DOI: 10.1111/j.1471-0528.2008.02022.

x
www.blackwellpublishing.com/bjog
Gynaecological surgery

Prospective randomised trial comparing

gonadotrophin-releasing hormone analogues
with triple tourniquets at open myomectomy
N Al-Shabibi, L Chapman, S Madari, A Papadimitriou, P Papalampros, A Magos
University Department of Obstetrics and Gynaecology, Royal Free Hospital, London, UK
Correspondence: Dr A Magos, University Department of Obstetrics and Gynaecology, Royal Free Hospital, Pond Street, Hampstead, London,
NW3 2QG, UK. Email a.magos@medsch.ucl.ac.uk

Accepted 6 October 2008. Published Online 4 February 2009.

Objective To compare intra-operative blood loss with triple
tourniquets to occlude uterine blood supply against preoperative
treatment with gonadotrophin-releasing hormone (GnRH)
analogues at open myomectomy.
Design A prospective randomised controlled trial.
Setting University teaching hospital.
Population Forty women undergoing open myomectomy for
symptomatic fibroids.
Methods Women due to undergo open myomectomy were
randomised to either 3 months pre-treatment with a GnRH
analogue or the intra-operative application of triple tourniquets
(number 1 polyglactin suture [Vicryl
Ethicon Inc., Somerville, NJ,
USA] tied around the cervix and a size 10 polythene suction
catheter tied around the infundibulo-pelvic ligaments) to occlude
the uterine blood supply.
Main outcome measures The primary outcome measure was
intra-operative blood loss. Secondary outcome measures included
postoperative blood loss, blood transfusion rate and postoperative
morbidity.
Results The two groups were similar in baseline characteristics. An
average of 15 and 22 fibroids were removed from the GnRH
analogue and tourniquet groups respectively. Intra-operative
estimated blood loss was significantly higher in the GnRH
analogue group (median 2482 ml, 75% percentile 1744–3151) than
when triple tourniquets were used (median 640 ml, 75% percentile
418–881), giving a difference between means of 1842 ml (P <
0.001). Similarly, significantly more women required blood
transfusion in the GnRH analogue group (70 versus 30%, P <
0.025). Postoperative morbidity was similar between the two
groups. There were two serious complications in the tourniquet
group, but they were not considered to be directly related to
occlusion of the uterine blood supply.
Conclusions Triple tourniquets are significantly more effective
than preoperative treatment with GnRH analogues at reducing
intra-operative blood loss at open myomectomy.
Keywords GnRH analogues, leiomyoma, myomectomy,
tourniquets.

Please cite this paper as: Al-Shabibi N, Chapman L, Madari S, Papadimitriou A, Papalampros P, Magos A. Prospective randomised trial comparing
gonadotrophin-releasing hormone analogues with triple tourniquets at open myomectomy. BJOG 2009;116:681–687.

temporarily occlude the uterine blood supply at myomec-

Introduction
Despite advances in minimal access surgery and interven-
tional radiological techniques, open myomectomy remains
the principal treatment for multiple, large uterine fibroids
when preservation of fertility is desired. Significant morbidity
is attached to the procedure, mainly due to intra-operative
haemorrhage.1 Several methods have been described to re-
duce intra-operative bleeding at open myomectomy, includ-
ing the use of vasoconstrictors (e.g. vasopressin), uterine
artery ligation, preoperative misoprostol and the use of
specific dissection techniques.2 The use of tourniquets to
tomy has a long history,1,3 and we have shown previously in
a randomised controlled trial that ‘triple’ tourniquets (tour-
niquets applied to the uterine and ovarian vessels) are highly
effective.4
An alternative approach to reducing operative haemor-
rhage at myomectomy involves pre-treating women with
gonadotrophin-releasing hormone (GnRH) analogues.5 A
recent survey of UK consultant gynaecologists showed that
87% use this approach in contrast to a smaller percentage who
use other methods to limit bleeding (35% use myomectomy
clamps, 23% tourniquets and 19% use vasoconstrictors).6

ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 681
 Al-Shabibi et al.
We wished to determine if triple tourniquets are as effective
as preoperative treatment with GnRH analogues in reducing
blood loss.
Methods
Forty women undergoing open myomectomy for symptom-
atic fibroids were recruited from the ‘Fibroid Clinic’ in our
hospital for this study (Figure 1). Inclusion criteria included
symptomatic multiple (>3) uterine fibroids (with a uterine
size which was the gestation equivalent of between 12 and 22
weeks) in women who wished to preserve their fertility and
who had opted for surgical treatment rather than uterine
artery embolisation. The clinical diagnosis was confirmed
by imaging in all cases. Exclusion criteria included a history
of coagulopathy or treatment with anticoagulants, therapy
with GnRH analogues within the previous 6 months and
severe anaemia. Women with previous myomectomies were
not excluded, but those with anaemia (haemoglobin less than
10.5 g/dl) or with a uterine size ‡24 weeks gestation equiva-
lent were excluded as it was our practice to pre-treat such
Assessed for eligiblity
(n = 254)
Randomised
(n = 40)
Tourniquet group (n = 20)
Received allocated intervention (n = 20)
Lost to follow up
(n = 0)
Analysed
(n = 20)
Figure 1. Consort flow chart.
682 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
women with GnRH analogues as a matter of routine to cor-
rect the anaemia and to reduce the size of the uterus suffi-
ciently to increase the likelihood of carrying out the surgery
via a low transverse skin incision.
Women were randomized in the outpatient clinic once it
was decided that open myomectomy was an appropriate
treatment and informed consent had been obtained. Ran-
domisation was based on a random list of binary numbers
(1 GnRHa, 2 tourniquets). Women randomised to pre-treat-
ment with GnRH analogues were prescribed either Zoladex

(goserelin acetate; AstraZeneca, London, UK) 3.6 mg by
intramuscular injection every 28 days or nafarelin nasal spray
(Synarel
; Searle, Chicago, IL, USA) 200 mg twice a day for 3
months prior to surgery according to patient preference.
Women randomised to tourniquets were not given any pre-
treatment. Any woman whose haemoglobin was less than 11.0
g/dl was prescribed ferrous sulphate 200 mg twice a day.
We have described the technique of using ‘triple’ tourni-
quets previously.4 Briefly, the tourniquet group had a small
incision made into the broad ligament through the avascular
space just inferior to the insertion of the round ligament,
Excluded (n = 214):
Not meeting inclusion criteria (n = 179)
Refused to participate (n = 35)
GnRHa group (n = 20):
Received allocated intervention (n = 20)
Lost to follow up
(n = 0)
Analysed
(n = 20)

