Ovulation Cycle Monitoring and Management

• US 20100312137A1
• Filed: 10/24/2006
• Published: 12/09/2010
• Est. Priority Date: 10/24/2005
• Status: Abandoned Application

• Current Assignee: Leonard Francis Blackwell, Robert Gilmour
• Original Assignee: Leonard Francis Blackwell, Robert Gilmour
• Inventors: Blackwell, Leonard Francis, Gilmour, Robert
• Application Number:
  US12/084,166
• Publication Number:
  US 20100312137A1
• Time in Patent Office: Days
• US Class Current: 600/551
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G01N 33/689 related to pregnancy or the gonads

Abstract

Methods of monitoring the ovulation cycle of an animal by detecting specific analytes in body fluids, computer program products, devices, data processing systems, and kits for monitoring the ovulation cycle and determining the fertility of female mammals.

Claims

1. A method for measuring fertility in a mammal, comprising:

obtaining a body fluid sample from a mammalian female subject;

contacting said sample with a solid phase capture element, said capture element comprising a first binding agent and a second binding agent, wherein said first binding agent is capable of binding an estrogen metabolite and said second binding agent is capable of binding a progesterone metabolite;

determining the excretion rate of said estrogen metabolite and said progesterone metabolite; and

determining the ovulation cycle status of said female subject based upon the relative excretion rates of said estrogen metabolite and said progesterone metabolite.

2. The method according to claim 1 wherein said estrogen metabolite is estrone glucuronide.

3. The method according to claim 1 wherein said progesterone metabolite is pregnanediol glucuronide.

4. The method according to claim 1 wherein said estrogen metabolite is estrone glucuronide and said progesterone metabolite is pregnanediol glucuronide.

5. The method according to claim 4 wherein said first binding element comprises an antibody capable of binding estrone glucuronide and said second binding element comprises an antibody capable of binding pregnanediol glucuronide.

6. The method according to claim 5 wherein one or both of estrone glucuronide and pregnanediol glucuronide are detected by binding to a polyclonal antibody.

7. The method according to claim 5 wherein one or both of estrone glucuronide and pregnanediol glucuronide are detected by binding to a monoclonal antibody or a binding fragment thereof.

8. The method according to claim 1 wherein said binding element is a single solid phase membrane or strip and both analytes are detected following binding to said strip.

9. The method according to claim 8 wherein said capture element is a single lateral flow strip.

10. The method according to claim 9 wherein said test strip contains antibodies or antibody fragments that bind estrone glucuronide and pregnanediol glucuronide.

11. The method according to any one of claims 2 to 10 wherein the antibodies against estrone glucuronide and pregnanediol glucuronide on the test strip are capable of being associated with a detection element.

12. The method according to any one of claims 2 to 10 wherein the antibodies against estrone glucuronide and pregnanediol glucuronide on the test strip are conjugated to a detection element.

13. The method according to claim 11 or 12 wherein said detection element is not colorimetric.

14. The method according to claim 11 or 12 wherein said detection element is a paramagnetic particle.

15. The method according to claim 1 wherein the mammal is a farm animal.

16. The method according to claim 1 wherein the mammal is bovine.

17. A method according to claim 16 comprising the step of comparing the excretion rates of said estrogen metabolite and said progesterone metabolite with a compilation of bovine estrogen metabolite and progesterone metabolite values determined over the course of at least one bovine ovulation cycle.

18. The method according to claim 17 wherein said compilation of bovine estrogen metabolite and progesterone metabolite values is an electronic database.

19. The method according to claim 1 wherein the mammal is equine.

20. The method according to claim 1 wherein the mammal is a human.

21. The method according to claim 1 wherein the body fluid is urine.

22. The method according to claim 21 further comprising determining the volume of said urine sample.

23. The method according to claim 21 wherein said body fluid is urine that is collected once.

24. The method according to claim 21 wherein said body fluid is urine that is collected without reference to a time interval.

25. The method according to claim 21 wherein said body fluid is urine that is collected over a specified time period.

26. The method according to claim 21 wherein said body fluid is urine that is collected without respect to a specified time period.

