Seven days ex vivo perfusion of whole ewe ovaries with follicular maturation and oocyte retrieval: towards the development of an alternative fertility preservation method
Panagiotis Tsiartas A B , Claudia Mateoiu C , Meghshree Deshmukh D , Debashish Banerjee D , Arvind M. Padma A D , Milan Milenkovic B E , Fulvio Gandolfi F , Mats Hellström A D , Pasquale Patrizio G H and Randa Akouri
A D *
+ Author Affiliations
- Author Affiliations
A Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Blå stråket 6, 41345 Gothenburg, Sweden.
B Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
C Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
D Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
E BeoGyn Clinic, Belgrade, Serbia.
F Department of Agricultural and Environmental Sciences, University of Milano, Milano, Italy.
G Yale Fertility Center, Yale School of Medicine, New Haven, CT, USA.
H Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology and Reproductive Sciences, University of Miami, Miller School of Medicine, Miami, FL, USA.
Reproduction, Fertility and Development 34(3) 331-342 https://doi.org/10.1071/RD21197
Published online: 28 January 2022
© 2022 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)
Abstract
Fertility preservation methods for prepubertal women about to undergo gonadotoxic chemo and/or radiation therapy are limited. Therefore, the aim of this study was to investigate the feasibility to develop an alternative fertility preservation method based on an ex vivo perfusion platform for whole ewe ovaries. Thirteen ewe ovaries were divided into two groups (group 1 and 2) that were perfused in a bioreactor for up to 7 days. Group 1 (n = 3) were stimulated with human menopausal gonadotropin (hMG) administered in single daily dose, while group 2 (n = 10) were stimulated continuously for 24 h. The perfused ovaries in group 1 showed no significant differences in follicular density, sub-follicular morphology and oocyte quality after ischaemia and after ex vivo perfusion compared with non-perfused control ovaries. The perfused ovaries in group 2 showed a significant decrease in the follicular reserve and oocyte quality compared with the control group. In total, 16 GV–MI oocytes were retrieved from both groups. This study describes for the first time the ex vivo maintenance of viable follicles of ewe ovaries with oocyte integrity and the retrieval of oocytes after ex vivo hormonal perfusion with two different protocols for up to 7 days.
Keywords: bioreactor, endocrinology, ewes, ex vivo, fertility preservation, follicular development, ovary, perfusion.
References
Abrahamsson, G, Janson, PO, and Kullander, S (1990). An in vitro perfusion method for metabolic studies on human postmenopausal ovaries. Acta Obstetricia et Gynecologica Scandinavica 69, 527–532.| An in vitro perfusion method for metabolic studies on human postmenopausal ovaries.Crossref | GoogleScholarGoogle Scholar | 2178300PubMed |
Baby, TE, and Bartlewski, PM (2011). Circulating concentrations of ovarian steroids and follicle-stimulating hormone (FSH) in ewes with 3 or 4 waves of antral follicle emergence per estrous cycle. Reproductive Biology 11, 19–36.
| Circulating concentrations of ovarian steroids and follicle-stimulating hormone (FSH) in ewes with 3 or 4 waves of antral follicle emergence per estrous cycle.Crossref | GoogleScholarGoogle Scholar | 21455278PubMed |
Benedict, C, Thom, B, Friedman, DN, Pottenger, E, Raghunathan, N, and Kelvin, JF (2018). Fertility information needs and concerns post-treatment contribute to lowered quality of life among young adult female cancer survivors. Supportive Care in Cancer 26, 2209–2215.
| Fertility information needs and concerns post-treatment contribute to lowered quality of life among young adult female cancer survivors.Crossref | GoogleScholarGoogle Scholar | 29387996PubMed |
Brännström, M, and Flaherty, S (1995). Methodology and characterization of an in vitro perfusion model for the mouse ovary. Journal of Reproduction and Fertility 105, 177–183.
