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In the name of GOD the beneficent, the merciful. Early and late proctologic complications of delivery prevention and treatment.

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Presentation on theme: "In the name of GOD the beneficent, the merciful. Early and late proctologic complications of delivery prevention and treatment."— Presentation transcript:

1 In the name of GOD the beneficent, the merciful

2 Early and late proctologic complications of delivery prevention and treatment

3 The earliest evidence of severe perineal injury mummy of Henhenit, 22 yrs old Egyptian woman with rupture of the vagina into the bladder and the lower bowel was found protruding from the anus.

4 Childbirth Predisposing factors Tissue DamageNerve Injury Pelvic Floor Disorder Ageing Promoting Factors Obstetrical injury Obesity Menopause Smoking Caucasian race

5 PF Muscle Stretch during Labour During 2 nd stage the PF muscles stretch x 2-3 of their length Maximal stretch tolerated by nonpregnant animal muscle tissue = 1.5

6 Perineal problems Perineal pain, perineal haematoma, perineal wound Infection Bowel problems Anal Fissure, haemorrhoids, constipation Pelvic Organ Prolapse Cystocele, uterine prolapse. Enetrocele, rectocele, rectal mucosal or complete prolapse, descent of PF Incontinence Urinary, fecal (gas, liquid or solid stools) Recto-vaginal Fistula Sequelae of Childbirth

7 Pelvic Organ Prolapse Injury to the pelvic floor during childbirth number of vaginal deliveries macrosomic infant O’Boyle et al: the POPQ stage signifcantly higher in the third than in the first trimester Associated co-Risk factors defective collagen race advancing age Hysterectomy chronic raised intra-abdominal pressure

8 Childbirth and Pelvic Organ Prolapse Women’s Health Initiative: single childbirth associated with raised odds of: – Uterine prolapse (odds ratio 2.1; 95% CI 1.7–2.7) – Cystocoele (2.2; 1.8–2.7) – Rectocele (1.9; 1.7–2.2) Every additional delivery increased the risk of worsening prolapse by 10–20% (Hendrix, Am J Obstet Gynecol 2002).

9 Obstructed Defecation Alterations of anatomic morphology

10 Obstructed Defecation Syndrome Obstructed Defecation Syndrome (ODS) is defined as the normal desire to defecate, but an impaired ability to satisfactory evacuate the rectum

11 Causes of ODS 1.Descent (pelvic floor) 2.Rectocele 3.Internal mucosal prolapse 4.Intususception (recto-rectal/recto-anal) 5.Complete prolapse 6.Paradox puborectalis 7.SRU 8.Puborectalis insufficiency 9.Enterocele 10.Sigmoidocele 11.Genital Prolapse

12 Mechanical Outlet Obstruction - Dissipation of Force Vectore rectocele, descent - Causes Lying inside the Rectum Intussusception, mucosal or complete prolapse Functional Outlet Obstruction Dyssynergia Impaired Rectal Filling Sensation megarectum, Hirshprung Principal pathological Mechanisms Obstructed Defecation

13 Dissipation of Force Vector RectoceleDescent

14 Causes Lying Inside the Rectum Rectal intussusception Mucosal prolapse Complete rectal Prolapse Mechanical

15 Anatomical Rectal redundancy Rectocele Rectal prolapse Rectal mucosal prolapse Intussusception Complex Situations Rectocele ± intussusception ± descent ± rectal prolapse ± enterocele ± sigmoidocele ± urogenital prolapses

16 Symptoms Straining too much and repeatedly Long standing in toilet Frequent calls to defecate Assisted defecation Incomplete evacuation Fragmeted defecation Pelvic pressure Rectal discomfort Perineal pain Laxative or enema user Lack of continence Mucorrea Worsen Quality of Life

17 Treatment Options Non surgical Biofeedback Diet Exercise Behavioural therapy Surgical Abdominal approach (rectopexy ± sigmoidectomy, colpopexy, LAR) Vaginal approach (posterior coloporrhaphy) Perineal/Transanal approach (Altemeir, Delorme, Sleeve mucosal resection, Starr, Transtarr) SNS

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22 Anal sphincter rupture is highly associated with fecal incontinence

23 85% perineal trauma 69% stitches McCandlish R et al, Br J Obstet Gynaecol 1998

