[Dutch Society of Obstetrics and Gynaecology]

SUBMUCOUS MYOMAS—DIAGNOSIS AND THERAPY

Version 1.0

Date of approval 20 September 2006

Methodology Consensus-based
Discipline Multi-disciplinary

Responsibility NVOG

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 Aim and target group
This draft standard protocol aims to use critically reviewed scientific research to make recommendations concerning
the diagnostic and (chiefly hysteroscopic) therapeutic approach to submucous myomas. Principles of minimal
invasiveness both in diagnosis and in the treatment and prevention of complications are also considered.

Procedure
This subject came up at the Witte Raaf meetings (consensus meetings of gynaecologists interested in endoscopy)
on 7 and 8 March 2002 and 13–14 March 2003. The draft standard protocol was reviewed in accordance with the
AGREE instrument. The recommendations made have been classified into classes A1, A2, B, C, or D in accordance
with the NVOG Guideline Production Manual [1] based on the level of scientific evidence available.

Design of the literature search

No publications about this specific subject were found in the Cochrane Library or in the Cochrane Register
of controlled studies. There was indeed a review article about the role of GnRH analogues in the treatment
of myomas in general. In addition, a Pubmed search (1966–2002) was carried out in Medline. The databases were
searched using relevant MESH terms, including all subheadings, in combination with the use of the following key
terms: comparative study, diagnosis, diagnostic imaging, endometrium, endoscopy, female, humans, hysteroscopy,
leiomyoma, magnetic resonance imaging, methods, minimally invasive, myoma, pathology, predictive value of tests,
premenopause, submucous myoma, surgery, surgical procedures, treatment outcome, ultrasonography, uterine
hemorrhage, uterine neoplasms, and uterus. Cross-references were also searched for—albeit non-systematically
—in Medline journals and in journals not forming part ofthe Medline database.

1 Description of the problem

In the event of abnormal blood loss, in particular heavy menstrual blood loss, it is chiefly submucous
myomas that appear to be involved. Diagnostic and therapeutic options have burgeoned over the last decade;
the approach to submucous myomas and bleeding disorders in premenopause has improved greatly. Over-treatment
—e.g. extirpation of the uterus in the case of menorrhagia as a result of a small pedunculated submucous myoma
—can thereby be prevented. New (minimally invasive) treatment methods give rise, however, to specific problems.
Consequently, protocols need to be devised for these techniques.

2 Analysis of the available knowledge

2.1 Definition; classification
Leiomyomas are benign growths in the muscle of the uterus. They can be classified according to location
in the uterine wall:

• submucous: lying under the mucosa and protruding into the cavity of the body of the uterus
• subserous: lying under the serosa and protruding towards the abdominal cavity
• intramural: lying in the uterine wall.

Submucous myomas may also be further classified into types 0–II, known in the literature as the ESGE classification
(ESGE: European Society of Gynaecological Endoscopy, previously the ESH classification), which indicates the
degree of intramural extension (see figure 1) [2]. Although other sub-classifications are used, this classification
is the one applied most often internationally, due to the therapeutic consequences (see 2.5) [3].

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2.2 Epidemiology
Myomas can manifest clinically in 25% of cases [4]; asymptomatic myomas are described in 20–70%
of all women (and in well over 80% of black women) [5].

Myomas occur almost exclusively in women of reproductive age, with a progressive increase over the age
of 40. Globally, myomas are the most common indication for a hysterectomy: in Australia, accounting for
21.7% [6], in the USA, 27% [7], and in Finland, 50% [8]. In the various studies, an insufficient distinction is made,
however, according to the location of the myomas. In the literature, risk factors are listed for the occurrence of
myomas (positive family history, black ethnicity, radiation) and for the growth of myomas (nulliparity, obesity)
but these are not specific for the submucous location and to some extent have not yet been sufficiently researched.

Figure 1
ESGE classification of submucous myomas based on intramural extension.
Type 0: 0%, type I: < 50%, type II: >50% (borrowed with the consent of the ASRM: Fertil Steril 2000).

2.3 Symptomatology
There is the impression that, in myomas, the submucous forms are over-represented, despite the fact that these are
the type that occur least frequently (5–10%). As a result of diagnostic shortcomings, we do not, however, know enough
about the actual prevalence of submucous myomas, and the proportion of those in the overall symptomatology.
In the literature, the figures cited vary from 7.8% to 29.9% [9–11]. Most authors do not, however, make a distinction
between patients who are referred to their hospital in the first instance from primary care when abnormal uterine blood
loss occurs and patients referred by colleagues in secondary care. As the latter group comprises a highly selected
population, it is indeed important to make this distinction. In the group referred from primary care, a total prevalence
of submucous myomas of 14.7% (n = 675) is found [3].

2.3.1 Abnormal uterine blood loss

Of women with more than 200 ml of menstrual blood loss, 40% have myomas [12].
Only in the group referred from secondary care are more submucous myomas found in women with menorrhagia than
in women with metrorrhagia [3].
Although it is sometimes asserted that bleeding problems in the case of myomas are specifically associated with
a submucous location, this is contested by others [13]. For example, recent studies showed that, in patients in whom
a hysterectomy took place in connection with uterine myomatosis and menorrhagia, submucous myomas were found
in only 40% [14].
We know little about the causal link between myomas and blood loss. Possible explanations include enlargement
of the surface area of the cavity of the body of the uterus and venous stasis due to compression, which might explain
why myomas other than submucous myomas can cause bleeding.

