal for minimally invasive procedures such as myomectomy, laparoscopic supracervical hysterectomy, or total hysterectomy of a large uterus.

Tissue extraction using contained power morcellation has become favored over contained morcellation using a scalpel – not only because the latter approach is cumbersome but because of the risk of bag puncture and subsequent organ injury. Surgeons have experimented with various sizes and types of retrieval bags and with various techniques for contained power morcellation.

When I stopped performing uncontained power morcellation about 5 years ago, I developed an approach for enclosed morcellation that involves the creation of an artificial pneumoperitoneum inside a bag (J Minim Invasive Gynecol. 2012;19[6]:[Suppl] S75). This technique provides direct vision and a good, safe working space. In essence, for morcellation, the laparoscopic procedure moves from an inflated abdomen into an inflated bag.

Courtesy Dr. Tony Shibley

To standardize this approach and make it more efficient, I subsequently collaborated with Advanced Surgical Concepts to design a morcellation containment device consisting of a specialized bag that opens automatically and assists in capturing the specimen. The PneumoLiner device was approved by the Food and Drug Administration in April 2016.

Courtesy Olympus

The PneumoLiner carries the same restrictions as do other laparoscopic power morcellation systems – namely that it should not be used in surgery in which the tissue to be morcellated is known or suspected to contain malignancy, and that it should not be used in women who are peri- or postmenopausal. Moreover, to further enhance safety, physicians must have successfully completed the FDA-required validated training program run by Advanced Surgical Concepts and Olympus in order to use the device.

The FDA reviewed the PneumoLiner through a regulatory process known as the de novo classification process. This regulatory process is for first of its kind, low- to moderate-risk medical devices. The PneumoLiner was tested in laboratory conditions to ensure that it could withstand stress force in excess of the normal forces of surgery, and was found to be impervious to substances similar in molecular size to tissues, cells, and body fluids. There could be no cellular migration or leakage.

As surgeons were advancing the idea of inflated bag morcellation, one promising adaptation was to puncture the inflated bag to place accessory ports. However, recent research has shown that contained morcellation involving intentional bag puncture with a trocar may result in tissue or fluid leakage.

Spillage was noted in 7 of 76 cases (9.2%) in a multicenter prospective cohort of women who underwent hysterectomy or myomectomy using a contained power morcellation technique that involved perforation of the containment bag with a balloon-tipped lateral trocar. Investigators had injected blue dye into the bag prior to morcellation and examined the abdomen and pelvis after removing the bag for signs of spillage of dye, fluid, or tissue. In all cases, the containment bags were intact (Am J Obstet Gynecol. 2016 Feb;214[2]:257.e1-6).

The authors prematurely closed this study and recommended against this puncture technique. For complete containment, it appears to be important that we morcellate using a bag that has a single opening and is not punctured with accessory trocars.

Courtesy Dr. Tony Shibley

My partners and I have successfully used my technique in hundreds cases since 2011. The PneumoLiner is specifically designed for this procedure and should provide a solid platform for improving safety and preserving, for our patients, the advantages of minimally invasive surgery. Further studies may broaden the indications for use within and outside of gynecology.

The technique

The PneumoLiner comes loaded in an insertion tube for placement. It has a plunger to deploy the device and a retrieval lanyard that closes the bag around the specimen, enabling retrieval of the neck of the bag outside the abdomen.

Courtesy Olympus

Included with the PneumoLiner is a multi-instrument port that can be used during the laparoscopic procedure and then converted to the active port for morcellation. The port has an opening for the laparoscope (either a 5-mm 30-degree straight or a 5-mm articulating laparoscope) and an opening for the morcellator, as well as two small openings for insufflation and for smoke exhaustion.

Surgery may be performed using this single-port or a multiport laparoscopic or robotic approach. For morcellation, the approach converts to a single-site technique that involves only one entry point for all instruments and no perforation of the bag.

At the beginning of the procedure (or at the end of the case if preferred), a 25-mm incision is made in the umbilicus and the system’s port is inserted and trimmed. The port cap is placed, the abdomen is insufflated, and the laparoscope is inserted. If placed at the beginning of the case, this port can be used as a camera or accessory port.

Before deployment of the PneumoLiner, the uterus or target tissue is placed out of the way; I recommend the upper right quadrant. The PneumoLiner is then inserted with its directional tab pointing upward, and the system’s plunger is depressed while the sleeve is pulled back. In essence, the PneumoLiner is advanced while the sleeve is simultaneously withdrawn, laying it flat in the pelvis.
 

With an atraumatic grasper, the uterus is placed within the opening of the bag, and the bag is grasped at the collar and elevated up and around the specimen. When full containment of the specimen is visualized, the retrieval lanyard is withdrawn until an opening ring partially protrudes outside the port. All lateral trocars must have been withdrawn prior to inflation of the bag to prevent it from being damaged.

At this point, the port cap is removed and the PneumoLiner neck is withdrawn until a black grid pattern on the bag is visible. The surgeon should then ensure there are no twists in the bag before replacing the port cap and insufflating the bag to a pressure of 15 mm Hg.*

The bag must be correctly in place and fully insufflated before the laparoscope is inserted. The laparoscope must be inserted prior to the morcellator. When the morcellator is inserted, care must be taken to ensure that the morcellator probe is in place.

Once the morcellator is placed, the probe is withdrawn and a closed tenaculum is placed. With the closed tenaculum, the surgeon can manipulate tissue and gauge depth and bearings without inadvertently grabbing the bag. The black grid pattern on the bag assists with estimation of tissue fragment size; morcellation proceeds under direct vision until the tissue fragments are smaller than four printed grids.

Instrumentation is removed in a set order, with the morcellator first and the laparoscope last. The port cap is detached and the PneumoLiner is removed while allowing fumes to escape. The morcellator, camera, tenaculum, and port cap are considered contaminated at this point and should not re-enter the field.

 

Pearls for morcellation

• The single-site nature of the procedure can sometimes be challenging. If you’ve placed your laparoscope and are having difficulty locating the morcellator, bring your laparoscope and morcellator shaft in parallel to each other, and you’ll be able to better orient yourself.
• To enlarge your field of view after you’ve inflated the PneumoLiner and captured the tissue within the bag, level the patient a bit and move the tissue further away from the laparoscope.
• If the morcellator tube is limiting visualization of the tenaculum tip, slide the morcellator back while leaving the tenaculum in a fixed position.

  The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

Courtesy Dr. Tony Shibley and Olympus

Dr. Shibley is an ob.gyn. in private practice in the Minneapolis area. He receives royalties from Advanced Surgical Concepts and serves as a consultant for Olympus.

*Correction 3/8/17: An earlier version of this article misstated the name of the Pneumoliner device in a photo caption. The pressure of the morcellation bag also was misstated.

Experience with electromechanical power morcellation in a bag has advanced in the last several years in an effort to achieve safe tissue removal for minimally invasive procedures such as myomectomy, laparoscopic supracervical hysterectomy, or total hysterectomy of a large uterus.

Tissue extraction using contained power morcellation has become favored over contained morcellation using a scalpel – not only because the latter approach is cumbersome but because of the risk of bag puncture and subsequent organ injury. Surgeons have experimented with various sizes and types of retrieval bags and with various techniques for contained power morcellation.

When I stopped performing uncontained power morcellation about 5 years ago, I developed an approach for enclosed morcellation that involves the creation of an artificial pneumoperitoneum inside a bag (J Minim Invasive Gynecol. 2012;19[6]:[Suppl] S75). This technique provides direct vision and a good, safe working space. In essence, for morcellation, the laparoscopic procedure moves from an inflated abdomen into an inflated bag.

Courtesy Dr. Tony Shibley

To standardize this approach and make it more efficient, I subsequently collaborated with Advanced Surgical Concepts to design a morcellation containment device consisting of a specialized bag that opens automatically and assists in capturing the specimen. The PneumoLiner device was approved by the Food and Drug Administration in April 2016.

Courtesy Olympus

The PneumoLiner carries the same restrictions as do other laparoscopic power morcellation systems – namely that it should not be used in surgery in which the tissue to be morcellated is known or suspected to contain malignancy, and that it should not be used in women who are peri- or postmenopausal. Moreover, to further enhance safety, physicians must have successfully completed the FDA-required validated training program run by Advanced Surgical Concepts and Olympus in order to use the device.

The FDA reviewed the PneumoLiner through a regulatory process known as the de novo classification process. This regulatory process is for first of its kind, low- to moderate-risk medical devices. The PneumoLiner was tested in laboratory conditions to ensure that it could withstand stress force in excess of the normal forces of surgery, and was found to be impervious to substances similar in molecular size to tissues, cells, and body fluids. There could be no cellular migration or leakage.

As surgeons were advancing the idea of inflated bag morcellation, one promising adaptation was to puncture the inflated bag to place accessory ports. However, recent research has shown that contained morcellation involving intentional bag puncture with a trocar may result in tissue or fluid leakage.

Spillage was noted in 7 of 76 cases (9.2%) in a multicenter prospective cohort of women who underwent hysterectomy or myomectomy using a contained power morcellation technique that involved perforation of the containment bag with a balloon-tipped lateral trocar. Investigators had injected blue dye into the bag prior to morcellation and examined the abdomen and pelvis after removing the bag for signs of spillage of dye, fluid, or tissue. In all cases, the containment bags were intact (Am J Obstet Gynecol. 2016 Feb;214[2]:257.e1-6).

The authors prematurely closed this study and recommended against this puncture technique. For complete containment, it appears to be important that we morcellate using a bag that has a single opening and is not punctured with accessory trocars.

Courtesy Dr. Tony Shibley

My partners and I have successfully used my technique in hundreds cases since 2011. The PneumoLiner is specifically designed for this procedure and should provide a solid platform for improving safety and preserving, for our patients, the advantages of minimally invasive surgery. Further studies may broaden the indications for use within and outside of gynecology.

The technique

The PneumoLiner comes loaded in an insertion tube for placement. It has a plunger to deploy the device and a retrieval lanyard that closes the bag around the specimen, enabling retrieval of the neck of the bag outside the abdomen.

Courtesy Olympus

Included with the PneumoLiner is a multi-instrument port that can be used during the laparoscopic procedure and then converted to the active port for morcellation. The port has an opening for the laparoscope (either a 5-mm 30-degree straight or a 5-mm articulating laparoscope) and an opening for the morcellator, as well as two small openings for insufflation and for smoke exhaustion.

Surgery may be performed using this single-port or a multiport laparoscopic or robotic approach. For morcellation, the approach converts to a single-site technique that involves only one entry point for all instruments and no perforation of the bag.

