Patent Description:
Assisted reproductive technologies, including in vitro fertilization (hereinafter "IVF"), are commonly utilized by those suffering infertility. Historically, embryos have been cultured in Petri dishes. The embryos housed in these Petri dishes are maintained in embryonic culture media, which is then overlaid with mineral oil. The Petri dishes are placed in laboratory incubators which maintain the temperature of the embryonic culture media and embryos. The incubators are set at <NUM>° C, and the incubators are filled with a premixed gas comprising approximately <NUM>% Oxygen and <NUM>% Carbon Dioxide. This specific temperature and gas concentration enables an adequate pH of the culture media to be maintained, and is designed to simulate the in vivo conditions thought to be required for early embryonic development.

Attempts have been made to create an in vivo culture system that would allow human embryos to develop within the female body, specifically within the vaginal canal. The conditions inside the vaginal canal are similar to the natural environment for embryonic development (e.g. within the uterus). Intravaginal Culture (hereinafter "IVC") permits the embryos to develop in advanced contemporary culture media that supports embryo development to day <NUM>, which is the blastocyst stage.

As IVC devices are housed within the patient's vagina, the embryos will develop at a temperature that is unique to that specific patient, and will be exposed to the normal temperature variations of the human body. Rather than culturing embryos statically in an IVF incubator in the lab, women with IVC devices are mobile for the entire <NUM> days of culture and development. The conditions to which the IVC devices are exposed mimic the in utero condition of embryonic development, rather than the static conditions of a laboratory incubator. The costs associated with IVC devices are typically less than traditional in incubator culturing. Additionally, there is an emotional component where a woman feels more involved with the development of their embryo(s) when the embryo cultures internal to her body, rather than in a laboratory.

<CIT> and <CIT> teach of exemplary IVC devices of the prior art. The product embodying the teachings of <CIT> is sold commercially under the trade name INVOCELL®. The INVOCELL® device is believed to be the only IVC device that is presently commercially available. At least one study has shown that embryo quality and pregnancy rates with the INVOCELL® device are equivalent to conventional IVF.

However, there are numerous drawbacks to the IVC devices of the prior art, including the INVOCELL® device. For the INVOCELL® device to function properly, a high CO<NUM> gas concentration is required in a buffer chamber. This buffer chamber substantially surrounds an inner vessel which contains the gametes/embryos and culture medium. The CO<NUM> enriched atmosphere contained in the buffer chamber diffuses through the wall of the inner vessel to maintain an adequate pH within the buffer chamber. The INVOCELL® device must be assembled in an IVF chamber to provide the high CO<NUM> atmosphere in the buffer chamber. The high economic cost of IVF chambers prevents many practitioners from having ready access to IVF chambers; therefore, few practitioners are able to utilize the INVOCELL® device. This high economic cost has proven prohibitive to the adoption of the INVOCELL® device in fertility clinics.

Moreover, the conical shape of the inner vessel of the INVOCELL® device places the embryos at great risk of wide temperature fluctuations when the device is removed from the vagina, prior to embryo removal for eventual embryo transfer. The human body temperature is <NUM>, and the typical laboratory temperature is about <NUM>-<NUM>. The temperature of the media and the embryos housed within the conical inner vessel will drop significantly within minutes due to large surface area provided by the conical shape of the inner vessel. Temperature is extremely important in oocyte/embryo culture and development.

In order to reduce the rapid heat loss when the embryos are removed, the INVOCELL® device utilizes a heating block. This heating block is warmed in an incubator for several hours prior to use, and is then placed on a microscope stage, with the inner vessel of the INVOCELL® device plugged into the side. Once inserted into the heating block, a lab technician can then look through a small opening to identify the gametes and/or embryos to be removed. This process is cumbersome and time consuming. The heating block adds economic cost to the use of the INVOCELL® device.

