Discussion
It is a medical consensus that UFs have adverse effects on fertility[12-14]. With the global fertility decline, it is still a problem to be solved to establish a minimally invasive, safe and effective treatment method that can effectively improve the uterine pregnancy conditions and pregnancy outcomes of the patients with UFs.
The MWA treatment for UFs is a new minimally invasive treatment technology that has been applied to the clinic for more than ten years. Research reports show that this method has the advantages of minimally invasiveness, effectively making fibroids shrink or disappear on the basis of preserving the uterus, and no damage to ovarian function[6, 8]. Our previous study found that many patients with symptomatic UFs had unplanned pregnancies and safe production after MWA[9], suggesting that the MWA treatment for UFs may have no negative impact on the patient’s reproductive function and may even improve the patient’s reproductive function. Therefore, this paper makes a further systematic and prospective observational study.
Endometrial integrity and better receptivity are the basic conditions for pregnancy. In order to effectively protect the endometrium from thermal damage during MWA, for patients who already have sexual life, a hysterosalpingography catheter was inserted into the uterine cavity through the cervix 5 minutes before treatment, so as to identify the endometrium compressed and deformed by UFs during treatment. During the ablation of FIGO 0–4 UFs, cooling saline is injected into the uterine cavity through the catheter to form water isolation on the surface of the endometrium to protect the endometrium. The menstrual cycle and menstrual period of patients were normal after treatment, indicating that the protective measures were effective.
The subjects of this study were patients with fertility requirements, seeking treatment due to large UFs, bleeding, compression and other symptoms, which were in line with the clinical guidelines for the treatment for UFs of the International Society of Obstetrics and gynecology[15]. Because this cohort of patients have fertility requirements after treatment, the follow-up observation of fertility status after treatment can better reflect the impact of this treatment technology on conception and continuous pregnancy.
In this study, the median follow-up time after treatment was 64 months (1–124 months), and the pregnancy rate after treatment was 55.56%, which was higher than the reported 38.3% after uterine artery embolization (UAE)[16] and 53.6%~55.9% after surgical myomectomy[17]. Among continuing pregnancy patients, sustained pregnancy and safe productivity were 96.2%(25/26), and the babies were all healthy, indicating that US-guided MWA therapy can be used for symptomatic UFs with fertility requirements. Among the 18 patients diagnosed as primary infertility before treatment, the successful pregnancy rate after treatment was 22.22%, and among the successful pregnancy patients, the successful delivery rate was 50%, suggesting that the reason of primary infertility could be UFs, the shrinkage of fibroids after MWA improved the fertility status of patients.
With respect to the appropriate pregnancy time after ablation treatment, the results of this study showed that 6% of the 50 pregnancies of 45 patients were pregnant within 3 months after treatment, of which 1 case became pregnant naturally 2 months after treatment and continued to pregnancy smoothly until full-term delivery; 12% were pregnant 3 ~ 6 months after treatment, and 82% were pregnant 6 months after MWA treatment. This data has certain guiding significance for the preparation time of patients after MWA treatment. However, in respect of when it is safer for specific patients to become pregnant after treatment, personalized pregnancy guidance should be given according to the type, size and treatment effect of the patient’s UFs. It is recommended that the patient be rechecked 3 months after treatment. If the shrinkage rate of UFs is ≥50%, the symptoms related to fibroids disappear, and the menstruation is normal, then pregnancy preparation can be considered. The average pregnancy preparation time of patients after MWA treatment was shorter than that after surgical myomectomy, and there was no uterine rupture in pregnancy cases, suggesting local tissue necrosis of UFs after MWA. MWA will not increase the risk of uterine rupture. Because the treatment was completed under the US-guidance and monitoring. during the treatment, the microwave thermal field can be effectively controlled in the UFs capsule, and the damage to the tissues outside the adjacent UFs was small. Therefore, there was no obvious damage to the elastic fibers and collagen fibers of the myometrium. After treatment, the volume of the UFs is significantly reduced[6, 7],but there is no scar formation in the tissues of the myometrium outside the UFs. The risk of collagen fiber hyperplasia is small, which can theoretically reduce the risk of uterine rupture during pregnancy caused by scars caused by UFs surgical myomectomy. For the elderly patients who urgently need to get pregnant as soon as possible, this treatment may be a more appropriate treatment option.
