Executive Editor-in-Chief's introduction for This Special Issue

Prof. Ri-Cheng Chian is Director at Center for Reproductive Medicine, Shanghai 10th People's Hospital of Tongji University, China. Before joining the current position, Dr. Chian was an Associate Professor with Tenure at Department of Obstetrics and Gynecology, Faculty of Medicine, McGill University, Montreal, Canada. Dr. Chian is the key person in the development of in vitro maturation (IVM) of human oocytes for clinical application and for cryopreservation of human oocytes which resulted in pregnancies and live births at McGill University Health Center (MUHC) in Canada. Dr. Chian's research interests are included: 1) Simplifying infertility treatment with Assisted Reproductive Technologies (ARTs); 2) Fertility preservation. Dear Colleagues, As an Executive Editor-in-Chief, I have edited this Special Issue (SI), entitled “Fertility preservation” in the journal Reproductive and Developmental Medicine (RDM, ISSN: 2096-2924, CN:10-1442/R), the first ever English journal in the field of reproductive medicine and developmental biology in mainland China. Since its launch in 2017, RDM has been dedicated to providing a good platform for academic exchanges among scientists, both at home and abroad. Over the last few decades, the incidence of cancer in patients has increased by 20%, even as mortality rates have declined due to progress in cancer treatments. More than 90% of teenage girls and young women with malignancies who underwent aggressive chemotherapy and/or radiotherapy coupled with bone marrow transplantation have survived. However, chemotherapy with alkylating agents and radiation therapy in fields that includes the pelvis has an adverse effect on ovarian reserve, which may lead to premature ovarian failure (POF) and infertility. The number of cancer survivors is increasing every year, leaving a growing number of women of reproductive age facing the risk of POF and infertility. One of the major concerns is whether these women will be able to have healthy children after cancer treatment. Therefore, fertility preservation is an important issue that should be addressed in women who are at risk of POF after gonadotoxic chemotherapy or radiotherapy treatment for cancer and autoimmune and hematologic disorders or potentially sterilizing surgical procedures. Several strategies for female fertility preservation in patients with cancer have been proposed. The clinical options for female fertility preservation can be divided into 2 broad categories: surgical interventions and cryopreservation of cells/tissues. Surgical procedures include ovarian transposition in patients who require pelvic irradiation and radical trachelectomy for a select few low-grade and early-stage cancer patients, such as those with cervical, endometrial, or epithelial ovarian cancer. Female patients have 3 main cryopreservation options for fertility preservation: embryos, oocytes, and ovarian tissues. The American Society of Clinical Oncology and the American Society for Reproductive Medicine have published guidelines for female fertility preservation before gonadotoxic oncologic treatment, indicating that embryo cryopreservation is currently the only viable strategy. Embryo production involves ovarian stimulation with gonadotropin, followed by retrieval of mature oocytes and in vitro fertilization using sperm from a male partner or donor. This procedure may require several weeks for preparation. The window of opportunity for fertility preservation is small. Ovarian stimulation with follicle-stimulating hormone (FSH) may not be suitable for some patients who cannot delay their cancer treatment. Therefore, embryo cryopreservation may not be a feasible option for many patients with cancer. Moreover, embryo cryopreservation is not a feasible option for women who lack a male partner or those who object to the use of donor sperm. Furthermore, embryo cryopreservation is excluded for prepubertal girls who are at risk of POF, for whom cryopreservation of ovarian tissues is the only method of fertility preservation. Although there have been more than 130 successful live births after ovarian tissue cryopreservation and orthotopic transplantation, these procedures are still considered experimental. Oocyte cryopreservation may be considered a prime option for preserving female fertility. Normally, oocyte cryopreservation involves ovarian stimulation, mature oocyte retrieval, and cryopreservation. However, the standard ovarian stimulation procedure may not be feasible for some cancer patients. Breast cancer remains the most common cancer in women and accounts for approximately 30% of all female cancers. The risk of breast cancer is associated with persistently elevated blood estrogen levels. Ovarian stimulation using FSH causes a state of high estrogen concentrations in serum; hence, the safety of ovarian stimulation with FSH in breast cancer patients is a primary concern, especially in women with estrogen-positive breast cancer. Although the special stimulation protocol with the combination of letrozole and low-dose FSH has been applied for ovarian stimulation in breast cancer patients, the effect of a temporary increase in the level of estrogen in serum increases the risk of breast cancer recurrence. Recent findings also suggest that estrogen has an indirect mitogenic effect on hormone receptornegative breast cancer. In addition, other oncologic or non-oncologic diseases, such as systemic lupus erythematosus, desmoid tumors, or severe endometriosis, are also considered estrogensensitive. The influence of estrogen elevation on some cancer patients remains unclear and controversial. It has been suggested that, if possible, avoiding the elevation of estrogen concentrations to supraphysiologic levels is a good option for fertility preservation in breast cancer patients, regardless of their estrogen receptor status. Immature oocyte retrieval from the ovaries without prior ovarian stimulation followed by in vitro maturation (IVM) and cryopreservation is a promising fertility preservation option for women who cannot undergo hormonal ovarian stimulation or for those who cannot delay their gonadotoxic cancer treatment. As a result, immature oocyte retrieval followed by IVM and cryopreservation has been proposed as a safer alternative. The advantages of this method for fertility preservation are that the patients are not at the risk of elevated estrogen levels, and that the treatment can be completed in a shorter period of time compared with the standard protocols of ovarian stimulation for oocyte or embryo cryopreservation. This SI included 6 papers, which were as follows: Source of oocytes for infertility treatment and fertility preservation. This suggests that the source of oocytes is directly related to the success of infertility treatment and fertility preservation. Different protocols for ovarian stimulation are used to obtain oocytes. However, the quality of oocytes retrieved should be considered the most important factor for effective infertility treatment and fertility preservation. A high dose of ovarian stimulation may be a potential risk for both women and infants. Successful infertility treatment and fertility preservation should be defined as the birth of a healthy baby at term, without compromising the health and safety of the women and infants. Offspring from oocytes grown in frozen-thawed ovarian tissues transplanted into male and female bodies. This demonstrated that the follicles can survive and develop in the frozen-thawed ovarian tissues following subcutaneous transplantation to adult male mice, regardless of the basal endocrinal environment. These fully grown oocytes can produce healthy and fertile offspring, which provides the possibility for further mechanistic understanding of the endocrinology of folliculogenesis. Effect of vitrification on clinical outcomes of cleavage-stage embryos with poor quality for human embryo cryopreservation. This suggests that vitrification methods do not effectively improve survival outcomes for embryos of poor quality, and it is necessary to develop a comprehensive vitrification protocol that considers all practical aspects, including the current limitation regarding the poor quality of cleavage-stage embryos. Study on the mechanism ofSalvia miltiorrhiza-Codonopsis pilosuladrug pair in the treatment of POF based on network pharmacology-molecular docking. In this paper, it has been indicated that S. miltiorrhiza-C. pilosula is effective in treating POF. As there is a lack of knowledge regarding the mechanisms of the drug pair in the treatment of POF, the authors conducted a network pharmacology and molecular docking technique to clarify this issue. The authors demonstrated that S. miltiorrhiza-C. pilosula can inhibit ovarian granulosa cell apoptosis and improve ovarian hemodynamics in the treatment of POF through multiple targets and pathways. How fertility preservation guidelines have progressed worldwide: Potential implications and inspiration. In this paper, it was concluded that, with promising cancer survival rates and diversified family decisions, more attention should be paid to improving and updating accessible guidelines and regulatory infrastructure, informing patients about the available options, and empowering them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain fertility preservation techniques for the right candidates to initiate pregnancy conception. Chinese expert consensus on the clinical practice of female fertility preservation. The consensus includes 2 parts: (a) indications for female fertility preservation and related techniques, in which we sought to be inclusive regarding the indications for fertility preservation; and (b) practical guidance for the clinical application of female fertility preservation technologies. Although fertility preservation is still relatively new in the field of reproductive medicine and assisted reproductive technologies, I hope that this SI contributes to its increased availability. We believe that this SI of fertility preservation will offer many valuable information to colleagues in the field. Ri-Cheng Chian, MSc., PhD Executive Editor-in-Chief Reproductive and Developmental Medicine (RDM)

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