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...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.展开更多
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 w...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 P<0.01),BYHD also resulted in E2 elevation(P<0.05),ovary enlargement(P<0.05),AFC increase(P<0.01),and RI of ovarian 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.展开更多
1.Introduction With the increase in older populations worldwide1 comes an increased health burden related to chronic diseases.2–4One of the most disabling of these is knee osteoarthritis(OA),which occurs in million...1.Introduction With the increase in older populations worldwide1 comes an increased health burden related to chronic diseases.2–4One of the most disabling of these is knee osteoarthritis(OA),which occurs in millions of older adults who subsequently live with joint pain and stiffness,leading to chronic disability and a diminished quality of life.5,6 Epidemiological evidence shows a higher prevalence of OA in older adults living in urban and展开更多
Objective:To observe whether electro-acupuncture(EA) is better in improving hormone levels among women with diminished ovarian reserve(DOR) compared with oral medicine [Chinese herbs with or without hormone replacemen...Objective:To observe whether electro-acupuncture(EA) is better in improving hormone levels among women with diminished ovarian reserve(DOR) compared with oral medicine [Chinese herbs with or without hormone replacement therapy(HRT)] that is often used in gynecology clinics in China.Methods:Eligible participants entered the EA group or medication group according to their preferences.Participants in the EA group received EA treatment,and participants the medication group received herbal decoction alone or combined with HRT.Reproductive hormone levels of the participants were tested before and during treatment in both groups.Results:A total of 80 women with DOR were screened and 57 cases were included(29 in the EA group and 28 in the medication group) in the final analysis.The differences in the change from baseline between the EA and medication group in mean follicle-stimulating hormone(FSH) levels were-6.6(95% Cl,-17.03 to 3.72),(P=0.848) and-7.09(95% CI,-15.86 to 1.66),(P=0.539) at weeks 12 and 24,respectively.The proportion of women with regular FSH levels in the EA and medication group was 51.3% vs 32.1% at week 12(P=0.134) and 51.3% vs 25.0% at week 24(P=0.038).Conclusion:EA might influence regulating the levels of FSH,luteinizing hormone(LH),estrogen and the FSH/LH ratio,and no difference was found between the effects of EA and oral medicine in changes of reproductive hormone levels.展开更多
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 reser...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 P<0.05).No significant differences were found in MII,fertilization,or continued pregnancy rates at the first frozen embryo transfer(FET),in-vitro fertilization(IVF)cancellation,or early medical abortion rates between the groups(all P>0.05).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.展开更多
OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From Septe...OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From September 2014 to September2016,46 patients with DOR who received NYTYST and Climen(treatment group)and 51 patients who received Climen only(control group)at the Jiangsu Provincial Traditional Chinese Medicine Hospital(Nanjing,China)were retrospectively reviewed.Before and at 3 months after treatment,serum levels of follicle-stimulating hormone(FSH),FSH/luteinizing hormone(LH),estradiol(E2),and anti-Mullerian hormone(AMH),the antral follicle count(AFC),stromal peak systolic velocity(PSV),symptom scores,and the clinical effectiveness rate were measured and compared between the two groups.RESULTS:After treatment,serum levels of FSH,FSH/LH and E2,and symptom scores were significantly decreased compared with before treatment(all P<0.05)in the two groups.AMH levels,AFC,and PSV were significantly increased after treatment compared with before treatment in both groups(all P<0.05).Serum levels of FSH,FSH/LH,and E2 after treatment were significantly lower in the treatment group than in the control group(all P<0.05).However,AMH levels and the AFC were significantly higher after treatment in the treatment group than in the control group(both P<0.05).The clinical effectiveness rate was significantly higher in the treatment group than in the control group(87%vs 68.6%,P<0.05).CONCLUSION:NYTYST combined with Climen may be more effective in treating DOR than Climen alone.展开更多
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 tr...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 P<0.05).After treatment with ZYPs,a significant regulation of serum sex hormones was observed,including progesterone and estradiol.Both hormones were up-regulated compared with the control group(P=0.014 and 0.008),respectively.No significant differences were observed with regard to pregnancy outcomes including implantation rates,biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and pregnancy loss rates(all P>0.05).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展开更多
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 physi...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.展开更多
