Fecal incontinence can be one of the most psychologically and socially debilitating conditions in an otherwise healthy individual. It can lead to social isolation, loss of self-esteem and self-confidence, and depression. This article is devoted to fecal incontinence relating to the adult female patient.

Problem: Anal incontinence is the loss of anal sphincter control leading to the unwanted or untimely release of feces or gas. True anal incontinence must be distinguished from other conditions that lead to stool passing through the anus. Stool seepage that produces soilage of undergarments may result from hemorrhoids, enlarged skin tags, poor hygiene, fistula-in-ano, and rectal mucosal prolapse. Other conditions that result in poor bowel control are inflammatory bowel disease, laxative abuse, parasitic infection, and toxins. Fecal urgency also must be differentiated from fecal incontinence because urgency may be related to medical problems other than anal sphincter disruption.

Frequency: Fecal incontinence is a devastating condition. More than $400 million is spent each year for adult diapers that control urinary and fecal incontinence. It is the second leading cause of admission to long-term care facilities in the United States. Exact data on the prevalence of fecal incontinence are difficult to obtain. This is partly because patients are reluctant to volunteer information about their condition to their health care provider. Johanson and Lafferty found that only 20% of patients mentioned the condition to their physician during a physician visit.

The reported incidence rate in the general population is 1-5%. Nelson and colleagues found a prevalence rate of 2.2% in the general population. In their study, 30% of the individuals were older than 65 years and 63% were women. Johanson and Lafferty observed an overall prevalence rate of 18.4% among individuals seen by primary care physicians. However, in this study, any involuntary loss of stool or soiling was considered to be incontinence, and, therefore, patients with soilage for reasons other than true incontinence may have been included.

Johanson and Lafferty and others have found an increasing prevalence of fecal incontinence associated with advancing age. In individuals younger than 30 years, the prevalence rate was 12.3%, compared to 19.4% in those older than 70 years. The long-term cost of fecal incontinence per patient, secondary to obstetric injury alone, is estimated to be $17,166.

Nygaard and colleagues evaluated the prevalence of anal incontinence 30 years postpartum in 3 groups of women. One group had disruption of the anal sphincter with vaginal delivery, the second group had an episiotomy without disruption of the anal sphincter, and the third group delivered by cesarean. They found no significant difference in the frequency of flatus incontinence among the 3 groups, at a rate of 30-40%. Approximately 58% of the sphincter disruption group had bothersome flatus incontinence, compared to 30% and 15% of the episiotomy and cesarean groups, respectively. The percentage of bothersome fecal incontinence was similar among the 3 groups, at around 20%. Other authors have suggested that anal incontinence affects approximately 10% of adult females.

Etiology

: Fecal incontinence has many etiologies. One or a combination of several factors can lead to the inability to control passage of stool or flatus. Congenital abnormalities such as spina bifida and myelomeningocele with resultant spinal cord damage can result in fecal incontinence. Damage to the anal sphincter from vaginal delivery, surgical procedures, inflammatory conditions, and neoplastic processes can contribute to the development of fecal incontinence. Several inflammatory bowel conditions lead to decreased compliance of the rectum and may manifest as fecal urgency, frequency, soilage, or incontinence. Medical conditions that may result in fecal incontinence include diabetes mellitus, stroke, spinal cord trauma, and degenerative disorders of the nervous system. These conditions may alter normal sensation, feedback, or function of the complex mechanism of anal continence.

Childbirth is widely accepted as the most common predisposing factor to fecal incontinence in women. This has led to an incidence of fecal incontinence in women that is 8 times greater compared to men. Childbirth may result in internal or external anal sphincter disruption or more subtle damage to the pudendal nerve through overstretching and/or prolonged compression and ischemia. Abramowitz and colleagues found a de novo sphincter defect rate of 16.7% after vaginal delivery. They also found that 13% of primiparous and 20.6% of multiparous women had new-onset anal incontinence after delivery. Sultan et al demonstrated that 35% of primiparous women and 44% of multiparous women demonstrated sphincter disruption after delivery but were asymptomatic. In this same study, 13% of primiparous patients and 23% of multiparous patients undergoing vaginal delivery complained of fecal incontinence or fecal urgency at 6 weeks postpartum.

In another study, Sultan et al found that approximately half the women who sustain a third-degree obstetric anal sphincter tear experience some impairment of anal continence despite a primary repair. They relate the cause as a persistent mechanical sphincter disruption rather than pudendal nerve damage. In fact, Nielsen et al found that 13 of 24 (54%) patients who underwent primary repair for sphincter disruption at the time of delivery demonstrated external sphincter defects at 3- and 12-month follow-up. In a study evaluating urinary and anal incontinence in women with obstetric anal sphincter rupture, Tetzschner et al found that women who had sustained an anal sphincter rupture had a 17% chance of anal incontinence at 3 months, which then increased to 42% at 2-4 years postpartum.

Successive vaginal deliveries increase the risk of developing fecal incontinence if a patient has had damage to the sphincter in a prior delivery or was symptomatic with anal incontinence after a prior delivery. Ryhammer et al found a significant long-term association between the number of vaginal deliveries and several anorectal parameters in perimenopausal women. They noted lower perineal position at rest, increased perineal descent with maximal straining, decreased anal sensibility to electrical stimulus, and prolonged latency in pudendal nerves to be associated with increasing parity. Nelson et al found that age, female sex, poor general health, and physical limitations are predisposing factors to fecal incontinence.

Additional factors that appear to increase risk are primiparity, occiput posterior presentation, use of forceps, fetal weight greater than 4000 g, perineal tears, episiotomy, and prolonged second stage of labor. Evidence of neurologic damage from the forces of labor is illustrated in a study by Fynes et al, who evaluated anorectal physiology in women undergoing cesarean delivery at different stages of labor. They found that anorectal function was unaltered in women undergoing cesarean delivery early in labor. In women with advanced cervical dilation (>8 cm) at the time of cesarean delivery, they found delayed pudendal nerve terminal motor latency (PNTML) and reduced anal squeeze pressures.

Allen et al found that 80% of patients had electromyelogram (EMG) evidence of nerve damage after their first vaginal delivery. Several authors demonstrated lower resting pressures on manometric evaluation and delayed PNTML after a single vaginal delivery. Both Cornes et al and Ryhammer et al demonstrated that anal sensation and sampling are negatively impacted after childbirth.

