IRCT | Evaluation of the effects of exosome therapy on the return of menstrual cycles and improvement of premature menopause symptoms in patients with premature ovarian failure (POF)

Protocol summary

Study aim: Evaluation of the therapeutic effects of stem cell exosomes on the return of the menstrual cycle and improvement of premature menopause symptoms in patients with premature ovarian failure (POF)
Design: This study is a randomized, single-blind, parallel-group clinical trial in which eligible participants are assigned to two groups of exosome and PRP in a 1:1 block randomization with variable block sizes using a sequence generated by statistical software. Allocation concealment is performed through opaque, sealed, and numbered envelopes. The study sample size is 18 people, divided equally between the two groups.
Settings and conduct: Location: Fatemeh Hospital, Hamadan. Participants: Premature ovarian failure (POF) patients with informed consent. Grouping: Randomized into two groups: exosome and PRP. Blinding: Single-blind; assessors and data analysts are blinded.
Participants/Inclusion and exclusion criteria: Inclusion criteria: definite POF/POI (high FSH, low estradiol), adequate ovarian reserve (AFC), informed consent. Exclusion criteria: genetic/chromosomal causes (Turner, mutations), active autoimmune diseases, hormonal cancers, or severe systemic diseases.
Intervention groups: Intervention group: Intraovarian injection of mesenchymal stem cell-derived exosomes (MSC-Exosomes). These exosomes are prepared from Wharton’s gel mesenchymal cells and are injected by a gynecologist in an infertility clinic. Control group: Intraovarian injection of platelet-rich plasma (PRP). This group serves as an “active placebo” or “alternative standard of care” for comparison with exosomes and is administered in the same manner as the intervention group.
Main outcome variables: Return of menstrual cycle - spontaneous or clinical pregnancy

General information

Reason for update
Acronym
IRCT registration information: IRCT registration number: IRCT20251118068036N2

Registration date: 2026-05-16, 1405/02/26

Registration timing: registered_while_recruiting

Last update: 2026-05-16, 1405/02/26

Update count: 0
Registration date: 2026-05-16, 1405/02/26

Registrant information: Name

omid ghorbani

Name of organization / entity

Country

Iran (Islamic Republic of)

Phone

+98 81 3131 0000

Email address

ghorbaniomid213@gmail.com

Recruitment status: recruiting
Funding source

Expected recruitment start date: 2026-05-13, 1405/02/23
Expected recruitment end date: 2027-05-13, 1406/02/23
Actual recruitment start date: empty
Actual recruitment end date: empty
Trial completion date: empty

Scientific title: Evaluation of the effects of exosome therapy on the return of menstrual cycles and improvement of premature menopause symptoms in patients with premature ovarian failure (POF)

Public title: Effects of exosomes on premature menopause and return of menstruation in POF patients
Purpose: Treatment
Inclusion/Exclusion criteria: Inclusion criteria:

Definitive diagnosis of POF/POI: High FSH levels (usually greater than 25 or 40 IU/L on two occasions one month apart) and low estradiol levels. Ovarian reserve: The presence of a minimum number of antral follicles (AFC) on ultrasound. informed consent

Exclusion criteria:

Genetic or chromosomal causes: The presence of syndromes such as Turner Syndrome or specific mutations that are the main cause of ovarian failure. Underlying diseases: Active autoimmune diseases, hormone-dependent cancers, or severe systemic diseases (heart, kidney, liver).
Age: From 25 years old to 40 years old
Gender: Female

Phase

2

Groups that have been masked

Outcome assessor

Sample size

Target sample size: 18

Randomization (investigator's opinion)

Randomized

Randomization description

In this study, participants will be assigned to two intervention (exosome) and control (PRP) groups using a 1:1 block randomization. To avoid predictability of allocation, blocks of variable size (4 and 6) will be used. The randomization sequence will be prepared by statistical software and by an individual independent of the treatment team. The randomization unit in this study is the individual and each participant will be individually allocated to one of the two groups. For allocation concealment, opaque, closed, sealed and numbered envelopes will be used in the order of arrival. These envelopes will only be opened at the time of allocation and after the patient has been definitively entered the study to avoid selection bias.

Blinding (investigator's opinion)

Single blinded

Blinding description

The study will be conducted in a single-blinded manner; that is, the outcome assessor will be unaware of the group allocation of patients. Given the intrinsic differences between exosome and PRP interventions, blinding of the participant and the intervention provider is not possible. Patient allocation will be coded and performed using sealed envelopes.

Placebo

Used

Assignment

Parallel

Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee: Name of ethics committee

Research Ethics Committee of Hamadan University of Medical Sciences

Street address

Shahid Fahmideh Street

City

Hamadan

Province

Hamadan

Postal code

6517835678
Approval date: 2026-03-14, 1404/12/23
Ethics committee reference number: IR.UMSHA.REC.1404.991

Health conditions studied

1

Description of health condition studied: Evaluation of the effects of exosome therapy on the return of menstrual cycles and improvement of premature menopause symptoms in patients with premature ovarian failure (POF)
ICD-10 code: E28.3
ICD-10 code description: Primary ovarian failure

Primary outcomes

1

Description: Menstrual Cyclicity: Percentage of patients who show regular or significant return of menstruation during the follow-up period (3 to 6 months after injection).
Timepoint: Measurements will be taken at the beginning of the study (before treatment), the second month (ultrasound), the third month (hormones, ultrasound, menstruation, pregnancy), the fourth month (ultrasound), and the sixth month (hormones, ultrasound, menstruation, pregnancy).
Method of measurement: Patient-reported outcome recording and confirmation by the physician based on observation of bleeding pattern and cycle regularity.

