Infertility, FemaleFERTIOVONCT06724471
Preservation of Women's Fertility: Evaluation of Innovative Methods for Ovarian Tissue Cryopreservation
An observational study of Infertility, Female, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
The recent innovations in cancer diagnosis and therapy have improved the five-year survival for patients. However, anticancer treatments may impair patient fertility; therefore fertility preservation is recommended before therapy initiation. Read more about this study
- Who is it for?
- Ages 18 to 37 years, women only
- Conditions the study is for
- Infertility, Female
- What is being tested?
- Human ovarian tissue cryopreservation using thermosoldered or screwed cryovials
- Type of treatment
- Medical device
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 5 May 2022to 31 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 37 years
- Women only
- No healthy volunteers
- Adult
Study population: Adult woman scheduled for benign ovarian cyst resection in the University Hospital Center of Clermont-Ferrand.
Who may be able to join
- Adult woman scheduled for benign ovarian cyst resection (dermoid, functional, mucinous or serous cysts)
- Below 37 years old and above 18 years old
- Capable of giving written informed consent to participate in the research study
- Affiliated to social welfare service
Who cannot join
- Women above 37 years old and below 18 years old
- Polycystic ovary syndrome
- Diminished ovarian reserve
- Severe endometriosis
- Malignant and endometrial cysts
Trial locations and contacts
1 site in 1 country.
About this study
The recent innovations in cancer diagnosis and therapy have improved the five-year survival for patients. However, anticancer treatments may impair patient fertility; therefore fertility preservation is recommended before therapy initiation. The sole method for preserving young prepubescent girls' fertility, which can also be used for pubescent women, is ovarian tissue cryopreservation (OTC) with later auto-transplantation. Although 200 births have been reported worldwide after OTC and transplantation, significant improvements are required. Indeed, freezing and thawing protocols vary according to laboratories (media, cryoprotectants, freezing curve, etc…) and selection criteria are not justified. In addition, most of the laboratories use unsafe devices (e.g. screw cap cryovials) for OTC, exposing ovarian tissues to biological hazards during sample storage in nitrogen tanks. To eliminate these risks, novel "high security" devices have been commercialized (welded cryotubes). However, while thermal welding could alter tissue quality, the functionality of the human ovarian tissue frozen with these innovative devices has not yet been evaluated. The objectives of this study are i) to optimize the freezing and the thawing protocols for human OTC according to thermodynamic properties of the freezing medium and the type of device (welded or screwed cryotube) and ii) to determine if the type of cryotube influences the quality of human ovarian tissue.
This project will enable to reach a better understanding of the impact of freezing on ovarian tissue functionality, as well as the implementation of an optimal protocol for OTC within the ART laboratory of Clermont-Ferrand hospital to optimize patient care.
Read the detailed description
The aim of this project is to determine whether the type of cryogenic tube (with screw caps or thermosoldered) influences the quality and functionality of ovarian tissue after cryopreservation. First, a characterization of the thermodynamic properties of the freezing medium using a differential scanning calorimeter (Diamond DSC, PerkinElmer) will be carried out to optimize freezing and thawing protocols. This analysis will define important parameters such as crystallization temperature (Tc), end-of-melting temperature (Tm), and transition temperatures (Tg'1). Once freezing and thawing protocols are optimized, the investigators will use human ovarian cortex surrounding benign cysts, a model previously validated by our laboratory, to determine whether the type of cryotube influences the quality of human ovarian tissue. These ovarian cortical samples usually destroyed in clinics share similar characteristics with normal ovarian cortex. Ovarian tissue will be cut into 1mm3 fragments and divided into three groups: fresh ovarian cortex (group1, control), ovarian cortex cryopreserved in thermosoldered cryogenic tubes (group 2) or in screw cap (group 3). The investigators will assess ovarian tissue quality immediately after resection for group 1 or after thawing for group 2 and 3 by analyzing follicle density and morphology (HES staining) and proliferation/apoptosis balance (Immunohistochemistry (IHC) for KI67 and cleaved caspase 3). To assess the functionality of the ovarian tissue after thawing, ovarian cortex fragments will be in vitro cultured. The investigators will analyze i) follicle density, type and morphology (HES staining), ii) the proliferation/apoptosis balance (IHC for KI67 and cleaved caspase 3), iii) the expression levels of major folliculogenesis regulators (IHC for GDF-9) and iv) the levels of folliculogenesis-associated hormones (AMH, estrogen) secreted in culture medium.
