Meeting proceedings: International Society for Fertility Preservation Tokyo, 15–17 November, 2024

Abstract

The 8 th International Congress of the ISFP was held in Tokyo, Japan, from November 15 to 17, 2024. The theme of this year’s Congress was “Rethinking Personalized Fertility Preservation and Cancer Survivors-Opening a New Frontier”. The congress featured special lectures, keynote addresses, and 25 sessions—including a dedicated session on nursing and oral presentations by young doctors and researchers—making it one of the largest and most comprehensive events in the ISFP’s history. Additionally, the program incorporated sessions featuring the Japanese, Korean, and Chinese Societies for Fertility Preservation, providing a convenient platform for international participants from across the globe to showcase their work and discuss the unique characteristics and challenges of these areas within Asia. Participants also had the opportunity to attend workshops on ovarian tissue cryopreservation and oocyte cryopreservation, conducted by leaders in their respective fields exploring the latest technological and clinical advances and translational prospects for the future.

Graphical Abstract

Introduction and overview

The 8 th World Congress of the International Society for Fertility Preservation (ISFP) was held from November 15 to 17, 2024, at JP Tower and Conference in Tokyo, Japan, bringing together more than six hundred participants, including internationally renowned experts in fertility preservation. The congress provided a platform for specialists to present significant updates on the achievements of the past 20 years as well as future research directions. In addition, the Chinese Society for Fertility Preservation (CSFP), the Korean Society for Fertility Preservation (KSFP), the Japan Society for Fertility Preservation (JSFP), and the Asian Society for Fertility Preservation (ASFP) actively engaged in discussions with experts from around the world, addressing key challenges in the Asian region. Furthermore, a nursing session was introduced to discuss topics concerning the relationship between co-medical staff and patients. What follows is a daily summary of key activities and a detailed summary of each day’s sessions with commentary and referencing to the major issues covered reflecting upon and contextualizing the “state-of-the art” in fertility preservation from a global perspective.

Friday, November 15, 2024

On Friday, workshops on oocyte vitrification and ovarian tissue cryopreservation (vitrification) were held. Simultaneously, ASFP and ISFP committee members conducted case discussions on challenging clinical scenarios. Additional sessions covered a variety of topics (including sessions held by the CSFP and KSFP), spanning from in vitro maturation (IVM) to ovarian transport, Preimplantation genetic testing (PGT), ovarian tissue transplantation, and ovarian protection.

Saturday, November 16, 2024

Saturday began with the President Lecture by Congress Chair Nao Suzuki (Japan), followed by Honorary Lectures delivered by Samuel Kim (USA) and Jacques Donnéz (Belgium). The program also included a JSFP session, a nursing session, and a session on fertility preservation in benign gynecological diseases, such as endometriosis.

Sunday, November 17, 2024

On Sunday, the day commenced with a special lecture by Jennifer J. Mueller (USA) on uterine transposition, followed by sessions on the ASFP session, artificial ovaries, testicular tissue cryopreservation, fertility preservation in Turner syndrome, and ovarian tissue cryopreservation. Overall, the congress spanned three days and featured 25 sessions, making it a highly successful and impactful meeting.

Detailed report of scientific events:

Day 1: Friday, November 15

Session 1: ASFP session with ISFP—case discussion

• Case 1: Fertility preservation in breast cancer

• Case 2: Case report: fertility preservation in a patient with endometrial cancer

• Case 3: Fertility preservation in endometriosis

The session opened with remarks from the session chairs, Mohd Faizal (Malaysia) and Arby Jane Rouque Igualada (Philippines). ISFP representatives Kenny Rodriguez-Wallberg (USA) and Marie-Madeleine Dolmans (Belgium) joined as panelists for all three cases. During the session, three crucial fertility preservation (FP) management cases were discussed, focusing on breast cancer, endometrial cancer, and endometriosis. Representatives from various countries and ASFP discussed these cases with the ISFP panelists, underscoring the importance of the topics addressed.

Everlyn Wong (Hong Kong) presented the breast cancer case, with input from ASFP panelists Jennifer K Ys Ko (Hong Kong) and Nalini Kaul Mahajan (India). The discussion revealed a unanimous agreement among the panelists on the benefits of estrogen-sparing stimulation using an aromatase inhibitor or tamoxifen to reduce the risk of elevated estrogen levels during controlled ovarian stimulation (COS), providing a reassuring consensus [1]. All panelists also agreed on the importance of discussing proper surgical staging with the breast endocrine surgeon—including histological subtype confirmation—prior to COS for safety purposes. Moreover, the role of preimplantation genetic testing (PGT) for BRCA mutations or other known mutations was highlighted as a concurrent strategy for FP among breast cancer patients, further reinforcing a comprehensive approach to the case [2].

Subsequently, Jasneet Kaur (India) presented the endometrial cancer case, with discussants Madhuri Patil (India) and Budi Wiweko (Indonesia). The discussion emphasized the promising potential of progestogen supplementation—administered either via intrauterine devices (IUDs) or orally—for the regression of endometrial cancer [3]. The progestin-primed ovarian stimulation (PPOS) regimen, which shows promise as an effective strategy, offers a hopeful outlook. In addition, the ISFP panel stressed the utility of molecular classification to guide FP strategies, citing the prognostic evaluation of pathogenic somatic mutations in the replicative DNA polymerase epsilon (POLE) domain [4]. However, the limited availability and high cost of such testing may hinder its implementation in the FP field, underscoring the need for further research and development.

The session was concluded with the final presentation on a benign gynecological condition—fertility preservation in an endometriosis case—delivered by Budi Wiweko (Indonesia), followed by a discussion led by JR Lee (Korea) and Chii-Ruey Tzeng (Taiwan), who provided valuable insights and feedback. The discussion aligned with current recommendations from the European Society of Human Reproduction and Embryology (ESHRE) regarding endometriosis-associated fertility, suggesting that operative laparoscopy can be offered as a treatment option for stage I/II endometriosis-associated subfertility, as it improves the rate of ongoing pregnancy. Furthermore, according to ESHRE, clinicians may consider operative laparoscopy for the treatment of endometrioma-associated infertility, as it may increase the chance of natural pregnancy [5]. Nevertheless, the issue of oocyte and embryo freezing in endometriosis cases was also highlighted. Most discussants agreed that embryo or oocyte freezing can be performed either before or after surgery, provided that the anti‑Müllerian hormone (AMH) level remains within acceptable limits. Surgery may also be indicated if the location and size of the ovarian endometrioma hinders the feasibility of oocyte retrieval. In conclusion, endometriosis is a chronic condition with significant fertility concerns—stemming both from its inherent pathophysiology and from the potential depletion of the follicular reserve due to treatment interventions. Therefore, fertility preservation should be offered accordingly.

Session 2: IVM

Jesús Cadenas (Denmark) described human in vitro maturation (IVM) in connection with ovarian tissue cryopreservation (OTC).

He introduced collecting immature oocytes from the medullary ovarian tissue in OTC protocol. The medullary tissue contains many small antral follicles (SAFs) (0.5–3 mm) and from his data about 25–36 oocytes are obtained per patient. He noted the oocytes from SAFs recovered during OTC have the capacity to mature, to be fertilized and to develop into a blastocyst in vitro. However, the reduced expression of FSH receptors on cumulus cells require high concentrations of FSH to secure the induction of LHR [6]. LHR expression on cumulus cells from SAFs is central to MII transition. LHR expression is probably reduced by GDF9 secretion from the immature oocyte [7]. GDF9 becomes downregulated by exposure to high FSH levels. Collectively FSH and reduced GDF9 release the “brake” for oocyte maturation and LH-induced inhibin-A and potentially other hormones accelerate the process.

Michel De Vos (Belgium) spoked about IVM and its application in oncofertility. He emphasized that ovarian tissue oocyte (OTO)-IVM is an important additional reproductive option for FP patients and particularly suitable for patients at high risk of malignant cell metastasis in ovarian tissue. Of note, in his own data he emphasized that the utility of OTO-IVM in very young girls is doubtful [8]. He also introduced the biphasic IVM [9] and co-culture of COCs with engineered ovarian support cells [10].

Ri-Cheng Chian (China) described pre-IVF incubation system to improve the quality of oocytes for fertility preservation. He showed that even a short time (average of 5 h) of pre-IVF incubation for COCs after oocyte pick up (OPU) in specially designed maturation medium can improve oocyte quality as evidenced by oocyte maturity, fertilization, embryonic development, and clinical outcomes following embryo transfer [11].

The last speaker of this session, Sanaz Dereh Haim Tzfanya (Israel), spoke about the effect of local environment on primordial follicle activation. She showed the role of ECM in follicle activation on mice and provided new insights into local primordial follicle environment, particularly collagen IV in basal lamina, in maintaining follicles dormancy, whole its digestion triggers activation. AMH, as a main negative regular of activation, may inhibit the follicle activation triggered by partial digestion of collagen IV in basal lamina.

Session 3: Ovarian tissue transportation

The third session of the day focused on the transportation and preservation of ovarian tissue, particularly in the context of fertility preservation for cancer patients. Claus Yding Andersen (Denmark) initiated the session, discussing the current situation in Japan regarding declining birth rates and the aging population. He highlighted the challenges faced by hospitals, including centralization and the impact of natural disasters on healthcare delivery. He emphasized the need for a robust transportation network for ovarian tissue, referencing establishment of designated cancer centers and the limited number of facilities capable of performing ovarian tissue cryopreservation. He presented a paper from 20 years ago that reported that cryopreservation of ovarian tissue by transporting ovarian cortex on ice for up to four hours could allow survival of primordial follicles after cryopreservation and transplantation into immunodeficient mice [12]. OTC is primarily used for fertility preservation in girls and women undergoing gonadotoxic treatment. It has been suggested that ovarian tissue preserved at reproductive age could be used to avoid premature ovarian failure (POI) in cases of familial predisposition or to delay menopause in patients at high risk for osteoporosis or cardiovascular disease [13].

Jana Bender-Liebenthron (Germany) presented overnight transport of ovarian tissue for cryopreservation in a central cryobank. The ovaries contain different cell types each with different needs, which are essential for the survival and growth of the implanted follicles. To minimize tissue damage during transport, it is essential to maintain the temperature at 2.9 °C and the pH as close as possible to physiological levels of 7.3. Previous studies have shown that human ovarian tissue can be transported at 4℃ for up to 24 h without significant limitations. A challenge during the transport of ovarian tissue is that an ischemic process begins immediately after the ovaries are removed, resulting in follicular apoptosis. A process is needed to protect the cells during the long transport period. Jana Liebenthron et al. investigated the feasibility of transporting ovarian tissue overnight prior to cryopreservation and reported that overnight transport for central cryobanking is a feasible concept that results in high, reproducible success rates through standardized, specialized tissue freezing media and storage [14]. Recent data from the FertiPROTEKT network show that, if appropriate cryopreservation techniques are used, the quality of ovarian tissue is not significantly affected by the transport of ovarian tissue. There is no negative effect on endocrine activity, pregnancy rate, or live birth rate. In conclusion, there is sufficient evidence to support the feasibility and efficacy of ovarian tissue transport, cryopreservation, and subsequent transplantation. However, further technical improvements, such as a deeper look into how to best protect the different ovarian cells and improved freezing and thawing/rewarming techniques, remain to be done.

Koichi Kyono (Japan) presented data about the safe and secure ovarian tissue transportation in the Human Ovarian-tissue Preservation Enterprise (HOPE). In Japan, there are about 480 designated cancer centers, but most of them lack the equipment and the know-how for OTC, and as a result, the percentage of facilities performing OTC and ovarian tissue transplantation (OTT) is low compared to countries such as Denmark. Aiming for “the woman stays, the tissue moves” paradigm, which achieves maximum value at minimum cost, the HOPE initiative was established in Tokyo in 2016. He reported two fundamental studies. The first aimed at evaluating the effect of long-term cold transport on the survival of preantral follicles. The results strongly suggest that long-term cold transport of ovarian tissue may be useful when no local system for fertility preservation is available [15]. The second study investigated the effectiveness of ovarian tissue transport networks for fertility preservation (FP) in cancer patients in Japan. The Danish model (“women stay, tissues move”) was considered to be the best method in Japan, since it allows maximum benefit with minimum effort [16]. HOPE is located near Haneda Airport and Shinagawa train Station, making it convenient for transportation and resistant to natural disasters. Ovarian tissue samples are stored in two LN2 tanks, so if an accident occurs in one tank, the tissue stored in the other tank can be used. In addition, by collaborating with cancer treatment hospitals that do not have OTC capabilities and facilities that can perform laparoscopic surgery, it is possible to provide optimal medical care to patients. In addition, it is necessary to hand over the FP management to people with a long history, management skills, and foresight, such as Adachi Hospital (Kyoto, Japan) and Mayo Clinic (Minnesota, USA), and to collaborate with other OTC centers.

In conclusion, this model is called the Danish model. Not only is it truly patient-centered medicine and a way to achieve the most benefit with the least effort, but it may also be optimal for medical professionals.

Session 4: KSFP session

This session consists of seven speakers. Endometriotic cysts are typically treated with laparoscopic surgery. However, Haeun Jung (Korea) hypothesized that aspiration, rather than surgical intervention, is a better method for preserving ovarian reserve. He performed transvaginal aspiration of endometriotic cysts, washed the cysts with saline, and then administered a progestin (Dienogest) for 3 months. The results showed a significant decrease in CA125 levels and improvement in dysmenorrhea and dyspaurenia symptoms using the visual analogues scale (VAS) scores, while AMH levels were maintained. Additionally, a pathological evaluation of the aspirated fluid did not reveal any cancer cells. Other reports have shown that the aspiration method results in a 10.2% reduction in endometriotic cyst size after 3 months and a 27.3% reduction after 6 months [17, 18]. Further case studies are needed, but this method may be a viable option for preserving AMH levels.

In Korea, the most common cause of POI is cancer treatment, particularly chemotherapy. While numerous studies have reported the efficacy of platelet-rich plasma (PRP) for POI, the detailed mechanism remains unclear. To investigate this, Jungwoo Shin (Korea) conducted an experiment using rats treated with cyclophosphamide and administered PRP to their ovaries, followed by single-cell RNA sequencing. The data suggested that PRP improved the ovarian microenvironment, particularly angiogenesis. Single-cell RNA sequencing revealed that high-dose PRP groups exhibited more folliculogenesis and fewer atretic follicles. Furthermore, PRP treatment showed significant enhancement in antioxidant response, DNA repair, and autophagy, but there was no significant difference in apoptosis compared to the control group. These findings indicate that PRP therapy may be effective in treating POI following cyclophosphamide treatment.

The impact of PD- 1 inhibitors, a type of immune checkpoint inhibitor (ICI), on female fertility remains largely unknown. Inha Lee (Korea) explored how a combination of traditional chemotherapy and ICIs affects primordial follicles. Using a mouse model, they administered cyclophosphamide, pembrolizumab, or a combination of both. Histological analysis revealed significant differences in follicle counts (primordial, primary, secondary, and antral follicles) compared to the control group in both the cyclophosphamide and combination groups. Additionally, staining for the phospho-H2 AX (γH2 AX), a marker of DNA-double-stranded breaks, showed increased DNA damage in the pembrolizumab, cyclophosphamide, and combination groups compared to the control. CASP- 3 and Bcl- 2 analyses did not show statistically significant differences. These results suggest that ICIs may require consideration for fertility preservation.

From 2016 to 2019, Euna Choi (Korea) conducted fertility preservation counseling for 545 cancer patients. The most common types of cancer among these patients were breast cancer, followed by hematologic, gynecologic, and gastrointestinal cancer. Among these patients, 99 received only counseling, 158 underwent GnRH agonist therapy, 94 opted for oocyte cryopreservation, and 47 underwent embryo cryopreservation. The pregnancy rates were 24.1% for the counseling-only group, 22.7% for the GnRH agonist group, 22.0% for the oocyte cryopreservation group, and 63.4% for the embryo cryopreservation group. These results indicate that embryo cryopreservation is the most effective fertility preservation method for patients wishing to conceive.

For patients with severe Asherman’s syndrome, Hye Kyung Yoon (Korea) evaluated a minimally invasive treatment using autologous peripheral mobilized bone marrow-derived stem cells (BMDSCs) and PRP administered via hysteroscopy. From 2019 to 2021, they treated and assessed ten cases. The results showed not only improved hysteroscopic findings but also increased endometrial thickness. Furthermore, in frozen-thawed embryo transfer for IVF, the pregnancy rate was 40%. This treatment is minimally invasive, cost-effective, and may serve as a promising option for patients with severe Asherman’s syndrome.

Why is a shared decision-making essential for cancer patients considering fertility preservation? Sokbom Kang (Korea) evaluated the effectiveness of a fertility preservation decision aid (FP-DA) module. The results showed that FP-DA was well-received by cancer patients and considered convenient and helpful. Further development of a web-based decision aid is necessary. This tool is expected to play a significant role in supporting patients in understanding their fertility preservation options before cancer treatment, helping them make informed decisions.

Oocyte quality declines with age. Hyewon Min (Korea) investigated whether humanin treatment (HNG) could help in slowing this decline. The investigators administered HNG to 6-month-old mice and evaluated them 6 months later. Results showed that aged mice without HNG treatment exhibited increased chromosomal abnormalities and spindle defects, whereas HNG-treated aged mice had significantly lower rates of these abnormalities. Transcriptome analysis indicated that the HNG-treated group had DNA damaged profiles more like those of young control mice. Additionally, oocyte ROS levels, DNA damage, and apoptosis were reduced in the HNG-treated group compared to untreated aged mice. Long-term HNG treatment appears to improve oocyte quality and may have the potential to extend reproductive age.

Session 5: PGT

Glen L Schattman (USA) reviewed the outcomes of PGT-A and explained that this method is minimally effective at identifying and eliminating embryos with potential aneuploidy or poor viability, and does not improve embryo quality. He also highlighted its invasive nature and other drawbacks. The conclusion was that PGT-A can reduce clinical pregnancy loss in older patients by selecting viable embryos, but it may lead to a lower cumulative live birth rate.

Richard Choy (Hong Kong) emphasized the impact of genetic factors, such as chromosomal abnormalities, point mutations, and copy number variations, on the viability of embryos in oncofertility patients. He noted that 8.5% to 19% of cancer patients have germline mutations, depending on the type of cancer [19, 20]. He also stressed the importance of expanded carrier screening to identify couples at risk of genetic conditions. Based on this, he proposed that genetic factors should be considered when oncofertility patients freeze their oocytes for medical reasons and recommended exploring the new “PGT plus” testing. The “PGT plus” test combines PGTA and PGTM into a single procedure, integrating genetic information, copy number variations, and linkage analysis into a comprehensive profile. This allows for the precise selection of viable embryos by excluding those with genetic abnormalities. Choy concluded that"PGT plus"is a valuable tool for understanding patients’ genetic backgrounds and identifying embryos suitable for transfer.

The discussion also addressed mosaicism, highlighting the limitations of PGT-A, which analyzes only a small portion of an embryo’s trophectoderm cells and may not accurately reflect the embryo’s overall viability. Issues such as the lack of standardized reporting for mosaicism and the precision of sequencing technologies were discussed. Additionally, less invasive methods for embryo evaluation, such as non-invasive PGT-A using culture media and AI-based testing, were discussed.

So far, reports have suggested that the usefulness of PGT-A varies based on specific indications, such as in older patients or cases with many embryos, while its benefits are limited for younger patients or those undergoing their first pregnancy. In conclusion, current technologies and testing methods have their limitations, and it is important to critically evaluate the role of mosaicism and the effectiveness of these tests in clinical practice before recommending their universal application.

Session 6: Ovarian tissue transplantation

Catherine J Poirot (France) talked about “Age at ovarian tissue cryopreservation is negatively correlated with pregnancy and graft function duration”. The collaborative publication of OTT cases by 5 European teams (Belgium, Denmark, Spain, France, FertiPROTEK network), based on individual patient data, has produced consistent and robust results. Thus, it was shown that ① the percentage of resumption of ovarian function was 88.7% after an average delay of 4.5 ± 2.2 months, ② the percentage of women who had at least one child was 26% (30% if pregnancy was obtained naturally and 21% after assisted reproductive technologies), ③ chemotherapy before OTC should not be considered as a contraindication for OTC, ④ patients may have cancer recurrence, ⑤ effects of pelvic irradiation are dose-related, and ⑥ age at OTC is negatively correlated with pregnancy and length of graft function [21].

Luciana Cacciottola (Belgium) talked about “Effectiveness of ovarian tissue transplantation and available experimental strategies for future improvement”. The primary challenge to the success of ovarian grafts is the significant loss of follicles that occurs shortly after transplantation. Follicle loss post-transplantation is mainly due to (i) delayed revascularization and oxygen supply and (ii) premature and massive activation of the primordial follicle pool. Enhancing revascularization and reducing oxidative stress with growth factors, antioxidants, and stem cell therapy may improve fertility outcomes by addressing these issues [22–27]. Some of these approaches published in recent years may find their way to clinical application in the near future. Future issues need to be considered regarding oncological risk, vascular damage (thrombosis), ethical issues, and technical challenges.

Jung Ryeol Lee (Korea) talked about “Addressing Unmet Needs in Ovarian Tissue Cryopreservation and Transplantation”. In this lecture, recent research aimed at overcoming these obstacles was presented. Strategies to mitigate cryodamage and ischemic damage, as well as approaches to reduce the risk of primary cancer recurrence, was discussed. Local application of safer agents is essential for enhancement of angiogenesis after transplantation (platelet-derived fibrin hydrogel encapsulation) [28]. Techniques such as artificial ovaries are currently being investigated, particularly for women at a higher risk of ovarian metastasis (injectable ECM-based artificial ovary, structure mimicking GelMA-based artificial ovary) [29]. Innovative techniques and advancements in the field, which are still experimental, hold promise for improving the outcomes of OTC and OTT.

Session 7: CSFP session

Advancements in fertility preservation techniques and protocols were a major focus of the ISFP Congress. Researchers showcased innovations designed to optimize the outcomes of ovarian tissue cryopreservation (OTC), sperm cryopreservation, and in vitro maturation (IVM).

Sun Ningxia’s (China) presentation on hyperbaric oxytherapy (HBOT) revealed its capacity to improve oxygen supply and mitigate oxidative stress during ovarian tissue transplantation, potentially enhancing graft survival and function [30].

Zhang Xinyu’s (China) examination of cryopreservation methods for pediatric ovarian tissue [31] suggested that slow freezing may offer advantages over vitrification in preserving follicular morphology and viability in this unique population.

Jing Yue (China) detailed consideration and thought of patients undergoing fertility preservation [32].

Gang Zhao’s (China) novel methods for ultra-rapid cooling and warming during vitrification, aiming to minimize ice crystal formation and reduce the concentrations of cryoprotective agents (CPAs) required [33]. The session underscored the need for further research to optimize protocols for OTC across diverse patient populations.

Sperm cryopreservation techniques were also highlighted. Li Chunyi (China) presented data indicating that cryopreserved sperm can achieve comparable outcomes to fresh sperm in ICSI cycles, providing reassurance about the effectiveness of this widely used method [34, 35].

The Congress also recognized the importance of IVM as a valuable tool in fertility preservation, particularly for cancer patients. Tao Hui Min (China) presented research on the use of letrozole during ovarian stimulation, highlighting its potential to improve oocyte quality and fertilization rates [36]. The session further addressed the challenges of managing poor responders and emphasized the potential of IVM to overcome these limitations.

Beyond the technical aspects of fertility preservation, the ISFP Congress placed a significant emphasis on patient-centered care and ethical considerations. Jing Yue (China) underscored the crucial role of multidisciplinary teams, including oncologists, reproductive medicine specialists, and mental health professionals, in providing comprehensive support to patients facing fertility-threatening conditions.

The importance of personalized counseling to address patient anxieties, treatment-related concerns, and financial burdens was also highlighted. Yuan Xiaolin’s (China) survey of Chinese healthcare providers revealed gaps in fertility preservation knowledge, emphasizing the need for improved education and training to ensure informed patient decision-making.

The session also tackled the ethical implications of emerging techniques, such as uterine transplantation. Discussions centered on the balance between expanding reproductive options and ensuring patient safety and well-being. Long-term outcome data and rigorous evaluation of risks and benefits were deemed essential for responsible implementation of these innovative procedures.

Session 8: Ovarian protection

Oren Kashi (Israel) investigated the effects of combined administration of the mTOR inhibitor temsirolimus (Tem), an inhibitor of the follicle-stimulating pathway, and recombinant anti-Mullerian hormone (rAMH) on chemotherapy-induced loss of ovarian reserve in a mouse model of chemotherapy.

