Advertisement

Ovarian tissue transportation: a systematic review

Published:November 09, 2020DOI:https://doi.org/10.1016/j.rbmo.2020.11.001

      Abstract

      In recent years, some countries and fertility preservation networks have started adopting 24 h transportation for ovarian tissue, a practice that has the potential to spread very quickly due to the high costs and bureaucracy involved in the establishment of ovarian tissue cryobanks. While pregnancies and live births have been reported after such long periods of transportation, this, however, remains an empirical procedure. This review aims to prompt reflection on ovarian tissue transport, highlighting the lack of knowledge in humans by providing a counterpoint looking into more than 40 studies published in different animal models. By discussing these studies in animals, the findings of various models can be deciphered, and light shed on the patterns identified. Like the development of different assisted reproductive technology procedures, this is an important step in creating guidelines for future studies on human ovarian tissue transportation.

      Keywords

      Introduction

      Assisted reproductive technology (ART) is vital for the preservation of animal and human gametes. In animals, techniques have been developed for the selection of species/breeds of economic interest and also the conservation of endangered species (
      • Comizzoli P.
      • Crosier A.E.
      • Songsasen N.
      • Gunther M.S.
      • Howard J.G.
      • Wildt D.E.
      Advances in reproductive science for wild carnivore conservation.
      ;
      • Barberino R.S.
      • Silva J.R.V.
      • Figueiredo J.R.
      • Matos M.H.T.
      Transport of domestic and wild animal ovaries: A review of the effects of medium, temperature, and periods of storage on follicular viability.
      ). In humans, ART has several applications, including fertility preservation in cancer patients (
      • Donnez J.
      • Dolmans M.-M.
      Fertility preservation in women.
      ).
      One of the most recent ART strategies, ovarian tissue cryopreservation and transplantation, is now considered an established procedure in a growing number of countries, yielding more than 130 live births to date (
      • Donnez J.
      • Dolmans M.-M.
      Fertility preservation in women.
      ;
      • Liebenthron J.
      • Montag M.
      • Reinsberg J.
      • Köster M.
      • Isachenko V.
      • Van Der Ven K.
      • Van Der Ven H.
      • Krüssel J.-S.
      • Von Wolff M.
      Overnight ovarian tissue transportation for centralized cryobanking: A feasible option.
      ). While this procedure is being increasingly applied all over the world (
      • Von Wolff M.
      • Dittrich R.
      • Liebenthron J.
      • Nawroth F.
      • Schüring A.N.
      • Bruckner T.
      • Germeyer A.
      Fertility-preservation counselling and treatment for medical reasons: Data from a multinational network of over 5000 women.
      ;
      • Beckmann M.W.
      • Lotz L.
      • Toth B.
      • Baston-Büst D.M.
      • Fehm T.
      • Frambach T.
      • Germeyer A.
      • Goeckenjan M.
      • Häberlin F.
      • Henes M.
      • Hirchenhain J.
      • Hübner S.
      • Korell M.
      • Krüssel J.-S.
      • Müller A.
      • Reinsberg J.
      • Schwab R.
      • Seitz S.
      • Sütterlin M.
      • Van Der Ven H.
      • Van Der Ven K.
      • Winkler-Crepaz K.
      • Wimberger P.
      • Von Wolff M.
      • Liebenthron J.
      • Dittrich R.
      Concept paper on the technique of cryopreservation, removal and transplantation of ovarian tissue for fertility preservation.
      ), it is important to stress that there are still many challenges. Tissue cryopreservation requires specialized equipment, trained staff as well as designated time and space to prepare and freeze the ovarian cortex. Due to strict European rules, specific protocols and high costs, only large hospitals can maintain an ovarian tissue cryobank. One way of increasing access to this strategy is improving ovarian tissue transportation and creating a network for fertility preservation, which would allow small clinics and less developed countries to extend the availability of ovarian tissue cryopreservation and transplantation (
      • Duncan F.E.
      • Zelinski M.
      • Gunn A.H.
      • Pahnke J.E.
      • O'neill C.L.
      • Songsasen N.
      • Woodruff R.I.
      • Woodruff T.K.
      Ovarian tissue transport to expand access to fertility preservation: From animals to clinical practice.
      ;
      • Kyono K.
      • Hashimoto T.
      • Toya M.
      • Koizumi M.
      • Sasaki C.
      • Shibasaki S.
      • Aono N.
      • Nakamura Y.
      • Obata R.
      • Okuyama N.
      • Ogura Y.
      • Igarashi H.
      A transportation network for human ovarian tissue is indispensable to success for fertility preservation.
      ;
      • Liebenthron J.
      • Montag M.
      • Reinsberg J.
      • Köster M.
      • Isachenko V.
      • Van Der Ven K.
      • Van Der Ven H.
      • Krüssel J.-S.
      • Von Wolff M.
      Overnight ovarian tissue transportation for centralized cryobanking: A feasible option.
      ). Currently, there are two such networks operating successfully: the Danish network and FertiPROTEKT (
      • Von Wolff M.
      • Andersen C.Y.
      • Woodruff T.K.
      • Nawroth F.
      Fertiprotekt, oncofertility consortium and the danish fertility-preservation networks - what can we learn from their experiences? Clinical medicine insights.
      ).
      While kidney, heart and liver transportation protocols are well established and widely implemented (
      • Guibert E.E.
      • Petrenko A.Y.
      • Balaban C.L.
      • Somov A.Y.
      • Rodriguez J.V.
      • Fuller B.J.
      Organ preservation: Current concepts and new strategies for the next decade.
      ;
      • Ricci Z.J.
      • Oh S.K.
      • Stein M.W.
      • Kaul B.
      • Flusberg M.
      • Chernyak V.
      • Rozenblit A.M.
      • Mazzariol F.S.
      Solid organ abdominal ischemia, part i: Clinical features, etiology, imaging findings, and management.
      ), with adapted medium composition, temperature and time for transport, the same cannot be said for ovarian tissue. Indeed, there are still no standard procedures for ovarian tissue transportation (
      • Duncan F.E.
      • Zelinski M.
      • Gunn A.H.
      • Pahnke J.E.
      • O'neill C.L.
      • Songsasen N.
      • Woodruff R.I.
      • Woodruff T.K.
      Ovarian tissue transport to expand access to fertility preservation: From animals to clinical practice.
      ;
      • Beckmann M.W.
      • Lotz L.
      • Toth B.
      • Baston-Büst D.M.
      • Fehm T.
      • Frambach T.
      • Germeyer A.
      • Goeckenjan M.
      • Häberlin F.
      • Henes M.
      • Hirchenhain J.
      • Hübner S.
      • Korell M.
      • Krüssel J.-S.
      • Müller A.
      • Reinsberg J.
      • Schwab R.
      • Seitz S.
      • Sütterlin M.
      • Van Der Ven H.
      • Van Der Ven K.
      • Winkler-Crepaz K.
      • Wimberger P.
      • Von Wolff M.
      • Liebenthron J.
      • Dittrich R.
      Concept paper on the technique of cryopreservation, removal and transplantation of ovarian tissue for fertility preservation.
      ;
      • Liebenthron J.
      • Montag M.
      • Reinsberg J.
      • Köster M.
      • Isachenko V.
      • Van Der Ven K.
      • Van Der Ven H.
      • Krüssel J.-S.
      • Von Wolff M.
      Overnight ovarian tissue transportation for centralized cryobanking: A feasible option.
      ), even though its impact can be considerable.
      The effects of ischaemia, for example, have mainly been studied after tissue transplantation (
      • Van Eyck A.-S.
      • Jordan B.F.
      • Gallez B.
      • Heilier J.-F.
      • Van Langendonckt A.
      • Donnez J.
      Electron paramagnetic resonance as a tool to evaluate human ovarian tissue reoxygenation after xenografting.
      ;
      • Van Eyck A.-S.
      • Bouzin C.
      • Feron O.
      • Romeu L.
      • Van Langendonckt A.
      • Donnez J.
      • Dolmans M.-M.
      Both host and graft vessels contribute to revascularization of xenografted human ovarian tissue in a murine model.
      ;
      • Van Langendonckt A.
      • Romeu L.
      • Ambroise J.
      • Amorim C.
      • Bearzatto B.
      • Gala J.L.
      • Donnez J.
      • Dolmans M.M.
      Gene expression in human ovarian tissue after xenografting.
      ;
      • Cacciottola L.
      • Manavella D.D.
      • Amorim C.A.
      • Donnez J.
      • Dolmans M.-M.
      In vivo characterization of metabolic activity and oxidative stress in grafted human ovarian tissue using microdialysis.
      ), when the blood supply is re-established, but it does not only occur after grafting. In fact, ischaemia begins when ovarian tissue is taken from the patient and continues until its cryopreservation and/or transplantation (
      • Jing L.
      • Yao L.
      • Zhao M.
      • Peng L.-P.
      • Liu M.
      Organ preservation: From the past to the future.
      ). Since the ovary is a complex organ, with a diversity of cells and structures of great importance for ensuring follicle survival and development, its transportation is not straightforward. Media used for human ovarian tissue transportation at present, such as alpha-minimum essential medium (α-MEM) (
      • Rosendahl M.
      • Schmidt K.T.
      • Ernst E.
      • Rasmussen P.E.
      • Loft A.
      • Byskov A.G.
      • Andersen A.N.
      • Andersen C.Y.
      Cryopreservation of ovarian tissue for a decade in denmark: A view of the technique.
      ), IVF medium (
      • Schmidt K.L.T.
      • Ernst E.
      • Byskov A.G.
      • Nyboe Andersen A.
      • Yding Andersen C.
      Survival of primordial follicles following prolonged transportation of ovarian tissue prior to cryopreservation.
      ), Leibovitz-15 (L-15) (
      • Isachenko V.
      • Dittrich R.
      • Keck G.
      • Isachenko E.
      • Rahimi G.
      • Van Der Ven H.
      • Montag M.
      • Hoffmann I.
      • Müller A.
      • Distler W.
      • Beckmann M.W.
      • Mallmann P.
      Cryopreservation of ovarian tissue: Detailed description of methods for transport, freezing and thawing.
      ), HEPES-MEM (
      • Van Langendonckt A.
      • Romeu L.
      • Ambroise J.
      • Amorim C.
      • Bearzatto B.
      • Gala J.L.
      • Donnez J.
      • Dolmans M.M.
      Gene expression in human ovarian tissue after xenografting.
      ) or Custodiol (Essential Pharmaceuticals, USA) (
      • Liebenthron J.
      • Montag M.
      • Reinsberg J.
      • Köster M.
      • Isachenko V.
      • Van Der Ven K.
      • Van Der Ven H.
      • Krüssel J.-S.
      • Von Wolff M.
      Overnight ovarian tissue transportation for centralized cryobanking: A feasible option.
      ), were actually developed for different purposes. After understanding the current status of ovarian tissue transport in humans (
      • Duncan F.E.
      • Zelinski M.
      • Gunn A.H.
      • Pahnke J.E.
      • O'neill C.L.
      • Songsasen N.
      • Woodruff R.I.
      • Woodruff T.K.
      Ovarian tissue transport to expand access to fertility preservation: From animals to clinical practice.
      ) and animals (
      • Barberino R.S.
      • Silva J.R.V.
      • Figueiredo J.R.
      • Matos M.H.T.
      Transport of domestic and wild animal ovaries: A review of the effects of medium, temperature, and periods of storage on follicular viability.
      ), the aim here is to systematically review studies on ovarian tissue transportation in both animals and humans. Species, media, timepoints, temperatures, analyses and optimal transport conditions were addressed for each study to better understand practices that are well established, as well as possible gaps in knowledge and future strategies that can be implemented to prepare guidelines for ovarian tissue transport.

      Materials and methods

      This review was carried out according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) (
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      Preferred reporting items for systematic reviews and meta-analyses: The prisma statement.
      ), and registered on PROSPERO on 6 January 2020 (CRD42020155900).

      Search strategy

      A PubMed search was conducted of the literature in English, from 1990 to 2020, focusing on transportation of human and animal ovarian tissue, using the following keywords: ‘ovary and transportation’, ‘ovarian tissue and transportation’, ‘ovary and transport’, ‘ovarian tissue and transport’, ‘ovary and storage’ and ‘ovarian tissue and storage’. Results were downloaded to EndNote software (Thomson Reuters, Canada), references were merged and duplicates were removed. Any risk of bias was avoided.

      Screening and eligibility

      Screening was carried out for article titles and abstracts containing the keywords by J.M.V.V. and C.A.A. Only full-text English reports that specifically compared different conditions for ovarian tissue transportation were included. Scientific articles reporting successful outcomes of cryopreservation were excluded, unless the main goal of the research was to analyse tissue transport.
      A data-charting table was developed by the authors to extract the main variables. This table was continually updated while writing this review. Disagreements were resolved through discussion and consensus. Charting was implemented using Airtable (USA), a customizable online platform.

      Data items

      Data were extracted on article characteristics (such as authors, year, country and institution), tested temperatures, timepoints and media, and analyses and best conditions were scrutinized for each study. Data were cross-checked by the authors.

      Results

      A total of 324 records were found through database searches and a further 28 were identified from studies’ references. Of those, 293 were excluded and 58 were screened, based on the title and abstract that matched the study's criteria. From those, 52 full-text articles were considered as potentially eligible, of which 46 were included in the qualitative synthesis (Figure 1). Selected studies dated from 1992 to 2020 (Supplementary Figure 1). The studies were grouped by country, research group and species, outlined tested media, temperatures and timepoints, and considered applied analyses, as well as the main findings and best conditions in each study.
      Figure 1
      Figure 1PRISMA flow diagram for ovarian transportation studies.

