The Fertilization Enigma: How Sperm and Egg Fuse.

Fertilization is a multistep process that culminates in the fusion of sperm and egg, thus marking the beginning of a new organism in sexually reproducing species. Despite its importance for reproduction, the molecular mechanisms that regulate this singular event, particularly sperm-egg fusion, have remained mysterious for many decades. Here, we summarize our current molecular understanding of sperm-egg interaction, focusing mainly on mammalian fertilization. Given the fundamental importance of sperm-egg fusion yet the lack of knowledge of this process in vertebrates, we discuss hallmarks and emerging themes of cell fusion by drawing from well-studied examples such as viral entry, placenta formation, and muscle development. We conclude by identifying open questions and exciting avenues for future studies in gamete fusion.

3D Chromatin Structures of Mature Gametes and Structural Reprogramming during Mammalian Embryogenesis.

High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-long-range interactions (>4 Mb) and interchromosomal interactions occur frequently. The high-order structures of both the paternal and maternal genomes in zygotes and two-cell embryos are obscure but are gradually re-established through development. The establishment of the TAD structure requires DNA replication but not zygotic genome activation. Furthermore, unmethylated CpGs are enriched in A compartment, and methylation levels are decreased to a greater extent in A compartment than in B compartment in embryos. In summary, the global reprogramming of chromatin architecture occurs during early mammalian development.

The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein.

Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa-animals, plants, and protists (including important human pathogens like Plasmodium)-suggests that many eukaryotic organisms share a common gamete fusion mechanism. Here, we report combined bioinformatic, biochemical, mutational, and X-ray crystallographic studies on the unicellular alga Chlamydomonas reinhardtii HAP2 that reveal homology to class II viral membrane fusion proteins. We further show that targeting the segment corresponding to the fusion loop by mutagenesis or by antibodies blocks gamete fusion. These results demonstrate that HAP2 is the gamete fusogen and suggest a mechanism of action akin to viral fusion, indicating a way to block Plasmodium transmission and highlighting the impact of virus-cell genetic exchanges on the evolution of eukaryotic life.

How to Switch from Mitosis to Meiosis: Regulation of Germline Entry in Plants.

One of the major cell fate transitions in eukaryotes is entry into meiosis. While in single-celled yeast this decision is triggered by nutrient starvation, in multicellular eukaryotes, such as plants, it is under developmental control. In contrast to animals, plants have only a short germline and instruct cells to become meiocytes in reproductive organs late in development. This situation argues for a fundamentally different mechanism of how plants recruit meiocytes, and consistently, none of the regulators known to control meiotic entry in yeast and animals are present in plants. In recent years, several factors involved in meiotic entry have been identified, especially in the model plant Arabidopsis, and pieces of a regulatory network of germline control in plants are emerging. However, the corresponding studies also show that the mechanisms of meiotic entry control are diversified in flowering plants, calling for further analyses in different plant species.

A genome-wide perspective of the maternal mRNA translation program during oocyte development.

Transcriptional and post-transcriptional regulations control gene expression in most cells. However, critical transitions during the development of the female gamete relies exclusively on regulation of mRNA translation in the absence of de novo mRNA synthesis. Specific temporal patterns of maternal mRNA translation are essential for the oocyte progression through meiosis, for generation of a haploid gamete ready for fertilization and for embryo development. In this review, we will discuss how mRNAs are translated during oocyte growth and maturation using mostly a genome-wide perspective. This broad view on how translation is regulated reveals multiple divergent translational control mechanisms required to coordinate protein synthesis with progression through the meiotic cell cycle and with development of a totipotent zygote.

Biological sex is binary, even though there is a rainbow of sex roles: Denying biological sex is anthropocentric and promotes species chauvinism: Denying biological sex is anthropocentric and promotes species chauvinism.

Biomedical and social scientists are increasingly calling the biological sex into question, arguing that sex is a graded spectrum rather than a binary trait. Leading science journals have been adopting this relativist view, thereby opposing fundamental biological facts. While we fully endorse efforts to create a more inclusive environment for gender-diverse people, this does not require denying biological sex. On the contrary, the rejection of biological sex seems to be based on a lack of knowledge about evolution and it champions species chauvinism, inasmuch as it imposes human identity notions on millions of other species. We argue that the biological definition of the sexes remains central to recognising the diversity of life. Humans with their unique combination of biological sex and gender are different from non-human animals and plants in this respect. Denying the concept of biological sex, for whatever cause, ultimately erodes scientific progress and may open the flood gates to "alternative truths."

Theoretical and experimental assessment of genome-based prediction in landraces of allogamous crops.

Discovery and enrichment of favorable alleles in landraces are key to making them accessible for crop improvement. Here, we present two fundamentally different concepts for genome-based selection in landrace-derived maize populations, one based on doubled-haploid (DH) lines derived directly from individual landrace plants and the other based on crossing landrace plants to a capture line. For both types of populations, we show theoretically how allele frequencies of the ancestral landrace and the capture line translate into expectations for molecular and genetic variances. We show that the DH approach has clear advantages over gamete capture with generally higher prediction accuracies and no risk of masking valuable variation of the landrace. Prediction accuracies as high as 0.58 for dry matter yield in the DH population indicate high potential of genome-based selection. Based on a comparison among traits, we show that the genetic makeup of the capture line has great influence on the success of genome-based selection and that confounding effects between the alleles of the landrace and the capture line are best controlled for traits for which the capture line does not outperform the ancestral population per se or in testcrosses. Our results will guide the optimization of genome-enabled prebreeding schemes.

DMP8 and 9 regulate HAP2/GCS1 trafficking for the timely acquisition of sperm fusion competence.

Sexual reproduction involves the fusion of two gametes of opposite sex. Although the sperm-expressed fusogen HAPLESS 2 (HAP2) or GENERATIVE CELL SPECIFIC 1 (GCS1) plays a vital role in this process in many eukaryotic organisms and an understanding of its regulation is emerging in unicellular systems [J. Zhang et al., Nat. Commun. 12, 4380 (2021); J. F. Pinello et al. Dev. Cell 56, 3380-3392.e9 (2021)], neither HAP2/GCS1 interactors nor mechanisms for delivery and activation at the fusion site are known in multicellular plants. Here, we show that Arabidopsis thaliana HAP2/GCS1 interacts with two sperm DUF679 membrane proteins (DMP8 and DMP9), which are required for the EGG CELL 1 (EC1)-induced translocation of HAP2/GCS1 from internal storage vesicle to the sperm plasma membrane to ensure successful fertilization. Our studies in Arabidopsis and tobacco provide evidence for a conserved function of DMP8/9-like proteins as HAP2/GCS1 partner in seed plants. Our data suggest that seed plants evolved a DMP8/9-dependent fusogen translocation process to achieve timely acquisition of sperm fusion competence in response to egg cell-derived signals, revealing a previously unknown critical step for successful fertilization.

miR-210 promotes immune- and suppresses oocyte meiosis-related genes in the zebrafish ovarian cells.

microRNA-210 (miRNA), a well-documented miRNA, has been implicated in a myriad of biological processes, including responses to hypoxia, angiogenesis, cell proliferation, and male infertility in humans. However, a comprehensive understanding of its functions in fish requires further investigation. This study pursued to elucidate the downstream effect of dre-miR-210-5p on primary ovarian cell culture in zebrafish (Danio rerio), an animal model. A protocol was settled down by incubations with either an miR-210 mimic or a scrambled miRNA in the isolated ovaries. RNA-sequencing analysis identified ∼6000 differentially expressed target genes revealing that downregulated genes were associated with reproduction-related pathways while immune-related pathways displayed an upregulated pattern. To identify molecular markers, predicted target genes were classified into reproduction and immune cell types. These findings underscore the existence of a profound interplay between the reproductive and immune systems, with miR-210 emerging as a pivotal player in orchestrating transcriptomic alterations within fish ovaries.

Involvement of cellular protrusions in gamete interactions.

