UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000038075
Receipt number R000042387
Scientific Title Future fertility preservation strategies for patients with ovarian endometrioma undergoing laparoscopic cystectomy: Cryopreservation, activation and autografting of ovarian tissues.
Date of disclosure of the study information 2019/10/01
Last modified on 2019/09/21 20:13:31

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Basic information

Public title

Future fertility preservation strategies for patients with ovarian endometrioma undergoing laparoscopic cystectomy: Cryopreservation, activation and autografting of ovarian tissues.

Acronym

Future fertility preservation strategies for patients with ovarian endometrioma undergoing laparoscopic cystectomy.

Scientific Title

Future fertility preservation strategies for patients with ovarian endometrioma undergoing laparoscopic cystectomy: Cryopreservation, activation and autografting of ovarian tissues.

Scientific Title:Acronym

Future fertility preservation strategies for patients with ovarian endometrioma undergoing laparoscopic cystectomy.

Region

Japan


Condition

Condition

Ovarian endometrioma

Classification by specialty

Obstetrics and Gynecology

Classification by malignancy

Others

Genomic information

YES


Objectives

Narrative objectives1

Endometriosis affect 10% of reproductive age women and 50% of infertile women. Ovarian cystectomy is preferred procedure for excision of endometriosis lesion and improvement of endometriosis-associated symptoms, however, a potential risk of post-surgical reduction in the ovarian reserve is concerned.
Recently, a new infertility treatment by ovarian tissue cryopreservation, in vitro activation (IVA) and autografting procedure is reported to improve fertility outcomes in cases of extremely low ovarian reserve women.
In this study, we aimed to apply the procedure of ovarian tissue cryopreservation, IVA and autografting for women with endometrioma undergoing laparoscopic cystectomy and evaluate the effectiveness for improving their future fertility outcome.

Basic objectives2

Efficacy

Basic objectives -Others


Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase III


Assessment

Primary outcomes

Primary outcomes are to compare the postoperative pregnancy rate and birthrate between the cases with or without ovarian tissue cryopreservation when performing laparoscopic cystectomy for ovarian endometrioma.

Key secondary outcomes

1.Basic information: age, medical history, diameter of the ovarian cyst, unilateral/bilateral lesion, preoperative hormone therapy, serum hormone level (E2, P4, FSH, LH, AMH, inhibin B), tumor marker level (C125, CA19-9).
2.Initial surgical findings (Laparoscopic cystectomy, partial resection and cryopreservation of ovarian tissue): operative duration, blood loss, weight of excised cyst, pathological findings, tumor diameter, unilateral/bilateral lesion, revised American Society of Reproductive Medicine (rASRM) score, obtained site of ovarian tissue for cryopreservation (distance from ovarian hilum and endometriosis lesion).
3. Clinical course from initial surgery to second surgery (In vitro activation and laparoscopic autografting of ovarian tissue): age trying to conceive, prophylactic hormone therapy, endometrioma recurrence, serum hormone level (E2, P4, FSH, LH, AMH), protocol used and outcomes of infertility treatment.
4. Second surgical findings: operative duration, blood loss, endometrioma recurrence, rASRM score, number of autografting ovarian tissue pieces, autografting site of ovarian tissue.
Using part of the ovarian tissue, we measure a variety of molecular markers to evaluate the efficacy of Hippo signaling suppression, and we perform ultrasound/ Far infrared ray scanning and histological examination (follicle count, fibrotic evaluation, and inflammatory change) to evaluate the effect of IVA and the presence of residual follicles. We measure the serum angiogenesis factors to evaluate the angiogenic response of autografting ovarian tissue.
5. Clinical course after laparoscopic autografting of ovarian tissue: We measure vesicular ovarian follicle count and serum hormone level (E2, P4, FSH, LH, AMH). We record infertility treatment outcomes including number of oocytes retrieved, percentage of mature oocytes, fertility rate, acquisition rate of good-morphology embryos, cycle cancellation rate, pregnancy rate, birthrate and miscarriage rate.