Figure 2. Uterine size in the GnRH analogue and tournique group.
fallopian tube and ovarian ligament into the uterus on each
side. A number 1 polyglactin suture (Vicryl) was threaded
through the incisions and tied around the cervix above the
level of the bladder to occlude the uterine arteries; we no
longer open the uterovesical fold as a matter of routine unless
the dome of the bladder is high and requires dissection off the
cervix. The uterine tourniquet was tied with a Roeder slip-
knot and was re-tightened during the procedure as required.
Two 20-cm lengths of size 10 suction catheter tubing (Uno-
medical A/S, Redditch, UK) were also passed through the
broad ligament incision on each side and tied around the
infundibulo-pelvic ligaments to occlude the ovarian vessels.
At the end of the procedure, the ovarian ties were released
while the uterine suture was left in situ to dissolve over the
following weeks.
Operative blood loss was carefully assessed by weighing all
swabs and measuring blood collected by suction; special col-
lecting drapes were put on either side of the laparotomy inci-
sion to facilitate accurate estimation. A 10-mm suction drain
(Redovac
400; B. Braun, Melsungen, Germany) was left
in situ for 48 hours in all cases and haemoglobin was checked
on the first postoperative day. All women received antibiotic
cover, usually in the form of amoxicillin/clavulanate potas-
sium (Augmentin; SmithKlineBeecham, Worthing, UK)
intraoperatively and for 5 days after surgery, as well as throm-
boprophylaxis with TED anti-embolic stockings and Enoxa-
parin (Clexane; Sanofi-Aventis, Guildford, UK).
Our primary outcome measure was intra-operative blood
loss. Secondary outcome measures included postoperative
blood loss, blood transfusion rate and postoperative morbid-
ity. A decision was made to transfuse blood to women if their
haemoglobin levels dropped below 8.0 g/dl. Women were
discharged from hospital when clinically well enough.
ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
Open myomectomy: triple tourniquets versus GnRHa
Table 1. Characteristics of the participants
GnRHa Tourniquets P value
No. participants 20 20
Age in years (SD) 39.4 (5.2) 40.2 (5.3) NS
Uterine size in 18.2 (2.9) 16.3 (3.9) NS
weeks (SD)
Previous myomectomy 5 5 NS
Preoperative Hb (g/dl)(SD) 13.1 (1.1) 12.6 (1.0) NS
NS, not significant.
Ethical approval was obtained for this study from the local
ethics committee (No. 6905). We estimated that we would
need 20 women in each arm based on the assumption that
40% of them would bleed >1 l in the GnRH analogue group
compared with 20% in the tourniquet group. Data were
analysed using the student t test or Mann–Whitney U test
depending the distribution of the data, and Fisher’s exact
test for ordinal data. We used GraphPad Prism 4 software
(GraphPad Software, San Diego, CA, USA) to analyse our
results and assumed statistical significance at P < 0.05 level
at 80% power.
Results
The two groups were similar in their baseline characteristics
including the number of women with a history of a previ-
ous open myomectomy (Table 1, Figure 2). All procedures
were completed successfully and no woman required
a hysterectomy.
There were no significant differences in the numbers of
fibroids removed or in the total weight of fibroids between
the two groups (Table 2, Figures 3 and 4). However, the mea-
sured intra-operative blood loss was significantly higher in the
GnRH analogue group (median 2482 ml, 95% CI 1744–3151)
compared with when triple tourniquets were used (mean 640
ml, 95% CI 418–881), giving a difference between means of
1842 ml (P < 0.001) (Figure 5). Similarly, significantly more
women required blood transfusion after GnRH analogues
compared with tourniquets (70 versus 30%, P < 0.025). There
was no significant difference between the two groups in the
volume of drainage from the Redovac drains in the first
48 hours.
The overall incidence of postoperative complications was
similar in the two groups (Table 2). Most complications were
minor, with postoperative pyrexia accounting for most of the
cases (7 and 4 cases in the analogue and tourniquet groups
respectively). One participant in the tourniquet group bled
from the drain puncture site and had to return to the oper-
ating theatre within 24 hours of her myomectomy for sutur-
ing. Two other women from the tourniquet group sustained
683
 Al-Shabibi et al.

Table 2. Operative details

GnRHa Tourniquets P value

Incision*
Midline 19 17 0.6050
Transverse 1 3
No. fibroids removed** 15.2 (9.3–21.3) 22.7 (14.9–30.5) 0.1295
Weight of fibroids (g)*** 429.5 (221–675) 384.5 (170–589) 0.6716
Estimated blood loss (ml)*** 2600 (1100–3150) 500 (295–700) ,0.001
Redivac drain at 48 hours (ml)*** 255 (50–410) 195 (60–639) 0.6894
Blood transfusion (n)*
Intra-operative 9 2 0.0256
Postoperative 8 5
Not at all 6 14
No. participants with a postoperative complication****,* 10 4 0.332
Hospital stay (days)*** 5 (5–8) 6***** (5–7) 0.6097

*Fisher’s exact test.

