Fertility Preservation Strategies Research Articles

Bleomycin in vitro exposure decreases markers of human male gamete competence

To investigate the in vitro impact of bleomycin on human sperm DNA integrity, functionality, and morphology, with the aim of elucidating the underlying mechanism and anticipating potential repercussions on patients' reproductive function. Controlled laboratory-based in vitro investigation. Surplus human ejaculate donated for research by 45 reproductive-age participants exhibiting normozoospermic sperm parameters following clinical semen analysis. None of the participants had received a cancer diagnosis or undergone radiotherapy, chemotherapy, or both. After clinical semen analysis, sperm samples were centrifuged, diluted in sperm preparation medium (SPM), and exposed to bleomycin (100 μg/mL) for two hours at 37ºC in a humidified incubator with 5% CO2. In vitro human sperm competence was evaluated by comparing raw sperm, sperm incubated with SPM, and sperm exposed to bleomycin. Competence indicators included sperm motility, vitality, DNA and acrosome integrity, and mitochondrial membrane potential. Transmisson electron microscopy was employed to correlate the ultrastructural morphological findings with functional assays. Exposure to bleomycin for two hours in vitro significantly (P < 0.001) decreased sperm vitality, motility, and chromatin condensation compared to raw and control sperm. It also significantly (P < 0.001) increased sperm DNA fragmentation and the proportion of sperm with low mitochondrial membrane potential. Additionally, bleomycin significantly (P < 0.05) retarded the acrosomal response compared to control but did not affect the formation of intracellular and extracellular reactive oxygen species. Bleomycin-induced ultrastructural morphological changes supported the detected functional alterations. Bleomycin negatively impacts male gamete competency in humans. Healthcare professionals should vigilantly monitor and further investigate the gonadotoxicity effects of bleomycin, in addition to its recognized lung toxicity. Meanwhile, it is recommended that cancer patients undergoing bleomycin-containing chemotherapy regimens receive guidance on fertility preservation strategies.

Controlled Ice Nucleation With a Sand-PDMS Film Device Enhances Cryopreservation of Mouse Preantral Ovarian Follicles.

Ovarian follicle cryopreservation is a promising strategy for fertility preservation; however, cryopreservation protocols have room for improvement to maximize post-thaw follicle viability and quality. Current slow-freezing protocols use either manual ice-seeding in combination with expensive programmable-rate freezers or other clinically incompatible ice initiators to control the ice-seeding temperature in the extracellular solution, a critical parameter that impacts post-cryopreservation cell/tissue quality. Previously, sand has been shown to be an excellent, biocompatible ice initiator, and its use in cryopreservation of human induced pluripotent stem cells enables high cell viability and quality after cryopreservation. This study applies sand as an ice initiator to cryopreserve multicellular microtissue, preantral ovarian follicles, using a simple slow-freezing protocol in the mouse model. Ovarian follicles cryopreserved using the sand partially embedded in polydimethylsiloxane (PDMS) film to seed ice in the extracellular solution exhibit healthy morphology, high viability, and the ability to grow similarly to fresh follicles in culture post-thaw. This sand-based cryopreservation strategy can facilitate convenient ovarian follicle cryopreservation using simple equipment, and this study further demonstrates the translatability of this strategy to not only single cells but also multicellular tissues.

Effects of Chemotherapy on Fertility and Fertility Preservation Strategies for the Women of Childbearing Potential Undergoing Chemotherapy: A Comprehensive Review

Effects of Chemotherapy on Fertility and Fertility Preservation Strategies for the Women of Childbearing Potential Undergoing Chemotherapy: A Comprehensive Review

Combined removal of ovarian teratoma and oocyte retrieval by laparoscopic surgery under regional anesthesia

