A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

In Vitro Effects of Charged and Zwitterionic Liposomes on Human Spermatozoa and Supplementation with Liposomes and Chlorogenic Acid during Sperm Freezing.

Semen handling and cryopreservation induce oxidative stress that should be minimized. In this study, human semen was supplemented during cryopreservation with formulations of handmade liposomes and chlorogenic acid (CGA), an antioxidant compound. Zwitterionic (ZL), anionic (AL), and cationic (CL) liposomes were synthesized and characterized. Three aliquots of swim-up-selected sperm were incubated with ZL, AL, and CL (1:10,000), respectively. The percentages of sperm with progressive motility, high mitochondrial membrane potential (MMP; JC-1), double-stranded DNA (dsDNA acridine orange), and acrosome integrity (Pisum sativum agglutinin) were assessed. Then, human semen was frozen using both 1:10,000 ZL and CGA as follows: freezing medium/empty ZL (EL), freezing medium/empty ZL/CGA in the medium (CGA + EL), freezing medium/CGA loaded ZL (CGA), freezing medium (CTR). The same sperm endpoints were evaluated. ZL were the most tolerated and used for semen cryopreservation protocols. All the supplemented samples showed better endpoints versus CTR (p < 0.001). In particular, spermatozoa from the CGA and CGA + EL A samples showed increased motility, dsDNA, and acrosome integrity versus CTR and EL (p < 0.001; motility EL vs. CGA + EL p < 0.05). ZL and CGA can improve post-thaw sperm quality, acting on both cold shock effect management and oxidative stress. These findings open new perspectives on human and animal reproduction.

Oocyte vitrification for fertility preservation is an evolving practice requiring a new mindset: societal, technical, clinical, and basic science-driven evolutions.

Infertility is a condition with profound social implications. Indeed, it is not surprising that evolutions in both medicine and society affect the way in vitro fertilization is practiced. The keywords in modern medicine are the four principles, which implicitly involve a constant update of our knowledge and our technologies to fulfill the "prediction" and "personalization" tasks, and a continuous reshaping of our mindset in view of all relevant societal changes to fulfill the "prevention" and "participation" tasks. A worldwide aging population whose life priorities are changing requires that we invest in fertility education, spreading actionable information to allow women and men to make meaningful reproductive choices. Fertility preservation for both medical and nonmedical reasons is still very much overlooked in many countries worldwide, demanding a comprehensive update of our approach, starting from academia and in vitro fertilization laboratories, passing through medical offices, and reaching out to social media. Reproduction medicine should evolve from being a clinical practice to treat a condition to being a holistic approach to guarantee patients' reproductive health and well-being. Oocyte vitrification for fertility preservation is the perfect use case for this transition. This tool is acquiring a new identity to comply with novel indications and social needs, persisting technical challenges, brand-new clinical technologies, and novel revolutions coming from academia. This "views and reviews" piece aims at outlining the advancement of oocyte vitrification from all these tightly connected perspectives.

Views and reviews: fertility preservation from different perspectives.

Fertility preservation for different conditions provides women the chance to buy time that can be invested in improving their well-being, by curing their condition from a holistic perspective, in line with the precepts of modern medicine.

Body image disturbances in adolescent and young adult cancer patients confronting infertility risk and fertility preservation decisions.

PURPOSE: Body image is a major psychosocial concern for all cancer patients but can affect the adolescent and young adult (AYA) population in distinct ways. Similarly, the prospect of infertility and the fertility preservation process can create additional stress during cancer treatment. Discussions regarding infertility inherently implicate the body and its reproductive function, but downstream effects on self-perception have not been previously described. The aim of this study was to explore the experiences of AYAs as they considered their risk of infertility and options for fertility preservation (FP), specifically the ways in which this impacted body image and FP decision-making. METHODS: AYA cancer patients (n = 27) aged 12-25 years whose cancer and treatment conferred risk of infertility were recruited through electronic health record query at an NCI-Designated Comprehensive Cancer Center. Participants completed semi-structured interviews, which were recorded, transcribed, and deductively coded for themes related to information needs, knowledge of treatment effects on fertility, and reproductive concerns after cancer. Emergent, inductive themes related to body image were identified. RESULTS: Body image concerns, related to both physical appearance and body functioning emerged. Common concerns included anticipating change as it pertains to the body and its functions, physical discomfort, fear of judgment, and meeting expectations of the body. While these themes are broad in nature, they have been previously explored in relation to body image in general and their emergence in the oncofertility space provides guidance for further optimization of infertility and fertility preservation discussions. CONCLUSIONS: AYA cancer patients experience a multitude of body image related disturbances when faced with the possibility of infertility and fertility preservation. In identifying and exploring these themes, future opportunities for improving oncofertility practice and discussions among AYAs with a focus on body image positivity are called upon.

