A Prospective Multicenter Observational Real-world Study of Retained Products of Conception
Conditions: Retained Products of Conception, RPOC
Sponsor: The Third Xiangya Hospital of Central South University

A multicenter prospective observational real- world study of 
retained products of conception. 
                   Research Plan 
 
 
Sponsor: Xiangya Third Hospital, Central South University 
 
Team Leader: Xiangya Third Hospital, Central South 
University 
 
Research Leader: Xu Dabao 
 
Project Number: fkky 2022001 
 
Version number: 1.1 
 
Version Date: 2022-05-10 
 
 
 
 

 
 
List of research institution numbers 
Name of research institution 
serial number 
Xiangya Third Hospital of Central South 
University 
01 
Changsha Maternal and Child Health 
Hospital 
02 
Zhuzhou Central Hospital 
03 
Xiangtan Central Hospital 
04 
Xiangtan 
Maternal 
and 
Child 
Health 
Hospital 
05 
Yiyang Maternal and Child Health Hospital 
06 
Yueyang First People's Hospital 
07 
Changde First People's Hospital 
08 
The First Affiliated Hospital of Shaoyang 
University 
09 
Huaihua First People's Hospital 
10 
Hengyang Central Hospital 
11 
Chenzhou Maternal and Child Health 
Hospital 
12 
Yongzhou Central Hospital 
13 

Hunan Provincial People's Hospital 
14 
Changsha County Maternal and Child 
Health Hospital 
15 
Liuyang People's Hospital 
16 
 
 
 
 
 
I. Research Background and Significance 
Retained products of conception (RPOC) refers to the phenomenon where 
embryonic or placental tissue remains in the uterine cavity or even implants in the 
myometrium after miscarriage or delivery. Its clinical symptoms are mainly persistent 
vaginal bleeding, fever, or abdominal pain and other signs of pelvic infection after 
termination of pregnancy. The incidence of RPOC after delivery is about 1%, while the 
incidence after miscarriage and mid-pregnancy termination of pregnancy is as high as 
2.3%-21.3% [1] . If the patient has intrauterine diseases, such as uterine fibroids, 
adenomyosis, uterine malformations, etc., the incidence is even higher. 
In the diagnosis of RPOC, clinical practice usually combines the patient's history 
of delivery or miscarriage, symptoms of persistent or recurrent vaginal bleeding, serum 
β-HCG level, and transvaginal/abdominal Doppler ultrasound showing heterogeneous 
masses in the uterus to make a definitive diagnosis. The sensitivity of transvaginal 
Doppler ultrasound can reach 94%, and the specificity can reach 98% [ 2] , so it is widely 
used in the diagnosis of retained products of pregnancy. As a supplementary means of 
ultrasound, pelvic MRI has more characteristic features and can clearly show the 
anatomical structure of the uterus, assess the relationship between the placenta and the 
myometrium, and clarify the location and depth of implantation, which is of great 
significance for the diagnosis and differentiation of RPOC [ 3] . 
The short-term complications of RPOC include vaginal bleeding and infection, 
while the long-term complications include intrauterine adhesions and infertility [ 4 ] . A 
study by Ben - Ami I proposed that retained products of conception are an independent 
risk factor for infertility [ 5] . 
In terms of the treatment of retained products of pregnancy, the main clinical 
treatment methods are divided into surgical treatment and non-surgical treatment. Non-

