Recovery Of Ovarian Function Research Articles

Intraovarian injection of 3D-MSC-EVs-ECM gel significantly improved rat ovarian function after chemotherapy

BackgroundRestoring the function of the ovary is important for chemotherapy-induced ovarian failure (COF) patients. Stem cell and extracellular vesicles (EVs) therapy show promise but need further improvement.MethodsHuman umbilical cord mesenchymal stem cells (hUC-MSCs) were primarily cultured and further three-dimensional (3D) cultured using an ultra-low attachment surface method. The expression levels of nutritional cytokines and immunomodulatory and stemness-related genes of 3D-cultured hUC-MSCs were analyzed. EVs were isolated by ultracentrifugation and characterized. Ovaries were decellularized with sodium dodecyl sulfate to obtain extracellular matrix (ECM). Lyophilized EVs from three-dimensional (2D) or 3D hUC-MSCs were mixed with ECM to prepare the 2D/3D-MSC-EVs-ECM gels. The therapeutic effect of the MSC-EVs-ECM gel on cyclophosphamide (CTX) -treated rats was analyzed through various tests. RNA sequencing was used to analyze the expression changes of genes before and after treatment.ResultsAfter culturing in ultra-low attachment dishes, hUC-MSCs aggregated into spheroids and significantly upregulated the expression levels of immunomodulatory and stemness-related genes. The total EVs yield was also upregulated (5.6-fold) after 3D culture. The cell viability of CTX-treated ovarian granulosa cells (OGCs) was significantly rescued by coculture with the 3D-MSC-EVs-ECM gel. Hormones indicative of ovarian function, AMH, E2, and FSH, were recovered in both the CTX + 2D-MSC-EVs-ECM gel group and the CTX + 3D-MSC-EVs-ECM gel group, while the apoptosis-related protein Bax was significantly downregulated. The 3D-MSC-EVs-ECM gel was more effective than the 2D-MSC-EVs-ECM gel. Significantly differentially expressed genes, such as Hbb-b1, Gpd1, and Sirpa, were detected by RNA sequencing. Hbb-b1 was increased in the ovaries of CTX-treated rats, and this increase was attenuated by injecting the 2D/3D-MSC-EVs-ECM gel. Gpd1 was increased after CTX treatment, and this increase was reversed by the 3D-MSC-EVs-ECM gel. Sirpa was decreased in the ovaries of CTX-treated rats, and this decrease was attenuated by injecting the 3D-MSC-EVs-ECM gel.ConclusionsOur study demonstrated that the 3D-MSC-EVs-ECM gel is an efficient strategy for the recovery of ovarian function in CTX-induced ovarian failure.

8265 Premature Ovarian Insufficiency in Pediatric Cancer Patients: a 10-Year Rady Children's Hospital Experience

Abstract Disclosure: M. Robinson: None. L. Meller: None. M.E. Patterson: None. Objective: To highlight the occurrence of premature ovarian insufficiency in cancer patients treated at a children’s hospital and to determine which patient characteristics or treatment modalities are associated with ovarian failure and subsequent recovery of ovarian function. Study design: A retrospective chart review. Setting: Rady Children’s Hospital San Diego. Subjects and Methods: Between August 2011 and August 2021, the cases of 36 patients with cancer and ovarian failure were reviewed. Data collected included type of cancer, age at diagnosis, types of chemotherapy used in treatment, whether a bone marrow transplant or radiation was part of the treatment plan, peak FSH value and age when this occurred, peak AMH value, whether GnRHa treatment was used, type of hormone replacement therapy used, and whether there was recovery of ovarian function. Results: The most common type of cancer identified in this group of patients was acute lymphoblastic leukemia (ALL) (13, 36.1%). The mean age of diagnosis was 8.5 ± 4.3 years and the mean age of peak FSH value was 12.6 ± 2.8 years. Nearly all patients (97.2%) were treated with alkylating agents as part of their chemotherapy regimen and 72.2% received some form of radiation. Most patients (26, 72.2%) also received some form of hormone therapy, most commonly transdermal hormone therapy (13, 36.1%) or oral contraceptive pill (10, 27.8%), and 15.8% of patients were treated with the GnRHa Lupron. Fertility planning was offered or discussed in 36.1% of patients. Ten patients (27.8%) were noted to have some degree of recovery in their ovarian function. Age at diagnosis and type of cancer treatment were significant predictors of recovery in multivariate regression modeling. Specifically, each year older in age was associated with a 30% decrease in odds of recovery (OR: 0.7, CI: 0.5-0.95, P = 0.035), and treatment with an alkylating agent without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI:2.7-564, P = 0.007). Conclusion: This retrospective review demonstrates that, while uncommon, POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on the potential long-term effects of cancer treatment and routine surveillance for these complications. This study also confirmed that recovery of ovarian function is possible in these patients, especially when diagnosed at a younger age, so continued monitoring is essential. Presentation: 6/3/2024

