Approaches and Technologies in Male Fertility Preservation

Male fertility preservation is required when treatment with an aggressive chemo-/-radiotherapy, which may lead to irreversible sterility. Due to new and efficient protocols of cancer treatments, surviving rates are more than 80%. Thus, these patients are looking forward to family life and fathering their own biological children after treatments. Whereas adult men can cryopreserve their sperm for future use in assistance reproductive technologies (ART), this is not an option in prepubertal boys who cannot produce sperm at this age. In this review, we summarize the different technologies for male fertility preservation with emphasize on prepubertal, which have already been examined and/or demonstrated in vivo and/or in vitro using animal models and, in some cases, using human tissues. We discuss the limitation of these technologies for use in human fertility preservation. This update review can assist physicians and patients who are scheduled for aggressive chemo-/radiotherapy, specifically prepubertal males and their parents who need to know about the risks of the treatment on their future fertility and the possible present option of fertility preservation.

Download Full-text

Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo

Clinical Medicine Insights Reproductive Health ◽

10.1177/1179558119848007 ◽

2019 ◽

Vol 13 ◽

pp. 117955811984800 ◽

Cited By ~ 9

Author(s):

Taichi Akahori ◽

Dori C Woods ◽

Jonathan L Tilly

Keyword(s):

Fertility Preservation ◽

Ovarian Tissue ◽

Mammalian Species ◽

Reproductive Age ◽

Embryo Cryopreservation ◽

Novel Approach ◽

Future Fertility ◽

Female Fertility Preservation

Historically, approaches designed to offer women diagnosed with cancer the prospects of having a genetically matched child after completion of their cytotoxic treatments focused on the existing oocyte population as the sole resource available for clinical management of infertility. In this regard, elective oocyte and embryo cryopreservation, as well as autologous ovarian cortical tissue grafting posttreatment, have gained widespread support as options for young girls and reproductive-age women who are faced with cancer to consider. In addition, the use of ovarian protective therapies, including gonadotropin-releasing hormone agonists and sphingosine-1-phosphate analogs, has been put forth as an alternative way to preserve fertility by shielding existing oocytes in the ovaries in vivo from the side-effect damage caused by radiotherapy and many chemotherapeutic regimens. This viewpoint changed with the publication of now numerous reports that adult ovaries of many mammalian species, including humans, contain a rare population of oocyte-producing germ cells—referred to as female germline or oogonial stem cells (OSCs). This new line of study has fueled research into the prospects of generating new oocytes, rather than working with existing oocytes, as a novel approach to sustain or restore fertility in female cancer survivors. Here, we overview the history of work from laboratories around the world focused on improving our understanding of the biology of OSCs and how these cells may be used to reconstitute “artificial” ovarian tissue in vitro or to regenerate damaged ovarian tissue in vivo as future fertility-preservation options.

Download Full-text

A Novel Approach of Tracing in Vivo Bioluminescence Imaging Expression of Vitrified Immature Testicular Tissue Grafts Until Adulthood: A Translational Transgenic Mouse Model

10.21203/rs.3.rs-1223618/v1 ◽

2022 ◽

Author(s):

Buo-Jia Lu ◽

Yung-Liang Liu ◽

Bou-Zenn Lin ◽

Chi-Huang Chen

Keyword(s):

Fertility Preservation ◽

Male Fertility ◽

Caspase 3 ◽

Bioluminescence Imaging ◽

Testicular Tissue ◽

Control Group ◽

Optimal Method ◽

Intact Cells

Abstract Background: The optimal method for cryopreserving immature testicular tissue (ITT) remains unknown and there is no standardized protocol. Controlled slow freezing remains the mainstream method of choice in human prepubertal male fertility preservation. Currently, the outcomes for ITT vitrification are conflicting, and most data are limited to in vitro animal studies.Methods: A total of 12 pairs of donor and recipient mice were included in our experiments. The donors were immature transgenic mice, and the recipients were wild-type male mice. In the vitrification group, ITT was vitrified and thawed before transplantation. In the control group, ITT was transplanted to the recipients immediately. After thawing, we measured the expression of apoptosis-related mRNA caspase-3. More importantly, we monitored to adulthood all the transplanted grafts in vivo using noninvasive bioluminescence imaging (BLI) technology. On day 31, we removed the grafts for evaluation via hematoxylin and eosin staining and immunohistochemistry (IHC).Results: We traced the survival of the grafts by in vivo BLI on days 1, 2, 5, 7, and 31 after transplantation. In both the vitrification and the control groups, bioluminescence decreased between days 2 and 5. Subsequently, the bioluminescence showed an upward trend until day 31. Compared with day 1, the bioluminescence was significantly stronger on day 31 after transplantation (P = 0.009). The differences between the two groups were constantly insignificant after analysis. These results indicate that both fresh and frozen–thawed testicular tissues can survive for at least 31 days after transplantation. Moreover, the vitrification group showed BLI signals comparable with those of fresh tissues. Compared with the control group, expression of the caspase-3 gene was significantly increased after vitrification (P = 0.04). Histology and IHC showed that both tissue structure and protein expression were intact in both groups.Conclusions: Transplanted vitrified ITT grafts could survive till adulthood with BLI intensity comparable to that of the fresh control. Intact cells and structures for spermatogenesis in vitrified ITT grafts were as well-preserved as those in the control group. This translational model of self-repairing vitrified ITT grafts in vivo, lends weight to the role of vitrification in prepubertal male fertility preservation.

Download Full-text

Oncofertility: Pharmacological Protection and Immature Testicular Tissue (ITT)-Based Strategies for Prepubertal and Adolescent Male Cancer Patients

International Journal of Molecular Sciences ◽

10.3390/ijms20205223 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5223 ◽

Cited By ~ 3

Author(s):

Elissavet Ntemou ◽

Chrysanthi Alexandri ◽

Pascale Lybaert ◽

Ellen Goossens ◽

Isabelle Demeestere

Keyword(s):

Fertility Preservation ◽

Fertility Restoration ◽

Childhood Cancer Survivors ◽

Testicular Tissue ◽

Adolescent Male ◽

Medical Centers ◽

Preservation Method ◽

Prepubertal Boys

While the incidence of cancer in children and adolescents has significantly increased over the last decades, improvements made in the field of cancer therapy have led to an increased life expectancy for childhood cancer survivors. However, the gonadotoxic effect of the treatments may lead to infertility. Although semen cryopreservation represents the most efficient and safe fertility preservation method for males producing sperm, it is not feasible for prepubertal boys. The development of an effective strategy based on the pharmacological protection of the germ cells and testicular function during gonadotoxic exposure is a non-invasive preventive approach that prepubertal boys could benefit from. However, the progress in this field is slow. Currently, cryopreservation of immature testicular tissue (ITT) containing spermatogonial stem cells is offered to prepubertal boys as an experimental fertility preservation strategy by a number of medical centers. Several in vitro and in vivo fertility restoration approaches based on the use of ITT have been developed so far with autotransplantation of ITT appearing more promising. In this review, we discuss the pharmacological approaches for fertility protection in prepubertal and adolescent boys and the fertility restoration approaches developed on the utilization of ITT.

Download Full-text

Sperm Selection Procedures for Optimizing the Outcome of ICSI in Patients with NOA

Journal of Clinical Medicine ◽

10.3390/jcm10122687 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2687

Author(s):

Kaan Aydos ◽

Oya Sena Aydos

Keyword(s):

In Vitro Selection ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Testicular Sperm Extraction ◽

Obstructive Azoospermia ◽

Sperm Retrieval ◽

Vitro Fertilization ◽

Great Hope ◽

Future Fertility

Retrieving spermatozoa from the testicles has been a great hope for patients with non-obstructive azoospermia (NOA), but relevant methods have not yet been developed to the level necessary to provide resolutions for all cases of NOA. Although performing testicular sperm extraction under microscopic magnification has increased sperm retrieval rates, in vitro selection and processing of quality sperm plays an essential role in the success of in vitro fertilization. Moreover, sperm cryopreservation is widely used in assisted reproductive technologies, whether for therapeutic purposes or for future fertility preservation. In recent years, there have been new developments using advanced technologies to freeze and preserve even very small numbers of sperm for which conventional techniques are inadequate. The present review provides an up-to-date summary of current strategies for maximizing sperm recovery from surgically obtained testicular samples and, as an extension, optimization of in vitro sperm processing techniques in the management of NOA.

