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Effects of Bushen Yiqi Huoxue Decoction in Treatment of Patients with diminished ovarian reserve:A Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2022年第3期28卷 195-201页

作者： ZHOU Jing PAN Xin-yao LIN Jin ZHOU Qi LAN Li-kun ZHU Jun DUAN Ru WANG Lan SUN Yan WANG Ling Laboratory for Reproductive Immuno logy Hospital&Institute of Obstetrics and Gyn ecologyShan ghai Medical CollegeFudan UniversityShanghai(200000)China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai(200000)China Academy of Integrative Medicine of Fudan University Shanghai(200000)China Yangpu Hospital of Traditional Chinese Medicine Shanghai(200000)China Second Affiliated Hospital of Hexi University ZhangyeGansu Province(743000)China Department of Obstetrics and Gyn ecology Wenling People's HospitalWenzhou Medical UniversityWenzhouZhejiang Provinee(325000)China Regulatory Commissi on Office of the New Cooperative Medical Scheme Eryuan CountyDaliYunnan Province(671000)China

Objective:To explore the therapeutic effect of Bushen Yiqi Huoxue Decoction BYHD)in patients with diminished ovarian reserve(DOR).Methods:A total of 180 patients with DOR diagnosed from December2013 to December 2014 were equally assigned into progynova and duphaston(E+D)group,Zuogui Pill group and BYHD group with 60 cases in each by computerized randomization.Patients received E+D,Zuogui Pill or BYHD for 12 months,respectively.Follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E_(2)),anti-Mullerian hormone(AMH),antral follicle count(AFC),ovarian volume,endometrial thickness,and the resistance indices(Rls)of ovarian arteries and uterine arteries were observed before and after treatment.Results:Nine women(4 from the E+D group,3 from the Zuogui Pill group,and 2 from the BYHD group)withdrew from the study.After 6 months,Zuogui Pill and BYHD significantly decreased FSH and LH and increased endometrial thickness and AMH(all Povarian arteries decrease(P<0.05).After 12 months,further improvements were observed in the Zuogui Pill and BYHD groups(all P<0.01),but BYHD showed better outcomes,with lower FSH,larger ovaries and a thicker endometrium compared with the Zuogui Pill group(all P<0.01).However,E+D only significantly increased endometrial thickness(P<0.01)and no significant improvements were observed in the RI of uterine arteries in the three groups.Conclusions:BYHD had a favorable therapeutic effect in patients with DOR by rebalancing hormone levels,promoting ovulation,and repairing the thin endometrium.The combination of tonifying Shen(Kidney),benefiting qi and activating blood circulation may be a promising therapeutic strategy for DOR.

关键词： Bushen Yiqi Huoxue Decoction diminished ovarian reserve randomized controlled trial Chinese medicine

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Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with diminished ovarian reserve:A Prospective,Open-Labeled,Randomized and Controlled Study

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Chinese Journal of Integrative Medicine 2023年第4期29卷 291-298页

作者： LI Xiu-fang WANG Zhong-qing XU Hai-yan LIU Hong SHENG Yan XU Jin LI Yuan-mei LIAN Fang The First Clinical College Shandong University of Traditional Chinese MedicineJinan 250014China Center for Reproductive Medicine Shandong UniversityJinan 250021China Medical College of Optometry and Ophthalmology Shandong University of Traditional Chinese MedicineJinan 250014China Department of Traditional Chinese Medicine Jinan Golden Time Health Nursing HospitalJinan 250000China Reproductive and Genetic Center of Integrated Traditional and Western Medicine Affiliated Hospital of Shandong University of Traditional ChineseJinan 250011China Medicine

