Activation of Primordial FolliclesNCT04608695
Ovarian Needle Puncture for Follicle Activation in IVF Patients With Diminished Ovarian Reserve
A study testing Ovarian puncture in people with Activation of Primordial Follicles, run by Hacettepe University at 1 site in Turkey (Türkiye).
Trial summary
Premature ovarian insufficiency (POI), is cessation of ovarian function characterized by hypergonadotropic amenorrhea and hypoestrogenic syndrome before 40 years of age. About 1% of women younger than 40 years old and 0.1% before 30 are affected. Read more about this study
- Who is it for?
- Ages Up to 40 years, women only
- Conditions the study is for
- Activation of Primordial Follicles
- What is being tested?
- Ovarian puncture
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Jul 2020to 1 Sep 2023
- 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 Up to 40 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with diminished ovarian reserve
- <3 oocytes collected in previous cycle (with anti-mullerian hormone <0.5 ng/mL and/or antral follicle count <5)
- Cycles stimulated with flexible antagonist protocol
- Cycles triggered with recombinant hCG
- Fresh transfer cycles
- Patients with <40 years of age
- BMI <30 kg/m2
Who cannot join
- Preimplantation genetic testing
- Azospermia
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Hacettepe UniversityHacettepe University School of Medicine, Department of Ob/Gyn
Ankara, 06100
Sezcan Mumusoglu, Assoc. Prof., +905326404673, sezcanmumusoglu@gmail.com
Gurkan Bozdag, Prof.
About this study
Premature ovarian insufficiency (POI), is cessation of ovarian function characterized by hypergonadotropic amenorrhea and hypoestrogenic syndrome before 40 years of age. About 1% of women younger than 40 years old and 0.1% before 30 are affected. POI imposes a great challenge on women's reproductive and long-term health, such as infertility, amenorrhea, osteoporosis, and cardiovascular disease. Most patients already had impaired or complete loss of fecundity when diagnosed. Currently, no optimal regimen exists to ameliorate ovarian function. Typically, they end up with egg donation or adoption as an alternative way. Less severe form of POI is diminished ovarian reserve (DOR). Although lack of consensus according to Bologna criteria cut off for DOR was defined as (antral follicle count (AFC) <5-7 follicles or anti-Mullerian hormone (AMH) <0.5-1.1 ng/ml).
Previously it has been showed that 24% of women with POI had resumption of ovarian function and 4% resulted in baby births. These data indicates residual follicles are available in atrophic ovaries and have potential for development and even fertilization. In routine IVF practice 15% percent of patients have poor ovarian response to ovarian stimulation. Patients with DOR with a previous poor ovarian response (cycles cancelled or yielding ≤3 oocytes with a conventional protocol) might have benefit from the strategies increasing follicle activation and number of growing follicles and oocyte retrieved. Therefore, strategies enabling ovarian resumption predictable and follicle activation feasible are promising for POI/DOR treatment. Recently, In vitro Activation (IVA) approach has been proposed and live births have been achieved in patients with POI. Phosphatase and tensin homolog (PTEN) enzyme inhibitors and phosphatidylinositol-3 kinase activators could activate AKT pathway and activate the dormant follicles. Ovarian fragmentation could lead to ovarian primary follicle growth by interfering with Hippo signaling pathway. Residual follicles in patients with POI could be activated to develop for egg retrieval by combination of mechanical and chemical stimulation.
Read more
In 2019, Zhang et al retrospectively analyzed the follicle development and pregnancy outcome in 80 POI patients after laparoscopic ovarian biopsy/scratch without using chemical agents as was the case in IVA. 11 (13.75%) patients presented with ovarian function resumption, three metaphases II oocytes were retrieved in 10 patients and two embryos were formed and freshly transferred followed by a healthy singleton delivery in 1 (1.25%) patient. They concluded that the technique of ovarian biopsy/scratch without chemical activation could promote follicle development in vivo, suggesting it could bring promising benefits for some women with POI.