The INVOCELL® device includes a sealed, non-gas permeable outer container to prevent the egress of CO<NUM> from the buffer chamber into the vagina. An upper cap is utilized to seal the inner vessel of the INVOCELL® device. This cap includes a tiny hole that requires a small flexible pipette to be introduced in order to place or remove gametes or embryos. The embryos are typically found to be lodged into the far tip of the conical inner vessel, so the pipette has to bend in order to remove them easily. This is a very time consuming process, and embryos can be damaged.

The commercially available INVOCELL® device includes a seam along the bottom edge where the embryos tend to sit. When the embryos are removed toward day <NUM> of incubation, small portions of this ridged seam have been found to separate and appear as debris into the culture medium. This debris may be detrimental to the development of the embryos. In rare instances, this debris has been observed to puncture the embryos/oocytes.

<CIT> discloses an intravaginal culture container comprising a container body for the culture of one or more embryos in a culture medium, the container body being sized and configured for intravaginal accommodation, a resealable closure for the container body, the resealable closure permitting selective access to the interior of the container body, the container body interior including a main chamber and a microchamber in communication with the main chamber, the microchamber being configured for collecting and retrieval of the one or more embryos.

<CIT> describes a container assembly comprising a vessel for containing a biological medium, gametes and one or more embryo(s), the vessel having a CO2 permeable wall, a closure device for selective access to the interior of the vessel, and a buffer chamber for a CO2 enriched atmosphere cooperable with the vessel and in communication with the CO2 permeable wall, the buffer chamber having an open position for communication with a CO2 enriched atmosphere and a closed condition for closing off the buffer chamber from the surroundings.

Therefore, further technological developments are desirable.

The present invention concerns an intravaginal culture apparatus comprising the feaures defined in independent claim <NUM>.

It is an object to obviate or at least diminish one or more of the drawbacks mentioned above.

According to an aspect is provided an intravaginal culture apparatus. The intravaginal culture apparatus comprises an outer container configured for insertion into a vaginal canal. The intravaginal culture apparatus comprises a receiving cavity located internal to the outer container. An inner vessel is received in the receiving cavity. The inner vessel includes an interior chamber configured to house at least one of a gamete and an embryo. The intravaginal culture apparatus is devoid of a CO<NUM> enriched buffer chamber. As the intravaginal culture apparatus is free from a CO<NUM> enriched buffer chamber, i.e. does not include a CO<NUM> enriched buffer chamber, an IVF chamber is not required to load the intravaginal culture apparatus.

Optionally, the outer container includes an upper portion configured to sealingly engage with a lower portion. Preferably, the receiving cavity is located in the upper portion. Optionally, the upper portion removably couples with the lower portion through a threaded connection. Optionally, an interference seal is formed between the upper portion and the lower portion when in a closed configuration, and the outer container is configured to prevent the ingress of vaginal liquids when in the closed configuration.

Optionally, the intravaginal culture apparatus includes a second receiving cavity located in the lower portion. A second inner vessel can be received in the second receiving cavity. The second inner vessel can include a second interior chamber configured to house at least one of a gamete and an embryo. Thus a first inner vessel can be housed in a first receiving cavity located in the upper portion and a second inner vessel can be housed in a second receiving cavity located in the lower portion. The first inner vessel can include a first interior chamber configured to house at least one of a gamete and an embryo. The first inner vessel is preferably identical to the second inner vessel.

The (first) inner vessel can be configured to house a first plurality of embryos. The second inner vessel can be configured to house a second plurality of embryos.

Optionally, the (first) inner vessel is removably received in the upper portion and/or the second inner vessel is removably received in the lower portion.

Optionally, the (first) inner vessel and the second inner vessel each include a base and a removable lid configured to sealingly engage with the base. Optionally, the lid sealingly engages with the base through a threaded connection. The lid can be formed of a polymer.

Optionally, the outer container, the (first) inner vessel, and optionally the second inner vessel each include a gas permeable portion configured to permit the passage of CO<NUM> between the vaginal canal and the first and optionally the second interior chambers.

