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 (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, I(2) = 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, I(2) = 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, I(2) = 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, I(2) = 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.

Twenty years of Cochrane reviews in menstrual disorders and subfertility.

The past three decades have seen considerable change in the understanding of clinical research methods. There has been an acceptance that RCTs are the best way of establishing treatment effectiveness and a recognition that, while single studies are useful, pooling knowledge from a complete body of work is likely to provide the best evidence. Advances in methodology have been mirrored by the many advances in the field of reproductive medicine, such as assisted reproduction, assessment of male fertility, ovulation induction and laparoscopic surgery. Together, they have led to welcome improvements in the outcomes of fertility treatments. In particular, systematic reviews have become important tools enabling clinicians and patients to make health-care decisions based on evidence from all the available high-quality studies. The move towards identifying and aggregating the highest quality evidence has been led by the Cochrane Collaboration, which this year celebrates 20 years of preparing and publishing systematic reviews. This paper outlines the achievements, progress and challenges of this enterprise to date, with a particular focus on systematic reviews of reproductive medicine.

An Exploratory Analysis of Firefighter Reproduction through Survey Data and Biomonitoring.

Firefighters are occupationally exposed to chemicals that may affect fertility. To investigate this effect, firefighters were recruited to contribute blood, urine, breast milk or semen samples to (1) evaluate chemical concentrations and semen parameters against fertility standards and the general population; (2) assess correlations between chemical concentrations and demographics, fire exposure and reproductive history; and (3) consider how occupational exposures may affect reproduction. A total of 774 firefighters completed the online survey, and 97 firefighters produced 125 urine samples, 113 plasma samples, 46 breast milk samples and 23 semen samples. Blood, urine and breast milk samples were analysed for chemical concentrations (semivolatile organic compounds, volatile organic compounds, metals). Semen samples were analysed for quality (volume, count, motility, morphology). Firefighter semen parameters were below WHO reference values across multiple parameters. Self-reported rates of miscarriage were higher than the general population (22% vs. 12-15%) and in line with prior firefighter studies. Estimated daily intake for infants was above reference values for multiple chemicals in breast milk. More frequent fire incident exposure (more than once per fortnight), longer duration of employment (≥15 years) or not always using a breathing apparatus demonstrated significantly higher concentrations across a range of investigated chemicals. Findings of this study warrant further research surrounding the risk occupational exposure has on reproduction.

Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology.

BACKGROUND: Advances in cell culture media have led to a shift in in vitro fertilization (IVF) practice from early cleavage embryo transfer to blastocyst stage transfer. The rationale for blastocyst culture is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos thus resulting in higher implantation rates. OBJECTIVES: To determine if blastocyst stage (Day 5 to 6) embryo transfers (ETs) improve live birth rate and other associated outcomes compared with cleavage stage (Day 2 to 3) ETs. SEARCH METHODS: Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. The last search date was 21 February 2012. SELECTION CRITERIA: Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. DATA COLLECTION AND ANALYSIS: Of the 50 trials that were identified, 23 randomised controlled trials (RCTs) met the inclusion criteria and were reviewed (five new studies were added in this update). The primary outcome was rate of live birth. Secondary outcomes were rates per couple of clinical pregnancy, cumulative clinical pregnancy, multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos and cryopreservation. Quality assessment, data extraction and meta-analysis were performed following Cochrane guidelines. MAIN RESULTS: Twelve RCTs reported live birth rates and there was evidence of a significant difference in live birth rate per couple favouring blastocyst culture (1510 women, Peto OR 1.40, 95% CI 1.13 to 1.74) (Day 2 to 3: 31%; Day 5 to 6: 38.8%, I(2) = 40%). This means that for a typical rate of 31% in clinics that use early cleavage stage cycles, the rate of live births would increase to 32% to 42% if clinics used blastocyst transfer.There was no difference in clinical pregnancy rate between early cleavage and blastocyst transfer in the 23 RCTs (Peto OR 1.14, 95% CI 0.99 to 1.32) (Day 2 to 3: 38.6%; Day 5 to 6: 41.6%) and no difference in miscarriage rate (13 RCTs, Peto OR 1.18, 95% CI 0.86 to 1.60). The four RCTs that reported cumulative pregnancy rates (266 women, Peto OR 1.58, 95% CI 1.11 to 2.25) (Day 2 to 3: 56.8%; Day 5 to 6: 46.3%) significantly favoured early cleavage. Embryo freezing rates (11 RCTs, 1729 women, Peto OR 2.88, 95% CI 2.35 to 3.51) and failure to transfer embryos (16 RCTs, 2459 women, OR 0.35, 95% CI 0.24 to 0.51) (Day 2 to 3: 3.4%; Day 5 to 6: 8.9%) favoured cleavage stage transfer. AUTHORS' CONCLUSIONS: This review provides evidence that there is a small significant difference in live birth rates in favour of blastocyst transfer (Day 5 to 6) compared to cleavage stage transfer (Day 2 to 3). However, cumulative clinical pregnancy rates from cleavage stage (derived from fresh and thaw cycles) resulted in higher clinical pregnancy rates than from blastocyst cycles. The most likely explanation for this is the higher rates of frozen embryos and lower failure to transfer rates per couple obtained from cleavage stage protocols. Future RCTs should report miscarriage, live birth and cumulative live birth rates to enable ART consumers and service providers to make well informed decisions on the best treatment option available.

Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI).

BACKGROUND: Failure of implantation and conception may result from an inability of the blastocyst to escape from its outer coat, which is known as the zona pellucida. Artificial disruption of this coat is known as assisted hatching and has been proposed as a method for improving the success of assisted conception by facilitating embryo implantation. OBJECTIVES: To determine the effect of assisted hatching (AH) of embryos from assisted conception on live birth and multiple pregnancy rates.  SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (August 2012), MEDLINE (1966 to August 2012) and EMBASE (1980 to August 2012). SELECTION CRITERIA: Three authors identified and independently screened trials. We included randomised controlled trials (RCTs) of AH (mechanical, chemical or laser disruption of the zona pellucida prior to embryo replacement) versus no AH that reported live birth or clinical pregnancy. DATA COLLECTION AND ANALYSIS: Three authors independently performed quality assessments and data extraction. MAIN RESULTS: Thirty-one trials reported clinical pregnancy data, including 1992 clinical pregnancies in 5728 women. There was no significant difference in the odds of live birth in the AH group compared with the control group (9 RCTs; odds ratio (OR) 1.03, 95% confidence interval (CI) 0.85 to 1.26, moderate quality evidence), with no evidence of significant heterogeneity (P = 0.38) or inconsistency (I(2) = 6%). Analysis of the clinical pregnancy rates from the nine studies which reported live birth showed a non-significant result (OR 1.03, 95% CI 0.85 to 1.25 ).Analysis of all of the studies included in this update (31 RCTs) showed that the clinical pregnancy rate in women who underwent AH was slightly improved, but the level only just reached statistical significance (OR 1.13, 95% CI 1.01 to 1.27, moderate quality evidence). However, it is important to note that the heterogeneity for this combined analysis for clinical pregnancy rate was statistically significant (P = 0.001) and the I(2) was 49%. Subgroup analysis of women who had had a previous failed attempt at IVF found improved clinical pregnancy rates in the women undergoing AH compared with the women in the control group (9 RCTs, n = 1365; OR 1.42, 95% CI 1.11 to 1.81) with I(2) = 20%. Miscarriage rates per woman were similar in both groups (14 RCTs; OR 1.03, 95% CI 0.69 to 1.54, P = 0.90, moderate quality evidence). Multiple pregnancy rates per woman were significantly increased in women who were randomised to AH compared with women in the control groups (14 RCTs, 3447 women; OR 1.38, 95% CI 1.11 to 1.70, P = 0.004, low quality evidence). AUTHORS' CONCLUSIONS: This update has demonstrated that whilst assisted hatching (AH) does appear to offer a significantly increased chance of achieving a clinical pregnancy, the extent to which it may do so only just reaches statistical significance. The 'take home' baby rate was still not proven to be increased by AH. The included trials provided insufficient data to investigate the impact of AH on several important outcomes. Most trials still failed to report on live birth rates.

Effects of firefighting on semen parameters: an exploratory study.

Firefighters are occupationally exposed to heat intensities and chemical concentrations that may affect fertility. Twenty firefighters participated in an exploratory study assessing fertility of firefighters via an online survey and semen analysis. Data analysis included consideration of demographic characteristics, reproductive history and occupational exposures. Overall, firefighter semen parameters were below World Health Organisation reference values designating fertility in men. Firefighters younger than 45 years had a higher incidence of abnormal semen parameters (42%) than those aged 45 years or greater (9%). Increased rank and higher levels of occupational and/or personal hygiene were associated with improved semen quality. Increased frequency of fire exposure was associated with a reduction in normal forms, volume, sperm concentration and total sperm count. Sperm clumping was greater than 10% in 26% of samples, suggesting reduced semen quality. This exploratory study provides novel data that support the hypothesis of an association between semen quality and firefighter's occupational exposure to toxic environments.

Adherence compounds in embryo transfer media for assisted reproductive technologies.

