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

NCT04586686 | Unknown

• 1 other identifier: 2019COIMBRA001
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Breast Cancer Female

Keywords

Fertility Preservation; Reproductive Techniques, assisted; Ovulation Induction; Oocyte Retrieval; Cryopreservation; Ovary

Outcome Measures

Primary Outcomes (1)

• Mature oocyte yield from biopsied versus non-biopsied ovary

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

  Immediately after the procedure of the transvaginal oocyte retrieval

Secondary Outcomes (3)

• Follicle Output Rate (FORT)

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

• COC yield

  During the procedure of the transvaginal oocyte retrieval

• Maturation Rate

  Immediately after the procedure of the transvaginal oocyte retrieval

Study Arms (2)

Group 1: right ovarian biopsy

OTHER

Patients 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.

Procedure: Ovarian biopsy via laparoscopy; Procedure: Transvaginal oocyte retrieval

Group 2: left ovarian biopsy

OTHER

Patients 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.

Procedure: Ovarian biopsy via laparoscopy; Procedure: Transvaginal oocyte retrieval

Interventions

Ovarian biopsy via laparoscopy PROCEDURE

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.

Group 1: right ovarian biopsy; Group 2: left ovarian biopsy

Transvaginal oocyte retrieval PROCEDURE

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.

Group 1: right ovarian biopsy; Group 2: left ovarian biopsy

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: lead
• Hopital Antoine Beclere: collaborator

Study Sites (2)

Universitair Ziekenhuis Brussel

Brussels, 1090, Belgium

NOT YET RECRUITING

UZ Gent

Ghent, 9000, Belgium

RECRUITING

Related Publications (12)

• 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.

  PMID: 25283571 BACKGROUND

• 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.

  PMID: 23465707 BACKGROUND

• 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.

  PMID: 29523398 BACKGROUND

• 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.

  PMID: 30383235 BACKGROUND

• 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.

  PMID: 31843073 BACKGROUND

• 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.

  PMID: 29069558 BACKGROUND

• 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.

  PMID: 29428307 BACKGROUND

• 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.

  PMID: 20971465 BACKGROUND

• 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.

  PMID: 16084576 BACKGROUND

• 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.

  PMID: 31208678 BACKGROUND

• 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.

  PMID: 28333356 BACKGROUND

• 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.

  PMID: 25296615 RESULT

MeSH Terms

Conditions

Helping Behavior

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Michel De Vos, MD PhD

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michel De Vos, MD PhD

CONTACT

(0)24776660; mdv@uzbrussel.be

Elsie Nulens

CONTACT

(0)24776648; Elsie.Nulens@uzbrussel.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: October 14, 2020
• Study Start: November 1, 2022
• Primary Completion: November 30, 2024
• Study Completion: December 31, 2024
• Last Updated: May 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The data will become available over the course of the study until 6 months after ending this study. This will give us the time to analyse the data of the different sites.
• Access Criteria: eCRF

Locations

BE (2)