UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000028031 |
|---|---|
| Receipt number | R000032031 |
| Scientific Title | Induction of secondary follicle growth by physical stimulation to ovary |
| Date of disclosure of the study information | 2017/07/01 |
| Last modified on | 2017/07/01 15:03:05 |
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Basic information
Public title
Induction of secondary follicle growth by physical stimulation to ovary
Acronym
Induction of secondary follicle growth by physical stimulation to ovary
Scientific Title
Induction of secondary follicle growth by physical stimulation to ovary
Scientific Title:Acronym
Induction of secondary follicle growth by physical stimulation to ovary
Region
| Japan |
Condition
Condition
Infertility patients with poor response to gonadotropins
Classification by specialty
| Obstetrics and Gynecology |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
In poor responders for ovarian stimulation, the numbers of oocytes retrieved from ovaries are low due to decreases in the number of developing antral follicles, resulting in poor clinical outcome of in vitro fertilization and embryo transfer. Recently, disruption of Hippo signaling pathway in ovarian somatic cells by fragmentation of ovarian cortex is shown to increase the number of antral follicles by induction of secondary follicle growth.
In this study, we sought to establish the method for increase in the number of retrieved oocytes by induction of secondary follicle growth followed by physical stimulation to the ovarian tissues. As the methods for physical stimulation, we perform laparoscopic surgery for (1) partial removal of cortex from ovary and subsequent auto-transplantation immediately after fragmentation, and/or (2) in situ incision of ovarian cortex, and the compare the effectiveness of these methods to induce secondary follicle growth.
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Confirmatory
Trial characteristics_2
Pragmatic
Developmental phase
Phase III
Assessment
Primary outcomes
Comparison of the number of oocytes retrieved after ovarian stimulation with those of base line numbers.
Key secondary outcomes
Comparison of proportions of fertilization, pregnancy and abortion with those of base line levels. Comparison of the levels of molecular markers reflecting the results of Hippo signal suppression in ovarian tissues and serum before and after culture and grafting operation, respectively. Also, we count the number of secondary follicles in grafting tissues by histological analysis. To evaluate the effect of in situ incision of ovarian cortex for secondary follicle growth, we measure the levels of serum AMH and inhibin B derived from granulosa cells of secondary follicles. Based on these data, we attempt to identify a suitable time point for initiation of ovarian stimulation.
Base
Study type
Interventional
Study design
Basic design
Parallel
Randomization
Non-randomized
Randomization unit
Blinding
Open -no one is blinded
Control
No treatment
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
3
Purpose of intervention
Treatment
Type of intervention
| Maneuver |
Interventions/Control_1
In situ incision of ovarian cortex
1) Correct serum from the patients before surgery to measure molecular markers to ensure suppression of Hippo signaling.
2) We directly cut ovarian cortex or scratch ovarian cortex to induce physical stimulation to the ovary. To measure the number of secondary follicles in the dissected ovarian tissue, 10% of volume of the tissue is fixed and then each developmental stage of follicles are counted under histological analyses.
3) Correct serum from the patients after surgery to measure molecular markers to ensure suppression of Hippo signaling. After grafting, patients receive ovarian stimulation using gonadotropin drugs to stimulate follicle growth and retrieve oocytes. Mature oocytes are fertilized by in vitro fertilization and preimplantation embryos are transplant into uterus. The treatment continues for 1-2 years. If first auto-transplantation is not successful and patients have cryopreserved ovarian tissues, patients can repeat these procedures.
Interventions/Control_2
Auto-transplantation of ovarian cortical fragments + in situ incision of ovarian cortex
1) Correct serum from the patients before surgery to measure molecular markers to ensure suppression of Hippo signaling.
