Gynecological endocrinological health and education for global women

1.Introduction Global Healtii Journal focuses on global health-related topics,including global health practice,global health education,and so on.In this special issue,we focus on following themes:(1)an advanced therapy;(2)management strategy of infertility in polycystic ovary syndrome(PCOS);(3)optimizing menopausal hormone therapy(MHT);and(4)an interpretation of expert consensus.All those works are the intense and painstaking efforts made by the researchers across the world,which cover some important topics on gynecological and reproductive endocrinology and improve the clinical routine as well further researches.

选择性雌激素受体调节药对雌激素受体α/β活性的诱导作用

目的 :探讨选择性雌激素受体调节药 (SERMs)对雌激素受体 (ER)α β活性的诱导作用。 方法 :通过基因转染方法将pSVhER和荧光素酶报道基因载体ER Etk Luc瞬时共转染至乳腺癌细胞株MDA MB 2 3 1,转染后的细胞分别用 1nmol·L 1 17β雌二醇 (E2 )、17αE2 、雌酮、雷洛昔芬、4羟基 他莫昔芬 (4OH TAM)和柠檬酸他莫昔芬处理细胞 2 4h ,采用荧光素酶报道基因分析方法测定ERα β活性。 结果 :雷洛昔芬和他莫昔芬具有明显激活ERα活性作用 ,他莫昔芬对ERβ活性的诱导作用明显较ERα弱 ,雷洛西芬几乎不诱导ERβ活性。 结论 :SERMs主要是通过激活ERα发挥抗雌激素作用 ,而对ERβ的诱导作用明显较弱。

GENISTEIN INHIBITS PROLIFERATION OF HUMAN ENDOMETRIAL ENDOTHELIAL CELL IN VITRO

Objective To explore the effect of genistein on proliferation of human endometrial endothelial cells （HEECs） and glandular epithelium. Methods In vitro HEECs and human endometrial cancer-1B cell （HEC-1B ） were cultured with 0, 1, 10, 50, 100, and 200 μmol/L of genistein alone or indicated concentrations of genistein combined with 0.2 or 1 nmol/L 17β- estradiol （ 17β-E2）. Cell proliferation was determined by [ 3H ] -thymidine incorporation and cell cycle was measured by flow cytometry. Results After 96 hours of treatment, genistein inhibited the proliferation of HEECs in a dose-dependent manner. The stimulation index reduced from 100% （ without genistein treatment ） to about 1% （ 200 μmol/L genistein ）. HEECs were arrested at G1/0 and G2/M phase when treated with genistein for 96 hours. When the concentration of genistein was 200 μmol/L, the percentages of HEECs at G1/0, G2/M, and S phase were 96. 0%, 2.1%, and 1.9%, respectively. However, when HEECs were treated without genistein, the percentages of HEECs at G1/0, G2/M, and S phase were 76. 7%, 8.5%, and 14. 7%, respectively. 1713-E2 could not influence the effects of genistein on the proliferation of HEECs. Meanwhile, genistein could suppress the proliferation of HEC-1B. If the stimulation index of HEC-IB was defined as 100% when HEC-1B was treated with different doses of 1713-E2 （without genistein）, it was 67%, 19%, as well as 32% when cell was supplemented with 200 μmol/L genistein combined with 0, 0. 2, or 1 nmol/L 17β-E2, respectively. Conclusion Genistein at the concentration of 200 μmol/L can sufficiently inhibit the proliferation of HEECs and endometrial glandular epithelium simultaneously in vitro.

Successfully Man aging Cornual Heterotopic Pregnancy: A Case Report and Literature Review

Cornual heterotopic pregnancy is an extremely rare,life-threatening complication during pregnancy.Here,we report a 33-year-old woman who suffered cornual heterotopic pregnancy after in vitro fertilization embryo transfer.To prevent rupture during heterotopic pregnancy,she received laparoscopic surgery to remove the ectopic gestational sac at 7^(+2) weeks of gestation.Ultimately,she delivered a healthy boy at 38^(+3) weeks of gestation.Here,we also review the clinical presentations,risk factors,treatment options and outcomes of cornual heterotopic pregnancy.