| Methodology and characterization of an in vitro perfusion model for the mouse ovary.Crossref | GoogleScholarGoogle Scholar | 8568758PubMed |
Brännström, M, Johansson, BM, Sogn, J, and Janson, PO (1987). Characterization of an in vitro perfused rat ovary model: ovulation rate, oocyte maturation, steroidogenesis and influence of PMSG priming. Acta Physiologica Scandinavica 130, 107–114.
| Characterization of an in vitro perfused rat ovary model: ovulation rate, oocyte maturation, steroidogenesis and influence of PMSG priming.Crossref | GoogleScholarGoogle Scholar | 3591383PubMed |
Bromer, JG, and Patrizio, P (2008). Preservation and postponement of female fertility. Placenta 29, 200–205.
| Preservation and postponement of female fertility.Crossref | GoogleScholarGoogle Scholar | 18708254PubMed |
Campbell, BK, Kendall, NR, and Baird, DT (2007). The effect of the presence and pattern of luteinizing hormone stimulation on ovulatory follicle development in sheep1. Biology of Reproduction 76, 719–727.
| The effect of the presence and pattern of luteinizing hormone stimulation on ovulatory follicle development in sheep1.Crossref | GoogleScholarGoogle Scholar | 17167168PubMed |
Chiti, MC, Dolmans, M-M, Hobeika, M, Cernogoraz, A, Donnez, J, and Amorim, CA (2017). A modified and tailored human follicle isolation procedure improves follicle recovery and survival. Journal of Ovarian Research 10, 71.
| A modified and tailored human follicle isolation procedure improves follicle recovery and survival.Crossref | GoogleScholarGoogle Scholar | 29061149PubMed |
Diaz-Garcia, C, Domingo, J, Garcia-Velasco, JA, Herraiz, S, Mirabet, V, Iniesta, I, Cobo, A, Remohi, J, and Pellicer, A (2018). Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study. Fertility and Sterility 109, 478–485.e2.
| Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study.Crossref | GoogleScholarGoogle Scholar | 29428307PubMed |
Dolmans, M-M, Marinescu, C, Saussoy, P, Van Langendonckt, A, Amorim, C, and Donnez, J (2010). Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood 116, 2908–2914.
| Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe.Crossref | GoogleScholarGoogle Scholar | 20595517PubMed |
Dolmans, M-M, Luyckx, V, Donnez, J, Andersen, CY, and Greve, T (2013). Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue. Fertility and Sterility 99, 1514–1522.
| Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue.Crossref | GoogleScholarGoogle Scholar | 23541406PubMed |
Donnez, J (2013). Introduction: fertility preservation, from cancer to benign disease to social reasons: the challenge of the present decade. Fertility and Sterility 99, 1467–1468.
| Introduction: fertility preservation, from cancer to benign disease to social reasons: the challenge of the present decade.Crossref | GoogleScholarGoogle Scholar | 23635347PubMed |
Donnez, J, and Dolmans, M-M (2013). Fertility preservation in women. Nature Reviews Endocrinology 9, 735–749.
| Fertility preservation in women.Crossref | GoogleScholarGoogle Scholar | 24166000PubMed |
Donnez, J, and Dolmans, MM (2017). Fertility preservation in women. New England Journal of Medicine 377, 1657–1665.
| Fertility preservation in women.Crossref | GoogleScholarGoogle Scholar |
Donnez, J, Martinez-Madrid, B, Jadoul, P, Van Langendonckt, A, Demylle, D, and Dolmans, M-M (2006). Ovarian tissue cryopreservation and transplantation: a review. Human Reproduction Update 12, 519–535.
| Ovarian tissue cryopreservation and transplantation: a review.Crossref | GoogleScholarGoogle Scholar | 16849817PubMed |
Donnez, J, Jadoul, P, Squifflet, J, Van Langendonckt, A, Donnez, O, Van Eyck, A-S, Marinescu, C, and Dolmans, M-M (2010). Ovarian tissue cryopreservation and transplantation in cancer patients. Best Practice & Research Clinical Obstetrics & Gynaecology 24, 87–100.