The results of the study showed that the combination of Tem + rAMH with cyclophosphamide (Cy) treatment was able to suppress the decrease in primordial follicles (PMF). In addition, the proliferation of granulosa cells in primary follicles was also significantly reduced in ovaries treated with Cy + Tem + rAMH. Furthermore, it was shown that phosphorylation of the ribosomal protein S6 (rpS6) and mTOR increased after Cy administration, but a significant decrease was observed in the Cy + Tem + rAMH treatment group, and a decrease in DNA damage and apoptosis was also observed.

From the above, it was shown that the combination of Tem and rAMH treatment can prevent follicular loss due to chemotherapy. Furthermore, the data from this study showed that the baseline level of non-lethal DNA damage was high in PMF oocytes [37].

Kenny A Rodriguez-Wallberg (Sweden) presented on the administration of gonadotrophin-releasing hormone (GnRHa), which is becoming widely used in combination with chemotherapy in the treatment of cancer in children and adolescent girls. There is no evidence from RCT’s that ovarian suppression with GnRH agonist has protective effect on future fertility and resumption of menstruation is not a surrogate marker for fertility. The probability of giving birth after cancer treatment using GnRHa during chemotherapy was examined using a Swedish database. After adjusting for factors such as age, type of cancer and previous delivery history, no significant difference was found between the group that used GnRHa and the group that did not [38]. A double-blind placebo controlled RCT has been initiated in Europe requiring sufficient time to measure reproductive outcome, with about 1300 patients needed to treat.

Day 2: Saturday, November 16

Honorary lecture 1

Ovarian transplantation, a field that dates back over 160 years, has evolved significantly with the advent of cryopreservation technologies. Initial animal studies in the nineteenth century laid the groundwork for clinical applications, culminating in the first successful human ovarian transplant in 1895. The field saw renewed interest with Roger Gosden’s work in sheep and the landmark 2004 study by Jacques Donnéz, demonstrating successful live births following ovarian tissue transplantation [39, 40]. Samuel Kim (USA) outlined three primary transplantation types: autotransplantation (self-donor, commonly used for cancer patients’ fertility preservation), allotransplantation (between individuals, hindered by immune rejection), and xenotransplantation (cross-species, mainly for research purposes). Surgical approaches include orthotopic transplantation (within the remaining ovary or peritoneal pocket) and heterotopic transplantation (extra-ovarian sites such as the forearm for hormonal restoration) [41–45]. Despite advances, challenges persist, particularly in immunosuppression management for allotransplantation [46]. Experimental approaches, such as preimplantation factor (PIF) administration in baboons, have demonstrated potential in preventing immune rejection [47]. The future of ovarian transplantation hinges on improving immunomodulatory strategies and optimizing transplantation techniques to enhance long-term ovarian function.

Honorary lecture 2

Jacques Donnéz (Belgium) provided a historical overview of ovarian tissue cryopreservation, beginning with Roger Gosden’s seminal work in the 1990 s and culminating in the first human birth following transplantation in 2004 [39, 40]. Since then, live birth rates following ovarian transplantation have been reported at 35–40% globally [21, 48]. Several fertility preservation strategies exist, including oocyte vitrification, immature oocyte aspiration, and ovarian tissue cryopreservation [49]. Recent innovations, such as the 2-for- 1 concept, involve simultaneous ovarian tissue cryopreservation and oocyte retrieval from the ovarian medulla, potentially increasing pregnancy success rates [50]. Emerging technologies in in vitro maturation (IVM) of ovarian follicles and oocytes remain a key area of research. Although promising, the maturation of primordial follicles to the metaphase II (MII) stage in vitro remains inefficient, with significant follicular loss occurring during development. Additionally, the creation of artificial ovaries using isolated follicles within 3D scaffolds represents a future avenue for fertility restoration, although challenges remain in optimizing scaffold composition and functionality [51]. A key concern is chemotherapy-induced ovarian toxicity. Mechanistic studies have elucidated the role of the PI3 K/PTEN/AKT pathway in chemotherapy-induced ovarian reserve depletion, highlighting the potential of pharmacological interventions such as AMH administration and PI3 K pathway inhibitors to mitigate damage [52]. Donnéz emphasized the urgency of developing gonadoprotective strategies to safeguard fertility in cancer patients undergoing treatment [53].

President’s Lecture

As a gynecologic oncologist, Nao Suzuki (Japan) faces cancer patients every day with gynecologic cancer of the adolescent and young adult generation for whom fertility preservation is not an easy consideration. The development of trachelectomy for young early-stage cervical cancer patients in the late 1990 s brought about a major revolution in the field of GYN oncology. The results of the study of a live birth after ovarian tissue cryopreservation and thawed ovarian tissue transplantation reported by Professor Jacques Donnez et al. in The Lancet in 2004 [40] represented a key moment for embracing and to further develop this emergent new technology. Since 2006, he has been working on basic research on ovarian tissue vitrification and thawed ovarian tissue transplantation with the aim of developing new innovations in these areas. In 2009, he had the opportunity to give two presentations on ovarian tissue vitrification at the 1 st World Congress of the International Society for Fertility Preservation held in Belgium, which was hosted by Professor Donnez himself. While continuing basic research, he established the Japan Society for Fertility Preservation in 2012 to expand the field of oncofertility not only clinically but also socially as an oncologist, and has contributed to the development of this field in Japan by being appointed as a national principal investigator. He also worked with many colleagues to develop this field across Asia with the establishment of the Asian Society for Fertility Preservation in 2015. This is a treasure that could not have been realized without the support of many of my colleagues.

In his presentation of the President’s Lecture titled “My 18-year journey with ovarian tissue cryopreservation – from an oncologist’s point of view”, he presented his journey as an expression of his sincere gratitude to his colleagues who have been instrumental for developing his field of study and the many successes achieved.

Session 10: New technology 1

Katsuhiko Hayashi (Japan) presented his research on the prospects for in vitro gamete formation with a lecture on “Reconstitution of ovarian tissue and incorporating germ cell lineage”. His research has shown that the local environment of the ovary controls the dormancy of oocytes, and in particular, suggested that hypoxia and pressure may be able to extend the dormancy of oocytes.

Takehiko Ogawa (Japan) developed chemically defined media that can induce spermatogenesis in mice for highly efficient spermatogenesis in in vitro spermatogenesis. It was suggested that lipids such as LPA, LPC, and LPS, as well as vit. E, glutathione, and vit. C are important in inducing spermatogenesis in mice [54]. Furthermore, the PDMS-sealing method (PC method), in which a polydimethylsiloxane (PDMS) chip is placed on the cultured tissue, and reducing the oxygen concentration to 10–15% were found to be advantageous for more efficient spermatogenesis.

Anastasia Kirillova (Australia) referred to influential factors in ovarian tissue oocytes in vitro maturation (OTO IVM), a promising method of fertility preservation for patients with gynecological neoplastic processes.

Ovarian cancer increased the probability of oocyte dysplasia by 2.2-fold, while gynecological surgery was associated with the presence of dark cytoplasmic oocytes and patient age over 35 years was associated with a 2.7-fold frequency of micropolar bodies (95% CI 1.195–6.18). The use of CAPA IVM medium also contributed to a reduced probability of large polar body formation compared to standard monophasic IVM medium (p = 0.034). Furthermore, transport at 4 °C was found to increase the likelihood of cytoplasmic granule formation by 2.5-fold (95% CI 1.301–5.179) [55]. Studies have also shown that an AMH of 2.11 or higher and a patient age of less than 37 years are factors for success.

