Discussion
Three decades ago, the World Health Organization (WHO) suggested that the rate of cesarean sections be maintained at 15%18. However, the rate of cesarean sections continues to increase, resulting in more severe complications such as abdominal bleeding, chronic pelvic pain, uterine scar pregnancy, placenta accrete, and uterine rupture due to incomplete healing of cesarean section scars. Effective treatments for CSD include laparotomy, laparoscopy, hysteroscopy, and vaginal repair. However, the outcomes of surgical intervention are not always successful, and there is no consensus on which surgical intervention is the best19. Our center is the largest vaginal repair center in China, and vaginal repair is offered to symptomatic women who wish to preserve the uterus and to asymptomatic women who wish to preserve fertility. A total of 278 patients underwent pre- and postoperative MRI or TVS. We found that gynecological symptoms, such as postmenstrual spotting, and the uterine morphology improved (Table S3). However, some scar defects could not be repaired.
Adenomyosis is a common gynecological disease characterized by the infiltration of ectopic endometrial glands and/or stroma into the myometrium, thereby causing dysmenorrhea, pelvic pain, abnormal uterine bleeding, and infertility6, 20, 21. Fifty out of 278 patients (18.0%) had adenomyosis, consistent with previous studies reporting an incidence of 20%22, 23. The mean preoperative CSD width was smaller and the TRM was thicker in patients with adenomyosis than that in patients without the disorder and this was due to the presence of hyperplastic and hypertrophic smooth muscle.
The duration of menstruation before cesarean section was longer in patients with adenomyosis than that in patients without the disorder; however, the results were not statistically different (p> 0.05). These patients suffered abnormal uterine bleeding after cesarean delivery. In addition, the duration of menstruation after cesarean section was significantly longer in patients with adenomyosis than that in patients without the disorder (p < 0.05), suggesting that adenomyosis might disrupt the tissue repair process. At follow-up, the duration of menstruation was optimal in patients with adenomyosis (p < 0.05). Furthermore, the optimal rate of class A healing after vaginal repair was not achieved in patients with adenomyosis (Table S4), revealing that adenomyosis was an adverse factor in the healing of uterine incisions.
Ectopic endometrial glands and the presence of stroma can cause repeated bleeding of the myometrium. Repeated tissue injury and repair caused by adenomyotic lesions increases the degree of fibrosis15. Ibrahim et al. reported the presence of myofibroblasts at the endometrial-myometrial junctional zone in the uteri of patients with adenomyosis, suggesting that the tissue injury and repair (TIAR) mechanism was activated 24-26. Estrogen plays important roles in proliferation and healing. In the uterus, estrogen induces uterine peristalsis, thereby further aggravating auto-traumatization. Repeated cycles of auto-traumatization at the endometrial-myometrial junctional zone can disrupt uterine muscular fibers, which eventually leads to endometrial basalis invagination and inhibits the healing process 15.
Adenomyosis and endometriosis are closely linked and estrogens are involved in both disorders27, 28. Endometriosis creates an inflammatory environment where many different types of chemokines, such chemokine C-X-C motif chemokine ligand 12 (CXCL12), are produced, thereby attracting bone marrow cells to the lesions29. The chemokine receptor 4 (CXCR4) and its specific ligand CXCL12 play important roles in the mobilization and homing of stem cells30. Compared to the eutopic endometrium, the expression of CXCl12 and CXCR4 was significantly increased in endometriosis, indicating that stem cells were recruited and circulating stem cells were limited29.
Stem cells can self-renew and produce more differentiated daughter cells31, 32, and these multipotent stem cells can be used in tissue engineering and regenerative medicine33, 34. Other studies have reported that bone marrow-derived stem cells are involved in uterine repair. Therefore, the repair of uterine damage is dependent on the population of stem cells 33. Randomized double-blind controlled studies are needed to confirm the correlation between adenomyosis treatment and myometrial repair.
It has been reported that 10 of 18 (55.6%) women who underwent laparoscopic repair achieved pregnancy 35. In another study, eight out of 18 infertile women (44.4%) became pregnant, delivering healthy babies by cesarean section 36. A total of 59.3% of the patients in our study achieved pregnancy after vaginal repair, with eight out of 12 women with adenomyosis achieving pregnancy, which was slightly higher than that in women without the disorder. Furthermore, fertility was not affected in both groups.
Uterine rupture is a catastrophic complication during pregnancy and labor, especially for women with a history of cesarean section. The TRM is an indicator of uterine rupture or dehiscence, and although many risk factors can lead to uterine rupture or dehiscence, there is an association between a thin TRM and uterine rupture or dehiscence37. However, the TRM cutoff remains controversial. It has been reported that the cutoff TRM value for the risk of uterine rupture be set at 2.5–3.0 mm2, 38, 39. In this study, we found that the TRM of women who achieved pregnancy and delivered infants increased significantly from 2.3 ± 0.8 mm before surgery to 7.6 ± 2.9 mm after surgery, and the TRM was not less than 3 mm. Therefore, the pregnancy outcome was good, and there were no cases of uterine rupture or dehiscence. Furthermore, vaginal repair not only reduced menstrual spotting but also reconstructed the uterus to improve fertility in patients with CSD.
Unfortunately, seven women experienced miscarriages, and 22 (40.7%) women failed to achieve pregnancy. Pregnancy is a complicated process, and the rate of spontaneous miscarriage is <15% of all pregnancies 40. For instance, Giakoumelou et al. reported that miscarriage occurred in one out of five pregnancies in women aged 31–36 years 41. In the this study, the pregnancy rate was 66.7% (8/12) and the miscarriage rate was 25.0% (2/8) in women with adenomyosis. Further studies with larger cohorts are needed to clarify the relationship between adenomyosis and pregnancy.
There were several limitations in this study. First, our study was a single-center retrospective study, although the sample size was fairly large. Second, information on the duration of menstruation was obtained by memory, which may have caused bias. Third, the sample size used to generate the data on subsequent pregnancies after treatment was small; therefore, the relationship between adenomyosis and pregnancy could not be assessed. Therefore, further prospective and large multi-center studies are needed in the future.