Maturation of oocytes in vitro: biological basis and prospects for clinical use

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

In vitro oocyte maturation (IVM) involves the aspiration of prophase I oocytes in oocyte-cumulus complexes from small antral follicles and their subsequent maturation to metaphase II (MII). IVM is a promising method for obtaining MII oocytes in cases where hormonal stimulation of the ovaries is undesirable or impossible. At the same time, in terms of maturation rates and developmental capacity, oocytes obtained as a result of the IVM procedure are inferior to oocytes obtained in stimulated cycles; therefore, improving IVM protocols is a hot topic. The review discusses the possibilities of the IVM procedure in the context of key stages of oocyte maturation and their achievement of nuclear and cytoplasmic maturity. The advantages and disadvantages of various IVM techniques and the main directions for their further improvement are highlighted.

Full Text

Restricted Access

About the authors

А. O. Drobintseva

Saint Petersburg State Pediatric Medical University

Author for correspondence.
Email: ao.drobintseva@gpmu.org
Russian Federation, Saint Petersburg

V. K. Frolov

Saint Petersburg State Pediatric Medical University

Email: ao.drobintseva@gpmu.org
Russian Federation, Saint Petersburg

I. O. Bogolyubova

Saint Petersburg State Pediatric Medical University; Institute of Cytology, Russian Academy of Sciences

