INtensity of OVarian Stimualtion and Euploid Embryos

Fertility Clinical Trial

— INOVEE  

Official title:

The Impact of Ovarian Stimulation Intensity on Embryo Euploidy in Advanced Age Women

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06154083
• Other study ID #: FSD-INO-2023-14
• Secondary ID: 2023-507028-22
• Status: Recruiting
• Phase: Phase 4
• Start date: December 12, 2023
• Est. completion date: May 15, 2026

Study information

• Verified date: December 2023
• Source: Institut Universitari Dexeus
• Contact: Nikolaos P Polyzos, MD, PhD
• Phone: 0034932274700
• Email: nikpol[@]dexeus.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized trial was designed as a no-inferiority trial aiming to evaluate if the intensity of stimulation (a milder vs a more intense approach) may have an impact on the number of euploid embryos and the morpho kinetic parameters in advanced age women undergoing PGT-A with a PPOS protocol.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: May 15, 2026
• Est. primary completion date: December 15, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 38 Years to 42 Years

Eligibility

Inclusion Criteria:

• Infertile patients with indication for IVF
• Undergoing preimplantation genetic screening cycles
• AMH >= 1.5 ng/ml and < 3.5 ng/ml (AMH result of up to one year will be valid)
• BMI 18.5 - 30 Kg/m2

Exclusion Criteria:

• Severe male factor requiring TESE (testicular sperm extraction)
• AMH < 1.5 ng/ml or >= 3.5 ng/ml
• Administration of any other drug potentially interfering with the treatment
• Contraindication for hormonal treatment
• Recent history of severe disease requiring regular treatment (clinically significant concurrent medical condition that could compromise subject safety or interfered with the trial assessment).
• Monogenic disease to be detected with PGT-M

Related Conditions & MeSH terms

• Fertility

Intervention

Drug:
• Follitropin-delta (Rekovelle) 20 mcg/day from D1
On day 2 or 3 of the menstrual cycle, daily injections of 20 mcg of Rekovelle (Stimulation Day 1) will be administered. Scan controls blood exams are performed on stimulation days 6, 8, 10 and, according to clinical needs, until trigger day. The dose will be the same during the whole course of stimulation and no dose adjustments will be performed.
• Follitropin-delta (Rekovelle) 15 mcg/day from D1
On day 2 or 3 of the menstrual cycle, daily injections of 15 mcg of Rekovelle (Stimulation Day 1) will be administered. Scan controls and blood exams are performed on stimulation days 6, 8, 10 and, according to clinical needs, until trigger day. The dose will be the same during the whole course of stimulation and no dose adjustments will be performed.

Locations

Country	Name	City	State
Spain	Hospital Universitario Quiron Dexeus	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Fundación Santiago Dexeus Font

Country where clinical trial is conducted

Spain, 

References & Publications (14)

Alper MM, Fauser BC. Ovarian stimulation protocols for IVF: is more better than less? Reprod Biomed Online. 2017 Apr;34(4):345-353. doi: 10.1016/j.rbmo.2017.01.010. Epub 2017 Jan 24. — View Citation

Arce JC, Larsson P, Garcia-Velasco JA. Establishing the follitropin delta dose that provides a comparable ovarian response to 150 IU/day follitropin alfa. Reprod Biomed Online. 2020 Oct;41(4):616-622. doi: 10.1016/j.rbmo.2020.07.006. Epub 2020 Jul 15. — View Citation

Baart EB, Martini E, Eijkemans MJ, Van Opstal D, Beckers NG, Verhoeff A, Macklon NS, Fauser BC. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007 Apr;22(4):980-8. doi: 10.1093/humrep/del484. Epub 2007 Jan 4. — View Citation

Briggs R, Kovacs G, MacLachlan V, Motteram C, Baker HW. Can you ever collect too many oocytes? Hum Reprod. 2015 Jan;30(1):81-7. doi: 10.1093/humrep/deu272. Epub 2014 Oct 31. — View Citation

Devesa M, Tur R, Rodriguez I, Coroleu B, Martinez F, Polyzos NP. Cumulative live birth rates and number of oocytes retrieved in women of advanced age. A single centre analysis including 4500 women >/=38 years old. Hum Reprod. 2018 Nov 1;33(11):2010-2017. doi: 10.1093/humrep/dey295. — View Citation

Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, Scott RT Jr. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril. 2014 Mar;101(3):656-663.e1. doi: 10.1016/j.fertnstert.2013.11.004. Epub 2013 Dec 17. — View Citation

Irani M, Canon C, Robles A, Maddy B, Gunnala V, Qin X, Zhang C, Xu K, Rosenwaks Z. No effect of ovarian stimulation and oocyte yield on euploidy and live birth rates: an analysis of 12 298 trophectoderm biopsies. Hum Reprod. 2020 May 1;35(5):1082-1089. doi: 10.1093/humrep/deaa028. — View Citation

