Oocyte DonorsLadyDeNCT05521828
Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone
A study testing Follitropin delta (Rekovelle), Duphaston and GnRH agonist (Gonapeptyl) in people with Oocyte Donors and Oocyte Donation, run by CRG UZ Brussel at 1 site in Belgium.
Trial summary
The last decade has shown a progressive scientific interest for new strategies to improve the outcomes of controlled ovarian stimulation (COS). Given the fact that interovulatory period has been described to have multiple waves of follicular recruitment, luteal phase ovarian stimulation (LPOS) has been proposed as new… Read more about this study
- Who is it for?
- Ages 18 to 36 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Oocyte Donors, Oocyte Donation
- What is being tested?
- Follitropin delta (Rekovelle), Duphaston and GnRH agonist (Gonapeptyl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Apr 2023to 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 36 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Body mass Index (BMI) ≥18 to < 28
- Signed informed consent
- Regular menstrual cycle length i.e. 24-35 days
Who cannot join
- Contraindications to the use of gonadotropins
- Endometriosis grade 3-4
- Patients with Anti-mullerian hormone (AMH) <1.1 ng/ml and/or antral follicular count (AFC)<7
- Patients with Follicle Number Per Ovary (FNPO) ≥ 19 and/or AMH >5ng/ml
- Patients under contraception with hormonal intrauterine device (IUD)
- Any untreated endocrine abnormality
Trial locations and contacts
1 site in 1 country.
Elsie Nulens contact
Belgium1 site, 1 recruiting
- Recruiting
Brussels Ivf
Brussels, 1090
Christophe Blockeel, Professor
About this study
Official title: Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone: a Randomized Cross Over Pilot Trial
The last decade has shown a progressive scientific interest for new strategies to improve the outcomes of controlled ovarian stimulation (COS).
Given the fact that interovulatory period has been described to have multiple waves of follicular recruitment, luteal phase ovarian stimulation (LPOS) has been proposed as new protocol for COS, with satisfactory ovarian response and pregnancy outcomes. On the other hand progestin-primed ovarian stimulation (PPOS) is today considered an innovative protocol aiming to achieve multi-follicle recruitment and block the luteinizing hormone (LH) surge through progesterone administration in place of the traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist. This protocol has been shown to be equally effective as LH suppression with GnRH antagonist reporting equivalent oocyte retrieval rates, endocrine profiles, viable embryo numbers, and pregnancy outcomes. Due to the feasibility and patients-friendly characteristics of PPOS in oocytes donors, the current study aims to investigate the impact on the number of cumulus-oocyte complexes (COCs) when a PPOS protocol is associated to both conventional follicular phase stimulation and LPOS for vitrification of oocytes in oocyte donors. Moreover, it aims to determine whether LPOS using PPOS protocol has comparable outcomes to conventional follicular phase stimulation with PPOS protocol, in oocyte donor patients.
Read the detailed description
The current study is a single centre randomized, crossover, open label, pilot trial.
The study will be conducted on 50 patients who wish to donate their oocytes. All participants will be informed about the nature of the study and informed consent will be taken from all of them.
Patients will randomly undergo two treatment sequences, treatment sequence 1 and treatment sequence 2. Treatment sequence 1 consists of treatment A followed by treatment B; treat-ment sequence 2 consists of treatment B followed by treatment A. The time-interval between the two treatments (washout period) will be minimum two months after trigger and maximum twelve months. All patients will undergo PPOS: one cycle with follicular phase ovarian stimulation and one cycle with LPOS.
Work up: Complete history, hormonal investigations (FSH, LH, E2, Progesterone, Prolactine, AMH, TSH), Basal transvaginal ultrasound
Treatment A: Ovarian stimulation is started on day 2 of the follicular phase with daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 6 until the day of trigger.
Patients response will be monitored by:
Serum E2, P, FSH, LH and human chorionic gonadotropin (HCG) levels on day 2 of the follicular phase. Patients will be reevaluated on stimulation day 8 every 2 days with ultrasound scan to assess follicular growth and endocrine monitoring with E2, P, FSH and LH levels until the criteria for oocyte trigger are achieved.
Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered.
Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 6 or when serum LH > 10 IU/L until day of trigger.
