Review Management of chronic pelvic pain: evidence from randomised controlled trials

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1 Review 2006;8: /toag The Obstetrician & Gynaecologist Review Management of chronic pelvic pain: evidence from randomised controlled trials Authors Ying Cheong / R William Stones Chronic pelvic pain is a common condition in women and rates of consultation in general practice are similar to those for asthma and migraine. USA and UK population-based studies, together with data from UK hospital settings, demonstrate a substantial impact of chronic pelvic pain on health related quality of life. In this review we examine the current evidence for treatment of the condition, focusing on randomised controlled trials and including some insights from studies of women with dysmenorrhoea. Keywords adhesiolysis / chronic pelvic pain / progestogen / randomised controlled trials / ultrasound Please cite this article as: Cheong Y, Stones RW. Management of chronic pelvic pain: evidence from randomised controlled trials. The Obstetrician & Gynaecologist 2006;8: Author details Ying Cheong MRCOG Specialist Registrar Princess Anne Hospital, Southampton SO16 5YA, UK yingcheong@hotmail.com (corresponding author) R William Stones FRCOG Senior Lecturer and Consultant in Obstetrics and Gynaecology University of Southampton, UK 32

2 The Obstetrician & Gynaecologist 2006;8:32 38 Review Introduction Chronic pelvic pain (CPP) is a common condition in women of reproductive age. Current data from the USA and UK suggest that it occurs in 14 24% of women aged between years. 1,2 The differences in estimated prevalence may be due to the design and type of study performed; for example, the use of different definitions of the condition. Most research has, however, used six months as the duration of symptoms to identify CPP. It is a common condition at the population level. Further work has indicated that rates of consultation for CPP in general practice are similar to those for asthma and migraine; it is important to note that consulting rates are actually higher in the postmenopausal age group, which has not been studied as yet at the population level. 2 The USA and UK population-based studies, together with data from UK hospital settings, demonstrate a substantial impact of CPP on health related quality of life. Typical laparoscopic findings in women investigated for CPP are, in increasing order of frequency: adhesions (24%), endometriosis (33%), and no pathology (35%). 3 Patterns of symptoms and received diagnosis in the population-based studies cited above suggest a broad pattern of pathophysiology, with urinary (31%) and gastrointestinal (37%) problems being more common than specifically gynaecological (20%) problems. The spectrum of symptoms and diagnoses reported by these women no doubt reflects the populations studied, the limited diagnostic scope of conventional clinical methods and the different approaches to the management of the condition in the community as opposed to hospital or tertiary centres. More interestingly, up to a third of women with CPP do not consult a physician and of those who do, about 60% will not be referred on to tertiary centres. We do not yet fully understand what precipitates care seeking in women with CPP. It is possible that those women with the condition who do not seek care have less disruptive symptoms, as indicated by better scores for health related quality of life, but there is still a burden of physical and functional impairment among this group. Pathology such as adhesions or endometriosis may not correlate with the site or severity of pain. This discrepancy can be explained in part by the complex neurophysiology of visceral sensation; in other words, sensation arising from the internal organs such as the uterus and ovaries. Normal body sensation can be perceived as painful because of alteration in processing of spinal cord and brain stimuli. 4 Thus, a significant number of women with CPP will not have a definite diagnosis. Explanations for CPP without pathology have included irritable bowel syndrome, which is often present in women referred to gynaecologists for investigation but missed without appropriate history taking. Pelvic congestion syndrome refers to dilated uterine and ovarian veins with reduced venous clearance and is present in a proportion of those in the reproductive age group with CPP. Endometriosis, pelvic inflammatory disease and isolated symptoms of dysmenorrhoea and dyspareunia are outside the scope of this review. The current approaches to treatment of CPP include psychotherapy or counselling, reassurance via laparoscopy, hormonal manipulation using medroxyprogesterone acetate (MPA), surgery to interrupt nerve pathways such as presacral neurectomy and uterosacral nerve ablation, or hysterectomy with or without bilateral oophorectomy. Other novel approaches have included