journal article·2026-06Open access

Innovative technologies to support reproductive medicine: High-resolution synchrotron radiation nanotomography to explore cryopreserved oocytes ultrastructures

Elena Longo, Cristina Tufoni, Giulia Saccomano, Marina Eckermann, Stefania Luppi, Simone A.M. Lemmers, Elena Giolo, Sara Bozzer, Marina Zweyer, Giuliana Tromba, Giuseppe Ricci, Lorella Pascolo

Materials & Design· Volume 266

Abstract

• Oocyte vitrification: a fertility preservation option in young cancer patients. • X-ray nanoimaging has been used for visualizing intact human cryopreserved oocytes. • The 3D approach enables to identify morphological markers of cold shock injuries. • This cutting-edge technology proved as a powerful tool to evaluate oocyte quality. Oocyte vitrification represents a tangible option for preserving fertility in patients of reproductive age undergoing oncological treatments. Evaluation of oocyte quality, especially the detection of potential ultrastructural damage induced by cryostorage and subsequent thawing, is crucial to safeguard successful in vitro fertilization. In this work, synchrotron radiation-based X-ray phase-contrast nanotomography (nanoCT) is used for the first time to assess the quality of intact human cryopreserved oocytes. This novel experimental pipeline has been implemented i) at room temperature following the oocytes’ cooling-warming procedure and ii) in cryogenic conditions simulating real-time oocyte freezing by in-situ cryo-nanoCT. Both three-dimensional (3D) explorations provide morphological insights of relevance for the overall gamete review, even allowing the identification of structural defects attributable to cryo-injuries. Here, X-ray nanoCT results are compared with images obtained by standard techniques routinely used to observe oocytes integrity, such as light microscopy and transmission electron microscopy (TEM). This proof-of-concept evidences that X-ray nanoimaging can effectively complement the well-established approaches thanks to its non-destructive nature and its capacity to deliver 3D information. Thus, our study introduces a novel methodological framework aiming to integrate cutting-edge imaging with cryotechnology in order to drive advances in assisted reproduction research.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Reproductive Biology and Fertility · Advanced X-ray Imaging Techniques · Advanced Electron Microscopy Techniques and Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (67)