Impact of low- or moderate-risk gonadotoxic chemotherapy prior to testicular tissue freezing on spermatogonia quantity in human (pre)pubertal testicular tissue.

STUDY QUESTION: What is the impact of low- or moderate-risk gonadotoxic chemotherapy received prior to testicular tissue freezing (TTF), and of the cancer itself, on spermatogonia quantity in testicular tissue from (pre)pubertal boys? SUMMARY ANSWER: Vincristine, when associated with alkylating agents, has an additional adverse effect on spermatogonia quantity, while carboplatin has no individual contribution to spermatogonia quantity, in testicular tissue of (pre)pubertal boys, when compared to patients who have received non-alkylating chemotherapy. WHAT IS KNOWN ALREADY: The improved survival rates after cancer treatment necessitate the inclusion of fertility preservation procedures as part of the comprehensive care for patients, taking into consideration their age. Sperm cryopreservation is an established procedure in post-pubertal males while the TTF proposed for (pre)pubertal boys remains experimental. Several studies exploring testicular tissue of (pre)pubertal boys after TTF have examined the tubular fertility index (TFI, percentage of seminiferous tubule cross-sections containing spermatogonia) and the number of spermatogonia per seminiferous tubule cross-section (S/T). All studies have demonstrated that TFI and S/T always decrease after the introduction of chemotherapeutic agents, especially those which carry high gonadotoxic risks such as alkylating agents. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 79 (pre)pubertal boys diagnosed with cancer (from 6 months to 16 years of age) were cryopreserved between May 2009 and June 2014. Their medical diagnoses and previous chemotherapy exposures were recorded. We examined histological sections of (pre)pubertal testicular tissue to elucidate whether the chemotherapy or the primary diagnosis affects mainly TFI and S/T. PARTICIPANTS/MATERIALS, SETTING, METHODS: (Pre)pubertal boys with cancer diagnosis who had been offered TTF prior to conditioning treatment for hematopoietic stem cell transplantation were included in the study. All the patients had previously received chemotherapy with low- or moderate-risk for future fertility. We have selected patients for whom the information on the chemotherapy received was complete. The quantity of spermatogonia and quality of testicular tissue were assessed by both morphological and immunohistochemical analyses. MAIN RESULTS AND THE ROLE OF CHANCE: A significant reduction in the number of spermatogonia was observed in boys treated with alkylating agents. The mean S/T values in boys exposed to alkylating agents were significantly lower compared to boys exposed to non-alkylating agents (P = 0.018). In contrast, no difference was observed for patients treated with carboplatin as the sole administered alkylating agent compared to the group of patients exposed to non-alkylating agents. We observed an increase of S/T with age in the group of patients who did not receive any alkylating agent and a decrease of S/T with age when patients received alkylating agents included in the cyclophosphamide equivalent dose (CED) formula (r = 0.6166, P = 0.0434; r = -0.3759, P = 0.0036, respectively). The TFI and S/T decreased further in the group of patients who received vincristine in combination with alkylating agents (decrease of 22.4%, P = 0.0049 and P < 0.0001, respectively), but in this group the CED was also increased significantly (P < 0.0001). Multivariate analysis, after CED adjustment, showed the persistence of a decrease in TFI correlated with vincristine administration (P = 0.02). LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from (pre)pubertal boys who were at risk of infertility. The study population is quite heterogeneous, with a small number of patients in each sub-group. Our results are based on comparisons between patients receiving alkylating agents compared to patients receiving non-alkylating agents rather than chemotherapy-naive patients. The French national guidelines for fertility preservation in cancer patients recommend TTF before highly gonadotoxic treatment. Therefore, all the patients had received low- or moderate-risk gonadotoxic chemotherapy before TTF. Access to testicular tissue samples from chemotherapy-naive patients with comparable histological types of cancer was not possible. The functionality of spermatogonia and somatic cells could not be tested by transplantation or in vitro maturation due to limited sample sizes. WIDER IMPLICATIONS OF THE FINDINGS: This study summarizes the spermatogonial quantity of (pre)pubertal boys prior to TTF. We confirmed a negative correlation between the cumulative exposure to alkylating agents and spermatogonial quantity. In addition, the synergistic use of vincristine in combination with alkylating agents showed a cumulative deleterious effect on the TFI. For patients for whom fertility preservation is indicated, TTF should be proposed for chemotherapy with a predicted CED above 4000 mg/m2. However, the data obtained from vincristine and carboplatin use should be confirmed in a subsequent study including more patients. STUDY FUNDING/COMPETING INTEREST(S): This study had financial support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. The sponsors played no role in the study. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Understanding Causes of Inferior Outcomes in Adolescents and Young Adults With Cancer.