Email: ibogol@mail.ru
Russian Federation, Saint Petersburg; Saint Petersburg

O. E. Savelyeva

Saint Petersburg State Pediatric Medical University

Email: ao.drobintseva@gpmu.org
Russian Federation, Saint Petersburg

S. A. Kuleva

Saint Petersburg State Pediatric Medical University

Email: ao.drobintseva@gpmu.org
Russian Federation, Saint Petersburg

References

  1. Адамян Л. В., Носов В. Б., Степанян А. А. 2024. Лечение, сохраняющее фертильность у онкологических пациентов: чем мы можем помочь в XXI веке? Проблемы репродукции. Т. 30. № 1. С. 26. (Adamyan L. V., Nosov V. B., Stepanyan A. A. 2024. Fertility-sparing treatment in cancer patients: What can we offer in the XXI century? Russian Journal of Human Reproduction. V. 30. No. 1. P. 26.)
  2. Буняева Е. С., Кириллова А. О., Назаренко Т. А., Джанашвили Л. Г., Гаджимагомедова К. К., Хабас Г. Н., Бирюкова А. М., Гависова А. А. 2022. Показания и эффективность технологии получения незрелых ооцит-кумулюсных комплексов из ткани яичника с последующим их дозреванием in vitro. Акушерство и гинекология. № 6. С. 75. (Bunayeva E. S., Kirillova A. O., Nazarenko T. A., Dzhanashvili L. G., Gadzhimagomedova K. K., Khabas G. N., Biryukova A. M., Gavisova A. A. 2022. Indications and efficacy of the technique for retrieving immature oocyte-cumulus complexes from ovarian tissue followed by their in vitro maturation. Obstetrics and Gynecology. No. 6. P. 75.) https://dx.doi.org/10.18565/aig.2022.6.75-82
  3. Иванов Д. О., Тайц А. Н., Дитковская Л. В., Матвеева Н. Н., Красногорская О. Л., Поздняков А. В., Мызникова Н. Н., Малышева А. А., Кузьминых С. В., Орлова А. Д., Веретенникова А. А. 2022. Неонатальный сахарный диабет и поликистоз яичников у ребенка с тяжелой инсулинорезистентностью, обусловленной вариантом в гене INSR. Описание клинического случая. Педиатр. Т. 13. № 6. С. 109.
  4. Корсак В. С., Смирнова А. А., Шурыгина О. В. 2021. Регистр ВРТ Российской ассоциации репродукции человека. Отчет за 2018 год. Проблемы репродукции. Т. 27. № 2. С. 6. (Korsak V. S., Smirnova A. A., Shurygina O. V. 2021. The ART Register of the Russian Association of Human Reproduction: 2018 Report. Russian Journal of Human Reproduction. V. 27. No. 2. P. 6.)
  5. Корсак В. С., Смирнова А. А., Шурыгина О. В. 2021.Регистр ВРТ Российской ассоциации репродукции человека. Отчет за 2019 год. Проблемы репродукции. Т. 27. № 6. С. 14. (Korsak V. S., Smirnova A. A., Shurygina O. V. 2021. The ART Register of the Russian Association of Human Reproduction: 2019 Report. Russian Journal of Human Reproduction. V. 27. No. 6. P. 14.)
  6. Корсак В. С., Смирнова А. А., Шурыгина О. В. 2023. Регистр ВРТ Общероссийской общественной организации «Российская ассоциация репродукции человека». Отчет за 2021 год. Проблемы репродукции. Т. 29. № 6. С. 25. (Korsak V. S., Smirnova A. A., Shurygina O. V. 2023. The ART Register of the Russian Association of Human Reproduction: 2021 Report. Russian Journal of Human Reproduction. V. 29. No. 6. P. 25.)
  7. Корсак В. С., Смирнова А. А., Шурыгина О. В. 2024. Регистр ВРТ Общероссийской общественной организации «Российская ассоциация репродукции человека». Отчет за 2022 год. Проблемы репродукции. Т. 30. № 6. С. 8. (Korsak V. S., Smirnova A. A., Shurygina O. V. 2024. The ART Register of the Russian Association of Human Reproduction: 2022 Report. Russian Journal of Human Reproduction. V. 30. No. 6. P. 8.)
  8. Лавринович О. Е., Татищева Ю. А., Берлев И. В., Яковлева М. Г., Карицкий А. П., Калугина А. С. 2024. OТО-IVM — метод сохранения фертильности пациенткам с опухолевым поражением яичников. Сибирский онкологический журнал. Т. 23. № 4. С. 96. (Lavrinovich O. E., Tatishcheva Yu.A., Berlev I. V., Yakovleva M. G., Karitsky A. P., Kalugina A. S. 2024. OTO-IVM: A fertility preservation method for patients with ovarian tumor involvement. Siberian Journal of Oncology. V. 23. No. 4. P. 96.) https://doi.org/10.21294/1814-4861-2024-23-4-96-107
