Accepted Manuscript

Title: Techniques to reduce blood loss during open

myomectomy: a qualitative review of literature
Author: Alessandro Conforti Antonio Mollo Carlo Alviggi
Ioannis Tsimpanakos Ida Strina Adam Magos Giuseppe De
Placido
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DOI:
Reference:

S0301-2115(15)00182-7
http://dx.doi.org/doi:10.1016/j.ejogrb.2015.05.027
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5-1-2015
20-5-2015
23-5-2015

Please cite this article as: Conforti A, Mollo A, Alviggi C, Tsimpanakos I, Strina1 I,
Magos A, De Placido G, Techniques to reduce blood loss during open myomectomy:
a qualitative review of literature., European Journal of Obstetrics and Gynecology and
Reproductive Biology (2015), http://dx.doi.org/10.1016/j.ejogrb.2015.05.027
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Title: Techniques to reduce blood loss during open myomectomy: a qualitative review of literature.

Authors: Alessandro Conforti1 (MD), Antonio Mollo1 (MD-PHD), Carlo Alviggi1 (MD-PHD), Ioannis
Tsimpanakos2 (MD, Consultant), Ida Strina1(MD PHD), Adam Magos2 (BSc MB BS MD FRCOG

University Department of Neuroscience, Reproductive Medicine, Odontostomatology - University of Naples

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Consultant) and Giuseppe De Placido1 (MD-PHD-Consultant Prof)

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"Federico II", Naples, Italy -

University Department of Obstetrics and Gynaecology Royal Free Hospital London NW3 United Kingdom

Corresponding author: Alessandro Conforti confale@hotmail.it 1Dipartimento di Neuroscienze, Scienze

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Riproduttive ed Odontostomatologiche -Universit degli Studi di Napoli Federico II, Via Sergio Pansini, 5
80131, Naples, Italy Universit degli Studi di Napoli Federico II, Via Sergio Pansini, 5 80131, Naples,

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Italy+39 081-7462699

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Running title: Reducing blood loss during open myomectomy

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Declaration of interest

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All authors declare not potential conflict of interest.

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Abstract
Open myomectomy is the most adopted surgical strategy in the conservative treatment of uterine fibroids.
According to several studies the likelihood that a woman could develop uterine myomas is estimated around
75% by the age of 50. Open myomectomy is nonetheless a complicated surgery considering the high rate of
blood loss and blood transfusion rate. Many strategies were published with the aim of limiting the intra and

Keyword: open myomectomy, uterine fibroids, haemorrhage, surgery

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reported in literature focusing on their validity and safety.

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post-operative complications. The scope of this review is to describe in detail the different techniques

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Abbreviations List: IVF: in vitro fertilizations; GnRHa: gonadotrophin releasing hormone analogues

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Introduction
Uterine fibroids are considered one of the most common gynaecological problems affecting women in fertile
age. Their incidence is significant considering that about the 70% of women at the age of 50 years could be
affected (1).
Fibroids are smooth cell and connective cell-type tumors which could be sited in different location and

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sometimes developed inside the uterine cavity (submucous, intramural, subserosal). The commonest

symptoms are menorrhagia and those related to pressure against surrounding organs (sporadic constipation,
voiding disturbance, pelvic pain, dyspareunia), which in turn depend on the size and position of fibroids (2).

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Another important aspect is the potential impact of fibroids on fertility. Data suggest that the incidence of
infertility is strictly related to the location of fibroids with demonstrated negative effects of the submucosal

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fibroids, whilst there is still uncertainty with regards to the effect of intramural fibroids (3). Subserosal
fibroids seem to have negligible significance both for IVF techniques and spontaneous conception (4, 5).

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Currently, there are several strategies for the treatment of fibroids but the surgical myomectomy seems to be
the most common and at the same time the most efficient uterine-sparing treatment (6). Nevertheless, this
procedure is associated with known risks, among which is undesirable hysterectomy due to intraoperative

complications and peri or postoperative blood loss.

These complications depend on the number, the size and the position of fibroids removed. In order to reduce
intraoperative haemorrhage many authors have proposed different strategies both for laparoscopic and

abdominal myomectomy (7). In this paper we focus particularly on strategies during abdominal
myomectomy, where the number of fibroids and their size are considerably higher and consequently the risk

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Material and Method

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of haemorrhage is increased (Table 1).

A systematic research was undertaken in MEDLINE/EMBASE database with no restriction of time period.
Only techniques adopted during open myomectomy were evaluated. Randomized controlled trial has been
preferred by the authors in the elaboration of the manuscript, although several comparative trials has been
also considered. The following keywords have been adopted: open myomectomy, blood loss,
laparotomy, uterine fibroids.

