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Breast Cancer FemaleCoimbraNCT04586686

Combining Interventions of Fertility Preservation to Mitigate Fertility Loss After Breast Cancer

A study testing Ovarian biopsy via laparoscopy and Transvaginal oocyte retrieval in people with Breast Cancer Female, run by Universitair Ziekenhuis Brussel at 2 sites in Belgium.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This clinical prospective randomised controlled trial will evaluate the impact of an ovarian biopsy on the oocyte yield after controlled ovarian stimulation before chemotherapy in view of breast cancer. Read more about this study

Who is it for?
Ages 18 to 35 years, women only
Conditions the study is for
Breast Cancer Female
What is being tested?
Ovarian biopsy via laparoscopy and Transvaginal oocyte retrieval
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
2 sitesBelgium
Study dates
1 Nov 2022to 31 Dec 2024
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 18 to 35 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Age ≥ 18 and ≤ 35 years
  • BMI ≥ 18 and ≤ 35 kg/m²
  • Diagnosis of breast cancer
  • Presence of 2 ovaries
  • Signed informed consent form
  • Medically fit for general anesthesia (ASA score 1-3)
Show all 9Show fewer
  • Permission of oncology team (with agreement to postpone chemo/radiotherapy for at least 2 weeks)
  • Random start controlled ovarian stimulation
  • AFC minimum (ie antral follicles measuring between 2-9 mm): 8 antral follicles

Who cannot join

  • Age <18 or >35 years
  • BMI <18 or >35 kg/m²
  • Difference in AFC between the ovaries of more than 7 antral follicles
  • Diagnosis of PCOS
  • Previous radiotherapy and/or chemotherapy (neo-adjuvant chemotherapy included)
  • Endometriose rAFS 3-4
  • Allergy or reaction to the use of Elonva®, Puregon®, Orgalutran®, Pregnyl® Gonapeptyl®, Decapeptyl® or letrozole in the past

Trial locations and contacts

2 sites in 1 country.

Michel De Vos, MD PhD contact

(0)24776660 ext. 0032

mdv@uzbrussel.be

Elsie Nulens contact

(0)24776648 ext. 0032

Elsie.Nulens@uzbrussel.be

Belgium2 sites, 2 recruiting

  • Universitair Ziekenhuis Brussel

    Brussels, 1090

    Michel De Vos, MD, (0)24776660 ext. 0032, mdv@uzbrussel.be

    Michel De Vos, MD PhD

    Not yet recruiting

  • UZ Gent

    Ghent, 9000

    Dominic Stoop, MD PhD

    Dominic Stoop, MD PhD

    Recruiting

Other trials in Belgium

About this study

Official title: Combining Interventions of Fertility Preservation to Mitigate Fertility Loss After

This clinical prospective randomised controlled trial will evaluate the impact of an ovarian biopsy on the oocyte yield after controlled ovarian stimulation before chemotherapy in view of breast cancer. The purpose of this trial is to learn about the possibility to combine these two fertility preservation procedures without decreasing the number of oocytes collected after an ovarian stimulation.

Read the detailed description

All patients will undergo a biopsy of the ovarian cortex via laparoscopy, after patient eligibility has been established and patient consent has been obtained. The side of the ovarian biopsy will be randomized on the day of the laparoscopy either from the right side (group 1) or from the left side (group 2). The ovarian tissue will be cryopreserved. A small part will also be evaluated by the pathologist to screen for malignant contamination and follicle density. All patients will then continue with a controlled ovarian stimulation.

In both groups, a first blood analysis with hormonal assessment (E2, P, LH, FSH, hCG and AMH) will be performed at first visit, independent of their cycle. At that time a transvaginal ultrasound (frequency ≥ 7 MHz) will be done as well to assess the antral follicle count and the ovarian volume. The antral follicle count will be assessed using real-time 2D-US evaluation, the standard use in clinical practice. The ovarian volume will be measured using the prolate ellipsoid formula (volume = length x width x height x 0.523). If a dominant follicle is noted, choriongonadotropin (Pregnyl ® 5000 IU), choriongonadotropin Alfa (Ovitrelle ® 250 µg) or triptorelin (Gonapeptyl ® or Decapeptyl ® 0.2 mg) will be given to the patient to trigger ovulation. Thereafter, the controlled ovarian stimulation can be initiated in the luteal phase.