Optionally, the outer container, the (first) inner vessel, and optionally the second inner vessel are formed of a CO<NUM> permeable polymer, such as polystyrene, preferably crystal polystyrene. Such a crystal polystyrene construction is CO<NUM> permeable, and can be transparent.

Optionally, the receiving cavity further includes an internal fillet.

Optionally, the (first) inner vessel and optionally the second inner vessel are configured to be received in a well of a <NUM>-well laboratory dish.

According to an aspect is provided an intravaginal culture apparatus. This intravaginal culture apparatus includes an outer housing configured for vaginal insertion. The outer housing includes an upper portion and a lower portion. The upper portion removably couples with the lower portion. A first inner vessel is located at the upper portion, and the first inner vessel is configured to house a first plurality of embryos. A second inner vessel is located at the lower portion, and the second inner vessel is configured to house a second plurality of embryos.

The first inner vessel can be removably received in the upper portion, and the second inner vessel can be removably received in the lower portion. The first inner vessel and the second inner vessel can each include a base and a removable lid configured to sealingly engage with the base. The lid can be formed of a polymer.

Preferably, the outer housing and the base are CO<NUM> permeable. The outer housing and the base can be formed of crystal polystyrene. The upper portion can removably couple with the lower portion through a threaded connection. The intravaginal culture apparatus is preferably devoid of a CO<NUM> enriched buffer chamber. As such, an IVF chamber is not required to load the intravaginal culture apparatus.

According to an aspect is provided an apparatus which includes an outer vessel configured for insertion into a vaginal canal. The outer vessel includes an upper portion configured to sealingly engage with a lower portion. A first inner vessel defines a first receiving chamber, and the first inner vessel is removably received in the upper portion. A second inner vessel defines a second receiving chamber, and the second inner vessel is removably received in the lower portion. The first receiving chamber and the second receiving chamber are each configured to house a culture medium and at least one of a gamete and an embryo.

The outer vessel, the first inner vessel, and the second inner vessel preferably each include a gas permeable portion. The gas permeable portion permits the passage of CO<NUM> between the vaginal canal and the first receiving chamber, and permits the passage of CO<NUM> between the vaginal canal and the second receiving chamber. The outer vessel, the first inner vessel, and the second inner vessel are preferably formed of crystal polystyrene. Such a crystal polystyrene construction is CO<NUM> permeable, and can be transparent.

A first lid can be removably coupled to the first vessel to selectively provide access to the first receiving chamber. A second lid can be removably coupled to the second vessel to selectively provide access to the second receiving chamber. The first receiving chamber can include an internal fillet. Preferably, a base of the first inner vessel can be configured to be received in a well of a <NUM>-well laboratory dish.

The upper portion can threadingly engage with the lower portion. An interference seal can be formed between the upper portion and the lower portion when in a closed configuration to prevent the ingress of vaginal liquids into the outer vessel when the outer vessel is in the closed configuration.

It will be appreciated that all features and options mentioned in view of the first aspect apply equally to the other aspects, and vice versa. It will also be clear that any one or more of the above aspects, features and options can be combined.

Other embodiments include unique intravaginal culture apparatuses, systems, and methods. Further embodiments, inventions, forms, objects, features, advantages, aspects, and benefits of the present application are otherwise set forth or become apparent from the description and drawings included herein.

The description herein makes reference to the accompanying drawings wherein like reference numerals refer to like parts throughout the several views, and wherein:.

Referring now to <FIG>, an exemplary intravaginal culture device <NUM> will now be described. The intravaginal culture device <NUM> includes an outer vessel <NUM> and a first inner vessel <NUM>. The first inner vessel <NUM> is removably contained within an interior cavity <NUM> of the outer vessel <NUM>. The first inner vessel <NUM> is configured to house embryos and/or gametes and a suitable culture medium.

A second inner vessel <NUM> can also be contained within the interior cavity <NUM> of the outer vessel <NUM>. The second inner vessel <NUM> is configured to house embryos and/or gametes, similar to the first inner vessel <NUM>. It is contemplated that one or both of the first inner vessel <NUM> and the second inner vessel <NUM> can be inserted into the outer vessel <NUM>, depending upon the specific application as well as the number of embryos and/or gametes to be cultured.

The outer vessel <NUM> will be inserted into the vaginal canal of a patient, and will be retained within the vaginal canal for the duration of the desired culture period. A typical culture period can approximate <NUM> days for embryonic development to the blastocyst stage; however, it is contemplated that the embryos and/or gametes can be cultured within the intravaginal culture device <NUM> for various durations to achieve the culture period desired by a fertility provider.

The outer vessel <NUM> includes an upper portion <NUM> and a lower portion <NUM>. The upper portion <NUM> removably couples with the lower portion <NUM>. The upper portion <NUM> is depicted as being selectively coupled to the lower portion <NUM> through a closure mechanism <NUM>. In one preferred, non-limiting form the closure mechanism <NUM> is a twist-lock mechanism <NUM>.

In this example, the twist-lock mechanism <NUM> includes tab engaging members <NUM> which cooperate with outwardly extending tabs <NUM>. The tabs <NUM> extend outwardly from the lower portion <NUM>. The tabs <NUM> are located near an upper rim <NUM> of the lower portion <NUM>.

The upper portion <NUM> includes a plurality of tab engaging members <NUM>. These tab engaging members <NUM> are located near a lower rim <NUM> of the upper portion <NUM>. Each tab engaging member <NUM> includes a substantially vertically extending tab receiving opening <NUM> and a horizontally extending channel <NUM>.

To close the outer vessel <NUM>, each tab <NUM> of the lower portion <NUM> is aligned with and inserted into a vertically extending tab receiving opening <NUM> of the upper portion <NUM>. Once the tabs <NUM> are fully inserted into the tab receiving openings <NUM>, the upper portion <NUM> can then be rotated relative the lower portion <NUM>, with the tabs <NUM> moving along the horizontally extending channels <NUM>. Once the tabs <NUM> are located in the horizontally extending channels <NUM>, a lower surface <NUM> of the tabs <NUM> abuts a lower surface <NUM> of the horizontally extending channels <NUM>. This closed configuration <NUM> of the outer vessel <NUM> is depicted in <FIG>.

The twist-lock mechanism <NUM> can additionally include an interference-type fit (not shown), or other locking-type mechanism, to further prevent the upper portion <NUM> from separating from the lower portion <NUM>. In further forms, it is contemplated that the closure mechanism <NUM> can take the form of a press-lock mechanism, a screw-type threaded mechanism, or other closure mechanism <NUM> which can securely retain the upper portion <NUM> and lower portion <NUM> together.

A sealing member <NUM> can be located between the upper portion <NUM> and the lower portion <NUM>. This sealing member <NUM> will contact the upper portion <NUM> and the lower portion <NUM> when the outer vessel <NUM> is in a closed configuration <NUM>. The sealing member <NUM> prevents the ingress of liquids through an interface <NUM> between the upper portion <NUM> and the lower portion <NUM>.

The sealing member <NUM> can take the form of an, e.g. silicone, o-ring; however, it is also contemplated that the sealing member <NUM> can be formed of a variety of biocompatible polymers, biocompatible rubbers, etc. to prevent the ingress of vaginal fluids through the interface <NUM>. The sealing member <NUM> can be disposed at a variety of locations within the upper portion <NUM> and the lower portion <NUM> such that the sealing member <NUM> will contact both the upper portion <NUM> and the lower portion <NUM> when the outer vessel <NUM> is placed in a closed configuration <NUM>. When in this closed configuration <NUM>, the outer vessel <NUM> is a liquid sealed enclosure, which prevents the ingress of liquids (e.g. vaginal fluids) into the interior cavity <NUM>.

