Intrinsic sphincteric deficiency (ISD) is a term commonly used in the urologic and uro-gynecologic literature to describe a type of urethral deficiency. Individuals disagree on the meaning and implications of the term. Despite the fact that there is no laboratory method to diagnose ISD precisely, differing surgical decisions have been made depending on the clinician’s impression of whether the patient has the condition or not.

Urethral sphincteric weakness is a continuum and the condition of ISD would be on the extreme end of this continuum, with the highest amount of urethral weakness or low urethral resistance. Yet even in patients that are on the ISD or weak end of this continuum, management as described in the literature is controversial if the patient also exhibits urethral hypermobility.

The last several years have seen an increasing trend for selection of the pubovaginal sling as a primary incontinence procedure in the United States. There were two phenomena that accelerated this trend. The first was accumulating data on the poor outcomes of needle-suspension procedures. The second was the development of a less invasive pubovaginal sling, in the form of the transvaginal tape procedure (TVT).¹ Additionally, the misconception of ISD as an entity with a possible laboratory diagnosis further resulted in increased numbers of patients receiving slings. Practice trends may reach the point where the majority of patients are simply relegated to a TVT procedure, with little clinical evaluation or attention to paravaginal anatomy.

If this were to advance to the point that all surgical patients receive a sling procedure, one might ask what the utility of diagnosing ISD would be. One answer might be to define which patients with ISD continue to have stress incontinence after a sling procedure. If such utility was established, a new name would need to be found, such as Super-ISD (the end of the continuum).

The point to be made here is that clinicians think they know exactly what ISD is and always know what to do when it is present. We actually know neither one of these things. What we need to do is to stop muddying the water by using single pressure measurements to define ISD. We can than take one giant step back (i.e., take one step back in thinking we know the best management until we have future technology available for an assessment that fully helps us with surgical decisions).

Having said this, we can do a lot for patients on the weak end of the continuum. The first step while we await refinement of technologies is to use a functional definition for ISD. This chapter reviews continence mechanisms, factors that predispose to ISD, technologies that assess these factors, and how to manage surgically patients on the weak side of the urethral-resistance continuum.

Many authors categorize patients with low urethral closure pressures as having ISD. Additionally, patients may be categorized as ISD by a single leak point determination while the clinician does not take into account the remainder of the patient’s history, physical, and other indices. Bump and colleagues² stated that ISD should be diagnosed by a composite of historic, urodynamic, anatomic, and clinical severity criteria.² (In the near future one may add collagen characteristics, electromyographic [EMG] findings, and urethral ultrastructural findings and scores). Bump and colleages² recommended that a maximum urethral closure pressure of 20 or less, a Valsalva leak point pressure of 50 or less, and a stress urethral axis of 20 or less be included in the composite.

Patients have often been relegated to sling procedures when diagnosed with ISD. Yet patients with low urethral pressures who have urethral hypermobility do not fit the functional definition of ISD. In addition the evidence-based data to support sling over the Burch urethropexy in patients with ISD (with hypermobility) does not exist. Several recent studies show commensurate cure rates in these patients when comparing sling and Burch urethropexy.

Patients with low urethral pressures who have urethral junction rotation are not at increased risk of failure after Burch urethropexy. Sand and associates³ performed a prospective randomized comparison of the pubovaginal sling procedure and the Burch urethropexy in patients with low urethral pressures. The cure rate was commensurate between the two procedures.

Hsieh and associates⁴ confirmed this in a separate study. The goal of their study was to determine whether an isolated low Valsalva leak point pressure could be an independent risk factor for Burch failure in patients with a normal maximum urethral closure pressure. Twenty-four women with objectively proven stress incontinence, Valsalva leak-point pressures less than 60 cm H₂O and maximum urethral closure pressure values greater than 20 cm H₂O were evaluated preoperatively and postoperatively. At follow-up greater than 1 year, 22 of the 24 (91.7%) patients were objectively continent after urethropexy.

The Marshall-Marchetti-Krantz (MMK) procedure is effective in patients with low urethral pressures if they have hypermobility of the urethra. Quadri and associates⁵ performed a prospective, randomized comparison of the MMK and the Burch urethropexy in patients with low urethral pressures who demonstrated urethral descent. Only 15 patients were studied in each group. At 1 year, stress tests were negative in 93% of women who underwent the MMK procedure and 53% of those who underwent the Burch procedure.

