The use of ICSI in ART: evidence for practice.

This article reviews the evidence regarding the safety and efficacy of intra-cytoplasmic sperm injection (ICSI). It provides evidence-based clinical and laboratory guidelines and recommendations for use of ICSI within an assisted reproductive technology (ART) service. The guidelines address the evidence for the use of ICSI rather than conventional IVF (cIVF); the use of ART techniques supplementary to ICSI; and risks associated with ICSI. This article is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs and medical history of the patient, available resources, and institutional or clinical practice limitations.

Human oocyte cryopreservation: revised evidence for practice.

This article reviews the evidence regarding human oocyte cryopreservation by slow freezing and vitrification and provides evidence-based clinical and laboratory guidelines on the effectiveness and safety of these technologies. The guidelines address the stage of oocyte maturity; cryopreservation and thawing/warming using slow cooling or vitrification; techniques used for insemination of thawed/warmed oocytes; information and support counselling. These are an update of previous guidelines. The following outcome measures were examined: cryosurvival, fertilisation rate, cleavage rate, implantation and clinical pregnancy rate, miscarriage rate, live birth rate, psychosocial wellbeing, health of resulting children. This update does not include recommendations specific to fertility preservation for defined patient groups and specific ovarian stimulation regimens as they are covered in detail in recent guidance from the European Society of Human Reproduction and Embryology (ESHRE).

Early oocyte denudation does not compromise ICSI cycle outcome: a large retrospective cohort study.

This retrospective cohort study of 2051 consecutive fresh non-donor intracytoplasmic sperm injection (ICSI) cycles investigated whether time from oocyte retrieval to denudation, precisely measured and recorded by an operator-independent automated radiofrequency-based system, affected cycle outcome. ICSI cycles were divided into two groups: group I (denudation within <2 h of oocyte retrieval, n = 1118) and group II (denudation 2-5 h after oocyte retrieval, n = 933). Univariate analysis by two-sample t-test or Mann-Whitney test was used, as appropriate. Both groups were comparable with regards to mean number of oocytes retrieved and fertilized normally after ICSI. The mean number of embryos transferred and surplus embryos cryopreserved at the blastocyst stage were similar. There was no significant difference in fertilization, embryo implantation, pregnancy, clinical pregnancy or live birth rates between the groups. Analysis of group I ICSI outcome after subdivision into immediate (up to 30 min) and early (31-119 min) denudation showed no statistically significant differences between the two subgroups. In conclusion, early oocyte denudation within <2 h after retrieval does not appear to compromise ICSI cycle outcome, permitting more efficiency and flexibility in scheduling laboratory workload. As this was a retrospective observational study, further prospective studies are required to confirm the findings.

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 in vitro system to culture human embryos through implantation stages in the absence of maternal tissues and reveal the 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.

How should we choose the 'best' embryo? A commentary on behalf of the British Fertility Society and the Association of Clinical Embryologists.

Embryo selection to improve pregnancy rates remains a significant challenge in IVF. Non-invasive and invasive methods of embryo selection include morphological assessment, metabolomics, time-lapse imaging and preimplantation genetic screening. To date, none has been shown conclusively to yield improved implantation and live birth rates. This review summarises current understanding of methods for embryo selection.

ACE consensus meeting report: culture systems.

The UK Association of Clinical Embryologists held a workshop on Culture Systems for assisted conception in Sheffield on 22 May 2013. The meeting was organised in the light of the availability of numerous commercial products for the culture of human preimplantation embryos in vitro and the absence of data comparing the performance of these products. Expert opinions were presented, along with survey data provided by participating IVF Centres. The workshop highlighted the lack of a sound evidence base to support the selection of any one commercial product over another, and raised concerns over the lack of information defining precisely the composition of media, and the potential for adverse long-term effects of such products following their use in assisted conception.

Influence of BMI on risk of miscarriage after single blastocyst transfer.

