Infertility treatment outcome in sub groups of obese population

<p>Abstract</p> <p>Background</p> <p>Obesity is a common disorder with a negative impact on IVF treatment outcome. It is not clear whether morbidly obese women (BMI >= 35 kg/m2) respond to treatment differently as compared to obese women (BMI = 30–34.9 kg/m2) in IVF. Our aim was to compare the outcome of IVF or ICSI treatments in obese patients to that in morbidly obese patients.</p> <p>Methods</p> <p>This retrospective cohort study was conducted in a tertiary care centre. Patients inclusion criteria were as follows; BMI ≥ 30, age 20–40 years old, first cycle IVF/ICSI treatment with primary infertility and long follicular pituitary down regulation protocol.</p> <p>Results</p> <p>A total of 406 obese patients (group A) and 141 morbidly obese patients (group B) satisfied the inclusion criteria. Average BMI was 32.1 ± 1.38 kg/m2 for group A versus 37.7 ± 2.99 kg/m²for group B. Patient age, cause of infertility, duration of stimulation, fertilization rate, and number of transferred embryos were similar in both groups. Compared to group A, group B had fewer medium size and mature follicles (14 vs. 16), fewer oocytes collected (7 vs. 9) and required higher doses of HMG (46.2 vs. 38.5 amps). There was also a higher cancellation rate in group B (28.3% vs. 19%) and lower clinical pregnancy rate per started cycle (19.9% vs. 28.6%).</p> <p>Conclusion</p> <p>In a homogenous infertile and obese patient population stratified according to their BMI, morbid obesity is associated with unfavorable IVF/ICSI cycle outcome as evidenced by lower pregnancy rates. It is recommended that morbidly obese patients undergo appropriate counseling before the initiation of this expensive and invasive therapy.</p

Transcriptome Analysis during Human Trophectoderm Specification Suggests New Roles of Metabolic and Epigenetic Genes

In humans, successful pregnancy depends on a cascade of dynamic events during early embryonic development. Unfortunately, molecular data on these critical events is scarce. To improve our understanding of the molecular mechanisms that govern the specification/development of the trophoblast cell lineage, the transcriptome of human trophectoderm (TE) cells from day 5 blastocysts was compared to that of single day 3 embryos from our in vitro fertilization program by using Human Genome U133 Plus 2.0 microarrays. Some of the microarray data were validated by quantitative RT-PCR. The TE molecular signature included 2,196 transcripts, among which were genes already known to be TE-specific (GATA2, GATA3 and GCM1) but also genes involved in trophoblast invasion (MUC15), chromatin remodeling (specifically the DNA methyltransferase DNMT3L) and steroid metabolism (HSD3B1, HSD17B1 and FDX1). In day 3 human embryos 1,714 transcripts were specifically up-regulated. Besides stemness genes such as NANOG and DPPA2, this signature included genes belonging to the NLR family (NALP4, 5, 9, 11 and 13), Ret finger protein-like family (RFPL1, 2 and 3), Melanoma Antigen family (MAGEA1, 2, 3, 5, 6 and 12) and previously unreported transcripts, such as MBD3L2 and ZSCAN4. This study provides a comprehensive outlook of the genes that are expressed during the initial embryo-trophectoderm transition in humans. Further understanding of the biological functions of the key genes involved in steroidogenesis and epigenetic regulation of transcription that are up-regulated in TE cells may clarify their contribution to TE specification and might also provide new biomarkers for the selection of viable and competent blastocysts

A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

<p>Abstract</p> <p>Background</p> <p>Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.</p> <p>Methods/Design</p> <p>This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part^®Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10) days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10) days and 3 months (±14 days) after surgery.</p> <p>Discussion</p> <p>This trial aims to assess, whether the intra-peritoneal application of A-Part^®Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls.</p> <p>Trial registration</p> <p>NCT00646412</p

Comparative proteomic analysis of spermatozoa isolated by swim-up or density gradient centrifugation

