Microbiome and Metabolome Profiles in Couples Undergoing IVF and Reproductive Outcomes (Mi IVF)

Microbiome and Metabolome Profiles in Couples Undergoing IVF and Their Association With Reproductive Outcomes in a Prospective Longitudinal Cohort Study

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.

Study Overview

• Status: Recruiting
• Conditions: Infertility; Pregnancy Complications; Microbiome; Metabolome; Pregnancy Loss, Early; Assisted Reproductive Technology

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.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Hanna Nilsson, PhD; Email: hanna.nilsson@ki.se
• Study Contact Backup: Name: Ola Larsson, PhD; Phone Number: +46 8 524 80000; Email: ola.larsson@ki.se

Study Locations

• Sweden
  • Malmo, Sweden
    • Recruiting
    • Reproduktionsmottagning Malmö, Skånes universitetssjukhus
    • Contact: Margareta Kitlinski, MD, PhD; Email: margareta.kitlinski@skane.se
    • Principal Investigator: Margareta Kitlinski, MD, PhD
  • Stockholm, Sweden, 146 32
    • Recruiting
    • Karolinska Universitetssjukhuset
    • Contact: Hana Shabana, MD; Phone Number: +46721775326; Email: hana.shabana@ki.se
    • Contact: Kenny A Rodriguez-Wallberg, MD, PhD; Phone Number: +46721775326; Email: hana.shabana@ki.se
    • Principal Investigator: Hana Shabana, MD., PhD candidate
  • Uppsala, Sweden
    • Recruiting
    • Reproduktionscenter, Akademiska sjukuhset
    • Contact: Farnaz Bazargani, MD; Email: farnaz.bazargani@akademiska.se
    • Principal Investigator: Farnaz Bazargani, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Couples undergoing in vitro fertilization (IVF) treatment at participating fertility clinics in Sweden. Eligible couples are consecutively recruited at the time of IVF treatment initiation and followed prospectively for reproductive outcomes through linkage with national health registers.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Couples Undergoing IVF Treatment; Prospective cohort of couples undergoing in vitro fertilization (IVF) treatment at participating in a multicenter fertility clinics in Sweden. Biological samples are collected from both partners for microbiome and metabolome profiling, and participants are followed longitudinally for reproductive and obstetric outcomes through linkage with national health registers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Live Birth	Delivery of a live-born infant after IVF treatment, identified through linkage with national health registers.	Through delivery, up to 12 months after embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Miscarriage Before 22 Weeks of Gestation	Pregnancy loss before 22 weeks of gestation identified through linkage with national pregnancy registers.	Up to 21 weeks and 6 days of gestation
Number of Participants With Preterm Birth Before 37 Completed Weeks of Gestation	Delivery before 37 completed weeks of gestation identified through national birth registers.	At delivery
Number of Participants With Preeclampsia	Diagnosis of preeclampsia recorded in national health registers according to ICD codes.	During pregnancy through 6 weeks postpartum
Relative Abundance of Prespecified Microbial Taxa in Female Reproductive Tract Samples	Relative abundance of prespecified microbial taxa measured in female reproductive tract samples collected at baseline using sequencing-based metagenomic profiling.	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
Concentration of Prespecified Metabolites in Female Reproductive Tract Samples	Concentrations of prespecified metabolites measured in female reproductive tract samples collected at baseline using metabolomics analysis.	Baseline, prior to initiation of IVF treatment
Number of Participants With Clinical Pregnancy Confirmed by Ultrasound	Presence of an intrauterine gestational sac with fetal heartbeat confirmed by ultrasound following embryo transfer.	6 to 8 weeks after embryo transfer
Number of Participants With Biochemical Pregnancy	Positive serum human chorionic gonadotropin (hCG) following embryo transfer without ultrasound-confirmed pregnancy.	10 to14 days after embryo transfer
Sperm concentration	Sperm concentration assessed according to WHO laboratory standards.	At oocyte retrieval, approximately 10 to 20 days after initiation of IVF stimulation
Relative Abundance of Prespecified Microbial Taxa in Seminal Fluid Samples	Relative abundance of prespecified microbial taxa measured in seminal fluid samples collected from male partners using sequencing-based metagenomic profiling.	At oocyte retrieval, approximately 10 to 20 days after initiation of IVF stimulation
Concentration of Prespecified Metabolites in Male Semen Samples	Concentrations of prespecified metabolites measured in semen samples collected from male partners using metabolomics analysis.	At oocyte retrieval, approximately 10 to 20 days after initiation of IVF stimulation
Fertilization Rate per Retrieved Mature Oocyte	Proportion of oocytes that are successfully fertilized following IVF or ICSI.	Day 1 after oocyte retrieval
Normal sperm morphology	Percentage of sperm with normal morphology assessed according to WHO laboratory standards.	At oocyte retrieval, approximately 10 to 20 days after initiation of IVF stimulation
Levels of Immune Markers in Female Blood Samples	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.	Baseline (Day 0), prior to initiation of IVF stimulation

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Kenny A. Rodriguez-Wallberg, MD., PhD, Oncology-pathology, Karolinska Institutet; Study Director: Hana Shabana, MD, PhD candidate, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Estimated): August 20, 2028
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Microbiome; IVF; Metabolome; Male fertility; Pregnancy outcome
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases and Pregnancy Complications; Abortion, Spontaneous; Infertility; Pregnancy Complications
• Other Study ID Numbers: 2024-07146-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data may be shared with qualified researchers upon reasonable request after publication of the study results. Data sharing will be subject to ethical approval, institutional policies, and applicable data protection regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No