Study inclusion and data collection
Trials and patients
Effectiveness of LUNA on relieving pain
Strengths and limitations of the review
Individual patient data meta-analysis
of randomized evidence to assess
the effectiveness of laparoscopic
uterosacral nerve ablation in chronic
J.P.Daniels1,2,*, L.Middleton2, T.Xiong3, R.Champaneria1,
N.P.Johnson4, E.M.Lichten5, C.Sutton6, P.Vercellini7, R.Gray2,
R.K.Hills8, K.D.Jones9, G.Aimi7, and K.S.Khan1as the International
LUNA IPD Meta-analysis Collaborative Group
1University of Birmingham, Birmingham Women’s Hospital, Edgbaston, Birmingham B15 2TG, UK2Birmingham Clinical Trials Unit, University
of Birmingham, Robert Aitken Institute, Birmingham B15 2RR, UK3School of Medicine, Health Policy and Practice, University of East Anglia,
Norwich NR4 7TJ, UK4Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand5Hutzel Hospital, 540
Henrietta Street, Birmingham, MI 48009, USA6Faculty of Health Sciences, University of Surrey, Guildford GU2 7TE, UK7First Department of
Obstetrics and Gynaecology, University of Milan, Via Commenda 12, 20122 Milan, Italy8Department of Haematology, Cardiff University,
Cardiff CF14 4XN, UK9Great Western Hospital, Marlborough Road, Swindon SN3 6BB, UK
*Correspondence address. Jane Daniels Academic Department of Obstetrics & Gynaecology, University of Birmingham, Birmingham
Women’s Hospital, Metchley Park Road, Birmingham B15 2TT, UK. E-mail: firstname.lastname@example.org
Submitted on November 30, 2009; resubmitted on April 13, 2010; accepted on June 18, 2010
table of contents
background: There have been conflicting results in randomized trials of the effects of laparoscopic uterosacral nerve ablation (LUNA)
in chronic pelvic pain. Our objective was to perform a meta-analysis using individual patient data (IPD) to provide the most comprehensive
and reliable assessment of the effectiveness of LUNA.
& The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
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Human Reproduction Update, Vol.16, No.6 pp. 568–576, 2010
Advanced Access publication on July 15, 2010doi:10.1093/humupd/dmq031
by guest on December 28, 2015
methods: Electronic searches were conducted in the Medline, Embase, PsycInfo and Cochrane Library databases from database incep-
tion to August 2009. The reference lists of known relevant papers were searched for any further articles. Randomized trials comparing LUNA
with no additional intervention were selected and authors contacted for IPD. Raw data were available from 862 women randomized into five
trials. Pain scores were calibrated to a 10-point scale and were analysed using a multilevel model allowing for repeated measures.
results: There was no significant difference between LUNA and No LUNA for the worst pain recorded over a 12 month time period
(mean difference 0.25 points in favour of No LUNA on a 0–10 point scale, 95% confidence interval: 20.08 to 0.58; P ¼ 0.1).
conclusions: LUNA does not result in improved chronic pelvic pain.
Key words: individual patient data / meta-analysis / chronic pelvic pain / dysmenorrhoea / neuroablation
Chronic pelvic pain, defined as lower abdominal pain or pelvic pain of
longer than 6 months’ duration, is a common condition (Zondervan
et al., 1999). It has multiple causes (Latthe et al., 2006a), and preva-
lence varies widely globally (Latthe et al., 2006b). It remains one of
the most challenging of women’s health problems with a major
impact on health-related quality of life, productivity (Sundell et al.,
1990) and health care utilization, costing an estimated £250 million
(at 2005/2006 prices) on its management in the UK (Davies et al.,
1992). Only 20–25% patients respond to initial conservative manage-
ment (Henzl, 1985). When such treatment fails, a diagnostic laparo-
scopy is frequently performed (Royal College of Obstetricians and
Gynaecologists, 2005). The cause of the pain is not always obvious
as no pathology is seen in 35% (range 3–92%) of the cases
(Porpora and Gomel, 1997; Howard, 2000). In the absence of pathol-
ogy there is no established gynaecological treatment.
