Indications for myomectomy during pregnancy and its outcomes

In recent years, one of the most challenging problems of obstetrics and gynecology practice remains the preservation of reproductive function in reproductive age with uterine fibroids. Reproductive function of modern women is associated with several new aspects. The first of them is the phenomenon of advanced maternal age, observed many authors, which requires obstetricians and gynecologists to address the need of their patients to preserve reproductive capacities [1-13]. The second aspect is the growing incidence of uterine fibroids and their occurrence at a younger age, which leads to an increase in the proportion of pregnant women with uterine fibroids among patients of maternal services [1, 7-14]. The latter raises the issue of improving management strategies in providing obstetric care for pregnant women with uterine fibroids.

Women with uterine fibroids can complete pregnancy successfully, but the incidence of complications at all stages of gestation is significantly higher than that of women without fibroids.

The most common pregnancy complications in women with fibroids are threatened miscarriage and placental insufficiency affecting from 14 to 25% and 39.6% of this patient category, respectively. Fetal growth restriction syndrome (18.4%) is also considered as one of the complications of pregnancy in women with fibroids. Placental abruption and abnormal fetal position and presentation occur in 2.8% and 1.4-2.5% cases, respectively. Other complications include cervical insufficiency caused by isthmic fibroid nodules, pelvic venous thrombosis secondary to compression by large fibroid nodules [5, 15–20]. Childbirth complication in women with uterine fibroids comprise preterm rupture of membranes, anomalies of uterine contractions, placenta accreta, fetal respiratory distress syndrome, and placental abruption resulting in coagulopathic bleeding [7, 8, 15, 15], 22].

Postpartum complications with uterine fibroids include uterine subinvolution (22.5%), destruction of the fibroid nodule (15-25%), and postpartum hemorrhage (1.4-2.5%) [6, 12, 14, 21].

In every third woman, fibroids during pregnancy grow under the influence of progesterone conferring the risk of adverse maternal and outcomes and compromising their reproductive function [1, 2, 10, 13, 22].

With the development of surgical techniques, the emergence of new suture material, advancements in anesthesia and development of antibacterial agents to prevent postoperative complications, the surgeon has the opportunity to perform reconstructive surgery using a uterine-sparing approach [1,6,9,26-26].

Currently, the problem of uterine fibroids in pregnancy is now more often solved in favor of continuing the pregnancy [2, 6–9, 12, 15, 16, 18, 27, 28].

Despite the constant attention to the problem of pregnancy and childbirth in patients with uterine fibroids and uterine scarring after myomectomy, several aspects require clarification and updating. In particular, the literature is lacking studies investigating the immediate and long-term results of myomectomy during pregnancy.

This study aimed to reduce reproductive losses in women with uterine fibroids.

Material and methods

The study comprised 249 pregnant women with uterine fibroids aged from 21 to 44 (mean 34 ± 0.3) years, who sought medical attention at Moscow Regional Research Institute of Obstetrics and Gynecology

The inclusion criteria for the study patient selection were as follows: the patient’s desire to maintain the pregnancy; large (from 10 to 20 cm in diameter) and giant (more than 20 cm in diameter) fibroids that can affect pregnancy and impair the functions of the abdominal cavity; atypical location of large and giant fibroids; rapid growth of fibroids during pregnancy; ultrasound-confirmed destruction of the nodule [6-9, 12]. All patients had symptoms of threatened miscarriage. The patients were selected in outpatient settings; all pregnant women underwent standard clinical and laboratory examination using clinical, biochemical, microbiological, hemostasiologic, functional, and morphological methods. Tests included measurement of serum levels placental complex hormones, detection of sexually transmitted infections using the polymerase chain reaction, and ultrasound examinations.

At gestational age up to 12 weeks and in the absence of indications for emergency hospitalization, the patients received outpatient therapy aimed at prolonging the pregnancy. The patients were admitted for the planned therapy to the Department of Pathological Pregnancy at a gestational age of 14-15 weeks to prepare for surgery. Patients with large or giant atypically located fibroids and vaginal bleeding, indicating the beginning of a miscarriage were admitted urgently to the gynecological department, regardless of gestational age [6-9, 12, 13].