Objective:To explore the effects of Zishen Yutai Pills(ZYPs)on the quality of oocytes and embryos,as well as pregnancy outcomes in patients with diminished ovarian reserve(DOR)receiving in vitro fertilizationembryo transfer(IVF-ET).The possible mechanisms,involving the regulation of bone morphogenetic protein 15(BMP15)and growth differentiation factor 9(GDF9),were also investigated.Methods:A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio.The patients in the treatment group(60 cases)received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone(Gn RH)antagonist protocol.The patients in the control group(60 cases)received the same protocol but without ZYPs.The primary outcomes were the number of oocytes retrieved and high-quality embryos.Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes.Adverse events were assessed by comparison of the incidence of ectopic pregnancy,pregnancy complications,pregnancy loss,and preterm birth.Contents of BMP15 and GDF9 in the follicle fluids(FF)were also quantified with enzymelinked immunosorbent assay.Results:Compared with the control group,the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group(both P0.05).The administration of ZYPs did not increase the incidence of adverse events.The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group(both P<0.05).Conclusions:ZYPs exhibited beneficial effects in DOR pa

关键词： Zishen Yutai Pills diminished ovarian reserve in vitro fertilization-embryo transfer oocytes embryos

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Treatment Progress in diminished ovarian reserve:Western and Chinese Medicine

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Chinese Journal of Integrative Medicine 2023年第4期29卷 361-367页

作者： ZHANG Qiao-li LEI Ya-ling DENG Yan MA Rui-lin DING Xue-song XUE Wei SUN Ai-jun Department of Human Reproductive Medicine Beijing Obstetrics and Gynecology HospitalCapital Medical UniversityBeijing Maternal and Child Health Care HospitalBeijing 100026China Department of Encephalopathy Shaanxi Provincial Hospital of Chinese MedicineXi'an 710000China Department of Obstetrics and Gynecology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China

diminished ovarian reserve(DOR),generally defined as a decreased number or quality of oocytes,has a significant impact on quality of life and fertility in women.In recent years,the incidence of DOR has been increasing and the ages of patients are younger.The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health.An effective DOR therapy would improve ovarian function,fertility,and quality of life in patients.In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine,and elucidated the characteristics of each treatment.

关键词： diminished ovarian reserve treatment Chinese medicine Western medicine

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Clinical Application of Double Ovulation Stimulation in Patients with diminished ovarian reserve and Asynchronous Follicular Development Undergoing Assisted Reproduction Technology

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Current Medical Science 2023年第2期43卷 304-312页

作者： Yi-zhuo YANG Ming ZHANG Sha MU Xin-meng Guo Hui WANG Zhe TANG Hong-mei PENG Department of Obstetrics and Gynecology First Medical Center of the Chinese People’s Liberation Army General HospitalBeijing100853China College of Medicine Nankai UniversityTianjin300071China

Objective This study aimed to compare the clinical effects of double ovulation stimulation(DouStim)applied during the follicular and luteal phases with the antagonist protocol in patients with diminished ovarian reserve(DOR)and asynchronous follicular development undergoing assisted reproductive technology(ART).Methods The clinical data of patients with DOR and asynchronous follicular development receiving ART from January 2020 to December 2021 were retrospectively analyzed.The patients were divided into two groups according to their ovulation stimulation protocol:DouStim group(n=30)and antagonist group(n=62).Assisted reproduction and clinical pregnancy outcomes were compared between the two groups.Results In the DouStim group,the number of oocytes retrieved,metaphase II(MII)oocytes,two-pronuclei(2PN),day 3(D3)embryos,D3 high-quality embryos as well as blastocyst formation,implantation,and human chorionic gonadotropin-positive rates were significantly greater than those in the antagonist group(all P0.05).Except for the early medical abortion rate,the DouStim group generally had favorable outcomes.In the DouStim group,the dosage and duration of gonadotropin and the fertilization rate were significantly greater in the first ovulation stimulation induction than in the second ovulation stimulation induction(P<0.05).Conclusion The DouStim protocol efficiently and economically obtained more mature oocytes and high-quality embryos for patients with DOR and asynchronous follicular development.

