Cytokine profiling in endometrial secretions: a non-invasive window on endometrial receptivity.

Investigation of human embryo implantation requires a non-disruptive means of studying the endometrium during the window of implantation. This study describes a novel approach of cytokine profiling in endometrial secretions. Endometrial secretions aspirated prior to embryo transfer from 210 women undergoing IVF or intracytoplasmic sperm injection were analysed by a multiplex immunoassay. Ten mediators [interleukin (IL)-1beta, IL-6, IL-12, IL-18, tumour necrosis factor-alpha, macrophage migration inhibitory factor, eotaxin, monocyte chemotactic protein-1, interferon-gamma inducible protein-10, vascular endothelial growth factor] were detectable in 90-100% of the samples. Heparin-binding epidermal growth factor, IL-5, IL-17, IL-10, Dickkopf homologue-1 and IL-15 were detected in 23-76%, whereas interferon-gamma was not detectable in any of the samples. To assess possible contamination of samples, cervical mucus was also aspirated for comparative analysis in 22 women. The endometrial cytokine profile differed significantly from cervical mucus. Pregnancy rates of the study participants who underwent endometrial secretion aspiration were compared with 210 controls matched for important prognostic variables; no significant differences were found. In conclusion, cytokine profiling in endometrial secretion offers an objective, non-disruptive means of analysing the in-vivo milieu encountered by the embryo and offers a new and potentially valuable approach to studying the endometrial factor in human embryo implantation.

Cost-effectiveness of a mild compared with a standard strategy for IVF: a randomized comparison using cumulative term live birth as the primary endpoint.

BACKGROUND Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. METHODS Four hundred and four patients were randomly assigned to undergo either mild ovarian stimulation/GnRH antagonist co-treatment combined with single embryo transfer, or standard stimulation/GnRH agonist long protocol and the transfer of two embryos. The main outcome measures are total costs of treatment within a 12 months period after randomization, and the relationship between total costs and proportion of cumulative pregnancies resulting in term live birth within 1 year of randomization. RESULTS Despite a significantly increased average number of IVF cycles (2.3 versus 1.7; P < 0.001), lower average total costs over a 12-month period (8333 versus euro10 745; P = 0.006) were observed using the mild strategy. This was mainly due to higher costs of the obstetric and post-natal period for the standard strategy, related to multiple pregnancies. The costs per pregnancy leading to term live birth were euro19 156 in the mild strategy and euro24 038 in the standard. The incremental cost-effectiveness ratio of the standard strategy compared with the mild strategy was euro185 000 per extra pregnancy leading to term live birth. CONCLUSIONS Despite an increased mean number of IVF cycles within 1 year, from an economic perspective, the mild treatment strategy is more advantageous per term live birth. It is unlikely, over a wide range of society's willingness-to-pay, that the standard treatment strategy is cost-effective, compared with the mild strategy.

Anti-Müllerian hormone: a marker for oocyte quantity, oocyte quality and embryo quality?

Serum anti-Müllerian hormone (AMH) concentrations decline with increasing age and constitute a sensitive marker for ovarian ageing. In addition, basal serum AMH concentrations predict ovarian response during IVF cycles. Concomitantly, oocyte quantity and embryo quality decrease with advancing age. Hence, it was postulated that AMH in serum constitutes a marker for embryo quality. Women aged 37 years and younger with regular menstrual cycles, normal body mass index and partners with normal semen parameters were randomly assigned to either a standard or mild stimulation protocol for IVF treatment. Blood samples were drawn at cycle day 3 and at the day of human chorionic gonadotrophin administration. Embryo quality was assessed using embryo morphology score and preimplantation genetic screening. Serum AMH concentrations on cycle day 3 were correlated with the number of oocytes retrieved in both groups. AMH and embryo morphology were correlated after mild stimulation, but not after conventional ovarian stimulation. AMH and the chromosomal competence of embryos were not correlated. Serum AMH is predictive for ovarian response to stimulation. However, the lack of a consistent correlation with embryo morphology and embryo aneuploidy rate is not in favour of a direct relationship between oocyte quantity and embryo quality.