  9. Лапина И. А., Доброхотова Ю. Э., Сорокин Ю. А., Малахова А. А., Чирвон Т. Г., Таранов В. В., Германович Н. Ю., Ковальская Е. В., Кайкова О. В., Гомзикова В. М., Твердикова М. А. 2022. Сохранение репродуктивного материала при помощи метода in vitro maturation у пациенток с онкологическими заболеваниями. Гинекология. Т. 24. № 1. С. 41. (Lapina I. A., Dobrokhotova Yu.E., Sorokin Yu.A., Malakhova A. A., Chyrvon T. G., Tarantov V. V., Germanovich N. Yu., Kovalskaya E. V., Kaykova O. V., Gomzikova V. M., Tverdikova M. A. 2022. Fertility preservation using in vitro maturation method in cancer patients. Gynecology. V. 24. No. 1. P. 41.) https://doi.org/10.26442/20795696.2022.1.201350
  10. Макарова Н. П., Сысоева А. П., Силачев Д., Непша О. С., Горюнов К. В., Шевцова Ю. А., Калинина Е. А., Зингеренко Б. В., Сухих Г. Т. 2023. Технология дозревания ооцитов человека на стадии GV с помощью внеклеточных везикул фолликулярной жидкости в программах экстракорпорального оплодотворения. Патент. Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В. И. Кулакова МЗРФ. (Makarova N. P., Sysoeva A. P., Silachev D., Nepsha O. S., Goryunov K. V., Shevtsova Yu.A., Kalinina E. A., Zingerenko B. V., Sukhikh G. T. 2023. Technology for human oocyte maturation at GV stage using extracellular vesicles from follicular fluid in in vitro fertilization programs. Patent. Academician V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation.)
  11. Михайлова Н. Д., Мишиева Н. Г., Кириллова А. О., Мартазанова Б. А., Джинчарадзе Л. Г. 2021. Дозревание ооцитов in vitro. Акушерство и гинекология. № 11. С. 64. (Mikhailova N. D., Misheva N. G., Kirillova A. O., Martazanova B. A., Dzhincharaдze L. G. 2021. In vitro oocyte maturation. Obstetrics and Gynecology. No. 11. P. 64.) https://dx.doi.org/10.18565/aig.2021.11.64-70
  12. Петров И. А., Дмитриева М. Л., Тихоновская О. А., Петрова М. С., Логвинов С. В. 2017. Тканевые и молекулярные основы фолликулогенеза. Механизмы раннего фолликулярного роста. Проблемы репродукции. Т. 23. № 5. С. 33. (Petrov I. A., Dmitrieva M. L., Tikhonovskaya O. A., Petrova M. S., Logvinov S. V. 2017. Tissue and molecular basis of folliculogenesis: Mechanisms of early follicular growth. Russian Journal of Human Reproduction. V. 23. No. 5. P. 33.) https://doi.org/10.17116/repro201723533-41
  13. Смирнова А. А., Сергеев С. А., Жорданидзе Д. О., Аншина М. Б. 2020. IVM у пациенток с высоким риском развития СГЯ. Проблемы репродукции. Т. 26. № 2. С. 47. (Smirnova A. A., Sergeev S. A., Zhordanidze D. O., Anshina M. B. 2020. IVM for patients at high risk of OHSS. Russian Journal of Human Reproduction. V. 26. No. 2. P. 47.)
  14. Соколова Ю. В., Мартиросян Я. О., Назаренко Т. А., Бирюкова А. М., Хубаева Д. Г., Краснова В. Г. 2022. Молекулярно-биологические основы внутри яичникового фолликулогенеза, созревания и рекрутинга фолликулов. Акушерство и гинекология. № 1. С. 22. (Sokolova Yu.V., Martirosyan Ya.O., Nazarenko T. A., Biryukova A. M., Khubaeva D. G., Krasnova V. G. 2022. Molecular and biological basis of intraovarian folliculogenesis, follicle maturation and recruitment. Obstetrics and Gynecology. No. 1. P. 22.)
  15. Элленбоген А., Шалом-пац Е., Аншина М. Б., Смирнова А. А. 2015. Дозревание ооцитов in vitro. Показания, техника и результаты. Проблемы репродукции. Т. 21. № 1. С. 32. (Ellenbogen A., Shalom-Paz E., Anshina M. B., Smirnova A. A. 2015. In vitro oocyte maturation: Indications, techniques and outcomes. Russian Journal of Human Reproduction. V. 21. No. 1. P. 32.)
  16. Anderson R. A., Wallace W. H.B., Telfer E. E. 2017. Ovarian tissue cryopreservation for fertility preservation: clinical and research perspectives. Hum. Reprod. Open. 2017: Article ID: hox001. https://doi.org/10.1093/hropen/hox001
