Modern approaches to the management of pregnancy in uterine myoma

Introduction

To this date, the problem of preserving the reproductive function of women with uterine myoma is of great social and medical significance. The increasing rate of uterine myoma in women of fertile age is a challenge for obstetricians and gynecologists with respect to their supporting efforts on the possibility of the onset and successful completion of pregnancy at this pathology [1]. According to the latest data, up to 2.7–10.7% of all pregnancies are combined with uterine myoma [2]. Nevertheless, from the standpoint of evidence-based medicine, there is a lack of accumulated data on this issue.

It is expedient, in the authors’ opinion, to highlight a few aspects of this problem including the management of women with uterine myoma who are planning a pregnancy, the determination of indications for surgical treatment at the pregravid stage, the choice of tactics at the event of pregnancy, and the features of delivery.

The management of women with uterine myoma who are planning a pregnancy has special peculiarities. The main task is the implementation of organ-preserving tactics under the condition that it is possible and does not involve risks of serious complications.

It is known that asymptomatic leiomyomas are subject to dispensary observation once every six months with the determination of growth, size, and risk of malignant transformation. Medical or surgical treatment of asymptomatic myoma is not included in clinical guidelines¹, ². It should be considered that in most cases, the size of myomatous nodes progressively increases during dynamic observation [3][4], which can complicate the implementation of reproductive plans. Predictive drug therapy of asymptomatic myomas in patients with reproductive plans has not yet been confirmed from the standpoint of evidence-based medicine, which attests to the demand for further investigations.

In the presence of symptomatic myomas in women with unrealized reproductive function, tactics are determined individually based on the age of the patient and the size and location of the tumor.

Appropriate drug therapy can be prescribed to reduce the severity of symptoms of uterine myomas [5]; however, the used hormonal medications interfere with impregnation, which limits their administration to patients trying to become pregnant [6]. Existing clinical guidelines do not specify drug therapy as an independent method of treating uterine myomas in patients with infertility².

The question of surgical treatment of uterine myoma at the stage of pregravid preparation arises in the following cases:

- in case of infertility or recurrent pregnancy loss associated with myoma;

- at an atypical arrangement of nodes (cervical, isthmus, intraligamentary, and submucosal);

- at persistent pain syndrome, compression of adjacent organs by myoma;

- in case of large sizes and rapid growth of the tumor;

- at uterine bleeding caused by myoma;

- in case of dystrophic changes in the myomatous node.

The most optimal operation is myomectomy, which can be performed through laparotomy, laparoscopy, or hysteroscopy access.

Laparotomy

Laparotomy is indicated for the localization of such nodes, the removal of which is associated with technical difficulties, for example, with retrovesicular and parametric nodes, large myomas, and suspected malignancy. Laparoscopic and laparotomic myomectomy are similar in terms of long-term results of fertility restoration [7]. Laparoscopic access is considered to be preferable due to less postoperative discomfort, less blood loss, and less risk of postoperative adhesions [6][8]. However, laparoscopic surgery is also associated with a higher risk of complications (intraoperative bleeding, organ damage during morcellation, increased risk of uterine scar failure), which demands specialized surgical skills [9]. There are no clear indications regarding the size, amount, and location of nodes at which myomectomy should be performed by laparotomic access³. It has been established that the probability of complications is significantly higher when a tumor size is more than 5 cm, the amount of myomas is more than three, and there are deep or intramural nodes [10]. The feasibility of the operation in each case depends on the experience of the surgical team and the availability of modern specialized equipment [9].

The use of bipolar, ultrasonic, and plasma instruments allows the operation to be performed with the least traumatization of tissues and promotes better healing of the surgical wound and tissues, as well as a decrease in the incidence of adhesion formation [11]. It is appropriate to use intraoperative anti-adhesion agents [12].

Hysteroscopic myomectomy is performed to remove small submucosal myomas of type 0 or type 1 [6], which are not larger than 4–5 cm in diameter³. Some myomas cannot be removed in one operation. In case of incomplete myomectomy, gonadotropin-releasing hormone (GnRH) agonists can be prescribed for a course of 2–3 months to cause the migration of the residual intramural component into the uterine cavity; repeat outpatient hysteroscopy is performed before a new surgical intervention [13].