surgical treatment mainly includes expectant management and drug treatment. A 
retrospective cohort study by Wada Yoshimitsu [ 6] included 54 patients with RPOC, of 
whom 44 patients chose expectant management. 34 patients (77%) had their retained 
pregnancy tissue expelled spontaneously without intervention and did not require 
surgical treatment. The other 10 patients (23%) underwent hysteroscopic surgery for 
"persistent vaginal bleeding" and concluded that expectant management is effective and 
can reduce the number of intrauterine operations. Zeng Wenjuan [ 7 ] et al. found that 
although the vaginal bleeding time was longer after expectant management than after 
curettage, no serious hemorrhage occurred. They also suggested that expectant 
management is equally safe and effective compared with curettage and can replace 
some curettage treatment. However, expectant management has a long follow-up time 
and requires high patient compliance. A meta-analysis by Li Mengxi [ 8] believed that 
expectant management is an effective treatment method and that patients with retained 
products of pregnancy <50mm in diameter and stable vital signs are suitable for 
expectant management. However, there is a difference in the effectiveness of expectant 
management compared to surgical management. Patients who undergo curettage can 
completely expel the remaining pregnancy tissues through surgery in a short period of 
time, so curettage is considered to be a more effective treatment method. In fact, 
clinicians are usually worried that the continued presence of pregnancy tissues in the 
uterus may lead to serious complications such as bleeding or infection. Therefore, they 
tend to actively treat the disease to reduce the incidence of complications. However, 
some studies have shown that there is no statistically significant difference in the risk 
of patients needing emergency curettage for massive bleeding, whether they undergo 
expectant management or curettage. On the contrary, curettage may increase the risk of 
postoperative infection [ 8] . With repeated intrauterine operations, the incidence of 
intrauterine adhesions gradually increases. Intrauterine adhesions seriously affect 
menstrual recovery and subsequent pregnancy, and have become an important cause of 
infertility. Some studies have reported that the incidence of intrauterine adhesions after 
curettage is about 29.6%, and the incidence of intrauterine adhesions in patients who 
undergo curettage again after incomplete abortion due to pregnancy tissue residue can 
increase to 40%, of which 75% are moderate to severe intrauterine adhesions [ 9 ] . 83.1% 
of patients with severe intrauterine adhesions had related curettage for pregnancy [1 0 ] . 
In fact, the incidence of intrauterine adhesions may be more than that. Since the typical 
clinical manifestation of intrauterine adhesions is reduced menstrual flow, and severe 
cases are accompanied by secondary infertility, it mainly affects the patient's fertility, 
but has no significant impact on daily life. Therefore, some patients do not seek medical 
attention or receive related treatment. Therefore, for patients who want to have children, 
expectant management is a good choice to reduce the number of intrauterine procedures, 
prevent the occurrence of intrauterine adhesions, and protect the patient's fertility. 
Studies have reported that adding sequential estrogen-progesterone therapy to 
expectant management can improve the effectiveness of expectant management, 
shorten the duration of vaginal bleeding, and reduce the amount of bleeding. The 
success rate of this treatment is 66.7-96% [ 11-14] . The principle is mainly that estrogen 
promotes endometrial proliferation and repair, which loosens the remnants from the 

basal layer, while progesterone can cause stroma atrophy, promote the formation of 
cervical mucus plug , and reduce intrauterine infection. When using sequential 
estrogen-progesterone therapy to treat retained products of conception, withdrawal 
bleeding occurs after drug discontinuation, which promotes the expulsion of 
intrauterine remnants. Qin Huandi 's study [ 15] proposed that the success rate of 
estrogen-progesterone therapy decreases as the maximum diameter of the lesion 
increases. When the diameter of the remnant exceeds 2.5 cm, the success rate of drug 
treatment is less than 50%. 
With the development of medical technology, the surgical treatment of retained 
products of pregnancy has become more diversified. Traditional curettage is simple to 
operate and has a clear therapeutic effect. It can expel the retained products of 
pregnancy from the uterus in a short time and solve the symptoms of vaginal bleeding. 
Moreover, curettage has low requirements for surgical equipment, is easy to carry out, 
and is relatively inexpensive. Therefore, it is widely carried out in primary hospitals 
and is still the main treatment method. However, due to its blind nature, this treatment 
method is prone to incomplete curettage, requiring repeated curettage, or excessive 
curettage, which damages the basal layer of the endometrium, leading to intrauterine 
adhesions and subsequent abnormal implantation of the placenta. At present, 
hysteroscopic surgery is considered the preferred method for treating retained products 
of pregnancy [ 16] . It greatly reduces the blindness of intrauterine operation, reduces 
damage to the endometrium, and thus reduces the risk of intrauterine adhesions. 
Hysteroscopic electrosurgical resection of pregnancy has a short operation time 
and less intraoperative bleeding. Direct visualization during the operation can avoid 
extensive curettage of the endometrium and significantly reduce complications such as 
incomplete curettage. For patients with uterine malformations, it can avoid blind 
curettage that misses part of the uterine cavity and leads to incomplete curettage, and 
can also treat uterine malformations simultaneously under hysteroscopy. However, the 
electrosurgical ring brings thermal radiation damage during treatment, which can easily 
damage the surrounding endometrial tissue, increase the risk of intrauterine adhesions, 
and in severe cases, damage the basement membrane or even the deep myometrium, 
leading to abnormal placental implantation in subsequent pregnancies [1 7 ]. 
Hysteroscopic cold knife removal of pregnancy tissue has no electrothermal 
damage, which is beneficial to protect the endometrium and reduce the risk of 
intrauterine adhesions and infertility after curettage. It is increasingly widely 
recognized [ 18 ]. Literature [19 ] compared the treatment of intrauterine diseases with 
electrocautery system and cold knife system and found that the latter reduced the 
incidence of intrauterine adhesions by 90% after surgery and could effectively avoid 
damage to the surrounding endometrial tissue by electroradiation. At present, the 
application of giant cold knife instruments is becoming more and more widespread. For 
example, the 4mm (i.e. 12 Fr ) spoon forceps can directly remove residual tissue under 
vision, which has a great advantage over traditional micro forceps . The hysteroscopic 
shaving system uses a blunt head and side window operation to remove lesion 
fragments while removing lesions, avoiding repeated entry and exit from the uterine 
cavity. Its operation time is significantly shorter than that of the electrocautery group, 