Kok JD, Looman CW, Weima SM, te Velde ER. A high number of oocytes obtained after ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection is not associated with decreased pregnancy outcome. Fertil Steril. 2006 Apr;85(4):918-24. doi: 10.1016/j.fertnstert.2005.09.035. — View Citation

La Marca A, Minasi MG, Sighinolfi G, Greco P, Argento C, Grisendi V, Fiorentino F, Greco E. Female age, serum antimullerian hormone level, and number of oocytes affect the rate and number of euploid blastocysts in in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril. 2017 Nov;108(5):777-783.e2. doi: 10.1016/j.fertnstert.2017.08.029. Epub 2017 Oct 4. — View Citation

Neves AR, Montoya-Botero P, Sachs-Guedj N, Polyzos NP. Association between the number of oocytes and cumulative live birth rate: A systematic review. Best Pract Res Clin Obstet Gynaecol. 2023 Mar;87:102307. doi: 10.1016/j.bpobgyn.2022.102307. Epub 2022 Dec 27. — View Citation

Polyzos NP, Drakopoulos P, Parra J, Pellicer A, Santos-Ribeiro S, Tournaye H, Bosch E, Garcia-Velasco J. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including approximately 15,000 women. Fertil Steril. 2018 Sep;110(4):661-670.e1. doi: 10.1016/j.fertnstert.2018.04.039. — View Citation

Ubaldi FM, Cimadomo D, Vaiarelli A, Fabozzi G, Venturella R, Maggiulli R, Mazzilli R, Ferrero S, Palagiano A, Rienzi L. Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment. Front Endocrinol (Lausanne). 2019 Feb 20;10:94. doi: 10.3389/fendo.2019.00094. eCollection 2019. — View Citation

Venetis CA, Tilia L, Panlilio E, Kan A. Is more better? A higher oocyte yield is independently associated with more day-3 euploid embryos after ICSI. Hum Reprod. 2019 Jan 1;34(1):79-83. doi: 10.1093/humrep/dey342. — View Citation

Wu Q, Li H, Zhu Y, Jiang W, Lu J, Wei D, Yan J, Chen ZJ. Dosage of exogenous gonadotropins is not associated with blastocyst aneuploidy or live-birth rates in PGS cycles in Chinese women. Hum Reprod. 2018 Oct 1;33(10):1875-1882. doi: 10.1093/humrep/dey270. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of euploid embryos	Number of euploid embryos	Trough study completion, an average of 20-30 days.
Secondary	Gonadotropin dose	Total gonadotropin dose used	Up to oocyte pickup, an average of 10-20 days
Secondary	Length of stimulation	Days of stimulation	Up to oocyte pickup, an average of 10-20 days
Secondary	Estradiol	Estradiol level	Up to oocyte pickup, an average of 10-20 days
Secondary	Progesterone	Progesterone level	Up to oocyte pickup, an average of 10-20 days
Secondary	LH	LH level	Up to oocyte pickup, an average of 10-20 days
Secondary	Follicular Output RaTe (FORT)	ratio of the number of preovulatory follicles and the number of antral follicles available at the start of stimulation	Day one of stimulation. 1 Day
Secondary	Cycle cancelation rate	Cycle cancelation rate	Up to oocyte pickup, an average of 10-20 days
Secondary	Fertilization rate	Fertilization rate	Up to one day after oocyte pickup, an average of 10-20 days
Secondary	Time of appearance of the 2nd polar body (tPB2)	Time of appearance of the 2nd polar body (tPB2)	Up to one day after oocyte pickup, an average of 10-20 days
Secondary	Time of pronuclei disappearance (tPNf)		Up to one day after oocyte pickup, an average of 10-20 days
Secondary	Time of division from 2 to 8 cells		Until 1, or 4 days after insemination
Secondary	Time of compactation (tSC)		Until 3, or 4 days after insemination
Secondary	Time of morula (tM)		Until 4 or 7 days after insemination
Secondary	Time of cavitation (tSB)		Until 4 or 7 days after insemination
Secondary	Time of full blastulation (tB)		Until 4 or 7 days after insemination
Secondary	Total number of day 5 blastocysts		Until 5, 6 or 7 days after insemination
Secondary	Total number of good quality blastocysts		Until 5, 6 or 7 days after insemination
Secondary	Total number of embryos		Until 5, 6 or 7 days after insemination
Secondary	Blastocyst formation rate	proportion of 2PN zygotes that reach the blastocyst stage	Until 5, 6 or 7 days after insemination
Secondary	Number of embryos cryopreserved		Until 5, 6 or 7 days after insemination
Secondary	Embryo stage		Until 5, 6 or 7 days after insemination
Secondary	Clinical pregnancy rate	defined as the visualization of one or more gestational sacs	5-6 weeks after transfer
Secondary	Ongoing pregnancy rate	defined as a viable intrauterine pregnancy	8-10 weeks after transfer

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