Optimising health after early menopause.

The typical age at menopause is 50-51 years in high-income countries. However, early menopause is common, with around 8% of women in high-income countries and 12% of women globally experiencing menopause between the ages of 40 years and 44 years. Menopause before age 40 years (premature ovarian insufficiency) affects an additional 2-4% of women. Both early menopause and premature ovarian insufficiency can herald an increased risk of chronic disease, including osteoporosis and cardiovascular disease. People who enter menopause at younger ages might also experience distress and feel less supported than those who reach menopause at the average age. Clinical practice guidelines are available for the diagnosis and management of premature ovarian insufficiency, but there is a gap in clinical guidance for early menopause. We argue that instead of distinct age thresholds being applied, early menopause should be seen on a spectrum between premature ovarian insufficiency and menopause at the average age. This Series paper presents evidence for the short-term and long-term consequences of early menopause. We offer a practical framework for clinicians to guide diagnosis and management of early menopause, which considers the nature and severity of symptoms, age and medical history, and the individual's wishes and priorities to optimise their quality of life and short-term and long-term health. We conclude with recommendations for future research to address key gaps in the current evidence.

Ovarian Suppression: Early Menopause, Late Effects.

PURPOSE OF REVIEW: Pre-menopausal women diagnosed with hormone receptor (HR) breast cancer are candidates for prolonged hypoestrogenism to improve cancer outcomes. However, the disease benefit eclipses the toxicities associated with ovarian function suppression (OFS), which are often under-reported. RECENT FINDINGS: Increased risk of mortality from cardiovascular disease, bone disorders, and metabolic disorders is well reported in women with no history of cancer, after surgical oophorectomy or premature ovarian failure. Vasomotor symptoms, urogenital atrophy, weight gain, sexual dysfunction, cognitive decline, and sleep disturbances contribute to the increased non-compliance associated with OFS, especially in younger women. Balancing the toxicities of prolonged OFS with its benefits should be critically analyzed by providers when making recommendations for their patients. Supportive care to manage multi-system toxicities and to counteract the long-term impact on all-cause mortality should be emphasized by every cancer program. Future studies with OFS should incorporate patient outcomes and strategies for symptom management in addition to focusing on improving disease outcomes.

Psychological stressors involved in the pathogenesis of premature ovarian insufficiency and potential intervention measures.

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.

Development and validation of age-specific risk prediction models for primary ovarian insufficiency in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study and St Jude Lifetime Cohort.

BACKGROUND: Female survivors of childhood cancer are at risk for primary ovarian insufficiency (POI), defined as the cessation of gonadal function before the age of 40 years. We aimed to develop and validate models to predict age-specific POI risk among long-term survivors of childhood cancer. METHODS: To develop models to predict age-specific POI risk for the ages of 21-40 years, we used data from the Childhood Cancer Survivor Study (CCSS). Female survivors aged 18 years or older at their latest follow-up, with self-reported menstrual history information and free of subsequent malignant neoplasms within 5 years of diagnosis, were included. We evaluated models that used algorithms based on statistical or machine learning to consider all predictors, including cancer treatments. Cross-validated prediction performance metrics (eg, area under the receiver operating characteristic curve [AUROC]) were compared to select the best-performing models. For external validation of the models, we used data from 5-year survivors in the St Jude Lifetime Cohort (SJLIFE) with ovarian status clinically ascertained using hormone measurements (menopause defined by follicle stimulating hormone >30 mIU/mL and oestradiol <17 pg/mL) and medical chart or questionnaire review. We also evaluated an SJLIFE-based polygenic risk score for POI among 1985 CCSS survivors with genotype data available. FINDINGS: 7891 female CCSS survivors (922 with POI) were included in the development of the POI risk prediction model, and 1349 female SJLIFE survivors (101 with POI) were included in the validation study. Median follow-up from cancer diagnosis was 23·7 years (IQR 18·3-30·0) in CCSS and 15·1 years (10·4-22·9) in SJLIFE. Between the ages of 21 and 40 years, POI prevalence increased from 7·9% (95% CI 7·3-8·5) to 18·6% (17·3-20·0) in CCSS and 7·3% (5·8-8·9) to 14·9% (11·6-19·1) in SJLIFE. Age-specific logistic regression models considering ovarian radiation dosimetry or prescribed pelvic and abdominal radiation dose, along with individual chemotherapy predictors, performed well in CCSS. In the SJLIFE validation, the prescribed radiation dose model performed well (AUROC 0·88-0·95), as did a simpler model that considered any exposures to pelvic or abdominal radiotherapy or alkylators (0·82-0·90). Addition of the polygenic risk predictor significantly improved the average positive predictive value (from 0·76 [95% CI 0·63-0·89] to 0·87 [0·80-0·94]; p=0·029) among CCSS survivors treated with ovarian radiation and chemotherapy. INTERPRETATION: POI risk prediction models using treatment information showed robust prediction performance in adult survivors of childhood cancer. FUNDING: Canadian Institutes of Health Research, US National Cancer Institute.

