Self-Administered Vaginal Misoprostol at Home for Cervical Ripening Prior to Outpatient Hysteroscopy: a Randomised Placebo-Controlled Trial.

In gynaecological practice, diagnostic and therapeutic hysteroscopy is one of the most common methods for diagnosing intrauterine pathology. The complications encountered during hysteroscopy, such as cervical tears, creation of false passages, and uterine perforation, are mainly related to the difficulty of cervical dilatation in nulliparous and postmenopausal patients. GnRH agonist use, previous cone biopsy, and markedly retroverted uterus are additional risk factors for complications.

Cervical ripening may be achieved either by mechanical means, such as with osmotic dilators, or biochemically with prostaglandins. Solid evidence supports the efficacy of misoprostol for cervical ripening before first-trimester suction curettage abortion. A consensus has emerged that the optimal treatment regimen to use is 400-μg misoprostol 3-4 hours pre-operatively, with vaginal administration being superior to the oral administration. However, two studies using 400-μg misoprostol via the oral and vaginal routes have previously shown that this does not result in satisfactory pre-operative dilatation in the majority of Norwegian women, and we have recommended that the minimum dosage be greater than 400-μg vaginal misoprostol fours hours pre-operatively.

The first trials describing prostaglandin priming of the cervix to reduce the frequency of traumatic cervical and uterine lesions in non-pregnant women prior to hysteroscopy were published in 1985.

Misoprostol for cervical priming in non-pregnant women is not well established. 16 published randomised controlled trials have shown different cervical response and outcomes. Most of the studies have separately, but not systematically compared the effect on different patient groups, such as nulliparous women and postmenopausal women. Seven of the studies included less than 50 patients, and almost all the trials were underpowered as regards to evaluating primary outcome measures. In the study with the largest number of patients included (Thomas et al), the authors have not explained why or how they converted the primary outcome measure from "the largest-number Hegar dilator that could be inserted without resistance" to a binary variable ("Hegar > 8/Hegar < 8) after they had analysed their results - an apparent protocol violation. It appears that none of the trials have been designed and conducted in accordance with the CONSORT statement. The dosages used in the studies have varied between 200 and 1000-μg misoprostol given between 2 and 24 hours before hysteroscopy, via the oral, sublingual and vaginal routes. Trials that have used higher dosages of misoprostol, via the vaginal route, using the longest interval between administration of misoprostol and hysteroscopy have tended to show more favourable outcomes as regards to cervical priming.

The hospital pharmacist will manufacture both active misoprostol ground up as a whitish powder in capsules (500-μg per capsule), as well as an inactive ingredient with an identical appearance (lactose) in capsules as placebo. The hospital pharmacist will prepare numbered, opaque, sealed envelopes. The envelopes will be numbered according to a randomisation list. The hospital pharmacy will then insert the prepared capsules into the envelopes. Each envelope will contain two capsules. Half of the envelopes will contain two capsules with 500-μg misoprostol each, while the other half will contain two placebo capsules.