INtensity of OVarian Stimualtion and Euploid Embryos

Study Overview
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Brief Summary
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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.

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

Conditions
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Fertility

Intervention / Treatment
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* Drug: Follitropin-delta (Rekovelle) 20 mcg/day from D1
* Drug: Follitropin-delta (Rekovelle) 15 mcg/day from D1


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 38 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Follitropin-delta 20 mcg/day from D1<br> | Drug: Follitropin-delta (Rekovelle) 20 mcg/day from D1<br>* 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.<br>|
| Active Comparator: Follitropin-delta 15 mcg/day from D1<br> | Drug: Follitropin-delta (Rekovelle) 15 mcg/day from D1<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of euploid embryos | Number of euploid embryos | Trough study completion, an average of 20-30 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gonadotropin dose | Total gonadotropin dose used | Up to oocyte pickup, an average of 10-20 days | 
| Length of stimulation | Days of stimulation | Up to oocyte pickup, an average of 10-20 days | 
| Estradiol | Estradiol level | Up to oocyte pickup, an average of 10-20 days | 
| Progesterone | Progesterone level | Up to oocyte pickup, an average of 10-20 days | 
| LH | LH level | Up to oocyte pickup, an average of 10-20 days | 
| 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 | 
| Cycle cancelation rate | Cycle cancelation rate | Up to oocyte pickup, an average of 10-20 days | 
| Fertilization rate | Fertilization rate | Up to one day after oocyte pickup, an average of 10-20 days | 
| 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 | 
| Time of pronuclei disappearance (tPNf) |  | Up to one day after oocyte pickup, an average of 10-20 days | 
| Time of division from 2 to 8 cells |  | Until 1, or 4 days after insemination | 
| Time of compactation (tSC) |  | Until 3, or 4 days after insemination | 
| Time of morula (tM) |  | Until 4 or 7 days after insemination | 
| Time of cavitation (tSB) |  | Until 4 or 7 days after insemination | 
| Time of full blastulation (tB) |  | Until 4 or 7 days after insemination | 
| Total number of day 5 blastocysts |  | Until 5, 6 or 7 days after insemination | 
| Total number of good quality blastocysts |  | Until 5, 6 or 7 days after insemination | 
| Total number of embryos |  | Until 5, 6 or 7 days after insemination | 
| Blastocyst formation rate | proportion of 2PN zygotes that reach the blastocyst stage | Until 5, 6 or 7 days after insemination | 
| Number of embryos cryopreserved |  | Until 5, 6 or 7 days after insemination | 
| Embryo stage |  | Until 5, 6 or 7 days after insemination | 
| Clinical pregnancy rate | defined as the visualization of one or more gestational sacs | 5-6 weeks after transfer | 
| Ongoing pregnancy rate | defined as a viable intrauterine pregnancy | 8-10 weeks after transfer |