At the beginning of the procedure (or at the end of the case if preferred), a 25-mm incision is made in the umbilicus and the system’s port is inserted and trimmed. The port cap is placed, the abdomen is insufflated, and the laparoscope is inserted. If placed at the beginning of the case, this port can be used as a camera or accessory port.

Before deployment of the PneumoLiner, the uterus or target tissue is placed out of the way; I recommend the upper right quadrant. The PneumoLiner is then inserted with its directional tab pointing upward, and the system’s plunger is depressed while the sleeve is pulled back. In essence, the PneumoLiner is advanced while the sleeve is simultaneously withdrawn, laying it flat in the pelvis.
 

With an atraumatic grasper, the uterus is placed within the opening of the bag, and the bag is grasped at the collar and elevated up and around the specimen. When full containment of the specimen is visualized, the retrieval lanyard is withdrawn until an opening ring partially protrudes outside the port. All lateral trocars must have been withdrawn prior to inflation of the bag to prevent it from being damaged.

At this point, the port cap is removed and the PneumoLiner neck is withdrawn until a black grid pattern on the bag is visible. The surgeon should then ensure there are no twists in the bag before replacing the port cap and insufflating the bag to a pressure of 15 mm Hg.*

The bag must be correctly in place and fully insufflated before the laparoscope is inserted. The laparoscope must be inserted prior to the morcellator. When the morcellator is inserted, care must be taken to ensure that the morcellator probe is in place.

Once the morcellator is placed, the probe is withdrawn and a closed tenaculum is placed. With the closed tenaculum, the surgeon can manipulate tissue and gauge depth and bearings without inadvertently grabbing the bag. The black grid pattern on the bag assists with estimation of tissue fragment size; morcellation proceeds under direct vision until the tissue fragments are smaller than four printed grids.

Instrumentation is removed in a set order, with the morcellator first and the laparoscope last. The port cap is detached and the PneumoLiner is removed while allowing fumes to escape. The morcellator, camera, tenaculum, and port cap are considered contaminated at this point and should not re-enter the field.

 

Pearls for morcellation

• The single-site nature of the procedure can sometimes be challenging. If you’ve placed your laparoscope and are having difficulty locating the morcellator, bring your laparoscope and morcellator shaft in parallel to each other, and you’ll be able to better orient yourself.
• To enlarge your field of view after you’ve inflated the PneumoLiner and captured the tissue within the bag, level the patient a bit and move the tissue further away from the laparoscope.
• If the morcellator tube is limiting visualization of the tenaculum tip, slide the morcellator back while leaving the tenaculum in a fixed position.

  The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel

Courtesy Dr. Tony Shibley and Olympus

Dr. Shibley is an ob.gyn. in private practice in the Minneapolis area. He receives royalties from Advanced Surgical Concepts and serves as a consultant for Olympus.

*Correction 3/8/17: An earlier version of this article misstated the name of the Pneumoliner device in a photo caption. The pressure of the morcellation bag also was misstated.

 

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Twin births are the most common multiple births and, in the United States, account for a little more than 3% of all live births. Active vigilance on the part of the mother and her ob.gyn. begins once twins have been identified and their chorionicity is established, ideally within the first trimester. Dichorionic twins and monochorionic twins cannot be treated in exactly the same manner. For example, according to the American College of Obstetricians and Gynecologists, dichorionic twins with no complications should be delivered at 38 weeks’ gestation, and monochorionic twins with no complications should be delivered between 34 and 38 weeks’ gestation (Obstet Gynecol. 2013;121:908-10).

This month, we focus on the range of tools and approaches used to treat complications that can occur in monochorionic twin pregnancies, including twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion. Despite the challenges these conditions pose, increased ultrasonographic and echocardiographic surveillance allow for earlier detection and possible intervention to slow progression or, in some cases, correct defects that would have terminated the pregnancy not too long ago. Additionally, fetal therapy programs utilizing in-utero surgical techniques, such as fetoscopic laser coagulation, have significantly broadened the management and treatment options we can now offer these patients.

Dr. M. Ozhan Turan, an associate professor and director of fetal therapy and complex obstetric surgery in the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, provides an overview of these techniques and technologies which, when applied appropriately, can significantly improve pregnancy outcomes.
 

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

 

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Twin births are the most common multiple births and, in the United States, account for a little more than 3% of all live births. Active vigilance on the part of the mother and her ob.gyn. begins once twins have been identified and their chorionicity is established, ideally within the first trimester. Dichorionic twins and monochorionic twins cannot be treated in exactly the same manner. For example, according to the American College of Obstetricians and Gynecologists, dichorionic twins with no complications should be delivered at 38 weeks’ gestation, and monochorionic twins with no complications should be delivered between 34 and 38 weeks’ gestation (Obstet Gynecol. 2013;121:908-10).

This month, we focus on the range of tools and approaches used to treat complications that can occur in monochorionic twin pregnancies, including twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion. Despite the challenges these conditions pose, increased ultrasonographic and echocardiographic surveillance allow for earlier detection and possible intervention to slow progression or, in some cases, correct defects that would have terminated the pregnancy not too long ago. Additionally, fetal therapy programs utilizing in-utero surgical techniques, such as fetoscopic laser coagulation, have significantly broadened the management and treatment options we can now offer these patients.

Dr. M. Ozhan Turan, an associate professor and director of fetal therapy and complex obstetric surgery in the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, provides an overview of these techniques and technologies which, when applied appropriately, can significantly improve pregnancy outcomes.
 

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

 

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Twin births are the most common multiple births and, in the United States, account for a little more than 3% of all live births. Active vigilance on the part of the mother and her ob.gyn. begins once twins have been identified and their chorionicity is established, ideally within the first trimester. Dichorionic twins and monochorionic twins cannot be treated in exactly the same manner. For example, according to the American College of Obstetricians and Gynecologists, dichorionic twins with no complications should be delivered at 38 weeks’ gestation, and monochorionic twins with no complications should be delivered between 34 and 38 weeks’ gestation (Obstet Gynecol. 2013;121:908-10).

This month, we focus on the range of tools and approaches used to treat complications that can occur in monochorionic twin pregnancies, including twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion. Despite the challenges these conditions pose, increased ultrasonographic and echocardiographic surveillance allow for earlier detection and possible intervention to slow progression or, in some cases, correct defects that would have terminated the pregnancy not too long ago. Additionally, fetal therapy programs utilizing in-utero surgical techniques, such as fetoscopic laser coagulation, have significantly broadened the management and treatment options we can now offer these patients.

Dr. M. Ozhan Turan, an associate professor and director of fetal therapy and complex obstetric surgery in the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, provides an overview of these techniques and technologies which, when applied appropriately, can significantly improve pregnancy outcomes.
 

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

 

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Monochorionic twins should be identified in the first trimester. Chorionicity is a straightforward determination at this time but can be difficult to determine in the second trimester if a single placental mass is all that is visible on an ultrasound. Most important, however, is the need for early surveillance of monochorionic twin pregnancies and the detection of potential problems and complications.

Increased ultrasonographic surveillance recommended for monochorionic twin pregnancies has been outlined in a recent consensus statement from the North American Fetal Therapy Network (Obstet Gynecol. 2015 Jan;125[1]:118-23). Beginning at 16 weeks’ gestation, monochorionic twins should be assessed every 2 weeks using amniotic fluid balance, presence/absence of fluid within the fetal bladder, and with fetal Doppler (umbilical artery, middle cerebral artery, and ductus venosus) studies. Fetal growth should also be assessed at least every 4 weeks.

Since monochorionic twins are at increased risk for congenital heart disease, echocardiography is also performed between 18 and 22 weeks, with surveillance intervals of 2 weeks or shorter if potential complications are identified. Early detection of these and other complications allows for earlier intervention, earlier referral if necessary, and potentially better outcomes.
 

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

 

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

 

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Monochorionic twins should be identified in the first trimester. Chorionicity is a straightforward determination at this time but can be difficult to determine in the second trimester if a single placental mass is all that is visible on an ultrasound. Most important, however, is the need for early surveillance of monochorionic twin pregnancies and the detection of potential problems and complications.

Increased ultrasonographic surveillance recommended for monochorionic twin pregnancies has been outlined in a recent consensus statement from the North American Fetal Therapy Network (Obstet Gynecol. 2015 Jan;125[1]:118-23). Beginning at 16 weeks’ gestation, monochorionic twins should be assessed every 2 weeks using amniotic fluid balance, presence/absence of fluid within the fetal bladder, and with fetal Doppler (umbilical artery, middle cerebral artery, and ductus venosus) studies. Fetal growth should also be assessed at least every 4 weeks.

Since monochorionic twins are at increased risk for congenital heart disease, echocardiography is also performed between 18 and 22 weeks, with surveillance intervals of 2 weeks or shorter if potential complications are identified. Early detection of these and other complications allows for earlier intervention, earlier referral if necessary, and potentially better outcomes.
 

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

 

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

 

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Monochorionic twins should be identified in the first trimester. Chorionicity is a straightforward determination at this time but can be difficult to determine in the second trimester if a single placental mass is all that is visible on an ultrasound. Most important, however, is the need for early surveillance of monochorionic twin pregnancies and the detection of potential problems and complications.

Increased ultrasonographic surveillance recommended for monochorionic twin pregnancies has been outlined in a recent consensus statement from the North American Fetal Therapy Network (Obstet Gynecol. 2015 Jan;125[1]:118-23). Beginning at 16 weeks’ gestation, monochorionic twins should be assessed every 2 weeks using amniotic fluid balance, presence/absence of fluid within the fetal bladder, and with fetal Doppler (umbilical artery, middle cerebral artery, and ductus venosus) studies. Fetal growth should also be assessed at least every 4 weeks.

Since monochorionic twins are at increased risk for congenital heart disease, echocardiography is also performed between 18 and 22 weeks, with surveillance intervals of 2 weeks or shorter if potential complications are identified. Early detection of these and other complications allows for earlier intervention, earlier referral if necessary, and potentially better outcomes.
 

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

 

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

 

One in seven women suffer with abnormal uterine bleeding during their reproductive years, according to Fraser et al. (Exp Rev Obstet Gynecol. 2009;4:179-89). Heavy menstrual bleeding (menorrhagia) is the most common pattern. Global endometrial ablation has become a very popular surgical technique for women complaining of menorrhagia, disinterested in either medical management or definitive therapy – hysterectomy – or where medical management has failed. With proper patient selection, endometrial ablation yields an 80%-90% success rate in reducing heavy menstrual flow and is associated with a 90% patient satisfaction rate (Cochrane Database Syst Rev. 2009 Oct 7;[4]:CD001501).

