Silent Miscarriage
Conditions
Keywords
silent miscarriage, mifepristone, misoprostol, letrozole
Brief summary
Management of first trimester silent miscarriage can be by expectant, medical or surgical management. Surgical management by suction evacuation is associated with surgical risks (including risks to the womb that can affect further pregnancy), anaesthetic risks and hospital stay. Medical management of first trimester silent miscarriage using misoprostol is another common option that can reduce the risk of bleeding and those associated with surgery. However, the current standard management of using misoprostol for the management of first trimester miscarriage only has a success rate of 70-80%, which is suboptimal. Recent large studies have shown that adding mifepristone pre-treatment before misoprostol in the management of silent miscarriage can improve the success rates of complete miscarriage after medical management. There are 2 problems with mifepristone. Firstly, it is not widely available in many countries for cultural and religious reasons because it is labelled as an 'abortifacient'. Secondly, it is expensive. One tablet of Mifepristone costs $500 HK dollars. There is a need to look for an alternative to mifepristone. Letrozole is an aromatase inhibitor which can reduce estrogen levels. Some studies have shown that it can improve the success rate of medical management of silent miscarriage and termination of pregnancy. It is safe, more widely available and cheaper than mifepristone. This is a randomized double blinded trial comparing the use of mifepristone versus letrozole as pre-treatment in the medical management of first trimester silent miscarriage using misoprostol.
Detailed description
This is a randomized double blinded trial comparing the use of mifepristone versus letrozole as pre-treatment in the medical management of first trimester silent miscarriage using misoprostol. Both groups will receive misoprostol (which is the standard management for medical management of silent miscarriage locally), but they will be randomized to either adding mifepristone or letrozole as pre-treatment. Mifepristone is usually taken once 2 days before misoprostol, whereas letrozole is taken 10mg daily for 3 days before misoprostol. Placebo of letrozole and mifepristone will be given to maintain double blindness of the groups.
Interventions
DRUGLetrozole
Letrozole pre-treatment in addition to misoprostol as medical management for silent miscarriage
DRUGMifepristone
Mifepristone pre-treatment in addition to misoprostol as medical management for silent miscarriage
Sponsors
Queen Mary Hospital, Hong Kong
Pamela Youde Nethersole Eastern Hospital
Kwong Wah Hospital
Princess Margaret Hospital, Canada
The University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with silent miscarriage \<= 12 weeks of gestation by ultrasonography * Single intrauterine gestational sac * No heavy per-vaginal bleeding * No severe abdominal pain * No features of intrauterine infection * Able to understand the proposed research and able to comply with instructions * Having given voluntary written informed consent
Exclusion criteria
* Known allergy to mifepristone, misoprostol or letrozole * On drugs with potential drug interactions with mifepristone e.g. aspirin, clopidogrel, anti-coagulants etc. * Suspected ectopic or molar pregnancy or multiple pregnancy * Distorted uterine cavity by uterine septum or submucosal fibroids * Presence of intrauterine contraceptive device * History of bleeding tendencies e.g. haemorrhagic diseases, current anti-coagulant treatment * Previous history of retained products of gestation/ failed medical management of miscarriage * Opt for expectant or surgical management of miscarriage
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gestational sac expulsion | 2 weeks, 30 days | Gestational sac expulsion by the first follow up visit after 2 weeks of misoprostol administration and no additional surgical or medical intervention within 30 days after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Return of normal menses | 6 weeks | Return of normal menses without additional intervention |
| Requirement of repeated intervention | 6 weeks | Requirement of repeated intervention including repeated course of medical treatment or surgery |
| Unplanned re-admission | 6 weeks | Number of unplanned re-admission |
| Analgesics | 6 weeks | Use of analgesics |
| Time of tissue expulsion | 6 weeks | Time of tissue expulsion |
| Vaginal bleeding | 6 weeks | Duration and amount of vaginal bleeding |
| Complications | 6 weeks | Including severe vaginal bleeding requiring transfusion, infection |
| Return of menstruation | 6 weeks | Timing of return of menses |
| Women's satisfaction | 6 weeks | Client satisfaction questionnaire |
| Side effects | 6 weeks | Vomiting |
Contacts
Primary ContactJennifer Ko
Outcome results
None listed