and the incidence of serious complications such as uterine perforation and massive 
bleeding is significantly reduced. At the same time, it avoids electrothermal radiation 
damage and significantly reduces intrauterine adhesions. However, it is important to 
emphasize the correct use method when using it, especially to avoid damage caused by 
excessive cutting of the endometrium. 
In summary, hysteroscopic surgery is the most effective treatment for patients with 
large retained products of conception. However, due to the large size of the lesion, 
especially in cases of a large uterus, high serum HCG levels, and rich blood supply , 
the likelihood of needing repeat or even multiple curettage procedures increases, raising 
the risk of infection and endometrial damage. This not only increases costs but also 
leads to intrauterine adhesions and infertility. For these patients, appropriate drug 
treatment or expectant management followed by hysteroscopic surgery may be a wise 
choice and warrants further clinical research. Drug treatment and expectant 
management are also effective and safe under certain conditions for managing retained 
products of conception. Previous studies have shown that expectant management can 
allow some patients to expel the retained products of conception spontaneously, 
avoiding curettage; when curettage is performed 1-3 months after termination of 
pregnancy, serum HCG levels drop to low levels, reducing the difficulty of 
hysteroscopic surgery, intraoperative risks, and the likelihood of repeat surgery, as well 
as the incidence of postoperative intrauterine adhesions. Therefore, we propose the 
following scientific hypothesis: for patients with retained products of conception, in the 
absence of infection and active bleeding, expectant management should be maintained 
until the appropriate surgical time, thereby reducing the likelihood of repeat surgery 
and protecting the endometrium. To verify this scientific hypothesis, we designed a 
prospective, observational, multicenter, real-world study. The study subjects were 
patients with retained products of conception without bleeding or infection. Under the 
guidance of the physicians in the treatment group and with full informed consent, 
patients were selected according to their wishes to either the active surgery group 
(control group) or the expectant management group (study group). The diagnosis and 
treatment procedures were standardized, and detailed clinical data were collected to 
explore the optimal treatment strategy for retained products of conception, especially 
the best treatment plan for the protection of fertility. 
II. Research Objectives 
 This study aims to explore optimized treatment strategies for retained products 
of pregnancy in the uterine cavity. In the absence of infection and active bleeding, a 
prospective observational study with medication-assisted expectant management until 
the appropriate surgical time can reduce the number of curettage procedures and 
endometrial damage, decrease the incidence of intrauterine adhesions, and thus protect 
fertility compared to aggressive surgical treatment. 
III. Project Overview 
Leveraging the advantageous resources of the Hunan Provincial 
Medical Association's Hysteroscopy Group, the Hunan Provincial 

Alliance for the Prevention and Treatment of Major Obstetric and 
Gynecological Diseases (already approved), the Hunan Provincial 
Demonstration 
Base 
for 
Minimally 
Invasive 
Hysteroscopic 
and 
Laparoscopic Techniques, and the Hunan Provincial Quality Control 
Center for Gynecological Disease Diagnosis and Treatment, and under 
the guidance of the Gynecological Intelligent Diagnosis and Treatment 
Branch of the National Health Industry Enterprise Management 
Association, this multicenter prospective observational real- world 
study, led by the Third Xiangya Hospital of Central South University, 
selected 13 or more provincial and municipal hospitals willing to 
participate to explore the optimal surgical timing for retained 
products of conception. For patients meeting the inclusion and 
exclusion criteria, with the guidance of the treatment team physicians 
and full informed consent, patients were given the option of either 
active surgery or expectant management until a certain timeframe, with surgery 
performed only when necessary . Detailed clinical data (including follow-
up clinical data) were collected. This study did not intervene in the 
study subjects, nor did it add any additional examinations or tests to 
the patients. All procedures were conducted according to standard 
medical practice, with only the pre-designed treatment plan and data 
collection. After treatment, patients were divided into active surgery 
and expectant management groups based on their treatment plans, and 
data were statistically analyzed. Before the study began, standardized 
training was provided in diagnosis and treatment, especially in the 
standardization of ultrasound measurement of relevant indicators; 
expectant management, perioperative care , surgical record keeping, 
and 
postoperative 
follow-up 
all 
followed 
the 
corresponding 
standardized diagnosis and treatment protocols. 
IV. Research Design 
1. Research Subjects 
who were diagnosed with retained products of pregnancy by 
ultrasound at outpatient clinics of various research units between June 
2022 and June 2024, and who met the inclusion criteria but did not 
meet the exclusion criteria, were all enrolled consecutively. 
Inclusion criteria: age 18-45 years, clinical diagnosis of retained 
products of conception, and ultrasound showing a lesion with a maximum 
diameter ≥ 0.5 cm . 
Exclusion criteria: 1) Active bleeding requiring immediate 
surgical intervention; 2) Significant infection; 3) Severe organ 
dysfunction, including coagulation disorders. 
Note: Patients with cervical tissue impacted in the cervical canal 
who have undergone clamping treatment and do not meet the exclusion 