Premature ovarian insufficiency and chance of pregnancy after childhood cancer: A population-based study (the Fex-Can study).

Endocrine complications are a common late effect after childhood cancer. Our study assessed the prevalence and predictors of premature ovarian insufficiency (POI) and prospects of pregnancy in young female survivors. This nationwide study combined registry and survey data for female childhood cancer survivors aged 19 to 40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Of 1989 approached young women, 1333 (67%) participated by completing a survey. Median age at diagnosis 1981 to 2017 was 6 (range 0-17) and at study 28 (19-40) years. There were two indicators of POI, induced puberty reported in 5.3% and estrogen replacement therapy (ERT) in 9.3% at assessment. In separate logistic regression analyses (P < .001), induced puberty and ERT were significantly predicted by hematopoietic stem cell transplantation (HSCT), abdominal irradiation, central nervous system irradiation and chemotherapy. ERT was also associated with older age at diagnosis. Of the 626 women (48% of responders) who had tried to become pregnant, 25% had undergone fertility investigations and 72% reported having a biological child. Treatment with HSCT was associated with 5.4 times the odds of needing fertility investigations (P < .001). Having a biological child was associated with non-HSCT treatment, but also with ever having had a partner and older age at the time of study (all P < .001). In conclusion, the majority of those female childhood cancer survivors who had tried to conceive were able to successfully give birth. However, a small identifiable group of female survivors are at risk of subfertility and early menopause.

Gonadal function in pediatric Fanconi anemia patients treated with hematopoietic stem cell transplant.

Gonadal dysfunction and reduced fertility are clinical manifestations well described in patients with Fanconi anemia (FA) and following hematopoietic stem cell transplantation (HSCT). It is difficult to differentiate gonadal dysfunction from the primary disease itself or from HSCT procedures. Therefore, it is important to manage expectations about gonadal failure and infertility for all patients with FA, regardless of the HSCT status. We performed a retrospective analysis of 98 pediatric patients with FA who were transplanted between July 1990 and June 2020 to evaluate the incidence of gonadal dysfunction in female and male patients with FA. New-onset premature ovarian insufficiency (POI) was diagnosed in a total of 30 (52.6%) patients. Follicle-stimulating hormone and luteinizing hormone levels were increased in patients diagnosed with POI. Anti- Mullerian hormone levels declined in POI patients after HSCT (r2=0.21; P=0.001). Twenty (48.8%) male patients were diagnosed with testicular failure. Follicle-stimulating hormone levels increased after HSCT even in patients without testicular failure (r2=0.17; P=0.005). Inhibin B levels decreased over time after HSCT in patients with testicular failure (r2=0.14; P=0.001). These data indicate brisk decline in already impaired gonadal function in transplanted children with FA.

Evidence for a fragile X messenger ribonucleoprotein 1 (FMR1) mRNA gain-of-function toxicity mechanism contributing to the pathogenesis of fragile X-associated premature ovarian insufficiency.