Over time however, the rate of failure increases. Failure rates between 16% at 5 years to nearly 26% at 8 years have been reported.

Literature is replete with conditions believed to increase risk of endometrial ablation failure. This list includes untreated uterine cornua, endometrial regrowth, the presence of submucous leiomyomas or polyps, abnormal uterine cavity, enlarged uterine cavity (width and/or length), endometrial ablation in a young patient, parity of five or greater, unsuspected adhesiolysis, postablation tubal sterilization syndrome, history of dysmenorrhea, smoking, obesity, prior cesarean section, previous gynecologic surgery, and procedure length. Interestingly, type of global endometrial ablation procedure or original bleeding pattern does not influence failure rate.

In this edition of the Master Class in Gynecologic Surgery, Dr. Morris Wortman discusses not only the prevention of endometrial ablation failure, but also how to treat the problem via conservative surgical management.

Dr. Wortman is a clinical associate professor of obstetrics and gynecology at the University of Rochester (N.Y.) and is the director at the Center for Menstrual Disorders and Reproductive Choice, also in Rochester. Dr. Wortman has lectured extensively on endometrial ablation and has authored several scientific articles in peer reviewed journals.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported being a subinvestigator on a study sponsored by Channel Medsystems. Email him at obnews@frontlinemedcom.com.

Why failures occur and how to correct them

BY MORRIS WORTMAN, MD

Since the introduction almost 20 years ago of devices for nonresectoscopic – or “global” – endometrial ablation, the procedure has been widely adopted as the treatment of choice for abnormal uterine bleeding that is refractory to medical management.

Between 400,000 and 500,000 endometrial ablations are done in the United States every year in women who have completed childbearing, and it probably won’t be long before the procedure surpasses hysterectomy in prevalence for the management of abnormal bleeding.

Endometrial ablation (EA) dates back to the late 19th century, but global endometrial ablation (GEA) – its latest evolution – has offered improved safety, acceptable outcomes, and technical simplicity. Along with its success, however, has come awareness that a substantial number of women will eventually experience complications: persistent or recurrent vaginal bleeding, cyclic pelvic pain, or the inability to adequately sample the endometrium in cases of postmenopausal bleeding.

In recent years, the literature has begun to address the incidence of these delayed complications and the requirement for subsequent hysterectomy. A 2007 practice bulletin issued by the American College of Obstetricians and Gynecologists stated that hysterectomy rates within 4 years of endometrial ablation are at least 24% (Obstet Gynecol. 2007 May;109[5]:1233-48). And a study published the following year reported that 26% of 3,681 women undergoing EA at Kaiser Permanente facilities in Northern California required hysterectomy within 8 years (Obstet Gynecol. 2008 Dec;112[6]:1214-20).

It appears that the vast majority of what we now refer to as late-onset EA failures – complications attributable to EA that occur beyond a perioperative period of 1 month – will occur within 5 years. Some EA failures have occurred over 5-10 years, however, and in my practice we have seen late-onset complications occurring 17 or more years after the initial ablation.

In our practice, we are successfully managing delayed complications after GEA using ultrasound-guided reoperative hysteroscopy to fully explore the uterine cavity and excise areas of endometrial growth and other disease. In 2014, we published a retrospective review of 50 women whom we treated for delayed complications after a variety of GEA techniques; almost 90% avoided hysterectomy during a mean follow-up period of 18 months (J Minim Invasive Gynecol. 2014 Mar-Apr;21[2]:238-44).

Our experience since then has included reoperative surgery on more than 115 GEA failures. Additionally, we’ve managed 220 patients who have undergone various hysteroscopic and resectoscopic endometrial ablations, some of which date back to the use of the Nd:YAG laser in the late 1980s.

The fact that late-onset EA failures occur does not mean that hysterectomy should routinely be performed as a first-line treatment for intractable uterine bleeding. Overall, there is much more morbidity associated with hysterectomy than with EA.

What failures do suggest is that there are certain risk factors for late-onset EA complications. Our experience in treating women who have experienced late-onset EA failure has provided us with insight into who may be at greatest risk for late-onset EA failure and how patients can best be selected for the procedure. We’ve also learned more about the diagnosis of delayed complications.
 

 

Causes of EA failure

Untreated uterine cornua, and untreated submucous leiomyomas and endometrial polyps, are common causes of EA failure. Among the 50 women included in our retrospective review of ultrasound-guided reoperative hysteroscopy after GEA failure, 44% had intraoperative evidence of untreated cornua and nearly one-fourth had persistent or enlarging submucous leiomyomas.

Contrary to what some believe, most endometrial ablations will not adequately destroy submucous or intramural leiomyomas. Therefore, we recommend that these fibroids be entirely removed immediately before EA.

Moreover, GEA will not always provide adequate thermal destruction to the entire endometrial cavity. The cornua regions are particularly at risk; they are difficult to reach under ideal circumstances, and especially difficult to treat in patients who have a uterine septum or a T-shaped uterus (with the ostia and cornua deeply recessed). We have also seen late-onset EA failures in patients with an extended uterine transverse diameter. The limits of GEA are greatest when a device with a fixed configuration or geometry is used.

A history of abnormal hysteroscopy or other evidence of such anatomic distortions are therefore among the reported risk factors for GEA failure (J Minim Invasive Gynecol. 2015 Mar-Apr;22[3]:323-31). A history of tubal ligation also confers risk; the procedure further increases susceptibility for failure when functioning endometrial tissue remains or regrows at the cornua, because any retrograde menstrual bleeding that occurs will be constrained by the obstructed proximal portion of the fallopian tubes.

Obesity is another risk factor for GEA failure in that the condition increases the risk of endometrial cancer, making the need for reliable biopsies in the case of spotting or other signs or symptoms even more important. On the other hand, obesity may also worsen a patient’s status as a candidate for hysterectomy.

There is much to consider with these patients. For some obese patients, GEA may be less risky than hysterectomy while for others, such as those who also have polycystic ovarian syndrome (in whom the risk for developing endometrial cancer is further increased) the scale may tip in favor of hysterectomy.

Age at the time of the primary GEA may be the single most important risk factor for GEA failure and is an important predictor of success in patient selection. Numerous investigators have shown that women younger than 35 years of age at the time of their EA had a significantly increased risk for hysterectomy, compared with women who were at least 45 years old. The younger the patient, the longer the “bridge” to menopause and the greater the likelihood that bridge will fail.

While age is not necessarily a contraindication, it is worthy of serious consideration. We generally discourage GEA for patients younger than 35. We also advise ensuring that each patient undergoing initial EA is highly self-motivated to have a uterine-sparing procedure; if not, symptoms she may experience later will likely drive her toward hysterectomy anyway.

Additionally, we caution against performing GEA in patients who have chronic pelvic pain; these patients tend to have poorer outcomes with any type of hysteroscopic surgery.
 

Diagnosing failed EA

Delayed complications manifest in several ways: Renewed and increasing vaginal bleeding after a period of improvement, cyclic pelvic pain (unilateral, bilateral, or suprapubic), or both bleeding and pain. Some women – likely an underreported number of them – present with postmenopausal bleeding and proceed to have unsuccessful attempts at an endometrial biopsy due to EA-associated endometrial scarring.

The cyclic pelvic pain associated with endometrial persistence or regrowth tends to worsen over time and is often described as sharp or laborlike. In our experience, a description of “laborlike” pain and a history of EA is almost fully predictive of a finding of endometrial growth. Often a hematometra can be demonstrated on transvaginal ultrasound, but this isn’t always the case.

Pain typically precedes bleeding in patients who demonstrate both. In such cases, blood from functioning endometrial tissue or other sources becomes blocked from exiting the uterine cavity by EA-induced intrauterine scarring and contracture. Painful uterine contractions then aim to expel the pooled blood. In other cases of pain – mainly those without significant vaginal bleeding – the pain is often attributed to cornual and central hematometra.

For the majority of EA failures, the diagnosis lies in the history and current symptoms. Unfortunately, the traditional methods of assessing the endometrial cavity have little merit for women presenting with delayed-onset EA complications. A sonographically assisted pelvic examination can be useful in evaluating complications, but the interpretation of ultrasounds in women with a prior EA can be challenging and is often beyond the training of most radiologists and gynecologists.

It is not uncommon for images to be incorrectly interpreted in the emergency department or physicians’ offices as “normal” and for such readings to set off a chain of CT scans, MRIs, laparoscopies, ovarian cystectomies, and other procedures that miss the root causes of pain.

Unfortunately, there is little in the literature that describes and defines ultrasound findings after EA. We do know that sonography should be timed with episodes of pain, and that the absence of a demonstrable hematometra does not exclude a diagnosis of EA failure.
 

 

Correcting late-onset failures

Our office-based operating room is fitted with side-by-side monitors that enable simultaneous sonographic and hysteroscopic views for correction of GEA failures; the rest of the set-up is similar to that of other operative hysteroscopies. However, we do employ a wide variety of resectoscopes with diameters ranging from 13 to 28 Fr. The smaller-diameter scopes are particularly useful for evaluating postmenopausal bleeding in women with a prior EA.

Courtesy Dr. Morris Wortman

Nearly all patients are seen the day before surgery for placement of a laminaria. The cervix is dilated 3-4 mm with the adjuvant use of IV sedation and sonographic guidance that combines sagittal and transverse scanning to ensure placement of the laminaria in the midline. This preparatory work provides an easily identifiable channel – the next day – that extends past the internal os.

For those inexperienced with ultrasound-guided surgery, the initial resection is often the most challenging. The initial tissue removal is carried out on the thickest observed uterine wall – usually the posterior or anterior wall – and is done with near complete reliance on the ultrasound image. Hysteroscopic visualization is poor at this time because the outflow ports of the continuous flow resectoscope are obstructed by tissue in the narrow tubular cavity.

Courtesy Dr. Morris Wortman

The loop is advanced approximately 7-8 mm, and a strip of tissue from the upper reaches of the cavity to the internal os is removed as the entire resectoscope and loop assembly are maneuvered together and withdrawn. A full-size resectoscope loop will resect no more than 4 mm of depth and thus poses no risk of compromising the integrity of the uterus. The thickest wall should be no less than 12-15 mm thick until one masters this technique.

We then actually remove the resectoscope and clean the outflow ports of clots and debris that may have accumulated. When the scope is reinserted, there is typically sufficient room in the uterine cavity for continuous flow and excellent hysteroscopic visualization.