the use of photographic reinforcement after surgery as part of the counselling of women with CPP, use of magnetic field treatment and writing therapy. Although only preliminary data are available for these novel approaches, they merit consideration as treatment options are limited for this often challenging condition. While non-surgical approaches are less physically invasive they are more time consuming and may not always be acceptable to women who desire a rapid resolution of their problem. Surgery carries irreversible consequences and evidence on which to base advice to women about the outcomes is limited. Surgical trials in this area are difficult to conduct and are certainly few and far between. Approaches to the treatment of CPP can also be considered in terms of single specialist versus multidisciplinary management. The latter comprises a team of specialists including a gynaecologist, a clinical psychologist, a physician with a special interest in pain management and specialist nurses to provide care and support (Figure 1). Multidisciplinary management is a common approach to many chronic conditions such as asthma, diabetes and other conditions associated with chronic pain. This type of care is certainly slowly gaining recognition as relevant to the management of women with CPP. However, the limiting factor in setting up such services is often the cost and the availability of interested specialists. There are unresolved health service organisational questions about the appropriate setting of care and referral arrangements. In this review we examine the current evidence for treatment of CPP, focusing on the randomised controlled trials that are available to date. Randomised controlled trials of treatment for CPP There are 13 randomised controlled trials (Table 1) on the management of CPP. Interventions identified as the subject of randomised controlled trials for chronic pelvic pain were: progestogen 33

3 Review 2006;8:32 38 The Obstetrician & Gynaecologist Figure 1 Flow chart of referral and management of women with chronic pelvic pain within the multidisciplinary team setting. Investigations +/- referral to pain team Gynaecologist with special interest in pain management Review 1. Pain physician 2. Psychotherapist for cognitive behavioural therapy 3. Specialist pain nurse 4. Physiotherapist Discharge or shared care with referral GP Chronic or acute admissions General practitioners (MPA) alone or in combination with psychotherapy; goserelin; sertraline; lofexidine hydrochloride; ultrasound scanning as an aid to counselling and reassurance; intravenous dihydroergotamine for acute exacerbations of chronic pelvic pain; and the use of a Polaroid photograph to assist in the woman s postoperative consultation. Other interventions also identified were: writing therapy to improve symptoms; static magnetic fields to improve pain; adhesiolysis via laparoscopy or laparotomy; and a multidisciplinary approach to investigation, including physiotherapy, psychology and attention to dietary and environmental factors. While hormonal therapy aims to achieve benefits in a non-specific manner by inhibiting ovarian activity (based on the observation that many women with CPP experience resolution at the time of the menopause), psychological approaches aim to enhance coping skills and reduce pain-associated distress. Although many of these randomised controlled trials of treatment have robust methodology, the outcomes can be difficult to compare because of the usage of different outcome indicators. Similarly, comparing trials with the same outcome indicators but different methodology quality can also lead to misleading results. In this review we have attempted to compare results from trials that use the same outcome indicators and which have reasonable methodology. It should be emphasised that many conclusions are drawn from a single study; thus, more studies of comparable design are needed in the future. Medical treatment Combining results from the two available studies, progestogen (MPA) was effective at the end of treatment as reflected in pain scores (OR [odds ratio] 2.64, 95% CI , n 5 146) and a selfrating scale (OR 6.81, 95% CI , n 5 44), but benefit was not sustained nine months post treatment. 5,6 MPA plus psychotherapy was effective in terms of pain scores (OR 3.94, 95% CI , n 5 43) but not the self-rating scale at the end of treatment. Farquhar et al. 6 showed an interaction between the effects of MPA and psychotherapy such that the group receiving both interventions did have a sustained benefit nine months post treatment. However, for reasons that are unclear, the placebo alone group had an unexpectedly poor outcome, which makes the overall results more difficult to interpret. In a study of Turkish women, venography scores, symptom and examination scores, mood and sexual function were improved to a greater extent one year after treatment with goserelin compared with progestogen. 7 Weighted mean differences 34