Premature ovarian insufficiency in pediatric cancer patients: a 10 year Rady Children's Hospital experience.

To highlight the occurrence of premature ovarian insufficiency in pediatric cancer patients and determine which patient characteristics or treatment modalities are associated with ovarian failure and recovery. Between August 2011-August 2021, 36 of 2,661 patients with cancer were identified to have subsequent ovarian failure. Data collected included cancer type, diagnosis age, types of chemotherapy, bone marrow transplant or radiation treatment, peak follicle-stimulating hormone (FSH), peak anti-Mullerian hormone (AMH), gonadotropin releasing hormone agonist (GnRHa) treatment, type of hormone replacement therapy, and if ovarian function recovery occurred. The most common cancer type identified was ALL. The mean age of diagnosis was 8.5±4.3 years and mean age of peak FSH value was 12.6±2.8 years. Most patients (97.2 %) were treated with alkylating agents and 72.2 % received radiation. Most patients (72.2 %) received hormone therapy, and 15.8 % of patients received GnRHa Lupron. Ten patients (27.8 %) had ovarian function recovery. Diagnosis age and treatment type were recovery predictors in multivariate regression modeling. Each year older in age was associated with a 30 % decrease in odds of recovery (OR: 0.7, CI: 0.5-0.95, p=0.035), and alkylating agent treatment without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI: 2.7-564, p=0.007). This retrospective review demonstrates that POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on potential long-term effects of cancer treatment and importance of routine surveillance. This study confirmed that recovery of ovarian function is possible, especially when diagnosed at a younger age, making continued monitoring essential.

Progress in the Treatment of Ovarian Cysts by Combination of Traditional Chinese and Western Medicine

Ovarian cyst is a common benign tumor in gynecology, often occurring in women of childbearing age. Its essence is a solid or liquid cystic filling structural disease formed inside or on the surface of the ovary, which is not easy to be detected in the early stage, the onset is slow, and serious symptoms and signs such as abdominal fullness, menstrual disorders, and touching mass will occur, affecting women's work and life. At present, both Chinese medicine and Western medicine have certain cognition and advantages in the treatment of ovarian cysts. Chinese medicine can be divided into internal treatment and external treatment, while Western medicine can be divided into drug treatment and surgical treatment. Clinical treatment should be fully considered in the selection of patients' clinical conditions. This paper analyzes the advantages of TCM and Western medicine in clinical treatment, aiming to improve clinical efficacy, reduce cyst recurrence, promote ovarian function recovery, and better protect female ovarian health through the combination of traditional Chinese and Western medicine.

Ovarian function recovery in breast cancer patients receiving adjuvant anastrozole treatment: updated results from the phase 3 DATA trial

PurposePatients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results.MethodsPostmenopausal women with HR+ BC who were 45–57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method.ResultsThis study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85–2.81), DRFS (HR = 1.51; 95% CI 0.73–3.11), OS (HR = 1.64; 95% CI 0.75–3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84–4.63) when compared with patients without OFR.ConclusionIn patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients.

Fertility Assessment after Ovarian Transposition in Children and Young Women Treated for a Malignant Tumor.