Session 11: Benign disease 1: gynecological conditions and uterus

Tommaso Falcone (USA) opened a session on fertility preservation, emphasizing its increasing significance and the ethical considerations surrounding invasive procedures for patients. He contributed by discussing the prevalence of benign diseases like fibroids and the critical need to preserve uterine function. He shared findings from a Cleveland Clinic survey indicating that many patients prioritize retaining their uterus, even if they do not plan for future fertility. He compared the long-term quality of life outcomes between women who underwent myomectomy (removal of fibroids) and hysterectomy (removal of the uterus), concluding that there is no significant difference in health-related quality of life between the two procedures. However, he noted that while myomectomy can facilitate pregnancy, success rates depend on the number of fibroids removed [56]. He highlighted the ongoing debate regarding the management of non-distorting intramural fibroids, mentioning a meta-analysis that associates FIGO type 3 fibroids with lower birth odds but acknowledging the lack of consensus on their removal’s impact on IVF outcomes [57]. The discussion then shifted to adenomyosis, which he described as more challenging to manage than fibroids and linked to lower pregnancy rates [58]. He suggested that pretreatment with long-acting agonists might be beneficial but did not reach a definitive conclusion on its effects. Key points discussed included the following: 1. Patients with adenomyosis often face lower clinical pregnancy rates and higher miscarriage rates, particularly with larger uterine sizes [59]. 2. Endometriosis connection: Adenomyosis frequently coexists with endometriosis, complicating treatment and necessitating a combined approach to improve live birth rates [60]. 3. Treatment strategies: Proposed strategies for managing adenomyosis included using a freeze-all strategy to enhance cumulative live birth rates and hormonal suppression protocols before planning embryo transfer. 4. Surgical considerations: When surgery is required, he emphasized careful techniques to preserve uterine function and discussed the complexities of removing adenomyosis tissue. The conversation concluded with a discussion on varying pregnancy rates post-surgery for adenomyosis and associated risks, such as uterine rupture, advocating for caution in surgical options and considering medical therapies first. In summary, he advocated for a comprehensive approach to treating adenomyosis, balancing medical management with surgical options while prioritizing the preservation of uterine function and improving reproductive outcomes [61].

Miyuki Harada (Japan) presented about fertility preservation for patients with endometriosis. The conversation centered on the impact of endometriosis on fertility, particularly regarding ovarian reserve and the complications arising from treatment. It was noted that endometriosis affects a significant percentage of reproductive-age women, with infertility rates between 30 and 50%. Key points discussed included mechanisms affecting fertility. Endometriosis negatively impacts both the quality and quantity of ovarian reserve due to chronic inflammation, oxidative stress, and mechanical stress on ovarian tissues, leading to reduced blood circulation and impaired neovascularization. She highlighted decreased follicle density and follicle burnout, where excessive recruitment of primary follicles depletes the follicle pool. Anti-Müllerian hormone (AMH) levels are used to assess ovarian reserve, showing that patients with endometriomas have significantly lower AMH levels. A study comparing blastocyst formation rates indicates that ovarian endometriomas may adversely affect oocyte quality [62]. On the other hand, it must be kept in mind the negative impacts of excising endometriomas on ovarian reserve and quality, with varying results regarding surgery’s effects on oocyte quality and pregnancy rates.

Fertility preservation for women with endometriosis is feasible but not recommended for all. Younger women are better candidates, and surgery should ideally occur before fertility preservation to maximize outcomes. However, there is evidence suggesting that fertility preservation should occur before surgery [63] as patients with prior surgeries retrieved significantly fewer eggs. When considering fertility preservation, factors such as quality of oocytes, risk of future infertility, and likelihood of using frozen materials must be assessed. Identifying patients at high risk for infertility is essential. A cost–benefit analysis is necessary to determine the viability of fertility preservation for women with endometriosis. Identifying specific patient groups that would benefit can lead to better insurance coverage for these procedures.

Lauren R Alesi (Australia) presented findings on the effects of radiotherapy on the uterus and its implications for pregnancy. The discussion began with an overview of the known impacts of radiotherapy on ovarian function, including infertility and early menopause, which can lead to serious health issues. While ovarian damage is well-documented, she noted growing evidence that radiotherapy also causes uterine damage, negatively affecting pregnancy outcomes. Clinical data indicated that women who underwent radiotherapy experienced lower pregnancy rates and higher complications, even with donor embryos [64]. To explore this further, the research team used a mouse model to study the direct effects of radiotherapy on the uterus. They exposed young female mice to gamma irradiation, observing significant DNA damage in various uterine tissues. Testing human endometrial cell lines revealed similar damage, providing initial evidence of direct uterine harm from radiotherapy [65]. The researchers hypothesized that radiotherapy permanently damages the uterus, impairing pregnancy establishment and maintenance. To isolate uterine damage from ovarian damage, they developed a novel embryo transfer model, surgically removing ovaries from irradiated mice and transferring healthy embryos to study pregnancy outcomes related specifically to uterine health [66]. The experimental design included hormone supplementation to compensate for lost ovarian function and various treatment groups to assess different radiation doses. Initial results showed healthy pregnancies in non-irradiated controls, while further analysis aimed at determining the impact of irradiation on pregnancy success and viability. She presented data indicating significant pregnancy loss due to radiotherapy, evidenced by decreased viable implantation sites and increased resorbing implantation sites in irradiated groups compared to controls. To investigate mechanisms behind pregnancy loss, they collaborated with Dr. Fiona Cousins to implement an artificial decidualization protocol. Results indicated impaired decidualization in irradiated mice, with significant reductions in uterine weight ratios and altered gene expression related to decidualization [65]. The discussion also covered the impact of radiotherapy on uterine artery function, revealing significant impairments in endothelial relaxation potential but not in smooth muscle relaxation. The role of Puma, a key member of the intrinsic apoptosis pathway, was explored; loss of Puma could prevent apoptosis and restore pregnancy outcomes in knockout mice. The conclusion drawn from the research is that radiotherapy causes direct and lasting damage to the uterus, independent of ovarian or hypothalamic-pituitary–gonadal (HPG) axis damage [65]. She emphasized the importance of protecting both ovaries and uterus during cancer treatment to maximize pregnancy success for young women and girls who are cancer survivors. Future research directions include investigating chemotherapy’s effects on uterine function and exploring pharmacological inhibition of Puma as a therapeutic option.

Session 12: JSFP session

The Japan Society for Fertility Preservation (JSFP) session showcased Japan’s initiatives in oncofertility and fertility preservation. Yasushi Takai (Japan) began by introducing the JSFP, highlighting its dual focus on fertility preservation for non-malignant conditions and oncofertility for cancer survivors. He emphasized JSFP’s interdisciplinary nature and the support it receives from the Ministry of Health, Labor, and Welfare (MHLW) [67].

Masahito Tachibana (Japan) presented on the standardization and sustainable development of the oncofertility network in Japan. He outlined the challenges faced by cancer patients seeking fertility preservation, including high costs, variable quality of care, and limited access. He described OC Japan’s efforts to establish a nationwide network involving oncologists, fertility specialists, nurses, counselors, and administrative agencies. Key initiatives included securing government subsidies, developing a registry system (JOFR), providing information resources, and promoting human resource development. He noted the progress in establishing regional networks but also acknowledged the need to address disparities in access and quality of care across different prefectures. He also mentioned the organization of mini-workshops and national workshops to support network development and address challenges. The OC Japan advisory board plays a role in interpreting eligibility criteria and expanding indications for fertility preservation based on the latest evidence.

Miyuki Harada (Japan) discussed the public subsidy program for fertility preservation and assisted reproductive technology (ART) following fertility preservation, which was launched by the MHLW as part of a research promotion project. The subsidy program covers cryopreservation of oocytes, embryos, ovarian tissue, and sperm, as well as ART procedures using frozen materials. Dr. Harada presented data on the eligible diseases and treatments, facility requirements, and subsidy amounts. She also described the Japan Oncofertility Registry (JOFR), which is linked to the subsidy program and serves as a valuable resource for collecting data on the efficacy and safety of fertility preservation. Dr. Harada highlighted the increasing number of patients registered in JOFR and the trends in fertility preservation methods. She also noted the importance of linking JOFR to other cancer registries to analyze long-term outcomes.

Masao Ono (Japan) presented a new approach to enhancing human resource development in fertility preservation through a JSFP-developed certification system. He discussed the MHLW’s guidelines for designated regional cancer centers and hospitals, which require multidisciplinary support teams for young adult and adolescent (AYA) cancer patients. The JSFP certification system aims to increase the number of healthcare providers engaged in fertility preservation and establish oncofertility facilities. He outlined the requirements for oncofertility navigators and facilities, including JSFP membership, completion of educational courses, presentation at JSFP meetings, professional qualifications, and experience supporting cancer patients. He also described the e-learning materials developed by JSFP, which cover various topics related to fertility preservation, cancer care, and ethical issues. Dr. Ono presented data demonstrating the effectiveness of the e-learning program in improving knowledge and confidence among healthcare professionals [68]. The session concluded with a Q&A session, where participants discussed various issues related to fertility preservation, including disparities in access, the impact of new cancer drugs, ethical considerations, and international collaboration.