In patient with POI/DOR, activation of residual follicles is a promising option and further studies are warranted. Previous studies included laparoscopic surgery which may lead to possible surgical complications. Without using chemical agents and laparoscopic surgery, main object of this study is mechanical follicle activation with trans-vaginal ovarian needle puncture with 17 gauge oocyte pickup needle in IVF patients with DOR.
- Conditions
- Activation of Primordial Follicles
- Being tested
- Ovarian puncture
- Keywords
- Follicle Activation, Premature Ovarian Insufficiency, Diminished Ovarian Reserve, Ovarian Puncture
- Medical subject headings
- Primary Ovarian Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ovarian punctureProcedure or surgery
One side ovary of each patient included in the study, will be punctured 10 times under trans-vaginal ultrasound guidance with 17 gauge ovarian pick up needle, 1 month before the scheduled IVF cycle. Control group will be the other side ovary for each patient. Number of ≥ 14 mm follicle and collected oocytes will be compared.
| Study group | Role | What they receive |
|---|---|---|
| Control ovary | No intervention | Not described |
| Punctured ovary | Experimental | Not described Receives: Procedure: Ovarian puncture |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of ≥14 mm follicle
Number of ≥14 mm follicle on the trigger day
Measured: 4 month after intervention as a response to ovarian stimulation
Antral follicle count
Antral follicle count
Measured: 4 month after intervention on the second/third day of menstrual cycle
Secondary outcomes (1)
Number of collected oocytes
Number of collected oocytes on the oocyte pick-up day
Measured: 4 month after intervention as a response to ovarian stimulation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2020
- Study start1 Jul 2020
- Primary completion1 Jul 2023 (estimated)
- Study completion1 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Activation of Primordial FolliclesStudies of the same condition, open and under way.
- More trials run by Hacettepe UniversityThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hacettepe University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sezcan Mumusoglu, Hacettepe University
- Investigators
- Sezcan Mumusoğlu, Assoc. Prof., Principal investigator, Hacettepe University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04608695
- Sponsor's protocol ID
- HU02
- Status last verified
- Sep 2022
- First submitted
- 25 Oct 2020
- Last updated
- 21 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010 Sep 11;376(9744):911-21. doi: 10.1016/S0140-6736(10)60355-8. Epub 2010 Aug 11.
PubMed 20708256Torrealday S, Kodaman P, Pal L. Premature Ovarian Insufficiency - an update on recent advances in understanding and management. F1000Res. 2017 Nov 29;6:2069. doi: 10.12688/f1000research.11948.1. eCollection 2017.
PubMed 29225794Ferraretti AP, Gianaroli L. The Bologna criteria for the definition of poor ovarian responders: is there a need for revision? Hum Reprod. 2014 Sep;29(9):1842-5. doi: 10.1093/humrep/deu139. Epub 2014 Jul 9.
PubMed 25008235Bachelot A, Nicolas C, Bidet M, Dulon J, Leban M, Golmard JL, Polak M, Touraine P. Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency. Clin Endocrinol (Oxf). 2017 Feb;86(2):223-228. doi: 10.1111/cen.13105. Epub 2016 Jun 14.
PubMed 27177971Chen X, Chen SL, Ye DS, Liu YD, He YX, Tian XL, Xu LJ, Tao T. Retrospective analysis of reproductive outcomes in women with primary ovarian insufficiency showing intermittent follicular development. Reprod Biomed Online. 2016 Apr;32(4):427-33. doi: 10.1016/j.rbmo.2015.12.011. Epub 2016 Jan 14.
PubMed 26825246Kawamura K, Kawamura N, Hsueh AJ. Activation of dormant follicles: a new treatment for premature ovarian failure? Curr Opin Obstet Gynecol. 2016 Jun;28(3):217-22. doi: 10.1097/GCO.0000000000000268.