      Description of studies

      Results from the 46 studies selected for systematic review are summarized in Table 1 (humans) and Table 2 (animals). They involved 13 countries, namely Italy (n = 2), Brazil (n = 15), Germany (n = 4), Iran (n = 1), the USA (n = 7), Japan (n = 7), Belgium (n = 2), China (n = 1), Turkey (n = 3), South Korea (n = 1), the UK (n = 1), Spain (n = 1) and Argentina (n = 1), and 28 different research groups, the majority being from Brazil (six groups) and Japan (six groups) (Supplementary Table 1).
      Table 1Studies on ovarian tissue transportation in humans
      Authors, yearCountrySample sizeTissue sizeTested mediumAdditives in mediaTemperatures testedTimepointsAnalyses inBest conditions
      Best conditions within the parameters observed in each study. Not applicable = the conclusion of this study was that transport duration should be limited to a minimum to avoid damage.
      • Klocke S.
      • Tappehorn C.
      • Griesinger G.
      Effects of supra-zero storage on human ovarian cortex prior to vitrification–warming.
      Germany12Ovarian fragmentsCelsior4°C24 h, 48 hOvarian tissue, mediumNot applicable
      • Kyoya T.
      • Nakamura Y.
      • Miyatani S.
      • Miyagawa T.
      • Tomiyama T.
      • Kyono K.
      Evaluation of oxygen consumption in human vitrified and warmed pre-antral follicles after prolonged low temperatures.
      Japan6Whole ovaryL-15Antibiotics, ascorbic acid, sodium pyruvate, glutamine4°C6 h, 18 hOvarian tissue, follicles18 h
      • Isachenko E.
      • Isachenko V.
      • Nawroth F.
      • Rahimi G.
      • Weiss J.M.
      Effect of long-term exposure at suprazero temperatures on activity and viability of human ovarian cortex.
      Germany5Ovarian fragmentsBrama I4°C, 10°C8 h, 15 h, 26 h, 36 hOvarian tissue4°C, 26 h
      • Isachenko V.
      • Isachenko E.
      • Mallmann P.
      • Rahimi G.
      Increasing follicular and stromal cell proliferation in cryopreserved human ovarian tissue after long-term precooling prior to freezing: In vitro versus chorioallantoic membrane (cam) xenotransplantation.
      Germany6Ovarian fragmentsL-15Dextran serum substitute5°C24 hOvarian tissue24 h
      a Best conditions within the parameters observed in each study. Not applicable = the conclusion of this study was that transport duration should be limited to a minimum to avoid damage.
      Table 2Studies on ovarian tissue transportation in animals
      Authors, yearSpeciesCountrySample sizeTissue sizeTested mediumAdditives in mediaTemperatures testedTimepointsAnalyses inBest conditions
      Best conditions within the parameters observed in each study. Not applicable = the study aimed to verify metabolic activity in different media. The authors did not report best conditions ACP, powdered coconut water; BSA, bovine serum albumin; DPBS, Dulbecco's PBS; EGCG, epigallocatechin gallate; GSH, glutathione; ITS, insulin–transferrin–selenium; MEM, minimum essential medium; m-PBS, modified PBS; PBS, phosphate-buffered saline; SOD, superoxide dismutase; UW, University of Wisconsin
      • Wang Y.S.
      • Zhao X.
      • Su J.M.
      • An Z.X.
      • Xiong X.R.
      • Wang L.J.
      • Liu J.
      • Quan F.S.
      • Hua S.
      • Zhang Y.
      Lowering storage temperature during ovary transport is beneficial to the developmental competence of bovine oocytes used for somatic cell nuclear transfer.
      CowChina10Whole ovaryPBS15°C, 25°C, 35°C4 hOocytes, embryos15°C, 4 h
      • Nagao Y.
      • Harada Y.
      • Yamaguchi M.
      • Igarashi A.
      • Ooshima Y.
      • Kato Y.
      Antioxidant treatment during preservation of bovine ovaries increased the development potential of embryos.
      CowJapanNot informedWhole ovarySaline solution, DPBS, UW solutionAntibiotics, GSH, EGCG5°C, 15°C, 25°C, 35°C24 hOocytes15°C, 24 h, Use of additives
      • Lucci C.M.
      • Kacinskis M.A.
      • Rumpf R.
      • Báo S.N.
      Effects of lowered temperatures and media on short-term preservation of zebu (bos indicus) preantral ovarian follicles.
      CowBrazil4Ovarian fragmentsSaline solution, coconut water4°C, 20°C6 h, 12 h, 18 hOvarian tissue4°C, 18 h
      • Matsushita S.
      • Tani T.
      • Kato Y.
      • Tsunoda Y.
      Effect of low-temperature bovine ovary storage on the maturation rate and developmental potential of follicular oocytes after in vitro fertilization, parthenogenetic activation, or somatic cell nucleus transfer.
      CowJapanNot informedWhole ovarySaline solutionAntibiotics0°C, 10°C, 20°C24 h, 48 h, 72 hOocytes10°C, 24 h
      • Nakao H.
      • Nakatsuji N.
      Effects of storage conditions of bovine ovaries and oocytes on the success rate of in vitro fertilization and culture.
      CowJapanNot informedWhole ovaryRinger's solution, TCM-1994°C, 20°C, 39°C5 hOocytes20°C
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      CowBelgium15Ovarian fragmentsPBS, Saline solution, L-15, IVF mediumAntibiotics4°C1 h, 4 h, 24 hMedium, ovarian cells, ovarian tissueNot applicable
      • Martins J.L.A.
      • Lopes M.D.
      • De Souza F.F.
      • Possebon F.S.
      • Wibbelt G.
      • Jewgenow K.
      Cat preantral follicle survival after prolonged cooled storage followed by vitrification.
      CatBrazil12Whole ovaryDPBS4°C6 h, 24 h, 72 hOvarian tissue24 h
      • Piras A.R.
      • Burrai G.P.
      • Ariu F.
      • Falchi L.
      • Zedda M.T.
      • Pau S.
      • Gadau S.D.
      • Antuofermo E.
      • Bebbere D.
      • Ledda S.
      • Bogliolo L.
      Structure of preantral follicles, oxidative status and developmental competence of in vitro matured oocytes after ovary storage at 4 degrees c in the domestic cat model.
      CatItaly55Whole ovaryPBSCalcium dichloride hydrate, antibiotics4°C24 h, 48 h, 72 h, 96 hOocytes24 h
      • Cocchia N.
      • Corteggio A.
      • Altamura G.
      • Tafuri S.
      • Rea S.
      • Rosapane I.
      • Sica A.
      • Landolfi F.
      • Ciani F.
      The effects of superoxide dismutase addition to the transport medium on cumulus–oocyte complex apoptosis and ivf outcome in cats (felis catus).
      CatItaly76Whole ovaryPBSSOD4°C3 h, 24 h, 48 h, 72 hOocytes, RNA24 h, Use of additives
      • Evecen M.
      • Cirit Ü.
      • Demir K.
      • Karaman E.
      • Hamzaoğlu A.İ.
      • Bakırer G.
      Developmental competence of domestic cat oocytes from ovaries stored at various durations at 4°c temperature.
      CatTurkey25Whole ovarySaline solution4°C4 h, 24 h, 48 hOocytes24 h
      • Naoi H.
      • Otoi T.
      • Shimamura T.
      • Karja N.W.K.
      • Agung B.
      • Shimizu R.
      • Taniguchi M.
      • Nagai T.
      Developmental competence of cat oocytes from ovaries stored at various temperature for 24 h.
      CatJapanNot informedWhole ovarym-PBSAntibiotics4°C, 38°C, 25°C24 hOocytes, embryos4°C, 6 h
      • Wood T.C.
      • Montali R.J.
      • Wildt D.E.
      Follicle-oocyte atresia and temporal taphonomy in cold-stored domestic cat ovaries.
      CatUSA50Whole ovaryDPBSAntibiotics4°C4 h, 8 h, 12 h, 24 h, 48 hOvarian tissue48 h
      • Jewgenow K.
      • Wood T.C.
      • Wildt D.E.
      DNA degradation in mural granulosa cells of non- and slightly atretic follicles of fresh and cold-stored domestic cat ovaries.
      CatUSA12Whole ovaryDPBS4°C8 h, 12 h, 24 h, 48 hOvarian tissue12 h
      • Correia H.H.V.
      • Vieira L.A.
      • Maside C.
      • Paes V.M.
      • Silva R.F.
      • Alves B.G.
      • Santos F.W.
      • Apgar G.A.
      • Rodrigues A.P.R.
      • Figueiredo J.R.
      Ovarian transport temperature (4 vs 33°c) impacts differently the in vitro development of isolated goat preantral and antral follicles.
      GoatBrazil30Whole ovaryMEMHEPES4°C, 33°C4 hMedium, follicles, oocytes4°C
      • Gouveia B.
      • Barros V.R.P.
      • Gonçalves R.J.S.
      • Barberino R.S.
      • Menezes V.G.
      • Lins T.L.B.
      • Macedo T.J.S.
      • Santos J.M.S.
      • Rolim L.
      • Neto P.J.
      • Almeida J.R.G.S.
      • Matos M.H.T.
      Effect of ovarian tissue transportation in amburana cearensis extract on the morphology and apoptosis of goat preantral follicles.
      GoatBrazil10Ovarian fragmentsMEMAntibiotics, Amburana cearencis extract4°C6 h, 12 h, 24 hOvarian tissue4°C, 6 h, Use of additives
      • Chaves R.N.
      • Martins F.S.
      • Saraiva M.V.
      • Celestino J.J.
      • Lopes C.A.
      • Correia J.C.
      • Verde I.B.
      • Matos M.H.
      • Bao S.N.
      • Name K.P.
      • Campello C.C.
      • Silva J.R.
      • Figueiredo J.R.
      Chilling ovarian fragments during transportation improves viability and growth of goat preantral follicles cultured in vitro.
      GoatBrazil5Ovarian fragmentsMEMAntibiotics4°C, 20°C, 35°C2 h, 4 hOvarian tissue4°C, 4 h

      Santos, R.R.D., Silva, J.R.V., Costa, S.H.F., Rodrigues, A.P.R., Lôbo, R.N.B., Figueiredo, J.R.D., 2002. Effect of 0.9% saline solution and phosphate buffer saline at different temperatures and incubation times on the morphology of goat preantral follicles %j brazilian journal of veterinary research and animal science. 39, 254-259.

      GoatBrazil5Ovarian fragmentsSaline solution, PBS4°C, 20°C, 39°C4 h, 12 h, 24 hOvarian tissue4°C, saline solution, 12 h, PBS, 24 h
      • Carvalho F.C.A.
      • Lucci C.M.
      • Silva J.R.V.
      • Andrade E.R.
      • Báo S.N.
      • Figueiredo J.R.
      Effect of braun-collins and saline solutions at different temperatures and incubation times on the quality of goat preantral follicles preserved in situ.
      GoatBrazil5Ovarian fragmentsBraun-Collins solution, saline solution4°C, 20°C, 39°C4 h, 12 h, 24 hOvarian tissue4°C, 12 h
      • Silva J.R.
      • Lucci C.M.
      • Carvalho F.C.
      • Bao S.N.
      • Costa S.H.
      • Santos R.R.
      • Figueiredo J.R.
      Effect of coconut water and braun-collins solutions at different temperatures and incubation times on the morphology of goat preantral follicles preserved in vitro.
      GoatBrazil5Ovarian fragmentsBraun-Collins solution, coconut water-based medium4°C, 20°C, 39°C4 h, 12 h, 24 hOvarian tissue4°C, coconut water, 24 h
      • Goodarzi A.
      • Zare Shahneh A.
      • Kohram H.
      • Sadeghi M.
      • Moazenizadeh M.H.
      • Fouladi-Nashta A.
      • Dadashpour Davachi N.
      Effect of melatonin supplementation in the long-term preservation of the sheep ovaries at different temperatures and subsequent in vitro embryo production.
      SheepIranNot informedWhole ovaryPBSMelatonin4°C, 20°C24 hOocytes4°C, 24 h, Use of additives
      • Cavalcante A.
      • Barberino R.
      • Gouveia B.
      • Bezerra M.
      • Menezes V.G.
      • Rocha Souza G.
      • Rolim L.
      • Rolim-Neto P.
      • Almeida J.R.
      • Matos M.
      Effect of ovarian tissue storage in morus nigra extract on the morphology and DNA fragmentation of ovine preantral follicles.
      SheepBrazil8Ovarian fragmentsMEMAntibiotics, Morus nigra extract4°C6 h, 12 h, 24 hOvarian tissue6 h, Use of additives
      • Barberino R.
      • Gonçalves R.
      • Menezes V.G.
      • Barros V.
      • Lins T.
      • Gouveia B.
      • Macedo T.
      • Santos L.
      • Matos M.
      Influence of the ovarian fragmentation before storage at 4°c on the apoptosis rates and in vitro development of ovine preantral follicles.
      SheepBrazil15Ovarian fragmentsMEMHEPES, antibiotics4°C6 h, 12 h, 24 hOvarian tissue24 h
      • Henry L.
      • Fransolet M.
      • Labied S.
      • Blacher S.
      • Masereel M.-C.
      • Foidart J.-M.
      • Noel A.
      • Nisolle M.
      • Munaut C.
      Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival.
      SheepBelgium4Half ovaryL-15Z-VAD-FMK, S1P4°CNot informedOvarian tissueUse of antiapoptotic drugs
      • García-Álvarez O.
      • Maroto-Morales A.
      • Berlinguer F.
      • Fernandez-Santos M.R.
      • Esteso M.C.
      • Mermillod P.
      • Ortiz J.A.
      • Ramon M.
      • Perez-Guzman M.D.
      • Garde J.J.
      • Soler A.J.
      Effect of storage temperature during transport of ovaries on in vitro embryo production in iberian red deer (cervus elaphus hispanicus).
      SheepBrazil5Ovarian fragmentsMEM, MEM+Antibiotics, ITS, glutamine, hypoxanthine, BSA, FSH35°C6 h, 12 hOvarian tissueMEM+, 6 h
      • Evecen M.
      • Cirit U.
      • Demir K.
      • Ozdas O.B.
      • Tas M.
      • Birler S.
      • Pabuccuoglu S.
      Effects of estrous cycle stage and transport temperature of ovaries on in vitro maturation of canine oocytes.
      DogTurkey39Whole OvaryPBS4°C, 37°C4 hOocytes4°C
      • Lima G.L.
      • Costa L.L.
      • Cavalcanti D.M.
      • Rodrigues C.M.
      • Freire F.A.
      • Fontenele-Neto J.D.
      • Silva A.R.
      Short-term storage of canine preantral ovarian follicles using a powdered coconut water (acp)-based medium.
      DogBrazil9Ovarian fragmentsPBS, coconut water-based medium10°C12 h, 24 h, 36 hOvarian tissueACP medium, 24 h
      • Lopes C.A.
      • Dos Santos R.R.
      • Celestino J.J.
      • Melo M.A.
      • Chaves R.N.
      • Campello C.C.
      • Silva J.R.
      • Bao S.N.
      • Jewgenow K.
      • De Figueiredo J.R.
      Short-term preservation of canine preantral follicles: Effects of temperature, medium and time.
      DogBrazil15Ovarian fragmentsSaline solution, MEM4°C, 20°C, 38°C2 h, 6 h, 12 h, 24 hFollicles, ovarian tissue4°C, MEM+, 12 h
      • Hanna C.
      • Long C.
      • Hinrichs K.
      • Westhusin M.
      • Kraemer D.
      Assessment of canine oocyte viability after transportation and storage under different conditions.
      DogUSANot informedWhole ovaryPBS, TCM-199, TL-HEPESHanks salts, HEPES20°C, 37°CNot informedOocytes37°C, TL-HEPES
      • Lee H.S.
      • Yin X.J.
      • Kong I.K.
      Sensitivity of canine oocytes to low temperature.
      DogSouth Korea30Whole ovarySaline solutionAntibiotics4°C, 38°C5 hOocytes38°C
      • Tas M.
      • Evecen M.
      • Ozdas O.B.
      • Cirit U.
      • Demir K.
      • Birler S.
      • Pabuccuoglu S.
      Effect of transport and storage temperature of ovaries on in vitro maturation of bitch oocytes.
      DogTurkey23Whole ovarySaline solution4°C, 38°C4 hOocytes4°C
      • Gastal G.D.
      • Alves B.G.
      • Alves K.A.
      • Souza M.E.
      • Vieira A.D.
      • Varela Jr., A.S.
      • Figueiredo J.R.
      • Feugang J.M.
      • Lucia Jr., T.
      • Gastal E.L.
      Ovarian fragment sizes affect viability and morphology of preantral follicles during storage at 4 degrees c.
      HorseUSA18Whole ovary, ovarian fragmentsa-MEMAntibiotics, BSA4°C6 h, 12 h, 24 hOvarian tissue24 h, ovarian fragments
      • Gomes R.G.
      • Andrade E.R.
      • Lisboa L.A.
      • Ciquini A.
      • Barreiros T.R.
      • Fonseca N.A.
      • Seneda M.M.
      Effect of holding medium, temperature and time on structural integrity of equine ovarian follicles during the non-breeding season.
      HorseBrazil10Ovarian fragmentsPBS, MEM4°C, 20°C, 39°C4 h, 12 h, 24 hOvarian tissuePBS, 4°C, 4 h
      • Ribeiro B.I.
      • Love L.B.
      • Choi Y.H.
      • Hinrichs K.
      Transport of equine ovaries for assisted reproduction.
      HorseUSA2Whole ovaryNo medium24°C, 35°C10 h, 20 hOocytes, embryos7 h
      • Pedersen H.G.
      • Watson E.D.
      • Telfer E.E.
      Effect of ovary holding temperature and time on equine granulosa cell apoptosis, oocyte chromatin configuration and cumulus morphology.
      HorseUKNot informedWhole ovaryM-199Hanks salts, HEPES20°C, 30°C, 37°C12 hOocytes, DNA6 h, 37°C
      • Love L.B.
      • Choi Y.H.
      • Love C.C.
      • Varner D.D.
      • Hinrichs K.
      Effect of ovary storage and oocyte transport method on maturation rate of horse oocytes.
      HorseUSANot informedWhole ovaryM-199HEPES, Hanks salts4°C, 25°C9 h, 18 hOocytesNot applicable
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      PigArgentina15?Whole ovarySaline solutionAntibiotics15°C, 25°C, 35°C2 h, 4 h, 6 hOocytes12 h, 25°C
      • Lucci C.M.
      • Schreier L.L.
      • Machado G.M.
      • Amorim C.A.
      • Bao S.N.
      • Dobrinsky J.R.
      Effects of storing pig ovaries at 4 or 20 degrees c for different periods of time on the morphology and viability of pre-antral follicles.
      PigUSA3Whole ovarySaline solution4°C, 20°C6 h, 12 h, 18 hFollicles4°C, 18 h
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      PigJapanNot informedWhole ovarySaline solution35°C, 4°C, 15°C, 25°C3 h, 6 h, 9 h, 12 hOocytes, embryos25°C, 6 h
      • Raffel N.
      • Dittrich R.
      • Orlowski P.
      • Tischer H.
      • Söder S.
      • Erber R.
      • Hoffmann I.
      • Beckmann M.W.
      • Lotz L.
      Is ovarian tissue transport at supra-zero temperatures compared to body temperature optimal for follicle survival?.
      PigGermany10Ovarian fragmentsPBS4°C, 38°C4 h, 12 h, 24 hOvarian tissue, follicles4°C

