Assisted Reproductive Technology, Infertility, Metabolome, Microbiome, Pregnancy Complications, Pregnancy Loss, Early
Conditions
Keywords
IVF, Microbiome, Metabolome, Male fertility, Pregnancy outcome
Brief summary
This prospective observational cohort study investigates the role of the microbiome and metabolome in couples undergoing in vitro fertilization. Biological samples will be collected from both female and male partners, including semen, vaginal, and blood samples, to characterize microbial composition and metabolic profiles. The study aims to examine how these biological profiles are associated with reproductive outcomes such as fertilization, pregnancy, miscarriage, and live birth. Participants will be followed longitudinally, and reproductive and obstetric outcomes will be obtained through linkage with national health registers.
Detailed description
Infertility affects a substantial proportion of couples worldwide, and in vitro fertilization (IVF) is an important treatment option for many individuals experiencing infertility. Increasing evidence suggests that the human microbiome and metabolome may play a role in reproductive health and fertility outcomes. However, the contribution of microbial communities and metabolic profiles in both female and male partners to IVF outcomes remains insufficiently understood. This prospective observational cohort study aims to investigate the microbiome and metabolome profiles in couples undergoing IVF treatment and their association with reproductive and obstetric outcomes. Heterosexual couples undergoing IVF treatment at participating fertility clinics will be recruited. Biological samples will be collected from both partners, including semen samples from male partners and vaginal and blood samples from female partners. These samples will be stored and analyzed using sequencing-based microbiome profiling and metabolomic analyses. The study will evaluate microbial composition, diversity, and metabolic signatures in relation to fertility parameters such as semen quality, fertilization rate, embryo development, and clinical pregnancy. Participants will be followed longitudinally to assess reproductive outcomes including miscarriage, preterm birth, preeclampsia, and live birth. Outcome data will be obtained through clinical records and linkage with national health registers. The overall aim of the study is to improve the understanding of how microbiome and metabolome profiles in both partners may influence reproductive success and pregnancy outcomes in couples undergoing IVF.
Interventions
None listed
Sponsors
Karolinska Institutet
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Women aged 18 to 40 years at enrolment. * Men aged between 18 to 56 years at enrolment. * Couples planning to undergo IVF treatment at a participating centre. * Sufficient understanding of spoken and written Swedish or English to provide informed consent and complete the web-based questionnaire.
Exclusion criteria
* Pregnancy at the time of enrolment (confirmed or suspected). * Recent systemic antibiotic use within the past 4 weeks * Active vaginal or genital tract infection at the time of sampling
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Live Birth | Through delivery, up to 12 months after embryo transfer | Delivery of a live-born infant after IVF treatment, identified through linkage with national health registers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Miscarriage Before 22 Weeks of Gestation | Up to 21 weeks and 6 days of gestation | Pregnancy loss before 22 weeks of gestation identified through linkage with national pregnancy registers. |
| Number of Participants With Preterm Birth Before 37 Completed Weeks of Gestation | At delivery | Delivery before 37 completed weeks of gestation identified through national birth registers. |
| Number of Participants With Preeclampsia | During pregnancy through 6 weeks postpartum | Diagnosis of preeclampsia recorded in national health registers according to ICD codes. |
| Relative Abundance of Prespecified Microbial Taxa in Female Reproductive Tract Samples | Time Frame: Baseline (Day 0, prior to initiation of IVF stimulation); early pregnancy confirmation visit (gestational weeks 7 to 9); and at miscarriage, if applicable, during pregnancy up to gestational age 21 weeks 6 days | Relative abundance of prespecified microbial taxa measured in female reproductive tract samples collected at baseline using sequencing-based metagenomic profiling. |
| Concentration of Prespecified Metabolites in Female Reproductive Tract Samples | Baseline, prior to initiation of IVF treatment | Concentrations of prespecified metabolites measured in female reproductive tract samples collected at baseline using metabolomics analysis. |
| Number of Participants With Clinical Pregnancy Confirmed by Ultrasound | 6 to 8 weeks after embryo transfer | Presence of an intrauterine gestational sac with fetal heartbeat confirmed by ultrasound following embryo transfer. |
| Number of Participants With Biochemical Pregnancy | 10 to14 days after embryo transfer | Positive serum human chorionic gonadotropin (hCG) following embryo transfer without ultrasound-confirmed pregnancy. |
| Sperm concentration | At oocyte retrieval, approximately 10 to 20 days after initiation of IVF stimulation | Sperm concentration assessed according to WHO laboratory standards. |
| Relative Abundance of Prespecified Microbial Taxa in Seminal Fluid Samples | At oocyte retrieval, approximately 10 to 20 days after initiation of IVF stimulation | Relative abundance of prespecified microbial taxa measured in seminal fluid samples collected from male partners using sequencing-based metagenomic profiling. |
| Concentration of Prespecified Metabolites in Male Semen Samples | At oocyte retrieval, approximately 10 to 20 days after initiation of IVF stimulation | Concentrations of prespecified metabolites measured in semen samples collected from male partners using metabolomics analysis. |
| Fertilization Rate per Retrieved Mature Oocyte | Day 1 after oocyte retrieval | Proportion of oocytes that are successfully fertilized following IVF or ICSI. |
| Normal sperm morphology | At oocyte retrieval, approximately 10 to 20 days after initiation of IVF stimulation | Percentage of sperm with normal morphology assessed according to WHO laboratory standards. |
| Levels of Immune Markers in Female Blood Samples | Baseline (Day 0), prior to initiation of IVF stimulation | Levels of immune markers measured in blood samples collected from female participants at baseline using laboratory-based immunologic assays. Associations with female reproductive tract microbiome composition and metabolomic profiles will be evaluated in exploratory analyses. |
Countries
Sweden
Contacts
CONTACTOla Larsson, PhD
CONTACTHanna Nilsson, PhD
PRINCIPAL_INVESTIGATORKenny A. Rodriguez-Wallberg, MD., PhD
Oncology-pathology, Karolinska Institutet
STUDY_DIRECTORHana Shabana, MD, PhD candidate
Karolinska Institutet
Outcome results
None listed