Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001671853
Ethics application status
Approved
Date submitted
15/08/2021
Date registered
6/12/2021
Date last updated
6/12/2021
Date data sharing statement initially provided
6/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Hyperbaric Oxygen in “poor ovarian responders” - fertility evaluation

Scientific title
Impact of hyperbaric oxygen in poor ovarian responders on assisted reproduction technology treatment pregnancy rate
Secondary ID [1] 305046 0
NONE
Universal Trial Number (UTN)
Trial acronym
FertyOx
Linked study record

Health condition
Health condition(s) or problem(s) studied:
poor ovarian responder 323239 0
Infertility 323240 0
Condition category
Condition code
Reproductive Health and Childbirth 320814 320814 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group A (Intervention group) will be submitted to Hyperbaric Oxygen (HBO) therapy for the first 5 days of stimulation with recombinant follicle stimulating hormone (rFSH) in a gonadotropin-releasing hormone antagonist protocol
rFSH with 300 internacional unit (IU) /Day, Day 3 of the 28-day treatment cycle, until trigger (either recombinant human chorionic gonadotropin (hCG) 250 µg equivalent to 6,500 IU, or Gonadotrophin-releasing hormone agonists (GnRHa) triptorelin 0.2–0.4 mg) will be administered as soon as two follicles reached a size of equal or greater than 17 mm. For the hormone treatment process participants will be allocated between recombinant hCG or GnRHa triptorelin per standard clinic protocol.
All medication will be self-administrated by a diabetic-style pen.
The adherence to the intervention will be monitored by laboratory tests and ultrasound.
HBO consists of the administration of an inspired fraction of oxygen close to 1 (pure or 100% oxygen) via hood in a compressed chamber environment with a pressure higher (usually 2 to 3 times) than atmospheric pressure at sea level. This increase in pressure will result in a very significant increase in blood pressure and tissue oxygen (close to 2000 mmHg and 400 mmHg respectively), which will underlie most of the physiological and therapeutic effects of oxygen in a hyperbaric environment. The treatment will be done at a hyperbaric medicine centre by a qualified specialist in hyperbaric medicine, with a length of 1 hour in the morning of each day (from Days 1-5). The adherence to the intervention will be monitored by a daily attendance record.
Intervention code [1] 321442 0
Treatment: Other
Comparator / control treatment
Group B (control group) will receive only a daily injection of rFSH in a gonadotropin-releasing hormone antagonist protocol.

rFSH with 300 UI /Day, Day 3 of the 28-day treatment cycle until trigger (either recombinant hCG 250 µg equivalent to 6,500 IU, or GnRHa triptorelin 0.2–0.4 mg) will be administered as soon as two follicles reached a size of equal or greater than 17 mm.
For the hormone treatment process participants will be allocated between recombinant hCG or GnRHa triptorelin per standard clinic protocol.
All medication will be self-administrated by a diabetic-style pen.
The adherence to the intervention will be monitored by laboratory tests and ultrasound.
Control group
Active

Outcomes
Primary outcome [1] 328620 0
Pregnancy rate collected by participant fertility clinic records
Timepoint [1] 328620 0
1 month post completion of 28-day treatment cycle,
Secondary outcome [1] 399668 0
implantation rate collected by participant fertility clinic records
Timepoint [1] 399668 0
1 month post completion of 28-day treatment cycle
Secondary outcome [2] 399669 0
miscarriage rate collected by participant fertility clinic records
Timepoint [2] 399669 0
3 months post completion of 28-day treatment cycle
Secondary outcome [3] 399670 0
multiple pregnancy rate collected by participant fertility clinic records
Timepoint [3] 399670 0
2 months post completion of 28-day treatment cycle

