Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency

Suzuki, Nao; Yoshioka, Nozomu; Takae, Seido; Sugishita, Yodo; Tamura, Masachika; Hashimoto, Shu; Morimoto, Yoshiharu; Kawamura, Kazuhiro

doi:10.1093/humrep/deu353

Cited by 402 publications

(317 citation statements)

References 27 publications

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“…The issue of fertility preservation in AYA cancer patients has become more important because improved survival after cancer treatment has heightened awareness in regard to long-term quality of life, and the development of cryopreservation techniques for gamete, embryo and gonadal tissues [1,[3][4][5][6][7]. The term ''fertility preservation'' is applied to medical techniques that help cancer survivors preserve their fertility options before undergoing gonadotoxic cancer treatments such as chemotherapy and radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

An evaluation of the Gifu Model in a trial for a new regional oncofertility network in Japan, focusing on its necessity and effects

Furui

Takenaka

Makino

et al. 2015

Reprod Medicine & Biology

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Section: Discussionmentioning

confidence: 99%

An evaluation of the Gifu Model in a trial for a new regional oncofertility network in Japan, focusing on its necessity and effects

Furui

Takenaka

Makino

et al. 2015

Reprod Medicine & Biology

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“…Based on these successes of basic findings, we named this approach as IVA (in vitro activation) and applied it for clinical studies to treat infertility in patients with POI. We reported two deliveries of healthy babies after IVA (Kawamura et al 2012, Suzuki et al 2015 (Fig. 3).…”

Section: Development Of New Therapy For Poi Based On Pi3k-akt Signalingmentioning

confidence: 95%

Disorganization of the germ cell pool leads to primary ovarian insufficiency

Kawashima

Kawamura

2017

Reproduction

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The mammalian ovary is an organ that controls female germ cell development, storing them and releasing mature oocytes for transporting to the oviduct. During the fetal stage, female germ cells change from a proliferative state to meiosis before forming follicles with the potential for the growth of surrounding somatic cells. Understanding of molecular and physiological bases of germ cell development in the fetal ovary contributed not only to the elucidation of genetic disorders in primary ovarian insufficiency (POI), but also to the advancement of novel treatments for patients with POI. Accumulating evidence indicates that mutations in NOBOX, DAZL and FIGLA genes are associated with POI. In addition, cell biology studies revealed the important roles of these genes as essential translational factors for germ cell development. Recent insights into the role of the PI3K (phosphatidylinositol 3-kinase)-AKT signaling pathway in primordial follicle activation allowed the development of a new infertility treatment, IVA (in vitro activation), leading to successful pregnancy/delivery in POI patients. Furthermore, elucidation of genetic dynamics underlying female germ cell development could allow regeneration of oocytes from ES (embryonic stem)/iPS (induced pluripotent stem) cells in mammals. The purpose of this review is to summarize basic findings related to female germ cell development and potential clinical implications, especially focusing on POI etiologies. We also summarize evolving new POI therapies based on IVA as well as oocyte regeneration.Reproduction (2017) 153 R205-R213

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“…Here, we examined the mitigation of freezing stress on the ovarian tissue and the enclosed follicles that are critical for fertility preservation strategies [29][30][31]. Knowing that slow freezing procedures have resulted in most of the reports of live birth in human ovarian tissue cryopreservation followed by grafting [2,32,33], we investigated the cryopreservation method by using a protocol previously published [16].…”

Section: Discussionmentioning

confidence: 99%

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model

Tanpradit

Chatdarong

Comizzoli

2016

J Assist Reprod Genet

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Purpose Temporary and reversible downregulation of metabolism may improve the survival of tissues exposed to nonphysiological conditions during transport, in vitro culture, and cryopreservation. The objectives of the study were to (1) optimize the concentration and duration of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP-a mitochondrial uncoupling agent) exposures for biopsies of domestic cat ovarian tissue and (2) examine the effects of FCCP preexposures on follicle integrity after tissue culture and/or cryopreservation. Methods Biopsies of cat ovarian tissue were first treated with various concentrations of FCCP (0, 10, 40, or 200 nM) for 10 or 120 min to determine the most suitable pre-exposure conditions. Based on these results, tissues were pre-exposed to 200 nM FCCP for 120 min for the subsequent studies on culture and cryopreservation. In all experiments and for each treatment group, tissue activity and integrity were measured by mitochondrial membrane potential (relative optical density of rhodamine 123 fluorescence), follicular viability (calcein assay), follicular morphology (histology), granulosa cell proliferation (Ki-67 immunostaining), and follicular density.Results Ovarian tissues incubated with 200 nM FCCP for 120 min led to the lowest mitochondrial activity (1.17 ± 0.09; P < 0.05) compared to control group (0 nM; 1.30 ± 0.12) while maintaining a constant percentage of viable follicles (75.3 ± 7.8 %) similar to the control group (71.8 ± 11.7 %; P > 0.05). After 2 days of in vitro culture, percentage of viable follicles (78.8 ± 8.9 %) in similar pre-exposure conditions was higher (P < 0.05) than in the absence of FCCP (61.2 ± 12.0 %) with percentages of morphologically normal follicles (57.6 ± 17.3 %) not different from the fresh tissue (70.2 ± 7.1 %; P > 0.05). Interestingly, percentages of cellular proliferation and follicular density were unaltered by the FCCP exposures. Based on the indicators mentioned above, the FCCP-treated tissue fragments did not have a better follicle integrity after freezing and thawing. Conclusions Pre-exposure to 200 nM FCCP during 120 min protects and enhances the follicle integrity in cat ovarian tissue during short-term in vitro culture. However, FCCP does not appear to exert a beneficial or detrimental effect during ovarian tissue cryopreservation.

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Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency

Abstract: UMIN000010828.

Cited by 402 publications

References 27 publications

An evaluation of the Gifu Model in a trial for a new regional oncofertility network in Japan, focusing on its necessity and effects

An evaluation of the Gifu Model in a trial for a new regional oncofertility network in Japan, focusing on its necessity and effects

Disorganization of the germ cell pool leads to primary ovarian insufficiency

Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) pre-exposure ensures follicle integrity during in vitro culture of ovarian tissue but not during cryopreservation in the domestic cat model

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