The HYsteroscopic Miscarriage MaNagement Trial: A Pilot RCT Investigating a Novel Management Pathway for RPOC
Condition: Retained Products After Miscarriage
MeSH terms: Abortion, Spontaneous; Abortion, Incomplete
Study type: Interventional

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'.
    

Intervention name(s): Outpatient hysteroscopy; Expectant management; Medical management; Antibiotic; Surgical management
Intervention type(s): Procedure; Behavioral; Drug; Drug; Procedure
Intervention description(s): Direct visualisation and careful extraction of retained pregnancy tissue using a specific hysteroscopic technology known as a hysteroscopic tissue retrieval system.; Leaving the retained pregnancy tissue alone to pass by itself; Giving medications to contract the womb to pass the retained pregnancy tissue; Giving antibiotics to reduce any inflammation/infection caused by the retained pregnancy tissue allowing it to pass by itself; Passing a small cannula/catheter/currette into the womb and mechanically scraping the womb lining to remove the retained pregnancy tissue
Other intervention name(s): misoprostol; mifepristone; Augmentin; Co-amoxiclav; Metronidazole; Clindamycin; manual vacuum aspiration; suction evacuation of the uterus; dilatation and currettage
Intervention MeSH terms: Anti-Bacterial Agents; Metronidazole; Clindamycin; Amoxicillin-Potassium Clavulanate Combination; Misoprostol; Mifepristone
Allocation: Randomized
Intervention model: Parallel Assignment
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.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ultrasound; hysteroscopy; miscarriage; retained products of conception