Clinical trial NCT03535480: Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
Official title: Autologous Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure Patients. Pilot Study ASCOT-2
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Premature Ovarian Failure (POF)
Keywords: ovarian reserve
Lead sponsor: Instituto de Investigacion Sanitaria La Fe
Sponsor class: OTHER
First posted: 2018-05-24
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Antral follicle count (AFC)
timeFrame: 6 months
Secondary outcomes:
measure: Time to Menses recovery
timeFrame: 6 months
measure: serum follicle stimulating hormone (FSH) and estradiol
timeFrame: 6 months
measure: ovarian reserve dynamics
timeFrame: 6 months
measure: Controlled Ovarian Hyperstimulation (COH) response
timeFrame: 6 months
measure: pregnancy rate
timeFrame: 2 years
measure: Number of good quality embryos
timeFrame: 6 months
measure: Number of participants with treatment-related adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico la Fe-IIS la Fe
Study officials:
affiliation: IIS la Fe
name: Antonio Pellicer, Professor
role: PRINCIPAL_INVESTIGATOR
References: