Autologous Bone Marrow Transplantation for Premature Ovarian Insufficiency

Premature Ovarian Failure Clinical Trial

— BMT-POI  

Official title:

Autologous Bone Marrow Transplantation for Treatment of Premature Ovarian Insufficiency

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02779374
• Other study ID #: OBGYN002
• Status: Terminated
• Phase: N/A
• Start date: July 2016
• Est. completion date: June 2018

Study information

• Verified date: September 2021
• Source: South Valley University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: June 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Menopause, Premature
• Premature Birth
• Premature Ovarian Failure
• Primary Ovarian Insufficiency

Intervention

Other:
• Autologous bone marrow transplantation
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.

Locations

Country	Name	City	State
Egypt	South Valley University, Qena Faculty of Medicine, Obstetrics and Gynecology Department	Qena

Sponsors (1)

Lead Sponsor	Collaborator
South Valley University

Country where clinical trial is conducted

Egypt, 

References & Publications (9)

Bhartiya D, Anand S, Parte S. VSELs may obviate cryobanking of gonadal tissue in cancer patients for fertility preservation. J Ovarian Res. 2015 Nov 17;8:75. doi: 10.1186/s13048-015-0199-2. — View Citation

Dan S, Haibo L, Hong L. Pathogenesis and stem cell therapy for premature ovarian failure. OA Stem Cells 2014 Feb 10;2(1):4.

Edessy M, Hosni HN, Shady Y, Waf Y, Bakr S, Kamel M. Autologous stem cells therapy, the first baby of idiopathic premature ovarian failure. Acta Medica International. 2016;3(1):19-23.

Ghadami M, El-Demerdash E, Zhang D, Salama SA, Binhazim AA, Archibong AE, Chen X, Ballard BR, Sairam MR, Al-Hendy A. Bone marrow transplantation restores follicular maturation and steroid hormones production in a mouse model for primary ovarian failure. PLoS One. 2012;7(3):e32462. doi: 10.1371/journal.pone.0032462. Epub 2012 Mar 7. — View Citation

Hanna CB, Hennebold JD. Ovarian germline stem cells: an unlimited source of oocytes? Fertil Steril. 2014 Jan;101(1):20-30. doi: 10.1016/j.fertnstert.2013.11.009. Review. — View Citation

Hershlag A, Schuster MW. Return of fertility after autologous stem cell transplantation. Fertil Steril. 2002 Feb;77(2):419-21. — View Citation

Lee HJ, Selesniemi K, Niikura Y, Niikura T, Klein R, Dombkowski DM, Tilly JL. Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure. J Clin Oncol. 2007 Aug 1;25(22):3198-204. — View Citation

Santiquet N, Vallières L, Pothier F, Sirard MA, Robert C, Richard F. Transplanted bone marrow cells do not provide new oocytes but rescue fertility in female mice following treatment with chemotherapeutic agents. Cell Reprogram. 2012 Apr;14(2):123-9. doi: 10.1089/cell.2011.0066. — View Citation

Vassena R, Eguizabal C, Heindryckx B, Sermon K, Simon C, van Pelt AM, Veiga A, Zambelli F; ESHRE special interest group Stem Cells. Stem cells in reproductive medicine: ready for the patient? Hum Reprod. 2015 Sep;30(9):2014-21. doi: 10.1093/humrep/dev181. Epub 2015 Jul 22. Review. — View Citation

Outcome

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