| Ovarian tissue cryopreservation and transplantation in cancer patients.Crossref | GoogleScholarGoogle Scholar |
Edson, MA, Nagaraja, AK, and Matzuk, MM (2009). The mammalian ovary from genesis to revelation. Endocrine Reviews 30, 624–712.
| The mammalian ovary from genesis to revelation.Crossref | GoogleScholarGoogle Scholar | 19776209PubMed |
Eppig, JJ, and Schroeder, AC (1989). Capacity of mouse oocytes from preantral follicles to undergo embryogenesis and development to live young after growth, maturation, and fertilization in vitro. Biology of Reproduction 41, 268–276.
| Capacity of mouse oocytes from preantral follicles to undergo embryogenesis and development to live young after growth, maturation, and fertilization in vitro.Crossref | GoogleScholarGoogle Scholar | 2508774PubMed |
Figueiredo, JR, Rodrigues, APR, Silva, JRV, and Santos, RR (2011). Cryopreservation and in vitro culture of caprine preantral follicles. Reproduction, Fertility and Development 23, 40–47.
| Cryopreservation and in vitro culture of caprine preantral follicles.Crossref | GoogleScholarGoogle Scholar |
Gandolfi, F, Paffoni, A, Papasso Brambilla, E, Bonetti, S, Brevini, TA, and Ragni, G (2006). Efficiency of equilibrium cooling and vitrification procedures for the cryopreservation of ovarian tissue: comparative analysis between human and animal models. Fertility and Sterility 85, 1150–1156.
| Efficiency of equilibrium cooling and vitrification procedures for the cryopreservation of ovarian tissue: comparative analysis between human and animal models.Crossref | GoogleScholarGoogle Scholar | 16616087PubMed |
Hamada, Y, Bronson, RA, Wright, KH, and Wallach, EF (1977). Ovulation in the perfused rabbit ovary: the influence of prostaglandins and prostaglandin inhibitors. Biology of Reproduction 17, 58–63.
| Ovulation in the perfused rabbit ovary: the influence of prostaglandins and prostaglandin inhibitors.Crossref | GoogleScholarGoogle Scholar | 884187PubMed |
Hamada, Y, Wright, KH, and Wallach, EE (1979). The effects of progesterone and human chorionic gonadotropin on ovulation in the in vitro perfused rabbit ovary. Fertility and Sterility 32, 335–339.
| The effects of progesterone and human chorionic gonadotropin on ovulation in the in vitro perfused rabbit ovary.Crossref | GoogleScholarGoogle Scholar | 573708PubMed |
Hosgood, SA, Thompson, E, Moore, T, Wilson, CH, and Nicholson, ML (2018). Normothermic machine perfusion for the assessment and transplantation of declined human kidneys from donation after circulatory death donors. British Journal of Surgery 105, 388–394.
| Normothermic machine perfusion for the assessment and transplantation of declined human kidneys from donation after circulatory death donors.Crossref | GoogleScholarGoogle Scholar |
Kobayashi, Y, Santulli, R, Wright, KH, and Wallach, EE (1981a). Fertilizability of ova ovulated and recovered from rabbit ovaries perfused in vitro. Science 213, 1127–1128.
| Fertilizability of ova ovulated and recovered from rabbit ovaries perfused in vitro.Crossref | GoogleScholarGoogle Scholar | 7268420PubMed |
Kobayashi, Y, Wright, KH, Santulli, R, and Wallach, EE (1981b). Ovulation and ovum maturation in the rabbit ovary perfused in vitro. Biology of Reproduction 24, 483–490.
