Infertility
Conditions
Brief summary
Ovarian stimulation (OS) is a key component of IVF, aimed at increasing oocyte yield and improving embryo development potential. While early protocols relied solely on FSH, newer approaches incorporate hMG and LH-based stimulation, allowing more individualized treatments for specific patient populations. Evidence suggests that hMG and recombinant FSH (rFSH) have comparable effectiveness in stimulation outcomes, and current guidelines support the use of both. However, the impact of different gonadotropins on embryo quality remains unclear, with mixed findings across protocols. Given the increasing use of combined rFSH and hMG and the limited data in PPOS protocols, this study proposes a randomized controlled trial to compare embryo quality between two different rFSH-hMG dosing strategies.
Interventions
DRUG10 mcg of follitropin-delta + 150 of hMG
On day 2 or 3 of the menstrual cycle, daily injections of 10 mcg of Rekovelle + 150 IU of Menopur (Stimulation Day 1) will be administered. Scan controls and blood exams will be performed on stimulation days 6, 8 and on trigger day. Further blood exams will add according to clinical needs. The dose will be the same during the whole course of stimulation and no dose adjustments will be performed.
DRUG5 mcg of follitropin-delta + 225 of hMG
On day 2 or 3 of the menstrual cycle, daily injections of 5 mcg of Rekovelle + 225 IU of Menopur (Stimulation Day 1) will be administered. Scan controls and blood exams will be performed on stimulation days 6, 8 and on trigger day. Further blood exams will add according to clinical needs. The dose will be the same during the whole course of stimulation and no dose adjustments will be performed.
Sponsors
Fundacion Dexeus
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
38 Years to 41 Years
Healthy volunteers
No
Inclusion criteria
* Undergoing preimplantation genetic screening cycles * AMH 0.5 - 3.5 ng/ml or AFC 5-20 (results of up to one year will be valid) * BMI 18.5 - 30 Kg/m2 * Normal karyotypes in both partners
Exclusion criteria
* Previous poor ovarian response (≤3 oocytes with a conventional stimulation protocol), according to Bologna criteria * Severe male factor requiring TESE (testicular sperm extraction) * 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 interfere with the trial assessment) * Monogenic disease to be detected with PGT-M * Biochemical and/or ultrasonographic evidence of polycystic ovarian syndrome * Endocrinological and/or autoimmune disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Good quality blastocysts | From Day 5 to Day 7 after insemination | number of good quality blastocysts based on the Istanbul consensus workshop criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Gonadotropin Dose Administered | From initiation of ovarian stimulation until day of trigger (up to 15 days) | Cumulative dose of gonadotropins (IU) administered during ovarian stimulation. |
| Duration of Ovarian Stimulation | From first day of stimulation until trigger day (up to 15days) | Number of days of gonadotropin administration required to reach criteria for triggering final oocyte maturation. |
| Total Number of Oocytes Retrieved | At oocyte retrieval | Total number of oocytes collected during oocyte retrieval procedure following ovarian stimulation. |
| Number of mature oocytes (MII) retrieved | At oocyte retrieval | Number of metaphase II (MII) oocytes identified among retrieved oocytes |
| Serum levels of estradiol (E2) | At baseline, mid-stimulation (e.g., Day 5-7), and trigger day (up to 5 days) | Serum levels of estradiol (E2) measured at predefined time points during stimulation |
| Serum levels of progesterone (P4) | At baseline, mid-stimulation (e.g., Day 5-7), and trigger day (up to 5 days) | Serum levels progesterone (P4) measured at predefined time points during stimulation |
| Serum levels of follicle-stimulating hormone (FSH) | At baseline, mid-stimulation (e.g., Day 5-7), and trigger day (up to 5 days) | Serum levels follicle-stimulating hormone (FSH) measured at predefined time points during stimulation |
| Serum levels of luteinizing hormone (LH) | At baseline, mid-stimulation (e.g., Day 5-7), and trigger day (up to 5 days) | Serum levels luteinizing hormone (LH) measured at predefined time points during stimulation |
