Treatment Of Premature Ovarian Failure Research Articles

RETRACTED: Network optimization of hospital computer processing system and clinical effect of alendronate in the treatment of premature ovarian failure

Abstract Mental perception, this information assortment in metropolitan zones, empowers the human body and physiology to be driven by the requirement for gathered information in the space accessible from the most recent available people of innovation. The cycle of activity is the rise of clinical remote sensor networks as of late. With this investigation, the well-being field has some basic applications because of their necessary degrees of unwavering quality and clinical information protection. Since need to guarantee security, examine the difficulties of remote sensor networks in sending cites. These difficulties are exacerbated by the shortage of assets inalienable in remote sensor network destinations. The enormous scope of physiological and conduct examines the utilization of columns from perception physiology and capacity area examination to introduce a model structure that features progressing issues. Illnesses that distinguish themselves other than estragon lack incorporate essential parathyroids, thyroid harmfulness, and cardiac infection. It builds the danger of cracks more than estrogen and bisphosphonates, particularly non-vertebral breaks, causing expanded thyroid hormone treatment. It doesn't invigorate bone development and acts by forestalling bone devastation if this everyday mixture follows.

Curcumin and Hesperidin alleviates oxidative stress and hormonal alterations in a rat model of cyclophosphamide-induced premature ovarian failure

Premature ovarian failure (POF) is a cessation of ovarian function in women under 40 years of age. Ovarian atrophy leads to a reduced follicle reserve, which leads to menstrual irregularities, ovarian dysfunction, and infertility. The beneficial effects of curcumin (CRC) and hesperidin (HSP) on Cyclophosphamide –induced Premature ovarian failure (POF) in a rat model were studied. POF was induced by intraperitoneal (i.p) injection of cyclophosphamide (200 mg/kg b.wt) at day one, and then (8 mg/kg b.wt/day) for the following 14 days. Two weeks after POF induction, treatment with CRC (100 mg/kg b.wt/day, i.p) and HSP (80 mg/kg b.wt/day, i.p) were started and continued for 14 days. Ninety female rats were divided into six equal groups. Group 1( Control normal group) rats received no drugs, Group 2 (POF-induced group), Group 3 (POF + CRC treated), Group 4 ( POF + HSP treated), Group5 ( POF + CRC+HSP treated) and Group 6 (Normal+CRC+HSP treated). Serum follicle-stimulating hormone (FSH) and ovarian tissues Malonedialdehyde (MDA) concentrations were significantly increased while serum estradiol (E2) level, ovarian superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration were markedly decreased in POF group as compared with control group. However, a significant increase in serum E2 , ovarian tissues SOD activity and GSH level and marked decrease in FSH and MDA concentrations were observed in rats treated with CRC or/and HSP compared with the POF group. Conclusively, curcumin and hesperidin provided an effective treatment for Premature ovarian failure induced by Cyclophosphamide in rats.

Protective Effects of Puerarin on Premature Ovarian Failure via Regulation of Wnt/β-catenin Signaling Pathway and Oxidative Stress.

This study was designed to investigate the protective effects of puerarin (PUE), which work via the Wnt/β-catenin signaling pathway, and oxidative stress in the premature ovarian failure (POF) model. Two-month-old female mice were randomly divided into four groups. One group was used as the control, and the other three groups were injected with cyclophosphamide and busulfan to create POF models. Two POF treatment groups were gavaged with 100 or 200mg/kg PUE for 28days. Next, the ovaries were fixed, and the numbers of different stage follicles were measured, and the ovarian surface epithelium (OSE) was collected. Oct4 and Mvh expression, Wnt/β-catenin signaling pathway activity, the oxidative stress factors SOD2 and Nrf2, and the apoptosis-related proteins Bcl-2 and Bax were detected by IHC, RT-QPCR, and western blotting. We found that the number of follicles, Oct4 and Mvh expression, and Wnt/β-catenin-signaling activity were reduced in the POF groups (p < 0.05 or p < 0.001). After PUE treatment, the follicle number and the primordial follicle ratio increased (p < 0.01), while the atresia ratio decreased (p < 0.01). In addition, the expression levels of Oct4, Mvh, Wnt1, β-catenin, cyclin D1, SOD2, and Nrf2 showed obvious recovery compared with levels in the POF group (p < 0.01, p < 0.05, or p < 0.001). The Bcl-2/Bax ratio in the POF model had reduced by about 60% compared with the control group (p < 0.001) and improved by about 50% after PUE treatment (p < 0.001). In conclusion, PUE may improve the survival of female reproductive stem cells (FGSCs) and play a protective role against POF via a mechanism involving the Wnt/β-catenin signaling pathway, as well as relieving oxidative stress. Further investigations should focus on the culture of oocytes and FGSCs in vitro in a PUE environment with inhibitors or agonists of the Wnt signaling pathway.

Mesenchymal Stem Cell Therapy Using Human Umbilical Cord in a Rat Model of Autoimmune-Induced Premature Ovarian Failure.

Premature ovarian failure (POF) is one of the principal causes of female infertility, and although its causes are complex and diverse, autoimmune deficiency may be involved. Human umbilical cord mesenchymal stem cells (UCMSCs) can be used for tissue regeneration and repair. Therefore, the present study was designed to determine the role of UCMSCs in immune factor-induced POF in rats. In this study, different concentrations of UCMSCs were injected into induced POF rats. Ovarian functions were examined by evaluating the estrus cycle, follicular morphology, hormonal secretion, and the proliferation and apoptosis of granulosa cells. Our results showed that the estrus cycle of rats returned to normal and follicular development was significantly improved after transplantation of UCMSCs. In addition, serum concentrations of 17-estradiol (E2), progesterone (P4), and anti-Müllerian hormone (AMH) increased significantly with treatment. Transplantation of UCMSCs also reduced the apoptosis of granulosa cells and promoted the proliferation of granulosa cells. All of these improvements were dose dependent. Furthermore, the results of related gene expression showed that transplanted human UCMSCs upregulated the expression of Bcl-2, AMH, and FSHR in the ovary of POF rats and downregulated the expression of caspase-3. These results further validated the potential mechanisms of promoting the release of cell growth factors and enhancing tissue regeneration and provide a theoretical basis for the clinical application of stem cells in the treatment of premature ovarian failure.

Progress in treatment of premature ovarian failure using Chinese and Western medicine

Progress in treatment of premature ovarian failure using Chinese and Western medicine

Deficiency of Pdk1 contributes to primordial follicle activation via the upregulation of YAP expression and the pro‑inflammatory response.

The molecular mechanisms underlying the activation of primordial follicles are poorly understood. The serine/threonine protein kinase phosphoinositide‑dependent kinase1 (PDK1), a pivotal downstream effector of phosphatidyl inositol‑3 kinase (PI3K) signaling, plays a vital role in cellular signaling. In order to identify the function of PDK1 in ovarian follicle development, this study used conditional Pdk1 deletion in mouse oocytes by crossing Pdk1loxP/loxP mice with transgenic mice carrying Gdf‑9 promoter‑mediated Cre recombinase and found that Pdk1flx/flxGdf9Cre mice were subfertile with increased serum follicle‑stimulating hormone (FSH) and luteinizing hormone (LH) levels compared with Pdk1flx/flx mice. The deletion of Pdk1 in oocytes induced massive primordial follicle activation, leading to premature ovarian failure (POF). Further investigation revealed that enhanced Yes‑associated protein (YAP) expression and an increased pro‑inflammatory response also contributed to massive primordial follicle activation. PDK1 formed the complex with the core kinases of Hippo signaling and regulated the expression levels of YAP. On the whole, the findings of the present study demonstrate that PDK1 serves as an indispensable gatekeeper for maintaining the primordial follicle pool and provide a deeper understanding of POF treatment.

Fetal liver mesenchymal stem cells restore ovarian function in premature ovarian insufficiency by targeting MT1

BackgroundWith the development of regenerative medicine and tissue engineering technology, almost all stem cell therapy is efficacious for the treatment of premature ovarian failure (POF) or premature ovarian insufficiency (POI) animal models, whereas little stem cell therapy has been practiced in clinical settings. The underlying molecular mechanism and safety of stem cell treatment in POI are not fully understood. In this study, we explored whether fetal mesenchymal stem cells (fMSCs) from the liver restore ovarian function and whether melatonin membrane receptor 1 (MT1) acts as a regulator for treating POI disease.MethodsWe designed an in vivo model (chemotherapy-induced ovary damage) and an in vitro model (human ovarian granulosa cells (hGCs)) to understand the efficacy and molecular cues of fMSC treatment of POI. Follicle development was observed by H&E staining. The concentration of sex hormones in serum (E2, AMH, and FSH) and the concentration of oxidative and antioxidative metabolites and the enzymes MDA, SOD, CAT, LDH, GR, and GPx were measured by ELISA. Flow cytometry (FACS) was employed to detect the percentages of ROS and proliferation rates. mRNA and protein expression of antiapoptotic genes (SURVIVIN and BCL2), apoptotic genes (CASPASE-3 and CASPASE-9), and MT1 and its downstream genes (JNK1, PCNA, AMPK) were tested by qPCR and western blotting. MT1 siRNA and related antagonists were used to assess the mechanism.ResultsfMSC treatment prevented cyclophosphamide (CTX)-induced follicle loss and recovered sex hormone levels. Additionally, fMSCs significantly decreased oxidative damage, increased oxidative protection, improved antiapoptotic effects, and inhibited apoptotic genes in vivo and in vitro. Furthermore, fMSCs also upregulated MT1, JNK1, PCNA, and AMPK at the mRNA and protein levels. With MT1 knockdown or antagonist treatment in normal hGCs, the protein expression of JNK1, PCNA, and AMPK and the percentage of proliferation were impaired.ConclusionsfMSCs might play a crucial role in mediating follicular development in the POI mouse model and stimulating the activity of POI hGCs by targeting MT1.

Systems Pharmacology Uncovers Multiple Mechanisms of Erxian Decoction () for Treatment of Premature Ovarian Failure.

To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction (, EXD) as a treatment for premature ovarian failure (POF) using a systems pharmacology approach. The compounds present in EXD were obtained from three databases. The active ingredient was identified by analyzing the values of oral bioavailability (OB), drug-likeness (DL), and Lipinski's rule (LR). The active ingredients were further searched in research articles, drug targets in the DrugBank database, and the C-T and T-P networks, as well as by pathway analysis using the Cytoscape platform. A total of 728 compounds were identified in EXD. Of these, 59 were identified as active compounds that conformed to the criteria with OB ⩾30% and DL ⩾0.18. By further searches in the literature, 126 related targets were identified that could interact with the active compounds. Additionally, it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immune system, modulation of estrogen levels, and anti-oxidative activities, and that it may act in a synergistic or cooperative manner with other therapeutic agents. The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF. The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.

Meta-analysis on modified Zuogui Pill combined with hormone in the treatment of premature ovarian failure

Objective To evaluate the effectiveness and safety of modified Zuogui Pill combined with hormone in the treatment of premature ovarian failure (POF). Methods Randomized controlled trials were carried out by searching Chinese and English databases from the establishing to June, 2018. The methodological quality was assessed in the included randomized controlled trials. The treatment of premature ovarian failure by modified Zuogui Pill combined with hormone was systematically evaluated by RevMan 5.3 software. Results 11 randomized controlled trials involving 1 004 patients were included. Meta-analysis results showed that total effective rate (OR=4.44, 95% CI: 3.10-6.36, P<0.00001), Tranditional Chinese Medcine (TCM ) syndromes (including dizziness, tinnitus, hot flash night sweats, five upset fever, waist and knees), serum follicle stimulating hormone (FSH) level [standardised mean difference(SMD)=0.54, 95% CI: 0.13-0.95, P=0.01], luteinizing hormone (LH) level (SMD=0.90, 95% CI: 0.45-1.36, P<0.0001), estradiol (E2 )level (SMD=1.26, 95% CI: 0.12-2.40, P=0.03), endometrial thickness [weighted mean difference (WMD)=2.03, 95% CI: 0.07-3.99, P=0.04] improvement and the incidence of adverse reactions (OR=0.34, 95% CI: 0.12-0.95, P=0.04) in modified Zuogui Pill combined with hormone therapy were superior to those of pure hormone therapy. Conclusions The modified Zuogui Pill combined with hormone therapy shows better therapeutic effect and safety than hormone therapy on premature ovarian failure. Key words: Primary ovarian insufficiency; ZUOGUI PILL; Hormone replacement therapy; Meta-analysis

Kuntai Capsule plus Hormone Therapy vs. Hormone Therapy Alone in Patients with Premature Ovarian Failure: A Systematic Review and Meta-Analysis.

The aim of this study was to evaluate the efficacy and safety of Kuntai capsules (KTC) plus hormone therapy (HT) compared to HT alone for the treatment of premature ovarian failure (POF). Databases including PubMed, MEDLINE, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), and the Wanfang database were searched up to October 2018 for randomized controlled trials (RCTs). After screening the studies, extracting the data, and assessing the study quality, Cochrane RevMan 5.3 software was used to conduct a meta-analysis. Twelve RCTs involving 1178 patients were included. Regarding the therapeutic effects, total effective treatment rate was higher for the KTC+HT groups compared to the HT-only groups. Furthermore, compared with HT, KTC+HR effectively altered endocrine indexes involving serum levels of luteinizing hormone (weighted mean difference [WMD]=-3.47, 95% CI [5.68, -1.26], P=0.002]), follicle-stimulating hormone [WMD=-8.15, 95% CI [-10.44, -5.86], P<0.00001], estrogen [WMD=17.21, 95% CI [10.16, 24.26], P<0.00001], and anti-Müllerian hormone [WMD=1.07, 95% CI [0.78, 1.36], P<0.00001]; blood lipid indexes involving serum levels of triglyceride (WMD=-0.55, 95% CI [-0.76, -0.43], P<0.00001), total cholesterol (WMD=-0.63, 95% CI [-0.74, -0.52], P<0.00001), and low-density lipoprotein cholesterol (WMD=-0.62, 95% CI [-0.75, -0.49], P<0.00001); and B-ultrasound results involving ovarian resistance index (WMD=-0.20, 95% CI [-0.35, -0.04], P=0.01), perfusion index (WMD=-0.41, 95% CI [-0.57, -0.24], P<0.00001), peak systolic velocity (WMD=2.43, 95% CI [1.52, 3.34], P<0.00001), antral follicle count (WMD=1.20, 95% CI [0.41, 2.00], P=0.003), and mean ovarian diameter in the plane containing the longest axis of the ovary (WMD=4.34, 95% CI [2.94, 5.74], P<0.00001). There were no serious adverse events in either group. There is evidence that KTC+HT is more effective and safer than HT alone for treating POF. However, the trials had low methodological quality and small samples, so further standardized research is required.

