Single Embryo Transfer: Clinical and Immunological aspects.

Contains fulltext : 26931_singemtr.pdf (publisher's version ) (Open Access)RU Radboud Universiteit Nijmegen, 01 juni 2005Promotor : Braat, D.D.M. Co-promotores : Joosten, I., Kremer, J.A.M.208 p

Cost analysis of singleton versus twin pregnancies after in vitro fertilization.

Contains fulltext : 58647.pdf (publisher's version ) (Closed access)OBJECTIVE: To determine the difference in costs between singleton and twin pregnancies after IVF treatment from pregnancy to 6 weeks after delivery from a health care perspective. DESIGN: Retrospective cost analysis. SETTING: IVF department at the University Medical Center Nijmegen, The Netherlands. PATIENT(S): A representative sample of singleton and twin pregnancies after IVF treatment between 1995 and 2001 at the University Medical Center Nijmegen. INTERVENTION(S): IVF with or without intracytoplasmic sperm injection and with or without cryopreservation. MAIN OUTCOME MEASURE(S): Medical costs per singleton and twin pregnancy after IVF. RESULT(S): In patients pregnant with twins, the incidence of hospital antenatal care, complicated vaginal deliveries, and cesarean sections was higher and was associated with more frequent and longer maternal and neonatal hospital admissions. Maternal and neonatal hospital admissions were the major cost drivers. The medical cost per twin pregnancy was found to be more than five times higher than per singleton pregnancy, 13,469 and 2,550, respectively. CONCLUSION(S): The medical cost per twin pregnancy was more than 10,000 higher than per singleton pregnancy. A reduction in the number of twin pregnancies by elective single ET will save substantial amounts of money. This money might be used for the additional IVF cycles that will probably be needed to achieve similar success rates between single ET and two-embryo transfer

House dust mite avaidance measures improve peak flow and symtoms in patients with allergy but without asthma: A possble delay in the manifestation of clinical asthma?

Contains fulltext : 26000___.PDF (publisher's version ) (Open Access

Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial.

BACKGROUND: With the aim of reducing the number of multiple pregnancies after IVF we investigated the effectiveness of two cycles with single embryo transfer (SET) and one cycle with double embryo transfer (DET) after IVF and calculated the cost-effectiveness of both strategies. Methods: A randomized controlled trial was performed in 107 women, aged <35 years, in their first IVF cycle, with at least one good quality embryo. They were randomized to the SET (n = 54) or DET (n = 53) group using a computer-generated random block number table, stratified for primary or secondary infertility. RESULTS: The cumulative live birth rates per woman randomized of two consecutive cycles of SET [41%; 95% confidence interval (CI) 27-54] versus one cycle of DET (36%; 95% CI 23-49) were comparable, whereas the multiple pregnancy rate was significantly higher: 37% (95% CI 15-59) in the DET and 0% in the in the SET group (P = 0.002). Combining the medical costs of the IVF treatments (where 1.5 more SET cycles were required to achieve each live birth) and of pregnancies up to 6 weeks after delivery, the total medical costs of DET per live birth were 13,680 and 13,438 for SET. CONCLUSIONS: Two cycles with SET were equally effective as one cycle with DET, and the medical costs per live birth up to 6 weeks after delivery were the same. However, if lifetime costs for severe handicaps are included, more than 7000 per live birth will be saved after implementing SET. Because of the high probability of multiple pregnancies in this group of IVF patients, only SET should be performed

The proportion of follicular fluid CD16+CD56DIM NK cells is increased in IVF patients with idiopathic infertility.

Item does not contain fulltextOne-fifth of all in-vitro fertilization (IVF) patients suffer from idiopathic infertility. A low fertilization rate is one of the most characteristic features of IVF in this group, probably caused by oocyte dysfunction. We speculate that an altered lymphocyte profile in follicular fluid (FF) may affect oocyte function and thus play a role in idiopathic infertility. Therefore, we compared levels of lymphocyte populations present in FF of 11 patients with idiopathic infertility (study group) with 29 patients in the control group, i.e. severe male factor infertility (n=17) or tubal factor infertility (n=12). Triple color flow cytometry was used to discriminate between T cells and NK cell subpopulations. In the idiopathic infertility group, a shift from T to NK cells was observed in FF as compared to the control group, caused mainly by a significant higher level of NK cells--20.3 and 13.6% (P<0.05), respectively. This high level of NK cells was due to a rise of the CD16+CD56dim NK cell subset. In peripheral blood, the NK cell levels showed a similar although not significant trend (P=0.08). As the CD16+CD56dim NK cell subpopulation is known for its cytotoxic properties, this subpopulation may negatively affect folliculogenesis and oocyte maturation, reflected by a diminished fertilization rate in the idiopathic infertility group. An altered lymphocyte profile in FF could therefore influence fertility in these patients

Membrane-bound HLA-G activates proliferation and interferon-gamma production by uterine natural killer cells.