应对辅助生殖技术中的风险安全管理挑战:一种积极性方案

医学各专业在安全保障方面远落后于其他行业,借助于辅助生殖技术的不育诊疗概莫能外。航空业多年来所开发实施的安全风险管理(RSM)让如今的全球航空安全上升到了一个卓越的水平,而将它们的技术经验应用到医学行业,相信将会在医疗效能和安全上带来极大的助益。本文描述了在不育和辅助生殖技术领域贯彻实施这类RSM的依据,而这一特殊的医学专业领域有望成为在整个医学行业实施RSM的试验田。

The progress and prospect of assessment measures of uterine cavity function for infertility patients

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,endometrium 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 ovulation 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,hut also with great application value in shorten the ovulation cycle in infertility patients and increase the pregnancy rate.

Management strategy of infertility in polycystic ovary syndrome

Polycystic ovary syndrome(PCOS)is the most common endocrine and metabolic disease in women of reproductive 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 fertility,patients with PCOS require standardized individualized therapy.

Advanced therapy of overweight or obese polycystic ovary syndrome:a prospective study

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/m^(2)]were recruited within the Department of Gynecological Endocrinology,Beying Obstetrics and Gynecology Hospital,Capital Medical University,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 monitoring 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.

Cytogenetic and andrological status and ICSI-results in couples with severe male factor infertility

Aim: To pursue whether cytogenetic aberrations correlate with specific spermatological or hormonal abnormalities.Methods: 305 infertile couples were investigated. All male partners were referred to a complete andrological work-up with physical examination, determination of hormones, HIV testing and semen analysis. Cytogenetic analysis wascarded out in both partners by means of standard techniques using cultured lymphocytes from peripheral blood. Re-suits: Among the 305 couples, 10 men (3.2%) and 10 women (3.2%) showed constitutional chromosomal aber-rations, including reciprocal translocations (n = 7), Robertsonian translocations (n = 3), inversions (n = 3), otherstructural aberrations (n = 4) and sex chromosome aberrations (n = 3). In addition to the impaired sperm count inmost of the patients, a tendency to an increased proportion of spermatozoa with acrosome defect was observed. Con-clusion: Chromosomal aberrations may contribute to the low fertilization and pregnancy rates in the infertile couples.(Asian J Androl 2000 Dec; 2: 293-296)

Interpretation of expert consensus on prevention and treatment of osteoporosis in perimenopausal and postmenopausal women

Osteoporosis and associated fractures are the most common chronic metabolic bone disease and represent a major global health problem.With the aging of the population,osteoporosis has been a severe threat to the health of the middle-aged and elderly,especially middle-aged and older women,the prevalence rate of osteoporosis in women is three times higher than that in men.By 2020,the number of patients with osteoporosis increased to 286.6 million.The number of hip fractures reached to 1.6382 million.The number of patients with osteoporosis will rise to 533.3 million in 2050.1 The theme for World Menopause Day 2021 was"Bone Health",which was decided by the Board of the International Menopause Society(IMS).

Prevention and treatment of iatrogenic premature ovarian insufficiency:r interpretation of the first Chinese guideline on ovarian tissue cryopreservation and transplantation

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,radiotherapy,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 cryopreservation 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.

Optimizing menopausal hormone therapy:for treatment and prevention,menstrual regulation,and reduction of possible risks

Menopausal hormone therapy(MHT)is used to treat menopausal complaints including the genitourinary syndrome 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.Additional 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 Kwindow 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 endometrial 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 progestogens.

Reproductive health for global women

1.Introduction Global Health Journal(GHJ)covers general and special issues of health with importance for the global women across the globe.Many topics published in GHJ are related to"Reproductive Health"which certainly is one of the important challenges in all countries of the world,especially in developing countries.The special issue on"Reproductive health for global women"has been designed by Prof.Xiangyan Ruan as guest Editor,who is the Medical Director of the Department of Gynecological Endocrinology in the Beijing Obstetrics and Gynecology Hospital,Capital Medical University,China,and Guest Professor of the University Women's Hospital in Tuebingen,Germany.