To describe the simultaneous laparoscopic approach for teratoma removal and oocyte retrieval performed under regional anesthesia in a woman, desiring to preserve fertility. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites, and other applicable sites. Video case report demonstrating the clinical management and laparoscopicteratoma removal combined with oocyte retrievalaccomplished underregional anesthesia. University tertiary care hospital. We present a case of a 31-year-old woman who referred to our Fertility Center with a previous history of right salpingo-oophorectomy for mucinous ovarian cystadenoma and the presence of a large ovarian teratoma of ten centimeters of the contralateral ovary. The ovarian stimulation started in the early follicular phase. Not being able to visualize follicular growth during the ovarian stimulation, it was decided to adopt fixed protocol with antagonist on the 5th day and to proceed, on 15th day, with a laparoscopic pick-up and simultaneous removal of the cyst. Laparoscopic surgery was performed: the left ovary appeared larger in size for the presence of the suspicious mature dermoid cyst and multiple follicles, previously not identified at ultrasound imaging. The follicles contained oocytes that were aspirated with an aspiration needle of 17 G connected to a craft suction pump. Then, practicing the stripping technique, an enucleation of the ovarian cyst was performed. Surprisingly, the removal of the cyst revealed other follicles that were readily aspirated. The patient remained awake during the entire procedure and a low pressure of 10 mmHg was maintained at 15° of Trendelenburg position. A total of seven follicles were aspirated, seven oocytes were retrieved, and six mature oocytes were cryopreserved. The cyst was totally removed and no intracavitary spillage was caused. Simultaneous laparoscopic approach for teratoma removal and oocyte cryopreservation should be considered an effective fertility preservation strategy in patients in whom the presence of an ovarian neoformation does not allow visualization of growing follicles by ultrasound. Laparoscopic oocyte retrieval under regional anesthesia is a safe and well-tolerated technique and should be considered for patients where the transvaginal approach could not be performed.

Local delivery of platelet-derived factors mitigates ischemia and preserves ovarian function through angiogenic modulation: A personalized regenerative strategy for fertility preservation

As the most prominent and ideal modality in female fertility preservation, ovarian tissue cryopreservation, and transplantation often confront the challenge of ischemic damage and follicular loss from avascular transplantation. To surmount this impediment, we engineered a novel platelet-derived factors-encapsulated fibrin hydrogel (PFH), a paradigmatic biomaterial. PFH encapsulates autologous platelet-derived factors, utilizing the physiological blood coagulation cascade for precise local delivery of bioactive molecules. In our study, PFH markedly bolstered the success of avascular ovarian tissue transplantation. Notably, the quantity and quality of follicles were preserved with improved neovascularization, accompanied by decreased DNA damage, increased ovulation, and superior embryonic development rates under a Low-concentration Platelet-rich plasma-derived factors encapsulated fibrin hydrogel (L-PFH) regimen. At a stabilized point of tissue engraftment, gene expression analysis mirrored normal ovarian tissue profiles, underscoring the effectiveness of L-PFH in mitigating the initial ischemic insult. This autologous blood-derived biomaterial, inspired by nature, capitalizes on the blood coagulation cascade, and combines biodegradability, biocompatibility, safety, and cost-effectiveness. The adjustable properties of this biomaterial, even in injectable form, extend its potential applications into the broader realm of personalized regenerative medicine. PFH emerges as a promising strategy to counter ischemic damage in tissue transplantation, signifying a broader therapeutic prospect. (197 words)

Knowledge, attitudes, and practices of healthcare providers among women oncofertility in Iran: a cross-sectional study

BackgroundIn recent years, Iran has witnessed a remarkable increase in the incidence of cancer. This has led to an emerging challenge in the field of oncofertility, which seeks to address the impact of cancer treatments on fertility and endeavors to preserve reproduction. The study assessed healthcare providers’ awareness, attitudes, and practices regarding fertility preservation (FP) in Iran.MethodsA cross-sectional study was conducted to assess healthcare providers’ knowledge, attitudes, and practices regarding oncofertility. An online self-made oncofertility survey of twenty-four items was administered to randomly selected participants from a list of healthcare providers registered with the Medical Council. The data were collected anonymously via Google Forms. Descriptive statistics, including number (n), prevalence (%), mean, and standard deviation, were calculated using SPSS 26.0. Additionally, chi-square tests were used to examine associations between categorical variables. Participants were categorized into oncology, obstetrics and gynecology (OB/GYN), and other specialties.ResultsA total of 423 responses were received and analyzed. Approximately 60% of the participants were obstetrics and gynecology subspecialists, while the remaining participants represented various disciplines such as surgery (9.7%), radiotherapy (6.4%), nuclear medicine (5.2%), and pediatrics (1.4%). More than 30% of the participants had not received any specific education about oncofertility, and more than 20% stated that FP strategies are not part of their routine treatment plan for young cancer patients. Oncologists had more education than those in the Obstetrics & Gynecology group. Half the participants were unaware of insurance coverage, and FP options were infrequently recommended.ConclusionsThese findings highlight the urgent need to enhance healthcare workers’ knowledge and attitudes toward FP in Iran and enable them to provide comprehensive support and guidance to cancer patients.

Molecular Factors Predicting Ovarian Chemotoxicity in Fertile Women: A Systematic Review.

