Container assembly for intravaginal fertilization and culture and embryo transfer and method of intravaginal fertilization and culture employing such a container

• US 6,050,935 A
• Filed: 05/09/1997
• Issued: 04/18/2000
• Est. Priority Date: 05/09/1997
• Status: Expired due to Term

• Current Assignee: Bio X Cell, Inc. (INVO BioScience, Inc.), Louisville Laboratories., Inc.
• Original Assignee: Biofertec Limited
• Inventors: Gleason, Francis G. Jr., Ranoux, Claude
• Primary Examiner(s): Gilbert, Samuel G.
• Application Number:
  US08/854,272
• Time in Patent Office: 1,075 Days
• Field of Search: 600/33-35, 604/403, 604/408, 604/411, 604/415, 604/416, 604/906, 435/240.2, 435/240.4
• US Class Current: 600/33
• CPC Class Codes: A61B 17/425 for reproduction or fertilisation specially adapted for use with animals A61D19/00
• CPC Class Codes: A61B 17/435 for embryo or ova transplantation
• CPC Class Codes: A61B 50/00 Containers, covers, furniture or holders specially adapted for surgical or diagnostic appliances or instruments, e.g. sterile covers drapes specially adapted for instruments A61B46/10
• CPC Class Codes: A61D 19/022 Containers for animal semen, e.g. pouches or vials A61D19/027 takes precedence; Methods or apparatus for treating or handling animal semen containers, e.g. filling or closing
• CPC Class Codes: A61D 19/04 for embryo transplantation
• CPC Class Codes: C07C 229/64 the carbon skeleton being further substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 233/54 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
• CPC Class Codes: C07C 311/21 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: Y10S 604/906 Artificial insemination

Abstract

An intravaginal fertilization and culture container includes a main chamber and a microchamber. A culture medium, one or more oocytes and sperm are introduced through an access opening having an associated resealable closure device. The container is enveloped in a capsule of soft elastic material prior to lodgment in the posterior fornix. A loop on one capsule part adapts the length to anatomic variations. The microchamber has a channel which receives the catheter tip to facilitate embryo retrieval while eliminating risk of injury thereto. The microchamber permits embryos to be microscopically inspected in situ before transfer to the uterine cavity.

Claims

1. Fertilization and culture container comprising a container body having an orifice for introducing a culture medium, one or more oocytes and sperm and subsequent retrieval of an embryo or embryos with a retrieval catheter, resealable closure means for selectively opening and closing the container body orifice, said container body having a main chamber for receiving the culture medium, oocytes and sperm and a microchamber for collecting for retrieval of one or more embryos, the container body having means for restricting access of a retrieval catheter or pipette relative to the microchamber.

2. Fertilization and culture container according to claim 1, wherein at least a portion of a sidewall of the container body defining said microchamber is transparent and of optical quality for microscopic inspection of embryos.

3. Fertilization and culture container according to claim 1, wherein the means for restricting access of the retrieval catheter or pipette is defined by an inlet port of the microchamber through the main chamber thereby restricting penetration in the microchamber.

4. Fertilization and culture container according to claim 1, wherein the means for restricting access of the retrieval catheter is defined by a channel extending from the main chamber into the microchamber and complementary in configuration to an end portion of a retrieval catheter or pipette to position a catheter or pipette tip spaced from a forward endwall of the microchamber in a fully penetrated position of a catheter or pipette in the container body.

5. Fertilization and culture container according to claim 4, wherein the container body has opposed parallel transparent sidewalls of optical quality extending laterally from said channel.

6. Fertilization and culture container according to claim 5, wherein the width of the microchamber measured between the opposed parallel sidewalls is between about 0.3 and about 0.8 mm.

7. Fertilization and culture container according to claim 6, wherein the average diameter of the forward portion of the catheter channel is between about 2 and about 3 mm.

8. Fertilization and culture container according to claim 1, wherein the volume of the microchamber is less than about 100 μ

l.

9. Fertilization and culture container according to claim 1, wherein the volume of the microchamber is between about 25 μ

l and about 70 μ

l.

10. Fertilization and culture container according to claim 1, wherein the orifice of the container includes means for positioning a catheter or pipette end relative to the main chamber for introducing oocytes or sperm forwardly of the resealable closure means.

11. Fertilization and culture container for intravaginal use according to claim 1, further comprising a soft, pliable capsule for enclosing the container including at least two parts adapted to be slipped over the container from opposite ends thereof, said capsule parts having free edge portions overlappable for sealing the capsule.

12. Intravaginal fertilization and culture container according to claim 11, further comprising a tubular capsule for enveloping the container including at least two parts adapted to be slipped over the container from opposite ends thereof, said capsule parts having overlappable free edge portions for sealing the capsule.

13. Fertilization and culture container according to claim 1, wherein said container is dimensionally configured for intravaginal residence during fertilization and culture.

46. Fertilization and culture container according to claim 1, wherein said resealable closure means comprises a valve member having a passage selectively communicable with said container body orifice, said valve member being rotatable about a transverse axis between open and closed positions.

