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

Phase 3

Terminated

• Conditions: HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin
• Interventions: Drug: hCG; Drug: Placebo

• Registration Number: NCT03423537
• Lead Sponsor: National and Kapodistrian University of Athens

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.

Study Timeline

• Study First Submitted: 2018-01-21
• Study First Submitted QC: 2018-02-03
• Study First Posted: 2018-02-06
• Study Start: 2018-06-01
• Primary Completion: 2019-04-30
• Study Completion: 2019-04-30
• Status Verified: 2020-09
• Last Update Submitted: 2021-03-25
• Last Update Posted: 2021-03-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 [HCG (+) group]	hCG	"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
Group 2 [placebo]	Placebo	"Group 2" will indicate the application of the standard GnRH agonist protocol without the addition of hCG, but placebo, instead

Primary Outcome Measures

Name	Time	Method
The rate of clinical pregnancy	7 weeks after the initiation of treatment	Positive heart rate at 7 weeks of gestation in ultrasound
number of transferred embryos	21 days after the beginning of ovarian stimulation	number of high quality transferred embryos at day 3

Secondary Outcome Measures

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

Trial Locations

Locations (1)

3rd Department of Obstetrics and Gynecology, Assisted Reproduction Unit; 🇬🇷 Athens, Chaidari, Greece