This observational study examines the safety and effects of injecting Muse cells (a type of naturally occurring stem like cells found in adult tissues such as fat or bone marrow) directly into the ovaries of women aged 28 to 70 who are going through peri-menopause.

Perimenopause is the transition time before menopause when hormone levels fluctuate, periods become irregular, and many women experience symptoms like hot flashes, night sweats, sleep problems, mood changes, and reduced energy. Current treatments mainly manage symptoms but do not restore natural ovarian function.

Muse cells have special properties: they can help repair tissues, reduce inflammation, support cell energy production, and promote a healthier environment in the ovaries. In this study, women who choose to receive ultrasound guided Muse cell injections into their ovaries as part of their own regenerative care will be carefully followed.

Researchers will monitor safety, hormone levels (such as FSH, estrogen, and AMH), ovarian follicle counts via ultrasound, menstrual patterns, and quality of life improvements using questionnaires. The study does not assign treatment - participants and their doctors decide on the procedure, and information is collected in a standardized way over 24 months (with longer safety follow-up).

The goal is to gather real world data on whether this approach can help stabilize hormones and support ovarian tissue during perimenopause. No placebos or experimental drugs are used in this observational study.

Background:

Perimenopause involves progressive ovarian follicular depletion, erratic hypothalamic pituitary ovarian (HPO) axis function, oxidative stress, mitochondrial dysfunction, chronic low grade inflammation, and epigenetic changes. These processes lead to hormonal instability and associated symptoms. While hormone replacement therapy alleviates symptoms, it does not restore endogenous ovarian activity.

Muse cells (Multilineage-differentiating Stress-Enduring cells) are endogenous, non-tumorigenic, pluripotent like mesenchymal stem cells naturally residing in adult bone marrow, adipose tissue, and connective tissues. They demonstrate spontaneous tri-lineage differentiation potential, high stress tolerance, immune-privileged properties, and selective homing to damaged sites without genetic reprogramming or requirement for HLA matching/immunosuppression in many contexts.

Study Design

This prospective, single arm, single center observational cohort study evaluates real world safety, feasibility, and outcomes following ultrasound-guided intra-ovarian Muse cell injection in women aged 28-70 meeting STRAW+10 criteria for perimenopause. Participants self-select the procedure as part of clinical regenerative medicine care at the study site; no randomization or protocol-driven intervention assignment occurs.

Rationale and Mechanisms

Preclinical and analogous mesenchymal stem cell research in premature ovarian insufficiency (POI) and perimenopausal models suggests potential benefits through interconnected pathways, including paracrine/exosomal signaling (VEGF, IGF-1, FGF2, miR-21/miR-132), mitochondrial transfer via tunneling nanotubes, reduction of reactive oxygen species, anti-apoptotic effects (Bcl-2/Akt/survivin), immunomodulation (TGF-β1, IL-10, PGE2; shift toward Treg phenotype and reduced dendritic cell maturation), and epigenetic remodeling (delivery of DNMTs/HATs, reactivation of folliculogenesis-related genes such as FOXL2, GDF9, BMP15). Additional upstream effects on hypothalamic GnRH pulsatility and pituitary responsiveness may support overall HPO axis coordination.

Similar intra-ovarian autologous or allogeneic mesenchymal stem cell approaches in POI/perimenopausal cohorts have reported signals of improved hormonal parameters, antral follicle counts, menstrual regularity, and symptom relief with acceptable shortterm safety profiles.

Intervention Overview (high-level only) Clinical-grade Muse cells (autologous preferred from adipose or bone marrow; or allogeneic where authorized) are prepared under GMP conditions and administered via transvaginal ultrasound-guided bilateral ovarian stromal injection (laparoscopic alternative if indicated), with optional systemic intravenous support. Dosing follows a safety-informed range (0.5-2.0 × 10⁶ cells/kg total, divided between ovaries).

Objectives

Primary: Characterize safety (adverse events per CTCAE v5.0), procedural tolerability, and ovarian morphology changes over 24 months.

Secondary: Document longitudinal changes in hormonal profiles, ultrasound-based follicular parameters, menstrual cyclicity, and patient-reported outcomes (MENQOL).

Exploratory: Assess candidate mechanistic biomarkers (exosomal miRNAs, epigenetic clocks, cytokines, oxidative stress markers).

Follow-up

Standardized evaluations occur at baseline and at 1, 3, 6, 12, and 24 months, with extended annual safety monitoring up to 5 years via a registry. Assessments include serial hormone panels, transvaginal ultrasound, symptom diaries, quality-of-life measures, and safety surveillance. Optional biobanking supports future analyses.

This observational framework enables ethical collection of standardized real-world evidence on an emerging regenerative approach while generating hypothesis generating data to guide subsequent controlled trials. Information already captured elsewhere in the record (e.g., eligibility criteria, outcome measures, study type) is not repeated here.

Inclusion Criteria:

Women aged 28 to 70 years at the time of enrollment.

Diagnosis of perimenopause according to STRAW+10 criteria, including irregular menstrual cycles (cycle length variation >7 days), elevated FSH (>25 IU/L on two occasions), low AMH (<1.0 ng/mL), and/or presence of perimenopausal symptoms (vasomotor symptoms, sleep disturbance, mood changes, or cognitive complaints).

Willingness to receive ultrasound-guided intra-ovarian Muse cell injection as part of elective clinical regenerative medicine care.

Ability to provide written informed consent and comply with scheduled follow-up visits, blood draws, ultrasounds, and questionnaires for 24 months.

Adequate general health to undergo the procedure under sedation or local anesthesia, as determined by the treating physician.

Exclusion Criteria:

History of ovarian/gynecologic malignancy (active or <5 years remission). Active autoimmune disease requiring immunosuppression.

Uncontrolled comorbidities (e.g., severe cardiovascular disease, coagulopathy, uncontrolled diabetes or thyroid disease).

Current pregnancy or lactation.

Recent hormone therapy (within 3 months).

BMI >40 kg/m² or other factors increasing procedural risk.

Inability to comply with study procedures.

Female

This is a prospective observational cohort study using convenience sampling. Participants are women aged 28-70 experiencing perimenopause who independently elect to receive ultrasound guided intra ovarian Muse cell injection as part of their routine clinical regenerative medicine care at the study center.

No random sampling, probability based recruitment, or protocol-mandated intervention assignment occurs. Enrollment is open to eligible women who present seeking regenerative options for perimenopausal symptoms and ovarian support.

The sampling approach reflects real world clinical practice, allowing collection of standardized longitudinal data on safety and outcomes in a self selected population. Potential selection bias toward motivated individuals interested in regenerative therapies is acknowledged and will be addressed through transparent reporting and subgroup analyses.

Individual participant data (IPD) may be shared in the future following study completion, subject to appropriate de-identification, ethical approvals, and compliance with applicable regulatory and privacy standards. Data sharing will be considered to support scientific transparency and collaboration while protecting participant confidentiality and respecting international data governance requirements.