Ursula Bentin-Ley

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.

Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model

OBJECTIVE To investigate the effect of levonorgestrel and mifepristone on the expression of endometrial receptivity markers in a three-dimensional endometrial construct. DESIGN In vitro study. SETTING University hospital and research laboratory. PATIENT(S) Twelve fertile donors. INTERVENTION(S) Timed endometrial biopsy. MAIN OUTCOME MEASURE(S) Examine the effect of levonorgestrel along with another well-studied fertility-regulating drug, mifepristone, on the expression of endometrial receptivity factors in a three-dimensional stromal and epithelial cell coculture model by immunohistochemistry. RESULT(S) Both epithelial and stromal cells of in vitro endometrial construct showed the presence of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptors-(A+B), vascular endothelial growth factor, leukemia inhibitory factor, interleukin-1 beta, and cyclooxygenase-2, whereas the expression of progesterone receptor-B (AR), integrin alpha(V)beta(3,) and MUC1 were confined to epithelial cells. Mifepristone up-regulated expression of epithelial estrogen receptor-beta and progesterone receptor-B and down-regulated stromal vascular endothelial growth factor and surface molecules MUC1 and integrin alpha(V)beta(3) as observed in vivo. Levonorgestrel had no effect on the expression of endometrial receptivity markers studied. CONCLUSION(S) This in vitro model expresses progesterone-regulated endometrial receptivity factors seen in the physiologic condition. Treatment with levonorgestrel did not affect the expression of these endometrial receptivity markers in contrast to mifepristone. This in vitro model holds the potential to study endometrial receptivity, the embryo-endometrial interaction, and develop new agents for fertility control.

Ultrastructure of endometrial epithelial cells in a three-dimensional cell culture system for human implantation studies

PurposeA three-dimensional cell culture system imitating normal uterine endometrium has previously been established. To what degree do cultured epithelial cells retain their morphological characteristics as compared to in vivomaterial obtained simultaneously from the same tissue donor.ResultsWe found a high degree of similarity between the in vivoand in vitrosituations. The present culture system furthermore imitates the day-to-day morphology of the cycle.ConclusionsThis indicates, that a correct timing of the biopsy tissue is important for future human implantation studies.

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.