Negative-pressure wound therapy as an adjunct to treating pyoderma gangrenosum.

Negative-pressure wound therapy has been shown to be effective in re-epithelialisation in recalcitrant pyoderma gangrenosum. This case documents a patient whose co-morbidities limited the standard treatment options and required an alternative management plan. The STOP GAP randomised control trial found that both oral prednisolone and ciclosporin were equally effective in the treatment of pyoderma gangrenosum. However, in this case, the patient had type 2 diabetes and prednisolone resulted in persistently elevated blood glucose levels. Lower doses were ineffective and it was subsequently stopped once other treatments showed a clinical improvement. A recent diagnosis of breast cancer prevented the use of ciclosporin and other immunosuppressive treatments. After multidisciplinary discussion, involving breast surgeons, oncology, dermatology and tissue viability, doxycycline was commenced alongside a portable negative-pressure device with twice weekly tissue viability input. The introduction of this device resulted in a rapid reduction in the wound size and facilitated healing with an excellent outcome.

Endometrial scratch to increase live birth rates in women undergoing first-time in vitro fertilisation: RCT and systematic review.

BACKGROUND: In vitro fertilisation is a widely used reproductive technique that can be undertaken with or without intracytoplasmic sperm injection. The endometrial scratch procedure is an in vitro fertilisation 'add-on' that is sometimes provided prior to the first in vitro fertilisation cycle, but there is a lack of evidence to support its use. OBJECTIVES: (1) To assess the clinical effectiveness, safety and cost-effectiveness of endometrial scratch compared with treatment as usual in women undergoing their first in vitro fertilisation cycle (the 'Endometrial Scratch Trial') and (2) to undertake a systematic review to combine the results of the Endometrial Scratch Trial with those of previous trials in which endometrial scratch was provided prior to the first in vitro fertilisation cycle. DESIGN: A pragmatic, multicentre, superiority, open-label, parallel-group, individually randomised controlled trial. Participants were randomised (1 : 1) via a web-based system to receive endometrial scratch or treatment as usual using stratified block randomisation. The systematic review involved searching electronic databases (undertaken in January 2020) and clinicaltrials.gov (undertaken in September 2020) for relevant trials. SETTING: Sixteen UK fertility units. PARTICIPANTS: Women aged 18-37 years, inclusive, undergoing their first in vitro fertilisation cycle. The exclusion criteria included severe endometriosis, body mass index ≥ 35 kg/m2 and previous trauma to the endometrium. INTERVENTIONS: Endometrial scratch was undertaken in the mid-luteal phase of the menstrual cycle prior to in vitro fertilisation, and involved inserting a pipelle into the cavity of the uterus and rotating and withdrawing it three or four times. The endometrial scratch group then received usual in vitro fertilisation treatment. The treatment-as-usual group received usual in vitro fertilisation only. MAIN OUTCOME MEASURES: The primary outcome was live birth after completion of 24 weeks' gestation within 10.5 months of egg collection. Secondary outcomes included implantation, pregnancy, ectopic pregnancy, miscarriage, pain and tolerability of the procedure, adverse events and treatment costs. RESULTS: One thousand and forty-eight (30.3%) women were randomised to treatment as usual (n = 525) or endometrial scratch (n = 523) and were followed up between July 2016 and October 2019 and included in the intention-to-treat analysis. In the endometrial scratch group, 453 (86.6%) women received the endometrial scratch procedure. A total of 494 (94.1%) women in the treatment-as-usual group and 497 (95.0%) women in the endometrial scratch group underwent in vitro fertilisation. The live birth rate was 37.1% (195/525) in the treatment-as-usual group and 38.6% (202/523) in the endometrial scratch group: an unadjusted absolute difference of 1.5% (95% confidence interval -4.4% to 7.4%; p = 0.621). There were no statistically significant differences in secondary outcomes. Safety events were comparable across groups. No neonatal deaths were recorded. The cost per successful live birth was £11.90 per woman (95% confidence interval -£134 to £127). The pooled results of this trial and of eight similar trials found no evidence of a significant effect of endometrial scratch in increasing live birth rate (odds ratio 1.03, 95% confidence interval 0.87 to 1.22). LIMITATIONS: A sham endometrial scratch procedure was not undertaken, but it is unlikely that doing so would have influenced the results, as objective fertility outcomes were used. A total of 9.2% of women randomised to receive endometrial scratch did not undergo the procedure, which may have slightly diluted the treatment effect. CONCLUSIONS: We found no evidence to support the theory that performing endometrial scratch in the mid-luteal phase in women undergoing their first in vitro fertilisation cycle significantly improves live birth rate, although the procedure was well tolerated and safe. We recommend that endometrial scratch is not undertaken in this population. TRIAL REGISTRATION: This trial is registered as ISRCTN23800982. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 10. See the NIHR Journals Library website for further project information.