Tourniquet techniques
The use of tourniquet in uterine surgery was reported about 60 years ago (8, 9). It consists in interrupting the
blood supply to the uterus by compressing the main feeding vessels. In the single tourniquet technique a
single suture is applied around the cervix to occlude both uterine arteries, while in the triple tourniquet the
ovarian vessels are occluded lateral to the ovaries. To prevent ovarian injuries due to ischaemic damage, the
occlusion of the vessels is performed medial to the ovaries.

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Two randomized control trials have been published assessing the role of triple tourniquet during
myomectomy. In the study by Taylor et al., 28 patients with a uterine size of more than 14 weeks, were
randomized to have triple tourniquet. The control group received standard myomectomy. None of these
patients had a history of bleeding disorders, and the preoperative haemoglobin was over 10.5gr/dl. During
the procedure, a size 1 polyglactin suture was applied around the cervix and a 3 mm Westcott anaesthetic

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anti-syphon tube was hitched around both infundibolopelvic ligaments. The average of estimated blood loss
was significantly lower in the treated group (2359mL versus 489mL) as well as the number of patients
needing blood transfusion (11 versus 1) (6).

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Subsequently, the same authors have used a different instrument to improve their triple tourniquet technique.
For the tourniquet around the cervix, good results were demonstrated both with the Roeder knot or sterile

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cable ties which allows retightening the suture when necessary (10). A specific vascular clamp was designed
to protect the fallopian tubes from any damage. The ovarian artery clamp is a standard 18 cm vascular clamp

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with a circular hole just below the hinge. The clamp was placed medial to both ovaries with both fallopian
tubes inside the aperture. The results appeared comparable with the conventional ovarian artery clamps (11).
The most recent randomized control trial involved 93 patients randomly allocated to tourniquet group or

standard open myomectomy (12). In this study, the authors used a Foley catheter applied at the base of the
cervix in proximity of uterosacral ligament. Blood flow from infundibolopelvic ligaments was not clamped
during the myomectomy. Even only with the single cervical tourniquet, the authors have demonstrated

valuable results in terms of blood loss (515.7 292.8 ml tourniquet group versus 756.5 258.7, p < 0.001)
and transfusion rate (0.24 0.51 unit versus 1.0 1.14 unit, p < 0.001) (12).

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The tourniquet was also compared with other techniques such as intramyometrial injection of vasopressin,
pretreatment with Gonadotrophin releasing hormone analogues (GnRHa) or uterine artery ligation.

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There is only one randomized control trial comparing the vasopressin injection with the single tourniquet
technique. From 1994 to 1995, 52 women with symptomatic fibromas were randomized to receive either
perivascular injection of 20UI of vasopressin or a single tourniquet around the cervix performed with a Foley
catheter. Specifically, vasopressin was injected into the broad ovarian ligament in proximity to the insertion
of both ovarian and round ligament. Subsequently, vasopressin was injected superficially into the false
capsule of largest fibroid. The vasopressin group had showed less blood loss than the single tourniquet group
(287.3ml versus 512.7ml, p 0.036) (13). Currently, there are no studies comparing vasopressin injection with
the triple tourniquet technique.

Pre-treatment with a GnRHa has been compared with triple tourniquet in reducing blood loss during
myomectomy. In a prospective randomized control trial, 40 women with symptomatic uterine multiple
fibroid were enrolled. The triple tourniquet technique was performed (n = 20) including the occlusion of
infundibolopelvic ligaments and pericervical tourniquet, while in the GnRHa group (n = 20) pre-treatment
with goserelin acetate or nafarelin was administrated for three months (3.6 mg by intramuscular injection
every 28 day and 200g twice a day respectively). The triple tourniquet group showed better results with

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regards to intra-operative blood loss (median 500ml versus a median of 2600ml in control group, p < 0.001)
and number of patients requiring transfusion (2 versus 9, p < 0.02) (14).

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Uterine artery ligation

Uterine artery ligation was demonstrated as a valid strategy in the treatment of haemorrhage following
caesarean section (15).

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It consists in suturing of both uterine arteries, a technique which can also be accomplished by laparoscopy
(16, 17). Artery ligation before open myomectomy was compared in two prospective randomized studies

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with single tourniquet technique in reducing blood loss (18, 19). Sapmaz et al., (19) reported no difference
with respect to intraoperative blood loss and total operation time duration among 52 women randomly

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allocated either to tourniquet (n = 26) or bilateral artery ligation (n = 26) during caesarean myomectomy.
On the other hand, Helal et al. (18) reported significant differences in operative blood loss (433.8ml
285.21 versus 823.23 237.33 ml, p < 0.001), mean operation times (50.5 8.7 versus 76.3 9.4 min, p <

0.001), post-operative stay (4.1 0.1 versus 5.1 0.2 days p < 0.001) and number of patient needing blood
transfusion (3 - 5.8% versus 32 - 62.7%, p < 0.001). In this study, the single tourniquet was accomplished by
a Foley catheter tied firmly around cervix. No randomized control trials are available in literature.

