Peter Braude

Transcatheter uterine artery embolisation to treat large uterine fibroids

Bilateral uterine artery embolisation was performed to treat eight women with symptomatic large fibroids requiring treatment. Uterine volume was quantitatively assessed by magnetic resonance imaging. Both uterine arteries were occluded effectively in all women, and the procedure was well tolerated, with a 24–36 hour admission for pain relief. The level of pain experienced was variable, but well controlled. Some women experienced intermittent vaginal discharge and pain following the procedure. Improvement of symptoms occurred in six of the seven women and the eighth woman conceived. There were no significant complications. At three months four women had a uterine volume of < 350 cm 3 . Embolisation appears to be a good alternative to surgery, but longer follow up is required to evaluate the long term effects and to determine those patients for whom the procedure is suitable.

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

BACKGROUND Intracytoplasmic 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. METHODS 415 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. FINDINGS The 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). INTERPRETATION ICSI 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.

PREIMPLANTATION GENETIC DIAGNOSIS

Preimplantation genetic diagnosis (PGD) is an evolving technique that provides a practical alternative to prenatal diagnosis and termination of pregnancy for couples who are at substantial risk of transmitting a serious genetic disorder to their offspring. Samples for genetic testing are obtained from oocytes or cleaving embryos after in vitro fertilization. Only embryos that are shown to be free of the genetic disorders are made available for replacement in the uterus, in the hope of establishing a pregnancy. PGD has provided unique insights into aspects of reproductive genetics and early human development, but has also raised important new ethical issues about assisted human reproduction.

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.

Generation of a human embryonic stem cell line encoding the cystic fibrosis mutation ΔF508, using preimplantation genetic diagnosis

Human embryonic stem (hES) cells are pluripotent cells isolated from early human embryos. They can be grown in vitro and made to differentiate into many different cell types. These properties have suggested that they may be useful in cell replacement therapy for many degenerative diseases. However, if hES cells could also be manufactured with mutations significant in human disease, they could provide a powerful in-vitro tool for modelling disease processes and progression in a number of different cell types, as well as providing an ideal system for studying in-vitro toxicity and efficacy of drugs and other therapeutic systems such as gene therapy. Embryos with such mutations are generated as part of routine genetic testing during preimplantation genetic diagnosis, providing the opportunity to generate cell lines with significant mutations. A human embryonic stem cell line homozygous for the most common mutation leading to cystic fibrosis in humans (delta F508) has been generated and characterized. This cell line has the same morphology and expresses proteins typical of other unaffected hES cell lines. This cell line represents an important in-vitro tool for understanding the pathophysiology of cystic fibrosis, and presents exciting opportunities to test the efficacy and toxicity of new therapies relevant to CF.

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.

Infertility therapy associated-multiple pregnancies (births): an ongoing epidemic

Multiple gestation is now recognized as a major problem associated with both assisted reproductive technologies (ART) and also with ovulation induction therapies. Although some countries are beginning to adopt measures to address this issue, either through legislation or the development of clinical guidelines, there is a clear need to ensure recognition and a consistent approach to this problem worldwide. In particular, there is a need to educate both healthcare professionals and the lay population that multiple gestations are not a desirable outcome for the infertile couple.

Proof of principle and first cases using preimplantation genetic haplotyping--a paradigm shift for embryo diagnosis.

Preimplantation genetic haplotyping (PGH) proof-of-principle was demonstrated by multiple displacement amplification (MDA) of single buccal cells from a female donor and genotyping using 12 polymorphic markers within the dystrophin gene; the known paternal genotype enabled identification of the paternal haplotype in the MDA products despite 27% allele dropout. MDA amplified DNA from 49 single human blastomeres with 100% success. The MDA products were genotyped using a total of 57 polymorphic markers for chromosomes 1, 7, 13, 18, 21, X and Y; 72% of alleles amplified providing results at 90% of the loci tested. A PGH cycle was carried out for Duchenne muscular dystrophy. One embryo was biopsied: PGH showed a non-carrier female, which was transferred with no resulting pregnancy. A PGH cycle was carried out for cystic fibrosis. Seven embryos were biopsied and PGH allowed the exclusion of 2 affected embryos; a carrier and a non-carrier embryo were transferred resulting in an on-going twin pregnancy. PGH represents a paradigm shift in embryo diagnosis, as one panel of markers can be used for all carriers of the same monogenic disease, bypassing the need for development of mutation-specific tests, and widening the scope and availability of preimplantation genetic testing.

Natural killer cells, miscarriage, and infertility.

Enthusiasm for new treatments aimed at natural killer cells in women with reproductive failure is unfortunately not backed up by the science

Which career first

The most secure age for childbearing remains 20-35