BACKGROUND: Debate exists regarding the effect of raised BMI on the outcome of pregnancies after assisted reproduction technology. We assessed the effect of BMI on the risk of miscarriage in women conceiving following single blastocyst transfer (SBT) after controlling for confounding factors. METHODS: Fresh and cryo-thawed cycles of SBT that resulted in a pregnancy between January 2006 and March 2010 were included. Patients with BMI < 18.5 kg/m(2) or older than 40 years were excluded. Patients were grouped according to their BMI at the start of treatment cycle. The main outcome measure was the miscarriage rate before 23 weeks gestation. Confounding variables examined included female age, duration and cause of infertility, previous miscarriage, smoking status and quality of blastocyst replaced. RESULTS: A total of 413 women conceived following SBT in fresh (n = 325) or cryo-thawed (n = 88) IVF cycles, of whom 244 had a normal BMI (18.5-24.9) and 169 had a raised BMI of ≥ 25. Overall, 27% (113/413) of women miscarried before 23 weeks gestation. Women with a BMI of ≥ 25 had more than double the risk of miscarriage compared with women who had normal BMI [38 versus 20%, odds ratio (OR): 2.4, 95% confidence interval (CI) 1.6-3.8, P < 0.001, respectively]. After adjusting for confounding variables, having a BMI of ≥ 25 significantly increased the risk of clinical miscarriage before 23 weeks gestation in both fresh (adjusted OR = 2.7, 95% CI 1.5-4.9, P = 0.001) and cryo-thawed IVF cycles (OR = 6.8, 95% CI 1.5-31.1, P = 0.012). CONCLUSIONS: Raised BMI is independently associated with higher miscarriage rate after IVF treatment.

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

BACKGROUND: There are conflicting results on whether the rate of blastocyst development before freezing influences the outcome of frozen-thawed blastocyst transfers. METHODS: We 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. RESULTS: We 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). CONCLUSION: Slower 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.

Reduction of the multiple pregnancy rate in a preimplantation genetic diagnosis programme after introduction of single blastocyst transfer and cryopreservation of blastocysts biopsied on day 3.

BACKGROUND: An elective single-embryo transfer (SET) policy has not been applied to preimplantation genetic diagnosis (PGD) for inherited genetic disorders because of concerns regarding post-thaw survival of biopsied embryos. Our objective was to evaluate the survival and pregnancy potential of embryos biopsied for PGD at the cleavage stage and cryopreserved at the blastocyst stage and its contribution to the overall success of an elective SET policy in a PGD programme. METHODS: From January 2006, all couples who had two or more transferable PGD blastocysts biopsied on Day 3 of culture were offered single-blastocyst transfer (SBT) and cryopreservation of surplus blastocyst(s) using a slow-freezing technique. We compared the outcome of 32 cryo-thawed PGD cycles with that of 191 cryo-thawed conventional in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles performed between January 2006 and July 2008. We also compared the outcome of all fresh PGD cycles performed before and after January 2006. RESULTS: The cryo-thawed blastocyst survival rate was similar between the PGD and IVF/ICSI groups (87% versus 88%, P = 0.94). There was no significant difference in the implantation and clinical pregnancy rates between the two groups (35% versus 29%, P = 0.45 and 34% versus 36%, P = 0.77, respectively). During the same period, the multiple pregnancy rate in the fresh PGD programme dropped from 36% to 10% (OR = 0.20, 95% CI 0.08-0.48, P < 0.001) with no reduction in pregnancy rates. CONCLUSIONS: The survival and implantation potential of biopsied PGD embryos cryopreserved at the blastocyst stage is comparable to that of non-biopsied IVF/ICSI cryopreserved blastocysts. Elective SBT and cryopreservation of surplus blastocysts for later use should extend to include PGD for inherited genetic disorders.

Preimplantation genetic diagnosis as a novel source of embryos for stem cell research.

The generation of human embryonic stem (hES) cells has captured the public and professional imagination, largely due their potential as a means of overcoming many debilitating and degenerative diseases by cell replacement therapy. Despite this potential, few well-characterized hES cell lines have been derived. Indeed, in the UK, despite several centres having been active in this area for more than 2 years, there are as yet no published reports of human embryonic stem cells having been generated. Part of the reason for this lack of progress may relate to the quality of embryos available for research. Embryos surplus to therapeutic requirements following routine assisted reproduction treatment are often of poor quality and a large proportion may be aneuploid. This study reports a new approach to hES cell derivation. Embryos surplus to therapeutic requirements following preimplantation genetic diagnosis were used. Although unsuitable for embryo transfer due to the high risk of genetic disease, these embryos are from fertile couples and thus may be of better quality than fresh embryos surplus to assisted reproduction treatment cycles. Embryos donated after cryopreservation were also used, and putative hES lines were derived from both sources of embryos. The cell lines described here are thought to be the first reported hES cell lines to have been derived in the UK.

The Human Fertilisation and Embryology Act 1990 -- a British case history for legislation on bioethical issues.

Dr. Virginia Bolton, Sir John Osborn, and Denise Servante present an account of the process whereby legislation was enacted in Britain. Each is a member of PROGRESS (the Campaign for Research into Human Reproduction), which was established in 1985 to present the case regulating research using human embryos to the British parliament and public.