Diminishing the appearance of a fence in an image is a challenging research area due to the characteristics of fences(thinness, lack of texture, etc.) and the need for occluded background restoration. In this paper, w...Diminishing the appearance of a fence in an image is a challenging research area due to the characteristics of fences(thinness, lack of texture, etc.) and the need for occluded background restoration. In this paper, we describe a fence removal method for an image sequence captured by a user making a sweep motion, in which occluded background is potentially observed. To make use of geometric and appearance information such as consecutive images, we use two well-known approaches: structure from motion and light field rendering. Results using real image sequences show that our method can stably segment fences and preserve background details for various fence and background combinations. A new video without the fence, with frame coherence, can be successfully provided.展开更多
Objective: To get more insight in the pathophysiological basis of periodic lim b movement disorder (PLMD) with or without restless legs syndrome (RLS), we inve stigated whether these patients have spontaneous changes ...Objective: To get more insight in the pathophysiological basis of periodic lim b movement disorder (PLMD) with or without restless legs syndrome (RLS), we inve stigated whether these patients have spontaneous changes in H-reflexes or show altered reflex patterns after (external) inhibition or excitation of the relevan t spinal segment. Methods: The ratio of the peak-to-peak values of the maximal soleus H-reflex and the maximal direct muscle potential (H/M ratio), H-reflex recruitment curves, vibratory inhibition and recovery curves of the soleus H-r eflexin double stimulus experiments were measured in 9 PLMD patients and 11 cont rols. Results: In comparison to controls the vibratory inhibition, predominantly reflecting pre-synaptic inhibitory action, was depressed in PLMD patients. The soleus H-reflex recovery curves showed increased late facilitation and depress ed late inhibition, both reflecting diminished inhibition due to post-synaptic central activity. Conclusions: Our data indicate diminished inhibition at spinal level in PLMD patients. This is probably due to altered function of the descend ing spinal tracts, peripheral influence or changes at the inter-neural circuitr y at spinal level itself, or combinations of these 3 possibil ities. Significance: The results of this study give further insight in the pat hophysiology of PLMD and RLS by stressing the importance of diminished central i nhibition.展开更多
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...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.展开更多
Objective:To observe the clinical efficacy of herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve(DOR).Methods:A total of 60 patients with DOR were randomized into a spre...Objective:To observe the clinical efficacy of herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve(DOR).Methods:A total of 60 patients with DOR were randomized into a spreading moxibustion group and a Western medicine group by the random number table method,with 30 cases in each group.The Western medicine group was treated with climen,starting from the 5th day of the menstrual cycle for 21 d.The spreading moxibustion group was treated with herb-partitioned spreading moxibustion at Baliao points on the basis of the medication in the Western medicine group,1 h per time,once a week.The treatment was performed for 1 month as one treatment course in both groups,for 3 courses in total.The serum follicle-stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)in the patients were measured before and after treatment.The peak systolic velocity(PSV)and resistance index(RI)were also detected.The traditional Chinese medicine(TCM)symptom score was evaluated.The clinical efficacy was evaluated after treatment.Results:The total effective rate in the spreading moxibustion group was 93.3%,which was significantly higher than 80.0%in the Western medicine group,and the difference between the groups was statistically significant(P<0.05).After treatment,the TCM symptom scores,the serum FSH levels,FSH/LH ratios and RI in both groups decreased,and the intra-group differences were all statistically significant(all P<0.05).The serum E2 level and PSV increased compared with those in the same group before treatment,and the intra-group differences were statistically significant(all P<0.05).After treatment,the TCM symptom score,the serum FSH level,FSH/LH ratio and RI in the spreading moxibustion group were lower than those in the Western medicine group,while the serum E2 level and PSV were higher than those in the Western medicine group,and the differences between the groups were statistically significant(all P<0.05).Conclusion:Herb-partitioned spreading moxibustion at Baliao points plus 展开更多