Show source-provided references
1. Fertility in female cancer survivors: a systematic review and meta-analysis10.1016/j.rbmo.2020.02.008 ↗
2. Fertility after cancer: risks and successes10.3390/cancers14102500 ↗
3. J. Himpe, S. Lammerant, L. den Bergh, L. Lapeire, C. De Roo, The impact of systemic oncological treatments on the fertility of adolescents and young adults—a systematic review. 13 (2023). https://doi.org/10.3390/life13051209.10.3390/life13051209 ↗
4. K.A. Rodriguez-Wallberg, Y. Jiang, T. Lekberg, H.P. Nilsson, The Late Effects of Cancer Treatment on Female Fertility and the Current Status of Fertility Preservation—A Narrative Review. 13 (2023). https://doi.org/10.3390/life13051195.10.3390/life13051195 ↗
5. High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: a systematic review and meta-analysis10.1016/j.breast.2025.104514 ↗
6. Psychosocial aspects of infertility and decisions about reproduction in young cancer survivors: a review10.1002/(SICI)1096-911X(199907)33:1<53::AID-MPO10>3.0.CO;2-K ↗
7. Trends in patient age at planned oocyte cryopreservation10.1007/s10815-024-03237-z ↗
8. Optimizing patient information material for a new psycho-oncological care program using a participatory health research approach in Germany10.3390/ijerph19031518 ↗
9. The ESHRE Guideline Group on Female Fertility Preservation, R.A. Anderson, F. Amant, D. Braat, A. D’Angelo, S.M. Chuva De Sousa Lopes, I. Demeestere, S. Dwek, L. Frith, M. Lambertini, C. Maslin, M. Moura-Ramos, D. Nogueira, K. Rodriguez-Wallberg, N. Vermeulen, ESHRE guideline: female fertility preservation, Hum. Reprod. Open 2020 (2020) hoaa052. https://doi.org/10.1093/hropen/hoaa052.10.1093/hropen/hoaa052 ↗
10. Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org., Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion, Fertil. Steril. 112 (2019) 1022–1033. https://doi.org/10.1016/j.fertnstert.2019.09.013.10.1016/j.fertnstert.2019.09.013 ↗
11. Fertility preservation: the challenge of freezing and transplanting ovarian tissue10.1016/j.molmed.2020.11.003 ↗
12. Fertility preservation in women10.1038/nrendo.2013.205 ↗
13. Use of in vitro fertilization — ethical issues10.1080/03009734.2019.1684405 ↗
14. Human oocyte cryopreservation: revised evidence for practice10.1080/14647273.2023.2190987 ↗
15. Clinical outcome of emergency egg vitrification for women when sperm extraction from the testicular tissues of the male partner is not successful10.3109/19396368.2011.566666 ↗
16. Failed sperm retrieval from severely oligospermic or non-obstructive azoospermic patients on oocyte retrieval day: emergent oocyte cryopreservation is a feasible strategy10.1371/journal.pone.0224919 ↗
17. Cryoprotective agents10.1016/0011-2240(71)90024-1 ↗
18. A two-factor hypothesis of freezing injury: evidence from chinese hamster tissue-culture cells10.1016/0014-4827(72)90303-5 ↗
19. Developmental consequences of cryopreservation of mammalian oocytes and embryos10.1016/S1472-6483(10)62126-8 ↗
20. A brief history of oocyte cryopreservation: arguments and facts10.1111/aogs.13569 ↗
21. The causes of reduced fertility with cryopreserved semen10.1016/S0378-4320(00)00099-3 ↗
22. The effect of cryopreservation on the genome of gametes and embryos: principles of cryobiology and critical appraisal of the evidence10.1093/humupd/dmu063 ↗
23. The history and principles of cryopreservation10.1055/s-2002-23515 ↗
25. Significance of egg’s zona pellucida glycoproteins in sperm-egg interaction and fertilization
26. Oocyte zona pellucida dysmorphology is associated with diminished in-vitro fertilization success10.1186/s13048-014-0111-5 ↗
27. Human metaphase II oocytes with narrow perivitelline space have poor fertilization, developmental, and pregnancy potentials10.1007/s10815-024-03084-y ↗
28. Does first polar body morphology predict oocyte performance during ICSI treatment?10.1007/s10815-009-9368-9 ↗
29. Effect of oocyte morphology on embryo development and implantation10.1016/S1472-6483(10)61187-X ↗
30. Morphology of in-vitro matured oocytes: impact on fertility potential and embryo quality10.1093/humrep/16.8.1714 ↗
31. Fertilization and embryo quality of mature oocytes with specific morphological abnormalities10.5653/cerm.2015.42.4.156 ↗
32. The ultrastructural nature of human oocytes’ cytoplasmic abnormalities and the role of cytoskeleton dysfunction