The sequence of resection from this point on will vary. If we’ve begun on the anterior wall, we’ll move to the posterior and then the two lateral walls to further restore the cavity. Areas of endometrial regrowth will typically be identified at this point and resected. The dissection then will extend upward, usually to within 10 mm of the fundus in the midline as measured by ultrasound. Reconfiguring the loop electrode to a 135- to 160-degree angle can be helpful in the delicate dissection that is required at the fundus.

Courtesy Dr. Morris Wortman

Once the upper limit of dissection is established, we sweep laterally using both ultrasound and hysteroscopic visualization. We commonly dissect tissue in and around the cornua, and we often identify intramural fibroids and sometimes gross areas of adenomyosis as we explore the entire uterus. Sonography is critically important as we work in the uterine cornua; our sonographer switches frequently between sagittal and transverse views.

Once all areas of endometrium have been identified and excised, we will deeply coagulate exposed myometrium with a ball-end electrode. Rarely, we will reach our maximum allowable fluid absorption limit prior to completing the case, a scenario seen in less than 1% of our patients.

In more than 330 reoperative hysteroscopic procedures, we’ve had only one uterine perforation that occurred when we switched ultrasound machines. Very likely, we were too aggressive in removing tissue at the fundus. The patient required a diagnostic laparoscopy but sustained no visceral injury.
 

Dr. Wortman is a clinical associate professor of obstetrics and gynecology at the University of Rochester (N.Y.) and the director of the Center for Menstrual Disorders and Reproductive Choice in Rochester. He reported having no relevant financial disclosures.

 

One in seven women suffer with abnormal uterine bleeding during their reproductive years, according to Fraser et al. (Exp Rev Obstet Gynecol. 2009;4:179-89). Heavy menstrual bleeding (menorrhagia) is the most common pattern. Global endometrial ablation has become a very popular surgical technique for women complaining of menorrhagia, disinterested in either medical management or definitive therapy – hysterectomy – or where medical management has failed. With proper patient selection, endometrial ablation yields an 80%-90% success rate in reducing heavy menstrual flow and is associated with a 90% patient satisfaction rate (Cochrane Database Syst Rev. 2009 Oct 7;[4]:CD001501).

Over time however, the rate of failure increases. Failure rates between 16% at 5 years to nearly 26% at 8 years have been reported.

Literature is replete with conditions believed to increase risk of endometrial ablation failure. This list includes untreated uterine cornua, endometrial regrowth, the presence of submucous leiomyomas or polyps, abnormal uterine cavity, enlarged uterine cavity (width and/or length), endometrial ablation in a young patient, parity of five or greater, unsuspected adhesiolysis, postablation tubal sterilization syndrome, history of dysmenorrhea, smoking, obesity, prior cesarean section, previous gynecologic surgery, and procedure length. Interestingly, type of global endometrial ablation procedure or original bleeding pattern does not influence failure rate.

In this edition of the Master Class in Gynecologic Surgery, Dr. Morris Wortman discusses not only the prevention of endometrial ablation failure, but also how to treat the problem via conservative surgical management.

Dr. Wortman is a clinical associate professor of obstetrics and gynecology at the University of Rochester (N.Y.) and is the director at the Center for Menstrual Disorders and Reproductive Choice, also in Rochester. Dr. Wortman has lectured extensively on endometrial ablation and has authored several scientific articles in peer reviewed journals.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported being a subinvestigator on a study sponsored by Channel Medsystems. Email him at obnews@frontlinemedcom.com.

Why failures occur and how to correct them

BY MORRIS WORTMAN, MD

Since the introduction almost 20 years ago of devices for nonresectoscopic – or “global” – endometrial ablation, the procedure has been widely adopted as the treatment of choice for abnormal uterine bleeding that is refractory to medical management.

Between 400,000 and 500,000 endometrial ablations are done in the United States every year in women who have completed childbearing, and it probably won’t be long before the procedure surpasses hysterectomy in prevalence for the management of abnormal bleeding.

Endometrial ablation (EA) dates back to the late 19th century, but global endometrial ablation (GEA) – its latest evolution – has offered improved safety, acceptable outcomes, and technical simplicity. Along with its success, however, has come awareness that a substantial number of women will eventually experience complications: persistent or recurrent vaginal bleeding, cyclic pelvic pain, or the inability to adequately sample the endometrium in cases of postmenopausal bleeding.

In recent years, the literature has begun to address the incidence of these delayed complications and the requirement for subsequent hysterectomy. A 2007 practice bulletin issued by the American College of Obstetricians and Gynecologists stated that hysterectomy rates within 4 years of endometrial ablation are at least 24% (Obstet Gynecol. 2007 May;109[5]:1233-48). And a study published the following year reported that 26% of 3,681 women undergoing EA at Kaiser Permanente facilities in Northern California required hysterectomy within 8 years (Obstet Gynecol. 2008 Dec;112[6]:1214-20).

It appears that the vast majority of what we now refer to as late-onset EA failures – complications attributable to EA that occur beyond a perioperative period of 1 month – will occur within 5 years. Some EA failures have occurred over 5-10 years, however, and in my practice we have seen late-onset complications occurring 17 or more years after the initial ablation.

In our practice, we are successfully managing delayed complications after GEA using ultrasound-guided reoperative hysteroscopy to fully explore the uterine cavity and excise areas of endometrial growth and other disease. In 2014, we published a retrospective review of 50 women whom we treated for delayed complications after a variety of GEA techniques; almost 90% avoided hysterectomy during a mean follow-up period of 18 months (J Minim Invasive Gynecol. 2014 Mar-Apr;21[2]:238-44).

Our experience since then has included reoperative surgery on more than 115 GEA failures. Additionally, we’ve managed 220 patients who have undergone various hysteroscopic and resectoscopic endometrial ablations, some of which date back to the use of the Nd:YAG laser in the late 1980s.

The fact that late-onset EA failures occur does not mean that hysterectomy should routinely be performed as a first-line treatment for intractable uterine bleeding. Overall, there is much more morbidity associated with hysterectomy than with EA.

What failures do suggest is that there are certain risk factors for late-onset EA complications. Our experience in treating women who have experienced late-onset EA failure has provided us with insight into who may be at greatest risk for late-onset EA failure and how patients can best be selected for the procedure. We’ve also learned more about the diagnosis of delayed complications.
 

 

Causes of EA failure

Untreated uterine cornua, and untreated submucous leiomyomas and endometrial polyps, are common causes of EA failure. Among the 50 women included in our retrospective review of ultrasound-guided reoperative hysteroscopy after GEA failure, 44% had intraoperative evidence of untreated cornua and nearly one-fourth had persistent or enlarging submucous leiomyomas.

Contrary to what some believe, most endometrial ablations will not adequately destroy submucous or intramural leiomyomas. Therefore, we recommend that these fibroids be entirely removed immediately before EA.

Moreover, GEA will not always provide adequate thermal destruction to the entire endometrial cavity. The cornua regions are particularly at risk; they are difficult to reach under ideal circumstances, and especially difficult to treat in patients who have a uterine septum or a T-shaped uterus (with the ostia and cornua deeply recessed). We have also seen late-onset EA failures in patients with an extended uterine transverse diameter. The limits of GEA are greatest when a device with a fixed configuration or geometry is used.

A history of abnormal hysteroscopy or other evidence of such anatomic distortions are therefore among the reported risk factors for GEA failure (J Minim Invasive Gynecol. 2015 Mar-Apr;22[3]:323-31). A history of tubal ligation also confers risk; the procedure further increases susceptibility for failure when functioning endometrial tissue remains or regrows at the cornua, because any retrograde menstrual bleeding that occurs will be constrained by the obstructed proximal portion of the fallopian tubes.

Obesity is another risk factor for GEA failure in that the condition increases the risk of endometrial cancer, making the need for reliable biopsies in the case of spotting or other signs or symptoms even more important. On the other hand, obesity may also worsen a patient’s status as a candidate for hysterectomy.

There is much to consider with these patients. For some obese patients, GEA may be less risky than hysterectomy while for others, such as those who also have polycystic ovarian syndrome (in whom the risk for developing endometrial cancer is further increased) the scale may tip in favor of hysterectomy.

Age at the time of the primary GEA may be the single most important risk factor for GEA failure and is an important predictor of success in patient selection. Numerous investigators have shown that women younger than 35 years of age at the time of their EA had a significantly increased risk for hysterectomy, compared with women who were at least 45 years old. The younger the patient, the longer the “bridge” to menopause and the greater the likelihood that bridge will fail.

While age is not necessarily a contraindication, it is worthy of serious consideration. We generally discourage GEA for patients younger than 35. We also advise ensuring that each patient undergoing initial EA is highly self-motivated to have a uterine-sparing procedure; if not, symptoms she may experience later will likely drive her toward hysterectomy anyway.

Additionally, we caution against performing GEA in patients who have chronic pelvic pain; these patients tend to have poorer outcomes with any type of hysteroscopic surgery.
 

Diagnosing failed EA

Delayed complications manifest in several ways: Renewed and increasing vaginal bleeding after a period of improvement, cyclic pelvic pain (unilateral, bilateral, or suprapubic), or both bleeding and pain. Some women – likely an underreported number of them – present with postmenopausal bleeding and proceed to have unsuccessful attempts at an endometrial biopsy due to EA-associated endometrial scarring.

The cyclic pelvic pain associated with endometrial persistence or regrowth tends to worsen over time and is often described as sharp or laborlike. In our experience, a description of “laborlike” pain and a history of EA is almost fully predictive of a finding of endometrial growth. Often a hematometra can be demonstrated on transvaginal ultrasound, but this isn’t always the case.

Pain typically precedes bleeding in patients who demonstrate both. In such cases, blood from functioning endometrial tissue or other sources becomes blocked from exiting the uterine cavity by EA-induced intrauterine scarring and contracture. Painful uterine contractions then aim to expel the pooled blood. In other cases of pain – mainly those without significant vaginal bleeding – the pain is often attributed to cornual and central hematometra.

For the majority of EA failures, the diagnosis lies in the history and current symptoms. Unfortunately, the traditional methods of assessing the endometrial cavity have little merit for women presenting with delayed-onset EA complications. A sonographically assisted pelvic examination can be useful in evaluating complications, but the interpretation of ultrasounds in women with a prior EA can be challenging and is often beyond the training of most radiologists and gynecologists.

It is not uncommon for images to be incorrectly interpreted in the emergency department or physicians’ offices as “normal” and for such readings to set off a chain of CT scans, MRIs, laparoscopies, ovarian cystectomies, and other procedures that miss the root causes of pain.