2) Excise one side of whole ovary or partial ovarian tissues under laparoscopic surgery. After removal of medulla tissues to prepare ovarian cortex, the ovarian cortex was dissected into 3x3cm with 1-2mm thickness of tissue stripes and further fragmented into 1-2 mm cubes. To measure the number of secondary follicles in the dissected ovarian tissue, 10% of volume of the tissue is fixed and then each developmental stage of follicles are counted under histological analyses.
3) The ovarian cubes are auto-transplanted beneath of the serosa of both Fallopian tubes, remaining ovaries and/or Douglus' pouch. We also directly cut ovarian cortex of the contra lateral side of ovary inside of the body to induce physical stimulation to the ovary.
4) Correct serum from the patients after surgery to measure molecular markers to ensure suppression of Hippo signaling. After grafting, patients receive ovarian stimulation using gonadotropin drugs to stimulate follicle growth and retrieve oocytes. Mature oocytes are fertilized by in vitro fertilization and preimplantation embryos are transplant into uterus. The treatment continues for 1-2 years. If first auto-transplantation is not successful and patients have cryopreserved ovarian tissues, patients can repeat these procedures.
Interventions/Control_3
To determine the effectiveness of these two different methods for physical stimulation to induce secondary follicle growth, we perform (1) bilateral In situ incision of ovarian cortex, (2) auto-transplantation of ovarian cortical fragments in one side of ovary + in situ incision of ovarian cortex on the contra lateral side of ovary, and (3) auto-transplantation of ovarian cortical fragments in both side of ovaries.
In patients with poor response to gonadotropins, a considerable number of patients show follicle growth from one side of ovary only. Therefore, we enroll the patients who experienced follicle growth at both side of ovaries to the method (2). Because the physical stimulation to one ovary could affect the contra lateral side of ovary via endocrine manner, we perform method (1) and (3) as controls.
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 20 | years-old | <= |
Age-upper limit
| 51 | years-old | > |
Gender
Female
Key inclusion criteria
All following four features must be present:
1) Advanced maternal age (=>40 years) or any other risk factor for POR
2) A previous POR (<=3 oocytes with a conventional stimulation protocol)
3) An abnormal ovarian reserve test (i.e. AFC, 5-7 follicles or AMH, 0.5-1.1 ng/ml).
4) Married women
Key exclusion criteria
1)Patients with severe ovarian dysfunction who can not retrieve oocytes after ovarian stimulation.
2)Patients with high risk for laparoscopy.
3)anovulatory amenorrhea patient
4)Male infertility patients with Y chromosome microdeletion and chromosome abnormalities.
5)Patients who can not obtain written informed consent.
6)Patients judged to be inappropriate for the study by the physicians.
Target sample size
200
Research contact person
Name of lead principal investigator
| 1st name | |
| Middle name | |
| Last name | Atsushi Tanaka |
Organization
Saint Mother Hospital
Division name
Medical office
Zip code
Address
4-9-12 Orio Yahatanishiku Kitakyusyu, Fukuoka, Japan
TEL
093-601-2000
incho@stmother.com
Public contact
Name of contact person
| 1st name | |
| Middle name | |
| Last name | Atsushi Tanaka |
Organization
Saint Mother Hospital
Division name
Medical office
Zip code
Address
4-9-12 Orio Yahatanishiku Kitakyusyu, Fukuoka, Japan
TEL
093-601-2000
Homepage URL
incho@stmother.com
Sponsor or person
Institute
Saint Mother Hospital
Institute
Department
Personal name
Funding Source
Organization
None
Organization
Division
Category of Funding Organization
Self funding
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Address
Tel
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2017 | Year | 07 | Month | 01 | Day |
Related information
URL releasing protocol
Publication of results
Unpublished
Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Open public recruiting
Date of protocol fixation
| 2017 | Year | 04 | Month | 27 | Day |
Date of IRB
Anticipated trial start date
| 2017 | Year | 07 | Month | 01 | Day |
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
Management information
Registered date
| 2017 | Year | 07 | Month | 01 | Day |
Last modified on
| 2017 | Year | 07 | Month | 01 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032031