Individuals diagnosed with cancer as adolescents and young adults (AYAs; ages 15-39 years) face unique vulnerabilities. Compared with individuals diagnosed when younger (≤14 years) or older (≥40 years), AYAs have not seen the same improvement in survival. Furthermore, they sit at a complex moment of social, emotional, and cognitive development, and have a unique interface with the healthcare system. With these observations, NCI prioritized addressing the unique vulnerabilities among AYAs with cancer, and NCCN developed guidelines regarding optimal AYA cancer care. Improvements in certain locales have been seen in the wake of this focus on AYAs, suggesting that continuing to consider AYA outcomes in the context of their specific needs is critical as we strive toward additional improvements. However, it is key to consider the drivers of these outcomes to continue this trajectory. This review presents a holistic conceptual model that includes factors that influence outcomes among AYAs with cancer, including domains in these levels that influence both clinical outcomes (such as relapse and survival) and health-related quality of life (HRQoL). These include domains at the patient level, such as social constructs (race/ethnicity, socioeconomic status), behavior (adherence, risk-taking), biologic characteristics (cancer biology, host genetics), medical treatment (treatment regimen, risk-based survivorship care), and treatment-related toxicities. The model also includes domains at the system level, which include treatment location (NCI designation, facility model, AYA program presence), clinical trial enrollment, transdisciplinary communication, fertility preservation, and psychosocial support. Recognizing these multiple factors at the level of the individual and the healthcare system influence AYA outcomes (from HRQoL to survival), it is key not only to consider patient-level interventions and development of novel cancer agents but also to develop systems-level interventions that can be executed in parallel. In this way, the impact can be expanded to a vast number of AYAs.

[Fertility and fertility preservation in men]. / Fertilität und Fertilitätserhalt des Mannes.

Fertility preservation is of high importance for patients prior to treatment that can impair fertility. The individual risk of becoming infertile after a fertility-reducing therapy depends on the type and duration of therapy, surgical technique, dose and combination of gonadotoxic drugs or radiation applied, and individual predisposition. Cryopreservation of ejaculated sperm is the standard procedure for creating a fertility reserve in men. In cases of azoospermia or inability to obtain semen by masturbation, testicular sperm can be obtained by (micro-)testicular sperm extraction (TESE) and cryopreserved. In case of retrograde ejaculation, sperm collection can be attempted by rectal electrostimulation or after off-label administration of imipramine from postmasturbatory urine. The cryopreserved sperm can be stored permanently in the gaseous phase of liquid nitrogen before being used in fertility therapy. In Germany, approval according to § 20b of the German Medicines Act (AMG) is a mandatory requirement for performing cryopreservation of sperm and testicular tissue; approval according to § 20c of the AMG must be obtained for use. For prepubertal boys, it is possible to cryopreserve dormant spermatogonial stem cells as part of an experimental procedure.