Unfortunately, there is little in the literature that describes and defines ultrasound findings after EA. We do know that sonography should be timed with episodes of pain, and that the absence of a demonstrable hematometra does not exclude a diagnosis of EA failure.
 

 

Correcting late-onset failures

Our office-based operating room is fitted with side-by-side monitors that enable simultaneous sonographic and hysteroscopic views for correction of GEA failures; the rest of the set-up is similar to that of other operative hysteroscopies. However, we do employ a wide variety of resectoscopes with diameters ranging from 13 to 28 Fr. The smaller-diameter scopes are particularly useful for evaluating postmenopausal bleeding in women with a prior EA.

Courtesy Dr. Morris Wortman

Nearly all patients are seen the day before surgery for placement of a laminaria. The cervix is dilated 3-4 mm with the adjuvant use of IV sedation and sonographic guidance that combines sagittal and transverse scanning to ensure placement of the laminaria in the midline. This preparatory work provides an easily identifiable channel – the next day – that extends past the internal os.

For those inexperienced with ultrasound-guided surgery, the initial resection is often the most challenging. The initial tissue removal is carried out on the thickest observed uterine wall – usually the posterior or anterior wall – and is done with near complete reliance on the ultrasound image. Hysteroscopic visualization is poor at this time because the outflow ports of the continuous flow resectoscope are obstructed by tissue in the narrow tubular cavity.

Courtesy Dr. Morris Wortman

The loop is advanced approximately 7-8 mm, and a strip of tissue from the upper reaches of the cavity to the internal os is removed as the entire resectoscope and loop assembly are maneuvered together and withdrawn. A full-size resectoscope loop will resect no more than 4 mm of depth and thus poses no risk of compromising the integrity of the uterus. The thickest wall should be no less than 12-15 mm thick until one masters this technique.

We then actually remove the resectoscope and clean the outflow ports of clots and debris that may have accumulated. When the scope is reinserted, there is typically sufficient room in the uterine cavity for continuous flow and excellent hysteroscopic visualization.

The sequence of resection from this point on will vary. If we’ve begun on the anterior wall, we’ll move to the posterior and then the two lateral walls to further restore the cavity. Areas of endometrial regrowth will typically be identified at this point and resected. The dissection then will extend upward, usually to within 10 mm of the fundus in the midline as measured by ultrasound. Reconfiguring the loop electrode to a 135- to 160-degree angle can be helpful in the delicate dissection that is required at the fundus.

Courtesy Dr. Morris Wortman

Once the upper limit of dissection is established, we sweep laterally using both ultrasound and hysteroscopic visualization. We commonly dissect tissue in and around the cornua, and we often identify intramural fibroids and sometimes gross areas of adenomyosis as we explore the entire uterus. Sonography is critically important as we work in the uterine cornua; our sonographer switches frequently between sagittal and transverse views.

Once all areas of endometrium have been identified and excised, we will deeply coagulate exposed myometrium with a ball-end electrode. Rarely, we will reach our maximum allowable fluid absorption limit prior to completing the case, a scenario seen in less than 1% of our patients.

In more than 330 reoperative hysteroscopic procedures, we’ve had only one uterine perforation that occurred when we switched ultrasound machines. Very likely, we were too aggressive in removing tissue at the fundus. The patient required a diagnostic laparoscopy but sustained no visceral injury.
 

Dr. Wortman is a clinical associate professor of obstetrics and gynecology at the University of Rochester (N.Y.) and the director of the Center for Menstrual Disorders and Reproductive Choice in Rochester. He reported having no relevant financial disclosures.

 

One in seven women suffer with abnormal uterine bleeding during their reproductive years, according to Fraser et al. (Exp Rev Obstet Gynecol. 2009;4:179-89). Heavy menstrual bleeding (menorrhagia) is the most common pattern. Global endometrial ablation has become a very popular surgical technique for women complaining of menorrhagia, disinterested in either medical management or definitive therapy – hysterectomy – or where medical management has failed. With proper patient selection, endometrial ablation yields an 80%-90% success rate in reducing heavy menstrual flow and is associated with a 90% patient satisfaction rate (Cochrane Database Syst Rev. 2009 Oct 7;[4]:CD001501).

Over time however, the rate of failure increases. Failure rates between 16% at 5 years to nearly 26% at 8 years have been reported.

Literature is replete with conditions believed to increase risk of endometrial ablation failure. This list includes untreated uterine cornua, endometrial regrowth, the presence of submucous leiomyomas or polyps, abnormal uterine cavity, enlarged uterine cavity (width and/or length), endometrial ablation in a young patient, parity of five or greater, unsuspected adhesiolysis, postablation tubal sterilization syndrome, history of dysmenorrhea, smoking, obesity, prior cesarean section, previous gynecologic surgery, and procedure length. Interestingly, type of global endometrial ablation procedure or original bleeding pattern does not influence failure rate.

In this edition of the Master Class in Gynecologic Surgery, Dr. Morris Wortman discusses not only the prevention of endometrial ablation failure, but also how to treat the problem via conservative surgical management.

Dr. Wortman is a clinical associate professor of obstetrics and gynecology at the University of Rochester (N.Y.) and is the director at the Center for Menstrual Disorders and Reproductive Choice, also in Rochester. Dr. Wortman has lectured extensively on endometrial ablation and has authored several scientific articles in peer reviewed journals.
 

Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported being a subinvestigator on a study sponsored by Channel Medsystems. Email him at obnews@frontlinemedcom.com.

Why failures occur and how to correct them

BY MORRIS WORTMAN, MD

Since the introduction almost 20 years ago of devices for nonresectoscopic – or “global” – endometrial ablation, the procedure has been widely adopted as the treatment of choice for abnormal uterine bleeding that is refractory to medical management.

Between 400,000 and 500,000 endometrial ablations are done in the United States every year in women who have completed childbearing, and it probably won’t be long before the procedure surpasses hysterectomy in prevalence for the management of abnormal bleeding.

Endometrial ablation (EA) dates back to the late 19th century, but global endometrial ablation (GEA) – its latest evolution – has offered improved safety, acceptable outcomes, and technical simplicity. Along with its success, however, has come awareness that a substantial number of women will eventually experience complications: persistent or recurrent vaginal bleeding, cyclic pelvic pain, or the inability to adequately sample the endometrium in cases of postmenopausal bleeding.

In recent years, the literature has begun to address the incidence of these delayed complications and the requirement for subsequent hysterectomy. A 2007 practice bulletin issued by the American College of Obstetricians and Gynecologists stated that hysterectomy rates within 4 years of endometrial ablation are at least 24% (Obstet Gynecol. 2007 May;109[5]:1233-48). And a study published the following year reported that 26% of 3,681 women undergoing EA at Kaiser Permanente facilities in Northern California required hysterectomy within 8 years (Obstet Gynecol. 2008 Dec;112[6]:1214-20).

It appears that the vast majority of what we now refer to as late-onset EA failures – complications attributable to EA that occur beyond a perioperative period of 1 month – will occur within 5 years. Some EA failures have occurred over 5-10 years, however, and in my practice we have seen late-onset complications occurring 17 or more years after the initial ablation.

In our practice, we are successfully managing delayed complications after GEA using ultrasound-guided reoperative hysteroscopy to fully explore the uterine cavity and excise areas of endometrial growth and other disease. In 2014, we published a retrospective review of 50 women whom we treated for delayed complications after a variety of GEA techniques; almost 90% avoided hysterectomy during a mean follow-up period of 18 months (J Minim Invasive Gynecol. 2014 Mar-Apr;21[2]:238-44).

Our experience since then has included reoperative surgery on more than 115 GEA failures. Additionally, we’ve managed 220 patients who have undergone various hysteroscopic and resectoscopic endometrial ablations, some of which date back to the use of the Nd:YAG laser in the late 1980s.

The fact that late-onset EA failures occur does not mean that hysterectomy should routinely be performed as a first-line treatment for intractable uterine bleeding. Overall, there is much more morbidity associated with hysterectomy than with EA.

What failures do suggest is that there are certain risk factors for late-onset EA complications. Our experience in treating women who have experienced late-onset EA failure has provided us with insight into who may be at greatest risk for late-onset EA failure and how patients can best be selected for the procedure. We’ve also learned more about the diagnosis of delayed complications.
 

 

Causes of EA failure

Untreated uterine cornua, and untreated submucous leiomyomas and endometrial polyps, are common causes of EA failure. Among the 50 women included in our retrospective review of ultrasound-guided reoperative hysteroscopy after GEA failure, 44% had intraoperative evidence of untreated cornua and nearly one-fourth had persistent or enlarging submucous leiomyomas.

Contrary to what some believe, most endometrial ablations will not adequately destroy submucous or intramural leiomyomas. Therefore, we recommend that these fibroids be entirely removed immediately before EA.

Moreover, GEA will not always provide adequate thermal destruction to the entire endometrial cavity. The cornua regions are particularly at risk; they are difficult to reach under ideal circumstances, and especially difficult to treat in patients who have a uterine septum or a T-shaped uterus (with the ostia and cornua deeply recessed). We have also seen late-onset EA failures in patients with an extended uterine transverse diameter. The limits of GEA are greatest when a device with a fixed configuration or geometry is used.

A history of abnormal hysteroscopy or other evidence of such anatomic distortions are therefore among the reported risk factors for GEA failure (J Minim Invasive Gynecol. 2015 Mar-Apr;22[3]:323-31). A history of tubal ligation also confers risk; the procedure further increases susceptibility for failure when functioning endometrial tissue remains or regrows at the cornua, because any retrograde menstrual bleeding that occurs will be constrained by the obstructed proximal portion of the fallopian tubes.

Obesity is another risk factor for GEA failure in that the condition increases the risk of endometrial cancer, making the need for reliable biopsies in the case of spotting or other signs or symptoms even more important. On the other hand, obesity may also worsen a patient’s status as a candidate for hysterectomy.

There is much to consider with these patients. For some obese patients, GEA may be less risky than hysterectomy while for others, such as those who also have polycystic ovarian syndrome (in whom the risk for developing endometrial cancer is further increased) the scale may tip in favor of hysterectomy.

Age at the time of the primary GEA may be the single most important risk factor for GEA failure and is an important predictor of success in patient selection. Numerous investigators have shown that women younger than 35 years of age at the time of their EA had a significantly increased risk for hysterectomy, compared with women who were at least 45 years old. The younger the patient, the longer the “bridge” to menopause and the greater the likelihood that bridge will fail.