The size of the ovarian cortex biopsy will be calculated as 20% of the ovarian volume measured at the initial ultrasound. Immediately after the ovarian biopsy, the objective measurements of the biopsy will be noted in weight (gram) and volume (length x width x height mm³) because the biopsy fragment can be considered a rectangular box. A correction factor will be used afterwards in the statistical analysis if the volume of the ovarian biopsy is not equal to 20%.

The laparoscopic procedure by which the ovarian cortex biopsy will be performed, will be standardised: The technique developed by ProFam will be used and adapted if needed at the surgeon's discretion. A three to four-port laparoscopy will be used. The ovarian cortex biopsy will be performed using a curved scissor. Bipolar or unipolar cauterisation will be avoided as much as possible. If necessary for approximation or for hemostatic reasons, the ovarian edges can be stitched or Surgicel® Absorbable Hemostat can be used.

During the course of the study, there will be a number of blood analyses and ultrasounds, to evaluate follicular growth. This will be arranged at specific time points starting from day 6 of the stimulation and will be performed every other day, until the day of trigger. If necessary and based on clinician's decision, a supplementary blood analysis and/or ultrasound can be scheduled. At the follow-up ultrasounds the follicular growth will be noted for each ovary separately to assess difference in reaction and/or growth after the ovarian biopsy.

The controlled ovarian stimulation will start the day of the laparoscopy. It can start either in basal circumstances, or in the early follicular or luteal phase. A fixed GnRH antagonist protocol will be used. Ovarian stimulation will be started with Corifollitropin alfa 0.15 mg (Elonva®). On day six the antagonist, Ganirelix (Orgalutran®), will be added to prevent a premature LH surge. If needed ovarian stimulation can be continued after seven days using follitropin beta (Puregon®). The dosage of Puregon® is dependent on the AMH level at the first visit. Patients with AMH > 2 µg/L, will be started with 200-225 IE Puregon® daily. If the initial AMH level is <2 µg/L, patients will receive 225-300 IE Puregon® daily. Elonva ® and Puregon ® will be administered in the evening, whereas Orgalutran ® will be injected in the morning. Agonist trigger Triptorelin 0.2 mg (Gonapeptyl®) will be ministered as soon as at least three follicles reach a mean diameter of 18 mm or wider, with intermediary follicles 14 mm or wider. In case of LH levels <2 IU/L at the start of ovarian stimulation, a dual ovulation strategy will be adapted: Triptorelin 0.2mg and hCG 2500 IU (or ovitrelle 250 µg) will be given. Oocyte retrieval will be planned 36 hours after triggering. This will be performed as a transvaginal oocyte pick-up. Oocyte vitrification will be carried out after denudation and assessment of maturity.

Being tested
Ovarian biopsy via laparoscopy, Transvaginal oocyte retrieval
Keywords
Fertility Preservation, Reproductive Techniques, assisted, Ovulation Induction, Oocyte Retrieval, Cryopreservation, Ovary
Medical subject headings
Helping Behavior

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ovarian biopsy via laparoscopyProcedure or surgery

    A laparoscopy will be performed to achieve an ovarian cortical biopsy of one of both ovaries. Approximately twenty % of the ovarian volume as initially measured on the baseline ultrasound at the first visit will be removed to be processed in the lab for cortex freezing. The laparoscopic procedure in order to take the ovarian cortex biopsy will be standardised as much as possible. The technique developed by ProFam will be followed and adapted if needed by the surgeon's discretion. A three to four port laparoscopy will be used. The ovarian cortex biopsy will be taken using a curved scissor. Bipolar or unipolar cauterisation will be avoided as much as possible. If necessary for approximation or for hemostatic reasons, the ovarian edges can be stitched or Surgicel ® Absorbable Hemostat can be used.

  • Transvaginal oocyte retrievalProcedure or surgery

    After ovarian stimulation, a transvaginal oocyte retrieval will be performed either under local or general anaesthetics (patient's choice). The oocyte yield between the biopsied and non-biopsied ovary will be evaluated.