| Ovulation and ovum maturation in the rabbit ovary perfused in vitro.Crossref | GoogleScholarGoogle Scholar | 7236814PubMed |
Koos, RD, Jaccarino, FJ, Magaril, RA, and Le Maire, WJ (1984). Perfusion of the rat ovary in vitro: methodology, induction of ovulation, and pattern of steroidogenesis. Biology of Reproduction 30, 1135–1141.
| Perfusion of the rat ovary in vitro: methodology, induction of ovulation, and pattern of steroidogenesis.Crossref | GoogleScholarGoogle Scholar | 6733206PubMed |
Lambertsen, CJ, Greenbaum, DF, Wright, KH, and Wallach, EE (1976). In vitro studies of ovulation in the perfused rabbit ovary. Fertility and Sterility 27, 178–187.
| In vitro studies of ovulation in the perfused rabbit ovary.Crossref | GoogleScholarGoogle Scholar | 1248664PubMed |
Laronda, MM, Rutz, AL, Xiao, S, Whelan, KA, Duncan, FE, Roth, EW, Woodruff, TK, and Shah, RN (2017). A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nature Communications 8, 15261.
| A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice.Crossref | GoogleScholarGoogle Scholar | 28509899PubMed |
Letourneau, JM, Ebbel, EE, Katz, PP, Katz, A, Ai, WZ, Chien, AJ, Melisko, ME, Cedars, MI, and Rosen, MP (2012). Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer 118, 1710–1717.
| Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer.Crossref | GoogleScholarGoogle Scholar | 21887678PubMed |
Maffei, S, Galeati, G, Pennarossa, G, Brevini, TAL, and Gandolfi, F (2016). Extended ex vivo culture of fresh and cryopreserved whole sheep ovaries. Reproduction, Fertility and Development 28, 1893–1903.
| Extended ex vivo culture of fresh and cryopreserved whole sheep ovaries.Crossref | GoogleScholarGoogle Scholar |
McLaughlin, M, Albertini, DF, Wallace, WHB, Anderson, RA, and Telfer, EE (2018). Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Molecular Human Reproduction 24, 135–142.
| Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system.Crossref | GoogleScholarGoogle Scholar | 29390119PubMed |
Milenkovic, M, Gharemani, M, Bergh, A, Wallin, A, Mölne, J, Fazlagic, E, Eliassen, E, Kahn, J, and Brännström, M (2011a). The human postmenopausal ovary as a tool for evaluation of cryopreservation protocols towards whole ovary cryopreservation. Journal of Assisted Reproduction and Genetics 28, 453–460.
| The human postmenopausal ovary as a tool for evaluation of cryopreservation protocols towards whole ovary cryopreservation.Crossref | GoogleScholarGoogle Scholar | 21350836PubMed |
Milenkovic, M, Wallin, A, Ghahremani, M, and Brännström, M (2011b). Whole sheep ovary cryopreservation: evaluation of a slow freezing protocol with dimethylsulphoxide. Journal of Assisted Reproduction and Genetics 28, 7–14.
| Whole sheep ovary cryopreservation: evaluation of a slow freezing protocol with dimethylsulphoxide.Crossref | GoogleScholarGoogle Scholar | 20842419PubMed |
Moravek, MB, Confino, R, Smith, KN, Kazer, RR, Klock, SC, Lawson, AK, Gradishar, WJ, and Pavone, ME (2018). Long-term outcomes in cancer patients who did or did not pursue fertility preservation. Fertility and Sterility 109, 349–355.
