Single-embryo transfer reduces clinical pregnancy rates and live births in fresh IVF and Intracytoplasmic Sperm Injection (ICSI) cycles: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>It has become an accepted procedure to transfer more than one embryo to the patient to achieve acceptable ongoing pregnancy rates. However, transfers of more than a single embryo increase the probability of establishing a multiple gestation. Single-embryo transfer can minimize twin pregnancies but may also lower live birth rates. This meta-analysis aimed to compare current data on single-embryo versus double-embryo transfer in fresh IVF/ICSI cycles with respect to implantation, ongoing pregnancy and live birth rates.</p> <p>Methods</p> <p>Search strategies included on-line surveys of databases from 1995 to 2008. Data management and analysis were conducted using the Stats Direct statistical software. The fixed-effect model was used for odds ratio (OR). Fixed-effect effectiveness was evaluated by the Mantel Haenszel method. Seven trials fulfilled the inclusion criteria.</p> <p>Results</p> <p>When pooling results under the fixed-effect model, the implantation rate was not significantly different between double-embryo transfer (34.5%) and single-embryo transfer group (34.7%) (<it>P </it>= 0.96; OR = 0.99, 95% CI 0.78, 1.25). On the other hand, double-embryo transfer produced a statistically significantly higher ongoing clinical pregnancy rate (44.5%) than single-embryo transfer (28.3%) (<it>P </it>< 0.0001; OR:2.06, 95% CI = 1.64,2.60). At the same time, pooling results presented a significantly higher live birth rate when double-embryo transfer (42.5%) (P < 0.001; OR: 1.87, 95% CI = 1.44,2.42) was compared with single-embryo transfer (28.4%).</p> <p>Conclusion</p> <p>Meta-analysis with 95% confidence showed that, despite similar implantation rates, fresh double-embryo transfer had a 1.64 to 2.60 times greater ongoing pregnancy rate and 1.44 to 2.42 times greater live birth rate than single-embryo transfer in a population suitable for ART treatment.</p

A specific controlled ovarian stimulation (COS) protocol for fertility preservation in women with breast cancer undergoing neoadjuvant chemotherapy

Aim of the study : The authors present a novel and specific controlled ovarian stimulation protocol for fertility preservation in women with estrogen-positive receptor breast cancer undergoing neoadjuvant chemotherapy. The protocol foresees random start ovarian stimulation and the use of letrozole associated to tamoxifen. Material and methods : Forty breast cancer patients were included in the study. COS was performed either with recombinant FSH or hMG. Concomitantly with COS, letrozole in a dose of 5 mg and tamoxifen in a dose of 20 mg were given orally on a daily basis. The trigger was performed with 0.2 mg of triptorelin, in the presence of follicles ≥ 19 mm. Oocyte retrieval was scheduled 35–36 hours after triptorelin injection. Our main outcome measures were the number of oocytes collected and number of oocytes vitrified, the length of ovarian stimulation, total dose of gonadotropins administered, and levels of estradiol on the day of the trigger. Results : The mean age of patients was 30.43 ±4.25 years. Nineteen women commenced COS in the luteal phase, eleven in the early follicular phase and ten in the late follicular phase. The mean number of collected oocytes was 11.78 ±9.12 and the mean number of vitrified oocytes was 9.72 ±7.36. The mean duration of COS was 10.03 ±1.33 days. The mean estradiol concentrations on the triggering day was 623.10 ±441.27, and the mean dose of gonadotropins administered was 2540 ±713.10. Conclusions : The authors suggest that the protocol is efficient and may be a safe option for oocyte vitrification in these patients

An Integrative Genomic and Transcriptomic Analysis Reveals Potential Targets Associated with Cell Proliferation in Uterine Leiomyomas

<div><p>Background</p><p>Uterine Leiomyomas (ULs) are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40–50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs). Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs.</p> <p>Methodology</p><p>We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC) and gene expression microarrays (SAM). The CONEXIC algorithm was applied to integrate the data.</p> <p>Principal Findings</p><p>The integrated analysis identified the top 30 significant genes (<i>P</i><0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional <i>in silico</i> analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (<i>P</i> = 0.006 and <i>P</i><0.01, respectively) and IGFBP5 (<i>P</i> = 0.0002 and <i>P</i> = 0.006, respectively) were up-regulated in the tumours when compared with the adjacent normal myometrium.</p> <p>Conclusions</p><p>The integrative genomic and transcriptomic approach indicated that <i>FGFR1</i> and <i>IGFBP5</i> amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs.</p> </div

Data validation.

<p>(A) Boxplot illustrating MM (normal) and ULs (tumour) normalised to obtain relative expression values for all samples evaluated by RT-qPCR. <i>P</i> = paired <i>t</i> test significance. **<i>P</i> = 0.006; ***<i>P</i> = 0.0002; Immunostaining frequency for the (B) FGFR1 and (C) IGFBP5 proteins. The <i>P</i> values (Fisheŕs test) were obtained based on the comparison of the MM and ULs immunostaining results.</p

Seventy-five modulators obtained from integrative analysis.

<p><b>In bold</b>, the top 30 modulators based on the highest scores on CONEXIC; Hg18: Human genome version 18 (Mar 2006 NCBI36); ^*miRNA target prediction; positive (+) and negative (−) signs indicate the gene status with regard to the genomic gains and losses and up- or down-regulated gene expression, respectively. ^£Regions which usually not are involved in chromosomal breakpoints.</p

FGFR1 and IGFBP5 protein expression by immunohistochemistry in uterine leiomyomas.

<p>(A) FGFR1-adjacent normal myometrium showing FGFR1 low level expression (score 1); (B) and (C) FGFR1 cytoplasmic positive expression in uterine leiomyoma tissue (scores 2 and 3/intensity, respectively); (D) adjacent normal myometrium showing IGFBP5 negative expression (score 0); (E) and (F) IGFBP5 cytoplasmic positive expression in uterine leiomyoma tissue (scores 2 and 3/intensity, respectively) (200×).</p

Protein-protein interaction network of 75 modulators.

<p>The 75 modulators were used to query the I2D database to obtain their interacting partners (and also interactions among the modulators). I2D v. 2.0 contained data on 62 modulators, which resulted in a large network of 1,456 proteins and 29,530 interactions. The upward triangles represent up-regulated genes, and the downward triangles represent down-regulated genes. The red and green triangle lines represent genes in amplified and deleted regions, respectively. The biological processes that the modulators are involved are represented by different colours, per the legend, and the triangle size corresponds with the score, i.e., larger triangles depict the highest scores. Direct physical interactions between modulators are represented by blue lines. The remainder of the network is partially transparent to reduce the clutter. The network visualisation and analysis was performed in NAViGaTOR 2.3.</p

Canonical pathway from hepatic fibrosis/hepatic stellate cell activation.

<p>Cell proliferation and extracellular matrix deposition process with high similarity observed in ULs. FGFR1 and IGFBP5 were selected as potential molecular markers in ULs treatment.</p

Hierarchical clustering.

<p>The patients were grouped according to the menstrual cycle phase (proliferative and secretory), number of samples evaluated and diagnosis of multiple or solitary tumours. These results show that the genomic and transcriptomic data were useful to clustering the samples regardless of the clinical features, indicating that could be markers to tumour biology (TMeV v.4.5).</p