Advances in the Management of Menopausal Symptoms, Fertility Preservation, and Bone Health for Women With Breast Cancer on Endocrine Therapy.

In patients with hormone receptor-positive early-stage breast cancer, adjuvant endocrine treatment administered for up to 5-10 years after diagnosis significantly reduces the risk of recurrence and death. However, this benefit comes with the cost of short- and long-term side effects that may negatively affect patients' quality of life (QoL) and treatment adherence. Among them, the prolonged estrogen suppression associated with the use of adjuvant endocrine therapy in both premenopausal and postmenopausal women can induce life-altering menopausal symptoms, including sexual dysfunction. Moreover, a decrease in bone mineral density and an increased risk of fractures should be carefully considered and prevented whenever indicated. For young women diagnosed with hormone receptor-positive breast cancer with unfulfilled childbearing plans, several challenges should be addressed to manage their fertility and pregnancy-related concerns. Proper counseling and proactive management of these issues are critical components of survivorship and should be pursued from diagnosis through the breast cancer care continuum. This study aims to provide an updated overview of the available approaches for improving the QoL of patients with breast cancer receiving estrogen deprivation therapy, focusing on advances in the management of menopausal symptoms, including sexual dysfunction, fertility preservation, and bone health.

Current Issues in Fertility Preservation Among Pediatric and Adolescent Cancer Patients.

PURPOSE OF REVIEW: Although fertility preservation is not yet fully integrated into the comprehensive cancer care of pediatric and adolescent patients, advances continue to take place. This review summarizes recent updates and trends for health care professionals caring for these patients. RECENT FINDINGS: The creation of standardized infertility risk assessment guidelines offers the opportunity to provide greater consistency in clinical care and to provide a current baseline for future research studies seeking to refine risk stratification for individual patients. New agents are being introduced into cancer care; as their use increases, information about their impact on fertility is being studied. Ovarian tissue cryopreservation offers a new standard of care option for fertility preservation, but additional studies are needed to further assess efficacy and impact on ovarian reserve among pediatric and adolescent patients. Standardization of fertility preservation recommendations among certain sub-populations may also make it easier to provide greater consistency in clinical care. Advances continue to be made in the field of fertility preservation, but dissemination of this information is critical to moving toward fertility preservation truly being a part of comprehensive cancer care.

Fertility Preservation Practices at Pediatric Oncology Institutions in the United States: A Report From the Children's Oncology Group.

PURPOSE: Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS: A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS: One hundred forty-four programs (65.5%) returned surveys. Of these, 65 (45.1%) reported routine discussions of fertility with all female patients and 55 (38.5%) all male patients (P = .25). Ninety-two (63.8%) reported no specific criteria for offering females fertility preservation (FP), compared with 40 (27.7%) for males (P < .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION: Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.

Expecting more: the case for incorporating fertility services into comprehensive sickle cell disease care.

Assisted reproductive technologies (ART) are not yet systematically available to people with sickle cell disease or their parents. Fertility care for these groups requires addressing sickle cell disease-associated infertility risks, fertility preservation options, pregnancy possibilities and outcomes, and, when needed, infertility treatment. People with a chance of having a child with sickle cell disease can use in-vitro fertilisation with preimplantation genetic testing to conceive a child unaffected by sickle cell disease. Also, parents of children with sickle cell disease can use this technology to identify embryos to become potential future matched sibling donors for stem cell transplant. In the USA, disparities in fertility care for the sickle cell disease community are especially stark. Universal screening of newborn babies' identifies sickle cell disease and sickle cell trait, guidelines direct preconception genetic carrier screening, and standard-of-care fertility preserving options exist. However, potentially transformative treatments and cures for patients with sickle cell disease are not used due to iatrogenic infertility concerns. In diversely resourced care settings, obstacles to providing fertility care to people affected by sickle cell disease persist. In this Viewpoint, we contend that fertility care should be incorporated into the comprehensive care model for sickle cell disease, supporting alignment of treatment goals with reproductive life plans and delivering on the promise of individualised high-quality care for people with sickle cell disease and their families. We consider the obligation to provide fertility care in light of medical evidence, with acknowledgment of formidable obstacles to optimising care, and powerful historical and ethical considerations.