It would seem that risk of failure after urethropexy relates more to preoperative urethral hypermobility than urethral closure pressure. Bergman and colleagues⁶ performed a study showing that patients who have less than 30 degrees of urethral descent with urinary stress incontinence have a 55% failure rate associated with Burch urethropexy. Current data on the TVT procedure show that individuals with a nonmobile urethra and stress incontinence are also at increased risk of failure with TVT surgery.⁷

Patients with preoperative hypermobility of the urethra who demonstrate stress incontinence postoperatively despite restoration of urethral support have ISD. This may occur after any operation for stress incontinence including, on occasion, the pubovaginal sling procedure. This failure must be secondary to occult deficiency in nerve, muscle, and connective tissue that could not be diagnosed preoperatively. This occult deficiency results in deficient urethral resistance despite restored urethral support after surgery. Currently we have no urodynamic parameters that predict which preoperative patients will fall into this group. The future may hold promise in diagnosing this tendency through laboratory assessment of deficient muscle, nerve, and connective tissue.

Intrinsic sphincteric deficiency describes a combination of urethral anatomic and physiologic factors that fail to prevent stress urinary incontinence despite the presence or potential achievement of complete urethrovesical junction support. The type and amount of precise physiologic compromise that result in ISD have not been well described. Functionally, the bladder neck and urethra under dynamic conditions of abdominal pressure do not maintain a level of pressure resistance necessary to prevent escape of urine despite the absence of a bladder contraction.

Thus, the three factors present that result in a functional definition of are: (1) lack of urethral mobility (less than 20 of urethral excursion with straining); (2) the presence of stress urinary incontinence; and (3) the absence of a detrusor contraction at the time of stress leakage.

Urinary Continence

If a combination of desirable physiologic characteristics maintains continence under abdominal stress conditions, the absence of some or all of these factors in the presence of complete urethrovesical junction support will contribute to the existence of ISD. These beneficial intrinsic physiologic factors may include viscoelastic properties, integrity of striated muscle function (rhabdosphincter or internal striated sphincter), optimal neurologic innervation, normal ultrastructure of muscle and nerve, healthy connective tissue, urethral vascularity, mucosal surface tension, and importantly, other factors not yet described or appreciated. Other factors include a functional bladder neck and the distal striated urethral sphincter. It is unclear to what degree that each of these factors contribute individually to a multifactorial cause of ISD or whether any sole factor can be so compromised as to result in ISD when the remainder of physiologic support is intact. In order to define the contributions of these factors, they must be measured or evaluated by meaningful physiologic testing, ultrastructure, and EMG assessment. Such measurement or testing is difficult and currently may be fraught with artifact.

Urethral Muscle and Nerve

Carlile and colleages⁸ have shown that the content of striated muscle in the female urethra decreases with aging and is replaced with connective tissue.⁸ Peruchinni and colleagues⁹ in a cadaveric study have also shown that striated muscle was lost at the bladder neck and along the dorsal wall of the urethra as women aged. In an associated study, the same group of investigators showed that the number and density of urethral striated muscle fibers decline with age.¹⁰ Strohbehn and colleagues¹¹ performed a study comparing anatomy by magnetic resonance imaging (MRI) and histology. The authors showed that the internal urethral anatomy is visible on MRI and can be identified as it correlates to histology. Thus, it is possible to assess the amount and distribution of striated muscle in a living patient by MRI. Quick and colleagues¹² performed urethral MRI in human female cadavers with the use of an endourethral coil. The enabled a dramatic improvement in the signal to noise ratio and histologic correlation was again achieved.

In addition to the amount and distribution of muscle, the neurologic support of the muscle also has significant impact on function. Patients may have neural injury that is not detected on urodynamic testing. Such injury may be detected on EMG testing. As an example of such assessment, Kenton and associates¹³ reported on the role of urethral electromyography in predicting patients who have preoperative urethral hypermobility, but fail to have their stress leakage repaired with Burch urethropexy. Eighty-nine women who underwent preoperative testing with urethral EMG and cystometrograms were also assessed postoperatively. Fifty-nine of 74 women (80%) were objectively cured and 15 women had persistent urinary stress incontinence at 3 months. Women who were cured did not differ from those who failed in age, parity, menopausal status, maximum urethral closure pressure, Valsalva leak point pressure, maximum cystometric capacity, and detrusor instability or prolapse stage. Electrical activity of the urethra was calculated in these patients during rest, voluntary urethral squeezing, repetitive coughing, and bladder filling. There was no difference in any EMG parameters between the two groups when measured at rest, urethral squeezing or during bladder filling. Women who were cured did demonstrate better motor unit action potential activation with repetitive coughing than those with persistent leakage.

Pandit and associates¹⁴ found quantified intramuscular nerves within the female striated urogenital sphincter muscle. Significant variation in the quantity of intramuscular nerves was found. Women with sparse intramuscular nerves had fewer striated muscle cells. The finding supports the neurogenic hypothesis for stress urinary incontinence, i.e., nerve injury leading to loss of muscle. The authors found the largest nerves in the sphincter arrive in the region of the urogenital diaphragm supporting the concept of the pudendal nerve as the source of nerve supply to the striated sphincter. Damage to the pudendal nerve can affect nerve supply and ultimately the amount of muscle in the intrinsic urethral striated sphincter.

