A new stoma for an older person-An association with quality of life and physical function: A systematic review.

BACKGROUND: Older people are more likely to have a stoma postabdominal surgery than younger people. Few studies have examined the effect of a stoma on older people. The aim of this review was to explore the effect of a stoma on functional independence of an older person. We explored secondary outcomes of poststoma formation length of hospital stay, quality of life and factors affecting stroma independence. METHODS: An exploratory systematic review was developed by our multidisciplinary group including an expert patient, colorectal surgeon, stoma nurse, physiotherapist, geriatrician, and methodologist. Four databases were searched including studies with participants 60 years old or older, who had undergone abdominal surgery for any pathology resulting in an abdominal stoma. RESULTS: We identified 857 studies, of which we included 25 in the final review incorporating 6972 participants (average age 67.4 years). There was a strong association between presence of stoma and (1) worse physical function (standardized MD = 0.7; 95% CI 0.21-1.19; I2  = 95) and (2) worse quality of life (standardized MD = 1.61; 95% CI 0.5-2.72, I2  = 98). The same effect was seen in fecal ostomy and urinary diversion. Few studies measured stoma independence and only one examined factors affecting this. No studies examined length of stay. CONCLUSIONS: Stoma have a negative association with the physical function and quality of life of older people. Future studies should focus on identifying modifiable factors that may affect physical function, quality of life, and stoma independence.

Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of the long GnRH agonist vs. the short GnRH agonist vs. the GnRH antagonist regimens in poor responders undergoing IVF. DESIGN: Randomized controlled trial. SETTING: Tertiary referral fertility units. PATIENT(S): Women with previous poor ovarian response undergoing IVF. INTERVENTION(S): One hundred eleven women were randomized to the long GnRH agonist, short agonist, and antagonist regimens. MAIN OUTCOME MEASURE(S): The primary outcome was the number of oocytes retrieved. Secondary outcome measures were gonadotropin consumption, duration of stimulation, cycle cancellation rate, mature oocytes retrieved, fertilization rate, cycles reaching ET, and clinical and ongoing pregnancy rates. RESULT(S): Number of oocytes retrieved was significantly higher with long GnRH agonist compared with the short agonist regimen (4.42 ± 3.06 vs. 2.71 ± 1.60), while there was no significant difference between long agonist and antagonist regimens (4.42 ± 3.06 vs. 3.30 ± 2.91). Duration of stimulation and total gonadotropin dose were significantly higher with long agonist compared with short agonist and antagonist regimens. The ongoing pregnancy rate was 8.1% with long and short agonist regimens and 16.2% with the antagonist regimen. CONCLUSION(S): Long GnRH agonist and antagonist regimens offer a suitable choice for poor responders, whereas the short agonist regimen may be less effective because of fewer eggs retrieved.

Evidence-based medicine and the role of the private sector in assisted reproduction: a response to Dr Fishel's commentary 'Evidenced-based medicine and the role of the National Health Service in assisted reproduction'.

We respond to Dr Fishel's commentary on evidenced-based medicine in assisted reproduction and the role of the UK's National Health Service. We agree that proper randomised clinical trials are not easy to set up or execute. Recruitment is also challenging but requires that all personnel involved in the study, clinicians, embryologists and nurses, agree with its aims and buy in to the need for an answer. Those who believe fervently in the method under scrutiny prior to the availability of robust evidence are likely to undermine the success of any trial. New technologies are not necessarily better technologies. Neither is the supposed 'logic' of a treatment nor anecdotal clinical experience a substitute for evidence properly gained and fairly demonstrated. Dr Fishel would agree that the first obligation of healthcare professionals, whether they are in the public or private sector, is not to do harm to their patients. Adopting new interventions without rigorous assessment of the potential for harm flies in the face of this basic principle.

The procurement of cells for the derivation of human embryonic stem cell lines for therapeutic use: recommendations for good practice.

The donation of human embryos for the derivation of embryonic stem cell lines that may be used in the development of therapeutic products raises more complex ethical, practical and regulatory problems than the donation of embryos for non-clinical research. This review considers these issues and offers recommendations for good practice.

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.

Preimplantation genetic diagnosis for a carrier of a Y;autosome translocation resulting in a healthy male offspring.

OBJECTIVE: To demonstrate the feasibility of establishing a successful pregnancy for a carrier of a balanced Y;autosome translocation. DESIGN: Four locus-specific fluorescence in situ hybridization (FISH) probes, informative for the translocation, were identified and tested on peripheral lymphocyte metaphase chromosomes and interphase preparations from the translocation carrier and his partner. SETTING: National health service genetics center, cytogenetics laboratory, and assisted conception unit. PATIENT(S): An infertile man, presenting with a balanced Y;13 translocation, and his reproductive partner. INTERVENTION(S): After ovarian stimulation, 15 eggs were collected, nine were injected, and three were suitable for blastomere biopsy on day 3; a single blastomere was taken from each embryo and tested with four locus-specific FISH probes. MAIN OUTCOME MEASURE(S): Birth of a healthy child. RESULT(S): One embryo showed a triploid signal pattern and one had fragmented nuclei; neither was suitable for transfer. One embryo showed a balanced male signal pattern and was transferred. A singleton pregnancy was established, resulting in the birth of a healthy male child. CONCLUSION(S): This first report of successful preimplantation genetic diagnosis treatment for infertile males with y:autosome translocations demonstrates that this treatment option can result in successful pregnancies and healthy offspring.

Preimplantation genetic haplotyping: 127 diagnostic cycles demonstrating a robust, efficient alternative to direct mutation testing on single cells.

Preimplantation genetic diagnosis using whole genome amplification and a haplotyping approach (PGH) was first described in 2006 and suggested as an efficient alternative to single-cell PCR for monogenic disorders. DNA from single cells was amplified using multiple displacement amplification; the resulting products were then tested using disease-specific PCR multiplexes applied under standard laboratory conditions to determine the haplotypes in the embryo. This study reports on a total of 127 completed biopsy cycles for 101 couples at risk of: autosomal recessive disease (71 cycles, 53 couples including one germ-line mosaic carrier), autosomal dominant disease (31 cycles, 26 couples including one germ-line mosaic carrier), X-linked recessive disease (18 cycles, 16 couples including one germ-line mosaic carrier), X-linked dominant disease (six cycles, five couples) and a double inheritance of both autosomal and X-linked recessive diseases (one cycle, one couple). Of these, 107 cycles reached embryo transfer. Overall success rates were: fetal heart beat-positive pregnancies (FHB+)/biopsy cycle=28%; FHB+/embryo transfer=34%; FHB+/couple=36%; 26 babies born, 13 ongoing pregnancies. These data demonstrate that PGH provides a robust, efficient and successful alternative to single-cell PCR for monogenic diseases.

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

BACKGROUND: The 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. METHODS: A 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. RESULTS: The 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). CONCLUSIONS: Internet resources available to infertile patients are variable. Differences in the quality of infertility information exist between the different types of websites.

The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles.

OBJECTIVE: To examine the relationship between endometrial thickness and outcome of medicated frozen-thawed embryo replacement (FER) cycles. DESIGN: A retrospective observational study. SETTING: Assisted conception unit at a university hospital. PATIENT(S): All patients who underwent an FER cycle between 1997 and April 2006 and met the inclusion criteria. INTERVENTION(S): For endometrial preparation, a daily dose of 6 mg of oral E(2) valerate was started on menstrual day 1, and P pessaries (800 mg daily) were administrated when the endometrial thickness had reached 7 mm or more, with ET taking place 2-3 days later. The FER cycles were categorized according to endometrial thickness measurement on the day of P supplementation. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, ongoing pregnancy, and live birth rates. RESULT(S): In all, 768 consecutive medicated FER cycles were analyzed. The lowest pregnancy rates were associated with endometrial thickness <7 mm (n = 13) and >14 mm (n = 12; 7% in both groups). Significantly higher implantation (19% vs. 12%), clinical pregnancy (30% vs. 18%), ongoing pregnancy (27% vs. 16%), and live birth (25% vs. 14%) rates were achieved in cycles where endometrial thickness was 9-14 mm (n = 386), compared with those in which endometrial thickness was 7-8 mm (n = 357). These differences remained significant after adjusting for confounding variables (adjusted odds ratio [OR] = 1.83 [confidence interval {CI} = 1.3-2.6] for clinical pregnancy, 1.8 [CI = 1.2-2.6] for ongoing pregnancy and 1.9 [CI = 1.3-2.8] for live birth). CONCLUSION(S): In medicated FER cycles, an endometrial thickness of 9-14 mm measured on the day of P supplementation is associated with higher implantation and pregnancy rates compared with an endometrial thickness of 7-8 mm.