Background: Recent advances in cancer diagnosis and treatment have significantly improved survival rates among women of reproductive age facing cancer. However, the potential iatrogenic loss of fertility caused by chemotherapeutic agents underscores the need to understand and predict chemotherapy-induced ovarian damage. This study addresses this gap by systematically reviewing the literature to investigate genetic markers associated with chemotherapy-induced ovarian failure (CIOF). Objective: The primary objective is to identify genetic markers linked to CIOF, contributing to a comprehensive understanding of the factors influencing fertility preservation in female cancer survivors. Methods: A systematic review was conducted using PubMed, EMBASE, Web of Science, Scopus, and OVID electronic databases from inception through December 2023. Studies were included if they featured genomic assessments of genes or polymorphisms related to CIOF in women with histologically confirmed tumors. Exclusion criteria comprised in vitro and animal studies, reviews, and pilot studies. The resulting four human-based studies were scrutinized for insights into genetic influences on CIOF. Results: Of the 5179 articles initially identified, four studies met the inclusion criteria, focusing on alkylating agents, particularly cyclophosphamide, and anthracyclines. Su et al. explored CYP3A41B variants, revealing modified associations with CIOF based on age. Charo et al. investigated GSTA1 and CYP2C19 polymorphisms, emphasizing the need to consider age and tamoxifen therapy in assessing associations. Oktay et al. delved into the impact of BRCA mutations on anti-Müllerian hormone (AMH) levels post-chemotherapy, supported by in vitro assays. Van der Perk et al. focused on childhood cancer survivors and revealed significant associations of CYP3A43 and CYP2B6*2 SNPs with AMH levels. Conclusions: This systematic review analyzes evidence regarding genetic markers influencing CIOF, emphasizing the complex interplay of age, specific genetic variants, and chemotherapy regimens. The findings underscore the need for a personalized approach in assessing CIOF risk, integrating genetic markers with traditional ovarian reserve testing. The implications of this study extend to potential advancements in fertility preservation strategies, offering clinicians a comprehensive baseline assessment for tailored interventions based on each patient's unique genetic profile. Further research is essential to validate these findings and establish a robust framework for integrating genetic markers into clinical practice.

Pathways to motherhood: A single-center retrospective study on fertility preservation and reproductive outcomes in patients with breast cancer

BackgroundBreast cancer treatments often have negative effects on fertility, which pose challenges among patients who want to be parents in the future. This study aimed to examine the efficacy of oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation in patients with breast cancer. MethodsThis retrospective review evaluated 42 patients with breast cancer who underwent fertility preservation at our center from January 2012 to December 2022. This review encompassed the demographic characteristics of the patients, cancer stages, treatment details, and types of fertility preservation procedures and their outcomes. ResultsThe average age at disease diagnosis was 33.4 years. Approximately 90.4% of patients presented with early-stage cancer (≤2). Of 42 patients, 26 underwent oocyte cryopreservation; 17, embryo cryopreservation; and 2, ovarian tissue cryopreservation. Further, three patients received mixed treatment. The overall live birth rate was 63.2%. There are more live births in embryo cryopreservation group. The successful pregnancy group was significantly younger and had a remarkably higher quantity of preserved oocytes/embryos than the nonsuccessful pregnancy group. The oocyte and embryo utilization rates in cryopreservation were 7.69% and 52.94%, respectively. These findings underscored the importance of prompt, informed discussions about fertility preservation options. ConclusionFertility preservation in patients with breast cancer have promising reproductive outcomes, with embryo cryopreservation being particularly effective. Prompt counseling and individualized fertility preservation strategies are important for improving the likelihood of posttreatment pregnancy. Nevertheless, future research on the long-term psychological and emotional effects of different fertility preservation methods must be performed.

Three-Dimensionally Printed Agarose Micromold Supports Scaffold-Free Mouse Ex Vivo Follicle Growth, Ovulation, and Luteinization.

Ex vivo follicle growth is an essential tool, enabling interrogation of folliculogenesis, ovulation, and luteinization. Though significant advancements have been made, existing follicle culture strategies can be technically challenging and laborious. In this study, we advanced the field through development of a custom agarose micromold, which enables scaffold-free follicle culture. We established an accessible and economical manufacturing method using 3D printing and silicone molding that generates biocompatible hydrogel molds without the risk of cytotoxicity from leachates. Each mold supports simultaneous culture of multiple multilayer secondary follicles in a single focal plane, allowing for constant timelapse monitoring and automated analysis. Mouse follicles cultured using this novel system exhibit significantly improved growth and ovulation outcomes with comparable survival, oocyte maturation, and hormone production profiles as established three-dimensional encapsulated in vitro follicle growth (eIVFG) systems. Additionally, follicles recapitulated aspects of in vivo ovulation physiology with respect to their architecture and spatial polarization, which has not been observed in eIVFG systems. This system offers simplicity, scalability, integration with morphokinetic analyses of follicle growth and ovulation, and compatibility with existing microphysiological platforms. This culture strategy has implications for fundamental follicle biology, fertility preservation strategies, reproductive toxicology, and contraceptive drug discovery.

