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

Primary Purpose

Infertility, Female

Status

Completed

Phase

Phase 4

Locations

Russian Federation

Study Type

Interventional

Intervention

Corifollitropin alfa and menotropin

Follitropin alfa and lutropin alfa

About this trial

This is an interventional treatment trial for Infertility, Female focused on measuring suboptimal response, Corifollitropin alfa, IVF, Ovarian stimulation

Eligibility Criteria

35 Years - 41 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Corifollitropin alfa and menotropin

Follitropin alfa and lutropin alfa

Arm Description

Elonva 150 mcg, Merional 150-300 IU

Pergoveris 300 IU

Outcomes

Primary Outcome Measures

Number of cumulus-oocyte complexes (COCs)

Number of COCs, obtained during oocyte pick up (OPU), after controlled ovarian stimulation (COS) in two protocols

Secondary Outcome Measures

Duration of stimulation

total days of COS: from the first gonadotropins administration to ovulation triggering

Number of follicles at the end of stimulation

measured for follicles ≥17 mm and ≥14 mm

Dose adjustment frequency

number of participants with menopausal or recombinant human follicle stimulating hormone (FSH) dose increase

Number of participants with optimal or suboptimal response to COS

≥ 5 COCs at at oocyte recovery day

Number of mature (MII) oocytes

assessment is done only for ICSI cycles at oocyte recovery day

Cycle cancellation rate

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)

Frequency of side reactions

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

Implantation rate

ratio of the number of intrauterine gestational sacs to the number of transferred embryos

Clinical pregnancy rate

presence of intrauterine gestational sac at transvaginal ultrasound measured per embryo transfer

Full Information

NCT ID

NCT03177538

First Posted

May 23, 2017

Last Updated

September 10, 2019

Sponsor

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

1. Study Identification

Unique Protocol Identification Number

NCT03177538

Brief Title

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

Acronym

TEMPER

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

September 4, 2017 (Actual)

Primary Completion Date

November 2, 2018 (Actual)

Study Completion Date

September 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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).

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infertility, Female

Keywords

suboptimal response, Corifollitropin alfa, IVF, Ovarian stimulation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Corifollitropin alfa and menotropin

Arm Type

Active Comparator

Arm Description

Elonva 150 mcg, Merional 150-300 IU

Arm Title

Follitropin alfa and lutropin alfa

Arm Type

Active Comparator

Arm Description

Pergoveris 300 IU

Intervention Type

Drug

Intervention Name(s)

Corifollitropin alfa and menotropin

Other Intervention Name(s)

Elonva, Merional

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Follitropin alfa and lutropin alfa

Other Intervention Name(s)

Pergoveris

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of cumulus-oocyte complexes (COCs)

Description

Number of COCs, obtained during oocyte pick up (OPU), after controlled ovarian stimulation (COS) in two protocols

Time Frame

3-4 weeks after ET

Secondary Outcome Measure Information:

Title

Duration of stimulation

Description

total days of COS: from the first gonadotropins administration to ovulation triggering

Time Frame

2-4 weeks after randomization

Title

Number of follicles at the end of stimulation

Description

measured for follicles ≥17 mm and ≥14 mm

Time Frame

2-4 weeks after randomization

Title

Dose adjustment frequency

Description

number of participants with menopausal or recombinant human follicle stimulating hormone (FSH) dose increase

Time Frame

2-4 weeks after randomization

Title

Number of participants with optimal or suboptimal response to COS

Description

≥ 5 COCs at at oocyte recovery day

Time Frame

2-4 weeks after randomization

Title

Number of mature (MII) oocytes

Description

assessment is done only for ICSI cycles at oocyte recovery day

Time Frame

2-4 weeks after randomization

Title

Cycle cancellation rate

Description

Time Frame

6-7 weeks after randomization

Title

Frequency of side reactions

Description

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

Time Frame

2-4 weeks after randomization

Title

Implantation rate

Description

ratio of the number of intrauterine gestational sacs to the number of transferred embryos

Time Frame

3-4 weeks after ET

Title

Clinical pregnancy rate

Description

presence of intrauterine gestational sac at transvaginal ultrasound measured per embryo transfer

Time Frame

5-6 weeks after randomization

Other Pre-specified Outcome Measures:

Title

Biochemical pregnancy rate

Description

positive ß-hCG test (≥30 IU/L) following ET without clinical pregnancy confirmation

Time Frame

3-4 weeks after ET

Title

Fertilization rate

Description

number of two-pronuclear zygotes on day 1 after fertilization

Time Frame

1 day after OPU

Title

Embryo quality

Description

number of best and good quality embryos per transfer

Time Frame

3-5 days after oocyte recovery

Title

Cost-effectiveness of COS

Description

ratio of total cost of stimulation (on investigated drugs) to the number of patients with clinical pregnancy

Time Frame

6-7 weeks after randomization

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

35 Years

Maximum Age & Unit of Time

41 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexdandr Gzgzyan, Prof, PhD

Organizational Affiliation

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

Official's Role

Principal Investigator

Facility Information:

Facility Name

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

City

Saint Petersburg

ZIP/Postal Code

199034

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34937512

Citation

Ob'edkova KV, Kogan IY, Muller VC, Tapilskaya NI, Krikhely IO, Dzhemlikhanova LK, Abdulkadirova ZK, Mekina ID, Lesik EA, Komarova EA, Ishchuk MA, Gzgzian AM. IVF protocol efficacy in women with expected suboptimal response depending on ovary stimulation mode. Gynecol Endocrinol. 2021;37(sup1):44-48. doi: 10.1080/09513590.2021.2006526.

Results Reference

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

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