24 Anal sphincter defects occur at first delivery Primips: Before 0% After 35% Multips: Before 40% After 44% Incontinence associated with defect: p= % with defects had postpartum incontinence Sultan et al. NEJM 325:1905;1993 Fecal Incontinence and Parturition

25 Childbirth & Fecal Incontinence 259 consecutive women delivered single unit 31 elective CS no FI Primaparous delivered vaginally 13% FI Abromowitz Dis Colon Rectum prospective fecal urgency vag 7.3% vs CS 3.1% Chaliha 99 Obstet Gyn

26 Anal Endosonography before and after Delivery in a Primiparous Woman with a Postpartum Defect of the External Anal Sphincter Abdul H. Sultan et al, NEJM, 1993

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28 MRI defects in parous womnen Unilateral

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30 1. First degree, superficial – skin and subcutaneous tissue – vaginal mucosa – combination of the (multiple superficial lacerations) 2. Second degree, deeper – superficial perineal muscles (B. spongiosus, T. perineal) – perineal body. less trauma next deliver less pain and infection the wound heals faster vaginal birth Suture or not suture unacceptable aesthetics Impaired sexual function Impaired PF muscle strength Incontinence and prolapse

31 Inadequate anatomy trainingIdentifying 3 rd degree tears Doctors91%60% Midwives84%61%. Sultan et al. NEJM, 1993

32 Intact anal sphincter

33 Partial tear in EAS

34 Buttonhole tear of rectal mucosa with an intact EAS

35 Traditional 3 Layer Suturing Continuous suturing technique

36 Endo to end Overlap

37  Repair of third and fourth degree tears End– to – end or overlap repair?

38 Internal sphincter repair

39 Postoperative management  Antibiotics  Bladder catheterisation  Analgesia  Stool softener  Patient information

40 Sphincter rupture rate No episiotomy: % Episiotomy: % Thacker. Ob Gyn Survey 38:332;1983 Zetterstrom. Obstet Gynecol 94:21;1999 Hartmann K et al. JAMA 293(17):2141-8;2005 Fitzgerald for PFDN, Obstet Gynecol 109:29;2007 Midline episiotomy is highly associated with anal sphincter rupture

41 Sphincteric Rupture Odds Ratio (p value) Forceps delivery6.7 (p<0.001) Episiotomy3.3 (p<0.001) OP position 2.4 (p=0.002) Vacuum delivery 2.3 (p=0.001) Fitzgerald MP for PFDN, Obstet Gynecol 109:29;2007 Operative delivery is associated with sphincter rupture

42 What Is Recommended Practice?

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44 Planned Caesarean vs. Planned Vaginal Birth Exercise in Pregnancy Antenatal Pelvic Massage Position during Labor and Birth Epidural vs. Narcotics Pain Relief Early vs. Delayed Pushing Second stage pushing advice Spontaneous vs. Forceps birth Water Birth Interventions to Prevent Obstetrical Perineal Trauma

45 Asymptomatic Women Asymptomatic women who have minimal compromise of their anal sphincter function (satisfactory pressure measurements and ultrasound images) should be allowed to have a vaginal delivery. These women should be counselled that they have a 95% chance of not sustaining recurrent OASIS 9 or developing de novo anal incontinence following delivery. 68 However, the delivery should be conducted by an experienced doctor or midwife.If an episiotomy is considered necessary, e.g. because of a thick inelastic or scarred perineum,a mediolateral episiotomy should be performed.There is no evidence that routine episiotomies prevent recurrence of OASIS. The threshold at which these women may be considered for a CS may be lowered if a traumatic delivery is anticipated, e.g. in the presence of one or more additional relative risk factors such as a big baby, shoulder dystocia, prolonged labour, diffi cult instrumental delivery. However,

46 All symptomatic women are first treated conservatively symptomatic women Conservative management of anal incontinence is described in detail in Chapter 11 and is summarised as follows: All women are included in the biofeedback programme (Chapter 11). If muscle contractility is weak or absent, electrical muscle stimulation is commenced. Women with flatus incontinence are given dietary advice, especially the avoidance of gasproducing foods such as legumes. Women with faecal incontinence are commenced on a low residue diet and constipating agents such as loperamide can be used.

