Clinical trial NCT04751500: The HYsteroscopic Miscarriage MaNagement Trial: A Pilot RCT Investigating a Novel Management Pathway for RPOC
Official title: The HYsteroscopic Miscarriage MaNagement (HYMMN) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Retained Products After Miscarriage
Keywords: ultrasound
hysteroscopy
miscarriage
retained products of conception
Lead sponsor: Birmingham Women's and Children's NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Tommy's
First posted: 2021-02-12
Enrollment: 149
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study involves two phases: 1) All recruited women will be scanned for RPOC at 8 weeks post-miscarriage diagnosis. 2) Women that have RPOC on this scan will then be randomised in a 1:1 manner to either outpatient hysteroscopy or standard treatment.
Primary purpose: TREATMENT

Brief summary: Pregnancy tissue can be found remaining in the womb in up to 20% of women following a miscarriage. These "retained products of conception" (RPOC), which are diagnosed by transvaginal ultrasound, can cause prolonged bleeding, pain, infection, impaired fertility and therefore further psychological distress. Ineffective medical and surgical interventions place considerable burden on affected women and utilise scarce health care resources. Additionally, surgery is performed 'blindly' using a suction tube or metal curette where risks include perforation of the womb and scarring of the womb lining, both of which lead to delayed fertility and in the worst circumstances, infertility.

There is no current guidance on how to best investigate and manage RPOC. New surgical equipment allows RPOC removal under vision, using a specially designed telescope placed inside the womb (hysteroscopy). This precise technique may more successfully and less traumatically remove RPOC, minimising ongoing bleeding, the risk of womb perforation and scar tissue formation, thereby reducing the risk of infertility.

The investigators propose a pilot randomised controlled trial using routine transvaginal ultrasound to diagnose RPOC in women who choose non-surgical management of a first-trimester (≤14 weeks) miscarriage. This scan will be done 8 weeks post-miscarriage diagnosis. Women who have RPOC on this scan will be randomised (in a 1:1 ratio) to receive outpatient hysteroscopy ('OPH') or 'standard treatment' (expectant, medical, surgical and/or antibiotic treatment).

Women who had RPOC will be followed-up at 14 weeks after randomisation to explore clinical outcomes (symptoms, quality of life) and use of additional healthcare resources (e.g. additional investigations / treatments / hospitalisations). All patients, no matter whether they were diagnosed with RPOC or not, will be followed up at 26 weeks and 52 weeks after randomisation/ultrasound scan to determine clinical pregnancy rates and pregnancy outcomes. All patients who have had a miscarriage or have not fallen pregnant since entering the trial will be offered a hysteroscopy to see if there are any conditions affecting the womb lining which may be contributing to pregnancy failure.

Detailed description: The diagnosis of retained products of conception (RPOC) following miscarriage causes physiological and emotional stress to women and their partners. Additional hospital visits, inpatient admissions and non-evidence-based treatments impose an additional burden on women and healthcare services. Ineffective medical and surgical treatments can prolong symptoms such as bleeding, pain and psychological distress which impacts adversely on quality of life. In addition, future fertility can be delayed or worse, permanently impaired, because of damage and scarring of the womb lining arising from chronic infection or mechanical trauma after conventional 'blind' mechanical evacuation of the uterine cavity.

Recent technological advances in hysteroscopy allow RPOC to be directly visualised and simultaneously removed with greater precision and less trauma to the endometrium with promising results. These 'hysteroscopic tissue removal systems' represent the latest advance in uterine surgery. This technology allows complete excision and removal of intrauterine pathology under direct vision, including removal of RPOC in the inpatient and more recently, the outpatient setting with complete resection and resolution of symptoms without apparent complications. Current evidence suggests that hysteroscopic resection of RPOC is associated with the formation of less intrauterine adhesions, lower rates of incomplete evacuation, and shorter time to subsequent conception, but is based on limited numbers of studies, too small sample sizes to statistically detect differences between treatments, poor reporting of confounders and the absence of randomised studies.

To date, there are no randomised controlled trials investigating the use of outpatient hysteroscopy in the management of RPOC against standard treatment. The investigators therefore aim to perform a pilot randomised control trial to assess the feasibility of undertaking a future substantive full-scale trial to compare routine transvaginal ultrasound scanning and outpatient hysteroscopy for the treatment of RPOC against current standard practice to see if it is more effective in improving fertility and minimising symptomatic morbidity. Furthermore, health service resource use will be evaluated against clinical outcomes to determine the cost-effectiveness of this new pathway.

All women who choose non-surgical management of a first trimester (≤14 weeks gestation) miscarriage will be eligible for recruitment into the study, where informed consent will be taken and baseline assessments will be conducted.

All patients who then have RPOC diagnosed on transvaginal ultrasound scan (TVS) at 8 weeks after the diagnosis of their miscarriage will then be randomised (in a 1:1 ratio) to receive outpatient hysteroscopy ('OPH') or 'standard treatment'. At 'OPH', if RPOC are present, then these will be removed on an intention-to-treat basis. If randomised to the 'standard treatment' arm, management will be based according to current practice (expectant, medical, antibiotic, surgical treatment). Immediately after OPH, all women will be asked to complete a questionnaire exploring the acceptability of the procedure and clinicians will be asked to complete a questionnaire exploring the efficacy of OPH in diagnosing and removing RPOC.