27. The method according to claim 21, wherein prior to quantifying the excretion rate of said estrogen metabolite and said progesterone metabolite, the volume of said urine sample is adjusted.

28. The method according to claim 1 wherein said body fluid is urine that is collected without respect to a specified time period and, before said excretion rates are determined, a sample volume adjustment step is performed by a sample dispensing device that makes a sample volume adjustment as needed.

29. The method according to claim 1 wherein said body fluid is urine that is collected without respect to a specified time period and a sample volume adjustment step is preformed according to an algorithm.

30. The method according to claim 1 wherein said body fluid is urine that is collected without respect to a specified time period and a sample volume adjustment step is preformed according to an algorithm based upon a spectroscopic analysis of the urine sample.

31. The method according to claim 1 wherein said body fluid is urine that is collected without respect to a specified time period and a sample volume adjustment step is preformed according to an algorithm based upon the specific gravity of the urine sample.

32. The method according to any one of claim 29, 30, or 31 wherein said algorithm is a computer algorithm.

33. The method according to claim 1 wherein said body fluid is urine that is collected over at least a 3 hour time period.

34. The method according to claim 1 wherein said body fluid is urine that is collected over at least a 3 hour time period and the volume is adjusted to a normalized volume.

35. The method according to claim 1 wherein said body fluid is urine that is collected over at least a 3 hour time period and the volume is adjusted to a normalized volume equal to about 150 ml/hr.

36. The method of claim 1 wherein the time frame for optimal fertility is determined.

37. The method of claim 1 wherein the day of ovulation is determined.

38. The method according to claim 1 further comprising the step of determining a time frame for optimal fertility for performing an in vitro fertilization of said female subject.

39. The method according to claim 32 wherein the step of adjusting said volume comprises normalizing the volume.

40. The method according to claim 1, further comprising the step of using an algorithm for correction of urinary volume bias before excretion rates are determined.

41. The method of claim 1 wherein a solid phase test strip with paramagnetic particles is used, wherein each said estrogen metabolite is detected by a first paramagnetic particle and said progesterone metabolite is detected by a second paramagnetic particle.

42. The method according to claim 1 wherein the amount of said estrogen metabolite and said progesterone metabolite is quantified.

43. The method according to claim 1 wherein a threshold amount of said estrogen metabolite and said progesterone metabolite are detected as a positive or negative value.

44. The method according to claim 1 that is used to determine a period of maximal fertility within a menstrual cycle.

45. The method according to claim 1 wherein a sample is taken daily and the excretion rates of said estrogen metabolite and said progesterone metabolite are quantified daily for a set interval of time.

46. The method according to claim 1 comprising the step of using a portable detector to measure excretion rate.

47. The method according to claim 22 wherein said portable detector is in communication with database comprising historical values of excretion rates for progesterone or a progesterone metabolite.

48. The method according to claim 22 wherein said portable detector is in communication with database comprising historical values of excretion rates for estrogen or a estrogen metabolite.

49. A test strip for performing the method of claim 1.

51. The test strip according to claim 42 wherein said first binding element and said second binding element are antibodies or fragments thereof.

53. A kit for performing the method of claim 1, said kit comprising a container for a solid phase capture element and instructions for use of the kit, said capture element comprising a first binding agent and a second binding agent, wherein said first binding agent is capable of binding an estrogen metabolite and said second binding agent is capable of binding a progesterone metabolite.

54. A reader for performing the method of claim 1, said reader comprising:

a holder for a solid phase capture element;

a detection element for detecting a photometric or electroactive signal; and

means for transmitting and/or analyzing said photometric or electroactive signal.

57. A computer program for home users for providing information on the use of the method of claim 1 and to permit display of the data on a periodic basis.

50. A test strip comprising a first binding element capable of binding a estrogen metabolite and a second binding element capable of binding a progesterone metabolite.

52. A quantitative test strip for detecting and quantifying estrone glucuronide and pregnanediol glucuronide.

55. A method for measuring fertility in a mammal, comprising:

obtaining a body fluid sample from a mammalian female subject;

contacting said sample with a first binding agent and a second binding agent, wherein said first binding agent is capable of binding an estrogen metabolite and said second binding agent is capable of binding a progesterone metabolite;

determining the excretion rate of said estrogen metabolite and said progesterone metabolite; and

determining the ovulation cycle status of said female subject based upon the relative excretion rates of said estrogen metabolite and said progesterone metabolite.

56. A fertility monitor comprising:

a sample dispenser;

a sensor for detecting the presence of at least two analytes in the sample;

a processor for calculating;

communication means to central database or internal data storage comprising estrone glucuronide and pregnanediol glucuronide excretion rate data.

58. A computer program product for the display and analysis of urinary estrone glucuronide and pregnanediol glucuronide excretion rates suitable for use with a computer in communication with an electronic database of menstrual cycle comprising historical estrone glucuronide and pregnanediol glucuronide excretion rate values.

59. A method for measuring fertility in an mammal, said method comprising the steps of

obtaining a body fluid sample from a female subject;

contacting said sample with a capture element comprising a binding agent capable of binding a progesterone metabolite;

quantifying the excretion rate of said progesterone metabolite;

determining the ovulation cycle status of said female subject based upon the excretion rate of the progesterone metabolite.

60. A method for measuring fertility in an mammal, said method comprising the steps of:

obtaining a body fluid sample from a female subject;

contacting said sample with a capture element capable of binding an estrogen metabolite;

quantifying the excretion rate of said estrogen metabolite;

comparing the excretion rate of said estrogen metabolite against an estrogen metabolite excretion rate made within the same ovarian cycle; and

determining the ovulation cycle status of said female.

61. A method for measuring fertility in an non-human mammal, said method comprising the steps of

obtaining a body fluid sample from a non-human female subject;

contacting said sample with a capture element, said capture element comprising a first binding agent and a second binding agent, wherein said first binding agent is capable of binding an estrogen metabolite and said second binding agent is capable of binding a progesterone metabolite;

quantifying the excretion rates for said estrogen metabolite and said progesterone metabolite;

determining the ovulation cycle status of said female subject based on the relative excretion rates of said estrogen metabolite and said progesterone metabolite.

62. A method of monitoring the physiologic status of one or more remotely located subjects wherein a central data processing system is configured to communicate with and receive data from one or more subject monitoring systems, wherein each subject monitoring system is capable of one or more of receiving, storing, and analyzing subject data, the method-comprising the steps of:

obtaining a sample from a subject for analysis;

contacting the sample with an analyte detector associated with a subject monitoring system;

measuring a photometric or electroactive signal corresponding to an analyte on the detection device and detecting one or more analyte;

performing an exchange of data between said subject monitoring system and said central data processing system;

generating a computer program product output comprising historical or real time physiologic status assessment data of said subject, wherein said computer program product output is in communication with the central data processing system;

analyzing said subject data from one or more subject monitoring systems;

determining the status of the subject based on the analysis performed by said computer program; and

communicating, transmitting, or displaying the identified subject status and a therapeutic management recommendation for one or more subjects.

66. The method according to any one of claims 62-65, wherein the subject sample is selected from crevicular fluid, sweat, sebum, vaginal fluid, whole blood, serum, plasma, cerebrospinal fluid, urine, lymph fluids, external secretions of the respiratory, intestinal and genitourinary tracts, tears, saliva, milk, or white blood cells.

67. The method according to claim 69, wherein sample comprises urine.

68. The method according any one of claims 62-65, wherein said detection devices comprises a solid phase capture element selected from porous materials, glass fiber, membranes, papers, strips, pads, nylon, nitrocellulose, or polyester materials.

69. The method according to claim 68, wherein said analyte detection device comprises a lateral flow suitable for detection of one or more metabolites.

70. The method according to claim 68, wherein said detection device comprises a paramagnetic particle embedded assay detection pad.

71. The method according to claim 68, wherein said analyte generates photometric or electroactive detection signals.

72. The method according to claim 68, wherein said electroactive analytes are conjugated to paramagnetic particles.

73. The method according to claim 68, wherein said analytes is selected from hormones or hormone metabolites.

74. The method according to claim 73, wherein said analyte is selected from the group comprising estrogen, progesterone, testosterone or metabolites thereof.