47 Women whose symptoms are adequately controlled by conservative measures are offered CS in any subsequent delivery so as to minimise the risk of further compromise to anal sphincter function. Women with faecal incontinence in whom conservative measures have failed should be offered anal sphincter surgery (Chapter 12A), while others may need advanced surgical techniques as described in Chapter 12B. All women who have undergone successful incontinence surgery should be delivered by CS. A management dilemma arises in women who suffer from faecal incontinence but who wish further pregnancies. These women could avoid a CS and undergo a vaginal delivery followed by a secondary sphincter repair at a later date. The only rationale behind this is that most of the damage that occurs during childbirth occurs with the first vaginal delivery 68,70 and therefore the risk of further damage during a subsequent vaginal delivery is relatively small. However, there is a potentially unquantifi ed risk of deteriorating pudendal neuropathy.

48 The Effect of Pregnancy Hormones on Connective Tissue Connective tissue in the area of the urogenital organs is sensitive to hormones. During pregnancy, collagen is depolymerized by placental hormones, and the ratios of the glycosaminoglycans change. (The term ‘proteoglycans’ is used here interchangeably with ‘glycosaminoglycans’.) The vaginal membrane becomes more distensile, allowing dilatation of the birth canal during delivery. There is a concomitant loss of structural strength in the suspensory ligaments. This explains the uterovaginal prolapse so often seen during pregnancy. Laxity in the hammock may remove the elastic closure force, causing urine loss on effort. This condition is described as stress incontinence. Loss of membranous support may cause gravity to stimulate the nerve endings (N) at the bladder base, so causing premature activation of the micturition reflex, expressed as symptoms of ‘bladder instability’. This condition is perceived by the pregnant patient as frequency, urgency and nocturia. Laxity may also cause pelvic pain, due to loss of structural support for the unmyelinated nerve fibres contained in the posterior ligaments. The action of gravity on these nerves causes a ‘dragging’ pain. Removal of the placenta restores connective tissue

49 Following the advent of endoanal ultrasound (see Chapter 10), Sultan et al. 14 demonstrated that 33% of women sustained “occult” OASIS that were not identifi ed at delivery (see Chapter 8 for pathophysiology). Prospective studies 11 have identifi ed “occult” injuries ranging between and 41%. occult or in fact unrecognised at delivery. It was alarming to find that 87% and 27% of OASIS were not identified by midwives and doctors respectively.

50 Lal et al. 20 showed that signifi cantly more women develop anal incontinence following a second degree tear than with an intact perineum (23% vs 3%, P = 0.01). Benifl a et al. 21 identifi ed a 16-fold increase in anal incontinence following a second degree tear (P < 0.05). Both these studies support the fi ndings of Andrews et al. that a large number of OASIS were undiagnosed and wrongly classifi ed as second degree tears.

51 Faltin et al. 22 randomised 752 primiparous women with second degree lacerations to conventional examination (control group) and additional postpartum endoanal ultrasound (experimental group) and demonstrated that a considerable number of women have full-thickness OASIS that are not recognised at delivery. However, they excluded partial-thickness sphincter tears from their study. On identifying new injuries in the experimental group, a formal sphincter repair was performed. Overall, severe faecal incontinence was signifi cantly reduced from 8.7% in the control group to 3.3% in the experimental group.

52 The morbidity associated with perineal injury related to childbirth constitutes a major health problem, affecting millions of women worldwide. In the UK, up to 44% of women will continue to have pain and discomfort for 10 days following birth 3 and 10% of women will continue to have long-term pain at 18 months postpartum. 4 Furthermore, 23% of women will experience superfi - cial dyspareunia at 3 months postpartum; 5 up to 10% will report faecal incontinence 6 and approximately 19% will have urinary problems. 7 The rates of complications reported by women depend on the severity of perineal trauma

53 A treatment during pregnancy is usually limited to emergency care, consisting of palliation for symptomatic prolapsing internal hemorrhoids, temporizing sclerosing injections for bleed ing hemorrhoids, incision and expression of painful external anal thromboses and drainage for the rela tively uncommon perianal abscess.