Patients response will be monitored by:
Serum estradiol E2, P, FSH, LH and HCG levels on day 20 of the follicular phase In case of absence of luteal phase values (progesterone > 1.5 ng/ml) at the blood sample of day 20, stimulation will not be started. In this case, hormonal serum assessment with evaluation of E2, P, FSH and LH levels will be repeated every 2 days until luteal phase values will be achieved, and the stimulation will be started. Patient will be reevaluated on stimulation day 8 every 2 days with ultrasound scan to assess follicular growth and endocrine monitoring with E2, P, FSH and LH levels until the criteria for oocyte trigger are achieved.
Both treatments: Oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (0.2 mg Gonapeptyl). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated
Statistical Considerations and Sample size Justification
Fifty - patients (25 for each sequence) need to be included. Considering a dropout rate of about 15%, 66 patients will probably be required to reach an adequate sample size.This is a pilot study, and 50 subjects is considered both practically feasible and sufficient to get reliable results in order to guide further trials in this research area.
The primary endpoint, the total number of cumulus-oocyte complexes, will be compared between the two treatments using an analysis of variance model with subject, period, and treatment as factors. The mean difference between the two treatments and its 95% confidence interval will be estimated from the model.
- Conditions
- Oocyte Donors, Oocyte Donation
- Being tested
- Follitropin delta (Rekovelle), Duphaston, GnRH agonist (Gonapeptyl)
- Keywords
- cumulus-oocyte complexes, progestin primed ovarian stimulation, controlled ovarian stimulation, luteal phase ovarian stimulation, follicular phase ovarian stimulation, follitropin delta, dydrogesterone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Follitropin delta (Rekovelle)Drug
12 mcg/day will be used for ovarian stimulation in both arms
DuphastonDrug
20 mg/day will be used for pituitary suppression in both arms
GnRH agonist (Gonapeptyl)Drug
(2 ampules:0.2 mg) will be used for ovulation triggering in both arms
| Study group | Role | What they receive |
|---|---|---|
| Follitropin delta and dydrogesterone (treatment A followed by treatment B) | Other | Treatment A: Ovarian stimulation is started with daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 until the criteria for oocyte trigger are achieved.
Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 or when serum LH > 10 IU/L until day of trigger.
For both treatment (A and B) oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (Gonapeptyl 0.2 mg). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated. Receives: Drug: Follitropin delta (Rekovelle); Drug: Duphaston; Drug: GnRH agonist (Gonapeptyl) |
| Follitropin delta and dydrogesterone (treatment B followed by treatment A) | Other | Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 or when serum LH > 10 IU/L until day of trigger.
Treatment A: Ovarian stimulation is started with daily subcutaneous injections of Follitropin delta12 mcg/daily (Rekovelle) from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 until the criteria for oocyte trigger are achieved.
For both treatment (B and A) oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (Gonapeptyl 0.2 mg). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated. Receives: Drug: Follitropin delta (Rekovelle); Drug: Duphaston; Drug: GnRH agonist (Gonapeptyl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of retrieved COCs in both treatment groups
number of retrieved cumulus-oocyte complexes
Measured: 10-20 minutes after oocyte retrieval
Secondary outcomes (5)
Endocrine profile in both treatment groups
evaluation of serum E2, FSH, LH, Progesterone
Measured: through study completion, an average of 1 year
Consumption of gonadotrophins in both treatment groups
(mcg) of gonadotrophins used during ovarian stimulation
Measured: through study completion, an average of 1 year
Duration of ovarian stimulation in both treatment groups
days of ovarian stimulation
Measured: through study completion, an average of 1 year
Days of progestin use in both treatment groups
days of progestin use during ovarian stimulation
Measured: through study completion, an average of 1 year
Total number of MII oocytes in both treatment groups
the number of MII oocytes retrieved that will be assessed after denudation
Measured: 1-2 hours after oocyte retrieval
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2022
- Study start1 Apr 2023
- Primary completion30 Sep 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Oocyte DonorsStudies 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CRG UZ Brussel
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Federica Di Guardo, CRG UZ Brussel
- Investigators
- Christophe Blockeel, Prof, MD, Study director, Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05521828
- Sponsor's protocol ID
- CS-10459
- Acronym
- LadyDe
- Status last verified
- Feb 2024
- First submitted
- 25 Aug 2022
- Last updated
- 8 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012 Jan-Feb;18(1):73-91. doi: 10.1093/humupd/dmr039. Epub 2011 Nov 8.
PubMed 22068695Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2.
PubMed 12849812Bosch E, Havelock J, Martin FS, Rasmussen BB, Klein BM, Mannaerts B, Arce JC; ESTHER-2 Study Group. Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind Phase 3 safety trial. Reprod Biomed Online. 2019 Feb;38(2):195-205. doi: 10.1016/j.rbmo.2018.10.012. Epub 2018 Dec 14.