Download Full-text

Reduced High-Dose Radiation-Induced Residual Genotoxic Damage by Induction of Radioadaptive Response and Prophylactic Mild Dietary Restriction in Mice

Dose-Response ◽

10.1177/1559325820982166 ◽

2021 ◽

Vol 19 (1) ◽

pp. 155932582098216

Author(s):

Bing Wang ◽

Kaoru Tanaka ◽

Takanori Katsube ◽

Kouichi Maruyama ◽

Yasuharu Ninomiya ◽

...

Keyword(s):

Dietary Restriction ◽

High Dose ◽

Cancer Treatments ◽

Hematopoietic Stem ◽

Beneficial Effects ◽

Radiation Induced ◽

Potential Strategy ◽

Higher Doses

Radioadaptive response (RAR) describes a phenomenon in a variety of in vitro and in vivo systems that a low-dose of priming ionizing radiation (IR) reduces detrimental effects of a subsequent challenge IR at higher doses. Among in vivo investigations, studies using the mouse RAR model (Yonezawa Effect) showed that RAR could significantly extenuate high-dose IR-induced detrimental effects such as decrease of hematopoietic stem cells and progenitor cells, acute radiation hematopoietic syndrome, genotoxicity and genomic instability. Meanwhile, it has been demonstrated that diet intervention has a great impact on health, and dietary restriction shows beneficial effects on numerous diseases in animal models. In this work, by using the mouse RAR model and mild dietary restriction (MDR), we confirmed that combination of RAR and MDR could more efficiently reduce radiogenotoxic damage without significant change of the RAR phenotype. These findings suggested that MDR may share some common pathways with RAR to activate mechanisms consequently resulting in suppression of genotoxicity. As MDR could also increase resistance to chemotherapy and radiotherapy in normal cells, we propose that combination of MDR, RAR, and other cancer treatments (i.e., chemotherapy and radiotherapy) represent a potential strategy to increase the treatment efficacy and prevent IR risk in humans.

Download Full-text

International legal framework for the criminal legal protection of the embryo

Current Issues of the State and Law ◽

10.20310/2587-9340-2021-5-18-296-308 ◽

2021 ◽

pp. 296-308

Author(s):

Nikolai A. Ognerubov

Keyword(s):

Criminal Law ◽

Legal Status ◽

Assisted Reproductive Technologies ◽

Legal Protection ◽

Reproductive Technologies ◽

Legal Framework ◽

Criminal Code ◽

International Aspects

In connection with the active development and use of assisted reproductive technologies, protection of the human embryo and its legal status issue is currently being actualized. We make an attempt to reveal and explain some of the international aspects of the criminal law protection of the life and rights of the embryo. We consider the concept of “embryo” not only from the point of view of various scientific approaches (medicine, biology, embryology, jurisprudence), but also from the legislative side. We present and analyze the first mention of the embryo in Roman private law in connection with modern domestic law. We carry out an analysis of international legal acts that provide protection of embryos both “in vitro” and “in vivo”, followed by consideration of specific criminal law norms of foreign countries, namely Brazil and Colombia. We pay attention to some of the most famous cases from the jurisprudence of the European Court of Human Rights in order to understand the applied international legal acts “de facto”. The study also takes into account modern domestic legislation and considers point “g” of part 2 of Article 105 of the Criminal Code of the Russian Federation.

Download Full-text

Characterization of Iron Core–Gold Shell Nanoparticles for Anti-Cancer Treatments: Chemical and Structural Transformations During Storage and Use

Materials ◽

10.3390/ma11122572 ◽

2018 ◽

Vol 11 (12) ◽

pp. 2572 ◽

Cited By ~ 6

Author(s):

Ya-Na Wu ◽

Dar-Bin Shieh ◽

Li-Xing Yang ◽

Hwo-Shuenn Sheu ◽

Rongkun Thordarson ◽

...

