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A Randomised, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of Combined Treatment of Lutropin Alpha and Recombinant Human Luteinizing Hormone in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve

Primary Purpose

Infertility, Ovulation Induction

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Recombinant human follicle stimulating hormone (r-hFSH)
Recombinant human luteinizing hormone (r-hLH)
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring Reproductive technology, Assisted, Recombinant human follicle stimulating hormone (r-hFSH), Recombinant leutinizing hormone (r-hLH), Ovulation induction, Infertility

Eligibility Criteria

35 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

All subjects must meet the following inclusion criteria within the 6 months prior to starting the pituitary suppression unless otherwise specified:

  • Postmenopausal woman aged between 35 and 40 years that wishes to become pregnant
  • Subjects with basal serum level (beginning of the follicular phase, Day 2-5) of Follicle-Stimulating Hormone (FSH) less than 10 IU/L determined within the 6 months prior as well as Luteinizing hormone (LH) and Estradiol (E2) levels within the normal interval according to standard data for the area where the study was carried out
  • Subjects with a regular menstrual cycles between 25-35 days
  • Subjects with infertility that justifies treatment with IVF/ET or ICSI
  • Subjects undergoing controlled ovarian stimulation (COS) with r-hFSH using a long protocol with GnRH-a
  • Sperm availability from the subject's current partner unless it is planned to use sperm from a donor
  • Subjects with both ovaries
  • Subjects with uterine cavity capable of withstanding the implantation of the embryo and pregnancy
  • Subjects whose vaginal smear (PAP) was normal within the 3 years prior to starting the stimulation
  • Subjects with body mass index (BMI) between 18 and 30 at the time of participation in the study
  • Subjects in whom at least 30 days have elapsed since the last dose of clomiphene citrate or gonadotropins before beginning treatment with GnRH-a
  • Subjects with a negative pregnancy test result using the beta human chorionic gonadotropin (beta-hCG) test (in urine or blood) before beginning treatment with GnRH-a
  • Subjects willing to and capable of following the protocol during the entire study
  • Subjects who have provided informed written consent before carrying out any procedure related with the study (that is not part of the normal medical treatment followed by the subject)

Exclusion Criteria:

  • Subject who were human immunodeficiency virus, hepatitis B and C virus positive
  • Subjects suffering from any clinically important systematic disease, hypothalmic or pituitary tumour, ovarian, uterine or breast cancer, endocrinopathy and/or medical alterations, biochemical or hematological that as per the investigators judgement, may interfere with the gonadotropin treatment
  • Subjects who have been subjected to more than 2 assisted reproductive cycles in the past
  • Subjects who have cancelled 2 cycles in the past
  • Subjects who have cryopreserved embryos from previous assisted reproductive cycles
  • Subjects with non explained vaginal haemorrhages
  • Subjects with polycystic ovary, enlarged ovary or ovarian cysts of unknown aetiology
  • Subjects with any contraindication for getting pregnant or taking the pregnancy to full term
  • Subjects with known allergy to the gonadotropin preparations or any of its excipients
  • Subjects with current drug use or prior personal history of alcohol, drug or psychiatric drug dependency in the past five years
  • Subjects with prior participation in this study or simultaneous participation in a different clinical study with a medication under investigation
  • Subjects who were not willing to or incapable of following the study protocol

Sites / Locations

  • Hospital de Cruces, Plaza de Cruces, 12, 48903

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

r-hFSH + r-hLH

r-hFSH alone

Arm Description

Outcomes

Primary Outcome Measures

Mean Number of Metaphase II (M-II) Oocytes Retrieved
Mean number of M-II oocytes were calculated for subjects undergoing ovum pick up for Intra-cytoplasmic Sperm Injection (ICSI). ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. 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.