Although it has been reported that pregnancy can occur after uterine artery ligation (16, 17, 20), there are
concerns about the impact of this technique on future fertility. In addition, it seems that the chronic hypo-

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intrauterine adhesions (20).

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vascularization following this kind of procedure could be directly involved in the pathogenesis of subsequent

Vasopressin

Vasopressin is a vasoconstrictor that can modulate the intrinsic vessel resistance stimulating the contraction
of the smooth vascular muscle and increasing water absorption in the collecting ducts of the kidney. It seems
that the vasopressin receptor type 1a (V1a) is the most widely expressed receptor subtype in uterus (21). The
haemostatic effect of vasopressin has been long used successfully in treatment of an oesophageal varices.
With respect to its use in gynaecology, it was first reported to have a good haemostatic effect in 17 women
with refractory bleeding that occurred after submucosal fibroid resection. In this study the authors used a 1
inch gauze pack soaked with 20UI of vasopressin diluted with 30 ml of normal saline (22).
In a subsequent randomized placebo control trial involving 20 patients with diagnosis of uterine fibroids,
perivascular injection of vasopressin before myomectomy resulted in a median estimated blood loss 225 ml
(range 150-400 ml) compared with 675 ml (range 500-800 ml) in the placebo group (p < 0.001). Moreover,
the treated group had a significantly lower fall in both haemoglobin (median 1.7 g/dl versus 5.3 g/dl, p <
0.001) and haematocrit (median 5 % versus 13 %, p = 0.001) (23). The administration of vasopressin was
applied in the same way by Fletcher et al. (13).

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The use of vasopressin was also evaluated alone or associated with GnRH preoperative treatment. Same
efficacy with regards to intraoperative blood loss, and postoperative haemoglobin fall was observed
irrespectively of GnRH administration (21).
The randomized control trial comparing vasopressin treatment versus tourniquet technique was mentioned in

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the previous paragraph.

The use of vasopressin is not without risks and is contraindicated in patients with vascular disease and
impaired renal function. The side effects described in literature included the loss of peripheral pulse, severe

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hypotension, bradycardia ,even death (24).

The optimal dosage during the procedure is not well-established. The most common dosage used was 20U

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diluted to 20ml with normal saline. Nonetheless, bradycardia was reported even with a concentration of
0.4U/ml. According to Alexander et al., the safest concentration of vasopressin is in the range of 0.05-0.3

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U/ml (21, 25). It seems that it is the accidental intravascular administration of vasopressin, that may occur
during its local administration, that was associated with side effects, thus it is strongly recommended to

avoid this route (13).

GnRH agonist

GnRHa is yet another accepted strategy to prevent blood loss during myomectomy (Table 2) or to correct

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anaemia prior to surgery. In a meta-analysis of 26 randomized trials on the benefit of GnRHa prior to surgery
for leiomyomas was analysed and GnRHa have been shown to have a valuable impact on blood loss rate, pre

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and post operative haemoglobin and haematocrit rate. Therefore, hysterectomy seemed to be easier after the
treatment due to consequently shrinkage of fibroids (26).
Even before hysteroscopic myomectomy many authors suggested a pre-treatment with GnRHa especially in
patients who showed secondary anaemia or large submucous fibroid (>3-4cm) (27).
The duration of therapy, the route and the dosage are still unclear. Several GnRH analogues have been used
such as Leuprolide acetate at dosage of 3.75 mg, goserelin at 3.2 mg, nafarelin 200mcg twice a day by nasal
spray. The duration of therapy generally ranged from two to three months up to a maximum of 6 months.
Previous studies described a significant size reduction of fibroids after only 6-8 weeks of treatment (28, 29).
Nevertheless, many authors have raised doubt about GnRHa administration. In a randomized control trial
involving 100 premenopausal patients there was no difference in terms of blood loss between the treated and
control group (30).
In addition cost and menopausal symptoms (hot flushes, vaginitis) during the treatment is often not tolerated
and one of the main cause of therapy dropout. To attenuate the sequelae of hypoestrogenism without
compromising the effects in reducing the volume of myomas, an add-on treatment with tibolone could be a
worthwhile option (31)

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Another side effects are the association with fibroid recurrence after the surgery and the alteration of tissue
planes which caused a more difficult enucleation of the fibroids during myomectomy (32, 33).
The former phenomenon is probably due to underestimation of the real number of the fibroid during the
surgery (33). The latter is provoked by hypoestrogenic environment which altered myomas delimitation and

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sometimes increased the necrosis of the tissue

Tranexamic acid, uterotonic agents

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Tranexamic acid is an anti-fibrinolytic drug commonly used in the management of menstrual disorders. It
competitively inhibits the activation of plasminogen to plasmin which is the main degradation product of

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pro-coagulation agents. Tranexamic acid significantly reduces blood loss after caesarean section and cervical
procedures (34).