Age also plays a significant role in the development of fecal incontinence. Haadem et al evaluated 49 continent, healthy women with a mean age of 51 years (range, 20-79 y). Findings from anal manometry studies showed a decrease in maximum anal resting pressure and maximum squeeze pressure that was associated with age. These parameters declined more rapidly after menopause. This same study found that with aging, anal closing pressure (the difference between maximum resting pressure and rectal pressure) is reduced, which is an important determinant of anal continence. Similar findings of decreased anal pressures on manometry results were reported by Bannister et al, who also found that aging resulted in lower rectal volumes needed to inhibit anal sphincter tone.

When evaluating the effects of aging on anorectal sphincters, Laurberg and Swash found no significant changes in resting anal pressure. However, in women older than 50 years, they found that anal canal squeeze pressure was significantly lower compared to that found in younger women. Johanson and Lafferty found that the prevalence rate of fecal incontinence in individuals younger than 30 years was 12.3%, compared to 19.4% in those older than 70 years. Approximately 56% of psychogeriatric patients and 32% of geriatric patients in long-term care facilities are anally incontinent on a regular basis. Increasing age is also associated with slowed pudendal nerve conduction, perineal descent at rest, and decreased anorectal sensory function.

The external anal sphincter has been shown to have a higher concentration of estrogen receptors when compared to rectus muscle in the same patient and when compared to estrogen receptor concentration of external anal sphincter in men. This may play a role in this complex disorder.

The patient’s ambulatory status is also important when considering the etiology of the disorder. Wheelchair-bound patients and those who are dependent on others for access to bathroom facilities may have episodes of functional incontinence, yet have totally normal anorectal function.

Pathophysiology: Anal continence requires the complex integration of signals among the anal sphincters, puborectalis muscle, and the smooth muscle of the colon and rectum. Anal continence also requires the ability to adequately determine anorectal contents and the ability to access the necessary facilities to evacuate the rectum. Damage at any level in this system may lead to anal incontinence.

As colonic contents are presented to the rectum, the rectum distends. This results in a parasympathetically mediated relaxation of the internal anal sphincter and a contraction of the external anal sphincter. Rectal contents are allowed to come into contact with the very sensitive epithelial lining of the upper anal canal. The contents are then sampled as to their nature, ie, gas, liquid, or solid. Gowers originally described this as the rectal anal inhibitory response (RAIR). The epithelial lining of the upper anal canal has a rich supply of sensory nerve endings, especially in the region of the anal valves. This sampling is described as an equalization of the rectal and upper anal canal pressures.

Miller et al found that sampling occurred spontaneously in 16 of 18 control patients but in only 6 of 18 incontinent patients. It is likely that decreased anorectal sensation and abnormal sampling contribute in the pathogenesis of anal incontinence. Several disease processes can alter sensation of the anoderm and sampling.

If evacuation of the rectum is not appropriate, sympathetically mediated inhibition of the smooth muscle of the rectum and voluntary contraction of external anal sphincter and puborectalis musculature occur. The bolus of material is then pushed back up the rectum into the rectal reservoir. A decrease in the compliance of this rectal reservoir has been associated with fecal urgency and anal incontinence. The exact mechanism of this is unclear, and debate continues as to whether it is a cause or result of anal incontinence.

Contraction of the puborectalis increases the anorectal angle and keeps the bolus of material above the internal anal sphincter until the internal sphincter is able to recover. The anorectal angle is created as the rectum perforates the levator complex. The most medial fibers of the pubococcygeus muscle are referred to as the puborectalis muscle. These fibers create a sling around the rectum. They are fused to the sacrum posteriorly via the levator plate. This creates an anterior displacement of the anal canal as it perforates the pelvic diaphragm. The angle created by a midluminal line in the anal canal above the levators and one below the levators is referred to as the anorectal angle. The anorectal angle varies considerably but averages from 80-105°.

As this complex of muscles contracts and the rectum is pulled forward, the anorectal angle becomes more acute and prevents the bolus of stool from descending further. The contents of the rectum are forced back into the compliant rectal reservoir above the levators, which allows the internal anal sphincter to contract again. The internal anal sphincter is responsible for 50-80% of the resting tone in the rectum. The external sphincter contributes 25-30% of the resting tone, and the anal cushions contribute 15% of the resting tone. Also, the activity to the puborectalis and external anal sphincter, which are capable of generating much stronger contraction but fatigue after 30-60 seconds, is increased.

Any process that interferes with this mechanism, such as trauma from vaginal delivery or insult to the neuromuscular integrity from a variety of causes, can result in a failure of the mechanism to function and lead to anal incontinence.

Clinical: Patients who present for evaluation of fecal incontinence usually have had to overcome extreme embarrassment over their condition prior to their office visit. Care should be given to the manner in which the topic is approached in order to promote an open and comfortable discussion.

Obtain a thorough history, including duration of anal incontinence, type of incontinence experienced, frequency of incontinent episodes, type of stool lost, impact of the disorder on the patient’s life, history of associated trauma or surgery, and associated factors such as protective garment use. Review medications and dietary habits to determine if an easily remedied cause exists. A review of systems for systemic medical conditions that contribute to fecal incontinence is important.

Information about the number of vaginal deliveries and the presence of any factors pertaining to those deliveries that may have contributed to the incontinence helps in determining the cause of the incontinence. As previously mentioned, prolonged second stage of labor, forceps delivery, significant tears, and episiotomy, among other causes, are associated with increased risk for anal sphincter disruption and pudendal nerve injury.

Several fecal incontinence surveys attempt to quantify and qualify the severity of fecal incontinence. Two examples are the Fecal Incontinence Quality of Life Scale produced by Rockwood et al and the Fecal Incontinence Questionnaire by Reilly et al. The forms are largely designed as outcome measures and are most useful in a research setting. The benefit to the practitioner not in a research environment is that a great deal of information about patient symptoms and the impact of those symptoms can be obtained in a short period of time.

Patient evaluation begins with a careful history as previously described. Practitioners who routinely perform physical examinations on female patients should be familiar with normal perineal, vaginal, and anal sphincter anatomy. The examination should consist of a visual inspection of the perineal body and anus and a careful inspection of the vaginal epithelium. This is performed to look for skin tags, hemorrhoids, anal fissures, fistulae, and scars that may indicate prior trauma.

