The goal of this clinical trial is to evaluate FB301 during a mock frozen embryo transfer (FET) cycle in pre-menopausal women aged 18 to 40 years with a prior failed FET and a defined vaginal bacterial imbalance (dysbiosis). The main question it aims to answer is: • Does treatment with FB301 during a mock FET cycle change the proportion of participants who meet the predefined vaginal bacterial threshold compared with placebo? Researchers will compare: * FB301 given after an initial vaginal cleansing with chlorhexidine (an antiseptic solution), * FB301 given after an initial vaginal cleansing with saline (saltwater), and * A placebo capsule given after an initial vaginal cleansing with saline to determine whether these approaches affect vaginal bacterial composition and pregnancy outcomes. Participants will take study treatment for 15 days during a "mock" FET cycle. In a mock cycle, participants receive the hormones needed to prepare the uterus for embryo transfer, but no embryo is transferred. After completing the mock cycle, participants will proceed with their planned frozen embryo transfer and will be followed during pregnancy until birth. Participants will: * Undergo a vaginal cleansing before receiving the first dose of FB301 or placebo * Provide vaginal swab samples at up to 5 study visits * Attend the study centre for up to 8 visits and participate in up to 4 follow-up phone calls * Complete a mock FET cycle before proceeding with their planned frozen embryo transfer cycle Participants who become pregnant will be followed until birth.
Vaginal dysbiosis characterized by reduced relative abundance of Lactobacillus species has been associated with reproductive outcomes in women undergoing frozen embryo transfer (FET). This study evaluates the safety, tolerability, and molecular effects of FB301 in women undergoing FET who have no known underlying clinical gynecological conditions but are identified as having molecular dysbiosis by metagenomic sequencing of a vaginal swab collected at screening. Participants will be randomized to one of three arms: (1) FB301 following a single initial vaginal cleansing with chlorhexidine (an antiseptic solution), (2) FB301 following a single sham cleansing with saline, or (3) placebo following sham cleansing. Cleansing occurs once prior to initiation of study treatment. Participants will then receive 15 days of study treatment during a mock frozen embryo transfer (FET) cycle in which participants receive hormonal preparation of the endometrium but no embryo is transferred. Following completion of the mock cycle, participants will proceed with their planned frozen embryo transfer during the subsequent menstrual cycle, in accordance with standard clinical practice. Participants who become pregnant will be followed until birth. The primary objective is to evaluate whether treatment increases the proportion of participants achieving a predefined Lactobacillus-dominant vaginal bacterial profile following therapy. Secondary objectives include evaluation of biochemical pregnancy (confirmed by serum beta-hCG testing) and clinical pregnancy (confirmed by transvaginal ultrasound) following the subsequent planned FET cycle.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
30
Boston IVF
Waltham, Massachusetts, United States
Proportion of participants with ≥90% combined relative abundance of Lactobacillus crispatus, L. jensenii, L. mulieris, L. gasseri, and L. paragasseri as measured by metagenomic sequencing.
Metagenomic sequencing is performed on cervical vaginal swab samples. Relative abundance is expressed as a percentage of bacterial sequencing reads that are assigned to a specific bacterial species.
Time frame: Baseline to Day 16 (Mock FET cycle)
Percentage change from baseline in relative abundance of Lactobacillus crispatus, L. jensenii, L. mulieris, L. gasseri, and L. paragasseri as measured by metagenomic sequencing.
Metagenomic sequencing is performed on cervical vaginal swab samples. Relative abundance is expressed as a percentage of bacterial sequencing reads that are assigned to a specific bacterial species.
Time frame: Baseline to Day 16 (Mock FET cycle)
Biochemical pregnancy rate following frozen embryo transfer (FET), defined as a positive serum beta-human chorionic gonadotropin (hCG) test.
Time frame: 12-14 days after frozen embryo transfer (FET)
Clinical pregnancy rate following frozen embryo transfer (FET), defined as the presence of a fetal heartbeat confirmed by transvaginal ultrasound.
Time frame: 5-6 weeks after frozen embryo transfer (FET)
Frequency and intensity of all treatment-emergent adverse events (TEAEs), adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest) AESI
Time frame: Baseline to End of Study (up to neonatal follow-up assessment (Visit 11), approximately 10 months after FET)
The incidence of early pregnancy loss, defined as a positive beta-hCG test (biochemical pregnancy) at 12-14 days after FET but no transvaginal ultrasound-confirmed fetal heartbeat at 5-6 weeks after FET (Visit 7)
Time frame: 5-6 weeks after FET
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