  17. Ben-Haroush A., Abir R., Sapir O., Garor R., Fisch B. 2017. Aspiration of immature oocytes during cesarean section for fertility preservation. J. Matern. Fetal Neonatal Med. V. 30. P. 2112. https://doi.org/10.1080/14767058.2016.1238895
  18. Bosch E., Broer S., Griesinger G., Grynberg M., Humaidan P., Kolibianakis E., Kunicki M., La Marca A., Lainas G., Le Clef N., Massin N, Mastenbroek S., Polyzos N., Sunkara S. K., Timeva T., et al. 2020. ESHRE guideline: ovarian stimulation for IVF/ICSI. Hum. Reprod. Open. V. 2020. Article ID: hoaa009. https://doi.org/10.1093/hropen/hoaa009
  19. Cadenas J., la Cour Poulsen L., Mamsen L. S., Andersen C. Y. 2023. Future potential of in vitro maturation including fertility preservation. Fertil. Steril. V. 119. P. 550. https://doi.org/10.1016/j.fertnstert.2023.01.027
  20. Cekleniak N. A., Combelles C. M., Ganz D. A., Fung J., Albertini D. F., Racowsky C. 2001. A novel system for in vitro maturation of human oocytes. Fertil. Steril. V. 75. P. 1185. https://doi.org/10.1016/s0015-0282(01)01789-7
  21. Cha K. Y., Koo J. J., Ko J. J., Choi D. H., Han S. Y., Yoon T. K. 1991. Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles, their culture in vitro and their transfer in a donor oocyte program. Fertil. Steril. V. 55. P. 109. https://doi.org/10.1016/s0015-0282(16)54068-0
  22. Chian R. C., Gulekli B., Buckett W. M., Tan S. L. 1999. Priming with human chorionic gonadotropin before retrieval of immature oocytes in women with infertility due to the polycystic ovary syndrome. New Engl. J. Med. V. 341. P. 1624.
  23. Clarke H. 2017. Control of mammalian oocyte development by interactions with the maternal follicular environment. Results Probl. Cell Differ. V. 63. P. 17. https://doi.org/10.1007/978-3-319-60855-6_2
  24. Cobo A., Meseguer M., Remohí J., Pellicer A. 2010. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial. Hum. Reprod. V. 25. P. 2239. https://doi.org/10.1093/humrep/deq146
  25. Combelles C. M., Fissore R. A., Albertini D. F., Racowsky C. 2005. In vitro maturation of human oocytes and cumulus cells using a co-culture three-dimensional collagen gel system. Hum. Reprod. V. 20. P. 1349. https://doi.org/10.1093/humrep/deh750
  26. Conti M., Franciosi F. 2018. Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Hum. Reprod. Update. V. 24. P. 245. https://doi.org/10.1093/humupd/dmx040
  27. Coticchio G., Dal-Canto M., Guglielmo M. C., Mignini-Renzini M., Fadini R. 2012. Human oocyte maturation in vitro. Int. J. Dev. Biol. V. 56. P. 909. https://doi.org/10.1387/ijdb.120135gv
  28. Das M., Son W. Y. 2023. In vitro maturation (IVM) of human immature oocytes: is it still relevant? Reprod. Biol. Endocrinol. V. 21. P. 110. https://
  29. Das M., Son W. Y., Buckett W., Tulandi T., Holzer H. 2014. In vitro maturation versus IVF with GnRH antagonist for women with polycystic ovary syndrome: treatment outcome and rates of ovarian hyperstimulation syndrome. Reprod. Biomed. Online. V. 29. P. 545. https://doi.org/10.1016/j.rbmo.2014.07.019
  30. de Araujo C. H., Nogueira D., de Araujo M. C., de Martins W. P., Ferriani R. A., dos Reis R. M. 2009. Supplemented tissue culture medium 199 is a better medium for in vitro maturation of oocytes from women with polycystic ovary syndrome women than human tubal fluid. Fertil. Steril. V. 91. P. 509. https://doi.org/10.1016/j.fertnstert.2007.11.082
  31. De Vos M., Smitz J., Thompson J. G., Gilchrist R. B. 2016. The definition of IVM is clear-variations need defining. Hum. Reprod. V. 31. P. 2411. https://doi.org/10.1093/humrep/dew208
  32. Erickson G. F. 2008. Follicle growth and development. Glob. Libr. Women’s Med. (ISSN: 1756-2228). https://doi.org/10.3843/GLOWM.10289
  33. Escrich L., Galiana Y., Grau N., Insua F., Soler N., Pellicer A., Escribá M. 2018. Do immature and mature sibling oocytes recovered from stimulated cycles have the same reproductive potential? Reprod. Biomed. Online. V. 37. P. 667.