      Lima, G.L., Santos, E.a.A., Lima, L.F., Luz, V.B., Rodrigues, A.P.R., Silva, A.R., 2014. Short-term preservation of pecari tajacu ovarian preantral follicles using phosphate buffered saline (pbs) or powdered coconut water (acp(r)) media %j arquivo brasileiro de medicina veterinária e zootecnia. 66, 1623-1630.

      Pecari tajacuBrazil8Ovarian fragmentsPBS, coconut water-based mediumAntibiotics0°C4 h, 12 h, 24 h, 36 hOvarian tissue, mediumACP medium, 24 h
      • Kamoshita K.
      • Okamoto N.
      • Nakajima M.
      • Haino T.
      • Sugimoto K.
      • Okamoto A.
      • Sugishita Y.
      • Suzuki N.
      Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.
      MouseJapanNot informedWhole ovaryDulbecco's modified Eagle's medium4°C, 14°C, 37°C, 25°C4 h, 8 h, 24 hOvarian tissue, offspringPBS, 4°C, 4 h
      • Gonçalves R.J.
      • Cavalcante A.Y.
      • Gouveia B.B.
      • Lins T.L.
      • Barberino R.S.
      • Menezes V.G.
      • Barros V.R.
      • Macedo T.J.
      • Figueiredo J.R.
      • Matos M.H.
      Lower apoptosis rate in ovine preantral follicles from ovaries stored in supplemented preservation media.
      Iberian red deerSpain236Whole ovarySaline solution8°C, 0°C, 25°C12 hOocytes25°C
      a Best conditions within the parameters observed in each study. Not applicable = the study aimed to verify metabolic activity in different media. The authors did not report best conditionsACP, powdered coconut water; BSA, bovine serum albumin; DPBS, Dulbecco's PBS; EGCG, epigallocatechin gallate; GSH, glutathione; ITS, insulin–transferrin–selenium; MEM, minimum essential medium; m-PBS, modified PBS; PBS, phosphate-buffered saline; SOD, superoxide dismutase; UW, University of Wisconsin
      Four studies were conducted in humans (
      • Isachenko E.
      • Isachenko V.
      • Nawroth F.
      • Rahimi G.
      • Weiss J.M.
      Effect of long-term exposure at suprazero temperatures on activity and viability of human ovarian cortex.
      ;
      • Isachenko V.
      • Isachenko E.
      • Mallmann P.
      • Rahimi G.
      Increasing follicular and stromal cell proliferation in cryopreserved human ovarian tissue after long-term precooling prior to freezing: In vitro versus chorioallantoic membrane (cam) xenotransplantation.
      ;
      • Klocke S.
      • Tappehorn C.
      • Griesinger G.
      Effects of supra-zero storage on human ovarian cortex prior to vitrification–warming.
      ;
      • Kyoya T.
      • Nakamura Y.
      • Miyatani S.
      • Miyagawa T.
      • Tomiyama T.
      • Kyono K.
      Evaluation of oxygen consumption in human vitrified and warmed pre-antral follicles after prolonged low temperatures.
      ), six in bovines (
      • Nakao H.
      • Nakatsuji N.
      Effects of storage conditions of bovine ovaries and oocytes on the success rate of in vitro fertilization and culture.
      ,
      • Lucci C.M.
      • Kacinskis M.A.
      • Rumpf R.
      • Báo S.N.
      Effects of lowered temperatures and media on short-term preservation of zebu (bos indicus) preantral ovarian follicles.
      ;
      • Matsushita S.
      • Tani T.
      • Kato Y.
      • Tsunoda Y.
      Effect of low-temperature bovine ovary storage on the maturation rate and developmental potential of follicular oocytes after in vitro fertilization, parthenogenetic activation, or somatic cell nucleus transfer.
      ;
      • Nagao Y.
      • Harada Y.
      • Yamaguchi M.
      • Igarashi A.
      • Ooshima Y.
      • Kato Y.
      Antioxidant treatment during preservation of bovine ovaries increased the development potential of embryos.
      ,
      • Wang Y.S.
      • Zhao X.
      • Su J.M.
      • An Z.X.
      • Xiong X.R.
      • Wang L.J.
      • Liu J.
      • Quan F.S.
      • Hua S.
      • Zhang Y.
      Lowering storage temperature during ovary transport is beneficial to the developmental competence of bovine oocytes used for somatic cell nuclear transfer.
      ;
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      ), seven in cats (
      • Jewgenow K.
      • Wood T.C.
      • Wildt D.E.
      DNA degradation in mural granulosa cells of non- and slightly atretic follicles of fresh and cold-stored domestic cat ovaries.
      ;
      • Wood T.C.
      • Montali R.J.
      • Wildt D.E.
      Follicle-oocyte atresia and temporal taphonomy in cold-stored domestic cat ovaries.
      ;
      • Naoi H.
      • Otoi T.
      • Shimamura T.
      • Karja N.W.K.
      • Agung B.
      • Shimizu R.
      • Taniguchi M.
      • Nagai T.
      Developmental competence of cat oocytes from ovaries stored at various temperature for 24 h.
      ;
      • Evecen M.
      • Cirit U.
      • Demir K.
      • Ozdas O.B.
      • Tas M.
      • Birler S.
      • Pabuccuoglu S.
      Effects of estrous cycle stage and transport temperature of ovaries on in vitro maturation of canine oocytes.
      ;
      • Cocchia N.
      • Corteggio A.
      • Altamura G.
      • Tafuri S.
      • Rea S.
      • Rosapane I.
      • Sica A.
      • Landolfi F.
      • Ciani F.
      The effects of superoxide dismutase addition to the transport medium on cumulus–oocyte complex apoptosis and ivf outcome in cats (felis catus).
      ;
      • Martins J.L.A.
      • Lopes M.D.
      • De Souza F.F.
      • Possebon F.S.
      • Wibbelt G.
      • Jewgenow K.
      Cat preantral follicle survival after prolonged cooled storage followed by vitrification.
      ;
      • Piras A.R.
      • Burrai G.P.
      • Ariu F.
      • Falchi L.
      • Zedda M.T.
      • Pau S.
      • Gadau S.D.
      • Antuofermo E.
      • Bebbere D.
      • Ledda S.
      • Bogliolo L.
      Structure of preantral follicles, oxidative status and developmental competence of in vitro matured oocytes after ovary storage at 4 degrees c in the domestic cat model.
      ), six in goats (
      • Silva J.R.
      • Lucci C.M.
      • Carvalho F.C.
      • Bao S.N.
      • Costa S.H.
      • Santos R.R.
      • Figueiredo J.R.
      Effect of coconut water and braun-collins solutions at different temperatures and incubation times on the morphology of goat preantral follicles preserved in vitro.
      ;
      • Carvalho F.C.A.
      • Lucci C.M.
      • Silva J.R.V.
      • Andrade E.R.
      • Báo S.N.
      • Figueiredo J.R.
      Effect of braun-collins and saline solutions at different temperatures and incubation times on the quality of goat preantral follicles preserved in situ.
      ;

      Santos, R.R.D., Silva, J.R.V., Costa, S.H.F., Rodrigues, A.P.R., Lôbo, R.N.B., Figueiredo, J.R.D., 2002. Effect of 0.9% saline solution and phosphate buffer saline at different temperatures and incubation times on the morphology of goat preantral follicles %j brazilian journal of veterinary research and animal science. 39, 254-259.

      ;
      • Chaves R.N.
      • Martins F.S.
      • Saraiva M.V.
      • Celestino J.J.
      • Lopes C.A.
      • Correia J.C.
      • Verde I.B.
      • Matos M.H.
      • Bao S.N.
      • Name K.P.
      • Campello C.C.
      • Silva J.R.
      • Figueiredo J.R.
      Chilling ovarian fragments during transportation improves viability and growth of goat preantral follicles cultured in vitro.
      ;
      • Gouveia B.
      • Barros V.R.P.
      • Gonçalves R.J.S.
      • Barberino R.S.
      • Menezes V.G.
      • Lins T.L.B.
      • Macedo T.J.S.
      • Santos J.M.S.
      • Rolim L.
      • Neto P.J.
      • Almeida J.R.G.S.
      • Matos M.H.T.
      Effect of ovarian tissue transportation in amburana cearensis extract on the morphology and apoptosis of goat preantral follicles.
      ;
      • Correia H.H.V.
      • Vieira L.A.
      • Maside C.
      • Paes V.M.
      • Silva R.F.
      • Alves B.G.
      • Santos F.W.
      • Apgar G.A.
      • Rodrigues A.P.R.
      • Figueiredo J.R.
      Ovarian transport temperature (4 vs 33°c) impacts differently the in vitro development of isolated goat preantral and antral follicles.
      ), six in dogs (
      • Lee H.S.
      • Yin X.J.
      • Kong I.K.
      Sensitivity of canine oocytes to low temperature.
      ;
      • Tas M.
      • Evecen M.
      • Ozdas O.B.
      • Cirit U.
      • Demir K.
      • Birler S.
      • Pabuccuoglu S.
      Effect of transport and storage temperature of ovaries on in vitro maturation of bitch oocytes.
      ;
      • Hanna C.
      • Long C.
      • Hinrichs K.
      • Westhusin M.
      • Kraemer D.
      Assessment of canine oocyte viability after transportation and storage under different conditions.
      ;
      • Lopes C.A.
      • Dos Santos R.R.
      • Celestino J.J.
      • Melo M.A.
      • Chaves R.N.
      • Campello C.C.
      • Silva J.R.
      • Bao S.N.
      • Jewgenow K.
      • De Figueiredo J.R.
      Short-term preservation of canine preantral follicles: Effects of temperature, medium and time.
      ;
      • Evecen M.
      • Cirit U.
      • Demir K.
      • Ozdas O.B.
      • Tas M.
      • Birler S.
      • Pabuccuoglu S.
      Effects of estrous cycle stage and transport temperature of ovaries on in vitro maturation of canine oocytes.
      ;
      • Lima G.L.
      • Costa L.L.
      • Cavalcanti D.M.
      • Rodrigues C.M.
      • Freire F.A.
      • Fontenele-Neto J.D.
      • Silva A.R.
      Short-term storage of canine preantral ovarian follicles using a powdered coconut water (acp)-based medium.
      ), five in sheep (
      • Gonçalves R.J.
      • Cavalcante A.Y.
      • Gouveia B.B.
      • Lins T.L.
      • Barberino R.S.
      • Menezes V.G.
      • Barros V.R.
      • Macedo T.J.
      • Figueiredo J.R.
      • Matos M.H.
      Lower apoptosis rate in ovine preantral follicles from ovaries stored in supplemented preservation media.
      ;
      • Barberino R.
      • Gonçalves R.
      • Menezes V.G.
      • Barros V.
      • Lins T.
      • Gouveia B.
      • Macedo T.
      • Santos L.
      • Matos M.
      Influence of the ovarian fragmentation before storage at 4°c on the apoptosis rates and in vitro development of ovine preantral follicles.
      ;
      • Henry L.
      • Fransolet M.
      • Labied S.
      • Blacher S.
      • Masereel M.-C.
      • Foidart J.-M.
      • Noel A.
      • Nisolle M.
      • Munaut C.
      Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival.
      ;
      • Cavalcante A.
      • Barberino R.
      • Gouveia B.
      • Bezerra M.
      • Menezes V.G.
      • Rocha Souza G.
      • Rolim L.
      • Rolim-Neto P.
      • Almeida J.R.
      • Matos M.
      Effect of ovarian tissue storage in morus nigra extract on the morphology and DNA fragmentation of ovine preantral follicles.
      ;
      • Goodarzi A.
      • Zare Shahneh A.
      • Kohram H.
      • Sadeghi M.
      • Moazenizadeh M.H.
      • Fouladi-Nashta A.
      • Dadashpour Davachi N.
      Effect of melatonin supplementation in the long-term preservation of the sheep ovaries at different temperatures and subsequent in vitro embryo production.
      ), five in horses (
      • Love L.B.
      • Choi Y.H.
      • Love C.C.
      • Varner D.D.
      • Hinrichs K.
      Effect of ovary storage and oocyte transport method on maturation rate of horse oocytes.
      ;
      • Pedersen H.G.
      • Watson E.D.
      • Telfer E.E.
      Effect of ovary holding temperature and time on equine granulosa cell apoptosis, oocyte chromatin configuration and cumulus morphology.
      ;
      • Ribeiro B.I.
      • Love L.B.
      • Choi Y.H.
      • Hinrichs K.
      Transport of equine ovaries for assisted reproduction.
      ;
      • Gomes R.G.
      • Andrade E.R.
      • Lisboa L.A.
      • Ciquini A.
      • Barreiros T.R.
      • Fonseca N.A.
      • Seneda M.M.
      Effect of holding medium, temperature and time on structural integrity of equine ovarian follicles during the non-breeding season.
      ;
      • Gastal G.D.
      • Alves B.G.
      • Alves K.A.
      • Souza M.E.
      • Vieira A.D.
      • Varela Jr., A.S.
      • Figueiredo J.R.
      • Feugang J.M.
      • Lucia Jr., T.
      • Gastal E.L.
      Ovarian fragment sizes affect viability and morphology of preantral follicles during storage at 4 degrees c.
      ), four in pigs (
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      ;
      • Lucci C.M.
      • Schreier L.L.
      • Machado G.M.
      • Amorim C.A.
      • Bao S.N.
      • Dobrinsky J.R.
      Effects of storing pig ovaries at 4 or 20 degrees c for different periods of time on the morphology and viability of pre-antral follicles.
      ;
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      ;
      • Raffel N.
      • Dittrich R.
      • Orlowski P.
      • Tischer H.
      • Söder S.
      • Erber R.
      • Hoffmann I.
      • Beckmann M.W.
      • Lotz L.
      Is ovarian tissue transport at supra-zero temperatures compared to body temperature optimal for follicle survival?.
      ), one in mice (
      • Kamoshita K.
      • Okamoto N.
      • Nakajima M.
      • Haino T.
      • Sugimoto K.
      • Okamoto A.
      • Sugishita Y.
      • Suzuki N.
      Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.
      ), one in the Pecari tajacu (musk hog) (