关键词： diminished ovarian reserve double ovulation stimulation follicular phase stimulation luteal phase stimulation

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Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with diminished ovarian reserve

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Current Medical Science 2022年第5期42卷 1066-1070页

作者： Yu-meng REN Yan-bin WANG Min FU Qiu-xiang ZHANG Huan SHEN Hong-jing HAN Fu-mei GAO Reproductive Center of Peking University People’s Hospital Beijing100044China

Objective It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization(IVF)in high or normal ovarian responders.However,it is not clear whether dual triggering also benefits patients with diminished ovarian reserve(DOR).The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone(GnRH)agonist combined with human chorionic gonadotropin(hCG)for final follicular maturation improves the cumulative live birth rate(CLBR)during the GnRH-antagonist cycle in patients with DOR.Methods This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection(IVF-ICSI)cycles at Peking University People’s Hospital from January 1,2017 through December 31,2017.Oocyte maturation was triggered by GnRH combined with hCG(n=110)or hCG alone(n=71).Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle.Patients were followed up for 3 years.Results The dual trigger treatment did not affect CLBR,which is an overall determinant of the success rate of assisted reproductive technology(ART).Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group(90.1%vs.83.9%,P=0.040).Conclusion Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR,but did slightly improve fertilization rate,oocyte count,and embryo quality.

关键词： dual trigger gonadotropin releasing hormone antagonist protocols diminished ovarian reserve cumulative live birth rate

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Efficacy and Safety of the Chinese Herbal Compound TJAOA101 in Treating diminished ovarian reserve: A Protocol for Multicenter, Prospective, and Pre-Post Study

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Current Medical Science 2023年第2期43卷 284-296页

作者： Yan ZHANG Jian-guo FANG Sheng-hao TU Zhuo CHEN Wei XIE Ai-yue Luo Yan LI Chen-chen REN Zeng-hui MAO Hui Xing Qiong-fang WU Zhi-ying LI Jin-jin ZHANG Shi-xuan WANG National Clinical Research Center for Obstetrical and Gynecological Diseases Wuhan430030China Key Laboratory of Cancer Invasion and Metastasis Ministry of EducationWuhan430030China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Pharmacy Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Integrated Traditional Chinese and Western Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Obstetrics and Gynecology the Third Affiliated Hospital of Zhengzhou UniversityZhengzhou450015China Department of Obstetrics and Gynecology Changsha Hospital for Maternal and Child Health Care of Hunan Normal UniversityChangsha410007China Department of Obstetrics and Gynecology Xiangyang Central HospitalHubei University of Arts and ScienceXiangyang441057China Department of Obstetrics and Gynecology Maternal and Child Health Hospital of Jiangxi ProvinceNanchang330006China Department of Obstetrics and Gynecology Renhe Hospital Affiliated to Three Gorges UniversityYichang443001China

Objective diminished ovarian reserve(DOR)can lead to early menopause,poor fecundity,and an increased risk of disorders such as osteoporosis,cardiovascular disease,and cognitive impairment,seriously affecting the physical and mental health of women.There is still no safe and effective strategy or method to combat DOR.We have developed a novel Chinese herbal formula,Tongji anti-ovarian aging 101(TJAOA101),to treat DOR.However,its safety and efficacy need to be further validated.Methods In this prospective and pre-post clinical trial,100 eligible patients aged 18–45 diagnosed with DOR will be recruited.All participants receive TJAOA101 twice a day for 3 months.Then,comparisons before and after treatment will be analyzed,and the outcomes,including anti-mullerian hormone(AMH)and follicle-stimulating hormone(FSH)levels and the antral follicle count(AFC),the recovery rate of menopause,and the Kupperman index(KMI),will be assessed at baseline,every month during medication(the intervention period),and 1,3 months after medication(the follow-up period).Assessments for adverse events will be performed during the intervention and follow-up periods.Conclusion A multicenter,prospective study will be conducted to further confirm the safety and efficacy of TJAOA101 in treating DOR and to provide new therapeutic strategies for improving the quality of life in DOR patients.

