InfertilityFAPPORNCT02354963
Follicular Activation in Poor Responders
A study testing In vitro fragmentation of the ovarian tissue in people with Infertility, run by César Díaz García at 1 site in Spain.
Trial summary
This study aims to assess whether activation of primordial follicles through ovarian cortex fragmentation may increase the number of antral follicles present in the ovary of patients with diminished ovarian reserve. Secondary outcomes include number of oocytes retrieved and pregnancy rates after IVF. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- In vitro fragmentation of the ovarian tissue
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteSpain
- Study dates
- Nov 2014to Dec 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- At least two episodes of poor ovarian response (≤ 3 oocytes retrieved with a standard protocol).
- A previous IVF cycle with ≤ 3 oocytes (following a standard stimulation protocol) and presence of an abnormal ovarian reserve test (antral follicle count of ≤ 5 or antimüllerian hormone ≤ 5pm).
Who cannot join
- Patients under 18 or over 40 years.
- Clinical signs of endometriosis.
- Previous ovarian surgery.
- Genital tract malformations.
- Anovulatory patient (defined by the presence of irregular cycles and serum progesterone ≤ 10 ng / mL on cycle day 21).
- Partner with severe male factor: severe oligoasthenozoospermia, oligoasthenoteratozoospermia and azoospermia.
- All those patients who do not voluntarily give their express written consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Follicle Activation in Patients With Poor Ovarian Response Through Fragmentation of the Ovarian Tissue.
This study aims to assess whether activation of primordial follicles through ovarian cortex fragmentation may increase the number of antral follicles present in the ovary of patients with diminished ovarian reserve. Secondary outcomes include number of oocytes retrieved and pregnancy rates after IVF.
Hypothesis; Evaluate whether the proposed intervention increases the pool of antral follicles (potentially stimulable ones).
Read the detailed description
Controlled, randomized, assessor-blind clinical trial.
Thirty-six patients of La Fe University Hospital (Valencia), previously confirmed as poor responders according to the European Society of Human Reproduction and Embryology (ESHRE) criteria, will be randomized to two treatment arms:
- Arm 1 (control): no intervention.
- Arm 2 (intervention): ovarian cortex extraction by unilateral laparoscopic biopsy and ovarian tissue fragmentation in aliquots of 1 mm2. These fragments will be grafted under the ovarian cortex and meso-ovarium ipsilateraly.
Subsequently the number of antral follicles in both intervention groups will be compared and also will be the number of antral follicles in the native ovary and the grafted one in each of the patients.
Patients will receive a standard IVF treatment for poor responders according to the protocols of the assisted reproduction unit of La Fe University Hospital.
The final aim is to assess the pregnancy rate in both groups, as well as parameters related to the reproduction technique when required.
- Conditions
- Infertility
- Being tested
- In vitro fragmentation of the ovarian tissue
- Keywords
- Poor ovarian response, Salvador/Warts/Hippo pathway, Follicular activation, Poor ovarian reserve
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
In vitro fragmentation of the ovarian tissueProcedure or surgery
Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
| Study group | Role | What they receive |
|---|---|---|
| Control arm | No intervention | No intervention is performed. Assessment of antral follicle count. IVF treatment. |
| Experimental arm | Experimental | Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue.
Assessment of antral follicle count. IVF treatment. Receives: Procedure: In vitro fragmentation of the ovarian tissue |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Metaphase II (MII)
Number of mature MII oocytes retrieved in the IVF cycles after triggering.
Measured: 36 hours after triggering
Secondary outcomes (9)
Total Antral Follicle Count (AFC) - Initial Measure
AFC assessment was done on day 2-5 of the menstrual cycle. Ultrasound scan was performed using a GE iVoluson (General Electric, Spain) equipped with a 3D vaginal probe (6.5-9MHz). A bilateral two-dimensional scan was performed and the mean of the two largest diameters of each intra-ovarian avascular anechoic image was recorded. Antral follicles with a mean diameter from 2 to 10 mm were counted to establish AFC. Initial data refers to the measure taken before treatment.