Ovarian transposition (OT) has been proposed as a protective measure against radiation-induced damage to ovarian function and fertility. Despite its historical use, limited research has focused on evaluating endocrine and exocrine ovarian function after OT performed in adolescents and young adults (AYAs) before or during puberty. The purpose of our study was to investigate the fertility, pubertal development, and ovarian function of women with a previous history of OT during childhood, adolescence or young adulthood. In an observational bicentric retrospective study, we included 32 young female cancer patients who underwent OT before the age of 26 between 1990 and 2015 at Lyon Léon Bérard Cancer Center or Nancy University Hospital. The mean age at the time of OT was 15.6 years with a cancer diagnosis at 15 ± 4.8 years. Among the 10 women attempting pregnancy post-treatment, 60% achieved successful pregnancies. After a mean follow-up of 9.6 ± 7 years, 74% (17 out of 23) of women recovered spontaneous menstrual cycles (seven out of eight evaluable women with OT before or during puberty). Notably, 35% of women who did not attempt pregnancy demonstrated adequate ovarian reserve. Ovarian reserve and function recovery were influenced by the specific chemotherapy received. Importantly, our findings suggest that OT's effectiveness on ovarian activity resumption does not significantly differ when performed before or during puberty compared to pubertal stages. This study contributes valuable insights into the long-term reproductive outcomes of young women undergoing OT, emphasizing its potential efficacy in preserving ovarian function and fertility across different developmental stages.

Enhancement of Vascularization and Ovarian Follicle Survival Using Stem Cells in Cryopreserved Ovarian Tissue Transplantation-A Systematic Review.

The increase in cancer survival rates has put a focus on ensuring fertility preservation procedures for cancer patients. Ovarian tissue cryopreservation presents the only option for prepubertal girls and patients who require immediate start of treatment and, therefore, cannot undergo controlled ovarian stimulation. We aimed to provide an assessment of stem cells' impact on cryopreserved ovarian tissue grafts in regard to the expression of growth factors, angiogenesis promotion, tissue oxygenation, ovarian follicle survival and restoration of endocrine function. For this systematic review, we searched the Scopus and PubMed databases and included reports of trials using murine and/or human cryopreserved ovarian tissue for transplantation or in vitro culture in combination with mesenchymal stem cell administration to the grafting site. Of the 1201 articles identified, 10 met the criteria. The application of stem cells to the grafting site has been proven to support vascular promotion and thereby shorten the period of tissue hypoxia, which is reflected in the increased number of remaining viable follicles and faster recovery of ovarian endocrine function. Further research is needed before implementing the use of stem cells in OT cryopreservation and transplantation procedures in clinical practice. Complex ethical dilemmas make this process more difficult.

Abstract PO2-12-06: Comparative Study on Bone Mineral Density in Premenopausal Patients with Estrogen Receptor-Positive Breast cancer in ASTRRA study: a 5-year follow-up study