- Conditions
- Infertility, Female
- Being tested
- Human ovarian tissue cryopreservation using thermosoldered or screwed cryovials
- Keywords
- Human ovarian tissue, Cryopreservation, Fertility Preservation, Organotypic culture, Female infertility
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human ovarian tissue cryopreservation using thermosoldered or screwed cryovialsDevice
Human ovarian tissue Cryopreservation: immediately after cyst resection, pericystic ovarian cortex will be cut into 1mm3 fragments and cryopreserved in screwed or thermosoldered cryovials using a slow programmable freezing device (Nano Digitcool, Cryo Bio System).
| Study group | Role | What they receive |
|---|---|---|
| Fresh ovarian cortex fragments | Pericystic ovarian cortex will be cut into 1mm3 fragments and either directly analyzed on the day of collection (D0) or after organotypic culture (D7 and D14). | |
| Fragments of ovarian cortex frozen in thermosoldered cryovials. | Pericystic ovarian cortex will be cut into 1mm3 fragments, frozen using a slow programmable freezing device (Nano Digitcool, Cryo Bio System) in thermosoldered cryovials and stored in liquid nitrogen (-196°C). Then, fragments will be thawed before being analyzed on the day of thawing (D'0) and after 7 and 14 days (D7 and D14) of organotypic culture. Receives: Device: Human ovarian tissue cryopreservation using thermosoldered or screwed cryovials | |
| Fragments of ovarian cortex frozen in screwed cryovials. | Pericystic ovarian cortex will be cut into 1mm3 fragments, frozen using a slow programmable freezing device (Nano Digitcool, Cryo Bio System) in screwed cryovials and stored in liquid nitrogen (-196°C). Then fragments will be thawed before being analyzed on the day of thawing (D'0) and after 7 and 14 days (D7 and D14) of organotypic culture. Receives: Device: Human ovarian tissue cryopreservation using thermosoldered or screwed cryovials |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-thawing Ovarian Follicle morphology
Follicle morphology of fresh versus frozen (with thermosoldered or screwed cryovials)/thawed ovarian cortex will be assessed on serial sections stained with hematoxylin-eosin-saffron. Fragments will be fixed on the day of collection for group 1 and directly after thawing for groups 2 and 3. Morphology of follicles will be evaluated according to the parameters described by Keros et al. Hum Reprod. 2009.
Measured: 24 months
Secondary outcomes (11)
Post-thawing Ovarian Follicle density
Follicle density (=number of follicle/mm2) of fresh versus frozen (with thermosoldered or screwed cryovials)/thawed ovarian cortex will be assessed on serial sections stained with hematoxylin-eosin-saffron. Fragments will be fixed on the day of collection for group 1 and directly after thawing for groups 2 and 3.
Measured: 24 months
Post-thawing Ovarian Follicle proliferation
the percentage of proliferative (oocyte or granulosa cells positive for KI-67 in fresh and frozen (with thermosoldered or screwed cryovials) /thawed ovarian cortex will be assessed on immunostained serial sections. Fragments will be fixed on the day of collection for group 1 and directly after thawing for groups 2 and 3.
Measured: 24 months
Post-thawing Ovarian Follicle apoptosis
the percentage of apoptotic (oocyte or granulosa cells positive cleaved caspase 3) in fresh and frozen (with thermosoldered or screwed cryovials) /thawed ovarian cortex will be assessed on immunostained serial sections. Fragments will be fixed on the day of collection for group 1 and directly after thawing for groups 2 and 3.
Measured: 24 months
Ovarian Follicle stage after organotypic culture
Follicle stages (% of primordial, primary, secondary and antral follicles) in fresh versus frozen (with thermosoldered or screwed cryovials)/thawed ovarian cortex will be assessed on serial sections stained with hematoxylin-eosin-saffron. Fragments will be fixed after 7 or 14 days of organotypic culture.
Measured: 36 months
Ovarian Follicle morphology after organotypic culture
Follicle morphology of fresh versus frozen (with thermosoldered or screwed cryovials)/thawed ovarian cortex will be assessed on serial sections stained with hematoxylin-eosin-saffron. Fragments will be fixed after 7 or 14 days of organotypic culture. Morphology of follicles will be evaluated according to the parameters described by Keros et al. Hum Reprod. 2009.
Measured: 36 months
GDF-9 expression after organotypic culture
the percentage of GDF9 positive follicles (i.e. with an oocyte positive for GDF-9) in fresh and frozen (with thermosoldered or screwed cryovials) /thawed ovarian cortex will be assessed on immunostained serial sections. Fragments will be fixed after 7 or 14 days of organotypic culture.
Measured: 36 months
Proliferation after organotypic culture
the percentage of proliferative (oocyte or granulosa cells positive for KI-67) in fresh and frozen (with thermosoldered or screwed cryovials) /thawed ovarian cortex will be assessed on immunostained serial sections. Fragments will be fixed after 7 or 14 days of organotypic culture.