The endometrial scratch is a simple procedure that involves 'scratching' the lining of the womb (the endometrium). Several small studies have shown that undertaking this before the first in vitro fertilisation cycle may improve live birth rates; however, other studies have contradicted this. This large study was carried out to confirm whether or not having an endometrial scratch before the first in vitro fertilisation cycle would increase the number of women having a live birth compared with those having 'usual' in vitro fertilisation treatment (known as the 'control' group). We collected information about pregnancy, miscarriage, stillbirth, pain during the procedure and costs of treatment to find out if there were any meaningful differences. A total of 1048 women aged between 18 and 37 years were randomly allocated to the two groups, so participants had a 50% chance of having the endometrial scratch. Women were followed up throughout their pregnancy to ascertain the outcome of their in vitro fertilisation cycle. Although the live birth rate was 1.5% higher in the endometrial scratch group (38.6%) than in the control group (37.1%), the difference was not large enough to show any benefit of having the procedure. Other outcomes did not differ significantly between the two groups. However, the procedure was safe and tolerable. We found that the cost of treatment was, on average, £316 per participant higher in the group that received endometrial scratch than in the control group; the difference was not large enough to show that receiving endometrial scratch was more cost-effective. We combined the results of this trial with those of previous trials that looked to answer a similar question, and found that, overall, the endometrial scratch procedure does not enhance the chances of achieving a live birth. We conclude that endometrial scratch before first-time in vitro fertilisation does not improve the outcome of treatment, and we recommend that this procedure is not undertaken prior to a first cycle of in vitro fertilisation.

Cryopreserved-thawed embryo transfer in natural or down-regulated hormonally controlled cycles: a retrospective study.

OBJECTIVE: To assess the implantation, pregnancy, and live birth rates after the transfer of frozen-thawed embryos (FET) in a natural or hormonal control cycle. DESIGN: Retrospective study. SETTING: National Health Service tertiary referral center for reproductive medicine in Manchester, United Kingdom. PATIENT(S): Two comparable groups of women with regular menstrual cycles: Group A (n = 212) had FET in a natural cycle after spontaneous ovulation; group B (n = 205) had FET in a pituitary-desensitized hormonally controlled cycle. INTERVENTION(S): In group B, GnRH agonist was commenced in the midluteal phase of the previous cycle and discontinued 3 days before embryo transfer. Oral estradiol valerate and vaginal progesterone pessary were used to prepare the endometrium. Embryo transfer was carried out 3 days after detection of the endogenous LH surge in group A and on day 3 of progesterone administration in group B. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and live birth rates per cycle and per embryo transfer (ET). RESULT(S): In the 212 women who had natural-cycle FET, 172 ETs were performed and 247 embryos replaced. The implantation rate was 14.1% (35/247). Twenty clinical pregnancies (20/172, 11.6%) were achieved. In the 205 women who had down-regulated hormone replacement-cycle FET, 173 embryo transfers were performed and 243 embryos replaced. The implantation rate was 13.5% (33/243). Eighteen clinical pregnancies (18/173, 10.2%) were achieved. There were no significant differences between the two groups with regard to the implantation, clinical pregnancy, or live birth rates per cycle or per ET. CONCLUSION(S): These findings suggest that both FET protocols are equally effective in terms of implantation rate and pregnancy outcome in women with regular menstrual cycles.

Case study: managing and caring for a patient undergoing stoma formation.

A 75-year-old man had attended his GP, as he was worried that his altered bowel habits and slight rectal bleeding was more sinister than haemorrhoids. This article describes the subsequent investigations, care and treatment that he received. It highlights how early detection, prompt treatment, appropriate care and management can enable a person to cope with the devastating diagnosis of bowel cancer, surgery and the need for a stoma. This patient was otherwise well which contributed both to the treatment decision and successful outcome. Unfortunately, not all patients have such an experience, and the measures taken to prevent complications are described.

Expression of 11 members of the BCL-2 family of apoptosis regulatory molecules during human preimplantation embryo development and fragmentation.

Apoptosis during preimplantation development has received much interest because of its potential role in eliminating defective cells. Although development in humans is characterised by a high degree of genetic abnormality, little is known of the regulation of apoptosis in embryos. By PolyA PCR we analysed expression of 11 BCL-2 genes in individual human embryos representative of normal development and in severely fragmented embryos. We demonstrate constitutive expression of BAX in virtually all embryos at all stages of development, and variable expression of BCL2, BCL-XL, BCL-W, MCL-1 BAK, BAD, BOKL, BID, BIK, and BCL-XS. The frequency of expression of pro- and anti-apoptotic BCL-2 members was similar throughout development, except at the two-cell stage where pro-apoptotic genes predominated. Protein expression was confirmed for BCL-2, MCL-1, BCL-X, BAX, BAD, and activated caspase 3. BCL-2 protein was associated with mitochondria but expressed inconsistently in the blastocyst inner cell mass. Consistent differences between morphologically intact and fragmented embryos included the expression of BAK in fragmented but not intact four-cell embryos. Our study addresses the importance of examining single human embryos representative of the viable population for a large number of genes, in order to establish meaningful expression profiles and provide information on overlapping function in a large gene family.