Abstract Background With the positive outcomes associated with Ovarian Function Suppression (OFS) treatment as reported in the ASTRRA study, which compare two therapeutic strategies, tamoxifen alone and ovarian function suppression (OFS) in premenopausal patients after chemotherapy, the role of OFS has getting important. However, considering the increased risk of bone density reduction associated with postmenopause in women, the understanding these effects is crucial in devising strategies that not only effectively combat the cancer but also concurrently safeguard the patients’ bone health. This study aimed to compare the impacts of two therapeutic strategies, tamoxifen alone and OFS on bone mineral density (BMD) in premenopausal patients after chemotherapy. Methods Of the 1483 premenopausal enrolled in ASTRRA study, we focused on a subset of 522 patients who had undergone BMD examinations at diagnosis, 3 years and 5 years after diagnosis. Patients were stratified into three categories: normal, osteopenia, osteoporosis, and we examined the changes in their classifications over the 3-year and 5-year periods from baseline to identify any deterioration in bone density. Also, Patients were examined ovarian function every 6 months for 2 years and have different randomization times. Further categorization was carried out according to the time of randomization, which means starting time of OFS after recovery of ovary function. Lastly, we conducted a subset analysis using data from the Asan Medical Center (AMC), specially focused on the absolute value of one density measured in g/cm3. Results The median age of 522 patients was 41.1 and at baseline, a higher incidence of osteopenia was observed in the OFS addition group (p=0.028). Both analysis of change in BMD categories of from baseline to 3-year and baseline to 5-year period showed no significant differences between TAM only and TAM+OFS group (3-year: p=0.567, 5-year: p=0.600). However, there was a significant increased risk of bone density deterioration in the OFS addition group, when randomization occurred at the first visit (HR= 2.970, p=0.008). Within the AMC subset, statistically significant decrease in BMD were observed in the OFS addition group at the spine (p=0.023) and femur (p=0.040) over a baseline to 3-year period. Although a decrease in BMD was also observed over a baseline to 5-year period at both the spine and femur, this change was not statistically significant. Conclusion This study revealed a deleterious impact on bone density associated with the addition of OFS, compared to tamoxifen-only treatment. Remarkably, our findings also indicated that early suppression of ovarian function exerts even more detrimental influence on bone health in premenopausal, estrogen receptor-positive breast cancer patients, who have recovered ovarian function. Change between baseline to 5 years according to randomization time interval The table shows the risk associated with bone health deterioration according to the duration of randomization, thus specifying the time interval between the recovery and suppression of ovarian function. Citation Format: Eunju Shin, Seung Il Kim, Min-ho Park, Hyun-Ah Kim, Yongsik Jung, Jai Min Ryu, Eun Hwa Park, Sung Yong Kim, Eun-Gyeong Lee, Min Hyuk Lee, Jung Ho Park, Seock-Ah Im, Soong June Bae, Su Hwan Kang, Woosung Lim, Hyun Jo Youn, Heung Kyu Park, Kyong Hwa Park, Tae-Hyun Kim, Shin-Young Park, Cheol wan Lim, Geum-Hee Kwak, Chanheun Park, Hyuk-Jae Shin, Young Bum Yoo, Sun Hee Kang, Bong Kyun Kim, Hee Jeong Kim. Comparative Study on Bone Mineral Density in Premenopausal Patients with Estrogen Receptor-Positive Breast cancer in ASTRRA study: a 5-year follow-up study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-06.

The mechanisms of MicroRNA 21 in premature ovarian insufficiency mice with mesenchymal stem cells transplantation

Umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation has been deeply explored for premature ovarian insufficiency (POI) disease. However, the associated mechanism remains to be researched. To explore whether and how the microRNA 21 (miR-21) functions in POI mice with UCMSCs transplantation, the autoimmune-induced POI mice model was built up, transplanted with or without UCMSCs transfect with the LV-hsa-miR-21-5p/LV-hsa-miR-21-5p-inhibition, with the transfection efficiency analyzed by QRT-PCR. Mice hormone secretion and the anti-Zona pellucida antibody (AZPAb) levels were analyzed, the ovarian morphological changes and folliculogenesis were observed, and the ovarian apoptosis cells were detected to evaluate ovarian function. The expression and localization of the PTEN/Akt/FOXO3a signal pathway-related cytokines were analyzed in mice ovaries.Additionally, the spleen levels of CD8 + CD28-T cells were tested and qualified with its significant secretory factor, interleukin 10 (IL-10). We found that with the LV-hsa-miR-21-5p-inhibition-UCMSCs transplantation, the mice ovarian function can be hardly recovered than mice with LV-NC-UCMSCs transplantation, and the PTEN/Akt/FOXO3a signal pathway was activated. The expression levels of the CD8 + CD28-T cells were decreased, with the decreased levels of the IL-10 expression. In contrast, in mice with the LV-hsa-miR-21-5p-UCMSCs transplantation, the injured ovarian function can be reversed, and the PTEN/AKT/FOXO3a signal pathway was detected activated, with the increased levels of the CD8 + CD28-T cells, and the increased serum levels of IL-10. In conclusion, miR-21 improves the ovarian function recovery of POI mice with UCMSCs transplantation, and the mechanisms may be through suppressing the PTEN/AKT/FOXO3a signal pathway and up-regulating the circulating of the CD8 + CD28-T cells.