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The effectiveness of tranexamic acid was evaluated in only one prospective randomized placebo controlled
trial involving 100 patients undergoing caesarean section. The drug was administrated 15 min before surgical
incision (10 mg/Kg/h) and continuously by infusion of 1mg/Kg/h diluted in 1000ml of saline for 10h.

The authors found a statistical difference in terms of total blood loss (804ml 482 versus 1047ml 617, p =
0.03) and duration of surgery (72 min 22 in treated group versus 84 min 29 in control group, p = 0.03).

No thromboembolic events or side effects were reported (35).

Oxytocin is the most used uterotonic drug and the first line treatment in postpartum haemorrhagia and was

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demonstrated to stimulate proliferation of both myometrial and fibroid cells (36). Although the expression
of oxytocin receptors is believed to be strictly related to pregnancy, their presence was demonstrated also in

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leiomyomatous uterus (37).

The first randomized placebo control study on the use of oxytocin was carried out in 2005. Ninety-four
patients were randomized to receive oxytocin during myomectomy. The protocol adopted was 15 UI
dissolved in 125ml of normal saline solution. There was no significant difference in terms of perioperative
blood loss and transfusion rate between placebo and treated group (38).
On the other hand, the infusion of oxytocin at a rate of 40 mU/ml during laparoscopic myomectomy seems to
have beneficial effects (39).

Misoprostol is a prostaglandin E1 analog and it is prescribed for the induction of labour in women with
intrauterine fetal death. This drug may decrease blood loss during myomectomy increasing myometrium
contraction and through a direct vasoconstrictive effect on uterine artery (40, 41).
There is only one study in literature including a small number of patients (n = 25) where misoprostol was
administrated during open myomectomy. Misoprostol was given vaginally at a dosage of 400g before the
operation. Compared with placebo group (n =12), patients who were given misoprostol (n = 13) showed
reduced blood loss (472ml 77 versus 621ml 121,p < 0.05) and operation time (48.5min 7.4 versus

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58min 8.8, p < 0.05) as well as reduced need for blood transfusion (2 - 15.3% versus 4 - 33.3%, p < 0.05)
(42).

The use of Prostaglandin analog type 2 (dinoprostone) has been evaluated in a recent double blind placebo
randomized control trial. 108 patients were randomized to receive 20mg vaginal suppository of dinoprostone

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(n = 54) or no treatment (n = 54) before abdominal myomectomy. Significant reduction in terms of blood
loss (485.7 361.3 ml versus 364.1 279.4 ml, p = 0.02) and Hb fall was observed in the treated group (1.4
g/dl 0.2 versus 1.9 0.1 g/dl, p = 0.03). Moreover, the number of units transfused was higher in the

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Chemically dissection of tissue

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control group (10 - 18.5% versus 2 - 3.7%, p = 0.04) (43).

Sodium 2 mercaptoethanesulfonate (mesna) is a thiolic drug able to lyse tissue connection (44). Benassi et

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al., first used mesna during open myomectomy in order to facilitate the enucleation of fibroids (45). Fortyeight patients were randomized to receive a local injection of mesna (n = 24) during open myomectomy, but
the authors did not report the dosage. Mesna was injected locally through a surgical needle at the dissection

zone, starting from the incision of the visceral peritoneum up to complete enucleation of the myoma. A
ureteral spoon was used to enucleate myomas during surgery despite the ordinary surgical scissors.
The operating time was significantly shorter in mesna group compared with the control group (median 70

min versus 90 min, p < 0.05) and the reduction in haemoglobin 24 hours after operation was less in patients
treated with mesna (0.9 g/dl versus 1.7 g/dl), p = 0.006).

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Moreover, the haematocrit levels appeared more elevated in treated group. Although the chemically
dissection was demonstrated valid also in other surgical procedure

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(46, 47) more data about its use in gynaecological surgery is demanded.

Gelatin thrombin matrix

Gelatin-thrombin matrix (FloSeal Matrix; Baxter Healthcare Corp, Fremont, CA) is a haemostatic sealant
successfully used in different surgical procedures (48, 49).
It is a compound of gelatin matrix and thrombin components which can be applied with the use of special
applicator. When spread over a damaged area it potentiates the local haemostasis process. There is only one
study in the literature investigating his role during abdominal myomectomy (50). Fifty women with
symptomatic fibroids were prospectively randomized to receive gelatin-thrombin matrix (n = 25) during
open myomectomy. Diluted vasopressin was applied both in the control and in treated group. Patients with
history of coagulopathy and preoperative haemoglobin level < 10 g/dl were excluded. The mean
intraoperative (625ml 120.5 versus 80ml 25.5, p = 0.01) and postoperative blood loss (250ml 75
versus 25ml 5, p = 0.01) were significantly higher in the control group. In terms of hospital stay, the usage
of Floseal Matrix resulted in shorter recovery time (2.5 1.2 versus 4.5 1.3 p =0.005). While No

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transfusion episode was observed in gelatin thrombin matrix group, 20 patients was transfused in control
group (<0.01).

