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.