Gamete fusion is of considerable importance in reproductive events, as it determines the gamete pairs or chromosomes that the next generation will inherit. To preserve species specificity with an appropriate karyotype, the fusion between gametes requires regulatory mechanisms to ensure limited fusion competency. In many organisms, gamete surfaces are not smooth, but present constitutive or transient cellular protrusions suggested to be involved in gamete fusion. However, the molecular mechanisms and the factors essential for the membrane-membrane fusion process and cellular protrusion involvement have remained unclear. Recent advances in the identification and functional analysis of the essential factors for gamete interaction have revealed the molecular mechanisms underlying their activity regulation and dynamics. In homogametic fertilization, dynamic regulation of the fusion core machinery on cellular protrusions was precisely uncovered. In heterogametic fertilization, oocyte fusion competency was suggested to correlate with the compartmentalization of the fusion essential factor and protrusion formation. These findings shed light on the significance of cellular protrusions in gamete fusion as a physically and functionally specialized site for cellular fusion. In this review, we consider the developments in gamete interaction research in various species with different fertilization modes, highlighting the commonalities in the relationship between gamete fusion and cellular protrusions.

Histone Variant H3.3 Controls Arabidopsis Fertility by Regulating Male Gamete Development.

Reprograming of chromatin structures and changes in gene expression are critical for plant male gamete development, and epigenetic marks play an important role in these processes. Histone variant H3.3 is abundant in euchromatin and is largely associated with transcriptional activation. The precise function of H3.3 in gamete development remains unclear in plants. Here, we report that H3.3 is abundantly expressed in Arabidopsis anthers and its knockout mutant h3.3-1 is sterile due to male sterility. Transcriptome analysis of young inflorescence has identified 2348 genes downregulated in h3.3-1 mutant, among which 1087 target genes are directly bound by H3.3, especially at their 3' ends. As a group, this set of H3.3 targets is enriched in the reproduction-associated processes including male gamete generation, pollen sperm cell differentiation and pollen tube growth. The function of H3.3 in male gamete development is dependent on the Anti-Silencing Factor 1A/1B (ASF1A/1B)-Histone regulator A (HIRA)-mediated pathway. Our results suggest that ASF1A/1B-HIRA-mediated H3.3 deposition at its direct targets for transcription activation forms the regulatory networks responsible for male gamete development.

Anisogamy Does Not Always Promote the Evolution of Mating Competition Traits in Males.

AbstractAnisogamy has evolved in most sexually reproducing multicellular organisms allowing the definition of male and female sexes, producing small and large gametes. Anisogamy, as the initial sexual dimorphism, is a good starting point to understand the evolution of further sexual dimorphisms. For instance, it is generally accepted that anisogamy sets the stage for more intense mating competition in males than in females. We argue that this idea stems from a restrictive assumption on the conditions under which anisogamy evolved in the first place: the absence of sperm limitation (assuming that all female gametes are fertilized). Here, we relax this assumption and present a model that considers the coevolution of gamete size with a mating competition trait, starting in a population without dimorphism. We vary gamete density to produce different scenarios of gamete limitation. We show that while at high gamete density the evolution of anisogamy always results in male investment in competition, gamete limitation at intermediate gamete densities allows for either females or males to invest more into mating competition. Our results thus suggest that anisogamy does not always promote mating competition among males. The conditions under which anisogamy evolves matter, as does the competition trait.

A cytoplasmic protein kinase couples engagement of Chlamydomonas ciliary receptors to cAMP-dependent cellular responses.

The primary cilium is a cellular compartment specialized for receipt of extracellular signals that is essential for development and homeostasis. Although intraciliary responses to engagement of ciliary receptors are well studied, fundamental questions remain about the mechanisms and molecules that transduce ciliary signals into responses in the cytoplasm. During fertilization in the bi-ciliated alga Chlamydomonas reinhardtii, ciliary adhesion between plus and minus gametes triggers an immediate ∼10-fold increase in cellular cAMP and consequent responses in the cytoplasm required for cell-cell fusion. Here, we identify a new participant in ciliary signaling, Gamete-Specific Protein Kinase (GSPK). GSPK is essential for the adhesion-induced cAMP increase and for rapid gamete fusion. The protein is in the cytoplasm, and the entire cellular complement responds to a signal from the cilium by becoming phosphorylated within 1 min after ciliary receptor engagement. Unlike all other cytoplasmic events in ciliary signaling, GSPK phosphorylation is not responsive to exogenously added cAMP. Thus, during ciliary signaling in Chlamydomonas, a cytoplasmic protein is required to rapidly interpret a still uncharacterized ciliary signal to generate a cytoplasmic response.

Integrative taxonomic analyses reveal that rapid genetic divergence drives Acropora speciation.

