This project wants to determinate whether there is a relationship between the N680S polymorphism genotype of the FSHR gene and the nature of the FSH used in controlled ovarian stimulation.

It is a non-interventional, observational, cross-sectional and retrospective, national and multicenter study, in which a genetic test will be carried out to determine the genotype of the N680S polymorphism in samples of blood of patients who have undergone two cycles of controlled ovarian stimulation in the last 8 months.

The investigators want to investigate whether the N680S polymorphism of the FSRH gene could affects ovarian response with different nature of the FSH used (human FSH and recombinant FSH) in patients undergoing two consecutive cycles of IVF/ICSI with controlled ovarian stimulation.

All patients who agree to participate in the study will have a blood sample taken on the same day as a routine extraction performed for the 2nd cycle of the controlled ovarian stimulation in accordance with the standard clinical practice of each hospital. The sample will be sent to the central laboratory to determine the genotype of the afore mentioned polymorphism and correlate it with the clinical results obtained with the two cycles of controlled ovarian stimulation.

In order to avoid any bias, the study population will follow a crossover design with respect to the type of FSH used in the first and second cycles of the COS (i.e., half of the recruited patients must have undergone a first cycle of COS with recombinant FSH and a second cycle with human FSH; and, conversely, the other half must have undergone a first cycle with human FSH and a second cycle with recombinant FSH). In order to avoid potential modifications to the inclusion criteria, the time elapsed between the two cycles should not exceed 6 months.

Inclusion criteria:

• Signature of Informed Consent
• Age ≤ 37 years
• BMI < 30 kg/m2
• Antral follicles count 1st cycle COS = 5-15
• Antimüllerian hormone basal 1st cycle COS > 1,1 ng/ml and < 3,1 ng/ml
• COS protocol: equal starting dose in the 2 cycles of COS (150-225 UI/day) with dose adjustment from the 5th day of COS; pituitary suppression protocol in the 2 cycles of COS with GnRH antagonist with onset when ≥ 1 follicle of ≥ 14 mm in diameter or E2 ≤ 600 pg/ml; and triggering with hCGr or GnRH agonist
• Optional the use of oral contraceptives (OC) (however, same in the 2 cycles)
• 4-9 recovered oocytes in the 1st cycle of COS
• ≤ 6 months between the 2 cycles of COS

Exclusion criteria:

• Use of the LH activity during the cycles of COS
• Presence of severe male factor
• Grade III-IV endometriosis
• Patients with polycystic ovary syndrome, a history of uterine or ovarian surgeries, hydrosalpinx visible by ultrasound, or uterine fibroids measuring > 30 mm
• Major systemic or uncontrolled endocrine-metabolic diseases affecting the pituitary gland, the thyroid gland, the adrenal glands, the pancreas, the liver, or the kidneys

Patients undergoing two cycles of IVF/ICSI who achieved a suboptimal response after the 1st cycle, did not become pregnant, and consequently underwent another cycle of COS in which the protocol was amended during the 2nd cycle to change the nature of the FSH used during the 1st cycle.