criteria can be included in this study; 
2. Grouping 
Because there is currently no unified treatment plan for retained products of 
pregnancy in uterus, the timing of active surgical evacuation versus expectant 
management until the planned surgery remains controversial, and the optimal timing 
for surgical evacuation is not uniform. In clinical practice, physicians , based on fully 
informed consent, choose active surgical treatment or expectant management according 
to the patient's wishes, and perform surgery when necessary. This study does not 
interfere with patient treatment; it only designs and collects relevant data in advance. 
No additional examinations or tests are performed on patients during the study process, 
and all procedures are conducted according to standard clinical practice. After treatment, 
patients are divided into an active surgical group and an expectant management group 
based on their chosen treatment plan, and data are statistically analyzed. 
3. Sample size and allocation 
The sample size was determined based on the incidence of 
intrauterine adhesions, the primary outcome measure. According to 
previous research results, the intrauterine adhesion rate in the 
expected group was 5.38% , and the intrauterine adhesion rate in the 
patients undergoing active surgery was 14.29% . The Type I error was 
0.05, the power was 90%, and the sample size was calculated using PASS 
to obtain a total of 460 cases. Based on a 20% follow-up dropout rate, 
the sample size was calculated to be 576 cases. It is expected that 
600 cases will be included, with 120 cases from the lead institution 
and an average of 40 cases from the other 12 research institutions. 
4. Research Process 
4.1 Pre-hospitalization treatment 
4.1.1 Active surgery group: Patients were admitted directly after enrollment and 
were scheduled to undergo hysteroscopic removal of pregnancy tissue. 
4.1.2 Expectant Treatment Group 
1) In the outpatient clinic, complete routine examinations of vaginal secretions, 
blood β-HCG, complete blood count, CRP, procalcitonin (optional), chlamydia and 
gonococcus, and other infection indicators. If the 4D color ultrasound indicates placenta 
accreta or retained products of conception in special locations such as the uterine horn 
or cesarean section incision site ( CSP) , and if necessary (especially when CSP or 
interstitial retained products of conception cannot be ruled out), complete a pelvic MRI 
plain scan with contrast. At the same time, complete liver and kidney function tests and 
coagulation function tests . 
2) For patients without contraindications , administer 2mg of Progynova twice 
daily (or a similar dose of Estradiol) until postoperatively (generally, continue using 
Progynova for 2-4 weeks postoperatively with progesterone withdrawal bleeding); then 

discontinue oral administration of Leonurus japonicus granules or Acanthopanax 
senticosus capsules for 2 weeks. 
4D color Doppler ultrasound of the uterus and adnexa every 2-3 weeks ; until the 
predetermined surgical timing is reached : 1) Blood β-HCG <50mmol / L; 2) 
Ultrasound measurement of the length from the internal cervical os to the fundus ≤
6cm; 3) At least 4 weeks between the previous surgery; 4) Color Doppler ultrasound 
showing blood flow grade 1-3 at the pregnancy tissue and attachment site . This 
predetermined surgical timing is proposed based on our hospital's summary of previous 
patient data and literature analysis. Research hospitals can adjust the surgical timing 
parameters according to clinical experience. Patients who reach the predetermined 
surgical timing will be hospitalized, undergo relevant examinations, and undergo 
hysteroscopic removal of the pregnancy tissue (hysteroscopic surgery using a large cold 
knife instrument is recommended ; refer to the surgical video). 
4) If massive bleeding (more than twice the amount of menstrual flow) occurs 
during the expected treatment, emergency hospitalization should be performed, and a 
detailed record should be kept (including the bleeding situation, whether interventional 
treatment was performed, and the surgical curettage). If infection occurs during the 
expected treatment, emergency hospitalization should be performed, and after 
aggressive anti-infection treatment, a curettage procedure should be performed as 
appropriate (generally, curettage should not be performed), and a detailed record should 
be kept (including the infection situation and the surgical curettage). Both of the above 
situations should be reported as adverse events. 
If, during the waiting period, the pregnancy tissue is expelled and the remaining 
tissue is less than 0.5 cm in diameter, an artificial cycle will be performed. After the 
next menstrual period, a follow-up ultrasound and HCG test will be conducted to 
determine whether further surgery is needed. 
The expectant treatment group can be hospitalized at any time if the patient's 
condition is relatively complex or the risk of bleeding and infection is high, after the 
patient gives informed consent, based on the physician's assessment. 
4.2 Perioperative management after hospitalization 
4.2.1 Preoperative management: After admission, complete the following 
examinations: routine blood tests, liver and kidney function tests, electrolyte tests, 
coagulation function tests, thyroid function tests, CRP tests, procalcitonin (optional), 
serum β-HCG, anti-Müllerian hormone tests, pre-transfusion examinations, routine 
vaginal discharge tests, HPV/TCT tests, electrocardiogram, chest X-ray, and 3D color 
Doppler ultrasound of the uterus and bilateral adnexa. Patients must fast and abstain 
from drinking after midnight the night before surgery and sign a consent form. 
routine vaginal discharge tests, HPV /TCT tests, and 3D color Doppler ultrasound 
have already been completed at the outpatient clinic and meet the requirements, there 
is no need to repeat these tests during hospitalization. 
4.2.2 Surgical Procedure: Generally, intravenous general anesthesia is used 