Reef-building corals provide the structural basis for one of Earth's most spectacular and diverse but increasingly threatened ecosystems. The reef-building coral genus Acropora may have undergone substantial speciation during the Pleistocene climate and sea-level changes. Here, we aimed to evaluate the speciation history of four morphologically similar tabular Acropora species (Acropora aff. hyacinthus, A. cf. bifurcata, A. cf. cytherea, and A. cf. subulata) using an integrative approach with morphology, genetic, and reproduction methodology. Extensive morphological analyses showed that these four species are distinct and exhibited high gamete incompatibility, preventing hybridization. Furthermore, population structure and principal component analyses with SNPs (>60,000) indicated that these species were genetically distinct, and the ABBA-BABA test did not support introgression among these species. Many of their coding and noncoding RNA sequences showed high genetic variance at loci with high Fst values along the genome. Comparison of these orthologs with those of other Acropora species suggested that many of these genes are under positive selection, which could be associated with spawning time, gamete, and morphological divergence. Our findings show that the speciation of tabular Acropora occurred without hybridization, and the divergence accompanying the rapid evolution of genes in species-rich Acropora could be associated with speciation.

Survey on ART and IUI: legislation, regulation, funding, and registries in European countries-an update.

STUDY QUESTION: How are ART and IUI regulated, funded, and registered in European countries, and how has the situation changed since 2018? SUMMARY ANSWER: Of the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding varies across and sometimes within countries (and is lacking or minimal in four countries), and national registries are in place in 33 countries; only a small number of changes were identified, most of them in the direction of improving accessibility, through increased public financial support and/or opening access to additional subgroups. WHAT IS KNOWN ALREADY: The annual reports of the European IVF-Monitoring Consortium (EIM) clearly show the existence of different approaches across Europe regarding accessibility to and efficacy of ART and IUI treatments. In a previous survey, some coherent information was gathered about how those techniques were regulated, funded, and registered in European countries, showing that diversity is the paradigm in this medical field. STUDY DESIGN, SIZE, DURATION: A survey was designed using the SurveyMonkey tool consisting of 90 questions covering several domains (legal, funding, and registry) and considering specific details on the situation of third-party donations. New questions widened the scope of the previous survey. Answers refer to the situation of countries on 31 December 2022. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: All members of the EIM were invited to participate. The received answers were checked and initial responders were asked to address unclear answers and to provide any additional information considered relevant. Tables resulting from the consolidated data were then sent to members of the Committee of National Representatives of ESHRE, requesting a second check. Conflicting information was clarified by direct contact. MAIN RESULTS AND THE ROLE OF CHANCE: Information was received from 43 out of the 45 European countries where ART and IUI are performed. There were 39 countries with specific legislation on ART, and artificial insemination was considered an ART technique in 33 of them. Accessibility is limited to infertile couples only in 8 of the 43 countries. In 5 countries, ART and IUI are permitted also for treatments of single women and all same sex couples, while a total of 33 offer treatment to single women and 19 offer treatment to female couples. Use of donated sperm is allowed in all except 2 countries, oocyte donation is allowed in 38, simultaneous donation of sperm and oocyte is allowed in 32, and embryo donation is allowed in 29 countries. Preimplantation genetic testing (PGT)-M/SR (for monogenetic disorders, structural rearrangements) is not allowed in 3 countries and PGT-A (for aneuploidy) is not allowed in 10; surrogacy is accepted in 15 countries. Except for marital/sexual situation, female age is the most frequently reported limiting criterion for legal access to ART: minimal age is usually set at 18 years and the maximum ranges from 42 to 54 with some countries not using numeric definition. Male maximum age is set in very few countries. Where third-party donors are permitted, age is frequently a limiting criterion (male maximum age ranging from 35 to 50; female maximum age from 30 to 37). Other legal restrictions in third-party donation are the number of children born from the same donor (or, in some countries, the number of families with children from the same donor) and, in 12 countries, there is a maximum number of oocyte donations. How countries deal with the anonymity is diverse: strict anonymity, anonymity just for the recipients (not for children when reaching legal adulthood age), a mixed system (anonymous and non-anonymous donations), and strict non-anonymity. Inquiring about donors' genetic screening showed that most countries have enforced either mandatory or scientific recommendations that exclude the most prevalent genetic diseases, although, again, diversity is evident. Reimbursement/compensation systems exist in more than 30 European countries, with around 10 describing clearly defined maximum amounts considered acceptable. Public funding systems are extremely variable. One country provides no financial assistance to ART/IUI patients and three offer only minimal support. Limits to the provision of funding are defined in the others i.e. age (female maximum age is the most used), existence of previous children, BMI, maximum number of treatments publicly supported, and techniques not entitled for funding. In a few countries reimbursement is linked to a clinical policy. The definitions of the type of expenses covered within an IVF/ICSI cycle, up to which limit, and the proportion of out-of-pocket costs for patients are also extremely dissimilar. National registries of ART are in place in 33 out of the 43 countries contributing to the survey and a registry of donors exists in 19 of them. When comparing with the results of the previous survey, the main changes are: (i) an extension of the beneficiaries of ART techniques (and IUI), evident in nine countries; (ii) public financial support exists now in Albania and Armenia; (iii) in Luxembourg, the only ART centre expanded its on-site activities; (iv) donor-conceived children are entitled to know the donor identity in six countries more than in 2018; and (v) four more countries have set a maximum number of oocyte donations. LIMITATIONS, REASONS FOR CAUTION: Although the responses were provided by well-informed and committed individuals and submitted to double checking, no formal validation by official bodies was in place. Therefore, possible inaccuracies cannot be excluded. The results presented are a cross-section in time, and ART and IUI frameworks within European countries undergo continuous modification. Finally, some domains of ART activity were deliberately left out of the scope of this survey. WIDER IMPLICATIONS OF THE FINDINGS: Our results offer a detailed updated view of the ART and IUI situation in European countries. It provides extensive answers to many relevant questions related to ART usage at the national level and could be used by institutions and policymakers at both national and European levels. STUDY FUNDING/COMPETING INTEREST(S): The study has no external funding, and all costs were covered by ESHRE. There were no competing interests.

