Fan Qu

Overweight and obesity negatively affect the outcomes of ovarian stimulation and in vitro fertilisation: a cohort study of 2628 Chinese women

Objective. To explore the effects of overweight and obesity on the outcomes of in vitro fertilisation (IVF) in Chinese infertile patients. Study design. A retrospective cohort study was carried out in 2222 normal weight (18.5 ≤ BMI < 25), 379 overweight (25 ≤ BMI < 30) and 27 obese (BMI ≥ 30) women who underwent their first IVF cycles between 2002 and 2008. Cycle characteristics and IVF outcomes were analysed. Results. Obese women required significantly higher dose of rFSH (3272 IU vs. 2587 IU, p < 0.001) and days of stimulation (11.89 ± 4.57 vs. 10.42 ± 2.03, p < 0.001), but exhibited less oocytes retrieved and significantly lower fertilisation rate (54.1% vs. 61.1%, p < 0.001) than normal weight women. Compared with normal weight women, overweight women displayed significantly less oocytes retrieved (12.98 ± 6.91 vs. 14.49 ± 7.96, p < 0.001), lower fertilisation rate (60.8 ± 23.3 vs. 61.1 ± 23.0, p < 0.001), less cleavaged embryos (7.55 ± 4.86 vs. 8.67 ± 5.90, p < 0.001), less high-grade embryos (4.65 ± 3.96 vs. 5.59 ± 4.81, p < 0.001) and cryopreserved embryos (4.44 ± 4.55 vs. 5.49 ± 5.55, p < 0.001). All parameters of pregnancy outcomes, including pregnancy rate, miscarriage rate and live birth rate, were comparable among three groups. Conclusions. Overweight and obesity are related with impared ovarian response, and negatively affect the outcomes of IVF.

Electro-Acupuncture in Relieving Labor Pain

To study the efficacy of electro-acupuncture for the relief of labor pain, and to build a better understanding of how electro-acupuncture might influence the neuroendocrine system, 36 primiparas were randomly divided into an electro-acupuncture group and a control group. Assessments of pain intensity and degree of relaxation during labor were analyzed. The differences between the electro-acupuncture group and the control group on the concentration of β-endorphin (β-EP) and 5-hydroxytryptamine (5-HT) in the peripheral blood were compared. The electro-acupuncture group was found to exhibit a lower pain intensity and a better degree of relaxation than the control group (p = 0.018; p = 0.031). There existed a significant difference in the concentration of β-EP and 5-HT in the peripheral blood between the two groups at the end of the first stage (p = 0.037; p = 0.030). Electro-acupuncture was found to be an effective alternative or complementary therapy in the relief of pain during labor. The benefit of electro-acupuncture for relieving labor pain may be based on the mechanism of producing a synergism of the central nervous system (CNS) with a direct impact on the uterus through increasing the release of β-EP and 5-HT into the peripheral blood.

Insufficient maintenance DNA methylation is associated with abnormal embryonic development

BackgroundEarly pregnancy loss (EPL) is a frustrating clinical problem, whose mechanisms are not completely understood. DNA methylation, which includes maintenance methylation and de novo methylation directed by DNA methyltransferases (DNMTs), is important for embryo development. Abnormal function of these DNMTs may have serious consequences for embryonic development.MethodsTo evaluate the possible involvement of DNA methylation in human EPL, the expression of DNMT proteins and global methylation of DNA were assessed in villous or decidua from EPL patients. The association of maintenance methylation with embryo implantation and development was also examined.ResultsWe found that DNMT1 and DNMT3A were both expressed in normal human villous and decidua. DNMT1 expression and DNA global methylation levels were significantly down-regulated in villous of EPL. DNMT3A expression was not significantly changed in the EPL group compared to controls in either villous or decidua. We also found that disturbance of maintenance methylation with a DNMT1 inhibitor may result in a decreased global DNA methylation level and impaired embryonic development in the mouse model, and inhibit in vitro embryo attachment to endometrial cells.ConclusionsOur results demonstrate that defects in DNA maintenance methylation in the embryo, not in the mother, are associated with abnormal embryonic implantation and development. The findings of the current study provide new insights into the etiology of EPL.

A molecular mechanism underlying ovarian dysfunction of polycystic ovary syndrome: hyperandrogenism induces epigenetic alterations in the granulosa cells

The objective of this study was to explore whether hyperandrogenism induces epigenetic alterations of peroxisome proliferator-activated receptor gamma 1 (PPARG1), nuclear corepressor 1 (NCOR1), and histone deacetylase 3 (HDAC3) genes in granulosa cells (GCs) of polycystic ovary syndrome (PCOS) women and whether these alterations are involved in the ovarian dysfunction induced by hyperandrogenism. Thirty-two infertile PCOS women and 147 infertile women with tubal blockage were recruited. PCOS women were divided into the hyperandrogenism (HA) PCOS group (n = 13) and nonhyperandrogenism (N-HA) PCOS group (n = 19). Sixty female Sprague-Dawley rats were used for PCOS model establishment. In GCs of HA PCOS women, PPARG1 mRNA expression was lower, whereas NCOR1 and HDAC3 mRNA expression were higher than N-HA PCOS women and controls (P < 0.05). When all women were divided into successful and failed pregnancy subgroups according to the following clinical pregnancy outcome, we found lower PPARG1 mRNA levels and higher NCOR1 and HDAC3 mRNA levels in the failed subgroup of HA PCOS (P < 0.05). Two hypermethylated CpG sites in the PPARG1 promoter and five hypomethylated CpG sites in the NCOR1 promoter were observed only in HA PCOS women (P < 0.01 to P < 0.0005). The acetylation levels of histone H3 at lysine 9 and p21 mRNA expression were decreased in human GCs treated with dihydrotestosterone in vitro (P < 0.05). PCOS rat models also showed alterations of PPARG1, NCOR1, and HDAC3 mRNA expression and methylation changes of PPARG1 and NCOR1, consistent with the results from humans. Hyperandrogenism induces the epigenetic alterations of PPARG1, NCOR1, and HDAC3 in GCs, which are involved in the ovarian dysfunction of HA PCOS.

Functions of water channels in male and female reproductive systems.

Twelve water channels (aquaporins) are expressed in mammalian reproductive systems, and play very important roles in maintaining water homeostasis in reproductive cells. Impairment of their functions can result in attenuated male and female fertility. Alteration of AQPs expression is also found in reproductive tissues of the patients with polycystic ovarian syndrome, endometriosis or endometrium carcinoma. A lot of data have increased understanding of the functions and mechanisms of regulation of aquaporins at both the molecular and the clinical level. Researches have also focused on aquaporins as therapeutic targets. This review discusses recent advances in uncovering the physiological and pathophysiological roles of aquaporins in the reproductive systems.

Altered aquaporin expression in women with polycystic ovary syndrome: hyperandrogenism in follicular fluid inhibits aquaporin-9 in granulosa cells through the phosphatidylinositol 3-kinase pathway

BACKGROUND The present study was designed to evaluate whether the alteration of aquaporin-9 (AQP-9) expression in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS) was associated with the hyperandrogenism in follicular fluid (FF). METHODS We recruited infertile women with PCOS (n = 14) and infertile women with tubal blockage (controls, n = 31) for this study. We examined total testosterone (TT), free androgen index (FAI), sex hormone-binding globulin (SHBG), FSH, LH and estradiol in FF. Real-time PCR and western blotting were performed to assess AQP-9 expression in GCs, including effects of dihydrotestosterone (DHT) in vitro. RESULTS AQP-9 protein was localized in the nucleus, cytoplasm and cell membrane of the human GCs. The TT, FAI and LH levels were all higher, and SHBG levels lower, in the FF of women with PCOS versus controls (P = 0.0145, 0.0001, 0.0191, 0.0001, respectively). AQP-9 mRNA level in GCs of patients with PCOS was tightly correlated with the TT, SHBG levels and FAI in FF (P = 0.0020, 0.0001, 0.0020, respectively). In vitro, DHT (10(-9) mol/l) decreased AQP-9 mRNA (lowest at 12 h) and protein levels in control GCs (P = 0.0005, 0.0247, respectively). The inhibitory effect of DHT on AQP-9 mRNA was attenuated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor (P = 0.0013). Fifty micromolar 4-(hydroxymercuri) benzoic acid sodium salt (PMB) and 10(-9) mol/l DHT blunted the swelling of GCs in hypotonic medium, respectively (P = 0.0350, 0.0027). CONCLUSION Hyperandrogenism in FF of women with PCOS inhibited AQP-9 in GCs through the PI3K pathway.

FSH regulates fat accumulation and redistribution in aging through the Gαi/Ca2+/CREB pathway

Increased fat mass and fat redistribution are commonly observed in aging populations worldwide. Although decreased circulating levels of sex hormones, androgens and oestrogens have been observed, the exact mechanism of fat accumulation and redistribution during aging remains obscure. In this study, the receptor of follicle‐stimulating hormone (FSH), a gonadotropin that increases sharply and persistently with aging in both males and females, is functionally expressed in human and mouse fat tissues and adipocytes. Follicle‐stimulating hormone was found to promote lipid biosynthesis and lipid droplet formation; FSH could also alter the secretion of leptin and adiponectin, but not hyperplasia, in vitro and in vivo. The effects of FSH are mediated by FSH receptors coupled to the Gαi protein; as a result, Ca2+ influx is stimulated, cAMP‐response‐element‐binding protein is phosphorylated, and an array of genes involved in lipid biosynthesis is activated. The present findings depict the potential of FSH receptor‐mediated lipodystrophy of adipose tissues in aging. Our results also reveal the mechanism of fat accumulation and redistribution during aging of males and females.

Acupuncture and Auricular Acupressure in Relieving Menopausal Hot Flashes of Bilaterally Ovariectomized Chinese Women: A Randomized Controlled Trial

The objective of this study is to explore the effects of acupuncture and auricular acupressure in relieving menopausal hot flashes of bilaterally ovariectomized Chinese women. Between May 2006 and March 2008, 46 bilaterally ovariectomized Chinese women were randomized into an acupuncture and auricular acupressure group (n = 21) and a hormone replacement therapy (HRT) group (Tibolone, n = 25). Each patient was given a standard daily log and was required to record the frequency and severity of hot flashes and side effects of the treatment felt daily, from 1 week before the treatment started to the fourth week after the treatment ended. The serum levels of follicle stimulating hormone (FSH), LH and E2 were detected before and after the treatment. After the treatment and the follow-up, both the severity and frequency of hot flashes in the two groups were relieved significantly when compared with pre-treatment (P <  .05). There was no significant difference in the severity of hot flashes between them after treatment (P >  .05), while after the follow-up, the severity of hot flashes in the HRT group was alleviated more. After the treatment and the follow-up, the frequency of menopausal hot flashes in the HRT group was reduced more (P <  .05). After treatment, the levels of FSH decreased significantly and the levels of E2 increased significantly in both groups (P <  .05), and they changed more in the HRT group (P <  .05). Acupuncture and auricular acupressure can be used as alternative treatments to relieve menopausal hot flashes for those bilaterally ovariectomized women who are unable or unwilling to receive HRT.

Effects of Acupuncture on the Outcomes of In Vitro Fertilization: A Systematic Review and Meta-Analysis

OBJECTIVES The objective of this article was to conduct a systematic review with meta-analysis of the trials of acupuncture during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment on the outcomes of clinical pregnancy, biochemical pregnancy, ongoing pregnancy, implantation rate, live birth, and miscarriage. SEARCH STRATEGY The search was conducted by using MEDLINE(®), SCISEARCH, the Cochrane Menstrual Disorders and Subfertility Group trials register, AMED, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Wanfang Database, China Academic Journal Electronic full text Database in China National Knowledge Infrastructure, Index to Chinese Periodical Literature, ISI Proceedings for conference abstracts, and ISRCTN Register and Meta-register for randomized controlled trials. DATA COLLECTION AND ANALYSIS Study selection, quality appraisal, and data extraction were performed independently and in duplicate. The measures of treatment effect were the pooled relative risks (RR) of achieving clinical pregnancy, biochemical pregnancy, ongoing pregnancy, implantation rate, live birth, or miscarriage for women in the acupuncture group compared with women in the control group. RESULTS Using the random-effects model, pooling of the effect estimates from all of the 17 trials showed no significant difference in the clinical pregnancy outcome between the acupuncture and the control groups (RR=1.09, 95% confidence interval (CI) 0.94-1.26, p=0.25). No significant differences in the biochemical pregnancy, ongoing pregnancy, implantation rate, live birth, or miscarriage outcomes were found between the acupuncture and the control groups (biochemical pregnancy: RR=1.01, 95% CI 0.84-1.20, p=0.95; ongoing pregnancy: RR=1.20, 95% CI 0.93-1.56, p=0.16; implantation rate: RR=1.22, 95% CI 0.93-1.62, p=0.16; live birth: RR=1.42, 95% CI 0.92-2.20, p=0.11; miscarriage outcomes: RR=0.94, 95% CI 0.67-1.33, p=0.74). CONCLUSIONS No significant benefits of acupuncture are found to improve the outcomes of IVF or ICSI.

Comparison of semen quality and outcome of assisted reproductive techniques in Chinese men with and without hepatitis B.

In this study, we aimed to determine the effects of hepatitis B virus (HBV) infection on sperm quality and the outcome of assisted reproductive technology (ART). A total of 916 men (457 HBV-positive and 459 HBV-negative) seeking fertility assistance from January 2008 to December 2009 at the Womens Hospital in the School of Medicine at Zhejiang University were analysed for semen parameters. Couples in which the men were hepatitis B surface antigen (HBsAg)-seropositive were categorized as HBV-positive and included 587 in vitro fertilisation (IVF) and 325 intracytoplasmic sperm injection (ICSI) cycles from January 2004 to December 2009; negative controls were matched for female age, date of ova retrieval, ART approach used (IVF or ICSI) and randomized in a ratio of 1:1 according to the ART treatment cycles (587 for IVF and 325 for ICSI). HBV-infected men exhibited lower semen volume, lower total sperm count as well as poor sperm motility and morphology (P < 0.05) when compared to control individuals. Rates of two-pronuclear (2PN) fertilisation, high-grade embryo acquisition, implantation and clinical pregnancy were also lower among HBV-positive patients compared to those of HBV-negative patients after ICSI and embryo transfer (P < 0.05); IVF outcomes were similar between the two groups (P > 0.05). Logistic regression analysis showed that HBV infection independently contributed to increased rates of asthenozoospermia and oligozoospermia/azoospermia (P < 0.05) as well as decreased rates of implantation and clinical pregnancy in ICSI cycles (P < 0.05). Our results suggest that HBV infection in men is associated with poor sperm quality and worse ICSI and embryo transfer outcomes but does not affect the outcome of IVF and embryo transfer.