Measured: 36 months
Apoptosis after organotypic culture
the percentage of apoptotic (oocyte or granulosa cells positive cleaved caspase 3) in fresh and frozen (with thermosoldered or screwed cryovials) /thawed ovarian cortex will be assessed on immunostained serial sections. Fragments will be fixed after 7 or 14 days of organotypic culture.
Measured: 36 months
AMH secretion after organotypic culture
AMH levels will be quantified in culture medium during organotypic culture of fresh and frozen (with thermosoldered or screwed cryovials) /thawed ovarian cortex. Culture media will be harvested every three days of culture for 14 days. AMH will be quantified by electrochemiluminescence
Measured: 36 months
Estrogen secretion after organotypic culture
Estrogen levels will be quantified in culture medium during organotypic culture of fresh and frozen (with thermosoldered or screwed cryovials) /thawed ovarian cortex. Culture media will be harvested every three days of culture for 14 days. Estrogen will be quantified by electrochemiluminescence
Measured: 36 months
Thermodynamic properties of freezing medium
A differential scanning calorimeter (DiamondDSC, PerkinElmer) will be used to determine the crystallization temperature (Tc), end-of-melting temperature (Tm), and transition temperature (Tg'1) of the freezing medium (Leibovitz with 4 mg/mL HSA, 1.5M DMSO and 0.1M sucrose).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2024
- Study start5 May 2022
- Primary completion1 Jun 2025
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Collaborators
- CryoBioSystem, Université d'Auvergne
- Responsible party
- Sponsor
- Investigators
- Florence Brugnon, MD, PhD, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06724471
- Sponsor's protocol ID
- 2022_Brugnon_FERTIOVO
- Acronym
- FERTIOVO
- Status last verified
- Jun 2025
- First submitted
- 5 Dec 2024
- Last updated
- 29 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preservation of Women's Fertility: Evaluation of Innovative Methods for Ovarian Tissue Cryopreservation
- ClinicalTrials.gov ID
- NCT06724471
- Acronym / sponsor ID
- FERTIOVO / 2022_Brugnon_FERTIOVO
- Conditions
- Infertility, Female
- Keywords
- Human ovarian tissue, Cryopreservation, Fertility Preservation, Organotypic culture, Female infertility
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Collaborators
- CryoBioSystem, Université d'Auvergne
- Study start
- 5 May 2022 (actual)
- Primary completion
- 1 Jun 2025 (actual)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 9 Dec 2024 (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.
The recent innovations in cancer diagnosis and therapy have improved the five-year survival for patients. However, anticancer treatments may impair patient fertility; therefore fertility preservation is recommended before therapy initiation. The sole method for preserving young prepubescent girls' fertility, which can also be used for pubescent women, is ovarian tissue cryopreservation (OTC) with later auto-transplantation. Although 200 births have been reported worldwide after OTC and transplantation, significant improvements are required. Indeed, freezing and thawing protocols vary according to laboratories (media, cryoprotectants, freezing curve, etc…) and selection criteria are not justified. In addition, most of the laboratories use unsafe devices (e.g. screw cap cryovials) for OTC, exposing ovarian tissues to biological hazards during sample storage in nitrogen tanks. To eliminate these risks, novel "high security" devices have been commercialized (welded cryotubes). However, while thermal welding could alter tissue quality, the functionality of the human ovarian tissue frozen with these innovative devices has not yet been evaluated. The objectives of this study are i) to optimize the freezing and the thawing protocols for human OTC according to thermodynamic properties of the freezing medium and the type of device (welded or screwed cryotube) and ii) to determine if the type of cryotube influences the quality of human ovarian tissue.
This project will enable to reach a better understanding of the impact of freezing on ovarian tissue functionality, as well as the implementation of an optimal protocol for OTC within the ART laboratory of Clermont-Ferrand hospital to optimize patient care.