Pharmacological Protection of Ovaries During Program Drug Chemotherapy in Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma Patients

Aim. To assess the efficacy of ovarian protection and options for fertility preservation with the use of gonadotropin-releasing hormone agonists (a-GnRH) in patients with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphomas (NHLs) during program drug chemotherapy.
 Materials & Methods. The study enrolled 247 female patients (187 with cHL and 60 with NHLs) undergoing program drug chemotherapy from 2019 to 2023. The patients were aged 13–42 years (median 24 years). Prior to chemotherapy and after it was completed, the serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol levels were measured. Besides, antral follicle count was estimated by pelvic ultrasound. To provide ovarian protection during chemotherapy, a-GnRH was administered to 67 (27 %) out of 247 patients. Ovarian reserve was assessed based on ultrasound and AMH, FSH, and estradiol levels in 2–3 months after completing the program of drug chemotherapy or after spontaneous menstrual recovery.
 Results. Menstrual cycle recovered in 194 (78.5 %) out of 247 patients, regardless of lymphoid malignancy variant. Among them, there were 79.7 % (n = 149) of cHL patients and 75 % (n = 45) of NHL patients. Accordingly, ovarian function was lost in 20.3 % (n = 38) of cHL patients and 25 % (n = 15) of NHL patients. Predictors of ovarian function recovery appeared to be age ≤ 28 years and AMH level > 2.45 ng/mL. Pharmacological protection of ovaries did not impact the probability of menstrual cycle recovery. Regardless of immunomorphological variant of lymphoid malignancy, a regular menstrual cycle was completely restored in 48 (71.6 %) out of 67 a-GnRH recipients and in 146 (81.1 %) out of 180 patients without a-GnRH treatment.
 Conclusion. Most of cHL and NHL patients of early reproductive age (≤ 30 years) have a fair chance of menstrual cycle recovery after completing the program drug chemotherapy similar to BEACOPP, EACODD(PP)-14, R-CHOP, R-Da-EPOCH and other regimens. Ovarian reserve cannot be preserved by means of a-GnRH administration during chemotherapy. High baseline FSH and low baseline AMH levels indirectly indicate evidence of impaired ovarian reserve. Patients belonging to this category are those who, if intensive combined cytostatic therapy regimens are planned, should undergo prior oocyte/embryo retrieval with subsequent cryopreservation due to the risk of premature loss of ovarian function.

Microfluidic Encapsulation of Exosomes Derived from Lipopolysaccharide-Treated Mesenchymal Stem Cells in Hyaluronic Acid Methacryloyl to Restore Ovarian Function in Mice.

Premature ovarian failure (POF) features an upward incidence nowadays, and the human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived exosomes (MSC-Exos) have shown applied values in the recovery of ovarian function. Here, a novel exosome-encapsulated microcarrier prepared by microfluidic technology for ovarian repair after chemotherapy damage is presented. The exosomes derived from lipopolysaccharide (LPS)-preconditioned hUC-MSCs are encapsulated with hyaluronic acid methacryloyl (HAMA) via microfluidic electrospray, which is named HAMA/MSC-Exos. Attributing to the biocompatibility and semipermeable property of HAMA, the encapsulated exosomes show great viability and controllable release behavior from HAMA. It is demonstrated that in situ transplantation of HAMA/MSC-Exos can rescue ovarian functions of cyclophosphamide-induced ovarian failure in mice by increasing ovarian volume, improving the number of antral follicles and restoring fertility. It is believed that the transplantation of HAMA/MSC-Exos will provide a new concept for the treatment of POF in clinical practice.

The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency.

To evaluate the effects and mechanisms of action of growth hormone (GH) in the recovery of ovarian function in ovarian insufficiency induced by cyclophosphamide (CP) in a mouse model. After inducing ovarian insufficiency by administering 400 mg/kg of CP intraperitoneally to 6-week-old ICR mice, the mice were divided into four groups (control, CP, 1 mg/kg GH, and 2 mg/kg GH) with 10 mice in each group. GH was administered a week later for 7 days. Five mice from each group were sacrificed the next day, and their ovaries were collected for histological examination. The remaining mice were superovulated for in vitro fertilization (IVF). The terminal deoxynucleotidyl transferase dUTP-nick end labeling assay was performed to detect apoptosis. Masson's trichrome staining was used to analyze the degree of fibrosis. To quantify angiogenesis, CD31 immunohistochemistry was performed. Angiogenesis-related gene expression profiles were assessed using quantitative reverse transcription polymerase chain reaction. CP induced the loss of non-growing (primordial and primary) follicles while GH significantly protected primordial follicles and increased follicular quality. The CP group showed a decrease in fertilization and blastocyst formation rates in IVF. In contrast, the GH treatment group showed dose-dependent enhanced IVF outcomes. Furthermore, GH treatment decreased apoptosis and stromal fibrosis and increased angiogenesis. Many genes involved in angiogenesis, especially Leptin (Lep), platelet endothelial cell adhesion molecule 1 (Pecam-1), and angiogenin (Ang) were up-regulated in the GH treatment groups. GH treatment may promote the recovery of ovarian function in ovarian insufficiency induced by the administration of CP via decreasing apoptosis and stromal fibrosis and upregulating Lep, Pecam-1, and Ang genes.