Hydrogel encapsulation facilitates a low-concentration cryoprotectant for cryopreservation of mouse testicular tissue

Cryopreserved testicular tissue offers a promising method to restore fertility in male infertility patients. Current protocols rely on high concentrations of penetrating cryoprotectants (pCPAs), such as dimethyl sulfoxide (DMSO), which necessitating complex washing procedures and posing risks of toxicity. Hydrogel encapsulation presents a non-toxic alternative for cellular cryopreservation. This study investigates the effects of various types, concentrations, and thicknesses of hydrogel encapsulation on the cryopreservation of mouse testicular tissue. Testicular tissues loaded with varying concentrations of DMSO were encapsulated in alginate or gelatin-methacryloyl (GelMA) hydrogels. We evaluated hydrogels as potential CPAs to reduce pCPA concentrations and determine optimal combinations for cryopreservation. Post-cryopreservation, tissues were cultured using organ culture methods to assess spermatogenesis progression. Cryomicroscopy and differential scanning calorimetry (DSC) were used to examine ice crystal formation, melting enthalpy, and non-freezing water content in different hydrogels during cooling. Results indicate that 3 % alginate or 5 % GelMA hydrogel with thin encapsulation optimally preserves mouse testicular tissue. Using 20 % DMSO in 5 % GelMA thin encapsulation showed comparable apoptosis rates, improved morphology, higher mitochondrial activity, and enhanced antioxidant capacity compared to conventional 30 % DMSO without encapsulation. This suggests that hydrogel encapsulation reduces pCPA concentration by 10 %, thereby mitigating toxic damage. Hydrogel encapsulation can reduce basement membrane shrinkage of testicular tissue during cryopreservation. Moreover, frozen tissues remained viable with preserved germ cells after being cultured for one week on alginate methacryloyl (AlgMA) hydrogel using the gas-liquid interphase method. Cryomicroscopy and DSC studies confirmed the hydrogel's ability to inhibit ice crystal growth. In conclusion, this study introduces novel strategies for male fertility preservation and advances cryopreservation technology for clinical applications in assisted reproduction.

O-234 Indication for fertility preservation in patients with endometriosis

Abstract Endometriosis is a complex gynecological condition that not only causes debilitating symptoms but also significantly impacts fertility. As the disease affects approximately 10% of women of reproductive age, addressing fertility preservation strategies becomes paramount. The conventional treatments for endometriosis, such as medical therapy and surgery, often fail to fully address its adverse effects on ovarian reserve and reproductive potential. Consequently, there is a growing interest in exploring fertility preservation options, particularly oocyte cryopreservation (OOC), for endometriosis patients. Despite the prevalence and impact of endometriosis on fertility, comprehensive data and guidelines specifically tailored to fertility preservation in this population remain scarce. The available evidence suggests that endometriosis, particularly when it involves ovarian endometriomas, is associated with a significant reduction in ovarian reserve, as indicated by lower levels of anti-Müllerian hormone (AMH). Surgical interventions, often necessary for managing endometriosis-related complications, can further compromise ovarian function and diminish fertility prospects. However, recent studies have shed light on the potential benefits of OOC in preserving fertility for endometriosis patients. OOC offers a minimally invasive approach with no impact on ovarian reserve compared to other fertility preservation techniques. Despite the lack of randomized controlled trials, our retrospective data have demonstrated promising outcomes, with a notable number needed to treat (NNT) of 16 for one successful pregnancy. This underscores the significance of discussing and considering OOC as part of the treatment plan for endometriosis patients, especially those at risk of ovarian compromise due to the disease or its management. The decision to pursue fertility preservation through OOC should be made on a case-by-case basis, taking into account various factors such as disease severity, patient age, ovarian reserve, and treatment history. French guidelines recommend considering OOC for endometriosis patients with bilateral ovarian endometriomas larger than 3 cm or those with endometriomas on a single ovary. Initiating fertility preservation discussions early, preferably before surgical intervention, allows patients to make informed decisions regarding their reproductive future. It is crucial to acknowledge the challenges and uncertainties associated with fertility preservation in endometriosis patients. Socio-economic factors, patient preferences, and the lack of clear criteria for selecting candidates for OOC pose significant hurdles. Furthermore, the effectiveness and cost-effectiveness of OOC in this population warrant further investigation. In addition to OOC, alternative fertility preservation options, such as ovarian tissue preservation, could be considered, particularly in cases where ovarian stimulation is not feasible or declined by the patient. However, data on the efficacy and safety of ovarian tissue preservation specifically in endometriosis patients are limited, highlighting the need for further research in this area. In conclusion, fertility preservation, particularly through OOC, holds promise for mitigating the adverse effects of endometriosis on ovarian function and fertility. While uncertainties persist, integrating fertility preservation discussions into the comprehensive management of endometriosis is essential. This ensures that patients are empowered to make informed decisions about their reproductive health and maximizes their chances of achieving desired fertility outcomes despite the challenges posed by endometriosis.

