Fertility Preservation Programme in a Tertiary-Assisted Reproduction Unit in Hong Kong

Background: Fertility preservation is increasingly important with improving cancer survival rates and the delay in childbearing in modern societies. The objective of our study was to review the experience of the fertility preservation programme in a tertiary-assisted reproduction unit in Hong Kong. Methods: This is a retrospective study involving men and women who were seen at a tertiary-assisted reproduction unit for fertility preservation counselling before gonadotoxic treatment from January 2005 to December 2020. Their medical records in paper and electronic forms were reviewed. Results: There were 75 consultations for female fertility preservation from 2010 to 2020 involving 72 women. Twenty women underwent 22 cycles of ovarian stimulation for oocyte or embryo cryopreservation, two of whom subsequently transported their oocytes abroad for further management and another two achieved natural conception. Additional four women who did not have oocyte or embryo cryopreservation achieved natural conception after cancer treatment. Eleven (15.2%) women were followed up at a reproductive endocrinology clinic after their cancer treatment. From 2005 to 2020, 265 men had sperm cryopreserved. Twenty-six (9.8%) came back to use the cryopreserved sperms, the wives of 13 (50.0%) of whom achieved an on-going pregnancy. Six of them transferred out and 40 discarded the cryopreserved sperms. Conclusions: There was generally an increasing number of patient consultations for fertility preservation in our Centre over the past decade but a consistently low rate of utilisation of cryopreserved gametes for both women and men. Post-cancer treatment fertility evaluation and monitoring was a major area of deficiency in Hong Kong. More structured post-cancer treatment fertility follow-up is needed.

Actinomycin D causes oocyte maturation failure by inhibiting chromosome separation and spindle assembly†

Actinomycin D (ActD) has been considered as one of the most effective and safe chemotherapeutic medications for treating a number of cancers. Although ActD has been used in the treatment of gynecological tumors and pediatric tumors for more than 50 years, the toxic effects of ActD on mammalian oocytes remain unknown. In this study, the influence of ActD on mouse and human oocyte maturation and the possible mechanisms were investigated. Notably, ActD inhibited oocyte maturation and arrested oocytes at the metaphase I (MI) stage in a dose-dependent manner. In addition, ActD arrested oocyte maturation when the oocytes were treated at different successive stages, including the germinal vesicle (GV), germinal vesicle breakdown, and MI stages. In ActD-treated oocytes, disordered chromosome condensation and irregular spindle assembly occurred, resulting in incomplete chromosome segregation and oocytes arresting at the MI phase; these results possibly occurred because ActD triggered the formation of reactive oxygen species, resulting in DNA damage and decreased ATP in mouse GV oocytes. Besides, in vivo treatment with ActD also inhibited mouse oocyte maturation. Similar effects were seen in human oocytes. Collectively, our results indicated that ActD exposure disrupted oocyte maturation by increasing DNA damage, which is a finding that might help with optimizing future methods for female fertility preservation before undergoing chemotherapy.

Oocyte Cryopreservation in Emergency Situations: Perspectives and Reality

Increased incidence of global recorded cancer, unforeseen circumstances in assisted reproductive technology, a pandemic situation, and surgical interventions which can cause impairment of the reproductive system all necessitate urgent fertility preservation. Unfortunately, the application of successfully developed methods for oocyte and embryo cryopreservation is not possible in some situations because of contraindications for inducing superovulation, inability to delay other treatments, or in the case of prepubertal patients; in these cases, cryopreservation of ovarian tissue may be an alternative method. Despite current achievements in ovarian tissue low-temperature preservation, only 130 children have been born using this method. Further development of this technique and methods for in vitro maturation of immature oocytes, following their cryopreservation and use in assisted reproductive technology, as well as a differentiated approach for the selection of mature oocytes obtained without preliminary superovulation are needed. This review outlines the modern achievements and future prospects of female fertility preservation in emergency situations by cryopreservation of oocytes with different quality and maturity states.

Fertility navigators in female oncofertility care in an academic medical center: a qualitative evaluation

Purpose To explore patients’ and professionals’ experiences with fertility navigators in female oncofertility care. Methods Semi-structured in-depth interviews were conducted with nine female cancer patients and six healthcare professionals to explore their experiences. They were recruited from an academic medical center (referral clinic for female fertility preservation care). Data were analyzed using the concepts of grounded theory. Results Patients were satisfied about the supportive role of the fertility navigator in their fertility preservation process: fertility navigators added value as they became “familiar faces” and provided information, emotional support, personal care, and served as patients’ primary contact person. The fertility navigators had a pleasant collaboration with professionals and supported professionals by taking over tasks. To improve the role of fertility navigators, it was suggested that they should always be present in fertility preservation counseling, and attention should be paid to their availability to improve continuity of care. Conclusion Fertility navigators provide personal care, improve satisfaction in patients in their oncofertility process, and support professionals. The overview of issues that need to be addressed when assigning fertility navigators in female oncofertility care combined with the improvement suggestions could be used by other centers when considering implementing fertility navigators.