Digital rectal examination with the index finger in the rectum and thumb of the same hand or the index finger of the opposite hand in the vagina is mandatory to palpate the anal sphincters, determine perineal body thickness, evaluate anal sphincter and levator tone, and test for perineal body hypermobility. This examination is likely the single most useful and informative part of patient evaluation. Rectal examination is recommended as a routine part of a woman’s annual well-woman examination, but it is often deferred. It is mandatory in the evaluation of fecal incontinence and associated pelvic organ prolapse.

As the provider is beginning the rectal examination, resistance is met at the anal verge. A great deal of experience is required on the part of the provider in order to determine the degree of normal resistance. If the examining finger meets little resistance and the anus feels patulous, further questioning about symptoms of anal incontinence can be asked.

While performing the rectal examination, the patient is asked to tighten the sphincter around the examining finger. A circumferential increase in the pressure should be felt. Patients who have a disrupted anal sphincter may have adequate innervation to the existing muscle bellies, and pressure may be felt on the examining finger. Evaluating the nature and location of increases in muscle tone is important. Pressure may be placed on the finger laterally from existing functional muscle, but no or very little pressure may be felt anteriorly. Disruption of the muscle sphincter allows the muscle bellies to retract laterally and posteriorly, similar to the ends of a rubber band that is cut after being placed on gentle stretch. Scar tissue may develop anteriorly between the 2 ends of muscle and, with contraction of the lateral muscle bellies, gives the impression of an intact anal sphincter. Palpation of the muscle can assist in this situation.

The external anal sphincter is palpable as a 1.5-2 cm moderately firm doughnut-shaped mass within the perineal body. If, upon palpation of the perineal body, the examining fingers are not separated by much tissue or the muscle mass is not palpated, damage to the anal sphincter is likely. Palpation from a midline position laterally helps to define where normal muscle exists. Importantly, these findings can be subtle and may require come degree of experience to elicit.

During rectal examination, the tip of the examining finger is gently flexed and traction is placed on the perineal body. The perineal body is normally supported by the perineal membrane (urogenital diaphragm), which originates from the ischiopubic rami bilaterally. The perineal membrane, along with other fascial supports, inhibits the caudad displacement of the perineal body. Birth trauma sufficient enough to result in detachment or tearing of this support also may have resulted in damage to the anal sphincters, and this history finding may prompt further questioning and evaluation.

INDICATIONS

Indications for surgical repair for fecal incontinence are largely based on physical findings and the degree to which the patient is symptomatic. Surgical repair of the anal sphincter is not without potential complications and discomfort. Importantly, the physician should counsel the patient about the risks of the procedure and the potential for recurrence.

Examination may reveal a sphincter defect that is discovered in association with other defects in pelvic support. The patient may be asymptomatic or only mildly symptomatic for anal incontinence. Whether surgical repair should be performed in this situation is controversial and must be a decision reached between the patient and the physician. The evidence presented suggesting that age alone is a risk factor for the development of anal incontinence must be factored into the equation if a known anatomic defect is present. Clearly, this type of patient is at increased risk of anal incontinence in the future. Additionally, surgical outcomes of sphincter repair have been shown to be poorer in older women.

RELEVANT ANATOMY AND CONTRAINDICATIONS

Relevant Anatomy: A clear understanding of anatomy is mandatory for any surgical procedure, including surgical procedures of the perineum and anal sphincter. The perineal body is composed of a fusion of several structures. The Denonvilliers fascia is fused, which serves to suspend the perineal body from the sacrum via the endopelvic fascia. The bulbospongiosus and superficial transverse perineum muscles insert onto the perineal body. The bulbospongiosus originates from the pubic rami and inserts into the anterior aspect of the central tendon of the perineum. The superficial transverse perineum muscle originates on the ischial tuberosities and approaches the perineal body from a lateral position. The perineum is innervated by the labial nerve and inferior rectal nerve, which are branches of the pudendal nerve. The external anal sphincter is fused to the perineal body more posteriorly.

The anatomy of the external anal sphincter continues to undergo debate. Some suggest that it composed of 3 parts that are fused, while others maintain that it is composed of 2 more distinct parts. A subcutaneous portion just deeper than the perineal skin, a superficial portion, and a deep portion exist. Some combine the subcutaneous and superficial components into a single component. The separation of these components is indistinct in a surgical repair. The deep portion of the external anal sphincter is fused to the puborectalis muscle of the levator complex, and some even suggest that it is a continuation of it. It receives innervation from the pudendal nerve.

The internal anal sphincter is a continuation of the inner circular smooth muscle of the bowel wall. This musculature thickens over the last 2.5-4 cm of the rectum. The internal anal sphincter lies deep to the external anal sphincter, and an identifiable and surgically important plane exists between them. The internal anal sphincter begins at the level of the levator complex, and its distal extent is just proximal to the subcutaneous portion of the external sphincter. The internal anal sphincter is supplied by the autonomic nervous system. It exists in a state of continuous maximal contraction and provides a barrier to the involuntary loss of stool.

The levator complex is composed of the pubococcygeus, the iliococcygeus, and the coccygeus muscles. The most medial fibers of the pubococcygeus make up the puborectalis. These fibers loop around the posterior aspect of the rectum and create an anterior displacement of the rectum known as the anorectal angle. The pelvic surface of the levator complex is innervated by sacral efferents from S2 through S4. The inferior surface is supplied by the perineal and inferior rectal branches of the pudendal nerve.

Contraindications: Contraindications to surgery for anal incontinence occur when the etiology for incontinence is uncertain; when a nonsurgical therapy, such as medication or diet alteration, would provide relief of symptoms; a woman is pregnant; or when surgical repair would place the patient at risk for complications from other medical conditions.

WORKUP

Lab Studies:

 
• Surgical repair for fecal incontinence is usually an elective procedure. Evaluation and treatment of anemia, infection, or other abnormalities indicated by findings from a complete blood cell count should be initiated prior to surgical repair.  
• A pregnancy test should be performed at or near the time of surgery on every female patient who may be pregnant.