2

Description: Spontaneous or Clinical Pregnancy Rate: The percentage of patients who become pregnant during the study period (and up to 6 months after injection).
Timepoint: Follow-up in the third and sixth months. (If pregnancy symptoms appear earlier, an evaluation will be done at the appropriate time).
Method of measurement: Positive serum beta hCG test (≥25 IU/L) and confirmation of clinical pregnancy by visualization of the gestational sac via ultrasound.

Secondary outcomes

1

Description: AMH hormone level
Timepoint: AMH levels, as a secondary outcome, will be measured at three time points: baseline (before intervention), three months after intervention, and six months after intervention, using blood samples and ELISA. The unit of measurement is nanograms per milliliter (ng/mL).
Method of measurement: After serum separation, the venous blood sample is stored at -80°C and then measured using an ELISA kit (the name of the kit should be mentioned if known). The final results will be reported in nanograms per milliliter (ng/mL).

2

Description: Levels of FSH, LH, and estradiol (E2) hormones
Timepoint: It will be measured at three time points, including the beginning of the study (before the intervention), three months after the intervention, and six months after the intervention, using a blood sample and ELISA method. The unit of measurement is nanograms per milliliter (ng/mL).
Method of measurement: Blood sample and ELISA-based assays - measured on days 3 to 5 of the cycle if the cycle returns

Intervention groups

1

Description: Intervention group: Treatment type: Intraovarian injection of mesenchymal stem cell-derived exosomes (MSC-Exosomes).Technical details:Exosomes are prepared from mesenchymal cells extracted from Wharton’s Jelly tissue.Cells are cultured at passages 3 to 5 and exosomes are separated from the supernatant by ultracentrifuge.Purified exosomes are stored in PBS at -80°C until use.Administration: Intraovarian injection (by a gynecologist in an infertility clinic)
Category: Treatment - Drugs

2

Description: Control group: In this group, autologous platelet-rich plasma (PRP) is used as a comparative intervention. PRP is prepared from the subject's own venous blood sample and, after processing by centrifugation, is injected intraovarianly under transvaginal ultrasound guidance. The injection volume, frequency, and details of PRP preparation will be determined according to the study protocol.
Category: Treatment - Drugs

Recruitment centers

1

Recruitment center: Name of recruitment center

Fatemeh Hospital, Hamadan

Full name of responsible person

Mahnaz Yavangi

Street address

Shahid Fahmideh Street

City

Hamadan

Province

Hamadan

Postal code

6517835678

Phone

+98 81 3131 0000

Email

yavangi@umsha.ac.ir

1

Sponsor: Name of organization / entity

Hamedan University of Medical Sciences

Full name of responsible person

Alireza Soltanian

Street address

Shahid Fahmideh St

City

Hamadan

Province

Hamadan

Postal code

6517838678

Phone

+98 81 3131 0000

Email

yavangi@umsha.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?: Yes
Title of funding source: Hamedan University of Medical Sciences
Proportion provided by this source: 100
Public or private sector: Public
Domestic or foreign origin: Domestic
Category of foreign source of funding: empty
Country of origin
Type of organization providing the funding: Academic

Person responsible for general inquiries

Contact: Name of organization / entity

Hamedan University of Medical Sciences

Full name of responsible person

Mahnaz Yavangi

Position

Faculty member, Hamadan University of Medical Sciences

Latest degree

Specialist

Other areas of specialty/work

Gynecology and Obstetrics

Street address

Shahid Fahmideh St

City

Hamadan

Province

Hamadan

Postal code

6517838678

Phone

+98 81 3131 0000

Email

yavangi@umsha.ac.ir

Person responsible for scientific inquiries

Contact: Name of organization / entity

Hamedan University of Medical Sciences

Full name of responsible person

Mahnaz Yavangi

Position

Faculty member, Hamadan University of Medical Sciences

Latest degree

Specialist

Other areas of specialty/work

Gynecology and Obstetrics

Street address

Shahid Fahmideh St

City

Hamadan

Province

Hamadan

Postal code

657838678

Phone

+98 81 3131 0000

Email

yavangi@umsha.ac.ir

Person responsible for updating data

Contact: Name of organization / entity

Hamedan University of Medical Sciences

Full name of responsible person

Mahnaz Yavangi

Position

Faculty member, Hamadan University of Medical Sciences

Latest degree

Specialist

Other areas of specialty/work

Gynecology and Obstetrics

Street address

Shahid Fahmideh St

City

Hamadan

Province

Hamadan

Postal code

657838678

Phone

+98 81 3131 0000

Email

yavangi@umsha.ac.ir

Sharing plan

Deidentified Individual Participant Data Set (IPD): Undecided - It is not yet known if there will be a plan to make this available
Study Protocol: Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan: Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form: Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report: Undecided - It is not yet known if there will be a plan to make this available
Analytic Code: Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary: Undecided - It is not yet known if there will be a plan to make this available

Evaluation of the effects of exosome therapy on the return of menstrual cycles and improvement of premature menopause symptoms in patients with premature ovarian failure (POF)