Research progress on animal models of diminished ovarian reserve / 中国实验动物学报

Diminished ovarian reserve(DOR)is associated with a reduced quantity and/or quality of retrieved oocytes,usually leading to low numbers of retrieved oocytes and poor reproductive outcomes.DOR may potentially progress to premature ovarian insufficiency and premature ovarian failure,which have adverse impacts on women's health.There is currently no effective clinical treatment to rescue ovarian function.The limited availability of human ovarian tissues and medical ethics issues mean that animal models are crucial for improving our understanding of the molecular pathogenesis of DOR and identifying preventive and therapeutic targets.This review thus aims to summarize the techniques and strategies used to establish rodent models of DOR,to provide a reference for future studies.

Clinical observation of letrozole combined with methylprednisolone in the treatment of infertile patients with polycystic ovary syndrome resistant to clomiphene / 中国药房

OBJECTIVE To explore the effects of letrozole combined with methylprednisolone on clinical outcomes， ovarian reserve function， serum sex hormones， and safety in infertile patients with polycystic ovary syndrome resistant to clomiphene. METHODS The clinical data of 78 infertile patients with polycystic ovary syndrome resistant to clomiphene in the Department of Gynecology of Qingdao Central Hospital from February 2021 to January 2022 was analyzed retrospectively， and all patients were divided into control group （42 cases） and observation group （36 cases） based on the treatment methods. The control group took letrozole 5 mg/d orally on the 5th to 9th day of the menstrual cycle. Vaginal ultrasound was used to monitor the development of the endometrium and follicles； estradiol valerate was used to correct endometrial thickness， and measures such as inducing ovulation with follicle-stimulating hormone were taken to promote pregnancy. On the basis of treatment in the control group， the observation group began taking methylprednisolone orally at a dose of 4 mg/d starting from the third day of natural menstruation or withdrawal bleeding. Both groups were treated for 6 menstrual cycles. The ovulation and pregnancy within one year， serum levels of sex hormones [estradiol （E2）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， testosterone] and anti-Müllerian hormone （AMH）， ovulation indicators （follicle growth time， the number of ovulations， and the number of dominant follicles）， and the occurrence of adverse drug reactions were compared between the two groups. RESULTS After treatment， the biochemical pregnancy rate （72.22%） and clinical pregnancy rate （47.22%） of the observation group were significantly higher than those of control group （47.62%， 19.05%）； the serum levels of E2， LH， FSH， testosterone and AMH were significantly lower than the control group； the follicle growth time was significantly shorter than the control group； the number of ovulation and dominant follicles were significantly higher than the control group （P＜0.05）. There was no statistically significant difference in ovulation rate （94.44% vs. 83.33%） and total incidence of adverse drug reactions （8.33% vs. 9.52%） between the observation group and the control group （P＞0.05）. CONCLUSIONS Compared with letrozole alone， the combination of letrozole and methylprednisolone can significantly improve the pregnancy rate， the sex hormone levels and ovarian reserve function in infertile patients with polycystic ovary syndrome resistant to clomiphene， with high safety profiles.

Effect of laparoscopic salpingectomy on ovarian reserve function and serum neuropeptide Y and cortisol in patients with ectopic pregnancy / 实用医学杂志

