Recovery and processing of human embryos formed in vivo

• US 9,247,960 B2
• Filed: 04/10/2014
• Issued: 02/02/2016
• Est. Priority Date: 12/22/2011
• Status: Active Grant

• Current Assignee: Butterfly Biosciences Incorporated
• Original Assignee: Previvo Genetics, LLC
• Inventors: Carson, Sandra Ann, Buster, John E.
• Primary Examiner(s): Marmor, II, Charles A
• Assistant Examiner(s): Dorna, Carrie R
• Application Number:
  US14/250,240
• Publication Number:
  US 20140309486A1
• Time in Patent Office: 663 Days
• Field of Search: 600 33- 35
• US Class Current: 1/1
• CPC Class Codes: A61B 17/42 Gynaecological or obstetrical instruments or methods ligaturing clamps or clips for the umbilical cord A61B17/122; curettage A61B17/320708; dilators A61M29/00
• CPC Class Codes: A61B 17/435 for embryo or ova transplantation
• CPC Class Codes: A61B 2017/00154 pulsed
• CPC Class Codes: A61B 2017/003 Steerable
• CPC Class Codes: A61B 2017/00557 inflatable A61B2017/22051 takes precedence
• CPC Class Codes: A61B 2090/0807 Indication means
• CPC Class Codes: A61B 2217/005 with suction drainage system
• CPC Class Codes: A61B 2217/007 with irrigation system
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61M 1/77 Suction-irrigation systems aspiration tips supplying fluids A61M1/85; specific for negative pressure wound therapy A61M1/92; combined with tracheal tubes A61M16/0463
• CPC Class Codes: A61M 2210/1433 Uterus
• CPC Class Codes: A61M 2210/145 Embryo, fetus
• CPC Class Codes: A61M 3/0283 with at least two inner passageways, a first one for irrigating and a second for evacuating suction-irrigation systems A61M1/77; aspiration tips with fluid supply means A61M1/85; for negative pressure wound therapy A61M1/92
• CPC Class Codes: A61M 31/00 Devices for introducing or retaining media, e.g. remedies, in cavities of the body A61M25/00 takes precedence ; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008
• CPC Class Codes: C12N 5/0604 Whole embryos; Culture medium therefor
• CPC Class Codes: G16H 10/60 : for patient-specific data, e.g. for electronic patient records

Abstract

Among other things, uterine lavage is performed to withdraw at least 50% of in vivo fertilized preimplantation embryos produced after superovulation of a woman and artificial insemination using sperm of her sexual partner. After genetic diagnosis or sex determination or gene therapy, or any combination of any two or more of them, of the recovered embryos and selection of at least one of the embryos to be implanted, the selected embryos are returned to the woman for implantation in her uterus.

Claims

1. A process for recovering one or more blastocysts from a uterus of a human, comprising:

causing superovulation in the human in a way to form multiple corpora lutea that undergo apoptosis and cannot support development of a viable implanted pregnancy;

causing fertilization in vivo of multiple oocytes produced by the superovulation;

permitting the fertilized oocytes to mature to form multiple mature preimplantation embryos that present to the uterus as blastocysts;

placing a device trans-vaginally into a cervical canal of the human;

automatically delivering fluid through the device to the uterus and automatically applying a vacuum to the uterus to aspirate fluid and entrained one or more blastocysts from the uterus without introducing air into the uterus; and

causing desynchronization of the endometrium to reduce the chance that any embryos remaining in the uterus will form a viable pregnancy, wherein desynchronization comprises administering GnRH antagonist on the day on which the one or more blastocysts are recovered to induce further corpus luteum apoptosis, suppress luteal phase progesterone, and further decrease risk of a retained pregnancy.

2. The process of claim 1, wherein automatically delivering fluid through the device to the uterus and automatically applying a vacuum to the uterus includes infusing fluid in periodic pulses and applying a vacuum intermittently.

3. The process of claim 1, wherein the device includes an outer guide member and an inner catheter located within the outer guide member, the outer guide member including a seal for isolating the uterus from an external environment;

the process including advancing the inner catheter relative to the outer guide member positioning a distal region of the inner catheter within the uterus.

4. The process of claim 3, wherein placing the device comprises locating the seal in the cervical canal.

5. The process of claim 4, wherein locating the seal comprises locating the seal between the internal cervical os and the external cervical os such that the seal does not extend into the vagina or the uterus.