Session 13: Nurse session

This session provided challenges in oncofertility care, with a focus on fertility preservation for adolescent and young adult (AYA) cancer patients. Olivia Jaworek Frias (USA), Chie Watanabe (Japan), and Kathryn McFadden (Australia) emphasized the importance of multidisciplinary collaboration, involving oncologists, reproductive specialists, nurses, and patient navigators to ensure effective and timely fertility preservation interventions within cancer treatment plans [69]. Key fertility preservation techniques discussed included oocyte and embryo cryopreservation, ovarian and testicular tissue cryopreservation, and the administration of GnRH agonists [70–72]. Despite technological advancements, significant challenges remain in access to fertility preservation services, the provision of adequate patient information, and ethical decision-making processes [73]. Particular attention was given to pediatric patients, where discrepancies between parental and patient decision-making often present complex ethical and psychological challenges.

A major theme of this session was the critical role of fertility preservation nurse coordinators and patient navigators, who facilitate care coordination, psychosocial support, and decision-making assistance for patients undergoing fertility preservation [74]. Case studies from Japan, the USA, and Australia highlighted the effectiveness of integrated fertility preservation programs in improving patient outcomes. The conference also addressed policy advancements, particularly Japan’s national subsidy program, which has significantly reduced the financial burden associated with fertility preservation [75, 76]. However, ongoing issues, such as disparities in access to services, a lack of standardized clinical guidelines, and gaps in communication between healthcare institutions, were identified as areas for improvement [77].

Future research directions discussed included the development of artificial ovaries [78], in vitro folliculogenesis [79], and genetic interventions aimed at enhancing fertility preservation techniques [80]. Overall, the conference reaffirmed that fertility preservation is an essential component of cancer care, advocating for continued technological innovation, interdisciplinary collaboration, and policy support to optimize reproductive health outcomes for cancer survivors.

Session 14: Clinical practice

Fertility preservation practice and achievements were reported by Yichun Guan (China). She described the development of fertility preservation in Hunan, China and their set up with Multi-Divisional Conference (MDT) to provide an opportunity to discuss FP from various angles. Since their establishment in 2019, her group completed 58 cases, including egg freezing, embryo freezing, IVM, and ovarian freezing. The survival rate after thawing of frozen eggs is 90.7%, the fertilization rate, embryo developmental rate, and good embryo rates are lower than those of fresh eggs (69.5%, 95.1%, 74.41% vs. 79.5%, 97.3%, 84.65%, p < 0.05), but there were no difference in clinical pregnancy rates (56.3% vs. 51.6%, P = 0.483).

Ozgur Oktem (Turkey) described that IVF characteristics and the molecular luteal features of random start IVF cycles are not different from conventional cycles in cancer patients. As there is often an urgent need to quickly start cancer treatment, new protocols of random start to facilitate ovarian stimulation and oocyte/embryo cryopreservation process have been proposed. Several papers had already reported the usefulness of random start protocols [81–84]. He reported the molecular reproductive parameter of ovarian stimulation and the number of obtained mature oocytes in random start protocols are comparable to conventional stimulation [85, 86].

Eileen Manalo (Philippines) introduced progestin-primed ovarian stimulation (PPOS) protocol as optimized ovarian stimulation regimen, more patient-friendly, easy, and affordable. She described PPOS protocol as high-quality evidence supporting the effectiveness in retrieving a similar number of oocytes without affecting the duration if stimulation and gonadotropin consumption, and no effect on oocyte competence, similar blastocysts euploidy rate, no difference in live birth rate (LBR) with GnRH protocols. And she showed a meta-analysis on 9274 newborn-babied: no increased risk of congenital malformations and LBWs between women treated with PPOS protocol and those related with GnRHa [87].

And she reported on different progestogens noting that MPA 10 mg has a lower oocyte pickup cancellation rate (OPCR) than MPA 4 mg, (OR 2.27,95%CL 0.90–5.74; one RCT, N = 300, moderate-certainty evidence), lower OPCR in dydrogesterone group versus MPA 10 mg (OR1.49, 95%CI 0.80–2.80, one RCT, N = 520, moderate-certainty evidence), little or no differences in LBR between MPA 4 mg and GNRH agonists in normal responders [88]. She noted PPOS seemed similarly effective and safe in comparison to gonadotrophin-releasing hormone analogues in all types of patients undergoing assisted reproductive technology cycles without an intent for fresh embryo transfer. Cumulative LBR in PGT cycles is lower in PPOS than that of GnRH antagonists in NOR. In patients with PCOS, cumulative LBR of PPOS protocol appears to be lower than that of GnRH antagonist but not statistically significant. No difference in cumulative LBR between PPOS and GnRH groups in patients with diminished ovarian reserve, and the need for caution when choosing PPOS protocol to achieve live births especially for normal and high ovarian responders [89]. She also explained the use of oral progestin despite requiring longer treatment time, and that it is effective in relation to the GnRH antagonist protocol and offers greater comfort at a lower cost in progesterone receptor negative breast cancer patients undergoing cancer fertility preservation [90]. And she noted random start PPOS with hMG and dual trigger represents an easy and affordable ovarian stimulation protocol for FP in women with cancer, showing similar efficacy and being more friendly and economical [91].

W Hamish Wallace (UK) described a Scottish study of live birth in childhood and adolescent cancer survivors under 18 years at diagnosis [92]. The cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33–40%) for cancer survivors at 30 years of age vs. 58% (57–60%) for controls. The deficit varying by diagnosis: for lymphoid leukemia, the cumulative incidence at 30 years was 29% (23–36%) vs. 57% (52–61%) for controls with similar deficits in CNS tumors and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently. He showed a reduced chance of livebirth in female survivors of cancer diagnosed before age 18. The deficit is present for all diagnoses. And he introduced the European study for possibility without gonadotoxic chemotherapy [93, 94]. He noted the cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33–40%) for cancer survivors at 30 years of age vs. 58% (57–60%) for controls. The deficit varying by diagnosis: for lymphoid leukemia, the cumulative incidence at 30 years was 29% (23–36%) vs. 57% (52–61%) for controls with similar deficits in CNS tumors and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently.

Day 3 Sunday, November 17

Special lecture

Jennifer J Mueller (USA) presented about “Uterine and ovarian transposition”. In this session, she reviewed what ovarian and uterine transposition entails, the global experience to date, outline patient selection criteria, and the rationale for offering this procedure to young patients with pelvic cancers [95–97]. Two video materials were incorporated into the session [98, 99]. The first reviewed robotic uterine transposition and the second reviewed uterine anastomosis with low anterior resection.

Session 18: Artificial ovary

Monica Laronda (USA) provided an explanation on bioprosthetic ovary and follicle growth. She also demonstrated that the protein EMILIN1 is associated with the promotion of oocyte growth [100]. Furthermore, she suggested that co-culturing ovarian stromal cells with follicles may enhance follicle growth, indicating that paracrine factors from stromal cells play a role in follicular development. In particular, she presented results showing that follicles influenced by prepubertal stromal cells exhibited a higher rate of oocyte maturation.

Malene Johannsen (Denmark) explained the importance of theca cells and the method for isolating and culturing functional theca cells from human ovaries. Theca cells were isolated using CYP17 A1, which is specifically expressed in theca cells, and the cell surface protein ANPEP [101]. Additionally, she demonstrated that both LH and IGF are required for theca cells to produce androgens.

Pasquale Patrizio (USA) discussed the world’s first experiment using ex vivo ovarian perfusion. This method was perfected in ewe’s ovary showing that the ovary was maintained viable for up to 8 days, and that by perfusing it with gonadotropins, it was possible to retrieve mature oocytes. Furthermore, he reported on preliminary research using perfusion protocols using human ovaries donated by transgender men, including the evaluation of the retrieved oocytes and histological analysis. He demonstrated that this technique could serve as a valuable new research model for understanding human folliculogenesis. Additionally, a discussion was held on the rigidity of the ovarian cortex and medulla, the differences in ovarian stiffness between PCOS patients and normal patients, and the challenge of maintaining follicular quiescence after follicle isolation due to the loss of its surrounding environment.

Session 19: ASFP session: fertility preservation in developing countries

The second ASFP session, which focused on fertility preservation in developing countries, was held on the last day of the conference. Achmad Kemal Harzif (Indonesia) opened the session with a lecture on “Patient’s, Healthcare provider’s knowledge, and referral system in fertility preservation”. Exploring the knowledge of patients, studies show that the majority still are unaware of fertility preservation options, and some do not know that cancer treatments can be gonadotoxic. However, they would be very interested if these treatments were discussed with them, Turner syndrome patients included [102–104]. Furthermore, most patients strongly believe that fertility preservation is a high priority to discuss with newly diagnosed cancer patients of reproductive age. In a qualitative study among breast cancer patients, most of the patients have positive attitudes toward ovarian preservation. Patients would have chosen ovarian preservation if they knew it was an option; young patients would not want to go into early menopause, and they agree that there is a need for disseminated information regarding ovarian preservation. In addition, the KAP of healthcare practitioners was also explored. Several barriers to discussing fertility preservation among oncologists were mentioned, and the top factors include lack of infrastructure of fertility services, limited knowledge in fertility preservation, the patient being too ill to delay treatment, and that fertility treatment may present a risk for cancer patients [105, 106]. Different Asian countries were also examined to determine the strength of their FP services. Parameters include the establishment of the FP Society, local guidelines, dissemination of information to patients, referral system, legal involvement, and insurance coverage. Among the Asian countries included in the survey, Japan has the most complete FP program, while others are still in the process of establishing their own society [104, 107]. Lastly, another significant aspect highlighted by him is the referral system for fertility preservation (FP). A national survey conducted in Indonesia revealed that while a majority of doctors engage in conversations about fertility preservation with cancer patients, only a small number actually refer them to fertility specialists. Among Asian countries, Japan stands out as the only nation with a well-established referral system [104]. Implementing a referral system could be highly advantageous for countries facing disparities in FP services, ensuring that patients receive the specialized care they need.

The second lecture was delivered by Padma Jirge (India), and focused on the challenges and opportunities to establish FP in developing countries. Medical barriers include lack of awareness among oncologists, gynecologists, and patients; lack of interinstitutional communications; lack of referral from oncologists; lack of fertility preservation options; lack of oncofertility specialists; and lack of advances in early diagnosis and treatment of cancer. Economic barriers include lack of health insurance coverage, most fertility services being provided in private clinics, and lack of institutional research and funding. Social barriers include the different rules governing sperm and egg donation, surrogacy, and adoption [108]. Exploring the opportunities in establishing an FP program, the lecturer suggested learning from the different models that have already created successful networking [109]. FertiPROTEKT (Germany, Switzerland, and Austria) has established centralized services, including cryobanks with efficient transport logistics, ongoing education, proper data collection, a national registry, and continuous publications in their field. Oncofertility Consortium, which has achieved similar projects, is another big network focused on bridging the gap between programs in low, middle, and high-income countries thru global networking that shares standards, resources, methodologies, and experiences. This initiative aims to build competencies even in smaller organizations, enabling them to operate independently. Another opportunity mentioned is to establish a national registry. Examples of this are the Danish Registry, Australian Oncofertility Registry, and Japan Oncofertility Registry, among others. Additionally, some human factors are mentioned as the primary obstacle in establishing the program. This includes scientific competition, lack of time for documentation, lack of interest, awareness, and willingness to cooperate. Some solutions that may help include considering all individuals involved as co-authors, using high-quality documentation software, introducing certificates for members, promoting awareness at regional and national levels, and developing political activities to encourage cooperation. Some solutions that may help include considering all individuals involved as co-authors, using high-quality documentation software, introducing certificates for members, promoting awareness at regional and national levels, and developing political activities to encourage cooperation. Another opportunity mentioned is disseminating important learnings from international conferences and translating it into local languages where everyone in their society can learn. This minimizes duplicative efforts. Successful fertility preservation programs indeed require collaboration among various stakeholders, including health professionals (such as reproductive medicine specialists, oncologists, and gynecologists), patients, researchers, and additional members like lawyers, policymakers, religious leaders, advocacy groups, insurance experts, and the general public.

The last lecture was from Ji Hyang Kim (Korea), which focused on the challenges and opportunities in POI and fertility preservation. Resulting from multiple ovulations causing repeated cycles of connective tissue remodeling and wound healing, inflammation, and fibrosis has become associated with reproductive aging. In fact, the onset of fibrosis is an early hallmark of ovarian aging [110]. Ovarian aging is also associated with decreased vascularity, which is brought about by decreased number and caliber of blood vessels, age-related impairment of angiogenesis, and reduced ovarian stromal blood flow [111–113]. To address this ovarian damage, Ji Kim and her team are exploring the use of stem cells and platelet-rich plasma (PRP) to result in ovarian rejuvenation. These treatments aim to reverse or stop inflammation and fibrosis and promote angiogenesis and proliferation. Stem cells are used to infuse cells, producing growth factors. The most studied sources of stem cells would be the umbilical cord, bone marrow, and adipose tissue. Among the POI clinical trials presented, a very hopeful outcome came from Yan (China), where injection of umbilical cord mesenchymal stem cell resulted in four live births [114]. The challenges and future directions of SCT should consider limited progression in clinical research and the high expenses being used in this kind of research. Autologous adult stem cells are used due to tumorigenic concerns, but the use of allogenic SCT could pave the way for future research. Currently, Ji Y Hyang Kim and her team are in phase 1 clinical trial of “Single dose clinical trial to evaluate the safety and tolerability of allogenic US-MSC therapy in patients with POI”. On the other hand, PRP is a rich source of autologous factors and anti-aging proteins [115]. Among the available studies using PRP in POI, positive outcomes are associated with a higher concentration of PRP. In a rat POI model, high concentrations of PRP are associated with an increased number of primary and secondary follicles, and increased vascularity. Although there is no standard preparation method for PRP in numerous studies, Dr. Kim’s lab uses 27 mL of blood from the patient to produce 1 mL of PRP. They perform single intramedullary injections of 0.5 mL to each ovary, trying their best to prevent any leakage, especially since some of the patients would present decreased ovarian size. For the ovaries, which will meet resistance from the needle, the operator will use the injected air as a marker to identify where to inject the PRP. Among the 36 patients included in their pilot study, there is a 92% ovulation rate for those patients who received the PRP without leakage. The ovaries increased in size by 1.2–1.5 mL, with restoration of ovulation after a median of 34.5 days. The clinical pregnancy rate is 14%, and the live birth rate is 8.3%. The effect of PRP may be extended up to 3 months but repeat PRP is a good option to increase the outcome. Even without ovulation, some patients have reported a decrease in their menopausal symptoms. The potential of PRP includes a promising strategy for restoring ovarian function; it is safe and less invasive and could maximize the natural healing process. However, limitations would suggest the need for further experimental and clinical studies with a larger sample size and the need for establishing standard protocol.

Session 20: Testicular tissue cryopreservation

Hiroshi Okada (Japan) gave a presentation on the current situation regarding the preservation of male fertility at his institution. Methods for preserving male fertility include sperm freezing and testicular freezing. The most difficult part is obtaining sperm from the testicular tissue of a child whose spermatogenesis has not yet been established. Testicular tissue transplantation, TSS transplantation, and in vitro spermatogenesis have been successful in various animals, but have not yet been established in humans, and a major breakthrough is needed for in vitro spermatogenesis.

Kyle E Orwig (USA) explained about the infrastructure of the PMC Magee Reproductive Medicine Center and the current state of technology for using cryopreserved testicular tissue for reproduction.

Autologous germ cell tissue or germ cell stem cell transplantation methods have the potential for application in human clinical practice. His research has shown that they are not suitable for patients with leukemia or gender identity disorder. He mentioned that in the future, it will be necessary to develop methods for maturing germ cell tissue outside the patient’s body and producing sperm, such as testicular/ovarian tissue organ culture, in vitro maturation of oocytes, xenografting to animal hosts, and in vitro gametogenesis [116].

Session 21: Benign disease 2: Turner syndrome

Marie-Madeleine Dolmans (Belgium) talked about “Fertility preservation in young patients with Turner syndrome (TS)” [117–121]. Using a mouse xenograft model, their study evaluating the impact of aneuploid granulosa cells and stromal cells on folliculogenesis of small ovarian follicles from patients with mosaic TS was presented. This study demonstrated that small follicles from patients with mosaic TS do undergo folliculogenesis, despite the presence of aneuploid granulosa and stromal cells. Ovarian tissue cryopreservation could therefore be a valid option to preserve fertility in young patients with mosaic TS if sufficient numbers of follicles are present, hence before the age of 12.