4 The Obstetrician & Gynaecologist 2006;8:32 38 Review Study Number in study Intervention Outcome measurements Results OR (95% CI) Comments Brown 32 Static magnetic fields control: no treatment Duration: 2 4 weeks Engel 25 Sertraline 50 mg twice daily Control: placebo The McGill Pain Questionaire, Pain Disability Index, Clinical Global Impressions Scale Composite pain score SF-36 Duration: 6 weeks Hamilton depression rating scale Farquhar 102 Treatments: medroxyprogesterone acetate (MPA) 50 mg daily VAS pain score Pain improvement rating scale Walton 165 Treatment: medroxyprogesterone acetate 50 mg daily Control: placebo tablets Duration: 4 months Follow-up: only until end of treatment Soysal 47 Goserelin 3.6 mg subcutaneous implant monthly for 6 months versus medroxyprogesterone acetate tablets 30 mg daily for 6 months VAS pain score Pain improvement rating: better/not better Venography score, pelvic symptom and physical examination score (modified from Biberoglu and Behrman), Hospital Anxiety, Depression and Total Scores, revised Sabbatsberg Sexual Rating Scale Ghaly 100 Treatments: ultrasound scan and education/counselling session McGill pain score: at least 5-point improvement Hospital Anxiety Depression Scale: improvement in category (normal, borderline, depressed) Norman 78 The control group wrote about their positive experiences and the study group about their negative experiences of pain and their health status was assessed at the end of 2 months Onwude 233 Intervention: Polaroid photograph of pelvis taken after surgery and shown to patient postoperatively while surgeon explained findings Control: photograph not shown to patient while surgeon explained findings intravenously Peters 106 Treatments: integrated gynaecological surgery n Drug treatment n 5 16 Diet/nutritional advice n 5 22 Physiotherapy n 5 28 Psychosocial n 5 43 Ultrasound scans Control: laparoscopy and psychotherapy Ultrasound scans Duration: 6 months Follow-up: 1 year Reginald 6 Dihydroergotamine 1 mg in 10 ml saline administered over 10 minutes, or saline alone Stones 39 Treatment: lofexidine 200 mg twice daily increasing to 600 mg twice daily (first 3 weeks) Control: placebo tablets Duration: 8 weeks Follow-up: until the end of treatment Peters 48 Treatments: laparotomy adhesiolysis Control: no surgery NS High attrition rate (44%) between 2 and 4 weeks NS Improvement in pain score: 4.16 ( ) Not blinded to psychotherapy NS Note very high drop-out rate in MPA and placebo groups. Published report does not give SD for mean VAS, so data entered in table are the numbers reporting 50% reduction in VAS at completion of the study. This allowed comparison with Farquhar as the drug, dose and duration of therapy are the same. There was no response to requests for more data from investigators and sponsor Improvement in venography score 1.1 ( ) Improvement in pelvic symptom score 3 ( ) Improvement in mood score 4.63 ( ) Improvement in pain score 6.77 ( ) Quality score provisionally A, further info on blinding awaited from investigators. Note no drop-outs McGill Pain Questionaire NS Quality score C because of flawed randomisation methodology (deck of cards) Gynaecological pain questionaire (Stout, et al.), McGill pain score, Pain Beliefs and Perceptions Inventory (PBPI) General pain experience Disturbance of daily activities Associated symptoms McGill score VAS for pain at 4 hours, 8 hours and 2, 3, 4 and 5 days VAS pain score. Subject s self rating of pain as worst, unchanged, somewhat relieved, considerably relieved or completely relieved McGill pain score (Delta) improvement Subjective improvement Duration: 9 to 12 months follow-up Disturbance of daily activities Swank 100 Treatment: laparoscopic adhesiolysis Control: diagnostic laparoscopy only treatment VAS at 3, 6 and 12 months, pain change score, use of analgesics and quality-of-life score NS Intervention group had a trend for greater pain intensity compared to controls. 233 women were entered into the trial compared to the target of 450, so the final comparisons were somewhat different to those originally planned NS See comments Data only entered into data tables for 4, 8 and 48 hours. Results non-significant at 3 and 5 days but significant at 4 days NS Note high drop-out rate in treatment group (9 out of 14 completed 8 weeks of treatment) NS Subgroup analysis showed adhesiolysis beneficial in severe adhesions. OR % CI ( ) NS Study was on abdominal pain rather than pelvic pain. No mention of exclusion of pathology such as endometriosis in female patients. Male and female patients included, although re-analysis using female patients showed no difference in outcome NS 5 non-significant SD 5 standard variation VAS 5 visual analogue scale Table 1 Characteristics of randomised controlled trials in management of chronic pelvic pain 35