54 The first description of rectal prolapse is said to be in the Ebers papyrus 1500 BC. The first treatment as outlined by Hippocrates involved hanging patients by their heels and shaking them. 10 Obviously, this was rarely successful in the long term.The true incidence of rectal prolapse (mucosal or complete) is unknown mostly because of underreporting. It is associated with long-standing constipation, chronic straining, pregnancy, prior surgery, female gender, aging, neurologic disease, mental illness (up to 53% in a study by Vongsangnak et al.), and other pelvic floor disorders. 11,12

55 Obstetric trauma is the most important etiologic factor in the pathogenesis of fecal incontinence in women. There is evidence that hormonal changes during pregnancy lead to smooth muscle relaxation attributed to progesterone. Relaxin is an ovarian hormone that peaks late during pregnancy and leads to connective tissue remodeling in the pelvic floor. 23 With parturition, there is stretching of the levators, stretching and tearing of the rectovaginal septum, stretching of the vaginal wall, and compression of the pudendal nerves against the pelvic side wall. All these factors may contribute to fecal incontinence. A published study by Sultan et al. 24 revealed anal sphincter defects in 30% to 40% of asymptomatic postpartum females. Fortunately, the minority of these patients were symptomatic (32%). However, these patients may become symptomatic later in life or with subsequent vaginal deliveries. In addition, pudendal nerve injury documented by electromyography has been demonstrated in 42% of postpartum females by Snooks et al. 25,26 Sixty percent of these patients recovered nerve function 2 months after delivery, but 40% did not. Four percent of 906 postpartum women in a study by MacArthur et al. 27 reported new symptoms of incontinence after childbirth. Sultan et al. 28 showed a 1% incidence of frank fecal incontinence and a 25% incidence of decreased flatal control at 9 months’ follow-up after vaginal delivery.

56 The incidence of sphincter injury is higher in patients with perineal tears. Up to 25% of patients developed fecal incontinence symptoms after a third degree tear in a study by Wood et al. 29 Third degree tears, involving the sphincter muscle, occur in approximately 0.6% of all vaginal deliveries. Episiotomies, similar to tears, are associated with incontinence. Sultan et al. 31 found episiotomy to be associated with an increased risk of sphincter injury. Signorello et al. 33 showed a threefold increase in fecal incontinence after midline episiotomy as compared with spontaneous laceration; therefore, a mediolateral episiotomy is recommended 3

57 Perineal pain is a common symptom following vaginal delivery, regardless of the presence of perineal trauma. However, the severity of perineal pain is directly proportional to the severity of perineal trauma. 5,15 Perineal pain occurs in 42% of women immediately after delivery but signifi cantly reduces to 22% and 10% at 8 and 12 weeks respectively. Compared to a normal delivery, perineal pain occurs more frequently and persists for a longer period after assisted delivery (forceps, vacuum delivery, vaginal breech delivery).

58 Perineal Pain Soft tissue trauma (regardeless of suturing) Asceptic technique Poor surgical techniques Inflammation

59 Perineal Pain Often associated with dyspareunia Systemic Treatment Local Treatment Ice packs Sit baths Local anestetics Hydrocortisone 1% Antenatale perineal massage Paracetamole NSAIDS Rectal supp

60 Perineal Pain Local Treatment

61 Perineal Haematoma 1 : 500 and 1 : 900 vaginal deliveries. infralevator (vulval, perineal,vaginal) supralevator (in the broad ligament or paravaginal area) frequently after an episiotomy But about 20% of cases in apparently intact perineum A supralevator haematoma forms in the broad ligament and could be due to an extension of a tear of the cervix, vaginal fornix or uterus. swelling pain, restlessness, inability to pass urine rectal tenesmus within a few hours after delivery Shock in sopraelevator hematomas

62 Perineal Haematoma If < 5 cm Ice packing Pressure Analgesics If > 5 cm expanding Incision & drainage Infraelevator sopraelevator Conservative with transfusions Evacuation of clots and packing for 24 hrs Embolising the bleeding vessel

63 Anal Fissure Anal fissure is an ulcer in the squamous epithelium of the anus located just distal to the mucocutaneous junction; In a prospective study before and after delivery of 163 consecutive women (84 primiparous), Abramowitz et al.37 reported anal fi ssures in 15% during the fi rst 2 months postpartum.

