Advancements in Human Embryonic Stem Cell Research: Clinical Applications and Ethical Issues.

BACKGROUND: The development and use of human embryonic stem cells (hESCs) in regenerative medicine have been revolutionary, offering significant advancements in treating various diseases. These pluripotent cells, derived from early human embryos, are central to modern biomedical research. However, their application is mired in ethical and regulatory complexities related to the use of human embryos. METHOD: This review utilized key databases such as ClinicalTrials.gov, EU Clinical Trials Register, PubMed, and Google Scholar to gather recent clinical trials and studies involving hESCs. The focus was on their clinical application in regenerative medicine, emphasizing clinical trials and research directly involving hESCs. RESULTS: Preclinical studies and clinical trials in various areas like ophthalmology, neurology, endocrinology, and reproductive medicine have demonstrated the versatility of hESCs in regenerative medicine. These studies underscore the potential of hESCs in treating a wide array of conditions. However, the field faces ethical and regulatory challenges, with significant variations in policies and perspectives across different countries. CONCLUSION: The potential of hESCs in regenerative medicine is immense, offering new avenues for treating previously incurable diseases. However, navigating the ethical, legal, and regulatory landscapes is crucial for the continued advancement and responsible application of hESC research in the medical field. Considering both scientific potential and ethical implications, a balanced approach is essential for successfully integrating hESCs into clinical practice.

Comparison of resumption of ovulation after cessation of oral contraceptives and medroxyprogesterone acetate in women with polycystic ovary syndrome.

OBJECTIVE: Both oral contraceptive pills (OCPs) and cyclic medroxyprogesterone acetate (MPA) are widely used to control menstrual abnormalities in women with polycystic ovary syndrome (PCOS). We aimed to evaluate the chance of ovulation resumption after cessation of OCPs and MPA in women with PCOS. METHODS: A retrospective study was conducted of women with PCOS who were treated with OCPs or cyclic MPA from September 2015 to March 2019. After cessation of medication, ovulation was assessed using basal body temperature and/or measurement of serum progesterone. The odds ratio for ovulation resumption was assessed with multivariable logistic regression. Additionally, doubly robust analysis was performed with inverse-probability-weighted analysis and regression adjustment based on the covariate balancing propensity score to adjust for the effect of covariates on the treatment assignment. RESULTS: Among 272 women with PCOS, 136 were prescribed OCPs and 136 were prescribed cyclic MPA. Ovulation resumed in 18.4% of women (n = 25) after cessation of MPA and in 24.3% of women (n = 33) after cessation of OCPs. The odds of ovulation resumption in MPA users were comparable with those in OCP users (adjusted odds ratio (aOR) 1.00, 95% confidence interval (CI) 0.89-1.12). After multiple imputation due to missing values, the results did not change substantially (aOR 0.99, 95% CI 0.89-1.10). CONCLUSIONS: Among women with PCOS, MPA users have a similar chance of ovulation resumption as OCP users after cessation of medication. Cyclic MPA can be a good alternative to OCPs in women for whom OCPs are contraindicated or who decline to take OCPs.

Effects of Melatonin, GM-CSF, IGF-1, and LIF in Culture Media on Embryonic Development: Potential Benefits of Individualization.

The implantation of good-quality embryos to the receptive endometrium is essential for successful live birth through in vitro fertilization (IVF). The higher the quality of embryos, the higher the live birth rate per cycle, and so efforts have been made to obtain as many high-quality embryos as possible after fertilization. In addition to an effective controlled ovarian stimulation process to obtain high-quality embryos, the composition of the embryo culture medium in direct contact with embryos in vitro is also important. During embryonic development, under the control of female sex hormones, the fallopian tubes and endometrium create a microenvironment that supplies the nutrients and substances necessary for embryos at each stage. During this process, the development of the embryo is finely regulated by signaling molecules, such as growth factors and cytokines secreted from the epithelial cells of the fallopian tube and uterine endometrium. The development of embryo culture media has continued since the first successful human birth through IVF in 1978. However, there are still limitations to mimicking a microenvironment similar to the reproductive organs of women suitable for embryo development in vitro. Efforts have been made to overcome the harsh in vitro culture environment and obtain high-quality embryos by adding various supplements, such as antioxidants and growth factors, to the embryo culture medium. Recently, there has been an increase in the number of studies on the effect of supplementation in different clinical situations such as old age, recurrent implantation failure (RIF), and unexplained infertility; in addition, anticipation of the potential benefits from individuation is rising. This article reviews the effects of representative supplements in culture media on embryo development.

Transcriptomic Profiling of Reproductive Age Marmoset Monkey Ovaries.

The decline in ovarian reserve and the aging of the ovaries is a significant concern for women, particularly in the context of delayed reproduction. However, there are ethical limitations and challenges associated with conducting long-term studies to understand and manipulate the mechanisms that regulate ovarian aging in human. The marmoset monkey offers several advantages as a reproductive model, including a shorter gestation period and similar reproductive physiology to that of human. Additionally, they have a relatively long lifespan compared to other mammals, making them suitable for long-term studies. In this study, we focused on analyzing the structural characteristics of the marmoset ovary and studying the mRNA expression of 244 genes associated with ovarian aging. We obtained ovaries from marmosets at three different reproductive stages: pre-pubertal (1.5 months), reproductive (82 months), and menopausal (106 months) ovaries. The structural analyses revealed the presence of numerous mitochondria and lipid droplets in the marmoset ovaries. Many of the genes expressed in the ovaries were involved in multicellular organism development and transcriptional regulation. Additionally, we identified the expression of protein-binding genes. Within the expressed genes, VEGFA and MMP9 were found to be critical for regulating ovarian reserve. An intriguing finding of the study was the strong correlation between genes associated with female infertility and genes related to fibrosis and wound healing. The authors suggest that this correlation might be a result of the repeated rupture and subsequent healing processes occurring in the ovary due to the menstrual cycle, potentially leading to the indirect onset of fibrosis. The expression profile of ovarian aging-related gene set in the marmoset monkey ovaries highlight the need for further studies to explore the relationship between fibrosis, wound healing, and ovarian aging.

Current Position of Oncofertility in Adolescent Female Cancer Patients: A Comparative Review on Society Guidelines.

Fertility preservation (FP) in pediatric and adolescent oncology patients presents a complex interplay between cancer treatment imperatives and reproductive aspirations, demanding a multi-disciplinary approach. Essential guidelines emphasize the importance of early referrals to FP specialists, ensuring timely counseling on oocyte and ovarian tissue cryopreservation options. Proper patient selection and risk assessment, considering intrinsic and extrinsic factors, is crucial for judicious resource utilization and optimal outcomes. Gonadotoxic effects of cancer treatments pose significant threats to reproductive capabilities. Oocyte cryopreservation (OC) is preferred in post-pubertal adolescents without partners. Cultural and religious concerns, especially regarding hymenal integrity, influence FP decisions, necessitating culturally sensitive consent processes. Ovarian tissue cryopreservation (OTC) offers an alternative for those unfit for OC. Despite its experimental label in some societies, emerging data support the efficacy of OTC, with ovarian tissue transplantation (OTT) showing promise in restoring ovarian function. However, the reintroduction of potentially malignant cells during transplantation remains a concern. Overall, while FP offers hope for future parenthood, the intricacies of decision-making and the potential medical, ethical, and cultural challenges underscore the importance of a personalized, multi-disciplinary approach. In this review, guidelines from various societies have been comprehensively reviewed and analyzed to provide insight into the clinical practice of oncofertility.

Effects of Cetrorelix on Ovary and Endometrium Prior to Anti-PD-L1 Antibody in Murine Model.

BACKGROUND: Recent anti-cancer agents, immune checkpoint inhibitors (ICIs), have emerged as effective agents targeting the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. While the administration of gonadotropin-releasing hormone (GnRH) analogs before cytotoxic agents is known to preserve female reproductive organ function, the potential effects of ICIs and the protective impact of GnRH analogs on female reproductive organs, especially concerning ovarian reserve and endometrial receptivity, remain unknown. In this study, we attempted to elucidate the protective or regenerative effect on the female reproductive organ of cetrorelix prior to anti-PD-L1 antibody administration. METHOD: Using a murine model, we examined the effects of Anti-PD-L1 antibody treatment on ovarian and uterine morphology, compared them with controls, and further assessed any potential protective effect of cetrorelix, a GnRH analog. Histological examinations and quantitative reverse transcription polymerase chain reaction were employed to study the morphological changes and associated gene expression patterns. RESULTS: Anti-PD-L1 treatment led to a significant depletion of primordial/primary ovarian follicles and impaired decidualization in uterine stromal cells. However, while pretreatment with cetrorelix could restore normal decidualization patterns in the uterus, it did not significantly ameliorate ovarian follicular reductions. Gene expression analysis reflected these observations, particularly with marked changes in the expression of key genes like Prl and Igfbp1, pivotal in uterine decidualization. CONCLUSION: Our study underscores the potential reproductive implications of cetrorelix treatment prior to Anti-PD-L1 therapy, shedding light on its short-term protective effects on the uterus. Further studies are necessary to understand long-term and clinical implications.

Risk Factors for Treatment-Related Amenorrhea in Female Survivors of Childhood and Adolescent Cancer: 10-Year Experiences at Oncofertility Clinic in Korean Tertiary Center.

Purpose: This study investigates the impact of gonadotoxic cancer treatment on treatment-related amenorrhea (TRA) and hormonal status in pediatric and adolescent females who underwent fertility preservation (FP) consultation. Methods: A retrospective review was conducted on 143 females under 21 with cancer referred to the FP clinic at Seoul National University Hospital between 2011 and 2022. We analyzed variables, including age, menarche status, cancer type, and treatment. Subsequently, subjects were evaluated to identify clinical factors affecting TRA at 1-year intervals following the completion of treatment. Upon cancer diagnosis, all patients received FP counseling and underwent semiannual evaluations for menstrual resumption and hormonal status. Results: The median age at diagnosis was 15; menarche was reported in 76.9%. Bone sarcoma (16.1%) and acute lymphoblastic leukemia (14.7%) were predominant. Most consultations (74.8%) occurred pretreatment. After FP consultations, 9.8% of patients underwent oocyte cryopreservation, and 99.3% used gonadotropin-releasing hormone agonists during systemic chemotherapy. One year after treatment completion, TRA was shown in 29.4% of this cohort. Cyclophosphamide-equivalent dose >4000 mg/m2 (adjusted odds ratio [aOR], 2.279; 95% confidence interval [CI]; 1.018-5.105, p = 0.045) and pelvic irradiation (aOR, 16.271; 95% CI, 1.545-171.408; p = 0.020) were independent clinical factors predicting TRA. Conclusion: The study delineates the clinical factors affecting TRA in pediatric and adolescent cancer survivors, revealing the significant impact of specific treatment. The data highlight the critical role of personalized oncofertility consultations in this demographic, offering valuable insights for designing targeted FP strategies at tertiary centers.

Effect of topical estrogen cream compared with observation in prepubertal girls with labial adhesions.

BACKGROUND: Topical estrogen treatment has been considered the first-line treatment of labial adhesions in prepubertal girls. However, the effect of topical estrogen cream is different according to studies, and no study compared estrogen cream to observation. OBJECTIVE: This study aims to investigate the efficacy of topical estrogen cream treatment compared with observation in prepubertal girls with labial adhesions. STUDY DESIGN: The medical records of prepubertal girls diagnosed with labial adhesions from April 2005 to June 2019 were retrospectively analyzed. Baseline characteristics such as age at diagnosis and initial symptoms were collected. The primary outcome was the resolution of labial adhesion. Secondary outcomes were recurrence and side effects. RESULTS: A total of 114 patients were enrolled and divided into two groups, topical estrogen cream (n = 94), and observation (n = 20). Girls who were treated with estrogen cream had older age (24.6 ± 19.0 vs. 16.7 ± 15.3 months, p = 0.037) and higher resolution rate than the observation group (100.0% vs. 85.0%, respectively, p = 0.005). Girls younger than 23.3 months showed a significantly higher resolution rate to topical estrogen treatment (100% vs. 86.7%, p = 0.043). Side effects and recurrences occurred exclusively in children treated with topical estrogen therapy without significant differences compared to the observation group. CONCLUSION: Topical estrogen therapy showed a higher resolution rate than observation for the treatment of prepubertal girls with labial adhesions, especially in younger girls.