Endovascular uterine artery embolization (UAE) can be considered an alternative to myomectomy, but for patients with unfulfilled reproductive plans, this procedure is not the perfect treatment for myomas due to the potential impact on fertility [14]. Large systematic reviews show an increase in the risk of miscarriage (35.2% vs. 16.5%; OR, 2.8; 95% CI, 2.0–3.8), risk of preterm birth and operative delivery rate (66% vs. 48.5%; OR, 2.1; 95% CI, 1.4–2.9), and the probability of postpartum hemorrhage (13.9% vs. 2.5%; OR, 6.4; 95% CI, 3.5–11.7) [15]. In the Russian Federation, the current clinical protocol for the treatment of uterine myoma does not recommend UEA for patients planning a pregnancy⁴, with a high level of evidence. However, there is ample evidence that pregnancy after UAE is achievable, and many of these pregnancies are uneventful and end in successful delivery [16]. Nevertheless, Ludwig et al. (2020) in the analysis of the available evidence-based investigations on pregnancy outcomes after UAE, taken as the basis for the preparation of clinical guidelines, point to certain limitations that affect the accuracy of the conclusions [16]. The above facts make actual the conduct of further scientific work in this area and indicate the demand for additional randomized controlled trials of fertility after UAE.

Postoperative period

In the postoperative period, in order to prevent the growth of myomatous nodes, the patient may be recommended the administration of GnRH agonists or progesterone receptor modulators for 3 months, with further using oral contraceptives.

GnRH agonists have long been regarded as the gold standard therapy for reducing the size of the nodes. Furthermore, in recent decades, a group of new drugs has emerged among leaders; one of them is represented by Ginestril (mifepristone 50 mg), which can affect the volume of the uterus or myomatous nodes with good tolerance. The Russian experience has confirmed the effectiveness of the Ginestril administration for uterine myoma [17–19]. Against the background of using this drug, negative dynamics of the volume of the uterus and the dominant myomatous node were noted, as well as a positive effect on the quality of the patient’s life with uterine myoma. In addition, it is confirmed by other scientific works, indicating a sufficient evidence base regarding the safety of Ginestril⁵ [20][21].

Planning a pregnancy after a conservative myomectomy is recommended after 8–12 months. Allowing for the risk of serious complications, it is necessary to reasonably approach myomectomy before pregnancy, assessing all the indications. The most serious problem is the risk of uterine rupture along the scar (0.2–3.7%), the probability of which is significantly higher during the first year after myomectomy [22][23].

Since there is insufficient evidence that myomectomy improves pregnancy outcomes, the scientific societies [24], including the American Society for Reproductive Medicine (ASRM) and the Society of Obstetricians and Gynecologists of Canada (SOGC), are opposed to myomectomy in women with asymptomatic myomas, which do not deform the uterine cavity [22][25][26].

Management of pregnant women with uterine myoma

Management of pregnant women with uterine myoma has definite peculiarities. It is known that uterine myoma is not a contraindication for the realization of a woman's reproductive potential. However, monitoring of pregnant women with uterine myoma in the antenatal clinic should be carried out as for patients of a high-risk group.

It is known that the pregnancy course in women with uterine myoma can be complicated [23][27][28]. This depends on the size and localization of myomatous nodes and can be manifested by the following conditions: threatened miscarriage, fetoplacental insufficiency, fetal growth retardation, placental abruption, abnormal position and presentation of the fetus, mechanical obstruction in childbirth, untimely discharge of water, anomaly of contractile activity of the uterus, tight attachment placenta, fetal distress, hypotonic bleeding, and subinvolution of the uterus in the postpartum period [23][27][28].

Specific complications can be expected, such as placental ingrowth into the myomatous node (5%), malnutrition of the node (2.5%), and growth of the node during pregnancy (2.5%) [23]. A tumor of a considerable size contributes to the incorrect position of the fetus (pelvic, transverse, or oblique) [27][28].

Most myomas during pregnancy are asymptomatic, but 10–20% cause complications [29]. The most common complication is abdominal pain, usually caused by the degeneration of the myoma or torsion of the pedicle of the subserous myoma.

When malnutrition occurs in the myomatous node, conservative treatment is most often performed (bed rest, hydration, analgesics) [30] depending on the gestational age. Prostaglandin synthetase inhibitors (non-steroidal anti-inflammatory drugs (NSAIDs)) should be used with caution, especially in the third trimester. In case of revealing signs of tumor necrosis, its surgical treatment through laparotomy is recommended, which implies the determination of the scope of the operation by a medical commission, the obligatory indication of strict medical features, and receiving informed voluntary consent from the woman; as well as the participation of at least two obstetrician-gynecologists in the operation who master the full range of surgical intervention [31].