Objective To explore the effect of laparoscopic salpingectomy on ovarian reserve function and serum neuropeptide Y(NPY)and cortisol(Cor)in patients with ectopic pregnancy.Methods 82 patients with ectopic pregnancy who had visited Chaohu Hospital Affiliated to Anhui Medical University from June 2018 to June 2021 were randomly divided into two groups,with 41 in each group.The control group underwent laparoscopic salpingostomy and suturing for embryo retrieval,while the study group underwent laparoscopic salpingectomy.Surgical duration,intraoperative blood loss,time to postsurgical mobilization,length of hospital stay,serum NPY and Cor levels,antral follicle count(AFC),indexes for peak flow velocity and resistance of ovarian artery were compared between the two groups.Follow-up was conducted for two years after surgery,and the success rate of pregnancy and the ectopic pregnancy rate were recorded.Results The surgical duration in the study group was shorter than that in the control group(P<0.05).The differences in serum NPY and Cor values between the two groups immediately after surgery and at postoperative week one were not statistically significant(P>0.05).At postoperative months1 and 6,the peak flow velocity of the affected ovary was lower in the study group than in the control group,whereas the resistance index was higher(P<0.05).At postoperative month 6,both groups showed an increase in peak flow velocity and a decrease in resistance index(P<0.05).There were no statistically signifi-cant differences in AFC and the success rate of pregnancy between the two groups postoperatively(P>0.05).The ectopic pregnancy rate in the study group was lower than that in the control group(P<0.05).Conclusion As compared with laparoscopic salpingostomy,laparoscopic salpingectomy for ectopic pregnancy can also preserve postoperative ovarian antral follicle count(AFC),and it has greater advantage in reducing the risk of recurrent ectopic pregnancy after surgery.

circRAF1 regulates the proliferation and apoptosis of human ovarian granulosa cells / 实用医学杂志

Objective To investigate the expression of circRAF1 in primary ovarian insufficiency(POI)and explore its effect on cell proliferation and apoptosis of human ovarian granulosa cells(GCs)line(KGN cells).Methods The expression of circRAF1 in GCs and serum of patients with normal ovarian reserve function(n = 50)and patients with POI(n = 50)were detected with RT-qPCR.The correlation of circRAF1 with ovarian reserve function indexes was analyzed.Small interfering RNA(siRNA)targeting circRAF1 was constructed and trans-fected into KGN cells,with the cell proliferation detected by CCK-8 and EdU assay,and the cell apoptosis detected by JC-1 and Tunel assay.The mRNA and protein levels of genes related to cell proliferation and apoptosis(FSHR,PCNA,Bcl-2,Casp-9,Bax)were detected by RT-qPCR and WB.Results The expression of circRAF1 decreased in GCs and serum of POI patients.The expression of circRAF1 was positively correlated with serum E2 and AMH levels(P<0.001),but negatively correlated with serum FSH and LH levels(P<0.001).At the same time,the expression of circRAF1 was positively correlated with AFC(P<0.001).Interfering with the expression of circRAF1 could inhibit the proliferation of KGN cells and promote their apoptosis.Conclusion The expression of circRAF1 in the GCs and serum of POI patients is down-regulated,which is correlated with the decline of ovarian reserve function.Interfering with circRAF1 can inhibit the proliferation of GCs and promote their apoptosis.

Clinical observation of goserelin combined with estradiol valerate in the treatment of endometriosis in patients of childbearing age after laparoscopic surgery / 中国药房

OBJECTIVE To observe the efficacy and safety of goserelin combined with estradiol valerate in the treatment of endometriosis （EMs） in patients of childbearing age after laparoscopic surgery. METHODS The clinical data of 144 patients with EMs of childbearing age who underwent laparoscopic surgery in our hospital from January 2020 to December 2022 were collected retrospectively， and those patients were divided into control group （70 cases） and combination group （74 cases） based on different postoperative medication regimens. Control group was given Acetate goserelin sustained-release implant on the 1st to 5th day of their first menstrual cycle after laparoscopic surgery， while combination group was additionally given Estradiol valerate tablets on the basis of control group. The short-term and long-term efficacy of 2 groups were observed； preoperative and postoperative pain scores， ovarian reserve function， and the incidence of adverse reactions were all recorded in 2 groups. RESULTS There was no statistically significant difference in short-term total effective rate， 1-year postoperative recurrence rate and the incidence of decreased libido， vaginal dryness， gastrointestinal reactions， rash， or arrhythmia between two groups （P＞0.05）. The natural pregnancy rate of combination group was significantly higher than control group at 1 year after surgery， while the incidence E-mail：wanghuiling0518@126.com of early miscarriage， hot flashes and sweating， emotional fluctuations， insomnia and fatigue， joint muscle pain， dizziness and headache were significantly lower than control group （P＜0.05）. However， at 6 months after surgery， pain scores and the levels of anti-Müllerian hormone， follicle stimulating hormone， luteinizing hormone， estradiol of both groups were significantly lower than before surgery in the same group， while the number of antral follicle count was significantly higher than before surgery in the same group； the levels of anti-Müllerian hormone， luteinizing hormone， estradiol， and the number of antral follicles in the combination group were significantly higher than control group， while pain score and follicle stimulating hormone level were significantly lower than control group （P＜0.05）. CONCLUSIONS The combination of goserelin and estradiol valerate after laparoscopic surgery has a significant therapeutic effect and good safety in the treatment of EMs of childbearing age.

Zuoguiwan Prevent Decreased Ovarian Reserve in Prenatal Stressed Offspring Rats via TLR4/NF-κB p65 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress （PS） and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 （TLR4/NF-κB p65） signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups （n=8）： control， model， Zuoguiwan （18.9 mg·kg-1）， and vitamin E （1.44 mg·kg-1）. Except the control group， the other three groups were subjected to chronic unpredictable mild stress （CUMS） from day 11 of pregnancy， and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test， open field test， and serum corticosterone （CORT） level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol （E2）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， and anti-Mullerian hormone （AMH） in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay （ELISA） to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence （IF） assay. The expression of TLR4， NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group， the model group showed reduced primordial follicles in the offspring on the day of birth （P<0.01） as well as disturbed estrous cycle， decreased ovary index and uterus index （P<0.01）， reduced corpus luteum， increased atretic follicles （P<0.01）， lowered serum levels of AMH and E2 （P<0.01）， elevated serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and up-regulated protein levels of TLR4， NF-κB p65， recombinant myeloid differentiation factor 88 （MyD88）， and phosphorylated NF-κB inhibitor （p-IκBα） （P<0.01） in the 75-day-old offspring rats. Compared with the model group， Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth （P<0.01）. Moreover， they resumed the estrous cycle， increased the ovary and uterine indices （P<0.05， P<0.01） and corpus luteum （P<0.01）， reduced atretic follicles （P<0.01）， elevated the serum levels of AMH and E2 （P<0.05， P<0.01）， lowered the serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and down-regulated the expression of TLR4， NF-κB p65， MyD88， and p-IκB-α （P<0.05， P<0.01） in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.

Effect of Zishen-Yutai pills on refrozen-thawed embryo transfer in patients with diminished ovarian reserve / 中国组织工程研究

BACKGROUND:Currently,hormone replacement therapy is the main treatment in Western medicine for patients with decreased ovarian function,but these patients are not sensitive to exogenous hormones,leading to unsatisfactory therapeutic effect.Zishen-Yutai pills can nourish the blood and calm the fetus,tonify the kidney and spleen,invigorate qi and strengthen the body.Studies have confirmed that Zishen-Yutai pill is effective in reducing follicle-stimulating hormone index and improving traditional Chinese medicine symptoms in patients with diminished ovarian reserve.However,few studies have been conducted to improve the implantation rate of patients by improving endometrial receptivity. OBJECTIVE:To evaluate the effect of Zishen-Yutai pills on the clinical outcome of patients with diminished ovarian reserve undergoing frozen-thawed embryo transfer again. METHODS:A total of 300 patients with diminished ovarian reserve who underwent frozen-thawed embryo transfer to assist pregnancy after the first failure in the Center of Reproductive Medicine,Changzhou Maternal and Child Health Care Hospital from January 2019 to December 2021 were selected as the study subjects.Subjects were randomly treated with a placebo or Zishen-Yutai pills in a ratio of 1:2,with 100 cases in the treatment group and 200 cases in the control group.However,13 patients fell off due to lack of contact,refusal to take medicine or other reasons.Finally,90 cases in the treatment group and 197 cases in the control group were included in the study.Oral medication was administered 7 days before frozen-thawed embryo transfer transplantation at a dose of 5 g/time,3 times/day.To investigate whether taking Zishen-Yutai pills could improve the clinical outcome of patients with diminished ovarian reserve after frozen-thawed embryo transfer again,the primary outcome measures included clinical pregnancy rate,implantation rate,abortion rate,live birth rate,offspring birth weight and birth defects. RESULTS AND CONCLUSION:Compared with the control group,the clinical pregnancy rate(P<0.05)and implantation rate(P=0.009)were significantly increased after the oral administration of Zishen-Yutai pills.Correlation analysis showed that taking the Zishen-Yutai pill was positively correlated with the number of implanted embryos(r=0.200,P=0.001)and clinical pregnancy(r=0.235,P=0.000).There was no correlation between taking Zishen-Yutai pills and indexes of endometrial thickness and blood flow.It is indicated that Zishen-Yutai pills can improve the clinical pregnancy rate and implantation rate of frozen-thawed embryo transfer recurrence in patients with diminished ovarian reserve.

Effect of high intensity focused ultrasound treatment on ovarian reserve capacity in adenomyosis / 医疗卫生装备

Objective To explore the impact of high intensity focused ultrasound(HIFU)treatment on ovarian reserve capacity in adenomyosis.Methods Clinical data of 106 adenomyosis patients who underwent HIFU treatment from May 2019 to December 2020 at some hospital were analyzed retrospectively.All the patients were treated with HIFU,and color Doppler ultrasonography was performed before and after 6 months of treatment,respectively.The resistance index,pulsatility index,vascularization index,blood flow index,vascularization blood flow index and sinus follicle number were obtained,and serum anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH)and luteinizing hormone(luteinizing hormone)were measured.The correlation between serum AMH levels and FSH and LH levels was analyzed.SPSS 21.0 statistical software was used for data analysis.Results After 6 months of treatment serum FSH,LH,value of FSH/LH,resistance index and pulsatility index significantly decreased while vascularization index,blood flow index,vascularization blood flow index,number of sinus follicles,and serum AMH level obviously increased when compared with those before treatment,with the differences being statistically significant(P＜0.05).Serum AMH levels were negatively correlated with FSH and LH levels(r=-0.448,-0.527,P＜0.05)after 6 months of treatment.Conclusion HIFU treatment reduces sex hormone levels,elevates serum AMH levels and sinus follicle number,and may improve ovarian reserve capacity in patients with adenomyosis.[Chinese Medical Equipment Journal,2024,45(1):67-70]

Fertilización asistida con óvulos propios en mujeres mayores de 40 años: indicaciones y resultados

Las mujeres posponen su maternidad por el deseo de superación personal y profesional. Se conoce que la cantidad y calidad de los óvulos por ciclo dependen de la edad de la paciente. Las tasas de éxito en tratamientos de reproducción asistida disminuyen con la edad, especialmente después de los 40 años. Se observan tasas más altas de nacidos vivos en mujeres más jóvenes y las tasas disminuyen significativamente en mujeres mayores debido a la disminución de la fertilidad y el aumento de abortos espontáneos. Por ello, la edad es crucial al evaluar la posibilidad de un embarazo exitoso mediante tratamientos de reproducción asistida (TRA). Las indicaciones para realizar fertilización in vitro (FIV) con óvulos propios en mujeres mayores de 40 años incluyen iniciar lo más pronto procedimientos de alta complejidad, buena evaluación de la reserva ovárica con análisis de la hormona antimülleriana y conteo de folículos antrales para realizar asesoramiento genético, proponer FIV-inyección intracitoplasmática de espermatozoides (ICSI) antes de los 44 años, generar expectativas realistas y realizar consentimiento informado, con estadisticas propias. En la REDLARA, de todos los procedimientos de FIV-ICSI, el 34% de las pacientes tienen más de 40 años; se prefiere transferir blastocistos con prueba genética preimplantacional de aneuploidías (PGT-A) para seleccionar embriones euploides. Las tasas de éxito son bajas, inclusive cuando son tasas de embarazo por transferencia de un embrión en el grupo de mujeres ≥ 40 años (18,2% sin PGT, 42,7% con PGT en el IMRCRP). Se recomienda acumular óvulos o embriones realizando múltiples estimulaciones ováricas. Se debe optar por transferir un solo embrión para evitar complicaciones obstétricas con embarazos múltiples en pacientes ≥ 40 años, por el alto riesgo debido a la edad.

Women postpone motherhood because of their desire for personal and professional improvement. It is known that the quantity and quality of oocytes per cycle depends on the patient's age. Success rates in assisted reproduction treatments decrease with age, especially after 40 years of age. Higher live birth rates are observed in younger women, and rates decrease significantly in older women due to decreased fertility and increased miscarriages. Therefore, age is crucial when assessing the possibility of a successful pregnancy through assisted reproductive treatments (ART). The indications to perform in vitro fertilization (IVF) with own ovules in women older than 40 years include starting as soon as possible highly complex procedures, good evaluation of ovarian reserve with antimüllerian hormone analysis (AMH) and antral follicle count (AFC) for genetic counseling, proposing IVF-intracytoplasmatic sperm injection (ICSI) before the age of 44 years, generating realistic expectations and informed consent, with own statistics. At REDLARA, of all IVF-ICSI procedures, 34% of patients are over 40 years old; preference is given to transfer blastocysts with preimplantation genetic testing for aneuploidy (PGT-A) to select euploid embryos. Success rates are low, even when they are pregnancy rates per embryo transfer in the group of women ≥ 40 years (18.2% without PGT, 42.7% with PGT in IMRCRP). It is recommended to bank ovules or embryos by performing multiple ovarian stimulations. A single embryo transfer should be chosen to avoid obstetric complications with multiple pregnancies in patients ≤ 40 years, because of the high risk due to age.

Estimulación ovárica en síndrome de Mayer-Rokitansky: reporte de caso y revisión de la literatura / Controlled ovarian stimulation in Mayer-Rokitansky syndrome: case report and literature review

Resumen El síndrome de Mayer-Rokitansky-Küster-Hauser (SMRKH) es una anomalía del tracto genital femenino caracterizada por ausencia congénita del útero y porción superior de la vagina. Ocurre en uno de cada 4,500 nacimientos y se diagnostica normalmente durante la adolescencia al presentarse amenorrea primaria. Su función ovárica está preservada, pero la información actual respecto al potencial reproductivo de estas pacientes es limitada. Se presenta el caso de una mujer con diagnóstico de SMRKH sometida a estimulación ovárica para transferencia de embriones a útero subrogado y se discute su potencial reproductivo: técnicas de reproducción asistida, intervenciones e impacto psicológico.

Abstract Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is a congenital anomaly of the female genital tract characterized by congenital absence of the uterus and upper part of the vagina. It occurs in 4,500 female births and diagnosis is usually made during adolescence when primary amenorrhea presents. They have functioning ovaries but data regarding their reproductive potential is limited. We hereby report the case of a woman diagnosed with MRKH syndrome in whom assisted reproductive techniques were used to try to achieve pregnancy by gestational surrogacy and their reproductive potential is discussed: assisted reproductive techniques, procedures, and psychological impact.

Ovarian reserve in adolescent girls with autoimmune thyroiditis

ABSTRACT Objectives: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusions: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

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 / 中国结合医学杂志

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 fertilization-embryo 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 (GnRH) 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 enzyme-linked 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. ChiCTR2100048441).

Prevention and Treatment of Age-related Ovarian Hypofunction with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Age-related ovarian hypofunction includes a decrease in follicle quantity and quality as well as alterations in the ovarian microenvironment，the mechanisms of which are mainly related to mitochondrial dysfunction，free radical and antioxidant systems，telomere and telomerase alterations，and apoptosis，and is one of the major factors contributing to infertility in advanced maternal age （AMA）. Despite the tremendous progress in assisted reproductive technology in recent decades，few breakthroughs have been made in alleviating age-related ovarian hypofunction and improving reproductive outcomes for AMA. In recent years，there has been an increasing number of studies on the multi-level and multi-targeted mechanisms of traditional Chinese medicine （TCM） to improve age-related ovarian hypofunction by modulating mitochondrial homeostasis，alleviating oxidative stress，and inhibiting apoptosis，while more high-quality randomized controlled trials have demonstrated the clinical efficacy of TCM in assisted reproductive technology. Given this，this article presented a systematic review of recent research and randomized controlled trials on the mechanism of Chinese medicine active ingredients，single Chinese medicine， and Chinese medicine compounds in delaying age-related ovarian hypofunction，to clarify the current status and shortcomings of the research. This paper provides medication management of TCM for effectively alleviating age-related ovarian hypofunction and improving reproductive outcomes for AMA.

Mechanism of Liuwei Dihuang Pills in treatment of mice with diminished ovarian reserve based on proteomics / 中国中药杂志

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.

Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics / 中国中药杂志

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

Factors affecting decreased ovarian reserve among women of childbearing age / 预防医学

Objective@#To investigate the factors affecting decreased ovarian reserve (DOR) among women of childbearing age, so as to provide insights into prevention of DOR.@*Methods@#Women with DOR at ages of 18 to 40 years that were admitted to Department of Gynecology, Ningbo Women and Children's Hospital during the period from January 2021 to June 2022 were recruited (DOR group), while healthy women at ages of 18 to 40 years during the same period served as normal controls. Participants' demographics, exercise, diet, previous medical history, childbearing history and menstruation were collected using questionnaire surveys. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and estradiol (E2) levels were tested. Factors affecting DOR were identified among women of childbearing age using a multivariable logistic regression model.@*Results@#There were 200 participants in the DOR group, with a median (interquartile range) age of 32 (9) years, and 200 participants in the normal group, with a median (interquartile range) age of 29 (12) years. Multivariable logistic regression analysis showed that underweight (OR=2.935, 95%CI: 1.374-6.269), overweight/obesity (OR=2.612, 95%CI: 1.335-5.065), high-oil-high-glucose-high-salt diet (OR=2.653, 95%CI: 1.616-4.357), menstrual disorder (OR=1.977, 95%CI: 1.284-3.041) and lack of exercise (OR=3.392, 95%CI: 2.052-5.606) were statistically correlated with the development of DOR among women of childbearing age.@*Conclusions@#Underweight, overweight/obesity, high-oil-high-glucose-high-salt diet, menstrual disorder and lack of exercise are factors affecting the development of DOR among women of childbearing age.

Treatment Progress in Diminished Ovarian Reserve: Western and Chinese Medicine / 中国结合医学杂志

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.

Evaluation and Analysis of Modeling Methods for Animal Models with Diminished Ovarian Reserve / 实验动物与比较医学

ObjectiveTo analysis the modeling characteristics of diminished ovarian reserve (DOR) animal models, and provide the reference for the standardization of DOR animal models.MethodsThe research articles on DOR animal models were retrieved. Microsoft Excel 2010 software was used to summarize the experimental animal species, modeling methods, modeling cycles, high-frequency detection indexes and types of positive drugs documented in the literature, and the data results were evaluated and analyzed by NoteExpress software.ResultsA total of 93 research articles on DOR that met the criteria were enrolled. And it was found that, SD rat was the most frequently used animal type (68 times, 73.12%), followed by C57BL/6 mouse (13 times, 13.98%), while the tripterygium wilfordii treatment was the most frequently used modeling method (38 times, 40.86%), followed by the cyclophosphamide treatment (28 times, 30.11%) for DOR animal models. The high frequency detection indicators were vaginal exfoliation cytology detection (93 times, 23.97%) and HE staining to observe histopathological changes (72 times, 18.56%). Among these 64 research articles containing positive control drugs, the most frequently used western drug was estrogen (50 times,62.50%) and Chinese Traditional medicine was Kuntai capsules (2 times, 2.50%).ConclusionsSD rats are mostly used to induce modeling in animal experiments on DOR through tripterygium wilfordii and cyclophosphamide, which can effectively improve the experimental efficiency. It is recommended to integrate the results of ovarian histopathology and serum biochemical indexes for model assessment.

Exploration on the medication law of Hu Guohua in treating diminished ovarian reserve based on data mining / 国际中医中药杂志

Objective:To explore the medication law and academic thought of Professor Hu Guohua in treating diminished ovarian reserve (DOR) based on data mining.Methods:Collecting the medical records of DOR patients treated by Prof. Hu from January 1, 2021 to March 31, 2022. The TCM symptoms, tongue and pulse conditions, as well as the frequency, taste, meridian tropism and efficacy categories of TCM were analyzed by using the Traditional Chinese Medicine Inheritance Computing Platform V3.0 software. Commonly used drug combination analysis, high-frequency drug network relationship analysis, association rule analysis based on Apriori algorithm, cluster analysis based on K-means clustering algorithm, and core prescriptions were summarized.Results:A total of 85 DOR patients were included, involving 76 TCM symptoms, 15 tongue images, 11 pulse images. A total of 415 prescriptions were included, involving 164 kinds of Chinese materia medica. High-frequency drugs included Ligustri Lucidi Fructus, Angelicae Sinensis Radix, Astragali Radix, Cuscutae Semen, Herba Leonuri and Rhizoma Atractylodis Macrocephalae. The medicines were mostly warm, mild and cold in property, and the tastes were mostly sweet, bitter and pungent, mainly belonging to the liver, spleen and kidney meridians. 42 high-frequency drug combinations and 6 core prescriptions were obtained.Conclusions:Professor Hu treats DOR with the principle of tonifying the kidney and spleen to regulate body constitution, conditioning Chong Vessel and Conception Vessel to regulate the menstruation, soothing the liver and tranquillizing the heart to regulate the spirit. Professor Hu selects the medicines which are simplified and condensed, and is good at using drugs. The prescriptions are persistent and flexible, concerning the balance.

Clinical analysis of the effect of pituitrin in laparoscopic stripping of ovarian cystectomy / 中国医师进修杂志

Objective:To discusse the value of pituitin in laparoscopic ovarian cyst removal.Methods:From October 2015 to June 2018 in Dalian Medical University Affiliated Dalian Maternity Hospital, useing prospective research methods, 90 patients with unilateral ovarian cyst (except endometriomas) were randomly divided in 3 groups of pituitrin group,control group 1 and control group 2. The pituitrin group: laparoscopic cystectomy with the injection of diluted pituitrin 6 U, the total amount of diluted pituitrin 10 - 20 ml, ovarian hemostasis was achieved by sutura. The control group 1: ordinary laparoscopic cystectomy without injection suture hemostasis. The control group 2: laparoscopic cystectomy with the injection of normal saline 10 - 20 ml, ovarian hemostasis was same to pituitrin group. The operation time and the amount of bleeding were compared among the three groups. The ovarian reserve was compared between before and 3 months after operation by estradiol (E 2), follicle-stimulating hormone (FSH), luteinizing hormone (LH). Results:The amount of bleeding in the pituitrin group was less than that in the control group1: (14.00 ± 5.48) ml vs. (18.33 ± 6.99) ml, P<0.05. The operation time in the pituitrin group and control group 2 was less than that in the control group1: (43.50 ± 7.21) min, (45.00 ± 10.29) min vs. (50.17 ± 8.95) min, P<0.05. The level of FSH after operatiaon in the pituitrin group and control group 2 was less than that in the control group1: (7.20 ± 1.55) U/L, (7.43 ± 1.52) U/L vs. (8.31 ± 0.97) U/L, P<0.05. The level of E 2 3 months after operation in the pituitrin group was higher than that in the control group 1 and control group 2: (54.20 ± 10.90) ng/L vs. (46.63 ± 10.76) ng/L, (43.90 ± 18.23) ng/L, P<0.05. There was no significant difference of LH 3 months after operation among the three groups ( P>0.05). Conclusions:This study shows that diluted pituitrin decreases operation time and the amount of bleeding during operation, at the same time,the pituitrin injection is valued of ovarian reserve.