Clinical trial NCT05703308: Menstrual Blood Stem Cells in Poor Ovarian Responders
Official title: Outcome of Pregnancy in Poor Ovarian Responders by Intraovarian Administration of Autologous Menstrual Blood Derived-Mesenchymal Stromal Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Poor Ovarian Response
Infertility, Female
Keywords: Poor Ovarian Responders
Menstrual Blood Stem cells
Infertility
Cell therapy
ICSI
Lead sponsor: Avicenna Research Institute
Sponsor class: OTHER
First posted: 2023-01-30
Enrollment: 180
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Spontaneous pregnancy rate
timeFrame: 3 months after stem cell injection
measure: Pregnancy rate after ICSI
timeFrame: 4 weeks after embryo transfer
Secondary outcomes:
measure: Hormone levels
timeFrame: 2 and 4 months after stem cell injection
measure: Number of oocytes
timeFrame: Day 0 after follicle puncture
measure: Number of MII oocytes
timeFrame: Day 0 after follicle puncture
measure: Number of embryos
timeFrame: Day 3-5 after follicle puncture
measure: Number of high quality embryos number
timeFrame: Day 3-5 after follicle puncture
measure: Clinical pregnancy rate
timeFrame: 4 weeks after embryo transfer
measure: Biochemical pregnancy rate
timeFrame: 12-16 days after oocyte pick-up
measure: Live birth rate
timeFrame: at a follow-up time of 30 days after delivery
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: at a follow-up time after 1 year
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Avicenna Research Institute
Study officials:
affiliation: Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.
name: Simin Zafardoust, MD
role: STUDY_DIRECTOR
affiliation: Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.
name: Somaieh Kazemnejad
role: STUDY_CHAIR
affiliation: Nanbiotechnology Research Center Avicenna Research Institute, ACECR, Tehran, Iran.
name: Mina Fathi Kazerooni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: