Clinical trial NCT01110707: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infertility
Ovulation Induction
Keywords: Reproductive technology, Assisted
Recombinant human follicle stimulating hormone (r-hFSH)
Recombinant leutinizing hormone (r-hLH)
Ovulation induction
Infertility
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2010-04-27
Enrollment: 131
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Mean Number of Metaphase II (M-II) Oocytes Retrieved
timeFrame: 36 hours post r-hCG administration
Secondary outcomes:
measure: Number of Fertilized Oocytes (2 Pronuclei [2PN])
timeFrame: 36 hours post r-hCG administration
measure: Quality of Embryos
timeFrame: Day 2-3 post r-hCG administration
measure: Embryo Implantation Rate
timeFrame: 35-42 days post r-hCG administration
measure: Clinical Pregnancy Rate
timeFrame: 35-42 days post r-hCG administration
measure: Mean Number of Follicles Greater Than or Equal to (>=) 14 Millimeter (mm)
timeFrame: r-hCG day (end of stimulation cycle [approximately 28 days])
measure: Endometrial Thickness
timeFrame: r-hCG day (end of stimulation cycle [approximately 28 days])
measure: Number of Cycles Cancelled Due to Unsatisfactory Response
timeFrame: r-hCG day (end of stimulation cycle [approximately 28 days])
measure: Mean Number of Oocytes Retrieved
timeFrame: 36 hours post r-hCG administration
Other outcomes:
Locations:
city: Vizcaya
country: Spain
facility: Hospital de Cruces, Plaza de Cruces, 12, 48903
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
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.
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.