6. The process of claim 1, further comprising storing recovered one or more blastocysts in a container.

7. The process of claim 1, further comprising diagnosing at least one of the one or more blastocysts.

8. The process of claim 7, further comprising treating at least one of the one or more blastocysts.

9. The process of claim 1, further comprising selecting at least one of the one or more blastocysts for implantation.

10. The process of claim 1, further comprising returning at least one of the one or more blastocyst to the uterus.

11. The process of claim 1, further comprising receiving electronically at a clinic information from a host, the information derived from containers that uniquely identify the one or more blastocysts and associates the one or more blastocysts with the human, the information including data that tracks transportation and processing of the one or more blastocysts.

12. The process of claim 1, further comprising:

storing recovered one or more blastocysts in a container;

diagnosing at least one of the one or more blastocysts;

treating at least one of the one or more blastocysts;

selecting at least one of the one or more blastocysts for implantation;

returning the at least one selected from the one or more blastocyst to the uterus; and

receiving electronically at a clinic information from a host, the information derived from the container that uniquely identifies the one or more blastocysts and associates the one or more blastocysts with the human, the information including data that tracks transportation and processing of the one or more blastocysts.

13. The process of claim 12, further comprising transporting the container in an anti-shock insulated transport block.

14. The process of claim 12, wherein the recovered one or more blastocysts are stored in a physiologic transport media.

15. The process claim 1, comprising delivery of FSH to the human'"'"'s body.

16. The process of claim 15, in which the FSH is delivered by self-injection.

17. The process of claim 15, in which the dosage of FSH is appropriate for induction of superovulation, in vivo fertilization, and embryonic maturation.

18. The process of claim 15, in which the FSH is self-injected using 5 to 15 daily injections at ranges of 37.5 to 600 mIU per day.

19. The process of claim 15, in which the FSH comprises at least one of injectable menotropins containing both FSH and LH, purified FSH given as urofollitropins, recombinant pure FSH, or single doses of long acting pure FSH (recombinant depot FSH).

20. The process of claim 1, comprising administering GnRH antagonists to quiet the ovaries while causing superovulation.

21. The process of claim 20, in which the GnRH antagonists administered while causing superovulation comprise receptor blocker peptides.

22. The process of claim 21, comprising administering a single dose of GnRH agonist subcutaneously or snuffed to trigger the superovulation.

23. The process of claim 20, in which the GnRH antagonists administered while causing superovulation comprise at least one of Ganirelix, Abarelix, Cetrorelix, or Degarelix.

24. The process of claim 20, in which the GnRH antagonists administered while causing superovulation comprise doses ranging from 0.25 to 3.0 mg.

25. The process of claim 1, in which causing superovulation comprises administering GnRH.

26. The process of claim 25, in which the GnRH comprises at least one of Leuprorelin, Leuprolide acetate, nafarelin, or naferilin acetate snuff.

27. The process of claim 1, comprising administering LH or hCG without GnRH agonist.

28. The process of claim 1, comprising administering LH or hCG in combination with GnRH agonist.

29. The process of claim 1, in which impaired corpus luteum estradiol and progesterone production is supplemented to maintain embryonic viability and maturation.

30. The process of claim 29, comprising administrating progesterone and estradiol until recovery of the one or more blastocysts.

31. The process of claim 30, in which the progesterone comprises at least one of vaginal progesterone, or oral progesterone and the estradiol comprises at least one of oral or transdermal estradiol.

32. The process of claim 31, in which the progesterone comprises vaginal progesterone administered at 1 application per day or in 200 mg doses at 3 applications per day, or oral progesterone administered in 200 mg doses at 3 oral capsules per day, and the estradiol comprises transdermal estradiol patches 400 μ

g per day or oral estradiol 4.0 mg per day.

33. The process of claim 30, in which blastocyst implantation is prevented by discontinuing administration of estradiol and progesterone starting on the day of blastocysts recovery on the day of lavage.

34. The process of claim 1, in which desynchronization comprises administering progesterone receptor antagonist.

35. The process of claim 34, in which the administering comprises a single dose of progesterone receptor antagonist comprising Mifepristone at a dosage amount of 600 mg injected into the uterus with a second dose comprising Mifepristone at a dosage of 600 mg given by mouth one day prior to expected menses.

36. The process of claim 1, in which administering the GnRH antagonist comprises administering a single 3.0 mg dose of the GnRH antagonist.

