Yakoub Khalaf

Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial

BACKGROUNDnIntracytoplasmic sperm injection (ICSI) is a more invasive option than conventional in-vitro fertilisation (IVF), which can be successful even when semen characteristics are poor. Reports of higher fertilisation rates after ICSI suggest that this technique may be better than the conventional method for all couples seeking IVF. We undertook a multicentre randomised controlled trial comparing clinical outcome after ICSI or traditional IVF in couples with non-male-factor infertility.nnnMETHODSn415 eligible and consenting couples at four UK centres were randomly assigned IVF or ICSI (total 435 treatment cycles: IVF 224; ICSI 211). Usual clinical and laboratory protocols for the two treatment procedures were followed in each of four participating centres. The primary outcome was the implantation rate (number of gestation sacs per embryo replaced expressed as a percentage). Secondary outcomes were pregnancy and fertilisation rates associated with each treatment. Analyses were by intention to treat.nnnFINDINGSnThe implantation rate was higher in the IVF group than in the ICSI group (95/318 [30%] vs 72/325 [22%]; relative risk 1.35 [95% CI 1.04-1.76]). The pregnancy rate per cycle was also higher after IVF (72 [33%] vs 53 [26%]; 1.17 [0.97-1.35]). Mean associated laboratory time was significantly shorter with IVF than with ICSI (22.9 [SD 12.1] vs 74.0 [38.1] min; 95% CI for difference 45.6-56.6).nnnINTERPRETATIONnICSI offers no advantage over IVF in terms of clinical outcome in cases of non-male-factor infertility. Our results support the current practice of reserving ICSI only for severe male-factor problems.

A systematic review of the effect of oral antioxidants on male infertility

The use of antioxidants in treatment of infertile men has been suggested, although the evidence base for this practice is unclear. A systematic review of randomized studies was conducted to evaluate the effects of oral antioxidants (vitamins C and E, zinc, selenium, folate, carnitine and carotenoids) on sperm quality and pregnancy rate in infertile men. MEDLINE, EMBASE, Cochrane Library and CINAHL were searched for relevant trials published from respective database inception dates to May 2009. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Seventeen randomized trials, including a total of 1665 men, were identified, which differed in the populations studied and type, dosage and duration of antioxidants used. Only two-thirds of the studies (11/17) reported using allocation concealment and three studies (18%) used intention-to-treat analysis. Despite the methodological and clinical heterogeneity, 14 of the 17 (82%) trials showed an improvement in either sperm quality or pregnancy rate after antioxidant therapy. Ten trials examined pregnancy rate and six showed a significant improvement after antioxidant therapy. The use of oral antioxidants in infertile men could improve sperm quality and pregnancy rates. Adequately powered robust trials of individual and combinations of antioxidants are needed to guide clinical practice.

Self-organization of the human embryo in the absence of maternal tissues

Remodelling of the human embryo at implantation is indispensable for successful pregnancy. Yet it has remained mysterious because of the experimental hurdles that beset the study of this developmental phase. Here, we establish an inxa0vitro system to culture human embryos through implantation stages in the absence of maternal tissues and revealxa0the key events of early human morphogenesis. These include segregation of the pluripotent embryonic and extra-embryonic lineages, and morphogenetic rearrangements leading to generation of a bilaminar disc, formation of a pro-amniotic cavity within the embryonic lineage, appearance of the prospective yolk sac, and trophoblast differentiation. Using human embryos and human pluripotent stem cells, we show that the reorganization of the embryonic lineage is mediated by cellular polarization leading to cavity formation. Together, our results indicate that the critical remodelling events at this stage of human development are embryo-autonomous, highlighting the remarkable and unanticipated self-organizing properties of human embryos.

A systematic review and meta-analysis of acupuncture in in vitro fertilisation.

Backgroundu2002 Numerous randomised studies have reported pregnancy outcome in women who received acupuncture during their in vitro fertilisation (IVF) treatment cycle.

Outpatient hysteroscopy and subsequent IVF cycle outcome: a systematic review and meta-analysis

A systematic review of studies evaluating the influence of outpatient (office) hysteroscopy on the outcome of the subsequent IVF cycle was conducted. MEDLINE, EMBASE, the Cochrane Library, National Research Register, ISI Conference Proceedings, ISRCTN Register and Meta-register were searched for randomized controlled trials (up to July 2007). All trials comparing the outcome of IVF treatment performed in patients who had outpatient hysteroscopy in the cycle preceding their IVF treatment with a control group in which hysteroscopy was not performed were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Study authors were contacted for additional information. The main outcome measure was pregnancy rate. In total, 1691 participants were included in two randomized (n = 941) and three non-randomized controlled studies (n = 750). The quality of the studies was variable. Meta-analyses of the results of five studies showed evidence of benefit from outpatient hysteroscopy in improving the pregnancy rate in the subsequent IVF cycle (pooled relative risk = 1.75, 95% CI 1.51-2.03). The evidence from randomized trials was consistent with that from non-randomized controlled studies. Future robust randomized trials comparing outpatient hysteroscopy or mini-hysteroscopy with no intervention before IVF treatment would be a useful addition to further guide clinical practice.

Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre‐ and postintervention study

Objectiveu2002 To examine the clinical pregnancy rate (CPR) and multiple pregnancy rate (MPR) in a large in vitro fertilisation (IVF) programme before and after the introduction of single blastocyst transfer (SBT) strategy in a selected group of women.

