Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Corifollitropin alfa and menotropin | Active Comparator | Elonva 150 mcg, Merional 150-300 IU |
|
| Follitropin alfa and lutropin alfa | Active Comparator | Pergoveris 300 IU |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Corifollitropin alfa and menotropin | Drug | 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 |
| 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 |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Alexdandr Gzgzyan, Prof, PhD | D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology | Saint Petersburg | 199034 | Russia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34937512 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Follitropin alfa and lutropin alfa | Drug | 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. |
|
|
| 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 |
| 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 |
| ID | Term |
|---|---|
| D007247 | Infertility, Female |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D007246 | Infertility |
Not provided
Not provided
| ID | Term |
|---|---|
| C437186 | follicle stimulating hormone, human, with HCG C-terminal peptide |
| D008596 | Menotropins |
| C527545 | hMG-IBSA |
| C571801 | follitropin alfa |
| D037101 | Luteinizing Hormone, beta Subunit |
| C551396 | pergoveris |
| ID | Term |
|---|---|
| D006065 | Gonadotropins, Pituitary |
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D007986 | Luteinizing Hormone |
Not provided
Not provided