Imaging Studies:

 
• Ultrasound
       
  1. The standard diagnostic imaging study for the anal sphincters is transanal or endoanal ultrasound. Much of the early work on endoanal ultrasound was performed at St. Marks Hospital in the United Kingdom by Law, Burnett, and Sultan et al. Multiple reports have qualified ultrasound as the criterion standard in the diagnostic evaluation of the anal sphincters.      
  2. Ultrasound allows the provider to perform a real-time evaluation of both the internal and external anal sphincters. Sensitivity and specificity of ultrasound findings are 98-100% for the external anal sphincter and 95.5% for the internal anal sphincter. Burnett et al have shown that 90% of women presenting with anal incontinence and a history of a vaginal delivery had ultrasonographic evidence of damage to the external anal sphincter, internal anal sphincter, or both.      
  3. Endoanal ultrasound is preformed in the left lateral or lithotomy position. The lithotomy position in females allows for the evaluation of other pelvic support defects.      
  4. Traditionally, 3 regions of the rectum are evaluated ultrasonographically. The areas of focus are distal, where only the external anal sphincter is observed (Image 1); at the level where both the internal and external anal sphincters can be observed in the mid anal canal (Image 2); and proximal at the level of the levators (pubococcygeus) (Image 3).      
  5. Normal thickness for the external anal sphincter is consistently described as 8.3 mm (95% confidence interval [CI], 7.6-9 mm). Mean internal anal sphincter thickness is described as 6.5 mm (95% CI, 5.8-7.2 mm), although reports vary from 1-3 mm to 10 mm based on modality. Inflammatory disorders can increase the thickness of these sphincters.      
  6. The external anal sphincter appears as a hyperechoic ring that is circumferential. It is striated muscle, which is echogenic in nature. The internal anal sphincter is composed of smooth muscle and appears as a hypoechoic or sonolucent ring that is medial to the external anal sphincter. It can be viewed from the level of the levators to just inside the anal verge. The puborectalis muscle appears as a hyperechoic U-shaped muscle approximately 4 cm into the anal canal (Image 3).      
  7. Tjandra and colleagues evaluated patients with ultrasound of the anal sphincters and EMG. They found that ultrasound helped identified both internal and external sphincter defects with 100% accuracy compared to EMG findings, with considerably less discomfort. They state that ultrasound is preferable to EMG in mapping anal sphincter defects, especially for evaluation of the internal anal sphincter.

Diagnostic Procedures:

 
• Anal manometry
  •   Anal manometry is used to evaluate both the resting and squeeze pressures of the rectum. It can also be used to evaluate the rectoanal inhibitory reflex, rectal capacity, and rectal compliance.
  •   Normal values for manometry vary among institutions. Currently, no uniformly accepted standard exists for performing manometry, and what is considered typical pressure is also quite variable. Normal resting pressures are 40-70 mm Hg (55-95 cm water) from Wexner and 60 cm water (standard deviation [SD], 20 cm water) from St. Marks Physiology Unit in London. Normal squeeze pressures are 100-180 mm Hg (136-244 cm water) from Wexner and 100 cm water (SD, 30 cm water) from St. Marks Physiology Unit in London.
  •   Mean resting and mean squeeze pressures are lower in women who have had a vaginal delivery, regardless of sphincter disruption. Low manometric pressures are not predictive of anal sphincter defects. Women with known sphincter defects tend to have lower mean resting pressures; however, mean squeeze pressures may be unaffected. Squeeze pressures are not significantly related to the presence of an external anal sphincter defect. Tetzschner et al found decreased pressures in continent and incontinent women after vaginal delivery. Both groups had low pressures compared to controls.
  •   The majority of studies that evaluate fecal incontinence in women use manometry as part of their assessment. The results of these studies are variable, and no patients have forgone surgical repair based on a finding of low manometric pressures.
  •   Several studies are available that demonstrate that manometry results are not able to help predict surgical outcomes for anal sphincter repairs. Rasmussen and colleagues found that patients with incontinence persisting after surgical repair had lower anal maximum squeeze pressures compared to continent patients. In patients who are continent after surgery, no difference in anal pressures existed before and after surgery. Felt-Bersma et al found that manometry is not valuable when comparing an individual patient’s pressure to the reference range because of the large variability in the reference range. They suggest that evaluation of an individual’s pressure changes preoperatively and postoperatively makes more sense. In fact, several investigators have found improvement in manometry pressures postoperatively.

   

• Pudendal nerve terminal motor latency

  •   PNTML helps evaluate the length of time required for a fixed electrical stimulus to travel along the pudendal nerve from the ischial spine to the anal verge. Findings reflect the myelin function of the peripheral nerve, and the test allows for the evaluation of pelvic floor neuromuscular integrity. The pudendal nerve is stimulated at the ischial spine transanally. The latency period between stimulation of the nerve and evoked response of the muscle is measured. Any damage to the neuromuscular unit results in the prolongation of the latency. Normal latency has been described as 2 milliseconds (SD, 0.2 ms).
  •   Several studies have found that prolongation of PNTML occurs after uncomplicated vaginal delivery. PNTML approaches the reference range at 3 months postpartum; however, Tetzschner et al found a significant and persistent prolongation of PNTML between incontinent and continent women 3 months postpartum. In addition, the only predictor for the development of anal incontinence at 2-4 years postpartum in women who had rupture of the anal sphincter was abnormal PNTML. Ryhammer and colleagues evaluated the long-term effects of vaginal delivery on anorectal function and found that PNTML increased with parity. They found the greatest change in PNTML between the second and third deliveries; however, the range of values within groups was large. In a separate study, Tetzschner et al also found a wide range of values within incontinent and continent groups. The incontinent group values ranged from 1.35-3 milliseconds, and the continent group values ranged from 1.44-2.47 milliseconds.
  •   Others investigators have not shown a decrease from normal values between the third and fifth day postpartum and 2 months postpartum. Sultan et al found no relationship between the change in predelivery and postdelivery PNTML and the development of symptoms of anal incontinence. In a different study, Sultan and colleagues found no difference in PNTML when either vacuum delivery or forceps delivery was compared to the control group.
  •   Many investigators have suggested that PNTML is the most significant predictor of functional outcome of a sphincteroplasty. Gilliland et al found that prolonged latency was correlated with outcome. In their series, only 16% of patients with pudendal latency greater than 2.2 milliseconds subjectively described their results as successful (excellent or good, based on telephone interview). In a study of patients with unilaterally prolonged latencies (2 ms; SD, 0.2 ms), Sangwan et al found that only 1 of 7 patients who underwent sphincteroplasty had improvement in their incontinence score. Six patients had either (1) no improvement in incontinence score but less frequent incontinent episodes or (2) no improvement at all.
  •   The difficulty with interpreting findings in the literature is that no consensus has been reached for agreed-upon standard and nonstandard values. Also, variability exists in how PNTML correlates with other physiologic findings. All of the studies previously mentioned used the St. Marks electrode produced by Dantec.
  •   Fynes et al considered latency to be prolonged if longer than 2.4 milliseconds in duration. While evaluating the neurophysiologic changes in fecal incontinence, Osterberg et al used a latency period of longer than 2.5 milliseconds duration (based on a mean of 2 ms and 2 SD to reduce their false-positive rate) as an abnormal value. In the same study, they found no differences in resting pressures, incremental pressures, or rectal sensibility in patients with unilaterally or bilaterally prolonged PNTML compared to patients with normal PNTML. They question the routine use of PNTML in the investigation of patients with fecal incontinence.
  •   As with anal manometry, prolonged PNTML values have not been used as a reason to deny surgical repair. Chen et al found that in patients with prolonged latencies, surgical repair of sphincter defects resulted in improvement of incontinence scores. Felt-Bersma et al, when evaluating anorectal function and ultrasonographic images after sphincter repair, found no relationship between preoperative neurologic function (based on EMG and PNTML findings) and clinical outcome. Acknowledging the fact that PNTML has contributed greatly to the understanding of anorectal pathophysiology, Felt-Bersma’s group suggests that PNTML has no place in the routine preoperative assessment of patients. They go one step further by suggesting that withholding a sphincter repair from a patient with a prolonged PNTML may be unethical.
  •   Although prolonged PNTML indicates pudendal neuropathy, normal latency does not exclude nerve injury because only the fastest remaining conducting fibers are recorded. Also, overlap has been shown to exist in the innervation of the external sphincter.