O-088 Effect of low, medium and high risk chemotherapy on the ovarian reserve in children: results of the interim analysis of a prospective multicentric trial (CHANCE)

Abstract Study question How does the ovarian reserve of children diagnosed with cancer recover after chemotherapy that is considered as low or medium risk of future infertility? Summary answer The study showed no evidence that low and medium risk treatments impact the future ovarian function in children. What is known already Acute premature ovarian insufficiency (POI) post childhood cancer treatment is estimated around 6%, varying with treatment type and age at diagnosis. Long-term risk of treatment-related infertility is challenging to assess in this population as most of the data comes from retrospective trials involving adult cohorts of childhood cancer survivors. Benefit of fertility preservation at diagnosis is evident for high risk patients. However, for low or medium risk patients, the lack of knowledge on treatment effect on the ovarian reserve and on marker reliability in children complicates counselling. Study design, size, duration CHANCE is a prospective multicentric observational trial enrolling patients aged between 3 and 14 years at cancer diagnosis. We evaluated factors associated with the risk of future infertility such as hormonal levels, puberty and menstruation, and investigated the fertility preservation strategy. Parameters were assessed at screening, one year post-screening, end of the treatment, and during follow-up (FU) until 18 years of age. An interim analysis was planned considering the duration to reach the final endpoint. Participants/materials, setting, methods Between 2014 and 2023, 144 patients were enrolled. Patients were categorized in 3 groups by cumulative equivalent dose of cyclophosphamide (CED) received: &amp;lt;4000mg/m2 (low), 4000 to 8000mg/m2 (medium) and &amp;gt;8000 mg/m2 (high). Ninety-four patients with at least one year post-treatment follow-up were included in this analysis. Mean age at diagnosis was 8.4±4 years and 38% were prepubertal, with no difference between groups (p = 0.06 and 0.26, respectively). The median time of follow-up was 32.7 months. Main results and the role of chance Patients were categorized as low (n = 58), medium (n = 18) and high (n = 18) risk based on CED. Sarcoma were most frequent in high risk, while leukemia in low/medium risk groups (p &amp;lt; 0.0001). Fertility preservation was performed in 55.6%, 27.8% and 8.6% in high, medium and low risk group, respectively (p &amp;lt; 0.0001). The majority of them underwent ovarian tissue cryopreservation. POI was defined as induced puberty and/or FSH&amp;gt;25IU/l during FU. POI occurred in 10 out of 18 (55.6%) patients in high risk group, while in no patient in the low/medium risk groups except 1 with disease recurrence. POI was associated with high doses of chemotherapy (p &amp;lt; 0.0001) and increased age (p &amp;lt; 0.007). AMH levels significantly decreased in high and medium risk group during treatment. Recovery occurs in medium but not high risk groups (p = 0.84 and 0.02 between screening and values at 1-2 years and &amp;gt;3 years of FU using repeated measures analysis). Low AMH values (&amp;lt;0.5ng/ml) was observed at 2 years of FU in 14.3%, 28.6% and 69.2% of the patients in low, medium and high risk groups respectively. The impact of treatment, particularly in medium risk group, needs confirmation as around 35% of the patients were still prepubertal at the time of the analysis. Limitations, reasons for caution This is an interim analysis of a prospective trial designed to include 275 patients. Data should be cautiously interpreted due to not reaching the calculated optimal power population. Wider implications of the findings Our data confirmed that fertility preservation should be offered to all children and adolescent treated with high risk regimen. We did not provide evidence supporting its benefit for low/medium risk pre-pubertal children. For post-pubertal medium risk patients, fertility preservation may be considered during the FU based on patient decision. Trial registration number NCT02595255