Pregnant women with uterine fibroids were divided into three clinical groups. Group I included 137 patients who underwent myomectomy during current pregnancy from 2001 to 2011 at Moscow Regional Research Institute of Obstetrics and Gynecology. In this group, a retrospective analysis of all medical records was carried out, including the results of patients’ examination during gestation, indications for surgery, and pregnancy outcomes. This group was divided into subgroup IA (n = 106) comprising women who underwent myomectomy without breaching the endometrial cavity and subgroup IB (n = 31) with patients who had a myomectomy, accompanied by the breach of the endometrial cavity and termination of pregnancy (planned loss).

Group II included 82 patients (a prospective study) who underwent myomectomy during pregnancy from 2012 to 2016. This group was also divided into subgroup IIA (n = 75) comprising patients who underwent myomectomy without the breach of the endometrial cavity and subgroup IIB (n = 7) with patients who had a myomectomy, accompanied by breaching the endometrial cavity and termination of pregnancy (planned loss).

The comparison group (group III) included 30 pregnant women with uterine fibroids, who were denied surgical treatment during gestation due to the lack of vital indications for surgery and a high risk of fetal loss.

Before surgery, on days 6–7 postoperatively and several times during pregnancy the patients underwent pelvic ultrasound performed on the Medison Accuvix V20 Ultrasound System using transabdominal 2–6 MHz and transvaginal 4–9 MHz probe. Color Doppler mapping of uterine artery branches and intratumoral vessels (both on the periphery and in the central sections of fibroids) was carried out. The sonographic assessment included evaluation the fetus, pelvic organs, the size of fibroid nodules, their location and the direction of growth, the distance from the nodule to the uterine cavity, signs of destruction, myometrial tone, and ovarian size [6-9, 29, 30].

All excised specimens were subjected to histological examination

Results and discussion

Among the study participants, 201 (80.7%) of 249 women had various non-obstetric comorbidities, and in 42 (17.9%) patients had two or more of them.

Forty-six (18.5%) patients had a hereditary predisposition to developing uterine fibroids (35 patients had mothers with fibroids, and 11 patients had the grandmother or other female family members suffering from fibroids), that is, a family history of hereditary genital tumors was quite common [6, 7, 9, 10]. Seventy-one (28.5%) patients had a history of normal vaginal delivery.

Among the study participants, 122 (49%) patients had a history of 1 to 6 medical terminations of pregnancy. Two patients had a history of an ectopic tubal pregnancy and underwent tubectomy. Forty-two (17%) patients experienced spontaneous miscarriages and early fetal demise related to uterine fibroids [6, 7, 9].

Uterine fibroids were diagnosed during the first five years before the onset of the current pregnancy in 62 (45.3%), 37 (45.1%), and 9 (30%) patients in group I, group II, and the control group, respectively. Seventy-five (55%), 30 (36.6%), and 21 (70%) patients in group I, group II, and the control group, respectively were found to have uterine fibroids during the current pregnancy.

The chief complaint during early pregnancy was abdominal pain (n = 208, 83.5%); 138 (55.4%) patients reported frequent urination, and 2.1% of patients experienced acute urinary retention, which required catheterization, and difficulty in defecation (in the presence of isthmic and intraligamentary fibroid nodules) [6, 7, 9, 13].

Symptoms of growing fibroids, including rapidly growing ones, were observed in 191 (76.7%) patients, and they were always combined with impaired function of adjacent organs.

When examining pregnant women with uterine fibroids, we paid attention to the size of the uterus, the location of fibroids, their structure, myometrial tone, and the state of the cervix. In 39 (28.5%) patients in the group, I and 24 (29.3%) in group II the size of the uterus including the fibroids, was about the size of an 11-14 week pregnancy.

Multiple and solitary uterine fibroids were seen on ultrasound in 126 (50.6%) and 123 (49.4%) patients, respectively. By the ultrasound-detected location, intramural (n = 174, 70%) and subserosal (n = 75, 30%) fibroids were the most common types of fibroid. 45 (18.1%) patients had fibroids with centripetal growth. Signs of circulatory disorders in fibroids were detected in 157 (63.1%) patients [6–9, 10, 30].

To assess the risk of breaching the endometrial cavity during surgery and minimize the risk of pregnancy termination in patients with intramural fibroids and, especially, those with the centripetal growth, we measured the distance from the fibroid capsule to the uterine cavity, that is, the thickness of the intact myometrium. This distance should be at least 3-5 mm with the collateral location of the placenta from the fibroid and 5 mm if the placenta implants over a fibroid. Forty-three (17.3%) patients, whose placentas were completely or partly implanted over fibroids, showed signs of a miscarriage that occurred at 7-14 weeks’ gestation [11, 12].

Based on the analysis of pregnancy outcomes in group I (retrospective analysis), we optimized the indications for myomectomy for the patients in group II (prospective analysis) and identified a comparison group (group III), which included pregnant women with uterine fibroids who had no indications for surgery, but had a high risk of breaching the endometrial cavity and placental abruption (surgery is not advisable).

Indications for myomectomy during pregnancy in group II were the fibroids that impair the health of the patient and confer the risk of reproductive losses, such as:

• large (from 10 to 20 cm in diameter) and giant (over 20 cm in diameter) fibroids that prevent the continuation of the pregnancy, occupying the entire abdominal cavity, and impairing the function of adjacent organs;
• ultrasound confirmed symptomatic necrosis of fibroids of any location and size;
• large intramural fibroids associated with pelvic pain without endometrial deformation with the placenta located collaterally to the fibroid;
• placental implantation over a fibroid of no than 1/3 of the placental site;
• full placental implantation over a fibroid or 2/3 of the placental site; the thickness of the intact myometrium between the fibroid and the endometrial cavity should be at least 5 mm [6, 7, 9, 12, 29].

All patients in group I and II underwent open myomectomy during pregnancy.

Myomectomy in pregnancy should be performed under the following conditions:

• minimizing fetal trauma and blood loss, reducing the risk of infectious complications;
• the choice of a rational uterine incision, taking into account subsequent abdominal delivery and the presence of an expanded vascular network.
• selection of suture material of sufficient strength, minimal allergenicity, and contributing to the formation of a competent uterine scar.

Other conditions include the safety of the mother during the surgery, maintaining normal uteroplacental blood flow, providing maximum protection of the fetus and avoidance of an increase in the myometrial tone. Planned operations were carried out at 14 to 16 weeks’ gestational age since by this time the placenta is functioning, the risk of teratogenic action of many drugs is reduced, and the possibilities of using drugs are expanding, both during surgery and in the postoperative period.

We consider an epidural blockade anesthesia of choice that allows long-lasting and effective pain relief during surgery and its continuation in the postoperative period. We used a naropin solution as the safest local anesthetic [6, 7, 9, 11-13].

The technique of surgery is similar to the technique of myomectomy in non-pregnant patients. However, unlike myomectomy in non-pregnant patients, when it is preferable to remove all fibroids, only problem nodules that prevent continuing with the pregnancy are resected. This reduces the risk of massive blood loss, which creates unfavorable conditions for the blood supply to the myometrium and the risk of fetal loss [6, 7, 9, 11, 12].

In group I, 31 (22.6%) of 137 patients (subgroup IB) had the gestational sacs removed during myomectomy. Of them, in 23 patients, the pregnancy could not be saved due to submucosal or centripetally growing fibroids and placental implantation over the fibroids. Eight patients experienced a miscarriage at 6–9 weeks’ gestation. All these patients had multiple large or giant fibroids with predominantly intramural location, centripetal growth and signs of destruction, and placental site overlying fibroids. In these patients, the main goal was to conserve the uterus for future pregnancy.