The determinants of delivery mode of pregnant women after MWA are not only obstetric disease factors, but also social and patient psychological factors. In this study, the cesarean section rate was 76%, which was only partly attributed to obstetric factors. Among the 19 cases of cesarean section, 1 case (5.3%) chose cesarean section because of breech position; 7 cases (36.8%) had a history of cesarean section;2 cases (10.5%) were conceived by ART, and the fetus was precious, cesarean section was strongly required to complete delivery;1 case (5.3%) has a history of 2 artificial abortions; 1 case (5.3%) refused to try vaginal delivery due to a history of ectopic pregnancy, fear of pain during delivery and delivery complications; and 7 cases (36.8%) opted for cesarean section because of the lack of confidence in natural childbirth at the older age of pregnant women. Therefore, the mode of delivery followed up in this study cannot accurately reflect the obstetric delivery state formed by the treatment of UFs. No uterine rupture occurred in all patients with continuous pregnancy and delivery, suggesting that it is safe for patients with UFs to conceive and give birth after microwave ablation treatment.
Although the relationship and mechanism between UFs and infertility are not completely clear, studies have shown that UFs at different locations have different effects on pregnancy. Submucosal fibroids of any size and intramural fibroids >4cm significantly impair patient fertility and in vitro fertilization results[1]. Among the 45 pregnant patients in this study, there were 7 cases of submucosal fibroids, 15 cases of intramural fibroids, and 23 cases of subserosal fibroids. The average maximum diameter of fibroids was 5.87±2.13cm (3–16.7cm), the ablation rate averaged 86.40±7.49% (56.85–99.56%). After ablation of some submucosal or intramural UFs close to the fibroids, the coagulated and necrotic fibroids were discharged through vagina, the fibroids disappeared completely, and the uterus returned to normal size and shape, indicating that UFs were completely ablated, the endometrium was effectively protected under real-time US-guidance, and the pregnancy ability of patients can be unaffected or even effectively improved.
In this study, 1 pregnant patient had placental abruption. Because there are many factors related to the occurrence of placental abruption, even pregnant women without UFs can also have placental abruption. At present, there is no evidence that premature placental contractions are caused by MWA treatment. It also needs to be verified by researches with large sample sizes.
There are many factors affecting women’s fertility. The success of pregnancy after MWA treatment of UFs is also related to many factors. This study found that there were significant differences in age, history of pregnancy, history of spontaneous abortion, history of infertility and type of fibroids between the pregnant group and the non-pregnant group after MWA treatment.
The OR value of the age of the pregnant group and the non-pregnant group was 0.858, indicating that the older the patients, the lower the pregnancy rate after MWA. The pregnancy rate of patients in the group<35 years old was significantly higher than that in the group≥35 years old. The pregnancy outcome analysis of pregnant patients showed that after pregnancy, the spontaneous abortion rate was 22%, but the spontaneous abortion rate was only 13.33% for patients<35 years old, and 23.33% for patients≥35 years old. This suggests that for patients with UFs who have not given birth, interventions should be taken as soon as possible. Previous studies believe that UFs that change the shape of uterine cavity and make endometrial deformation and abnormal contour have a greater impact on fertility, and surgery and other treatments can improve and correct this damage [18].
This study found that the pregnancy rate after MWA for UFs close to the serosal layer was higher than that close to the mucosal layer. This may be due to the changes in the morphology of the uterine cavity caused by submucosal fibroids, changes in the receptivity of the endometrium, and the influence of the intrauterine environment[2] , which also verifies the previous study research that submucosal fibroids has a negative impact on fertility, and the existence of subseroal fibroids has little or no impact on fertility[1]. Among patients with UFs with a history of spontaneous abortion, the pregnancy rate after the MWA treatment was higher than that without a history of spontaneous abortion, and they could give birth smoothly and successfully. It is suggested that these patients have their own fertility conditions and ability, and the occurrence of spontaneous abortion might be closely related to UFs. After MWA treatment, the fertility disorders related to fibroids can be lifted or disappeared, which provides good conditions for smooth conception and delivery. It is also consistent with the fact that fibroids increase perinatal risks such as spontaneous abortion[4]. Although this study showed more optimistic results, the prospective comparation study of pregnancy status of MWA and UAE, as well as MWA and myomectomy is still worthy of further research, in order to obtain objective research data and guide doctors to give individualized and accurate treatment suggestions according to the requirements and specific conditions of the patients.
Conclusion
Patients with symptomatic UFs have a higher pregnancy rate after MWA treatment, and the interval between preparations for pregnancy is shorter than myomectomy. For patients who are infertile due to UFs and plan to pregnant as soon as possible, the MWA therapy can be used as an alternative safe minimally invasive treatment method. Vaginal delivery appeared to be feasible and safe after MWA. For patients with infertility and adverse pregnancy history caused by UFs, the MWA treatment could improve the uterine conditions, and it is possible to increase the natural conception rate and the ART conception rate. For the patients with UFs and wanting to be pregnancy earlier treatment is important.