37. The process of claim 1, wherein the vacuum is applied in between each pulsation of the fluid.

38. The process of claim 1, wherein the process avoids delivering fluid and the entrained one or more blastocysts into the Fallopian tubes of the human.

39. A process for recovering one or more blastocysts from a uterus of a human, comprising:

placing a device trans-vaginally into a cervical canal of the human;

cyclically delivering fluid through the device to the uterus and applying a vacuum to the uterus to aspirate fluid and entrained one or more blastocysts from the uterus without introducing air into the uterus; and

causing desynchronization of the endometrium to reduce the chance that any embryos remaining in the uterus will form a viable pregnancy, wherein said causing desynchronization comprises administering GnRH antagonist on the day on which the one or more blastocysts are recovered to induce further corpus luteum apoptosis, suppress luteal phase progesterone, and further decrease risk of a retained pregnancy.

40. The process of claim 39, in which the GnRH antagonists comprise doses ranging from 0.25 to 3.0 mg.

41. The process of claim 39, in which administering the GnRH antagonist comprises administering a single 3.0 mg dose of the GnRH antagonist.

42. The process of claim 39, wherein the vacuum is applied in between each pulsation of the fluid.

43. The process of claim 39, wherein the process avoids delivering fluid and the entrained one or more blastocysts into the Fallopian tubes of the human.

44. The process of claim 39, further comprising storing recovered one or more blastocysts in a container.

45. The process of claim 39, further comprising diagnosing at least one of the one or more blastocysts.

46. The process of claim 45, further comprising treating at least one of the one or more blastocysts.

47. The process of claim 39, further comprising selecting at least one of the one or more blastocysts for implantation.

48. The process of claim 39, further comprising returning at least one of the one or more blastocyst to the uterus.

49. The process of claim 39, further comprising receiving electronically at a clinic information from a host, the information derived from containers that uniquely identify the one or more blastocysts and associates the one or more blastocysts with the human, the information including data that tracks transportation and processing of the one or more blastocysts.

50. A process for recovering one or more blastocysts from a uterus of a human, comprising:

placing a device trans-vaginally into a cervical canal of the human;

cyclically delivering fluid through the device to the uterus and applying a vacuum to the uterus to aspirate fluid and entrained one or more blastocysts from the uterus without introducing air into the uterus;

causing superovulation in the human in a way to form multiple corpora lutea that undergo apoptosis and cannot support development of a viable implanted pregnancy;

causing fertilization in vivo of multiple oocytes produced by the superovulation;

permitting the fertilized oocytes to mature to form multiple mature preimplantation embryos that present to the uterus as blastocysts; and

causing desynchronization of the endometrium to reduce the chance that any embryos remaining in the uterus will form a viable pregnancy, wherein said causing desynchronization comprises administering GnRH antagonist on the day on which the one or more blastocysts are recovered to induce further corpus luteum apoptosis, suppress luteal phase progesterone, and further decrease risk of a retained pregnancy.

51. A process for recovering one or more blastocysts from a uterus of a human, comprising:

causing superovulation in the human in a way to form multiple corpora lutea that undergo apoptosis and cannot support development of a viable implanted pregnancy;

causing fertilization in vivo of multiple oocytes produced by the superovulation;

permitting the fertilized oocytes to mature to form multiple mature preimplantation embryos that present to the uterus as blastocysts;

placing a device trans-vaginally into a cervical canal of the human;

automatically delivering fluid through the device to the uterus and automatically applying a vacuum to the uterus to aspirate fluid and entrained one or more blastocysts from the uterus without introducing air into the uterus; and

causing desynchronization of the endometrium to reduce the chance that any embryos remaining in the uterus will form a viable pregnancy,

wherein impaired corpus luteum estradiol and progesterone production is supplemented to maintain embryonic viability and maturation.

52. The process of claim 51, comprising administrating progesterone and estradiol until recovery of the one or more blastocysts.

53. The process of claim 52, in which the progesterone comprises at least one of vaginal progesterone, or oral progesterone and the estradiol comprises at least one of oral or transdermal estradiol.

54. The process of claim 53, in which the progesterone comprises vaginal progesterone administered at 1 application per day or in 200 mg doses at 3 applications per day, or oral progesterone administered in 200 mg doses at 3 oral capsules per day, and the estradiol comprises transdermal estradiol patches 400 μ

g per day or oral estradiol 4.0 mg per day.

55. The process of claim 52, in which blastocyst implantation is prevented by discontinuing administration of estradiol and progesterone starting on the day of blastocysts recovery on the day of lavage.