CD133 Transplantation to Generate Oocytes in Poor Ovarian Reserve

NCT ID: NCT01966536

Last Updated: 2014-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2015-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Ovarian Reserve

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Poor ovarian reserve

Autologous transplantation of CD133+ cells into ovarian artery

Group Type EXPERIMENTAL

CD133+ cells transplantation into ovarian artery of one ovary

Intervention Type PROCEDURE

Interventions

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CD133+ cells transplantation into ovarian artery of one ovary

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Hospital Universitario La Fe

OTHER

Sponsor Role lead

Responsible Party

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Dr. Antonio Pellicer Martínez

Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Antonio Pellicer, Doctor

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Fe

Locations

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Hospital Universitario y Politécnico La Fe

Valencia, Valencia, Spain

Site Status

Countries

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Spain

References

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Munne S, Cohen J, Sable D. Preimplantation genetic diagnosis for advanced maternal age and other indications. Fertil Steril. 2002 Aug;78(2):234-6. doi: 10.1016/s0015-0282(02)03239-9. No abstract available.

Reference Type BACKGROUND
PMID: 12137856 (View on PubMed)

Garcia-Velasco JA, Isaza V, Requena A, Martinez-Salazar FJ, Landazabal A, Remohi J, Pellicer A, Simon 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. doi: 10.1093/humrep/15.11.2292.

Reference Type BACKGROUND
PMID: 11056121 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19793843 (View on PubMed)

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. doi: 10.1038/nature02316.

Reference Type BACKGROUND
PMID: 15014492 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22366948 (View on PubMed)

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. doi: 10.1016/j.cell.2005.06.031.

Reference Type BACKGROUND
PMID: 16051153 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20028858 (View on PubMed)

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. doi: 10.1038/nature04929. Epub 2006 Jun 14.

Reference Type BACKGROUND
PMID: 16799565 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20479243 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22548074 (View on PubMed)

Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004 Jul 7;292(1):81-5. doi: 10.1001/jama.292.1.81.

Reference Type BACKGROUND
PMID: 15238594 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21772740 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 21772741 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22558265 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23467088 (View on PubMed)

Other Identifiers

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Neofol2013

Identifier Type: -

Identifier Source: org_study_id

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