ClinicalTrials.gov
ClinicalTrials.gov Menu

Corifollitropin Alfa Combined With Menotropin Versus Follitropin and Lutropin Alfa in Expected Suboptimal Responders (TEMPER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03177538
Recruitment Status : Recruiting
First Posted : June 6, 2017
Last Update Posted : September 20, 2017
Sponsor:
Information provided by (Responsible Party):
Valeria Muller, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

Brief Summary:
In an opened randomized study of women undergoing in vitro fertilization with expected suboptimal response to controlled ovarian stimulation (Poseidon Group 2b) investigators will examine clinical efficacy and safety of two stimulation protocols: Corifollitropin alfa (Elonva) in combination with menotropin (Merional) versus Follitropin alfa and lutropin alfa (Pergoveris).

Condition or disease Intervention/treatment Phase
Infertility, Female Drug: Corifollitropin alfa and menotropin Drug: Follitropin alfa and lutropin alfa Phase 4

Detailed Description:

Patients, found eligible for the study, will be randomized (envelope method) into two arms in 1:1 ratio at the start of stimulation (menstrual cycle day 2-3, randomization day): Arm A - ovarian stimulation with Corifollitropin alfa in combination with menotropin; Arm B - ovarian stimulation with Follitropin alfa and lutropin alfa.

At the first day of controlled ovarian stimulation (COS) participants in the first group will receive a single injection of Corifollitropin alfa 150 mcg followed by daily menotropin administration at the dose of 150 international unit (IU) from stimulation day 1 to day 7 and at the dose of 300 IU from day 8 up to the end of stimulation.

Ovarian stimulation in group B will be performed with daily 300 IU of Follitropin alfa and lutropin alfa starting on menstrual cycle day 2-3.

For all subjects, a fixed dose of gonadotropin-releasing hormone (GnRH) antagonist will be injected daily as soon as one of the follicles reaches the ≥14 mm diameter and stopped one day before oocyte pick up (OPU); ovulatory dose of human chorionic gonadotropin (hCG) could be administered when at least one follicle reaches 16.5 mm in diameter.

Retrieved oocytes following fertilization (conventional IVF or ICSI) will be cultured to morula or blastocyst stage followed by ultrasound guided single or double embryo transfer (ET day, performed 4-5 days after OPU).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Randomized Study Comparing Clinical Efficacy of Corifollitropin Alfa (Elonva) in Combination With Menotropin (Merional) With Follitropin and Lutropin Alfa (Pergoveris) for Ovarian Stimulation in Expected Suboptimal Responders
Actual Study Start Date : September 4, 2017
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Corifollitropin alfa and menotropin
Elonva 150 mcg, Merional 150-300 IU
Drug: Corifollitropin alfa and menotropin

Procedure: Ovarian stimulation is performed by the combination of a single Corifollitropin alfa 150 mcg injection on menstrual cycle day 2-3 and daily menotropin administration at the dose of 150 IU from stimulation day 1-7 and at the dose of 300 IU from day 8 to the end of stimulation (maximal dose adjustment to 450 IU).

Other interventions: conventional GnRH antagonist protocol and in vitro fertilization (IVF/ICSI) cycle

Other Name: Elonva, Merional

Active Comparator: Follitropin alfa and lutropin alfa
Pergoveris 300 IU
Drug: Follitropin alfa and lutropin alfa

Procedure: Ovarian stimulation is performed with daily 300 IU of Follitropin alfa and lutropin alfa starting on menstrual cycle day 2-3. Maximal allowed dose adjustment is 450 IU daily.

Other interventions: conventional GnRH antagonist protocol and in vitro fertilization (IVF/ICSI) cycle.

Other Name: Pergoveris




Primary Outcome Measures :
  1. Number of cumulus-oocyte complexes (COCs) [ Time Frame: 3-4 weeks after ET ]
    Number of COCs, obtained during oocyte pick up (OPU), after controlled ovarian stimulation (COS) in two protocols


Secondary Outcome Measures :
  1. Duration of stimulation [ Time Frame: 2-4 weeks after randomization ]
    total days of COS: from the first gonadotropins administration to ovulation triggering

  2. Number of follicles at the end of stimulation [ Time Frame: 2-4 weeks after randomization ]
    measured for follicles ≥17 mm and ≥14 mm

  3. Dose adjustment frequency [ Time Frame: 2-4 weeks after randomization ]
    number of participants with menopausal or recombinant human follicle stimulating hormone (FSH) dose increase