While age is not necessarily a contraindication, it is worthy of serious consideration. We generally discourage GEA for patients younger than 35. We also advise ensuring that each patient undergoing initial EA is highly self-motivated to have a uterine-sparing procedure; if not, symptoms she may experience later will likely drive her toward hysterectomy anyway.

Additionally, we caution against performing GEA in patients who have chronic pelvic pain; these patients tend to have poorer outcomes with any type of hysteroscopic surgery.
 

Diagnosing failed EA

Delayed complications manifest in several ways: Renewed and increasing vaginal bleeding after a period of improvement, cyclic pelvic pain (unilateral, bilateral, or suprapubic), or both bleeding and pain. Some women – likely an underreported number of them – present with postmenopausal bleeding and proceed to have unsuccessful attempts at an endometrial biopsy due to EA-associated endometrial scarring.

The cyclic pelvic pain associated with endometrial persistence or regrowth tends to worsen over time and is often described as sharp or laborlike. In our experience, a description of “laborlike” pain and a history of EA is almost fully predictive of a finding of endometrial growth. Often a hematometra can be demonstrated on transvaginal ultrasound, but this isn’t always the case.

Pain typically precedes bleeding in patients who demonstrate both. In such cases, blood from functioning endometrial tissue or other sources becomes blocked from exiting the uterine cavity by EA-induced intrauterine scarring and contracture. Painful uterine contractions then aim to expel the pooled blood. In other cases of pain – mainly those without significant vaginal bleeding – the pain is often attributed to cornual and central hematometra.

For the majority of EA failures, the diagnosis lies in the history and current symptoms. Unfortunately, the traditional methods of assessing the endometrial cavity have little merit for women presenting with delayed-onset EA complications. A sonographically assisted pelvic examination can be useful in evaluating complications, but the interpretation of ultrasounds in women with a prior EA can be challenging and is often beyond the training of most radiologists and gynecologists.

It is not uncommon for images to be incorrectly interpreted in the emergency department or physicians’ offices as “normal” and for such readings to set off a chain of CT scans, MRIs, laparoscopies, ovarian cystectomies, and other procedures that miss the root causes of pain.

Unfortunately, there is little in the literature that describes and defines ultrasound findings after EA. We do know that sonography should be timed with episodes of pain, and that the absence of a demonstrable hematometra does not exclude a diagnosis of EA failure.
 

 

Correcting late-onset failures

Our office-based operating room is fitted with side-by-side monitors that enable simultaneous sonographic and hysteroscopic views for correction of GEA failures; the rest of the set-up is similar to that of other operative hysteroscopies. However, we do employ a wide variety of resectoscopes with diameters ranging from 13 to 28 Fr. The smaller-diameter scopes are particularly useful for evaluating postmenopausal bleeding in women with a prior EA.

Courtesy Dr. Morris Wortman

Nearly all patients are seen the day before surgery for placement of a laminaria. The cervix is dilated 3-4 mm with the adjuvant use of IV sedation and sonographic guidance that combines sagittal and transverse scanning to ensure placement of the laminaria in the midline. This preparatory work provides an easily identifiable channel – the next day – that extends past the internal os.

For those inexperienced with ultrasound-guided surgery, the initial resection is often the most challenging. The initial tissue removal is carried out on the thickest observed uterine wall – usually the posterior or anterior wall – and is done with near complete reliance on the ultrasound image. Hysteroscopic visualization is poor at this time because the outflow ports of the continuous flow resectoscope are obstructed by tissue in the narrow tubular cavity.

Courtesy Dr. Morris Wortman

The loop is advanced approximately 7-8 mm, and a strip of tissue from the upper reaches of the cavity to the internal os is removed as the entire resectoscope and loop assembly are maneuvered together and withdrawn. A full-size resectoscope loop will resect no more than 4 mm of depth and thus poses no risk of compromising the integrity of the uterus. The thickest wall should be no less than 12-15 mm thick until one masters this technique.

We then actually remove the resectoscope and clean the outflow ports of clots and debris that may have accumulated. When the scope is reinserted, there is typically sufficient room in the uterine cavity for continuous flow and excellent hysteroscopic visualization.

The sequence of resection from this point on will vary. If we’ve begun on the anterior wall, we’ll move to the posterior and then the two lateral walls to further restore the cavity. Areas of endometrial regrowth will typically be identified at this point and resected. The dissection then will extend upward, usually to within 10 mm of the fundus in the midline as measured by ultrasound. Reconfiguring the loop electrode to a 135- to 160-degree angle can be helpful in the delicate dissection that is required at the fundus.

Courtesy Dr. Morris Wortman

Once the upper limit of dissection is established, we sweep laterally using both ultrasound and hysteroscopic visualization. We commonly dissect tissue in and around the cornua, and we often identify intramural fibroids and sometimes gross areas of adenomyosis as we explore the entire uterus. Sonography is critically important as we work in the uterine cornua; our sonographer switches frequently between sagittal and transverse views.

Once all areas of endometrium have been identified and excised, we will deeply coagulate exposed myometrium with a ball-end electrode. Rarely, we will reach our maximum allowable fluid absorption limit prior to completing the case, a scenario seen in less than 1% of our patients.

In more than 330 reoperative hysteroscopic procedures, we’ve had only one uterine perforation that occurred when we switched ultrasound machines. Very likely, we were too aggressive in removing tissue at the fundus. The patient required a diagnostic laparoscopy but sustained no visceral injury.
 

Dr. Wortman is a clinical associate professor of obstetrics and gynecology at the University of Rochester (N.Y.) and the director of the Center for Menstrual Disorders and Reproductive Choice in Rochester. He reported having no relevant financial disclosures.

BY E. ALBERT REECE, MD, PhD, MBA

Much attention has been given in the media to the incidence of prediabetes in the general population. The Centers for Disease Control and Prevention estimates that approximately 86 million adults have prediabetes, and that the incidence of this condition is similar across racial and ethnic groups. Indeed, the seriousness of this public health concern prompted the Centers for Medicare & Medicaid Services to expand Medicare coverage for interventions for people with prediabetes, a move that was finalized in November 2016.

Despite a widespread focus on the need to prevent prediabetes from becoming type 2 diabetes, women diagnosed with gestational diabetes mellitus (GDM), which accounts for about 9% of women in the United States, may not be receiving critical advice and care.

In September 2016, researchers at the University of Illinois at Chicago published a study indicating that women with a history of GDM did not receive adequate diabetes screening postpartum (Prev Chronic Dis. 2016;13:160106. doi: http://dx.doi.org/10.5888/pcd13.160106).

The investigators analyzed data collected via the National Health and Nutrition Examination Survey from 2007-2012, and identified 284 women with a history of GDM. Only 67% of these women received diabetes screening, and approximately one-third of women included in the study had undiagnosed prediabetes and diabetes. The authors concluded that prediabetes in women who have had GDM may be underdiagnosed. They argued that women with GDM should be encouraged to have additional health visits and screenings to prevent the development of prediabetes or diabetes. Considering the fact that a number of studies have shown that GDM predisposes a woman to developing type 2 diabetes, the University of Illinois findings are alarming.

As ob.gyns., we have increasingly become a woman’s only health care practitioner. Although individuals may skip annual exams with a primary care physician, during which blood work is typically drawn, many women will see their ob.gyn. for regular check-ups. Therefore, we have a unique role to play in our patients’ lifelong health. This is especially important during pregnancy, when it may be easy to focus only on the mother’s health as it pertains to the health of the baby, rather than her health in pregnancy as it may affect her long-term well-being.

We have invited Robert Ratner, MD, the chief scientific and medical officer at the American Diabetes Association, to discuss the need to carefully follow up with patients who have had GDM and to educate them about their risk for developing type 2 diabetes later in life.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

 

Why postpartum GDM follow-up is so important

BY ROBERT E. RATNER, MD

Much of the attention paid to diagnosing gestational diabetes has focused on the fetus and on babies being born very large. However, it is important to appreciate that the original definitions of the condition were based entirely on the long-term outcomes of the mother.

John O’Sullivan, MD, and statistician Claire Mahan published diagnostic criteria in 1964 after performing 3-hour oral glucose tolerance tests (OGTTs) in more than 500 unselected women during their pregnancies, and then following these women and babies out as far as 23 years. Retrospectively, Dr. O’Sullivan and Ms. Mahan defined gestational diabetes mellitus (GDM) as glucose values exceeding two standard deviations above the mean on two out of four OGTT values.

They came to their conclusions after tracking the later development of diabetes outside of pregnancy. More than 20 years later, 70% of women with the higher OGTT values had developed type 2 diabetes, compared with approximately 10% of women who did not have higher values during pregnancy. The O’Sullivan criteria were established, essentially, based on their association with the development of diabetes after pregnancy. In addition to being a significant predictor of subsequent diabetes, a history of GDM also conferred a three- to fourfold increase in maternal mortality.

Fifty-some years later, these findings have been affirmed through additional research and are the crux of what drives the current recommendations for postpartum follow-up of women with a history of GDM.

Long-term maternal risks

Postpartum, the current recommendation from both the American Diabetes Association and the American College of Obstetricians and Gynecologists is that women with GDM be tested at 6-12 weeks after delivery to ensure that the diabetes has resolved.

This recommendation for initial postpartum testing carries with it a stipulation that’s different from subsequent postpartum testing. It says that postpartum testing at 6-12 weeks should be performed with either a fasting glucose test or a 2-hour OGTT. Since hemoglobin A_1c may still be impacted by the rapid red blood cell turnover in pregnancy or blood loss at delivery, A_1c testing lacks sensitivity for identifying diabetes during this window of time.

Initial postpartum testing also serves as a way to identify whether the diabetes during pregnancy was preexisting or purely secondary to the hormonal changes associated with the pregnancy.

If this first postpartum test shows diabetes, the patient most likely had preexisting diabetes, and therapy must be initiated immediately. In the case of a normal result, the patient remains at higher risk for the development of type 2 diabetes essentially for the rest of her life and should be tested at least every 3 years for the occurrence of the disease.

Much of the increased risk for different ethnic groups occurs within 5 years of the index pregnancy. This was shown in a systematic review led by Catherine Kim, MD; the review examined more than two dozen studies with follow-up of up to 28 years postpartum. The cumulative incidence of type 2 diabetes increased markedly in the first 5 years and then appeared to plateau after 10 years (Diabetes Care. 2002 Oct;25[10]:1862-8).

The best data on late-occurring diabetes following GDM comes from the multicenter National Institutes of Health–sponsored Diabetes Prevention Program (DPP) trial, which randomized more than 3,000 individuals with baseline impaired glucose tolerance – or prediabetes – to one of two interventions: metformin therapy or intensive lifestyle intervention, or to placebo.