Maternal alcohol consumption is the leading known non-genetic cause of mental retardation.Prenatal alcohol exposure can cause a range of structural and functional birth defects,which are defined as Fetal Alcohol Spect...Maternal alcohol consumption is the leading known non-genetic cause of mental retardation.Prenatal alcohol exposure can cause a range of structural and functional birth defects,which are defined as Fetal Alcohol Spectrum Disorders(FASD).Growing evidence suggests that excessive cell death in selected cell populations is a major component of the pathogenesis of FASD.This suggests that a strategy for protecting against ethanol’s teratogenesis by epigenetically regulating the genes involved in the apoptotic pathway is promising for effective intervention and prevention of FASD.We have recently found that treatment with ethanol resulted in a significant decrease in miR-125b expression in neural crest cells(NCCs)and mouse embryos.We also validated that Bcl-2 antagonist killer 1(Bak1)and p53-upregulated modulator of apoptosis(PUMA)are the direct targets of miR-125b in NCCs.In addition,overexpression of miR-125b significantly reduced the ethanol-induced increase in Bak1 and PUMA protein expression,caspase-3 activation,and apoptosis in NCCs,indicating that miR-125b can modulate ethanol-induced apoptosis by the regulation of Bcl-2 and p53 pathways.Furthermore,microinjection of miR-125b mimic resulted in a significant increase in miR-125b expression and a decrease in the protein expression of Bak1 and PUMA in ethanol-exposed mouse embryos.Up-regulation of miR-125b also significantly reduced ethanol-induced caspase-3 activation and diminished ethanol-induced growth retardation in mouse embryos.Our studies have also shown that exposure to ethanol resulted in a significant increase in the activities of histone deacetylase(HDAC)and DNA methyltransferase(DNMT),and increased the methylation of Bcl-2 promoter in NCCs.In addition,ChIP-qPCR assay revealed that ethanol exposure significantly decreased acetyl-histone H3 binding to the Bcl-2 promoter and the expression of Bcl-2.Supplementing with sulforaphane(SFN),an isothiocyanate derived from cruciferous vegetables and a dual epigenetic regulator which can inhibit both DNMTs and HD展开更多
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 p...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.展开更多
As the highest portion among the central nervous system, the cerebral cortex is essential in sensory perception, especially in integration of sensation. Elaboration of visceral painful sensation and acupuncture sensat...As the highest portion among the central nervous system, the cerebral cortex is essential in sensory perception, especially in integration of sensation. Elaboration of visceral painful sensation and acupuncture sensation as well as their interaction展开更多
The corn borer spreading widely in China is a serious pest of corn, sorghum and the other crops. This species has been described by some authors as the European corn borer, Ostrinia nubilalis Hübner (Lepidoptera:...The corn borer spreading widely in China is a serious pest of corn, sorghum and the other crops. This species has been described by some authors as the European corn borer, Ostrinia nubilalis Hübner (Lepidoptera: Pyralidae), which is widely dis-展开更多
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 ffective...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 < 0.05), and the experimental group was significantly better than the control group. There was a linear correlation between PSV and FSH, PSV and E2, FSH and E2. Conclusion: Tiaojing decoction combined with climen has significant effect on diminished ovarian reserve patients with deficiency of Kidney-Yin. Uterine artery blood flow parameters can reflect the sex hormone levels.展开更多
Objective: We examined the hypothesis that cognitive dy-sfunction in Alzheimer’s disease is associated with abnormal spontaneous fluc tuations of EEG synchronization levels during an eyes-closed resting state. Met ho...Objective: We examined the hypothesis that cognitive dy-sfunction in Alzheimer’s disease is associated with abnormal spontaneous fluc tuations of EEG synchronization levels during an eyes-closed resting state. Met hods: EEGs were recorded during an eyes-closed resting state in Alzheimer patie nts (N=24;9 males; mean age 76.3 years; SD 7.8; range 59-86) and nondemented su bjects with subjective memory complaints (N=19;9males;mean age 76.1 years; SD 6. 7; range: 67-89). The mean level of synchronization was determined in different frequency bands with the synchronization likelihood and fluctuations of the syn chronization level were analysed with detrended fluctuation analysis (DFA). Resu lts: The mean level of EEG synchronization was lower in Alzheimer patients in th e upper alpha (10-13 Hz) and beta (13-30 Hz) band. Spontaneous fluctuations of synchronization were diminished in Alzheimer patients in the lower alpha (8-10 Hz) and beta bands. In patients as well as controls the synchronization fluctuat ions showed a scale-free pattern. Conclusions: Alzheimer’s disease is characte rized both by a lower mean level of functional connectivity as well as by dimini shed fluctuations in the level of synchronization.The dynamics of these fluctuat ions in patients and controls was scale-free which might point to self-organiz ed criticality of neural networks in the brain. Significance: Impaired functiona l connectivity can manifest itself not only in decreased levels of synchronizati on but also in disturbed fluctuations of synchronization levels.展开更多
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...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,P<0.0001);however,there was no difference in GDF-9 expression between the two groups(relative expression were 1.29±0.54 and 1.16±0.50 respectively,P>0.05)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 BM展开更多
基金Supported by the Fund for Beijing Science&Technology Development of Traditional Chinese Medicine(No.JJ-2018-73)。
文摘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.