64 Anal Fissure Risk factors dyschezia (painful defaecation), heavier babies, long second stage of labour, Anal incontinence after delivery, primiparity, forceps deliveries perineal damage Caesarean section did not appear to be protective against anal fissure

65 Anal Fissure Pain sorness during defecations Visual examination of anal margine Small ulcer at the level of mucocutaneous junction Treatment Relief of constipation diet fiber sit baths stool softeners Medicaltherapy local analgesics GTN Botulinium toxin

66 Management of Anal Fissure pregnancy and postpartum Anal fissures in postpartum are associated with low pressure resting tone

67 Haemorrhoids Risk factors straining at defaecation constipation, vascular enlargement due to increased intra-abdominal pressure erect posture heredity

68 Haemorrhoids Effect of Pregnancy Smooth muscle inhibition high levels of circulating progesterone mechanical obstruction by the gravid uterus Constipation

69 Increased blood volume by 25–40% Venous engorgement and dilatation Haemorrhoids Effect of Pregnancy

70 Haemorrhoids Risk factors include heavier baby long second stage of labour vaginal delivery instrumental delivery

71 In an observational study of 11,701 women, MacArthur et al.2 found that 8% reported haemorrhoids of more than 6 weeks’ duration for the fi rst time within 3 months of birth and an additional 10% reported these as ongoing or recurrent symptoms. Two thirds reported the presence of haemorrhoids 1–9 years after delivery. Glazener et al.1 found that 17% of postnatal women reported haemorrhoids (new and recurrent) when questioned in hospital, 22% between delivery and 8 weeks postpartum and 15% after 2 months.

72 intermittent bleeding (most common symptom) burning sensation itching Intermittent bleeding of the anus varying degrees of leakage of mucus, faeces or flatus sensation of fullness or a lump perianal hygienic problems discomfort and/or pain Compromission of the quality of life affecting the activities of everyday life walking sitting down emptying bowels sleeping caring for the family or a new baby Assessment include anoscopy digital examination

73 Treatment Haemorrhoids during pregnancy relief of symptoms, especially pain control Often symptoms will resolve spontaneously after birth, and so any corrective treatment is usually deferred to some time after birth. Complications of haemorrhoids acute thrombosis incarceration of prolapsed internal haemorrhoid Aggressive treatment such as closed excisional haemorrhoidectomy under local anaesthetic.

74 Treatment Haemorrhoids during pregnancy Conservative Management dietary modifications high fibre intake, high liquid intake, stool softeners stimulants or depressants of the bowel transit local treatments sitz baths, creams, ointments or suppositories containing anaesthetics, antiinflammatory drugs, steroids, etc., alone or incombination drugs of the flavonoid family such as rutosides that cause decreased capillary fragility

75 Treatment Haemorrhoids during pregnancy Alternative Management in severe and non-responsive cases ambulatory interventions that usually do not need anaesthetics, such as: injection sclerotherapy, rubber-band ligation cryotherapy, infrared photocoagulation, laser therapy Injection sclerotherapy has been used effectively during pregnancy. 86% of antenatal patients (24 of 28) became asymptomatic by means of injection of 5% phenol in almond oil.

76 Treatment Haemorrhoids during pregnancy excision surgery stapled anopexy no known trials that have specifically evaluated treatments for severe haemorrhoids during pregnancy and the postpartumperiod.

77 Planned Caesarean vs. Planned Vaginal Birth Exercise in Pregnancy Antenatal Pelvic Massage Position during Labor and Birth Epidural vs. Narcotics Pain Relief Early vs. Delayed Pushing Second stage pushing advice Spontaneous vs. Forceps birth Water Birth Interventions to Prevent Obstetrical Perineal Trauma

78 Routine Episiotomy to Prevent a Tear What Type of Episiotomy is Safest Vacuum vs. Forceps PerinealSupport: Hand on vs. Hand poised

79 85% of women who have a vaginal birth will sustain some form of perineal trauma and up to 69% of these will require stitches. Spontaneous or surgical McCandlish R et al, Br J Obstet Gynaecol 1998; 1. First degree, superficial – skin and subcutaneous tissue of the anterior or posterior perineum – vaginal mucosa – combination of the above resulting in multiple superficial lacerations 2. Second degree, deeper – superficial perineal muscles (bulbospongiosus, transverse perineal) – perineal body. Suture or not suture Not suture: less trauma next delivery, less pain and infection, the wound heals faster unacceptable aesthetics, sexual function, pelvic floor muscle strength incontinence and prolapse