BACKGROUND: In order to increase the success rate of assisted reproductive technologies (ART), adherence compounds such as hyaluronic acid and fibrin sealant have been introduced into subfertility management. Adherence compounds are added to the embryo transfer medium in order 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 affect the live birth rate in ART compared to transfer media without adherence compounds. SEARCH STRATEGY: The Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO electronic databases were searched (to 26th May 2009) for publications which described randomised controlled trials of the addition of adherence compounds to embryo transfer media. Furthermore, reference lists of all obtained studies were checked and conference abstracts handsearched. SELECTION CRITERIA: Only truly randomised controlled trials comparing embryo transfer media containing adherence compounds with transfer media without (or with lower doses of) adherence compounds were included. The adherence compounds that were evaluated were hyaluronic acid and fibrin sealant. DATA COLLECTION AND ANALYSIS: One review author selected the trials for inclusion according to the above criteria, after which two authors independently extracted the data for subsequent analysis. The statistical analysis was performed in accordance with the guidelines developed by The Cochrane Collaboration. MAIN RESULTS: Sixteen studies with a total of 3698 participants were analysed. One studied fibrin sealant, the other 15 studied hyaluronic acid. There was no evidence of a treatment effect of fibrin sealant as an adherence compound. For hyaluronic acid, there was no evidence of a treatment effect on live birth rate. Evidence of treatment effects could be found for the clinical pregnancy rate (OR 1.41, 95% CI 1.22 to 1.63; P < 0.00001) and the multiple pregnancy rate (OR 1.86, 95% CI 1.49 to 2.31; P < 0.00001), with higher rates in the hyaluronic acid groups. No evidence of treatment effect was found for the other outcomes. AUTHORS' CONCLUSIONS: There is evidence of an improved clinical pregnancy rate with the use of adherence compounds in ART cycles but no evidence of an effect on live birth rate. The increase in multiple pregnancy rate may be the result of the 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.

Assisted hatching on assisted conception (IVF and ICSI).

BACKGROUND: Failure of implantation and conception may result from an inability of the blastocyst to escape from its outer coat, known as the zona pellucida. Artificial disruption of this coat is known as assisted hatching (AH) and has been proposed as a method for improving the success of assisted conception. OBJECTIVES: To determine whether assisted hatching (AH) of embryos facilitates live births and clinical pregnancy. SEARCH STRATEGY: We previously searched the Cochrane Menstrual Disorders and Subfertility Group Specialsed Register (February 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). SELECTION CRITERIA: Two authors identified and independently screened trials. We included randomised controlled trials (RCTs) of AH (mechanical, chemical or laser disruption of the zona pellucida prior to embryo replacement) versus no AH, which reported live birth or clinical pregnancy rates. DATA COLLECTION AND ANALYSIS: Two authors independently performed qualitative assessments and data extraction. MAIN RESULTS: Twenty-eight trials reported clinical pregnancy data, including 1228 clinical pregnancies in 3646 women. There was no significant difference in the odds of live births in the AH compared with control groups (seven RCTs; OR 1.13, 95% CI 0.83 to 1.55; 255 births from 719 women, with no heterogeneity (P = 0.37) or inconsistency I(2) = 8%)). We also analysed the clinical pregnancy rate from the seven studies that reported live births, which was non-significant (OR 1.13, 95% CI 0.83 to 1.54). Inclusion of studies which were more robust in methodology showed an increase in clinical pregnancy rate which was just statistically significant (16 RCTs; OR 1.20, 95% CI 1.00 to 1.45, P = 0.05). Analysis of all the studies included in this update (28 RCTs) showed a marked increase in clinical pregnancy rate (OR 1.29, 95% CI 1.12 to 1.49).Miscarriage rates per women were similar in both groups (14 RCTs; OR 1.13, 95% CI 0.74 to 1.73). Multiple pregnancy rates per woman were significantly increased in women who were randomised to AH compared with women in control groups (12 RCTs; OR 1.67, 95% CI 1.24 to 2.26). AUTHORS' CONCLUSIONS: The improvement in clinical pregnancy rate (CPR) with AH means that a clinic with a success rate of 25% could anticipate improving the CPR to between 29% and 49%, all things being equal. The included trials provided insufficient data to investigate the impact of assisted hatching on several important outcomes.

Can reflexology maintain or improve the well-being of people with Parkinson's Disease?

This study explored whether reflexology could improve or sustain the wellbeing of people with Parkinosn's Disease [PD] using the PDQ39 wellbeing tool designed specifically for use with people with PD. The treatmnt protocal involved giving 8 therapy sessions to 16 people with varying derees of PD in a cross-over design to enable a longitudinal survey of impact. Whilst the results reflected the progressive nature of PD deterioration over time there was an improvement in wellbeing over the active therapy phase. These results suggest that continuous two- three weekly reflexology may limit further deteroration or maintain improvement of wellbeing. A further study is indicated to study this hypothesis.