Glycodelin in endometrial flushing fluid and endometrial biopsies from infertile and fertile women.

OBJECTIVE: To investigate in the natural cycle just before IVF, whether glycodelin levels in endometrial flushing fluid obtained days LH+1 and LH+7 can be used in predicting pregnancy in the following IVF cycle, and whether there are differences in women with tubal factor infertility compared to women with unexplained infertility and fertile controls. STUDY DESIGN: A prospective observational multicentre study of 21 fertile and 75 infertile women (25 showed abnormal tubes with no signs of hydrosalpinges, 18 had uni- or bi-lateral hydrosalpinges, 17 were salpingectomised because of hydrosalpinges, and 15 women had unexplained infertility). Endometrial flushing at days LH+1 and LH+7, endometrial biopsy, and blood sampling at day LH+7 were performed before down-regulation for IVF. Glycodelin levels in endometrial flushing fluids (EFF), biopsies, and plasma samples were related to tubal pathology, endometrial dating and IVF outcome. Furthermore, total protein concentration was measured in EFF to investigate the influence of normal endometrial maturation on protein concentrations from days LH+1 and LH+7. RESULTS: At day LH+1, EFF glycodelin levels were higher in infertile women with abnormal tubes compared to fertile women, particularly in women conceiving after the following IVF. For women with unexplained infertility, a higher level at day LH+1 was present only in women not conceiving after the following IVF. ROC curve analysis showed that at day LH+1 EFF glycodelin levels had no predictive value for IVF outcome. At day LH+7, glycodelin levels in endometrial flushing fluids and biopsies depended on endometrial dating. CONCLUSIONS: At day LH+1, glycodelin concentration is increased in endometrial flushing fluid from infertile women with abnormal tubes compared to fertile controls without being a valuable predictor of subsequent pregnancy. At day LH+7 the glycodelin level depends on endometrial dating.

Identification of differences in gene expression in primary cell cultures of human endometrial epithelial cells and trophoblast cells following their interaction.

BACKGROUND: The interaction between epithelial cells of endometrium and trophoblast cells during implantation is presumed to be accompanied by a change in gene expression in the cell types involved. The objective of this study was to identify such differentially expressed genes. METHODS: The interaction between the cell types was simulated in vitro by growing primary cell cultures of human endometrial epithelial cells and trophoblast cells together (co-culture) and separately (control cultures). Gene expression in the cell cultures was compared using the Differential Display method and confirmed using a modified Northern Blot method. RESULTS: Twelve transcripts were identified as being differentially expressed following the interaction between trophoblast and endometrial cells. Some of these sequences show homology to known human genes while other sequences are coding for potential novel genes: (1) one sequence was homologous to the to Homer 1 gene, (2) one identical to the mRNA for XP-G factor, (3) one similar to a hypothetical protein, (4) transcripts showing homologies to a mRNA coding for a cellular proapoptotic protein, and (5) sequences homologous to regions on human chromosomes 5 and 16. Besides, some differentially expressed transcripts have sequences, which could be translated into ribosomal proteins or possibly code for novel proteins. CONCLUSION: These sequences may be important to the course of events following the interaction between endometrial epithelial and trophoblast cells and responsible for implantation.

The antiprogesterone Org 31710 inhibits human blastocyst-endometrial interactions in vitro.

OBJECTIVE: To investigate the effect of the anti-P Org 31710 on human blastocyst attachment to cultured endometrial epithelial cells. DESIGN: Experimental in vitro study. SETTING: University hospital. PATIENT(S): Eleven fertile endometrial donors. INTERVENTION(S): Timed endometrial biopsy for cell cultures. MAIN OUTCOME MEASURE(S): Blastocyst attachment rate on endometrial cell cultures; secretion of glycodelin and leukemia inhibitory factor into the culture medium measured by RIA and ELISA techniques; and expression of progesterone receptors, interleukin-1 receptor type-1, and integrin subunit beta(3) on endometrial epithelial cells examined by immunohistochemistry. Endometrial pinopodes visualized by scanning electron microscopy. RESULT(S): Eleven of 16 human blastocysts attached to control cultures, whereas none of 10 blastocysts attached when Org 31710 was added to the culture medium (P=.0007). Immunohistochemical studies demonstrated no significant differences between groups. Biochemical analyses displayed a trend toward higher glycodelin secretions and, by scanning electron microscopy, a tendency toward less pinopode formation in the Org 31710 group, but the results did not reach statistical significance. The presence of swollen microvilli, precursors of endometrial pinopodes, was significantly reduced on cultures with Org 31710 (P=.03). CONCLUSION(S): The study presents a model for human blastocyst-endometrial interactions responding to an anti-P drug. The exact mechanism for the anti-attachment properties of Org 31710 on the cultured endometrial cells and the blastocysts needs further evaluations.

Biochemical evaluation of endometrial function at the time of implantation.

OBJECTIVE: To review the literature on various endometrial factors assumed to be of importance to implantation and to evaluate their potential clinical value in the assessment of endometrial function at the time of implantation in infertile women in natural and stimulated cycles. DESIGN: Literature review. RESULT(S): Cytokines such as leukemia inhibitory factor, colony-stimulating factor-1, and interleukin-1 have all been shown to play important roles in the cascade of events that leads to implantation. They participate in a synchronized cooperation between the endometrium and the preimplanting embryo under the influence of steroid hormones. The same applies to the integrin alpha(v)beta(3), glycodelin, and the polymorphic mucin 1. The usefulness of these factors to assess endometrial receptivity and to estimate the prognosis for pregnancy in natural and artificial cycles remains to be proven. CONCLUSION(S): The studies performed to date have mostly included only small groups of patients with a lack of fertile controls, and only a few prospective, controlled trials have been carried out. Therefore, definite conclusions about the clinical value of these factors in the assessment of endometrial function and prognosis for pregnancy after artificial reproductive therapy cannot be drawn at present. Further evaluation of their importance for and function during implantation is needed.