75. The method according to claim 74, wherein said analyte is urinary hormone metabolites.

76. The method according to claim 75, wherein said urinary metabolite is selected from the group comprising estrone 3-sulfate, 2-hydroxyestrone, 4-hydroxyestrone, 2-methoxyestrone, 4-methoxyestrone, 2-methoxyestrone 3-sulfate, 2-methoxyestrone 3-glucuronide, 16 alpha-hydroxyestrone, estradiol-17α

, estradiol 17β

, 16-glucuronide-estriol;

estradiol-17beta 3-glucuronide;

estradiol-17beta 3-sulfate, 2-hydroxy-estradiol-17β

, 2-methoxy-estradiol-17β

, 2-methoxyestradiol-17beta 3-sulfate, 2-methoxy-estradiol-17beta 3-glucuronide, 6β

-hydroxy-estradiol-17β

, 2-methoxyestradiol, 17-epiestriol, 2-hydroxyestradiol, 16-ketoestradiol, 16β

-hydroestrone, 16-epiestriol.

77. The method according to claim 76, wherein said estrogen or metabolite thereof is selected from the group comprising estradiol, estrone, estriol, 2(OH) Estrone, 4 hydroxy-estrone, 16α

-hydroxy-estrone, 2-methoxyestrone, and 4-methoxyestrone.

78. The method according to claim 77, wherein said estrogen metabolite is estrone glucuronide (E1G).

79. The method according to claim 76, wherein said progesterone or progesterone metabolite is selected from the group comprising 5β

-pregnan-3α

,20α

-diol glucuronide, 5β

-pregnan-3α

-ol-20-1-(5β

-pregnenolone) and 5α

-pregnan-3α

-ol-20-1-(5α

-pregnenolone).

80. The method according to claim 79, wherein said progesterone metabolite is pregnanediol glucuronide (PdG).

81. The method according to claims 62-65, wherein said analysis and or assessment is performed by a computer executable algorithm.

82. The method according to claim 81, wherein said database comprises historical and real time physiologic status assessment data of said subject or subjects in communication with the central data processing system.

83. The method according to claim 82, wherein said database comprises historical and real time fertility status assessment data of said subject or subjects in communication with the central data processing system.

84. The method according to claim 83, wherein said database comprises historical and real time urinary metabolite excretion rates status assessment data of said subject or subjects in communication with the central data processing system.

85. The method according to claim 84, wherein said database comprises historical and real time urinary glucuronide excretion rates status assessment data of said subject or subjects in communication with the central data processing system.

86. The method according to claim 81, wherein said subject'"'"'s clinical or physiologic status are determined based on comparison against clinical or physiologic status assessment data from broader subject populations and or said individual.

87. The method according to claim 81, wherein said communication is performed by a device selected from the group comprising a transmitter, a beeper, a receiver, a telephone, a modem, a cellular phone, a cable, an internet connection, a world wide web link, a television, a closed circuit monitor, a computer, a display screen, a telephone answering machine, facsimile machine, or a printer.

88. The method according to claim 81, wherein said database consists of data selected from the group consisting of physiologic data and behavioral data.

89. The method according to claim 90, wherein said data is selected from the group consisting of urinary metabolite data;

blood glucose measurement;

body temperature measurement;

assessments data related to diet, exercise, stress, and the presence of illness.

90. The method according to claim 81, wherein said algorithm optimizes efficacy of the specific fertility regimen based on particular subject'"'"'s reproductive condition;

91. The method according to claim 89, wherein said algorithm is configured to make automatic adjustments to a subject'"'"'s self-monitoring and fertility management regimen based on subject-entered data.

92. The method according to claim 89, wherein said algorithm contain a database useful for evaluation of the effects of concurrent therapy for other non-fertility indication which might affect the fertility or ovulation cycle of the subject.

93. The method according to claim 81, wherein said SMS suitable for monitoring fertility management data of subjects is capable of detecting paramagnetic analyte signals.

94. The method according to claim 81, wherein said database contains data directed to fertility status-associated values, health status, diet, exercise, and medications taken;

date and time information of the last measurement; and

prescribed course of action regimen.

95. The method according to claim 81, wherein said algorithm calculates adjustments for a subject'"'"'s ovulation variation according to a physician or health care professionals prescription as applied to the data entered into the SMS by the subject.