Within this population, there were more than 1,700 women who had a previous live birth. Of these women, 350 reported a history of GDM at a mean of 12 years since the delivery of their first GDM pregnancy. The DPP gave us the opportunity, therefore, to look at a large group of women about 12 years away from their GDM pregnancy who had abnormal glucose levels but had not reached the level of type 2 diabetes, and compare them with women with similarly impaired glucose tolerance who did not have a history of GDM.

There were interesting similarities and differences. Women with a GDM history were on average 8 years younger than women without a GDM history, but they had comparable BMIs. In addition, within the placebo arm, we could observe the natural history of glucose intolerance in women with and without a history of GDM. Despite both groups entering the study with equivalent degrees of impaired glucose tolerance and similar BMI, women with a history of GDM had a 71% higher risk of developing diabetes during the 3-year intervention period than that of parous women without a history of GDM (J Clin Endocrinol Metab. 2008 Dec;93[12]:4774-9).

Clearly, there was something about the history of GDM that puts these women at greater risk for diabetes than women who had the same impaired glucose tolerance, but no GDM. The study demonstrated that GDM is an exceptionally strong predictor of the development of type 2 diabetes, even for those who manage to escape diabetes for the first 10 years.

 

Postpartum prevention

The DPP demonstrated, moreover, that intensive lifestyle therapy and metformin not only were both effective, but that they were equally effective, in delaying or preventing diabetes in women with impaired glucose tolerance and a history of GDM. Both reduced the risk by about 50% at 3 years. This was striking because in parous women without GDM, the reductions were 49% and 14%, respectively. Metformin thus appeared to be more effective in women with a history of GDM.

The effects of the interventions persisted over a 10-year follow up of the DPP population. In women with a history of GDM, the intensive lifestyle intervention and metformin reduced progression to diabetes by 35% and 40%, respectively, over 10 years (J Clin Endocrinol Metab. 2015 Apr;100[4]:1646-53).

Pregnancy presents a stress test for beta cell function, and gestational diabetes clearly is a harbinger of further deterioration in beta-cell function and metabolic abnormalities in the mother. Because of these risks and because early intervention makes a difference, surveillance is critically important. Most women see their ob.gyn. as their primary care physician in the 10 years following a pregnancy – the time when more than 50% of all cases of subsequent diabetes will occur – and many continue to see their ob.gyns. in the longer term, as their risk continues to linger.

Immediately after a pregnancy with GDM, ob.gyns. can counsel women not only about their risks of developing type 2 diabetes and the importance of screening, but also about the beneficial impact of lifestyle modification, caloric restriction and weight loss if necessary, and increased exercise. Mothers should also know that GDM is a family affair, and that lifestyle changes that are beneficial for the mother will be equally beneficial for the baby.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study taught us that there are continuous linear relationships between maternal glucose and adverse fetal outcomes like birth weight and percent body fat greater than the 90th percentile. Longitudinal studies of the Pima Indians showed us that offspring of women who had diabetes during pregnancy were more likely to be obese and more likely to develop diabetes than offspring of women who did not have diabetes during pregnancy. Even when GDM has been well treated and controlled, we should have heightened awareness to the potential risks in the fetus and the growing child and adolescent.

Patients who are found to have subsequent type 2 diabetes should know that aggressive therapy early on in the natural history of the disease reduces the risk of microvascular and macrovascular complications. And as the DPP has demonstrated, lifestyle interventions and metformin may also keep women who are found to have prediabetes outside of pregnancy from progressing on to diabetes.
 

Dr. Ratner is the chief scientific and medical officer for the American Diabetes Association. He reported having no financial disclosures relevant to this Master Class.

BY E. ALBERT REECE, MD, PhD, MBA

Much attention has been given in the media to the incidence of prediabetes in the general population. The Centers for Disease Control and Prevention estimates that approximately 86 million adults have prediabetes, and that the incidence of this condition is similar across racial and ethnic groups. Indeed, the seriousness of this public health concern prompted the Centers for Medicare & Medicaid Services to expand Medicare coverage for interventions for people with prediabetes, a move that was finalized in November 2016.

Despite a widespread focus on the need to prevent prediabetes from becoming type 2 diabetes, women diagnosed with gestational diabetes mellitus (GDM), which accounts for about 9% of women in the United States, may not be receiving critical advice and care.

In September 2016, researchers at the University of Illinois at Chicago published a study indicating that women with a history of GDM did not receive adequate diabetes screening postpartum (Prev Chronic Dis. 2016;13:160106. doi: http://dx.doi.org/10.5888/pcd13.160106).

The investigators analyzed data collected via the National Health and Nutrition Examination Survey from 2007-2012, and identified 284 women with a history of GDM. Only 67% of these women received diabetes screening, and approximately one-third of women included in the study had undiagnosed prediabetes and diabetes. The authors concluded that prediabetes in women who have had GDM may be underdiagnosed. They argued that women with GDM should be encouraged to have additional health visits and screenings to prevent the development of prediabetes or diabetes. Considering the fact that a number of studies have shown that GDM predisposes a woman to developing type 2 diabetes, the University of Illinois findings are alarming.

As ob.gyns., we have increasingly become a woman’s only health care practitioner. Although individuals may skip annual exams with a primary care physician, during which blood work is typically drawn, many women will see their ob.gyn. for regular check-ups. Therefore, we have a unique role to play in our patients’ lifelong health. This is especially important during pregnancy, when it may be easy to focus only on the mother’s health as it pertains to the health of the baby, rather than her health in pregnancy as it may affect her long-term well-being.

We have invited Robert Ratner, MD, the chief scientific and medical officer at the American Diabetes Association, to discuss the need to carefully follow up with patients who have had GDM and to educate them about their risk for developing type 2 diabetes later in life.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

 

Why postpartum GDM follow-up is so important

BY ROBERT E. RATNER, MD

Much of the attention paid to diagnosing gestational diabetes has focused on the fetus and on babies being born very large. However, it is important to appreciate that the original definitions of the condition were based entirely on the long-term outcomes of the mother.

John O’Sullivan, MD, and statistician Claire Mahan published diagnostic criteria in 1964 after performing 3-hour oral glucose tolerance tests (OGTTs) in more than 500 unselected women during their pregnancies, and then following these women and babies out as far as 23 years. Retrospectively, Dr. O’Sullivan and Ms. Mahan defined gestational diabetes mellitus (GDM) as glucose values exceeding two standard deviations above the mean on two out of four OGTT values.

They came to their conclusions after tracking the later development of diabetes outside of pregnancy. More than 20 years later, 70% of women with the higher OGTT values had developed type 2 diabetes, compared with approximately 10% of women who did not have higher values during pregnancy. The O’Sullivan criteria were established, essentially, based on their association with the development of diabetes after pregnancy. In addition to being a significant predictor of subsequent diabetes, a history of GDM also conferred a three- to fourfold increase in maternal mortality.

Fifty-some years later, these findings have been affirmed through additional research and are the crux of what drives the current recommendations for postpartum follow-up of women with a history of GDM.

Long-term maternal risks

Postpartum, the current recommendation from both the American Diabetes Association and the American College of Obstetricians and Gynecologists is that women with GDM be tested at 6-12 weeks after delivery to ensure that the diabetes has resolved.

This recommendation for initial postpartum testing carries with it a stipulation that’s different from subsequent postpartum testing. It says that postpartum testing at 6-12 weeks should be performed with either a fasting glucose test or a 2-hour OGTT. Since hemoglobin A_1c may still be impacted by the rapid red blood cell turnover in pregnancy or blood loss at delivery, A_1c testing lacks sensitivity for identifying diabetes during this window of time.

Initial postpartum testing also serves as a way to identify whether the diabetes during pregnancy was preexisting or purely secondary to the hormonal changes associated with the pregnancy.

If this first postpartum test shows diabetes, the patient most likely had preexisting diabetes, and therapy must be initiated immediately. In the case of a normal result, the patient remains at higher risk for the development of type 2 diabetes essentially for the rest of her life and should be tested at least every 3 years for the occurrence of the disease.

Much of the increased risk for different ethnic groups occurs within 5 years of the index pregnancy. This was shown in a systematic review led by Catherine Kim, MD; the review examined more than two dozen studies with follow-up of up to 28 years postpartum. The cumulative incidence of type 2 diabetes increased markedly in the first 5 years and then appeared to plateau after 10 years (Diabetes Care. 2002 Oct;25[10]:1862-8).

The best data on late-occurring diabetes following GDM comes from the multicenter National Institutes of Health–sponsored Diabetes Prevention Program (DPP) trial, which randomized more than 3,000 individuals with baseline impaired glucose tolerance – or prediabetes – to one of two interventions: metformin therapy or intensive lifestyle intervention, or to placebo.

Within this population, there were more than 1,700 women who had a previous live birth. Of these women, 350 reported a history of GDM at a mean of 12 years since the delivery of their first GDM pregnancy. The DPP gave us the opportunity, therefore, to look at a large group of women about 12 years away from their GDM pregnancy who had abnormal glucose levels but had not reached the level of type 2 diabetes, and compare them with women with similarly impaired glucose tolerance who did not have a history of GDM.

There were interesting similarities and differences. Women with a GDM history were on average 8 years younger than women without a GDM history, but they had comparable BMIs. In addition, within the placebo arm, we could observe the natural history of glucose intolerance in women with and without a history of GDM. Despite both groups entering the study with equivalent degrees of impaired glucose tolerance and similar BMI, women with a history of GDM had a 71% higher risk of developing diabetes during the 3-year intervention period than that of parous women without a history of GDM (J Clin Endocrinol Metab. 2008 Dec;93[12]:4774-9).

Clearly, there was something about the history of GDM that puts these women at greater risk for diabetes than women who had the same impaired glucose tolerance, but no GDM. The study demonstrated that GDM is an exceptionally strong predictor of the development of type 2 diabetes, even for those who manage to escape diabetes for the first 10 years.

 

Postpartum prevention

The DPP demonstrated, moreover, that intensive lifestyle therapy and metformin not only were both effective, but that they were equally effective, in delaying or preventing diabetes in women with impaired glucose tolerance and a history of GDM. Both reduced the risk by about 50% at 3 years. This was striking because in parous women without GDM, the reductions were 49% and 14%, respectively. Metformin thus appeared to be more effective in women with a history of GDM.

