CD133 Transplantation to Generate Oocytes in Poor Ovarian Reserve

Ovarian Reserve Clinical Trial

Official title:

CD133+ Autologue Transplantation to Promote Ovarian Follicles Development in Women With Poor Ovarian Reserve.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01966536
• Other study ID #: Neofol2013
• Status: Withdrawn
• Phase: N/A
• First received: October 17, 2013
• Last updated: September 11, 2014
• Start date: November 2013
• Est. completion date: June 2015

Study information

• Verified date: September 2014
• Source: Hospital Universitario La Fe
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Women delay maternity and, as a consequence, available oocyte number and their quality decrease (9-18% of all IVF patients). Different treatment protocols have been developped nevertheless none of them optimal: the number of oocytes retrieved depends on the present ones. New generation of oocytes and follicles has been defended by some authors and bone marrow seems to be involved. What seems crucial is the niche that produces paracrine signals able to activate dormant cells and to attract undifferentiated cells from other tissues (homing). This phenomenon has been described by our group in other human reproductive tissues like endometrium. The purpose of the study is to improve ovarian reserve in unfertile women with poor ovarian reserve by means of bone marrow protective capacity.

CD133+ cells obtained from bone marrow will be delivered into the ovarian artery allowing them to colonize ovarian niche.

The study hypothesis is that CD133+ cells will improve ovarian reserve differentiating themselves into germ cells or, more likely, stimulating the niche to activate dormant follicles.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2015
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• < or= 40 years old

• FSH<15UI/L

• poor ovarian response after controlled ovarian stimulation with conventional doses (<3 oocytes) or two episodes of poor ovarian response after ovarian stimulation with maximal doses even if young or normal ovarian reserve study.

• Antral follicle count>2

• >1 antral follicle in the perfunded ovary

• AMH between 0,5 and 1pmol/L

• regular menstrual bleeding each 21-35 days

• To be candidate to autologous hematopoietic progenitors transplantation

Exclusion Criteria:

• Ovarian endometriosis

• Anovulation

• Any ovarian surgery considered risk factor of low ovarian response.

• Genetic factors associated to low ovarian response (Turner syndrome, FMR1 mutations...)

• Adquired conditions determining low response (chemotherapy, radiotherapy...)

• BMI > or = 30kg/m2

• Allergie to iodine

• Kidney failure

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Reserve

Intervention

Procedure:
• CD133+ cells transplantation into ovarian artery of one ovary

Locations

Country	Name	City	State
Spain	Hospital Universitario y Politécnico La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario La Fe

Country where clinical trial is conducted

Spain, 

References & Publications (15)

Bhartiya D, Sriraman K, Parte S. Stem cell interaction with somatic niche may hold the key to fertility restoration in cancer patients. Obstet Gynecol Int. 2012;2012:921082. doi: 10.1155/2012/921082. Epub 2012 Apr 2. — View Citation

Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ. Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature. 2006 Jun 29;441(7097):1109-14. Epub 2006 Jun 14. — View Citation

Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G, Nikitin AY. Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature. 2013 Mar 14;495(7440):241-5. doi: 10.1038/nature11979. Epub 2013 Mar 6. — View Citation

Garcia-Velasco JA, Isaza V, Requena A, Martínez-Salazar FJ, Landazábal A, Remohí J, Pellicer A, Simón C. High doses of gonadotrophins combined with stop versus non-stop protocol of GnRH analogue administration in low responder IVF patients: a prospective, randomized, controlled trial. Hum Reprod. 2000 Nov;15(11):2292-6. — View Citation

Gargett CE, Healy DL. Generating receptive endometrium in Asherman's syndrome. J Hum Reprod Sci. 2011 Jan;4(1):49-52. — View Citation

Hong H, Yen HY, Brockmeyer A, Liu Y, Chodankar R, Pike MC, Stanczyk FZ, Maxson R, Dubeau L. Changes in the mouse estrus cycle in response to BRCA1 inactivation suggest a potential link between risk factors for familial and sporadic ovarian cancer. Cancer Res. 2010 Jan 1;70(1):221-8. doi: 10.1158/0008-5472.CAN-09-3232. Epub 2009 Dec 22. — View Citation

Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, Tschudy KS, Tilly JC, Cortes ML, Forkert R, Spitzer T, Iacomini J, Scadden DT, Tilly JL. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 2005 Jul 29;122(2):303-15. — View Citation

Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004 Mar 11;428(6979):145-50. Erratum in: Nature. 2004 Aug 26;430(7003):1062. — View Citation

La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010 Mar-Apr;16(2):113-30. doi: 10.1093/humupd/dmp036. Epub 2009 Sep 30. Review. — View Citation

Li J, Kawamura K, Cheng Y, Liu S, Klein C, Liu S, Duan EK, Hsueh AJ. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10280-4. doi: 10.1073/pnas.1001198107. Epub 2010 May 17. — View Citation

Munné S, Cohen J, Sable D. Preimplantation genetic diagnosis for advanced maternal age and other indications. Fertil Steril. 2002 Aug;78(2):234-6. — View Citation

Nagori CB, Panchal SY, Patel H. Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman's syndrome. J Hum Reprod Sci. 2011 Jan;4(1):43-8. doi: 10.4103/0974-1208.82360. — View Citation

Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004 Jul 7;292(1):81-5. — View Citation

White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012 Feb 26;18(3):413-21. doi: 10.1038/nm.2669. — View Citation

Zeng H, Li L, Chen JX. Overexpression of angiopoietin-1 increases CD133+/c-kit+ cells and reduces myocardial apoptosis in db/db mouse infarcted hearts. PLoS One. 2012;7(4):e35905. doi: 10.1371/journal.pone.0035905. Epub 2012 Apr 27. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ovarian reserve	Measured by FSH-LH, oestradiol, AMH, antral follicle count	6 months	Yes
Secondary	Ovarian response to stimulation for oocyte retrieval	Number of MII oocytes obtained	6 months	Yes