Clinical trial NCT06732843: 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?
Official title: 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?
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: OVARIAN STIMULATION
Telomere Length
Telomere Length, Mean Leukocyte
Keywords: recombinant human follicle-stimulating hormone (rFSH)
uman-menopausal-gonadotropin (hMG
ocyte quality
embryo quality
blastocyst development
Menopur
GonalF
GnRH antagonist cycles
trophectoderm
cumulus cells
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-12-13
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Normo-ovarian response patients who undergo an IVF treatment.

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: In this study the investigators will investigate the telomere length of cumulus cells between two stimulation cycles, using different stimulation medication (rFSH versus hMG) within same patient/woman
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: ART Fertility Clinics LLC
name: Barbara Lawrenz, PhD
role: STUDY_DIRECTOR
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