Australian women's views concerning non-medical egg freezing and factors motivating freezing decisions.

OBJECTIVE: We aimed to determine women's views about egg freezing for non-medical reasons and the factors motivating freezing decisions. DESIGN: In this study, 514 women aged 18-44 years completed an online cross-sectional survey exploring fertility knowledge, reproductive intentions and views concerning non-medical egg freezing. METHODS: Data were analysed descriptively. Additionally, 14 variables noted as potential motivators in prior literature were entered into a multinomial regression to explore factors that would motivate women to consider freezing their eggs for non-medical reasons. RESULTS: Views concerning non-medical egg freezing were generally positive, with 61.3% of participants reporting that they would consider egg freezing ('Yes' or 'Maybe'). Factors motivating decisions to freeze varied among women who responded 'Yes', 'Maybe' and 'I don't know' to whether they would consider freezing. The availability of Medicare subsidization and the procedure not affecting future fertility were significant predictors for all three groups of women. CONCLUSIONS: Acceptability of egg freezing for non-medical reasons was moderate to high. However, there is a need for targeted fertility information to educate women about fertility and optimal times to conceive and freeze their eggs. Future research about views concerning non-medical egg freezing among diverse populations and examining the health economics of this procedure would be beneficial.

Bioactive compounds as potential alternative treatments to prevent cancer therapy-induced male infertility.

About 8-12% of couples experience infertility, with male infertility being the cause in 50% of cases. Several congenital and acquired conditions, including chronic diseases and their treatments, can contribute to male infertility. Prostate cancer incidence increases annually by roughly 3%, leading to an increment in cancer treatments that have adverse effects on male fertility. To preserve male fertility post-cancer survival, conventional cancer treatments use sperm cryopreservation and hormone stimulation. However, these techniques are invasive, expensive, and unsuitable in prepubertal patients lacking mature sperm cells. Alternatively, nutritional therapies enriched with bioactive compounds are highlighted as non-invasive approaches to prevent male infertility that are easily implementable and cost-effective. In fact, curcumin and resveratrol are two examples of bioactive compounds with chemo-preventive effects at the testicular level. In this article, we summarize and discuss the literature regarding bioactive compounds and their mechanisms in preventing cancer treatment-induced male infertility. This information may lead to novel opportunities for future interventions.

Fertility Preservation Discussions Between Young Adult Rectal Cancer Survivors and Their Providers: Sex-Specific Prevalence and Correlates.

BACKGROUND: Young adults (YA) diagnosed with rectal cancer are disproportionately impacted by the gonadotoxic effects of treatment and potential subsequent infertility. OBJECTIVE: The purpose of this study was to characterize the prevalence of fertility preservation measures used, reasons why such measures were not used, and correlates of discussion between providers and YA rectal cancer survivors. DESIGN: An online, cross-sectional survey was administered on the Facebook page of a national colorectal cancer (CRC) advocacy organization. Eligible participants were rectal cancer survivors diagnosed before age 50, between 6 and 36 months from diagnosis or relapse, and based in the US. RESULTS: Participants were 148 rectal cancer survivors. Over half of the survivors reported that their doctor did not talk to them about potential therapy-related fertility complications. Only one-fifth of survivors banked sperm (males) or eggs/embryos (females) prior to their cancer therapy. Older age at diagnosis and greater quality of life were significantly associated with a higher likelihood of fertility discussions among males. Greater quality of life was significantly associated with a higher likelihood of fertility discussion among females. CONCLUSIONS: These findings indicate that the majority of YA rectal cancer survivors do not receive, or cannot recall, comprehensive cancer care, and help to identify patients with rectal cancer who may be at risk for inadequate fertility counseling. Clinicians should provide proper counseling to mitigate this late effect and to ensure optimal quality of life for YA rectal cancer survivors.