Intraoperative blood salvage

Intraoperative blood savage has been successfully used during hysterectomy and for postpartum

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haemorrhage. It consists in the recycle of the blood shed during the operation which is filtered and washed
and eventually transfused back to the patient. It offers the valuable advantage of avoiding the various risk
associated with autologous blood transfusion such as immunological reaction and production of irregular

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antibodies. Therefore, it could be really useful for those women who refuse allogenic blood transfusion

(Jehovahs Witness) with relative reduce of blood transfusion by 39% (51). Intraoperative blood salvage has

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been used both in orthopaedic and cardiac surgery with satisfactory results in terms of reduction of blood
transfusion butthere are still few data involving gynaecological surgery. Only one prospective non

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randomized trial has investigated the safety and the efficacy of this procedure during open myomectomy.
Only patients with blood loss higher than 500ml was enrolled. The group who received autologous
transfusion showed and higher intraoperative blood loss compared with control group who did not received

autologous transfusion (842 353ml versus 626 103ml p < 0.05). Conversely a higher post-operative
haemoglobin was observed in the group where intraoperative blood savage technique was adopted. (12.4
1.1 versus 12.7 1.2, p < 0.05). No adverse reaction were reported associated with cell salvage technique

(52). Intraoperative blood salvage requires specific expertise and should only be used by healthcare team
with proven experience (53). Moreover, in cases where massive haemorrhage occurs the addition of

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Conclusion

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homologous transfusion could be unavoidable.

Haemorrhage is still the most important concern with open myomectomy. Blood loss during surgery largely
depend on number/dimension of fibroids removed and technique adopted during myomectomy. Of course all
predisposing factors to haemorrhage during surgery (low platelets concentrations, haemophilia, won
Willembrand disease, use of anticoagulation/antiaggregant medications) should be taken into account during
clinical assessment.

Although laparoscopic and vaginal technique have been shown to have satisfactory results in term of fertility
and symptoms resolution, open myomectomy is still the only option when the number and size of fibroids
does not allow any other surgical route. However, in this case there is the risk of significant haemorrhage.
Despite the number of studies on methods to achieve good haemostasis during the open myomectomy, there
is still not enough data from well-designed comparative randomized controlled trails. Therefore, differences
in patient characteristics (age, ethnicity, size, position and number of fibroids removed) make difficult to
attempt any comparison between currently available randomized trials. Consequently, there is still no
agreement on the preferred method (7). In addition, there are not enough data regarding their long term

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impact fertility, an outcome of particular importance considering that the commonest indication for
myomectomy is the preservation of fertility.

Funding:

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No funding was granted for the preparation of the manuscript.

