Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000242628
Ethics application status
Approved
Date submitted
30/01/2014
Date registered
6/03/2014
Date last updated
18/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Cycle outcome assessment of patients with Anti-Mullerian-Hormone (AMH) levels above 4ng/mL that are undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) with short antagonist ovarian stimulation
Scientific title
Cycle Outcome Assessment of Patients with Anti-Mullerian-Hormone (AMH) levels above 4ng/mL that are Undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) with Short Antagonist Ovarian Stimulation
Secondary ID [1] 284005 0
none
Universal Trial Number (UTN)
U1111-1152-7648
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertile patients requiring IVF/ICSI treatment with AMH level above 4ng/mL 291041 0
Condition category
Condition code
Reproductive Health and Childbirth 291381 291381 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A cohort of infertile patients with AMH levels above 4ng/mL that require IVF/ICSI treatment will be included in this trial. After scheduling the treatment procedure, controlled ovarian stimulation (COH) using 150IU recombinant gonadotropin will be initiated. Beginning from the 6th day of the cycle, all patients will receive Gonadotropin releasing hormone (GnRH) antagonist shot 0,25mg daily untill final oocyte maturation (when leading follicle reaches diameter of 18 mm). Following COH, ovulation triggering (final oocyte maturation) will be planned and ultrasound guided oocyte retrieval process will be performed 34-36 hours after triggering ovulation for each patient. After obtaining enough number of mature oocytes per patient, intra cytoplasmic sperm injection will be performed on the retrieval day. Depending on the number and quality of embryos, embryo transfer procedure will be performed under ultrasound guidance for each patient. Finally, all cycle outcomes including hormone profiles, total duration of cycles, total gonadotropin consumption, peak estradiol levels, number of retrieved and good quality embryos, pregnancy rates and ovarian hyper stimulation syndrome rates will be determined. Estimated total duration of observation is 1 to 3 months.
Intervention code [1] 288691 0
Treatment: Other
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291372 0
ovarian hyper stimulation syndrome (OHSS) incidence of patients undergoing IVF/ICSI treatment with short-antagonist protocol will be determined by both clinical and laboratory assessments. In order to define a case as OHSS; relevant symptoms such as dyspnea, bloating should be present and free fluid along with pelvis and Douglas pouch should be defined with ultrasound investigation. Additional laboratory parameters such as high hematocrit levels and liver enzymes could also helpful.
Timepoint [1] 291372 0
approximately 3 months after the embryo transfer procedure for each patient
Secondary outcome [1] 306620 0
peak estradiol levels during cycle in terms of pg/mL per patient and per sub-groups along with the review of patient medical records
Timepoint [1] 306620 0
following completion of the cycle of all patients
Secondary outcome [2] 306954 0
total number of retrieved oocytes (metaphase 2 oocytes) in numbers per patient along with the review of patient medical records
Timepoint [2] 306954 0
following completion of the cycle of all patients
Secondary outcome [3] 306955 0
total number of mature (metaphase2) oocytes in numbers per patient along with the review of patient medical records
Timepoint [3] 306955 0
following completion of the cycle of all patients
Secondary outcome [4] 306956 0
total amount of gonadotropin consumption in terms of IU per patient in cycle along with the review of patient medical records
Timepoint [4] 306956 0
following completion of the cycles of all patients
Secondary outcome [5] 306957 0
total duration of ovarian stimulation begining from second day of cycle till final oocyte maturation per patient in terms of days along with the review of patient medical records
Timepoint [5] 306957 0
following completion of the cycles of all patients
Secondary outcome [6] 306958 0
implantation rate per patient (ratio of gestational sac to transferred embryos per patient) (%) along with the review of patient medical records
Timepoint [6] 306958 0
following completion of the cycles of all patients
Secondary outcome [7] 306959 0
positive pregnancy test per patient in terms of serum B-hCG mIU/mL along with the review of patient medical records
Timepoint [7] 306959 0
following completion of all cycles

Eligibility
Key inclusion criteria
Patients with primary or secondary infertility who require IVF/ICSI procedure with Anti Mullerian Hormone levels above 4 ng/mL
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
-patients with severe male factor infertility
-patients who will receive GnRH agonist for ovulation triggering due to excessive ovarian response
-inadequate or poor ovarian response to gonadotropins
-patients with AMH levels lower than 4 ng/mL
-patients with hypogonadotropic hypogonadism (WHO group 1 infertility)
-Patients with medical disorder that provides contraindication to assisted reproduction techniques.


Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Phase 4
Type of endpoint/s
Statistical methods / analysis
Approximately, 150 infertile patients will be allocated in the study to assess the ovarian hyperstimulation incidence and cycle outcomes per patient. After completion of IVF/ICSI cycles, primary and secondary objectives will be assessed. Following initial data assessment, all study outcomes including cycle dynamics and pregnancy rates will be compared between sub-groups as:
*AMH levels between 4 and 5 ng/mL, 5-6 ng/mL and above 6 ng/mL
*body mass index values below 20kg/m2, between 20-25 kg/m2, between 25-30 kg/m2 and above 30kg/m2
*HOMA index values (insulin resistance parameter): above and equal to 2,1 means resistant and below 2,1 means not resistant
Statistically significant parameters will be assessed between mentioned sub-groups.
Another statistical objective is to perform regression analysis to determine the factors that mostly influence biochemical pregnancy rates, clinical pregnancy rates and OHSS rates.
To predict 20% more OHSS cases in one of the mentioned sub-groups, total of 117 patients should be allocated within 0,05 type 1 error and 0,80 power. Power calculations was performed using NCSS PASS 2007.
Estimated total duration of the observation will be 3 months beginning from the allocation of first subject till collecting all cycle datas following completion of all cycles.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/03/2014
Actual
20/03/2014
Date of last participant enrolment
Anticipated
1/10/2014
Actual
1/10/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
150
Accrual to date
Final
120
Recruitment outside Australia
Country [1] 5793 0
Turkey
State/province [1] 5793 0

Funding & Sponsors
Funding source category [1] 288639 0
Self funded/Unfunded
Name [1] 288639 0
Country [1] 288639 0
Primary sponsor type
Individual
Name
Recai Pabuccu, Proff., M.D.
Address
Centrum Clinic IVF Center, Ankara
Ufuk University Faculty of Medicine, Ankara
Nenehatun caddesi No 59 GOP-Ankara
Turkey
06550
Country
Turkey
Secondary sponsor category [1] 287351 0
None
Name [1] 287351 0
Address [1] 287351 0
Country [1] 287351 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290494 0
Turgut Ozal University Faculty of Medicine
Ethics committee address [1] 290494 0
Anadolu Bulvari 16/A Gimat - Yenimahalle / ANKARA
06370
Ethics committee country [1] 290494 0
Turkey
Date submitted for ethics approval [1] 290494 0
23/01/2014
Approval date [1] 290494 0
24/01/2014
Ethics approval number [1] 290494 0

Summary
Brief summary
Infertile patients undergoing IVF/ICSI procedure with AMH levels greater than 4ng/mL represents clear risk for excessive ovarian response and ovarian hyper stimulation syndrome development under literature findings. Novel ovarian stimulation protocols and gonadotropin dose modifications have been proposed to prevent OHSS and achieve successful pregnancies so far. In the current study, fix 150 IU of gonadotropin stimulation along with fix day 6 antagonist protocol will be investigated in terms of excessive ovarian response and cycle outcomes in high responder infertile patients with AMH levels above 4ng/mL. Comparison of cycle outcomes will be performed between different sub-groups of AMH, body mass index and insulin resistancy situation. Also, most determining factors that may influence pregnancy and OHSS rates will be investigated.
Trial website
Trial related presentations / publications
there is currently no trials/publications available.
Public notes

Contacts
Principal investigator
Name 45910 0
Dr Emre Goksan Pabuccu
Address 45910 0
Ufuk University Faculty of Medicine, Department of Obstetrics and Gynecology
Ankara-Turkey
06520
Country 45910 0
Turkey
Phone 45910 0
+90 532 414 7844
Fax 45910 0
Email 45910 0
[email protected]
Contact person for public queries
Name 45911 0
Dr Emre Goksan Pabuccu
Address 45911 0
Ufuk University Faculty of Medicine, Department of Obstetrics and Gynecology
Ankara-Turkey
06520
Country 45911 0
Turkey
Phone 45911 0
+90 532 414 7844
Fax 45911 0
Email 45911 0
[email protected]
Contact person for scientific queries
Name 45912 0
Prof Recai Pabuccu
Address 45912 0
Ufuk University Faculty of Medicine, Department of Obstetrics and Gynecology
Ankara-Turkey
06520
Country 45912 0
Turkey
Phone 45912 0
+90 312 240 4000
Fax 45912 0
Email 45912 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
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Documents added automatically
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