Sherman J Silber (USA) talked about “A Series of Four Ovary Allotransplants Requiring Immunosuppression”. He described numerous successful ovarian tissue transplants in patients with TS. They have demonstrated successful OTT with spontaneous pregnancy and healthy live birth to TS females using a safe immunosuppression protocol. The fact that ABO incompatibility did not cause rejection indicates that an ovary tissue graft can survive on diffusion alone without revascularization. Furthermore, an HLA mismatch does not preclude success with this immunosuppression protocol. Ovary allotransplant is likely to become more commonly employed than ovary transplant between identical twins, or frozen autotransplantation.

Session 24: Ovarian tissue cryopreservation

Even within slow freezing, there are multiple recipes involving different cryoprotectants. Ovarian function is restored within four months after thawing [122]. In the presenter’s facility (Debra A Gook, Australia), the thawing process involves melting at 95 °C and gradually reducing the concentration of PROH in the thawing solution. At that time, a concentration of 0.2 M sucrose is used.

Regarding transplantation methods, ovarian sites, pelvic sites, and abdominal sites are used. Among 45 patients, 12 resulted in childbirth. A comparative study between abdominal site and ovarian site transplantation has also been conducted. To avoid the risk of cross-contamination, the safety of the freezing method has been ensured by adopting vapor-phase freezing. In terms of safety, numerous case reports have demonstrated successful pregnancies and childbirth after long-term storage and thawing [31, 123–125]. In conclusion, slow freezing yields stable birth rates and allows transplantation to sites other than the ovaries. It also preserves the number of primordial follicles after thawing and is capable of withstanding long-term storage.

Globally, ovarian tissue cryopreservation is primarily performed using the slow freezing method. Yodo Sugishita (Japan) has developed an ovarian tissue cryopreservation method using vitrification like embryos and oocytes, which is a super rapid cooling technique. In the process of developing an ovarian tissue cryopreservation method, some reports indicated that ovarian tissue could experience cross-contamination in liquid nitrogen. Based on this, a closed-system ovarian tissue cryopreservation device that prevents direct contact with liquid nitrogen was developed, confirming that it is comparable to open devices in terms of effectiveness [126]. Next, he analyzed the survival rates of primordial follicles and primary follicles in human ovarian tissue preserved using both the slow freezing method and vitrification histologically. Since no significant differences were observed, vitrification could be technically equivalent to slow freezing [127]. However, vitrification requires a high concentration of cryoprotectants, which may cause ovarian tissue damage. To address this, he examined cellular damage after ovarian tissue cryopreservation. The results showed that after culturing the tissue for 1-h post-thawing, the high concentration of cryoprotectants was almost eliminated, mitigating the associated risks [128]. Furthermore, he investigated the optimal timing for transplantation after thawing cryopreserved ovarian tissue. We confirmed that transplantation within 1–2 h after thawing increases the likelihood of successful ovarian tissue engraftment [129]. Finally, he introduced the ovarian tissue vitrification method and reported that, to date, he has performed 15 cases of cryopreserved-thawed ovarian tissue transplantation, resulting in seven pregnancies and the birth of five newborns from four cases. These findings suggest that vitrification could become a viable alternative fertility preservation technique to slow freezing.

Nicole Sänger (Germany) has joined Fertiprotekt, a network for fertility preservation. In 2023, the Federal Joint Committee created regulations for the insurance system. Ovarian tissue cryopreservation is predominantly conducted in university hospitals. Additionally, fertility preservation through controlled ovarian stimulation is gradually increasing. Their research on ovarian tissue cryopreservation began in 2020, and by 2024, they had established a vitrification system for ovarian tissue cryopreservation. Currently, they have preserved approximately 3000 ovarian tissue samples [130]. Alongside slow freezing, they have established a vitrification system, and successful births have already been achieved [131]. While slow freezing remains the standard, vitrification has the potential to become a superior technology in the future by eliminating losses related to devices and time.

Session 25: New technology 2

This session highlighted the advancements in oncofertility research, focusing on fertility preservation techniques, extracellular matrix (ECM) dynamics, and organoid-based reproductive models [132–134]. Key discussions revolved around ovarian tissue cryopreservation, vitrification methodologies, and bioengineered models for reproductive applications.

Emna Ouni (France) presented pioneering work on extracellular matrix proteomics, demonstrating its critical role in ovarian function, aging, and disease progression [135–138]. Her research revealed collagen type VI as the dominant structural component of the ovarian cortex, challenging previous assumptions [136, 139]. Additionally, novel methodologies such as data sonification and in vivo mass spectrometry were introduced as potential diagnostic tools for ovarian pathologies [140, 141].

Wen Li (China) addressed challenges in ovarian tissue vitrification, emphasizing the impact of cryopreservation on stromal cells, perivascular cells, and oocyte viability. Single-cell RNA sequencing identified significant alterations in cellular adhesion, apoptotic pathways, and oxidative stress responses, highlighting the need for improved cryoprotective strategies.

Young Sik Choi (Korea) introduced vascularized ovarian chips as a potential platform for hormonal restoration and reproductive organ bio fabrication. His study demonstrated the feasibility of engineered ovarian spheroids composed of granulosa and theca cells, capable of sustained estradiol and progesterone production. The integration of microfluidic organ-on-a-chip systems was proposed as an innovative approach to preclinical reproductive research and artificial ovary development [142].

They underscored the importance of multidisciplinary approaches in advancing oncofertility. Future research priorities include optimizing biomimetic scaffolds, refining vitrification techniques, and exploring ECM-targeted therapies to improve fertility preservation outcomes for cancer patients [132]. These findings contribute to the growing recognition of fertility preservation as an essential component of cancer care, necessitating further collaboration between reproductive medicine, bioengineering, and oncology.

Session 9, 15, 16, 17, 22, 23 and oral sessions 1–6

Six more selected oral sessions were presented by young scientists. Three Best Oral Presentation Award were selected for awards. The first was presented by Limor Man (USA), who addressed inflammatory signaling is activated downstream of cyclophosphamide exposure and is sufficient to induce damage to mouse ovarian reserve. Laura Detti (USA) then proposed AMHR2BP for the prevention of cyclophosphamide (CX)-induced ovarian follicle depletion in mice. Finally, Nanum Chung (Korea) showed us that fertility preservation and live birth using a gelatin-methacryloyl-based bioprosthetic ovary mimicking natural ovarian function.

In addition, the following excellent lectures were presented as part of the corporate sessions: improving ovarian transplantation and in vitro primordial follicle growth outcomes with cryopreserved tissue (Kutluk Oktay, USA); preservation of fertility in patients with hematological malignancies (Yoshinobu Kanda, Japan); safe and successful ovarian transplantations post leukemia after combined various MRD excluding tests future novel options for contaminated tissue (Dror Meirow, Israel); introduction to CAP reproduction laboratory accreditation program (Erica J Behnke, USA); fertility issues in cancer patients and survivors—from an oncologist’s perspective (Chikako Shimizu, Japan); iatrogenic POI treatment options after cancer (Petra Stute, Switzerland); fertility preservation and infertility treatment in women with very low ovarian reserve (Michael von Wolf, Switzerland); incorporating reproductive genetics into IVF: carrier screening, PGT-M and PGT-A (Chun-I Lee, Taiwan); fertility preservation, oocyte vitrification, and ovarian tissue cryopreservation (Debra A Gook, Australia); ovarian tissue cryopreservation—Bench to Bedside Technological development for fertility preservation (Shu Hashimoto, Japan); ovarian tissue cryopreservation: bench-to-bedside—from an oncological perspective: practice in pediatric patients (Kai Yamasaki, Japan); ovarian tissue cryopreservation from the reproductive medicine side (Tomoko Inoue, Japan); the efficacy and safety of pembrolizumab + chemotherapy in patients with early triple negative breast cancer (Shinji Ohno, Japan); basic research results on the ovarian toxicity of immunotherapies (Karla Hutt, Australia).

Finally, Nao Suzuki (Japan), the outgoing president, led the closing ceremony of the congress, inviting Claus Yding Andersen (USA) to the stage to appoint him new president of the ISFP. He announced that the 2026 ISFP congress will be held in Miami, Florida, USA.

Author contribution

KM, HI, YA, YA, NF, TY, AM, AI, MA, YOH, PP, and NS contributed to the writing and proofreading of the manuscript.

Data availability

As this manuscript summarizes the proceedings of a scientific meeting, no individual data or materials were used.

Declarations

Ethics approval

As this manuscript summarizes the proceedings of a scientific meeting, approval from an ethics committee was not required. Consent to participate in and publish this paper was obtained from all authors.

Competing interests

The authors declare no competing interests.