   

• Electromyelogram

  •   EMG helps evaluate the electrical activity generated by muscle fibers during voluntary muscle contraction, rest, and Valsalva-type activities. The motor unit includes the anterior horn cell, its axon with axonal branches, the motor end plates, and the muscle fibers supplied. Information on the innervation and functional status of motor unit potentials is obtained. Results can be used to map normal muscle fibers. Several methods are available. Electrodes that are available for use are the surface anal plug, concentric needle electrodes, single-fiber electrodes, and monopolar wire electrodes. Injured or damaged muscle results in a lack of electrical activity or a polyphasic pattern. Incomplete damage may allow for reinnervation from adjacent undamaged nerves or regrowth of damaged axons. The result is that a greater number of muscle fibers are innervated by a single nerve, leading to an increase in the amplitude and a more prolonged motor unit action.
  •   Abnormal findings after EMG evaluation are present in more than 90% of patients with fecal incontinence. In a study of 72 patients with fecal incontinence, Osterberg and colleagues found that fiber density observed with single-fiber electrodes correlated with clinical and manometric variables; PNTML did not.
  •   Although EMG is able to help quantitate denervation, findings do not alter clinical management. Similar to PNTML, Felt-Bersma et al suggest that EMG as a means to locate the sphincter defect has also lost its place in the preoperative assessment of anal sphincter defects. EMG studies can be uncomfortable, especially the single-fiber technique, and they may result in incomplete studies due to patient refusal to continue.

TREATMENT

Medical therapy:  Medical therapy involves bulking agents and biofeedback. After history and physical examination findings have helped exclude systemic disease and local anal pathology as the source of the patient’s problem, the provider can initiate treatment.

Attempts at medical treatment of anal incontinence are based on the type and severity of symptoms. Bulking agents, such as methylcellulose (Citrucel) or psyllium (Metamucil, Fiberall, Hydrocil), may add bulk to the stool and allow for better control. Additional firming of the stool can be obtained by restricting fluid with intake of the bulking agent. This may be helpful therapy in the patient who has incontinence of soft stool or liquid stool. Each dose of Metamucil contains 2.3 g of soluble fiber.

Agents that slow the motility of the gut have also been used. Loperamide hydrochloride has been used in this setting. Transit time is increased, allowing for increased absorption of water from the volume of stool, which results in a firmer bolus of stool. The maximum daily dosage is 16 mg. The usual dose regimen is 2-4 mg bid-tid to control symptoms. Diphenoxylate hydrochloride/atropine (Lomotil) has also been used; however, diphenoxylate hydrochloride can cause dependence and is a schedule V medication under the Controlled Substance Act.

Biofeedback, as related to fecal incontinence, is a safe and minimally invasive behavioral technique that uses auditory or visual feedback to educate or reeducate the pelvic floor musculature. Exactly how biofeedback works remains unclear. It involves contraction and relaxation of the pelvic diaphragm using a sensor placed in the vagina or rectum. The sensor provides feedback that the desired activity is being performed correctly. Its effectiveness has been established for neurogenic and idiopathic anal incontinence and for incontinence related to disruption of anal sphincters. It has resulted in a 90% reduction in episodes of incontinence in more than 60% of patients. Augmentation of biofeedback by electrical stimulation of the anal sphincter has shown improvement in symptoms over biofeedback alone and has resulted in improvement in manometric parameters.

Two methods are prominent in the treatment of anal incontinence. One method uses anal and rectal distention with an inflatable device. The patient is educated on contraction of the pelvic floor and external sphincter in response to ever-smaller volumes of distention. The second technique uses a sensor, usually EMG, as the patient contracts the pelvic floor and anal sphincter. Personal units are now available (without prescription) for home use after initial clinical instruction (Persist, Deschutes Medical, Bend, Ore). They use a vaginally placed, air-filled sensor that provides information on force and duration of contractions. Results from biofeedback can diminish over time, but home devices provide the patient the opportunity for a prolonged course of therapy and intermittent reeducation in a private setting.

Surgical therapy: Several surgical procedures are available for treatment of anal incontinence. The type of procedure used is based on the patient history, physical examination findings, and results of diagnostic evaluation. The current philosophy in pelvic reconstructive surgery is restoration of normal anatomy. The standard procedure for anal incontinence due to anal sphincter disruption is the anterior overlapping sphincteroplasty. This procedure was first proposed by Parks et al in 1971 and modified by Slade et al in 1977. Morbidity was reduced when Fleshman et al initiated a mechanical bowel preparation preoperatively rather than a diversionary procedure.

The procedure consists of dissecting the external anal sphincter, dividing the scar tissue in the midline, and then overlapping the scar so that muscle is approximated to muscle as closely as possible. Controversy exists as to the need to identify and plicate the internal anal sphincter. Its value in the continence mechanism has been discussed. Several postoperative studies have demonstrated improvement in resting and squeeze pressures, which suggest that either the internal sphincter was plicated intentionally or that the internal anal sphincter was also unintentionally plicated in the process of overlapping the scar mass. In an older study, Fang and colleagues suggest not separating the internal from the external anal sphincters; however, they do not discuss the reasoning for this.