      Lima, G.L., Santos, E.a.A., Lima, L.F., Luz, V.B., Rodrigues, A.P.R., Silva, A.R., 2014. Short-term preservation of pecari tajacu ovarian preantral follicles using phosphate buffered saline (pbs) or powdered coconut water (acp(r)) media %j arquivo brasileiro de medicina veterinária e zootecnia. 66, 1623-1630.

      ), and one in Iberian red deer (
      • García-Álvarez O.
      • Maroto-Morales A.
      • Berlinguer F.
      • Fernandez-Santos M.R.
      • Esteso M.C.
      • Mermillod P.
      • Ortiz J.A.
      • Ramon M.
      • Perez-Guzman M.D.
      • Garde J.J.
      • Soler A.J.
      Effect of storage temperature during transport of ovaries on in vitro embryo production in iberian red deer (cervus elaphus hispanicus).
      ) (Supplementary Table 2). A total of 26 studies evaluated transportation of whole ovaries, one of half-ovaries and 16 of ovarian fragments, and one compared whole ovaries and fragments.

      Tested parameters and assessment

      Of the 46 publications analysed, 28 evaluated different temperatures, 34 monitored the effect of time, 13 investigated different media, six assessed the impact of additives in media and only two considered the influence of tissue size (Table 3). Tested temperatures ranged from 0 to 39°C, 4°C (n = 34) and 20°C (n = 13) being the most frequently evaluated. Timepoints varied from 1 to 96 h, 4 (n = 16), 12 (n = 20) and 24 h (n = 24) being the periods most commonly investigated. In total, 20 different media were tested over all the studies, with saline solution (n = 14) and phosphate-buffered saline (PBS; n = 12) emerging as the most prevalent, followed by MEM (n = 8) (Figure 2). The best study conditions for each species are summarized in Table 4.
      Table 3Analysed parameters in ovarian tissue transport
      ParameterHumanCowCatGoatSheepDogHorsePigPecari tajacuMouseIberian red deerTotal
      Additives in media11
      Additives in media × time1113
      Media × temperature112
      Media × temperature × additives in media11
      Media × temperature × time13116
      Temperature1113118
      Temperature × time11124110
      Temperature × time × additives in media11
      Time358
      Time × media11114
      Time × tissue size112
      Total4676565411146
      Figure 2
      Figure 2Temperature (A), timepoints (B), and media (C) tested in ovarian tissue transportation studies.
      Table 4Best conditions for each species
      Best temperatureBest timeBest medium
      4°C10°C15°C20°C25°C37°C38°C4 h6 h7 h12 h18 h24 h26 h48 hACP mediumCoconut waterMEM+PBSSaline solutionTL-HEPESUse of additivesUse of antiapoptotic drugs
      Human1111
      Cow11211121
      Cat111411
      Goat611221111
      Sheep122121
      Dog31111111
      Horse1111111
      Pig22111
      Pecari tajacu11
      Mouse111
      Iberian red deer1
      Total1712132146153141121231151
      ACP, powdered coconut water; MEM, minimum essential medium; PBS, phosphate buffered saline.

      Analyses performed

      Most studies focused their analysis on oocytes (43.7%, 20 studies) and ovarian tissue (50%, 23 studies) (Supplementary Figure 2). Regarding DNA/RNA analyses, one study applied the polymerase chain reaction (
      • Cocchia N.
      • Corteggio A.
      • Altamura G.
      • Tafuri S.
      • Rea S.
      • Rosapane I.
      • Sica A.
      • Landolfi F.
      • Ciani F.
      The effects of superoxide dismutase addition to the transport medium on cumulus–oocyte complex apoptosis and ivf outcome in cats (felis catus).
      ) and one evaluated chromatin configuration (
      • Pedersen H.G.
      • Watson E.D.
      • Telfer E.E.
      Effect of ovary holding temperature and time on equine granulosa cell apoptosis, oocyte chromatin configuration and cumulus morphology.
      ). DNA fragmentation (using TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling [TUNEL], in-situ end-labelling [ISEL] or other techniques) was performed in 10 studies (
      • Jewgenow K.
      • Wood T.C.
      • Wildt D.E.
      DNA degradation in mural granulosa cells of non- and slightly atretic follicles of fresh and cold-stored domestic cat ovaries.
      ;
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      ;
      • Gonçalves R.J.
      • Cavalcante A.Y.
      • Gouveia B.B.
      • Lins T.L.
      • Barberino R.S.
      • Menezes V.G.
      • Barros V.R.
      • Macedo T.J.
      • Figueiredo J.R.
      • Matos M.H.
      Lower apoptosis rate in ovine preantral follicles from ovaries stored in supplemented preservation media.
      ;
      • Gouveia B.
      • Barros V.R.P.
      • Gonçalves R.J.S.
      • Barberino R.S.
      • Menezes V.G.
      • Lins T.L.B.
      • Macedo T.J.S.
      • Santos J.M.S.
      • Rolim L.
      • Neto P.J.
      • Almeida J.R.G.S.
      • Matos M.H.T.
      Effect of ovarian tissue transportation in amburana cearensis extract on the morphology and apoptosis of goat preantral follicles.
      ;
      • Kamoshita K.
      • Okamoto N.
      • Nakajima M.
      • Haino T.
      • Sugimoto K.
      • Okamoto A.
      • Sugishita Y.
      • Suzuki N.
      Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.
      ;
      • Cavalcante A.
      • Barberino R.
      • Gouveia B.
      • Bezerra M.
      • Menezes V.G.
      • Rocha Souza G.
      • Rolim L.
      • Rolim-Neto P.
      • Almeida J.R.
      • Matos M.
      Effect of ovarian tissue storage in morus nigra extract on the morphology and DNA fragmentation of ovine preantral follicles.
      ;
      • Gastal G.D.
      • Alves B.G.
      • Alves K.A.
      • Souza M.E.
      • Vieira A.D.
      • Varela Jr., A.S.
      • Figueiredo J.R.
      • Feugang J.M.
      • Lucia Jr., T.
      • Gastal E.L.
      Ovarian fragment sizes affect viability and morphology of preantral follicles during storage at 4 degrees c.
      ;
      • Barberino R.S.
      • Silva J.R.V.
      • Figueiredo J.R.
      • Matos M.H.T.
      Transport of domestic and wild animal ovaries: A review of the effects of medium, temperature, and periods of storage on follicular viability.
      ;
      • Piras A.R.
      • Burrai G.P.
      • Ariu F.
      • Falchi L.
      • Zedda M.T.
      • Pau S.
      • Gadau S.D.
      • Antuofermo E.
      • Bebbere D.
      • Ledda S.
      • Bogliolo L.
      Structure of preantral follicles, oxidative status and developmental competence of in vitro matured oocytes after ovary storage at 4 degrees c in the domestic cat model.
      ;
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      ). Four studies used embryo analyses (
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      ;
      • Naoi H.
      • Otoi T.
      • Shimamura T.
      • Karja N.W.K.
      • Agung B.
      • Shimizu R.
      • Taniguchi M.
      • Nagai T.
      Developmental competence of cat oocytes from ovaries stored at various temperature for 24 h.
      ;
      • Ribeiro B.I.
      • Love L.B.
      • Choi Y.H.
      • Hinrichs K.
      Transport of equine ovaries for assisted reproduction.
      ;
      • Wang Y.S.
      • Zhao X.
      • Su J.M.
      • An Z.X.
      • Xiong X.R.
      • Wang L.J.
      • Liu J.
      • Quan F.S.
      • Hua S.
      • Zhang Y.
      Lowering storage temperature during ovary transport is beneficial to the developmental competence of bovine oocytes used for somatic cell nuclear transfer.
      ) and five assessed isolated follicles (
      • Lucci C.M.
      • Schreier L.L.
      • Machado G.M.
      • Amorim C.A.
      • Bao S.N.
      • Dobrinsky J.R.
      Effects of storing pig ovaries at 4 or 20 degrees c for different periods of time on the morphology and viability of pre-antral follicles.
      ;
      • Lopes C.A.
      • Dos Santos R.R.
      • Celestino J.J.
      • Melo M.A.
      • Chaves R.N.
      • Campello C.C.
      • Silva J.R.
      • Bao S.N.
      • Jewgenow K.
      • De Figueiredo J.R.
      Short-term preservation of canine preantral follicles: Effects of temperature, medium and time.
      ;

      Lima, G.L., Santos, E.a.A., Lima, L.F., Luz, V.B., Rodrigues, A.P.R., Silva, A.R., 2014. Short-term preservation of pecari tajacu ovarian preantral follicles using phosphate buffered saline (pbs) or powdered coconut water (acp(r)) media %j arquivo brasileiro de medicina veterinária e zootecnia. 66, 1623-1630.

      ;
      • Correia H.H.V.
      • Vieira L.A.
      • Maside C.
      • Paes V.M.
      • Silva R.F.
      • Alves B.G.
      • Santos F.W.
      • Apgar G.A.
      • Rodrigues A.P.R.
      • Figueiredo J.R.
      Ovarian transport temperature (4 vs 33°c) impacts differently the in vitro development of isolated goat preantral and antral follicles.
      ;
      • Raffel N.
      • Dittrich R.
      • Orlowski P.
      • Tischer H.
      • Söder S.
      • Erber R.
      • Hoffmann I.
      • Beckmann M.W.
      • Lotz L.
      Is ovarian tissue transport at supra-zero temperatures compared to body temperature optimal for follicle survival?.
      ). One study considered offspring after IVF (
      • Kamoshita K.
      • Okamoto N.
      • Nakajima M.
      • Haino T.
      • Sugimoto K.
      • Okamoto A.
      • Sugishita Y.
      • Suzuki N.
      Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.
      ).
      Four studies analysed media; Klocke and colleagues (
      • Klocke S.
      • Tappehorn C.
      • Griesinger G.
      Effects of supra-zero storage on human ovarian cortex prior to vitrification–warming.
      ) measured oestradiol concentrations in culture medium after vitrification/warming to assess transported tissue, Lima and colleages (

      Lima, G.L., Santos, E.a.A., Lima, L.F., Luz, V.B., Rodrigues, A.P.R., Silva, A.R., 2014. Short-term preservation of pecari tajacu ovarian preantral follicles using phosphate buffered saline (pbs) or powdered coconut water (acp(r)) media %j arquivo brasileiro de medicina veterinária e zootecnia. 66, 1623-1630.

      ) measured pH values, while Correia and co-workers (
      • Correia H.H.V.
      • Vieira L.A.
      • Maside C.
      • Paes V.M.
      • Silva R.F.
      • Alves B.G.
      • Santos F.W.
      • Apgar G.A.
      • Rodrigues A.P.R.
      • Figueiredo J.R.
      Ovarian transport temperature (4 vs 33°c) impacts differently the in vitro development of isolated goat preantral and antral follicles.
      ) evaluated reactive oxygen species (ROS) levels in culture medium after storage, and Vilela and co-workers (
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      ) evaluated glucose, pyruvate and lactate concentrations, as well as pH and lactate dehydrogenase activity in media used for transportation. Two other studies analysed follicular fluid; Tellado and colleagues (
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      ) quantified lactate, glucose and pH, and Wongsrikeao and co-workers (
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      ) calculated the pH of follicular fluid in antral follicles after storage of pig ovarian tissue.
      In ovarian tissue, follicle morphology and ultrastructure were the focus of analyses, conducted using haematoxylin and eosin staining (23 studies) or transmission electron microscopy (TEM; 7 studies). For assessment of the transportation protocol, ovarian tissue fragments were cultured after storage in nine studies, and transplanted in one study (
      • Kamoshita K.
      • Okamoto N.
      • Nakajima M.
      • Haino T.
      • Sugimoto K.
      • Okamoto A.
      • Sugishita Y.
      • Suzuki N.
      Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.
      ). In oocytes, investigations were largely related to oocyte development after in-vitro maturation (IVM; 16 studies), nine of which involved IVF (results summarized in Table 2).