**Student’s unpaired t test (Mean [95% CI]).
***Mann–Whitney U test (median [25th to 75th percentile]).
****Mostly postoperative pyrexia .38C.
*****One participant stayed in hospital for 35 days.

serious complications. One woman developed disseminated
intravascular coagulation (DIC) and acute renal failure after
an otherwise uncomplicated myomectomy; the ovarian tour-
niquets were tied for 24 minutes, the operative blood loss was
300 ml and three fibroids (total weight 502 g) were removed.
She became oliguric within 48 hours but recovered fully. The
diagnosis was uncertain, but disseminated intravascular coag-
ulation or haemolytic uraemic syndromes are two possibilities.
Another woman undergoing her second open myo-
mectomy developed severe uterine sepsis postoperatively
because of a retained intra-cavity fibroid, which was
missed at the initial surgery, and subsequently developed
Asherman’s syndrome.
Postoperative hospital stay was similar between the two
groups and no woman was readmitted to hospital in the early
(£6 weeks) postoperative period.

Figure 3. Number of fibroids removed from the GnRH analogue and Figure 4. Weight of fibroids removed in the tourniquet group and
tournique group. GnRH analogue group.

684 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology

Figure 5. Estimated blood loss in the tourniquet group and GnRH
analogue group.
Discussion
A recent randomized controlled trial from our unit and
Cochrane review confirmed that ‘triple’ tourniquets applied
to the uterine and ovarian vessels significantly reduce oper-
ative blood loss, the need for blood transfusion and perio-
perative morbidity at open myomectomy.4,7 This
intervention was considered to produce the largest beneficial
effect on blood loss during myomectomy when compared
with no treatment or placebo by a recent Cochrane review.7
We have now shown in this study that triple tourniquets are
also significantly more effective than pre-treatment with
GnRH analogues in reducing operative blood loss and the
need for transfusion.
Many gynaecologists use GnRH analogues prior to myo-
mectomy (and hysterectomy) in the belief that they will
reduce the size of the uterus, the incidence of anaemia and
operative blood loss.6 There is good evidence that pre-
treatment with GnRH analogues prior to hysterectomy or
myomectomy for uterine fibroids will reduce both uterine
volume and fibroid size and correct anaemia.5,8,9 However,
the published literature is by no means unanimous on their
effect on operative blood loss. For instance, a recent random-
ized controlled trial could find no benefit when comparing
depot triptorelin against no pre-treatment.10 The average
blood loss in this study was considerably less than in our
study, but the average number of fibroids removed was 3
per patient (in contrast to over 15 in our study), and the
average uterine size was 12 weeks gestation equivalent com-
pared with 18 weeks in our study, differences which are likely
to explain the greater blood loss seen in our participants. It is
also worth noting that the women treated with GnRH ana-
ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
Open myomectomy: triple tourniquets versus GnRHa
logues in our current study experienced similar blood loss to
the control group in our previous study (2.6 and 2.3 l, respec-
tively).4 This confirms suggestions that not only is such pre-
treatment ineffective when there are relatively few fibroids to
remove, but also when there is considerable uterine enlarge-
ment secondary to numerous fibroids.
There are, of course, well known disadvantages to the use of
GnRH analogue pre-treatment prior to myomectomy. Fibrosis
between the tissue planes can result in more difficult surgery
after GnRH analogue treatment.7,11 Furthermore, GnRH ana-
logues are expensive and cause unpleasant oestrogen deficiency
symptoms. More worryingly, they are associated with an
increase in fibroid recurrence as early as 6 months after sur-
gery.11,12 Although statistically insignificant, on average seven
more fibroids per participant were removed from the tourniquet
group than those pretreated with GnRH analogues, a finding
which may be explained by the fact that small fibroids became
too small to be identifiable at surgery in the latter group.
The intra-operative injection of vasopressin, an anti-diuretic
hormone, and its derivates has been reported to produce a
significant reduction in blood loss during myomectomy.7,13
One study compared intramyometrial vasopressin with