33. Ultrastructure of human oocytes after in vitro maturation10.1093/molehr/gav071 ↗
34. Oocyte vitrification technology has made egg-sharing donation easier in China10.1016/j.rbmo.2011.11.002 ↗
35. Hard and soft X-ray imaging to resolve human ovarian cortical structures10.1107/S1600577519003680 ↗
36. Three-dimensional micro-computed tomography of the adult mouse ovary10.3389/fcell.2020.566152 ↗
37. Three-dimensional imaging and reconstruction of the whole ovary and testis: a new frontier for the reproductive scientist10.1093/molehr/gaab007 ↗
38. Morphological and chemical investigation of ovarian structures in a bovine model by contrast-enhanced X-ray imaging and microscopy10.3390/ijms24043545 ↗
39. Endothelial cell supplementation promotes xenograft revascularization during short-term ovarian tissue transplantation
40. Hard X-ray nanoholotomography: large-scale, label-free, 3D neuroimaging beyond optical limit
41. Three-dimensional architecture of human diabetic peripheral nerves revealed by X-ray phase contrast holographic nanotomography10.1038/s41598-020-64430-5 ↗
42. 3D virtual pathohistology of lung tissue from Covid-19 patients based on phase contrast X-ray tomography10.7554/eLife.60408 ↗
43. X-ray structural analysis of single adult cardiomyocytes: tomographic imaging and microdiffraction10.1016/j.bpj.2020.08.019 ↗
44. Origin and temperature dependence of radiation damage in biological samples at cryogenic temperatures10.1073/pnas.0905481107 ↗
45. Dynamics of topological defects and structural synchronization in a forming periodic tissue10.1038/s41567-020-01069-z ↗
46. Experimental comparison of X-ray ptychographic and holographic nanotomography of metal-stained neuronal tissue10.1364/OE.563186 ↗
47. Cryo X‐ray microscopy10.1080/08940889508602810 ↗
48. Cryocooling and radiation damage in macromolecular crystallography10.1107/S0907444905034207 ↗
49. High resolution protein localization using soft X-ray microscopy10.1046/j.1365-2818.2001.00845.x ↗
50. Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography10.1073/pnas.1801678115 ↗
51. 3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography10.7554/eLife.71359 ↗
52. Investigating gut alterations in Alzheimer’s disease: In-depth analysis with micro- and nano-3D X-ray phase contrast tomography10.1126/sciadv.adr8511 ↗
53. Embryo development of fresh ‘versus’ vitrified metaphase II oocytes after ICSI: a prospective randomized sibling-oocyte study10.1093/humrep/dep346 ↗
54. The biology and dynamics of mammalian cortical granules10.1186/1477-7827-9-149 ↗
55. Does morphological assessment predict oocyte developmental competence? A systematic review and proposed score10.1007/s10815-021-02370-3 ↗
56. Genetics of oocyte maturation defects and early embryo development arrest10.3390/genes13111920 ↗
57. genetic abnormalities of oocyte maturation: mechanisms and clinical implications
58. Ultrastructure of human mature oocytes after vitrification10.4081/ejh.2012.e38 ↗
59. The effects of vitrification on oocyte quality10.1093/biolre/ioab239 ↗
60. Oocyte vitrification: advances, progress and future goals10.1007/s10815-014-0180-9 ↗
61. Freeze/thaw stress induces organelle remodeling and membrane recycling in cryopreserved human mature oocytes10.1007/s10815-016-0798-x ↗
62. T.E.G.G. on O. Stimulation, E. Bosch, S. Broer, G. Griesinger, M. Grynberg, P. Humaidan, E. Kolibianakis, M. Kunicki, A. La Marca, G. Lainas, N. Le Clef, N. Massin, S. Mastenbroek, N. Polyzos, S.K. Sunkara, T. Timeva, M. Töyli, J. Urbancsek, N. Vermeulen, F. Broekmans, ESHRE guideline: ovarian stimulation for IVF/ICSI†, Hum. Reprod. Open 2020 (2020) hoaa009. https://doi.org/10.1093/hropen/hoaa009.10.1093/hropen/hoaa009 ↗
63. Phase objects in synchrotron radiation hard x-ray imaging10.1088/0022-3727/29/1/023 ↗
64. Holotomography: quantitative phase tomography with micrometer resolution using hard synchrotron radiation X rays10.1063/1.125225 ↗
65. Evaluation of phase retrieval approaches in magnified X-ray phase nano computerized tomography applied to bone tissue10.1364/OE.26.011110 ↗
66. P. Paleo, J. Lesaint, H. Payno, A. Mirone, N. Vigano, C. Nemoz, Nabu 2024.1, (2024). https://doi.org/10.5281/ZENODO.11104029.
67. Fiji: an open-source platform for biological-image analysis10.1038/nmeth.2019 ↗