      Effects on ovarian tissue

      Analyses of ovarian tissue were performed in humans (
      • Isachenko E.
      • Isachenko V.
      • Nawroth F.
      • Rahimi G.
      • Weiss J.M.
      Effect of long-term exposure at suprazero temperatures on activity and viability of human ovarian cortex.
      ;
      • Isachenko V.
      • Isachenko E.
      • Mallmann P.
      • Rahimi G.
      Increasing follicular and stromal cell proliferation in cryopreserved human ovarian tissue after long-term precooling prior to freezing: In vitro versus chorioallantoic membrane (cam) xenotransplantation.
      ;
      • Klocke S.
      • Tappehorn C.
      • Griesinger G.
      Effects of supra-zero storage on human ovarian cortex prior to vitrification–warming.
      ;
      • Kyoya T.
      • Nakamura Y.
      • Miyatani S.
      • Miyagawa T.
      • Tomiyama T.
      • Kyono K.
      Evaluation of oxygen consumption in human vitrified and warmed pre-antral follicles after prolonged low temperatures.
      ), cows (
      • Lucci C.M.
      • Kacinskis M.A.
      • Rumpf R.
      • Báo S.N.
      Effects of lowered temperatures and media on short-term preservation of zebu (bos indicus) preantral ovarian follicles.
      ;
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      ), cats (
      • Jewgenow K.
      • Wood T.C.
      • Wildt D.E.
      DNA degradation in mural granulosa cells of non- and slightly atretic follicles of fresh and cold-stored domestic cat ovaries.
      ;
      • Wood T.C.
      • Montali R.J.
      • Wildt D.E.
      Follicle-oocyte atresia and temporal taphonomy in cold-stored domestic cat ovaries.
      ;
      • Smitz J.
      • Dolmans M.M.
      • Donnez J.
      • Fortune J.E.
      • Hovatta O.
      • Jewgenow K.
      • Picton H.M.
      • Plancha C.
      • Shea L.D.
      • Stouffer R.L.
      • Telfer E.E.
      • Woodruff T.K.
      • Zelinski M.B.
      Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: Implications for fertility preservation.
      ;
      • Martins J.L.A.
      • Lopes M.D.
      • De Souza F.F.
      • Possebon F.S.
      • Wibbelt G.
      • Jewgenow K.
      Cat preantral follicle survival after prolonged cooled storage followed by vitrification.
      ), goats (
      • Silva J.R.
      • Lucci C.M.
      • Carvalho F.C.
      • Bao S.N.
      • Costa S.H.
      • Santos R.R.
      • Figueiredo J.R.
      Effect of coconut water and braun-collins solutions at different temperatures and incubation times on the morphology of goat preantral follicles preserved in vitro.
      ;
      • Carvalho F.C.A.
      • Lucci C.M.
      • Silva J.R.V.
      • Andrade E.R.
      • Báo S.N.
      • Figueiredo J.R.
      Effect of braun-collins and saline solutions at different temperatures and incubation times on the quality of goat preantral follicles preserved in situ.
      ;

      Santos, R.R.D., Silva, J.R.V., Costa, S.H.F., Rodrigues, A.P.R., Lôbo, R.N.B., Figueiredo, J.R.D., 2002. Effect of 0.9% saline solution and phosphate buffer saline at different temperatures and incubation times on the morphology of goat preantral follicles %j brazilian journal of veterinary research and animal science. 39, 254-259.

      ;
      • Chaves R.N.
      • Martins F.S.
      • Saraiva M.V.
      • Celestino J.J.
      • Lopes C.A.
      • Correia J.C.
      • Verde I.B.
      • Matos M.H.
      • Bao S.N.
      • Name K.P.
      • Campello C.C.
      • Silva J.R.
      • Figueiredo J.R.
      Chilling ovarian fragments during transportation improves viability and growth of goat preantral follicles cultured in vitro.
      ;
      • Gouveia B.
      • Barros V.R.P.
      • Gonçalves R.J.S.
      • Barberino R.S.
      • Menezes V.G.
      • Lins T.L.B.
      • Macedo T.J.S.
      • Santos J.M.S.
      • Rolim L.
      • Neto P.J.
      • Almeida J.R.G.S.
      • Matos M.H.T.
      Effect of ovarian tissue transportation in amburana cearensis extract on the morphology and apoptosis of goat preantral follicles.
      ), sheep (
      • Gonçalves R.J.
      • Cavalcante A.Y.
      • Gouveia B.B.
      • Lins T.L.
      • Barberino R.S.
      • Menezes V.G.
      • Barros V.R.
      • Macedo T.J.
      • Figueiredo J.R.
      • Matos M.H.
      Lower apoptosis rate in ovine preantral follicles from ovaries stored in supplemented preservation media.
      ;
      • Barberino R.
      • Gonçalves R.
      • Menezes V.G.
      • Barros V.
      • Lins T.
      • Gouveia B.
      • Macedo T.
      • Santos L.
      • Matos M.
      Influence of the ovarian fragmentation before storage at 4°c on the apoptosis rates and in vitro development of ovine preantral follicles.
      ;
      • Henry L.
      • Fransolet M.
      • Labied S.
      • Blacher S.
      • Masereel M.-C.
      • Foidart J.-M.
      • Noel A.
      • Nisolle M.
      • Munaut C.
      Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival.
      ;
      • Cavalcante A.
      • Barberino R.
      • Gouveia B.
      • Bezerra M.
      • Menezes V.G.
      • Rocha Souza G.
      • Rolim L.
      • Rolim-Neto P.
      • Almeida J.R.
      • Matos M.
      Effect of ovarian tissue storage in morus nigra extract on the morphology and DNA fragmentation of ovine preantral follicles.
      ), dogs (
      • Lima G.L.
      • Costa L.L.
      • Cavalcanti D.M.
      • Rodrigues C.M.
      • Freire F.A.
      • Fontenele-Neto J.D.
      • Silva A.R.
      Short-term storage of canine preantral ovarian follicles using a powdered coconut water (acp)-based medium.
      ), horses (
      • Gomes R.G.
      • Andrade E.R.
      • Lisboa L.A.
      • Ciquini A.
      • Barreiros T.R.
      • Fonseca N.A.
      • Seneda M.M.
      Effect of holding medium, temperature and time on structural integrity of equine ovarian follicles during the non-breeding season.
      ;
      • Gastal G.D.
      • Alves B.G.
      • Alves K.A.
      • Souza M.E.
      • Vieira A.D.
      • Varela Jr., A.S.
      • Figueiredo J.R.
      • Feugang J.M.
      • Lucia Jr., T.
      • Gastal E.L.
      Ovarian fragment sizes affect viability and morphology of preantral follicles during storage at 4 degrees c.
      ), mice (
      • Kamoshita K.
      • Okamoto N.
      • Nakajima M.
      • Haino T.
      • Sugimoto K.
      • Okamoto A.
      • Sugishita Y.
      • Suzuki N.
      Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.
      ) and musk hogs (

      Lima, G.L., Santos, E.a.A., Lima, L.F., Luz, V.B., Rodrigues, A.P.R., Silva, A.R., 2014. Short-term preservation of pecari tajacu ovarian preantral follicles using phosphate buffered saline (pbs) or powdered coconut water (acp(r)) media %j arquivo brasileiro de medicina veterinária e zootecnia. 66, 1623-1630.

      ).

      Human ovarian tissue

      In humans, ovarian tissue pieces cultured for 15 days after 26 h of transportation in Brama I medium at 4°C showed no evidence of morphological damage (
      • Isachenko E.
      • Isachenko V.
      • Nawroth F.
      • Rahimi G.
      • Weiss J.M.
      Effect of long-term exposure at suprazero temperatures on activity and viability of human ovarian cortex.
      ). Another study by Isachenko and colleagues (
      • Isachenko V.
      • Isachenko E.
      • Mallmann P.
      • Rahimi G.
      Increasing follicular and stromal cell proliferation in cryopreserved human ovarian tissue after long-term precooling prior to freezing: In vitro versus chorioallantoic membrane (cam) xenotransplantation.
      ) exhibited increased follicle viability after 24 h of transport at 5°C and culture of ovarian pieces in vitro and in the chorioallantoic membrane of chick embryos for 5 days. Kyoya and co-workers (
      • Kyoya T.
      • Nakamura Y.
      • Miyatani S.
      • Miyagawa T.
      • Tomiyama T.
      • Kyono K.
      Evaluation of oxygen consumption in human vitrified and warmed pre-antral follicles after prolonged low temperatures.
      ) transported ovarian tissue in L-15 for up to 18 h at 4°C and cultured vitrified fragments for 24 h. They analysed oxygen consumption rates by scanning electrochemical microscopy and found no difference in follicle morphology or oxygen consumption from fresh controls. After transport in Celsior medium at 4°C for 24 or 48 h, Klocke and colleagues (
      • Klocke S.
      • Tappehorn C.
      • Griesinger G.
      Effects of supra-zero storage on human ovarian cortex prior to vitrification–warming.
      ) performed vitrification and tissue culture for 18 days, reporting that malondialdehyde concentrations increased in the medium, indicative of oxidative stress. Oestradiol was also measured and its concentrations progressively fell with storage time. Apoptosis was assessed with anti-active caspase-3 after vitrification and warming, and the proportion of apoptotic follicles was not found to be significantly different from that in non-transported (fresh) tissue.

      Animal ovarian tissue

      Cow ovaries were stored at 4°C or 20°C for up to 18 h in saline or coconut water. Conservation at 4°C for up to 18 h and 20°C for up to 6 h kept the percentage of morphologically normal follicles similar to fresh controls, but the solution had little effect on the results (
      • Lucci C.M.
      • Kacinskis M.A.
      • Rumpf R.
      • Báo S.N.
      Effects of lowered temperatures and media on short-term preservation of zebu (bos indicus) preantral ovarian follicles.
      ). Another study (
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      ) compared concentrations of glucose, pyruvate and lactate after transporting cow ovaries in IVF medium, L-15 medium, saline solution and PBS for up to 24 h at 4°C, and reported no glucose consumption, low pyruvate consumption and comparable lactate release in all media. Viability assays were performed using TUNEL and fluorescence-activated cell sorting, and showed low apoptosis and necrosis rates, indicating anaerobic metabolism during ovarian tissue transportation.
      In cats, Jewgenow and co-workers (
      • Jewgenow K.
      • Wood T.C.
      • Wildt D.E.
      DNA degradation in mural granulosa cells of non- and slightly atretic follicles of fresh and cold-stored domestic cat ovaries.
      ) stored ovarian tissue for up to 48 h in Dulbecco's PBS at 4°C and analysed follicle atresia by histology and DNA fragmentation using ISEL. They detected significant DNA degradation in granulosa cells after 12 h of storage. Using the same media and temperature, Wood and colleagues (
      • Wood T.C.
      • Montali R.J.
      • Wildt D.E.
      Follicle-oocyte atresia and temporal taphonomy in cold-stored domestic cat ovaries.
      ) observed that cold storage inhibited taphonomic changes to tissue for 48 h after removal from the animal. The authors reported that atresia found in samples was natural and not a result of cold storage. In a recent study, Martins and co-workers (
      • Martins J.L.A.
      • Lopes M.D.
      • De Souza F.F.
      • Possebon F.S.
      • Wibbelt G.
      • Jewgenow K.
      Cat preantral follicle survival after prolonged cooled storage followed by vitrification.
      ) evaluated follicle morphology before and after storage followed by vitrification. They used MEM at 4°C for 24 or 72 h and encountered higher survival rates in the 24 h storage group, with no difference in pre-antral follicle survival rates between fresh tissue and ovaries stored for 24 h.
      All studies using goat ovarian tissue were from the same research group in Brazil. They tested five different media at four temperatures (4, 20, 35 and 39°C). Using histology or TEM, they observed better preservation of follicles with coconut water at 4°C than with Braun-Collins solution (
      • Silva J.R.
      • Lucci C.M.
      • Carvalho F.C.
      • Bao S.N.
      • Costa S.H.
      • Santos R.R.
      • Figueiredo J.R.
      Effect of coconut water and braun-collins solutions at different temperatures and incubation times on the morphology of goat preantral follicles preserved in vitro.
      ). Similarly, saline solution yielded higher rates of morphologically normal follicles than Braun-Collins (
      • Carvalho F.C.A.
      • Lucci C.M.
      • Silva J.R.V.
      • Andrade E.R.
      • Báo S.N.
      • Figueiredo J.R.
      Effect of braun-collins and saline solutions at different temperatures and incubation times on the quality of goat preantral follicles preserved in situ.
      ) or PBS (

      Santos, R.R.D., Silva, J.R.V., Costa, S.H.F., Rodrigues, A.P.R., Lôbo, R.N.B., Figueiredo, J.R.D., 2002. Effect of 0.9% saline solution and phosphate buffer saline at different temperatures and incubation times on the morphology of goat preantral follicles %j brazilian journal of veterinary research and animal science. 39, 254-259.

