Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Importance: Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate. Objective: To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure. Design, Setting, and Participants: A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021). Interventions: Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy. Main Outcomes and Measures: The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life. Results: Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, -1.0% [95% CI, -8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P = .78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P = .04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P = .04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights. Conclusions and Relevance: Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800018783.

Androgen Excess Increases Food Intake in a Rat Polycystic Ovary Syndrome Model by Downregulating Hypothalamus Insulin and Leptin Signaling Pathways Preceding Weight Gain.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus and subsequently on the food intake and obesity in females. METHODS: A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus and primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR, respectively. The leptin levels in the serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of the hypothalamus. RESULTS: The excessive prepuberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of neuropeptide Y and agouti-related peptide mRNAs was upregulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake. CONCLUSIONS: Androgen excess increased food intake in rats and promoted obesity by downregulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

Single-cell analysis of nonhuman primate preimplantation development in comparison to humans and mice.

BACKGROUND: Genetic programs underlying preimplantation development and early lineage segregation are highly conserved across mammals. It has been suggested that nonhuman primates would be better model organisms for human embryogenesis, but a limited number of studies have investigated the monkey preimplantation development. In this study, we collect single cells from cynomolgus monkey preimplantation embryos for transcriptome profiling and compare with single-cell RNA-seq data derived from human and mouse embryos. RESULTS: By weighted gene-coexpression network analysis, we found that cynomolgus gene networks have greater conservation with human embryos including a greater number of conserved hub genes than that of mouse embryos. Consistently, we found that early ICM/TE lineage-segregating genes in monkeys exhibit greater similarity with human when compared to mouse, so are the genes in signaling pathways such as LRP1 and TCF7 involving in WNT pathway. Last, we tested the role of one conserved pre-EGA hub gene, SIN3A, using a morpholino knockdown of maternal RNA transcripts in monkey embryos followed by single-cell RNA-seq. We found that SIN3A knockdown disrupts the gene-silencing program during the embryonic genome activation transition and results in developmental delay of cynomolgus embryos. CONCLUSION: Taken together, our study provided new insight into evolutionarily conserved and divergent transcriptome dynamics during mammalian preimplantation development.

Morphological and anatomical characteristics of exserted stigma sterility and the location and function of SlLst (Solanum lycopersicum Long styles) gene in tomato.

KEY MESSAGE: Anatomical changes in and hormone roles of the exserted stigma were investigated, and localization and functional analysis of SlLst for the exserted stigma were performed using SLAF-BSA-seq, parental resequencing and overexpression of SlLst in tomato. Tomato accession T431 produces stigmas under relatively high temperatures (> 27 °C, the average temperature in Harbin, China, in June-August), so pollen can rarely reach the stigma properly. This allows the percentage of male sterility exceed 95%, making the use of this accession practical for hybrid seed production. To investigate the mechanism underlying the exserted stigma male sterility, the morphological changes of, anatomical changes of, and comparative endogenous hormone (IAA, ABA, GA3, ZT, SA) changes in flowers during flower development of tomato accessions DL5 and T431 were measured. The location and function of genes controlling exserted stigma sterility were analyzed using super SLAF-BSA-seq, parental resequencing, comparative genomics and the overexpression of SlLst in tomato. The results showed that an increase in cell number mainly caused stigma exsertion. IAA played a major role, while ABA had an opposite effect on stigma exertion. Moreover, 26 candidate genes related to the exserted stigma were found, located on chromosome 12. The Solyc12g027610.1 (SlLst) gene was identified as the key candidate gene by functional analysis. A subcellular localization assay revealed that SlLst is targeted to the nucleus and cell membrane. Phenotypic analysis of SlLst-overexpressing tomato showed that SlLst plays a crucial role during stigma exsertion.

Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial.