2.3.2 Dysmenorrhoea
Secondary dysmenorrhoea has been shown to be specifically associated with submucous myomas.
In the case of dysmenorrhoea, a significant over-representation of these myomas is found [3].
The contractions as a result of the tendency of the uterus to expel an intracavitary structure are viewed
as the most important explanation for the symptoms of pain that occur [13].
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 2.3.3 Sub-fertility
No causal relationship between myomas and fertility disorders has ever been demonstrated, but it is tempting
for many to regard a diagnosed submucous myoma in a woman with an unfulfilled desire to have children
as a possible cause of her problem. Pregnancy figures are cited between 31% and 65% after myomectomy
(by means of hysteroscopy or laparotomy), but no randomised studies have been carried out into this [13, 15].
It is striking that the results of hysteroscopy, laparoscopy, and laparotomy do not differ significantly [16]. Although
it has been described that sub-fertility occurs in 27–40% of women with multiple myomas, other possible causes
of the sub-fertility are also found in most cases [17]. A meta-analysis shows that only myomas with a submucous
or intracavitary component are associated with a reduced likelihood of reproduction and that hysteroscopic
treatment might well be advantageous in such cases [18].

2.4 Diagnosis
2.4.1 Curettage
Curettage should not be carried out to diagnose myomas but remain reserved as a method of obtaining endometrial
tissue for histological assay if there are no local abnormalities [3, 17, 19].

2.4.2 Ultrasound
The sensitivity of transvaginal ultrasound to diagnose myomas averages 94% (range: 62–100%) with a specificity
of 98% (PPV 82–90%, NPV 96–98%) [20–22].
For the diagnosis of intracavitary abnormalities, a likelihood ratio has been found of 0.04 in the case of a normal
vaginal echo and 9.09 for an abnormal echo, in comparison with hysteroscopy as the golden standard [3].
Ever more diagnostic hysteroscopies and curettages could be avoided by using transvaginal ultrasound to exclude
polyps, myomas, or malignant abnormalities (NVOG guideline 4, Abnormal blood loss in postmenopausal women,
and 52, Diagnosis and treatment of menorrhagia [23, 24]).

2.4.3 Contrast-enhanced ultrasound

In the case of contrast-enhanced ultrasound, the uterine cavity is filled with NaCl 0.9% as a contrast medium
before the ultrasound is carried out. This technique is also referred to as hysterosonography, or SIS (saline infusion
sonohysterography). Depending on the logistical options, the examination can be carried out after
an ultrasound or immediately after a hysteroscopy, using the distension medium used in that examination.
In studies comparing different methods of intrauterine diagnosis, contrast-enhanced ultrasound has been shown
to be more reliable than transvaginal ultrasound alone, and its predictive value is just as high as that of hysteroscopy.
The reliability of vaginal ultrasound increases through the addition of water as a contrast medium [22, 25–28].
In a meta-analysis by de Kroon, the following data were found in this regard: sensitivity 0.95 (95% CI, 0.93–0.97),
specificity 0.88 (95% CI, 0.85–0.92), and likelihood ratios: 8.23 (95% CI, 6.2–11) and 0.06 (95% CI, 0.04–0.09) [1].
In a study involving 52 women just before extirpation of the uterus (with histology as the golden standard), even in the
case of an abdominal contrast-enhanced ultrasound, values of 100% were found for sensitivity, specificity, and positive
and negative predictive values [21]. The added value of contrast-enhanced ultrasound over and above hysteroscopy
lies in the fact that information can be obtained not just about the cavity of the body of the uterus but also about the
uterine wall. Using this technique, the presence, size, and location of the myoma is easier to establish [29, 30], and
operability and the likelihood of complications can be better assessed [3, 29]). Also, the distance between the myoma
and the serosa can generally be effectively determined—this is an important piece of information preoperatively,
in order to prevent perforation. In addition, the examination, if there is significant blood loss, is subject to less
reduced visibility than in the case of hysteroscopy in an analogous situation. Finally, contrast-enhanced ultrasound
is experienced as less painful than hysteroscopy [31], but it can be disputed whether this still applies in comparison
with the vaginoscopic technique of hysteroscopy. There are no systematic studies into this, but the literature that is
available suggests that the differences then disappear or might actually ‘tip’ in the other direction [2, 3].

2.4.4 Hysteroscopy
Many authors regard a diagnostic hysteroscopy as the golden standard for the diagnosis of the cavity of the body
[32–34], but this examination has limitations (see 2.4.3, ultrasound with contrast medium). A number of studies show
that, when the presence of submucous myomas is being determined, sensitivity, specificity, and the positive and
negative predictive values of hysteroscopy do not differ significantly from those of ultrasound with contrast medium
[20, 21, 31]; they are, however, lower in other authors: sensitivity 82% and specificity 87% [27].

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2.4.5 Hysterosalpingography (HSG)
The suspicion of a submucous myoma commonly arises for the first time in particular in the case of a fertility
examination when HSG is carried out. HSG, however, should not be recommended as a primary examination,
due to the very low reliability in relation to intracavitary abnormalities: up to 32% false positive results have been
described [35–38]. Furthermore, this examination has the further disadvantage of giving rise to a
radiation load.

2.4.6 MRI
Although some people promote magnetic resonance (MRI) to diagnose submucous myomas, the limited availability
and the costs of a routine scan will restrict use. Nonetheless, the use of MRI has been shown to be better in terms
of accurately determining the size of the myoma and the degree of intramural extension [26]. An MRI should therefore
be considered in the case of complex, minimally invasive procedures (e.g. large, type-II myomas). Depending on
availability, MRI can in any case be an alternative if ultrasound with contrast medium fails or is contraindicated.