In group II, 7 (8.5%) of 82 patients (subgroup IIB) had the gestational sacs removed during myomectomy (planned loss). They had intramural fibroids with deformation of the endometrial cavity and the placental site overlying fibroids. The myometrium between the lower pole of the fibroid and boundary of the endometrium could not be determined, and the endometrial cavity was breached when the fibroids were removed.

There were no intraoperative complications, and in no case, it was necessary to extend surgery to perform a hysterectomy.

Postoperative management of pregnant women undergoing myomectomy has its specific features, due to the need to create favorable conditions for tissue repair, adequate bowel functioning, prevent septic complications, eliminate the threat of termination of pregnancy and improve uteroplacental blood flow. After surgery, the patients receive intensive infusion therapy for 2–3 days and postoperative antibacterial prophylaxis for the prevention of infectious complications. Depending on the severity of the clinical signs of threatened miscarriage, from the first hours after the operation, the patients were administered therapy aimed at continuing with the pregnancy (tocolytics, antispasmodics, magnesium sulfate, and micro-dose progesterone according to generally accepted schemes). Later, if necessary, oral medications were administered up to 36 weeks of gestation with a gradual decrease in dose [6, 7, 9, 11-13, 16].

The most common pregnancy complication was threatened miscarriage. After discharge from the hospital, 53 (50%) patients in group I and 12 (16%) patients in group II received inpatient treatment at the place of residence for threatened miscarriage or threatened preterm birth in the second half of pregnancy. In the comparison group, seven patients with uterine fibroids had an uncomplicated pregnancy. Twenty-one (70%) patients underwent repeat inpatient treatment at the place of residence at various gestational ages [6, 7, 9, 12, 13].

Analysis of threatened miscarriages among the study participants and the reasons for hospital admission showed that in every third woman, hospitalization was associated with the feeling of discomfort or fear for the pregnancy outcome. In patients with uterine fibroids or post-myomectomy uterine scar, threatened miscarriage may be over-diagnosed because of psychological factors, for example, due to the desire to preserve the pregnancy. Almost every second woman in group III received inpatient treatment for threatened miscarriage and placental insufficiency.

The second most common pregnancy complication was fetal growth restriction associated with uterine fibroids, which was observed in 11 (10.4%), 7 (9.3%), and almost every second patient in group I, II, and III, respectively [6, 7, 9, 12, 13].

Six (5.7%) of 106 patients in subgroup IA had a spontaneous miscarriage on day 3–5 after the operation (unplanned loss). One patient had a placental abruption at 20-21 weeks’ gestation followed by bleeding, which required an emergency small cesarean section. The remaining 99 (92.5%) patients in subgroup IA gave birth to live infants.

Twelve (12.1%) patients in subgroup IA experienced preterm rupture of membranes at 32–34 weeks’ gestation, and they underwent an emergency cesarean section. The infants were born with Apgar score 6 and 7-8 and were transferred to the second stage of nursing. In group I, 55 (55.6%) patients underwent a full term cesarean section; of them, 32 (58.2%) patients had a planned cesarean section indicated due to multiple uterine scars, including located on the back of the uterus and uterine rib. Twenty (40%) patients in subgroup IA underwent an emergency cesarean section because of preterm rupture of membranes and multiple post-myomectomy uterine scars. Three (5.5%) patients had cesarean section due to acute fetal hypoxia during childbirth. Thirty-two (32.3%) patients in group I gave birth at full-term. The infants were born in a satisfactory condition with Apgar scores of 8 and 9. As described earlier, 31 (22.6%) patients in subgroup IB had the gestational sacs removed during myomectomy. In 28 of them, a pregnancy occurred within 1 to 3 years after surgery; 3 patients refused to plan a subsequent pregnancy.