The Oncology Association of Bosnia and Herzegovina's recommendations for fertility preservation in oncologic patients.

Malignancy is one of the major public health problems in Bosnia and Herzegovina. Along with breakthroughs in specific oncological therapy, improving the quality of life of cancer patients and management of therapy-induced side effects need to be recognized as a priority in the comprehensive cancer patient care. Fertility loss after cancer treatment is a field requiring special attention due to its various consequences on patients themselves.  Although oncofertility is well-recognized area of oncology, low- to middle-income countries are facing issues with its implementation in everyday practice. Increased awareness about fertility preservation is of high priority for all specialists who participate in the medical care of cancer patients. The absence of a systemic solution and lack of expertise led to the founding of Fertility Preservation Working Group of the Oncology Association of Bosnia and Herzegovina. We have made recommendationsas an expert consensus with the ultimate goal of making the first step towards enhancement of oncofertility implementation in Bosnia and Herzegovina.

An assessment of oncofertility content on reproductive endocrinology and infertility clinic websites.

PURPOSE: To assess oncofertility content on fertility clinic websites as indicated by eight relevant keywords. Additionally, we sought to describe the relationship between oncofertility content and five predetermined clinic characteristics. METHODS: We examined 381 fertility clinic websites that are members of the Society for Associated Reproductive Technology (SART). Extracted data included clinic location, practice type (private vs academic), size (cycles/year), type of NCI designated center (cancer center vs comprehensive cancer center), and distance from the nearest NCI center. Additionally, we documented whether the clinic was located in a state mandating reproductive and infertility services and/or included fertility preservation for "iatrogenic infertility" as reported by the American Society for Reproductive Medicine (ASRM). Data were summarized using descriptive statistics and compared using chi-squared or t-test as appropriate. RESULTS: Of the 381 fertility clinic websites analyzed, 322 (85%) contained at least one oncofertility-related keyword. Most frequently used terms included cancer (79%) and fertility preservation (78%), while less frequently used terms included suppression (9.4%) and shielding (5.0%). Practices that initiated ≥ 501 cycles per year were more likely to mention one of the oncofertility keywords (OR 1.2; 95% CI 1.1-1.3). The associations of oncofertility website content with practice type, state-mandated fertility insurance coverage, and distance from an NCI-designated cancer center were not statistically significant. Large clinic size was the only predictive factor for inclusion of oncofertility website content. Further studies are required to evaluate whether inclusion of oncofertility content on clinic websites impacts the use of these services by patients with cancer. CONCLUSION: This is the first study correlating availability of oncofertility content on SART fertility clinic websites with consideration of geographic proximity to NCI designated cancer centers. Large clinic size was the only predictive factor for inclusion of oncofertility website content.

Evaluation of an alternative heterotopic transplantation model for ovarian tissue to test pharmaceuticals improvements for fertility restoration.

BACKGROUND: Ovarian tissue cryopreservation and transplantation (OTCTP) is currently the main option available to preserve fertility in prepubertal patients undergoing aggressive cancer therapy treatments. However, a major limitation of OTCTP is follicle loss after transplantation. The mouse is a model of choice for studying ovarian function and follicle development after ovarian tissue grafting in vivo. In these mouse models, ovarian tissue or ovaries can be transplanted to different sites. Our aim was to evaluate a new alternative to heterotopic transplantation models that could be useful to test pharmaceutical improvement for ovarian grafts after OTCTP. METHODS: Slow frozen murine whole ovaries were transplanted into the mouse ears (between the external ear skin layer and the cartilage). Ovarian transplants were recovered after 3, 14 or 21 days. Grafts were analyzed by immunohistochemistry and follicle density analyses were performed. RESULTS: An increase of ovarian vascularization (CD31 and Dextran-FITC positive staining), as well as cellular proliferation (Ki67 staining) were observed 3 weeks after transplantation in comparison to 3 days. Fibrosis density, evaluated after Van Gieson staining, decreased 3 weeks after transplantation. Furthermore, transplantation of cryopreserved ovaries into ovariectomized mice favored follicle activation compared to transplantation into non-ovariectomized mice. CONCLUSION: The present study indicates that surgical tissue insertion in the highly vascularized murine ear is an effective model for ovarian grafting. This model could be helpful in research to test pharmaceutical strategies to improve the function and survival of cryopreserved and transplanted ovarian tissue.