基金Supported by the 2018 Program to Guide Medicine of the Shanghai Municipal Science and Technology Commission(No.18401902200)Special Project of the China Resources Sanjiu Medical and Pharmaceutical Co.and the Obstetrics&Gynecology Special Committee,the Chinese Association for the Integration of Traditional and Western Medicine(No.CR1901FC01)。
文摘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 P<0.01),BYHD also resulted in E2 elevation(P<0.05),ovary enlargement(P<0.05),AFC increase(P<0.01),and RI of ovarian 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.
基金Supported by grants from the National Institute on Aging (Nos. AG034956, AG045094)
文摘1.Introduction With the increase in older populations worldwide1 comes an increased health burden related to chronic diseases.2–4One of the most disabling of these is knee osteoarthritis(OA),which occurs in millions of older adults who subsequently live with joint pain and stiffness,leading to chronic disability and a diminished quality of life.5,6 Epidemiological evidence shows a higher prevalence of OA in older adults living in urban and
文摘Objective:To observe whether electro-acupuncture(EA) is better in improving hormone levels among women with diminished ovarian reserve(DOR) compared with oral medicine [Chinese herbs with or without hormone replacement therapy(HRT)] that is often used in gynecology clinics in China.Methods:Eligible participants entered the EA group or medication group according to their preferences.Participants in the EA group received EA treatment,and participants the medication group received herbal decoction alone or combined with HRT.Reproductive hormone levels of the participants were tested before and during treatment in both groups.Results:A total of 80 women with DOR were screened and 57 cases were included(29 in the EA group and 28 in the medication group) in the final analysis.The differences in the change from baseline between the EA and medication group in mean follicle-stimulating hormone(FSH) levels were-6.6(95% Cl,-17.03 to 3.72),(P=0.848) and-7.09(95% CI,-15.86 to 1.66),(P=0.539) at weeks 12 and 24,respectively.The proportion of women with regular FSH levels in the EA and medication group was 51.3% vs 32.1% at week 12(P=0.134) and 51.3% vs 25.0% at week 24(P=0.038).Conclusion:EA might influence regulating the levels of FSH,luteinizing hormone(LH),estrogen and the FSH/LH ratio,and no difference was found between the effects of EA and oral medicine in changes of reproductive hormone levels.
基金supported by a Chinese Military family planning project grant(No.17JS014).
文摘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 P<0.05).No significant differences were found in MII,fertilization,or continued pregnancy rates at the first frozen embryo transfer(FET),in-vitro fertilization(IVF)cancellation,or early medical abortion rates between the groups(all P>0.05).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.
基金Supported by the Clinical Medical Science and Technology Special of Jiangsu Provincial Science and Technology Project(No.BL2013039).
文摘OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From September 2014 to September2016,46 patients with DOR who received NYTYST and Climen(treatment group)and 51 patients who received Climen only(control group)at the Jiangsu Provincial Traditional Chinese Medicine Hospital(Nanjing,China)were retrospectively reviewed.Before and at 3 months after treatment,serum levels of follicle-stimulating hormone(FSH),FSH/luteinizing hormone(LH),estradiol(E2),and anti-Mullerian hormone(AMH),the antral follicle count(AFC),stromal peak systolic velocity(PSV),symptom scores,and the clinical effectiveness rate were measured and compared between the two groups.RESULTS:After treatment,serum levels of FSH,FSH/LH and E2,and symptom scores were significantly decreased compared with before treatment(all P<0.05)in the two groups.AMH levels,AFC,and PSV were significantly increased after treatment compared with before treatment in both groups(all P<0.05).Serum levels of FSH,FSH/LH,and E2 after treatment were significantly lower in the treatment group than in the control group(all P<0.05).However,AMH levels and the AFC were significantly higher after treatment in the treatment group than in the control group(both P<0.05).The clinical effectiveness rate was significantly higher in the treatment group than in the control group(87%vs 68.6%,P<0.05).CONCLUSION:NYTYST combined with Climen may be more effective in treating DOR than Climen alone.