The effects of human umbilical cord mesenchymal stem cell transplantation on female fertility preservation in mice

Female fertility is the capacity to produce oocytes and achieve fertilization and pregnancy, and these outcomes are impaired by age, diseases, environment and social pressure. However, there is no effective therapy that preserves female reproductive ability. Mesenchymal stromal cells (MSCs) can exhibit multidirectional differentiation potential, and they have gained great attention as a tool for preserving female fertility. Therefore, this study uses human umbilical cords-MSCs (Huc-MSCs) to preserve and restore fertility in aging female mice and chemotherapy-damaged mice through the rescue of ovarian function and the reconstruction of the fallopian tubes and uterus. In our study, 2 mouse models were generated: aging mice (37 weeks old) and chemotherapy-damaged mice. Then, we injected Huc-MSCs into mice through the tail vein. After treatment, the effect of MSCs on the ovary, fallopian tubes and uterus was evaluated by analyzing gonadal hormone levels and by performing morphological analysis and statistical analysis. The levels of E2 and FSH exhibited a significant recovery after HUC-MSC transplantation both in aging mice and mice treated with chemotherapy. Huc-MSC treatment also increased the numbers of primordial, developing and preovulatory follicles in the ovaries of mice. Meanwhile, MSCs have been shown to rescue the morphology of the fallopian tubes and uterus through mechanisms such as regenerating the cilia in fallopian tubes and reforming glands and chorionic villi in the uterus. Therefore, it is suggested that Huc-MSCs may represent an effective potential treatment for preserving female fertility through recovery from chemotherapy damage and rescuing female reproductive organs from the effects of aging.

ESHRE guideline: female fertility preservation†

STUDY QUESTION What is the recommended management for women and transgender men with regards to fertility preservation (FP), based on the best available evidence in the literature? SUMMARY ANSWER The ESHRE Guideline on Female Fertility Preservation makes 78 recommendations on organization of care, information provision and support, pre-FP assessment, FP interventions and after treatment care. Ongoing developments in FP are also discussed. WHAT IS KNOWN ALREADY The field of FP has grown hugely in the last two decades, driven by the increasing recognition of the importance of potential loss of fertility as a significant effect of the treatment of cancer and other serious diseases, and the development of the enabling technologies of oocyte vitrification and ovarian tissue cryopreservation (OTC) for subsequent autografting. This has led to the widespread, though uneven, provision of FP for young women. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 November 2019 and written in English were included in the review. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help providers meet a growing demand for FP options by diverse groups of patients, including those diagnosed with cancer undergoing gonadotoxic treatments, with benign diseases undergoing gonadotoxic treatments or those with a genetic condition predisposing to premature ovarian insufficiency, transgender men (assigned female at birth), and women requesting oocyte cryopreservation for age-related fertility loss. The guideline makes 78 recommendations on information provision and support, pre-FP assessment, FP interventions and after treatment care, including 50 evidence-based recommendations—of which 31 were formulated as strong recommendations and 19 as weak—25 good practice points and 3 research only recommendations. Of the evidence-based recommendations, 1 was supported by high-quality evidence, 3 by moderate-quality evidence, 17 by low-quality evidence and 29 by very low-quality evidence. To support future research in the field of female FP, a list of research recommendations is provided. LIMITATIONS, REASONS FOR CAUTION Most interventions included are not well studied in FP patients. As some interventions, e.g. oocyte and embryo cryopreservation, are well established for treatment of infertility, technical aspects, feasibility and outcomes can be extrapolated. For other interventions, such as OTC and IVM, more evidence is required, specifically pregnancy outcomes after applying these techniques for FP patients. Such future studies may require the current recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in female FP, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in FP. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. R.A.A. reports personal fees and non-financial support from Roche Diagnostics, personal fees from Ferring Pharmaceuticals, IBSA and Merck Serono, outside the submitted work; D.B. reports grants from Merck Serono and Goodlife, outside the submitted work; I.D. reports consulting fees from Roche and speaker’s fees from Novartis; M.L. reports personal fees from Roche, Novartis, Pfizer, Lilly, Takeda, and Theramex, outside the submitted work. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.) †ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.