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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin

Intervention / Treatment
-----------------
* Drug: hCG
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: between 35 and 40 years of age, Physiological menstrual cycles (24-35 day cycle), Normal endocrine function (normal PRL and TSH, FSH ≤ 15 IU / ml), Transvaginal ultrasound (TVS) without pathological findings, Free personal medical history, Indication for IVF / ICSI (NICE, 2016) 1st or 2nd IVF / ICSI cycle Exclusion Criteria: Endocrine or metabolic disorders, e.g. PCO (S) Pathology of the uterus and / or endometrium, Pelvic inflammatory disease (PID), Basal FSH levels> 15 IU / ml, Surgery in the ovaries, Body Mass Index (BMI) ≥ 35 kg / m2, Age: <35 years &> 41 years old

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 [HCG (+) group]<br>Group 1 will indicate the application of the protocol by adding hCG with the initiation of standard GnRH agonist protocol for IVF / ICSI with rFSH | Drug: hCG<br>* the addition of hCG (Pregnyl®, MSD Greece) will begin with the administration of gonadotrophin at a dose of 100 IU per day, administered subcutaneously, and will continue until the administration of hCG for follicular maturation.<br>* Other names: Pregnyl;|
| Placebo Comparator: Group 2 [placebo]<br>Group 2 will indicate the application of the standard GnRH agonist protocol without the addition of hCG, but placebo, instead | Drug: Placebo<br>* 100IU per day containing N/S 0.9% will be injected<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of transferred embryos | number of high quality transferred embryos at day 3 | 21 days after the beginning of ovarian stimulation | 
| The rate of clinical pregnancy | Positive heart rate at 7 weeks of gestation in ultrasound | 7 weeks after the initiation of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of follicles | (> 11,> 14,> 18 mm) on the day of triggering with hCG | 2 weeks after the initiation of treatment | 
| The thickness of the endometrium | On the day of follicular maturation (triggering) with hCG | 2 weeks after the initiation of treatment | 
| Automatic abortion rates - miscarriage | (Lss of pregnancy after positive heart function up to 20 weeks of gestation | up to 20 weeks of gestation | 
| The percentage of ovarian hyperstimulation syndrome | After triggering with hCG | 2 weeks after the hCG triggering |