The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis

A systematic review and meta-analysis was conducted to evaluate the relationship between the extent of sperm DNA damage and live birth rate (LBR) per couple and the influence of the method of fertilization on treatment outcome. Searches were conducted on MEDLINE, EMBASE and Cochrane Library. Six studies were eligible for inclusion in the meta-analysis. Overall, LBR increased signficantly in couples with low sperm DNA fragmentation compared with those with high sperm DNA fragmentation (RR 1.17, 95% CI 1.07 to 1.28; P = 0.0005). After IVF and intracytoplasmic sperm injection (ICSI), men with low sperm DNA fragmentation had significantly higher LBR (RR 1.27, 95% CI 1.05 to 1.52; P = 0.01) and (RR 1.11, 95% CI 1.00 to 1.23, P = 0.04), respectively. A sensitivity analysis showed no statistically significant difference in LBR between low and high sperm DNA fragmentation when ICSI treatment was used (RR 1.08, 95% CI 0.39 to 2.96; P = 0.88). High sperm DNA fragmentation in couples undergoing assisted reproduction techniques is associated with lower LBR. Well-designed randomized studies are required to assess the role of ICSI over IVF in the treatment of men with high sperm DNA fragmentation.

The influence of delayed blastocyst formation on the outcome of frozen-thawed blastocyst transfer: a systematic review and meta-analysis

BACKGROUNDnThere are conflicting results on whether the rate of blastocyst development before freezing influences the outcome of frozen-thawed blastocyst transfers.nnnMETHODSnWe conducted a systematic review and meta-analysis of controlled studies to compare pregnancy outcomes following transfer of thawed blastocysts that were frozen either on Day 5 or Day 6 following fertilization in vitro. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science. Study selection and data extraction were conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment.nnnRESULTSnWe identified 15 controlled studies comprising 2502 frozen-thawed transfers involving blastocysts that were either frozen on Day 5 or Day 6. Meta-analysis of these studies showed significantly higher clinical pregnancy rate [relative risk (RR) = 1.14, 95% confidence interval (CI): 1.03-1.26, P = 0.01] and ongoing pregnancy/live birth rate (RR = 1.15, 95% CI: 1.01-1.30, P = 0.03) with Day 5 compared with Day 6 frozen-thawed blastocyst transfers. Sensitivity analysis of those studies where blastocysts frozen on Day 5 or Day 6 were at the same stage of development showed no significant difference in the clinical pregnancy rate (RR = 1.07, 95% CI: 0.87-1.33, P = 0.51) and ongoing pregnancy/live birth rate (RR = 1.08, 95% CI: 0.92-1.27, P = 0.36).nnnCONCLUSIONnSlower developing blastocysts cryopreserved on Day 6 but at the same stage of development as those developing to the blastocyst stage on Day 5 have similar clinical pregnancy and ongoing pregnancy/live birth rates following frozen-thawed blastocyst transfers.

Effect of androgen supplementation or modulation on ovarian stimulation outcome in poor responders: a meta-analysis

Many trials have evaluated the use of androgen supplements and androgen-modulating agents to improve outcome of poor responders undergoing IVF treatment. This study conducted a systematic review and meta-analysis of controlled trials of androgen adjuvants (testosterone, dehydroepiandrostereone) and the androgen-modulating agent (letrozole) in poor responders undergoing IVF treatment. Searches were conducted on MEDLINE, EMBASE, Cochrane Library, ISRCTN Register and ISI proceedings. All randomized and non-randomized controlled trials were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The main outcome measure was clinical pregnancy rate. The secondary outcome measures were dose and duration of gonadotrophin use, cycles cancelled before oocyte retrieval, oocytes retrieved and ongoing pregnancy rates. A total of 2481 cycles in women considered as poor responders undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included in nine controlled trials. Meta-analyses of these studies did not show any significant difference in the number of oocytes retrieved and ongoing pregnancy/live-birth rates with androgen supplementation or modulation compared with the control groups. There is currently insufficient evidence from the few randomized controlled trials to support the use of androgen supplementation or modulation to improve live birth outcome in poor responders undergoing IVF/ICSI treatment.

Infertility information on the World Wide Web: a cross-sectional survey of quality of infertility information on the internet in the UK

BACKGROUNDnThe internet is a frequently used source of information for infertile couples. Previous studies suggested that the quality of health information on the internet is poor. The aim of this study was to assess the quality of websites providing information on infertility and its management in the UK. Differences between website types and affiliations were assessed.nnnMETHODSnA Google search for the keyword infertility was performed and 107 relevant websites were identified and categorized by type. Websites were assessed for credibility, accuracy and ease of navigation using predefined criteria.nnnRESULTSnThe total scores for all types of websites were low, particularly in the accuracy category. Websites affiliated to the UK National Health Service (NHS) scored higher than those affiliated to private fertility clinics and other clinics providing non-conventional fertility treatment. Specifically, NHS websites were more likely to report success rates (92.9% versus 60% and 0%, P < or = 0.05) and display information about their sources of funding (85.7% versus 15% and 14.8%, P < or = 0.0001).nnnCONCLUSIONSnInternet resources available to infertile patients are variable. Differences in the quality of infertility information exist between the different types of websites.