  34. Filali M., Hesters L., Fanchin R., Tachdjian G., Frydman R., Frydman N. 2008. Retrospective comparison of two media for invitro maturation of oocytes. Reprod. Biomed. Online. V. 16. P. 250. https://doi.org/10.1016/s1472-6483(10)60582-2
  35. Fortune J. E. 2003. The early stages of follicular development: activation of primordial follicles and growth of preantral follicles. Anim. Reprod. Sci. V. 78. P. 1353. https://doi.org/10.1016/s0378*4320(03)00088-5
  36. Gong X., Li H., Zhao Y. 2022. The improvement and clinical application of human oocyte in vitro maturation (IVM). Reprod. Sci. V. 29. P. 2127. https://doi.org/10.1007/s43032-021-00613-3
  37. Gougeon A. 1986. Dynamics of follicular growth in the human: a model from preliminary results. Hum. Reprod. V. 1. P. 81.
  38. https://doi.org/10.1093/oxfordjournals.humrep.a136365
  39. Gougeon A. 2010. Human ovarian follicular development: from activation of resting follicles to preovulatory maturation. Ann. Endocrinol. (Paris). V. 71. P. 132. https://doi.org/10.1016/j.ando.2010.02.021
  40. Hanfling S. N., Parikh T., Mayhew A., Robinson E., Graham J., Gomez-Lobo V., Maher J. Y. 2021. Case report: two cases of mature oocytes found in prepubertal girls during ovarian tissue cryopreservation. F. S. Rep. V. 2. P. 296. https://doi.org/10.1016/j.xfre.2021.03.007
  41. Ho V. N.A., Braam S. C., Pham T. D., Mol B. W., Vuong L. N. 2019. The effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilization in women with a high antral follicle count. Hum. Reprod. V. 34. P. 1055. https://doi.org/10.1093/humrep/dez060
  42. Humaidan P., Nelson S. M., Devroey P., Coddington C. C., Schwartz L. B., Gordon K., Frattarelli J. L., Tarlatzis B. C., Fatemi H. M., Lutjen P., Stegmann B. J. 2016. Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials. Hum. Reprod. V. 31. P. 1997. https://doi.org/10.1093/humrep/dew149
  43. Khalili M. A., Shahedi A., Ashourzadeh S., Nottola S. A., Macchiarelli G., Palmerini M. G. 2017. Vitrification of human immature oocytes before and after in vitro maturation: a review. J. Assist. Reprod. Genet. V. 34. P. 1413. https://doi.org/10.1007/s10815-017-1005-4
  44. Macklon N. S., Fauser B. C. 1999. Aspects of ovarian follicle development throughout life. Horm. Res. V. 52. P. 161. https://doi.org/10.1159/000023456
  45. Madkour A., Bouamoud N., Kaarouch I., Louanjli N., Saadani B., Assou S., Aboulmaouahib S., Sefrioui O., Amzazi S., Copin H., Benkhalifa M. 2018. Follicular fluid and supernatant from cultured cumulus-granulosa cells improve in vitro maturation in patients with polycystic ovarian syndrome. Fertil. Steril. V. 110. P. 710. https://doi.org/10.1016/j.fertnstert.2018.04.038
  46. Mao L., Lou H., Lou Y., Wang N., Jin F. 2014. Behaviour of cytoplasmic organelles and cytoskeleton during oocyte maturation. Reprod. Biomed. Online. V. 28. P. 284. https://doi.org/10.1016/j.rbmo.2013.10.016
  47. McLaughlin M., Albertini D. F., Wallace W. H.B., Anderson R. A., Telfer E. E. 2018. Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Mol. Hum. Reprod. V. 24. P. 135. https://doi.org/10.1093/molehr/gay002
  48. Mu Z., Shen S., Lei L. 2022. Resistant ovary syndrome: pathogenesis and management strategies. Front. Med. (Lausanne). V. 19. Article ID: 1030004.
  49. Nogueira D., Fajau-Prevot C., Clouet M., Assouline P., Deslandres M., Montagut M. 2023. Outcomes of different in vitro maturation procedures for oocyte cryopreservation for fertility preservation and yet another live birth in a cancer patient. Life. V. 13. Article ID: 1355. https://doi.org/10.3390/life13061355
  50. Pincus G., Enzmann E. V. 1935. The comparative behavior of mammalian eggs in vivo and in vitro: I. The activation of ovarian eggs. J. Exp. Med. V. 62. P. 665. https://doi.org/10.1084/jem.62.5.665
