Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

Kidney Mesenchymal stem cells alleviate cisplatin-induced kidney injury and apoptosis in rats.

OBJECTIVE: This experiment was designed to demonstrate Mesenchymal stem cells (MSCs) derived from kidney can alleviate cisplatin-induced kidney injury and renal cell apoptosis through paracrine pathway. METHODS: Firstly, MSCs were isolated from kidney of young rats, and their surface-specific markers were identified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunofluorescence staining. Self-renewal ability of Kidney Mesenchymal Stem Cells (KMSCs) was observed by cell counting and 5-Bromo-2'-deoxyuridine (BrdU) fluorescence staining. KMSCs at logarithmic growth stage were traced and injected into rat through tail vein. RESULTS: The results showed that KMSCs homed in the kidney tissues, decreased the secretion of inflammatory factors (CRP, TNFα, IL-1ß, IL-6), and alleviated renal function. Hematoxylin and Eosin (H＆E), Masson and Periodic Acid-silver Methenamine (PASM) staining showed that KMSCs could alleviate pathological damage in rats. Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) assay showed that KMSCs could reduce the apoptosis of rat kidney cells induced by cisplatin. Finally, Immunohistochemistry (IHC) results showed that cisplatin could induce higher expression of the pro-apoptotic protein Bax and lower expression of anti-apoptotic Bcl-2 in kidney tissues. However, KMSCs could reverse the pro-apoptotic effect of cisplatin on kidney cells and improve the survival rate of rats. CONCLUSIONS: In conclusion, KMSCs were successfully isolated from kidney tissues, and KMSCs have therapeutic effects on rat kidney injury induced by cisplatin.

Efficacy of acupuncture for endometriosis-associated pain: a multicenter randomized single-blind placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of acupuncture in the treatment of endometriosis-associated pain. DESIGN: A multicenter, randomized, single-blind, placebo-controlled trial. INSTITUTIONS: Four tertiary hospitals in Jiangxi and Hainan Provinces. SUBJECTS: Women with endometriosis-associated pain aged between 20 and 40 years. INTERVENTION: Subjects were assigned randomly to receive either acupuncture or sham acupuncture treatment for 12 weeks, starting one week before each expected menstruation and administered as a 30-minute session once per day, 3 times a week. During the menstruation period, acupuncture was administered daily when pelvic pain associated with endometriosis occurred. After acupuncture or sham acupuncture treatment, the subjects were followed for another 12 weeks. MAIN OUTCOME MEASURES: Changes in maximum pain as assessed with the visual analog scale (VAS) for various pelvic pain, duration of dysmenorrhea, and scores on the Multidimensional Pain Inventory, Beck Depression Inventory, Profile of Mood States, and Endometriosis Health Profile from baseline to week 12 and week 24. RESULTS: A total of 106 women were assigned randomly to the acupuncture and sham groups. In the acupuncture group, the reduction in the dysmenorrhea VAS score was significantly greater after treatment, but not at the end of the trial, compared to the sham group. The duration of pain was significantly shorter in the acupuncture group. All test scores were improved to a significantly greater extent in the acupuncture group than in the sham group at week 12 but not at week 24. Changes in nonmenstrual pelvic pain and dyspareunia VAS scores were not different between the groups. No severe adverse events or differences in adverse events were recorded. CONCLUSION: Acupuncture is an effective and safe method of relieving dysmenorrhea, shortening the pain duration, and improving wellbeing and quality of life in women with endometriosis-associated pain, although its efficacy fades after treatment is discontinued. CLINICAL TRIAL REGISTRATION NUMBER: NCT03125304.

[Treatment of refractory polycystic ovary syndrome by bushen huoxue method combined with ultrasound-guided follicle aspiration].

OBJECTIVE: To observe the clinical effect of traditional Chinese medicine Bushen Houxue (BSHX) method combined with ultrasound-guided follicle aspiration (MFA) in treating refractory polycystic ovary syndrome (PCOS). METHODS: Forty-four patients with PCOS were randomly assigned to two groups by randomizing digital table, 20 in the observation group and 24 in the control group. MFA was performed on both groups, and the decoction of BSHX, which consisted of dodder seed 20 g, prepared rehmannia root 10 g, mulberry mistletoe 20 g, epimedium 15 g, psoralea fruit 10 g, solomonseal rhizome 10 g, honeylocust thorn 15 g, peach kernel 10 g, pleione bulbocodioides 10 g, red sage root 20 g, and licorice root 6 g, was given to the observation group one dose every day for 14 days every menstrual cycle. Changes of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) were determined before and after MFA. The impacts on quantity of HMG used, number of sinus follicle, mature follicle, incidence of ovarian hyperstimulating syndrome (OHSS), luteinized unrupture follicular syndrome (LUFS) and pregnance rate were also observed. RESULTS: MFA had been performed for 42 cycles in the observation group and 56 cycles in the control group. Levels of T, LH and LH/FSH ratio markedly reduced after aspiration, showing significant difference as compared with those of before treatment in both groups (P < 0.01), and difference of LH/FSH between groups was of statistical significance (P <0.01). In the observation group, 18 patients (90.0%) had their sinus follicle decreased to < 10 after MFA, while in the control group, it reached to <10 in 22 patients (91.70%), all were different to those before treatment (P <0.01). In the observation group, the quantity of HMG used for promoting ovulation was (585.0 +/- 195.0) IU, number of mature follicle at the day of HCG injection was 1.1 +/- 0.3, while in the control group, the corresponding data were (1470.0 +/- 532.5) IU and 3.1 +/- 1.4, all with significant difference between groups (P <0.01). None of OHSS and 1 case of LUFS occurred in the former group, while 1 mild OHSS and 2 LUFS in the latter. After ovulation promoting therapy and in the 3-month secutive follow-up period, pregnancy was found in 8 out of the 18 patients in the observation group (one twins and 7 single), with the pregnancy rate of 44.4%; while in the control group, 7 in 22 (2 twins and 5 single) was found, the pregnancy rate being 31.8%. CONCLUSION: BSHX method combined with MFA is a safe and effective treatment for refractory PCOS, with few trauma. The combined usage of Chinese herbal medicine could significantly reduce dosage of HMG used for promoting follicle and the production of multiple mature follicles, thus to avoid the risk of OHSS.

Ping-Chong-Jiang-Ni Formula Induces Apoptosis and Inhibits Proliferation of Human Ectopic Endometrial Stromal Cells in Endometriosis via the Activation of JNK Signaling Pathway.

Endometriosis is a common gynecological condition in childbearing age women and its therapy in modern medicine achieves usually temporary cure. Ping-Chong-Jiang-Ni formula (PCJNF), a Chinese herbal medicine (CHM), was shown to be clinically effective on endometriosis. Meanwhile, c-Jun N-terminal kinase (JNK) signaling pathway was involved in the therapeutic process of CHM on endometriosis. Here, we explored the effect of PCJNF on the ectopic endometrial stromal cells (EESCs) from endometriosis and test whether JNK signaling was involved. After being treated with PCJNF-containing serum obtained from Sprague Dawley rat, cell proliferation, migration, invasion, and apoptosis were evaluated in EESCs, and the total and phosphorylated JNK, ERK, and p38 proteins were detected. Our results showed that PCJNF could suppress cell proliferation, migration, and invasion and induce apoptosis in EESCs. The suppressed proliferation and increased apoptosis were dependent on JNK activation. Additionally, PCJNF caused cell cycle arrest at G2/M phase and this effect was mediated by JNK signaling, while the decreased cell migration and invasion treated by PCJNF were independent of JNK signaling. In summary, our results provided the first evidence that PCJNF could suppress cell proliferation, migration, and invasion, while increasing apoptosis in EESCs, and the suppressed proliferation and enhanced apoptosis were mediated by JNK signaling.

[Effects of combined therapy of salpingostomy and Bushen Huoxue drugs on fallopian tube obstructive infertility].

OBJECTIVE: To compare the effect of treatment of fallopian tube obstructive infertility by salpingostomy alone and in combination with TCM drugs for Bushen Huoxue (invigorating Shen and promoting blood circulation). METHODS: To all the patients, salpingostomy was performed 3 to 7 days after menstruation and hydrotubation with Xiangdan Injection (XI) was applied once in the next menstrual cycle. Bushen Huoxue Decoction (BHD) was administrated additionally to patients in the treated group, 1 dose every day starting from the 5th day of menstrual cycle for 14 days. Three months' treatment was taken as one therapeutic course and the observation lasted for 4 courses. RESULTS: The condition of follicular development, thickness of endometrium and level of serum estradiol in the preovulatory phase after treatment were all significantly increased in the two groups (P < 0.05 and P < 0.01); but the improvement in the treated group was significantly superior to that in the control group, showing significant difference. Moreover, the pregnancy rate was also higher in the former than in the latter (P < 0.05). CONCLUSION: The combined therapy of salpingostomy and TCM drugs for invigorating Shen and promoting blood circulation is an effective therapy for fallopian tube obstructive infertility, it has the effect of enhancing follicular development and increasing thickness of endometrium, and could elevate the pregnancy rate in patients.

Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome.

OBJECTIVE: To study whether a combination of berberine and letrozole results in higher live births than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). DESIGN: A multicenter randomized double-blinded placebo-controlled trial. SETTING: Reproductive and developmental network sites. PATIENT(S): Eligible women had PCOS as defined by the Rotterdam criteria. We enrolled 644 participants randomized 1:1:1 among letrozole, berberine, and combination groups. INTERVENTIONS(S): Berberine or berberine placebo were administrated orally at a daily dose of 1.5 g for up to 6 months. Patients received an initial dose of 2.5 mg letrozole or placebo on days 3-7 of the first three treatment cycles. This dose was increased to 5 mg on the last three cycles if not pregnant. MAIN OUTCOMES MEASURE(S): Cumulative live births. RESULTS: The cumulative live births were similar between the letrozole and combination groups after treatment (36% and 34%), and were superior to those in the berberine group (22%). Likely, conception, pregnancy, and ovulation rates were similar between the letrozole and combination groups, and these were significantly higher than in the berberine group. There was one twin birth in the letrozole group, three twin births in the combination group, and none in the berberine group. CONCLUSION(S): Berberine did not add fecundity in PCOS when used in combination with the new ovulation agent letrozole. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-09000376 (http://apps.who.int/trialsearch/).