Does time-lapse imaging have favorable results for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization? A meta-analysis and systematic review of randomized controlled trials

<div><p>Objective</p><p>The present study aimed to undertake a review of available evidence assessing whether time-lapse imaging (TLI) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization (IVF).</p><p>Methods</p><p>Using PubMed, EMBASE, Cochrane library and ClinicalTrial.gov up to February 2017 to search for randomized controlled trials (RCTs) comparing TLI versus conventional methods. Both studies randomized women and oocytes were included. For studies randomized women, the primary outcomes were live birth and ongoing pregnancy, the secondary outcomes were clinical pregnancy and miscarriage; for studies randomized oocytes, the primary outcome was blastocyst rate, the secondary outcome was good quality embryo on Day 2/3. Subgroup analysis was conducted based on different incubation and embryo selection between groups.</p><p>Results</p><p>Ten RCTs were included, four randomized oocytes and six randomized women. For oocyte-based review, the pool-analysis observed no significant difference between TLI group and control group for blastocyst rate [relative risk (RR) 1.08, 95% CI 0.94–1.25, I2 = 0%, two studies, including 1154 embryos]. The quality of evidence was moderate for all outcomes in oocyte-based review. For woman-based review, only one study provided live birth rate (RR 1,23, 95% CI 1.06–1.44,I2 N/A, one study, including 842 women), the pooled result showed no significant difference in ongoing pregnancy rate (RR 1.04, 95% CI 0.80–1.36, I2 = 59%, four studies, including 1403 women) between two groups. The quality of the evidence was low or very low for all outcomes in woman-based review.</p><p>Conclusions</p><p>Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection. In consideration of the limitations and flaws of included studies, more well designed RCTs are still in need to comprehensively evaluate the effectiveness of clinical TLI use.</p></div

Flow chart for the systematic review of RCTs comparing TLI with conventional method.

<p>Flow chart for the systematic review of RCTs comparing TLI with conventional method.</p

Characteristics of included randomized controlled studies.

<p>Characteristics of included randomized controlled studies.</p

Risk of bias of included studies.

<p>Risk of bias of included studies.</p

1286391_Table 1_Associations between urinary phthalate concentrations and antral follicle count among women undergoing in vitro fertilization.docx

BackgroundPhthalates are ubiquitously used in a variety of products and have an adverse effect on folliculogenesis. However, previous epidemiological studies on the associations between phthalate exposure and antral follicle count (AFC) produced conflicting results. The present study aimed to evaluate the associations between urinary phthalate metabolite concentrations and AFC among women undergoing in vitro fertilization (IVF).MethodsWe collected 525 urine samples and measured 8 phthalate metabolites from IVF patients. Poisson regression models were conducted to evaluate the associations between phthalate metabolite concentrations and AFC. In addition, participants were stratified into a younger group (ResultsSignificant positive associations were observed among urinary MBP, MEOHP and ∑PAEs concentrations and AFC after adjusting for age, BMI, year of study and infertility diagnosis. Compared with women in the first tertile, women in the third tertile of MBP and MEOHP had 7.02% (95% CI: 1.18%, 12.9%) and 8.84% (95% CI: 2.83%, 14.9%) higher AFC, respectively, and women in the second and third tertiles of ∑PAEs had 6.19% (95% CI: 0.37%, 12.0%) and 9.09% (95% CI: 3.22%, 15.0%) higher AFC, respectively. In addition, MBP, MEOHP and ∑PAEs also had significant positive associations with AFC in trend tests for dose-response. In the age-stratified analysis, we found a stronger relationship between phthalate metabolite concentrations and AFC among older women and an inverse association among younger women. We observed similar results in the sensitivity analyses.ConclusionWe found positive associations between phthalate exposure and AFC, which support the idea that phthalate exposure may accelerate primordial follicle recruitment and lead to higher AFC in women undergoing IVF. More studies are needed to better understand their relationships.</p

Forest plot showing the results of meta-analysis and subgroup analysis of the woman-based review.

<p>Forest plot showing the results of meta-analysis and subgroup analysis of the woman-based review.</p

Enzyme activities analysis of C4H and TAT in transgenic lines and controls of <i>S. miltiorrhiza</i>.

<p>Data presented here are the mean of three replicates with error bars indicating ± SD. The asterisks indicate statistically significant differences (<i>P</i><<i>0.05</i>) compared to the empty vector control. control: untransformed plant; ox-VC, RNAi-VC: empty vector controls of <i>SmMYB39</i>-overexpressing lines and <i>SmMYB39</i>-RNAi lines; ox-3, ox-17, ox-28: <i>SmMYB39</i>-overexpressing lines; RNAi-11, RNAi-19, RNAi-25: <i>SmMYB39</i>-RNAi lines; C4H: cinnamic acid 4-hydroxylase; TAT: tyrosine aminotransferase.</p

Relative expression levels of <i>SmMYB39</i> (A) and total phenolics content (B) in different tissues of <i>S. miltiorrhiza</i>.

<p>The results were analyzed using the comparative Ct method and presented as fold-changes compared with the root. The <i>S. miltiorrhiza actin</i> gene was used as an internal control to normalize expression levels. Data presented here are the mean of three replicates with error bars indicating ± SD.</p

Analysis of related phenolic compounds contents in transgenic lines and controls of <i>S. miltiorrhiza</i>.

<p>Data presented here are the mean of three replicates with error bars indicating ± SD. The asterisks indicate statistically significant differences (<i>P</i><<i>0.05</i>) compared to the empty vector control. control: untransformed plant; ox-VC, RNAi-VC: empty vector controls of <i>SmMYB39</i>-overexpressing lines and <i>SmMYB39</i>-RNAi lines; ox-3, ox-17, ox-28: <i>SmMYB39</i>-overexpressing lines; RNAi-11, RNAi-19, RNAi-25: <i>SmMYB39</i>-RNAi lines.</p

Phenolic acids biosynthetic pathway in <i>S. miltiorrhiza</i>.

<p>Multiple enzymatic steps are represented by dotted lines. The ‘circle’ and ‘square’ are used to distinguish between the downstream pathway of RA and other branches of phenylpropanes metabolism. C3H, coumarate 3-hydroxylase; C4H, cinnamic acid 4-hydroxylase; 4CL, 4-coumaric acid CoA-ligase; COMT, caffeic acid O-methyltransferase; HPPR, 4-hydroxyphenylpyruvate reductase; PAL, phenylalanine ammonia-lyase; RAS, rosmarinic acid synthase; TAT, tyrosine aminotransferase.</p