METABOLOMIC DETERMINATION IN ASSISTED REPRODUCTIVE TECHNOLOGY

Abstract

The present invention relates to a method for determining the ideal time for and outcome of reproductive health procedures including in vitro fertilization by establishing a correlation between the successful outcome of said procedure and the spectra of a body fluid obtained using a chosen analytical modality for a population of patients, acquiring for a patient a spectrum of the body fluid of the patient using said chosen modality.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

Further features and advantages of the present invention will become apparent from the following detailed description, taken in combination with the appended drawings, in which:

FIG. 1 is a schematic drawing of an optical oxidative stress measurement device having a 50 μL sample cell with a 1 cm path length supplied with light from a broadband Tungsten Halogen lamp via a first optical fiber, a short wavelength near infrared (SWNIR) spectrophotometer coupled to an opposite end of the sample cell via a second optical fiber for detecting CW intensity in the 600 nm to 1100 nm range, and a computer connected to the spectrophotometer for recording and analyzing the spectra.

FIG. 2 is graph showing absorption levels from a variety of molecular species in the 600 to 1000 nm wavelength range.

FIG. 3 shows a Raman spectra of 20 IVF embryo culture media samples.

FIG. 4 shows mean Raman spectra with Standard Deviation.

FIG. 5 shows spectra for viable samples.

FIG. 6 shows cross validation.

FIG. 7 is a graph of metabolomic signatures of the oxidative stress constituents in the developing embryo obtained using capillary electrophoresis with ultraviolet optical detection which identifies nutrient and metabolite fractions of the media.

Claims

1. An assisted reproductive technology (ART) method which comprises: growing in vitro at least one embryo in a culture medium;analytically testing the culture medium of said at least one embryo at intervals during growth of said embryo to determine state of said embryo;using the state of said embryo to determine at least one of: a time to transfer the embryo into a uterus;a time to subject the embryo to short term storage for future transfer into a uterus;a time to subject the embryo to cryopreservation for future transfer into a uterus;an adjustment to said culture medium to continue growing of said embryo; anda time to transfer the embryo into a different culture medium to continue growing of said embryo.

2. The method of claim 1, wherein said embryo is obtained by in vitro fertilizing at least one oocyte using spermatozoa.

3. The method of claim 1, wherein said using the state of said embryo comprises repeatedly determining said adjustment to said culture medium.

4. The method of claim 1, wherein said state is viability of the embryo for implantation, said time to transfer the embryo being the earliest time at which the embryo reaches a good probability threshold for implantation.

5. The method of claim 1, wherein said uterus is a mammal uterus, said mammal is chosen from human, bovine, equine, feline, canine, caprine, and cetacean.

6. The method of claim 2, further comprising determining a viability of said oocyte, said spermatozoa and said uterus by analytically testing a respective follicular fluid, seminal plasma and uterine lining fluid, wherein said single embryo is transferred when said viability of said oocyte, said spermatozoa, said uterus indicates a good probability of implantation or pregnancy for transfer of said embryo.

7. The method of claim 2, wherein a number of said oocytes are fertilized and a number of said embryos are grown, and wherein said embryos are selected for transfer using at least said state.

8. The method of claim 6, wherein a number of said oocytes are fertilized and a number of said embryos are grown, and wherein said embryos are selected for transfer using at least in part said state.

9. The method of claim 1, wherein said analytically testing comprises obtaining a spectrum of the culture medium.

10. The method of claim 9, further comprising calibrating said spectrum by: determining an effective correlation between recorded spectrum of the culture medium of a number of embryos and recorded success of pregnancy using said number of embryos;wherein said state is determined from performing said correlation on said spectrum.

11. The method of claim 10, wherein said spectrum is an optical spectrum.

12. The method of claim 11, wherein said spectrum contains information related to oxidative stress components of said culture medium.

13. The method of claim 11, wherein said embryo is cryopreserved, the method further comprising periodically obtaining an optical spectrum of the cryopreserved culture medium and determining said state from said cryopreserved culture medium optical spectrum to monitor said cryopreserved embryo during cryopreservation.

14. The method of claim 10, wherein a number of said oocytes are fertilized and a number of said embryos are grown, and wherein said embryos are selected for transfer using at least said state.

