Pipelle® Under Ultrasound Guidance (PUG) to Investigate Post-menopausal Bleeding: Randomised Controlled Trial.

BACKGROUND Uterine cancer is the most common gynaecological cancer in the United Kingdom with approximately 9,400 new cases diagnosed each year, over 95% arising from the endometrium. Almost all endometrial cancers are diagnosed after the menopause, with most being detected after a woman presents with bleeding. Any woman presenting to her general practitioner or accident and emergency department with post-menopausal bleeding in the United Kingdom should receive an urgent two week wait referral to rapid access gynaecology services. At this appointment women will typically undergo a transvaginal ultrasound scan to assess the gynaecological anatomy, in particular the endometrium. If the endometrium is deemed to be thickened, at more than 4 or 5mm depending on local guidance, sampling is required to rule out endometrial cancer or its precursor, endometrial hyperplasia.

There are two well established routes for obtaining an endometrial biopsy. These are 'blind' office endometrial sampling and hysteroscopy. If ultrasound has shown any focal pathology such as an endometrial polyp or a submucosal fibroid, then the patient must undergo hysteroscopy so this can be directly visualised and confidently removed. Whilst a highly effective procedure, its primary drawbacks are higher costs, a larger side-effect profile and potentially greater pain than the alternative, blind office endometrial sampling.

If a patient has a uniformly thickened endometrium without any suspicion of focal endometrial pathology they can undergo blind office sampling of the endometrium. This is performed with a variety of thin, specially designed plastic biopsy devices that obtain the sample via localised trauma and vacuum suction. This procedure is less invasive, quicker and simpler to perform than a hysteroscopy, however it has a higher failure rate with roughly 4 in 10 patient not having an adequate sample obtained. This is due to either the endometrial sampler not being successfully introduced into the endometrial cavity, or when successfully introduced, the sample obtained being inadequate for histopathological assessment. These patients are then committed to a hysteroscopy so their endometrium can be safely assessed.

PROPOSED STUDY It is theorised that by using ultrasound guidance, the failure rate of office endometrial biopsies could be reduced. We propose to test in an adequately sized randomised controlled trial, the hypothesis that Pipelle® (Pipelle de Cornier) endometrial biopsies, performed under transabdominal ultrasound guidance, will have a higher success rate than blind biopsies. Potential benefits to patients of positive findings in this study include a reduced number of investigations, reductions in pain and increases in patient satisfaction, and a reduction in time from presentation to definitive treatment.

STUDY DESIGN This will be a single centre, prospective, non-blinded randomised controlled trial carried out in the outpatient gynaecological oncology department at Queen Charlotte's and Chelsea Hospital, part of Imperial College Healthcare NHS Trust. The trial will be carried out by gynaecology doctors of registrar and consultant grade who are deemed competent in gynaecological ultrasound and endometrial sampling. Both the doctor and patient will be aware of the study arm allocated. The trial will aim to have the same number of participants in each arm. The study arms are: (i) Blind Endometrial Biopsy and (ii) Ultrasound Guided Endometrial Biopsy. 92 patients will be enrolled, with 46 in each arm.