Outcomes of cesarean myomectomy via trans-endometrial approach in women with single intramural fibroid in the posterior uterine wall

Abstract Objective To evaluate the feasibility and effectiveness of cesarean myomectomy (CM) via trans-endometrial approach in pregnant women with single intramural fibroid in the posterior uterine wall. Methods Ninety-eight patients with single intramural fibroids in the posterior uterine wall who underwent CM were divided into two groups depending on surgical style. The study group consisted of 50 patients who underwent trans-endometrial myomectomy (EM), whereas the control group included 48 patients who had trans-serosal myomectomy (SM). Patients’ demographic data, intraoperative and postoperative outcomes were analyzed retrospectively. Results No significant differences were found in the baseline characteristics of the two groups, including demographic data, size, location of fibroids, comorbidities, and indications for cesarean section. During the perioperative period, we did not observe significant differences between the two groups in terms of intraoperative hemorrhage, blood transfusion rate, postoperative fever incidence and postoperative hospitalization (all p > .05). It’s worth noting that the time of operation and postoperative ventilation in the EM group was shorter than that in the SM group (p < .05). More importantly, estimated blood loss and postoperative hemoglobin decline were less in the EM group than in the SM group (p < .05). Conclusion EM seems to be a viable approach to CM for the treatment of single intramural fibroids in the posterior wall, with the potential advantages of short operative time, low intraoperative bleeding, and low risk of pelvic adhesions.


Introduction
Uterine fibroids are the most common benign genital tract tumors in women of reproductive age [1].According to the latest research, the overall prevalence of uterine fibroids was reported to be 9.6%, increasing with age until menopause [2].The incidence of uterine fibroids associated with pregnancy varies from 2.7% to 10.7% [3,4].Most pregnant women with uterine fibroids will not experience any discomfort during pregnancy, whereas approximately 10% to 28% will develop complications such as spontaneous abortion, preterm labor, dystocia, intrauterine growth restriction, placental abruption, and postpartum hemorrhage [5].Pregnant women with larger fibroids are at greater risk of these complications than those with smaller fibroids, and may eventually require cesarean section to end the pregnancy [6].With progressive increases in reproductive age and cesarean delivery rates, obstetricians may encounter more patients requesting myomectomy during cesarean section (CS) in the coming years [7].
It is still controversial whether the fibroids should be removed during CS.The main concern is that cesarean myomectomy (CM) may increase the risk of intractable hemorrhage and eventually lead to hysterectomy [8].For this reason, some scholars believe that it is not recommended to remove fibroids during CS, except for pedunculated fibroids [9].However, with advances in surgical hemostasis techniques, numerous studies and meta-analyses demonstrated that CM could relieve the symptoms related to uterine fibroids and avoid the additional cost caused by the secondary operation without increasing the incidence of serious complications [10][11][12].Although many CM studies have agreed that pedunculated and subserosal fibroids can be safely removed, the proper management of intramural fibroids in pregnant women who are scheduled for cesarean delivery remains unclear.
Serosal myomectomy (SM) is currently the main method to accomplish CM, but it has significant limitations in the management of larger intramural fibroids in the posterior uterine wall.The main reason for this is the difficulty in exposing and enucleating large intramural fibroids as well as firm suturing to achieve hemostasis.Pelvic adhesions caused by a history of pelvic and abdominal surgery or pelvic endometriosis may make these procedures more challenging.The novel surgical method referred to as endometrial myomectomy (EM) seems to have unique advantages in treating intramural fibroids in the above situations, such as better exposure of the fibroids and a better surgical field of view even with severe pelvic adhesions, in addition to reducing the risk of future adhesions by not requiring further incisions in the uterine plasma.
This study aimed to confirm the feasibility and safety of the EM procedure by comparing the surgical data of SM and EM, which may contribute to obstetricians and pregnant women developing appropriate therapeutic strategies for managing intramural fibroids in the posterior uterine wall during CS.