5 Review 2006;8:32 38 The Obstetrician & Gynaecologist (95% CI) were: venography 1.1 ( ); symptom score 3 ( ); Hospital Anxiety and Depression Scale (HADS) anxiety score 1 ( ); HADS depression score 0.3 (20.34 to 0.94); HADS total score 1.3 ( ); revised Sabbatsberg Sexual Rating Scale (rssrs) 15.5 ( ). No improvement in pain scores was seen in women taking sertraline compared with placebo. The SF-36 health perception subscale showed a small improvement in the sertraline arm, while the role-functioning emotional subscale showed a large fall in the sertraline arm. 8 Outcomes with lofexidine hydrochloride were no better than for placebo (OR for reduction in pain visual analogue scale 2.5, 95% CI ). 9 Pain scores after dihydroergotamine were reduced up to 48 hours post injection. 10 Multidisciplinary management The use of a multidisciplinary approach led to a positive outcome in a self-rating scale (OR 4.15, 95% CI , n 5 106) and daily activity, but not in pain scores. 11 There are no other randomised controlled trials of treatment examining multidisciplinary care, mainly because individual treatment effects would be difficult to ascertain; thus, in general, trials for the treatment of pelvic pain are aimed at the examination of an individual medical or surgical treatment. The core elements of a multidisciplinary team will include a gynaecologist and physician with a special interest in pain management, a psychologist, a pain clinic nurse and a physiotherapist. Figure 1 shows a typical referral and management flow chart for women referred to the pain team at the Princess Anne Hospital in Southampton. The multidisciplinary package in the UK, even when available, is quite varied but can include cognitive behavioural psychotherapy, nursing support (such as between clinic times where medications need readjusting), and the use of complementary therapy, including acupuncture. In our unit, the team includes: a gynaecologist; a pain physician, who is able to offer pain management advice and nerve blocks where appropriate; a clinical psychologist, who focuses on cognitive behavioural aspects; and a clinic nurse. The main evidence to show that a multidisciplinary team approach works comes from Leiden, in the Netherlands. 11 This randomised controlled trial showed that a multidisciplinary approach is beneficial compared with a conventional approach in terms of improvement of quality of life scores, although the McGill pain scores were not different in the two approaches. The study, however, also suggested a strong functional component in many women with CPP and that this group of women benefited from the integrated multidisciplinary treatment, which included psychotherapy. Indeed, counselling supported by ultrasound scanning was effective both in terms of pain scores (OR 6.77, 95% CI , n 5 90) and mood. 12 There are important questions about the optimal use of this approach as it is time consuming and expensive. Realistically, many women will continue to be seen by a single specialist, emphasising the need for relevant CPP skills in gynaecological specialist training. Surgical treatment Adhesiolysis The outcome in women undergoing adhesiolysis via laparotomy 13,14 was the same as in women who did not undergo surgery on any outcome measure (OR 1.54, 95% CI , n 5 148). However, the small subgroup with severe adhesions did show a significant benefit for surgery (OR for self-rating scale 16.59, 95% CI , n 5 15). Adhesiolysis was performed via laparotomy in the study by Peters et al. 14 in contrast with that by Swank et al, 13 in which adhesiolysis was performed via laparoscopy. Theoretically, laparotomy could result in more adhesions compared with laparoscopy, thus making the two studies incomparable. Moreover, Swank et al. 13 performed surgery on patients (88% women and 12% men) with abdominal pain in contrast with Peters et al., 14 in which only women with CPP were included. Our conclusions should be interpreted with caution given that the pathophysiology of abdominal and pelvic pain may differ between men and women and the presence of gynaecological conditions such as endometriosis or pelvic inflammatory disease could, if left untreated, give rise to persistent pain. Thus, there is still uncertainty about the place of adhesiolysis among women presenting to gynaecologists and the conclusion of this review is that there is no evidence of benefit rather than evidence of no benefit. Two possible conclusions can be drawn: that further large trials of adhesiolysis recruiting gynaecology patients should be undertaken to provide the necessary level of evidence, or that, given the uncertainties about pathophysiology, clinical subgroups such as those with adhesions involving the ovaries, and the influence on outcomes of psychological and sociocultural variables, should be examined. Researchers should also concentrate on careful observational studies including full psychological assessment of participants, laboratory characterisation of adhesion tissues and physiological investigation of intraperitoneal inflammatory and nociceptive processes. 36