Fragile X-associated premature ovarian insufficiency (FXPOI) is among a family of disorders caused by expansion of a CGG trinucleotide repeat sequence located in the 5' untranslated region (UTR) of the fragile X messenger ribonucleoprotein 1 (FMR1) gene on the X chromosome. Women with FXPOI have a depleted ovarian follicle population, resulting in amenorrhea, hypoestrogenism, and loss of fertility before the age of 40. FXPOI is caused by expansions of the CGG sequence to lengths between 55 and 200 repeats, known as a FMRI premutation, however the mechanism by which the premutation drives disease pathogenesis remains unclear. Two main hypotheses exist, which describe an mRNA toxic gain-of-function mechanism or a protein-based mechanism, where repeat-associated non-AUG (RAN) translation results in the production of an abnormal protein, called FMRpolyG. Here, we have developed an in vitro granulosa cell model of the FMR1 premutation by ectopically expressing CGG-repeat RNA and FMRpolyG protein. We show that expanded CGG-repeat RNA accumulated in intranuclear RNA structures, and these aggregates were able to cause significant granulosa cell death independent of FMRpolyG expression. Using an innovative RNA pulldown, mass spectrometry-based approach we have identified proteins that are specifically sequestered by CGG RNA aggregates in granulosa cells in vitro, and thus may be deregulated as consequence of this interaction. Furthermore, we have demonstrated reduced expression of three proteins identified via our RNA pulldown (FUS, PA2G4 and TRA2ß) in ovarian follicles in a FMR1 premutation mouse model. Collectively, these data provide evidence for the contribution of an mRNA gain-of-function mechanism to FXPOI disease biology.

Evaluation of ovarian reserve in young females with non-iatrogenic ovarian insufficiency to establish criteria for ovarian tissue cryopreservation.

RESEARCH QUESTION: Can ovarian reserve parameters predict the outcome of ovarian tissue cryopreservation (OTCP) in patients ≤18 years with non-iatrogenic premature ovarian insufficiency (POI)? DESIGN: Retrospective cohort analysis carried out in a single tertiary hospital between August 2010 and January 2020. Thirty-seven patients ≤18 years with non-iatrogenic POI (27 with Turner syndrome, six with POI of unknown aetiology, three with galactosemia and one with blepharophimosis, ptosis, epicanthus inversus syndrome) were included. Three parameters were used to evaluate ovarian reserve: anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and transabdominal antral follicle count. Fertility preservation (most commonly OTCP) was offered if ovarian reserve was diminished and one or more parameters was positive. Follicles were counted in ovarian samples obtained at the time of OTCP. RESULTS: Ovarian reserve was diminished in 34 patients and 19 of them had one or more positive parameter. Fourteen (11 aged ≥12 years and 3 aged <12) underwent OTCP, one (14 years old) underwent ovarian stimulation and oocyte cryopreservation and four declined fertility preservation. Follicles were detected in 11 of 14 patients who underwent OTCP with one or more positive parameters (79%), and in all those (100%) who had two or three positive parameters. The median number of follicles was 27 (range 5-64) and 48 (range 21-75) in patients ≥12 years and those <12 years, respectively. CONCLUSION: This study shows that if OTCP is performed in patients with one or more positive parameters of ovarian activity, a 79% positive predictive value is achieved for the detection of follicles. The incorporation of this criterion for OTCP will minimize the risk of harvesting ovarian tissue with a low number of follicles.

The global prevalence of premature ovarian insufficiency: a systematic review and meta-analysis.

OBJECTIVE: The objective of this review was to answer the global prevalence of premature ovarian insufficiency (POI), and explore the associated factors including etiopathology and regions with POI. METHODS: The search was conducted on reports from a total of eight databases that comprised Chinese National Knowledge Infrastructure (CNKI), Wanfang, China BioMedical Literature Database (CBM), PubMed, the Cochrane Library, Embase, Web of Science and Ovid MEDLINE® between 1946 and 2021. To analyze the source of heterogeneity, we performed subgroup analysis based on different etiologies and regions. Meta-analysis was carried out by Stata14.0 software. RESULTS: The results showed that the global overall prevalence of POI among women was 3.5%. By subgroup analysis, the prevalence of POI among women with iatrogenic etiology was 11.2%, followed by autoimmunity (10.5%); the prevalence of POI by region was 11.3% at the highest in North America followed by South America (5.4%); and the prevalence of POI was 5.3% in a developing country, higher than 3.1% in a developed country. The trend of prevalence of POI over the past 20 years was on the rise (although p > 0.05). CONCLUSION: We recommend that health and medical institutions strengthen public health awareness, achieve health-education goals related to POI and increase women's awareness of and attention to POI.

COVID-19-related premature ovarian insufficiency: case report and literature review.

OBJECTIVE: The aim of this study is to present the case report of a 36-year-old woman developing premature ovarian insufficiency (POI) after COVID-19 and review the literature referring to the possible impact of SARS-CoV-2 infection on female reproduction. METHODS: A 36-year-old nulligravida with normal menstrual cycles, non-smoker, with a normal body mass index and no pelvic surgery or oncological treatment in her medical history presented to the Infertility Center of the Institute of Mother and Child in Warsaw after a year of unsuccessful attempts to get pregnant. During diagnostic process she was affected by COVID-19 with a mild manifestation and thereafter she presented amenorrhea with intense hot flushes. Further diagnostic confirmed the diagnosis of POI. RESULTS: There is a strong molecular basis for a possible effect of SARS-CoV-2 infection on the female reproductive system; however, the results of available research are conflicting. All of these aspects are discussed in detail. CONCLUSIONS: SARS-CoV-2 infection may cause serious complications that cast a long shadow on a patient's future life and health. Further research is needed to assess the real impact of SARS-CoV-2 infection on female reproductive health, as well as potential preventive and therapeutic strategies for women affected with COVID-19.

Live birth in woman with premature ovarian insufficiency and 46, XY karyotype after chemotherapy and bone marrow transplant: a case report.

BACKGROUND: Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian function before the age of 40 years, characterized by elevated serum gonadotropin levels and decreased estrogen levels with menstrual disturbance. POI can be natural or iatrogenic such as after chemotherapy, radiotherapy and surgery. CASE PRESENTATION: In this study, we describe a successful live birth in a 31-year-old woman with POI and 46, XY Karyotype after being treated with chemotherapy and bone marrow transplant (BMT) for acute non-lymphocytic leukemia when she was 17 years old. With amenorrhea or oligomenorrhea for 11 years, her serum level of FSH was up to 35.0 IU/L and 53.0 IU/L taken 4 weeks apart, which can be diagnosed as POI. After controlled ovarian stimulation treatment for three cycles with different protocols and frozen-thawed embryo transfer (FET), she finally got a successful pregnancy and had a live birth later. CONCLUSIONS: This case report serves as a reminder that karyotype of peripheral blood may mislead the diagnosis as disorders of sex development (DSD). It also demonstrates that it is possible for a woman with chemotherapy and bone marrow transplant induced POI can have successful pregnancy and live birth with appropriate therapy. Furthermore, as age may plays a predominant role in fertility rather than residual ovarian reserve, active treatment may be concerned for women with POI at younger age.

Expert consensus on fertility preservation in hematopoietic stem cell transplantation in girls in China.

Aims: Preconditioning before hematopoietic stem cell transplantation (HSCT) seriously damages the ovarian function and causes female infertility. This consensus focuses on the fertility preservation(FP) for girls needing HSCT, aim to make doctors in different disciplines aware of the importance, necessity and technique of ovarian protection.Materials and methods: Summarizing relevant literature and organizing multidisciplinary experts, including obstetrics and gynecology, reproductive medicine, oncology, pediatrics and hematology for full discussion.Results: Individuals exposed to HSCT in childhood are at higher risk of loss of fertility. Considering the high risk of premature ovarian insufficiency (POI) after conditioning and negative impact of POI on fertility, physical and mental health, it is absolutely necessary to protect fertility before HSCT conditioning. Ovarian tissue cryopreservation is the main fertility preservation option for these population.Conclusions: Fertility preservation before HSCT conditioning is crucial. Ovarian tissue cryopreservation is often the only option for these population.

Premature ovarian insufficiency in female adolescent and young adult survivors of non-gynecological cancers: a population-based cohort study.