Correlation Between Pre-Chemotherapy AMH Level, Menstrual Status, and Prediction of Ovarian Function Recovery after FAC Chemotherapy AMH in Breast Cancer Patients

Around 52.6% of women aged <50 years in Indonesia are diagnosed with breast cancer. One of the chemotherapy regimens with a toxicity effect on reproductive function, especially ovarian follicles, is 5-fluorouracil-doxorubicin-cyclophosphamide (FAC). Anti-Mullerian Hormone (AMH) is a biomarker that can be used to assess the ovarian function. This study aimed to determine the correlation between pre-chemotherapy AMH serum level, menstrual status, and whether the AMH serum level can predict ovarian function recovery in pre-menopausal women receiving FAC chemotherapy. This was an analytical observational study with a prospective cohort design performed in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia, during 2021-2022. Data were analyzed using correlation analysis. Subjects were breast cancer patients aged ≤45 years, still of reproductive age, with no prior history of chemotherapy, and were undergoing the FAC chemotherapy. All 32 patients who met the inclusion criteria were included in this study. There was a significant difference (p 0.0001) between pre- and post-6 cycles of chemotherapy AMH levels. Post-6 cycles of chemotherapy showed lower AMH levels. There was a high correlation (p 0.0034) between pre-chemotherapy AMH level and menstrual status six months after six cycles of chemotherapy. The correlation test between post-chemotherapy AMH level and menstrual status showed a non-significant result. Thus, there is a high statistical correlation between pre-chemotherapy anti-Mullerian hormone levels in pre-menopausal women with breast cancer and the menstrual status after FAC chemotherapy which demonstrates that the AMH level could also be used to predict ovarian function recovery.

Efficacy of GnRH-α combined with Mirena in the treatment of adenomyosis and its impact on ovarian function

Objective : To discuss and analyze the clinical effects and changes of ovarian function after GnRH-α combined with Mirena treatment in patients with adenomyosis. Methods: The research subjects in this study were all adenomyosis patients (60 cases) who were admitted to our hospital from January 2020 to June 2022. They were randomly divided into control group (30 cases, receiving Mirena treatment) and observation group (30 cases, receiving GnRH-α combined with Mirena treatment). Compare the relevant indicators of the two groups. Results: After treatment, the uterine volume of the observation group and the control group were smaller than before treatment, the thickness of endometrium was thinner than before treatment, the VAS score, PBAC score, serum FSH, LH, E2 levels were all lower than before treatment, the serum AMH level, and various FSFI scores were higher than before treatment, and the trend of the former was more obvious. The comparison of the total incidence of adverse reactions between the observation group and the control group showed that the former was lower (all P < 0.05 ). Conclusion: The application of GnRH-α combined with Mirena in patients with adenomyosis can reduce the amount of menstrual bleeding, reduce the volume of the uterus, relieve pain, promote the recovery of ovarian function, improve the quality of sexual life, and have high safety. It is worthy of extensive follow-up application.

The roles of anti-Müllerian hormone in breast cancer.