BACKGROUND: Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer. METHODS: This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405. FINDINGS: 825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 [50%] vs 329 [40%]; relative risk [RR] 1·26, 95% CI 1·14-1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 [0·5%] in frozen single blastocyst transfer vs nine of 825 [1·1%] in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 [23·0%] vs 124 of 481 [25·8%]; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 [3·1%] vs four of 401 [1·0%]; RR 3·13, 95% CI 1·06-9·30, p=0·029). INTERPRETATION: Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies. FUNDING: The National Key Research and Development Program of China.

[High-level androgen enhances the differentiation of hESCs into male primordial germ cells].

OBJECTIVE: To observe the effects of different concentrations of testosterone on the differentiation of human embryonic stem cells (hESCs) into early male germ cells and investigate the potential impact of high-level androgen exposure in early pregnancy in women with polycystic ovary syndrome (PCOS) on the fertility and primordial germ cell reserve of the male offspring in adulthood. METHODS: We used 2 µmol/L retinoic acid to induce the differentiation of hESCs (46, XY) into male germ cells in vitro and meanwhile treated them with testosterone (T) at 0 mol/L, 3×10－7 mol/L, 5×10－7 mol/L, 15×10－7 mol/L, 45×10－7 mol/L, and 135×10－7 mol/L, respectively. We collected the cell samples at 0, 4, 7 and 14 days to determine the expressions of the specific genes and compare the differentiation process and efficiency of the male germ cells in different stages. RESULTS: There was no difference in the morphology of the hESCs treated with different concentrations of testosterone in the same differentiation stage. The expression of the marker gene DAZL in the primordial germ cells peaked on the 4th day of differentiation, significantly higher in the 15×10－7, 45×10－7 and 135×10－7 mol/L groups than in the 3×10－7 mol/L group (P < 0.05), and that of the specific gene SCP3 in the early-meiosis germ cells began to increase on the same day, more significantly in the 45×10－7mol/L than in the 3×10－7 mol/L and 5×10－7 mol/L groups (P < 0.01), and peaked on the 7th day, dramatically higher in the 15×10－7, 45×10－7 and 135×10－7 mol/L groups than in the 3×10－7 mol/L group (P < 0.01). Immunofluorescence staining and flow cytometry showed a T concentration-dependent increase in the expression of DAZL at 4 days and those of SCP3 and VASA at 7 days. Moreover, the expression of the androgen receptor (AR) in the hESCs began to rise on the 4th day and kept going up till the 14th day, higher in the high-concentration than in the low-concentration T groups in the same stage of differentiation, though with no statistically significant difference (P > 0.05). CONCLUSIONS: Exposure to high-level androgen during the differentiation of hESCs into early male germ cells can induce earlier expression of AR and earlier differentiation of hESCs into early male germ cells, which may result in insufficient reserve of male primary germ cells in the male offspring of PCOS women and affect their fertility after adulthood. hESCs can be used as an in vitro model to study the effects of intrauterine hyperandrogen on the reproductive development of male offspring in PCOS patients, which is also contributive to researches on the etiology of male infertility.

[Peroxiredoxin 4 protects the testis from heat stress].