Fertility preservation in lymphoma patients treated with immunochemotherapy regimens with or without radiotherapy: results of a retrospective multicenter Italian study (Ferty care)

This is a retrospective, multicentric study, aimed to describe the real-life application of fertility preservation methods during treatment in female lymphoma patients, aged 18–40 years old, diagnosed between Oct 1st/2010 and May 31st/2018. Among 414 women included, median age was 28 years old, histologies were: HL 74%, PMBCL 13%, DLBCL 10%, others 3%. First line treatments were: ABVD in 295 (71%), R-CHOP like in 102 (25%), higher intensity regimens in 17 (4%) cases. Fertility preservation strategies were: GnRHa in 315 (78%), Oral Contraceptive in 41 (10%), oocytes and ovarian tissue cryopreservation in 55 and 42 patients, respectively. After therapy, we observed a restored regular period in 293 (70%) and premature ovarian failure (POF) in 33 (8%), Furthermore we recorded 43 pregnancies, all spontaneous with 5 years median follow-up. Median age at diagnosis and number of lines of treatment correlate with higher rate of amenorrhea, risk of POF and menopause (p < 0.001).

Reproductive Strategies for Declining Fertility: Fertility Preservation

There is a global trend of declining fertility among people of childbearing age and mankind is confronted with great challenges of fertility problems. As a result, fertility preservation technology has emerged. Fertility preservation involves interventions and procedures aimed at preserving the patients' chances of having children when their fertility may have been impaired by their medical conditions or the treatments thereof, for example, chemotherapy and/or radiotherapy for cancer. The changes in patients' fertility can be temporary or permanent damage. Fertility preservation can help people diagnosed with cancer or other non-malignant diseases. More and more fertility preservation methods are being used to preserve the fertility of cancer patients and protect their reproductive organs from gonadotoxicity. Fertility preservation may be appropriate for young patients with early-stage cancers and good prognosis before they undergo treatments (chemotherapy and/or radiotherapy) that can negatively affect their fertility. It is also appropriate for patients with chronic conditions or those who have encountered environmental exposures that affect their gonadal function. Fertility preservation methods include oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation (OTC) for women and sperm freezing and testicular tissue freezing for men. The survival rates of children and adolescents diagnosed with malignant tumors have been steadily increasing as a result of advances in cancer treatments. Cryopreservation of oocytes and sperm is recognized as a well-established and successful strategy for fertility preservation in pubertal patients. OTC is the sole option for prepubertal girls. On the other hand, cryopreservation of immature testicular tissue remains the only alternative for prepubertal boys, but the technology is still in the experimental stage. A review showed that the utilization rate of cryopreserved semen ranged from 2.6% to 21.5%. In the case of cryopreserved female reproductive materials, the utilization rate ranged from 3.1% to 8.7% for oocytes, approximately from 9% to 22.4% for embryos, and from 6.9% to 30.3% for ovarian tissue. When patients have needs for fertility treatment, cryopreserved vitrified oocytes are resuscitated and in vitro fertilization-embryo transfer (IVF-ET) was performed to help patients accomplish their reproductive objectives, with the live birth rate (LBR) being 32%. On the other hand, when cryopreserved embryos are resuscitated and transferred, the LBR was 41%. OTC has the advantage of restoring natural fertility and presents a LBR of 33%, compared with the LBR of 19% among 266 IVF patients. In addition, OTC has the benefit of restoring the endocrine function. It has been observed that the shortest recovery time of the first menstruation after transplantation was 3.9 months, and the recovery rate of ovarian function reached 100%. To date, a growing number of cancer survivors and patients with other diseases are benefiting from fertility preservation measures. In the face of declining human fertility, fertility preservation provides a new approach to human reproduction. Fertility preservation should be applied in line with the ethical principles so as to fully protect the rights and interests of patients and their offsprings.

Utero-Ovarian “out of field” Transposition Before Pelvic Radiation in a Patient with Rectal Cancer: A First Swiss Experience