关键词： diminished ovarian reserve Chinese herbs TJAOA101 multicenter study study protocol

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Recent progress in the treatment of women with diminished ovarian reserve

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Gynecology and Obstetrics Clinical Medicine 2021年第4期1卷 186-189页

作者： Jingwen Yin Hsun-Ming Chang Rong Li Peter C.K.Leung Center for Reproductive Medicine Department of Obstetrics and GynecologyPeking University Third HospitalChina National Clinical Research Center for Obstetrics and Gynecology(Peking University Third Hospital) China Key Laboratory of Assisted Reproduction(Peking University) Ministry of EducationChina Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology China Department of Obstetrics and Gynelogy University of British ColumbiaAnd BC Children's Hospital Research InstituteVancouverBritish ColumbiaV5Z 4H4Canada

diminished ovarian reserve(DOR)refers to a decrease in the number and/or quality of oocytes in the ovary,accompanied by a decline in reproductive potential,which is generally related to advanced age or ovarian disease.In in vitro fertilization(IVF)clinical practice,managing patients with DOR remains one of the most challenging tasks.In recent years,increased research on improving ovarian function has provided us with new insights into treating patients with DOR.Many therapeutic options have been proposed to improve the ovarian function of patients with DOR,yet they are not widely utilized in clinical practice because of limited evidence of safety and effectiveness.In this review,we focus on the mechanisms from animal models and clinical trials that have been applied to the treatment of DOR in recent years,intending to improve IVF outcomes in patients with DOR.Furthermore,new insights and perspectives on the molecular and cellular regulation of follicular development and ovarian reserve are emphasized to provide more clues for research on the treatment of DOR.

关键词： diminished ovarian reserve Infertility In vitro fertilization ovarian function Oocyte quality Embryo quality

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Analysis of uterine artery and sex hormones in treating diminished ovarian reserve with tiaojing decoction

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TMR Theory and Hypothesis 2019年第4期2卷 252-259页

作者： Meng-Jie Wang Hui-Jun Xu Master of Science in Integrated Traditional Chinese and Western Medicine Center College of Basic Medical SciencesQingdao UniversityQingdaoChina Women's Division Qingdao Haici Medical GroupQingdaoChina

Objective: To observe the effect of tiaojing decoction and climen on diminished ovarian reserve patients with de ficiency of Kidney-Yin by sex hormone and uterine artery blood flow parameters. To verify the e ffectiveness of tiaojing decoction on diminished ovarian reserve and uterine artery blood flow parameters, explore the correlation between uterine artery blood flow parameters and sex hormones. Methods: Total 60 diminished ovarian reserve patients with deficiency of Kidney-Yin were randomly divided into the experimental group (n=30, taking tiaojing decoction and climen) and the control group (n=30, taking climen) and they were treated in 3 months. Observe bFSH, bE2, uterine artery PSV, EDV, S/D, RI before and after the treatment in the 2-4 day of menstruation. Results: After treatment, serum sex hormone levels and uterine artery blood flow parameters of the two groups were significantly different (P diminished ovarian reserve patients with deficiency of Kidney-Yin. Uterine artery blood flow parameters can reflect the sex hormone levels.

关键词： diminished ovarian reserve Tiaojing decoction Uterine artery blood flow

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Effect of Progestin-Primed ovarian Stimulation Protocol in Infertile Women with Basal Follicle-Stimulating Hormone Levels ≥15 IU/L: A Retrospective Analysis

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Reproductive and Developmental Medicine 2020年第2期4卷 97-102页

作者： Lu Fang Xiu-Juan Qi Hong Zhu Department of Assisted Reproduction Shanghai TOWAKO HospitalShanghai 200013China