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References

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1.
Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative
incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet
Gynecol. 2003;188(1):100-7.
2.
Buttram VC, Jr. Uterine leiomyomata--aetiology, symptomatology and management.
Prog Clin Biol Res. 1986;225:275-96.
3.
Gambadauro P. Dealing with uterine fibroids in reproductive medicine. J Obstet
Gynaecol. 2012;32(3):210-6.
4.
Casini ML, Rossi F, Agostini R, Unfer V. Effects of the position of fibroids on
fertility. Gynecol Endocrinol. 2006;22(2):106-9.
5.
Farhi J, Ashkenazi J, Feldberg D, Dicker D, Orvieto R, Ben Rafael Z. Effect of
uterine leiomyomata on the results of in-vitro fertilization treatment. Hum Reprod.
1995;10(10):2576-8.
6.
Taylor A, Sharma M, Tsirkas P, Di Spiezio Sardo A, Setchell M, Magos A. Reducing
blood loss at open myomectomy using triple tourniquets: a randomised controlled trial.
BJOG. 2005;112(3):340-5.
7.
Kongnyuy EJ, Wiysonge CS. Interventions to reduce haemorrhage during
myomectomy for fibroids. Cochrane Database Syst Rev. 2011(11):Cd005355.
8.
Bieren R, McKelway W. The use of a tourniquet in uterine surgery. Am J Obstet
Gynecol. 1956;71(2):433-5.
9.
Rubin IC. Uterine fibromyomas and sterility. Clin Obstet Gynecol. 1958;1(2):501-18.
10.
Al-Shabibi N, Korkontzelos I, Gkioulekas N, Stamatopoulos C, Tsibanakos I, Magos
A. Cable ties as tourniquets at open myomectomy. Int J Gynaecol Obstet. 2010;110(3):265-6.
11.
Magos A, Al-Shabibi N, Korkontzelos I, Gkioulekas N, Tsibanakos I, Gkoutzioulis
A, et al. Ovarian artery clamp: initial experience with a new clamp to reduce bleeding at open
myomectomy. J Obstet Gynaecol. 2011;31(1):73-6.
12.
Ikechebelu JI, Ezeama CO, Obiechina NJ. The use of torniquet to reduce blood loss at
myomectomy. Niger J Clin Pract. 2010;13(2):154-8.
13.
Fletcher H, Frederick J, Hardie M, Simeon D. A randomized comparison of
vasopressin and tourniquet as hemostatic agents during myomectomy. Obstet Gynecol.
1996;87(6):1014-8.
14.
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(5):681-7.
15.
O'Leary JA. Uterine artery ligation in the control of postcesarean hemorrhage. J
Reprod Med. 1995;40(3):189-93.
16.
Liu WM, Tzeng CR, Yi-Jen C, Wang PH. Combining the uterine depletion procedure
and myomectomy may be useful for treating symptomatic fibroids. Fertil Steril.
2004;82(1):205-10.
17.
Liu WM, Wang PH, Chou CS, Tang WL, Wang IT, Tzeng CR. Efficacy of combined
laparoscopic uterine artery occlusion and myomectomy via minilaparotomy in the treatment
of recurrent uterine myomas. Fertil Steril. 2007;87(2):356-61.
18.
Helal AS, Abdel-Hady el S, Refaie E, El Shamy M, El Fattah RA, Mashaly Ael M.
Preliminary uterine artery ligation versus pericervical mechanical tourniquet in reducing
hemorrhage during abdominal myomectomy. Int J Gynaecol Obstet. 2010;108(3):233-5.
19.
Sapmaz E, Celik H, Altungul A. Bilateral ascending uterine artery ligation vs.
tourniquet use for hemostasis in cesarean myomectomy. A comparison. J Reprod Med.
2003;48(12):950-4.
20.
Blanc J, Courbiere B, Desbriere R, Bretelle F, Boubli L, d'Ercole C, et al. Is uterinesparing surgical management of persistent postpartum hemorrhage truly a fertility-sparing
technique? Fertil Steril. 2011;95(8):2503-6.
21.
Kimura T, Kusui C, Matsumura Y, Ogita K, Isaka S, Nakajima A, et al. Effectiveness
of Hormonal Tourniquet by Vasopressin during Myomectomy through Vasopressin V1a

Page 12 of 17

13

Ac
ce
p

te

an

us

cr

ip
t

Receptor Ubiquitously Expressed in Myometrium. Gynecologic and Obstetric Investigation.

2002;54(3):125-31.
22.
Townsend DE. Vasopressin pack for treatment of bleeding after myoma resection.
Am J Obstet Gynecol. 1991;165(5 Pt 1):1405-7.
23.
Frederick J, Fletcher H, Simeon D, Mullings A, Hardie M. Intramyometrial
vasopressin as a haemostatic agent during myomectomy. Br J Obstet Gynaecol.
1994;101(5):435-7.
24.
Riess ML, Ulrichs JG, Pagel PS, Woehlck HJ. Case report: Severe vasospasm mimics
hypotension after high-dose intrauterine vasopressin. Anesth Analg. 2011;113(5):1103-5.
25.
Alexander GD, Brown M. A safe dose of vasopressin for paracervical infiltration.
Anesth Analg. 1995;81(2):428.
26.
Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before
hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev.
2001(2):Cd000547.
27.
Donnez J, Polet R, Smets M, Bassil S, Nisolle M. Hysteroscopic myomectomy. Curr
Opin Obstet Gynecol. 1995;7(4):311-6.
28.
Donnez J, Nisolle M, Grandjean P, Gillerot S, Clerckx F. The place of GnRH agonists
in the treatment of endometriosis and fibroids by advanced endoscopic techniques. Br J
Obstet Gynaecol. 1992;99 Suppl 7:31-3.
29.
Perino A, Chianchiano N, Petronio M, Cittadini E. Role of leuprolide acetate depot in
hysteroscopic surgery: a controlled study. Fertil Steril. 1993;59(3):507-10.
30.
Vercellini P, Trespidi L, Zaina B, Vicentini S, Stellato G, Crosignani PG.
Gonadotropin-releasing hormone agonist treatment before abdominal myomectomy: a
controlled trial. Fertil Steril. 2003;79(6):1390-5.
31.
Gocmen A, Kara IH, Karaca M. The effects of add-back therapy with tibolone on
myoma uteri. Clin Exp Obstet Gynecol. 2002;29(3):222-4.
32.
Fedele L, Vercellini P, Bianchi S, Brioschi D, Dorta M. Treatment with GnRH
agonists before myomectomy and the risk of short-term myoma recurrence. Br J Obstet
Gynaecol. 1990;97(5):393-6.
33.
Fauconnier A, Chapron C, Babaki-Fard K, Dubuisson JB. Recurrence of leiomyomata
after myomectomy. Hum Reprod Update. 2000;6(6):595-602.
34.
Gai MY, Wu LF, Su QF, Tatsumoto K. Clinical observation of blood loss reduced by
tranexamic acid during and after caesarian section: a multi-center, randomized trial. Eur J
Obstet Gynecol Reprod Biol. 2004;112(2):154-7.
35.
Caglar GS, Tasci Y, Kayikcioglu F, Haberal A. Intravenous tranexamic acid use in
myomectomy: a prospective randomized double-blind placebo controlled study. Eur J Obstet
Gynecol Reprod Biol. 2008;137(2):227-31.
36.
Cesen-Cummings K, Houston KD, Copland JA, Moorman VJ, Walker CL, Davis BJ.
Uterine leiomyomas express myometrial contractile-associated proteins involved in
pregnancy-related hormone signaling. J Soc Gynecol Investig. 2003;10(1):11-20.
37.
Busnelli M, Rimoldi V, Vigano P, Persani L, Di Blasio AM, Chini B. Oxytocininduced cell growth proliferation in human myometrial cells and leiomyomas. Fertil Steril.
2010;94(5):1869-74.
38.
Agostini A, Ronda I, Franchi F, Bretelle F, Roger V, Cravello L, et al. Oxytocin
during myomectomy: a randomized study. Eur J Obstet Gynecol Reprod Biol.
2005;118(2):235-8.
39.
Wang CJ, Lee CL, Yuen LT, Kay N, Han CM, Soong YK. Oxytocin infusion in
laparoscopic myomectomy may decrease operative blood loss. J Minim Invasive Gynecol.
2007;14(2):184-8.
40.
Baxter GS, Clayton JK, Coleman RA, Marshall K, Sangha R, Senior J.
Characterization of the prostanoid receptors mediating constriction and relaxation of human
isolated uterine artery. Br J Pharmacol. 1995;116(1):1692-6.
41.
Wray S. Uterine contraction and physiological mechanisms of modulation. Am J
Physiol. 1993;264(1 Pt 1):C1-18.