Abnormal aggregation of myeloid-derived suppressor cells in a mouse model of cyclophosphamide-induced premature ovarian failure

Oocytes are extremely sensitive to radiation and chemotherapy, and premature ovarian failure (POF) is one of the side effects of anti-tumor therapy. The pathogenesis of POF is very complex and still not fully elucidated. A mouse POF model was established after 14 days of cyclophosphamide injection. POF mice presented ovarian atrophy, destroyed follicular structure, a reduction in the number of primordial and mature follicles, and an decrease in the number of corpora luteal along with increased level of follicle-stimulating hormone (FSH), decreased levels of estradiol (E2), and anti-Mullerian hormone (AMH). Additionally, the proportion of bone marrow myeloid-derived suppressor cells (MDSCs) in peripheral blood, spleen, and ovarian tissue increased. MDSCs were mainly distributed around follicles and corpora luteal. Levels of mTOR and p-mTOR increased in ovarian tissue and inhibition of mTOR with rapamycin reduced the aggregation of MDSCs in peripheral blood, spleen, and ovarian tissue. This investigation sheds new light on the modulatory role of mTOR and demonstrates that an increase in MDSC number may play a key role in the pathological reaction during POF. Inhibition of mTOR and reduction of MDSCs in the ovary may represent a novel strategy for the treatment of POF.

Zuogui Pills inhibit mitochondria-dependent apoptosis of follicles in a rat model of premature ovarian failure

Ethnopharmacological relevanceZuogui Pills (ZGP), which is a classical prescription of Traditional Chinese Medicine (TCM), has been reported to be widely used in the treatment of premature ovarian failure (POF). Aim of the studyTo investigate the therapeutic effects of ZGP on the treatment of POF induced by chemotherapy, and elucidate the potential molecular mechanism. Materials and methodsFemale 8-week-old Sprague-Dawley rats (N = 54) were randomized to six groups, containing the Control group, Model group, three ZGP groups and Triptorelin group which was served as a positive control. The Triptorelin group received triptorelin injection ten days before model establishment by cyclophosphamide. The three ZGP groups (high dose group, medium dose group and low dose group) were given a daily intragastric administration of ZGP at doses of 3.2, 1.6 and 0.8 g/kg for sixty days. We observed the general growth of rats and examed the estrous cycle and the rate of pregnancy, ovarian ultrastructures, follicles and corpora lutea numbers. The serum hormone concentrations were measured by Enzyme-linked immunosorbent assay (ELISA). To explore the molecular mechanism of the effect, gene and protein expression levels of Bax, Bcl-2 and Cyt-c related to apoptosis were determined by quantitative PCR (qPCR), Western Blot and Immunohistochemistry analysis, respectively. ResultsAfter treating with ZGP, though the rate of pregnancy showed no significant difference, the estrous cycle, ovarian ultrastructures, numbers of follicles and corpora lutea were improved significantly. And ZGP led to a significant lower concentration of follicle stimulating hormone (FSH) in the serum, and the concentration of oestradiol (E2) was increased. Furthermore, a significant downregulation of Bax, cytochrome c (Cyt-c), and upregulation of B cell lymphoma/leukemia-2 (Bcl-2) both on gene and protein levels were observed after the administration with ZGP. And effects showed a positive correlation with the dosages. ConclusionsOur study suggested that ZGP exerted significant effect on POF, which was meditated by inhibiting mitochondria-dependent apoptosis in the follicles.

The Role of Stem Cells on the Ovarian Failure Induced by Busulfan in Female Albino Rat

AbstractBackground: Many researches about stem cell therapy in premature ovarian failure treatment have been carried out. The adipose tissue has recently been identified as one of the alternative sources of multipotent resident stem cells in humans. One of the most devastating effects of chemotherapy is the damage of the reproductive system, which in young girls and women younger than 40 years of age is frequently associated with premature ovarian failure. Busulfan has a wide range of using as in a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myeloid leukemia and in patients undergoing bone marrow transplantation.Aim of the Study: The aim of the study was to evaluate the effect of administration of adipose tissue derived stem cells on the ovarian failure induced by the busulfan in female albino rats.Material and Methods: 70 female 8 weeks old albino rats were divided into 5 groups. Group I (control Group): They consisted of 20 female albino rats. They were received no treatment and served as untreated control. Group II (adipose tissue derived stem cells treated group): They consisted of 20 female albino rats. They were received adipose tissue derived stem cells (AT-ASCs). They received million and half of million units of AT-ASCs/single dose for each animal I.V. Group III (busulfan treated Group): They consisted of 10 female albino rats. In this group the ovarian failure was induced using busulfan therapy by a dose 2mg for successive 4 days. Group IV (busulfan treated, followed by AT-ASCs treated group): They consisted of 10 female albino rats. In this group the ovarian failure was induced by the same regimen as in group III. After one week of chemotherapeutic treatment, the animals received million and half of million units of AT-ASCs/single dose for each animal I.V. Group V (busulfan treated, followed by AT-AS Cs treated group): They consisted of 10 female albino rats. The rats in this group received the same regimen as group IV but they were sacrificed 4 weeks after the AT-ASCs injection. Biochemical study: Blood samples were taken from all rats from retro-orbital venous plexus and the serum samples were measured for FSH, LH and serum estrogen level using ELISA technique. Paraffin sections for female albino rat ovaries were prepared to be stained with H&E and Masson’s Trichrome stain for Light microscopic study. Specimens of the ovary were also prepared for electron microscopic study.Results: The AT-ASCs induced definite improvement in the histopathological changes associated with busulfan induced ovarian failure. This improvement was marked one week after AT-ASCs treated but after 4 weeks, there was some regression in this improvement.Conclusion: AT-ASCs transplantation can improve the ovarian damage induced by the busulfan. The need for second dose of AT-ASCs is suggested.

Progress on the Clinical Applications of Stem Cells for Premature Ovarian Failure

Premature ovarian failure (POF) is a heterogeneous disorder characterized by amenorrhea, infertility, lack of estrogen, and elevated gonadotropin levels before the age of 40. Most POF females have fertility problems due to defects of germ cell development or complete ovarian failure. Though hormonal therapy could partially restore ovarian function, effects of these treatments are transient, much less for regeneration and repair of the ovaries. With the rise of regenerative medicine, stem cells transplantation gives new hope for repairing POF related ovaries damage. Studies from animal models indicate that stem cell transplantation can, at least in part, repair ovarian structure, improve ovarian function and fertility in POF, i.e., the bone marrow mesenchymal stem cells (BMSCs) and umbilical cord mesenchymal stem cells (UC-MSCs) can differentiate to ovaries and facilitate fertility recovery. However, the underlying mechanisms remain unclear, which limits their clinical applications. Here, we discuss the recent progress on the clinical applications of stem cells for POF treatment, which would become promising therapies for POF patients.

Intravenous Infusion of Nucleated Peripheral Blood Cells Restores Fertility in Mice with Chemotherapy-Induced Premature Ovarian Failure.

Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study is to investigate if chemotherapeutic induced POF can be reversed by the infusion of autologous nucleated peripheral blood cells (PBMC). To reach our goal, mice were treated with a single intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This was followed by transfusion of PBMC. The ovarian morphology and functional parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence and immunohistochemistry analysis. Our study showed that chemotherapy (CTX) protracted estrous cycle period and repressed E2 production. In addition, CTX decreased the expressions of steroidogenesis markers, CYP-17 synthesis, StAR (steroidogenic acute regulatory protein), and Connexin-43 protein expression in the ovarian follicles. We also observed reduced numbers and sizes of the primordial and primary follicles in CTX-treated mice compared to untreated controls (p < 0.05). When both CTX and untreated control groups were stimulated with gonadotrophin, the control group produced ten times more ova than the CTX group. Finally, the treatment of premature ovarian failure induced by CTX with autologous PBMC transfusion resulted in over-expression and a statistically significant increase in several stem cell markers and restoration of fertility. Infusion with PBMC in CTX further decreased the estrous cycle length by 2.5 times (p < 0.01). We found that transfusion of autologous PBMC to mice with chemotherapy induced POF was very effective at restoring fertility. These results are similar to other studies using bone marrow derived mesenchymal stem cells.

Clinical research and the effect mechanism on premature ovarian failure treated with acupuncture in recent 20 years

To review and collect the study achievements and the effect mechanism of acupuncture in the treatment of premature ovarian failure (POF) in recent 20 years so as to provide more references for the clinical treatment of POF with acupuncture. Through retrieving PubMed, CNKI and VIP, the literature on acupuncture for POF was collected from January 1, 1998 through March 31, 2017 regarding the rule of acupoint selection and the therapeutic method. The potential effect mechanism was explored. Finally, 26 papers on the clinical treatment for POF with acupuncture and 5 ones on the laboratory mechanism were obtained. The differentiated syndromes and the top 3 acupoints for the treatment of POF included shaoyin syndrome [Taixi (KI 3), Sanyinjiao (SP 6) and Guanyuan (CV 4)], Taiyin syndrome [Sanyinjiao (SP 6), Zusanli (ST 36) and Ciliao (BL 32)], jueyin syndrome [Taichong (LR 3), Shenting (GV 24), Guanyuan (CV 4)], the mixed syndrome of shaoyin and jueyin [Sanyinjiao (SP 6), Ganshu (BL 18) and Shenshu (BL 23)], the mixed syndrome of shaoyin and taiyin [Pishu (BL 20), Sanyinjiao (SP 6) and Zusanli (ST 36)] and the dysfunction of the thoroughfare vessel and the conception vessel [Guanyuan (CV 4), Zigong (EX-CA 1) and Huangshu (KI 16)]. The top 5 acupoints of the 14 meridians were Guanyuan (CV 4), Shenshu (BL 23), Sanyinjiao (SP 6), Zhongji (CV 3), Pishu (BL 20), Taixi (KI 3) and Ganshu (BL 18). The local extraordinary points were dominant. According to the use frequency of the acupoints, the first top 5 meridians were the bladder meridian of foot-taiyang, the governor vessel, the conception vessel, the spleen meridian of foot-taiyin and the kidney meridian of foot-shaoyin. The most acupoints were distributed in the chest, the abdomen, the lumber region and the lower limbs. Many therapeutic methods were used, such as acupuncture with filiform needle, electroacupuncture, moxibustion and the acupoint thread-embedding therapy. The effect mechanisms possibly referred to the recovery of the sexual level through regulating the hypothalamus-pituitary gland-ovarian axle (HPOA) function, the improvement of the histological morphology of the uterine, the improvement of body immunity through affecting the nerve-endocrine-immune regulation system as well as the regulation of the genetic and protein expressions of the signal pathway relevant with POF. Even though acupuncture has achieved the therapeutic effects in the clinical treatment of POF, the research on the effect mechanism is still limited. The exploration of acupuncture for POF in terms of mechanism may guide the clinical practice. In the future study, the clinical pathway should be specified and the effect mechanism be explored through the rigorous laboratory design and more objective and rational evaluation system.

Human chorionic plate-derived mesenchymal stem cells transplantation restores ovarian function in a chemotherapy-induced mouse model of premature ovarian failure

