Grade of the inner cell mass, but not trophectoderm, predicts live birth in fresh blastocyst single transfers.

Debate continues over which morphological parameter is most important in selecting blastocysts for transfer. We aimed to investigate which parameter more accurately predicts the occurrence of a live birth by designing a retrospective cohort study of 1084 fresh elective single blastocyst transfers. Primary outcome was live birth rate (LBR) and secondary outcomes were implantation, clinical pregnancy and early pregnancy loss rates. Blastocyst expansion and inner cell mass (ICM), but not trophoectoderm, were associated with LBR in the definitive multivariable regression analysis. When ICM grade dropped from A to C the likelihood of achieving a live birth was reduced by 55% (OR= 0.45, 95% CI 0.26-0.79, p = .005). These results were similar for clinical pregnancy rates. Early pregnancy loss rates of embryos with ICM grade C were more than double (38.0%) compared to those of grades A (15.95%) and B (17.17%, p = .002). The transfer of an embryo with an optimal inner cell mass reduces early pregnancy loss and increases the likelihood of a live birth. We did not find any significant association between trophectoderm and LBR in the multivariable analysis in contrast with recent studies.

Preparation of medicines for children - a hierarchy of classification.

There is some confusion about the types of paediatric pharmaceutical preparation (in a regulatory and pharmaceutical development context) that are acceptable for approval by medicines regulators. Some of the confusion relates to terminology which may mean different things to different stakeholders. It may not always be possible to provide authorised, commercially manufactured, age appropriate, ready-to-administer preparations. In terms of assurance of quality and bioavailability there is a continuum from this ideal through intermediate products through authorised compounding and manipulation of commercial dosage forms to ad hoc compounding using only the skills and experience of the individual pharmacist. Additionally, it is widely known that caregivers may manipulate medicines at home, for example by segmenting tablets and by addition to foods or liquids. The first intent of the manufacturer should be to provide for children an age appropriate, ready-to-administer preparation which is commercially manufactured and approved by the competent authorities. However, there will still be a place for providing other age appropriate preparations such as approved products that are 'intermediates' requiring reconstitution before use, or instructions for compounding or manipulation of a dosage form. If compounding or manipulation is likely to be required it is preferable that data are generated by Industry, approved by the competent authorities and provided in the Summary of Product Characteristics (SmPC). It is acknowledged however, that ad hoc compounding or manipulation may also take place in certain circumstances such as logistical difficulties or to satisfy the needs of the child who does not find the authorised product to be 'age appropriate'. This paper explores compounding and manipulation of medicines in relation to approval by medicines regulators and non-approved preparation to fulfil the needs of the individual patient. Definitions are proposed to provide a hierarchical classification based on assurances of quality and bioavailability.

In vitro maturation or in vitro fertilization for women with polycystic ovaries? A case-control study of 194 treatment cycles.

OBJECTIVE: To compare the outcome of unstimulated in vitro maturation (IVM) and routine IVF/intracytoplasmic sperm injection (ICSI) for women with polycystic ovaries (PCO). DESIGN: Retrospective case-control study. SETTING: Fertility unit. PATIENT(S): Ninety-seven patients undergoing IVM were compared with 97 patients undergoing IVF. All had PCO and matched for age, infertility diagnosis, and ovulatory status. INTERVENTION(S): In vitro maturation cycles were unstimulated and hCG was administered 35-40 hours before oocyte retrieval. Oocytes were matured in vitro for 24-48 hours before insemination by ICSI. Endometrial priming with E(2) and P was commenced from the day of egg retrieval and one to two embryos were transferred on days 2-5 of development. Standard long protocol IVF/ICSI was used in the control group. MAIN OUTCOME MEASURE(S): Live birth rate per cycle and ovarian hyperstimulation syndrome (OHSS) rate. RESULT(S): Overall, 65% of IVM eggs matured in vitro in the IVM group. Implantation rates were significantly higher in the IVF group (19.4% vs. 12.9%) as clinical pregnancy rates (50.5% vs. 19.6%) and live birth rates (44.3% vs. 16.5%) than in the IVM group. The OHSS rate was significantly higher in the IVF group (8.2% vs. 0%). CONCLUSION(S): In vitro maturation is a safer and simpler alternative to conventional IVF for women with PCO. It avoids difficulties of gonadotropin stimulation and the risk of OHSS but has a significantly lower live birth rate. Current research projects aim to close the success gap between IVM and IVF.

Effects of cryopreservation and density-gradient washing on phospholipase C zeta concentrations in human spermatozoa.

Cryopreservation and density-gradient washing (DGW) are routinely used in infertility treatment. This study used quantitative immunofluorescence analysis to report how these techniques affect concentrations of the oocyte activation factor, phospholipase C zeta (PLCζ) in spermatozoa from fertile men. DGW significantly elevated the proportion of spermatozoa in which PLCζ could be detected (by 25­81%; P < 0.0001). In contrast, in four donors, cryopreservation significantly reduced PLCζ concentrations (by 20­56%; P < 0.0001). These findings indicate that while DGW positively selects spermatozoa with detectable PLCζ, cryopreservation has significant detrimental effects upon PLCζ concentrations. Since reduced PLCζ concentrations have been implicated in deficient oocyte activation and infertility, further study is highly warranted.