For those who had RPOC, regardless of which treatment they were randomised to, face-to-face consultations will be performed at 14 weeks post-randomisation. These will explore clinical outcomes (symptoms and generic quality of life) and use of additional healthcare resources (e.g. additional investigations / treatments / hospitalisations). All patients, no matter whether they were diagnosed with RPOC or not, will be followed up at 26 weeks and 52 weeks post-randomisation to determine clinical pregnancy rates and pregnancy outcomes. All patients who have had a miscarriage or have not fallen pregnant since entering the trial will be offered the chance to undergo a hysteroscopy to see if there is any scar tissue, chronic RPOC or other conditions affecting the womb lining which may be contributing to pregnancy failure; this data will be collected. At this point, patients will discharged from the trial.

The sample size of a future substantive study will partly be determined by the results of this study. This study will aim to recruit 200 women to give a better idea of the number of women with RPOC and the numbers willing to be recruited. After recruitment, the investigators will aim to scan 200 women over a six-month period. Predicated upon a sonographic RPOC rate of 20%, 40 women are expected to have RPOC; 20 women would be randomised to 'OPH' and 20 women to 'nOPH'.

Eligibility criteria: Inclusion Criteria:

* Women above 18 years
* Women choosing either expectant or medical management of a first-trimester miscarriage ≤14 weeks gestation
* Women wanting to conceive as soon as possible after their miscarriage
* Consent to trial processes: (1) undergo follow-up with transvaginal ultrasound for the investigation of RPOC; (2) be randomised to outpatient hysteroscopy for confirmation and treatment or standard management; (3) accept trial follow up procedures - questionnaires, telephone interviews

Exclusion Criteria:

* Women below 18 years
* Women with findings suspicious of gestational trophoblastic disease
* Women with fever (≥38°C) or sepsis secondary to genital tract infection/endometritis
* Women who are unable to understand spoken and written English

Primary outcomes:
measure: Number of eligible patients
timeFrame: During recruitment - 6 months
measure: Proportion of patients enrolled into the trial
timeFrame: During recruitment - 6 months
measure: Proportion of patients attending scan
timeFrame: At ultrasound scan 8 weeks post-miscarriage diagnosis
measure: Proportion of patients attending outpatient hysteroscopy (if randomised to this treatment)
timeFrame: During outpatient hysteroscopy (if randomised to this treatment)
measure: Proportion of patients attending 14-week follow-up
timeFrame: 14-week follow up
measure: Proportion of patients attending 26-week follow-up
timeFrame: 26-week follow up
measure: Proportion of patients attending 52-week follow-up
timeFrame: 52-week follow up
measure: Acceptability of trial to eligible women
timeFrame: Up to 8 months
measure: Acceptability of ultrasound scan to patients
timeFrame: At ultrasound scan 8 weeks post-miscarriage diagnosis
measure: Acceptability of outpatient hysteroscopy to patients
timeFrame: During outpatient hysteroscopy (if randomised to this treatment)
measure: Robustness of data collection tools
timeFrame: From recruitment of first patient to end of trial (up to 20 months)
Secondary outcomes:
measure: Clinical pregnancy rates
timeFrame: Assessed at 26 and 52 weeks post-randomisation/ultrasound scan
measure: Time to next pregnancy
timeFrame: Assessed at 26 and 52 weeks post-randomisation/ultrasound scan
measure: Symptoms
timeFrame: 14 weeks post-randomisation/ultrasound scan
measure: Impact on quality of life
timeFrame: 14 weeks post-randomisation/ultrasound scan
measure: Impact on work
timeFrame: 14 weeks post-randomisation/ultrasound scan
measure: Healthcare resource use
timeFrame: 14 weeks post-randomisation/ultrasound scan
measure: Patient satisfaction
timeFrame: 14 weeks post-randomisation/ultrasound scan
measure: Procedural findings at ultrasound
timeFrame: During ultrasound scan 8 weeks post-miscarriage diagnosis
measure: Ease of diagnosis of retained products of conception (RPOC)
timeFrame: During ultrasound scan 8 weeks post-miscarriage diagnosis
measure: Procedural findings at outpatient hysteroscopy (in women randomised to this treatment)
timeFrame: During outpatient hysteroscopy (in women randomised to this treatment)
measure: Ease of removal of RPOC during outpatient hysteroscopy (in women randomised to this treatment)
timeFrame: During outpatient hysteroscopy (in women randomised to this treatment)
measure: Pain experienced by patients undergoing outpatient hysteroscopy (in women randomised to this treatment)
timeFrame: During outpatient hysteroscopy (in women randomised to this treatment)
measure: Proportion of women with adverse pregnancy outcomes at 52 weeks
timeFrame: 52 weeks post-randomisation/ultrasound scan
measure: Hysteroscopic findings in women with adverse pregnancy outcomes at 52 weeks
timeFrame: During outpatient hysteroscopy after 52 weeks post-randomisation/ultrasound scan
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Women's Hospital
Study officials:
affiliation: Birmingham Women's NHS Foundation Trust
name: T Justin Clark, FRCOG
role: PRINCIPAL_INVESTIGATOR
References: