Clinical Application of Double Ovulation Stimulation in Patients with Diminished Ovarian Reserve and Asynchronous Follicular Development Undergoing Assisted Reproduction Technology

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.

Efficacy and Safety of the Chinese Herbal Compound TJAOA101 in Treating Diminished Ovarian Reserve: A Protocol for Multicenter, Prospective, and Pre-Post Study

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.

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

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.

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

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.

Rules and Characteristics of TCM Treatment Prescriptions for Patients with Decreased Ovarian Reserve

[Objectives]To analyze the characteristics and rules of traditional Chinese medicine(TCM)in the treatment of decreased ovarian reserve(DOR)in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine.[Methods]A total of 107 patients with DOR in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine were selected for sorting,and the usage,classification,nature,taste and meridian homing of the used drugs were statistically analyzed.[Results]A total of 107 patients were included in this stud and a total of 189 flavors of TCM are used.The total frequency of drugs was 4345 times,and a total of 535 prescriptions were issued.The top five frequency of drug use were 2261 times(50.04%)of Paeoniae Radix Alba(Cynanchum otophyllum Schneid.),2037 times(46.88%)of Corni Fructus(Cornus officinalis Sieb.et Zucc.),1818 times(41.84%)of Rehmanniae Radix Praeparata[Rehmannia glutinosa(Gaertn.)Libosch EX Fisch.et Mey.],1610 times(37.05%)of Guiban[Chinemys reevesii(Gray)],and 1303 times(29.99%)of Uncariae Ramulus Cum Uncis(Uncariar hynchophylla Miq.ex Havil.).Kidney deficiency syndrome accounted for the largest proportion at 51.40%,and the use frequency of tonic drugs accounted for the highest at 50.64%;heat-clearing drugs and qi and blood-boosting drugs separately accounted for 19.24%and 17.39%;the top 3 medicinal tastes are sweet(52.02%),pungent(20.71%)and bitter(20.32%);medicinal properties are ranked as warm(60.54%),cold(24.16%),hot(8.72%)and cool(6.49%);the main meridians are spleen,lung,liver,stomach and kidney.[Conclusions]The basic pathogenesis of DOR is deficiency of qi and blood,mainly due to dysfunction of the spleen,lung,liver,liver,stomach and other organs,and kidney deficiency and spleen deficiency are more common.

基于“肾主生殖”理论探讨中医治疗DOR型不孕症的生物学机制

在中医学“肾主生殖”的理论指导下,中医治疗不孕症多以补肾为主。卵巢储备功能下降(diminished ovarian reserve,DOR)是临床导致不孕症的主要病因,DOR型不孕症的发病率逐年增加且发病年龄呈年轻化趋势。中医补肾法在治疗DOR型不孕症方面具有独特优势,其生物学机制主要是调节下丘脑-垂体-卵巢轴神经内分泌功能、抑制卵巢颗粒细胞异常程序性死亡、调节免疫功能、改善卵巢过度氧化应激状态、改善线粒体功能、调节子宫内膜容受性,从而改善卵巢功能,提高生育能力。对近年来中医补肾法治疗DOR型不孕症的生物学机制进行总结,为临床应用“肾主生殖”理论治疗DOR型不孕症提供新思路。

DOR患者自然周期体外受精应用GnRH-a扳机对胚胎实验室技术指标的影响

目的:研究卵巢储备功能减退(diminished ovarian reserve,DOR)人群自然周期体外受精(in vitro fertilization,IVF)方案中,使用促性腺激素释放激素激动剂(gonadotropin-releasing hormone agonist,GnRH-a)扳机对胚胎实验室技术指标的影响。方法:回顾性分析2018年1月1日―2023年4月30日在南京医科大学附属妇产医院生殖医学中心行自然周期IVF助孕的DOR患者资料,根据是否使用GnRH-a扳机分为扳机组和未扳机组,扳机组300周期,未扳机组47周期,利用倾向性评分匹配进行1∶3匹配,分析比较两组患者的总获卵数、可移植胚胎数、优质胚胎数、正常受精率、卵子利用率、优质胚胎率和未获卵率的差异。结果:通过倾向性评分匹配后共纳入165周期(未扳机组46周期,扳机组119周期),扳机组优质胚胎率高于未扳机组(61.1%vs. 35.0%,P=0.045),两组总获卵数、可移植胚胎数、优质胚胎数、正常受精率、卵子利用率和未获卵率差异无统计学意义(P均> 0.05)。结论:自然周期使用GnRH-a扳机能提高DOR患者的优质胚胎率。

补肾养精汤分阶段治疗DOR引起月经过少的疗效及对淋巴细胞亚群的影响

目的:临床观察补肾养精汤分阶段治疗卵巢储备功能减退(DOR)引起月经过少(肾虚血瘀型)的疗效及对外周血淋巴细胞亚群表达的影响。方法:将70例肾虚血瘀型月经过少的DOR患者随机分成治疗组(补肾养精汤)和对照组(芬吗通),每组35例,分卵泡期和黄体期两阶段给药,连续治疗3个月经周期。观察两组患者治疗前、后的临床症状、血清激素水平、淋巴细胞亚群、窦卵泡数量以及卵巢间质血流变化,比较两组临床疗效及药物安全性。结果:治疗后,两组患者中医证候积分减少、经量积分增加,血清bFSH降低、bE2升高,CD8^(+)T细胞减少、CD4^(+)T细胞和B细胞增多(P<0.05或P<0.01);治疗组患者经期积分增加,卵巢间质PSV增加、RI降低,AMH和AFC均增高(P<0.05)。与对照组比较,治疗组患者中医证候积分、CD8^(+)细胞和PI均显著降低(P<0.05),经量积分、经期积分、AMH、AFC、PSV、CD4^(+)T细胞及B细胞均显著升高(P<0.05)。综合疗效比较,治疗组愈显率(48.57%)和总有效率(88.57%)较对照组(28.57%,65.71%)明显升高。研究过程中未出现不良事件。结论:补肾养精汤分阶段治疗可以有效改善DOR合并月经过少(肾虚血瘀型)患者的卵巢储备,增加经量、延长经期,还可以改善卵巢间质血流,调节机体免疫平衡,疗效优于激素替代治疗,值得临床推广应用。

疏肝滋肾方联合穴位针刺治疗对DOR患者IVF-ET妊娠结局的影响

目的探讨疏肝滋肾方联合穴位针刺治疗方案对卵巢储备功能下降(DOR)患者体外受精-胚胎移植(IVF-ET)妊娠结局的影响。方法选取2020年1月至2021年12月河北省沧州中西医结合医院收治的90例DOR患者作为研究对象,随机分为对照组和观察组,各45例。对照组采用拮抗剂固定治疗方案,观察组在对照组的基础上采用疏肝滋肾方联合穴位针刺治疗。观察两组患者的生殖激素水平及人绒毛膜促性腺激素(hCG)阳性率、临床妊娠率、胚胎种植率和活产率。结果两组治疗后雌二醇(E_(2))、睾酮(T)、催乳素(PRL)水平均比治疗前升高,卵泡刺激素(FSH)、黄体生成素(LH)水平比治疗前降低,观察组生殖激素指标水平改善程度均显著高于对照组,差异均具有统计学意义(P<0.05)。观察组hCG阳性率、临床妊娠率、胚胎种植率、活产率均高于对照组,差异均具有统计学意义(P<0.05)。结论疏肝滋肾方联合穴位针刺治疗能改善DOR患者的卵巢储备功能,提高DOR患者IVF-ET的妊娠率。

艾灸八髎穴区痧点治疗高龄肾虚血瘀证DOR的临床研究

目的:比较艾灸八髎穴区痧点结合激素治疗与单纯激素治疗高龄肾虚血瘀证卵巢储备功能减退的疗效差异。方法:将64例卵巢储备功能减退患者随机分为观察组和对照组各32例,观察组采用艾灸八髎穴区痧点结合激素周期治疗,艾灸每次1h,每周治疗3次,经期停用;对照组采用单纯激素周期治疗;两组均1个月经周期为1个疗程,治疗3个疗程结束,观察两组治疗前后卵泡刺激素(FSH)、促黄体生成素(LH)、雌二醇(E2)、抗苗勒管激素(AMH)、FSH/LH比值、中医证候积分及HAMD、HAMA评分的变化情况。结果:两组治疗后血清FSH、LH、FSH/LH、中医证候积分、HAMD、HAMA均显著降低,血清E2及AMH均显著提高(P<0.05),且观察组治疗后血清FSH、LH、FSH/LH、中医证候积分、HAMD、HAMA评分均低于对照组,而血清E2及AMH高于对照组,差异均有统计学意义(P<0.05)。结论:艾灸八髎穴区痧点联合激素周期疗法治疗高龄肾虚血瘀证卵巢储备功能减退在改善患者性激素、相关症状及情绪方面优于单纯激素周期治疗。

Treatment Progress in Diminished Ovarian Reserve:Western and Chinese Medicine

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.

Acupuncture versus oral medicine for women with diminished ovarian reserve:A cohort study

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.

Effects of Bushen Yiqi Huoxue Decoction in Treatment of Patients with Diminished Ovarian Reserve:A Randomized Controlled Trial

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.

Effectiveness of nourishing Yin and tonifying Yang sequential therapy in combination with Climen on diminished ovarian reserve: a retrospective study

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.

Clinical observation on herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve

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 climen can produce valid therapeutic efficacy for DOR.It can improve the clinical symptoms,regulate serum hormone levels and increase ovarian blood perfusion,thus improving ovarian reserve function,producing more significant efficacy than climen alone.

Recent progress in the treatment of women with diminished ovarian reserve

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.

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

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 patients undergoing IVF-ET,resulting in increments of oocytes and embryos,and up-regulation of BMP15 and GDF9 expressions in the FF.However,the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes(Trial reqistration No.Chi CTR2100048441).

Effects of Dehydroepiandrosterone on Embryo Quality and Follicular Fluid Markers in Patients with Diminished Ovarian Reserves

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 BMP-15 in the FF.

归肾丸对DOR小鼠卵巢超微结构的影响

目的探讨归肾丸对卵巢储备功能低下(diminished ovarian reserve,DOR)小鼠的颗粒细胞超微结构的影响。方法将20只C57BL/6J雌性小鼠随机分为正常组、模型组、归肾丸组和脱氢表雄酮(DHEA)组。连续序贯腹腔注射孕马血清(PMSG)、人绒毛膜促性腺激素(HCG)、前列腺素F2α(PGF2α)产生连续超数排卵,再结合臭氧吸入构建DOR模型。其后各治疗组给予相应药物灌胃,而正常组与模型组给予生理盐水灌胃。21d后,采用透射电镜观察各组小鼠卵巢颗粒细胞超微结构的变化。结果模型组中线粒体肿胀明显,还出现了空泡化改变,且较少看到脂滴,各治疗组卵巢超微结构较模型组有明显差异,颗粒细胞线粒体形态规则,管型明显,胞质内脂滴丰富。结论归肾丸对DOR模型小鼠卵巢超微结构有较明显的改善作用。