Abstract BACKGROUND: Reports about the morphologic and functional characteristics of spermatozoa prepared by density gradient centrifugation (DC) or swim-up (SU) have produced discordant results. We have performed a proteomic comparison of cells prepared by DC and SU providing a molecular insight into the differences between these two methods of sperm cell isolation. METHODS: Protein maps were obtained by 2-dimensional (2-D) separations consisting of isoelectrofocusing (IEF) from pI 3 to 11 followed by SDS-polyacrylamide gel electrophoresis. 2-D gels were stained with Sypro Ruby. Map images of DC and SU spermatozoa were compared using dedicated software. Intensities of a given spot were considered different between DC and SU when their group mean differed by >1.5-fold (p<0.05, Anova). RESULTS: No differences were observed for 853 spots, indicating a 98.7% similarity between DC and SU. Five spots were DC>SU and 1 was SU>DC. Proteins present in 3 of the differential spots could be identified. One DC>SU spot contained lactate dehydrogenase C and gamma-glutamylhydrolase, a second DC>SU spot contained fumarate hydratase and glyceraldehyde-3-phosphate dehydrogenase-2, and a SU>DC spot contained pyruvate kinase M1/M2. CONCLUSIONS: The differences in protein levels found on comparison of DC with SU spermatozoa indicate possible dissimilarities in their glycolytic metabolism and DNA methylation and suggest that DC cells may have a better capacitation potential

Approaches to improve the diagnosis and management of infertility

Recent advances in our understanding of the causes of infertility and of assisted reproductive technology (ART) have led to the development of complex diagnostic tools, prognostic models and treatment options. The Third Evian Annual Reproduction (EVAR) Workshop Meeting was held on 26-27 April 2008 to evaluate evidence supporting current approaches to the diagnosis and management of infertility and to identify areas for future research efforts. Specialist reproductive medicine clinicians and scientists delivered presentations based on published literature and ongoing research on patient work-up, ovarian stimulation and embryo quality assessment during ART. This report is based on the expert presentations and subsequent group discussions and was supplemented with publications from literature searches and the authors' knowledge. It was agreed that single embryo transfer (SET) should be used with increasing frequency in cycles of ART. Continued improvements in cryopreservation techniques, which improve pregnancy rates using supernumerary frozen embryos, are expected to augment the global uptake of SET. Adaptation and personalization of fertility therapy may help to optimize efficacy and safety outcomes for individual patients. Prognostic modelling and personalized management strategies based on individual patient characteristics may prove to represent real progress towards improved treatment. However, at present, there is limited good-quality evidence to support the use of these individualized approaches. Greater quality control and standardization of clinical and laboratory evaluations are required to optimize ART practices and improve individual patient outcomes. Well-designed, good-quality studies are required to drive improvements to the diagnosis and management of ART processes

Deletion of Genes Implicated in Protecting the Integrity of Male Germ Cells Has Differential Effects on the Incidence of DNA Breaks and Germ Cell Loss

Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1), MSH2 (MutS homolog 2, involved in mismatch repair pathway), and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage).We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA.These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility

Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Maintaining the integrity of sperm DNA is vital to reproduction and male fertility. Sperm contain a number of molecules and pathways for the repair of base excision, base mismatches and DNA strand breaks. The presence of Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues has recently been shown in male germ cells, specifically during stage VII of spermatogenesis. High PARP expression has been reported in mature spermatozoa and in proven fertile men. Whenever there are strand breaks in sperm DNA due to oxidative stress, chromatin remodeling or cell death, PARP is activated. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Therefore, cleaved PARP (cPARP) may be considered a marker of apoptosis. The presence of higher levels of cPARP in sperm of infertile men adds a new proof for the correlation between apoptosis and male infertility. This review describes the possible biological significance of PARP in mammalian cells with the focus on male reproduction. The review elaborates on the role played by PARP during spermatogenesis, sperm maturation in ejaculated spermatozoa and the potential role of PARP as new marker of sperm damage. PARP could provide new strategies to preserve fertility in cancer patients subjected to genotoxic stresses and may be a key to better male reproductive health