PubMed 30594482Cakmak H, Tran ND, Zamah AM, Cedars MI, Rosen MP. A novel "delayed start" protocol with gonadotropin-releasing hormone antagonist improves outcomes in poor responders. Fertil Steril. 2014 May;101(5):1308-14. doi: 10.1016/j.fertnstert.2014.01.050. Epub 2014 Mar 14.
PubMed 24636401Chian RC, Chung JT, Downey BR, Tan SL. Maturational and developmental competence of immature oocytes retrieved from bovine ovaries at different phases of folliculogenesis. Reprod Biomed Online. 2002 Mar-Apr;4(2):127-32. doi: 10.1016/s1472-6483(10)61929-3.
PubMed 12470574Cummins JM, Breen TM, Harrison KL, Shaw JM, Wilson LM, Hennessey JF. A formula for scoring human embryo growth rates in in vitro fertilization: its value in predicting pregnancy and in comparison with visual estimates of embryo quality. J In Vitro Fert Embryo Transf. 1986 Oct;3(5):284-95. doi: 10.1007/BF01133388.
PubMed 3783014Demirtas E, Elizur SE, Holzer H, Gidoni Y, Son WY, Chian RC, Tan SL. Immature oocyte retrieval in the luteal phase to preserve fertility in cancer patients. Reprod Biomed Online. 2008 Oct;17(4):520-3. doi: 10.1016/s1472-6483(10)60239-8.
PubMed 18854106Fernandez-Sanchez M, Visnova H, Yuzpe A, Klein BM, Mannaerts B, Arce JC; ESTHER-1 and ESTHER-2 Study Group. Individualization of the starting dose of follitropin delta reduces the overall OHSS risk and/or the need for additional preventive interventions: cumulative data over three stimulation cycles. Reprod Biomed Online. 2019 Apr;38(4):528-537. doi: 10.1016/j.rbmo.2018.12.032. Epub 2018 Dec 23.
PubMed 30713022Giles J, Alama P, Gamiz P, Vidal C, Badia P, Pellicer A, Bosch E. Medroxyprogesterone acetate is a useful alternative to a gonadotropin-releasing hormone antagonist in oocyte donation: a randomized, controlled trial. Fertil Steril. 2021 Aug;116(2):404-412. doi: 10.1016/j.fertnstert.2021.02.036. Epub 2021 Apr 2.
PubMed 33814126Guan S, Feng Y, Huang Y, Huang J. Progestin-Primed Ovarian Stimulation Protocol for Patients in Assisted Reproductive Technology: A Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2021 Aug 31;12:702558. doi: 10.3389/fendo.2021.702558. eCollection 2021.
PubMed 34531825Ioannidou PG, Bosdou JK, Lainas GT, Lainas TG, Grimbizis GF, Kolibianakis EM. How frequent is severe ovarian hyperstimulation syndrome after GnRH agonist triggering in high-risk women? A systematic review and meta-analysis. Reprod Biomed Online. 2021 Mar;42(3):635-650. doi: 10.1016/j.rbmo.2020.11.008. Epub 2020 Nov 28.
PubMed 33483281Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014 Dec;29(6):684-91. doi: 10.1016/j.rbmo.2014.08.009. Epub 2014 Sep 6.
PubMed 25444501Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, Shoham Z. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014 Jan;101(1):105-11. doi: 10.1016/j.fertnstert.2013.09.007. Epub 2013 Oct 23.
PubMed 24161646Maman E, Meirow D, Brengauz M, Raanani H, Dor J, Hourvitz A. Luteal phase oocyte retrieval and in vitro maturation is an optional procedure for urgent fertility preservation. Fertil Steril. 2011 Jan;95(1):64-7. doi: 10.1016/j.fertnstert.2010.06.064. Epub 2010 Aug 5.
PubMed 20688325McNatty KP, Hillier SG, van den Boogaard AM, Trimbos-Kemper TC, Reichert LE Jr, van Hall EV. Follicular development during the luteal phase of the human menstrual cycle. J Clin Endocrinol Metab. 1983 May;56(5):1022-31. doi: 10.1210/jcem-56-5-1022.