6 The Obstetrician & Gynaecologist 2006;8:32 38 Review Disruption of sensory pathways Presacral neurectomy (PSN) and laparoscopic uterine nerve ablation (LUNA) are both surgical procedures that involve the disruption of sensory nerve afferents that carry pain stimuli from the pelvis. In the LUNA procedure, the uterosacral ligaments are transected close to their insertion at the cervix, thus interrupting the Lee- Frankenhauser nerve plexus. In PSN, the presacral nerve plexus is isolated and cut proximally and distally. Complications associated with LUNA are rare; there have been isolated cases of uterine prolapse and bladder dysfunction, while PSN has been associated with more serious complications such as haematoma formation and major vessel injury, as well as constipation and bladder dysfunction, although, again, these complications are rare in experienced hands. Many uncontrolled studies have claimed that LUNA and PSN are effective for primary and secondary dysmenorrhoea. 15,16 Wilson et al. 17 reported some evidence of effectiveness of LUNA in the treatment of primary dysmenorrhoea when compared with controls; this result is largely derived from one small trial 18 in which the sample size was 21 and the allocation of randomisation was sequential, hence the results should be treated with caution. There is also a large decrease in the effectiveness of LUNA for dysmenorrhoea over time, suggesting a large placebo effect in the initial period. A multi-centre study examining the effectiveness of LUNA in CPP is underway. 19 Short term results for PSN and LUNA for dysmenorrhoea seem to be similar, although PSN has better results in the long term as suggested by the single trial comparing the two. 20 This trial showed no difference in the treatment groups up to six months (OR 0.7, 95% CI ) although when responses were assessed at 12 months, PSN appeared to be more effective. Other therapies Static magnetic therapy The effects of static magnetic therapy versus placebo 21 were analysed using the Wilcoxon rank sum test. The results showed no difference following two weeks of treatment. However, there were statistically significant differences with four weeks of treatment as assessed by the Pain Disability Index and the Clinical Global Impression Scale, but not the McGill Pain Questionnaire. For consistency, in this review we present the outcomes in terms of weighted mean differences, which show no significant differences. It is, however, important to note that in this study there was a high drop-out rate from the two week follow-up to the four week follow-up period (41% attrition rate). Photographic reinforcement Photographic reinforcement after surgery does not appear to have any beneficial effect. 22 Unfortunately, the intervention group had a trend for greater pain intensity compared with the controls, which may have confounded any possible beneficial effects of photographic reinforcement. Moreover, 233 women were entered into the trial, compared with the target of 450, so the final comparisons were somewhat different to those originally planned. Writing therapy The aim of this intervention is to allow patients to identify and express the thoughts and feelings associated with their pain as a means of reducing its impact. The main effects of writing about the stress of pelvic pain were limited; 23 the weighted mean differences (95% CI) on the various subcategories of McGill Pain Questionnaire were: sensory pain 0.07 (20.31 to 0.45), affective pain (20.42 to 0.18) and evaluation pain (21.96 to 20.36). Women with higher baseline ambivalence about emotional expression appear to respond more positively to this intervention, thus showing a subgroup who may benefit specifically from this type of psychological approach. Conclusion The information currently available about the treatment of women with chronic pelvic pain provides some support for the use of ultrasound scanning as an aid to counselling and reassurance, progestogen (MPA) or goserelin for pelvic congestion and (with the aim of improved function and self-rating) a multidisciplinary approach to assessment and treatment. Adhesiolysis is not shown to be of benefit other than in women with severe adhesions. Short-term results for PSN and LUNA seem to be similar, although PSN has better results in the long term. Selective serotonin reuptake inhibitors (SSRIs) have not been shown to be of benefit. Most of these conclusions are based on the outcome of single randomised trials and need replication. Writing therapy may have a place as part of a multidisciplinary programme. Areas of future research This review has shown that a limited range of interventions has been tested for the treatment of women with chronic pelvic pain, and that only single studies have been undertaken on most of these interventions, which greatly limits the available evidence on which clinical practice can be based. Further work is required to confirm the findings of existing studies. Given the prevalence and healthcare costs associated with chronic pelvic pain in women, randomised controlled trials of 37