Secondary Outcome Measures

Number of Fertilized Oocytes (2 Pronuclei [2PN])
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN.
Quality of Embryos
Embryos were classified into 5 different grades (1 to 5) based on their capacity of implantation. Grade 1 embryos were those with best capacity of implantation and Grade 5 embryos were those with worst capacity of implantation. Mean number of embryos for each of the 5 grades were reported.
Embryo Implantation Rate
Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.
Clinical Pregnancy Rate
Clinical pregnancy rate defined as the percentage of subjects with a ultrasound confirmation of a gestational sac, with or without fetal heart activity.
Mean Number of Follicles Greater Than or Equal to (>=) 14 Millimeter (mm)
Mean number of follicles as per the following categories were presented: >=14 mm and less than (<) 16 mm; >=16 mm and <18 mm and >=18 mm.
Endometrial Thickness
Number of Cycles Cancelled Due to Unsatisfactory Response
If the subject was not administered with r-hCG and withdrew prematurely from the trail, it is considered as cycle cancellation
Mean Number of Oocytes Retrieved
Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocyte from the ovary of the female subject, enabling fertilization outside the body.

Full Information

First Posted
April 22, 2010
Last Updated
August 28, 2017
Sponsor
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT01110707
Brief Title
A Randomised, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of Combined Treatment of Lutropin Alpha and Recombinant Human Luteinizing Hormone in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve
Official Title
Lutropin Alpha in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve: Comparative Study, in Phase II, With Parallel Control
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
January 10, 2005 (Actual)
Primary Completion Date
November 15, 2006 (Actual)
Study Completion Date
November 15, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

5. Study Description

Brief Summary
This was a prospective, randomized, Phase II, comparative study with a parallel control for evaluating the efficacy and safety of combined treatment of recombinant human follicle stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH). The combined treatment was administered at the middle of the follicular phase in subjects undergoing in-vitro fertilisation (IVF) through intracytoplasmic sperm injection (ICSI) and transfer of embryos (ET).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Ovulation Induction
Keywords
Reproductive technology, Assisted, Recombinant human follicle stimulating hormone (r-hFSH), Recombinant leutinizing hormone (r-hLH), Ovulation induction, Infertility

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
131 (Actual)

8. Arms, Groups, and Interventions

Arm Title
r-hFSH + r-hLH
Arm Type
Experimental
Arm Title
r-hFSH alone
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Recombinant human follicle stimulating hormone (r-hFSH)
Other Intervention Name(s)
GONAL-f, Follitrophin alpha
Intervention Description
Subjects will receive subcutaneous injection of recombinant human follicular stimulating hormone (r-hFSH) 300-450 International Units (IU) administered after pituitary desensitization according to the ovarian response with gonadotrophin-releasing hormone agonist (GnRH-a; at a dose of 0.1 milligram per day [mg/day]).
Intervention Type
Drug
Intervention Name(s)
Recombinant human luteinizing hormone (r-hLH)
Other Intervention Name(s)
Luveris, Lutrophin alpha
Intervention Description
Subjects will receive subcutaneous injection of recombinant human luteinizing hormone (r-hLH) 150 IU/day until the end of ovarian stimulation.
Primary Outcome Measure Information:
Title
Mean Number of Metaphase II (M-II) Oocytes Retrieved
Description
Mean number of M-II oocytes were calculated for subjects undergoing ovum pick up for Intra-cytoplasmic Sperm Injection (ICSI). ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. 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.
Time Frame
36 hours post r-hCG administration
Secondary Outcome Measure Information:
Title
Number of Fertilized Oocytes (2 Pronuclei [2PN])
Description
Oocytes were fertilized using Intra-cytoplasmic Sperm Injection (ICSI) technique which is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. The appearance of 2PN is the first sign of successful fertilization as observed during in vitro fertilization, and is usually observed after ICSI. The zygote is then termed 2PN.
Time Frame
36 hours post r-hCG administration
Title
Quality of Embryos
Description
Embryos were classified into 5 different grades (1 to 5) based on their capacity of implantation. Grade 1 embryos were those with best capacity of implantation and Grade 5 embryos were those with worst capacity of implantation. Mean number of embryos for each of the 5 grades were reported.
Time Frame
Day 2-3 post r-hCG administration
Title
Embryo Implantation Rate
Description
Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.
Time Frame
35-42 days post r-hCG administration
Title
Clinical Pregnancy Rate
Description
Clinical pregnancy rate defined as the percentage of subjects with a ultrasound confirmation of a gestational sac, with or without fetal heart activity.
Time Frame
35-42 days post r-hCG administration
Title
Mean Number of Follicles Greater Than or Equal to (>=) 14 Millimeter (mm)
Description
Mean number of follicles as per the following categories were presented: >=14 mm and less than (<) 16 mm; >=16 mm and <18 mm and >=18 mm.
Time Frame
r-hCG day (end of stimulation cycle [approximately 28 days])
Title
Endometrial Thickness
Time Frame
r-hCG day (end of stimulation cycle [approximately 28 days])
Title
Number of Cycles Cancelled Due to Unsatisfactory Response
Description
If the subject was not administered with r-hCG and withdrew prematurely from the trail, it is considered as cycle cancellation
Time Frame
r-hCG day (end of stimulation cycle [approximately 28 days])
Title
Mean Number of Oocytes Retrieved
Description
Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocyte from the ovary of the female subject, enabling fertilization outside the body.
Time Frame
36 hours post r-hCG administration

