CD133 Transplantation to Generate Oocytes in Poor Ovarian Reserve

NCT01966536 | Withdrawn

• 1 other identifier: Neofol2013
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ovarian Reserve

Outcome Measures

Primary Outcomes (1)

• Ovarian reserve

  Measured by FSH-LH, oestradiol, AMH, antral follicle count

  6 months

Secondary Outcomes (1)

• Ovarian response to stimulation for oocyte retrieval

  6 months

Study Arms (1)

Poor ovarian reserve

EXPERIMENTAL

Autologous transplantation of CD133+ cells into ovarian artery

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

Interventions

CD133+ cells transplantation into ovarian artery of one ovary PROCEDURE

Poor ovarian reserve

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \< 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Universitario La Fe: lead

Study Sites (1)

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46026, Spain

Location

Related Publications (15)

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  PMID: 15014492 BACKGROUND

• 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.

  PMID: 22366948 BACKGROUND

• 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.

  PMID: 16051153 BACKGROUND

• 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.

  PMID: 20028858 BACKGROUND

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  PMID: 16799565 BACKGROUND

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  PMID: 20479243 BACKGROUND

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  PMID: 22548074 BACKGROUND

• 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.

  PMID: 15238594 BACKGROUND

• 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.

  PMID: 21772740 BACKGROUND

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

  PMID: 21772741 BACKGROUND

• 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.

  PMID: 22558265 BACKGROUND

• 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.

  PMID: 23467088 BACKGROUND

Study Officials

• Antonio Pellicer, Doctor

  Hospital Universitario La Fe

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: October 21, 2013
• Study Start: November 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: June 1, 2015
• Last Updated: September 12, 2014

Record last verified: 2014-09

Locations

ES (1)