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

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.

Study Overview

• Status: Terminated
• Conditions: HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin
• Intervention / Treatment: Drug: hCG; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Greece
  • Chaidari
    • Athens, Chaidari, Greece, 12462
      • 3rd Department of Obstetrics and Gynecology, Assisted Reproduction Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 [HCG (+) group]; "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; 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.; Other Names: Pregnyl
Placebo Comparator: Group 2 [placebo]; "Group 2" will indicate the application of the standard GnRH agonist protocol without the addition of hCG, but placebo, instead	Drug: Placebo; 100IU per day containing N/S 0.9% will be injected

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

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: University of Thessaly
• Investigators: Principal Investigator: Charalampos Siristatidis, Ass Prof, National and Kapodistrian University of Athens

Publications and helpful links

General Publications

• Drakakis P, Loutradis D, Beloukas A, Sypsa V, Anastasiadou V, Kalofolias G, Arabatzi H, Kiapekou E, Stefanidis K, Paraskevis D, Makrigiannakis A, Hatzakis A, Antsaklis A. Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation. Reprod Biol Endocrinol. 2009 Oct 13;7:110. doi: 10.1186/1477-7827-7-110.
• Gomaa H, Casper RF, Esfandiari N, Chang P, Bentov Y. Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF. Reprod Biol Endocrinol. 2012 Aug 6;10:55. doi: 10.1186/1477-7827-10-55.
• Martins WP, Vieira AD, Figueiredo JB, Nastri CO. FSH replaced by low-dose hCG in the late follicular phase versus continued FSH for assisted reproductive techniques. Cochrane Database Syst Rev. 2013 Mar 28;(3):CD010042. doi: 10.1002/14651858.CD010042.pub2.
• Beretsos P, Partsinevelos GA, Arabatzi E, Drakakis P, Mavrogianni D, Anagnostou E, Stefanidis K, Antsaklis A, Loutradis D. "hCG priming" effect in controlled ovarian stimulation through a long protocol. Reprod Biol Endocrinol. 2009 Aug 31;7:91. doi: 10.1186/1477-7827-7-91.

Helpful Links

• Current guidelines

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): April 30, 2019
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: January 21, 2018
• First Submitted That Met QC Criteria: February 3, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Chorionic Gonadotropin
• Other Study ID Numbers: hCG-GR-001-2016; 2016-005208-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No