80 four European and one UK RCTs (n = 1,864 primiparous and multiparous women) continuous subcuticular technique of perineal skin closure, when compared to interrupted transcutaneous stitches, was associated with less perineal pain Kettle C et al, The Cochrane Library, Issue 3. Oxford: Update Software, Suture materia wound closure, control bleeding, minimise the risk of infection and expedite healing, minimal tissue reaction and be absorbed once the wound has healed

81 The first mention of the surgical management of severe perineal injury appears in Avicenna’s famous Arabic book, Al Kanoun. He recommended a form of a crossed or bootlace suture for the repairs of perineal injuries. However, success rates with primary wound union of perineal wounds reported in the late 1800s were in the region of 50–60%. However, in 1999, Sultan et al, described the overlap technique of primary repair of the EAS (described by Parks previously for secondary sphincter repair). In addition, Sultan et al, highlighted the importance of separate repair of the freshly torn internal anal sphincter (IAS), responsible for maintaining the resting tone of the anal sphincter. Damage to the IAS is associated with incontinence to gas and passive soiling

82 The prevalence of third and fourth degree tears, collectively referred to as obstetric anal sphincter injuries (OASIS), appears to be dependent upon the type of episiotomy practised. In centres where mediolateral episiotomies are practised, the rate of OASIS is 1.7% (2.9% in primiparae) 9 compared to 12% 10 (19% in primiparae) 11 in centres practising midline episiotomy.

83 Thirty-five studies over a 20 yr with follow-up ranging from 1 to 30 mons: Gas incontinence ranges between 15–61% (n = 35; mean = 39%) Faecal incontinence ranges between 2–29% (n = 25; mean = 14%) End-to-end repair

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85 Thirty-five studies over a 20 yr with follow-up ranging from 1 to 30 mons: following end-to-end repair Gas incontinence ranges between 15–61% (n = 35; mean = 39%) Faecal incontinence ranges between 2–29% (n = 25; mean = 14%)

86 Risk factors third/fourth degree tear Forceps delivery first vaginal delivery large baby shoulder dystocia persistent occipito-posterior position

87 Metanalysis of 21 studies, with good results ranging from 74% to 100% Jorge and Wexner et al, Dis Colon Rectum, patients with faecal incontinence good clinical outcome in 80% at 15 months. Engel et al. Br J Surg 1994 overlap technique Malouf AJ et al. Long-term results of overlapping anterior anal-sphincter repair for obstetric trauma. Lancet 2000;355(9200):260–5. Sultan et al, compared to matched historical controls who had an end-to-end repair, anal incontinence could be reduced from 41% to 8% using the overlap technique and separate repair of the internal sphincter Br J Obstet Gynaecol 1999;106:318–23.

88 Kairaluoma et al. Dis Colon Rectum 2004, 31 consecutive women who sustained OASIS (3b and fourth degree). All had an EAS overlap repair immediately after delivery performed by two colorectal surgeons. In addition to end-to-end repair of the IAS, they also performed a levatorplasty to approximate the levators in the midline with two sutures. At a median follow-up of 2 years, 23% complained of anal incontinence, 23% developed wound infection, 27% complained of dyspareunia and one developed a rectovaginal fi stula. Levatorplasty therefore should be avoided during primary anal sphincter repair.

89 Poen et al. 29 identifi ed 43 women (out of original cohort of 117) who had subsequent vaginal deliveries following previous OASIS. The rate of anal incontinence was 56% compared to 34% in those who did not subsequently deliver (relative risk 1.6; 95% confi dence interval 1.1– Sangalli et al. 14 studied 177 women some 13 years after OASIS (48 fourth degree tears). Anal incontinence was signifi cantly more common in women who had sustained fourth degree tears compared with those with third degree tears (25 vs 11.5%; P = 0.049). Unlike women with previous fourth degree tears, those who had sustained a previous third degree tear did not demonstrate an increase in anal incontinence symptoms after a subsequent vaginal delivery. This is in keeping with the fi ndings of Fenner et al., 25 who found that the symptom of worse bowel control was 10 times higher in women who sustained fourth as opposed to third degree tears. This could be attributed to persistent injury of the IAS.

90 Incontinence when stoma 1.When there is a cloacal injury. Some injuries are so extensive that the anterior half of the anus and the lower third of the vagina are one common cavity. 2. When there is an associated rectovaginal fistula. Fistulas to the vagina can be extremely hard to treat; 3. In the presence of Crohn’s disease or prior radiation therapy.


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