Comparing a 'wait and watch' approach vs medical treatment with misoprostol for first trimester retained products of pregnancy and using ultrasound to predict success
Comparison of misoprostol and conservative approach for managing first trimester retained products of conception and use of ultrasound to predict success– an open labelled randomized controlled trial
Nepean hospital
80 participants
Feb 6, 2025
Interventional
Conditions
Summary
Study hypothesis - This study hypothesizes that non surgical management of first trimester retained products of conception has a high success rate and various ultrasound parameters can help in more accurate treatment selection with either expectant or medical management. Brief summary Retained products of conception ( RPOC) is a common occurrence after first trimester expectantly, medically or surgically managed miscarriage or termination of pregnancy. However, there is lack of evidence on the most ideal way to manage these patients, Surgical management has been the fall-back due to immediate results but comes with a high rate of complications such as intra-uterine adhesions which can lead to sub-fertility. On the other hand, non-surgical methods, not known to cause such complications, have shown promise but lack robust evidence. Hence, the purpose of our study is to determine the efficacy of non-surgical options in successfully managing RPOC. Participants aged 16-45 years presenting to the early pregnancy assessment unit and Emergency department (ED) with symptoms and ultrasound diagnosis of retained products of conception in first trimester of pregnancy will be consented, recruited and randomized to either expectant management or medical management with misoprostol. They will be followed up at 4 and 8 weeks for symptom review and progress ultrasounds to note successful management of RPOC. Success rates, ultrasound factors influencing success, short- and long-term complications will be noted.
Eligibility
Inclusion Criteria15
- Transvaginal ultrasound scan showing the presence of a measurable focus of hyperechoic material within the endometrial cavity WITH any of the following will be considered for recruitment:
- Symptomatic patients with moderate bleeding and/or pain presenting after 48 hours of antecedent events a-e:
- a. Spontaneous miscarriage
- b. Primary medical management of miscarriage - as per Mifemiso trial
- c. Primary surgical D&C for miscarriage
- d. Medical termination of pregnancy - MS-2 step ( name of product)
- e. Surgical termination of pregnancy
- Persistent spotting or light bleeding beyond 3 weeks from antecedent event
- Positive urine B-HCG ( beta- human chorionic gonadotrophin) beyond 3 weeks from antecedent event
- Amenorrhea beyond 6 weeks from antecedent event
- There are no published grading systems for quantifying per vaginal blood loss during a miscarriage or termination and hence, for allowing for objective interpretation of symptomology, we have adopted a modified version of the pictographic scale by Higham et al. The frequency of pad use is based on experience.
- a. Only red/brown spotting per vaginum
- b. Light bleeding – changed every 4 hours or more
- c. Moderate bleeding – changed every 4 hours or more
- d. Heavy bleeding with clots (fully soaked pad)- change every 4 hours or less
Exclusion Criteria9
- Women who choose surgical management for proven retained products of conception (RPOC) on transvaginal ultrasound ( TVS)
- Allergies/ contraindications to the use of misoprostol
- Complete miscarriage on TVS or findings of uniform homogenous endometrium, with absence of vascularity and no measurable focus of hyperechoic material within the endometrial cavity or endocervical canal
- TVS showing only presence of avascular blood clot and absence of trophoblastic tissue irrespective of symptoms – given the difficulty in distinguishing between avascular blood clot and avascular trophoblastic tissue, recruiters will take a 2nd opinion from fellow recruiters prior to inclusion/exclusion
- Extrauterine pregnancy/ pregnancy of unknown location (PUL )
- Intact gestational sac on ultrasound ( which suggests failed miscarriage and would require primary management)
- Hemodynamic instability (severe vaginal haemorrhage) requiring immediate surgical intervention; Heavy bleeding with clots ( as defined by Higham et al) will also be excluded given the potential to lead to hemodynamic instability and will be considered for surgical management.
- Presence of infection / sepsis (Temperature > 38 degree Celsius, tachycardia, offensive vaginal discharge)
- Patients unable to consent
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Interventions
Patients with first trimester symptomatic retained products of conception ( RPOC) and proven on transvaginal ultrasound after antecedent events of spontaneous miscarriage, primary medically managed miscarriage, primary dilatation and curettage(D&C) for miscarriage, medical termination of pregnancy and surgical termination of pregnancy with D&C will be randomized to either the control arm (expectant management, i.e., 'wait and watch') or the intervention arm ( medical management with misoprostol) in a 1:1 ratio. The randomization is stratified based on colour doppler scores of the retained tissue on transvaginal ultrasound; i.e., scores 1-4; 1- no vascularity, 2- minimal vascularity, 3- moderate vascularity, 4 - strong vascularity. Intervention arm- Medical management (Group M) – With this method, patients will be advised to self-administer misoprostol 800 mcg (4 tablets of 200 mcg) buccally (2 tablets kept in each cheek until dissolved, not to swallow) as a once only administration. To manage side effects, they will also be prescribed regular oral pantoprazole 40 mg once daily and 4 mg ondansetron wafers three times daily or as needed, oral ibuprofen 400 mg three times daily after meals or as needed, oral paracetamol 1000 mg upto 4 times daily or as needed, and oral panadeine forte 500/30 (2 tabs) upto 4 times daily or as needed for 24 hours. Patients will be counselled about side effects like nausea, vomiting, diarrhoea and strong uterine cramping and will be advised to keep a symptom diary of their side effects. All patients will be advised about alert symptoms that should prompt a presentation to the nearest Emergency department including fever, foul-smelling discharge and heavy bleeding with clots with frequency of changing 1 full soaked pad every hour or less for over 4 hours. Patients from both control and intervention arms will be followed up at 4 weeks ( Interim visit) and 8 weeks ( final visit) with a repeat transvaginal ultrasound at each visit to look for persistent retained products. At either visit, ultrasound findings of an empty uterus with absence of retained products defined as homogenous endometrium with absent vascularity with no measurable focus of hyperechoic material suggesting trophoblastic tissue will be considered successful management. These patients will not require subsequent clinic follow up. The persistence of retained products at 4 weeks will prompt a further follow up at 8 weeks to draw final conclusions. If RPOC is present on transvaginal ultrasound at 8 weeks, non-surgical management is considered unsuccessful and the patient is advised surgical management via hysteroscopic resection or ultrasound guided dilatation and curettage within 1 week. This will be arranged in our centre. All participants will be consented at their baseline visit for a follow up phone call at 6 months to note long term sequelae of non surgical management of RPOC
Locations(1)
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ACTRN12624001463561