| Long-term outcomes in cancer patients who did or did not pursue fertility preservation.Crossref | GoogleScholarGoogle Scholar | 29338854PubMed |
Nasralla, D, Coussios, CC, Mergental, H, Akhtar, MZ, Butler, AJ, Ceresa, CDL, Chiocchia, V, Dutton, SJ, Garcia-Valdecasas, JC, Heaton, N, Imber, C, Jassem, W, Jochmans, I, Karani, J, Knight, SR, Kocabayoglu, P, Malago, M, Mirza, D, Morris, PJ, Pallan, A, Paul, A, Pavel, M, Perera, M, Pirenne, J, Ravikumar, R, Russell, L, Upponi, S, Watson, CJE, Weissenbacher, A, Ploeg, RJ, and Friend, PJ Nasralla, D, Coussios, CC, Mergental, H, Akhtar, MZ, Butler, AJ, Ceresa, CDL, Chiocchia, V, Dutton, SJ, Garcia-Valdecasas, JC, Heaton, N, Imber, C, Jassem, W, Jochmans, I, Karani, J, Knight, SR, Kocabayoglu, P, Malago, M, Mirza, D, Morris, PJ, Pallan, A, Paul, A, Pavel, M, Perera, M, Pirenne, J, Ravikumar, R, Russell, L, Upponi, S, Watson, CJE, Weissenbacher, A, Ploeg, RJ, and Friend, PJ (2018). A randomized trial of normothermic preservation in liver transplantation. Nature 557, 50–56.
| A randomized trial of normothermic preservation in liver transplantation.Crossref | GoogleScholarGoogle Scholar | 29670285PubMed |
O’Brien, MJ, Pendola, JK, and Eppig, JJ (2003). A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence. Biology of Reproduction 68, 1682–1686.
| A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence.Crossref | GoogleScholarGoogle Scholar | 12606400PubMed |
Padma, AM, Truong, M, Jar-Allah, T, Song, MJ, Oltean, M, Brännström, M, and Hellström, M (2019). The development of an extended normothermic ex vivo reperfusion model of the sheep uterus to evaluate organ quality after cold ischemia in relation to uterus transplantation. Acta Obstetricia et Gynecologica Scandinavica 98, 1127–1138.
| The development of an extended normothermic ex vivo reperfusion model of the sheep uterus to evaluate organ quality after cold ischemia in relation to uterus transplantation.Crossref | GoogleScholarGoogle Scholar | 30932168PubMed |
Paynter, SJ, Cooper, A, Fuller, BJ, and Shaw, RW (1999). Cryopreservation of bovine ovarian tissue: structural normality of follicles after thawing and culture in vitro. Cryobiology 38, 301–309.
| Cryopreservation of bovine ovarian tissue: structural normality of follicles after thawing and culture in vitro.Crossref | GoogleScholarGoogle Scholar | 10413573PubMed |
Picton, HM, Harris, SE, Muruvi, W, and Chambers, EL (2008). The in vitro growth and maturation of follicles. Reproduction 136, 703–715.
| The in vitro growth and maturation of follicles.Crossref | GoogleScholarGoogle Scholar | 19074213PubMed |
Rodriguez, C, Anel, L, Alvarez, M, Anel, E, Boixo, JC, Chamorro, CA, and de Paz, P (2006). Ovum pick-up in sheep: a comparison between different aspiration devices for optimal oocyte retrieval. Reproduction in Domestic Animals 41, 106–113.
| Ovum pick-up in sheep: a comparison between different aspiration devices for optimal oocyte retrieval.Crossref | GoogleScholarGoogle Scholar | 16519714PubMed |
Shapira, M, Raanani, H, Barshack, I, Amariglio, N, Derech-Haim, S, Marciano, MN, Schiff, E, Orvieto, R, and Meirow, D (2018). First delivery in a leukemia survivor after transplantation of cryopreserved ovarian tissue, evaluated for leukemia cells contamination. Fertility and Sterility 109, 48–53.
| First delivery in a leukemia survivor after transplantation of cryopreserved ovarian tissue, evaluated for leukemia cells contamination.Crossref | GoogleScholarGoogle Scholar | 29198847PubMed |
Shea, LD, Woodruff, TK, and Shikanov, A (2014). Bioengineering the ovarian follicle microenvironment. Annual Review of Biomedical Engineering 16, 29–52.