BackgroundPrevious studies have reported that transplantation of mesenchymal stem cells (MSCs) from many human tissues could ameliorate ovarian dysfunction. However, no study has revealed the therapeutic efficiency of MSCs derived from the chorionic plate (CP-MSCs) for premature ovarian failure (POF).MethodsWe investigated the restorative effects of CP-MSCs on cyclophosphamide (CTX)-induced POF. The POF mouse models were established via intraperitoneal injection of 50 mg/kg CTX into female mice for 15 consecutive days. After that, CP-MSCs were intravenously transplanted into the mice once a week for 4 weeks. The serum estradiol (E2) and follicle-stimulating hormone (FSH) levels in the mouse models were detected using enzyme-linked immunosorbent assay (ELISA) before and after treatment. Ovarian function was evaluated through counting the follicles, estrous cycles, and oocytes.ResultsCP-MSC transplantation restored the serum hormone level and ovarian function of the mice in the mouse model of POF induced by CTX. The levels of serum E2 and FSH in the POF model group was 232.33 ± 17.16 pg/mL and 4.48 ± 0.29 mIU/mL, respectively, after 6 weeks of treatment, which were similar to the values in the wild-type (WT) group. The superovulation demonstrated that ovarian function was significantly improved compared with nontreated POF model mice. The CP-MSC transplantation could restore CTX-induced ovarian dysfunction.ConclusionsOur results offer a potential application for human CP-MSCs in POF treatment.

Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility

Premature ovarian failure (POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study, umbilical cord mesenchymal stem cells on a collagen scaffold (collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.

Comparative observation of the effect of electroacupuncture combined with heat-sensitive moxibustion and western medicine for premature ovarian failure

ObjectiveTo compare the clinical efficacy between electroacupuncture combined with heat-sensitive moxibustion and western medicine for treatment of premature ovarian failure. MethodsEighty patients were randomly divided into an electroacupuncture combined with heat-sensitive moxibustion group (group A, n=40) and a western medicine group (group B, n=40). Zîgōng (▪ EX-CA 1), Xuèhâi (▪ SP 10), Gānshū (▪ BL 18) and Shènshū (▪ BL 23) were selected in group A, and acupuncture combined with heat-sensitive moxibustion were carried out. Climen was taken orally in group B. The score changes of menstrual cycle, tidal fever and sweatiness, emotional excitement, soreness and weakness of waist and knees, dizziness and tinnitus, as well as the cured and markedly effective rate of the patients in the two groups before and after two courses of treatment were compared. ResultsThe cured and markedly effective rate of group A was 72.5% (29/40), which was superior to that of group B (37.5%, 15/40) (P<0.05). The symptom scores were improved significantly in the two groups after treatment (all P<0.05), and the improvement in group A was superior to that in group B (all P<0.05). ConclusionThe efficacy of electroacupuncture combined with heat-sensitive moxibustion is superior to that of conventional western medicine in treatment of premature ovarian failure.

Professor LAI Xinsheng's clinical experience in the treatment of premature ovarian failure with tongyuan acupuncture technique and Chinese herbal medicine

In the treatment of premature ovarian failure (POF), professor LAI Xinsheng focuses on the determination of syndrome to seek for etiology, associating with the differentiation of meridian and collateral and that of zangfu organs. Professor LAI believes that POF is mainly manifested as amenorrhea and infertility, localized in the kidney, with the dysfunction of liver, spleen and heart. It is impacted by many pathological factors, such as cold blockage, qi stagnation, blood stagnation, blood deficiency, yin deficiency, etc., which leads to the damage of the thoroughfare vessel and the conception vessel and the blockage of menstrual flow. On the basis of four diagnostic Methods and syndrome differentiation, there are four common syndromes of POF, named qi and blood deficiency, qi and blood stagnation, liver and kidney deficiency and yang deficiency of spleen and kidney. Tongyuan acupuncture technique is summarized by Professor LAI Xinsheng on the basis of yinyang theory. It is an effective and scientific method for acupoint selection along the meridians. The acupoints on the back, communicating with the governor vessel and mind regulation, acting on the brain are selected to promote yang qi of the governor vessel. The back-shu points of five zang organs are selected to regulate the functions of internal organs. The acupoints on the abdomen and the conception vessel are selected to conduce qi to the primary so as to improve reproductive function. In the guidance of tongyuan acupuncture technique, the acupoint prescription is formed and the Chinese herbal medicines are selected in combination to improve ovarian function and regulate menstruation. Hence, the satisfactory therapeutic effects have been achieved.