2.4.7 Puncture biopsy

It is possible both transvaginally and transabdominally, on the basis of the ultrasound, to carry out a preoperative
histological examination of a myoma to differentiate between adenomyosis and sarcomas [39]. The question, however,
is whether an early detection of adenomyosis provides so much added value that it justifies an invasive diagnostic
procedure. This also applies mutatis mutandis to sarcomas: at least in the premenopause, these occur very rarely.
Furthermore, there is also the theoretical possibility that tumour cells may be disseminated though the puncture.
This form of diagnostic procedure is also not very popular.

2.4.8 Colour and pulsed Doppler ultrasound

Doppler ultrasound enables blood perfusion patterns to be determined in organs in the small pelvis [40]. Some
suggest that adenomyosis and sarcomas can be differentiated from myomas on the basis of various perfusion indices
[41], but that has not been confirmed in later studies. There is no consensus concerning methodology.

2.4.9 Three-dimensional ultrasound

The opportunities afforded by three-dimensional ultrasound appear promising. There is no evidence to date in the
literature, however, for significant added value in comparison with the techniques referred to above. We know that
the human brain itself is already able to provide the stereometric representation that the newer ultrasound devices
suggest. In a study on endometrial polyps, both three-dimensional ultrasound and three-dimensional contrast-
enhanced ultrasound were shown to have higher specificity than the comparable two-dimensional techniques (69.5%
vs 88.8% and 94.1% vs 100%, respectively); the two-dimensional contrast-enhanced ultrasound, however, was found
to score even better than three-dimensional conventional ultrasound [42]. For submucous myomas, no comparative
data are yet available, however.

2.5 Therapy
2.5.1 Hysteroscopy
The most commonly used treatment of submucous myomas is hysteroscopic transcervical resection (TCRM). In the
literature, success rates of 71–96% are cited for the treatment of menorrhagia [3, 15, 43–45]. The likelihood that one
treatment is sufficiently effective has been shown to be highly dependent on the degree of intramural extension: type
0: 96%, type I: 74%, type II: 67% (n = 93, 2–8 year follow-up) [44]. The deeper the myoma in the myometrium, the
greater the chance of an incomplete resection and the greater the likelihood of needing to repeat the procedure: from
0% in the case of type 0 to 36% in the case of type II [3]. There are also indications that, even after an incomplete
resection (via spontaneous regression or resorption of myoma tissue), the symptoms can abate: in one study, this
occurred in up to 66% of the cases [46] (it is not clear from the article whether there is a maximum proportion of the
myoma that can be left behind). Furthermore, success is partly dependent on the possible presence of other myomas,
which increase the likelihood of the problem recurring. There are indications that TCRM is most successful in uteruses
of normal size with no more than two submucous myomas and that this treatment would probably have to be limited
to this group [3]. A discussion of the likelihood of recurrence in these instances should in any case be recommended.
Also, for each myoma, the size that hysteroscopic removal permits is likewise limited: usually, a maximum of 4–5 cm
is considered achievable [2, 45]. If the diameter is greater, drug pre-treatment can be considered to try to bring the
myoma to within these bounds (see 2.6).
If the myoma is submucous, TCRM is obviously the least invasive approach.

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 2.5.2 Myoma enucleation, embolisation, extirpation of the uterus
In the literature, there is consensus concerning the fact that myoma enucleation, embolisation, and extirpation
of the uterus can be considered over-treatment in the case of relatively small submucous myomas [47].
These therapeutic options are reserved for cases in which the myomas are too large or do not respond to the
pre-treatment. An extensive discussion of these falls outside the scope of this guideline, as they are not specific
for the submucous location.
The submucous location, for some researchers, is a (relative) contraindication for embolisation, due to the likelihood
of necrosis in the cavity of the body of the uterus with risk of expulsion, and probably a greater chance of sepsis
[48, 49]. For all forms of surgical myoma treatment where the patient would still like to have children, the potential
consequences for pregnancy should be considered, such as rupture of the uterus and also, in theory, placenta accreta
or increta. There is no systematic research available about this; there are only anecdotal reports [50, 51].

2.6 Precautions in relation to therapy

All of the precautions are connected with one or more of the chief complications that should be avoidable
if such precautions are taken: intravasation, infection, perforation, and bleeding.