96. The method according to claim 81, wherein said fertility algorithm for use within a SMS include fertility management algorithm allows a physician or other health care professional to specify retrospective and/or supplemental adjustment regimens.

97. The method according to claim 81, wherein said database of medication interaction information is configured to allow a subject to query the database for information related to the subject'"'"'s use of multiple medications.

98. The method according to claim 81, wherein said database of medication interaction information is configured to allow a subject to query the database for specific historical fertility data profile for each subject and/or historical fertility profiles for populations of subjects.

63. A method of monitoring physiologic status of one or more remotely located subjects in need of therapeutic management wherein a central data processing system is configured to communicate with and receive data from a one or more subject monitoring systems, wherein each subject monitoring system is capable of one or more of receiving, storing, and analyzing subject data, the method-comprising the steps of:

obtaining a sample from a subject for analysis;

contacting the sample with an analyte detector associated with a subject monitoring system;

measuring a photometric or electroactive signal corresponding to an analyte on the detection device and detecting one or more analyte;

performing a volumetric correction for fluid volume bias using a computer executable algorithm;

quantifying the excretion rate of one or more analyte;

transmitting information from a subject monitoring system to a central data processing system;

generating a computer program product output comprising historical and/or real time physiologic status assessment data of said subject, wherein said computer program product output is in communication with the central data processing system;

analyzing said subject data from one or more subject monitoring systems;

optimizing accuracy of fertility status assessment and or fertility status prediction of individual fertility endpoints by statistical comparison by individual historical data and or subject population historical data;

determining the status of the subject based on the analysis performed by said computer program; and

communicating, transmitting, and/or displaying the identified subject status and a therapeutic management recommendation for one or more subjects via at least one remotely located client in communication with said central data processing system and/or subject monitor system.

64. A method of monitoring fertility status of a plurality of remotely located female subjects in need of fertility management wherein a central data processing system is configured to communicate with and receive data from a plurality of respective subject monitoring systems, wherein each subject monitoring system is capable of receiving, storing, and analyzing subject data, the method-comprising the steps of:

identifying a detection device associated with a subject;

verifying the identity of a detection device;

verifying the identity of a subject monitoring system associated with a subject;

obtaining a body fluid sample from said subject for analysis;

capturing said sample on detection device suitable for detection on the subject monitoring system;

assessing the detection device and measuring the signals from the analyte on the detection device to provide inputs to computer program product A (Algorithm A); and

/or computer program product B (Algorithm B);

analyzing the obtained subject data transmitted from a subject monitoring system substantially simultaneously with the transmission thereof to the subject computer CPU and/or central data processing system to determine the subject'"'"'s fertility status based on the analysis performed by said computer program product (Algorithm A);

generating a computer program product output A (database A) and/or computer program product output B (database B) comprising the fertility status assessment data from said computer program product A and/or computer program product B;

updating the computer program product output A (database A) and/or computer program product output B (database B) with additional fertility status assessment data inputs generated from detection and analysis of additional fertility status assessment data from the subject;

obtaining subject data from a plurality of subject monitoring systems at the central data processing system, wherein the subject data comprises fertility status assessment data;

analyzing said subject data transmitted from a plurality of subject monitoring systems at the central data processing system substantially simultaneously with the transmission thereof to the computer of a physician or designated health care professional;

determining the subject'"'"'s fertility status based on the analysis performed by said computer program product B (Algorithm B) and to identify fertility issues of individual Subjects including potential abnormalities when compared against fertility status assessment data from broader subject populations;

communicating, transmitting, and/or displaying the identified subject fertility status and fertility management recommendation for each respective subject via at least one remotely located client in communication with said central data processing system and/or respective subject monitor system; and

transmitting information pertaining to the fertility status and fertility issues of individual Subjects including potential abnormalities when compared against fertility status assessment data from broader subject populations.

