NCT02498210

Brief Summary

Poor ovarian response (POR) is one of the major therapeutic challenges in in vitro fertilization. Several therapeutic approaches for POR have been explored; yet, a single effective strategy has not yet been established. Recently, a live birth was reported after ovarian cortex fragmentation and in vitro disruption of the Hippo signaling pathway and activation of Akt signaling. During IVM procedure increased mechanical stimulation of the ovarian cortex takes place. , with the consequent disruption of the Hippo signaling pathway. Our aim is to investigate whether the mechanical manipulation and triggering of ovarian cortex caused by IVM can cause ovarian follicular activation and recruitment by the mechanisms mentioned above. Thus stimulation in the following regular IVF cycle will result in improved ovarian response and increased oocytes yield

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
25

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Oct 2016

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 31, 2015

Completed
2 months until next milestone

First Posted

Study publicly available on registry

July 15, 2015

Completed
1.2 years until next milestone

Study Start

First participant enrolled

October 1, 2016

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2020

Completed
Last Updated

November 27, 2019

Status Verified

November 1, 2019

Enrollment Period

3.8 years

First QC Date

May 31, 2015

Last Update Submit

November 26, 2019

Conditions

Infertility Female

Keywords

IVMHIPPO signaling

Outcome Measures

Primary Outcomes (1)

  • Number of oocytes

    IVF cycle after IVM results will be compared to the IVF cycle with poor ovarian response

    3 month

Study Arms (1)

IVF after IVM

EXPERIMENTAL

If the patients will not concive during the IVM cycle . results of this following IVF cycle will be compared to the initial IVF preformance Intervention : In Vitro Maturation Procedure

Other: In Vitro Maturation Procedure

Interventions

In Vitro Maturation ProcedureOTHER

POR patients will be treated in IVM cycle. After baseline evaluation on day 3, 150 IU/day recombinant FSH or HMG will be added for 3 days. A second evaluation will be performed on day 6 of the menstrual cycle. An injection of 10,000 IU hCG (Pregnyl; Organon, Oss, Holland) or Ovitrelle 250mcg (Merck Serono ) will be administered subcutaneously when the endometrial thickness will be ≥6 mm and the leading follicle will be at least 12 mm. Oocyte retrieval will be performed under ultrasound guidance with a 19G single-lumen aspiration needle (Cook; Queensland, Australia). The follicular fluid will be collected in culture tubes containing follicle flush buffer (Cook) with 2 IU/ml heparin. All aspirates were filtered to identify additional oocytes

IVF after IVM

Eligibility Criteria

Age25 Years - 45 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Poor ovarian response IVF cycle

You may not qualify if:

  • Normal ovarian response

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sheba Medical Center

Kiryat Ono, 5229910, Israel

RECRUITING

Related Publications (10)

  • Venetis CA, Kolibianakis EM, Tarlatzi TB, Tarlatzis BC. Evidence-based management of poor ovarian response. Ann N Y Acad Sci. 2010 Sep;1205:199-206. doi: 10.1111/j.1749-6632.2010.05665.x.

    PMID: 20840273BACKGROUND

  • Shanbhag S, Aucott L, Bhattacharya S, Hamilton MA, McTavish AR. Interventions for 'poor responders' to controlled ovarian hyperstimulation (COH) in in-vitro fertilisation (IVF). Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004379. doi: 10.1002/14651858.CD004379.pub2.

    PMID: 17253503BACKGROUND

  • STEIN IF Sr. The management of bilateral polycystic ovaries. Fertil Steril. 1955 May-Jun;6(3):189-205. doi: 10.1016/s0015-0282(16)31980-x. No abstract available.

    PMID: 14380378BACKGROUND

  • Farquhar C, Brown J, Marjoribanks J. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2012 Jun 13;(6):CD001122. doi: 10.1002/14651858.CD001122.pub4.

    PMID: 22696324BACKGROUND

  • Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho CH, Kawamura N, Tamura M, Hashimoto S, Sugishita Y, Morimoto Y, Hosoi Y, Yoshioka N, Ishizuka B, Hsueh AJ. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17474-9. doi: 10.1073/pnas.1312830110. Epub 2013 Sep 30.

    PMID: 24082083BACKGROUND

  • Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, Gayyed MF, Anders RA, Maitra A, Pan D. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 2007 Sep 21;130(6):1120-33. doi: 10.1016/j.cell.2007.07.019.

    PMID: 17889654BACKGROUND

  • Hergovich A. Mammalian Hippo signalling: a kinase network regulated by protein-protein interactions. Biochem Soc Trans. 2012 Feb;40(1):124-8. doi: 10.1042/BST20110619.

    PMID: 22260677BACKGROUND

  • Maman E, Meirow D, Brengauz M, Raanani H, Dor J, Hourvitz A. Luteal phase oocyte retrieval and in vitro maturation is an optional procedure for urgent fertility preservation. Fertil Steril. 2011 Jan;95(1):64-7. doi: 10.1016/j.fertnstert.2010.06.064. Epub 2010 Aug 5.

    PMID: 20688325BACKGROUND

  • Li J, Xu Y, Zhou G, Guo J, Xin N. Natural cycle IVF/IVM may be more desirable for poor responder patients after failure of stimulated cycles. J Assist Reprod Genet. 2011 Sep;28(9):791-5. doi: 10.1007/s10815-011-9597-6. Epub 2011 Jun 22.

    PMID: 21695516BACKGROUND

  • Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.

    PMID: 21505041BACKGROUND

MeSH Terms

Conditions

Infertility, Female

Condition Hierarchy (Ancestors)

Genital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesInfertility

Study Officials

  • Ettie Maman, MD

    Sheba Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ettie Maman, MD

CONTACT

972526666451ettiemaman@gmail.com

Raoul Orvieto, MD

CONTACT

972-53-7678933Raoul.Orvieto@sheba.health.gov.il

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 31, 2015

First Posted

July 15, 2015

Study Start

October 1, 2016

Primary Completion

July 1, 2020

Study Completion

July 1, 2020

Last Updated

November 27, 2019

Record last verified: 2019-11

Locations

IL(1)