(with possible laryngeal mask airway support). (In special cases, local anesthesia, 
epidural anesthesia, or endotracheal intubation anesthesia may be chosen) . The patient 
is placed in the lithotomy position. If the anesthesia is satisfactory, normal saline is used 
for distension, and the distension pressure is maintained at 100-120 mmHg. It is 
recommended to use a diagnostic and therapeutic endoscope with an outer diameter < 
5 mm ( the specific type of endoscope and instruments used should be recorded) 
inserted through the cervix into the uterine cavity to determine the intrauterine 
condition: location and size of residual tissue, relationship to the uterine wall, whether 
the fallopian tube openings are visible, presence of adhesions in the uterine cavity, 
endometrial condition, etc. Then, the uterine depth is determined . (Under ultrasound 
monitoring) The cervix is dilated sequentially with dilators to size 8-10 (depending on 
the outer diameter of the hysteroscope used; hysteroscopic electrocautery is not 
recommended). Depending on the size of the pregnancy tissue , a 7mm outer diameter 
hysteroscope with 3mm diameter instruments is selected ( for pregnancy tissue with a 
maximum diameter less than 10mm) or approximately 9mm outer diameter instruments 
with 4mm diameter instruments. The hysteroscope is then re-entered into the uterine 
cavity. It is recommended to use double-jointed spoon-shaped forceps under direct 
vision to remove any remaining tissue (refer to the demonstration surgery video for 
specific techniques). Suction and curettage methods should be avoided ; ultrasound-
guided clamping with ovum forceps may be used appropriately. If a uterine septum or 
intrauterine adhesions are found during the procedure, they will not be addressed 
simultaneously if they do not affect the treatment of the remaining pregnancy tissue. 
For patients with pre-existing intrauterine adhesions, the location and nature of the 
adhesions should be described and recorded in detail during the procedure. The surgery 
should be performed by a physician with extensive experience in hysteroscopic 
procedures, with ultrasound or, if necessary, laparoscopic monitoring during the 
procedure to prevent uterine perforation. For patients with large surgical wounds, poor 
uterine contraction, and significant bleeding, slow intravenous infusion of oxytocin 
( 100ml NS + 20U ) or bimanual uterine massage can be used to promote uterine 
contraction and achieve hemostasis. If uncontrollable bleeding occurs, uterine artery 
embolization or even hysterectomy should be considered for hemostasis. If uterine 
perforation occurs during surgery, the operation should be terminated and the patient 
closely monitored; laparotomy or laparoscopic repair may be necessary. If a long 
operation is anticipated, a small dose of diuretic can be administered in advance and 
recorded. During surgery, endometrial damage should be minimized, and the distension 
pressure should be adjusted to the lowest possible level to reduce the absorption of 
distension fluid . The intake and output of distension fluid (a water intoxication 
detection instrument is preferable; refer to instruments developed by Hunan Comeson 
Company) and urine output should be recorded. Vital signs and blood oxygen saturation 
should be monitored, and blood gas analysis should be performed if necessary to 
prevent acute left heart failure . 
All surgeons are gynecologists with extensive experience in hysteroscopic surgery 
who have received standardized training . The following key points should be 
recorded during the procedure: uterine depth; location and size of the pregnancy 

tissue; operative time (from the start of uterine distension and insertion of the endoscope 
to its withdrawal ); intraoperative blood loss (a routine blood test is recommended on 
the first postoperative day) ; whether there is any retained pregnancy tissue after the 
procedure; clarity of the surgical field; volume of distension fluid intake and output; 
whether there is a decrease in blood oxygen saturation; and whether complications such 
as uterine perforation, acute left heart failure, or gas embolism occur. 
Note: 1) Hysteroscopic resection with a cold knife is recommended for removal of 
the pregnancy tissue. For surgical techniques, please refer to the surgical video. Link: 
https://pan.baidu.com/s/1F4RE6_g-gNtXsrhTs2B2UQ?pwd=1234 
Extraction code: 1234.
 
