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

HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin Clinical Trial

— HCG  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03423537
• Other study ID #: hCG-GR-001-2016
• Secondary ID: 2016-005208-24
• Status: Terminated
• Phase: Phase 3
• Start date: June 1, 2018
• Est. completion date: April 30, 2019

Study information

• Verified date: September 2020
• Source: National and Kapodistrian University of Athens
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: April 30, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 35 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin

Intervention

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.
• Placebo
100IU per day containing N/S 0.9% will be injected

Locations

Country	Name	City	State
Greece	3rd Department of Obstetrics and Gynecology, Assisted Reproduction Unit	Athens	Chaidari

Sponsors (2)

Lead Sponsor	Collaborator
National and Kapodistrian University of Athens	University of Thessaly

Country where clinical trial is conducted

Greece, 

References & Publications (4)

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: 10.11 — View Citation

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 an — View Citation

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. — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of transferred embryos	number of high quality transferred embryos at day 3	21 days after the beginning of ovarian stimulation
Primary	The rate of clinical pregnancy	Positive heart rate at 7 weeks of gestation in ultrasound	7 weeks after the initiation of treatment
Secondary	Number of follicles	(> 11,> 14,> 18 mm) on the day of triggering with hCG	2 weeks after the initiation of treatment
Secondary	The thickness of the endometrium	On the day of follicular maturation (triggering) with hCG	2 weeks after the initiation of treatment
Secondary	Automatic abortion rates - miscarriage	(Lss of pregnancy after positive heart function up to 20 weeks of gestation	up to 20 weeks of gestation
Secondary	The percentage of ovarian hyperstimulation syndrome	After triggering with hCG	2 weeks after the hCG triggering

External Links

•   Current guidelines