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Trial registered on ANZCTR


Registration number
ACTRN12609001060235
Ethics application status
Approved
Date submitted
25/10/2009
Date registered
10/12/2009
Date last updated
8/09/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of using Growth Hormone in Invitro Fertilisation on livebirth rates
Scientific title
A randomised, double blind placebo controlled study assessing the effect of recombinant human growth hormone (r-hGH) on live birth rates in women who are poor responders undergoing an Invitro Fertilisation(IVF) or Intracytoplasmic Sperm Injection(ICSI) cycle.
Secondary ID [1] 280843 0
nil known
Universal Trial Number (UTN)
U1111-1112-2826
Trial acronym
LIGHT study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
infertility 252054 0
poor response to ovarian stimulation in IVF cycle 252055 0
Condition category
Condition code
Reproductive Health and Childbirth 252251 252251 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
administration of Growth Hormone 12IU given daily as a subcutaneous injection from day 1of IVF ovarian stimulation using recombinant follicle stimulating hormone administration to day of oocyte maturation
Intervention code [1] 241452 0
Treatment: Drugs
Comparator / control treatment
administration of placebo (sterile water)given daily as a subcutaneous injection from day 1of IVF ovarian stimulation using recombinant follicle stimulating hormone administration to day of oocyte maturation
Control group
Placebo

Outcomes
Primary outcome [1] 253122 0
the effect of growth hormone co-stimulation on live birth rates assessed by reviewing medical records, health care correspondance or verbal confirmation by patient after delivery of infant
Timepoint [1] 253122 0
9 month after a positive pregancy test has been recorded at the end of the IVf cycle
Secondary outcome [1] 257992 0
Clinical pregnancy (presence of a gestational sac detected by ultrasound)
Timepoint [1] 257992 0
8 weeks after a positive pregancy test has been recorded at the end of the IVf cycle
Secondary outcome [2] 257993 0
Number of oocytes retrieved as visually assessed in the laboratory by embryologists viewing oocytes obtained
Timepoint [2] 257993 0
at end of oocyte collection
Secondary outcome [3] 257994 0
Fertilization and post-fertilization development as visually assessed in the laboratory by embryologists viewing fertilised oocytes after insemination or injection of sperm.
Timepoint [3] 257994 0
at days 1 to 5 after oocyte collection
Secondary outcome [4] 257995 0
Number and quality of embryos as visually assessed in the laboratory by embryologists viewing fertilised oocytes after insemination or injection of sperm.
Timepoint [4] 257995 0
at days 1 - 5 after oocyte collection
Secondary outcome [5] 257996 0
Oestrogen levels on day of Oocyte Pick Up as measured by assay in laboratory
Timepoint [5] 257996 0
on day of oocyte collection
Secondary outcome [6] 257998 0
Total recombinant Follicle Stimulating Hormone(FSH) dose required for follicular maturation assessed by counting doses patients have self administered during thier treatment cycle
Timepoint [6] 257998 0
data collected on day of r human chorioic gonadatrophin administration