2.6.1 Drug pre-treatment

When TUR (transurethral resection) syndrome occurs (see below), the duration of the procedure and the location of
the myoma have been shown to be the most important risk factors [3]. Even though the surgeon’s expertise obviously
plays an additional role (if only in as far as this affects the speed of the procedure), this has never been researched.
Other authors also cite the size of the myoma, but there is probably a correlation with the duration of the procedure
in this instance too, in fact an exponential one: the removal of tissue is linked to the volume of the myoma; for the
relationship between the volume and the radius of a (spherical) myoma, the formula 4/3 πr3 obviously applies.
Preoperative drug therapy can reduce the size of the myoma scheduled for removal. Although many drugs have been
researched, in practice only GnRH analogues have been shown to cause myomas to shrink to a significant degree,
with values ranging between 30% and 70%, if these drugs are administered for the 3–4 months prior to surgery
[52–27]. No distinction was made in these studies as to location of the myomas, and no endoscopic procedures were
included, but it seems possible to extrapolate some of the results to submucous myomas and TCRM. An additional
advantage in the preoperative administration of GnRH analogues is the correction of any anaemia that might be
present. During the operation, there is reduced blood loss [58–60].
There are no prospective randomised studies available, however, that show the effect of GnRH reduction specifically
on submucous myomas. Retrospective studies furthermore do suggest such an effect [61–63].
In the case of submucous myomas with a diameter of less than 3 cm, in one study no additional advantage
was found of pre-treatment either for the patient or the surgeon [64]. The question of the extent to which preoperative
myoma reduction using drugs is always necessary cannot effectively be answered, based on the literature available
to date. It is possible that the usually altered consistency of the myoma is advantageous, even if the diameter remains
the same.
Contrary to what one would expect, the addition of tibolone to treat vasomotor symptoms (add-back therapy) has been
shown not to have any adverse effect on myoma reduction [65, 66].
Also, an unfavourable location, e.g. in the uterine horn, is viewed by some as an indication for pre-treatment,
to prevent perforation [64].
In view of the high costs and side effects of GnRH analogues, it makes sense to determine indications and restrict
administration to this selected group.
On the basis of the above, premedication should be considered in the case of the following [67]:

• sub-fertility
• myomas with a diameter of 4 cm or more
• an adverse location in the cavity of the body of the uterus, e.g. in the uterine horn
• anaemia due to bleeding disorders
• type-II myomas.

These indications apply all the more if they occur in combination with each other. For the future, it should
be possible to consider establishing a scoring system in which the indications can be handled in a weighted manner.

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2.6.2 Distension media and instruments

• Distension medium

In the case of TCRM with hypotonic distension media (sorbitol, glycine, etc.), there is a consensus concerning the
need to use a system that makes it possible to measure the quantity of distension medium flowing in and out as a
measure of the quantity of intravasation, to prevent fluid overload [68].

There is no systematic research into this. In the meantime, systems have been developed that operate using bipolar
electrical current, which has the advantage that isotonic fluid can be used to this end. Although the safety margins
as regards intravasation are then greater, it is desirable nonetheless to monitor fluid load, particularly if there are
cardiopulmonary risk factors [69].
The consequences of intravasation can be subdivided into volume load, which can occur in the case of excessive
infusion with all media, and electrolyte imbalances, if the medium is not isotonic. The latter can lead to TUR syndrome,
which was first described in the case of transurethral resection [70]. The disruption in electrolyte imbalance caused by
the intravasation of non-isotonic, non-conductive fluids as a distension medium can potentially cause serious organ
damage.
A linear relationship has been shown between the intravasation of electrolyte-free (non-isotonic) fluid and the
occurrence of hyponatraemia: an approximately 1 mmol/L reduction in Na per 100 ml loss, with cerebral oedema
furthermore shown to be visible on a CT scan after a loss of just 500 ml [3, 71, 72].
The consequences of hyponatraemia are:

• 120–125 mmol/l: malaise, nausea, headache

• 110–120 mmol/l: headache, lethargy, confusion
• < 110 mmol/l: strokes, delirium, coma (beware of hypokalaemia: arrhythmias)

Based on an average value of 140 mmol/l for Na in the population, an Na level of < 125 mmol/L corresponds
to an approximately 1500 ml loss [3]. Determining osmotic concentration is probably a better measure of the degree
of electrolyte imbalance [73].
For the maximum acceptable loss of electrolyte-free distension fluid, the arbitrary thresholds set out below can
probably be used. The WGE (Gynaecological Endoscopy Working Group) achieved a consensus about this in 2002,
which is consistent with that of German-speaking countries [68], and the guidelines of the American Association of
Gynecologic Laparoscopists (AAGL) [74], the American College of Obstetrics and Gynecology (ACOG) [69], and the
Scottish Royal College of Physicians [75].

> 500 ml

• intensification of preoperative alertness and monitoring

• possible administration of mannitol 20% [74]

> 1000 ml

• aiming at the termination of the procedure (max. 1500 ml intravasation)

• administration of diuretics (e.g. furosemide, 20–40 mg)
• administration of NaCl 2.5% on the basis of electrolyte assays

In order to be able to determine this loss of rinsing fluid, an automatic pump system should be used, which determines
the pressure and the flow rate and continuously indicates the quantity of medium flowing in and out. It is equally
unclear from the literature what the optimal form of anaesthesia is. On one hand, regional analgesia through
vasodilation can increase the likelihood of intravasation, but on the other hand the first symptoms of hyponatraemia
thereby become evident more quickly than in the case of general anaesthesia. As bipolar systems (that have the great
advantage that NaCl 0.9% can be used as a distension medium) are used in only a few hospitals at the moment, just
the monopolar systems are discussed in this guideline. On the basis of the favourable experiences in these hospitals,
however, it should be anticipated that this guideline will need to be adjusted in this regard in due course. The ACOG
advises accepting a maximum loss of 2500 ml NaCl 0.9% [69]. There are no results of clinical studies concerning
this, however.

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 • Perforation

The likelihood of perforation probably rises as the distance of the myoma from the serosa of the uterus falls.
In the literature, an arbitrary safe threshold of 8 mm is cited [76]. As this distance reduces, more caution or alertness
is required, and carrying out the procedure under laparoscopic guidance or ultrasound monitoring can be considered.
In the case of perforation, it is advisable to terminate the procedure and restart it later, unless there is a suspicion
of intestinal injury, in which case laparoscopy and sometimes even laparotomy in cases of doubt are suitable [69, 75].

