Does Recombinant FSH (rFSH, I.g. Gonal F®) As Compared to Human Menopausal Gonadotrophin (hMG) Affect Telomere Length of Cumulus Cells During Antral Follicle Growth and Impact Blastocyst Status? (rFSH and hMG)

ART Fertility Clinics LLC

Status: Begins enrollment in 7 months

Conditions: OVARIAN STIMULATION; Telomere Length; Telomere Length, Mean Leukocyte

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT06732843

2212-ABU-012-DN

Details and patient eligibility

About

Gonal-F® (follitropin alfa) is a recombinant FSH without LH activity, while Menopur® contains both LH and hCG. The MEGASET trial compared Menopur® and Gonal-F® in GnRH antagonist cycles with SET, showing similar efficacy. A subsequent study (MEGASET-HR) in high responders found ongoing pregnancy rates of 35.5% for Menopur® and 30.7% for Gonal-F®, with a lower early pregnancy loss for Menopur® (14.5% vs 25.5%).

Telomere length (TL) in oocyte cumulus cells (CC) correlates with oocyte quality and embryo outcomes. This study aims to assess whether stimulation type (hMG vs. Gonal-F) affects TL in CC and subsequent blastocyst development. A randomized, open-label, cross-over study in normo-responders will analyze telomere length, embryo quality, and hormonal markers.

Full description

Gonal-F® (follitropin alfa) is a recombinant human follicle-stimulating hormone (rFSH), without LH activity. Urine-derived, human-menopausal-gonadotropin contains LH and hCG. A highly purified hMG, HP-HMG, Menopur® has been compared with Gonal-F® in terms of ongoing pregnancy rate in the so called MEGASET trial ("Menopur in GnRH Antagonist Cycles with Single Embryo Transfer") and both showed to be effective in GnRH antagonist cycles with SET. Another non-inferiority study was initiated in high responders - MEGASET-HR-, comparing Menopur with Gonal-F. After fresh transfer, the ongoing pregnancy rate was similar between groups: 35.5% for Menopur versus 30.7% for Gonal-F, and non-inferiority was established. However, cumulative early pregnancy loss from fresh embryo transfer cycles (ET) and frozen embryo transfer cycles (FETs) in patients treated with HP-hMG was significantly lower as compared to rFSH (14.5% vs 25.5%).

Telomere length (TL) has been long proposed as oocyte quality marker and, recently, has been correlated with pregnancy outcomes. During folliculogenesis, granulosa cells undergo successive cell divisions which can result in telomeric shortening. Telomerase is the enzyme complex that binds the chromosome ends (telomeres) and maintains telomere length and integrity. An association has been shown between telomere length in cumulus cells (CC), oocyte competence and embryo quality. Hence, with the present study, the investigators aim to explore whether the stimulation treatment type (hMG versus Gonal-F) affects the telomere length of oocytes cumulus cells reflecting on subsequent blastocyst development, to help understanding the underlying differences between both gonadotropins.

To the investigators best knowledge, there are no studies evaluating TL in CC from the same patient exposed to two different stimulations. With the present, we intend to perform a randomized, open-label, cross-over study in a selected normo-responders patient population. Patients will be submitted to hormonal analysis, to analysis of telomere length of their oocyte cumulus cells and to analysis of quality markers of its respective embryos/blastocysts. This includes morphokinetics development, euploidy and mitochondria status evaluation of cultured blastocysts.

Enrollment: 10 estimated patients

Sex: Female

Ages: 18 to 38 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Maternal age 18 - 38 years
2. Patients requested PGT-A
3. BMI 18- 30kg/m2
4. Expected normoresponders
5. Fresh autologous ejaculate (≥5 mill/ml)
6. Sperm abstinence: 2-3 days
7. Normal female/male karyotype
8. Regular menstrual cycle length: 25-32 days
9. AFC of 5-10 in each ovary at the beginning of the stimulation
10. Trigger: dual trigger: 2.500 IU urinary hCG + 0.3 mg Decapeptyl. (13)
11. A wash-out period between 1 to 3 months; an inter-cycle variation of 10% in AFC, measured by the same physician, is accepted.
12. Couple agrees to perform two stimulations before continuing with embryo transfer

Exclusion criteria

• 1. Uterine abnormalities as diagnosed by ultrasound 2. Any hormonal or oral contraceptive pretreatment of 3 months preceding the treatment 3. Endometriosis according to American Fertility Society (AFS) ≥3 4. ≥ 2 miscarriages 5. Bologna criteria poor responders (14)

Trial design

10 participants in 1 patient group

Normo-ovarian response patients who undergo an IVF treatment including PGT-A

Description:

Patients will follow the stimulation protocol outlined below: Initial doses will be based on ovarian reserve parameters, with the starting dosage identical for both stimulation cycles (Gonal-F® or hMG): Dose adjustments may be made starting from day 6 Antagonist suppression will be fixed from day 5 onwards Final oocyte maturation will be triggered with a dual trigger: 2,500 IU urinary hCG and 0.3 mg Decapeptyl.