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UMIN-CTR Clinical Trial |
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Name: | UMIN ID: |
Recruitment status | Open public recruiting |
Unique ID issued by UMIN | UMIN000028031 |
Receipt No. | 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 |
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 |
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Condition | ||
Condition | Infertility patients with poor response to gonadotropins | |
Classification by specialty |
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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 |
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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. |
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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. |
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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. |
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Eligibility | ||||
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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 |
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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. |
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Target sample size | 200 |
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Organization | Saint Mother Hospital | ||||||
Division name | Medical office | ||||||
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Address | 4-9-12 Orio Yahatanishiku Kitakyusyu, Fukuoka, Japan | ||||||
TEL | 093-601-2000 | ||||||
incho@stmother.com |
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Organization | Saint Mother Hospital | ||||||
Division name | Medical office | ||||||
Zip code | |||||||
Address | 4-9-12 Orio Yahatanishiku Kitakyusyu, Fukuoka, Japan | ||||||
TEL | 093-601-2000 | ||||||
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incho@stmother.com |
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Institute | Saint Mother Hospital |
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Organization | None |
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Category of Funding Organization | Self funding |
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Secondary IDs | NO |
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Publication of results | Unpublished |
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Recruitment status | Open public recruiting | ||||||
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Last modified on |
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Link to view the page | |
URL(English) | https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032031 |
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