Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.

Evaluating the safety and efficacy of cryopreserved ovarian tissue transplantation in leukemia patients with different bone marrow remission status using xenotransplantation.

Background: Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC). Objective: To explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation. Method: Cryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient's MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice. Results: Follicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (p<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (p<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (p<0.001) and emaciation (p<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse. Conclusion: For leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

Chinese Expert Consensus on ovarian function and fertility preservation of cervical cancer in pregnancy (2023).

Cervical cancer in pregnancy (CCIP) refers to cervical cancer diagnosed during pregnancy, the most common gynecological malignant tumor. Because of the special physiological changes of CCIP, although preserving ovarian function and fertility is very important, the methods are very limited. There is no guideline or consensus on the preservation methods of ovarian function and fertility in this special period. Therefore, the Committee of Fertility Protection and Preservation of China Association for the Promotion of Health Science and Technology, combined with the Chinese Society of Gynecological Endocrinology affiliated to the International Society of Gynecological Endocrinology, Society Endocrinology Branch of Beijing Institute of Obstetrics & Gynecology, combined with Society on Fertility Preservation affiliated with the Chinese Preventive Medicine Association, organized relevant experts from different disciplines to formulate this consensus, in order to guide ovarian function and fertility preservation of CCIP patients.

Optimizing menopausal hormone therapy:for treatment and prevention,menstrual regulation,and reduction of possible risks / 《全球健康杂志（英文）》

Menopausal hormone therapy(MHT)is used to treat menopausal complaints including the genitourinary syn-drome of menopause,to prevent osteoporosis,and to treat bleeding problems.Since these can be the indications also in young women,especially with POI(premature ovarian insufficiency)or with surgical menopause(bilateral oophorectomy),also the old term"Hormone Replacement Therapy(HRT)"is still used.The effective component is the estrogen component without relevant difference in the efficacy of the various MHT-preparations.Addi-tional preventive benefits are reduction of cardiovascular disease(including prevention of diabetes mellitus and metabolic syndrome),reduction of colon cancer,and perhaps also Alzheimer's disease,if started within a"win-dow of opportunity",i.e.in perimenopause or within 6-10 years after menopause.Primary indication for progestogen addition is to avoid the development of estrogen-dependent endome-trial cancer,i.e.addition not recommended in hysterectomized women.Two main schedules,sequential-or continuous-combined estrogen/progestogen regimens,are used for treatment of bleeding problems.For this and for optimizing menstrual regulation detailed recommendations are given including proposed dosages for the available different progestogens if added to oral or transdermal estradiol in different estrogen dosages.The WHI-study demonstrated the main risks using MHT within a"worst-case scenario",i.e.start of MHT in old women with high risk for breast cancer and cardiovascular diseases,whereby only"conjugated equine estro-gens"and"medroxprogesterone acetate"have been tested.One main result was that the progestogen component is decisive for the risk of breast cancer,which according to own experimental research and observational studies may be reduced using the physiological progesterone or its isomer dydrogesterone.In addition we propose to push forward research for screening patients with increased breast cancer risk like we have done in the past decade demonstrating that certain membrane-bound receptors in breast cancer tissue or blood can increase this risk.To reduce the risk of venous thromboembolism and stroke,transdermal estradiol(gels,patches,)should be used,in free combination with progesterone or dydrogesterone as"golden standard"in patients with increased risk.To increase the compliance in our patients without special risks we mostly use the available fix-combinations of estradiol/dydrogesterone getting strong efficacy,good menstrual regulation or amenorrhea,respectively,but also other combinations may be indicated to take advantage of for example androgenic or antiandrogenic pro-gestogens.

Management strategy of infertility in polycystic ovary syndrome / 《全球健康杂志（英文）》

Polycystic ovary syndrome(PCOS)is the most common endocrine and metabolic disease in women of reproduc-tive age.PCOS is characterized by ovulatory disruption,which can lead to infertility.Patients with PCOS are also more likely to have poor pregnancy outcomes.For obese women,lifestyle interventions are recommended first,which have general health benefits.For women who have difficulty changing their lifestyle,drugs for the treatment of obesity or bariatric surgery could be considered.Clomiphene citrate is the first-line medication after weight loss that has been utilized in the past.Letrozole is supplanting clomiphene as the best option for ovulation induction for now,particularly in patients with PCOS.Metformin can improve ovulation and pregnancy rates;however,it has minimal effects in terms of raising live birth rates.Second-line therapies include gonadotropins and laparoscopic ovary drilling.In vitro fertilization can be utilized as a third-line treatment for patients with PCOS who have failed ovulation induction therapy or have other infertility factors.In summary,to achieve fer-tility,patients with PCOS require standardized individualized therapy.

