Blood Trace Element Concentrations in Polycystic Ovary Syndrome: Systematic Review and Meta-analysis

Polycystic ovary syndrome (PCOS) is a prevalent condition in women of reproductive age. PCOS is characterized by androgen excess and chronic anovulation and associated with low-grade inflammation and metabolic comorbidities. Some trace elements have been linked to pathophysiological mechanisms of oxidative stress and inflammation in different disorders. Therefore, we conducted a systematic review and meta-analysis of the available evidence regarding trace element concentrations in PCOS. We reviewed MEDLINE and EMBASE in search of case-control, cross-sectional, and cohort studies published until September 2015. Of 183 studies identified, six were selected for systematic review. All used the Rotterdam criteria for the diagnosis of PCOS. Two studies evaluating chromium and one assessing cobalt levels did not observe differences between PCOS and controls. Another study recorded similar nickel and vanadium levels between the groups, but lower selenium concentrations in women with PCOS compared to controls. Four studies were included in the random effects model meta-analysis, for a total of 264 PCOS and 151 control women. Copper levels were found to be higher in women with PCOS than in controls [mean difference 0.12 ppm (95 % CI 0.07; 0.17 ppm); I ²?=?0 %]. Manganese [mean difference 0.04 ppm (95 % CI ?0.05; 0.13 ppm); I ²?=?94.4 %] and zinc concentrations [mean difference 0.02 ppm (95 % CI ?0.12; 0.16 ppm); I ²?=?92.4 %] were similar between the groups. The present results suggest a relationship between increased copper concentration and PCOS. This systematic review and meta-analysis is registered in PROSPERO under number CRD42016034036.     

Effects of Multivitamin/Mineral Supplementation on Trace Element Levels in Serum and Follicular Fluid of Women Undergoing in Vitro Fertilization (IVF)

We investigated effects of multivitamin/mineral supplementation on element levels in serum and follicular fluid of women undergoing IVF. We used three groups in this study. The first group was used as an age-matched and nonpregnant control (n = 13). Group 2 (n = 30) constituted the IVF group and women in the third group who were undergoing IVF also received a multivitamin/mineral tablet daily for 45 days. Follicular fluid and serum selenium and zinc levels and follicular fluid copper levels were lower in IVF patients than in controls although follicular fluid aluminum and iron levels were higher in IVF patients than in controls. However, follicular fluid and serum aluminum, copper, zinc and selenium levels, and serum magnesium levels were higher in the multivitamin/mineral group than in the IVF group although follicular fluid iron levels were lower in the multivitamin/mineral group than in the IVF group. In conclusion, we observed that copper, zinc, and selenium in serum and follicular fluid decreased in women undergoing IVF. Multivitamin/mineral supplementation in serum and follicular fluid of women undergoing IVF normalized the trace element levels.     

Poor Prognosis with In Vitro Fertilization in Indian Women Compared to Caucasian Women Despite Similar Embryo Quality

Background

Disease prevalence and response to medical therapy may differ among patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF) treatment have been previously shown in Indian women compared to Caucasian women, and some evidence suggests that poor embryo quality may be a cause for the discrepancy. In our center, only patients with the highest quality cleavage stage embryos are considered eligible for extending embryo culture to the blastocyst stage. We compared live birth rates (LBR) between Indian and Caucasian women after blastocyst transfer to investigate whether differences in IVF outcomes between these ethnicities would persist in patients who transferred similar quality embryos.

Methodology/Principal Findings

In this retrospective cohort analysis, we compared IVF outcome between 145 Caucasians and 80 Indians who had a blastocyst transfer between January 1, 2005 and June 31, 2007 in our university center. Indians were younger than Caucasians by 2.7 years (34.03 vs. 36.71, P = 0.03), were more likely to have an agonist down regulation protocol (68% vs. 43%, P<0.01), and were more likely to have polycystic ovarian syndrome (PCOS), although not significant, (24% vs. 14%, P = 0.06). Sixty eight percent of Indian patients had the highest quality embryos (4AB blastocyst or better) transferred compared to 71% of the Caucasians (P = 0.2). LBR was significantly lower in the Indians compared to the Caucasians (24% vs. 41%, P<0.01) with an odds ratio of 0.63, (95%CI 0.46–0.86). Controlling for age, stimulation protocol and PCOS showed persistently lower LBR with an adjusted odds ratio of 0.56, (95%CI 0.40–0.79) in the multivariate analysis.

