Menstrual Blood Stem Cells in Poor Ovarian Responders

NCT ID: NCT05703308

Last Updated: 2023-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-21
• Study Completion Date: 2022-10-22

Brief Summary

In this controlled trial, poor ovarian responder women will be treated with transplantation of autologous menstrual blood stem cells. The investigators will attempt to assess the safety and efficacy of this procedure for the treatment of infertility in POR patients compared to control group.

Detailed Description

With economic development, procreation delays have resulted in more women seeking medical help for infertility treatment. Because the quality and quantity of oocytes are affected by physiological age, despite advances in assisted reproductive technology (ART), managing infertility in women with poor ovarian response (POR) remains a daily challenge for physicians.

Adult mesenchymal stromal cell (MSC) therapy has gained particular interest in recent years because it may provide a supportive microenvironment for oocyte development from quiescent primordial follicles. Human MSC transplantation has been shown in preclinical studies to host ovaries and restore their function and structure premature ovarian failure (POF) animal models.

Because of their encouraging characteristics such as ease of access, high availability, monthly repeatability of sampling, less ethical considerations, lack of tumor-causing potential, protected property, and significant trans-differentiation capacity, endometrial-derived stromal cells have been considered in a wide range of studies since 2007. Menstrual blood-derived stromal cells (MenSCs), on the other hand, are derived from endometrial tissue and can be collected in a non-invasive manner, making them especially useful in the treatment of reproductive disorders. The investigators attempted to assess the safety and efficacy of intraovarian injection of MenSCs for the treatment of infertility in POR patients based on this evidence.

The results of this clinical trial's phases I and II indicated that Men-MSCs could be considered as a potential treatment to restore the fertility capability of POR women. Based on these findings, the investigators have designed a Phase III controlled trial of autologous MenSC therapy for patients with POR.

Conditions

Poor Ovarian Response; Infertility, Female

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

MenSCs group

Study group, treated with autologous intra-ovarian MenSCs injection and monitored for spontaneous pregnancy for 3 months after intervention. ICSI was used in cases where the pregnancy did not occur naturally.

Group Type: EXPERIMENTAL

Autologous Menstrual Blood Stem Cells

Intervention Type: BIOLOGICAL

The menstrual blood of patients in the MenSCs treatment group was collected in sterile menstrual cups on the second day of menstruation, and directly transferred to a class B clean room for MSC isolation and culture. All cell quality control studies were performed prior to the International Conference of Harmonization Q2 (ICH Q2) guidelines. The density of the final product was 20×106 cells/ml. 150 μl of the prepared suspension was injected intravaginally into each ovary of the patient under general anaesthesia

ICSI group

Control group, monitored for spontaneous pregnancy for 3 months after their last ovarian stimulation for ICSI or IVF. ICSI was used in cases where the pregnancy did not occur naturally.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Autologous Menstrual Blood Stem Cells

The menstrual blood of patients in the MenSCs treatment group was collected in sterile menstrual cups on the second day of menstruation, and directly transferred to a class B clean room for MSC isolation and culture. All cell quality control studies were performed prior to the International Conference of Harmonization Q2 (ICH Q2) guidelines. The density of the final product was 20×106 cells/ml. 150 μl of the prepared suspension was injected intravaginally into each ovary of the patient under general anaesthesia

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Serum AMH < 0.1 ng/ml (at the screening visit and in the absence of OC or sex-steroid intake)
• Antral follicular count (AFC) in both ovaries < 4 (at screening visit and in the absence of OC or sex-steroid intake)
• Positive history of at least1 standard previous IVF-ET or ICSI-ET
• Normal thyroid hormones (TSH and FT4)
• Normal level of prolactin,
• Normal level of fasting blood sugar
• Normal Liver tests (SGOT, SGPT)
• Normal level of BUN, creatinine
• Negative Infectious tests (HIV, HCV, HBS Ag, VDRL)
• Normal coagulation factors (PT, PTT, BT, CT)
• Normal serum levels of sodium, potassium, calcium, phosphorus
• Negative history of endometrioma or other ovarian cysts
• Negative history of previous ovarian surgery
• Negative history of cancer
• Negative history of a known autoimmune disorder.

Exclusion Criteria

• Positive history of hydrosalpinx or anatomical uterine disorders (In vaginal sonography or HSG)
• Severe male factors of their husbands (count <15 million/ml)

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Avicenna Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simin Zafardoust, MD

Role: STUDY_DIRECTOR

Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.

Somaieh Kazemnejad

Role: STUDY_CHAIR

Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.

Mina Fathi Kazerooni, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.

Locations

Avicenna Research Institute

Tehran, , Iran

Countries

Iran

References

Zafardoust S, Kazemnejad S, Fathi-Kazerooni M, Darzi M, Sadeghi MR, Sadeghi Tabar A, Sehat Z. The effects of intraovarian injection of autologous menstrual blood-derived mesenchymal stromal cells on pregnancy outcomes in women with poor ovarian response. Stem Cell Res Ther. 2023 Nov 15;14(1):332. doi: 10.1186/s13287-023-03568-1.

Reference Type: DERIVED

PMID: 37968668 (View on PubMed)

Other Identifiers

99008-1023

Identifier Type: -

Identifier Source: org_study_id