Eligibility
Key inclusion criteria
Have early follicular phase (Day 2-6) serum levels within the last 3 months prior to study entry of: FSH less than or equal to 15 IU/L and no recorded FSH level ever greater than 15IU/L
Have a regular spontaneous menstrual cycle between 21 and 35 days in length.
Have had a previous IVF/ICSI cycle resulting in collection of less than or equal to 5 oocytes.
Be ordered a starting dose of ovarian stimulation of r-FSH of greater than or equal to 250 and less than or equal to 450 IU
A body mass index (BMI) less than or equal to 32 kg/m2
Have access to ejaculatory sperm. If not, the subject can only be entered if donor sperm will be used.
Presence of both ovaries.
Have a uterine cavity without abnormalities, which, in the investigator’s opinion, could impair embryo implantation or pregnancy evolution as assessed within the last 3 years using ultrasound (US), hysteroscopy (HSC), or hysterosalpingography (HSG).
Have a negative cervical PAP test within the last 12 months prior to study entry, as evidenced by laboratory report in subject’s medical notes.
have a normal fasting blood glucose level
Minimum age
18 Years
Maximum age
41 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
A history or current presence of Polycystic Ovarian Syndrome (PCOS) (Rotterdam criteria)
Azoospermia requiring testicular sperm extraction
Undergoing Preimplantation Genetic Screening during her IVF/ICSI cycle
Previous chemotherapy and /or radiotherapy treatment
Had previous severe ovarian hyper stimulation syndrome (OHSS).
Any contraindication to being pregnant and/or carrying a pregnancy to term.
A history of or current presence of tumours of the hypothalamus and pituitary gland.
Current ovarian enlargement or ovarian cyst of unknown aetiology
Current or past history of clinically significant systemic disease, including chronic kidney or liver disease, diabetes mellitus type I & II, uncontrolled thyroid disease, any autoimmune disease
Current chronic infectious disease, including positive result for Hepatitis B, Hepatitis C, HumanImmunodeficency Virus (HIV)
Acute or severe illness during the previous 6 months considered clinically significant according to clinician assessment
Current or past history of malignancies including ovarian, uterine or breast cancer (except non-melanomatous skin malignancies)
Abnormal gynaecological bleeding of undetermined origin
Any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years, according to clinical assessment including current smoking.

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)
treatment will be allocated according to pre numbered sequential series drug containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be done by using a randomisation table created by computer software and will be done by the manufacturers of the study drug/placebo to maintain the blind
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/12/2009
Actual
25/10/2010
Date of last participant enrolment
Anticipated
16/10/2014
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
389
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 2161 0
5000
Recruitment postcode(s) [2] 2162 0
3002
Recruitment postcode(s) [3] 2163 0
3168
Recruitment postcode(s) [4] 2164 0
6008
Recruitment postcode(s) [5] 2165 0
2145
Recruitment postcode(s) [6] 2166 0
5065
Recruitment postcode(s) [7] 2167 0
5042
Recruitment outside Australia
Country [1] 2294 0
New Zealand
State/province [1] 2294 0
Auckland
Country [2] 2295 0
New Zealand
State/province [2] 2295 0

Funding & Sponsors
Funding source category [1] 243924 0
Commercial sector/Industry
Name [1] 243924 0
Merck Serono
Country [1] 243924 0
Australia
Funding source category [2] 243979 0
University
Name [2] 243979 0
University of Adelaide
Country [2] 243979 0
Australia
Primary sponsor type
University
Name
Robinson Institute
Address
University of Adelaide
Medical School North
Frome Rd Adelaide 5000
South Australia
Country
Australia
Secondary sponsor category [1] 251436 0
None
Name [1] 251436 0
Address [1] 251436 0
Country [1] 251436 0
Other collaborator category [1] 923 0
Other Collaborative groups
Name [1] 923 0
Fertility SA
Address [1] 923 0
120 Hutt St
Adelaide, South Australia 5000
Country [1] 923 0
Australia
Other collaborator category [2] 925 0
Other Collaborative groups
Name [2] 925 0
Repromed
Address [2] 925 0
180 Fullarton Road
Dulwich South Australia 5065
Country [2] 925 0
Australia
Other collaborator category [3] 926 0
Other Collaborative groups
Name [3] 926 0
IVF Australia Bondi Junction
Address [3] 926 0
16th / 101 Grafton St BondiJunction NSW 2022
Country [3] 926 0
Australia
Other collaborator category [4] 927 0
Other Collaborative groups
Name [4] 927 0
Genea
Address [4] 927 0
321 Kent St
SYDNEY NSW 2000
Country [4] 927 0
Australia
Other collaborator category [5] 928 0
Hospital
Name [5] 928 0
Westmead Fertility Centre
Address [5] 928 0
WESTMEAD HOSPITAL
Westmead NSW 2145
Country [5] 928 0
Australia
Other collaborator category [6] 929 0
Other Collaborative groups
Name [6] 929 0
Monash IVF Clayton
Address [6] 929 0
252 Clayton Road
Clayton 3168 VICTORIA
Country [6] 929 0
Australia
Other collaborator category [7] 930 0
Other Collaborative groups
Name [7] 930 0
Melbourne IVF
Address [7] 930 0
The Royal Women's Hospital
132 Grattan Street
Carlton 3053 VICTORIA
Country [7] 930 0
Australia
Other collaborator category [8] 931 0
Other Collaborative groups
Name [8] 931 0
Fertility Specialist of WA
Address [8] 931 0
Bethesda Hospital
25 Queenslea Drive
CLAREMONT WA 6010
Country [8] 931 0
Australia
Other collaborator category [9] 932 0
Other Collaborative groups
Name [9] 932 0
Fertility Associates
Address [9] 932 0
Level 3, 7 Ellerslie Racecourse Drive,
Remuera,
Auckland, 1051
Country [9] 932 0
New Zealand
Other collaborator category [10] 276930 0
Other Collaborative groups
Name [10] 276930 0
Pivet Medical Centre
Address [10] 276930 0
166-168 Cambridge St, Leederville PERTH WA 6008
Country [10] 276930 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 244035 0
Children's Youth Women's Health Service (CYWHS)
Ethics committee address [1] 244035 0
Women's and Children's Hospital, 72 Kermode St North Adelaide 5006
Ethics committee country [1] 244035 0
Australia
Date submitted for ethics approval [1] 244035 0
16/10/2009
Approval date [1] 244035 0
01/07/2010
Ethics approval number [1] 244035 0