  51. Plancha C. E., Rodrigues P., Marques M., Almeida J. M., Navarro-Costa P. 2021. The time is ripe for oocyte in vitro maturation. J. Assist. Reprod. Genet. V. 38. P. 1281. https://doi.org/10.1007/s10815-021-02209-x
  52. Pongsuthirak P., Songveeratham S., Vutyavanich T. 2015. Comparison of blastocyst and Sage media for in vitro maturation of human immature oocytes. Reprod. Sci. V. 22. P. 343. https://doi.org/10.1177/1933719114542027
  53. Sanchez F., Le A. H., Ho V. N.A., Romero S., Van Ranst H., De Vos M., Gilchrist R. B., Ho T. M., Vuong L. N., Smitz J. 2019. Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles. J. Assist. Reprod. Genet. V. 36. P. 2135. https://doi.org/10.1007/s10815-019-01551-5
  54. Sánchez F., Smitz J. 2012. Molecular control of oogenesis. Biochim. Biophys. Acta. V. 1822. P. 1896. https://doi.org/10.1016/j.bbadis.2012.05.013
  55. Telfer E. E. 2019. Future developments: In vitro growth (IVG) of human ovarian follicles. Acta Obstet. Gynecol. Scand. V. 98. P. 653. https://doi.org/10.1111/aogs.13592
  56. Telfer E. E., Andersen C. Y. 2021. In vitro growth and maturation of primordial follicles and immature oocytes. Fertil. Steril. V. 115. P. 1116. https://doi.org/10.1016/j.fertnstert.2021.03.004
  57. Telfer E. E., Grosbois J., Odey Y. L., Rosario R., Anderson R. A. 2023. Making a good egg: human oocyte health, aging, and in vitro development. Physiol. Rev. V. 103. P. 2623. https://doi.org/10.1152/physrev.00032.2022
  58. Torkashvand H., Shabani R., Artimani T., Amiri I., Pilehvari S., Torkashvand L., Mehdizadeh R., Mehdizadeh M. 2024. Oocyte competence develops: nuclear maturation synchronously with cytoplasm maturation. Zygote. V. 32. P. 421. https://doi.org/10.1017/S0967199424000169
  59. Trebichalská Z., Kyjovská D., Kloudová S., Otevřel P., Hampl A., Holubcová Z. 2021. Cytoplasmic maturation in human oocytes: an ultrastructural study. Biol. Reprod. V. 104. P. 106. https://doi.org/10.1093/biolre/ioaa174
  60. Woodruff T. K., Shea L. D. 2007. The role of the extracellular matrix in ovarian follicle development. Reprod. Sci. V. 14. P. 6. https://doi.org/10.1177/1933719107309818
  61. Wynn P., Picton H. M., Krapez J. A., Rutherford A. J., Balen A. H., Gosden R. G. 1998. Pretreatment with follicle stimulating hormone promotes the numbers of human oocytes reaching metaphase II by in vitro maturation. Hum. Reprod. V. 13. P. 3132. https://doi.org/10.1093/humrep/13.11.3132
  62. Xiao S., Zhang J., Romero M. M., Smith K. N., Shea L. D., Woodruff T. K. 2015. In vitro follicle growth supports human oocyte meiotic maturation. Sci. Rep. V. 5. Article ID: 17323. https://doi.org/10.1038/srep17323
  63. Yang H., Kolben T., Meister S., Paul C., van Dorp J., Eren S., Kuhn C., Rahmeh M., Mahner S., Jeschke U., von Schönfeldt V. 2021. Factors influencing the in vitro maturation (IVM) of human oocyte. Biomedicines. V. 9. Article ID: 1904. https://doi.org/10.3390/biomedicines9121904
  64. Yang S. H., Hur Y. S., Yoon S. H., Jung J. H., Lim J. H., Ko Y. 2020. A comparison of embryonic development and clinical outcomes between in vitro oocytes maturation using microvibration system and in vivo oocytes maturation in polycystic ovarian syndrome patients. Gynecol. Obstet. Invest. V. 85. P. 252. https://doi.org/10.1159/000507441
  65. Yang S. H., Yoon S. H., Jung J. H., Lim J. H., Ko Y. 2019. Improvement of embryonic development and clinical outcomes of germinal vesicle stage oocytes using a microvibration culture system. Syst. Biol. Reprod. Med. V. 65. P. 333. https://doi.org/10.1080/19396368.2019.1602681
  66. Yin H., Kristensen S. G., Jiang H., Rasmussen A., Andersen C. Y. 2016. Survival and growth of isolated pre-antral follicles from human ovarian medulla tissue during long-term 3D culture. Hum. Reprod. V. 31. P. 1531. https://doi.org/10.1093/humrep/dew049

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Russian Academy of Sciences