Efficacy and safety of Zi Gui Nv Zhen® capsules used in TCM for fertility preservation in patients with diminished ovarian reserve.

OBJECTIVE: To evaluate for the first time whether Zi Gui Nv Zhen® capsules (ZGNZC), until now used in traditional Chinese medicine (TCM) for menopausal complaints, can increase the fertility of Chinese women with diminished ovarian reserve (DOR). METHODS: Prospective, randomized, open-labeled 3-monthly study; 109 DOR patients (aged 20-40 years) receiving either ZGNZC (experimental group, n = 75) or not (control group, n = 34). Main outcomes: markers for ovarian function, thickness/type of the endometrium during ovulation, and pregnancy rate. Between-group analysis (A) comparing experimental vs. control group and within-group analysis (B) comparing data at baseline and after study in each of both groups. RESULTS: (A) Between-group-analysis: patients with ZGNZC had a higher endometrium thickness (0.75 vs. 0.62; p<.05) and higher anti-Müllerian hormone (AMH, 0.50 vs. 0.40; p<.05) than control group. Pregnancy rates were higher in the experimental than the control group (26.7% vs. 14.7%; n.s.). (B) Within-group-analysis: ZGNZC decreased levels of follicle-stimulating hormone (FSH, 11.42 vs. 8.69), increased estradiol-levels (E2, 56.09 vs. 73.36), and type A endometrium rates (5.3% vs. 39.7%) (all p< .05) and increased antral follicle count (AFC, 2 vs. 3). All hepato-renal biomarkers remained within the norm. The tolerability was good. There were no adverse events. CONCLUSIONS: In women with DOR who wish to conceive, three months' application of ZGNZC can improve ovarian function and oocyte quality by adjusting the neuroendocrine system, can improve endometrial properties and proliferation, necessary for a healthy pregnancy, and increased the clinical pregnancy rate in our prospective randomized observational study.

Infrastructure of Fertility Preservation Services for Pediatric Cancer Patients: A Report From the Children's Oncology Group.

PURPOSE: Fertility preservation (FP) services are part of comprehensive care for those newly diagnosed with cancer. The capacity to offer these services to children and adolescents with cancer is unknown. METHODS: A cross-sectional survey was sent to 220 Children's Oncology Group member institutions regarding institutional characteristics, structure and organization of FP services, and barriers to FP. Standard descriptive statistics were computed for all variables. The association between site-specific factors and selected outcomes was examined using multivariable logistic regression. RESULTS: One hundred forty-four programs (65.5%) returned surveys. Fifty-three (36.8%) reported a designated FP individual or team. Sperm banking was offered at 135 (97.8%) institutions, and testicular tissue cryopreservation at 37 (27.0%). Oocyte and embryo cryopreservation were offered at 91 (67.9%) and 62 (46.6%) institutions, respectively; ovarian tissue cryopreservation was offered at 64 (47.8%) institutions. The presence of dedicated FP personnel was independently associated with the ability to offer oocyte or embryo cryopreservation (odds ratio [OR], 4.7; 95% CI, 1.7 to 13.5), ovarian tissue cryopreservation (OR, 2.7; 95% CI, 1.2 to 6.0), and testicular tissue cryopreservation (OR, 3.3; 95% CI, 1.4 to 97.8). Only 26 (18.1%) participating institutions offered all current nonexperimental FP interventions. Barriers included cost (70.9%), inadequate knowledge or training (60.7%), difficulty characterizing fertility risk (50.4%), inadequate staffing (45.5%), and logistics with reproductive specialties (38%-39%). CONCLUSION: This study provides the most comprehensive view of the current landscape of FP infrastructure for children and adolescents with cancer and demonstrates that existing infrastructure is inadequate to offer comprehensive services to patients. We discuss modifiable factors to improve patient access to FP.