Keyword(s):

Au Nanoparticles ◽

Iron Core ◽

Cancer Treatments ◽

Shell Nanoparticles ◽

X Ray ◽

Anti Cancer ◽

One Year ◽

Means Of Transmission

Finding a cancer-selective drug that avoids damaging healthy cells and organs is a holy grail in medical research. In our previous studies, gold-coated iron (Fe@Au) nanoparticles showed cancer selective anti-cancer properties in vitro and in vivo but were found to gradually lose that activity with storage or "ageing.” To determine the reasons for this diminished anti-cancer activity, we examined Fe@Au nanoparticles at different preparation and storage stages by means of transmission electron microscopy combined with and energy-dispersive X-ray spectroscopy, along with X-ray diffraction analysis and cell viability tests. We found that dried and reconstituted Fe@Au nanoparticles, or Fe@Au nanoparticles within cells, decompose into irregular fragments of γ-F2O3 and agglomerated gold clumps. These changes cause the loss of the particles’ anti-cancer effects. However, we identified that the anti-cancer properties of Fe@Au nanoparticles can be well preserved under argon or, better still, liquid nitrogen storage for six months and at least one year, respectively.

Download Full-text

How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin

International Journal of Endocrinology ◽

10.1155/2016/4987436 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 36

Author(s):

Salvatore Giovanni Vitale ◽

Paola Rossetti ◽

Francesco Corrado ◽

Agnese Maria Chiara Rapisarda ◽

Sandro La Vignera ◽

...

Keyword(s):

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Oocyte Quality ◽

Fertilization Rate ◽

In Vitro Models ◽

The One ◽

High Level

Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.

Download Full-text

Reproductive fluids, used for the in vitro production of pig embryos, result in healthy offspring and avoid aberrant placental expression of PEG3 and LUM.

10.21203/rs.3.rs-42227/v2 ◽

2020 ◽

Author(s):

Evelynne Paris-Oller ◽

Sergio Navarro-Serna ◽

Cristina Soriano-Úbeda ◽

Jordana Sena Lopes ◽

Carmen Matas ◽

...

Keyword(s):

Reproductive Performance ◽

Assisted Reproductive Technologies ◽

Culture Media ◽

Reproductive Technologies ◽

In Vitro Production ◽

Aberrant Expression ◽

Low Efficiency ◽

The Impact

Abstract Background: In vitro embryo production (IVP) and embryo transfer (ET) are two very common assisted reproductive technologies (ART) in human and cattle. However, in pig, the combination of either procedures, or even their use separately, is still considered suboptimal due to the low efficiency of IVP plus the difficulty of performing ET in the long and contorted uterus of the sow. In addition, the potential impact of these two ART on the health of the offspring is unknown. We investigated here if the use of a modified IVP system, with natural reproductive fluids (RF) as supplements to the culture media, combined with a minimally invasive surgery to perform ET, affects the output of the own IVP system as well as the reproductive performance of the mother and placental molecular traits.Results: The blastocyst rates obtained by both in vitro systems, conventional (C-IVP) and modified (RF-IVP), were similar. Pregnancy and farrowing rates were also similar. However, when compared to in vivo control (artificial insemination, AI), litter sizes of both IVP groups were lower, while placental efficiency was higher in AI than in RF-IVP. Gene expression studies revealed aberrant expression levels for PEG3 and LUM in placental tissue for C-IVP group when compared to AI, but not for RF-IVP group.Conclusions: The use of reproductive fluids as additives for the culture media in pig IVP does not improve reproductive performance of recipient mothers but could mitigate the impact of artificial procedures in the offspring.

Download Full-text

DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids

eLife ◽

10.7554/elife.23670 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 49

Author(s):

Sebastian Canovas ◽

Elena Ivanova ◽

Raquel Romar ◽

Soledad García-Martínez ◽

Cristina Soriano-Úbeda ◽

...

Keyword(s):

Dna Methylation ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Cell Number ◽

Rna Seq ◽

Methylation Analysis ◽

Number Of Children ◽

Methylation Patterns

The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive fluids (Natur-IVF). Natur-IVF embryos were of higher quality than C-IVF in terms of cell number and hatching ability. RNA-Seq and DNA methylation analyses showed that Natur-IVF embryos have expression and methylation patterns closer to in vivo blastocysts. Genes involved in reprogramming, imprinting and development were affected by culture, with fewer aberrations in Natur-IVF embryos. Methylation analysis detected methylated changes in C-IVF, but not in Natur-IVF, at genes whose methylation could be critical, such as IGF2R and NNAT.

Download Full-text