14. Fertilization and culture container comprising a container body having an orifice for introducing a culture medium, one or more oocytes and sperm, resealable closure means for selectively opening and closing the container body orifice, said container body having a main chamber and a microchamber in communication therewith, the main chamber containing culture medium and being adapted to receive oocytes and sperm, said container having an embryo collection position in which the microchamber is disposed below said main chamber, said culture medium permitting the movement of the one or more embryos in and out of the microchamber and positioning the one or more embryos for retrieval from said container, the microchamber having one or more transparent sidewalls of optical quality for microscopically inspecting one or more embryos in the microchamber.

15. Fertilization and culture container according to claim 14, wherein at least a portion of the container body defining said microchamber has opposed parallel transparent sidewalls of optical quality.

16. Fertilization and culture container according to claim 14, wherein the volume of the microchamber is less than about 100 μ

l.

17. Fertilization and culture container according to claim 14, wherein the volume of the microchamber is between about 25 μ

l and about 70 μ

l.

18. Fertilization and culture container according to claim 15, wherein the width of the microchamber determined between the opposed parallel sidewalls is between about 0.3 and about 0.8 mm.

19. Fertilization and culture container according to claim 14, wherein he orifice of the container includes means for positioning a pipette relative to the main chamber for introducing oocytes or sperm forwardly of the resealable closure means.

20. Fertilization and culture container according to claim 14, wherein said resealable closure means comprises a valve member having a passage selectively communicable with said container body orifice, said valve member being rotatable about a transverse axis between open and closed positions.

21. Fertilization and culture container according to claim 14, wherein said container is dimensionally configured for intravaginal residence during fertilization and culture.

22. Fertilization and culture container according to claim 14, wherein said main has an internal volume of about 1 ml and about 5 ml, and the microchamber has an internal volume less than 100 μ

l, the microchamber having a maximum internal transverse dimension substantially smaller than a maximum transverse dimension of the main chamber.

23. Fertilization and culture container comprising a container body having an orifice for introducing culture medium, one or more oocytes and sperm, resealable closure means for selectively opening and closing the container body orifice, said container body having a main chamber and a microchamber in communication with the main chamber, the main chamber containing culture medium and and adapted to receive oocytes and sperm and having an internal volume between about 1 ml and about 5 ml and the microchamber having an internal volume of less than 100 μ

l and adapted to collect one or more embryos for retrieval, a free access zone being defined between the main chamber and the microchamber for the passage of the culture medium, and, after fertilization, the one or more embryos, said culture medium permitting movement of the one or more embryos in and out of the microchamber and positioning the one or more embryos for retrieval for embryo retrieval position.

24. Fertilization and culture container according to claim 23, wherein said microchamber is defined by sidewalls, at least a portion of said sidewalls is transparent and of optical quality for microscopically inspecting embryos.

25. Fertilization and culture container according to claim 23, wherein the width of the microchamber determined between the opposed sidewalls is between about 0.3 and about 0.8 mm.

26. Intravaginal fertilization and culture container according to claim 23, further comprising a tubular capsule of soft elastic material having a smooth and continuous outer surface, opposed rounded ends and a tubular body portion of substantially cylindrical configuration, said microchamber having an external configuration, said capsule having an internal compartment complementary to the external configuration of the microchamber for mating therewith at a thickened end of the capsule.

27. Intravaginal fertilization and culture container assembly according to claim 26, wherein the soft elastic material comprises a silicone composition.

28. Fertilization and culture container according to claim 23, wherein said resealable closure means comprises a valve member having a passage selectively communicable with said container body orifice, said valve member being rotatable about a transverse axis between open and closed positions.

29. Fertilization and culture container according to claim 23, wherein said container is dimensionally configured for intravaginal residence during fertilization and culture.

30. Intravaginal fertilization and culture container assembly comprising a container body having an orifice for introducing a culture medium, one or more oocytes and sperm, resealable closure means for selectively opening and closing the container body orifice, said container body having a main chamber and a microchamber in communication therewith, said microchamber having an external configuration, the microchamber having an outer surface defining an external protruding portion from an end of the main chamber and having external dimensions very substantially less than those of the main chamber, and a tubular capsule for entirely enveloping the container, said capusle being made of soft elastic material having a smooth and continuous outer surface, said capsule also having opposed rounded ends and a tubular body portion of substantially cylindrical configuration between the rounded ends, said capsule also having an internal compartment complementary to the external configuration of the microchamber for mating therewith at a thickened end of the capsule.

31. Intravaginal fertilization and culture container assembly according to claim 30, wherein said soft elastic material defines aseptic barrier means to prevent the tunneling of bacteria and viruses present in the vaginal cavity with the container body and reduce the risk of contamination of embryos when opening the container.

32. Intravaginal fertilization and culture container assembly according to claim 30, further comprising a tie attached to the capsule, for facilitating removal of the assembly from the posterior fornix.