PubMed 27022685Zhang X, Han T, Yan L, Jiao X, Qin Y, Chen ZJ. Resumption of Ovarian Function After Ovarian Biopsy/Scratch in Patients With Premature Ovarian Insufficiency. Reprod Sci. 2019 Feb;26(2):207-213. doi: 10.1177/1933719118818906. Epub 2018 Dec 12.
PubMed 30541396
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ovarian Needle Puncture for Follicle Activation in IVF Patients With Diminished Ovarian Reserve
- ClinicalTrials.gov ID
- NCT04608695
- Acronym / sponsor ID
- HU02
- Conditions
- Activation of Primordial Follicles
- Keywords
- Follicle Activation, Premature Ovarian Insufficiency, Diminished Ovarian Reserve, Ovarian Puncture
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Hacettepe UniversityUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 1 Jul 2023 (estimated)
- Study completion
- 1 Sep 2023 (estimated)
- First posted
- 29 Oct 2020 (actual)
- 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.
Premature ovarian insufficiency (POI), is cessation of ovarian function characterized by hypergonadotropic amenorrhea and hypoestrogenic syndrome before 40 years of age. About 1% of women younger than 40 years old and 0.1% before 30 are affected. POI imposes a great challenge on women's reproductive and long-term health, such as infertility, amenorrhea, osteoporosis, and cardiovascular disease. Most patients already had impaired or complete loss of fecundity when diagnosed. Currently, no optimal regimen exists to ameliorate ovarian function. Typically, they end up with egg donation or adoption as an alternative way. Less severe form of POI is diminished ovarian reserve (DOR). Although lack of consensus according to Bologna criteria cut off for DOR was defined as (antral follicle count (AFC) <5-7 follicles or anti-Mullerian hormone (AMH) <0.5-1.1 ng/ml).
Previously it has been showed that 24% of women with POI had resumption of ovarian function and 4% resulted in baby births. These data indicates residual follicles are available in atrophic ovaries and have potential for development and even fertilization. In routine IVF practice 15% percent of patients have poor ovarian response to ovarian stimulation. Patients with DOR with a previous poor ovarian response (cycles cancelled or yielding ≤3 oocytes with a conventional protocol) might have benefit from the strategies increasing follicle activation and number of growing follicles and oocyte retrieved. Therefore, strategies enabling ovarian resumption predictable and follicle activation feasible are promising for POI/DOR treatment. Recently, In vitro Activation (IVA) approach has been proposed and live births have been achieved in patients with POI. Phosphatase and tensin homolog (PTEN) enzyme inhibitors and phosphatidylinositol-3 kinase activators could activate AKT pathway and activate the dormant follicles. Ovarian fragmentation could lead to ovarian primary follicle growth by interfering with Hippo signaling pathway. Residual follicles in patients with POI could be activated to develop for egg retrieval by combination of mechanical and chemical stimulation.
In 2019, Zhang et al retrospectively analyzed the follicle development and pregnancy outcome in 80 POI patients after laparoscopic ovarian biopsy/scratch without using chemical agents as was the case in IVA. 11 (13.75%) patients presented with ovarian function resumption, three metaphases II oocytes were retrieved in 10 patients and two embryos were formed and freshly transferred followed by a healthy singleton delivery in 1 (1.25%) patient. They concluded that the technique of ovarian biopsy/scratch without chemical activation could promote follicle development in vivo, suggesting it could bring promising benefits for some women with POI.