Study groups in NCT04586686
Study groupRoleWhat they receive
Group 1: right ovarian biopsyOtherPatients in group 1 will undergo a laparoscopy for an ovarian biopsy from the right ovary. They will then continue with a controlled ovarian stimulation, using a GnRH antagonist protocol. This will be started with Corifollitropin alfa 0.15 mg in the evening. On day six the antagonist, Ganirelix, will be added in the morning. If needed stimulation can be continued after seven days using follitropin beta daily in the evening (dosage ranging from 200-300 IE depending on AMH levels). Agonist trigger Triptorelin 0.2 mg will be administered for ovulation induction. In case of LH levels <2 IU/L at the start of ovarian stimulation, a dual ovulation strategy will be adapted: Triptorelin 0.2mg and choriongonadotropin 2500 IU (or choriongonadotropin alfa 250 µg) will be given. A transvaginal oocyte retrieval will be planned 36 hours after triggering.
Receives: Procedure: Ovarian biopsy via laparoscopy; Procedure: Transvaginal oocyte retrieval
Group 2: left ovarian biopsyOtherPatients in group 2 will undergo a laparoscopy for an ovarian biopsy from the left ovary. They will then continue with a controlled ovarian stimulation, using a GnRH antagonist protocol. This will be started with Corifollitropin alfa 0.15 mg in the evening. On day six the antagonist, Ganirelix, will be added in the morning. If needed stimulation can be continued after seven days using follitropin beta daily in the evening (dosage ranging from 200-300 IE depending on AMH levels). Agonist trigger Triptorelin 0.2 mg will be administered for ovulation induction. In case of LH levels <2 IU/L at the start of ovarian stimulation, a dual ovulation strategy will be adapted: Triptorelin 0.2mg and choriongonadotropin 2500 IU (or choriongonadotropin alfa 250 µg) will be given. A transvaginal oocyte retrieval will be planned 36 hours after triggering.
Receives: Procedure: Ovarian biopsy via laparoscopy; Procedure: Transvaginal oocyte retrieval

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mature oocyte yield from biopsied versus non-biopsied ovary

    Evaluation of metaphase II oocyte yield between biopsied and non-biopsied ovary

    Measured: Immediately after the procedure of the transvaginal oocyte retrieval

Secondary outcomes (3)

  1. Follicle Output Rate (FORT)

    Evaluation of the proportion of follicles that were responsive to FSH and is calculated by dividing the number of preovulatory follicles (16-20 mm) × 100 by the antral follicle count (3-8 mm)

    Measured: From ovarian stimulation until the day of oocyte retrieval (2-3 weeks, depending on patient's response)

  2. COC yield

    Evaluation of cumulus oophorus complex yield between biopsied and non-biopsied ovary

    Measured: During the procedure of the transvaginal oocyte retrieval

  3. Maturation Rate

    Evaluation of proportion of metaphase II oocytes within the COC yield between biopsies and non-biopsied ovary

    Measured: Immediately after the procedure of the transvaginal oocyte retrieval

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2020
  2. Study start1 Nov 2022
  3. Primary completion30 Nov 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
All patients will undergo a laparoscopy for an ovarian biopsy (about 20% of the ovarian volume). The side of the ovarian biopsy will be randomized on the day of the laparoscopy either from the right side (group 1) or from the left side (group 2). All patients will then continue with a controlled ovarian stimulation, using corifollitropin alpha and follitropin beta in a GnRH antagonist protocol using ganirelix. The metaphase II oocyte yield will be evaluated between the biopsied versus non-biopsied ovary to proof a non-inferiority (assuming that a difference of 1 metaphase II oocyte yielded from the biopsied ovary compared to the non-biopsied ovary is not clinically relevant).
Masking
None (open label)
Enrolment
41 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04586686
Sponsor's protocol ID
2019COIMBRA001
Acronym
Coimbra
Status last verified
Apr 2023
First submitted
11 Aug 2020
Last updated
18 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: As this is a multicenter study, we plan to share IPD between the study sites. An electronical case report form (eCRF) will be set up and completed in all sites. Data will be handled in accordance with the general data protection regulation (GDPR).

Publications

  • De Vos M, Smitz J, Woodruff TK. Fertility preservation in women with cancer. Lancet. 2014 Oct 4;384(9950):1302-10. doi: 10.1016/S0140-6736(14)60834-5.