Measured: Baseline, day 2-5 of the menstrual cycle prior to treatment
Total Antral Follicle Count (AFC) - Final
AFC assessment was done on day 2-5 of the menstrual cycle and was followed for 6-month. To determine AFC, ultrasound scan was performed using a GE iVoluson (General Electric, Spain) equipped with a 3D vaginal probe (6.5-9MHz). A bilateral two-dimensional scan was performed and the mean of the two largest diameters of each intra-ovarian avascular anechoic image was recorded. Antral follicles with a mean diameter from 2 to 10 mm were counted to establish AFC. Final measure refers to the AFC count after ovarian fragmentation treatment.
Measured: Day 2-5 of the menstrual cycle 6 months after treatment
Initial Antimüllerian Hormone (AMH) Levels
AMH levels were determined on day 2-5 of the menstrual cycle to establish the initial baseline levels for each patient. A microparticle immunoassay kit integrated in the ABBOTT AxSYM® Plus system and software 5.20 (Abbott Laboratories, Abbot Park, IL, USA) was used to determine AMH levels prior treatment.
Measured: Baseline, day 2-5 of the menstrual cycle prior to treatment
Final AMH Levels
AMH levels were determined using a microparticle immunoassay kit integrated in the ABBOTT AxSYM® Plus system and software 5.20 (Abbott Laboratories, Abbot Park, IL, USA) 6 months after recruitment or basaline assessment.
Measured: Day 2-5 of the menstrual cycle 6 months after the treatment
Number of Cancelled IVF Cycles
Number of cancelled IVF cycles for low or no response to controlled ovarian stimulation. Cycles were cancelled because of a lack of an adequate follicular formation (one follicle of at least 17 mm) the day of triggering.
Measured: End of stimulation cycle (less than or equal to 30 days)
Fertilization Rate
All the mature oocytes retrieved were inseminated by intracytoplasmic sperm injection (ICSI). Percentage of successfully fertilized oocytes were registered 18 hours after oocyte insemination.
Measured: 18 hours after insemination
Number of Cycles With Embryo Transfer (ET)
One or 2 embryos were transferred on day 3 after egg collection. This outcome represents the number of cycles that culminate with embryo transfer.
Measured: On day 3 after egg collection
Number and Percentage of Cycles With Clinical Pregnancy
Clinical pregnancy was defined as the presence of a gestational sac and heart beat under ultrasonography
Measured: 6 weeks after embryo transfer
Live Birth Rate
Live birth rate was calculated by dividing the number of patients who achieved live birth in each cycle by the number of patients who initiated that cycle
Measured: 9 months or birth of one or more live babies
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2015 (estimated)
- Study startNov 2014
- Primary completionFeb 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)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
- Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- César Díaz García
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, César Díaz García, Instituto de Investigacion Sanitaria La Fe
- Investigators
- Cesar Diaz-Garcia, MD, Principal investigator, La Fe University Hospital. University of Valencia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02354963
- Sponsor's protocol ID
- FAPPOR (2014/0004)
- Acronym
- FAPPOR
- Status last verified
- Mar 2023
- First submitted
- 22 Jan 2015
- Last updated
- 8 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Diaz-Garcia C, Herraiz S, Pamplona L, Subira J, Soriano MJ, Simon C, Seli E, Pellicer A. Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trial. Fertil Steril. 2022 Apr;117(4):747-755. doi: 10.1016/j.fertnstert.2021.12.034.
PubMed 35367015
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Follicle Activation in Patients With Poor Ovarian Response Through Fragmentation of the Ovarian Tissue.
- ClinicalTrials.gov ID
- NCT02354963
- Acronym / sponsor ID
- FAPPOR / FAPPOR (2014/0004)
- Conditions
- Infertility
- Keywords
- Poor ovarian response, Salvador/Warts/Hippo pathway, Follicular activation, Poor ovarian reserve
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- César Díaz GarcíaUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Feb 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 3 Feb 2015 (estimated)
- Results
- Posted 8 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to assess whether activation of primordial follicles through ovarian cortex fragmentation may increase the number of antral follicles present in the ovary of patients with diminished ovarian reserve. Secondary outcomes include number of oocytes retrieved and pregnancy rates after IVF.
Hypothesis; Evaluate whether the proposed intervention increases the pool of antral follicles (potentially stimulable ones).
Detailed description
Controlled, randomized, assessor-blind clinical trial.
Thirty-six patients of La Fe University Hospital (Valencia), previously confirmed as poor responders according to the European Society of Human Reproduction and Embryology (ESHRE) criteria, will be randomized to two treatment arms:
- Arm 1 (control): no intervention.