The impact of sex steroids on osteonecrosis of the jaw.

Sex steroid hormones play a major role in bone homeostasis. Therefore, the use of sex hormones or drugs may increase the risk of osteonecrosis of the jaw (ONJ), a complication caused by damaged bone homeostasis. However, few are known the impact of medications changing sex hormone levels on ONJ. The pathophysiology of ONJ is not clearly understood and many hypotheses exist: cessation of bone remodeling caused by its anti-resorptive effect on osteoclasts; compromised microcirculation due to medication affecting angiogenesis, including bisphosphonate; and impairment of defense mechanism toward local infection. The use of high-dose intravenous bisphosphonate in cancer patients is associated with a high prevalence of ONJ. Exogenous estrogen or androgen replacement was reported to be associated with ONJ. Polycystic ovarian syndrome (PCOS) patients demonstrate an androgen excess status, and androgen overproduction serves as a protective factor in the bone mineral density of young women. To date, there are no reports of ONJ occurrence due to androgen overproduction. In contrast, few reports on the occurrence of ONJ due to estrogen deficiency induced by drugs, such as selective estrogen receptor modulator (SERM), aromatase inhibitors, and gonadotropin-releasing hormone (GnRH) agonists, are available. Thus, the role of sex steroids in the development of ONJ is not known. Further studies are required to demonstrate the exact role of sex steroids in bone homeostasis and ONJ progression. In this review, we will discuss the relationship between medication associated with sex steroids and ONJ.

The level of vitamin D in follicular fluid and ovarian reserve in an in vitro fertilization program: A pilot study.

BACKGROUND: The level of vitamin D in follicular fluid (FF) according to the ovarian reserve has never been investigated, and the effect of FF vitamin D on the outcome of assisted reproductive technology (ART) remains controversial. The aim of this study is to evaluate the association between FF vitamin D levels and baseline anti-Müllerian hormone (AMH) / ART outcomes. METHODS: Forty-seven patients who underwent controlled ovarian stimulation at the fertility clinic of an academic tertiary care center were enrolled for a prospective observational study. FF was collected from the first aspirated leading follicle of each ovary and assayed by an enzyme-linked immunosorbent assay. Multivariable linear regression analysis was used to assess the association between baseline AMH and FF vitamin D levels with adjustment for basal FSH and serum vitamin D levels. RESULTS: Both the AMH and serum vitamin D were significant predictors for FF vitamin D. The estimated marginal mean of FF vitamin D level was higher in women with decreased ovarian reserve (DOR) than those with normal ovarian reserve (24.1 ± 2.1 vs. 18.8 ± 1.4 ng/ml, p = 0.048). However, FF vitamin D did not demonstrate any significant associations with cycle outcomes, including fertilization rate and the number and proportion of good embryos at day three. CONCLUSION: We observed significantly higher FF vitamin D levels in women with DOR. However, FF vitamin D did not demonstrate any significant associations with the outcome of ART. A larger prospective study is needed to investigate the effect of FF vitamin D on the clinical pregnancy rate and live birth rate.

Prediction model of persistent ovulatory dysfunction in Korean women with polycystic ovary syndrome.