Anti-Müllerian hormone (AMH) is produced and secreted by granulosa cells of growing follicles, and its main role is to inhibit the recruitment of primordial follicles, reduce the sensitivity of follicles to follicle-stimulating hormone (FSH), and regulate FSH-dependent preantral follicle growth. It has become an effective indicator of ovarian reserve in clinical practice. Research on AMH and its receptors in recent years has led to a better understanding of its role in breast cancer. AMH specifically binds to anti-Müllerian hormone receptor II (AMHRII) to activate downstream pathways and regulate gene transcription. Since AMHRII is expressed in breast cancer cells and triggers apoptosis, AMH/AMHRII may play an important role in the occurrence, treatment, and prognosis of breast cancer, which needs further research. The AMH level is a potent predictor of ovarian function after chemotherapy in premenopausal breast cancer patients older than 35 years, either for ovarian function injury or ovarian function recovery. Moreover, AMHRII has the potential to be a new marker for the molecular typing of breast cancer and a new target for breast cancer treatment, which may be a link in the downstream pathway after TP53 mutation.

An unknown cause of persistent impaired ovarian function: Long-term mitotane exposure for adrenal cortical carcinoma: Successful fertility management with in vitro maturation of oocytes and late recovery of ovarian function

An unknown cause of persistent impaired ovarian function: Long-term mitotane exposure for adrenal cortical carcinoma: Successful fertility management with in vitro maturation of oocytes and late recovery of ovarian function

Gonadotropin-Releasing Hormone Agonists during Gonadal Chemotherapy for the Effect on Pregnancy Outcome and Ovarian Function in Premenopausal Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

The aim of this study was to evaluate the effects of gonadotropin-releasing hormone agonists (GnRHas) on pregnancy outcomes, premature ovarian failure (POF), menstrual recovery, disease-free survival (DFS), and adverse events in premenopausal breast cancer patients during gonadal chemotherapy. We systematically searched PubMed, Cochrane Library, and Embase databases. The trials were eligible if they included premenopausal breast cancer patients treated with chemotherapy alone or with concurrent GnRHa and reported ovarian function recovery data. Heterogeneity for the eligible data was assessed, and a pooled risk ratio (RR) with 95% confidence interval (CI) was calculated. A meta-analysis was conducted using a fixed-effect model. Fifteen randomized controlled trials were included in this analysis. The results indicated that GnRHa combined with chemotherapy significantly increased pregnancy rates compared with chemotherapy alone (RR = 1.76; 95% CI: 1.16-2.67) and decreased rates of POF (RR = 0.42; 95% CI: 0.35-0.51). For secondary endpoints, the GnRHa group improved menstrual recovery rates (RR = 1.20; 95% CI: 1.11-1.30) and decreased the rate of amenorrhea 1-2 years after chemotherapy (RR = 0.50; 95% CI: 0.40-0.63). Furthermore, the 5-year DFS and overall survival (OS) rates were significantly improved in the GnRHa group. For premenopausal breast cancer patients receiving gonadal toxic chemotherapy, adjuvant chemotherapy with GnRHa can better protect the ovarian function of patients, reduce the rate of POF and amenorrhea, and improve the pregnancy rate, menstrual recovery rate, DFS rate, and OS rate of patients.

HUMSCs Transplantation Regulates AMPK/NR4A1 Signaling Axis to Inhibit Ovarian Fibrosis in POI Rats.

The mechanism of human Umbilical Cord Mesenchymal Stem Cells (hUMSCs) transplantation to improve ovarian function in the rats with Premature Ovarian Insufficiency (POI) is still unclear. The aim of this study is to investigate the signal axis mechanism that is involved in the ovarian function recovery of POI rats following hUMSCs transplantation. The rat model with POI was established by intraperitoneal injection of cisplatin. The hUMSCs were transplanted by caudal vein injection into POI rats.Hematoxylin-eosin (H&E) staining was performed to examine the morphology of rat ovarian tissue.Masson staining, Sirus red staining and immunofluorescence were used to observe the fibrosis extent of ovarian tissue. The levels of serum sex hormones and the expression of fibrosis related markers in ovarian tissueswere measured by enzyme-linked immunosorbent assay (ELISA).The expression of NR4A1, Phospho-NR4A1 and AMP-activated protein kinase (AMPK) signaling in rat ovarian tissues was measured by immunohistochemistry and immunofluorescence. The role of AMPK/NR4A1 signaling axis in the regulation of ovarian function recovery in POI rats following hUMSCs transplantation was further investigated by adenovirus and siRNA intervention in isolated stromal cells. The results showed that the hUMSCs transplantation significantly inhibited ovarian tissue fibrosis and restored the ovarian function in POI rats.The level of NR4A1 and AMPK expression in ovarian tissue of POI rats after hUMSCs transplantation was significantly increased compared with the control group.In the cultured ovarian stromal cells, the similar results were obtained on the expression of NR4A1 and its regulation on fibrosis related molecular markers in Cisplatin (CDDP) damaged stromal cells following hUMSCs supernatant treatment. Both hUMSCs supernatant treatment and the addition of AMPK inhibitors increased NR4A1 expression in stromal cells. And after NR4A1 molecular intervention, fibrosis-related indicators in stromal cells changed. The data suggests that the AMPK/NR4A1 signaling axis is involved in the ovarian function changes in POI rats following hUMSCs transplantation. The data from this study indicate that the inhibition of tissue fibrosis and recovery of ovarian function is regulated by AMPK/NR4A1 signaling axis in POI rats following hUMSCs transplantation.