基金Supported by LUO Yuankai Research Fund for Young Scholars(No.20190810)National Natural Science Foundation of China(No.82174429)。
文摘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 P<0.05).After treatment with ZYPs,a significant regulation of serum sex hormones was observed,including progesterone and estradiol.Both hormones were up-regulated compared with the control group(P=0.014 and 0.008),respectively.No significant differences were observed with regard to pregnancy outcomes including implantation rates,biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and pregnancy loss rates(all P>0.05).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
基金supported by grants from the National Natural Science Foundation of China(No.82001498 and No.82002768)the Natural Science Foundation of Hubei Province(No.2020CFB544)The Clinical Research Pilot Project of Tongji Hospital,Huazhong University of Science and Technology(No.2019CR205).
文摘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.
基金supported in part by Grant-in-Aid from the Japan Society for the Promotion of Science, following Grant No. 16J05114
文摘Diminishing the appearance of a fence in an image is a challenging research area due to the characteristics of fences(thinness, lack of texture, etc.) and the need for occluded background restoration. In this paper, we describe a fence removal method for an image sequence captured by a user making a sweep motion, in which occluded background is potentially observed. To make use of geometric and appearance information such as consecutive images, we use two well-known approaches: structure from motion and light field rendering. Results using real image sequences show that our method can stably segment fences and preserve background details for various fence and background combinations. A new video without the fence, with frame coherence, can be successfully provided.
文摘Objective: To get more insight in the pathophysiological basis of periodic lim b movement disorder (PLMD) with or without restless legs syndrome (RLS), we inve stigated whether these patients have spontaneous changes in H-reflexes or show altered reflex patterns after (external) inhibition or excitation of the relevan t spinal segment. Methods: The ratio of the peak-to-peak values of the maximal soleus H-reflex and the maximal direct muscle potential (H/M ratio), H-reflex recruitment curves, vibratory inhibition and recovery curves of the soleus H-r eflexin double stimulus experiments were measured in 9 PLMD patients and 11 cont rols. Results: In comparison to controls the vibratory inhibition, predominantly reflecting pre-synaptic inhibitory action, was depressed in PLMD patients. The soleus H-reflex recovery curves showed increased late facilitation and depress ed late inhibition, both reflecting diminished inhibition due to post-synaptic central activity. Conclusions: Our data indicate diminished inhibition at spinal level in PLMD patients. This is probably due to altered function of the descend ing spinal tracts, peripheral influence or changes at the inter-neural circuitr y at spinal level itself, or combinations of these 3 possibil ities. Significance: The results of this study give further insight in the pat hophysiology of PLMD and RLS by stressing the importance of diminished central i nhibition.
基金the National Science Fund for Distinguished Young Scholars(No.81925013 to R.L.)。
文摘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.
文摘Objective:To observe the clinical efficacy of herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve(DOR).Methods:A total of 60 patients with DOR were randomized into a spreading moxibustion group and a Western medicine group by the random number table method,with 30 cases in each group.The Western medicine group was treated with climen,starting from the 5th day of the menstrual cycle for 21 d.The spreading moxibustion group was treated with herb-partitioned spreading moxibustion at Baliao points on the basis of the medication in the Western medicine group,1 h per time,once a week.The treatment was performed for 1 month as one treatment course in both groups,for 3 courses in total.The serum follicle-stimulating hormone(FSH),luteinizing hormone(LH)and estradiol(E2)in the patients were measured before and after treatment.The peak systolic velocity(PSV)and resistance index(RI)were also detected.The traditional Chinese medicine(TCM)symptom score was evaluated.The clinical efficacy was evaluated after treatment.Results:The total effective rate in the spreading moxibustion group was 93.3%,which was significantly higher than 80.0%in the Western medicine group,and the difference between the groups was statistically significant(P<0.05).After treatment,the TCM symptom scores,the serum FSH levels,FSH/LH ratios and RI in both groups decreased,and the intra-group differences were all statistically significant(all P<0.05).The serum E2 level and PSV increased compared with those in the same group before treatment,and the intra-group differences were statistically significant(all P<0.05).After treatment,the TCM symptom score,the serum FSH level,FSH/LH ratio and RI in the spreading moxibustion group were lower than those in the Western medicine group,while the serum E2 level and PSV were higher than those in the Western medicine group,and the differences between the groups were statistically significant(all P<0.05).Conclusion:Herb-partitioned spreading moxibustion at Baliao points plus