Advanced therapy of overweight or obese polycystic ovary syndrome:a prospective study / 《全球健康杂志（英文）》

Objective:To investigate the effects of orlistat combined with drospirenone/ethinylestradiol tablets(DRSP/EE)on anthropometric indices,sexual hormones,hepatorenal function parameters of overweight or obese patients with polycystic ovary syndrome(PCOS).Methods:75 overweight or obese PCOS patients[body mass index(BMI)＞24 kg/m2]were recruited within the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical Uni-versity,from April 2019 to January 2020,for a prospective,randomized,open-labelled comparing study.They were numbered one by one according to the order of recruitement and randomly divided into two groups,group 1 included 50 patients,orlistat plus DRSP/EE;group 2 included 25 patients treated with DRSP/EE alone.Both groups got the same comprehensive intervention in terms of individualized,standardized managment and mon-itoring of life-style like diet and exercise.The changes of anthropometric indices,sexual hormones,hepatorenal function parameters before and after three months of treatment in the two groups were compared.Results:After three months of treatment,body weight,waist circumference(WC),hip circumference(HC)and BMI of both groups were significantly decreased(P＜0.05).The decrease of body weight,WC,HC and BMI in group 1 was significantly greater than those in group 2(P＜0.05).Free testosterone and sex hormone-binding globulin in both groups were significantly changed(P＜0.05).There was no significant difference in the hepatorenal function parameters between the two groups after three months treatment(P＞0.05).Conclusion:To our knowledge our study is the first to investigate the effects of orlistat combined with DRSP/EE in overweight or obese PCOS patients comparing with the effect of using DRSP/EE alone.Orlistat combined with DRSP/EE was better than use DRSP/EE alone in getting weight loss,which provides an evidence for the choice of rational drug use in clinical practice.

Virtual academy of women's health / 《全球健康杂志（英文）》

In this paper,we explored to develop a new concept of computer-and internet-based learning and training method in medicine,especially in obstetrics and gynecology,which is named as Virtual Academy of Women'Health(VA).Especially in the times of infectious disease pandemics worldwide,learning at home rather than in big lectures hall,might be necessary and practical as never before.The VA is based on worldwide knowledge in medicine—free accessible on the internet—in terms of homepages,video and audio platforms,scientific papers,medical books,and different guidelines.A collection of different video-clips in various fields of women's health can assist the student or doctor in understanding the symptoms,diagnostics,and treatment of various diseases.There are two major targets of it—one is online education,and one is testing the knowledge by simulation of clinical cases.

Intrauterine contraception and menstrual bleeding / 《全球健康杂志（英文）》

After more than half a century of development,the intrauterine contraception (IUD) has become a relatively mature method of contraception and treatment of gynecological diseases.This paper reviewed the development of IUDs,different types of IUDs,and some problems due to them,such as bleeding,infection,malposition,dis-location,expulsion,etc.And the causes of clinical side effects,complications,and corresponding treatments of IUDs were overviewed as well.

Prevention and treatment of iatrogenic premature ovarian insufficiency:interpretation of the first Chinese guideline on ovarian tissue cryopreservation and transplantation / 《全球健康杂志（英文）》

In recent years,with the rapid development of medical research,cancer diagnosis and treatment technology have significantly improved young cancer patient's survival rate.Anticancer therapy such as chemotherapy,radiother-apy,or hematopoietic stem cell transplantation can lead to premature ovarian insufficiency.The endocrine and reproductive function of the ovary is critical to women's physical and mental health.Ovarian tissue cryopreser-vation and transplantation can protect not only female fertility but also preserve ovarian endocrine function.This paper interprets the guidelines for ovarian tissue cryopreservation and transplantation issued by the Chinese Society of Gynecological Endocrinology affiliated to the International Society of Gynecological Endocrinology.The purpose of this guideline's interpretation is to promote more medical workers to understand the technology of ovarian tissue cryopreservation and transplantation,which can provide patients with more choices of fertility protection methods and improve their quality of life.

The progress and prospect of assessment measures of uterine cavity function for infertility patients / 《全球健康杂志（英文）》

Objective:To explore the progress and prospect of evaluation methods for infertility patients.Methods:From September 2017 to December 2020,199 cases of infertility patients who have accepted mini-hysteroscopy examination in the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University.The patients who had primary ovary insufficiency,tubal infertility were excluded;patients with hysteroscopy contradiction,such as acute or sub-acute vaginal tract inflammation,en-dometrium lesion or endometrium carcinoma,severe cardiovascular,liver or kidney insufficiency were excluded.40 patients were excluded and 15 patients lost follow up,144 patients were eventually included in the analysis.The patient's age,body mass index,infertility etiology,preoperative and postoperative stimulate ovulation cycle,pregnancy state and pregnancy time were recorded.The effect of mini-hysteroscopy on ovulation induction cycle was analyzed in pregnant patients.Results:The average age of 144 patients was 32.10±4.67 years old.96 (66.67％) patients were found to have intrauterine abnormalities,while 48 (33.33％) patients were found to have normal intrauterine cavity.48 cases of pregnancy,accounting for 33.33％;the median and interquartile ranges[M (Q1,Q3)]of ovulation induction cycles before and after surgery were respectively[3 (0,5)],[2 (1,3)],the difference was statistically significant(P ＜ 0.05).Among the 48 pregnant patients,32 of them had no structural lesions in hysteroscopy,the ovula-tion induction cycle of these patients before and after hysteroscopy were respectively[5 (0,9)],[1 (0,3)],the difference was statistically significant (P ＜ 0.05).Conclusion:Uterine cavity evaluation is important for the assessments of fertility.As an advanced diagnosis instrument,mini-hysteroscopy can not only timely detect the intrauterine abnormalities of patients,but also with great application value in shorten the ovulation cycle in infertility patients and increase the pregnancy rate.