2.6.3 Antibiotic prophylaxis

The incidence of infection in the case of hysteroscopic operations is higher than in the case of diagnostic procedures
but is still very low [77]. In the case of TCRE (transcervical resection of the endometrium), the usefulness of antibiotic
prophylaxis has been studied and has not been shown effective in preventing clinically manifest infections, although
there was a significant reduction in the occurrence of bacteraemia (2% vs 16%) [78]. With reference to this latter,
somewhat paradoxical effect, the possibility cannot be excluded that if the study population had been larger,
a significant difference would indeed have been found in the prevention of infections.
The question is whether these data can simply be extrapolated to apply to TCRM; the fact that the wound surfaces
are smaller does not, however, suggest that the risks, in this instance, would be much greater.
On the other hand, there are a number of anecdotal reports of serious, sometimes fatal infections, on the
basis of which some practitioners have indeed carried out antibiotic prophylaxis [79, 80].
Recommending antibiotic prophylaxis on this basis and on the basis of a reduction in bacteraemia should
be considered until more clarity is achieved regarding how useful this measure is, certainly if the patient would
still like to have children. This is also consistent with the RCOG (Royal College of Obstetricians and Gynaecologists)
guideline concerning menorrhagia, which likewise tends towards recommending antibiotic prophylaxis in the case
of hysteroscopic procedures on the basis of extrapolating data from research on hysterectomies [47].
In a consensus discussion between gynaecologists with an interest in endoscopy in 2002, this recommendation
was endorsed.

2.6.4 Measures to control bleeding

Bleeding is a rare complication of TCRM: 0.25–0.4% [50, 81], although some report values up to 2.4% [69].
In a Dutch study in 100 hospitals, this complication was found in 0.75% of the cases [77].
To prevent postoperative bleeding after TCRM, if indicated (severe blood loss persisting after the natural uterine
contractions have been awaited immediately after the procedure), a 30 ml Foley balloon catheter or an intrauterine
balloon specially developed to this end (Cook intrauterine stent) is applied, 6–12 hours after the procedure, to tampon
the wound bed [82].
Tranexamic acid (Cycloapron) 500–1000 mg intravenous is known to be able to reduce postoperative blood loss,
but there is little data available in the literature on its use in TCRM. The ACOG suggests possible intracavitary
use of this drug, but without further references [69].

2.7 Expertise and training

In relation to the necessary expertise for the treatment of submucous myomas, refer to the Final Attainment
Specifications for the Core Gynaecology Package drawn up by the NVOG Gynaecology Council. The recommendations
contained therein suggest that TCRM of small type-0 and type-I myomas are viewed as part of the basic package
but that type-II myomas and / or large myomas should be treated by gynaecologists with additional training and
experience.

3 Minimum required care and core recommendations

3.1 Diagnosis
For the diagnosis of submucous myoma and before surgery, intrauterine diagnosis using ultrasound or hysteroscopy
is vital.

3.2 Therapy
Hysteroscopic treatment of submucous myomas is preferable, unless they are too large or numerous, in which
case abnormalities falling outside the core package (according to the final attainment specifications for trainee
gynaecologists) should be treated by a gynaecologist with supplementary training and experience.

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4 Conclusions and advice
4.1 Diagnosis

1. In cases of submucous myomas, transvaginal ultrasound is currently the best and most commonly used
first-line imaging technique (B).

2. For more precise diagnostic imaging, particularly if conventional ultrasound is insufficient and
in order to prepare sufficiently for surgery, the addition of physiological salt as a contrast medium
(contrast-enhanced ultrasound) is recommended (B).

3. Diagnostic hysteroscopy is nearly as effective for these purposes (B) and has the advantage that
there is plenty of evidence for the fact that it is an effective examination technique for the
straightforward determination and exclusion of intrauterine abnormalities (B).

4. MRI, as an alternative, is generally less available, but it is more reliable specifically for submucous
myomas than contrast-enhanced ultrasound and hysteroscopy and can be carried out preoperatively
if certain treatments are indicated (B).

4.2 Therapy

1. Submucous myomas no larger than 4 cm should preferably be removed hysteroscopically (B).

2. In the case of larger myomas, preoperative reduction is possible with GnRH analogues (A2);
pre-treatment with these drugs should be considered also in the case of other risk factors
(type II, unfavourable location, anaemia, sub-fertility) (B).

3. In the case of two or more myomas, an increased likelihood of recurrence should be discussed,
and surgical therapy other than hysterectomy can be considered (C). If the patient would like to have
children, the more intramural the location of the myoma, the more caution is required (and the
indication is accordingly weaker) (B).

4. If, in the case of resection of myoma, a hypotonic distension medium is used, an automatic pump
system is recommended that accurately monitors the difference between the volumes of fluid flowing
in and out. The aim of this is to limit the loss to 1000 ml (and in any case not to tolerate more than
1500 ml) (D). If the loss of medium is rising, additional mannitol, NaCl 2.5%, and / or a diuretic can
be administered (C).

5. Antibiotic prophylaxis is advisable (C).

6. In the case of serious postoperative blood loss, intrauterine tamponade with balloon catheter can
be considered (D).

7. Hysteroscopic surgery under laparoscopic or ultrasound guidance is rarely necessary but can
be considered if indicated (D).