Page 13 of 17

14

Ac
ce
p

te

an

us

cr

ip
t

42.
Celik H, Sapmaz E. Use of a single preoperative dose of misoprostol is efficacious for
patients who undergo abdominal myomectomy. Fertil Steril. 2003;79(5):1207-10.
43.
Shokeir T, Shalaby H, Nabil H, Barakat R. Reducing blood loss at abdominal
myomectomy with preoperative use of dinoprostone intravaginal suppository: a randomized
placebo-controlled pilot study. Eur J Obstet Gynecol Reprod Biol. 2013;166(1):61-4.
44.
James CA, Mant TG, Rogers HJ. Pharmacokinetics of intravenous and oral sodium 2mercaptoethane sulphonate (mesna) in normal subjects. Br J Clin Pharmacol. 1987;23(5):5618.
45.
Benassi L, Lopopolo G, Pazzoni F, Ricci L, Kaihura C, Piazza F, et al. Chemically
assisted dissection of tissues: an interesting support in abdominal myomectomy. J Am Coll
Surg. 2000;191(1):65-9.
46.
Vincenti V, Mondain M, Pasanisi E, Piazza F, Puel JL, Bacciu S, et al. Cochlear
effects of mesna application into the middle ear. Ann N Y Acad Sci. 1999;884:425-32.
47.
von Renteln D, Dulai PS, Pohl H, Vassiliou MC, Rosch T, Rothstein RI. Endoscopic
submucosal dissection with a flexible Maryland dissector: randomized comparison of mesna
and saline solution for submucosal injection (with videos). Gastrointest Endosc.
2011;74(4):906-11.
48.
Jorgensen S, Bascom DA, Partsafas A, Wax MK. The effect of 2 sealants (FloSeal
and Tisseel) on fasciocutaneous flap revascularization. Arch Facial Plast Surg. 2003;5(5):399402.
49.
User HM, Nadler RB. Applications of FloSeal in nephron-sparing surgery. Urology.
2003;62(2):342-3.
50.
Raga F, Sanz-Cortes M, Bonilla F, Casan EM, Bonilla-Musoles F. Reducing blood
loss at myomectomy with use of a gelatin-thrombin matrix hemostatic sealant. Fertil Steril.
2009;92(1):356-60.
51.
Carless PA, Henry DA, Moxey AJ, O'Connell D L, Brown T, Fergusson DA. Cell
salvage for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst
Rev. 2006(4):Cd001888.
52.
Yamada T, Yamashita Y, Terai Y, Ueki M. Intraoperative blood salvage in abdominal
uterine myomectomy. Int J Gynaecol Obstet. 1997;56(2):141-5.
53.
RCOG. Blood Transfusions in Obstetrics 2008.
54.
Golan A, Bukovsky I, Pansky M, Schneider D, Weinraub Z, Caspi E. Pre-operative
gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata. Hum
Reprod. 1993;8(3):450-2.
55.
Shaw RW. Mechanism of LHRH analogue action in uterine fibroids. Horm Res.
1989;32 Suppl 1:150-3.
56.
Bustos Lopez HH, Miranda Rodriguez JA, Kably Ambe A, Serviere Zaragoza C,
Espinoza De Los Monteros A, Alvarado Duran A. Pre-operative medical treatment of uterine
leiomyomatosis with hypophysiary gonadotropin releasing hormone analogues. Ginecologia y
Obstetricia de Mexico. 1995;63:356-64.
57.
Cetin MT, VardarMA, SC D, KibarM. Administration of preoperative gonadotropin
releasing hormone agonist (buserelin) for uterine leiomyomas. Ann Med Sci 1995 4 102-108.
58.
Friedman AJ, Rein MS, Harrison-Atlas D, Garfield JM, Doubilet PM. A randomized,
placebo-controlled, double-blind study evaluating leuprolide acetate depot treatment before
myomectomy. Fertil Steril. 1989;52(5):728-33.

