Low-dose HCG as an Adjunct to Ovarian Stimulation in Subfertile Women Undergoing ART

A Prospective, Multicenter, Double-blind, Placebo-controlled, Phase III Clinical Study, on the Efficacy and Safety of Low-dose hCG in a Short Protocol With GnRH Agonist and Ovarian Stimulation With Recombinant FSH (rFSH) During the Follicular Phase in Subfertile Women Undergoing ART

The objective of this prospective randomized clinical trial is to investigate whether the addition of low-dose hCG to a short GnRH-agonist protocol for IVF and ovarian stimulation with rFSH from the onset of the follicular phase and throughout stimulation in sub fertile women undergoing IVF, improves pregnancy rates.

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, two parallel group of patients, Phase IIIb clinical study to test the efficacy and safety of adding low-dose hCGs in a short protocol with GnRH agonist and ovarian stimulation with recombinant FSH (rFSH) from the onset of the follicular phase and throughout the duration of stimulation in enrolled women to the increase in the rate of clinical pregnancies.

Main end point will be the rate of clinical pregnancy (positive heart rate at 7 weeks of gestation in the ultrasound), while secondary endpoints will be

• The number of follicles (> 11,> 14,> 18 mm) on the day of triggering with hCG
• The thickness of the endometrium on the day of follicular maturation
• Live birth rates
• Automatic abortion rates (loss of pregnancy after positive heart function up to 20 weeks of gestation)
• The rate of ongoing pregnancy (positive heart function after 12 weeks of gestation),
• The percentage of ovarian hyperstimulation syndrome (after triggering) with hCG for the next 2 weeks
• The rate of multiple pregnancy.

Participants will be randomly divided into two groups: the intervention group (Group 1) and the control group (Group 2). Randomization will be done using sealed envelopes marked "Group 1" and "Group 2". The randomization list will be prepared centrally for the four participating clinics (research centers) and there will be a "stratification" per center, per 30, respectively, and will be shared among the participants.

"Group 1" will indicate the application of the protocol by adding hCG with the initiation of controlled ovarian stimulation protocol for IVF / ICSI with rFSH, and "Group 2" will indicate the application of the conventional protocol without the addition of hCG .

Each patient's assignment to a treatment group will be made by calling the unit's midwife who will have 2 envelopes with the above indications and who will not be present when the pair is informed by 2 members of the research team.

Inclusion Criteria:

1. Age: between 35 and 40 years of age,
2. Physiological menstrual cycles (24-35 day cycle),
3. Normal endocrine function (normal PRL and TSH, FSH ≤ 15 IU / ml),
4. Transvaginal ultrasound (TVS) without pathological findings,
5. Free personal medical history,
6. Indication for IVF / ICSI (NICE, 2016)
7. 1st or 2nd IVF / ICSI cycle

Exclusion Criteria:

1. Endocrine or metabolic disorders, e.g. PCO (S)
2. Pathology of the uterus and / or endometrium,
3. Pelvic inflammatory disease (PID),
4. Basal FSH levels> 15 IU / ml,
5. Surgery in the ovaries,
6. Body Mass Index (BMI) ≥ 35 kg / m2,
7. Age: <35 years &> 41 years old