Devices, systems, and methods for fluorescence lifetime imaging microscopy

Abstract

The invention provides novel non-invasive in vitro methods for assessing the metabolic condition of oocytes and / or embryos with fluorescence lifetime imaging microscope, that can be used, for example, in assessment of oocytes and embryos in assisted reproductive technologies.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application is a continuation of co-pending U.S. application Ser. No. 14 / 759,591 filed on Jul. 7, 2015 which is a 35 U.S.C. § 371 National Phase Entry Application of International Application No. PCT / US14 / 10435 filed Jan. 7, 2014, which claims benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 61 / 750,061 filed Jan. 8, 2013, the contents of which are incorporated herein by reference in their entireties.FIELD OF THE INVENTION[0002]The invention relates to methods for assessing the metabolic condition of oocytes and / or embryos, and can be used, e.g., in assessment of oocytes and embryos in assisted reproductive technologies.BACKGROUND[0003]Assisted Reproductive Technology (ART) has revolutionized the treatments of human infertility in the past 30 years and has become ubiquitous. ART currently accounts for over 1% of birth in the U.S. (SART, 2005). However, success rates for ART are low, only 10%-35% of cycles result in ...

AI Technical Summary

Benefits of technology

This patent describes a system that can quickly and reliably determine the quality of oocytes and embryos without harming them. The method uses fluorescence lifetime imaging microscopy (FLIM) to analyze the metabolic state of these cells by measuring the levels of NADH and FAD, which are molecules involved in energy metabolism. The results of the analysis can be used to improve the chances of successful embryo transfer during in vitro fertilization (IVF) procedures. The non-invasive method is minimally invasive and can be performed without harming the embryos or oocytes.

Problems solved by technology

However, success rates for ART are low, only 10%-35% of cycles result in successful birth, leading to high costs and use of multiple embryos, which in turn gives rise to high rates of multiple gestations.

Multiple gestations greatly increase mortality rates and suffering for both infant and mothers, and produce substantial financial costs.

One of the major reasons for the low success rate of ART is the absence of reliable methods for selecting the highest quality embryo(s) for transfer.

However, selection criteria generally remain subjective and only result in the ˜35% success rate quoted above.

Newly proposed non-microscopy based methods, using genomic, transcriptomic or proteomic based assays (Uyar, et al, 2012), require a biopsy of the embryo and are thus invasive and significantly reduce rates of embryo survival (Scott et al., 2006).

However, a prospective randomized trial has recently failed to show that utilization of such metabolomic assessment improves selection over morphologic evaluation alone (Vergouw et al, 2012).

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