Conclusions/Significance

Despite younger age and similar embryo quality, Indians had a significantly lower LBR than Caucasians. In this preliminary study, poor prognosis after IVF for Indian ethnicity persisted despite limiting analysis to patients with high quality embryos transferred. Further investigation into explanations for ethnic differences in reproduction is needed.     

猪卵母细胞的体外受精及多精受精

对用于猪体外受精(IVF)的研究方法和技术,如传统的液滴IVF、透明带下注射精子受精(SUZI)、卵母细胞质内单精注射受精(ICSI)及细管IVF等进行了简述。与其它动物相比,进行猪卵的体外受精研究,多精受精现象特别明显。大量的研究表明,猪卵的多精受精不但与其品种特性有关,而且与卵母细胞成熟的程度、透明带的异常、受精时获能精子的浓度、输卵管分泌物、受精液蛋白添加成分、NaHCO3浓度、咖啡因、pH值以及温度等因素密切相关。     

小鼠卵母细胞体外成熟、体外受精的效果观察

目的　研究不同培养条件对小鼠卵母细胞体外成熟及体外受精率的影响。方法　小鼠卵母细胞分别在含有FSH、BSA和胰岛素的培养液中体外成熟,在Whitten 氏液中体外受精,比较体外成熟率、体外受精率。结果　1- 裸卵(DO) 的体外成熟率、体外受精率(81-4% ,31-0 % ) 均高于卵丘卵母细胞复合体(COC)(48-6 % ,27-1% ) 。2- 在培养液中添加FSH、胰岛素和BSA,卵母细胞的体外成熟率为77-9 % ,82-3% 、60-7% ;体外受精率为77-2 % 、72-6 % 、26-7% ;2 - 细胞率为49-2 % 、34-2 % 、10-0% 。胰岛素组的卵母细胞IVM 率最高,但IVF率、2 - 细胞率低于FSH 组。3- 添加BSA的两组的体外受精率只有26-7 % 、25-8 % ,显著低于其他组,其体外成熟率也较添加FSH 和胰岛素的组成。4- 排出第一极体(PbI) 的卵母细胞的体外受精率和2 - 细胞率(85-9 % ,22-4% ) 均高于GV期卵母细胞(71-1 % ,12-9 % ) 。结论　1- 卵丘卵母细胞(COC) 较裸卵(DO) 的体外成熟率、体外受精率都低,差异显著(P成熟< 0-01;P受精< 0-05) 。2-FSH 和胰岛素均能提高小鼠卵母细胞的体外成熟率、体外受精率。3-BSA可以降低小鼠卵母细胞体外受精率,差异极显著。4-GV 期卵母细胞的体外受精率显著低于体外培养的排出第一极体的卵母细胞(P2 - cell < 0-05,P受精<0-05)     

Blood Cadmium Concentrations in Women with Ectopic Pregnancy

The purpose of this study is to investigate the relationship between the blood level of cadmium and the occurrence of ectopic pregnancy. Forty-one (41) case patients with ectopic pregnancy and 41 uncomplicated intrauterine pregnant patients as controls were recruited. The concentrations of cadmium (Cd) were measured from blood samples using atomic absorption spectrometry. The cases and controls were similar in age, body mass index, and smoking habits. The median blood level of Cd was 0.32 μg/l (interquartile range [IQR] 0.00–0.71) in the women with ectopic pregnancies and 0.34 μg/l (IQR 0.09–0.59) in the controls. There was no significant association between blood cadmium levels and ectopic pregnancy.     

牛卵母细胞体外受精及体外发育的研究

本研究利用从屠宰场收集到的牛卵巢,获取卵母细胞,经体外成熟后进行体外受精,其受精率为73±2％。受精卵分别用发育培养基TCM—199+10％FCS(MA)、颗粒细胞单层(MB)和卵管上皮单层(MC)进行培养,其8—16细胞的发育率分别为52％、54％和61％;而囊胚的发育率分别为20％、28％和42％。相比较而言,MB和MC培养基内突破8—16细胞阻断发育到囊胚的发育率优于MA。     

Noninvasive Digital Detection of Fetal DNA in Plasma of 4-Week-Pregnant Women following In Vitro Fertilization and Embryo Transfer

