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Background: Though outcome models have been proposed previously, it is unknown whether cutoffs in clinical pregnancy and live birth rates at all ages are able to classify in vitro fertilization (IVF) patients into good-, intermediate- and poor prognosis.Methods: We here in 3 infertile patient cohorts, involving 1247, 1514 and 632 women, built logistic regression models based on 3 functional ovarian reserve (FOR) parameters, including (1) number of good quality embryos, (2) follicle stimulating hormone (FSH, mIU/mL) and (3) anti-Müllerian hormone (AMH, ng/mL), determining whether clinical pregnancy and live birth rates can discriminate between good, intermediate and poor prognosis patients.Results: All models, indeed, allowed at all ages for separation by prognosis, though cut offs changed with age. In the embryo model, increasing embryo production resulted in linear improvement of IVF outcomes despite transfer of similar embryo numbers; in the FSH model outcomes and FSH levels related inversely, while the association of AMH followed a bell-shaped polynomial pattern, demonstrating "best" outcomes at mid-ranges. All 3 models demonstrated increasingly poor outcomes with advancing ages, though "best" AMH even above age 43 was still associated with unexpectedly good pregnancy and delivery outcomes. Excessively high AMH, in contrast, was at all ages associated with spiking miscarriage rates.Conclusions: At varying peripheral serum concentrations, AMH, thus, demonstrates hithero unknown and contradictory effects on IVF outcomes, deserving at different concentrations investigation as a potential therapeutic agent, with pregnancy-supporting and pregnancy-interrupting properties. [ABSTRACT FROM AUTHOR]

Background: Previously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated. We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScope™) and standard embryology. We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScope™ and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScope™ and standard embryology. We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo., Results: Part A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScope™ and standard embryology. The EmbryoScope™, however, more than doubled embryology staff time (P < 0.0001). In Part B, embryos grown in the EmbyoScope™ demonstrated significantly poorer day-3 quality (depending on embryo parameter between P = 0.005 and P = 0.01). Suspicion that conical culture dishes of the EmbryoScope™ (EmbryoSlide™) may be the cause was disproven when standard culture dishes demonstrated no outcome difference in standard incubation., Conclusions: Though due to small patient numbers preliminary, this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology. Appropriately designed and powered prospectively randomized studies appear urgently needed in well-defined patient populations before the uncontrolled utilization of these instruments further expands., Trial Registration: NCT02246309 Registered September 18, 2014.

Background: In successful reproduction, endocrine and immune systems closely interact. We here attempt to further elucidate the relationship between androgen levels, systemic activation of the immune system and reproductive success in infertile women, utilizing 2 distinct infertile patient cohorts., Methods: In Group 1, we investigated 322 women (ages 38.6+/-5.4 years) at initial presentation; in Group 2 125 women undergoing in vitro fertilization (169 IVF cycles, ages 38.9+/-5.5 years). In Group 1, we assessed androgens and an immune panel, previously demonstrated to discriminate between activated quiescent immune systems; in Group 2, utilizing the same immune panel, we investigated whether immune system activation relates to embryo quality in IVF cycles., Results: No individual immune test within the immune panel was associated with androgen levels. The total/free testosterone ratio (TT/FT) was, however, significantly associated with presence of gammopathies (in IgG, IgM, IgA, IgE; P=0.026). Surprisingly, immune system activation was associated with significantly improved embryo quality (P=0.008), a finding persistent after adjustment for age and repeat IVF cycles (P=0.006)., Conclusions: Association of immune system activation with improved embryo quality concurs with previously reported immune activation in association with normal functional ovarian reserve (FOR) and normal androgen levels, while, counter intuitively, hypoandrogenism and low FOR are associated with lack of immune system activation. Mild immune system activation, therefore, likely appears essential for establishment of pregnancy, and may be regulated by androgens.