The decision to perform a myomectomy during pregnancy should be accurately deliberated, as the operation is associated with significant risks. An increase in the volume and blood supply of the myometrium raises the probability of hemorrhagic complications with the possibility of intraoperative hysterectomy. Manipulations on the uterus can lead to adverse pregnancy outcomes (miscarriage within the range of 18–35%), premature birth, uterine scar dehiscence, and infectious complications. The risks get significantly higher when submucosal or multiple intramural myomas are removed.

Surgical treatment of uterine myoma during pregnancy, according to clinical guidelines in the Russian Federation, is carried out only at emergency indications including necrosis of the myomatous node, torsion of the pedicle of the myoma node, and the development of peritoneal symptoms⁶.

According to foreign sources [26][32], the main indications for myomectomy during pregnancy currently include the following:

• necrosis of the myomatous node followed by an inflammatory peritoneal reaction;
• torsion of the subserous node pedicle;
• spontaneous rupture of degenerated myoma;
• persistent pain syndrome, not amenable to conservative treatment within 72 hours;
• rapid growth of myoma associated with possible malignancy;
• large myomatous nodes located in the lower segment of the uterus, which cause deformation of the placentation place;
• large myomatous nodes causing compression of adjacent organs with intestinal obstruction or subobstruction [26, 32].

A number of authors define absolute contraindications to myomectomy during pregnancy, which include intramural myoma nodes, when they deform the uterine cavity or displace large vessels [8][12][13].

The operation of choice in complicated pregnancy is a myomectomy performed with laparotomic access. The most sparing operation is the enucleation of myoma nodes; it can be performed at any gestational age (if indicated), but it is preferable after the formation and engagement of the placenta function, that is, after 16 weeks of pregnancy. Enucleation focuses on nodes that are available for gentle intervention, that is, located subserous. The attempted enucleation of interstitial nodes during pregnancy was most often accompanied by failures, and the results of such operations during pregnancy cannot be considered satisfactory. A rare but serious complication demanding emergency surgery is related to the rupture of the vessels that feed the uterine myoma node. In this case, the presentation of an acute abdomen is caused by a rupture of a vessel on the surface of the tumor capsule and acute intra-abdominal bleeding [31].

When performing the operation after 22 weeks, the risks of premature delivery are high and one must be prepared for the birth of a preterm infant. Therefore, this option is considered by a number of domestic specialists as undesirable [30][33]. Upon completing the operation, an ultrasound investigation is performed to assess the viability of the fetus.

Enucleation of myoma during pregnancy demands the use of antispasmodics and tocolytics such as sodium hexoprenaline, nifedipine, etc. Drug administration begins parenterally during the operation and continues in the postoperative period by the oral route for 12–14 days.

Control ultrasound is performed on the 4th day of the postoperative period, and then repeated after 2 weeks. The patient is discharged on the 7th–10th day of the postoperative period [31].

An analysis of the immediate and long-term results of reconstructive plastic surgery for uterine myoma during pregnancy attests to the effectiveness of this intervention. The significance of this operation is stipulated by the possibility of providing favorable conditions for pregnancy carrying and implementing a reproductive function. Myomectomy during pregnancy, performed according to strict indications, allows preserving reproductive function, favorably completing this pregnancy in 80.3% of pregnant women with uterine myoma and in 31.2% of women with a history of reproductive losses [34][35].

Delivery

Hospitalization of pregnant women with uterine myoma should be carried out at 36–37 weeks of pregnancy to determine the tactics of labor management [36].

The decision on the mode of delivery in patients with uterine myoma should be made taking into account the woman's age, obstetric history, the nature and location of the myoma node, as well as the course of this pregnancy, the condition of the fetus, and further reproductive plans.

Functional examinations before childbirth or surgery necessarily include an assessment of the intrauterine fetus state by cardiotocography, a dopplerometry examination of the vessels in the uterus, the umbilical fetus cord, as well as the investigation of the blood flow of the myoma nodes.

A significant role in determining the indications for operative delivery and the degree of surgical intervention belongs to the ultrasound investigation, which estimates the size, amount, and location of myoma nodes, as well as their relation with the vascular bundles of the uterus. An ultrasound scan is always desirable to carry out in the presence of a doctor who will perform the operation, since ultrasound investigation estimates the node location and blood vessels, the technical possibilities of removing the node, and operation complexity with sorting out the indications for a cesarean section and the surgical treatment of myoma. The preferred delivery mode is childbirth through the natural birth canal [37]. With small myoma, the first and second periods of childbirth proceed without pronounced deviations.

