Clinical trial NCT03423537: Low-dose HCG as an Adjunct to Ovarian Stimulation in Subfertile Women Undergoing ART
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HCG; IVF; Pregnancy Rates; ART; Chorionic Gonadotropin
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
Collaborators: name: University of Thessaly
First posted: 2018-02-06
Enrollment: 80
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: number of transferred embryos
timeFrame: 21 days after the beginning of ovarian stimulation
measure: The rate of clinical pregnancy
timeFrame: 7 weeks after the initiation of treatment
Secondary outcomes:
measure: Number of follicles
timeFrame: 2 weeks after the initiation of treatment
measure: The thickness of the endometrium
timeFrame: 2 weeks after the initiation of treatment
measure: Automatic abortion rates - miscarriage
timeFrame: up to 20 weeks of gestation
measure: The percentage of ovarian hyperstimulation syndrome
timeFrame: 2 weeks after the hCG triggering
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 3rd Department of Obstetrics and Gynecology, Assisted Reproduction Unit
state: Chaidari
Study officials:
affiliation: National and Kapodistrian University of Athens
name: Charalampos Siristatidis, Ass Prof
role: PRINCIPAL_INVESTIGATOR
References:
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 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.
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.
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;2013(3):CD010042. doi: 10.1002/14651858.CD010042.pub2.
citation: 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.