PubMed 6403567
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Luteal Phase Ovarian Stimulation With Follitropin Delta and Dydrogesterone: a Randomized Cross Over Pilot Trial
- ClinicalTrials.gov ID
- NCT05521828
- Acronym / sponsor ID
- LadyDe / CS-10459
- Conditions
- Oocyte Donors, Oocyte Donation
- Keywords
- cumulus-oocyte complexes, progestin primed ovarian stimulation, controlled ovarian stimulation, luteal phase ovarian stimulation, follicular phase ovarian stimulation, follitropin delta, dydrogesterone
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- CRG UZ BrusselUniversity, hospital or other
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 30 Aug 2022 (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 last decade has shown a progressive scientific interest for new strategies to improve the outcomes of controlled ovarian stimulation (COS).
Given the fact that interovulatory period has been described to have multiple waves of follicular recruitment, luteal phase ovarian stimulation (LPOS) has been proposed as new protocol for COS, with satisfactory ovarian response and pregnancy outcomes. On the other hand progestin-primed ovarian stimulation (PPOS) is today considered an innovative protocol aiming to achieve multi-follicle recruitment and block the luteinizing hormone (LH) surge through progesterone administration in place of the traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist. This protocol has been shown to be equally effective as LH suppression with GnRH antagonist reporting equivalent oocyte retrieval rates, endocrine profiles, viable embryo numbers, and pregnancy outcomes. Due to the feasibility and patients-friendly characteristics of PPOS in oocytes donors, the current study aims to investigate the impact on the number of cumulus-oocyte complexes (COCs) when a PPOS protocol is associated to both conventional follicular phase stimulation and LPOS for vitrification of oocytes in oocyte donors. Moreover, it aims to determine whether LPOS using PPOS protocol has comparable outcomes to conventional follicular phase stimulation with PPOS protocol, in oocyte donor patients.
Detailed description
The current study is a single centre randomized, crossover, open label, pilot trial.
The study will be conducted on 50 patients who wish to donate their oocytes. All participants will be informed about the nature of the study and informed consent will be taken from all of them.
Patients will randomly undergo two treatment sequences, treatment sequence 1 and treatment sequence 2. Treatment sequence 1 consists of treatment A followed by treatment B; treat-ment sequence 2 consists of treatment B followed by treatment A. The time-interval between the two treatments (washout period) will be minimum two months after trigger and maximum twelve months. All patients will undergo PPOS: one cycle with follicular phase ovarian stimulation and one cycle with LPOS.
Work up: Complete history, hormonal investigations (FSH, LH, E2, Progesterone, Prolactine, AMH, TSH), Basal transvaginal ultrasound
Treatment A: Ovarian stimulation is started on day 2 of the follicular phase with daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 6 until the day of trigger.
Patients response will be monitored by:
Serum E2, P, FSH, LH and human chorionic gonadotropin (HCG) levels on day 2 of the follicular phase. Patients will be reevaluated on stimulation day 8 every 2 days with ultrasound scan to assess follicular growth and endocrine monitoring with E2, P, FSH and LH levels until the criteria for oocyte trigger are achieved.
Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered.
Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 6 or when serum LH > 10 IU/L until day of trigger.
Patients response will be monitored by:
Serum estradiol E2, P, FSH, LH and HCG levels on day 20 of the follicular phase In case of absence of luteal phase values (progesterone > 1.5 ng/ml) at the blood sample of day 20, stimulation will not be started. In this case, hormonal serum assessment with evaluation of E2, P, FSH and LH levels will be repeated every 2 days until luteal phase values will be achieved, and the stimulation will be started. Patient will be reevaluated on stimulation day 8 every 2 days with ultrasound scan to assess follicular growth and endocrine monitoring with E2, P, FSH and LH levels until the criteria for oocyte trigger are achieved.
Both treatments: Oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (0.2 mg Gonapeptyl). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated
Statistical Considerations and Sample size Justification
Fifty - patients (25 for each sequence) need to be included. Considering a dropout rate of about 15%, 66 patients will probably be required to reach an adequate sample size.This is a pilot study, and 50 subjects is considered both practically feasible and sufficient to get reliable results in order to guide further trials in this research area.