BACKGROUND: The risk of premature ovarian insufficiency (POI) is increased in adolescent and young adult (AYA) cancer survivors, with the prevalence depending on cancer diagnosis, treatment, and patient factors. Prior studies are limited by sample size and type of cancer included. The objective of this study was to assess the risk of POI in female AYA survivors of non-gynecologic cancers, using a population-based approach. METHODS: This population-based retrospective cohort study comprises 21,666 females, 15-39 years old, diagnosed with a single non-gynecologic cancer in Ontario, Canada from 1995 to 2015. Through health administrative data linkage, participants were followed until their 40th birthday, December 31, 2018, bilateral oophorectomy, loss of health insurance eligibility or death. Each cancer survivor was matched to 5 females who were not diagnosed with cancer (unexposed, n = 108,330). Women with bilateral oophorectomy or a prior menopause diagnosis were excluded. POI was identified through use of the ICD-9 code for menopause (ICD9-627). Modified Poisson regression models were used to calculate the adjusted relative risk (aRR) of POI for AYA cancer survivors compared to unexposed individuals, adjusted for income, parity, age, and immigration status. RESULTS: The occurrence of POI was higher in survivors of AYA cancer versus unexposed patients (5.4% vs. 2.2%). Survivors of AYA cancer had an increased risk of POI relative to unexposed patients (aRR 2.49; 95% CI 2.32-2.67). Risk varied by type of cancer: breast (4.32; 3.84-4.86), non-Hodgkin's lymphoma (3.77; 2.88-4.94), Hodgkin's lymphoma (2.37; 1.91-2.96), leukemia (14.64; 10.50-20.42), thyroid (1.26; 1.09-1.46) and melanoma (1.04; 0.82-1.32). Risk varied by age at time of cancer diagnosis, with a higher risk among females diagnosed at age 30-39 years (3.07; 2.80-3.35) than aged 15-29 years (1.75; 1.55-1.98). CONCLUSIONS: AYA survivors of non-gynecologic cancers are at an increased risk of POI, particularly survivors of lymphomas, leukemia, breast, and thyroid cancer. The risk of POI is increased for those diagnosed with cancer at an older age. These results should inform reproductive counseling of female AYAs diagnosed with cancer.

Premature ovarian insufficiency is the onset of premature menopause in individuals less than 40-years-old. Previous research has shown that there is a higher risk of premature ovarian insufficiency in adolescent and young adult cancer survivors, due to the toxicity of cancer treatments on reproductive organs. Prior research was limited in its applicability by having small sample sizes, only including childhood cancer, excluding young adults, and studying fewer types of cancer. This study was conducted using a large population-based approach, on all females aged 15­39 years old with cancer in Ontario, Canada from 1995 to 2015. We found that there was nearly a 2.5 times greater risk of premature ovarian insufficiency in cancer survivors compared patients without cancer. Compared to patients without cancer, this risk was highest for survivors of leukemia (14 times higher risk), followed by breast cancer (4 times higher risk), lymphomas (2­4 times higher risk), and thyroid cancer (1.2 times higher risk). There is no increased risk in melanoma survivors. The risk was higher in individuals diagnosed with cancer at a later age (30­39 years), with a risk 3 times higher than the population without cancer, while a younger age of diagnosis (15­29 years) carries a risk only 1.75 times higher than the population without cancer. These results should help improve healthcare provider and patient understanding of the risk of premature ovarian insuficiency in young cancer survivors, and guide counseling at the time of cancer diagnosis and during survivorship on future reproductive function.

Impact of Indication for Oocyte and Embryo Reception on Reproductive and Obstetric Outcomes.