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 References
1. NVOG. Guideline Production Manual: procedure and plan [translated title]. 2004.
2. Wamsteker K, Emanuel MH, De Kruif JH. Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine bleeding:
results regarding the degree of intramural extension. Obstet Gynecol 1993; 82(5): 736–40.
3. Emanuel MH. Submucous myomas and abnormal uterine bleeding, epidemiology, diagnosis and treatment. Dissertation. Universiteit van
Amsterdam, 1998.
4. Stewart EA. Uterine fibroids. Lancet 2001; 357 (9252): 293–8.
5. Day BD, Dunson DB, Hill MC, et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence.
Am J Obstet Gynecol 2003; 188(1): 100–7.
6. Renwick M. Variations in surgery rates: implications for quality. Aust Clin Rev 1991; 11(4): 159–63.
7. Pokras R, Hufnagel VG. Hysterectomy in the United States, 1965–84. Am J Public Health 1988; 78(7): 852–3.
8. Luoto R, Kaprio J, Keskimäki I, et al. Incidence, causes and surgical methods for hysterectomy in Finland, 1987–1989. Int J Epidemiol 1994;
23(2): 348–58.
9. Barbot J, Parent B, Dubuisson JB. Contact hysteroscopy: another method of endoscopic examination of the uterine cavity. Am J Obstet
Gynecol 1980; 136(6): 721–6.
10. Siegler AM, Lindemann HJ, eds. Hysteroscopy: principles and practice. Philadelphia: Lippincott, 1984.
11. Motashaw ND, Dave S. Diagnostic and therapeutic hysteroscopy in the management of abnormal uterine bleeding. J Reprod Med 1990;
35(6): 616–20.
12. Rybo G, Leman J, Tibbin R. Epidemiology of menstrual blood loss. In: Baird DT, Michie, EA [rectified], eds. Mechanisms of menstrual
bleeding. New York: Raven, 1985.
13. Lumsden MA, Wallace EM. Clinical presentation of uterine fibroids. Baillieres Clin Obstet Gynaecol 1998; 12(2): 177–95.
14. Lumsden MA. Fibroids and menorragia. In: Shaw RW, ed. Uterine fibroids: time for review. Carnforth: Parthenon, 1992.
15. American College of Obstetricians and Gynecologists (ACOG). Surgical alternatives to hysterectomy in the management of leiomyomas.
ACOG practice bulletin 16, 1–10. Washington: ACOG, 1-5-2000.
16. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate? Hum Reprod 2002; 17(6): 1424–30.
17. Word B, Gravlee LC, Wideman GL. The fallacy of simple uterine curettage. Obstet Gynecol 1958; 12(6): 642–8.
18. Pritts EA. Fibroids and infertility: a systematic review of the evidence. Obstet Gynecol Surv 2001; 56(8): 483–91.
19. Stock RJ, Kanbour A. Prehysterectomy curettage. Obstet Gynecol 1975; 45(5): 537–41.
20. Schwarzler P, Concin H, Bosch H, et al. An evaluation of sonohysterography and diagnostic hysteroscopy for the assessment of intrauterine
pathology. Ultrasound Obstet Gynecol 1998; 11(5): 337–42.
21. Dueholm M, Lundorf E, Olesen F. Imaging techniques for evaluation of the uterine cavity andendometrium in premenopausal patients before
minimally invasive surgery. Obstet Gynecol Surv 2002; 57(6): 388–403.
22. Bettocchi S. New Era of Office Hysteroscopy. J Am Assoc Gynecol Laparosc 1996; 3(4, Supplement): S4.
23. de Kroon CD, de Bock GH, Dieben SW, Jansen FW. Saline contrast hysterosonography in abnormal uterine bleeding: a systematic review
and meta-analysis. BJOG 2003; 110(10):938–947.
24. Sharma M, Taylor A, Di Spiezio SA, Buck L, Mastrogamvrakis G, Kosmas I et al. Outpatient hysteroscopy: traditional versus the ‘no-touch’
technique. BJOG 2005; 112(7):963–967.
25. NVOG guideline 4. Abnormal blood loss in postmenopausal women (revised) [translated title]. 2003.
26. NVOG guideline 52. Diagnosis and treatment of menorrhagia [translated title]. 2006.
27. Buttram VC, Jr, Reiter RC. Uterine leiomyomata: etiology, symptomatology, and management. Fertil Steril 1981; 36(4): 433–45.
28. Dueholm M, Lundorf E, Hansen ES, et al. Evaluation of the uterine cavity with magnetic resonance imaging, transvaginal sonography,
hysterosonographic examination, and diagnostic hysteroscopy. Fertil Steril 2001; 76(2): 350–7.
29. Dijkhuizen FP, De Vries LD, Mol BW, et al. Comparison of transvaginal ultrasonography and saline infusion sonography for the detection
of intracavitary abnormalities in premenopausal women. Ultrasound Obstet Gynecol 2000; 15(5): 372–6. 29.
30. De Vries LD, Dijkhuizen FP, Mol BW, et al. Comparison of transvaginal sonography, saline infusion sonography, and hysteroscopy
in premenopausal women with abnormal uterine bleeding. J Clin Ultrasound 2000; 28(5): 217–23. 30.
31. De Blok S. Hysteroscopy in the Netherlands [translated title]. Ned Tijdschr Obstet Gynaecol 1992; 1: 6–10.
32. Thurkow AL. Saline infusion sonohysterography (SIS). In: Slager E, ed. Infertility, gynaecology, and obstetrics [translated title], 1999.
Oss: Organon, 1999.
33. Widrich T, Bradley LD, Mitchinson AR, Collins RL. Comparison of saline infusion sonography with office hysteroscopy for the evaluation
of the endometrium. Am J Obstet Gynecol 1996; 174(4): 1327–34.
34. Gimpelson RJ, Rappold HO. A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage.
A review of 276 cases. Am J Obstet Gynecol 1988; 158(3 Pt 1): 489–92.
35. Gimpelson RJ, Whalen TR. Hysteroscopy as gold standard for evaluation of abnormal uterine bleeding. Am J Obstet Gynecol
1995; 173(5): 1637–8.
36. Valle RF. Hysteroscopic evaluation of patients with abnormal uterine bleeding. Surg Gynecol Obstet 1981; 153(4): 521–6.
37. Taylor PJ, Cumming DC. Hysteroscopy in 100 patients. Fertil Steril 1979; 31(3): 301–4.
38. Valle RF. Hysteroscopy in the evaluation of female infertility. Am J Obstet Gynecol 1980; 137(4): 425–31.
39. Randolph JF, Jr, Ying YK, Maier DB, et al. Comparison of real-time ultrasonography, hysterosalpingography, and laparoscopy/hysteroscopy
in the evaluation of uterine abnormalities and tubal patency. Fertil Steril 1986; 46(5): 828–32.
40. Hoetzinger H. Hysterosonography and hysterography in benign and malignant diseases of the uterus. A comparative in vitro study.
J Ultrasound Med 1991; 10(5): 259–63.
41. Wood C, Hurley VA, Fortune DW, Leoni M. Percutaneous ultrasound guided uterine needle biopsy. Med J Aust 1993; 158(7): 458–60.
42. Bourne TH. Transvaginal color Doppler in gynecology. Ultrasound Obstet Gynecol 1991; 1(5): 359–73.
43. Kurjak A, Zalud I. The characterization of uterine tumors by transvaginal color Doppler. Ultrasound Obstet Gynecol 1991; 1(1): 50–2.
44. La Torre R, De Felice C, De Angelis C, et al. Transvaginal sonographic evaluation of endometrial polyps: a comparison with two dimensional
and three dimensional contrast sonography. Clin Exp Obstet Gynecol 1999; 26(3–4): 171–3.
45. Broadbent JA, Magos AL. Menstrual loss after hysteroscopic myomectomy. Gynaecol Endoscopy 1994; 4: 41–4.