Summary
Brief summary
It is well known that the chance of live birth in assisted reproduction treatment decreases with increasing female age, and drops markedly after 40 years of age, however, some woman younger than this is an ‘unexpected poor responder’ during their IVF cycle. Tesarik reported in 2005 that the ability of human oocytes to form normal embryos is related to the concentration of different hormones in follicular fluid (Mendoza et al., 1999, 2002). Among the hormones studied, growth hormone (GH) showed the most consistent relationship with different parameters of embryo quality, and higher concentrations of GH in follicular fluid were associated with rapid embryo cell division, good embryo morphology and a high embryo implantation potential (Mendoza et al., 1999, 2002).He also reports a decrease in follicular fluid GH concentration in women aged 40 years as compared with young women.

Studies evaluating the benefits of co-treatment with recombinant human Growth Hormone (r-hGH) during controlled ovarian stimulation for human assisted reproduction treatment have reported controversial findings.
A Cochrane review (Harper et al. 2008) and updated as part of a review of the management of poor responders (Kyrou et al. 2008), suggest that there exists some evidence for the use of GH in the management of IVF cycles of poor responders.
The aim of this study is to determine the influence of GH treatment as an adjunct to stimulation with the maximal dose of Follicle Stimulating Hormone(FSH) stimulation in the unexpected poor responding IVF patient, ie patients requiring maximal dose of stimulation despite being under 41 years of age.
Trial website
http://www.adelaide.edu.au/light-study/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30415 0
Prof Robert Norman
Address 30415 0

Robinson Resarch Institute
Discipline of Obstetrics & Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide
Frome Road, Adelaide
South Australia 5000
Country 30415 0
Australia
Phone 30415 0
+61 8 8313 5100
Fax 30415 0
Email 30415 0
[email protected]
Contact person for public queries
Name 13662 0
Ms Helen Alvino
Address 13662 0
Level 6
Medical School North
Frome Road
Adelaide SA 5000
Country 13662 0
Australia
Phone 13662 0
+61 (0)419843418
Fax 13662 0
Email 13662 0
[email protected]
Contact person for scientific queries
Name 4590 0
Prof Professor Robert Norman
Address 4590 0
Director
Robinson Institute
Medical School North
Frome Rd
Adelaide South Australia 5000
Country 4590 0
Australia
Phone 4590 0
+61 8 8313 5100
Fax 4590 0
+61 8 83036100
Email 4590 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseHuman growth hormone for poor responders: a randomized placebo-controlled trial provides no evidence for improved live birth rate.2019https://dx.doi.org/10.1016/j.rbmo.2019.02.003
N.B. These documents automatically identified may not have been verified by the study sponsor.