OBJECTIVE: To explore the protective effect of Peroxiredoxin 4 (PRDX4) on the testes undergoing heat stress in PRDX4 knockout mice. METHODS: Twenty-four C57BL/6 mice underwent CRISPR/Cas9-mediated total knockout of the PRDX4 gene and another 24 wild-type mice were used as controls. At 9 weeks of age, the rats were subjected to 15-minute testicular heat stress in 43℃ water once a day for 3 days, or in 25℃ water as the control. Before and at 1 day and 5 weeks after treatment, 4 from each group were sacrificed respectively and their testes harvested for observation of histological changes by HE staining, detection of the apoptosis of spermatogenic cells by TUNEL and determination of the expression of PRDX4 by Western blot and those of the oxidative stress factors hydroxynonenal (HNE) and 8-OHdG by immunohistochemistry. RESULTS: No statistically significant differences were observed in testicular histology, the apoptosis rate of spermatogenic cells, and the expressions of HNE and 8-OHdG between the PRDX4 knockout mice and wild-type controls (P > 0.05). After 1-day 43℃ heat stress, the PRDX4 knockout mice showed a significantly increased apoptosis rate of spermatogenic cells as compared with the baseline (ï¼»38.65 ± 2.57ï¼½% vs ï¼»0.46 ± 0.06ï¼½%, P < 0.01), and so did the wild-type controls (ï¼»13.21 ± 1.43ï¼½% vs ï¼»0.33 ± 0.01ï¼½%, P < 0.01), higher in the PRDX4 knockout than in the wild-type control group even at 5 weeks after heat stress (ï¼»3.09 ± 0.16ï¼½% vs ï¼»1.45 ± 0.11ï¼½%, P < 0.01). The PRDX4 knockout mice also exhibited a markedly upregulated expression of 8-OHdG (38.25 ± 1.19 vs 19.54 ± 1.13, P < 0.01), and so did the wild-type controls (24.30 ± 1.65 vs 18.22 ± 1.18, P < 0.01), higher in the PRDX4 knockout than in the wild-type control group even at 5 weeks after heat stress (25.40 ± 1.57 vs 23.25 ± 1.48, P < 0.01). The expression of HNE, however, showed no statistically significant difference before and at 1 day after 43℃ heat stress either in the PRDX4 knockout mice or in the wild-type controls (P > 0.05), though remarkably higher in the former than in the latter group at 5 weeks after treatment (28.57 ± 0.56 vs 19.00 ± 1.35, P < 0.01). The expression of 8-OHdG was also higher in the PRDX4 knockout than in the wild-type control group at 5 weeks, but with no statistically significant difference (P > 0.05). CONCLUSIONS: PRDX4 can effectively protect the testis from heat stress and promote the restoration of its spermatogenic function.

Aminopeptidase N expression in the endometrium could affect endometrial receptivity.

Aminopeptidase N (ANPEP) is a membrane-bound zinc-dependent peptidase. Although it is widely believed that ANPEP acts as an important angiogenesis regulatory factor, there are few studies about its function in the female reproductive system. In our previous research, we applied Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) to analyze the influence of different controlled superovulation treatments for Assisted Reproductive Technology, In Vitro Fertilization and Embryo Transfer (IVF-ET)) patients from a global proteomic perspective to search for potential biomarkers associated with endometrium receptivity and embryo implantation. ANPEP is one of the proteins that demonstrated differential expression between different treatment groups and may be closely associated with endometrial receptivity. In this study, we assessed the expression of ANPEP in the endometrium of mice at different ages and found it to be highest in the mature period. We also detected ANPEP expression in the endometrium of IVF-ET patients in the proliferative, preimplantation and implantation stages, and the highest expression level of ANPEP was found in the last group. Human primary endometrial stromal cells were infected with an adenovirus expression vector containing the ANPEP gene and a green fluorescent protein (GFP) fusion protein; the mRNA levels of HOXA-10, LIF, and integrin ß3 were found to be increased. Therefore, we conclude that ANPEP could be involved in the regulation of endometrial receptivity.

Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing.

Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.

Can peri-ovulatory putrescine supplementation improve egg quality in older infertile women?

The aging-related decline in fertility is an increasingly pressing medical and economic issue in modern society where women are delaying family building. Increasingly sophisticated, costly, and often increasingly invasive, assisted reproductive clinical protocols and laboratory technologies (ART) have helped many older women achieve their reproductive goals. Current ART procedures have not been able to address the fundamental problem of oocyte aging, the increased rate of egg aneuploidy, and the decline of developmental potential of the eggs. Oocyte maturation, which is triggered by luteinizing hormone (LH) in vivo or by injection of human chorionic gonadotropin (hCG) in an in vitro fertilization (IVF) clinic, is the critical stage at which the majority of egg aneuploidies arise and when much of an egg's developmental potential is established. Our proposed strategy focuses on improving egg quality in older women by restoring a robust oocyte maturation process. We have identified putrescine deficiency as one of the causes of poor egg quality in an aged mouse model. Putrescine is a biogenic polyamine naturally produced in peri-ovulatory ovaries. Peri-ovulatory putrescine supplementation has reduced egg aneuploidy, improved embryo quality, and reduced miscarriage rates in aged mice. In this paper, we review the literature on putrescine, its occurrence and physiology in living organisms, and its unique role in oocyte maturation. Preliminary human data demonstrates that there is a maternal aging-related deficiency in ovarian ornithine decarboxylase (ODC), the enzyme responsible for putrescine production. We argue that peri-ovulatory putrescine supplementation holds great promise as a natural and effective therapy for infertility in women of advanced maternal age, applicable in natural conception and in combination with current ART therapies.

[Preimplantation genetic diagnosis for infertile males with autosomal dominant polycystic kidney disease].

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic renal diseases, which may cause oligoasthenospermia and azoospermia and result in male infertility. This study aimed to analyze the outcomes of preimplantation genetic diagnosis (PGD) in male patients with ADPKD-induced infertility. METHODS: We retrospectively analyzed the clinical data on 7 male patients with ADPKD-induced infertility undergoing PGD from April 2015 to February 2017, including 6 cases of oligoasthenospermia and 1 case of obstructive azoospermia, all with the PKD1 gene heterozygous mutations. Following intracytoplasmic sperm injection (ICSI), we performed blastomere biopsy after 5 or 6 days of embryo culture and subjected the blastomeres to Sureplex whole-genome amplification, followed by haplotype linkage analysis, Sanger sequencing, array-based comparative genomic hybridization to assess the chromosomal ploidy of the unaffected embryos, and identification of the unaffected euploid embryos for transfer. RESULTS: One PGD cycle was completed for each of the 7 patients. Totally, 26 blastocysts were developed, of which 12 were unaffected and diploid. Clinical pregnancies were achieved in 6 cases following 7 cycles of frozen embryo transplantation, which included 5 live births and 1 spontaneous abortion. CONCLUSIONS: For males with ADPKD-induced infertility, PGD may contribute to high rates of clinical pregnancy and live birth and prevent ADPKD in the offspring as well. This finding is also meaningful for the ADPKD patients with normal fertility.

[Differentiation of embryonic stem cells from the embryos of the couples with male asthenozoospermia and Robertsonian translocation into germ cells].

OBJECTIVE: To assess the risk of male infertility in the offspring conceived through assisted reproductive technology (ART) byin vitroinductionof the differentiation of embryonic stem cells (ESCs) derived from the embryos of the couples with male asthenozoospermia and Robertsonian translocation (RT) into germ cells. METHODS: We established a CCRM16ESC line with the karyotype of 46, XY, +14, rob(13; 14) (q10; q10) from the embryo donated by a patientwithasthenozoospermiaand RT and his wife by isolation of the inner cell mass of blastula, culturing, passaging, and amplification,followed by in vitro induction and differentiationof the ESCs into germ cells with ratinoic acid(RA) at 2 mol/L. Then, we analyzed the process of differentiation and the expressions of its related genes and compared them with those in the normal CCRM23ESCs. RESULTS: CCRM16 showed the typical characteristics of ESCs, expressing the pluripotency makers of NANOG, OCT4, TRA-1-181 and SSEA4, forming embryoid bodies, and differentiating into three germlayer tissues in vitro and in vivo. Intervention with 2 mol/LRAinduced direct differentiation of the ESCs into germ cells. The expressions of the primordial germ cell marker geneDAZLand the meiosis marker geneSCP3were markedly decreased in the CCRM16 as compared with those in the normal CCRM23 ESCs. CONCLUSIONS: The CCRM16ESC linewith the karyotype of46, XY, +14, rob(13; 14) (q10; q10) has thetypical characteristics of ESCs but an abnormal process of differentiation into germ cells in the early stage. In vitroinductionof the differentiation of ESCs into germ cells can be used for assessing the risk of male infertility in the offspring conceived through ART for asthenozoospermia patients.