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Condensation: Open myomectomy is a widespread uterine-sparing surgery.

Strategies to achieve good haemostasis during this procedure are illustrated in the
present review.

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Table. 1 Techniques to reduce blood loss in open myomectomy (placebo-controlled studies)

Uterine size (pw) Blood loss (ml) Hb post op fall (g/dl) Number of. fibroids

us

Sample size*

Percentage of women transfused.(%)

removed

Ikechebelu 2010 (12)

28

93

Treated 14

18 3.7

489 362

2.79 [0.33]

Control 14

17 3.4

2359 1241

2.96 [0.92]

Treated 54

n.a

516 293

n.a

Control 39

756 286

11 (79%)

n.a

11 (20%)
21 (54%)

Treated 10
Control 10

18 [14-24]

675 [500800]

5.3 [4.0-6.4]

8 [4-60]

5 (50%)

Raga 2009 (56)

50

Treated 25

18.2 2.7

80 25.5

0.5 0.2

3.2 1.2

Control 25

17.9 1.4

625 120.5

2.8 0.9

3.1 1.6

5 (20%)

15.7 2.6

472 77

n.a

5.5 1

2 (15.3%)

5.3 0.9

4 (33.3%)

0.9 [0.1-2.1]

9 [217]

n.a

1.7 [0.1-2.9]

6 [211]

n.a

3.3 3.7

Treated 13
Control 12

15.5 2.8

Benassi 2000 (53)

58

Treated 29

n.a

Control 29
Caglar 2008 (43)

100

Shokeir 2013 (51)

108

Treated 50
Control 50
Treated 54
Control 54

621 121

n.a

ce
pt

25

1.7 [0.7-2.3]

1 (7% )

4.5 [1-34]

20

Celik 2003 (50)

225 [150-400]

10.5 [1-24]

Frederick 1994 (27)

ed

17 [14-24]

M
an

Taylor 2005 (6)

14 [1-81]

n.a

804 482

2 1.8

10 (20%)

17 2.5

364 279

1.4 0.2

4.6 3.7

2 (4%)

16.7 2.9

485 361.3

1.9 0.1

4.4 3.5

10 (18.5%)

1047 617

15 (30%)

Data are presented as mean SD or median [range]

Ac

Pw: pregnancy week; Hb haemoglobin;

* data presented as study versus control group

n.a: not available

Page 16 of 17

Table 2. GnRH analog pretreatment in open myomectomy (placebo-controlled studies)

Sample (n)

Uterine size (ml)

Blood loss (ml)

Percentage of. woman

transfused (%)

Golan 1993
(60)

21

Shaw 1989
(61)

GnRH

432 165

GnRHa

235 62.2

Control 16

Control

486 131.8

Control

275 140

GnRHa 12

n.a

GnRHa

320 304.8

GnRHa

Control

476 258

Control

GnRHa

330 21.4

GnRHa

Control

457 151.4

Control

GnRHa

280 132.3

n.a

Control

422 416.4

n.a

GnRHa

135 77.5

Control

292 123.9

n.a

GnRHa

213 132

Control 9
GnRHa

15

Busto
28

n.a

Control 6
GnRHa

Lopez 1995

13

n.a

Control 15

(62)

(63)

GnRHa
30

Friedman
1989 (64)

Control 15
GnRHa

18

15

an

Cetin 1995

Control 9

Control

Data are presented as mean standard deviation

n.a

6/12 (50%)

ip
t

24

5/9 (56%)
0

1/6 (17%)

cr

(40)

GnRHa

us

Fedele 1990

302 129

n.a

GnRHa

2/9 (22%)

Control

2/9 (22%)

Ac
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te

GnRHa: Gonadotrophin releasing hormone agonist; n.a: not available

Page 17 of 17