Abstract Background Colorectal cancer represents the third most common cancer and the second leading cause of cancer-related mortality worldwide. The incidence of rectal cancer is rising faster and is increasing among young adults. Due to advances in diagnosis and treatment, most young patients with rectal cancer present long-term survival. Treatment-related infertility represents a largely unaddressed problem. Fertility preservation is essential in managing young women requiring chemo- and radiotherapy for rectal cancer. Ovaries and oocytes are very sensitive to radiation and chemotherapeutic agents, and current fertility preservation strategies include oocytes, embryos, or ovarian tissue cryopreservation and ovarian transposition out of the radiation field. Nevertheless, patients have little probability of procreating due to irreversible uterine radiation damages. Utero-ovarian “out of filed” Transposition [UOT] represent an interesting perspective specially in countries were pregnancy surrogacy is not allowed. Aims Demonstrate feasibility of an innovative surgical procedure permitting uterine functional preservation after long course neoadjuvant therapy for low rectal cancer including total chemo and radio-chemotherapy. Methods First Clinical Swiss experience case presentation. In addition, of a systematic review of the literature available to date on all cases of UOT was realized, and 13 patients from 9 articles were included. Results A 28-year-old nulligravida patient was diagnosed with a low-grade rectal adenocarcinoma. Before neoadjuvant therapies, the patient underwent laparoscopic UOT. The intervention was performed without complications, and the patient received neoadjuvant treatments as planned. TaTME and uterus repositioning were completed six weeks after the radiotherapy's end. No complications were observed during the first 9 postoperative months. Adequate utero-ovarian perfusion was assessed by Doppler ultrasound, cervicovaginal anastomosis appeared healed correctly, and the patient experienced menstrual bleeding. Data from the literature review of reported cases of UOT were presented. Conclusion UOT represents a valuable option to preserve fertility in patients requiring pelvic radiotherapy. This study provides additional evidence on the feasibility and safety of UOT.

Effect of breast cancer prognostic factors on ovarian reserve and response in fertility preservation

Research questionDo breast cancer prognostic factors influence ovarian reserve and response to ovarian stimulation in the context of fertility preservation? DesignObservational, bicentric retrospective study of 352 women with breast cancer who underwent ovarian stimulation using a random start gonadotrophin releasing hormone antagonist protocol and vitrified oocytes between November 2015 and August 2022. Serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) were measured. The number of oocytes recovered, maturation rate and follicular output rate (FORT) were analysed according to patients’ characteristics and breast cancer prognostic factors. ResultsMedian age was 34 years (31.1–37.1). Median AFC and serum AMH level were 17 (12–26) follicles and 2 (1.2–3.4) ng/ml, respectively. After ovarian stimulation, 10.5 (6.0–16.0) oocytes were recovered, with eight (4–13) being mature. Mean oocyte maturation rate was 79% (62–92). Antral follicle count (>12) significantly affected the risk of recovering fewer than eight mature oocytes (P < 0.0001, multivariate analysis). Follicular responsiveness to FSH, assessed by the follicular output rate (FORT index) and number of oocytes recovered, were 31% (21–50) and 10.5% (6.0–16.0), respectively. FORT index and ovarian stimulation outcomes were not influenced by breast cancer prognostic factors. ConclusionBreast cancer prognostic factors do not influence ovarian reserve markers or response to ovarian stimulation in fertility preservation. Therefore, tumour grade, triple-negative status, HER2 overexpression and high Ki67 should not alter the fertility-preservation strategy when considering ovarian stimulation for oocyte vitrification.

Fertility preservation in males with cancer of trends, region development, and efficacy in mainland China from 16 regions Chinese sperm banks.

Male cancer survivors experience confusion about fertility following cancer treatment. The aims of this study were to evaluate survivors' semen quality in different tumor type groups in China and to analyze the current situation and challenges of male cancer patients with sperm cryopreservation. This was a multicenter retrospective study of male patients with cancer who underwent sperm cryopreservation in 16 regions of the national sperm banks over an 11-year period from 2010 to 2020. The number of male cancer patients with sperm cryopreservation showed an overall upward trend. The development of male cancer fertility preservation (FP) in the eastern, central, and western regions of Chinese displayed imbalance. There are seven tumor types for sperm preservation in the top incidence ten tumor types, including lymphoma, leukemia, nasopharyngeal carcinoma, sarcoma, thyroid cancer, and brain tumor. Moreover, nasopharyngeal carcinoma is a high incidence rate in China, which is related to high sperm preservation rate, different from other countries. The most percentage of males receiving sperm cryopreservation in the testicular cancers (15-39years old) of China in 2020 was 5.55%, 1.29% in the lymphoma, and 0.39% in the leukemia. According to the type of cancer, a statistically significant lower pre-sperm density, total sperm output, and post-sperm density was observed in testicular cancers. It is worth noting that the prevalence of azoospermia 22.2% in leukemia patients attribute to urgent treatment before sperm cryopreservation. Disposition of cryopreserved sperm categories included continued storage (47.2%), discarded (9%), death (0.9%), and use (3.7%). This study provides the firstcomprehensive national statistical census and review of fertility preservation in male cancer patients with respect totrends, prevalence, and cancer types. The development of male cancer fertility preservation in China is imbalanced and percentage of males receiving sperm cryopreservation in the adolescent and young adult cancers was low. Sixteen human sperm banks from China analyze current problems and challenges, and then prioritize steps toward the achievement of the FP strategy framework for Healthy China 2030.

