Shangwei Li

Needle immersed vitrification can lower the concentration of cryoprotectant in human ovarian tissue cryopreservation

OBJECTIVE To investigate whether needle immersed vitrification (NIV) can further lower the concentration of cryoprotective agent (CPA). DESIGN Experimental cross-sectional controlled in vitro study. SETTING University teaching hospital. PATIENT(S) Human ovarian biopsy tissues were obtained from ten women undergoing gynecology operations. INTERVENTION(S) Ovarian cortical tissues were cryopreserved using slow freezing or vitrification. The vitrification solutions used were as follows: group A: 2.69 mol/L ethylene glycol (EG)+2.11 mol/L dimethylsulfoxide (DMSO)+0.5 mol/L sucrose; group B: 2.42 mol/L EG+1.90 mol/L DMSO+0.5 mol/L sucrose; group C: 2.15 mol/L EG+1.69 mol/L DMSO+0.5 mol/L sucrose; and group D: 1.88 mol/L EG+1.48 mol/L DMSO+0.5 mol/L sucrose. MAIN OUTCOME MEASURE(S) Histologic evaluations were performed using light and electron microscopy. Apoptosis was assessed by TUNEL staining. Tissue damage after cryopreservation was measured by the levels of lactate dehydrogenase (LDH) in culture. RESULT(S) The proportion of normal ultrastructure of granulosa cells and stromal cells in groups B and C was higher than that in group A. The proportion of TUNEL-positive primordial follicles and stromal cells in the NIV groups decreased with reduction of concentration. Additionally, LDH levels in groups B and C were lower than in group A. CONCLUSION(S) The NIV method could further lower the concentration of CPA. Therefore, we can use the CPA of group C as an optimal concentration for NIV.

X-Ray Repair Cross-Complementing Group 1 (XRCC1) Genetic Polymorphisms and Cervical Cancer Risk: A HuGE Systematic Review and Meta-Analysis

Background Previous studies investigating the association between X-ray repair cross-complementation group 1(XRCC1) polymorphisms and cervical cancer (CC) risk has provided inconsistent results. The aim of our study was to assess the association between the XRCC1 gene Arg399Gln, Arg194Trp, Arg280His polymorphisms and risk of CC. Methods Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before March 2011.Summary odds ratios (ORs) and 95% confidence intervals (CIs) for XRCC1 polymorphisms and CC were calculated in a fixed-effects model or a random-effects model when appropriate. Results Ultimately, 9, 5 and 2 studies were found to be eligible for meta-analyses of Arg399Gln, Arg194Trp and Arg280His, respectively. Our analysis suggested that the variant genotypes of Arg194Trp were associated with a significantly increased CC risk (Trp/Trp vs Arg/Arg, OR = 2.21, 95% CI = 1.60–3.06; Arg/Trp vs Arg/Arg, OR = 1.23, 95% CI = 1.02–1.49; dominant model, OR = 1.36, 95% CI = 1.14–1.63; recessive model, OR = 2.06, 95% CI = 1.51–2.82). For Arg280His polymorphism, no obvious associations were found for all genetic models. For Arg399Gln polymorphism, also no obvious associations were found for all genetic models. In the subgroup analyses by ethnicity/country, a significantly increased risk was observed among Asian, especially among Chinese. To get more precise evidences, adjusted ORs (95%CI) by potential confounders (such as age, ethnicity or smoking, etc) were also calculated for XRCC1 Arg399Gln and Arg194Trp, however, the estimated pooled adjusted OR still did not change at all. Conclusion This meta-analysis suggests that Arg194Trp polymorphism may be associated with CC risk, Arg399Gln polymorphism might be a low-penetrent risk factor for CC only in Asians, and there may be no association between Arg280His polymorphism and CC risk.

Baseline psychological stress and ovarian norepinephrine levels negatively affect the outcome of in vitro fertilisation

Objective. We determined the effect of baseline psychological stress and norepinephrine (NE) levels in the follicular fluid on the outcome of in vitro fertilisation (IVF). Methods. One hundred seven women with tubal factor infertility were evaluated before and during their first IVF treatment. On the first day of down-regulation, their psychological state was measured using the Zung Self-rating Anxiety (SAS) and Depression Scales (SDS), and defined as baseline psychological stress. On oocyte retrieval day, NE levels in the follicular fluid and peripheral plasma were measured by high-performance liquid chromatography. Results. On the first day of down-regulation, nearly 10% of the women with tubal factor infertility reported that they were experiencing both anxiety and depression. This baseline psychological stress was lower in pregnant (3.7%) than in non-pregnant women (15.7%, p < 0.05). On oocyte retrieval day, the NE levels in follicular fluid were almost twice the amount seen in peripheral plasma, but did not differ in pregnant and non-pregnant women (p > 0.05). NE levels in follicular fluid were negatively associated with the percentage of good quality embryos (r = −0.62, p < 0.05). Conclusions. Baseline psychological stress (both anxiety and depression) may negatively influence the clinical pregnancy rate of IVF treatment in women with tubal factor infertility. Furthermore, follicular NE levels are negatively associated with the percentage of good quality embryos.

CTLA4Ig gene transfer alleviates abortion in mice by expanding CD4+CD25+ regulatory T cells and inducing indoleamine 2,3-dioxygenase

Successful pregnancy requires a state of immunological tolerance since normally the maternal immune system does not reject the semi-allogeneic conceptus. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a ligand for B7, delivers negative signals to antigen presenting cells (APCs) to compete with CD28 for binding to B7 molecules and down-regulate proinflammatory responses, thus inhibiting T cell activation. Using CBA/J x DBA/2 matings as an abortion-prone model, we observed that adenovirus-mediated CTLA4Ig (Ad-CTLA4Ig) gene transfer improves pregnancy outcome. Ad-CTLA4Ig therapy skewed the ability of serum cytokine production toward a Th2 bias. Flow cytometry revealed that Ad-CTLA4Ig administration expanded peripheral CD4(+)CD25(+) regulatory T cell populations in CBA/J x DBA/2 matings. Furthermore, Ad-CTLA4Ig administration induced indoleamine 2,3-dioxygenase (IDO) and Foxp3 mRNA expression at the materno-fetal interface. Our results demonstrate that adenovirus-mediated CTLA4Ig gene transfer improves pregnancy outcome in a murine model of abortion by expanding the CD4(+)CD25(+) regulatory T cell population and inducing IDO mRNA expression.

Estrogen receptor-alpha gene PvuII (T/C) and XbaI (A/G) polymorphisms and endometriosis risk: a meta-analysis.

Estrogen receptor-alpha (ER-α) polymorphisms have been hypothesized to be associated with the risk of endometriosis (EMT) development by many epidemiological studies, however, the available results were conflicting. To derive a more precise estimation of association between the ER-α PvuII (T/C) and XbaI (A/G) polymorphisms and risk of EMT, we performed a meta-analysis. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for ER-α polymorphisms and EMT were calculated in a fixed-effects model and a random-effects model when appropriate. This meta-analysis included 20 case-control studies with 1752 cases and 1742 controls for PvuII polymorphism and 15 case-control studies with 1349 cases and 1411 controls for XbaI polymorphism. For PvuII T/C polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, country, HWE in controls and study sample size, a significantly increased risk was observed among Caucasians (recessive model, OR=2.56, 95% CI=1.06-6.16) and among studies without the HWE (recessive model, OR=1.85, 95% CI=1.20-2.84). For XbaI A/G polymorphism, also no obvious associations were found for all genetic models. In the subgroup analyses by ethnicity, country, HWE in controls and study sample size, still no obvious associations were found. No publication bias was found in the present study. This meta-analysis suggests that ER-α gene PvuII (T/C) and XbaI (A/G) polymorphisms may not be associated with EMT risk, while the observed increase in risk of EMT may be due to small-study bias.

Gonadotropin-releasing hormone for preservation of ovarian function during chemotherapy in lymphoma patients of reproductive age: a summary based on 434 patients.

Background Gonadotropin-releasing hormone agonists (GnRHa) might play a role in preserving ovarian function in lymphoma patients by inhibiting chemotherapy-induced ovarian follicular damage. However, studies of its clinical efficacy have reported conflicting results. Method We conducted a meta-analysis to determine the effect of the preservation of ovarian function by administering GnRHa in young patients with lymphoma undergoing chemotherapy. Seven studies were identified that met inclusion criteria and comprised 434 patients assigned to GnRHa combined chemotherapy or chemotherapy alone. Results The incidence of women with premature ovarian failure (POF) demonstrated a statistically significant difference in favor of the use of GnRHa (OR=0.32, 95% CI 0.13-0.77). In addition, the final level of FSH in the GnRH group was significantly lower than control group. (MD= -11.73, 95% CI,-22.25- -1.20), and the final level of AMH in the GnRH group was significantly higher than control group (MD=0.80; 95% CI, 0.61–0.98). However, there was no statistically significant difference between treatment and the control groups in the incidence of a spontaneous pregnancy (OR=1.11; 95% CI, 0.55–2.26). Conclusion This meta-analysis suggests that GnRHa may be effective in protecting ovarian function during chemotherapy in lymphoma patients. More well-designed prospective studies are needed to carry out for further understanding of this topic.

Fertility assistance program following the Sichuan earthquake in China

On May 12, 2008 an earthquake measuring 8.0 on the Richter scale hit Wenchuan in Sichuan province, a mountainous region in western China, and rendered many parents childless. Doctors from the Womens Fertility Program of the Second West China Hospital in Sichuan carried out a post earthquake fertility assistance program in the following 3 months. The program included 3 parts: sociomedical fertility health support; psychological counseling and intervention in reproductive health; and an assisted reproductive technology (ART) service. Couples whose children had died or were disabled in the earthquake were entitled to free fertility counseling and ART, if required. Some women are currently pregnant as a result of the program, which has been successful in helping some surviving couples achieve their reproductive desires.

ASSOCIATION BETWEEN INTERLEUKIN-10 PROMOTER POLYMORPHISMS AND ENDOMETRIOSIS: A META-ANALYSIS

To investigate the influence of the interleukin-10 gene promoter polymorphisms on the susceptibility of endometriosis, we examined the association by performing a meta-analysis. The PubMed, Embase, HuGE Navigator and CNKI were searched to identify eligible studies. We then conducted a meta-analysis to examine the association between interleukin-10 gene promoter polymorphisms and endometriosis. Eight case-control studies which examined the association between the IL-10 gene promoter polymorphisms and the susceptibility to endometriosis were finally included in the meta-analysis. Meta-analysis of the IL-10 -592 A/C polymorphisms showed a significant increased risk of endometriosis in the overall and Asian population in all genetic models and allele contrast. However, meta-analysis of the IL-10 -1082 A/G and IL-10 -819 T/C polymorphisms showed no association with endometriosis in all genetic models and allele contrast in the overall and Asian population samples. In addition, there was not a significant association between the IL-10 -592 A/C gene promoter polymorphisms with the severity of endometriosis. In conclusion, this meta-analysis suggests that the IL-10 -592 A/C polymorphisms conferred susceptibility to endometriosis. However, no associations were found between the IL-10 -1082 A/G and -819 T/C polymorphisms and susceptibility to endometriosis. Further studies are required to elucidate these associations more clearly.

Recombinant Luteinizing Hormone supplementation in poor responders undergoing IVF: a systematic review and meta-analysis

Abstract The results of several studies about the effectiveness of recombinant luteinizing hormone (rLH) supplementation in poor responder in vitro fertilization (IVF) patients were conflicting. To evaluate the current available data regarding the efficacy of rLH supplementation in poor responders, a meta-analysis was performed. A systemic search was performed without language limitation but restricted to randomized controlled trial (RCT). We mainly explored MEDLINE, EMBASE, CNKI and Cochrane Library for the relevant studies. Three studies were considered eligible for inclusion. The meta-analysis indicated that rLH supplementation did not increase the ongoing pregnancy rate in poor responders (OR 1.30, 95% CI: 0.80, 2.11). Furthermore, there was no significant difference in the number of oocytes retrieved, total dose of rFSH used, total duration of stimulation, number of retrieved metaphase II oocytes and cycle cancellation rate between the study and control groups. In conclusions, the available evidence does not support the addition of rLH in poor responders treated with rFSH and GnRHa for IVF. It was inconclusive. Future research should be based on strict criteria to define poor responders, and large, well-designed RCTs are necessary to definitively answer the important question of whether there was need to use rLH in poor responders undergoing IVF.

Polymorphism T → C of gene CYP17 promoter and polycystic ovary syndrome risk: A meta-analysis

The T→C polymorphism of CYP17 gene has been inconsistently associated with polycystic ovary syndrome (PCOS) risk. We examined the association by performing a meta-analysis. Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP17 polymorphism and PCOS were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed for co-dominant model (CC vs. TT, TC vs. TT), dominant model (CC+TC vs. TT), and recessive model (CC vs. TC+TT). Subgroup analyses were performed by ethnicity, country, Hardy-Weinberg equilibrium (HWE) in controls and study sample size. This meta-analysis included 10 case-control studies, which included 1321 PCOS cases and 1017 controls. Overall, the variant genotypes (CC and TC) were not associated with PCOS risk, compared with the wild-type TT homozygote. Similarly, no associations were found in the dominant and recessive models. Stratified analyses by ethnicity/country also detected no significant association. However, limiting the analysis to the studies within HWE, a significantly increased risk was observed (TC vs. TT, OR=1.44, 95% CI=1.10-1.88; dominant model, OR=1.41, 95% CI=1.10-1.81). Moreover, when stratifying by study sample size, a significantly elevated risk was found among small sample studies (≤200 subjects), but not among large sample studies (> 200 subjects). This meta-analysis suggests that the CYP17 T/C polymorphism may be not associated with PCOS risk, while the observed increase in risk of PCOS may be due to small-study bias.