Psychosocial outcomes of children born via embryo donation.

STUDY QUESTION: What are parents' perceptions of their relationships with and the psychosocial adjustments of their children who are born via embryo donation? SUMMARY ANSWER: Families created through embryo donation have well-adjusted parent-child relationships and reassuring child psychosocial outcomes. WHAT IS KNOWN ALREADY: Embryo donation is an effective and growing form of third-party reproduction, but there is limited research in this field. Prior studies suggest that families created through gamete donation function well regarding parent-child relationship quality and child behavioral and socioemotional adjustment. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional survey study with 187 total participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Parents of children born via embryo donation were recruited nationally by contacting all embryo donation programs registered with the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) as well as medically directed embryo donation or 'embryo adoption' centers. Participants completed three online Qualtrics questionnaires. The first was a survey including 33 questions on demographics, the procurement process, and self-reported obstetric outcomes. Participants also completed two standardized measures assessing children's behavior and parents' adjustment to parenthood: the Strengths and Difficulties Questionnaire (SDQ) and the Parental Acceptance-Rejection Questionnaire (PARQ). Scoring of the SDQ and PARQ was totaled and compared to standardized values (SDQ) or previously published results on other forms of gamete donation (PARQ), such as oocyte donation and sperm donation. MAIN RESULTS AND THE ROLE OF CHANCE: On the SDQ (n = 46), the average total difficulties scores by age were: 8.2 ± 0.98 for ages 2-4, 7.6 ± 0.93 for ages 5-10, and 3.5 ± 0.77 for ages 11-17; this is compared to the normal reported range of 0-13, which indicates that clinically significant psychosocial problems are unlikely. Across all ages and individual categories (emotional symptoms, conduct problem, hyperactivity, peer problem, prosocial), scores on the SDQ were within the normal ranges. The average PARQ score (n = 70) for all respondents was 27.5 ± 1.18 (range: 24-96), suggesting perceived parental acceptance. LIMITATIONS, REASONS FOR CAUTION: Because this study was cross-sectional, it could not capture familial relationships over time. This survey-based study design allows for potential selection bias (parents of well-adjusted children may be more likely to participate). Additionally, the overall sample size is relatively small; however, it remains one of the largest published to date. Another significant limitation to this study is the lack of generalizability: most participants were recruited from private, faith-based, embryo donation programs who are demographically similar. WIDER IMPLICATIONS OF THE FINDINGS: Though embryo donation is an established form of third-party reproduction, it is significantly less robustly studied compared to other forms of gamete donation (oocyte or sperm donation). This study provides a larger data set with a more expanded age range of children compared to the limited number of previously published studies. Furthermore, these findings indicate a high parental disclosure rate with respect to the use of embryo donation which contrasts previous findings. STUDY FUNDING/COMPETING INTEREST(S): No external funding source was utilized for the completion of this study. No conflicts are disclosed. TRIAL REGISTRATION NUMBER: N/A.

