Menstrual Blood Stem Cells in Poor Ovarian Responders

Outcome of Pregnancy in Poor Ovarian Responders by Intraovarian Administration of Autologous Menstrual Blood Derived-Mesenchymal Stromal Cells

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.

Study Overview

• Status: Completed
• Conditions: Infertility, Female; Poor Ovarian Response
• Intervention / Treatment: Biological: Autologous Menstrual Blood Stem Cells

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.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Avicenna Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: 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
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous pregnancy rate	Number of participants that establish a spontaneous clinical pregnancy after stem cell injection	3 months after stem cell injection
Pregnancy rate after ICSI	Number of participants that establish a clinical pregnancy after embryo transfer	4 weeks after embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hormone levels	Change from baseline in Anti-Müllerian hormone (AMH), serum follicle stimulating hormone (FSH), and antral follicle count (AFC)	2 and 4 months after stem cell injection
Number of oocytes	Mean number of retrieved COCs per protocol	Day 0 after follicle puncture
Number of MII oocytes	Mean number of metaphase II (MII) oocytes per protocol	Day 0 after follicle puncture
Number of embryos	Mean number of embryos	Day 3-5 after follicle puncture
Number of high quality embryos number	Grade A for cleavage stage embryo, >=3BB for blastocyst	Day 3-5 after follicle puncture
Clinical pregnancy rate	The incidence of gestational sac with heartbeat assessed by TVS	4 weeks after embryo transfer
Biochemical pregnancy rate	Incidence of serum beta-hCG test > 25 mIU/ml	12-16 days after oocyte pick-up
Live birth rate	Incidence of the birth of at least one live newborn after 22 weeks of gestation	at a follow-up time of 30 days after delivery
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Incidence of adverse and serious adverse events with potential relationship to treatment	at a follow-up time after 1 year

Collaborators and Investigators

• Sponsor: Avicenna Research Institute
• Investigators: Study Director: Simin Zafardoust, MD, Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.; Study Chair: Somaieh Kazemnejad, Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.; Principal Investigator: Mina Fathi Kazerooni, MD, PhD, Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2020
• Primary Completion (Actual): September 22, 2021
• Study Completion (Actual): October 22, 2022

Study Registration Dates

• First Submitted: January 15, 2023
• First Submitted That Met QC Criteria: January 26, 2023
• First Posted (Estimate): January 30, 2023

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Infertility; Cell therapy; ICSI; Poor Ovarian Responders; Menstrual Blood Stem cells
• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: 99008-1023

Drug and device information, study documents

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