The effects of the interventions persisted over a 10-year follow up of the DPP population. In women with a history of GDM, the intensive lifestyle intervention and metformin reduced progression to diabetes by 35% and 40%, respectively, over 10 years (J Clin Endocrinol Metab. 2015 Apr;100[4]:1646-53).

Pregnancy presents a stress test for beta cell function, and gestational diabetes clearly is a harbinger of further deterioration in beta-cell function and metabolic abnormalities in the mother. Because of these risks and because early intervention makes a difference, surveillance is critically important. Most women see their ob.gyn. as their primary care physician in the 10 years following a pregnancy – the time when more than 50% of all cases of subsequent diabetes will occur – and many continue to see their ob.gyns. in the longer term, as their risk continues to linger.

Immediately after a pregnancy with GDM, ob.gyns. can counsel women not only about their risks of developing type 2 diabetes and the importance of screening, but also about the beneficial impact of lifestyle modification, caloric restriction and weight loss if necessary, and increased exercise. Mothers should also know that GDM is a family affair, and that lifestyle changes that are beneficial for the mother will be equally beneficial for the baby.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study taught us that there are continuous linear relationships between maternal glucose and adverse fetal outcomes like birth weight and percent body fat greater than the 90th percentile. Longitudinal studies of the Pima Indians showed us that offspring of women who had diabetes during pregnancy were more likely to be obese and more likely to develop diabetes than offspring of women who did not have diabetes during pregnancy. Even when GDM has been well treated and controlled, we should have heightened awareness to the potential risks in the fetus and the growing child and adolescent.

Patients who are found to have subsequent type 2 diabetes should know that aggressive therapy early on in the natural history of the disease reduces the risk of microvascular and macrovascular complications. And as the DPP has demonstrated, lifestyle interventions and metformin may also keep women who are found to have prediabetes outside of pregnancy from progressing on to diabetes.
 

Dr. Ratner is the chief scientific and medical officer for the American Diabetes Association. He reported having no financial disclosures relevant to this Master Class.

BY E. ALBERT REECE, MD, PhD, MBA

Much attention has been given in the media to the incidence of prediabetes in the general population. The Centers for Disease Control and Prevention estimates that approximately 86 million adults have prediabetes, and that the incidence of this condition is similar across racial and ethnic groups. Indeed, the seriousness of this public health concern prompted the Centers for Medicare & Medicaid Services to expand Medicare coverage for interventions for people with prediabetes, a move that was finalized in November 2016.

Despite a widespread focus on the need to prevent prediabetes from becoming type 2 diabetes, women diagnosed with gestational diabetes mellitus (GDM), which accounts for about 9% of women in the United States, may not be receiving critical advice and care.

In September 2016, researchers at the University of Illinois at Chicago published a study indicating that women with a history of GDM did not receive adequate diabetes screening postpartum (Prev Chronic Dis. 2016;13:160106. doi: http://dx.doi.org/10.5888/pcd13.160106).

The investigators analyzed data collected via the National Health and Nutrition Examination Survey from 2007-2012, and identified 284 women with a history of GDM. Only 67% of these women received diabetes screening, and approximately one-third of women included in the study had undiagnosed prediabetes and diabetes. The authors concluded that prediabetes in women who have had GDM may be underdiagnosed. They argued that women with GDM should be encouraged to have additional health visits and screenings to prevent the development of prediabetes or diabetes. Considering the fact that a number of studies have shown that GDM predisposes a woman to developing type 2 diabetes, the University of Illinois findings are alarming.

As ob.gyns., we have increasingly become a woman’s only health care practitioner. Although individuals may skip annual exams with a primary care physician, during which blood work is typically drawn, many women will see their ob.gyn. for regular check-ups. Therefore, we have a unique role to play in our patients’ lifelong health. This is especially important during pregnancy, when it may be easy to focus only on the mother’s health as it pertains to the health of the baby, rather than her health in pregnancy as it may affect her long-term well-being.

We have invited Robert Ratner, MD, the chief scientific and medical officer at the American Diabetes Association, to discuss the need to carefully follow up with patients who have had GDM and to educate them about their risk for developing type 2 diabetes later in life.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

 

Why postpartum GDM follow-up is so important

BY ROBERT E. RATNER, MD

Much of the attention paid to diagnosing gestational diabetes has focused on the fetus and on babies being born very large. However, it is important to appreciate that the original definitions of the condition were based entirely on the long-term outcomes of the mother.

John O’Sullivan, MD, and statistician Claire Mahan published diagnostic criteria in 1964 after performing 3-hour oral glucose tolerance tests (OGTTs) in more than 500 unselected women during their pregnancies, and then following these women and babies out as far as 23 years. Retrospectively, Dr. O’Sullivan and Ms. Mahan defined gestational diabetes mellitus (GDM) as glucose values exceeding two standard deviations above the mean on two out of four OGTT values.

They came to their conclusions after tracking the later development of diabetes outside of pregnancy. More than 20 years later, 70% of women with the higher OGTT values had developed type 2 diabetes, compared with approximately 10% of women who did not have higher values during pregnancy. The O’Sullivan criteria were established, essentially, based on their association with the development of diabetes after pregnancy. In addition to being a significant predictor of subsequent diabetes, a history of GDM also conferred a three- to fourfold increase in maternal mortality.

Fifty-some years later, these findings have been affirmed through additional research and are the crux of what drives the current recommendations for postpartum follow-up of women with a history of GDM.

Long-term maternal risks

Postpartum, the current recommendation from both the American Diabetes Association and the American College of Obstetricians and Gynecologists is that women with GDM be tested at 6-12 weeks after delivery to ensure that the diabetes has resolved.

This recommendation for initial postpartum testing carries with it a stipulation that’s different from subsequent postpartum testing. It says that postpartum testing at 6-12 weeks should be performed with either a fasting glucose test or a 2-hour OGTT. Since hemoglobin A_1c may still be impacted by the rapid red blood cell turnover in pregnancy or blood loss at delivery, A_1c testing lacks sensitivity for identifying diabetes during this window of time.

Initial postpartum testing also serves as a way to identify whether the diabetes during pregnancy was preexisting or purely secondary to the hormonal changes associated with the pregnancy.

If this first postpartum test shows diabetes, the patient most likely had preexisting diabetes, and therapy must be initiated immediately. In the case of a normal result, the patient remains at higher risk for the development of type 2 diabetes essentially for the rest of her life and should be tested at least every 3 years for the occurrence of the disease.

Much of the increased risk for different ethnic groups occurs within 5 years of the index pregnancy. This was shown in a systematic review led by Catherine Kim, MD; the review examined more than two dozen studies with follow-up of up to 28 years postpartum. The cumulative incidence of type 2 diabetes increased markedly in the first 5 years and then appeared to plateau after 10 years (Diabetes Care. 2002 Oct;25[10]:1862-8).

The best data on late-occurring diabetes following GDM comes from the multicenter National Institutes of Health–sponsored Diabetes Prevention Program (DPP) trial, which randomized more than 3,000 individuals with baseline impaired glucose tolerance – or prediabetes – to one of two interventions: metformin therapy or intensive lifestyle intervention, or to placebo.

Within this population, there were more than 1,700 women who had a previous live birth. Of these women, 350 reported a history of GDM at a mean of 12 years since the delivery of their first GDM pregnancy. The DPP gave us the opportunity, therefore, to look at a large group of women about 12 years away from their GDM pregnancy who had abnormal glucose levels but had not reached the level of type 2 diabetes, and compare them with women with similarly impaired glucose tolerance who did not have a history of GDM.

There were interesting similarities and differences. Women with a GDM history were on average 8 years younger than women without a GDM history, but they had comparable BMIs. In addition, within the placebo arm, we could observe the natural history of glucose intolerance in women with and without a history of GDM. Despite both groups entering the study with equivalent degrees of impaired glucose tolerance and similar BMI, women with a history of GDM had a 71% higher risk of developing diabetes during the 3-year intervention period than that of parous women without a history of GDM (J Clin Endocrinol Metab. 2008 Dec;93[12]:4774-9).

Clearly, there was something about the history of GDM that puts these women at greater risk for diabetes than women who had the same impaired glucose tolerance, but no GDM. The study demonstrated that GDM is an exceptionally strong predictor of the development of type 2 diabetes, even for those who manage to escape diabetes for the first 10 years.

 

Postpartum prevention

The DPP demonstrated, moreover, that intensive lifestyle therapy and metformin not only were both effective, but that they were equally effective, in delaying or preventing diabetes in women with impaired glucose tolerance and a history of GDM. Both reduced the risk by about 50% at 3 years. This was striking because in parous women without GDM, the reductions were 49% and 14%, respectively. Metformin thus appeared to be more effective in women with a history of GDM.

The effects of the interventions persisted over a 10-year follow up of the DPP population. In women with a history of GDM, the intensive lifestyle intervention and metformin reduced progression to diabetes by 35% and 40%, respectively, over 10 years (J Clin Endocrinol Metab. 2015 Apr;100[4]:1646-53).

Pregnancy presents a stress test for beta cell function, and gestational diabetes clearly is a harbinger of further deterioration in beta-cell function and metabolic abnormalities in the mother. Because of these risks and because early intervention makes a difference, surveillance is critically important. Most women see their ob.gyn. as their primary care physician in the 10 years following a pregnancy – the time when more than 50% of all cases of subsequent diabetes will occur – and many continue to see their ob.gyns. in the longer term, as their risk continues to linger.

Immediately after a pregnancy with GDM, ob.gyns. can counsel women not only about their risks of developing type 2 diabetes and the importance of screening, but also about the beneficial impact of lifestyle modification, caloric restriction and weight loss if necessary, and increased exercise. Mothers should also know that GDM is a family affair, and that lifestyle changes that are beneficial for the mother will be equally beneficial for the baby.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study taught us that there are continuous linear relationships between maternal glucose and adverse fetal outcomes like birth weight and percent body fat greater than the 90th percentile. Longitudinal studies of the Pima Indians showed us that offspring of women who had diabetes during pregnancy were more likely to be obese and more likely to develop diabetes than offspring of women who did not have diabetes during pregnancy. Even when GDM has been well treated and controlled, we should have heightened awareness to the potential risks in the fetus and the growing child and adolescent.

Patients who are found to have subsequent type 2 diabetes should know that aggressive therapy early on in the natural history of the disease reduces the risk of microvascular and macrovascular complications. And as the DPP has demonstrated, lifestyle interventions and metformin may also keep women who are found to have prediabetes outside of pregnancy from progressing on to diabetes.
 

Dr. Ratner is the chief scientific and medical officer for the American Diabetes Association. He reported having no financial disclosures relevant to this Master Class.