Why so many polyploids? Accounting for environmental stochasticity in unreduced gamete formation lowers the perceived barriers to polyploid establishment.

While polyploids are common in nature, existing models suggest that polyploid establishment should be difficult and rare. We explore this apparent paradox by focussing on the role of unreduced gametes, as their union is the main route for the formation of neopolyploids. Production of such gametes is affected by genetic and environmental factors, resulting in variation in the formation rate of unreduced gametes (u). Once formed, neopolyploids face minority cytotype exclusion (MCE) due to a lack of viable mating opportunities. More than a dozen theoretical models have explored factors that could permit neopolyploids to overcome MCE and become established. Until now, however, none have explored variability in u and its consequences for the rate of polyploid establishment. Here, we determine the distribution that best fits the available empirical data on u. We perform a global sensitivity analysis exploring the consequences of using empirical distributions of u to investigate effects on polyploid establishment. We determined that in many cases, u is best fit by a log-normal distribution. We found environmental stochasticity in u dramatically impacts model predictions when compared to a static u. Our results help reconcile previous modelling results suggesting high barriers to the polyploid establishment with the observation that polyploids are common in nature.

Why it is important that we understand the information that gamete donors provide about themselves to recipients.

A personal description and goodwill message is often the only form of communication a gamete recipient receives from the donor. However, the nature of the information gamete donors leave for recipients is not well understood. This Viewpoint article discusses a recent study published in this journal that makes a significant contribution to our understanding of this area of research and raises important questions for research going forward.

Direct-to-consumer genetic testing and the changing landscape of gamete donor conception: key issues for practitioners and stakeholders.

RESEARCH QUESTION: What effect does direct-to-consumer genetic testing (DTCGT) have on information finding and sharing in relation to gamete donor conception? DESIGN: This study used in-depth qualitative interviews with parents through donor conception, donors, the relatives of donors and donor-conceived people who have used, or considered using, DTCGT. Interviews were conducted between September 2021 and February 2023. Sixty people defined themselves as having been affected by donor conception and DTCGT. Fifty-seven of these were resident in the UK at the time of interview. The final sample included 19 (spermatozoa, egg or embryo) donors, 25 donor-conceived people, 20 parents through donor conception and two relatives of donors. Five participants occupied more than one of these roles. RESULTS: The rise of DTCGT is affecting how information about donor conception is managed: it shifts patterns of knowledge about donor conception; increases flexibility regarding the age of access to information about donor relatives; can lead to a growing role for non-professionals, including wider family members, in gatekeeping information about donor conception; accentuates the effect of donor conception for donors' and the relatives of donor-conceived people; and shapes, and is shaped, by the formal regulatory donor information management systems. CONCLUSION: Fertility professionals should inform people using, or considering, donor conception, or (potential) donors, about the different ways DTCGT can affect sharing information about donor conception. Support is needed for those affected by these changes.

Fertility preservation in patients undergoing gonadotoxic treatments: a Canadian Fertility and Andrology Society clinical practice guideline.

The management of young patients with cancer presents several unique challenges. In general, these patients are ill prepared for the diagnosis and the impact on their fertility. With the improved survival for all tumour types and stages, the need for adequate fertility counselling and a multidisciplinary approach in the reproductive care of these patients is paramount. Recent advances in cryopreservation techniques allow for the banking of spermatozoa, oocytes, embryos and ovarian tissue without compromising survival. This Canadian Fertility and Andrology Society (CFAS) guideline outlines the current understanding of social and medical issues associated with oncofertility, and the medical and surgical technologies available to optimize future fertility.