Research institutions may choose ultrasound-guided curettage, micro-cold knife 
technique , intrauterine tissue excision system , or electrosurgical resection, depending 
on their own conditions, and should record the surgical method and instruments used. 
2) If the surgical field is obstructed due to massive bleeding or other reasons, it is 
not essential to remove the pregnancy tissue. The primary goal is to ensure surgical 
safety and protect the endometrium. The procedure can be performed in stages. 
4.2.3 Postoperative management 
Prevention of intrauterine adhesions: 1) Inject sodium hyaluronate gel 
(Gongankang or Yishukang ) into the uterine cavity according to the uterine depth ( 2-
3 ml for a uterine depth of 7 or 8 cm , 5 ml for a uterine depth of 10 cm). 2) If necessary, 
leave the uterine balloon in place for 48-72 hours and remove it. If there are adhesions 
in the lower segment of the uterine cavity, part of the internal cervical os, or complete 
adhesions, handle them according to the intraoperative situation; adjust the amount of 
water injected into the balloon according to the uterine depth ( 3 ml for a uterine depth 
of 7-8 cm, 3.5 ml for a uterine depth of 9 cm, and 4 ml for a uterine depth of 10 cm) . 
3) If there are no contraindications, administer 2 mg BID of estradiol valerate (or an 
equivalent dose of estradiol) orally for 21-28 days postoperatively. ( For patients with 
serum β-HCG levels not typically associated with pregnancy, oral administration until 
21 days post-surgery; for patients with β-HCG levels above 100 mmol /L, oral 
administration until 28 days post-surgery). For the following 6 days, add progesterone 
(or dydrogesterone) 200 mg orally before bedtime. Continue for a total of two menstrual 
cycles. Adjustments may be made based on the condition of patients with other 
intrauterine diseases. 

Treatment to promote uterine contraction: routine intravenous administration 
of uterine contraction agents ( ostomycin is routinely used, and ergonovine may be used 
if necessary ) for 48 hours after surgery ; oral administration of uterine contraction-
promoting drugs (such as Acanthopanax senticosus capsules, etc.) for 2 weeks. 
Infection prevention: If there are signs of infection or high-risk factors for 
infection, antibiotics may be used as appropriate, and the type of antibiotic, route of 
administration, dosage, frequency and duration of administration should be recorded 
accurately. 
Pathological examination: The pregnancy tissue removed during the operation is 
routinely sent for pathological examination. If endometritis is suspected, endometrial 
tissue can be sent for immunohistochemical examination of CD138 . CNVs can be 
performed if genetic testing is required . 
Postoperative follow-up indicators: β-HCG on the 3rd day after surgery (once 
a week thereafter until normal), complete blood count (days 1 and 3), CRP, 
procalcitonin (not mandatory); if necessary, transvaginal ultrasound on the 2nd-3rd day 
after surgery. A 4D ultrasound is performed on days 16-24 of the third menstrual period 
after surgery to assess the uterine cavity and blood flow (report templates are available, 
mainly assessing damage to the endometrium). 
Management of retained products of conception after surgery: If ultrasound 
shows that the diameter of the retained products of conception is less than 0.5 cm, an 
artificial cycle is given, and a follow-up color Doppler ultrasound and β-HCG test are 
performed after the next menstrual period to determine whether further surgery is 
needed; if ultrasound shows that the diameter of the retained products of conception is 
greater than 0.5 cm, the patient is put back into the expectant management process and 
managed as an outpatient. 
4.3 Data collection process 
4.3.1 Outpatient data collection: The patient's first outpatient visit data and 
each outpatient follow-up visit data include main symptoms, blood β -HCG, 
ultrasound and infection-related indicators. 
4.3.2 Data collection for inpatient surgery includes: preoperative 
symptoms; serum β-HCG, ultrasound and infection-related indicators; surgical data; 
and postoperative medication. 
4.3.3 Follow-up after surgical treatment: 
(1) If the ultrasound examination 3 days after the operation shows no pregnancy 
residue or the diameter of the residue is less than 0.5cm, follow up by phone or WeChat 
1 month later to ensure that the patient's menstruation is over and to have a follow-up 
examination of β-HCG, ultrasound and other indicators at the outpatient clinic to 
determine whether the treatment has ended. 
(2) If the ultrasound examination on the 3rd day after surgery shows that the 

