Lutropin Alfa in Women at Risk of Poor Response

Study Overview
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Brief Summary
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Evaluate the effectiveness of adding lutropin alfa (recombinant human luteinizing hormone [r-hLH]) in the middle of the follicular phase compared to no addition, in infertile women at risk of poor response stimulated with follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) under Gonadotropin Releasing Hormone (GnRH) antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), in the number and quality of oocytes, follicular development, fertilization oocyte, embryo quality, and pregnancy rate.

Official Title
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Lutropin Alfa (Luveris®) in Women at Risk of Poor Response Suppressed With Cetrorelix: an Exploratory Trial

Conditions
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Ovarian Stimulation

Intervention / Treatment
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* Drug: r-FSH
* Drug: r-hLH
* Drug: Analogous GnRH antagonist
* Drug: r-hCG
* Drug: Progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who were at risk of poor response by at least one of the following criteria: a) <3 follicles in last cycle, or less than or equal to (</=) 2 metaphase II oocytes, or estradiol (E2) <600 pg/mL; b) Cancellation of previous cycle; c) Early follicular serum Follicle-Stimulating Hormone (FSH) >8.5 milli IU/L Participants with normal baseline luteinizing hormone and E2 levels Regular menstrual cycles of 25-35 days Presence of both ovaries and uterus able to withstand pregnancy Exclusion Criteria: Participants who had any clinically significant disease including known human immunodeficiency virus (HIV), hepatitis-B virus (HBV)/hepatitis-C virus (HCV) positivity Participants with more than 3 previous assisted reproductive techniques (ART) cycles Participants with polycystic ovaries or cyst of unknown etiology; unexplained gynecological bleeding Participants who had any contraindication to being pregnant Active substance abuse Participants who had simultaneously participated in another clinical drug trial

Ages Eligible for Study
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Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: r-FSH + r-hLH<br>Lutropin alfa (r-hLH) will be administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) will be administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist. | Drug: r-FSH<br>* r-FSH will be administered as specified in the arm description.<br>* Other names: Follitropin alfa; Gonal-F®;Drug: r-hLH<br>* r-hLH will be administered as specified in the arm description.<br>* Other names: Lutropin alfa; Luveris®;Drug: Analogous GnRH antagonist<br>* Analogous GnRH antagonist will be administered as specified in the arm description.<br>* Other names: Cetrotide®;Drug: r-hCG<br>* r-hCG will be administered as specified in the arm description.<br>Drug: Progesterone<br>* Progesterone will be administered as specified in the arm description.<br>|
| Active Comparator: r-FSH<br>Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG will be administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist. | Drug: r-FSH<br>* r-FSH will be administered as specified in the arm description.<br>* Other names: Follitropin alfa; Gonal-F®;Drug: Analogous GnRH antagonist<br>* Analogous GnRH antagonist will be administered as specified in the arm description.<br>* Other names: Cetrotide®;Drug: r-hCG<br>* r-hCG will be administered as specified in the arm description.<br>Drug: Progesterone<br>* Progesterone will be administered as specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Oocytes Retrieved |  | At the end of stimulation (Day 2 up to Day 8) | 
| Number of Follicles Greater Than (>) 14 Millimeter (mm) in Diameter |  | At the end of stimulation (Day 2 up to Day 8) | 
| Oocytes Recovery Rate | Oocytes recovery rate (oocytes per >14 mm follicle) is defined as number of oocytes retrieved divided by number of follicles >14 mm in diameter. | At the end of stimulation (Day 2 up to Day 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oocyte Nuclear Maturity Rate | Oocyte nuclear maturity rate (metaphase II oocytes per retrieved oocyte) is defined as number of metaphase II oocytes divided by total number of oocytes retrieved. | At the end of stimulation (Day 2 up to Day 8) | 
| Fertilization Rate | The fertilization rate (2 pronuclei [PN] fertilized oocytes per inseminated oocyte) was defined as number of 2 PN fertilized oocytes divided by number of inseminated oocytes. | Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8) | 
| Number of Embryos by Quality | Embryo quality was graded according to morphological classification of Veeck. Grade 1: even blastomeres with no fragmentation; Grade 2: even blastomeres with slight fragmentation (less than 20%); Grade 3: uneven size blastomeres with no fragmentation; Grade 4: even or uneven size blastomeres with moderate fragmentation (20-25%); and Grade 5: unrecognizable blastomeres with severe fragmentation (>50%). | Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8) | 
| Number of Embryos Transferred by In Vitro Fertilization (IVF) |  | Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8) | 
| Number of Participants With Positive Pregnancy Test | The beta Human Chorionic Gonadotropin (beta-hCG) test was used as pregnancy test. | Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8) | 
| Number of Participants With Clinical Pregnancy | A clinical pregnancy is a pregnancy that is confirmed by both pregnancy test (beta-hCG test) and sonographic confirmation of a gestational sac or heartbeat (fetal sac). | Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8) | 
| Implementation Rate | Implementation rate (clinical pregnancy/embryo transferred) was defined as the number of clinical pregnancies divided by number of embryos transferred. | Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8) | 
| Plasma Level of Estradiol |  | At the time of r-hCG administration (any days between Day 2 to Day 8) | 
| Endometrial Thickness |  | At the time of r-hCG administration (any days between Day 2 to Day 8) | 
| Duration of Ovarian Stimulation | Duration of ovarian stimulation was defined as the time from start of study treatment to time of r-hCG administration. | Randomization to Day 8 | 
| rFSH Cumulative Dose |  | Randomization to Day 8 | 
| Plasma Levels of LH |  | At the time of r-hCG administration (any days between Day 2 to Day 8) | 
| Number of Participants in Whom At Least 1 Stimulation Cycle Was Cancelled |  | Randomization to Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lutropin alfa, Fertilization in vitro, Intracytoplasmic sperm injection, Reproductive techniques, assisted