Discussion
If the placenta does not separate from the uterus after delivery, the
NICE and the WHO guidelines recommend that the placenta should be
removed manually within 30 minutes to 1 hours after delivery with a
set-up to deal with heavy bleeding. If bleeding does not stop, UAE or
hysterectomy is required4). In Europe and the United
States, deliveries are centralized in regional general hospitals. This
allows obstetrical providers to perform MROP under anaesthesia, which is
performed by anaesthesiologists. In Japan, on the other hand, private
clinics handle half of all deliveries, and high-risk cases are
transported to advanced medical facilities. As a result, many cases with
RPOC have been referred to our hospital. In this study, 41 cases of RPOC
delivered after 34 weeks of gestation were successfully treated without
hysterectomy or death. The strengths of this retrospective study are as
follows: (i) The research period was relatively short (10 years), and
the participants were treated consistently. (ii) The clinical
characteristics of the participants were homogeneous and were limited to
cases delivered after 34 weeks of gestation. (iii) The detailed clinical
course of surgical removal and spontaneous disappearance of RPOC was
clarified in all cases.
In this study, 15 of 19 cases with MROP within 24 hours of delivery
experienced heavy bleeding during the procedure or the following day. A
Japanese multicentre retrospective study demonstrated that the incidence
of bleeding of 1000 ml or more at delivery was significantly higher in
41.1% of the women who underwent MROP than in 4.1% of those who did
not17). The cause of heavy bleeding during or after
MROP is considered to be that uterine contraction cannot prevent damage
to large blood vessel, which occurs after MROP when decidua formation is
insufficient or absent18). In one study, seven of 37
MROP cases were reported to have undergone hysterectomy due to massive
bleeding, and those cases were pathologically diagnosed with placenta
accreta and no decidua formation19). Interestingly, in
the current study, when MROP was performed on patients with no bleeding
or other emergencies, heavy bleeding and partially retained placenta
were frequently observed both intraoperatively and postoperatively
(Figure 1A). This result suggests that MROP immediately after delivery
should be avoided in cases of retained placenta without bleeding because
of extensive decidual defect and placental adhesion.
Of the 22 RPOC cases managed conservatively, six cases experienced
spontaneous heavy bleeding. Previous studies reported that the RPOC
diameters ≧ 4 - 4.4 cm6,8) or blood flow in
RPOC7,21) had been associated with heavy bleeding
during conservative management of RPOC. However, these studies differ
from the present study in several respects. First, these studies
included cases before 20 weeks’ gestation6-8, 21).
Although the size of RPOC is smaller, trophoblast cell viability is
higher in early and mid-pregnancy than in late
pregnancy20). Furthermore, these studies included
cases in which the placenta was manually removed within 24 hours after
delivery6,8). Therefore, the results of previous
studies were based on a heterogenous population and may have had various
biases. In the present study, there was no correlation between heavy
bleeding and RPOC size or blood flow (Table S1). Further research is
needed to determine the relationship between RPOC size, blood flow, and
heavy bleeding.
The median time for conservatively treated RPOC to develop massive
bleeding is reported to be 22-42 days, with a maximum of 38-43
days6,8). In this study, no events such as heavy
bleeding, blood transfusion, UAE, or infection, were observed after 60
days during conservative management (Figure 2). This result may help
patients understand when the risk of bleeding decreases during
conservative management. There were six cases in which placental removal
was attempted despite the absence of heavy bleeding (Figure 1B). None of
the cases resulted in the removal of the placenta, and afterwards, the
placenta spontaneously disappeared. Therefore, if conservative
management does not cause bleeding or infection, placental removal
should be avoided and spontaneous resolution can be expected. In this
study, the rate of RPOC disappearance during conservative management was
approximately 50% at 100 days and 80% at 1 year (Figure 3). In
previous studies, the time to spontaneous disappearance of RPOC ranged
from 48 to 84 days6,7,22,23), which was shorter than
that in the present study, likely due to the small size of RPOC in early
to mid-pregnancy. This study is the first to demonstrate the time until
spontaneous resolution of RPOC in late pregnancy. More research is
needed to determine whether these data can be validated under the same
conditions.
The half-life of serum hCG after intramuscular injection of hCG is 30-32
hours in the absence of hCG-producing tissues in the
body24). The longer half-life indicates that
hCG-producing trophoblast cells do exist, but gradually undergo
apoptosis. In RPOC cases delivered at before 22 weeks of gestation,
serum hCG has been reported to be below the measurable threshold at 67
(6-183) days postpartum, and no cases experienced heavy bleeding
afterwards22). The present study also showed that
heavy bleeding did not occur when serum hCG levels fell below the
measurable threshold. Therefore, it is important to measure serum hCG
levels over time to assess the risk of heavy bleeding. We previously
reported an average serum hCG half-life of 5.2 days in five cases of
RPOC25), similar to the average of 4.7 days in this
study (Figure 4A). Interestingly, in three cases, serum hCG levels
decreased rapidly after UAE (Figure 4B), suggesting that acute
interception of uteroplacental blood flow causes sudden death of
trophoblast cells. There were cases of RPOC after 20 weeks’ gestation in
which the half-life of hCG exceeded 10 days (Figure 4D), but there were
no such cases after 34 weeks. The molecular mechanisms of apoptosis in
post-partum trophoblast cells may differ between early and mid-term and
late pregnancy. Methotrexate is effective in treating ectopic pregnancy
and RPOC during early pregnancy26,27). Methotrexate
has also been used for RPOC in late pregnancy9), but
its effectiveness has yet to be proven. The effect of methotrexate on
RPOC in late pregnancy should be confirmed by measuring serum hCG
half-life and comparing it with the data obtained in this study.