Menstrual Blood Stem Cells in Poor Ovarian Responders

Sponsor

Avicenna Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT05703308

Collaborator

(none)

180

Enrollment

Location

Arms

Actual Duration (Months)

6.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Poor Ovarian Response Infertility, Female	Biological: Autologous Menstrual Blood Stem Cells	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

180 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 21, 2020

Actual Primary Completion Date :

Sep 22, 2021

Actual Study Completion Date :

Oct 22, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Spontaneous pregnancy rate [3 months after stem cell injection]
Number of participants that establish a spontaneous clinical pregnancy after stem cell injection
Pregnancy rate after ICSI [4 weeks after embryo transfer]
Number of participants that establish a clinical pregnancy after embryo transfer

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Avicenna Research Institute	Tehran		Iran, Islamic Republic of

Sponsors and Collaborators

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.