The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12611001133921
Ethics application status
Approved
Date submitted
25/10/2011
Date registered
31/10/2011
Date last updated
18/11/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomized Trial To Assess The Importance of Human Menopausal Gonadotropin Co-stimulation in In Vitro Fertilization Programs
Scientific title
The impact of human menopausal gonadotropin on follicular fluid hormone levels, embryo quality and IVF outcome in infertile women with mild male factor, unexplained and tubal factor infertility at ages between 25-35, undergoing controlled ovarian stimulation with recombinant FSH versus recombinant FSH+HMG
Secondary ID [1] 273262 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertility 279028 0
Condition category
Condition code
Reproductive Health and Childbirth 279213 279213 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The long COH (controlled ovarian hyperstimulation) protocol is used in which the GnRH analogue (Leuprolide acetate )was administered in a dose of 1 mg/day subcutaneously starting in the mid-luteal phase of the preceding cycle (on the 21st day of preceding cycle). After down regulation (that is, pituitary desensitization) with leuprolide acetate;
Arm 1 was stimulated only with subcutaneous recombinant FSH, the starting dose was between 150-450 IU depending on the patient's characteristics and the treatment was terminated when 2 or more follicules greater than 17mm in diameter was obtained;
Arm 2 was stimulated with subcutaneous recombinant FSH and intramuscular HMG (human menopausal gonadotropin, 1 or 2 ampoules depending on the patient's characteristics) from the beginning and both drugs were continued till 2 or more follicules of 17mm in diameter was obtained;
Arm 3 was stimulated with subcutaneous recombinant FSH and intramuscular HMG was added to the stimulation protocol when a 10 mm follicle developed and both drugs were continued till 2 or more follicules of 17mm in diameter was obtained
Intervention code [1] 269604 0
Treatment: Drugs
Comparator / control treatment
Active control [controlled ovarian stimulation with recombinant FSH (subcutaneous injection) and adding HMG (intramuscular injection) co-stimulation for differing durations of time] Recombinant FSH is started within a dose range of 150-450 U depending on the patient's characteristics and HMG co-stimulation is added as 1 or 2 ampoules as needed. All three arms of the study were compared with each other trying to assess the superiority of one arm to the others on the outcomes as embryo quality, implantation and clinical pregnancy rates and the hormonal milleu of the intrafollicular fluid. Arm 1 is actually the control treatment;however, recombinant FSH treatment is not the standart treatment in IVF stimulation protocols. Treatments can directly start with HMG stimulation or co-stimulation with HMG can be added as in Arms 2 and 3. With this study we tried to find out if co-stimulation with HMG and the duration of HMG stimulation was superior to pure recombinant FSH stimulation on the outcome measures as the embryo quality, the implantation and the clinical pregnancy rates. And if it happens that one is superior then, as the secondary outcome of the study the difference of the intrafollicular hormonal milleu of each arm will be assessed.
Control group
Active

Outcomes
Primary outcome [1] 279844 0
embryo quality
Quality of the day 3 embryos were assessed using the following criteria :
Grade 1 embryo (G1): no fragmentation, homogenous blastomeres
Grade 2 embryo (G2) : < %20 fragmantation, equal or unequal blastomeres
Grade 3 embryo (G3): %20- 50 fragmantation, unequal blastomeres
Grade 4 embriyo (G4) : >%50 fragmantation unequal blastomeres
An inverted phase contrast microscope (Olympus, Japan) at X200 or X400 magnification was used for the evaluation of embryo quality.
Timepoint [1] 279844 0
at cleavage stage on day 3 of fertilization
Primary outcome [2] 279845 0
implantation and clinical pregnancy rates
Timepoint [2] 279845 0
Transvaginal Ultrasonography 3-5 weeks after embryo transfer. Three weeks after the embryo transfer gestational sac/s were assessed on transvaginal ultrasonography in those who were beta HCG positive. And a second transvaginal ultrasound is performed on the fifth week of embryo transfer for assessment of fetal heart beat.
Secondary outcome [1] 294569 0
Follicular fluid hormone levels
Timepoint [1] 294569 0
At the time of ovum pick-up

Eligibility
Key inclusion criteria
mild male factor, tubal factor and unexplained infertility
Minimum age
25 Years
Maximum age
35 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
polycystic ovarian syndrome, poor responder patients (defined as having less than four follicles <15mm developed, or cycle cancellations in previous IVF attempts), previous fertilization failure (defined as fertilization rate less than 30% of the MII oocytes in a previous IVF cycle), any systemic, endocrine or metabolic illnesses, diminished ovarian reserve (defined as early follicular phase FSH>15 mIU/mL or AFC<5)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 3924 0
Turkey
State/province [1] 3924 0

Funding & Sponsors
Funding source category [1] 284091 0
University
Name [1] 284091 0
Scientific Research Commission of the Marmara University School of Medicine (BAPKO)
Address [1] 284091 0
Marmara University Main Campus
Fahrettin Kerim Gokay Caddesi Rektorluk Binasi 1. Kat, Goztepe, Kadikoy - Istanbul / TURKEY
34722
Country [1] 284091 0
Turkey
Primary sponsor type
Individual
Name
Gokce Anik Ilhan
Address
Merdivenkoyyolu Sokak
Hacibektasoglu Apt. No:30/7
Goztepe/Istanbul - TURKEY
Postal code:34732
Country
Turkey
Secondary sponsor category [1] 269054 0
Individual
Name [1] 269054 0
Prof. Dr. Fatih Durmusoglu
Address [1] 269054 0
Marmara University Hospital
Department of Obstetrics and Gynecology
Fevzi Cakmak Mahallesi, Mimar Sinan Cad
NO: 41 Ust Kaynarca /Pendik
Istanbul - TURKEY 34890
Country [1] 269054 0
Turkey

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Recombinant FSH and HMG (human menopausal gonadotropin) are commonly used in ovarian stimulation protocols. Several studies have evaluated the effectiveness of these two alternatives in IVF and reported conflicting results. The objective of this prospective randomized study is to analyze IVF outcomes of patients undergoing ovarian stimulation with FSH versus FSH-HMG for unexplained, tubal factor and mild male factor infertility.
Trial website
nil
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33302 0
Address 33302 0
Country 33302 0
Phone 33302 0
Fax 33302 0
Email 33302 0
Contact person for public queries
Name 16549 0
Gokce Anik Ilhan
Address 16549 0
Merdivenkoyyolu Sokak
Hacibektasoglu Apt. No:30/7
Goztepe/Istanbul - TURKEY
Postal code :34732
Country 16549 0
Turkey
Phone 16549 0
+905337721646
Fax 16549 0
Email 16549 0
gokceanik@yahoo.com
Contact person for scientific queries
Name 7477 0
Gokce Anik Ilhan
Address 7477 0
Merdivenkoyyolu Sokak
Hacibektasoglu Apt. No:30/7
Goztepe/Istanbul - TURKEY
Postal code :34732
Country 7477 0
Turkey
Phone 7477 0
+905337721646
Fax 7477 0
Email 7477 0
gokceanik@yahoo.com

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary