High-grade squamous intraepithelial lesions are caused by persistent high-risk human papillomavirus (hr-HPV) infections and are subdivided into cervical intraepithelial neoplasia (CIN) lesions: CIN II (moderate) and CIN III (severe). Current treatment options for CIN II include large loop excision of the transformation zone, imiquimod and expectant management. Each treatment option has its drawbacks, and therefore, a non-invasive treatment is desirable. Preliminary evidence shows that medical-grade honey (MGH) has antiviral activity and might be able to modulate the vaginal microbiome, reduce local inflammation or directly influence the intralesional immune response within cervical tissues. Therefore, this study aims to investigate the possible effect of MGH on hr-HPV clearance and to investigate the possible underlying mechanisms contributing to the regression of CIN II lesions.

This study is performed in the Zuyderland Medical Centre and Maastricht University Medical Centre+. A total of 60 eligible women with newly histologically confirmed CIN II will receive MGH (L-Mesitran Soft) for intravaginal use for 6 months. The primary objective is to investigate the effect of MGH on the hr-HPV clearance after 6 months. Secondary aims are the effect of MGH on the regression of CIN II lesions, clearance of hr-HPV at 12 and 24 months and the role of the vaginal microbiome, local immune system and intravaginal inflammatory status in response to MGH. Moreover, data on quality of life, side effects and compliance will be collected.

Ethical approval from the Medical Ethics Review Committee of the Zuyderland Medical Centre Heerlen has been obtained (NL86044.096.24 on 24 April 2024). The results will be presented to researchers and healthcare professionals through conferences, meetings and publications in international journals.

NCT06219018.

Differences in the profile of the vaginal microbiota (VMB) have been associated with pregnancy rates after medical assisted reproduction (MAR) such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Monitoring the VMB profile of IVF patients creates an opportunity to identify the best window for IVF treatment and embryo transfer. The ReceptIVFity test is a predictive test that assesses the chances of becoming pregnant in women undergoing IVF treatment based on the VMB composition. A VMB profile dominated by beneficial strains, most notably Lactobacillus species, is associated with increased pregnancy chances. However, to date, limited evidence is available on the effect of active modification strategies to facilitate the modulation of the VMB profile to help restore a VMB dominated by Lactobacillus species.

This is a randomised, placebo-controlled, double-blind intervention study. The study will involve 1:1 randomisation to one of the two arms: oral probiotic or placebo. Vaginal and rectal swabs will be collected at intake and 4, 6 and 8 weeks after the start of the treatment. Our objective is to determine if oral probiotic treatment improves the VMB profile of IVF patients from a low to a medium/high ReceptIVFity score, compared with placebo treatment. Secondary outcomes are: the potential of the bacterial strains in the oral probiotic to be detected in the vaginal tract and/or in the gut, and if the treatment leads to an increased ongoing pregnancy rate after IVF.

Ethical approval was obtained by the local medical ethical review committee at the Maastricht University Medical Centre. Findings from this study will be published in a peer-reviewed scientific journal and presented at one or more scientific conferences.

CCMO NL81210.068.22, registered 25 September 2023.