  4. Number of participants with optimal or suboptimal response to COS [ Time Frame: 2-4 weeks after randomization ]
    ≥ 5 COCs at at oocyte recovery day

  5. Number of mature (MII) oocytes [ Time Frame: 2-4 weeks after randomization ]
    assessment is done only for ICSI cycles at oocyte recovery day

  6. Cycle cancellation rate [ Time Frame: 6-7 weeks after randomization ]
    number of cancelled cycles during COS (no response), at OPU (premature ovulation, absence or degradation of COCs), during in vitro cultivation (fertilization failure, inadequate embryo quality) or due to other reasons (adverse events, ovarian hyperstimulation syndrome (OHSS), withdrawal)

  7. Frequency of side reactions [ Time Frame: 2-4 weeks after randomization ]
    number of patients with local reactions (redness, itching, swelling or pain) or abdominal discomfort evaluated using visual analogue scale at the end of COS and at ET day

  8. Implantation rate [ Time Frame: 3-4 weeks after ET ]
    ratio of the number of intrauterine gestational sacs to the number of transferred embryos

  9. Clinical pregnancy rate [ Time Frame: 5-6 weeks after randomization ]
    presence of intrauterine gestational sac at transvaginal ultrasound measured per embryo transfer


Other Outcome Measures:
  1. Biochemical pregnancy rate [ Time Frame: 3-4 weeks after ET ]
    positive ß-hCG test (≥30 IU/L) following ET without clinical pregnancy confirmation

  2. Fertilization rate [ Time Frame: 1 day after OPU ]
    number of two-pronuclear zygotes on day 1 after fertilization

  3. Embryo quality [ Time Frame: 3-5 days after oocyte recovery ]
    number of best and good quality embryos per transfer

  4. Cost-effectiveness of COS [ Time Frame: 6-7 weeks after randomization ]
    ratio of total cost of stimulation (on investigated drugs) to the number of patients with clinical pregnancy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   35 Years to 41 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female age between 35-41 years;
  • BMI 17,5-30 kg/m2;
  • Expected suboptimal responders (according to Poseidon classification, 2016, Group 2b): patients with suboptimal ovarian reserve prestimulation parameters in terms of antimüllerian hormone (AMH) and antral follicle count (AFC): AFC 5-9, AMH ≥0.8 ng/mL;
  • Early follicular phase follicle stimulating hormone (FSH) ≤15 IU/L;
  • Presence of viable spermatozoa in partner's sperm;
  • Signed informed consent.

Exclusion Criteria:

  • Pre-existing medical condition preventing or interfering with IVF treatment: any clinically significant systemic disease; inherited or acquires thrombophilia and thromboembolism; endocrine or metabolic abnormalities; moderate or severe impairment of renal or hepatic function; any oncological diseases in anamnesis; known history of recurrent miscarriage, abnormal karyotype of both partners; currently active pelvic inflammatory disease;
  • Abnormal IVF screening tests: Papanicolaou test, Syphilis, HIV 1&2, Hepatitis B, Hepatitis C, Chlamydia, and Gonorrhea;
  • Presence of uterine pathology: Asherman's Syndrome, endometrial polyps, nodus form of adenomyosis or uterine fibroids ≥3 mm in diameter;
  • Visualization of ovarian cysts ≥25 mm, endometriomas or hydrosalpinx;
  • One or more follicles ≥8 mm on randomization day.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03177538


Contacts
Contact: Alexdandr Gzgzyan, Prof, PhD +79213284156 agzgzyan@gmail.com
Contact: Valeria Muller, PhD, MD +79213470671 otts.muller@gmail.com

Locations
Russian Federation
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology Recruiting
Saint Petersburg, Russian Federation, 199034
Contact: Muller Valeria, PhD,MD    +78123253220    iagmail@ott.ru   
Sponsors and Collaborators
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
Investigators
Principal Investigator: Alexdandr Gzgzyan, Prof, PhD D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

Responsible Party: Valeria Muller, PhD, MD, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
ClinicalTrials.gov Identifier: NCT03177538     History of Changes
Other Study ID Numbers: 00001 (TEMPER-1)
First Posted: June 6, 2017    Key Record Dates
Last Update Posted: September 20, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Valeria Muller, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology:
suboptimal response
Corifollitropin alfa
IVF
Ovarian stimulation

Additional relevant MeSH terms:
Infertility
Infertility, Female
Genital Diseases, Male
Genital Diseases, Female
Follicle Stimulating Hormone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs