in Vitro ActivationIVADFPOINCT02322060

In Vitro Activation of Dormant Follicles for Patients With Primary Ovarian Insufficiency

An observational study of in Vitro Activation and Dormant Follicle, run by The First Affiliated Hospital of Zhengzhou University at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 39 years, women only
Conditions the study is for: in Vitro Activation, Dormant Follicle, Primary Ovarian Insufficiency
What is being tested?: Ovariotomy, Activate dormant follicles and Ovary tissue transplantation
Type of treatment: Surgery or procedure
How many people: 35 participants
Where: 1 siteChina
Study dates: Sep 2014to Oct 2021
How long will I take part?: 2 Years
Phase: Observational

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 39 years
Women only
No healthy volunteers
Adult

Study population: Women diagnosed with POI/ORS who also want to get pregnant by IVF/ICSI-ET with their own oocyte.

Who may be able to join

Married women (18-39) diagnosed with POI/ORS
With both ovaries present
With normal uterine cavity
Healthy and can stand surgery

Who cannot join

Any one that does not meet the inclusion criteria

Trial locations and contacts

1 site in 1 country.

China1 site

Reproductive Medical Center, First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052

Other trials in China

About this study

Official title: Ovarian Tissue Cryopreservation and Auto-transplantation for in Vitro Activation of Dormant Follicles for Patients With Primary Ovarian Insufficiency

In this study, the investigators used the newly developed technique i.e. in vitro activation of dormant follicles (IVA) to promote ovarian follicle growth much more efficiently than natural, in vivo process for women with Primary Ovarian Insufficiency (POI).Firstly, the investigators remove one ovary under laparoscopic surgery. Then, we dissect ovarian cortex from the ovarian medulla. The ovarian cortex is cut into small cubes and cultured with medium containing drugs to activate dormant follicles. After 2 days of culture, the ovarian cubes are transplanted mainly beneath the membrane of Fallopian tubes under laparoscopic surgery. The ovarian cortex could be cryopreserve for future re-transplantation and in some cases, for convenience to arrange second surgery. Once frozen, the ovary can be preserved semipermanently. After transplantation, patients receive ultrasound monitoring together with measurement of serum hormone levels for 10-12 months. If growing follicles are detected, follicle growth is stimulated by injection of hormones (gonadotropins). Using the same "ovum pick up" approach used in IVF (in vitro fertilization), we pick up oocytes from the follicles and fertilize them. Fertilized eggs are cultured and then cryopreserved for future embryo transfer.

Currently, we recurit patients diagnosed with POI, or Ovarian resistance syndrome (ORS). The procedure can also be: Only superficial cut of the ovarian cortex by laparoscopy or laparotomy, without taking ovary outside or cultured with medium.

Read the detailed description

I: Former IVA

Remove one ovary (maybe both ovaries depending on the condition) is performed by laparoscopic surgery. (Depending on the condition of patients, the investigators remove both ovaries to increase a chance to obtain residual follicles. Also, in some cases, the investigators need to perform laparotomy, i.e. open surgery, depending on the patient's condition).
Quickly dissect ovarian cortex from the ovarian medulla and cut into small stripes. Histological analyses are performed using small parts of the ovarian stripes to find residual follicles.
Optional: Cryopreserve the ovarian stripes by a vitrification method. Two days before the day of reimplantation, thaw the ovarian stripes.
The ovarian stripes are cut into small cubes (1 x1 mm2). The ovarian cubes are cultured with medium containing drugs to activate dormant follicles for 2 days before transplantation. After washing, the cubes are transplanted beneath the membrane of both Fallopian tubes and the remaining ovary under laparoscopic surgery.
Monitor follicle growth by ultrasound and serum hormone assays. Once follicles reach >16 mm in diameter, patients receive hCG, followed by egg retrieval in ~36 hours. Then the investigators will perform intracytoplasmic sperm injection (ICSI) using the husband's sperm. When embryos reached the four-cell stage, they were cryopreserved, waiting for frozen-thaw embryo transfer.

II Current procedure:

Only superficial cut of the ovarian cortex by laparoscopy or laparotomy, without taking ovary outside or cultured with medium.

Conditions: in Vitro Activation, Dormant Follicle, Primary Ovarian Insufficiency, Ovarian Resistance Syndrome
Being tested: Ovariotomy, Activate dormant follicles, Ovary tissue transplantation, Ovarian superficial cut
Keywords: IVA, ovary tissue grafting, POI, ORS
Medical subject headings: Primary Ovarian Insufficiency, Acidemia, isovaleric, Osteoarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OvariotomyProcedure or surgery
Remove one ovary (maybe both ovaries depending on the condition) by laparoscopic surgery or by laparotomy in some cases.
Activate dormant folliclesProcedure or surgery
Cut ovary into small cubes, which are then cultured with medium containing BPV(pic), a PTEN inhibitor, and 740YP, an activator of phosphoinositol 3 kinase, to activate dormant follicles for 2 days before transplantation.
Ovary tissue transplantationProcedure or surgery
After extensive washing to remove drugs, the ovary cubes are transplanted beneath the membrane of both Fallopian tubes and the remaining ovary under laparoscopic surgery.
Ovarian superficial cutProcedure or surgery
Superficial cut of the ovarian cortex by laparoscopy or laparotomy

Study groups in NCT02322060
Study group	Role	What they receive
Primary ovarian insufficiency		Primary ovarian insufficiency (POI; also known as premature ovarian failure/dysfunction/insufficiency or premature menopause) is characterised by amenorrhoea, sex hormone (oestrogen, progesterone and testosterone) deficiency and elevated gonadotrophins levels in a woman aged more than two standard deviations below the mean age of menopause estimated for her reference population. POI is defined as a disorder in ovarian function in any woman before the age of 40 years, irrespective of the cause. In our study, we mainly recruit POI patients who also desire to have a baby of their own. Receives: Procedure: Ovariotomy; Procedure: Activate dormant follicles; Procedure: Ovary tissue transplantation; Procedure: Ovarian superficial cut
Ovarian resistance syndrome		We currently also include patients diagnosed with Ovarian resistance syndrome, which means that follicles exist, but do not response to FSH. Receives: Procedure: Ovariotomy; Procedure: Activate dormant follicles; Procedure: Ovary tissue transplantation; Procedure: Ovarian superficial cut

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinical pregnancy
Clinical pregnancy was confirmed by detection of one or more gestational sacs during transvaginal scan 4 weeks after embryo transfer.
Measured: 1 year

Secondary outcomes (1)

Follicle growth
Detection of estrogen level elevation and follicle diameter increases reflecting follicle growth.
Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2014Oct 2021

First posted22 Dec 2014 (estimated)
Study startSep 2014
Primary completion1 Oct 2021
Study completionOct 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for in Vitro ActivationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case only
Time perspective: Prospective
Enrolment: 35 participants (actual)
Target duration: 2 Years

IDs, dates and publications

ClinicalTrials.gov ID: NCT02322060
Sponsor's protocol ID: RMCZZU-IVA
Acronym: IVADFPOI
Status last verified: May 2026
First submitted: 17 Dec 2014
Last updated: 27 May 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Donnez J, Martinez-Madrid B, Jadoul P, Van Langendonckt A, Demylle D, Dolmans MM. Ovarian tissue cryopreservation and transplantation: a review. Hum Reprod Update. 2006 Sep-Oct;12(5):519-35. doi: 10.1093/humupd/dml032. Epub 2006 Jul 18.
PubMed 16849817
Li J, Kawamura K, Cheng Y, Liu S, Klein C, Liu S, Duan EK, Hsueh AJ. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10280-4. doi: 10.1073/pnas.1001198107. Epub 2010 May 17.
PubMed 20479243
Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho CH, Kawamura N, Tamura M, Hashimoto S, Sugishita Y, Morimoto Y, Hosoi Y, Yoshioka N, Ishizuka B, Hsueh AJ. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17474-9. doi: 10.1073/pnas.1312830110. Epub 2013 Sep 30.
PubMed 24082083
Zhai J, Yao G, Dong F, Bu Z, Cheng Y, Sato Y, Hu L, Zhang Y, Wang J, Dai S, Li J, Sun J, Hsueh AJ, Kawamura K, Sun Y. In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary Ovarian Insufficiency Patients. J Clin Endocrinol Metab. 2016 Nov;101(11):4405-4412. doi: 10.1210/jc.2016-1589. Epub 2016 Aug 29.
PubMed 27571179