15. An assisted reproductive technology (ART) method comprising: extracting a plurality of oocytes in their own follicular fluid;analytically testing the follicular fluid of each one of said oocytes to determine a state of the oocyte; andselecting said oocytes using said state for one of cryopreservation and fertilization.

16. The method of claim 15, wherein said analytically testing comprising obtaining a spectrum of the follicular fluid.

17. The method of claim 16, further comprising calibrating said spectrum by: determining an effective correlation between recorded spectrum of the follicular fluid of a number of oocytes and recorded success of fertilization and/or pregnancy using said number of oocytes;wherein said state is determined from performing said correlation on said spectrum.

18. The method of claim 17, wherein said spectrum is an optical spectrum.

19. A method of generating probability data for the successful outcome of a reproductive health procedure in a patient which comprises: acquiring for at least one cell exchanging metabolites with a fluid medium, chosen from an oocyte, a spermatozoid, and an embryo, a spectrum of at least one metabolite in said fluid medium using a chosen analytical modality;generating probability data for the at least one cell using the acquired spectrum and an established correlation between the successful outcome of a reproductive health procedure and the spectra of a metabolite in a fluid medium obtained using the chosen analytical modality for a population of patients.

20. The method of claim 19 wherein said analytical modality is multiwavelength optical absorption.

21. The method of claim 19 wherein said analytical modality is one of optical Raman scattering and optical fluorescence.

22. The method of claim 20, wherein said optical spectrum is short wavelength near infrared.

23. The method of claim 21, wherein said optical spectrum is near infrared.

24. The method of claim 19, wherein said chosen analytical modality is NMR.

25. The method of claim 19, wherein said at least one cell is an oocyte.

26. The method of claim 19, wherein said at least one cell is an embryo.

27. The method of claim 19, wherein said reproductive health procedure is in vitro Fertilization.

28. The method of claim 19, wherein said reproductive health procedure relates to pre-eclampsia.

29. The method of claim 19, wherein said reproductive health procedure relates to IAI or intra-amniotic inflammation.

30. The method of claim 19, wherein said reproductive health procedure relates to pre-term labor/birth.

31. The method of claim 19, wherein said reproductive health procedure relates to recurrent miscarriage/abortion.

32. The method of claim 19, wherein said reproductive health procedure relates to embryo implantation.

33. The method of claim 19, wherein said reproductive health procedure relates to sex determination.

34. The method of claim 19, wherein said reproductive health procedure relates to environmental contamination/infection.

35. The method of claim 19, wherein said reproductive health procedure relates to ectopic pregnancy.

36. The method of claim 19, wherein said reproductive health procedure relates to normal pregnancy.

37. The method of claim 19, wherein said reproductive health procedure relates to endometriosis.

38. An assisted reproductive technology (ART) method comprising: providing a sample of one or more spermatozoa in seminal plasma;analytically testing the plasma of said spermatozoa to determine a state of the spermatozoa; andselecting said spermatozoa using said state for one of cryopreservation and fertilization.

39. The method of claim 38, wherein said analytically testing comprising obtaining a spectrum of the plasma.

40. The method of claim 39, further comprising calibrating said spectrum by: determining an effective correlation between recorded spectrum of the seminal fluid of a number of spermatozoa and recorded success of fertilization and/or pregnancy using said number of spermatozoa;wherein said state is determined from performing said correlation on said spectrum.

41. The method of claim 40, wherein said spectrum is an optical spectrum.

42. An assisted reproductive technology (ART) method comprising: analytically testing the endometrial fluid of a uterus of a patient to determine a viability of the uterus for implantation of an embryo; anddetermining a time of implantation using said viability.

43. The method of claim 42, wherein if said viability is weak, said testing is repeated, and said time of implantation is determined when said viability is stronger.

44. The method of claim 43, wherein at least one of dietary, rest/exercise, and medicinal intervention is provided to the patient to improve said viability.

45. The method of claim 44, wherein said endometrial fluid is measured optically in situ, said analytically testing comprising obtaining a spectrum.

46. The method of claim 45, further comprising calibrating said spectrum by: determining an effective correlation between recorded spectrum of the fluid of a number of patients and recorded success of pregnancy using said number of patients;wherein said state is determined from performing said correlation on said spectrum.

47. The method of claim 1, wherein said culture medium is frozen.