Uterine myoma of small sizes, as a rule, does not interfere with the course of spontaneous labor. If the node is large, then childbirth can be complicated by the weakness of labor. Cervical or isthmus myomas, which prevent the delivery of a child, are an indication for a cesarean section.

Postpartum hemorrhage is observed more than 2.5 times more often in women with uterine myoma [31][38]. Retained abscission of the placenta and delivery of afterbirth are more common in women with myoma located in the lower uterine segment [38].

Special attention should be paid to patients who have undergone conservative myomectomy and have a high risk of uterine rupture along the scar after myomectomy [39]. The incidence of uterine rupture was the highest at delivery within a year after myomectomy and decreased over time after myomectomy [22].

According to modern domestic clinical guidelines, a history of myomectomy is an indication for cesarean section [40]. Extra to this, in foreign protocols, a planned cesarean section is considered the priority mode of delivery in pregnant women after myomectomy related to the risk of complications of the uterine scar. The approximate risk is estimated to be less than 2% [6].

Cesarean section operation

The operation of cesarean section has certain peculiarities. The obstetrician-gynecologist is often faced with the question of what to do with uterine myoma. When diagnosing large myoma nodes, especially preventing the extraction of the fetus, the matter is resolved in favor of removing the tumor even before the surgery. According to certain data, the rate of myomectomy under the conditions of myoma during cesarean section is 24.48% [21].

The safety of myomectomy during cesarean section has been actively discussed in the world literature [41]. The removal of myomatous nodes was revealed to be associated with the risk of massive uncontrolled bleeding, hemotransfusion, and relaparotomy [42]. The probability of bleeding is significantly higher with large tumor sizes (above 5.5–7.5 cm), their intramural location, and multiple nodes. However, even without myomectomy, such nodes increase the risk of perioperative bleeding during operative delivery, which demands special preparation [43]. It is not recommended to remove myoma located near large vessels due to the probability of their damage, as well as near the fallopian tubes due to the risk of their further obstruction during myometrial contraction.

Removal during cesarean section of small myoma nodes less than 5 cm, located along the anterior wall, as well as subserous or pedunculated ones, is considered relatively safe. In other cases when myomectomy is necessary, it is extremely important to perform the operation by experienced surgeons using effective methods of hemostasis control including purse-string suture, U-shaped suture, ligation of the uterine or iliac arteries, and the administration of modern uterotonics [42]. The data presented in the literature are contradictory and do not allow assessing the safety of such operations in routine practice.

When delivering in patients with uterine myoma by cesarean section, modern domestic clinical guidelines point to the expediency of myomectomy only if there is a myomatous node that prevents the fetus extraction. If the risk of torsion of the subserous nodes on the pedicle in the postoperative period is obvious, they must also be removed. Protocols do not recommend expanding the scope of the operation without indications. In the case of uncomplicated multiple uterine myoma, it would be more correct to postpone its surgical treatment for a later time [40].

Patients with uterine myoma who have undergone pregnancy and childbirth need medical examination after delivery. Observation is carried out according to current clinical guidelines for non-pregnant patients with myoma. It is advisable to perform the first ultrasound investigation during the first scheduled postpartum examination, followed by dynamic monitoring with an ultrasound examination once every six months. Consideration must be given to the fact that uterine myomas undergo spontaneous regression after childbirth in a significant proportion of patients (partial regression 79%, complete regression 36%, according to Vitagliano, 2018 [29], Carpini, 2019) [45]). The protective effect of pregnancy and childbirth has been noted in many epidemiological investigations [7][17][25][37][44]. Researchers attribute this fact to the long-term stabilization of the hormonal background and global remodeling of the myometrium [45]. The positive role of long-term breastfeeding is also assumed; however, a clear relationship between reductions in myomatous nodes and feeding has not been found. To prevent the growth of myomatous nodes and to maintain the optimal intergenetic interval, oral contraceptives can be prescribed [15, 46]. However, progesterone-only contraceptives in the postpartum period are associated with a lower probability of myoma regression compared with women who do not use any contraception [47].

In case when indications for myomectomy emerge after childbirth, the operation is performed in a planned manner, after the completion of the postpartum involution of the uterus, which reduces the incidence of postoperative complications.

Conclusion

In conclusion, it should be noted that a timely diagnosis of uterine myoma development at the earliest possible stage, an individual and adequate approach to treatment, practicing modern modes of delivery in pregnant women, and the implementation of the necessary rehabilitation measures ensure the achievement of the desired result in most patients.