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46. De Blok S, Dijkman AB, Hemrika DJ. Transcervical resection of fibroids (TCRM): results related to hysteroscopic classification.
Gynaecol Endoscopy 1994; 4: 243–6.
47. Derman SG, Rehnstrom J, Neuwirth RS. The long-term effectiveness of hysteroscopic treatment of menorrhagia and leiomyomas.
Obstet Gynecol 1991; 77(4): 591–4.
48. Dueholm M, Forman A, Ingerslev J. Regression of residual tissue after incomplete resection of submucous myomas.
Gynaecol Endoscopy 1998; 7(6): 309–14.
49. RCOG. The management of menorrhagia in secondary care. London: RCOG Bookshop at the Royal College of Obstetricians and
Gynaecologists, 1999.
50. Jones K, Walker WJ, Sutton C. Sequestration and extrusion of intramural fibroids following uterine artery embolisation: a case series.
Gynaecol Endoscopy 2000; 9(5): 309–13.
51. McLucas B, Adler L, Perrella R. Uterine fibroid embolization: nonsurgical treatment for symptomatic fibroids. J Am Coll Surg 2001; 192(1):
95–105.
52. Konig M, Meyer A, Aydeniz B, et al. Hysteroscopic surgery; complications and their prevention. Contrib Gynecol Obstet 2000; 20: 161–70.
53. West CP. Hysterectomy and myomectomy by laparotomy. Baillieres Clin Obstet Gynaecol 1998; 12(2): 317–35.
54. Healy DL, Lawson SR, Abbott M, et al. Toward removing uterine fibroids without surgery: subcutaneous infusion of a luteinizing hormone-
releasing hormone agonist commencing in the luteal phase. J Clin Endocrinol Metab 1986; 63(3): 619–25.
55. Maheux R, Lemay-Turcot L, Lemay A. Daily follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in ten women
harboring uterine leiomyomas. Fertil Steril 1986; 46(2): 205–8.
56. West CP, Lumsden MA, Lawson S, et al. Shrinkage of uterine fibroids during therapy with goserelin (Zoladex): a luteinizing hormone-
releasing hormone agonist administered as a monthly subcutaneous depot. Fertil Steril 1987; 48(1): 45–51.
57. Friedman AJ, Harrison-Atlas D, Barbieri RL, et al. A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide
acetate depot in the treatment of uterine leiomyomata. Fertil Steril 1989; 51(2): 251–6.
58. Hackenberg R, Gesenhues T, Deichert U, et al. [Preoperative reduction of uterine leiomyoma by the GnRH-analog goserelin (zoladex)].
Geburtshilfe Frauenheilkd 1990; 50(2): 136–9.
59. 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.
60. Donnez J, Nisolle M, Clerckx F, et al. Advanced endoscopic techniques used in dysfunctional bleeding, fibroids and endometriosis, and the
role of gonadotrophin-releasing hormone agonis treatment. Br J Obstet Gynaecol 1994; 101 Suppl 10: 2–9.
61. Benagiano G, Kivinen ST, Fadini R, et al. Zoladex (goserelin acetate) and the anemic patient: results of a multicenter fibroid study. Fertil Steril
1996; 66(2): 223–9.
62. Romer T. [Hysteroscopic myoma resection of submucous myomas with largely intramural components]. Zentralbl Gynakol 1997; 119(8): 374–7.
63. Felberbaum RE, Kupker W, Krapp M, et al. Preoperative reduction of uterine fibroids in only 16 days by administration of a gonadotrophin-
releasing hormone antagonist (Cetrotide). Reprod Biomed Online 2001; 3(1): 14–8.
64. Parazzini F, Vercellini P, De Giorgi O, et al. Efficacy of preoperative medical treatment in facilitating hysteroscopic endometrial resection,
myomectomy and metroplasty: literature review. Hum Reprod 1998; 13(9): 2592–7.
65. Crosignani PG, Vercellini P, Meschia M, et al. GnRH agonists before surgery for uterine leiomyomas. A review. J Reprod Med
1996; 41(6): 415–21.
66. Romer T. [Value of premedication with gonadotropin releasing hormone agonists before transcervical resection of solitary submucous
myoma]. Gynakol Geburtsh Rundsch 1996; 36(4): 194–6.
67. 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.
68. Palomba S, Pellicano M, Affinito P, et al. Effectiveness of short-term administration of tibolone plus gonadotropin-releasing hormone analogue