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All subjects must meet the following inclusion criteria within the 6 months prior to starting the pituitary suppression unless otherwise specified: Postmenopausal woman aged between 35 and 40 years that wishes to become pregnant Subjects with basal serum level (beginning of the follicular phase, Day 2-5) of Follicle-Stimulating Hormone (FSH) less than 10 IU/L determined within the 6 months prior as well as Luteinizing hormone (LH) and Estradiol (E2) levels within the normal interval according to standard data for the area where the study was carried out Subjects with a regular menstrual cycles between 25-35 days Subjects with infertility that justifies treatment with IVF/ET or ICSI Subjects undergoing controlled ovarian stimulation (COS) with r-hFSH using a long protocol with GnRH-a Sperm availability from the subject's current partner unless it is planned to use sperm from a donor Subjects with both ovaries Subjects with uterine cavity capable of withstanding the implantation of the embryo and pregnancy Subjects whose vaginal smear (PAP) was normal within the 3 years prior to starting the stimulation Subjects with body mass index (BMI) between 18 and 30 at the time of participation in the study Subjects in whom at least 30 days have elapsed since the last dose of clomiphene citrate or gonadotropins before beginning treatment with GnRH-a Subjects with a negative pregnancy test result using the beta human chorionic gonadotropin (beta-hCG) test (in urine or blood) before beginning treatment with GnRH-a Subjects willing to and capable of following the protocol during the entire study Subjects who have provided informed written consent before carrying out any procedure related with the study (that is not part of the normal medical treatment followed by the subject) Exclusion Criteria: Subject who were human immunodeficiency virus, hepatitis B and C virus positive Subjects suffering from any clinically important systematic disease, hypothalmic or pituitary tumour, ovarian, uterine or breast cancer, endocrinopathy and/or medical alterations, biochemical or hematological that as per the investigators judgement, may interfere with the gonadotropin treatment Subjects who have been subjected to more than 2 assisted reproductive cycles in the past Subjects who have cancelled 2 cycles in the past Subjects who have cryopreserved embryos from previous assisted reproductive cycles Subjects with non explained vaginal haemorrhages Subjects with polycystic ovary, enlarged ovary or ovarian cysts of unknown aetiology Subjects with any contraindication for getting pregnant or taking the pregnancy to full term Subjects with known allergy to the gonadotropin preparations or any of its excipients Subjects with current drug use or prior personal history of alcohol, drug or psychiatric drug dependency in the past five years Subjects with prior participation in this study or simultaneous participation in a different clinical study with a medication under investigation Subjects who were not willing to or incapable of following the study protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Hospital de Cruces, Plaza de Cruces, 12, 48903
City
Vizcaya
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
20031032
Citation
Matorras R, Prieto B, Exposito A, Mendoza R, Crisol L, Herranz P, Burgues S. Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI cycles: a randomized controlled study. Reprod Biomed Online. 2009 Dec;19(6):879-87. doi: 10.1016/j.rbmo.2009.09.016.
Results Reference
result
PubMed Identifier
21575849
Citation
Matorras R, Prieto B, Exposito A, Mendoza R, Crisol L, Herranz P, Burgues S. Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI cycles: a randomized controlled study. Reprod Biomed Online. 2011 Feb;22 Suppl 1:S43-51. doi: 10.1016/S1472-6483(11)60008-4.
Results Reference
result

Learn more about this trial

A Randomised, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of Combined Treatment of Lutropin Alpha and Recombinant Human Luteinizing Hormone in the Middle of the Controlled Ovarian Stimulation Follicular Phase in Women With Reduced Ovarian Reserve

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