    PubMed 25283571

  • Garcia-Velasco JA, Domingo J, Cobo A, Martinez M, Carmona L, Pellicer A. Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications. Fertil Steril. 2013 Jun;99(7):1994-9. doi: 10.1016/j.fertnstert.2013.02.004. Epub 2013 Mar 1.

    PubMed 23465707

  • Decanter C, Cloquet M, Dassonneville A, D'Orazio E, Mailliez A, Pigny P. Different patterns of ovarian recovery after cancer treatment suggest various individual ovarian susceptibilities to chemotherapy. Reprod Biomed Online. 2018 Jun;36(6):711-718. doi: 10.1016/j.rbmo.2018.02.004. Epub 2018 Mar 2.

    PubMed 29523398

  • Cobo A, Garcia-Velasco J, Domingo J, Pellicer A, Remohi J. Elective and Onco-fertility preservation: factors related to IVF outcomes. Hum Reprod. 2018 Dec 1;33(12):2222-2231. doi: 10.1093/humrep/dey321.

    PubMed 30383235

  • Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2019 Dec;112(6):1022-1033. doi: 10.1016/j.fertnstert.2019.09.013.

    PubMed 31843073

  • Donnez J, Dolmans MM. Fertility Preservation in Women. N Engl J Med. 2017 Oct 26;377(17):1657-1665. doi: 10.1056/NEJMra1614676. No abstract available.

    PubMed 29069558

  • Diaz-Garcia C, Domingo J, Garcia-Velasco JA, Herraiz S, Mirabet V, Iniesta I, Cobo A, Remohi J, Pellicer A. Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study. Fertil Steril. 2018 Mar;109(3):478-485.e2. doi: 10.1016/j.fertnstert.2017.11.018. Epub 2018 Feb 7.

    PubMed 29428307

  • Deb S, Kannamannadiar J, Campbell BK, Clewes JS, Raine-Fenning NJ. The interovarian variation in three-dimensional ultrasound markers of ovarian reserve in women undergoing baseline investigation for subfertility. Fertil Steril. 2011 Feb;95(2):667-72. doi: 10.1016/j.fertnstert.2010.09.031. Epub 2010 Oct 25.

    PubMed 20971465

  • Ueland FR, Depriest PD, Desimone CP, Pavlik EJ, Lele SM, Kryscio RJ, van Nagell JR Jr. The accuracy of examination under anesthesia and transvaginal sonography in evaluating ovarian size. Gynecol Oncol. 2005 Nov;99(2):400-3. doi: 10.1016/j.ygyno.2005.06.030. Epub 2005 Aug 9.

    PubMed 16084576

  • Amorim CA, Leonel ECR, Afifi Y, Coomarasamy A, Fishel S. Cryostorage and retransplantation of ovarian tissue as an infertility treatment. Best Pract Res Clin Endocrinol Metab. 2019 Feb;33(1):89-102. doi: 10.1016/j.beem.2018.09.002. Epub 2018 Sep 13.

    PubMed 31208678

  • Rodgers RJ, Reid GD, Koch J, Deans R, Ledger WL, Friedlander M, Gilchrist RB, Walters KA, Abbott JA. The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review. Hum Reprod. 2017 May 1;32(5):1033-1045. doi: 10.1093/humrep/dex027.

    PubMed 28333356

  • Dolmans MM, Marotta ML, Pirard C, Donnez J, Donnez O. Ovarian tissue cryopreservation followed by controlled ovarian stimulation and pick-up of mature oocytes does not impair the number or quality of retrieved oocytes. J Ovarian Res. 2014 Aug 26;7:80. doi: 10.1186/s13048-014-0080-8.

    PubMed 25296615

Questions about this trial

What is this clinical trial studying?

A study testing Ovarian biopsy via laparoscopy and Transvaginal oocyte retrieval in people with Breast Cancer Female, run by Universitair Ziekenhuis Brussel at 2 sites in Belgium.

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 9 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: status not confirmed, as of the sponsor's last update on 18 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Belgium. 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 Michel De Vos, MD PhD ((0)24776660 ext. 0032, mdv@uzbrussel.be), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mature oocyte yield from biopsied versus non-biopsied ovary (time frame: Immediately after the procedure of the transvaginal oocyte retrieval). 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 NCT04586686, which also lists 12 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 18 May 2023.

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