Interruption of the Lee-Frankenhauser sensory nerve plexuses by
laparoscopic uterosacral nerve ablation (LUNA) may alleviate pain
(Doyle, 1955; Doyle and Des Rosiers, 1963). LUNA can be carried
out quickly and simply alongside diagnostic laparoscopy using lasers
or electro-diathermy and has become widely practised (Daniels
et al., 2000; Latthe et al., 2004), although clinicians’ beliefs about its
effectiveness vary widely (Latthe et al., 2005). The effects of this inter-
vention have been assessed in randomized controlled trials (Lichten
and Bombard, 1987; Sutton et al., 2001; Vercellini et al., 2003;
Johnson et al., 2004; Daniels et al., 2009) and summarized in published
data systematic reviews (Khan et al., 1999; Stones and Mountfield,
2000; Proctor et al., 2005). In a Cochrane review of surgical interrup-
tion for primary and secondary dysmenorrhoea (Proctor et al., 2005),
there was some evidence of the effectiveness of LUNA when com-
pared with a control or no treatment in the absence of endometriosis
[odds ratio 6.1, 95% confidence interval (CI) 1.8–21.0], but not
for secondary dysmenorrhoea (0.8, 95% CI 20.4 to 1.4). These
reviews concluded that there is insufficient evidence to recommend
the use of nerve interruption in the management of dysmenorrhoea,
regardless of cause, which was reiterated by the UK National Institute
of Health and Clinical Excellence (NICE, 2007).
Meta-analysis using individual patient data (IPD) from primary
studies has the potential to produce a more reliable estimate of treat-
ment effect than from meta-analysis of aggregate data and also to
allow exploration of subgroups (Stewart and Clarke, 1995; Stewart
and Tierney, 2002). The LUNA IPD Meta-analysis Collaborative
Group, a consortium of authors of all primary studies involving
LUNA, was established to use these advanced analytic techniques
to evaluate the effectiveness of LUNA in reducing chronic pelvic pain.
We undertook an IPD meta-analysis to examine the effectiveness of
LUNA in reducing chronic pelvic pain according to a pre-specified proto-
col (Xiong et al., 2007), developed using recommended methods (Stewart
et al., 2008).
The search methods previously described (Proctor et al., 2005) were
updated in August 2009 (from 2003 to current) to identify any trials pub-
lished since the last search and to identify ongoing trials to seek unpub-
lished data. A comprehensive database was constructed using Reference
Manager 12.0 to store all identified references. No language restrictions
Study inclusion and data collection
Studies were considered for inclusion if LUNA, as an intervention for
women of reproductive age with CPP, primary or secondary dysmenor-
rhoea, was compared against diagnostic laparoscopy in a randomized con-
trolled trial. Trials with concomitant ablation of endometrial lesions were
included provided ablation was an option in both study groups. Two
reviewers (J.P.D., R.C.) independently assessed trials for inclusion and
quality, with queries resolved by a third reviewer (K.S.K.). Criteria for
quality assessment were based initially on the reported characteristics
and included adequacy of sequence generation and allocation conceal-
ment; blinding of participants, and assessors where used, to treatment
allocation; intention to treat analysis performed and potential impact of
losses of follow-up data.
Primary authors of included randomized trials were invited to join the
collaborative group and to provide anonymized raw data on visual ana-
logue score (VAS) pain ratings, the presence or absence of visual pathol-
ogy, age at randomization and parity. Further assessment of data quality
on receipt of the data set included the ability to reproduce the published
results and discrepant patterns of data. Where discrepancies existed
authors were contacted for clarification.
The primary outcome was a derived measure of the worst pain level
experienced if data were received on different pain symptoms (e.g. dysme-
norrhoea, non-cyclical pain and dyspareunia). Pain scores using a VAS
were rescaled where necessary, to anchor the scale between 0 (no
pain) and 10 (worst pain imaginable). Rather than dichotomising the
data at an arbitrary threshold, as was the case in two of the included
IPD meta-analysis of LUNA for chronic pelvic pain
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