Eligibility
Key inclusion criteria
Inclusion criteria: poor ovarian responders
“Bologna Criteria”:
1) advanced women’s age (greater than 40 years) or any other risk factor for POR;
2) recovering a few numbers of oocytes (less than 3 oocytes) following previous ovarian stimulation;
3) abnormal ovarian reserve test (antral follicle counts 5–7 or anti-Mullerian hormone 0.5–1.1 ng/mL).
A poor responder is defined by the presence of two of these criteria.
Minimum age
19 Years
Maximum age
50 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
rFSH - recombinant follicle stimulating hormone
• Prior hypersensitivity to recombinant FSH preparations or one of their excipients
• High levels of FSH indicating primary gonadal failure
• Uncontrolled thyroid or adrenal dysfunction
• Sex hormone dependent tumors of the reproductive tract and accessory organs
• An organic intracranial lesion such as a pituitary tumor
• Abnormal uterine bleeding of undetermined origin (see Selection of Patients)
• Ovarian cyst or enlargement of undetermined origin (see Selection of Patients)
• Pregnancy

Hyperbaric oxygen
• Fever
• Epilepsy
• Pleural diseases: History of pneumothorax, post-pleurodesis status, thoracotomy or chest trauma with subsequent significant restriction of pleural mobility
• Lung diseases: Bullous emphysema
• Uncontrolled claustrophobia
• Drugs: bleomycin; cisplatin, doxorubicin and disulfiram
• Uncontrolled heart disease

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)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
sample size - Since this is a pilot study, there is no data available on the probability of finding positive results, so, according to the central limit theory which states that the sample distribution will be normal or almost normal if the sample size is large enough, generally assuming that a sample size of 30 is considered large enough, it is assumed that it will be necessary to include 30 patients in the study. Taking into account the possibility of withdrawing consent or leaving the study for another reason, it is intended to recruit 40 patients.

Statistical analysis
The statistical analysis will be done with Statistical Package for Social Science software (SPSS, Version 24.0).
Continuous variables will be expressed as means and standard deviations and compared using Student's t or Wilcoxon tests. Qualitative variables will be expressed as absolute and / or relative frequencies and correlated by the chi-square test or Fisher's Exact test. To correlate multiple variables, logistic regression analysis will be performed. A value of p <0.05 will be considered statistically significant.
All changes to the planned analysis will be documented, reported and justified in the final presentation of the results.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/01/2022
Actual
Date of last participant enrolment
Anticipated
3/01/2023
Actual
Date of last data collection
Anticipated
1/01/2024
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 24043 0
Portugal
State/province [1] 24043 0

Funding & Sponsors
Funding source category [1] 309443 0
Hospital
Name [1] 309443 0
Centro de Medicina Subaquática e Hiperbárica
Country [1] 309443 0
Portugal
Primary sponsor type
Individual
Name
José Miguel Raimundo
Address
Rua de Campolide n 351 edf I 9C, 1070-034 Lisboa
Country
Portugal
Secondary sponsor category [1] 310846 0
None
Name [1] 310846 0
Address [1] 310846 0
Country [1] 310846 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309235 0
Escola de Psicologia e Ciências da Vida - Universidade Lusófona
Ethics committee address [1] 309235 0
Ethics committee country [1] 309235 0
Portugal
Date submitted for ethics approval [1] 309235 0
01/06/2021
Approval date [1] 309235 0
20/07/2021
Ethics approval number [1] 309235 0
Ref. CEDIC-2021-05-09

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113446 0
Dr José Miguel Raimundo
Address 113446 0
Rua de Campoilide n 351 edf I 9C, 1070-034 Lisboa
TW Group - TW Clinic
Country 113446 0
Portugal
Phone 113446 0
+351917365234
Fax 113446 0
Email 113446 0
[email protected]
Contact person for public queries
Name 113447 0
José Miguel Raimundo
Address 113447 0
Twin Clinic
Rua de Campoilide n 351 edf I 9C, 1070-034 Lisboa
Country 113447 0
Portugal
Phone 113447 0
+351917365234
Fax 113447 0
Email 113447 0
[email protected]
Contact person for scientific queries
Name 113448 0
José Miguel Raimundo
Address 113448 0
Twin Clinic
Rua de Campoilide n 351 edf I 9C, 1070-034 Lisboa
Country 113448 0
Portugal
Phone 113448 0
+351917365234
Fax 113448 0
Email 113448 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
data protection law


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12876Study protocol  [email protected]
12877Informed consent form  [email protected]
12878Statistical analysis plan  [email protected]



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.