Materials and methods
From June 2016 to June 2019, a retrospective cohort study was carried out in the second Department of Obstetrics, Fujian Maternity and Child Health Hospital, a tertiary medical center with 18000 births per annum.Inclusion criteria were those who underwent concomitant resection of posterior uterine wall fibroids during CS, which was performed by the corresponding author of this study.The following conditions were excluded due to the potential for significantly longer operation times and increased risk of hemorrhage: Multiple fibroids, multiple pregnancies, placenta previa, placenta accreta, placental abruption, and coagulopathy.In addition to pregnancy with uterine fibroids, indications for CS included previous cesarean section, cephalopelvic disproportion, abnormalities of fetal heart rate monitoring, malpresentation, and pregnant's wishes.These fibroids were initially detected by prenatal ultrasonography.The location, size, and number of fibroids were further confirmed by intraoperative exploration, and all included were solitary uterine fibroids, which were larger than 3 cm in diameter.The pathological examination finally confirmed that it was a uterine leiomyoma.Patients were divided into two groups depending on surgical style: 50 patients had their fibroids enucleated through an endometrial incision, also referred to as endometrial myomectomy (EM group).A total of 48 patients in the control group had their fibroids enucleated through trans-serosal approach (SM group).All the operations in this study were performed by the same medical team.The patient's willingness and tolerance were fully evaluated before the operation.Written informed consent was obtained for all cases.
Age, body mass index (BMI), gravidity, parity, gestational week at delivery, indications for CS, pregnancy complications, neonatal weight, fibroid features (location, size and pathological diagnosis of fibroids), total operation time, pre-and postoperative hemoglobin level, estimated blood loss, intraoperative hemorrhage, blood transfusion request, postoperative fever, postoperative ventilation time and postoperative hospital stay were all collected from each participant's medical record.All the above data were analyzed anonymously.This study was approved by the Ethics Review Board of the Fujian Maternity and Child Health Hospital.
The fibroids were classified into three groups according to the diameter of the fibroids: 3-5 cm, 5-10 cm, and 10 cm.The size of the fibroid is ultimately measured by the pathologist, who also records the degeneration of the fibroid.Operation time was defined as the time from the beginning of the skin incision to the completion of skin suturing.The data for estimating blood loss during surgery is obtained from the surgical and anesthetic notes, usually by adding the volume collected in the aspirator and the blood volume calculated by weighing the gauze.Changes in preoperative and 24-h postoperative hemoglobin levels can also reflect the amount of blood loss.Intraoperative hemorrhage was defined as estimated blood loss greater than 1000 ml, the request for blood transfusion, and a decrease in the postoperative hemoglobin level greater than 40 g/L.

Surgical methods
All patients were treated with cefmetazole 1.0 g intravenously as prophylactic antibiotics before operation.The patients were held in a flat position after combined spinal-epidural anesthesia.The decision to make a longitudinal or transverse incision is based on the size and location of the fibroid and the history of previous abdomino-pelvic surgery.Posterior uterine wall fibroids usually do not impede routine lower uterine segment cesarean delivery, after delivery of the fetus and placenta, the uterine cavity was cleaned by sweeping with gauze, then the uterine incision was clamped to stop bleeding, and carbetocin 100 lG was administered routinely to promote uterine contraction.In the EM group, except for a few patients with oversized fibroids or severe adhesions to the posterior uterine wall, the uterus was held outside the abdominal incision, and the number, location, and size of fibroids were rapidly explored (Figures 1(a) and 2(a)) and then start to remove the fibroids: The fibroids were squeezed into the uterine cavity, forcing the fibroids to be more convex under the endometrial layer, and an endometrial incision was made at the most bulging point to reach the pseudocapsule of the fibroids (Figures 1(b), 2(b) and 2(c)).The fibroids were pulled outward with a single claw forceps, blunt and sharp dissection along the pseudocapsule until the complete exposure of the fibroids was achieved (Figures 1(c) and 1(d)), the root of the fibroid was clamped with curved pliers and the root tissue was ligated with 1-0 Vicryl sutures intermittently or in a figure-ofeight pattern (Figure 1(e)).Finally, after tightening the sutures, the fibroids were resected completely, and the death cavity was closed by continuous sutures with 1-0 Vicryl (Figures 1(f) and 2(d)).After definitive hemostasis and confirmation of no active bleeding, the lower uterine cesarean incision was routinely sutured.In the SM group, the lower uterine incision was sutured first, and then the fibroids were enucleated via the conventional serosal incision.The surface plasma membrane was incised, the fibroids were clamped with single claw forceps, the pseudocapsule was separated bluntly and sharply to remove the fibroids completely, the cavity was closed with 1-0 Vicryl sutures, and the plasma membrane was closed with continuous sutures [13].

