Autologous Bone Marrow Transplantation for Premature Ovarian Insufficiency

Study Overview
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Brief Summary
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Currently, There is no treatment for Premature ovarian insufficiency (POI). Very small embryonic-like stem cells (VSELs) are found in the ovary. VSELs are able to regenerate the affected ovary. Stimulation was achieved by injection of mesenchymal stem cells that is supposed to secrete trophic factors. Numerous studies in mice have proved the efficacy of bone marrow transplantation (BMT) in resuming the ovarian function after chemotherapy-induced ovarian insufficiency. Allogeneic BMT raised the moral conflict about the origin of the newly developed oocytes. Several small studies examined the use of autologous BMT both in animal and in human. The results of these studies were promising. Intravenous injection is simpler and less invasive than ovarian injection as the later involves the use of laparoscopy. However, intravenous injection has not tested until now.

Detailed Description
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Premature ovarian insufficiency (POI) has no curative treatment until now. It was noticed that some cases of POI to recover spontaneously. Furthermore, the concept of fixed prenatal pool of oogonia has been challenged and postnatal neo-oogenesis is currently proved. Very small embryonic-like stem cells (VSELs) are found in the ovary. VSELs are stem cells that have noticed to survive chemotherapy induced gonadal insufficiency. Data from animal studies showed that stimulation of these stem cells result in regeneration of the affected ovary. Stimulation was achieved by injection of mesenchymal stem cells that is supposed to secrete trophic factors. Numerous studies in mice have proved the efficacy of bone marrow transplantation (BMT) in resuming the ovarian function after chemotherapy-induced ovarian insufficiency. These studies have been followed by researches on human being. Human studies included the use of stem cells from different sites including BM, adipose tissue, and umbilical cord. Allogeneic BMT raised the moral conflict about the origin of the newly developed oocytes. Although studies proved that these newly developed oocytes to be genetically traced to the recipient; some other studies showed that the newly developed oocytes originate from the donor BM. Several small studies examined the use of autologous BMT both in animal and in human. The results of these studies were promising. Use of autologous BMT also avoids the need for chemotherapy for conditioning and other related complications associated with allogeneic BMT. Human studies mostly used the ovarian injection of the BM. Intravenous injection is simpler and less invasive than ovarian injection as the later involves the use of laparoscopy. However, intravenous injection has not tested until now.

Official Title
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Autologous Bone Marrow Transplantation for Treatment of Premature Ovarian Insufficiency

Conditions
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Premature Ovarian Failure

Intervention / Treatment
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* Other: Autologous bone marrow transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with POI: For the purpose of the research women is considered to have POI if she is aged less than 40 years and has amenorrhea of at least 4 month with FSH level above 25 IU/L (repeated twice >4 weeks apart). Exclusion Criteria: Abnormal karyotype Previous pelvic or abdominal radiotherapy Previous surgical management of ovarian pathology Chronic disease: renal, liver, cardiac, malignancy

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous bone marrow transplantation<br>autologous bone marrow will be given by intravenous infusion. the intervention will be preceded by a period of 6 months of follow up the a period of 12 months follow up | Other: Autologous bone marrow transplantation<br>* Bone marrow aspiration of 10 ml/kg is done from the posterior iliac crest. The sample is put in sterile container with appropriate amount of heparin then filtered to remove bone spicules, fat, and cellular debris. The filtered sample is injected unprocessed in a peripheral vein. The process is done once.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| menses | return of menses in a woman with previous ameneorrhea of at least 4 months before recruitment and during the 6 months of the pretest period | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy | Occurrence of pregnancy during the period of 12 months of the post-test follow up | 12 months | 
| FSH | normalization of FSH (below 10 IU/L) | 12 months | 
| Antimullarian hormone (AMH) | normalization of AMH (above 0.9 ng/mL) | 12 months | 
| follicular activity | Growth of ovarian follicles to a size at least 18 mm in diameter | 12 months | 
| Endometrial thickness | Increase in endometrial thickness at least 8 mm. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian insufficiency Bone Marrow