Abstract
Intramural myomas, the most common type of uterine leiomyoma, develop within the uterine wall and expand either inwards or outwards. According to the FIGO [1] leiomyoma classification system, fibroid types range from 0 to 8. Types 0, 1 and 2 are submucosal myomas, and subserosal myomas refer to type 5 to 7. Both type 3 and type 4 myomas are known as intramural myomas with no involvement of the endometrial cavity (Figure 13.1). The type 3 myomas, which are in the uterine wall but in contact with the endometrium, are more likely to distort the cavity under certain stimulations. Type 4 myomas stay entirely within the myometrium, which does not expand to either the endometrium or the serosa.
13.1 Intramural Myomas and Fertility
Intramural myomas, the most common type of uterine leiomyoma, develop within the uterine wall and expand either inwards or outwards. According to the FIGO [1] leiomyoma classification system, fibroid types range from 0 to 8. Types 0, 1 and 2 are submucosal myomas, and subserosal myomas refer to type 5 to 7. Both type 3 and type 4 myomas are known as intramural myomas with no involvement of the endometrial cavity (Figure 13.1). The type 3 myomas, which are in the uterine wall but in contact with the endometrium, are more likely to distort the cavity under certain stimulations. Type 4 myomas stay entirely within the myometrium, which does not expand to either the endometrium or the serosa.
Figure 13.1 Types of intramural myomas according to FIGO classification of uterine myomas published by Munro et al. [1]. Type 3 – the intramural myoma in contact with the endometrium; type 4 – the intramural myoma without the involvement of either the endometrium or the serosa.
It is generally accepted that intramural myomas may be associated with reproductive disorders such as infertility, miscarriage and other adverse pregnancy outcomes. Large intramural myomas (i.e. >5 cm) or intramural myomas distorting the uterine cavity appear to have more adverse impact on fertility. Oliveira et al. [2] evaluated 245 IVF-ICSI patients with uterine myomas and found that patients with intramural myomas more than 4 cm had lower pregnancy rates than those with smaller myomas. In two other studies, it was found that larger myomas (i.e. >5 cm) had a greater impact on the risk of pregnancy loss as compared to smaller myomas [3, 4]. Furthermore, Sudik et al. [5] noted that women who have myomas of more than 8 cm are more likely to conceive after myomectomy than those with smaller ones. A recent review article concluded that deeply infiltrating intramural myomas which distorted the endometrial cavity negatively affected fertility and so should be removed [6].
However, the impact of smaller intramural myomas on fertility, especially those without endometrial cavity distortion, is still a subject of controversy. There were many observational studies involving assisted conception cycles in which the outcomes in women with myomas were compared to those without (controls). Among published meta-analyses of these studies, three failed to confirm significant adverse impact of intramural myomas on IVF outcome, whereas five concluded significant negative impact [7–14].
The possible mechanisms whereby intramural myomas produce adverse effects on reproduction include cornual occlusion if the intramural myoma is adjacent to the intramural tubal segment [15], altered myometrial contractility, disruption of normal blood supply [16], endometrial inflammation, thinning and atrophy [17], alterations in gene expression [18], as well as adverse effects on gamete migration [19, 20].
13.2 Management of Intramural Myomas
The indication for myomectomy is different for submucosal and intramural myomas. However, the distinction between these two types of myoma is not always so clear-cut. From time to time, ultrasonography or office hysteroscopy may show non-distortion of the uterine cavity by a myoma in the dormant state, but when the uterus contracts, a type 3 intramural myoma may protrude into and distort the endometrial cavity (Figure 13.2). In this case, the intramural myoma should also be treated as a submucosal myoma and be removed, especially if it is associated with unexplained infertility, recurrent pregnancy loss, mid-trimester loss or other obstetric complications which could be attributed to the myoma.
It is accepted that hysteroscopic surgery is suitable for removal of submucosal myomas including types 0, 1 and 2. As the technique of operative hysteroscopy becomes more advanced, intramural myomas which do not reach and distort the uterine cavity may also be suitable for hysteroscopic myomectomy with a shorter healing time compared with laparoscopic myomectomy. Shen et al. [21] used Doppler ultrasonography to observe the healing of the myometrium after myomectomy and found that the hysteroscopic group had a significantly higher proportion with complete healing at 1, 3 and 6 months post-operation. They found that 88.4% (160/181) of women in the hysteroscopic group achieved complete muscular healing 3 months after the operation, and all cases in the hysteroscopic group achieved complete healing in 6 months; whereas in the laparoscopic group, only 95.2% (320/336) achieved complete healing at 6 months.
In our centre, hysteroscopic myomectomy is considered for intramural myoma if the distance between the endometrium and the myoma is less than 5 mm and the myoma is less than 4 cm in diameter.
In hysteroscopic resection of an intramural myoma (or submucosal myoma with significant intramural involvement), it is useful to determine the ‘serosa myoma thickness’ (SMT) or ‘myometrial free margin’, which is measured by ultrasonography and represents the minimal thickness between the outer margin of the myoma and the serosa (Figure 13.3). A minimum thickness of 5 mm is advisable to reduce the risk of uterine perforation during hysteroscopic myomectomy. However, some studies suggested that, during hysteroscopic resection of an intramural myoma, the SMT often increased progressively during the procedure, thereby increasing the safety margin of the resection [22–24]. In the prospective observational study by Casadio et al. [22], the median myometrial free margin increased from 3.9 mm at the beginning of the hysteroscopic surgery to 12.7 mm after the removal of the myoma.
In our centre [25], we have performed 18 cases of hysteroscopic resection of intramural myomas with SMT less than 5 mm under ultrasonographic guidance along with the use of several manoeuvres to promote uterine contractions, including ‘water massage’, mechanical stimulation with either the cutting loop or the tip of the scope, vacuum aspiration and intravenous oxytocin injection. The mean SMT was 3 mm at the beginning of the operation, which increased to 9 mm at the end of the operation. There was only one incidence of uterine perforation.
Shen et al. [21] carried out a retrospective study to compare the outcome of hysteroscopic myomectomy with laparoscopic myomectomy in women with intramural myoma. Pregnancy occurred significantly earlier in the hysteroscopic group compared with the laparoscopic group; in addition, miscarriage rate in the hysteroscopic group was significantly less than that in the laparoscopic group.
However, hysteroscopic resection of an intramural myoma remains a challenge. We describe below our experience at the Fuxing Hospital of the preoperative protocol, intraoperative techniques and post-operative management of hysteroscopic resection of intramural myomas [26].
13.2.1 Preoperative Assessment and Medication
13.2.1.1 Preoperative Assessment
Pelvic ultrasonography is an essential investigation prior to hysteroscopic resection of intramural fibroids. If the uterus is less than 12 weeks gestational size, transvaginal ultrasonography is preferred to transabdominal ultrasonography. If the uterus is more than 12 weeks gestational size, transabdominal ultrasonography may be more appropriate, but in the presence of significant uterine enlargement, hysteroscopic surgery may not be feasible. Three-dimensional ultrasonography, especially when combined with saline infusion sonography (SIS), is particularly useful to map out the exact location, size and number of the myomas. Not every intramural myoma needs to be removed. In the presence of multiple intramural myomas, the decision regarding which one should be removed or which one to leave undisturbed should be made prior to the operation based on detailed myoma mapping and informed discussion. Magnetic resonance imaging (MRI) may occasionally be required in situations when the margin of the myoma is not so well defined, raising the possibility of an alternative diagnosis such as adenomyoma. In any case, the two most important pieces of information are the minimal thickness between the endometrium and the myoma, and the serosa myoma thickness (SMT).
13.2.1.2 Preoperative Medication
Routine GnRH analogue (GnRHa) treatment is not necessary but it should be considered if the intramural myoma is more than 3 cm in diameter. A 3-month course of treatment may produce a number of advantages. Firstly, the treatment produces shrinkage in size of the myoma, thereby shortening the resection procedure. Secondly, the reduction in vascularity may help to reduce bleeding during operation. Thirdly, it may sometimes lead to the protrusion of the intramural myoma into the uterine cavity because the reduction of uterine volume may be greater than that of the myoma. In addition, the amenorrhoea induced by GnRHa may also help to improve the anaemia.
13.2.2 Operative Techniques
13.2.2.1 Locating the Myoma
By definition, the intramural fibroid to be resected does not normally protrude into the uterine cavity, and so it must be precisely located before the operation. Overdistension of the uterine cavity makes it more difficult to identify the location of the myoma and so should be avoided. Whilst the usual perfusing pressure for hysteroscopic surgery is set at 90–100 mmHg, it may be helpful in the beginning to use a lower pressure, say 40 mmHg, to facilitate the protrusion of the myoma into the cavity and identification under lower pressure.
13.2.2.2 Inducing Uterine Contractions
A number of strategies may be employed to stimulate uterine muscles to contract, which would help not only to reduce intraoperative bleeding but also the extrusion of the myoma into the uterine cavity. Several pharmacological agents such as misoprostol, oxytocin or vasopressin may be administered during the operation. Vasopressin, a potent vasoconstrictor, is particularly effective; it can be injected into the fundus of the uterus under direct vision at the beginning of the hysteroscopic procedure by using an oocyte retrieval needle. Uterine contractions may also be induced with a number of mechanical means including the application of vacuum aspiration, hydraulic uterine massage by rapidly alternating the intrauterine pressure, manual uterine massage and repeatedly stoking the uterine wall with the cutting loop or the beak of the scope. Repeated mechanical pushes on the myoma tissue with the cutting loop may also help to separate the myoma away from the myometrial tissue (Figure 13.4).
13.2.2.3 Ultrasound Guidance
Ultrasound guidance is essential in hysteroscopic resection of intramural myomas. It provides information on the proximity of the intramural myoma to both the endometrium and the serosa (Figure 13.5). Moreover, during the procedure, the changes in myometrial thickness between the myoma and the serosa (SMT), which may become thicker when the uterus contracts, can be serially measured (Figure 13.6). At the end of the operation, the shape of the endometrial cavity and the integrity of the uterine wall can be determined (Figure 13.7).
Figure 13.7 At the end of hysteroscopic myomectomy, ultrasonography showed normal appearance of the endometrial cavity.
13.2.3 Surgical Steps
In the Hysteroscopy Centre of Fuxing Hospital, we advocate the use of the following steps in sequence for the removal of myomas, namely: locating the myoma, opening the window, cutting, clamping, twisting, pulling and extraction. Cutting is the first step of the procedure.
The exact location is best ascertained by a combination of ultrasonographic examination and inspection of the uterine cavity with the resectoscope, which may sometimes reveal important clues such as a different degree of vascularization pattern of the endometrium beneath the myoma. If the location is not immediately apparent, a number of manoeuvres may be used, including decreasing the intrauterine perfusing pressure, scrapping the endometrium or applying vacuum aspiration which can stimulate the uterus to contract, making the myoma more easily identified (Figures 13.8 and 13.9) The latter manoeuvre is particularly useful if the endometrium is thickened.
Figure 13.8 Hysteroscopic view of a normal cavity in a woman with an intramural myoma in the posterior wall.
Figure 13.9 Hysteroscopic view of the uterine cavity after vacuum aspiration. An anterior wall intramural myoma was seen protruding into the cavity.
Once the exact location of the myoma is ascertained, a longitudinal incision of endometrium and myometrium above the myoma is made with a hysteroscopic cutting loop or cutting needle. The incision can be repeated until the myoma is visible via the hysteroscope (Figures 13.10 and 13.11). This step is called ‘opening the window’.
Figure 13.11 A left anterior intramural myoma is visualized after the myometrium covering it was incised by a cutting loop.
At this stage, vasoconstrictors such as vasopressin can be administered into the uterus via an oocyte retrieval needle, which will cause the uterus to contract, pushing the myoma via the window already created. The protrusion process may be facilitated by maintaining a low fluid perfusing pressure at this stage (Figure 13.12).
Figure 13.12 After the myometrium covering the myoma had been incised by a cutting needle, the intramural myoma in the left posterior wall could now be seen protruding into the cavity.
As the intramural myoma begins to protrude into the cavity, the intracavity component of the myoma should be resected. Meanwhile, the capsule of the fibroid should be identified to avoid resecting into the myometrial tissue. As the resection progresses, frequent mechanical pushes of the myoma or repeated withdrawal and reinsertion of the scope will continue to stimulate the uterus to contract, helping to push the myoma further into the cavity.
Sometimes, it may be possible to deliberately resect only the sidewalls of the myoma, while preserving the central portion, with the aim of converting the spherical myoma into a mushroom-shaped structure with a thick central stalk. In this way, it is possible to speed up the complete removal of the entire myoma by applying a pair of curved grasping forceps to grasp firmly on the thick stalk, followed by twisting either clockwise or anticlockwise, whilst applying a pulling force to loosen and detach the myoma from the surrounding myometrium tissue. With a combination of these manoeuvres, the myoma will descend gradually and be extracted out through the cervix. The steps could be applied repeatedly so that a large myoma can be removed in stages.
From time to time, in women with multiple myomas, following the removal of a submucosal myoma, the intramural myoma underneath it will be exposed to the cavity, leading to intracavity protrusion, especially if the uterus is stimulated to contract. In such a case, the hitherto intramural myoma should be removed (Figure 13.13).