The primary endpoint, the total number of cumulus-oocyte complexes, will be compared between the two treatments using an analysis of variance model with subject, period, and treatment as factors. The mean difference between the two treatments and its 95% confidence interval will be estimated from the model.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Follitropin delta and dydrogesterone (treatment A followed by treatment B) | Other | Drug: Follitropin delta (Rekovelle), Drug: Duphaston, Drug: GnRH agonist (Gonapeptyl)Treatment A: Ovarian stimulation is started with daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 until the criteria for oocyte trigger are achieved. Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 or when serum LH > 10 IU/L until day of trigger. For both treatment (A and B) oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (Gonapeptyl 0.2 mg). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated. |
| Follitropin delta and dydrogesterone (treatment B followed by treatment A) | Other | Drug: Follitropin delta (Rekovelle), Drug: Duphaston, Drug: GnRH agonist (Gonapeptyl)Treatment B: From day 20 of the menstrual cycle onwards, daily subcutaneous injections of Follitropin delta (Rekovelle) 12 mcg/daily will be administered. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 or when serum LH > 10 IU/L until day of trigger. Treatment A: Ovarian stimulation is started with daily subcutaneous injections of Follitropin delta12 mcg/daily (Rekovelle) from day 2 of the follicular phase onwards. Dydrogesterone (Duphaston) 20mg/day will be initiated on stimulation day 7 until the criteria for oocyte trigger are achieved. For both treatment (B and A) oocyte maturation trigger will be planned when transvaginal ultrasound shows at least 3 follicles >20mm in diameter with a single subcutaneous injection of GnRH agonist (Gonapeptyl 0.2 mg). Oocyte retrieval will be performed 36 hours after trigger. The retrieved cumulus oocyte complexes will be counted, denuded and the number of mature oocytes evaluated. |
Who may qualify
- Ages
- 18 to 36 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Body mass Index (BMI) ≥18 to < 28
- Signed informed consent
- Regular menstrual cycle length i.e. 24-35 days
Key exclusion criteria (6 listed)
- Contraindications to the use of gonadotropins
- Endometriosis grade 3-4
- Patients with Anti-mullerian hormone (AMH) <1.1 ng/ml and/or antral follicular count (AFC)<7
- Patients with Follicle Number Per Ovary (FNPO) ≥ 19 and/or AMH >5ng/ml
- Patients under contraception with hormonal intrauterine device (IUD)
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 |
|---|---|---|
| Follitropin delta (Rekovelle)12 mcg/day will be used for ovarian stimulation in both arms | Drug | Follitropin delta and dydrogesterone (treatment A followed by treatment B), Follitropin delta and dydrogesterone (treatment B followed by treatment A) |
| Duphaston20 mg/day will be used for pituitary suppression in both arms | Drug | Follitropin delta and dydrogesterone (treatment A followed by treatment B), Follitropin delta and dydrogesterone (treatment B followed by treatment A) |
| GnRH agonist (Gonapeptyl)(2 ampules:0.2 mg) will be used for ovulation triggering in both arms | Drug | Follitropin delta and dydrogesterone (treatment A followed by treatment B), Follitropin delta and dydrogesterone (treatment B followed by treatment A) |
Primary outcome
number of retrieved COCs in both treatment groups
Time frame: 10-20 minutes after oocyte retrieval
number of retrieved cumulus-oocyte complexes
5 secondary outcomes
Endocrine profile in both treatment groups
Time frame: through study completion, an average of 1 year
Consumption of gonadotrophins in both treatment groups
Time frame: through study completion, an average of 1 year
Duration of ovarian stimulation in both treatment groups
Time frame: through study completion, an average of 1 year
Days of progestin use in both treatment groups
Time frame: through study completion, an average of 1 year
Total number of MII oocytes in both treatment groups
Time frame: 1-2 hours after oocyte retrieval
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
- Background: PubMed 22068695Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012 Jan-Feb;18(1):73-91. doi: 10.1093/humupd/dmr039. Epub 2011 Nov 8.
- Background: PubMed 12849812Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2.
- Background: PubMed 30594482Bosch E, Havelock J, Martin FS, Rasmussen BB, Klein BM, Mannaerts B, Arce JC; ESTHER-2 Study Group. Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind Phase 3 safety trial. Reprod Biomed Online. 2019 Feb;38(2):195-205. doi: 10.1016/j.rbmo.2018.10.012. Epub 2018 Dec 14.
- Background: PubMed 24636401Cakmak H, Tran ND, Zamah AM, Cedars MI, Rosen MP. A novel "delayed start" protocol with gonadotropin-releasing hormone antagonist improves outcomes in poor responders. Fertil Steril. 2014 May;101(5):1308-14. doi: 10.1016/j.fertnstert.2014.01.050. Epub 2014 Mar 14.