泼尼松、阿司匹林、叶酸及孕酮联合治疗妇女原发性反复流产:一项病例对照研究

Objective: To compare a combination treatment of prednisone, aspirin, folate, and progesterone with no treatment in women with idiopathic recurrentmiscarriage (IRM).Design: Matched-pair study. Setting: Academic research institution. Subject(s): Women with a history of IRM, defined as three or more consecutive miscarriages before 20 weeks’ gestation without associated anatomic, cytogenetic, hormonal, and infectious pathologies or antiphospholipid syndrome. Intervention(s): Eighty of 210 eligible women consented to participate and were treated with prednisone (20mg/d) and progesterone (20mg/d) for the first 12 weeks of gestation, aspirin (100 mg/d) for 38 weeks of gestation, and folate (5 mg every second day) throughout their pregnancies. Fifty of 80 women became pregnant; they were compared with 52 women with IRM (matched for age and number of miscarriages), who became pregnant without treatment during the same observation period. Main Outcome Measure(s): Live birth rate, complications of pregnancy, such as preeclampsia, premature birth, and intrauterine growth restriction, and therapy- related side effects. Result(s): The overall live birth rates of the treatment and control groups were 77% (40 of 52) and 35% (18 of 52) (P = .04). The rates of first and second trimester miscarriage among the treatment and control groups were 19% (10 of 52) and 0 (0 of 52), and 63% (33 of 52) and 2% (1 of 52), respectively (P = .09 and P = 1.0, respectively). The median gestational age at birth and median birth weight did not differ between the groups. We observed two and three cases of premature birth among the treatment and control groups, respectively (P = .3) and no cases of intrauterine growth restriction and Cushing’s disease. Of 80 women who started treatment, one woman had an ectopic pregnancy and one woman terminated her pregnancy due to fetal chromosome aberration (trisomy 18). Three women stopped treatment due to nausea, depression, and tachycardia. Conclusion(s): A combination treatment of prednisone, aspirin, folate, and progesterone is associated with a higher live birth rate compared with no treatment in women with IRM.

Virtual academy of women's health

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.

Evaluation of Steroid Receptors mRNA Fingerprints in Two Groups of Normozoospermic Patients: Men from Unexplained Infertility Couples vs. Men from Couples with Tubal Factor Infertility

The study of sperm cellular components at molecular level is crucial for the diagnosis of male unexplained infertility. The aim of the study was to compare the molecular profile of steroid receptors and aromatase in spermatozoa obtained from two normozoospermic groups of patients issued from couples treated for infertility. We investigated 46 male patients from unexplained infertility couples and from men, 38 where female partners presented with tubal infertility. Sperm ERs (estrogen receptors: alpha and beta), GPER (G protein-coupled estrogen receptor), AR (androgen receptor) and aromatase mRNA expression levels by TaqMan qPCR were analyzed. AR transcript level was significantly lower in sperm of men from unexplained infertility couples vs. men from couples with tubal factor infertility (P = 0.04). Although the AR mRNA expression level did not had any effect on embryo development and its implantation, a significant correlation between AR mRNA levels and clinical pregnancy in unexplained infertility patients was observed. Taken together, AR transcript presence in ejaculated spermatozoa could be a potential marker for unexplained infertility.

Long-Term Metformin Effect on Endometrial Cancer Development Depending on Glucose Environment <i>In Vitro</i>

Objectives: Hyperinsulinemia as well as prolonged and elevated estrogen exposure are considered as risk factors for endometrial cancer (EC) development. Metformin, an anti-hyperglycemic and insulin-sensitizing biguanide, displayed anti-proliferative effects in recent studies. In the present study, the effects of long-term exposure of endometrial cancer cells to low and moderate concentrations of metformin on cell viability, proliferation, clonogenicity and migration were investigated under different metabolic conditions. Study Design: EC cell lines HEC-1A and Ishikawa were cultured under normo- (NG, 5.5 mM) or hyperglycemic (HG, 17.0 mM) conditions and treated with metformin (0.01 - 5.0 mM) in the presence of β-estradiol (E2) for 7 d. Results: A concentration-dependent decrease of cellular viability was observed in the MTT and ATP assays after metformin treatment. IC50 values were between 0.7 - 3.7 mM (NG) and 3.0 - 18.3 mM (HG), respectively. A protective effect of glucose on cellular viability was detected only in the ATP assay. Furthermore, metformin (0.5 - 5.0 mM) led to a significant decrease in proliferation by 12% - 55% (NG). However, a decreased proliferation rate was only induced at 5.0 mM metformin (40%) in the presence of high glucose levels in HEC-1A cells, indicating a glucose-related resistance to anti-proliferative metformin effects, which—to a lesser extent—was also observed in Ishikawa cells. Metformin treatment also caused concentration-dependent effects on clonogenicity and decreased the number and size of colonies. In HEC-1A cells, metformin (0.5 - 5.0 mM) reduced the colony formation by 44% - 80% (NG) and 29% - 81% (HG), respectively. Slightly higher metformin concentrations (1.0 - 5.0 mM) were necessary in Ishikawa cells to reduce clonogenicity by 36% - 86% independent of glucose levels. An investigation of migration in the wound healing assay revealed that the % wound closure decreased with increasing metformin concentrations, but independent of glucose levels. After treatment with 5.0 mM metformin, migration was significantly reduced in both cell lines. Conclusion: Our in vitro findings support the hypothesis that metformin has a direct effect on endometrial cancer cell lines and reflects the importance of the local glucose environment, suggesting that metformin may be considered as a potential adjuvant agent in endometrial cancer therapy due to its direct and indirect effects on endometrial development. However, further studies are necessary that confirm the relevance of our data for clinical applications.