      ) for up to 12 h. Coconut water was the only medium in which they could preserve follicle morphology for 24 h at 4°C (
      • Silva J.R.
      • Lucci C.M.
      • Carvalho F.C.
      • Bao S.N.
      • Costa S.H.
      • Santos R.R.
      • Figueiredo J.R.
      Effect of coconut water and braun-collins solutions at different temperatures and incubation times on the morphology of goat preantral follicles preserved in vitro.
      ). In another study, ovarian fragments cultured for up to 7 days after storage in MEM for 2 or 4 h exhibited follicle morphology similar to the fresh controls (
      • Chaves R.N.
      • Martins F.S.
      • Saraiva M.V.
      • Celestino J.J.
      • Lopes C.A.
      • Correia J.C.
      • Verde I.B.
      • Matos M.H.
      • Bao S.N.
      • Name K.P.
      • Campello C.C.
      • Silva J.R.
      • Figueiredo J.R.
      Chilling ovarian fragments during transportation improves viability and growth of goat preantral follicles cultured in vitro.
      ).
      Studies in sheep were the first to demonstrate that tissue size during transport affects follicle morphology (
      • Barberino R.S.
      • Silva J.R.V.
      • Figueiredo J.R.
      • Matos M.H.T.
      Transport of domestic and wild animal ovaries: A review of the effects of medium, temperature, and periods of storage on follicular viability.
      ), by comparing the transportation of a whole ovary with fragments of equivalent to half, a quarter and an eighth its size. In that study, the smallest fragments showed better preservation of the follicle capacity to grow in vitro for up to 24 h. Gonçalves and colleagues (
      • Gonçalves R.J.
      • Cavalcante A.Y.
      • Gouveia B.B.
      • Lins T.L.
      • Barberino R.S.
      • Menezes V.G.
      • Barros V.R.
      • Macedo T.J.
      • Figueiredo J.R.
      • Matos M.H.
      Lower apoptosis rate in ovine preantral follicles from ovaries stored in supplemented preservation media.
      ) reported that sheep ovarian fragments can be stored for up to 6 h at 35°C in MEM supplemented with additives like insulin–transferrin–selenium, hypoxanthine, glutamine, bovine serum albumin and FSH (which they named MEM+). Other studies have described the positive impact of two anti-apoptotic drugs, Z-VAD-FMK (a pan-caspase inhibitor) and SP1 (a bioactive lipid in follicular fluid) (
      • Henry L.
      • Fransolet M.
      • Labied S.
      • Blacher S.
      • Masereel M.-C.
      • Foidart J.-M.
      • Noel A.
      • Nisolle M.
      • Munaut C.
      Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival.
      ), and extracts from the plants Amburana cearensis (
      • Gouveia B.
      • Barros V.R.P.
      • Gonçalves R.J.S.
      • Barberino R.S.
      • Menezes V.G.
      • Lins T.L.B.
      • Macedo T.J.S.
      • Santos J.M.S.
      • Rolim L.
      • Neto P.J.
      • Almeida J.R.G.S.
      • Matos M.H.T.
      Effect of ovarian tissue transportation in amburana cearensis extract on the morphology and apoptosis of goat preantral follicles.
      ) and Morus nigra (
      • Cavalcante A.
      • Barberino R.
      • Gouveia B.
      • Bezerra M.
      • Menezes V.G.
      • Rocha Souza G.
      • Rolim L.
      • Rolim-Neto P.
      • Almeida J.R.
      • Matos M.
      Effect of ovarian tissue storage in morus nigra extract on the morphology and DNA fragmentation of ovine preantral follicles.
      ) in the transportation of sheep ovaries.
      In dogs, one study reported better preservation of follicle morphology when ovarian fragments were stored at 10°C in a coconut water-based medium compared with PBS. Indeed, while the percentage of morphologically normal follicles started to decrease after 24 h in PBS, it only started to fall after 36 h in coconut water-based medium (
      • Lima G.L.
      • Costa L.L.
      • Cavalcanti D.M.
      • Rodrigues C.M.
      • Freire F.A.
      • Fontenele-Neto J.D.
      • Silva A.R.
      Short-term storage of canine preantral ovarian follicles using a powdered coconut water (acp)-based medium.
      ). Another study on the transport of canine ovarian tissue fragments found follicle morphology to be preserved for 12 h in MEM at 4° or 20°C (
      • Lopes C.A.
      • Dos Santos R.R.
      • Celestino J.J.
      • Melo M.A.
      • Chaves R.N.
      • Campello C.C.
      • Silva J.R.
      • Bao S.N.
      • Jewgenow K.
      • De Figueiredo J.R.
      Short-term preservation of canine preantral follicles: Effects of temperature, medium and time.
      ).
      In horses, transportation of ovarian tissue fragments at 4°C for 4 h yielded a higher rate of morphologically normal follicles in PBS than MEM (
      • Gomes R.G.
      • Andrade E.R.
      • Lisboa L.A.
      • Ciquini A.
      • Barreiros T.R.
      • Fonseca N.A.
      • Seneda M.M.
      Effect of holding medium, temperature and time on structural integrity of equine ovarian follicles during the non-breeding season.
      ). Moreover, small fragments (2  ×  2  ×  12 mm) showed better preservation of follicle morphology over 24 h at 4°C than did transport of whole ovaries (
      • Gastal G.D.
      • Alves B.G.
      • Alves K.A.
      • Souza M.E.
      • Vieira A.D.
      • Varela Jr., A.S.
      • Figueiredo J.R.
      • Feugang J.M.
      • Lucia Jr., T.
      • Gastal E.L.
      Ovarian fragment sizes affect viability and morphology of preantral follicles during storage at 4 degrees c.
      ).
      The first report of reduced fertility after storage followed by transplantation of ovarian tissue comes from a study in mice (
      • Kamoshita K.
      • Okamoto N.
      • Nakajima M.
      • Haino T.
      • Sugimoto K.
      • Okamoto A.
      • Sugishita Y.
      • Suzuki N.
      Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.
      ). Although histology evidenced no significant changes after transport in Dulbecco's modified Eagle's medium, there was a significant reduction in implantation and live birth rates with prolonged tissue storage (>8 h).

      Effects on oocyte maturation and fertilization, and embryo production

      Studies on oocyte maturation and fertilization, as well as embryo production after ovarian tissue transportation, have only been conducted in animals. At the time of writing this review, no studies had been completed in humans. IVM of oocytes followed by IVF was performed after transport of bovine (
      • Nakao H.
      • Nakatsuji N.
      Effects of storage conditions of bovine ovaries and oocytes on the success rate of in vitro fertilization and culture.
      ;
      • Matsushita S.
      • Tani T.
      • Kato Y.
      • Tsunoda Y.
      Effect of low-temperature bovine ovary storage on the maturation rate and developmental potential of follicular oocytes after in vitro fertilization, parthenogenetic activation, or somatic cell nucleus transfer.
      ;
      • Nagao Y.
      • Harada Y.
      • Yamaguchi M.
      • Igarashi A.
      • Ooshima Y.
      • Kato Y.
      Antioxidant treatment during preservation of bovine ovaries increased the development potential of embryos.
      ;
      • Barberino R.
      • Gonçalves R.
      • Menezes V.G.
      • Barros V.
      • Lins T.
      • Gouveia B.
      • Macedo T.
      • Santos L.
      • Matos M.
      Influence of the ovarian fragmentation before storage at 4°c on the apoptosis rates and in vitro development of ovine preantral follicles.
      ), feline (
      • Naoi H.
      • Otoi T.
      • Shimamura T.
      • Karja N.W.K.
      • Agung B.
      • Shimizu R.
      • Taniguchi M.
      • Nagai T.
      Developmental competence of cat oocytes from ovaries stored at various temperature for 24 h.
      ;
      • Cocchia N.
      • Corteggio A.
      • Altamura G.
      • Tafuri S.
      • Rea S.
      • Rosapane I.
      • Sica A.
      • Landolfi F.
      • Ciani F.
      The effects of superoxide dismutase addition to the transport medium on cumulus–oocyte complex apoptosis and ivf outcome in cats (felis catus).
      ;
      • Piras A.R.
      • Burrai G.P.
      • Ariu F.
      • Falchi L.
      • Zedda M.T.
      • Pau S.
      • Gadau S.D.
      • Antuofermo E.
      • Bebbere D.
      • Ledda S.
      • Bogliolo L.
      Structure of preantral follicles, oxidative status and developmental competence of in vitro matured oocytes after ovary storage at 4 degrees c in the domestic cat model.
      ), ovine (
      • Goodarzi A.
      • Zare Shahneh A.
      • Kohram H.
      • Sadeghi M.
      • Moazenizadeh M.H.
      • Fouladi-Nashta A.
      • Dadashpour Davachi N.
      Effect of melatonin supplementation in the long-term preservation of the sheep ovaries at different temperatures and subsequent in vitro embryo production.
      ) and porcine (
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      ;
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      ) ovarian tissue. IVM was also carried out in four studies in dogs (
      • Lee H.S.
      • Yin X.J.
      • Kong I.K.
      Sensitivity of canine oocytes to low temperature.
      ;
      • Tas M.
      • Evecen M.
      • Ozdas O.B.
      • Cirit U.
      • Demir K.
      • Birler S.
      • Pabuccuoglu S.
      Effect of transport and storage temperature of ovaries on in vitro maturation of bitch oocytes.
      ;
      • Hanna C.
      • Long C.
      • Hinrichs K.
      • Westhusin M.
      • Kraemer D.
      Assessment of canine oocyte viability after transportation and storage under different conditions.
      ;
      • Evecen M.
      • Cirit U.
      • Demir K.
      • Ozdas O.B.
      • Tas M.
      • Birler S.
      • Pabuccuoglu S.
      Effects of estrous cycle stage and transport temperature of ovaries on in vitro maturation of canine oocytes.
      ), two in horses (
      • Love L.B.
      • Choi Y.H.
      • Love C.C.
      • Varner D.D.
      • Hinrichs K.
      Effect of ovary storage and oocyte transport method on maturation rate of horse oocytes.
      ;
      • Ribeiro B.I.
      • Love L.B.
      • Choi Y.H.
      • Hinrichs K.
      Transport of equine ovaries for assisted reproduction.
      ), one in goats (
      • Correia H.H.V.
      • Vieira L.A.
      • Maside C.
      • Paes V.M.
      • Silva R.F.
      • Alves B.G.
      • Santos F.W.
      • Apgar G.A.
      • Rodrigues A.P.R.
      • Figueiredo J.R.
      Ovarian transport temperature (4 vs 33°c) impacts differently the in vitro development of isolated goat preantral and antral follicles.
      ) and one in cats (
      • Evecen M.
      • Cirit Ü.
      • Demir K.
      • Karaman E.
      • Hamzaoğlu A.İ.
      • Bakırer G.
      Developmental competence of domestic cat oocytes from ovaries stored at various durations at 4°c temperature.
      ) after ovarian tissue transportation.
      In bovines, oocyte meiotic competence and the number of cells per embryo were the main factors used to evaluate storage effects. Two studies (
      • Nakao H.
      • Nakatsuji N.
      Effects of storage conditions of bovine ovaries and oocytes on the success rate of in vitro fertilization and culture.
      ;
      • Nagao Y.
      • Harada Y.
      • Yamaguchi M.
      • Igarashi A.
      • Ooshima Y.
      • Kato Y.
      Antioxidant treatment during preservation of bovine ovaries increased the development potential of embryos.
      ) focused on the effects of media and temperature, while one (
      • Matsushita S.
      • Tani T.
      • Kato Y.
      • Tsunoda Y.
      Effect of low-temperature bovine ovary storage on the maturation rate and developmental potential of follicular oocytes after in vitro fertilization, parthenogenetic activation, or somatic cell nucleus transfer.
      ) analysed the impact of time and temperature. Using PBS, saline or Ringer's solution, the studies suggest that bovine ovarian tissue is better preserved at 20°C for up to 5 h, but higher rates of maturation and blastocyst formation are obtained when storage was between 10 and 15°C when stored for 24 h. Moreover, Nagao and colleagues (
      • Nagao Y.
      • Harada Y.
      • Yamaguchi M.
      • Igarashi A.
      • Ooshima Y.
      • Kato Y.
      Antioxidant treatment during preservation of bovine ovaries increased the development potential of embryos.
      ) observed that use of glutathione and epigallocatechin gallate in the storage medium increased blastocyst formation.
      In cats, three studies evaluated oocyte meiotic competence (
      • Naoi H.
      • Otoi T.
      • Shimamura T.
      • Karja N.W.K.
      • Agung B.
      • Shimizu R.
      • Taniguchi M.
      • Nagai T.
      Developmental competence of cat oocytes from ovaries stored at various temperature for 24 h.
      ;
      • Evecen M.
      • Cirit Ü.
      • Demir K.
      • Karaman E.
      • Hamzaoğlu A.İ.
      • Bakırer G.
      Developmental competence of domestic cat oocytes from ovaries stored at various durations at 4°c temperature.
      ;
      • Piras A.R.
      • Burrai G.P.
      • Ariu F.
      • Falchi L.
      • Zedda M.T.
      • Pau S.
      • Gadau S.D.
      • Antuofermo E.
      • Bebbere D.
      • Ledda S.
      • Bogliolo L.
      Structure of preantral follicles, oxidative status and developmental competence of in vitro matured oocytes after ovary storage at 4 degrees c in the domestic cat model.
      ). Only one (
      • Naoi H.
      • Otoi T.
      • Shimamura T.
      • Karja N.W.K.
      • Agung B.
      • Shimizu R.
      • Taniguchi M.
      • Nagai T.
      Developmental competence of cat oocytes from ovaries stored at various temperature for 24 h.
      ) reported higher rates of meiosis resumption when storage was carried out at 4°C. At this temperature, these authors found decreased MII rates after 48 h of storage (
      • Naoi H.
      • Otoi T.
      • Shimamura T.
      • Karja N.W.K.
      • Agung B.
      • Shimizu R.
      • Taniguchi M.
      • Nagai T.
      Developmental competence of cat oocytes from ovaries stored at various temperature for 24 h.
      ;
      • Evecen M.
      • Cirit Ü.
      • Demir K.
      • Karaman E.
      • Hamzaoğlu A.İ.
      • Bakırer G.
      Developmental competence of domestic cat oocytes from ovaries stored at various durations at 4°c temperature.
      ;
      • Piras A.R.
      • Burrai G.P.
      • Ariu F.
      • Falchi L.
      • Zedda M.T.
      • Pau S.
      • Gadau S.D.
      • Antuofermo E.
      • Bebbere D.
      • Ledda S.
      • Bogliolo L.
      Structure of preantral follicles, oxidative status and developmental competence of in vitro matured oocytes after ovary storage at 4 degrees c in the domestic cat model.
      ), but they all agreed that with PBS or saline solution, cat ovarian tissue can be stored for up to 24 h at 4°C. Use of superoxide dismutase increased the viability of cumulus–oocyte complexes, embryo production and expression of the antiapoptotic gene Bcl-2, while reducing the expression of Bax, an apoptosis regulator (
      • Cocchia N.
      • Corteggio A.
      • Altamura G.
      • Tafuri S.
      • Rea S.
      • Rosapane I.
      • Sica A.
      • Landolfi F.
      • Ciani F.
      The effects of superoxide dismutase addition to the transport medium on cumulus–oocyte complex apoptosis and ivf outcome in cats (felis catus).
      ).
      In pigs, studies reported reduced oocyte viability and maturation rates at low temperatures in saline solution, suggesting that porcine ovaries should be stored for a short time (<6 h) at 25–35°C (
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      ;
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      ). In PBS, follicle viability declined over time, even at 4°C, but follicle morphology remained similar to fresh controls for up to 12 h (
      • Raffel N.
      • Dittrich R.
      • Orlowski P.
      • Tischer H.
      • Söder S.
      • Erber R.
      • Hoffmann I.
      • Beckmann M.W.
      • Lotz L.
      Is ovarian tissue transport at supra-zero temperatures compared to body temperature optimal for follicle survival?.
      ).
      There is no consensus on the influence of transport temperatures on canine ovarian tissue. While some authors found this tissue to be more sensitive to low temperatures (
      • Lee H.S.
      • Yin X.J.
      • Kong I.K.
      Sensitivity of canine oocytes to low temperature.
      ;
      • Hanna C.
      • Long C.
      • Hinrichs K.
      • Westhusin M.
      • Kraemer D.
      Assessment of canine oocyte viability after transportation and storage under different conditions.
      ), others observed higher maturation rates when ovaries were transported at 4°C (
      • Tas M.
      • Evecen M.
      • Ozdas O.B.
      • Cirit U.
      • Demir K.
      • Birler S.
      • Pabuccuoglu S.
      Effect of transport and storage temperature of ovaries on in vitro maturation of bitch oocytes.
      ), or showed that the oestrous stage affects transportation more than temperature (
      • Evecen M.
      • Cirit U.
      • Demir K.
      • Ozdas O.B.
      • Tas M.
      • Birler S.
      • Pabuccuoglu S.
      Effects of estrous cycle stage and transport temperature of ovaries on in vitro maturation of canine oocytes.
      ).
      Ovaries from sheep were stored in PBS with different concentrations of melatonin, and there was an improvement in embryo quality with increasing concentrations of melatonin in the medium after storage at 4°C for 24 h (
      • Goodarzi A.
      • Zare Shahneh A.
      • Kohram H.
      • Sadeghi M.
      • Moazenizadeh M.H.
      • Fouladi-Nashta A.
      • Dadashpour Davachi N.
      Effect of melatonin supplementation in the long-term preservation of the sheep ovaries at different temperatures and subsequent in vitro embryo production.
      ). Goat oocytes showed higher meiotic resumption rates and a greater diameter of early antral follicles after 18 days of culture following ovarian tissue storage at 4°C for 4 h (
      • Correia H.H.V.
      • Vieira L.A.
      • Maside C.
      • Paes V.M.
      • Silva R.F.
      • Alves B.G.
      • Santos F.W.
      • Apgar G.A.
      • Rodrigues A.P.R.
      • Figueiredo J.R.
      Ovarian transport temperature (4 vs 33°c) impacts differently the in vitro development of isolated goat preantral and antral follicles.
      ).

