INtensity of OVarian Stimualtion and Euploid Embryos

Official title

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

Overview

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.

Interventions

• 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.
• Drug 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.

Primary outcome measures

• Number of euploid embryos [Time frame: Trough study completion, an average of 20-30 days.]

Secondary outcome measures (12)

• Gonadotropin dose [Time frame: Up to oocyte pickup, an average of 10-20 days]
• Length of stimulation [Time frame: Up to oocyte pickup, an average of 10-20 days]
• Estradiol [Time frame: Up to oocyte pickup, an average of 10-20 days]
• Progesterone [Time frame: Up to oocyte pickup, an average of 10-20 days]
• LH [Time frame: Up to oocyte pickup, an average of 10-20 days]
• Follicular Output RaTe (FORT) [Time frame: Day one of stimulation. 1 Day]
• Cycle cancelation rate [Time frame: Up to oocyte pickup, an average of 10-20 days]
• Fertilization rate [Time frame: Up to one day after oocyte pickup, an average of 10-20 days]
• Time of appearance of the 2nd polar body (tPB2) [Time frame: Up to one day after oocyte pickup, an average of 10-20 days]
• Time of pronuclei disappearance (tPNf) [Time frame: Up to one day after oocyte pickup, an average of 10-20 days]
• Time of division from 2 to 8 cells [Time frame: Until 1, or 4 days after insemination]
• Time of compactation (tSC) [Time frame: Until 3, or 4 days after insemination]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 1 center

• Hospital Universitario Quiron Dexeus — Barcelona

Publications

• 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. PMID 28169189
• 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. PMID 32819842
• 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. PMID 17204525
• 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. PMID 25362088
• 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. PMID 30272168
• 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. PMID 24355045
• 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. PMID 32348476
• 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. PMID 16580375

Identifiers

NCT: NCT06154083 · FSD-INO-2023-14 · 2023-507028-22

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