33. Intravaginal fertilization and culture container assembly comprising a container body having an orifice for introducing a culture medium, one or more oocytes and sperm, resealable closure means for selectively opening and closing the container body orifice, said container body having a chamber for fertilizing oocytes and retrieving an embryo or embryos therefrom for implantation, and a tubular capsule for enveloping the container, said capsule being made of soft elastic material having a smooth and continuous outer surface, a deformable cushioning means disposed proximate an end of said capsule for adapting the longitudinal dimensions of the assembly to a chordal dimension of the posterior fornix when the container assembly is received therein.

34. Intravaginal fertilization and culture container assembly according to claim 33, wherein said capsule comprises at least two capsule parts, each of said capsule parts having an open end positioned adjacent each other when the capsules parts are received on the container, relative positions of free edges of said at least two capsule parts being adjustable to modify the overall length of the assembly.

35. Intravaginal fertilization and culture container assembly comprising a container body having an orifice for introducing a culture medium, one or more oocytes and sperm, resealable closure means for selectively opening and closing the container body orifice, said container body defining a main chamber and a microchamber in communication therewith, and a tubular capsule for enveloping the container, said capsule being made of soft elastic material having a smooth and continuous outer surface, said capsule also having opposed rounded ends and a tubular body portion of substantially cylindrical configuration between the rounded ends, said capsule comprising at least two parts, one of said parts having an inwardly extending central plug adapted to be received in and seal off said orifice when said capsule envelopes said container.

36. A method of fertilization and culture comprising the steps of:

providing a fertilization and culture container having an orifice and a main chamber for fertilization and culture and the microchamber for inspection and retrieval of one or more embryos, and resealable closure means for selectively opening and closing the orifice;

filling the container with the culture medium and introducing one or more oocytes and sperm into the culture medium, and thereafter closing the orifice;

incubating the closed container for 48 to 72 hours to allow fertilization and culture of the oocytes;

allowing migration of the resulting embryo or embryos into the microchamber;

microscopically inspecting the embryo or embryos in the microchamber; and

retrieving one or more embryos from the microchamber with a catheter and transferring one or more embryos from the catheter to the uterine cavity.

37. A method of fertilization and culture according to claim 36, wherein migration of the resulting embryo or embryos is assisted by orienting the container so that the microchamber is disposed below the main chamber.

38. A method of intravaginal fertilization and culture according to claim 36, further comprising the step of enveloping the container in a soft flexible capsule prior to vaginal incubation.

39. A method of intravaginal fertilization and culture according to claim 36, further comprising the step of gently elastically holding the container and capsule chordally in the posterior fornix during incubation.

40. A method of intravaginal fertilization and culture according to claim 38, further comprising the step of attaching a string to the capsule for facilitating retrieval of the container from the posterior fornix.

41. A method of fertilization and culture according to claim 36, further comprising the step of restricting access of the catheter into the microchamber and orienting the container so that the channel is disposed above the rest of the microchamber before introducing the catheter into the channel.

42. A method of fertilization and culture according to claim 36, further comprising the step of limiting the penetration of the free end of the catheter into the channel so as to accommodate at least five embryos between the free end of the catheter and the forward endwall of the microchamber.

43. A method of intravaginal fertilization and culture according to claim 36, further comprising the step of providing the container with an access passageway upstream of the resealable closure means and sealingly plugging the access passageway by encapsulation of the container.

44. A method of fertilization and culture according to claim 36, further comprising the step of heating the closed container for about one hour at about 37°

C. in an incubator prior to intravaginal incubation.

45. A method according to claim 36, wherein the step of incubating the closed container includes introducing the closed container into a vagina for vaginal residence for 48 to 72 hours.

47. Apparatus for fertilization and culture of oocytes and retrieval of embryos comprising a container having a body with an orifice for introducing a culture medium, one or more oocytes and sperm, resealable closure means for selectively opening and closing the container body orifice, said container body having a main chamber and a microchamber in communication therewith, the container body containing culture medium and being adapted to receive oocytes and sperm, said container having an embryo collection position in which the microchamber is disposed below said main chamber, said culture medium permitting the movement of the one or more embryos in and out of the microchamber and positioning the one or more embryos for retrieval from said container, said apparatus further comprising means for retrieving from the microchamber the one or more embryos in said culture medium, said microchamber having one or more transparent zones for viewing the one or more embryos therein.

48. Apparatus for fertilization and culture oocytes and retrieval of embryos comprising a container having a body with an orifice for introducing culture medium, one or more oocytes and sperm, resealable closure means for selectively opening and closing the container body orifice, said container body having a main chamber and a microchamber in communication with the main chamber, the container body containing culture medium and being adapted to receive oocytes and sperm, and said main chamber having an internal volume between about 1 ml and about 5 ml and the microchamber having an internal volume of less than 100 μ

l and adapted to collect one or more embryos for retrieval, a free access zone being defined between the main chamber and the microchamber for the passage of the culture medium and, after fertilization, the one or more embryos, said culture medium permitting movement of the one or more embryos in and out of the microchamber and positioning the one or more embryos for retrieval for embryo retrieval position, said apparatus further comprising means for retrieving from the microchamber the one or more embryos in said culture medium.