on the surgical outcome of laparoscopic myomectomy. Fertil Steril 2001; 75(2): 429–33.
69. Romer T, Schmidt T, Foth D. Pre- and postoperative hormonal treatment in patients with hysteroscopic surgery. Contrib Gynecol Obstet 2000;
20: 1–12.
70. Kochli OR, Wallwiener D, Brandner P, et al. Consensus of diagnostic and operative hysteroscopy. Consensus statements of a joint-meeting of
the Societies for Gynecological Endoscopy of Switzerland, Germany and Austria, October 1999. Contrib Gynecol Obstet 2000; 20: 182–7.
71. ACOG technology assessment in obstetrics and gynecology, number 4, August 2005: hysteroscopy. Obstet Gynecol 2005; 106(2): 439–42.
72. Iglesias JJ, Stams UK. [How to prevent the TUR-syndrome (author’s transl.)]. Urologe A 1975; 14(6): 287–91.
73. Istre O, Jellum E, Skajaa K, Forman A. Changes in amino acids, ammonium, and coagulation factors after transcervical resection of the
endometrium with a glycine solution used for uterine irrigation. Am J Obstet Gynecol 1995; 172(3): 939–45.
74. Istre O, Bjoennes J, Naess R, et al. Postoperative cerebral oedema after transcervical endometrial resection and uterine irrigation with 1.5%
glycine. Lancet 1994; 344(8931): 1187–9.
75. Gravenstein D. Transurethral resection of the prostate (TURP) syndrome: a review of the pathophysiology and management. Anesth Analg
1997; 84(2): 438–46.
76. Loffer FD, Bradley LD, Brill AI, Brooks PG, Cooper JM. Hysteroscopic fluid monitoring guidelines. J Am Assoc Gynecol Laparosc 2000; 7(3): 438.
77. Scottish Intercollegiate Guidelines Network RCOP. Hysteroscopic Surgery. 1-4-1999. Edinburgh: SIGN publication nr 37.
78. Brandner P, Neis KJ, Diebold P. Hysteroscopic resection of submucous myomas. Contrib Gynecol Obstet 2000; 20: 81–90.
79. Jansen FW, Vredevoogd CB, Van Ulzen K, et al. Complications of hysteroscopy: a prospective, multicenter study. Obstet Gynecol 2000;
96(2): 266–70.
80. Bhattacharya S, Cameron IM, Parkin DE, et al. A pragmatic randomised comparison of transcervical resection of the endometrium with
endometrial laser ablation for the treatment of menorrhagia. Br J Obstet Gynaecol 1997; 104(5): 601–7.
81. Jorgensen JCV, Pelle J, Philipsen T. Fatal infection following transvaginal fibroid resection. Gynaecol Endoscopy 1996; 5(4): 245–6.
82. Wood C, Maher P. Endoscopic treatment of uterine fibroids. Baillieres Clin Obstet Gynaecol 1998; 12(2): 289–316.
83. Hulka JF, Peterson HB, Phillips JM, Surrey MW. Operative hysteroscopy. American Association
of Gynecologic Laparoscopists 1991 membership survey. J Reprod Med 1993; 38(8): 572–3.
84. Goldrath MH. Uterine tamponade for the control of acute uterine bleeding. Am J Obstet Gynecol 1983; 147(8): 869–72. 84.

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 Imprint
Authors and reviewers
The author is A. L. Thurkow, St Lucas Andreas Ziekenhuis, Amsterdam.
The reviewers were Ms J. F. Admiraal, Dr M. H. Emanuel, Dr P. J. M. van Kesteren, and S. Veersema.

© 2006 Dutch Society of Obstetrics and Gynaecology

This standard protocol was drawn up by A. L. Thurkow in collaboration with the Gynaecological Endoscopy Working
Group (WGE) and adopted at the 588th members’ meeting on 20 September 2006 in Utrecht. A standard protocol
describes a clinical procedure and represents a supplement to legislation or documents drawn up by the NVOG.
Incidental circumstances can make it impossible to cover all aspects of a protocol. Deviations should be set down
in a report. NVOG, Postbus 200753502 LB Utrecht, http://www.nvog.nl

Disclaimer
The NVOG excludes all liability for the layout and content of its information leaflets or guidelines or for the possible
consequences of the application thereof in patient care. The NVOG is, however, open to (purported) errors in the
layout or content of these information leaflets or guidelines. Contact the NVOG office (email: info@nvog.nl).

This review has been translated from Dutch to English.

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