Pituitary suppression regimens in poor responders undergoing IVF treatment: a systematic review and meta-analysis.

Many randomized trials have evaluated the use of various pituitary suppression regimens to improve outcome of poor responders undergoing IVF treatment. A systematic review was conducted of the trials of gonadotrophin-releasing hormone (GnRH) agonist long regimen, GnRH agonist short regimen, GnRH antagonist regimen, as well as other pituitary suppression regimens in poor responders undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. The search included MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI proceedings, and all randomized controlled trials comparing the various pituitary suppression regimens in poor responders were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The main outcome measures were number of oocytes retrieved, cycles cancelled before oocyte retrieval and pregnancy rates. A total of 680 women considered as poor responders undergoing IVF/ICSI treatment were included in nine randomized controlled trials. The quality of these studies was variable: for example, only three of the studies had clear evidence of allocation concealment. Meta-analyses of the results of the studies did not show a consistent benefit for any one pituitary suppression regimen over the other regimens in improving outcome measures. Currently available evidence does not favour any one pituitary suppression regimen for women with poor ovarian response undergoing IVF/ICSI treatment.

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.

Generation of a human embryonic stem cell line encoding the cystic fibrosis mutation deltaF508, 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--an overview.

Since the early 1990s, preimplantation genetic diagnosis (PGD) has been expanding in scope and applications. Selection of female embryos to avoid X-linked disease was carried out first by polymerase chain reaction, then by fluorescence in situ hybridization (FISH), and an ever-increasing number of tests for monogenic diseases have been developed. Couples with chromosome rearrangements such as Robertsonian and reciprocal translocations form a large referral group for most PGD centers and present a special challenge, due to the large number of genetically unbalanced embryos generated by meiotic segregation. Early protocols used blastomeres biopsied from cleavage-stage embryos; testing of first and second polar bodies is now a routine alternative, and blastocyst biopsy can also be used. More recently, the technology has been harnessed to provide PGD-AS, or aneuploidy screening. FISH probes specific for chromosomes commonly found to be aneuploid in early pregnancy loss are used to test blastomeres for aneuploidy, with the aim of replacing euploid embryos and increasing pregnancy rates in groups of women who have poor IVF success rates. More recent application of PGD to areas such as HLA typing and social sex selection have stoked public controversy and concern, while provoking interesting ethical debates and keeping PGD firmly in the public eye.

Strategies and outcomes of the first 100 cycles of preimplantation genetic diagnosis at the Guy's and St. Thomas' Center.

OBJECTIVE: To establish strategies for the implementation of a successful preimplantation genetic diagnosis (PGD) service. DESIGN: Retrospective review of data from a single center. SETTING: A United Kingdom National Health Service hospital. PATIENT(S): Patients (60 couples) were referred for PGD from UK genetic centers. INTERVENTION(S): We followed the protocol of ovarian stimulation, oocyte retrieval, fertilization, single cell biopsy on day 3, and embryo transfer on day 4. Pregnancies unaffected by the familial genetic condition. RESULT(S): A total of 60 couples was treated for 20 different conditions. Early cycles using nonsequential embryo culture media were less successful (13% pregnancy rate/embryo transfer) than later cycles using sequential media (33.5%). Ninety-four percent of embryos (n = 473) had a single cell removed at biopsy. The overall pregnancy rate was 24% per cycle started, 29% per egg collection, 38% per transfer, and 40% per couple treated. In one cycle, an affected pregnancy followed PGD for spinal muscular atrophy (SMA). CONCLUSION(S): The use of sequential media and single cell biopsy results in a successful PGD program with encouraging pregnancy rates.

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.