Several other studies have performed ultrasound of the sphincters postoperatively, yet few specifically mention the condition of the internal sphincter. Briel et al compared 2 groups of patients who underwent surgical repair. One group had surgical repair of only the external sphincter between 1973 and 1989. The second group underwent surgical repair consisting of restoration of the rectovaginal septum, perineal body, and repair of the external and internal sphincters. These patients had surgical repair between 1989 and 1994. They found that the more complex repair conferred no advantage. The measured outcome focused on anal continence, which was restored or improved in 63% and 68%, respectively. A great deal of literature was subsequently produced promoting the benefits of correcting other pelvic support defects that are not directly related to anal continence at the time of sphincteroplasty.

Abou-Zeid performed isolated internal sphincter repair in 8 patients with ultrasonographically proven defects in the internal anal sphincter. All patients had anal incontinence of varying degrees. All had undergone a prior surgical procedure, such as hemorrhoidectomy or sphincterotomy, and had developed symptoms subsequently. All patients underwent preoperative ultrasound, and 6 patients underwent postoperative endoanal ultrasound to document internal sphincter anatomy. Continence scores improved in all patients, and 2 patients achieved complete continence.

The surgical approach requires dissection along the intersphincteric plane and identification of the internal anal sphincter. The sphincter is then dissected free from the rectal mucosa and mobilized. The surgical technique varies at this point based on the bulk of scar tissue. The scar tissue is either divided or left intact as the sphincter is plicated. It is unclear whether any benefit in outcome is achieved if the surgeon divides or does not divide the scar tissue. Unfortunately, with this alteration in surgical technique and the very few patients in the report, drawing conclusions based on this study is difficult. The improvement in continence scores is encouraging. Other authors have not found any benefit to isolated repair of the internal sphincter. Most of these case series also have a small number of subjects, again making it difficult to draw conclusions.

Most reconstructive surgeons are performing colporrhaphy and perineorrhaphy as part of the overall repair. Numerous articles describe the physiologic and supportive role of the rectovaginal septum and perineal body. In a study of 143 women, Weber and colleagues found that defects in the posterior compartment often coexist with bowel symptoms; however, they were unable to show a direct correlation between stage of prolapse and severity of bowel symptoms. This study did not proceed with surgical repair and evaluate for symptoms postoperatively. Wexner and Olivera support the philosophy of repair of all defects and suggest that failure to recognize and repair concomitant injuries of the anal sphincter mechanism is usually accompanied by continued anal incontinence.

The success rate for surgical repair is 50-80%. Some report rates of successful surgical outcome of as high as 90%. The surgery can be performed with the patient in the prone jackknife position or the dorsal lithotomy position.

Pudendal nerve neuropathy is associated with a higher failure rate. As discussed previously, Gilliland found that the only factor predictive of successful outcome of overlapping sphincteroplasty was bilaterally intact PNTML. Sangwan et al found that patients with unilaterally intact pudendal nerves had a less favorable outcome than those with bilaterally normal latencies. Chen et al evaluated patients who had normal (1), unilateral (7), or bilateral (4) prolongation of PNTML with preoperative and postoperative incontinence scores. They found significant improvement in incontinence scores among all groups. These results were sustained at 20- to 72-month follow-up. Different studies have demonstrated that anterior overlapping sphincter repair can improve continence scores, resting pressures, and squeeze pressures regardless of pudendal nerve latencies; therefore, if sphincter disruption is present, repair should be offered. Counseling patients regarding surgical outcomes and risks is imperative.

Some researchers perform postanal repair in patients with anal incontinence from a neurogenic or idiopathic cause. This type of anal incontinence is often associated with denervation of the pelvic floor. Patients have a decreased ability to sense impending defecation and may initially become aware of the need for a bowel movement only after they have passed stool and notice the odor or sensation of fecal material around the anus. The internal and external anal sphincters are usually intact. Evaluation often demonstrates an increase in the anorectal angle, which has also been described as a flattening of the anorectal angle.

The original theory behind postanal repair was restoration of the anorectal angle and lengthening of the anal canal. The incision is made posterior to the anal canal and carried to the levator plate. The dissection is carried in the intersphincteric plane between the internal and external anal sphincters. Once identified, the ileococcygeus, puborectalis, and pubococcygeus muscles are plicated posterior to the rectum. The internal anal sphincter, external anal sphincter, or both can also be plicated during the procedure. This approach was first described by Sir Alan Parks, whose initial series had an 83% success rate. Many subsequent series by different investigators have been unable to match this original success rate.

In an attempt to better understand the mechanism of postanal repair, several investigators have performed preoperative and postoperative physiologic evaluation of patients. In a review of 30 patients who had undergone postanal repair, using endoanal ultrasound, Setti Carraro et al found that 19 of the 30 patients had breaks in the internal anal sphincter (6), the external anal sphincter (4), or both (9). Matsuoka and colleagues performed preoperative PNTML, EMG, and manometry and found no predictive factor in the outcome of postanal repair. Scott et al performed manometry prior to postanal repair and were unable to show any correlation between manometry and successful outcome.

Laurberg et al performed extensive preoperative and postoperative evaluation including manometry, perineal descent, PNTML, and single-fiber EMG. They found minimal correlation with preoperative physiologic testing and successful surgical outcome. Of interest in this study is the finding of increased fiber density and prolonged PNTML in those patients who improved with surgery, suggesting damage as a result of postanal surgical repair. Setti Carraro et al also found postoperative prolongation of PNTML, from 2.2 milliseconds to 2.85 milliseconds, in patients with a successful surgical outcome. They found that the only preoperative factor predicting successful outcome was intact PNTML. Others also found that intact PNTML is associated with better surgical outcomes. These findings seem to indicate that the patient with idiopathic fecal incontinence and normal PNTML has a better chance of success compared to a patient with a neurogenic cause of incontinence.

Both Laurberg et al and Setti Carraro et al have found that postanal repair may cause trauma to the pudendal nerves that did not exist preoperatively. The potential consequences of this are not known. Jameson et al evaluated patients 2 years following postanal repair and found a decrease in the number of patients who had some benefit (83% to 53%), with only 28% who were markedly better at 2 years. Setti Carraro et al did find that anal canal length increased significantly, from 2 cm to 3.8 cm, after postanal repair.

