This study will assess the change in endometrial gene expression signature on the day of embryo transfer according to the type of exogenous gonadotropins administered.

Late-follicular elevated progesterone (LFEP) following ovarian stimulation for assisted reproductive technologies (ART) has been linked to abnormal endometrial receptivity expression profiles and lower pregnancy rates. For this reason, physicians frequently propose that patients with LFEP avoid performing a fresh embryo transfer, postponing instead it to a subsequent unstimulated cycle. Although this strategy may reduce the detrimental effect LFEP may have on cumulative ART pregnancy rates, it may also frustrate couples who wish to become pregnant as soon as possible.

With the intent of minimizing potentially-avoidable treatment delays, an increasing number of researchers are proposing that physicians revisit their current ovarian stimulation regimens. One strategy which may reduce the incidence of LFEP is to decrease the dose of gonadotropins administered at the end of stimulation (i.e. a stepdown protocol). A similar approach, using corifollitropin alpha (CFA), has also been recently advanced, taking advantage of the stepdown-like pharmacodynamic profile of this compound.

In order to assess the clinical usefulness of these strategies, the investigators propose a single-center, open-label, paired, randomized trial. The main objective of this study is to assess the changes in the endometrial gene expression profile on the day of fresh embryo transfer according to the type of gonadotropins administered for ovarian stimulation. In summary, all consenting subjects will first undergo an endometrial biopsy seven days after the luteinizing hormone peak in an unmedicated natural cycle. This biopsy will serve as the baseline endometrial biopsy (natural cycle biopsy) for a gene expression analysis. Following this baseline biopsy, subjects will be randomly allocated to a specific type of ovarian stimulation regimen in order to later perform a second endometrial biopsy, this time five days after oocyte retrieval (stimulated cycle biopsy). Subjects will be randomized to administer, on the third day of their menstrual cycle, either a single dose of 150 IU of CFA (study arms 1A and 1B) or a fixed daily dose of 200 or 300 IU of recombinant follicle stimulating (rFSH, study arm 2). On the eighth day of stimulation, it is expected that 15% to 30% of all subjects who performed CFA will have reached the follicular development criteria for final oocyte maturation and ovulation triggering.

Inclusion Criteria:

1. Informed consent form (ICF) dated and signed.
2. Age: ≥18 and ≤42 years old.
3. AFC <20.
4. AMH <2.5 ng/mL, performed in the 12 months prior to inclusion.
5. Body Mass Index (BMI): ≥18.5 Kg/m2 and <30 Kg/m2.
6. Weight: ≥50 kg and <80 kg.
7. First or second ART cycle (with pregnancy wish and planned for single blastocyst transfer) at the study site, or fertility preservation cycle.
8. Regular menstrual cycles (between 22 and 35 days).
9. Two ovaries present.

Exclusion Criteria:

1. Simultaneous participation in another clinical study.
2. Previous history of poor ovarian response (<4 oocytes retrieved) with a maximal dose of OS (≥300 IU/day) or OHSS, regardless of gonadotropin dose.
3. Known reasons for impaired implantation (i.e. hydrosalpinx, fibroid distorting the endometrial cavity, Asherman's syndrome, thrombophilia or endometrial tuberculosis).
4. Repeated miscarriages (>2 previous biochemical pregnancies or >2 spontaneous miscarriages).
5. Recurrent implantation failure (>3 failed cycles with good quality embryos).
6. Polycystic ovary syndrome (PCOS).
7. Tumours of the ovary, breast, uterus, pituitary or hypothalamus.
8. Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause.
9. Ovarian cysts or enlarged ovaries.
10. Fibroid tumours of the uterus incompatible with pregnancy.
11. Malformations of the reproductive organs incompatible with pregnancy.
12. Primary gonadal failure.
13. Renal impairment defined as estimated glomerular filtration rate of 90 ml/min/1.73 m2 determined by the Modified Diet and Renal Disease (MDRD) equation at screening.
14. Previous antibiotic hypersensitivity reactions (streptomycin and/or neomycin).
15. Risk factors for thromboembolic events, such as a personal or family history, severe obesity or thrombophilia.
16. Moderate or severe hepatic impairment.
17. Untreated and uncontrolled thyroid dysfunction.
18. Current use of oral contraceptive, anti-depressants, anti-psychotics, steroids, anti-epileptics or chemotherapy.
19. Administration of exogenous Estradiol (E2), Progesterone (P4) or gonadotropins in the preceding menstrual cycle.
20. Active female smoking.
21. Acceptors of donated oocytes/embryos.
22. Ongoing pregnancy.
23. Women who have previously enrolled in the trial.
24. Those unable to comprehend the investigational nature of the proposed study.