Fertility Preservation in the Era of Immuno-Oncology: Lights and Shadows.

In recent years, immuno-oncology has revolutionized the cancer treatment field by harnessing the immune system's power to counteract cancer cells. While this innovative approach holds great promise for improving cancer outcomes, it also raises important considerations related to fertility and reproductive toxicity. In fact, most young females receiving gonadotoxic anti-cancer treatments undergo iatrogenic ovarian exhaustion, resulting in a permanent illness that precludes the vocation of motherhood as a natural female sexual identity. Although commonly used, oocyte cryopreservation for future in vitro fertilization and even ovarian cortex transplantation are considered unsafe procedures in cancer patients due to their oncogenic risks; whereas, ovarian stem cells might support neo-oogenesis, providing a novel stemness model of regenerative medicine for future fertility preservation programs in oncology. Recent scientific evidence has postulated that immune checkpoint inhibitors (ICIs) might in some way reduce fertility by inducing either primary or secondary hypogonadism, whose incidence and mechanisms are not yet known. Therefore, considering the lack of data, it is currently not possible to define the most suitable FP procedure for young patients who are candidates for ICIs. In this report, we will investigate the few available data concerning the molecular regulation of ICI therapy and their resulting gonadal toxicity, to hypothesize the most suitable fertility preservation strategy for patients receiving these drugs.

Long-Term Ovarian Function Assessment After Haematopoietic Stem Cell Transplantation in Female Sickle Cell Anaemia Survivors.

Haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for sickle cell anaemia (SCA). While HSCT offers the possibility of disease remission, it can also lead to long-term complications, including gonadal dysfunction and premature menopause. We conducted a retrospective cohort study of female survivors who had hydroxyurea therapy and those who underwent post-HSCT follow-up for SCA at a teaching hospital in Lagos, Nigeria, between January 2019 and December 2022. Participants were eligible if they were at least five years post-HSCT or hydroxyurea treatment and had available serum samples for markers of ovarian function measurement. Demographic and clinical data were collected from the hospital register and patients' medical records. Serum levels of oestradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) were measured using the Abbott Architect i1000SR chemiluminescent immunoassay analyzer (Abbott Diagnostics, Abbott Park, IL). Descriptive statistics and inferential analyses were used to assess the relationship between markers of ovarian function (FSH and AMH) and clinical parameters. There were statistically significant differences in the median serum levels of all the assessed endocrine hormones between the HSCT and non-HSCT (hydroxyurea) groups of SCA survivors. Up to 82.6% of the SCA survivors experienced ovarian dysfunction after HSCT treatment. Impaired ovarian function in SCA survivors was associated with a longer median follow-up duration than in SCA survivors who had normal ovarian function (12.0 vs. 7.5 years, p = 0.048). There were higher odds of impaired ovarian function in the SCA survivors who had myeloablative regimens than in those who had reduced intensity conditioning regimens (94.1% vs. 50.0%, p = 0.040). Our study highlights the significant impact of HSCT on long-term ovarian function in female SCA survivors. However, further prospective studies with larger sample sizes and longer follow-up periods are required to confirm our findings and elucidate the factors influencing ovarian function in SCA survivors of HSCT. In addition, studies are also needed to further elucidate the optimal transplant protocols and fertility preservation strategies to minimize gonadal toxicity and preserve reproductive potential in female SCA patients undergoing HSCT.

Prevalence and impact of fertility concerns in young women with breast cancer

Survey data from the Mayo Clinic Breast Disease Registry were used to assess fertility counseling and fertility preservation strategies in a modern cohort of young women with breast cancer. One hundred respondents were identified who were under age 50 at the time of breast cancer diagnosis and who expressed interest in future childbearing near the time of diagnosis and/or 1 year later. Ninety-three percent of the 81 respondents to the year one survey recalled fertility counseling prior to cancer treatment. Most who reported a high level of fertility concern declared that this concern had impacted their treatment decisions, often shortening their planned duration of endocrine therapy. Approximately half had taken steps to preserve future fertility, and a third had used a gonadotropin-releasing hormone agonist either alone or combined with another method (e.g., embryo or oocyte cryopreservation).