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

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

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).

Study Overview

• Status: Completed
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: Corifollitropin alfa and menotropin; Drug: Follitropin alfa and lutropin alfa

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
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 199034
    • D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Pergoveris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of cumulus-oocyte complexes (COCs)	Number of COCs, obtained during oocyte pick up (OPU), after controlled ovarian stimulation (COS) in two protocols	3-4 weeks after ET

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of stimulation	total days of COS: from the first gonadotropins administration to ovulation triggering	2-4 weeks after randomization
Number of follicles at the end of stimulation	measured for follicles ≥17 mm and ≥14 mm	2-4 weeks after randomization
Dose adjustment frequency	number of participants with menopausal or recombinant human follicle stimulating hormone (FSH) dose increase	2-4 weeks after randomization
Number of participants with optimal or suboptimal response to COS	≥ 5 COCs at at oocyte recovery day	2-4 weeks after randomization
Number of mature (MII) oocytes	assessment is done only for ICSI cycles at oocyte recovery day	2-4 weeks after randomization
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)	6-7 weeks after randomization
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	2-4 weeks after randomization
Implantation rate	ratio of the number of intrauterine gestational sacs to the number of transferred embryos	3-4 weeks after ET
Clinical pregnancy rate	presence of intrauterine gestational sac at transvaginal ultrasound measured per embryo transfer	5-6 weeks after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical pregnancy rate	positive ß-hCG test (≥30 IU/L) following ET without clinical pregnancy confirmation	3-4 weeks after ET
Fertilization rate	number of two-pronuclear zygotes on day 1 after fertilization	1 day after OPU
Embryo quality	number of best and good quality embryos per transfer	3-5 days after oocyte recovery
Cost-effectiveness of COS	ratio of total cost of stimulation (on investigated drugs) to the number of patients with clinical pregnancy	6-7 weeks after randomization

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2017
• Primary Completion (Actual): November 2, 2018
• Study Completion (Actual): September 10, 2019

Study Registration Dates

• First Submitted: May 23, 2017
• First Submitted That Met QC Criteria: June 2, 2017
• First Posted (Actual): June 6, 2017

Study Record Updates

• Last Update Posted (Actual): September 12, 2019
• Last Update Submitted That Met QC Criteria: September 10, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: IVF; Ovarian stimulation; suboptimal response; Corifollitropin alfa
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Follicle Stimulating Hormone; Menotropins
• Other Study ID Numbers: 00001 (TEMPER-1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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