| Follicle-to-Oocyte Index (FOI) | From baseline AFC assessment to oocyte retrieval | Ratio between the total number of oocytes retrieved and the number of antral follicles counted at baseline before stimulation. |
| Follicular Output RaTe (FORT) | From baseline AFC assessment to trigger day | Ratio between the number of preovulatory follicles on the day of trigger and the number of antral follicles at baseline. |
| Cycle cancellation rate | From start of stimulation to planned oocyte retrieval | Proportion of initiated ovarian stimulation cycles that are cancelled before oocyte retrieval. |
| Reason for cycle cancellation | At time of cycle cancellation | Categorization of causes leading to cycle cancellation (e.g., poor response, hyper-response/risk of OHSS, premature ovulation, patient decision, or medical reasons). |
| Fertilization Rate | Assessed 16-20 hours post-insemination or ICSI | Proportion of oocytes that are successfully fertilized (2PN) relative to the number of inseminated or injected (ICSI) oocytes. |
| Time of appearance of the 2nd polar body (tPB2) | Within 0-6 hours post-ICSI/insemination | ime from insemination or ICSI to the extrusion of the second polar body, indicating completion of oocyte activation. |
| Time of pronuclei appearance (tPNa) | Within 0-20 hours post-ICSI/insemination | Time from insemination or ICSI to the first visualization of pronuclei. |
| Evaluation of both pronuclei | Within 0-20 hours post-ICSI/insemination | Time from insemination or ICSI to the visualization of both pronuclei. |
| Time to Pronuclear Fading (tPNf) | Within 20-30 hours post-ICSI/insemination | Time from insemination or ICSI to disappearance of pronuclei |
| Timing of Early Cleavage Stages (t2-t8) | From fertilization to Day 3 (up to 72 hours) | Time to reach each embryonic cell stage from 2 to 8 cells |
| Time of compaction (tSC) | Day 3-4 post-fertilization (up to ~96 hours) | Time from fertilization to the beginning of blastomere compaction. |
| Time of morula (tM) | Day 4 post-fertilization (up to 120 hours) | Time from fertilization to the formation of a compact morula stage embryo. |
| Time of cavitation (tSB) | Day 4-5 post-fertilization (up to ~120-132 hours) | Time from fertilization to the initiation of blastocoel cavity formation. |
| Time of full blastulation (tB) | Day 5-6 post-fertilization (up to ~144 hours) | Time from fertilization to formation of a fully expanded blastocyst. |
| Total number of Day 5 blastocysts | Day 5 post-fertilization | Number of embryos reaching the blastocyst stage by Day 5 of development. |
| Total number of Day 6 blastocysts | Day 5 post-fertilization | Number of embryos reaching the blastocyst stage by Day 6 of development. |
| Total number of Day 7 blastocysts | Day 5 post-fertilization | Number of embryos reaching the blastocyst stage by Day 7 of development. |
| Total number of euploid embryos | After genetic testing results (typically within 1-2 weeks post-biopsy) | Number of embryos identified as chromosomally normal following preimplantation genetic testing (PGT-A) |
| MII to blastocyst formation rate | From oocyte retrieval to blastocyst stage (up to Day 5-7) | Proportion of mature (MII) oocytes that develop into blastocysts. |
| Number of embryos cryopreserved | At end of embryo culture (Day 5-7) | Total number of embryos suitable for vitrification following culture. |
| Clinical pregnancy rate | At 5-7 weeks of gestation | Presence of one or more intrauterine gestational sacs confirmed by ultrasound. |
| Ongoing Pregnancy Rate | At 8-10 weeks of gestation | Proportion of pregnancies with a viable intrauterine fetus beyond 8-10 weeks of gestation confirmed by ultrasound. |
| Miscarriage Rate | From confirmation of clinical pregnancy up to 20 weeks of gestation | Proportion of clinical pregnancies that result in spontaneous pregnancy loss before 20 weeks of gestation. |
| Live birth rate | At delivery (up to ~40 weeks of gestation following embryo transfer) | Proportion of embryo transfer cycles resulting in at least one live-born infant, defined as the delivery of a living neonate after ≥24 weeks of gestation. |
Countries
Spain
Contacts
CONTACTIgnacio Rodriguez, MSc
PRINCIPAL_INVESTIGATORNikolaos P Polyzos, MD, PhD
Dexeus Universitary Hospital
Outcome results
None listed