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Non-randomized

Randomization unit


Blinding

Open -no one is blinded

Control

Active

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

Laparoscopic cystectomy, ovarian tissue cryopreservation, and autografting at the desire for pregnancy.
1. Part of unilateral or bilateral normal ovarian tissue are harvested when performing laparoscopic cystectomy for ovarian endometrioma. The tissue size for harvest is determined depending on their ovarian reserve, the degree of adhesion, and the size of ovarian cyst (one to six pieces of 1cm ovarian cortex are made). The obtained ovarian cortex tissues are cryopreserved. Using 10x1x1mm cube of ovarian cortex tissue, we perform hematoxylin eosin stain and immunohistochemistry to evaluate the presence of residual follicles.
2. Prophylactic hormone therapy by low dose estrogen progestin or dienogest is performed until the time desiring pregnancy. At the time desiring to conceive, infertility treatment including timing therapy, artificial insemination and assisted reproductive technology are performed. In failed cases by conventional treatments, autografting of ovarian tissue is performed. After thawing, ovarian tissue are fragmented into 1-2mm cubes and transplanted to the ovary or beneath serosa of fallopian tubes. In cases of extremely low ovarian reserves, fragmented ovarian tissues are cultured with IVA medium containing a PTEN inhibitor and PI3K activators for 48h to induce not only physical but also chemical stimulation. Using part of the ovarian tissue, we measure a variety of molecular markers to evaluate the efficacy of Hippo signaling suppression and perform ultrasound/ Far infrared ray scanning and histological examination (follicle count, fibrotic evaluation, and inflammatory change) to evaluate the effect of IVA and the presence of residual follicles. We measure the serum angiogenesis factors to evaluate the angiogenic response of autografting ovarian tissue.
3. After grafting, patients reinstitute infertility treatment by IVF-ET. The treatment continues for 1-2 years. If ovarian stimulation is not effective, patients can receive another autografting.

Interventions/Control_2

Laparoscopic cystectomy.
1. Laparoscopic cystectomy for ovarian endometrioma is performed.
2. Prophylactic hormone therapy by low dose estrogen progestin or dienogest is performed until the time desiring pregnancy. At the time desiring to conceive, infertility treatment including timing therapy, artificial insemination and assisted reproductive technology are performed.

Interventions/Control_3


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

50 years-old >=

Gender

Female

Key inclusion criteria

1. Reproductive age women who is 20 years old or older at the acquision of agreement.
2. Ovarian endometrioma larger than 4cm diameter.
3. Women having desire for future pregnancy.
4. Women who give their voluntary informed consent after receiving the enough explanation and understanding about the participation for this study.

Key exclusion criteria

1. Women under 20 years old or over reproductive age.
2. Women who does not have desire for future pregnancy.
3. Women with ovarian cancer.
4. Women who have some risk to undergo laparoscopic surgery by their fundamental disorders.
5. Women who are considered as inadequate for participating this study by lead principal investigator.

Target sample size

200


Research contact person

Name of lead principal investigator

1st name Mari
Middle name
Last name Kitade

Organization

Juntendo University Faculty of Medicine

Division name

Obstetrics and Gynecology

Zip code

113-8431

Address

3-1-3 Hongo, Bunkyo-ku, Tokyo

TEL

03-3813-3111

Email

kitade@juntendo.ac.jp


Public contact

Name of contact person

1st name Keisuke
Middle name
Last name Murakami

Organization

Juntendo University Faculty of Medicine

Division name

Obstetrics and Gynecology

Zip code

113-8431

Address

3-1-3 Hongo, Bunkyo-ku, Tokyo

TEL

03-3813-3111

Homepage URL


Email

kmuraka@juntendo.ac.jp


Sponsor or person

Institute

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine

Institute

Department

Personal name



Funding Source

Organization

Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine

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

Hospital Ethics Committee Office, Juntendo University Faculty of Medicine

Address

3-1-3 Hongo, Bunkyo-ku, Tokyo

Tel

03-5802-1584

Email

kenkyu5858@juntendo.ac.jp


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

順天堂大学医学部附属順天堂医院(東京都)


Other administrative information

Date of disclosure of the study information

2019 Year 10 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

Preinitiation

Date of protocol fixation

2019 Year 09 Month 21 Day

Date of IRB


Anticipated trial start date

2019 Year 10 Month 01 Day

Last follow-up date

2034 Year 03 Month 31 Day

Date of closure to data entry


Date trial data considered complete


Date analysis concluded



Other

Other related information



Management information

Registered date

2019 Year 09 Month 21 Day

Last modified on

2019 Year 09 Month 21 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042387


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name