文摘Maternal alcohol consumption is the leading known non-genetic cause of mental retardation.Prenatal alcohol exposure can cause a range of structural and functional birth defects,which are defined as Fetal Alcohol Spectrum Disorders(FASD).Growing evidence suggests that excessive cell death in selected cell populations is a major component of the pathogenesis of FASD.This suggests that a strategy for protecting against ethanol’s teratogenesis by epigenetically regulating the genes involved in the apoptotic pathway is promising for effective intervention and prevention of FASD.We have recently found that treatment with ethanol resulted in a significant decrease in miR-125b expression in neural crest cells(NCCs)and mouse embryos.We also validated that Bcl-2 antagonist killer 1(Bak1)and p53-upregulated modulator of apoptosis(PUMA)are the direct targets of miR-125b in NCCs.In addition,overexpression of miR-125b significantly reduced the ethanol-induced increase in Bak1 and PUMA protein expression,caspase-3 activation,and apoptosis in NCCs,indicating that miR-125b can modulate ethanol-induced apoptosis by the regulation of Bcl-2 and p53 pathways.Furthermore,microinjection of miR-125b mimic resulted in a significant increase in miR-125b expression and a decrease in the protein expression of Bak1 and PUMA in ethanol-exposed mouse embryos.Up-regulation of miR-125b also significantly reduced ethanol-induced caspase-3 activation and diminished ethanol-induced growth retardation in mouse embryos.Our studies have also shown that exposure to ethanol resulted in a significant increase in the activities of histone deacetylase(HDAC)and DNA methyltransferase(DNMT),and increased the methylation of Bcl-2 promoter in NCCs.In addition,ChIP-qPCR assay revealed that ethanol exposure significantly decreased acetyl-histone H3 binding to the Bcl-2 promoter and the expression of Bcl-2.Supplementing with sulforaphane(SFN),an isothiocyanate derived from cruciferous vegetables and a dual epigenetic regulator which can inhibit both DNMTs and HD
基金supported by grants from the Scientific Research Development Fund of Peking University People’s Hospital(No.RDY2020-27)Clinical Medicine Plus X-Young Scholars Project,Peking University,and the Fundamental Research Funds for the Central Universities(No.PKU2021LCXQ020).
文摘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.
文摘As the highest portion among the central nervous system, the cerebral cortex is essential in sensory perception, especially in integration of sensation. Elaboration of visceral painful sensation and acupuncture sensation as well as their interaction
文摘The corn borer spreading widely in China is a serious pest of corn, sorghum and the other crops. This species has been described by some authors as the European corn borer, Ostrinia nubilalis Hübner (Lepidoptera: Pyralidae), which is widely dis-
文摘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 < 0.05), and the experimental group was significantly better than the control group. There was a linear correlation between PSV and FSH, PSV and E2, FSH and E2. Conclusion: Tiaojing decoction combined with climen has significant effect on diminished ovarian reserve patients with deficiency of Kidney-Yin. Uterine artery blood flow parameters can reflect the sex hormone levels.
文摘Objective: We examined the hypothesis that cognitive dy-sfunction in Alzheimer’s disease is associated with abnormal spontaneous fluc tuations of EEG synchronization levels during an eyes-closed resting state. Met hods: EEGs were recorded during an eyes-closed resting state in Alzheimer patie nts (N=24;9 males; mean age 76.3 years; SD 7.8; range 59-86) and nondemented su bjects with subjective memory complaints (N=19;9males;mean age 76.1 years; SD 6. 7; range: 67-89). The mean level of synchronization was determined in different frequency bands with the synchronization likelihood and fluctuations of the syn chronization level were analysed with detrended fluctuation analysis (DFA). Resu lts: The mean level of EEG synchronization was lower in Alzheimer patients in th e upper alpha (10-13 Hz) and beta (13-30 Hz) band. Spontaneous fluctuations of synchronization were diminished in Alzheimer patients in the lower alpha (8-10 Hz) and beta bands. In patients as well as controls the synchronization fluctuat ions showed a scale-free pattern. Conclusions: Alzheimer’s disease is characte rized both by a lower mean level of functional connectivity as well as by dimini shed fluctuations in the level of synchronization.The dynamics of these fluctuat ions in patients and controls was scale-free which might point to self-organiz ed criticality of neural networks in the brain. Significance: Impaired functiona l connectivity can manifest itself not only in decreased levels of synchronizati on but also in disturbed fluctuations of synchronization levels.
基金supported by the Shanghai Municipal Commission of Health and Family Planning(No.20134Y096)the Shanghai Hospital Development Center(No.SHDC12014131).
文摘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,P<0.0001);however,there was no difference in GDF-9 expression between the two groups(relative expression were 1.29±0.54 and 1.16±0.50 respectively,P>0.05)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 BM