Couples and Microbial Diversity

Couples and Microbial Diversity (CLARITY) - study is a prospective study that investigates the risks and dynamics of different microbes and transmission among couples to optimize the prevention and control strategies as well as improvement for infertility treatments.

This research proposals main aim is to explore a variety of outcomes related to HPV-infection and other microbes and to evaluate how different variables of the mucosal ecosystem impacts these outcomes.

The study has three main parts:

PART 1. Describe couples' oral and genital HPV infections prevalence jointly with the other oral and genital microbial diversity in longitudinal setting.

PART 2. Investigate the role of different microbe infections and interactions in reproductive health and pregnancy success rate among couples enrolled for infertility treatments at the clinic.

PART 3. Provide information on the mother-child and father-child microbial vertical and horizontal transmission.

Study sets: We plan to recruit to a prospective cohort study 200 couples attending the Tampere University Hospital (TAUH) infertility clinic due to problems in conceiving during the past 12 months.

Samples: At recruitment (Baseline) we will take swab samples from vulva, cervix, vagina and anus, as well as saliva samples and gargle samples from oral cavity from all participating women. From the males otherwise same oral samples are taken as from the women, apart from genital samples that will be taken from the penile shaft, and additionally a semen sample is collected. The plan of infertility treatment itself is not affected and patients are treated according to routine practice guidelines. The follow-up samples are self-collected samples at 6, 12, 18 and 24 months (saliva, oral gargle, genital sample (in men genital sample is optional). With the extended CLARITY-Baby protocol at delivery the following additional samples will be collected: a breast milk from the mother, sample form the placenta and samples from the offspring (genital, saliva and oral brush sample).

Questionnaire: Background information of different behavioral and reproductive factors is collected using web-based self-completed questionnaires from all study participants at baseline. When necessary, the background information is completed using patient files. Secondary shorter questionnaires will be done at 12 months and 24 months of the CLARITY-protocol and at 6 months follow-up visit after delivery in the CLARITY-Baby Protocol.

Biological assays include: HPV genotyping, HLA typing, metagenomic sequencing, methylation analysis, and targeted sequencing.

Statistical analysis plans will vary by study objective and will include logistic regression, generalized estimating equations (GEE), ROC curve construction, and compositional methods for microbial profiling. All analyses will be conducted using STATA (STATA Corp., TX).

Schedule The study has been approved by the Wellbeing Services County of Pirkanmaa District Ethical Review Board. Recruitment will start in Janyary 2026.

Findings will support the development of prevention strategies, improved risk stratification, and innovative diagnostic and therapeutic approaches for couples to optimize the prevention and control strategies as well as improvement for infertility treatments.