The effect of postanal repair on the anorectal angle has also been evaluated. Bartolo and colleagues have shown that restoration of the anorectal angle does not correlate with the success of postanal repair. Failure of postanal repair to restore the anorectal angle has been confirmed by other investigators. Womack et al had improvement in 70% of 16 patients and found no significant change in the anorectal angle when measured radiographically. They recommend that the procedure not be limited to those patients with widening of the anorectal angle.

In a comparison of anterior sphincteroplasty and postanal repair, Orrom and colleagues found no postoperative advantage for either procedure. They found that patients who had undergone postanal repair had no change in anorectal angle, whereas those who had undergone anterior sphincteroplasty with anterior plication of the levators had a more obtuse anorectal angle. They concluded that restoration of the anorectal angle was not important, and their group has abandoned the postanal approach. Matsuoka et al concluded that although the success rate for postanal repair was low, it is a valid therapeutic approach because of low morbidity and the absence of mortality. The alternative for these patients, in whom other modalities have failed, is to live with this very disabling condition, undergo diverting colostomy, or undergo muscle transfer.

Gluteal and gracilis muscle transposition procedures have also been performed. The use of the gluteus muscle has largely been replaced by gracilis transfer. The procedure may be indicated in patients who have congenital absence of the anal sphincter or in those who have lost the anal sphincter as a result of disease, although some have undertaken this procedure after attempts at sphincter repair have failed.

The muscle is detached from its insertion and mobilized. The neurovascular bundle to the muscle enters in its proximal third; care is necessary to prevent devitalization of the muscle. The muscle is wrapped around the anus, and the distal end is attached to the contralateral ischial tuberosity. Modifications have been made using low-frequency stimulation to the muscle. Results have been good, with a success rate of 70-90%. The procedure has a high complication rate and is usually performed in the research setting. In patients with severe anal incontinence or those in whom other procedures have failed, muscle transposition may offer an improvement in quality of life.

An artificial anal sphincter is also under investigation and has had some success. The anal sphincter is produced by American Medical Systems and is similar to the artificial urinary sphincter. The inflatable cuff is placed around the anus, and an inflation reservoir is placed in the space of Retzius. As the patient feels the need to have a bowel movement, a control pump is squeezed and forces water out of the cuff and into the reservoir. This allows the patient to have a bowel movement. The cuff slowly refills over 7-10 minutes. The success of the artificial urinary sphincter has been good. Its use in persons with fecal incontinence has been experimental and limited to only a few centers, but improvement rates are 75%.

Preoperative details: Once the decision has been made to proceed with surgical repair, mechanical bowel cleansing is performed. This can be performed with a variety of agents. Full mechanical bowel preparation with large volumes of solution is probably unnecessary, although it has some benefits for postoperative management. Smaller volumes of solution are better tolerated by patients, with some surgeons using only Fleet enemas prior to repair. The value of a more thorough preparation, such as Fleet Phospho-soda or GoLYTELY, is in the postoperative period when most surgeons are concerned about delaying mechanical stretch to the newly repaired sphincter.

Pain medications can predispose the patient to constipation, and, if the patient had a more thorough preparation, the first bowel movement is delayed. The use of oral antibiotics before mechanical bowel preparation has not been shown to have any additional benefit over mechanical preparation alone in elective colorectal surgery. The once-common regimen of oral neomycin plus erythromycin on the day prior to surgery has been found to be inadequate. Other regimens that have been found to be inadequate are metronidazole alone, doxycycline alone, and piperacillin alone. Immediate perioperative dosing of antibiotics has been shown to decrease the infection rate by 75%. A single preoperative parenteral dose of antibiotics is sufficient.

Intraoperative details: Maintaining the scar tissue on the muscle belly and using this to decrease the likelihood of suture pull-through has been one of the most important factors improving surgical outcomes for the overlapping sphincter repair. The adequate mobilization of the existing scar tissue and separation of the scar in the midline to allow for overlap is also important. The judicious use of cautery to prevent devascularization is also wise.

Postoperative details: Postoperative management is probably the most varied aspect in the treatment of fecal incontinence. Agreement exists about the use of postoperative stool softeners, and several products are available that can be mixed with liquids and added to the diet (see Medical therapy). Several articles list a tablespoon of mineral oil (30 mL) PO qd for a short period of time postoperatively. Prolonged use of mineral oil is not recommended because it can lead to absorption problems.

A variety of ways exist to manage the patient’s diet after surgical repair. Some surgeons delay feeding and keep patients on clear liquid diets or soft foods for 2-7 days postoperatively. Others allow a regular diet and use stool softeners and mineral oil to decrease stool firmness. Many encourage patients to use sitz baths as a means of decreasing swelling and to assist with cleanliness. However, some believe that osmotic gradients actually allow for more swelling and tissue maceration, and they promote the use of peribottles to wash the perineum and rectum. The patients pat dry with tissue or a soft cloth.

Patients may shower for overall hygiene because the perineum is not submersed in water as it is in a bath. Some articles advise patients to use enemas postoperatively to prevent constipation. Multiple management styles exist and, as is often the case in medicine, most physicians normally adopt the practice style of their mentors. As a prior mentor of this author often quoted, “this area is unencumbered by data.”

The use of postoperative antibiotics also falls into this category. Due to the location and nature of the tissues, infection of the surgical site is a risk; however, the blood supply to this area is rich and, unless compromised with extensive electrocautery, the need for postoperative antibiotics is questioned.

A reasonable approach based on sound principles is probably best. Prolonged periods of dietary restriction are probably unnecessary. If one elects to use mechanical bowel preparation, the time to first bowel movement will be delayed, especially if the patient is kept NPO for the immediate postoperative period. The use of dietary fiber to keep stools soft is appropriate. The addition of mineral oil once a day to assist with this is not overly burdensome. Using sitz baths versus not using sitz baths is provider-dependent and more likely based on provider experience. Patients who have been fecally incontinent and who have a chance of becoming continent are usually compliant with most recommendations. Incumbent upon the physician is to make sound recommendations.

Follow-up care: Because of the nature and location of the surgical repair, pain control is an important issue. Patients need to have adequate access to their surgeon for additional medications as necessary. Because the risk rate of separation of superficial tissues is as high as 25% and because of the potential for infection, patient concerns must be taken seriously. Evaluation by trained providers, if only to reassure the patient, allows the surgeon to catch serious complications early.

