InfertilityNCT02792569
Follicle Activation by Inhibition of the Hippo Pathway
A study testing Biopsy of ovarian cortical tissue in people with Infertility, run by Anders Nyboe Andersen at 1 site in Denmark.
Trial summary
The aim of this project is to activate recruitment and growth of resting primordial follicles in the ovaries of women with diminished ovarian reserve, in attempt to increase the chance to become pregnant, either naturally or after assisted reproduction. Read more about this study
- Who is it for?
- Ages 25 to 39 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Biopsy of ovarian cortical tissue
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- Apr 2016to Jan 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Infertility with indication for IVF/ICSI
- Imminent POI, still cycling
- Age 25 - 39 years
- Two ovaries
- Serum AMH measurements < 5 pmol/l (two independent measurements)
- Antral follicle count (AFC) (sum of both ovaries < 5)
Who cannot join
- Ovarian pathology (endometriosis, cysts)
- Known chromosomal abnormality
- Known autoimmune disease (except TPO-antibodies)
- Patients who have contraindication for laparoscopy
Trial locations and contacts
1 site in 1 country.
Denmark1 site
The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital
Copenhagen, 2100
About this study
Official title: Auto-transplantation of Fragmented Ovarian Cortical Tissue in Infertile Patients With Premature Ovarian Oocyte Depletion - a Study to Promote Follicular Activation and Subsequent Fertility
The aim of this project is to activate recruitment and growth of resting primordial follicles in the ovaries of women with diminished ovarian reserve, in attempt to increase the chance to become pregnant, either naturally or after assisted reproduction.
Read the detailed description
For this study investigators will carefully select 20 women with low AMH and imminent POI.
They will be randomized to have cortical ovarian biopsies taken from either the left or right ovary. The biopsies will be fragmented in 1x1 mm2 pieces and immediately auto-transplanted in a peritoneal pocket under the right ovary.
The contralateral untouched ovary will act as the control, making each woman their own control.
Follow up: each week in 2,5 months the women will be assessed by transvaginal ultrasound and hormonal status. After 2,5-6 months the women will receive a FSH stimulation cycle (rFSH 300 IU or Corifollitropin) followed by standard IVF/ICSI,
Hypothesis: the ovaries contain a pool of resting primordial follicles. By fragmentation of cortical ovarian tissue, manipulation of the local environment in the tissue will inhibit the Hippo Pathway and hereby active recruitment and growth of primordial follicles.
- Conditions
- Infertility
- Being tested
- Biopsy of ovarian cortical tissue
- Keywords
- IVA, Hippo Pathway, Follicle activation, Low Responder, POI, Poor Ovarian Reserve, Poor Ovarian Response, Salvador/Warts/Hippo pathway
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy of ovarian cortical tissueProcedure or surgery
Biopsies will be taken from either right or left side. The cortical tissue will be isolated and fragmented in 1x1 mm2 pieces, followed by auto-transplantation to a peritoneal pocket.
| Study group | Role | What they receive |
|---|---|---|
| Biopsy at Right side | Experimental | Biopsy of ovarian cortical tissue (50% right side) Receives: Procedure: Biopsy of ovarian cortical tissue |
| Biopsy at Left side | Experimental | Biopsy of ovarian cortical tissue (50% left side) Receives: Procedure: Biopsy of ovarian cortical tissue |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of follicles > 12 mm
Number of follicles > 12 mm in response to controlled ovarian stimulation with corifollitropin from the biopsied ovary versus the contralateral untreated ovary
Measured: Up to 6 month after the auto-transplantation
Secondary outcomes (1)
Side of ovulation
Frequency of ovulations occurring at the "biopsy side" versus the contralateral side in the subsequent 4- 6 months
Measured: Up to 6 months after auto-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2016 (estimated)
- Study startApr 2016
- Primary completionDec 2018
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anders Nyboe Andersen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Anders Nyboe Andersen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Anders N Andersen, Professor, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02792569
- Sponsor's protocol ID
- H-15011975
- Status last verified
- Jan 2020
- First submitted
- 23 May 2016
- Last updated
- 30 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 24082083Hsueh AJ, Kawamura K, Cheng Y, Fauser BC. Intraovarian control of early folliculogenesis. Endocr Rev. 2015 Feb;36(1):1-24. doi: 10.1210/er.2014-1020. Epub 2014 Sep 9.
PubMed 25202833Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, Morimoto Y, Kawamura K. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015 Mar;30(3):608-15. doi: 10.1093/humrep/deu353. Epub 2015 Jan 6.