      Discussion

      This is the first systematic review of the current state of ovarian tissue transportation. The authors identified 46 studies addressing optimal conditions for ovarian tissue preservation. Indeed, papers on this subject have been consistently published from 2004 to 2018 (an average of two or three per year), and continue to this day, testament to growing interest in this emerging topic of research.
      While vital organ preservation has been developed and applied over the past 60 years (reviewed by
      • Petrenko A.
      • Carnevale M.
      • Somov A.
      • Osorio J.
      • Rodríguez J.
      • Guibert E.
      • Fuller B.
      • Froghi F.
      Organ preservation into the 2020s: The era of dynamic intervention.
      ), preservation of ovarian tissue is relatively new. Hence, ovarian tissue transportation has only been recently discussed, with the concept of ‘the woman stays, the tissue moves’ established by the Danish network (
      • Jensen A.K.
      • Kristensen S.G.
      • Macklon K.T.
      • Jeppesen J.V.
      • Fedder J.
      • Ernst E.
      • Andersen C.Y.
      Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in denmark.
      ). This practice has the potential to spread extremely quickly due to the costs and bureaucracy involved in the establishment of ovarian tissue cryobanks. Pregnancies and live births have been reported after such long periods of transportation, but this systematic review demonstrates that this remains an empirical procedure.
      The aim of this review was to prompt reflection on ovarian tissue transport, given the lack of knowledge there is in humans, by scrutinizing more than 40 studies published in different animal models. Among different domestic animal species, cows, sheep and goats have been used as models for humans thanks to their physiological ovarian similarities (
      • Fransolet M.
      • Labied S.
      • Henry L.
      • Masereel M.-C.
      • Rozet E.
      • Kirschvink N.
      • Nisolle M.
      • Munaut C.
      Strategies for using the sheep ovarian cortex as a model in reproductive medicine.
      ;
      • Lunardi F.O.
      • Bass C.S.
      • Bernuci M.P.
      • Chaves R.N.
      • Lima L.F.
      • Silva R.F.
      • Figueiredo J.R.
      • Rodrigues A.P.
      Ewe ovarian tissue vitrification: A model for the study of fertility preservation in women.
      ;
      • Sirard M.A.
      The ovarian follicle of cows as a model for human.
      ). While no animal models can replace studies in our own species, they nevertheless provide valuable information that can be used in human medicine. By discussing these results in animals, an attempt can be made to identify patterns within the studies. As in the development of different ART procedures, the authors believe this is an important step to create guidelines for future studies on human ovarian tissue transportation.
      This review found that, when ovaries are stored for longer periods, lower temperatures can preserve follicle morphology and yield better oocyte maturation rates. Only two studies in pigs reported better IVM results after storage at over 25°C for 6 h (
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      ;
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      ). This may have been due to high lipid concentrations in pig oocytes, which makes them more sensitive to low temperatures (
      • Dunning K.R.
      • Russell D.L.
      • Robker R.L.
      Lipids and oocyte developmental competence: The role of fatty acids and β-oxidation.
      ).
      In fact, vital organs exposed to normothermic ischaemia remain viable for less than 1 h. Warm ischaemia leads to rapid depletion of ATP, accumulation of lactic acid, decreased pH, proteolysis, lipolysis and lipid peroxidation (

      Finger, E.B., 2019. Organ preservation. In: Shapiro, R. (Ed.):https://emedicine.medscape.com/article/431140-overview#showall.

      ). Meanwhile, hypothermia lowers metabolism 12-fold (
      • Belzer F.O.
      • Southard J.H.
      Principles of solid-organ preservation by cold storage.
      ), reducing oxygen needs during the ischaemic period (
      • Calne R.Y.
      • Pegg D.E.
      • Pryse-Davies J.
      • Brown F.L.
      Renal preservation by ice-cooling: An experimental study relating to kidney transplantation from cadavers.
      ). However, it does not completely halt metabolic activity (
      • Connolly J.K.
      • Dyer P.A.
      • Martin S.
      • Parrott N.R.
      • Pearson R.C.
      • Johnson R.W.
      Importance of minimizing hla-dr mismatch and cold preservation time in cadaveric renal transplantation.
      ;
      • Bellini M.
      • Charalampidis S.
      • Herbert P.
      • Bonatsos V.
      • Crane J.
      • Muthusamy A.
      • Dor F.
      • Papalois V.
      Cold pulsatile machine perfusion versus static cold storage in kidney transplantation: A single centre experience.
      ). Cold ischaemia causes an energy crisis, leading to injuries that are normally expressed after graft reperfusion, such as metabolic disruptions, oedema, autolysis and oxidative stress (
      • Storey K.B.
      Cold ischemic organ preservation: Lessons from natural systems.
      ).
      In ovarian follicle metabolism, it is known that primordial germ cells consume twice as much pyruvate as glucose and primordial follicles release lactate, indicating glycolysis and mitochondrial pyruvate oxidation (
      • Harris S.E.
      • Leese H.J.
      • Gosden R.G.
      • Picton H.M.
      Pyruvate and oxygen consumption throughout the growth and development of murine oocytes.
      ). As follicles develop, they become predominantly glycolytic (
      • Boland N.I.
      • Humpherson P.G.
      • Leese H.J.
      • Gosden R.G.
      Characterization of follicular energy metabolism.
      ;
      • Harris S.E.
      • Adriaens I.
      • Leese H.J.
      • Gosden R.G.
      • Picton H.M.
      Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro.
      ). Amino acids, fatty acids and glycerol may also be used by follicles for ATP production (
      • Boland N.I.
      • Humpherson P.G.
      • Leese H.J.
      • Gosden R.G.
      Pattern of lactate production and steroidogenesis during growth and maturation of mouse ovarian follicles in vitro.
      ;
      • Boland N.I.
      • Humpherson P.G.
      • Leese H.J.
      • Gosden R.G.
      The effect of glucose metabolism on murine follicle development and steroidogenesis in vitro.
      ). While there is a lack of information about metabolism during ovarian tissue transport, it was shown that when pig ovaries were stored at 25°C for 6 h, follicular fluid exhibited lower pH values (
      • Wongsrikeao P.
      • Otoi T.
      • Karja N.W.
      • Agung B.
      • Nii M.
      • Nagai T.
      Effects of ovary storage time and temperature on DNA fragmentation and development of porcine oocytes.
      ;
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      ), glucose consumption, and lactate and ROS release (
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      ). Only one of the studies in this systematic review investigated metabolism immediately after storage at low temperatures (
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      ) and only a few analysed the medium for pH and/or ROS after IVM or in-vitro culture (

      Lima, G.L., Santos, E.a.A., Lima, L.F., Luz, V.B., Rodrigues, A.P.R., Silva, A.R., 2014. Short-term preservation of pecari tajacu ovarian preantral follicles using phosphate buffered saline (pbs) or powdered coconut water (acp(r)) media %j arquivo brasileiro de medicina veterinária e zootecnia. 66, 1623-1630.

      ;
      • Correia H.H.V.
      • Vieira L.A.
      • Maside C.
      • Paes V.M.
      • Silva R.F.
      • Alves B.G.
      • Santos F.W.
      • Apgar G.A.
      • Rodrigues A.P.R.
      • Figueiredo J.R.
      Ovarian transport temperature (4 vs 33°c) impacts differently the in vitro development of isolated goat preantral and antral follicles.
      ;
      • Gastal G.D.
      • Alves B.G.
      • Alves K.A.
      • Souza M.E.
      • Vieira A.D.
      • Varela Jr., A.S.
      • Figueiredo J.R.
      • Feugang J.M.
      • Lucia Jr., T.
      • Gastal E.L.
      Ovarian fragment sizes affect viability and morphology of preantral follicles during storage at 4 degrees c.
      ;
      • Piras A.R.
      • Burrai G.P.
      • Ariu F.
      • Falchi L.
      • Zedda M.T.
      • Pau S.
      • Gadau S.D.
      • Antuofermo E.
      • Bebbere D.
      • Ledda S.
      • Bogliolo L.
      Structure of preantral follicles, oxidative status and developmental competence of in vitro matured oocytes after ovary storage at 4 degrees c in the domestic cat model.
      ). In a more recent study, Vilela and colleagues (
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      ) compared cow ovarian tissue storage in saline solution, IVF medium and L-15 at 4°C for 24 h and observed an increased lactate release in the media, even though there was low consumption of pyruvate and no consumption of glucose in IVF medium or L-15. However, these metabolic responses are associated with the assembly of different ovarian cell types (
      • Wagner M.
      • Yoshihara M.
      • Douagi I.
      • Damdimopoulos A.
      • Panula S.
      • Petropoulos S.
      • Lu H.
      • Pettersson K.
      • Palm K.
      • Katayama S.
      • Hovatta O.
      • Kere J.
      • Lanner F.
      • Damdimopoulou P.
      Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells.
      ). It is important to stress that there is a lack of data on stromal ovarian cell metabolism, which, although not directly responsible for fertility, plays a significant role in the activation of primordial follicles and development of growing follicles (
      • Parrott J.A.
      • Skinner M.K.
      Kit ligand actions on ovarian stromal cells: Effects on theca cell recruitment and steroid production.
      ;
      • Tagler D.J.
      • Shea L.D.
      • Woodruff T.K.
      Contributions of ovarian stromal cells to follicle culture.
      ).
      Overall, for most species, ovarian tissue should be transported at low temperatures to reduce metabolic activity and injuries during this period, allowing the tissue to be preserved for up to 24 h with minimal damage.
      In terms of media, there is no consensus on the best medium for ovarian tissue transport and studies have been carried out with 20 different media, none of them specific for ovarian tissue. The main media used to transport ovarian tissue are PBS and saline solution. However, follicle morphology analyses in different species show that ovarian tissue requires nutrients that are not present in these solutions. Adenine nucleotide metabolism plays a key role in organ ischaemia, and preservation solutions that take this into account yield a better quality of preservation than saline solution (

      Pegg, D.R., 2012. Organ preservation: Basic and applied aspects a symposium of the transplantation society Springer Netherlands.

      ). Indeed, when ovaries stored in PBS or saline solution were compared with those in more complex media, the latter were able to maintain normal morphology for longer periods (
      • Silva J.R.
      • Lucci C.M.
      • Carvalho F.C.
      • Bao S.N.
      • Costa S.H.
      • Santos R.R.
      • Figueiredo J.R.
      Effect of coconut water and braun-collins solutions at different temperatures and incubation times on the morphology of goat preantral follicles preserved in vitro.
      ;
      • Lima G.L.
      • Costa L.L.
      • Cavalcanti D.M.
      • Rodrigues C.M.
      • Freire F.A.
      • Fontenele-Neto J.D.
      • Silva A.R.
      Short-term storage of canine preantral ovarian follicles using a powdered coconut water (acp)-based medium.
      ;

      Lima, G.L., Santos, E.a.A., Lima, L.F., Luz, V.B., Rodrigues, A.P.R., Silva, A.R., 2014. Short-term preservation of pecari tajacu ovarian preantral follicles using phosphate buffered saline (pbs) or powdered coconut water (acp(r)) media %j arquivo brasileiro de medicina veterinária e zootecnia. 66, 1623-1630.

      ). Use of antiapoptotic (
      • Henry L.
      • Fransolet M.
      • Labied S.
      • Blacher S.
      • Masereel M.-C.
      • Foidart J.-M.
      • Noel A.
      • Nisolle M.
      • Munaut C.
      Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival.
      ) or antioxidant (
      • Nagao Y.
      • Harada Y.
      • Yamaguchi M.
      • Igarashi A.
      • Ooshima Y.
      • Kato Y.
      Antioxidant treatment during preservation of bovine ovaries increased the development potential of embryos.
      ;
      • Cocchia N.
      • Corteggio A.
      • Altamura G.
      • Tafuri S.
      • Rea S.
      • Rosapane I.
      • Sica A.
      • Landolfi F.
      • Ciani F.
      The effects of superoxide dismutase addition to the transport medium on cumulus–oocyte complex apoptosis and ivf outcome in cats (felis catus).
      ;
      • Goodarzi A.
      • Zare Shahneh A.
      • Kohram H.
      • Sadeghi M.
      • Moazenizadeh M.H.
      • Fouladi-Nashta A.
      • Dadashpour Davachi N.
      Effect of melatonin supplementation in the long-term preservation of the sheep ovaries at different temperatures and subsequent in vitro embryo production.
      ) drugs also appeared to improve the quality of ovarian tissue, pointing to important factors to be studied in future experiments. For kidney, heart, lung and pancreas preservation, many substances have been used to avoid damage caused by reperfusion, such as xanthine oxidase inhibitors (
      • Clavien P.A.
      • Harvey P.R.
      • Strasberg S.M.
      Preservation and reperfusion injuries in liver allografts.
      ), interleukins and cytokine inhibitors (
      • Colletti L.M.
      • Burtch G.D.
      • Remick D.G.
      • Kunkel S.L.
      • Strieter R.M.
      • Guice K.S.
      • Oldham K.T.
      • Campbell Jr., D.A.
      The production of tumor necrosis factor alpha and the development of a pulmonary capillary injury following hepatic ischemia/reperfusion.
      ;
      • Strüber M.
      • Harringer W.
      • Ernst M.
      • Morschheuser T.
      • Hein M.
      • Bund M.
      • Haverich A.
      Inhaled nitric oxide as a prophylactic treatment against reperfusion injury of the lung.
      ), and other components that prevent cellular oedema, delay cell destruction and maximize organ function after revascularization (
      • Ali F.
      • Dua A.
      • Cronin D.C.
      Changing paradigms in organ preservation and resuscitation.
      ;

      Mundt, H.M., Yard, B.A., Krämer, B.K., Benck, U., Schnülle, P., 2016. Optimized donor management and organ preservation before kidney transplantation. 29, 974-984. 10.1111/tri.12712.