Postoperative evaluation should be scheduled for 4-6 weeks after the procedure. Patients should be asked about their symptoms, and most postoperative swelling and tissue distortion is usually resolved. A history of the patient’s bowel habits must be addressed. If patients need modification of their stool softener regimen, it can be done at this time. Mineral oil regimens should be stopped if the patient has continued these. Additional appointments can be scheduled depending on the individual practice of the physician.

COMPLICATIONS

The complication rate from surgical repair of the anal sphincter varies based on the series reviewed. The patient population requiring surgical repair may have significant comorbidities that predispose them to postoperative complications. A review of several series for both postanal repair and anterior sphincteroplasty reveals that most patients are in the fifth through seventh decade of life. Underlying medical conditions, such as obesity, diabetes, or heart disease, can increase the postoperative risk of myocardial infarction or deep vein thrombosis.

The most common complication is superficial separation of skin and subcutaneous tissues, and the frequency rate is as high as 25% in some series. Care must be taken to place as little tension as possible on these tissues. Conversion of the curvilinear incision into a Y-shaped incision at the time of closure can place a great deal of tension on the perineal skin and predispose it to separation. Plication of the bulbospongiosus and superficial transverse perineum muscles can remove tension from the overlying skin and serve to restore anatomy. Devascularization of the vaginal or rectal mucosa can result in necrosis of these tissues.

Risk of infection is 3-5%. Opening the wound to allow for drainage and treatment with antibiotics may allow the physician to salvage the surgical repair. Fistula formation occurs in fewer than 1% of the series reviewed, but it is more common in those cases in which infection develops.

Bleeding and hematoma formation are also possible complications. Bleeding can usually be controlled with pressure achieved with packing. Hematoma formation into the perirectal space can go unnoticed and result in the sequestration of large amounts of blood.

Other complications include anal stricture, fecal impaction, and pain. Pain may be associated with bowel movements and intercourse, leading to a great deal of frustration for both the provider and patient. Fortunately, this problem resolves over time. Most complications that arise do not affect the sphincter repair. Although patients may be distressed, they should be reassured that the risk of failure of the procedure is not increased.

OUTCOME AND PROGNOSIS

The rate of successful outcome for anterior sphincteroplasty or postanal repair is 70-90%. Three reports have suggested that the durability of postanal repair decreases over time. This may be due, in part, to damage to innervation that occurs at the time of surgical repair. This was demonstrated in studies by Snooks et al, Laurberg et al, and Setti Carraro et al. Results of sphincter repair from an anterior approach appear to have better longevity. The long-term prognosis for surgical repair is good, and the majority of patients experience an improvement in symptoms. Although some long-term data suggest a decrease in efficacy, the alternative of living with this very debilitating disorder favors surgical correction.

FUTURE AND CONTROVERSIES

Although the artificial anal sphincter is still under investigation, it has promise. Infection rates of the sphincter mechanism have been high, but with refinement of technique, these will surely decrease.

The trend in preoperative evaluation has been away from multiple neurophysiologic studies. A physician experienced in the diagnosis and treatment of anal incontinence can often determine the status of the internal and external anal sphincter based on physical examination findings alone.

Endoanal ultrasound has revolutionized diagnostic capability and follow-up care. The procedure is easily performed with minimal patient discomfort, and findings are easily interpreted with a very shallow learning curve; however, the equipment is expensive, and this factor may limit its use.

Several studies have been performed recently using sacral spinal nerve stimulation for patients with fecal incontinence. Sacral spinal nerve stimulation has been used extensively for the treatment of female patients with urinary incontinence associated with overactive bladder and nonobstructive urinary retention as well as other pelvic disorders. The results of this therapy have been encouraging. It follows that investigators would consider this modality for the treatment of fecal incontinence in those patients with normal sphincter anatomy and symptomatic fecal incontinence. Medtronic InterStim has been the modality of choice of investigators treating fecal incontinence.

Vaizey et al, in a double-blind crossover study, evaluated 2 patients using incontinence diaries, anorectal physiologic studies, and quality of life assessments. They found dramatic differences between the number and severity of episodes of incontinence when the stimulator was turned on versus turned off.

Ganio et al evaluated 16 patients (12 females) with fecal incontinence and found improvement in symptoms based on number of accidents in a 2-week period. They found a significant improvement in the manometric measures of mean maximal resting pressure and mean maximal squeeze pressure. Matzel et al studied 6 patients (5 females) and similarly found improvement in incontinence scores and in the function of striated anal sphincter as demonstrated by increased maximal squeeze pressure.

In addition to the stimulation of striated muscle fibers, Matzel and others have suggested the effect of low-frequency stimulation may result in the transformation of fast-twitch (type II) muscle fibers to a more fatigue-resistant slow-twitch (type I) muscle fiber. This may be the mechanism behind fewer episodes of fecal urgency seen in several studies. This was found in a study by Leroi et al, evaluating 9 patients (6 females) with fecal incontinence. Leroi et al found longer-lasting benefit in the number of fecal urgency episodes and in the ability to delay defecation and fewer improvements in mean squeeze pressures over time. Leroi offers a fatigue phenomenon of the striated muscle or possibly the conversion of fast-twitch to slow-twitch muscle fibers as possible explanations.

The use of sacral spinal nerve stimulation has given patients with fecal incontinence an option that is minimally invasive and appears to offer significant improvement. This modality is currently limited to those patients who do not have anatomic defects as demonstrated by endoanal ultrasonography. It has been applied to those patients who have undergone overlapping sphincteroplasty but have persistent symptoms. Leroi did include patients with anatomic defects in the external anal sphincter but whose symptoms were not attributed to the defect as determined by physiologic studies. As the number of trials and the number of patients treated increases, the value of this modality, its mechanism, and its long-term benefits will become better known.

BIBLIOGRAPHY

Author: Stephen D Seymour, DO, Chief, Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics and Gynecology, Womack Army Medical Center
Stephen D Seymour, DO, is a member of the following medical societies: American College of Obstetricians and Gynecologists

Editor(s): Jose A Perez, Jr, MD, MSEd, Director of Medical Education, Residency Program Director, Associate Professor, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Kern Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; David Chelmow, MD, Professor, Division of Obstetrics and Gynecology, Program Director, OB/GYN Residency Program, Tufts University School of Medicine; Consulting Staff, Tufts Womens Health Associates, Tufts-New England Medical Center; Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Assumption Community Hospital; and Lee P Shulman, MD, Professor of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University; Chief, Division of Reproductive Genetics, Department of Obstetrics and Gynecology, Prentice Women’s Hospital, Northwestern Memorial Hospital