Statistical analysis
Collected data were statistically analyzed by using SPSS software version 20.0 (IBM, Armonk, NY, USA).Normally distributed continuous variables were expressed as means ± standard deviation (SD), while non-normally continuous variables were reported as median (minimum-maximum).Differences between groups were evaluated using the Pearson Chi-square test or Fisher exact test for categorical variables.The Student's t-test or the Mann-Whitney test was utilized for continuous variables when appropriate.P values <.05 were defined to be statistically significant.

Results
During the study period, Ninety-eight pregnant women met the inclusion criteria, 50 and 48 patients were included in the EM group and the SM group, respectively.Both groups were comparable in maternal age, BMI, gravidity, parity, gestational weeks at delivery, indications for CS, primipara, and previous myomectomy.There was no significant difference in the distribution of pregnancy comorbidities between the two groups of patients (such as gestational diabetes mellitus, and gestational hypertension).There were two cases of fetal distress in each group, no stillbirths occurred in either group, and there was no significant difference in neonatal birth weight between the two groups.All data of clinical and demographic are shown in Table 1.
The diameter of fibroids was similar in the EM group compared to the SM group (3-15cm, median 7 cm versus 3-13cm, median 7 cm, p > .05).The EM and SM groups did not demonstrate significant differences after further subgrouping according to the size of the myoma.Among 98 patients, most of the posterior wall fibroids were located in the corpus of the uterus (94.9%), and the postoperative pathological diagnosis suggested no difference in the pathological classification of the fibroids between the two groups.The comparison of the characteristics of uterine fibroids is shown in Table 2 The operation time in the EM group was significantly shorter than the SM group (54.52 ± 8.62 min vs. 58.65 ± 10.22 min, p ¼ .033).The postoperative hemoglobin drop in the EM group was 5-45 g/L (median 16 g/L), which is less than the 9-50 g/L (median 20 g/L) in the SM group, and this difference was statistically significant (p < .001).The estimated blood loss in the EM group was slightly less than that in the SM group (median 423.5 ml vs. 454.5 ml, p ¼ .027).There were no cases of hysterectomy in this study, two groups were statistically similar in the blood transfusion rate, postoperative fever and postoperative hospitalization (p > .05).The incidence of intraoperative hemorrhage in the EM group was lower than that in the SM group (4.0% vs. 8.3%), but the difference was not statistically significant (p > .05).The postoperative ventilation time was significantly longer in the SM group than in the EM group (22.69 ± 3.08 h vs. 20.26± 3.40 h, p < .001).All intraoperative and postoperative outcomes are shown in Table 2.

Discussion
Since Victor Bonney first reported cesarean myomectomy in 1914 [14], obstetricians have debated whether myomectomy should be performed simultaneously during CS until today.Obstetricians who oppose the indicated procedure believe the CM may carry a higher risk of complications, such as intraoperative and postpartum hemorrhage, prolonged operation time, even obstetric hysterectomy [15].However, leaving the fibroids untouched may affect uterine contraction, which leads to uterine atony and postpartum hemorrhage [16].In the long run, the still existing fibroids may bring about degeneration, menorrhagia, anemia, and compression of surrounding organs.Moreover, the resection of fibroids is essential to improve the intrauterine microenvironment, increase the chance of conception, and improve subsequent pregnancy outcomes [17].
In a meta-analysis, Song et al. [18] suggested that CM may not be appropriate for pregnant women with intramural fibroids.Roman et al. [19] found that the incidence of hemorrhage in pregnant women with intramural fibroids was 21.2% when the fibroids were enucleated, compared with 12.8% for only cesarean section, but this increase did not reach statistical significance.Kim et al. [20] reported the types of fibroids in patients who received CM with complications and found that subserosal fibroids accounted for 10%, and the remaining 90% were intramural fibroids.
Contrary to the above point of view, our data revealed that intramural fibroids could be safely removed in CS.The incidence of intraoperative hemorrhage was 4.0% in the EM group and 8.3% in the SM group, blood transfusion rate was 2.0% and 8.3% in the above group, respectively.Furthermore, EM was associated with the shorter operation and postoperative ventilation time than SM.It seems to provide another feasible solution to deal with intramural fibroids in CS correctly.
The EM technique should be particularly applicable to enucleate the intramural fibroids in CS due to uterine anatomical features and the consideration of taking full advantage of the incision made in the lower uterine segment [21][22][23].Studies have shown that as the uterus increases in size during pregnancy, the pseudocapsule of the fibroids becomes larger and more elastic, making it easier to remove completely [24].Our experience suggests that EM technique is more suitable for  larger uterine fibroids.Because most of the uterine muscle wall is occupied by large fibroids, the remaining muscle layer becomes thinner, and it is easier to squeeze the fibroids into the uterine cavity, which facilitates the enucleation of the tumor nucleus through the endometrial incision during the operation.A thinner incision of the muscle layer is also conducive to less intraoperative bleeding.Conversely, it is difficult to expose smaller fibroids in the direction of the uterine cavity, and the transendometrial approach requires an incision of the same or deeper myometrium compared with SM, so the advantage is not obvious.
From the point of view of the anatomical characteristics of the uterus, the uterine artery originates from the anterior branch of the internal iliac artery, crosses the ureter from the base of the broad ligament of the uterus to 2 cm lateral to the cervix and enters the uterus via the plasma membrane, finally reaching the endometrium via the spiral uterine artery.Therefore, SM is more likely to cause injury to the large uterine vessels, which may lead to intraoperative bleeding difficulties or even refractory bleeding [24].On the contrary, EM is more likely to damage the uterine spiral artery.The small diameter of the uterine spiral artery makes it easy to stop bleeding quickly when the coagulation function is normal, and the endometrial regeneration and repair are rapid, which can accelerate the recovery of the basal wound after myoma removal and facilitate the uterine recovery after delivery.
In a multicenter study, Zhao et al. [25] suggested that CM did not cause additional intraoperative bleeding and blood transfusion risks.The incidence of blood transfusion was only 0.7% in this study, which is much lower than our findings.It is worth noting that only 13.4% of fibroids in their study were larger than 5 cm in diameter, while the proportion of fibroids larger than 5 cm in the EM group and SM group in the present study was 80% and 83.3%, respectively.Reviewing the literature, the incidence of major complications during CM is tightly correlated with the size of the fibroid, the cutoff point of fibroid size range from 5.0 cm to 8.0 cm in several studies [10,11,25], which could explain the significant differences in the incidence of blood transfusion.
In fact, this is not the first time our team has attempted to remove fibroids via lower uterine incision during CS.Previously, we successfully developed a surgical method to remove anterior uterine wall fibroids using the transverse incision in the lower uterine segment during CS.The principle of this procedure is squeezing the tumor in the direction of the lower uterine incision, then cut to the tumor wall at the most protruding part of the incisal margin, thus the tumor can be removed without additional incisions on the surface of the uterus.Previous studies have confirmed the efficacy of fibroids removal by transverse incision of the lower uterine segment [26], the perioperative indicators such as intraoperative blood loss, blood transfusion rate and postoperative fever rate were not significantly different from those of the control group underwent conventional trans-serosal method to remove the fibroids.However, the disadvantages of this procedure are obvious, as it cannot deal with fibroids in the posterior wall and those in the upper part of the uterine corpus and at the fundus, which are distant from the incision margin.
Uterine posterior wall fibroids with large size may make it difficult to expose the uterus from the abdominal incision.Extensive and tight adhesions of the bowel to the posterior uterine wall caused by severe endometriosis also contribute to the above circumstance.In that situation, enucleation of posterior wall fibroids through uterine serosa becomes extremely difficult.Furthermore, it will prolong the operation time and increase the risk of massive bleeding during the operation.Resection of intramural myoma of the posterior wall via endometrial approach without largescale adhesion separation is conducive to shortening the operation time and reducing the risk of bleeding.In addition, keeping the serosal surface intact prevents surgery interference on the intestine and reduces the incidence of postoperative ileus.This may explain why in the present study, the time of operation and postoperative ventilation were shorter than that in the SM group.
Theoretically, intrauterine adhesions may occur in EM group because the incision is in the uterine cavity.However, no intrauterine adhesions were found by routine saline infusion sonography at six weeks postpartum in Hatinaz's study [24].Further research conducted by Huang et al. [27] addressed this issue excellently.They longitudinally followed 63 patients who had undergone previous EM procedures, and compared the surgical and obstetric outcomes of subsequent cesarean section with data from the first pregnancy.Results showed that the incidence of preterm birth and premature rupture of membranes decreased in subsequent pregnancies, while gestational age and neonatal birth weight increased significantly.There was no difference in the incidence of placenta previa, placental abruption, and uterine rupture.Thus cited authors concluded that EM procedure might improve the obstetric outcomes of subsequent pregnancy by getting rid of the influence caused by fibroids.
The main strength of this study is that it provided more evidence on how to manage the intramural fibroids in the posterior wall of the uterus during CS properly.Despite much literature having investigated CM recently, there are few reports on intramural fibroids.Second, our data suggested that the dilemma of large fibroids in the posterior wall can be well resolved by EM procedure.The main limitation of this study is that it was a single-center retrospective analysis, In addition, data on long-term outcomes were not included in this study, especially effects on subsequent pregnancies such as the chance of conception, risk of uterine rupture, obstetric and surgical outcomes.
EM seems to be a safe and reliable technique for pregnant women with intramural fibroids in posterior wall during CS.It provides the possibility of minimizing the trauma, shortening the operation time, preventing the formation of postoperative adhesions, and promoting the recovery of gastrointestinal function.