OBJECTIVES: This study aimed to assess if the indication for oocyte reception (OR) or embryo reception (ER) impacts the reproductive and obstetric outcomes by evaluating our experience at a tertiary fertility centre and by performing a literature review on this subject. Several previous studies have reported that, in contrast to other types of fertility treatment, the indication for OR/ER seems to have little impact on the outcomes. However, the compared indication groups vary considerably between these studies, and some data indicates worse outcomes in patients who developed premature ovarian insufficiency (POI) due to Turner syndrome or treatment with chemotherapy/radiotherapy. DESIGN: A retrospective analysis of all cases of OR/ER at a tertiary fertility centre from 2001 until 2020 was conducted. We analysed 584 cycles from 194 individual patients. A literature review on the impact of indication on reproductive or obstetric outcomes of OR/ER was performed using the following databases: PubMed/MEDLINE, Embase, and the Cochrane Library. A total of 27 studies were included and analysed. PARTICIPANTS, SETTING, METHODS: For the retrospective analysis, patients were divided into three major indication groups: failure of autologous assisted reproductive technology, POI, and genetic disease carrier. To assess reproductive outcomes, we determined pregnancy rate, implantation rate, miscarriage rate, and live birth rate. For comparing obstetric outcomes, we reviewed the term of birth, mode of delivery, and birthweight. Outcomes were compared using Fisher's exact test, χ2 test, and one-way ANOVA utilizing the GraphPad tool. RESULTS: There were no significant differences in reproductive and obstetric outcomes between the three major indication groups in our population, in line with the findings reported by existing literature. Data on impaired reproductive outcomes in patients with POI after chemotherapy/radiotherapy are conflicting. Obstetrically, these patients are at higher risk of preterm birth and possibly also low birthweight, especially after abdomino-pelvic or total body irradiation. For patients with POI due to Turner syndrome, most data suggest similar pregnancy rates but a higher rate of pregnancy loss, and obstetrically an increased risk of hypertensive disorders and caesarean section. LIMITATIONS: The small number of patients in the retrospective analysis resulted in low statistical power when evaluating differences between smaller subgroups. There were some missing data on the occurrence of complications during pregnancy. Our analysis covers a period of 20 years, during which several technological innovations have also been made. CONCLUSIONS: Our study shows that the important heterogeneity in couples treated with OR/ER does not significantly impact their reproductive or obstetric outcomes, except for POI due to Turner syndrome or treatment with chemotherapy/radiotherapy, where there seems to be an important uterine/endometrial component that cannot be entirely overcome by providing a healthy oocyte.

Clinical pregnancy in Turner syndrome following re-implantation of cryopreserved ovarian cortex.

Turner syndrome (TS) leads to a characteristic phenotype, including premature ovarian insufficiency and infertility. Ovarian tissue cryopreservation (OTC) is becoming an established fertility preservation strategy for both pre- and post-pubertal females and may offer the chance of having a biological family to selected patients with TS. To date, women with TS have had ovarian tissue cryopreserved but there are few reports of autologous re-implantation and none of pregnancy. We herein report, to our knowledge, the first clinical pregnancy in a patient with TS, conceived naturally following re-implantation of cryopreserved ovarian tissue which had been removed soon after spontaneous puberty. This provides proof of concept for OTC as a means of fertility preservation in TS.

Analysis of Mexican young women with primary ovarian insufficiency induced by gynaecological and haematological cancer management.

This was a retrospective study that included 114 women younger than 40 years with induced primary ovarian insufficiency. Patients who presented vasomotor symptoms had a higher proportion (26 [63.41%] versus 58 [79.45%], OR 2.23, 95% CI 0.95-5.23, p = .065) to initiate hormone replacement therapy. Vasomotor symptoms were present in patients with ovarian cancer (OR 0.27, 95% CI 0.09-0.8, p = .18), haematologic cancer (OR 0.11, 95% CI 0.2-0.65, p = .014), radiotherapy (OR 2.62, 95% CI 1.04-6.54, p = .039) and chemotherapy with radiotherapy (OR 2.72, 95% CI 1.01-7.35, p = .049). Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy, and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.Impact StatementWhat is already known on this subject? In young women with cancer, induced primary ovarian insufficiency can result as an ovarian surgery or as an adverse effect of chemotherapy or radiotherapy. Regardless of aetiology, patients are going to manifest early climacteric symptoms with an increased risk for cardiovascular disease, metabolic syndrome and osteoporosis.What do the results of this study add? Patients who presented vasomotor symptoms had initially a higher proportion of hormone replacement therapy. Patients that were treated exclusively with radiotherapy or with chemotherapy and concomitant radiotherapy have a significantly increased risk to manifest vasomotor symptoms.What are the implications of these findings for clinical practice and/or future research? Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.

[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Premature ovarian failure in juvenile systemic lupus erythematosus patient: A rare presentation.

A 16-year-old girl was admitted to the hospital for the absence of a menstrual bleeding over 10 mounts. She has had regular menstrual periods since she was 13 years old and no history of systemic disease. Laboratory tests showed low estrogen (<11.8 ng/L, range 16-238 ng/L), elevated FSH (follicle stimulating hormone) (138.3 U/L), low AMH (anti-Mullerian hormone) (<0.01 µg/L), normal prolactin (7 µg/L), and thyroid hormone levels (TSH: 1.5 mU/L). The ovaries were prepubertal in size and diagnosed with primer ovarian failure. ANA titers, antiphospholipid antibody, and direct coombs were positive. Microscopic hematuria and nephritic proteinuria (34 mg/m2/hour) were also detected and renal biopsy was revealed stage 3-5 lupus nephritis. Premature ovarian failure is an extremely rare disease in childhood. When POF is detected in the adolescent, it is important to investigate the etiology. In this way, it may be possible to diagnose diseases with high morbidity and mortality that may cause POF.