Contains fulltext : 57297.pdf (publisher's version ) (Closed access)The expression of HLA-G by invading trophoblasts suggests a role for this molecule in embryo implantation. Putative targets for HLA-G are the uterine natural killer cells (uNK) that are abundantly present at the time of implantation. Since NK cells are potent producers of a variety of cytokines, interaction with HLA-G may result in the production of cytokines involved in trophoblast differentiation or tissue remodelling. In the present study we investigated the effect of membrane-bound HLA-G (mHLA-G) on the uterine mononuclear cell population (UMC) as a whole and on uNK cells in particular by measuring proliferation and cytokine production [interferon-gamma (IFN-gamma)/vascular endothelial growth factor (VEGF)/leukaemia inhibitory factor (LIF)/interleukin-3 (IL-3)]. Uterine cells were isolated from endometrium of non-pregnant women at the time that the endometrium is thought to be receptive to implantation, and then co-cultured with HLA-class I(-)/HLA-class II(+) 721.221 B-LCL cells transfected with mHLA-G. HLA-G suppressed the alloproliferative response of unfractionated UMC to 721.221 cells. Also, IFN-gamma and IL-3 production was strongly reduced. In contrast, purified uNK cells were stimulated by mHLA-G. Proliferation as well as IFN-gamma production was increased after co-culture with mHLA-G transfected 721.221 cells. HLA-G stimulated VEGF production by UMC as well as purified uNK cells. LIF-levels were below the detection level of our enzyme-linked immunosorbent assay. In conclusion, our data show that mHLA-G stimulates proliferation and cytokine production by NK cells, while down-modulating the response of unfractionated UMC

Hormonal stimulation for IVF treatment positively affects the CD56bright/CD56dim NK cell ratio of the endometrium during the window of implantation.

Contains fulltext : 58264.pdf (publisher's version ) (Closed access)The effects of hormone stimulation for IVF treatment on endometrial receptivity remain controversial. Since CD56(bright) natural killer (NK) cells in the endometrium positively contribute to implantation and decidualization whereas CD56(dim) NK cells are negatively associated with reproduction, shifts in the balance between those cells will affect receptivity. Therefore, we compared the leukocyte composition in the endometrium of IVF women (n=20) with non-pregnant women (n=18) in a natural cycle, as a parameter for endometrial quality. Biopsies were obtained 7 days after ovulation. Histological dating of the endometrium showed no increased endometrial advancement after IVF treatment as compared to the control group. Flow cytometric analysis of leukocyte subsets showed that hormonal stimulation positively affected the CD56(bright)/CD56(dim) ratio in the endometrium by a relative decrease in the cytotoxic CD56(dim)CD16(+) NK cell numbers. The relative number of T-cells remained unaffected, while the number of non-T and non-NK cells (i.e. B-cells and macrophages) was higher in the IVF group. These effects were restricted to the endometrium and not observed in peripheral blood. Within the CD56(bright) population we could identify a distinct subset of NK cells (CD56(superbright)) that was unique for the endometrium. We conclude that hormonal stimulation for IVF treatment positively affects the CD56(bright)/CD56(dim) ratio of the endometrium during the window of implantation and does not affect endometrial advancement

Soluble HLA-G promotes Th1-type cytokine production by cytokine-activated uterine and peripheral natural killer cells.

Contains fulltext : 52049.pdf (publisher's version ) (Closed access)Soluble forms of HLA-G (sHLA-G) have been implicated in immune regulation. Fetal trophoblast cells are a prime source of HLA-G. Hence, an interaction between sHLA-G and uterine lymphocytes in the decidual tissues can easily be envisaged. These lymphocytes, when properly activated, are implicated in successful trophoblast invasion, placental maturation and maintenance of pregnancy. However, so far, no data are available on the effect of sHLA-G on the function and phenotype of these cells. Herein, we used a recombinant sHLA-G construct to determine the effect of sHLA-G on uterine lymphocyte cells present in endometrium at the time that it is optimally receptive to trophoblast invasion. In addition, we ascertained the effect of sHLA-G on peripheral lymphocytes. We found that upon co-culture with sHLA-G, proliferation of unfractionated IL-15-stimulated uterine mononuclear cells (UMCs) was inhibited. However, sHLA-G increased both interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha production by these cells. Vascular endothelial growth factor (VEGF) production was reduced. Notably, in contrast to membrane-bound HLA-G, sHLA-G did not affect the natural cytolytic activity of UMCs. Similarly, sHLA-G inhibited proliferation but stimulated pro-inflammatory cytokine production by cytokine-activated, unfractionated peripheral blood mononuclear cells (PBMCs). In addition, we showed that the overall inhibitory effect of sHLA-G on proliferation of the whole cell population could be ascribed to selective inhibition of CD4(+) T cells. In contrast, sHLA-G induced proliferation and IFN-gamma production by both uterine and peripheral natural killer (NK) cells. In conclusion, our data show that the sHLA-G modulates both UMC and PBMC function. sHLA-G, by promoting IFN-gamma production by uterine NK cells, may contribute to vascular remodelling of spiral arteries to allow for successful embryo implantation