Study to Evaluate if the Addition of r-hLH (Luveris®) to FSH From Day 8 of Ovarian Stimulation is Able to Decrease Total FSH Dose and to Improve Cycle Outcome in Infertile Women Undergoing ART, Who Required High FSH Dose in a Previous Cycle (Luveris in ART)
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|ClinicalTrials.gov Identifier: NCT01071200|
Recruitment Status : Terminated
First Posted : February 19, 2010
Results First Posted : August 14, 2012
Last Update Posted : December 27, 2013
|Condition or disease||Intervention/treatment||Phase|
|Reproductive Techniques, Assisted||Drug: Recombinant human Follicle Stimulating Hormone (r-hFSH) and Recombinant human Luteinizing Hormone (r-hLH) Drug: r-hFSH||Phase 3|
Recombinant human follicle stimulating hormone (r-hFSH), which totally lacks LH activity, is widely used to induce multiple follicle development in women under pituitary desensitization, in order to submit them to treatment with assisted reproduction techniques (ART). Clinical experience from hypogonadotropic-hypogonadic women suggests that while FSH alone is sufficient to induce follicle development, LH plays a significant part in final follicle maturation, estrogen synthesis and optimal endometrium growth.
This was a phase III, multicentre, randomized, open-label comparative study to evaluate if the addition of r-hLH (Luveris) in a 2:1 ratio to FSH from day 8 of ovarian stimulation is able to decrease the total FSH dose and to improve cycle outcome in 250 infertile women undergoing ART, who required high FSH dose in a previous cycle (≥ 3500 IU). Subjects who have met all the inclusion criteria, achieved pituitary desensitization and started controlled ovarian hyperstimulation (COH) treatment with FSH, on stimulation day 8 (S8) received an identification number and will be allocated to one of the two following arms:
Arm : FSH + r-hLH (2:1 ratio of FSH:r-hLH), Arm : FSH alone. Treatment with Luveris was commenced on day 8 (S8) and continued until injection of hCG or cancellation of the treatment cycle.
Monitoring of stimulation, FSH dose escalation, criteria for injection of hCG, ovum pick up, embryo transfer and pregnancy confirmation took place according to standard management practice. The in-vitro fertilization (IVF) or intracytosolic sperm injection (ICSI) procedure, including luteal phase support, was performed according to each centres' normal procedures.
The subjects were followed up and the treatment outcome (menstruation or pregnancy) was recorded. The delivery outcome for any pregnant subjects was recorded in the Case Report Form (CRF).
Information on the delivery outcome for each pregnancy was collected. Information on adverse events was collected during the study period.
The primary objective of the study was:
To determine whether the addition of r-hLH (Luveris) from day 8 of ovarian stimulation reduces the FSH dose needed to obtain/retrieve each oocyte.
The secondary objectives of the study were:
- To determine whether the addition of Luveris to FSH at day 8 of ovarian stimulation improves cycle outcome based on secondary endpoints
- To determine the safety of Luveris in this indication
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||133 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase III, Multicentric, Randomized, Open, Comparative Study to Evaluate if the Addition of Recombinant Human Luteinising Hormone [r-hLH (Luveris®)] to Follicle Stimulating Hormone (FSH) From Day 8 of Ovarian Stimulation is Able to Decrease Total FSH Dose and to Improve Cycle Outcome in Infertile Women Undergoing Assisted Reproduction Technology (ART), Who Required High FSH Dose in a Previous Cycle|
|Study Start Date :||March 2005|
|Primary Completion Date :||April 2009|
|Study Completion Date :||April 2009|
Subjects treated with r-hFSH and r-hLH (2:1 ratio of r-hFSH:r-hLH)
Drug: Recombinant human Follicle Stimulating Hormone (r-hFSH) and Recombinant human Luteinizing Hormone (r-hLH)
One r-hFSH and one r-hLH injection subcutaneously (s.c.) once daily during the treatment phase from Day 8 of stimulation until injection of human chorionic gonadotropin (hCG) or cancellation of the treatment cycle.
Active Comparator: B
Subjects treated with r-hFSH alone
One r-hFSH injection s.c. once daily during the treatment phase from Day 8 of stimulation until injection of hCG or cancellation of the treatment cycle.
- Total Dose of Follicular Stimulating Hormone (FSH) for Retrieved Oocytes [ Time Frame: Baseline (Stimulation day 8 [S8]) until hCG day ]
- Mean Total Follicle Stimulating Hormone (FSH) and Recombinant Human Luteinizing Hormone (r-hLH) Dose [ Time Frame: Baseline (S8) until hCG day ]
- Mean Number of Ovarian Stimulation Days [ Time Frame: Baseline (S8) until hCG day ]
- Change From Baseline in Oestradiol (E2) Levels at Human Choriogonadotropin (hCG) Day [ Time Frame: Baseline (S8) and hCG day ]
- Mean Total Number of Retrieved Oocytes [ Time Frame: 34-36 hours post-hCG (OPU) ]Mean number of oocytes retrieved on the day of ovum pick up (OPU) was counted. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.
- Mean Number of Mature Oocytes (Metaphase II) [ Time Frame: 34-36 hours post-hCG (OPU) ]Mean number of metaphase II oocytes was counted for participants undergoing ovum pick up for IntraCytoplasmic Sperm Injection (ICSI). ICSI is a procedure in which a single spermatozoon is injected into the oocyte cytoplasm. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes.
- Fertilization Rate [ Time Frame: 12-18 day post-hCG and/or Week 7 ]Fertilization rate was measured as the ratio between number of fertilized oocytes and number of inseminated oocytes (maximum 3).
- Number of Obtained Embryos [ Time Frame: Day 3 post-hCG (Embryo transfer [ET]) ]Total number of obtained embryos with maximum 3 inseminated oocytes was calculated.
- Number of Transferred Embryos [ Time Frame: Day 3 post-hCG (ET) ]Embryo transfer is the procedure in which one or more embryos are placed in the uterus or Fallopian tube.
- Percentage of Participants With Pregnancy [ Time Frame: 12-18 day post-hCG and/or Week 7 ]
- Percentage of Participants With Clinical Pregnancy [ Time Frame: 12-18 day post-hCG and/or Week 7 ]Clinical pregnancy is defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy.
- Percentage of Participants With Implantation [ Time Frame: 12-18 day post-hCG and/or Week 7 ]Implantation is the attachment and subsequent penetration by the zona-free blastocyst (usually in the endometrium) that starts five to seven days after fertilization.
- Number of Participants With Ovarian Hyper Stimulation Syndrome (OHSS) [ Time Frame: Baseline (S8) until 12-18 day post-hCG and/or Week 7 ]OHSS is an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, haemodynamic and metabolic complications.
- Number of Cycles Cancelled Due to Risk of OHSS [ Time Frame: Baseline (S8) until 12-18 day post-hCG and/or Week 7 ]OHSS is an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, haemodynamic and metabolic complications.
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): NCT01071200
|Merck Serono S.p.A.|
|Study Director:||Salvatore Longobardi||Merck Serono S.P.A., Italy|