diameter of the retained pregnancy tissue is greater than 0.5cm, follow up by phone or 
WeChat half a month later to ensure that the patient goes to the outpatient clinic on 
schedule for β -HCG, ultrasound and infection indicators, and to determine the 
subsequent treatment plan. 
4.3.4 Data collection after treatment: Menstrual flow, ultrasound findings of 
intrauterine adhesions, and endometrial thickness were collected during outpatient 
follow-up examinations three times after the end of treatment. 
4.3.5 Data collection on reproductive outcomes: For patients who wish to 
have children, follow-up by telephone will continue every 3 months . If the patient has 
not become pregnant after 1 year of follow-up, the follow-up will be terminated. If the 
patient becomes pregnant within 1 year, follow-up will continue until the pregnancy is 
terminated, including whether there is spontaneous abortion, premature birth, full-term 
birth, stillbirth, or stillbirth. 
5. Data Collection 
5.1 General information: age, parity, number of previous intrauterine procedures, 
history of intrauterine adhesions, occupation, and education level. 
5.2 Preoperative data on retained products of pregnancy: gestational age 
at termination; time of termination; serum β -HCG; imaging data (including 
ultrasound and MRI: uterine size, distance from the internal cervical os to the fundus , 
location of the retained products of pregnancy, maximum diameter, blood flow, 
presence of arteriovenous fistula (blood flow grade 1-6 in the retained products of 
pregnancy and surrounding uterine wall on color Doppler ultrasound ) , presence of 
placenta accreta, presence of intrauterine adhesions, uterine septum , uterine fibroids, 
adenomyosis. For the expectant management group, complete blood count, serum β-
HCG, CRP, and ultrasound data from each follow-up examination should be collected. 
5.3 Preoperative routine examination data : routine vaginal discharge test, 
HPV/TCT, complete blood count, liver and kidney function tests, electrolytes, 
coagulation function tests, thyroid function tests, serum β-HCG, anti-Müllerian 
hormone test, pre-transfusion examination, electrocardiogram, chest X-ray, 3D color 
Doppler ultrasound of the uterus and bilateral adnexa, and other relevant examinations. 
If a 3D ultrasound has been completed within one week in the outpatient clinic , it does 
not need to be repeated during hospitalization. 
5.4 Surgical data: Date of surgery; depth of uterus; location and size of the 
gestational sac; operation time (from the start of the distension procedure to the 
withdrawal of the endoscope ); amount of intraoperative blood loss ; whether there is 
any retained gestational sac after surgery; clarity of the surgical field; volume of 
distension fluid in and out; whether there is a decrease in blood oxygen saturation; 

whether complications such as uterine perforation, acute left heart failure, or gas 
embolism occur. 
5.5 Postoperative follow-up data: serum β-HCG, complete blood count, CRP, 
procalcitonin (not required), ultrasound to check for retained products of conception, 
and if so, record the maximum diameter of the retained products. 
5.6 Three months after treatment , outpatient follow-up data will be 
collected, including menstrual flow, ultrasound findings of intrauterine adhesions, 
endometrial condition, whether intrauterine adhesion surgery was performed, and 
intrauterine adhesion score. 
5.7  Pregnancy outcome data collection: pregnancy rate after 1 year of 
trying to conceive ; miscarriage rate, premature birth rate, full-term birth rate, stillbirth 
rate, and stillbirth rate in subsequent pregnancies. 
6. Efficacy evaluation 
6.1 Main observation indicator: Incidence of intrauterine adhesions. 
6.2 Secondary observation indicators: reoperation clearance rate; 
incidence of active bleeding and infection during expectant treatment in 
the expectant treatment group; pregnancy rate, live birth rate, and 
miscarriage rate one year after treatment. 
7. Safety Assessment 
7.1 Safety indicators: the expected probability of active bleeding and infection 
during treatment. 
7.2 Reporting and follow-up of adverse events and 
serious adverse events 
Possible adverse events: active bleeding; infection; the following are considered 
serious adverse events: massive bleeding requiring emergency interventional treatment; 
severe infection with systemic toxicity symptoms or pelvic abscess are considered 
serious adverse events.  
Any adverse events or serious adverse events that occur during the research 
process must be reported to the responsible unit and other collaborating research units 
within 3 days, along with an analysis of the causes. 