mechanical occlusion of uterine vessels with a Foley catheter
and found them to be equally effective in controlling surgical
bleeding.14 There is, however, a concern about potential phar-
macological adverse effects associated with accidental intra-
vasation of these drugs, including bradycardia, hypotension,
pulmonary oedema, myocardial infarction and even cardiac
arrest, to the extent that their use has been banned in some
countries.15–17 Another concern that we have with the use of any
injectable vasoconstrictor is that the effect may either not cover
the entire procedure necessitating repeat injections, or worse, as
pointed out by the studies from Jamaica,13,14 it will mask a bleed-
ing vessel which will then become manifest postoperatively. The
same may also apply to drugs which work by inducing myome-
trial contractions during surgery, such as misoprostol.18 Miso-
prostol can also induce unpleasant adverse effects such as chills,
nausea and vomiting, diarrhoea, headaches and pyrexia.19,20 In
contrast, haemostasis, or lack of it, is immediately apparent
when vascular occlusion is reversed, and, of course, mechanical
devices do not have adverse pharmacological effects.
The main concern with mechanical occlusion of the blood
supply to the uterus, particularly the use of ovarian tourni-
quets, is that prolonged ischaemia may result in ovarian
damage and reduced ovarian reserve. However, we could
find no evidence for this in our previously published study,4
and despite using tourniquets regularly for the past 7 years,
we are not aware of any women who have become meno-
pausal unexpectedly. The woman in the tourniquet group
who became amenorrhoeic following her myomectomy had
a premenopausal ovarian hormone profile with proven
Asherman’s syndrome secondary to an infected intra-
cavitary myoma, which was missed both at her initial
685
 Al-Shabibi et al.
surgery and subsequent laparotomy for a pelvic collection.
The other major complication in our study involved a pre-
viously healthy woman who became anuric following an
otherwise uncomplicated myomectomy but recovered fully
after dialysis. We have been able to find one case report of
a woman who was diagnosed with haemolytic uraemic syn-
drome after open myomectomy, but we are not sure if this
was the diagnosis in our participant.21 Whatever the true
diagnosis, we do not believe that either of these two major
complications was related to the use of tourniquets.
It is our current practice not to remove the tourniquet from
around the cervix at the end of the myomectomy. Although
we have been unable to confirm this in this study, there is
some evidence that post-myomectomy bleeding from the
uterine incisions can be reduced if the uterine blood flow is
obstructed.22 Even if this effect is clinically small, inducing
a degree of temporary uterine ischaemia may reduce the
chances of fibroid recurrence as seems to the case after uterine
depletion and uterine artery embolisation prior to myomec-
tomy.23,24 In contrast to permanent procedures such as embo-
lisation and ligation of the uterine vessels, a peri-cervical
tourniquet produces only temporary occlusion of the main
uterine blood supply, which we feel is theoretically at least an
advantage in terms of future obstetric performance.25
In conclusion, our study confirms that the application of
‘triple’ tourniquets is more effective than preoperative treat-
ment with GnRH analogues at reducing intra-operative blood
loss at open myomectomy. This result is consistent with the
findings of the Cochrane Review group that of all the available
intra-operative techniques, triple tourniquets are associated
with the greatest reduction in blood loss at open myomectomy.7
Disclosure of interest
There are none.
Contribution to authorship
Ms Nawar Al-Shabibi performed the experiment, analysed the
data and co-wrote the paper. Dr Lynne Chapman performed the
experiment. Dr Sheethal Madari collected the data. Dr Angiliki
Papadimitrios collected the data. Dr Panos Papalampros performed
the experiment. Mr Adam Magos conceived and designed the exper-
iment, analysed the data and co-wrote the manuscript.
Details of ethics approval
Ethical committee reference number for this study was 04/Q0501/94
and the date of ethical committee approval 15 September 2004.
Funding
There was none.
Acknowledgements
We acknowledge the help of Nikolaos Papadopoulos and Alex Taylor
in this study. j
686 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology
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