The discovery of cell-free fetal DNA (cfDNA) circulating in the maternal blood has provided new opportunities for noninvasive prenatal diagnosis (NIPD). However, the extremely low levels of cfDNA within a high background of the maternal DNA in maternal circulation necessitate highly sensitive molecular techniques for its reliable use in NIPD. In this proof of principle study, we evaluated the earliest possible detection of cfDNA in the maternal plasma by a bead-based emulsion PCR technology known as BEAMing (beads, emulsion, amplification, magnetics). Blood samples were collected from in vitro fertilization (IVF) patients at 2 to 6 weeks following embryo transfer (i.e., 4 to 8 week pregnancies) and plasma DNA was extracted. The genomic regions of both X and Y chromosome-specific sequences (AMELX and AMELY) were concurrently amplified in two sequential PCRs; first by conventional PCR then by BEAMing. The positive beads either for AMELX or AMELY gene sequences were counted by a flow cytometer. Our results showed that the pregnancies yielding boys had significantly higher plasma AMELY gene fractions (0.512 ± 0.221) than the ones yielding girls (0.028 ± 0.003) or non-pregnant women (0.020 ± 0.005, P= 0.0059). Here, we clearly demonstrated that the BEAMing technique is capable of reliably detecting cfDNA in the blood circulation of 4-week-pregnant women, which is only two weeks after the embryo transfer. BEAMing technique can also be used to early detect fetal DNA alterations in other pregnancy-associated disorders.     

低温保存的小鼠卵母细胞的体外授精研究

采用75分钟和150分钟两种精卵作用时间,对经6℃低温处理2小时和6小时的小鼠卵母细胞进行体外受精。精卵作用75分钟后,经6℃处理的卵子无一受精,而对照组的受精率为30.7％。作用150分钟后,低温处理2小时、6小时和对照组的受精率分别为62.0％,36.55％和76.0％。并对试验所出现的现象作了讨论。     

Trace Element Concentrations in Beef Cattle Related to the Breed Aptitude

Environmental and occupational mercury exposure is considered a major public health issue. Despite being well known that MeHg exposure causes adverse effects in several physiologic functions, MeHg effects on salivary glands still not completely elucidated. Here, we investigated the cellular MeHg-induced damage in the three major salivary glands (parotid, submandibular, and sublingual) of adult rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by 0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three glands were collected. We evaluated total Hg accumulation, metallothionein I/II (MT I/II), α-smooth muscle actin (α-SMA), and cytokeratin 18 (CK18) immune expression. Our results have showed that MeHg is able to disrupt gland tissue and to induce a protective mechanism by MT I/II expression. We also showed that cell MT production is not enough to protect gland tissue against cellular structural damage seen by reducing marking of cytoskeletal proteins as CK18 and α-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able to induce cellular damage in rat salivary glands.     

Preconception Vitamin D Level and In Vitro Fertilization: Pregnancy Outcome

ObjectiveVitamin D deficiency impairs female fertility and the success of in vitro fertilization (IVF). The recommended serum 25-hydroxyvitamin D (25(OH)D) level in IVF-conceived pregnancies is still debated. We aimed to explore the relationship of the preconception serum 25(OH)D level with pregnancy outcome following IVF treatment. We also explored the utility of the currently recommended serum 25(OH)D cutoff of ≥50 nmol/L for women undergoing IVF therapy.MethodsRetrospective cohort of women who had undergone IVF therapy. Of the women who started IVF therapy (n = 354), 218 completed the study. They were divided into 2 groups: (1) women who achieved a successful pregnancy (pregnant group, n = 160) and (2) those who did not achieve a successful pregnancy (nonpregnant group, n = 58). Preconception serum samples were analyzed for reproductive hormones, fasting glucose, insulin, and 25(OH)D levels.ResultsOverall, the median (interquartile range) age, body mass index, and hemoglobin A1c level were 32 (6) years, 25.7 (7.4) kg/m², and 5.2% (0.6%), respectively. The 25(OH)D level was significantly higher at preconception in the pregnant group (56.4 [21.4] vs 47.9 [29.16] for nonpregnant, P = .001). The preconception 25(OH)D level was a significant predictor of IVF outcome (B = 0.04; 95% CI, 1.01-1.06; P = .001), with greater IVF success associated with a serum 25(OH)D level of ≥50 nmol/L (odds ratio, 0.46; P = .01).ConclusionPreconception 25(OH)D sufficiency (≥50 nmol/L) is associated with successful pregnancy outcome following IVF therapy.     

我国被子植物体外受精研究—十年回顾

简要回顾了十余年来我国被子植物体外受精领域的研究历程和主要成就。我国科学家在性细胞的分离 ,尤其是生活胚囊和雌配子的分离方面走在国际前列。在一定程度上我国科学家的开拓性工作引起了国际同行的广泛兴趣和重视 ,推动了该领域的迅速发展 ,为实现被子植物真正意义的体外受精做出了独特的贡献。十年来 ,我国已建立了自己独特的被子植物离体受精实验技术系统并利用该系统与国际同行合作进行了一系列研究 ,尤其在探讨配子相互作用、卵细胞激活、避免多精入卵的机制等方面做出了创新性工作 ,为正确认识体外受精系统的优越性与局限性 ,也为深入探讨受精机制提供了有价值的新资料。目前正以体外受精操作系统结合细胞生物学和分子生物学等多种手段对受精过程中的一些重要事态与机理做进一步探讨     

Significance and Interspecific Variability of Accumulated Trace Metal Concentrations in Antarctic Benthic Crustaceans

Trace metals (Cd, Cu, Pb and Zn) were analysed in crustaceans collected on Polarstern cruises ANT XVI/2 (1999) and ANT XXI/2 (2003/04, BENDEX) to the Weddell Sea. Our study provides further evidence for the frequently reported “Cd anomaly” in polar crustaceans, with data ranging from 1.2 (Ceratoserolis trilobitoides) to 6.2 mg Cd kg^–1 DW (Notocrangon antarcticus) in 1999 and from 1.2 (Waldeckia obesa) to 20.3 mg Cd kg^–1 (Tryphosella murrayi) in 2003. Pb concentrations well below 1 mg kg^–1 in most of the samples analysed might serve as a regional or even global background value for comparison in biomonitoring studies. Increasing Cu concentrations from eggs of decapods (e.g., 5 vs. 51 mg kg^–1 in N. antarcticus) or juveniles in the brood pouch of an amphipod species to adult females indicate that the enzymatic requirements and haemocyanin component demand for Cu in early life‐history stages is probably not met without a distinct bioaccumulation of this essential element after hatching. Most interestingly, Cd also increases (<0.1 vs. 6.2 mg kg^–1 in N. antarcticus). This could be the consequence of efficient uptake mechanisms for Cu that cannot discriminate between this element and Cd. Cu and Zn concentrations in decapods of this study are largely within the range reported worldwide (40–90 mg Cu kg^–1 and 40–80 mg Zn kg^–1), indicating that these elements are regulated. The enormous heterogeneity of Cd and Zn in many amphipod species investigated (e.g., from 0.6 in Gnathiphimedia mandibularis to 34.4 mg Cd kg^–1 in Orchomenopsis acanthura and from 41 in Eusirus antarcticus to 1244 mg Zn kg^–1 in Iphimediella bransfieldi) supports the hypothesis of the “Cd anomaly” and suggests that there is probably no consistent metabolic demand for the essential element Zn in this taxonomic group. The heterogeneity of Cu in amphipods is less pronounced. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

我国被子植物体外受精研究——十年回顾

简要回顾了十余年来我国被子植物体外受精领域的研究历程和主要成就.我国科学家在性细胞的分离, 尤其是生活胚囊和雌配子的分离方面走在国际前列. 在一定程度上我国科学家的开拓性工作引起了国际同行的广泛兴趣和重视, 推动了该领域的迅速发展, 为实现被子植物真正意义的体外受精做出了独特的贡献.十年来, 我国已建立了自己独特的被子植物离体受精实验技术系统并利用该系统与国际同行合作进行了一系列研究, 尤其在探讨配子相互作用、卵细胞激活、避免多精入卵的机制等方面做出了创新性工作, 为正确认识体外受精系统的优越性与局限性, 也为深入探讨受精机制提供了有价值的新资料.目前正以体外受精操作系统结合细胞生物学和分子生物学等多种手段对受精过程中的一些重要事态与机理做进一步探讨.     

Production of Haploid Zebrafish Embryos by In Vitro Fertilization

The zebrafish has become a mainstream vertebrate model that is relevant for many disciplines of scientific study. Zebrafish are especially well suited for forward genetic analysis of developmental processes due to their external fertilization, embryonic size, rapid ontogeny, and optical clarity – a constellation of traits that enable the direct observation of events ranging from gastrulation to organogenesis with a basic stereomicroscope. Further, zebrafish embryos can survive for several days in the haploid state. The production of haploid embryos in vitro is a powerful tool for mutational analysis, as it enables the identification of recessive mutant alleles present in first generation (F1) female carriers following mutagenesis in the parental (P) generation. This approach eliminates the necessity to raise multiple generations (F2, F3, etc.) which involves breeding of mutant families, thus saving the researcher time along with reducing the needs for zebrafish colony space, labor, and the husbandry costs. Although zebrafish have been used to conduct forward screens for the past several decades, there has been a steady expansion of transgenic and genome editing tools. These tools now offer a plethora of ways to create nuanced assays for next generation screens that can be used to further dissect the gene regulatory networks that drive vertebrate ontogeny. Here, we describe how to prepare haploid zebrafish embryos. This protocol can be implemented for novel future haploid screens, such as in enhancer and suppressor screens, to address the mechanisms of development for a broad number of processes and tissues that form during early embryonic stages.     

Improved in Vitro Fertilization Outcomes after Treatment of Subclinical Hypothyroidism in Infertile Women

ObjectiveTo assess the effect of treatment of maternal subclinical hypothyroidism on infertility outcome.MethodsBetween April 1, 2006, and April 22, 2007, we conducted a prospective, randomized trial in infertile women with subclinical hypothyroidism who elected to undergo in vitro at the Shatby University Hospital for Women in Alexandria, Egypt. Patients were randomly assigned to 2 groups: treatment group (group A) and placebo group (group B). Male-factor infertility was ruled out. One month before the assisted reproduction technology procedure, group A underwent levothyroxine treatment with a dosage of 50 to 100 mcg daily, while group B started placebo. All patients underwent controlled ovarian stimulation. Patients who achieved pregnancy were followed up throughout their pregnancy until delivery. Levothyroxine treatment and placebo were maintained throughout pregnancy in group A and group B, respectively.ResultsMean thyrotropin value was significantly lower in group A than in group B (1.1 ± 0.3 mIU/L vs 4.9 ± 0.7 mIU/mL, respectively). Mean number of retrieved oocytes was similar in both groups (6.19 ± 0.74 [group A] vs 6.08 ± 0.79 [group B]). Miscarriage rate was significantly lower in group A than in group B (9% vs 13%, respectively), and the clinical pregnancy rate and delivery rate were significantly higher in group A than in group B (35% and 10% vs 26% and 3%, respectively), indicating that the quality, not the quantity, of retrieved oocytes was more important.ConclusionThese preliminary data suggest that levothyroxine supplementation should be recommended to achieve clinical pregnancies in women with subclinical hypothyroidism who are undergoing in vitro fertilization–intracytoplasmic sperm injection. (Endocr Pract. 2010:16: 792-797)     

Hospital Mental Health Admissions in Women after Unsuccessful Infertility Treatment and In Vitro Fertilization: An Australian Population-Based Cohort Study

Objective

To examine the association between in vitro fertilization (IVF) and later admission to hospital with a mental health diagnosis in women who remained childless after infertility treatment.

Methods

This was a population-based cohort study using linked administrative hospital and registry data. The study population included all women commencing hospital treatment for infertility in Western Australia between the years 1982 and 2002 aged 20–44 years at treatment commencement who did not have a recorded birth by the end of follow-up (15 August 2010) and did not have a hospital mental health admission prior to the first infertility admission (n=6,567). Of these, 2,623 women had IVF and 3,944 did not. We used multivariate Cox regression modeling of mental health admissions and compared women undergoing IVF treatment with women having infertility treatment but not IVF.

Results

Over an average of 17 years of follow-up, 411 women in the cohort were admitted to hospital with a mental health diagnosis; 93 who had IVF and 318 who did not. The unadjusted hazard ratio (HR) for a hospital mental health admission comparing women who had IVF with those receiving other infertility treatment was 0.50 (95% confidence interval [CI] 0.40–0.63). After adjustment for age, calendar year and socio-economic status the HR was 0.56 (95% CI 0.44–0.71).

Conclusions

IVF treatment is associated with a reduced risk of hospital mental health admissions in women after unsuccessful infertility treatment. This may be explained by the healthy cohort effect.