AIM: There is no validated tool to predict persistent ovulatory dysfunction after medication with oral contraceptives in women with polycystic ovary syndrome (PCOS), which is the most severe subtype of PCOS. We aimed to build a model to predict persistent ovulatory dysfunction after medication of oral contraceptives in women with PCOS. METHODS: A total of 286 patients with PCOS were treated with and without oral contraceptives at a tertiary academic medical center. Data were obtained from the electronic medical record system between January 2016 and March 2019. A risk prediction model was developed using multivariable logistic regression. Model 1 was based on age and chief complaints and Model 2 further included predictors evaluated during a clinic visit. Model 3 additionally included laboratory findings. RESULTS: Of the study population, ovulatory dysfunction was persistent in 117 patients (40.9%). Compared with the simple model (Models 1 and 2), the full prediction model (Model 3) had better Akaike's information criterion (286, 244 vs. 225) and the area under the curve (AUC) increased from 0.74 and 0.79 to 0.84. The full model included 7 covariates measured during the evaluation of PCOS, and two covariates were significant predictors of persistent ovulatory dysfunction in PCOS: age (OR 0.91; 95% CI 0.84-0.97), and anti-Müllerian hormone (OR 1.17; 95% CI 1.09-1.26). This model demonstrated good discrimination (AUC, 0.84) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.74). CONCLUSIONS: This prediction model was shown to be a useful method for predicting persistent ovulatory dysfunction after oral contraceptive medication in patients with PCOS.

Identification of Stem Cell-Like Cells in the Ovary.

Understanding the function of stem cells and cellular microenvironments in in vitro oogenesis, including ovarian folliculogenesis, is crucial for reproductive biology. Because mammalian females cannot generate oocytes after birth, the number of oocyte decreases with the progression of reproductive age. Meanwhile, there is an emerging need for the neogenesis of female germ cells to treat the increasing infertility-related issues in cancer survivors. The concept of oocytes neogenesis came from the promising results of stem cells in reproductive medicine. The stem cells that generate oocytes are defined as stem cell-like cells in the ovary (OSCs). Several recent studies have focused on the origin, isolation, and characteristic of OSCs and the differentiation of OSCs into oocytes, ovarian follicles and granulosa cells. Hence, in this review, we focus on the experimental trends in OSC research and discuss the methods of OSC isolation. We further summarized the characteristics of OSCs and discuss the markers used to identify OSCs differentiated from various cell sources. We believe that this review will be beneficial for advancing the research and clinical applications of OSCs.

Synergistic Promoting Effects of X-Linked Inhibitor of Apoptosis Protein and Matrix on the In Vitro Follicular Maturation of Marmoset Follicles.

BACKGROUND: In vitro follicular maturation (IVFM) of ovarian follicles is an emerging option for fertility preservation. Many paracrine factors and two-dimensional or three-dimensional (3D) environments have been used for optimization. However, since most studies were conducted using the murine model, the physiological differences between mice and humans limit the interpretation and adaptation of the results. Marmoset monkey is a non-human primate (NHPs) with more similar reproductive physiology to humans. In this study, we attempted to establish a 3D matrix (Matrtigel)-based IVFM condition for marmoset ovarian follicles in combination with anti-apoptotic factor, X-linked inhibitor of apoptosis protein (XIAP). METHODS: Marmoset follicles were isolated as individual follicles and cultured in a single drop with the addition of 0, 10, and 100 µg/mL of XIAP molecules. Matured oocytes and granulosa cells from mature follicles were collected and analyzed. The average number of isolated follicles was less than 100, and primordial and antral follicles were abundant in the ovaries. RESULTS: IVFM of marmoset follicles in 3D matrix conditions with XIAP increased the rates of survival and in vitro follicle development. Furthermore, oocytes from the 3D cultures were successfully fertilized and developed in vitro. The addition of XIAP increased the secretion of estradiol and aromatase. Furthermore, expression of granulosa-specific genes, such as bone morphogenetic protein 15, Oct4, and follicle-stimulating hormone receptor were upregulated in the in vitro-matured follicles than in normal, well-grown, and atretic follicles. Apoptosis-related B-cell lymphoma-2 was highly expressed in the atretic follicles than in the XIAP-treated follicles, and higher caspase-3 was localized in the XIAP-treated follicles. CONCLUSION: In this study, we attempted to establish a 3D-matrix-based marmoset IVFM condition and demonstrated the synergistic effects of XIAP. The use of a 3D matrix may be applied as an optimal culture condition for marmoset ovarian follicles.

Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve.

Female endocrinological symptoms, such as premature ovarian inefficiency (POI) are caused by diminished ovarian reserve and chemotherapy. The etiology of POI remains unknown, but this can lead to infertility. This has accelerated the search for master regulator genes or other molecules that contribute as enhancers or silencers. The impact of regulatory microRNAs (miRNAs) on POI has gained attention; however, their regulatory function in this condition is not well known. RNA sequencing was performed at four stages, 2-(2 W), 6-(6 W), 15-(15 W), and 20-(20 W) weeks, on ovarian tissue samples and 5058 differentially expressed genes (DEGs) were identified. Gene expression and enrichment were analyzed based on the gene ontology and KEGG databases, and their association with other proteins was assessed using the STRING database. Gene set enrichment analysis was performed to identify the key target genes. The DEGs were most highly enriched in 6 W and 15 W groups. Figla, GDF9, Nobox, and Pou51 were significantly in-creased at 2 W compared with levels at 6 W and 20 W, whereas the expression of Foxo1, Inha, and Taf4b was significantly de-creased at 20 W. Ccnd2 and Igf1 expression was maintained at similar levels in each stage. In total, 27 genes were upregulated and 26 genes interacted with miRNAs; moreover, stage-specific upregulated and downregulated interactions were demonstrated. Increased and decreased miRNAs were identified at each stage in the ovaries. The constitutively expressed genes, Ccnd2 and Igf1, were identified as the major targets of many miRNAs (p < 0.05), and Fshr and Foxo3 interacted with miRNAs, namely mmu-miR-670-3p and mmu-miR-153-3p. miR-26a-5p interacted with Piwil2, and its target genes were downregulated in the 20 W mouse ovary. In this study, we aimed to identify key miRNAs and their target genes encompassing the reproductive span of mouse ovaries using mRNA and miRNA sequencing. These results indicated that gene sets are regulated in the reproductive stage-specific manner via interaction with miRNAs. Furthermore, consistent expression of Ccnd2 and Igf1 is considered crucial for the ovarian reserve and is regulated by many interactive miRNAs.

Epigenetic Regulation of Cardiomyocyte Differentiation from Embryonic and Induced Pluripotent Stem Cells.

With the intent to achieve the best modalities for myocardial cell therapy, different cell types are being evaluated as potent sources for differentiation into cardiomyocytes. Embryonic stem cells and induced pluripotent stem cells have great potential for future progress in the treatment of myocardial diseases. We reviewed aspects of epigenetic mechanisms that play a role in the differentiation of these cells into cardiomyocytes. Cardiomyocytes proliferate during fetal life, and after birth, they undergo permanent terminal differentiation. Upregulation of cardiac-specific genes in adults induces hypertrophy due to terminal differentiation. The repression or expression of these genes is controlled by chromatin structural and epigenetic changes. However, few studies have reviewed and analyzed the epigenetic aspects of the differentiation of embryonic stem cells and induced pluripotent stem cells into cardiac lineage cells. In this review, we focus on the current knowledge of epigenetic regulation of cardiomyocyte proliferation and differentiation from embryonic and induced pluripotent stem cells through histone modification and microRNAs, the maintenance of pluripotency, and its alteration during cardiac lineage differentiation.

Recent Advancements in Engineered Biomaterials for the Regeneration of Female Reproductive Organs.

Various gynecologic diseases and chemoradiation or surgery for the management of gynecologic malignancies may damage the uterus and ovaries, leading to clinical problems such as infertility or early menopause. Embryo or oocyte cryopreservation-the standard method for fertility preservation-is not a feasible option for patients who require urgent treatment because the procedure requires ovarian stimulation for at least several days. Hormone replacement therapy (HRT) for patients diagnosed with premature menopause is contraindicated for patients with estrogen-dependent tumors or a history of thrombosis. Furthermore, these methods cannot restore the function of the uterus and ovaries. Although autologous transplantation of cryopreserved ovarian tissue is being attempted, it may re-introduce malignant cells after cancer treatment. With the recent development in regenerative medicine, research on engineered biomaterials for the restoration of female reproductive organs is being actively conducted. The use of engineered biomaterials is a promising option in the field of reproductive medicine because it can overcome the limitations of current therapies. Here, we review the ideal properties of biomaterials for reproductive tissue engineering and the recent advancements in engineered biomaterials for the regeneration of female reproductive organs.

Current and Future Perspectives for Improving Ovarian Tissue Cryopreservation and Transplantation Outcomes for Cancer Patients.

Although advances in cancer treatment and early diagnosis have significantly improved cancer survival rates, cancer therapies can cause serious side effects, including ovarian failure and infertility, in women of reproductive age. Infertility following cancer treatment can have significant adverse effects on the quality of life. However, established methods for fertility preservation, including embryo or oocyte cryopreservation, are not always suitable for female cancer patients because of complicated individual conditions and treatment methods. Ovarian tissue cryopreservation and transplantation is a promising option for fertility preservation in pre-pubertal girls and adult patients with cancer who require immediate treatment, or who are not eligible to undergo ovarian stimulation. This review introduces various methods and strategies to improve ovarian tissue cryopreservation and transplantation outcomes, to help patients and clinicians choose the best option when considering the potential complexity of a patient's situation. Effective multidisciplinary oncofertility strategies, involving the inclusion of a highly skilled and experienced oncofertility team that considers cryopreservation methods, thawing processes and devices, surgical procedures for transplantation, and advances in technologies, are necessary to provide high-quality care to a cancer patient.

Correlation between bone mineral density and endometrial thickness over time in women with breast cancer history.

As the efficacy of chemotherapy and adjuvant endocrine therapy for breast cancer increase, the quality-of-life to cancer survivors could be more important issue in strategies of breast cancer treatment. Bone health has become more compelling in care of breast cancer survivor than ever before. This retrospective study was aimed to evaluate factors relating to the change in BMD and to ascertain the correlation between changes in BMD and EMT of women with breast cancer in follow-up. Records of 164 women who underwent surgery for breast cancer were reviewed in this study. The basal characteristics included parity, menopausal state, medication with vitamin D, bisphosphonate, selective estrogen modulator (SERM), aromatase inhibitor (AI), gonadotrophin releasing hormone agonist (GnRHa), chemotherapy, radiotherapy, cancer type including positivity of estrogen receptor, progesterone receptor and HER2, combined the other gynecologic disease or the other origin cancer. At initial and follow-up visit, all subjective were checked with BMD, endometrial thickness (EMT). The mean age was 52.1 ± 8.5 years old and overall interval between initial and follow-up visits were 17.6 ± 7.5 month in this study. The BMDs of L1-4 (1.040 ± 0.166 g/cm2 vs 1.070 ± 0.181 g/cm2, p < 0.001), femur neck (0.850 ± 0.121 g/cm2 vs 0.870 ± 0.136 g/cm2, p < 0.001), and femur total (0.902 ± 0.132 g/cm2 vs 0.915 ± 0.138 g/cm2, p < 0.001) at follow-up visit were significantly lower than those at initial visit. The change in BMDs of L1-4 (ΔBMDL1-4, r = 0.353, p < 0.001, and r = 0.228, p = 0.003), femur neck (ΔBMDNeck, r = 0.198, p = 0.011, and r = 0.282, p < 0.001), femur total (ΔBMDTotal, r = 0.294, p < 0.001, and r = 0.327, p < 0.001) had positive correlation with age and the change in EMT (ΔEMT). After age correction, ΔEMT had positive correlation with ΔBMDNeck (r = 0.245, p = 0.002) and ΔBMDTotal (r = 0.273, p < 0.001). ΔBMDL1-4 and ΔBMDNeck differed according to menopausal state (p < 0.001 and p = 0.035), bisphosphonate (p < 0.001 and p < 0.001), and GnRHa (p < 0.001 and p < 0.001). In follow-up of women with history of breast cancer, ΔEMT could be an alternative screening marker for BMD decrease.