65. A method of monitoring physiologic status of one or more remotely located subjects in need of therapeutic management, wherein a central data processing system is configured to communicate with and receive data from one or more subject monitoring systems, wherein each subject monitoring system is capable of receiving, storing, and analyzing subject data, the method-comprising the steps of:

obtaining a sample from said subject for analysis;

capturing said sample on detection device suitable for detection on the subject monitoring system;

assessing the detection device and measuring the signals from the analyte on the detection device;

analyzing the obtained subject data transmitted from a subject monitoring system substantially simultaneously with the transmission thereof to the central data processing system to determine the subject'"'"'s clinical or physiologic status;

generating a computer program product output (database) comprising historical and real time physiologic status assessment data of said subject or subjects in communication with the central data processing system;

analyzing said subject data transmitted from one or a plurality of subject monitoring systems at the central data processing system substantially simultaneously with the transmission thereof to the computer of a physician or designated health care professional;

determining the subject'"'"'s clinical or physiologic status based on the analysis performed by said computer program and to identify clinical or physiologic issues of individual subjects including potential abnormalities when compared against clinical or physiologic status assessment data from broader subject populations; and

communicating, transmitting, and/or displaying the identified subject physiologic status and therapeutic management recommendation, including potential abnormalities when compared against clinical or physiologic status assessment data from broader subject populations, via at least one remotely located client in communication with said central data processing system and/or respective subject monitor system.

99. A method for diagnosing and treating a post partum condition in a female, comprising:

obtaining a body fluid sample from a mammalian female subject;

contacting said sample with a solid phase capture element, said capture element comprising a binding agent capable of binding estrogen or an estrogen metabolite;

quantifying said estrogen or estrogen metabolite; and

diagnosing a post partum condition in said female subject based upon the amount of said estrogen or estrogen metabolite; and

treating said post partum condition based upon the upon the amount of said estrogen or estrogen metabolite detected.

100. The method according to claim 99 comprising administering a hormone replacement based upon the amount of said estrogen or estrogen metabolite.

101. A method for treating menopause and/or symptoms associated with menopause in a female, comprising:

obtaining a body fluid sample from a mammalian female subject;

contacting said sample with a solid phase capture element, said capture element comprising a binding agent capable of binding an estrogen or an estrogen metabolite;

quantifying said estrogen or estrogen metabolite; and

detecting a post partum condition in said female subject based upon the amount of said estrogen or estrogen metabolite detected; and

treating menopause and/or symptoms associated with menopause based upon the amount of said estrogen or estrogen metabolite detected.

102. A method of claim 101 wherein said menopause is characterized as one of natural menopause, perimenopause, induced menopause, premature menopause, or post menopause.

103. A method of detecting cancer in a mammal, comprising:

obtaining a body fluid sample from a mammalian subject;

contacting said sample with a solid phase capture element, said capture element comprising a binding agent capable of binding an hormone or hormone metabolite;

determining the amount or excretion rate of said metabolite; and

correlating the amount or excretion rate of said hormone or hormone metabolite with the probability of said mammalian subject having cancer; and

recommending a treatment protocol for said patient based upon the upon the amount or excretion rate of said hormone or hormone metabolite.

104. The method of detecting cancer of claim 103, wherein said subject is a female suspected of having breast cancer, wherein said hormone or hormone metabolite is estrogen or a estrogen metabolite.

105. A method detecting a reproductive disorder in a mammalian female, comprising:

obtaining a body fluid sample from a mammalian subject;

contacting said sample with a solid phase capture element, said capture element comprising a binding agent capable of binding a hormone or hormone metabolite;

determining the amount or excretion rate of said hormone or hormone metabolife; and

correlating the amount or excretion rate of said hormone or hormone metabolife with the probability of said mammalian subject having one or more disorder selected from anovulation associated with infertility, unexplained infertility, perimenopausal menorrhagia, postmenopausal bleeding, premature menopause, amenorrhea, a hormone imbalance, decreased libido, chronic fatigue, nervousness, osteoporosis, premenstral syndrome, ovulation bleeding, dysfunctional uterine bleeding, hormone replacement therapy, surgical menopause syndrome, hypomenorrhea, hyperstimulated ovaries, polycystic ovarian disease, habitual aborter, missed abortion, and threatened abortion; and

recommending a treatment protocol for said patient based upon the upon the amount or excretion rate of said hormone or hormone metabolife.