Multi-biofunctional graphene oxide-enhanced poly-L-lactic acid composite nanofiber scaffolds for ovarian function recovery of transplanted-tissue

In this study, we successfully constructed the new graphene oxide/poly-L-lactic acid (GO/PLLA) nanofiber scaffolds with a hydrophilic surface and porous network structure that were highly favorable for cell infiltration. When employed these new nanofiber scaffolds for a wide range of tissue engineering applications, it was expected to promote graft tissue survival and angiogenesis. The new GO/PLLA nanofiber scaffold with an appropriate concentration of 1.0 wt% was applied for the restoration of ovarian function and reserve in mice with primary ovarian insufficiency (POI). After co-transplanting the normal ovarian cortex loaded on these new nanomaterials into the in situ ovarian tissue of POI mice, the fusion of transplanted ovarian cortex with damaged ovarian tissue was improved, as well as the ovarian function and the follicle numbers. Moreover, angiogenesis was observed clearly and proved to exist in the transplanted tissue and nanomaterials, with the most conspicuous effect after co-transplantation with 1.0 wt% GO/PLLA nanofiber scaffold. In addition, nitric oxide (NO) production by phosphorylated endothelial nitric oxide synthase (p-eNOS) in vivo was proven to be involved in the effect of GO and PLLA on the improved survival rate of the transplanted ovarian cortex. This study provides a new method for the fertility preservation of ovarian tissue cryopreservation and transplantation, as well as a new strategy for the transplantation of other organs.

The probability and possible influence factors of intermittent ovarian function recovery in patients with premature ovarian insufficiency

Research questionWhat are the probability and underlying influence factors of intermittent ovarian function recovery in patients with idiopathic premature ovarian insufficiency (POI)? DesignThis was a retrospective cohort study conducted in tertiary hospitals recruiting 162 patients diagnosed with POI based on European Society of Human Reproduction and Embryology criteria from June 2015 to March 2022. The incidence of intermittent ovarian function recovery was evaluated, and the possible influence factors were investigated by univariate and multivariate analysis. ResultsAmong 162 POI patients, 48 (29.63%) presented intermittent ovarian function recovery, and 11 (6.79%) were natural pregnancies; 114 (70.37%) patients failed to show ovarian function recovery. No association was found between initial clinical features and intermittent ovarian function recovery. In contrast, the variables of FSH, LH, oestradiol, anti-Müllerian hormone (AMH), ovarian volume, passive smoking and weekly exercise time after diagnosis were correlated with intermittent ovarian function recovery in patients with POI and further analysis indicated that FSH concentration at diagnosis (odds ratio [OR] 0.964, 95% confidence interval [CI] 0.934–0.995, P = 0.023), passive smoking (OR 0.369, 95% CI 0.141–0.963, P = 0.042) and weekly exercise time after diagnosis (OR 5.592, 95% CI 1.83–17.088, P = 0.003) were influence factors of intermittent ovarian function recovery in POI patients. ConclusionsThe incidence of intermittent ovarian function recovery in patients with idiopathic POI was 29.63%, and the natural pregnancy rate was 6.79%. Lower FSH concentration at diagnosis, no passive smoking and a weekly exercise time ≥1.5 h after the diagnosis may be beneficial for intermittent ovarian function recovery in POI patients.