- Background: PubMed 12470574Chian RC, Chung JT, Downey BR, Tan SL. Maturational and developmental competence of immature oocytes retrieved from bovine ovaries at different phases of folliculogenesis. Reprod Biomed Online. 2002 Mar-Apr;4(2):127-32. doi: 10.1016/s1472-6483(10)61929-3.
- Background: PubMed 3783014Cummins JM, Breen TM, Harrison KL, Shaw JM, Wilson LM, Hennessey JF. A formula for scoring human embryo growth rates in in vitro fertilization: its value in predicting pregnancy and in comparison with visual estimates of embryo quality. J In Vitro Fert Embryo Transf. 1986 Oct;3(5):284-95. doi: 10.1007/BF01133388.
- Background: PubMed 18854106Demirtas E, Elizur SE, Holzer H, Gidoni Y, Son WY, Chian RC, Tan SL. Immature oocyte retrieval in the luteal phase to preserve fertility in cancer patients. Reprod Biomed Online. 2008 Oct;17(4):520-3. doi: 10.1016/s1472-6483(10)60239-8.
- Background: PubMed 30713022Fernandez-Sanchez M, Visnova H, Yuzpe A, Klein BM, Mannaerts B, Arce JC; ESTHER-1 and ESTHER-2 Study Group. Individualization of the starting dose of follitropin delta reduces the overall OHSS risk and/or the need for additional preventive interventions: cumulative data over three stimulation cycles. Reprod Biomed Online. 2019 Apr;38(4):528-537. doi: 10.1016/j.rbmo.2018.12.032. Epub 2018 Dec 23.
- Background: PubMed 33814126Giles J, Alama P, Gamiz P, Vidal C, Badia P, Pellicer A, Bosch E. Medroxyprogesterone acetate is a useful alternative to a gonadotropin-releasing hormone antagonist in oocyte donation: a randomized, controlled trial. Fertil Steril. 2021 Aug;116(2):404-412. doi: 10.1016/j.fertnstert.2021.02.036. Epub 2021 Apr 2.
- Background: PubMed 34531825Guan S, Feng Y, Huang Y, Huang J. Progestin-Primed Ovarian Stimulation Protocol for Patients in Assisted Reproductive Technology: A Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2021 Aug 31;12:702558. doi: 10.3389/fendo.2021.702558. eCollection 2021.
- Background: PubMed 33483281Ioannidou PG, Bosdou JK, Lainas GT, Lainas TG, Grimbizis GF, Kolibianakis EM. How frequent is severe ovarian hyperstimulation syndrome after GnRH agonist triggering in high-risk women? A systematic review and meta-analysis. Reprod Biomed Online. 2021 Mar;42(3):635-650. doi: 10.1016/j.rbmo.2020.11.008. Epub 2020 Nov 28.
- Background: PubMed 25444501Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014 Dec;29(6):684-91. doi: 10.1016/j.rbmo.2014.08.009. Epub 2014 Sep 6.
- Individual participant dataSharing planned: No
Related trials for Oocyte Donors
Active, not recruitingObservational study
Fresh Versus Vitrified-Warmed Donor Oocytes: Embryological and Clinical Outcomes
Infertility, Donor Oocyte Assisted Reproduction
RecruitingObservational study
Aurora Test for ART Donor Patients (AURORA-Donor)
Infertility
Recruiting
Validation of Donor Oocytes Semi-automated Vitrification
Vitrification, Egg Donor
Recruiting
SISTER: Sibling Oocyte Insemination With Frozen Sperm From Third Party Donors: Evaluation of Reproductive Techniques
Infertility, Female, Reproductive Techniques, Assisted
Recruiting
Usefulness of Corifollitropin α as Alternative to Conventional Daily rFSH Protocols in Oocyte Donors Undergoing Pituitary Suppression With Medroxiprogesterona Acetate (MPA)
Infertility, Female, Reproductive Sterility
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.
Elsie Nulens contact
Christophe Blockeel, Prof, MD study director
Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Belgium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Follitropin delta (Rekovelle), Duphaston and GnRH agonist (Gonapeptyl) in people with Oocyte Donors and Oocyte Donation, run by CRG UZ Brussel at 1 site 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 3 inclusion and 6 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 8 Feb 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 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 Christophe Blockeel, Prof, MD (+ 32 2 4776699, Christophe.Blockeel@uzbrussel.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of retrieved COCs in both treatment groups (time frame: 10-20 minutes after 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 NCT05521828, which also lists 19 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 8 Feb 2024.