PubMed 25567618Lunding SA, Pors SE, Kristensen SG, Landersoe SK, Jeppesen JV, Flachs EM, Pinborg A, Macklon KT, Pedersen AT, Andersen CY, Andersen AN. Biopsying, fragmentation and autotransplantation of fresh ovarian cortical tissue in infertile women with diminished ovarian reserve. Hum Reprod. 2019 Oct 2;34(10):1924-1936. doi: 10.1093/humrep/dez152.
PubMed 31593582
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Auto-transplantation of Fragmented Ovarian Cortical Tissue in Infertile Patients With Premature Ovarian Oocyte Depletion - a Study to Promote Follicular Activation and Subsequent Fertility
- ClinicalTrials.gov ID
- NCT02792569
- Acronym / sponsor ID
- H-15011975
- Conditions
- Infertility
- Keywords
- IVA, Hippo Pathway, Follicle activation, Low Responder, POI, Poor Ovarian Reserve, Poor Ovarian Response, Salvador/Warts/Hippo pathway
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Anders Nyboe AndersenUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- Dec 2018 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 7 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this project is to activate recruitment and growth of resting primordial follicles in the ovaries of women with diminished ovarian reserve, in attempt to increase the chance to become pregnant, either naturally or after assisted reproduction.
Detailed description
For this study investigators will carefully select 20 women with low AMH and imminent POI.
They will be randomized to have cortical ovarian biopsies taken from either the left or right ovary. The biopsies will be fragmented in 1x1 mm2 pieces and immediately auto-transplanted in a peritoneal pocket under the right ovary.
The contralateral untouched ovary will act as the control, making each woman their own control.
Follow up: each week in 2,5 months the women will be assessed by transvaginal ultrasound and hormonal status. After 2,5-6 months the women will receive a FSH stimulation cycle (rFSH 300 IU or Corifollitropin) followed by standard IVF/ICSI,
Hypothesis: the ovaries contain a pool of resting primordial follicles. By fragmentation of cortical ovarian tissue, manipulation of the local environment in the tissue will inhibit the Hippo Pathway and hereby active recruitment and growth of primordial follicles.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Biopsy at Right side | Experimental | Procedure: Biopsy of ovarian cortical tissueBiopsy of ovarian cortical tissue (50% right side) |
| Biopsy at Left side | Experimental | Procedure: Biopsy of ovarian cortical tissueBiopsy of ovarian cortical tissue (50% left side) |
Who may qualify
- Ages
- 25 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Infertility with indication for IVF/ICSI
- Imminent POI, still cycling
- Age 25 - 39 years
- Two ovaries
- Serum AMH measurements < 5 pmol/l (two independent measurements)
Key exclusion criteria (4 listed)
- Ovarian pathology (endometriosis, cysts)
- Known chromosomal abnormality
- Known autoimmune disease (except TPO-antibodies)
- Patients who have contraindication for laparoscopy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biopsy of ovarian cortical tissueBiopsies will be taken from either right or left side. The cortical tissue will be isolated and fragmented in 1x1 mm2 pieces, followed by auto-transplantation to a peritoneal pocket. | Procedure or surgery | Biopsy at Left side, Biopsy at Right side |
Primary outcome
Number of follicles > 12 mm
Time frame: Up to 6 month after the auto-transplantation
Number of follicles > 12 mm in response to controlled ovarian stimulation with corifollitropin from the biopsied ovary versus the contralateral untreated ovary
1 secondary outcome
Side of ovulation
Time frame: Up to 6 months after auto-transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2020.
- Background: PubMed 24082083Kawamura 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.
- Background: PubMed 25202833Hsueh AJ, Kawamura K, Cheng Y, Fauser BC. Intraovarian control of early folliculogenesis. Endocr Rev. 2015 Feb;36(1):1-24. doi: 10.1210/er.2014-1020. Epub 2014 Sep 9.
- Background: PubMed 25567618Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, Morimoto Y, Kawamura K. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015 Mar;30(3):608-15. doi: 10.1093/humrep/deu353. Epub 2015 Jan 6.
- Derived from this study: PubMed 31593582Lunding SA, Pors SE, Kristensen SG, Landersoe SK, Jeppesen JV, Flachs EM, Pinborg A, Macklon KT, Pedersen AT, Andersen CY, Andersen AN. Biopsying, fragmentation and autotransplantation of fresh ovarian cortical tissue in infertile women with diminished ovarian reserve. Hum Reprod. 2019 Oct 2;34(10):1924-1936. doi: 10.1093/humrep/dez152.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anders N Andersen, Professor principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Biopsy of ovarian cortical tissue in people with Infertility, run by Anders Nyboe Andersen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of follicles > 12 mm (time frame: Up to 6 month after the auto-transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02792569, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2020.