- Arm 2 (intervention): ovarian cortex extraction by unilateral laparoscopic biopsy and ovarian tissue fragmentation in aliquots of 1 mm2. These fragments will be grafted under the ovarian cortex and meso-ovarium ipsilateraly.
Subsequently the number of antral follicles in both intervention groups will be compared and also will be the number of antral follicles in the native ovary and the grafted one in each of the patients.
Patients will receive a standard IVF treatment for poor responders according to the protocols of the assisted reproduction unit of La Fe University Hospital.
The final aim is to assess the pregnancy rate in both groups, as well as parameters related to the reproduction technique when required.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control arm | No intervention | –No intervention is performed. Assessment of antral follicle count. IVF treatment. |
| Experimental arm | Experimental | Procedure: In vitro fragmentation of the ovarian tissuePerform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- At least two episodes of poor ovarian response (≤ 3 oocytes retrieved with a standard protocol).
- A previous IVF cycle with ≤ 3 oocytes (following a standard stimulation protocol) and presence of an abnormal ovarian reserve test (antral follicle count of ≤ 5 or antimüllerian hormone ≤ 5pm).
Key exclusion criteria (7 listed)
- Patients under 18 or over 40 years.
- Clinical signs of endometriosis.
- Previous ovarian surgery.
- Genital tract malformations.
- Anovulatory patient (defined by the presence of irregular cycles and serum progesterone ≤ 10 ng / mL on cycle day 21).
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 |
|---|---|---|
| In vitro fragmentation of the ovarian tissueUnilateral ovarian cortex extraction, in vitro fragmentation and reimplantation. | Procedure or surgery | Experimental arm |
Primary outcome
Number of Metaphase II (MII)
Time frame: 36 hours after triggering
Number of mature MII oocytes retrieved in the IVF cycles after triggering.
9 secondary outcomes
Total Antral Follicle Count (AFC) - Initial Measure
Time frame: Baseline, day 2-5 of the menstrual cycle prior to treatment
Total Antral Follicle Count (AFC) - Final
Time frame: Day 2-5 of the menstrual cycle 6 months after treatment
Initial Antimüllerian Hormone (AMH) Levels
Time frame: Baseline, day 2-5 of the menstrual cycle prior to treatment
Final AMH Levels
Time frame: Day 2-5 of the menstrual cycle 6 months after the treatment
Number of Cancelled IVF Cycles
Time frame: End of stimulation cycle (less than or equal to 30 days)
Fertilization Rate
Time frame: 18 hours after insemination
Number of Cycles With Embryo Transfer (ET)
Time frame: On day 3 after egg collection
Number and Percentage of Cycles With Clinical Pregnancy
Time frame: 6 weeks after embryo transfer
Live Birth Rate
Time frame: 9 months or birth of one or more live babies
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35367015Diaz-Garcia C, Herraiz S, Pamplona L, Subira J, Soriano MJ, Simon C, Seli E, Pellicer A. Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trial. Fertil Steril. 2022 Apr;117(4):747-755. doi: 10.1016/j.fertnstert.2021.12.034.
Related trials for Infertility
Active, not recruitingObservational study
Fresh Versus Vitrified-Warmed Donor Oocytes: Embryological and Clinical Outcomes
Infertility, Donor Oocyte Assisted Reproduction
RecruitingPhase 3
A Study to Compare the Efficacy and Safety of Follitropin Alfa/Lutropin Alfa Versus hMG in Japanese Participants With LH and FSH Deficiency Undergoing ART (HINATA)
Infertility
RecruitingObservational study
Safety and Efficacy of Corifollitropin Alfa N02 Injection in Elderly Women Undergoing Assisted Reproductive Technology (ART)
Infertility
Active, not recruiting
Automation of the In Vitro Fertilization Laboratory
Infertility, ART
Not yet recruiting
Implementing IVM for Fertility Treatment in Clinical Practice
Infertility
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.
Cesar Diaz-Garcia, MD principal investigator
La Fe University Hospital. University of Valencia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing In vitro fragmentation of the ovarian tissue in people with Infertility, run by César Díaz García at 1 site in Spain.
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 2 inclusion and 7 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 8 Jan 2024. 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 Spain. 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?
Yes. Results are posted in the registry (first posted 8 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Metaphase II (MII) (time frame: 36 hours after triggering). 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 NCT02354963, which also lists 1 linked publication.
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 8 Jan 2024.