吸烟破坏人卵母细胞成熟过程中的血管生成

Objective: This study determines whether smoking influences ovarian vascularization which thus may impair follicular development. Design: Prospective laboratory study of follicular fluids and granulosa cells from patients undergoing in vitro fertilization. Setting: University Hospital Aachen, Germany. Patient(s): Fifty smoking women and 50 nonsmoking women. Intervention(s): Cultivation of human granulosa cells. Cultivation of human umbilical vein endothelial cells (HUVECs) with either granulosa cell-conditioned medium or follicular fluid. Determination of clinical parameters. Main Outcome Measure(s): Quantification of soluble vascular endothelial growth factor receptor 1 (sVEGFR- 1) and cotinine. Result(s): Mean sVEGFR-1 concentration in follicular fluid of smokers was 499.6 pg/mL compared with 159.2 pg/mL in nonsmokers. Correspondingly, supernatant of HUVECs cultured with follicular fluid from smoking and nonsmoking women showed, respectively, 1,174.1 pg/mL versus 794.2 pg/mL sVEGFR-1. The HUVECs incubated with conditioned medium from smokers’ granulosa cells at culturing days 5, 9, 13, and 17 secreted, respectively, 1,712.4, 1,560.6, 1,619.0, and 1,635.0 pg/mL sVEGFR-1, whereas nons-mokers showed, respectively, 1,147.6, 1,067.2, 1,135.9, and 1,206.3 pg/mL sVEGFR-1. Mean cotinine concentration in smoking women was 83.9 ng/mL and in nonsmoking was 2.8 ng/mL. In all four comparisons, differences between groups reached statistical significance. Conclusion(s): This study showed that smokers secrete significantly higher amounts of sVEGFR- 1 than nonsmokers, whichmay result in decreased ovarian vascularization and reduced oocyte maturation.

来源于体外成熟卵母细胞的胚胎的多核化及卵裂情况

In patients with polycystic ovary syndrome (PCOS),the proportion of optimal embryos-blastomere number and fragmentation rate-derived from in vitro-matured oocytes after the hCG priming protocol was higher (43.3%) than the proportion of optimal embryos derived from oocyte in vitro maturation with the FSH priming protocol (11.1%). The embryos derived from in vitromatured oocytes after the hCG priming protocol also showed a lower incidence of multinucleated blastomeres. Pregnancies were recorded only in the hCG primed patients.

如果至多只能有3个胚胎培养超过原核期,长时间胚胎培养会减少第4天和第5天的种植率

Objectives: To study the potential of embryo transfer after 3, 4 or 5 days of embryo culture under the German embryo protection law according to which only a maximum of three zygotes are allowed to be cultured for embryo transfer. Study design: In a prospective study, 273 patients with assisted reproductive treatment were randomly allocated for transfer on days 3, 4 or 5. Pregnancy and implantation rates were evaluated in regard to day of transfer and results were compared by Chi-square or ANOVA test. Results: Out of 234 transfer cycles, 79 were performed on day 3, 76 on day 4 and 79 on day 5. Pregnancy and implantation rates were 41.8%/27.1%for transfer on day 3, 27.6%/14.1%for day 4 transfer and 16.5%/8.8%for transfer on day 5. These results were significantly different for pregnancy rates on day 3 versus day 5 (P < 0.001) and for implantation rates on day 3 versus day 4 (P < 0.005) and day 3 versus day 5 (P < 0.001). Conclusions: These findings suggest that extended embryo culture is not beneficial when the option for embryo selection at later stages of development is not available.