Objective:To evaluate the efficacy of progestin-primed ovarian stimulation(PPOS)protocol in infertile women with high basal follicle-stimulating hormone(FSH)levels≥15 IU/L.Methods:Patients with high basal FSH levels≥15 IU/L with autologous oocytes from September 2016 to March 2019 were reviewed.Either medroxyprogesterone acetate 4 mg/d or clomiphene citrate(CC)50 mg/d was administered daily from day 3 to the trigger day.When serum FSH levels decreased to≤15.0 IU/L,a low dose of human menopausal gonadotropin(hMG)75/150 IU/d was administered to promote late follicular development.Results:Two hundred and twenty women were retrospectively analyzed in this study.Among them,139 patients were administered with PPOS protocol as the study group,and 81 patients were administered with CC protocol as the control group.The numbers of received oocytes and viable embryos were higher in the study group than those in the control group(1.5±1.2 vs.1.2±0.8 and 0.8±0.8 vs.0.5±0.6,respectively,P<0.05).However,hMG duration and dosage were significantly higher in the study group than those in the control group(4.2±2.7 d vs.1.1±2.3 d and 609.1±424.5 IU vs.140.7±231.3 IU,respectively,P<0.01).Incidence of luteinizing hormone surge and cycle cancellation rate were lower in the study group than those in the control group with statistical difference(2.88%vs.16.05%and 36.50%vs.50.63%,respectively,P<0.05).Conclusions:PPOS protocol can effectively downregulate the endogenous FSH levels.Compared with CC protocol,treatment with PPOS protocol in patients with high basal FSH levels≥15 IU/L could receive more oocytes and more viable embryos.

关键词： diminished ovarian reserve Follicle-Stimulating Hormone In vitro Fertilization Progestin-Primed ovarian Stimulation Protocol

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Effects of Dehydroepiandrosterone on Embryo Quality and Follicular Fluid Markers in Patients with diminished ovarian reserves

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Reproductive and Developmental Medicine 2017年第1期1卷 1-8页

作者： Jing Fu Hua-Feng Jiang Lu Li Ai-Jie Xin Yi-Juan Sun Xiao-Xi Sun Shanghai Ji Ai Genetics and IVF Institute Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shi Men Second Road Community Health Service Center of Jingan District Shanghai 200041China Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China

Background:To examine the effects of dehydroepiandrosterone(DHEA)on in vitro fertilization(IVF)intracytoplasmic sperm injection(ICSI)and the levels of follicular fluid(FF)markers,namely,anti-Müllerian hormone(AMH),insulin-like growth factor(IGF)-1,bone morphogenetic protein(BMP)-15,and growth differentiation factor(GDF)-9,in patients with diminished ovarian reserves(DORs).Methods:116 patients with DOR were randomized into two groups,DHEA group and control group.Each group contained 58 patients.The DHEA group received 75 mg/d of DHEA for 12 weeks prior to the start of IVF treatment,while the control group entered IVF treatment directly.All patients were treated with the same ovarian stimulation protocol.The primary outcome was high-quality embryo yield.Other IVF parameters,such as the clinical pregnancy rate,embryo survival rate,and intact blastomere rate,were compared between the two groups.FF samples from patients of both groups were collected to measure the levels of AMH,IGF-1,DHEA-sulfate,BMP-15,and GDF-9.Blood was also collected on day 3 of the menstrual cycle to define the baseline hormonal profile and to examine ovarian reserve markers.Results:The high-quality embryo yield was higher in DHEA group than that in control group(P=0.033).AMH and IGF-1 concentrations in FF were significantly higher in DHEA group than that in the control group(2.83±1.14 ng/L vs.1.37±0.55 ng/L,P=0.000;94.02±38.28 ng/L vs.74.03±25.46 ng/L,P=0.004,respectively).The BMP-15 level was also higher in DHEA group(relative expression were 1.80±0.41)than that in control group(relative expression were 0.79±0.16,P0.05)and in the clinical pregnancy rate between the two groups(13.79%vs.7.27%,respectively,P>0.05).Conclusions:In women with DOR undergoing IVF treatment,pretreatment with DHEA may increase the number of high-quality embryos,which may be due to increased levels of AMH,IGF-1,and BMP-15 in t

关键词： Bone Morphogenetic Protein‑15 Dehydroepiandrosterone diminished ovarian reserve In vitro Fertilization

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