Figure 1 .
Figure 1.Enucleation of recurrent large fibroid in the posterior wall of the uterus via the trans-endometrial route.(a) There was a previous history of uterine fibroid enucleation.Intraoperative exploration revealed adhesion of the colonic mesentery to the posterior wall of the uterus.The posterior wall fibroid is about 8 cm in diameter.(b-d) The fibroid is squeezed into the uterine cavity and then gradually removed.(e) The root tissue of the fibroid is sutured with 1-0 vicryl in a seperated manner.(f) The posterior wall of the uterus after fibroid removal.

Figure 2 .
Figure 2. Enucleation of intramural fibroids in the uterine posterior wall through trans-endometrial approach.(a) Rapid exploration of the size, number and location of fibroids after delivery of the fetus and placenta.(b-c) Squeeze the fibroid in the direction of the uterine cavity and make an incision in the most prominent part of the endometrium to reach the pseudocapsule of fibroids.(d) After complete removal of the uterine fibroid, the cavity was closed with 1-0 vicryl continuous sutures.

Table 1 .
Patients' clinical and demographic characteristics.
BMI: Body Mass Index; CS: cesarean section; FHR: fetal heart rate; CPD: cephalopelvic disproportion.P value was calculated with a Pearson Chi-square test, Student's t test, or Mann-Whitney U test.

Table 2 .
Characteristics of uterine fibroids and surgical outcomes.
P value was calculated with a Pearson Chi-square test, Student's t test, or Mann-Whitney U test.