      ). Extrapolating knowledge acquired for different organs might well provide valuable insights into ovarian tissue preservation during transportation.
      Most studies in humans were not part this systematic review because they reported outcomes of ovarian tissue cryopreservation and transplantation in clinical settings. In this context, the FertiPROTEKT network validated Custodiol as a transportation medium for up to 22 h, even though there are no data on its efficacy for ovarian tissue (
      • Beckmann M.W.
      • Lotz L.
      • Toth B.
      • Baston-Büst D.M.
      • Fehm T.
      • Frambach T.
      • Germeyer A.
      • Goeckenjan M.
      • Häberlin F.
      • Henes M.
      • Hirchenhain J.
      • Hübner S.
      • Korell M.
      • Krüssel J.-S.
      • Müller A.
      • Reinsberg J.
      • Schwab R.
      • Seitz S.
      • Sütterlin M.
      • Van Der Ven H.
      • Van Der Ven K.
      • Winkler-Crepaz K.
      • Wimberger P.
      • Von Wolff M.
      • Liebenthron J.
      • Dittrich R.
      Concept paper on the technique of cryopreservation, removal and transplantation of ovarian tissue for fertility preservation.
      ;
      • Liebenthron J.
      • Montag M.
      • Reinsberg J.
      • Köster M.
      • Isachenko V.
      • Van Der Ven K.
      • Van Der Ven H.
      • Krüssel J.-S.
      • Von Wolff M.
      Overnight ovarian tissue transportation for centralized cryobanking: A feasible option.
      ). In Denmark, 12 women underwent 18 transplantations and three babies were born to two women whose ovarian fragments were transported in α-MEM for 4–5 h prior to cryopreservation (
      • Rosendahl M.
      • Schmidt K.T.
      • Ernst E.
      • Rasmussen P.E.
      • Loft A.
      • Byskov A.G.
      • Andersen A.N.
      • Andersen C.Y.
      Cryopreservation of ovarian tissue for a decade in denmark: A view of the technique.
      ). Only four studies were conducted on human ovarian tissue transport using three different media: Celsior (
      • Klocke S.
      • Tappehorn C.
      • Griesinger G.
      Effects of supra-zero storage on human ovarian cortex prior to vitrification–warming.
      ), L-15 (
      • Isachenko V.
      • Isachenko E.
      • Mallmann P.
      • Rahimi G.
      Increasing follicular and stromal cell proliferation in cryopreserved human ovarian tissue after long-term precooling prior to freezing: In vitro versus chorioallantoic membrane (cam) xenotransplantation.
      ;
      • Kyoya T.
      • Nakamura Y.
      • Miyatani S.
      • Miyagawa T.
      • Tomiyama T.
      • Kyono K.
      Evaluation of oxygen consumption in human vitrified and warmed pre-antral follicles after prolonged low temperatures.
      ) and Brama I (
      • Isachenko E.
      • Isachenko V.
      • Nawroth F.
      • Rahimi G.
      • Weiss J.M.
      Effect of long-term exposure at suprazero temperatures on activity and viability of human ovarian cortex.
      ). However, none of them is used in clinical practice for ovarian tissue transport prior to cryopreservation, stressing the importance of this topic for future research.
      Ultimately, it is clear that different media compositions influence follicle viability and fertility outcomes, which could be related to cell metabolism. Although low temperatures reduce metabolism 12-fold, studies in animal models have shown lactate release in media (
      • Vilela J.M.V.
      • Dolmans M.M.
      • Maruhashi E.
      • Blackman M.C.N.M.
      • Sonveaux P.
      • Miranda-Vilela A.L.
      • Amorim C.
      Evidence of metabolic activity during low-temperature ovarian tissue preservation in different media.
      ) and follicular fluid (
      • Tellado M.
      • Alvarez G.
      • Dalvit G.
      • Cetica P.
      The conditions of ovary storage affect the quality of porcine oocytes.
      ), suggesting that cells might be using internal sources of energy instead of nutrients present in the media. These data indicate that ovarian tissue metabolism is affected by storage, even at low temperatures, and might impact fertility after transplantation. Moreover, it reinforces the importance of understanding whole tissue dynamics, beyond ovarian follicles.
      The reliability of assessing transportation parameters was also considered in this review. Assessment of ovarian tissue transport differs according to application. In this sense, using IVM, IVF and in-vitro culture to analyse oocytes isolated from transported tissue provides important clues to how fertility is affected by storage time, temperature and medium. Results from species that rely on these techniques for fertility preservation offer direct answers on how maturation and embryo development rates are impacted by transportation. Unfortunately, findings of this type do not apply to follicles included in ovarian tissue.
      Most studies on ovarian tissue evaluated only follicle morphology after storage. While morphology is an important criterion to observe, it does not translate to normal follicle activity, so it is necessary to allow a re-establishment of tissue activity to gauge the effects of the procedure. Some studies have used in-vitro culture of ovarian fragments, but this system is not very well established for many species, yielding low rates of follicle survival in both short- and long-term culture (
      • Isachenko V.
      • Montag M.
      • Isachenko E.
      • Van Der Ven K.
      • Dorn C.
      • Roesing B.
      • Braun F.
      • Sadek F.
      • Van Der Ven H.
      Effective method for in-vitro culture of cryopreserved human ovarian tissue.
      ;
      • Smitz J.
      • Dolmans M.M.
      • Donnez J.
      • Fortune J.E.
      • Hovatta O.
      • Jewgenow K.
      • Picton H.M.
      • Plancha C.
      • Shea L.D.
      • Stouffer R.L.
      • Telfer E.E.
      • Woodruff T.K.
      • Zelinski M.B.
      Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: Implications for fertility preservation.
      ;
      • Vilela J.M.V.
      • Leonel E.C.R.
      • D'oliveira L.
      • Paiva R.E.G.
      • Miranda-Vilela A.L.
      • Amorim C.A.
      • Pic-Taylor A.
      • Lucci C.M.
      Culture of domestic cat ovarian tissue in vitro and in the chick embryo chorioallantoic membrane.
      ). Since ovarian tissue transplantation has already been validated for cryopreservation assessment (
      • Nottola S.A.
      • Camboni A.
      • Van Langendonckt A.
      • Demylle D.
      • Macchiarelli G.
      • Dolmans M.-M.
      • Martinez-Madrid B.
      • Correr S.
      • Donnez J.
      Cryopreservation and xenotransplantation of human ovarian tissue: An ultrastructural study.
      ;
      • Amorim C.A.
      • David A.
      • Dolmans M.-M.
      • Camboni A.
      • Donnez J.
      • Van Langendonckt A.
      Impact of freezing and thawing of human ovarian tissue on follicular growth after long-term xenotransplantation.
      ;
      • Luyckx V.
      • Scalercio S.
      • Jadoul P.
      • Amorim C.A.
      • Soares M.
      • Donnez J.
      • Dolmans M.-M.
      Evaluation of cryopreserved ovarian tissue from prepubertal patients after long-term xenografting and exogenous stimulation.
      ;
      • Ayuandari S.
      • Winkler-Crepaz K.
      • Paulitsch M.
      • Wagner C.
      • Zavadil C.
      • Manzl C.
      • Ziehr S.C.
      • Wildt L.
      • Hofer-Tollinger S.
      Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in scid mice: Dynamics and molecular aspects.
      ;
      • Ruan X.
      • Cui Y.
      • Du J.
      • Jin J.
      • Gu M.
      • Chen S.
      • Mueck A.O.
      Randomized study to prove the quality of human ovarian tissue cryopreservation by xenotransplantation into mice.
      ;
      • Vilela J.M.V.
      • Leonel E.C.R.
      • Gonçalves L.P.
      • Paiva R.E.G.
      • Amaral R.S.
      • Amorim C.A.
      • Lucci C.M.
      Function of cryopreserved cat ovarian tissue after autotransplantation.
      ), it might be a valuable technique to evaluate tissue transport. Indeed, transplantation of mouse ovarian tissue was used to assess ovarian tissue storage and revealed a significant reduction in both implantation and live birth rates, even though the morphology before transplantation did not show any difference in the percentage of morphologically normal follicles (
      • Kamoshita K.
      • Okamoto N.
      • Nakajima M.
      • Haino T.
      • Sugimoto K.
      • Okamoto A.
      • Sugishita Y.
      • Suzuki N.
      Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation.
      ).
      This systematic review was, however, limited by the fact it was based on full-text publications in English. Studies published in different languages were not included in the investigation.
      This review highlights the limited knowledge there is on ovarian tissue transportation conditions for all species addressed. Results from studies in this systematic review, as well as reports from clinical settings, demonstrate that finding a solution that meets ovarian tissue needs is essential to improving ART techniques. While there is mostly a consensus on maintaining ovarian tissue at low temperatures (namely 4°C), it is vital to consider different types of ovarian cells, as well as their interactions and needs, to be able to establish a standard protocol for ovarian tissue transport according to each species. Elucidating stromal cell metabolism and whole ovary dynamics is essential to developing a specific medium to transport ovarian tissue destined for transplantation. Moreover, interdisciplinary studies will play a crucial role in the development of ovarian tissue transport media; much has been learned and developed for vital organs, and this knowledge can be used to study how to improve the quality of ovarian tissue after transport. Assessment of follicle development and function should also be addressed in future studies to understand how fertility is affected by transport protocols once tissue vascularization has been restored (Figure 3).
      Figure 3
      Figure 3Guidelines for developing a standard protocol for ovarian tissue transportation.
      With increasing demand for ovarian tissue cryopreservation and transplantation around the world, creating standard protocols for efficient transport is imperative in order to reach more patients, who can then have biopsies taken in small clinics and hospitals, and frozen in national tissue bank centres. It is also important to stress that improving transport may also affect the quality of the grafts and reproductive outcomes, which in turn can have a positive impact on birth rates after ART.

      Conclusion

      Upon review of the current literature, it is clear that there are no set standards for ovarian tissue transportation and, to date, its evaluation has been largely empirical. Ovarian tissue should be transported at 4°C to minimize ischaemic damage, and it is vital to create guidelines for ovarian tissue transportation to enhance ART outcomes in all species. To be able to develop a medium that meets the needs of ovarian tissue, it is essential to study the metabolic activity of this tissue, and not only isolated follicles, to discern how whole-tissue dynamics affect fertility. Moreover, assessment of transported tissue should be conducted after its return to activity. Finally, to shed light on the effects of procuring ovarian tissue for grafting, xenotransplantation is still the best means of evaluating ovarian tissue transportation.

      Acknowledgments

      The authors would like to thank Mira Hryniuk, BA, for the English language revision of this manuscript. This study was supported by grants from Wallonia-Brussels International (WBI) (grant WBI-IN awarded to J. M. V. Vilela) and the Fonds National de la Recherche Scientifique de Belgique (FNRS) (C. A. Amorim is an FRS-FNRS Research Associate; grant 5/4/150/5 awarded to M. M. Dolmans).

      Appendix. Supplementary materials

      References

        • Ali F.
        • Dua A.
        • Cronin D.C.
        Changing paradigms in organ preservation and resuscitation.
        Current opinion in organ transplantation. 2015; 20: 152-158https://doi.org/10.1097/MOT.0000000000000180
        • Amorim C.A.
        • David A.
        • Dolmans M.-M.
        • Camboni A.
        • Donnez J.
        • Van Langendonckt A.
        Impact of freezing and thawing of human ovarian tissue on follicular growth after long-term xenotransplantation.
        Journal of assisted reproduction and genetics. 2011; 28: 1157-1165https://doi.org/10.1007/s10815-011-9672-z
        • Ayuandari S.
        • Winkler-Crepaz K.
        • Paulitsch M.
        • Wagner C.
        • Zavadil C.
        • Manzl C.
        • Ziehr S.C.
        • Wildt L.
        • Hofer-Tollinger S.
        Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in scid mice: Dynamics and molecular aspects.
        Journal of assisted reproduction and genetics. 2016; 33: 1585-1593https://doi.org/10.1007/s10815-016-0769-2
        • Barberino R.
        • Gonçalves R.
        • Menezes V.G.
        • Barros V.
        • Lins T.
        • Gouveia B.
        • Macedo T.
        • Santos L.
        • Matos M.
        Influence of the ovarian fragmentation before storage at 4°c on the apoptosis rates and in vitro development of ovine preantral follicles.
        Animal Reproduction. 2016; 13: 28-35https://doi.org/10.4322/1984-3143-AR772
        • Barberino R.S.
        • Silva J.R.V.
        • Figueiredo J.R.
        • Matos M.H.T.
        Transport of domestic and wild animal ovaries: A review of the effects of medium, temperature, and periods of storage on follicular viability.
        Biopreservation and Biobanking. 2018; 17: 84-90https://doi.org/10.1089/bio.2018.0057
        • Beckmann M.W.
        • Lotz L.
        • Toth B.
        • Baston-Büst D.M.
        • Fehm T.
        • Frambach T.
        • Germeyer A.
        • Goeckenjan M.
        • Häberlin F.
        • Henes M.
        • Hirchenhain J.
        • Hübner S.
        • Korell M.
        • Krüssel J.-S.
        • Müller A.
        • Reinsberg J.
        • Schwab R.
        • Seitz S.
        • Sütterlin M.
        • Van Der Ven H.
        • Van Der Ven K.
        • Winkler-Crepaz K.
        • Wimberger P.
        • Von Wolff M.
        • Liebenthron J.
        • Dittrich R.
        Concept paper on the technique of cryopreservation, removal and transplantation of ovarian tissue for fertility preservation.
        Geburtshilfe Frauenheilkd. 2019; 79: 53-62https://doi.org/10.1055/a-0664-8619
        • Bellini M.
        • Charalampidis S.
        • Herbert P.
        • Bonatsos V.
        • Crane J.
        • Muthusamy A.
        • Dor F.
        • Papalois V.
        Cold pulsatile machine perfusion versus static cold storage in kidney transplantation: A single centre experience.
        BioMed. Research International. 2019; 2019https://doi.org/10.1155/2019/7435248