8. Statistical Analysis: SPSS 26.0 software was used to process the data . 
Normally distributed measurement data were expressed as ( χ²±s ), and t-tests were used 
for comparisons between two groups; analysis of variance was used for comparisons 
among multiple groups. Non-normally distributed measurement data were expressed as 
the median, and a nonparametric rank-sum test was used. Count data were expressed as 
χ². The chi-square test or Fisher 's test was used. P < 0.05 was considered statistically 
significant. 
9. Clinical Research Management 
9.1 Ethical Issues 
The research protocol was initiated by clinicians and did not involve any economic 
interests. The implementation of the research protocol was first approved by the ethics 
committee of the lead institution and then filed with the ethics committees of each 
research institution before implementation. 
All research participants must provide fully informed consent and sign a 
participant informed consent form. 
Patient information and data are used solely for scientific research, and patient 
privacy is strictly protected. 
9.2 Bias Control 
The clinical research process strictly follows standard operating procedures, 
clearly defining pre-clinical research training, quality control, and other aspects. 
All research institutions conducted their studies concurrently, implementing a 
unified clinical research protocol. 
     Before a clinical study begins, training should be provided on the clinical 
study protocol and standard operating procedures, especially on ultrasound report 
content, perioperative management , surgical procedure specifications, and surgical 
records. 
The clinical research process includes monitoring and accountability procedures. 
By controlling bias through the above process, research error can be reduced. 
9.3 Pre-clinical training: Before a clinical trial, standard operating procedures 
should be developed in accordance with the clinical trial protocol, and all researchers 
participating in the trial should be trained on the clinical trial protocol, standard 
operating procedures, etc., to ensure consistency in all procedures during the trial; 
training should also be provided on ultrasound reporting standards, surgical operation 
standards, etc.; and training plans and records should be kept. 
9.4 Research Quality Control: All researchers participating in the clinical trial 
should complete training on the clinical trial protocol, standard operating procedures, 
and other relevant documents, and strictly adhere to the provisions of these documents 
during the trial. Training should also be provided on ultrasound reporting standards and 

surgical procedure standards. The lead institution will assign qualified monitors to 
conduct on-site monitoring visits to the clinical trial facility at different stages of the 
clinical trial to ensure that the clinical trial is conducted in accordance with relevant 
laws and regulations, the clinical trial protocol, and standard operating procedures. 
9.5 Data Management : Case report forms should be completed in accordance 
with the relevant requirements of the Good Clinical Practice (GCP) guidelines for 
clinical trials . Clinical trial data should be accurately, completely, clearly, and promptly 
entered into the case report forms. The case report forms must be signed by the 
investigator. All items on the case report forms must be completed; if an item is not 
applicable, write NA (Not Applicable). Original clinical trial records should not be 
arbitrarily modified. If modifications are necessary, the original record should be 
crossed out with a horizontal line, ensuring it remains clearly legible. The correct 
information should be noted in the adjacent blank space, and the person making the 
modification should sign and indicate the date of the modification. If necessary, the 
reason for the modification should also be noted. All trial data in clinical trials must be 
signed by the clinical trial operator and reviewer, and stamped by the clinical trial 
institution (both on the cover and across the binding). 
10. Other 
10.1 Responsibilities of Each Party (Intellectual Property) 
Responsibilities of the Sponsor: The sponsor is responsible for initiating, applying 
for, organizing, and monitoring clinical trials, and is accountable for the authenticity 
and reliability of the clinical trials. Before the clinical study, a suitable clinical trial 
institution should be selected. A clinical trial protocol, investigator's brochure, informed 
consent form, case report form, standard operating procedures, and other relevant 
documents should be developed. Relevant documents should be submitted to the 
clinical trial institution and ethics committee as required for their decision on whether 
to undertake the clinical trial. A clinical trial agreement should be signed with the 
clinical trial institution, reaching a written consensus on relevant specific content. The 
sponsor should organize researchers to discuss and finalize the clinical trial protocol, 
case report form, standard operating procedures, and other documents. 
Responsibilities of Collaborating Units and Personnel: Collaborators should 
possess the capability to design and implement relevant clinical research and be familiar 
with relevant diagnostic and treatment techniques. They should have appropriate 
preventative and emergency response methods for potential risks during the clinical 
research process. They should work with the sponsor to develop a scientifically sound 
clinical trial protocol and strictly adhere to it during the clinical trial. They should 
ensure that all personnel involved in the research fully understand the clinical research 
protocol, relevant regulations, and their responsibilities in the clinical trial. They should 
ensure a sufficient number of subjects who meet the corresponding sample selection 
criteria in the clinical trial protocol are enrolled in the study. They should ensure that 
the clinical trial is completed within the agreed-upon trial period and in accordance with 

relevant regulations. They should record and promptly report all adverse events 
occurring during the clinical research process and analyze the causes together with the 
sponsor. They may propose continuing, suspending, or terminating the trial as 
appropriate. Researchers should ensure that clinical data is accurately, completely, 
clearly, and promptly entered into the case report form. They must ensure that all data, 
documents, and records generated from the clinical trial are authentic, accurate, clear, 
and secure. As needed, after providing relevant training, relevant personnel may be 
authorized to undertake related work in the clinical trial. 
10.2 Intellectual Property: The responsible organization owns the intellectual 
property rights and ownership of the results of this clinical trial and has the right to use 
the data generated from the trial for research and regulatory submissions worldwide. 
All research findings must obtain the sponsor's prior written consent before public 
release. All publications must be submitted to the sponsor for review and approval 
before final publication. 
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