Detailed description
The aim of this project is to determine whether the type of cryogenic tube (with screw caps or thermosoldered) influences the quality and functionality of ovarian tissue after cryopreservation. First, a characterization of the thermodynamic properties of the freezing medium using a differential scanning calorimeter (Diamond DSC, PerkinElmer) will be carried out to optimize freezing and thawing protocols. This analysis will define important parameters such as crystallization temperature (Tc), end-of-melting temperature (Tm), and transition temperatures (Tg'1). Once freezing and thawing protocols are optimized, the investigators will use human ovarian cortex surrounding benign cysts, a model previously validated by our laboratory, to determine whether the type of cryotube influences the quality of human ovarian tissue. These ovarian cortical samples usually destroyed in clinics share similar characteristics with normal ovarian cortex. Ovarian tissue will be cut into 1mm3 fragments and divided into three groups: fresh ovarian cortex (group1, control), ovarian cortex cryopreserved in thermosoldered cryogenic tubes (group 2) or in screw cap (group 3). The investigators will assess ovarian tissue quality immediately after resection for group 1 or after thawing for group 2 and 3 by analyzing follicle density and morphology (HES staining) and proliferation/apoptosis balance (Immunohistochemistry (IHC) for KI67 and cleaved caspase 3). To assess the functionality of the ovarian tissue after thawing, ovarian cortex fragments will be in vitro cultured. The investigators will analyze i) follicle density, type and morphology (HES staining), ii) the proliferation/apoptosis balance (IHC for KI67 and cleaved caspase 3), iii) the expression levels of major folliculogenesis regulators (IHC for GDF-9) and iv) the levels of folliculogenesis-associated hormones (AMH, estrogen) secreted in culture medium.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fresh ovarian cortex fragments | – | –Pericystic ovarian cortex will be cut into 1mm3 fragments and either directly analyzed on the day of collection (D0) or after organotypic culture (D7 and D14). |
| Fragments of ovarian cortex frozen in thermosoldered cryovials. | – | Device: Human ovarian tissue cryopreservation using thermosoldered or screwed cryovialsPericystic ovarian cortex will be cut into 1mm3 fragments, frozen using a slow programmable freezing device (Nano Digitcool, Cryo Bio System) in thermosoldered cryovials and stored in liquid nitrogen (-196°C). Then, fragments will be thawed before being analyzed on the day of thawing (D'0) and after 7 and 14 days (D7 and D14) of organotypic culture. |
| Fragments of ovarian cortex frozen in screwed cryovials. | – | Device: Human ovarian tissue cryopreservation using thermosoldered or screwed cryovialsPericystic ovarian cortex will be cut into 1mm3 fragments, frozen using a slow programmable freezing device (Nano Digitcool, Cryo Bio System) in screwed cryovials and stored in liquid nitrogen (-196°C). Then fragments will be thawed before being analyzed on the day of thawing (D'0) and after 7 and 14 days (D7 and D14) of organotypic culture. |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Adult woman scheduled for benign ovarian cyst resection in the University Hospital Center of Clermont-Ferrand.
Key inclusion criteria (4 listed)
- Adult woman scheduled for benign ovarian cyst resection (dermoid, functional, mucinous or serous cysts)
- Below 37 years old and above 18 years old
- Capable of giving written informed consent to participate in the research study
- Affiliated to social welfare service
Key exclusion criteria (5 listed)
- Women above 37 years old and below 18 years old
- Polycystic ovary syndrome
- Diminished ovarian reserve
- Severe endometriosis
- Malignant and endometrial cysts
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 |
|---|---|---|
| Human ovarian tissue cryopreservation using thermosoldered or screwed cryovialsHuman ovarian tissue Cryopreservation: immediately after cyst resection, pericystic ovarian cortex will be cut into 1mm3 fragments and cryopreserved in screwed or thermosoldered cryovials using a slow programmable freezing device (Nano Digitcool, Cryo Bio System). | Device | Fragments of ovarian cortex frozen in screwed cryovials., Fragments of ovarian cortex frozen in thermosoldered cryovials. |
Primary outcome
Post-thawing Ovarian Follicle morphology
Time frame: 24 months
Follicle morphology of fresh versus frozen (with thermosoldered or screwed cryovials)/thawed ovarian cortex will be assessed on serial sections stained with hematoxylin-eosin-saffron. Fragments will be fixed on the day of collection for group 1 and directly after thawing for groups 2 and 3. Morphology of follicles will be evaluated according to the parameters described by Keros et al. Hum Reprod. 2009.
11 secondary outcomes
Post-thawing Ovarian Follicle density
Time frame: 24 months
Post-thawing Ovarian Follicle proliferation
Time frame: 24 months
Post-thawing Ovarian Follicle apoptosis
Time frame: 24 months
Ovarian Follicle stage after organotypic culture
Time frame: 36 months
Ovarian Follicle morphology after organotypic culture
Time frame: 36 months
GDF-9 expression after organotypic culture
Time frame: 36 months
Proliferation after organotypic culture
Time frame: 36 months
Apoptosis after organotypic culture
Time frame: 36 months
AMH secretion after organotypic culture
Time frame: 36 months
Estrogen secretion after organotypic culture
Time frame: 36 months
Thermodynamic properties of freezing medium
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2025.
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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.
Florence Brugnon, MD, PhD principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infertility, Female, run by University Hospital, Clermont-Ferrand at 1 site in France.
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 4 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 29 Jun 2025. 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 France. 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?
This study is still under way. Results are not available in the source record yet.
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?
Post-thawing Ovarian Follicle morphology (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jun 2025.