| Bioengineering the ovarian follicle microenvironment.Crossref | GoogleScholarGoogle Scholar | 24849592PubMed |
Sogn, J, Abrahamsson, G, and Janson, PO (1984). Release of cyclic AMP and progesterone from the isolated perfused luteal ovary of the PMSG treated rat. Acta Endocrinologica 106, 265–270.
| Release of cyclic AMP and progesterone from the isolated perfused luteal ovary of the PMSG treated rat.Crossref | GoogleScholarGoogle Scholar | 6328825PubMed |
Sogn, JH, Curry, TE, Brännström, M, Lemaire, WJ, Koos, RD, Papkoff, H, and Janson, PO (1987). Inhibition of follicle-stimulating hormone-induced ovulation by indomethacin in the perfused rat ovary. Biology of Reproduction 36, 536–542.
| Inhibition of follicle-stimulating hormone-induced ovulation by indomethacin in the perfused rat ovary.Crossref | GoogleScholarGoogle Scholar | 3109504PubMed |
Songsasen, N, Comizzoli, P, Nagashima, J, Fujihara, M, and Wildt, DE (2012). The domestic dog and cat as models for understanding the regulation of ovarian follicle development in vitro. Reproduction in Domestic Animals 47, 13–18.
| The domestic dog and cat as models for understanding the regulation of ovarian follicle development in vitro.Crossref | GoogleScholarGoogle Scholar | 23279457PubMed |
Stähler, E, Spätling, L, Bethge, HD, Daume, E, and Buchholz, R (1974). Induction of ovulation in human ovaries perfused in vitro. Archiv für Gynäkologie 217, 1–15.
| Induction of ovulation in human ovaries perfused in vitro.Crossref | GoogleScholarGoogle Scholar | 4479142PubMed |
Telfer, EE, and Zelinski, MB (2013). Ovarian follicle culture: advances and challenges for human and nonhuman primates. Fertility and Sterility 99, 1523–1533.
| Ovarian follicle culture: advances and challenges for human and nonhuman primates.Crossref | GoogleScholarGoogle Scholar | 23635350PubMed |
Vanacker, J, Dolmans, M-M, Luyckx, V, Donnez, J, and Amorim, CA (2014). First transplantation of isolated murine follicles in alginate. Regenerative Medicine 9, 609–619.
| First transplantation of isolated murine follicles in alginate.Crossref | GoogleScholarGoogle Scholar | 25372078PubMed |
Wallace, WHB, Anderson, RA, and Irvine, DS (2005). Fertility preservation for young patients with cancer: who is at risk and what can be offered? The Lancet Oncology 6, 209–218.
| Fertility preservation for young patients with cancer: who is at risk and what can be offered?Crossref | GoogleScholarGoogle Scholar |
Wallach, EE, Wright, KH, and Hamada, Y (1978). Investigation of mammalian ovulation with an in vitro perfused rabbit ovary preparation. American Journal of Obstetrics and Gynecology 132, 728–738.
| Investigation of mammalian ovulation with an in vitro perfused rabbit ovary preparation.Crossref | GoogleScholarGoogle Scholar | 102198PubMed |
Wallin, A, Ghahremani, M, Dahm-Kahler, P, and Brannstrom, M (2009). Viability and function of the cryopreserved whole ovary: in vitro studies in the sheep. Human Reproduction (Oxford, England) 24, 1684–1694.
| Viability and function of the cryopreserved whole ovary: in vitro studies in the sheep.Crossref | GoogleScholarGoogle Scholar |
Zhu, J, Moawad, AR, Wang, C-Y, Li, H-F, Ren, J-Y, and Dai, Y-F (2018). Advances in in vitro production of sheep embryos. International Journal of Veterinary Science and Medicine 6, S15–S26.
| Advances in in vitro production of sheep embryos.Crossref | GoogleScholarGoogle Scholar | 30761316PubMed |