In patient with POI/DOR, activation of residual follicles is a promising option and further studies are warranted. Previous studies included laparoscopic surgery which may lead to possible surgical complications. Without using chemical agents and laparoscopic surgery, main object of this study is mechanical follicle activation with trans-vaginal ovarian needle puncture with 17 gauge oocyte pickup needle in IVF patients with DOR.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control ovary | No intervention | – |
| Punctured ovary | Experimental | Procedure: Ovarian puncture |
Who may qualify
- Ages
- Up to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Patients with diminished ovarian reserve
- <3 oocytes collected in previous cycle (with anti-mullerian hormone <0.5 ng/mL and/or antral follicle count <5)
- Cycles stimulated with flexible antagonist protocol
- Cycles triggered with recombinant hCG
- Fresh transfer cycles
Key exclusion criteria (2 listed)
- Preimplantation genetic testing
- Azospermia
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 |
|---|---|---|
| Ovarian punctureOne side ovary of each patient included in the study, will be punctured 10 times under trans-vaginal ultrasound guidance with 17 gauge ovarian pick up needle, 1 month before the scheduled IVF cycle. Control group will be the other side ovary for each patient. Number of ≥ 14 mm follicle and collected oocytes will be compared. | Procedure or surgery | Punctured ovary |
Primary outcome
Number of ≥14 mm follicle
Time frame: 4 month after intervention as a response to ovarian stimulation
Number of ≥14 mm follicle on the trigger day
Antral follicle count
Time frame: 4 month after intervention on the second/third day of menstrual cycle
Antral follicle count
1 secondary outcome
Number of collected oocytes
Time frame: 4 month after intervention as a response to ovarian stimulation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2022.
- Background: PubMed 20708256De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010 Sep 11;376(9744):911-21. doi: 10.1016/S0140-6736(10)60355-8. Epub 2010 Aug 11.
- Background: PubMed 29225794Torrealday S, Kodaman P, Pal L. Premature Ovarian Insufficiency - an update on recent advances in understanding and management. F1000Res. 2017 Nov 29;6:2069. doi: 10.12688/f1000research.11948.1. eCollection 2017.
- Background: PubMed 25008235Ferraretti AP, Gianaroli L. The Bologna criteria for the definition of poor ovarian responders: is there a need for revision? Hum Reprod. 2014 Sep;29(9):1842-5. doi: 10.1093/humrep/deu139. Epub 2014 Jul 9.
- Background: PubMed 27177971Bachelot A, Nicolas C, Bidet M, Dulon J, Leban M, Golmard JL, Polak M, Touraine P. Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency. Clin Endocrinol (Oxf). 2017 Feb;86(2):223-228. doi: 10.1111/cen.13105. Epub 2016 Jun 14.
- Background: PubMed 26825246Chen X, Chen SL, Ye DS, Liu YD, He YX, Tian XL, Xu LJ, Tao T. Retrospective analysis of reproductive outcomes in women with primary ovarian insufficiency showing intermittent follicular development. Reprod Biomed Online. 2016 Apr;32(4):427-33. doi: 10.1016/j.rbmo.2015.12.011. Epub 2016 Jan 14.
- Background: PubMed 27022685Kawamura K, Kawamura N, Hsueh AJ. Activation of dormant follicles: a new treatment for premature ovarian failure? Curr Opin Obstet Gynecol. 2016 Jun;28(3):217-22. doi: 10.1097/GCO.0000000000000268.
- Background: PubMed 30541396Zhang X, Han T, Yan L, Jiao X, Qin Y, Chen ZJ. Resumption of Ovarian Function After Ovarian Biopsy/Scratch in Patients With Premature Ovarian Insufficiency. Reprod Sci. 2019 Feb;26(2):207-213. doi: 10.1177/1933719118818906. Epub 2018 Dec 12.
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.
Sezcan Mumusoğlu, Assoc. Prof. principal investigator
Hacettepe University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ovarian puncture in people with Activation of Primordial Follicles, run by Hacettepe University at 1 site in Turkey (Türkiye).
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 7 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 21 Sep 2022. 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 Turkey (Türkiye). 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sezcan Mumusoglu, Assoc. Prof. (+905326404673, sezcanmumusoglu@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of ≥14 mm follicle (time frame: 4 month after intervention as a response to ovarian stimulation). The study lists 2 primary outcomes in all. 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 NCT04608695, which also lists 7 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 21 Sep 2022.