Impact of FSH Dosage During Ovarian Stimulation for IVF/ICSI in Granulosa Cells

Impact of FSH Dosage During Ovarian Stimulation for IVF/ICSI on the Expression of FSH- and LH-receptors in Granulosa Cells

To study the influence of different daily rec-FSH dosages (150 IU versus 300 IU), performed in the same patient in consecutive cycles, on the relation between FSH- and LH-receptors of the granulosa cells of the growing follicle.

This is a prospective cross-over study. Investigators want to study the effect of different dosages of recombinant FSH in the same patient on the expression of the FSH- and LH-receptors in the granulosa cells and on the endocrine milieu in the blood and the follicular fluid. An improved understanding of the mechanism leading to progesterone elevation might initiate a change in the ovarian stimulation approach, thereby not only preventing progesterone elevation and its negative consequences on ART (Assisted Reproductive Technology) outcome, but also improving individualization of the ovarian stimulation treatment according to the patients' characteristics.

Ovarian stimulation, Granulosa cells, Follicle Stimulating Hormone Receptor, Luteinising Hormone Receptor, Elevated progesterone

Participants commence ovarian stimulation on day 2 or 3 of their menstrual cycle with a daily dosage of 150 IU rec-FSH. The dosage will remain constant throughout the course of the stimulation. From the morning of the 5th stimulation day, GnRH-antagonist will be administered daily to prevent LH-rise. As soon as ≥ 3 follicle of a size of 17mm are seen, 0.3 mg GnRH-Agonist will be administered for final oocyte maturation. During ovarian stimulation, follicle puncture procedures with the aspiration of follicular fluid will be performed at the following time: one follicle on the morning of day 5, before the administration of the first GnRH-antagonist one follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation. Oocyte retrieval of all other follicles will be carried out 36 hours after injection of the medication for final oocyte maturation.

Participants commence ovarian stimulation on day 2 or 3 of their menstrual cycle with a daily dosage of 300 IU rec-FSH. The dosage will remain constant throughout the course of the stimulation. From the morning of the 5th stimulation day, GnRH-antagonist will be administered daily to prevent LH-rise. As soon as ≥ 3 follicle of a size of 17mm are seen, 0.3 mg GnRH-Agonist will be administered for final oocyte maturation. During ovarian stimulation, follicle puncture procedures with the aspiration of follicular fluid will be performed at the following time: one follicle on the morning of day 5, before the administration of the first GnRH-antagonist one follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation. Oocyte retrieval of all other follicles will be carried out 36 hours after injection of the medication for final oocyte maturation.

Number of FSHR- and LHR of the GC, obtained from one follicle on the morning of day 5, before the administration of the first GnRH-antagonist, punctured during the ovarian stimulation cycle

Number of FSHR- and LHR of the GC, obtained from tone follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm, punctured during the ovarian stimulation cycle

Number of FSHR- and LHR of the GC, obtained from two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation, punctured during the ovarian stimulation cycle

Number of FSHR- and LHR of the GC, obtained from the follicular fluid of follicles aspirated during OPU

Level of E2 hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist

Level of P4 hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist

Level of FSH hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist

Level of LH hormone in the blood, the morning of day 5, before the administration of the first GnRH-antagonist

Level of E2 hormone in the blood, when there are at least 2 to 3 follicles with a size of 12 to 14 mm

Level of P4 hormone in the blood, when there are at least 2 to 3 follicles with a size of 12 to 14 mm

Level of FSH hormone in the blood, when there are at least 2 to 3 follicles with a size of 12 to 14 mm

Level of LH hormone in the blood, when there are at least 2 to 3 follicles with a size of 12 to 14 mm

Level of E2 hormone in the follicular fluid of one follicle on the morning of day 5, before the administration of the first GnRH-antagonist

Level of P4 hormone in the follicular fluid of one follicle on the morning of day 5, before the administration of the first GnRH-antagonist

Level of FSH hormone in the follicular fluid of one follicle on the morning of day 5, before the administration of the first GnRH-antagonist

Level of LH hormone in the follicular fluid of one follicle on the morning of day 5, before the administration of the first GnRH-antagonist

Level of E2 hormone in the follicular fluid of one follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm

Level of P4 hormone in the follicular fluid of one follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm

Level of FSH hormone in the follicular fluid of one follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm

Level of LH hormone in the follicular fluid of one follicle of the size of 12 to 14 mm, when at least 2 to 3 follicles have reached a size of 12 to 14 mm

Level of E2 hormone in the follicular fluid of two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation

Level of P4 hormone in the follicular fluid of two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation

Level of FSH hormone in the follicular fluid of two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation

Level of LH hormone in the follicular fluid of two follicles (= pre-ovulatory follicle) on the morning of the day of final oocyte maturation

Inclusion Criteria: Desire to perform oocyte freezing for social fertility preservation, age 18 - 38 years BMI of 18-32 kg/m2 Regular menstrual cycles with a length of 24-35 days Anti-Muellerian-Hormone levels between 1.3 - 6.25 ng/ml (Ferraretti and Gianaroli, 2014; Calzada et al., 2019) Exclusion Criteria: Occurrence of ovarian hyperstimulation syndrome (OHSS) Occurrence of poor ovarian response (AFC < 5 and AMH < 0,5ng/ml) in previous ovarian stimulation treatment (20) Polycystic ovary syndrome (PCOS) (21)

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