Fitzgerald and colleagues¹⁵ showed that those patients with weak sphincteric function (what some would classify as ISD), when compared to controls, had differences in the ultrastructure of the urethral muscle. Patients with weak function had smaller electron-dense portions of the sarcolemma. The authors stated that focal adhesion architecture is decreased in patients with intrinsic sphincteric deficiency.

Urethral Connective Tissue

Ulmsten and colleagues¹⁶ studied collagen in women with incontinence. The collagen content in biopsies from skin and ligamentum rotundum of seven women with a long history of stress incontinence was compared with that of continent controls. The skin of stress incontinent women contained 40% less collagen than that of continent women. The findings for ligamentum rotundum were similar. This suggested collagen as one of the factors predisposing these patients to develop incontinence.

Fitzgerald and colleagues¹⁷ performed a study assessing urethral collagen morphologic characteristics among women with stress urinary incontinence. This was a study of 31 women, 15 of whom served as controls. They found that collagen fibril diameter did not vary with continence status, presence of prolapse, age, race, or hormonal status. There were alterations in fibril morphologic characteristics in some patients with incontinence. Additional studies will be needed to understand the relation between morphology and function better.

Falconer and colleagues¹⁸ reported a study where stress-incontinent patients underwent transvaginal biopsy of paraurethral connective tissue. Collagen studies including ultrastructure assessment were performed. The biochemical and morphologic analyses exposed a significant difference in the paraurethral connective tissue between stress urinary incontinent women before menopause and comparable controls. The collagen concentration was almost 30% higher and the diameters of the collagen fibrils were 30% larger in the incontinent group of women.

Future assessment of ISD may include assessment of collagen, muscle characteristics, and aspects of innervation. It may include MRI of the urethra to assess the amount and distribution of muscle. It will include measurement of urethral pressure and Valsalva leak point pressure. The goal will become restoration these factors by increasing healthy collagen deposition and by injection of muscle-cell lines to proliferate lost muscle. Factors that may facilitate innervation may also be administered locally to the urethra. Growth factors may be injected into the tissue. These interventions will become a reality and in the long run may be less expensive than multiple operations for incontinence in patients predisposed to failure.

A Scale to Measure the Continuum of Sphincteric Weakness

Intrinsic sphincteric deficiency as a functional consideration in patients who have hypermobility refers to patients who have severe weakness and fail standard urethropexy. Currently we have no true method for determining which patients fall into this category. In the future it may involve a scale which scores such factors as: (1) collagen index (total collagen, ratio of type I to III collagen, morphology), (2) muscle EMG assessment by concentric needle, and (3) MRI assessment of the urethra.

Patients could than be divided into patients receiving surgery versus patients who are at high risk of failure and would benefit from procedures to increase muscle and other continent factors. Some patients may have their continent factors increased to the point that they would respond to restoration of vaginolevator support through surgery.

Management of Functional Intrinsic Sphincteric Deficiency

We can only confidently diagnose ISD in patients who have stress incontinence in the absence of urethral mobility. These patients are treated with periurethral injection. Patients who have hypermobility are treated either with pubovaginal sling or Burch urethropexy. Patients with hypermobility and a scarred, highly dysfunction urethra are treated with sling procedure.

Obstructive sling procedures are used in a small subgroup of patients with total lack of resistance between the inside and outside of the bladder. They are not discussed further in this chapter.

An example of collagen for periurethral injection is the study by Smith and colleagues¹⁹ in 94 patients with a 1-year follow-up. Sixty-seven percent achieved continence, of which 38.3% were dry and 28.7% became socially continent. An average of 2.1 procedures and 11.9 mL of collagen were required to achieve continence.¹⁹ Additional agents with potentially less shrinkage may soon be available with possible increased longevity of cure.

Intrinsic spincteric deficiency is an important entity that requires a higher degree of understanding and advanced technologies to assist in diagnosis. The future goal of understanding ISD is not to determine which surgical procedure is indicated for management. It is to determine a physiologic and structural basis for the patient’s problem and allow thoughtful rehabilitation and reconstruction at a cellular level. As the prevalence of incontinence continues to increase in a linear fashion we must be able to add the many factors back to the individual’s multifactorial mechanism or the outcomes will not be satisfactory over the long term.

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18. Falconer C, Blomgren B, Johansson O, et al: Different organization of collagen fibrils in stress-incontinent women of fertile age. Acta Obstet Gynecol Scand 77:87, 1998

19. Smith DN, Appell RA, Winters JC, et al: Collagen injection therapy for female intrinsic sphincteric deficiency. J Urol 157:1275, 1997