7 Review 2006;8:32 38 The Obstetrician & Gynaecologist other medical, surgical and psychological interventions are required. As causation and treatment of chronic pelvic pain is often complex, the design of research studies needs adequately to integrate baseline psychological and clinical assessment. Studies currently needed include trials of radiological embolisation versus surgery for pelvic congestion, assessment of the value of neuropathic pain medications, and formal comparisons of outcomes from different packages of care. References 1 Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege RF. Chronic pelvic pain: prevalence, health related quality of life, and economic correlates. Obstet Gynecol 1996;87: Zondervan KT, Yudkin PL, Vessey MP, Jenkinson CP, Dawes MG, Barlow DH, et al. The community prevalence of chronic pelvic pain in women with associated illness behaviour. Br J Gen Pract 2001;51: Howard FM. The role of laparoscopy in chronic pelvic pain: promise and pitfalls. Obstet Gynecol Survey 1993;48: Grace VM. Mind/body dualism in medicine: The case of chronic pelvic pain without organic pathology: a critical review of the literature. Int J Health Serv 1998;28: Walton SM, Batra HK. The use of medroxyprogesterone acetate 50 mg in the treatment of painful pelvic conditions: preliminary results from a multicentre trial. J Obstet Gynaecol 1992;12(Suppl):S Farquhar CM, Rogers V, Franks S, Pearce S, Wadsworth J, Beard RW. A randomised controlled trial of medroxyprogesterone acetate and psychotherapy for the treatment of pelvic congestion. BJOG 1989;96: Soysal ME, Soysal S, Vicdan K, Ozer S. A randomized controlled trial of goserelin and medroxyprogesterone acetate in the treatment of pelvic congestion. Hum Reprod 2001;16: Engel CC Jr, Walker EA, Engel AL, Bullis J, Armstrong A. A randomised, double-blind crossover trial of sertraline in women with chronic pelvic pain. J Psychosom Res 1998;44: Stones RW, Bradbury L, Anderson D. Randomized placebo controlled trial of lofexidine hydrochloride for chronic pelvic pain in women. Hum Reprod 2001;16: Reginald PW, Beard RW, Kooner JS, Mathias CJ, Samarage SU, Sutherland IA, et al. Intravenous dihydroergotamine to relieve pelvic congestion with pain in young women. Lancet 1987;2: Peters AA, van Dorst E, Jellis B, van Zuuren E, Hermans J, Trimbos JB. A randomized clinical trial to compare two different approaches in women with chronic pelvic pain. Obstet Gynecol 1991;77: Ghaly AF. The psychological and physical benefits of pelvic ultrasonography in patients with chronic pelvic pain and negative laparoscopy. A random allocation trial. J Obstet Gynaecol 1994;14: Swank DJ, Swank-Bordewijk SC, Hop WC, van Erp WF, Janssen IM, Bonjer HJ, et al. Laparoscopic adhesiolysis in patients with chronic abdominal pain: a blinded randomised controlled multi-centre trial. Lancet 2003;361: Peters AA, Trimbos-Kemper GC, Admiraal C, Trimbos JB. A randomized clinical trial on the benefit of adhesiolysis in patients with intraperitoneal adhesions and chronic pelvic pain. BJOG 1992;99: Ewen SP, Sutton CJG. A combined approach to painful heavy periods: laparoscopic laser uterine nerve ablation and endometrial resection. Gynaecol Endosc 1994;3: Perez JJ. Laparoscopic presacral neurectomy. Results of the first 25 cases. J Reprod Med 1990;35: Wilson ML, Farquhar CM, Sinclair OJ, Johnson NP. Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 2000;CD Lichten EM, Bombard J. Surgical treatment of primary dysmenorrhea with laparoscopic uterine nerve ablation. J Reprod Med 1987;32: The LUNA Trial Collaboration. A randomised controlled trial to assess the efficacy of Laparoscopic Uterosacral Nerve Ablation (LUNA) in the treatment of chronic pelvic pain: The trial protocol. BMC Women s Health 2003;3:6. [ 20 Chen FP, Chang SD, Chu KK, Soong YK. Comparison of laparoscopic presacral neurectomy and laparoscopic uterine nerve ablation for primary dysmenorrhea. J Reprod Med 1996;41: Brown CS, Ling FW, Wan JY, Pilla AA. Efficacy of static magnetic field therapy in chronic pelvic pain: A double-blind study. Am J Obstet Gynecol 2002;187: Onwude JL, Thornton JG, Morley S, Lilleyman J, Currie I, Lilford RJ. A randomised trial of photographic reinforcement during postoperative counselling after diagnostic laparoscopy for pelvic pain. Eur J Obstet Gynecol Reprod Biol 2004;112: Norman SA, Lumley MA, Dooley JA, Diamond MP. For whom does it work? Moderators of the effects of written emotional disclosure in a randomised trial among women with chronic pelvic pain. Psychosom Med 2004;66: