Background
This is an update of a Cochrane review first published in The Cochrane Library (2010, Issue 7).

To increase the success rate of assisted reproductive technologies (ART), adherence compounds such as hyaluronic acid (HA) and fibrin sealant have been introduced into subfertility management. Adherence compounds are added to the embryo transfer medium to increase the likelihood of embryo implantation, with the potential for higher clinical pregnancy and live birth rates.

Objectives
To determine whether embryo transfer media containing adherence compounds improved live birth and pregnancy rates in ART cycles.

Search methods
The Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE, EMBASE and PsycINFO electronic databases were searched (up to 13 November 2013) to look for publications that described randomised controlled trials on the addition of adherence compounds to embryo transfer media. Furthermore, reference lists of all obtained studies were checked, and conference abstracts were handsearched.

Selection criteria
Only truly randomised controlled trials comparing embryo transfer media containing functional (e.g. 0.5 mg/ml HA) concentrations of adherence compounds versus transfer media containing low or no concentrations of adherence compounds were included. The adherence compounds that were identified for evaluation were HA and fibrin sealant.

Data collection and analysis
Two review authors selected trials for inclusion according to the above criteria, after which two review authors independently extracted the data for subsequent analysis. Statistical analysis was performed in accordance with the guidelines developed by The Cochrane Collaboration.

Main results
Seventeen studies with a total of 3898 participants were analysed. One studied fibrin sealant, and the other 16 studied HA. No evidence was found of a treatment effect of fibrin sealant as an adherence compound. For HA, evidence of a positive treatment effect was identified in the six trials that reported live birth rates (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.17 to 1.69; six RCTs, N = 1950, I2 = 0%, moderate-quality evidence). Furthermore, the 14 trials reporting clinical pregnancy rates showed evidence of treatment benefit when embryos were transferred in media containing functional concentrations of HA (OR 1.39, 95% CI 1.21 to 1.60; 14 RCTs, N = 3452, I2 = 46%, moderate-quality evidence) as compared with low or no use of HA. The multiple pregnancy rate (OR 1.86, 95% CI 1.49 to 2.31; five RCTs, N = 1951, I2 = 0%, moderate-quality evidence) was significantly increased in the high HA group, but no significant differences in adverse event rates were found (OR 0.74, 95% CI 0.49 to 1.12; four RCTs, N = 1525, I2 = 0%, moderate-quality evidence).

Authors' conclusions
Evidence suggests improved clinical pregnancy and live birth rates with the use of functional concentrations of HA as an adherence compound in ART cycles. However, the evidence obtained is of moderate quality. The increase in multiple pregnancy rate may be the result of use of a combination of an adherence compound and a policy of transferring more than one embryo. Further studies of adherence compounds with single embryo transfer need to be undertaken.

/pdf/adherence-compounds-in-embryo-transfer-media-for-assisted-20lqz2vsfj.pdf

Adherence compounds in embryo transfer media for assisted reproductive technologies

Background This is an update of a Cochrane Review first published in the Cochrane Library (2010, Issue 7). To increase the success rate of assisted reproductive technologies (ARTs), adherence compounds such as hyaluronic acid (HA) have been introduced into subfertility management. Adherence compounds are added to the embryo transfer medium to increase the likelihood of embryo implantation, with the potential for higher clinical pregnancy and live birth rates. Objectives To determine whether adding adherence compounds to embryo transfer media could improve pregnancy outcomes, including improving live birth and decreasing miscarriage, in women undergoing assisted reproduction. Search methods We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, and PsycINFO electronic databases on 7 January 2020 for randomised controlled trials that examined the effects of adherence compounds in embryo transfer media on pregnancy outcomes. Furthermore, we communicated with experts in the field, searched trials registries, checked reference lists of relevant studies, and conference abstracts were handsearched. Selection criteria Only truly randomised controlled trials comparing embryo transfer media containing functional concentrations of adherence compounds to media with no or low adherence compound concentrations were included. Data collection and analysis Two review authors selected trials for inclusion according to the above criteria, after which the same two review authors independently extracted data for subsequent analysis. Statistical analysis was performed according to the guidelines developed by Cochrane. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We used GRADE methods to assess the overall quality of evidence for the main comparisons. Main results We analysed 26 studies with a total of 6704 participants. Overall, the certainty of evidence was low to moderate: the main limitations were imprecision and/or heterogeneity. Compared to embryos transferred in media containing no or low (0.125 mg/mL) HA, the addition of functional (0.5 mg/mL) HA concentrations to the transfer media probably increases the live birth rate (RR 1.21, 95% CI 1.1 to 1.31; 10 RCTs, N = 4066; I² = 33%; moderate-quality evidence). This suggests that if the chance of live birth following no HA addition in media is assumed to be 33%, the chance following HA addition would be between 37% and 44%. The addition of HA may slightly decrease miscarriage rates (RR 0.82, 95% CI 0.67 to 1.00; 7 RCTs, N = 3091; I² = 66%; low-quality evidence). Nevertheless, when only studies with low risk of bias were included in the analysis, there was no conclusive evidence of a difference in miscarriage rates (RR 0.96, 95% CI 0.75 to 1.23; N = 2219; I² = 36%). Adding HA to transfer media probably results in an increase in both clinical pregnancy (RR 1.16, 95% CI 1.09 to 1.23; 17 studies, N = 5247; I² = 40%; moderate-quality evidence) and multiple pregnancy rates (RR 1.45, 95% CI 1.24 to 1.70; 7 studies, N = 3337; I² = 36%; moderate-quality evidence). We are uncertain of the effect of HA added to transfer media on the rate of total adverse events (RR 0.86, 95% CI 0.40 to 1.84; 3 studies, N = 1487; I² = 0%; low-quality evidence). Authors' conclusions Moderate-quality evidence shows improved clinical pregnancy and live birth rates with the addition of HA as an adherence compound in embryo transfer media in ART. Low-quality evidence suggests that adding HA may slightly decrease miscarriage rates, but when only studies at low risk of bias were included in the analysis, the results were inconclusive. HA had no clear effect on the rate of total adverse events. The increase in multiple pregnancy rates may be due to combining an adherence compound and transferring more than one embryo. Further studies of adherence compounds with single embryo transfer need to be undertaken.

Hyaluronic acid in embryo transfer media for assisted reproductive technologies.

Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles?The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes.There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently.A systematic review with meta-analysis was performed. The Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL via Cochrane Register of Studies Online (CRSO), MEDLINE, Embase and PsycINFO electronic databases (until 8 January 2020) were searched for randomized controlled trials (RCTs) examining the effect of HA in embryo transfer medium on pregnancy outcomes.RCTs with separate donor and autologous oocyte data that compared embryo transfer medium with functional HA concentrations (0.5 mg/ml) to those containing no or low HA concentrations (0.125 mg/ml) were included. Two review authors independently selected trials for inclusion, extracted data and assessed the included studies using the Cochrane risk of bias assessment tool. Pooled risk ratios and 95% CIs were calculated. A summary of findings table was generated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Judgements about evidence quality were justified and incorporated into the reported results for each outcome.Fifteen studies, totalling 4686 participants, were analysed. In autologous oocyte cycles, live birth increased from 32% to 39% when embryo transfer media contained functional HA concentrations (risk ratio (RR) 1.22, 95% CI 1.11-1.34; nine studies, 3215 participants, I2 = 39%, moderate-quality evidence (number needed to treat (NNT) 14). HA-enriched media increased clinical pregnancy and multiple pregnancy rates by 5% and 8%, respectively (RR 1.11, 95% CI 1.04-1.18; 13 studies, 4014 participants, I2 = 0%, moderate-quality evidence, NNT 21) and (RR 1.49, 95% CI 1.27-1.76; 5 studies, 2400 participants, I2 = 21%, moderate-quality evidence, number needed to harm 13). Conversely, in donor oocyte cycles, HA addition showed little effect on live birth and clinical pregnancy (RR 1.12 95% CI 0.86-1.44; two studies, 317 participants, I2 = 50%, low-quality evidence) and (RR 1.06, 95% CI 0.97-1.28; three studies, 351 participants, I2 = 23%, low-quality evidence). There was insufficient available information on multiple pregnancy in donor oocyte cycles and on total adverse effects in both groups to draw conclusions.There were limited studies with separate data on donor oocyte cycles and limited information on oocyte quality. Additionally, one-third of the included studies did not include the main outcome, live birth rate.There is a moderate level of evidence to suggest that functional HA concentration in embryo transfer medium increases clinical pregnancy, live birth and multiple pregnancy rates in IVF cycles using autologous oocytes. This effect was not seen in donor oocyte cycles, indicating either intrinsic differences between donor and autologous oocytes or lack of statistical power. The combination of HA addition to transfer media in cycles using autologous oocytes and a single embryo transfer policy might yield the best combination, with higher clinical pregnancy and live birth rates without increasing the chance of multiple pregnancies.No financial assistance was received. The authors have no competing interests.N/A. 

OUP accepted manuscript

Many couples present fertility problems at their reproductive age, and although in the last years, the efficiency of assisted reproduction techniques has increased, these are still far from being 100% effective. A key issue in this field is the proper assessment of germ cells, embryos and endometrium quality, in order to determine the actual likelihood to succeed. Currently available analysis is mainly based on morphological features of oocytes, sperm and embryos and although these strategies have improved the results, there is an urgent need of new diagnostic and therapeutic tools. The emergence of the - OMICS technologies (epigenomics, genomics, transcriptomics, proteomics and metabolomics) permitted the improvement on the knowledge in this field, by providing with a huge amount of information regarding the biological processes involved in reproductive success, thereby getting a broader view of complex biological systems with a relatively low cost and effort.

OMICS: Current and future perspectives in reproductive medicine and technology.

/pdf/selected-oral-communication-session-session-17-embryology-58oqqcnihk.pdf

SELECTED ORAL COMMUNICATION SESSION, SESSION 17: EMBRYOLOGY AND GENETICS, Monday 4 July 2011 15:15 - 16:30

A novel tool for the assessment of IVF embryos

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SELECTED ORAL COMMUNICATION SESSION, SESSION 17: EMBRYOLOGY AND GENETICS, Monday 4 July 2011 15:15 - 16:30

A novel tool for the assessment of IVF embryos