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

Infertility, Female Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03177538
• Other study ID #: 00001 (TEMPER-1)
• Status: Completed
• Phase: Phase 4
• Start date: September 4, 2017
• Est. completion date: September 10, 2019

Study information

• Verified date: September 2019
• Source: D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: September 10, 2019
• Est. primary completion date: November 2, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 41 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infertility
• Infertility, Female

Intervention

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
• 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.

Locations

Country	Name	City	State
Russian Federation	D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology	Saint Petersburg

Sponsors (1)

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

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biochemical pregnancy rate	positive ß-hCG test (=30 IU/L) following ET without clinical pregnancy confirmation	3-4 weeks after ET
Other	Fertilization rate	number of two-pronuclear zygotes on day 1 after fertilization	1 day after OPU
Other	Embryo quality	number of best and good quality embryos per transfer	3-5 days after oocyte recovery
Other	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
Primary	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	Duration of stimulation	total days of COS: from the first gonadotropins administration to ovulation triggering	2-4 weeks after randomization
Secondary	Number of follicles at the end of stimulation	measured for follicles =17 mm and =14 mm	2-4 weeks after randomization
Secondary	Dose adjustment frequency	number of participants with menopausal or recombinant human follicle stimulating hormone (FSH) dose increase	2-4 weeks after randomization
Secondary	Number of participants with optimal or suboptimal response to COS	= 5 COCs at at oocyte recovery day	2-4 weeks after randomization
Secondary	Number of mature (MII) oocytes	assessment is done only for ICSI cycles at oocyte recovery day	2-4 weeks after randomization
Secondary	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
Secondary	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
Secondary	Implantation rate	ratio of the number of intrauterine gestational sacs to the number of transferred embryos	3-4 weeks after ET
Secondary	Clinical pregnancy rate	presence of intrauterine gestational sac at transvaginal ultrasound measured per embryo transfer	5-6 weeks after randomization