Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure

Premature Ovarian Failure (POF) Clinical Trial

— ASCOT-2  

Official title:

Autologous Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure Patients. Pilot Study ASCOT-2

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03535480
• Other study ID #: 2017/0251
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 2018
• Est. completion date: June 2022

Study information

• Verified date: May 2018
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: Monica Romeu, Doctor
• Phone: +34961244000
• Email: monicaromeuvillarroya[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to recover ovarian function in POF/POI patients. With this pueprose we designed a study protocol including two arms: ASCOT arm, were patients receive the stem cell mobilization treatment with Granulocyte colony stimulating factor (G-CSF) followed by apheresis and ovarian artery catheterism to selectively infuse the stem cells into the ovary and the G-CSF arm including patients that receive the mobilization treatment but not the ovarian artery catheterism to selectively infuse the cells into the ovary.

Description:

Ovarian aging appears early in life as a decline in function at 30s leading to a complete ovarian failure around 51 years of age in women. Women in modern society have delayed the age of childbearing due to socioeconomic changes and patient´s age has become the main determinant of infertility, since it is well known that both quantity and quality of the oocytes from aging patients are seriously impaired. Nevertheless, the low ovarian reserve is not only associated with age. Primary ovarian insufficiency (POI) is a cause of infertility in women, affecting 1% of the population. It is characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women younger than 40 years of age. Impairment of ovarian function in POI can be mixed up with a low ovarian reserve or poor ovarian response although represent different clinical entities and patients.

Thus, interventions to recover damaged gonads in POI patients should be developed in order to enhance their reproductive potential. Clinically, bone marrow (BM) transplant in patients with POI due to chemotherapy treatment rescues ovarian functions as demonstrated by several spontaneous pregnancies. Previous research demonstrates that autologous stem cell ovarian transplantation (ASCOT) improves ovarian reserve (AMH and AFC) in 81% of women. Three of the eleven included patients achieve 5 pregnancies and 3 healthy babies have born. Response is highly variable between patients and molecular mechanisms still unknown. New approach is mandatory to elucidate them.

Results obtained in our premature ovarian failure (POF) animal model (included chemotherapy, CT ovarian injury) demonstrate that bone marrow stem cells restore ovulation by means of increasing vascularization, proliferation and diminishing apoptosis within the ovarian niche. These ovarian niche improvements promotes follicular development, increased number of antral and preovulatory follicles and corpus luteum.

POF model is ideal to demonstrate effectivity of ASCOT technique as they represent the worst possible scene. Any improvement in those patients should be significant.

Trying to be less invasive, we designed a study protocol including two arms: ASCOT arm as previously described and Granulocyte colony stimulating factor (G-CSF) arm including patients that receive the treatment but not the apheresis nor the ovarian artery catheterism to selectively infuse the cells into the ovary.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: June 2022
• Est. primary completion date: June 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 38 Years

Eligibility

Inclusion Criteria:

• = 38 years old

• Oligo/Amenorrhea at least 4 months.

• Serum FSH > 25 IU/l, AMH < 5picomols (pM)

• Standard criteria for autologous bone marrow transplantation of our hospital.

Exclusion Criteria:

• Ovarian endometriosis

• Any ovarian surgery considered as risk factor of poor reserve.

• Genetic factors associated with poor ovarian reserve (Turner syndrome, FMR1 premutations…)

• Acquired poor ovarian reserve (Chemotherapy, radiotherapy...)

• BMI = 30kg/m2.

• Iodine allergy

• Kidney failure

• Severe male factor

Related Conditions & MeSH terms

• Menopause, Premature
• Premature Birth
• Premature Ovarian Failure (POF)
• Primary Ovarian Insufficiency

Intervention

Drug:
• G-CSF
G-CSF subcutaneously during five days

Combination Product:
• ASCOT
G-CSF subcutaneously during five days, aphaeresis to hematopoietic stem cell collection and catheterism for ovarian artery infusion

Locations

Country	Name	City	State
Spain	Hospital Universitario y Politécnico la Fe-IIS la Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antral follicle count (AFC)	every antral follicle is measured	6 months
Secondary	Time to Menses recovery	Spontaneous menstrual cycle restoration and its characteristics	6 months
Secondary	serum follicle stimulating hormone (FSH) and estradiol	serum extraction for biological measurements	6 months
Secondary	ovarian reserve dynamics	ultrasound observation of follicular development	6 months
Secondary	Controlled Ovarian Hyperstimulation (COH) response	ovarian response to gonadotropins	6 months
Secondary	pregnancy rate	pregnancy rate spontaneous and after COH	2 years
Secondary	Number of good quality embryos	Morphological criteria and developmental potential	6 months
Secondary	Number of participants with treatment-related adverse events	Secondary effects of the received interventions following hematological and gynecological medical criteria	6 months