Capsaicin prevents radiotherapy-induced premature ovarian failure in rats.

Ionising radiation exposure of 5-10gray (Gy) to the pelvic area induces premature ovarian failure (POF). Twenty-four young adult Wistar albino female rats were were treated with subcutaneous capsaicin 0.5mg/kg per day or placebo for 10days then exposed to whole body irradiation. Rats were randomly divided into four groups: (1) control; (2) capsaicin; (3) radiation only (IR): rats were injected with placebo before exposure to a single dose of 8.3-Gy whole body irradiation; (4) radiation-capsaicin (IR+CAP): rats were injected with capsaicin prior to whole body irradiation. Radiation triggered oxidative stress, increased ovarian inflammation, increased follicular apoptosis and diminished ovarian follicle pool. Capsaicin significantly ameliorated oxidative stress by decreasing serum total oxidant status, oxidative stress index, disulphide, and malondialdehyde levels (P ≤0.001); ovarian inflammatory status by decreasing expressions of TNF-α, IL-1ß, PARP-1 (P =0.002); apoptosis by decreasing expressions of active caspase-3 and p53 (P =0.015, P =0.002); and follicle counts by increasing primordial follicles and decreasing apoptotic follicles (P ≤0.001) in rats when administered before radiation exposure. The beneficial effects of capsaicin are demonstrated for the first time on ionising radiation exposed rat ovaries. Capsaicin pre-treatment before radiotherapy restores the primordial follicle pool, inhibits atresia of ovarian follicles and may be an acceptable therapeutic modality to prevent radiation-induced POF.

Endometriosis in women undergoing ovarian tissue transplantation due to premature menopause after gonadotoxic treatment or spontaneous premature ovarian failure.

INTRODUCTION: Cryopreservation of ovarian tissue with subsequent transplantation is an efficient option for restoring fertility in women at risk of premature ovarian failure. The association between infertility and endometriosis is well recognized. Although endometriosis usually ends with the onset of natural or iatrogen menopause due to declining estrogen levels, endometriosis can in rare cases occur after menopause. This study aims to investigate women with premature menopause who were diagnosed with endometriosis during laparoscopy for ovarian tissue transplantation, and to address the questions of how endometriotic lesions after cytotoxic treatment and premature menopause might be explained, whether endometriosis affects pregnancy rates, and whether there is an association between endometriosis and the original cancer. MATERIAL AND METHODS: Seventeen patients who had undergone ovarian tissue transplantation to restore their fertility and who were diagnosed with endometriosis during transplantation were included in this retrospective study. The endometriosis foci were completely removed and ovarian tissue was transplanted into the pelvic peritoneum. Preexisting conditions, use of hormonal preparations, endometriosis stage pain assessment, as well as pregnancy and live birth rate were evaluated. RESULTS: The mean age of the patients was 29.5 ± 6.3 years (range 14-39) at the time of ovarian tissue harvest and 34.6 ± 4.3 years (range 28-40) at transplantation. Prior to transplantation, four patients had taken hormone replacement therapy, four women oral contraceptives and two patients' tamoxifen. Twelve women had stage I endometriosis and five stage II endometrioses according to the rASRM classification. Four patients reported dysmenorrhea. None of the women complained of general pelvic pain or dyspareunia. The pregnancy rate in the study population was 41.2%, with a live birth rate of 35.3%. The pregnancies occurred in three cases after spontaneous conception, in four women after a natural cycle IVF/ICSI. CONCLUSIONS: This study highlights the under-researched association between endometriosis in women entering premature or early menopause either after gonadotoxic treatment or due to primary ovarian insufficiency. As more and more patients seek to have their cryopreserved ovarian tissue transplanted to fulfill their desire to have children, specialists will inevitably encounter women with this condition.