Therapeutic effect of acupuncture on the outcomes of in vitro fertilization: a systematic review and meta-analysis.

PURPOSE: Controversial results have been reported concerning the effect of acupuncture on in vitro fertilization (IVF) outcomes. The current review was conducted to systematically review published studies of the effects of acupuncture on IVF outcomes. METHODS: Women undergoing IVF in randomized controlled trials (RCTs) were evaluated for the effects of acupuncture on IVF outcomes. The treatment groups involved traditional, electrical, laser, auricular, and other acupuncture techniques. The control groups consisted of no, sham, and placebo acupuncture. The PubMed, Embase, and Web of Science databases were searched. The pregnancy outcomes data are expressed as odds ratios (ORs) with 95% confidence intervals (CIs) based on a fixed model or random model depending on the heterogeneity determined by the Q test and I2 statistic. The major outcomes were biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), live birth rate (LBR), and ongoing pregnancy rate (OPR). Heterogeneity of the therapeutic effect was evaluated by a forest plot analysis, and publication bias was assessed by a funnel plot analysis. RESULTS: Thirty trials (a total of 6344 participants) were included in this review. CPR data showed a significant difference between the acupuncture and control groups (OR 1.26, 95% CI 1.06-1.50, p = 0.01), but there was significant statistical heterogeneity among the studies (p = 0.0002). When the studies were restricted to Asian or non-Asian area trials with a sensitivity analysis, the results significantly benefited the CPR in Asian group (OR 1.51, 95% CI 1.04-2.20, p = 0.03). Based on the area subgroup analysis, we found that in the Asian group, the IVF outcomes from the EA groups were all significantly higher than those from the control groups (CPR: OR 1.81, 95% CI 1.20-2.72, p = 0.005; BPR: OR 1.84, 95% CI 1.12-3.02, p = 0.02; LBR: OR 2.36, 95% CI 1.44-3.88, p = 0.0007; OPR: OR 1.94, 95% CI 1.03-3.64, p = 0.04). Meanwhile, compared with other acupuncture time, the IVF outcome results were significantly superior in the acupuncture group when acupuncture was conducted during controlled ovarian hyperstimulation (COH) (CPR: OR 1.71, 95% CI 1.27-2.29, p = 0.0004; LBR: OR 2.41, 95% CI 1.54-3.78, p = 0.0001; BPR: OR 1.50, 95% CI 1.02-2.20, p = 0.04; OPR: OR 1.88, 95% CI 1.06-3.34, p = 0.03). However, when acupuncture was conducted at the time of embryo transfer, the BPR and OPR from the acupuncture groups were significantly lower than those of the controls in the Asian group (BPR: OR 0.67, 95% CI 0.48-0.92, p = 0.01; OPR: OR 0.68, 95% CI 0.49-0.96, p = 0.03). CONCLUSIONS: Based on an analysis of the studies, acupuncture improves the CPR among women undergoing IVF. When the studies were restricted to Asian or non-Asian area patients, compared with traditional acupuncture and other methods, electrical acupuncture yielded better IVF outcomes. Optimal positive effects could be expected using acupuncture in IVF during COH, especially in Asian area. However, as a limitation of this review, most of the included studies did not mention the number of embryos transferred.

[Impact of autosomal dominant polycystic kidney disease on the outcomes of intracytoplasmic sperm injection in infertile males].

OBJECTIVE: To summarize the features and treatment of male infertility induced by autosomal dominant polycystic kidney disease (ADPKD), and compare the outcomes of intracytoplasmic sperm injection (ICSI) for infertile men with ADPKD and those with congenital bilateral absence of vas deferens (CBAVD). METHODS: We retrospectively analyzed 21 cases of ADPKD-induced infertility, 15 treated by ICSI (group A), and another 164 cases of strictly matched CBAVD-induced infertility (group B). We compared the two groups in the couples' age, the number of ICSI oocytes, and the rates of fertilization, transferrable embryos, good embryos, embryos implanted, clinical pregnancy, biochemical pregnancy, early abortion, singleton and twins in the first cycle. RESULTS: After 28 cycles of ICSI, 10 of the 15 ADPKD-induced infertility patients achieved clinical pregnancy, including 7 cases of live birth, 1 case of spontaneous abortion, and 2 cases of pregnancy maintenance. No significant differences were observed between groups A and B in the couples' age, the wives' BMI, or the numbers of ICSI oocytes and embryos transplanted (P >0.05), nor in the rates of ICSI fertilization (72.64% vs 76.17%), transferrable embryos (51.28% vs 63.24%), quality embryos (38.46% vs 49.83%), embryo implantation (17.64% vs 38.50%), abortion (0 vs 9.23%), singleton (50% vs 81.54%) and twins (50% vs 18.46%). However, the rates of clinical pregnancy (13.33% vs 42.68%, P = 0.023 <0.05) and biochemical pregnancy (13.33% vs 39.63%, P = 0.032 <0.05) were significantly lower in group A than in B. CONCLUSION: ICSI is effective in the treatment of male infertility induced by either ADPKD or CBAVD, but the ADPKD cases have a lower success rate than the CBAVD cases in an individual cycle. The affected couples should be informed of the necessity of prenatal genetic diagnosis before embryo implantation and the inevitable vertical transmission of genetic problems to the offspring.

Association of cardiac development with assisted reproductive technology in childhood: a prospective single-blind pilot study.

AIMS: To examine the pattern and extent of cardiovascular developmental alterations among children conceived by assisted reproductive technology (ART) and its association with potential confounders. METHODS: The present study was a prospective single-blind pilot design lasting 15 months. The ART group was recruited by a non-random, consecutive sample on the basis of the unique personal identification number assigned to ART children, whereas spontaneous conception controls were recruited by a population-based random sample from the same hospital by age. Echocardiography was available for the measurement of 128 ART children and 100 controls with respect to cardiovascular geometric morphology and cardiac function. RESULTS: The majority of cardiac geometric morphology parameters were comparable among the study groups (P>0.05), except for significant increases in left ventricular (LV) relative wall thickness (P=0.038), LV mass index (P=0.005) and LV remodeling index (P=0.005) in ART children after adjustment for age, gender, body surface area and heart rate. The results showed similarity in LV systolic function characterized by ejection fraction (P=0.140) and shortening fraction (P=0.167) between the groups. However, ART children had a significant tendency toward a decrease in mitral A (P=0.008) and mitral E' (P=0.012) compared with controls after adjusting for confounders. Additionally, Cox analysis suggested an independent association (P<0.05) of anthropometrics and perinatal outcomes in addition to the ART procedure itself with the differences in cardiac developmental status. CONCLUSION: Our findings support the presence of remodeling in the left cardiac geometric morphology and diastolic dysfunction and the absence of any change to the aortocoronary morphometry or systolic function in ART children compared with controls, which may be independently associated with the anthropometrics and perinatal outcomes in addition to the ART procedure.

[Study on the factors associated with clinical pregnancy rate of in-vitro fertilization in endometriosis related infertility].

OBJECTIVE: To evaluate the factors associated with clinical pregnancy rate of in-vitro fertilization (IVF) in endometriosis related infertility. METHODS: Total of 326 patients with endometriosis related infertility undergoing IVF between January 2007 and December 2011 were studied in Department of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, retrospectively, which were divided into 141 cases in clinical pregnancy group and 185 cases in non-pregnancy group. Those factors including age, body mass index (BMI), basic FSH, antral follicle count (AFC), CA125 and CA199, endometriotic stage and history of surgery, stimulation scheme were analyzed by bivariate analysis and multivariable logistic regression. RESULTS: (1) Pregnancy rate:total of 141 pregnant cases and 185 non-pregnant cases treated by IVF were observed, pregnancy rate was 43.2% (141/326). (2) Basic parameters: there was no statistical difference in age, BMI, basic FSH, AFC, CA125 and CA199 between clinical pregnancy group and non-pregnancy group (P > 0.05). (3) Bivariate analysis: clinical pregnancy rate of 50.0% (87/174) among patients with infertility year less than five years was significantly higher than 35.5% (54/152) in patients with more than five years. Pregnancy rate of 56.1% (46/82) in stage I-II was significantly higher than 42.5% (79/186) in stage III-IV. Pregnancy rate of 46.6% (125/268) with history of surgery was significantly higher than 27.6% (16/58) with no history of surgery (P < 0.05). Pregnancy rate of 48.2% (79/164) in long-term scheme was higher than 38.3% (62/162) in short-term scheme, but there was no significant difference (P = 0.075). (4) Multivariable logistic regression: clinical pregnancy rate of infertility year with less than 5 years, stage I-II, history of surgery proved stage I-II and stage III-IV was significantly higher compared with infertility year more than 5 years, stage III-IV and no history of surgery respectively (adjusted OR and 95%CI: 2.003, 1.263 - 3.175; 1.899, 1.110 - 3.248; 3.769, 1.802 - 7.887, P < 0.05). CONCLUSION: Factors affecting clinical pregnancy rate of IVF in endometriosis related infertility were infertility year, stage and surgery.

[Impact of sperm DNA fragmentation index and sperm malformation rate on the clinical outcome of ICSI].

OBJECTIVE: To evaluate the sperm DNA fragmentation index (DFI) and sperm malformation rate (SMR) before intracytoplasmic sperm injection (ICSI) and their impact on the clinical outcome of ICSI. METHODS: This study included 79 cycles of ICSI because of oligoasthenozoospermia. We detected the sperm concentration, percentage of progressively motile sperm, DFI and SMR at 3 to 6 months before ICSI, and analyzed the relationship of DFI and SMR with the outcome parameters. RESULTS: Of the 79 oligoasthenozoospermia cases, DFI was found to be normal (< or = 25%) in 51 and abnormal (> 25%) in the other 28, significantly increased in the latter (14.18% vs 41.47%), and coincidently, SMR, too, was normal (< or = 96%) in 51 cases and abnormal (> 96%) in 28, significantly higher in the abnormal than in the normal cases (87.88% vs 98.46%). There were no significant differences between the normal and abnormal DFI groups in age, females'BMI, number of oocytes retrieved, and number of embryos transferred, nor between the normal and abnormal SMR groups in the number of fertilized oocytes and quality embryos, biochemical pregnancy, clinical pregnancy, and early pregnancy loss. Sperm DFI was significantly positively correlated with SMR (r = 0.231, P < 0.05). CONCLUSION: ICSI may reduce the rates of biochemical pregnancy and clinical pregnancy for men with increased sperm DFI (> 25%) and SMR (> 96%) by strict detection criteria, but with no statistically significant difference from normal males. Our findings need to be supported by further studies with larger sample sizes.

Oocyte vitrification technology has made egg-sharing donation easier in China.

When infertile women undergoing IVF or intracytoplasmic sperm injection (ICSI) have more than 20 mature oocytes retrieved, at least 15 oocytes are inseminated by their husband's spermatozoa. The extra oocytes are cryopreserved by vitrification. If the patients became pregnant and have healthy live births, the patients are encouraged to donate their remaining cryopreserved oocytes. Forty-seven egg-sharing donors were recruited after having normal deliveries and they donated their remaining oocytes, totalling 395 cryopreserved oocytes, to 75 recipients. The survival rate of vitrified-warmed oocytes was 83.0%. Following insemination by ICSI, the fertilization and cleavage rates were 83.8% and 89.8%, respectively. Out of 75 recipients, 71 recipients completed the treatment cycles and 30 of them became pregnant with clinical pregnancy and implantation rates of 42.3% and 25.5%, respectively. The birthweight of the new-born infants (22 from singleton and two from one set of twins) were 3344.5 ± 669.1g and 2425.0 ± 742.5 g, respectively. No birth defects were observed for the live births. These results indicate that oocyte vitrification is an effective methodology for an egg-sharing donation programme, with acceptable pregnancy and implantation rates.

Sensitive Silicon Nanowire Ultraviolet B Photodetector Induced by Leakage Mode Resonances.

Ultraviolet photodetectors (UVPDs) have played an important role both in civil and military applications. While various studies have shown that traditional UVPDs based on wide-band-gap semiconductors (WBSs) have excellent device performances, it is, however, undeniable that the practical application of WBS-based UVPDs is largely limited by the relatively high fabrication cost. In this work, we propose a new silicon nanowire (Si NW) UVPD that is very sensitive to UVB light illumination. The Si NWs with a diameter of about 36 nm are fabricated by a metal-assisted chemical etching method. Performance analysis revealed that the Si NW device was only sensitive to UVB light and almost blind to illumination in the visible and near-infrared regions. Such abnormal spectral selectivity was associated with the leakage mode resonances (LMRs) of the small diameter, according to our theoretical simulation. Under 300 nm illumination, the responsivity, external quantum efficiency, and specific detectivity were estimated to be 10.2 AW-1, 4.22 × 103%, and 2.14 × 1010 Jones, respectively, which were comparable to or even higher than those of some WBS-based UVPDs. These results illustrate that the small dimension Si NWs are potential building blocks for low-cost and high-performance UVPDs in the future.

Effect of estradiol on proliferation and differentiation of side population stem/progenitor cells from murine endometrium.

BACKGROUND: In our previous study, endometrium side population cells (SP cells) were isolated from postpartum murine uterus, and characterized by a heterogeneous population of stem/progenitor cells. In this study, we investigated the effect of estrogen on the proliferation and differentiation of SP cells. METHODS: SP and non-SP cells of postpartum murine endometrium were isolated by DNA dye Hoechst 33342. The expression of estrogen receptor 1 (ESR1) was measured by reverse transcription polymerase chain reaction (RT-PCR), Real-time PCR, Western blot, immunofluorescence and immunohistochemistry. The proliferation and differentiation of SP cells treated with different concentrations [10(-8) M-10(-6) M] of estradiol (E2) and E2+ ICI182780 (Faslodex, inhibitor of ESR1) were measured by 3-(4, 5-dimethylthiazoly1-2)-2,5-diphenyltetrazolium bromide(MTT) and clonogenic assays. RESULTS: (1) SP cells expressed ESR1 at a higher level than non-SP cells. (2) The level of E2 in the serum and the expression of ESR1 in the uterus of postpartum murine changed in the same manner with the ratio of SP cells to total uterus cells at a different postpartum time point. ESR1, as ABCG2 is also predominantly located in the stroma and the glandular epithelium of the uterus. (3) 10(-6) M E2 notably promoted the proliferation of SP cells after treatment for 24 h. This effect could be inhibited by ICI182780. E2 at the concentration of 10(-7) M or 10(-8) M was sent to impair the large cloning efficiency (CE) of SP cells. CONCLUSIONS: The effect of estrogen on the proliferation and differentiation of endometrium SP cells via ESR1 was observed and it was in a concentration dependent fashion. Clearly, more work is needed to understand the in vivo effect of E2 at the physiological concentration on the differentiation of SP cells.