One patient in subgroup IIA experienced spontaneous miscarriage after myomectomy at 16-17 weeks’ gestation. Eleven (15%) of 74 patients in subgroup IIA underwent an emergency cesarean section at 35-36 weeks’ gestation due to preterm rupture of membranes. The newborns had Apgar score 6 and 7-8 and were transferred to the second stage of nursing. In group II, 42 (57%) patients underwent a full term cesarean section. The indications for planned surgical delivery were multiple uterine scars and uterine scars with locations that rendered intrapartum ultrasound scanning difficult or impossible (n = 25, 60%). Nine (21%) patients underwent emergency cesarean section due to preterm rupture of membranes and multiple post-myomectomy uterine scars. Eight (19.0%) patients had cesarean section due to the onset of acute fetal hypoxia during childbirth. Twenty-one (28%) patients in group II gave birth at full-term without complications.

Of the 7 patients (subgroup IIB - planned losses), 3 patients became pregnant within a year, and 4 patients refused planning a subsequent pregnancy.

In the comparison group, placental abruption and bleeding occurred in 4 patients at 19-21 weeks’ gestation, and they underwent an emergency small cesarean section. Four (13.3%) patients had preterm rupture of membranes at 34–36 weeks’ gestation, and in one (3.3%) women a placental abruption occurred at 35 weeks. All of them underwent an emergency cesarean section. The newborns’ Apgar score was 5 and 7-8, and they were transferred to the second stage of nursing. In one case, an elderly primipara with a long history of infertility, who had fetoplacental insufficiency associated with placental implantation over a large intramural fibroid (15 cm in diameter), underwent a cesarean section at 34-35 weeks’ gestation delivering a newborn weighing 1750 grams with Apgar score of 5 and 7. Seventeen (56.7%) patients underwent a planned full term cesarean section. Of them, 11 (64.7%) patients had isthmic fibroids preventing vaginal delivery. Four (23.5%) pregnant women had several indications for the cesarean section including breech presentation, elderly primipara, long history of infertility, lack of readiness of the body for childbirth, fetoplacental insufficiency, high myopia, etc. Two (11.8%) parturient women underwent a cesarean section during labor, mainly due to abnormal uterine activity and the fetal hypoxia. In all women, no postoperative complications were observed.

Twelve (44.4%) patients of this group underwent myomectomy during cesarean section. Four (14.8%) patients with uterine fibroids underwent hysterectomy without adnexectomy.

Four patients with uterine fibroids in the comparison group ended up in spontaneous labor. As a rule, they had large fibroids located in the uterine body that did not interfere with spontaneous vaginal delivery. No complications were observed in the immediate postpartum period, and the newborns were discharged on days 5-7 in a satisfactory condition.

Thus, the analysis of the immediate and long-term outcomes of surgery for uterine fibroids with uterine reconstruction during pregnancy indicates the effectiveness of this intervention, which creates favorable conditions for continuing with the pregnancy and allows preservation of reproductive potential. Myomectomy during pregnancy, performed according to strict indications with the observance of surgical technique, allows the preservation of reproductive function and successful completion of pregnancy in 80.3% of patients with uterine fibroids and 31.2% of women with a history of reproductive loss.

Conclusion

The growing incidence of uterine fibroids in women of childbearing age motivates obstetricians and gynecologists to look into effective ways to prolong pregnancy in this patient category. The findings of our study show that the indications for myomectomy during pregnancy are not the mere presence of a fibroid, even of a large one, but an impaired abdominal function caused by fibroids: persistent abdominal and pelvic pain; acute urinary retention as a result of mechanical compression of the nerve endings and fibroid necrosis; giant fibroids that fill the abdominal cavity, making the pregnancy impossible to continue. The reproductive prognosis is more favorable if the thickness of the intact myometrium between the lower pole of the fibroid and the endometrial cavity is at least 5 mm, and the placenta is implanted over the fibroid of no more than 1/3 of the placental site. Myomectomy, especially in older women whose pregnancy may be the last and often the only chance of having a baby, is a treatment modality that allows this possibility.