As is illustrated in <FIG>, the outer vessel <NUM> can take the form of a substantially spherocylindrical, capsule-type shape <NUM>. The upper portion <NUM> can include a substantially hemispherical top <NUM>, and the lower portion <NUM> can include a substantially hemispherical bottom <NUM>. The mid-section <NUM> of the outer vessel <NUM> is depicted as having a cylindrical form <NUM>. Although it is contemplated that the outer vessel <NUM> can take other forms, the hemispherical bottom <NUM> and hemispherical top <NUM> are believed to ease the insertion and the removal of the outer vessel <NUM> from the vaginal canal of a patient, and are believed to increase patient comfort during use.

Referring now to <FIG> and <FIG>, a first form of an example of the first inner vessel <NUM> and the second inner vessel <NUM> will be described. The inner vessels <NUM> and <NUM> are each structured to contain embryos and/or gametes, as well as a suitable culture medium. In one non-limiting form, it is contemplated that each inner vessel <NUM>, <NUM> can house between one and ten embryos. As is illustrated, the first inner vessel <NUM> and the second inner vessel <NUM> are preferably identical, and therefore interchangeable. As such, the inner vessel <NUM> will be described hereinafter, with inner vessel <NUM> including identical features.

The inner vessel <NUM> includes a base <NUM> which sealingly engages with a lid <NUM>. The base <NUM> includes a sidewall <NUM> which extends between a closed lower portion <NUM> and an open upper portion <NUM>. A receiving chamber <NUM> is accessed via the open upper portion <NUM>. The base <NUM> can include a substantially cylindrical shape <NUM>. The base <NUM> can include a rounded lower edge <NUM>.

An inner lower edge <NUM> is located where the sidewall <NUM> abuts the closed lower portion <NUM>. This inner lower edge <NUM> preferably includes a fillet <NUM>. This fillet <NUM> directs the gametes and/or embryos stored within the receiving chamber <NUM> toward the center <NUM> of a lower surface <NUM> of the receiving chamber <NUM> when the base is placed in an upright orientation <NUM>, as shown in <FIG>. It is believed that this fillet <NUM> can ease the extraction of the gametes and/or embryos from the receiving chamber <NUM>, as there is not a sharp transition for the gametes and/or embryos to be "trapped" in. The lower surface <NUM> of the receiving chamber <NUM> preferably includes a smooth design, which is free from any seams or other potentially sharp and/or debris introducing surfaces.

Referring now to <FIG>, and <FIG>, the base <NUM> of the inner vessel <NUM> is sealingly closed with a lid <NUM>. The lid <NUM> is removably coupled to the base <NUM> through a closure mechanism <NUM>. In this example, this closure mechanism <NUM> is depicted as taking the form of a twist-lock mechanism <NUM>. The twist-lock mechanism <NUM>, e.g., takes a similar form as twist-lock mechanism <NUM>.

The twist-lock mechanism <NUM> includes a plurality of outwardly extending tabs <NUM> and a plurality of tab engaging members <NUM>. The outwardly extending tabs <NUM> are located near the upper portion <NUM> of the base <NUM>. The tab engaging members <NUM> are located in the lid <NUM>. Each tab engaging member <NUM> is depicted as including a vertically extending opening <NUM> and a horizontally extending channel <NUM>.

To attach the lid <NUM> to the base <NUM>, the tabs <NUM> are aligned with the openings <NUM> and the tabs <NUM> are pushed upwardly into the openings <NUM>, as shown at <NUM>. The lid <NUM> is then rotated with the tabs <NUM> cooperating with and extending along the horizontally extending channels <NUM>. The inner vessel <NUM> is then in a fully closed configuration <NUM>. In this closed configuration <NUM>, the inner vessel <NUM> is a liquid sealed enclosure that confines the culture medium and embryos within the receiving chamber <NUM>.

A sealing member (not shown) can be located at an interface of the base <NUM> and the lid <NUM>. This sealing member can take the form of an, e.g. silicone, o-ring located on a lower surface <NUM> of the lid <NUM>. In this manner, the sealing member will contact an upper rim <NUM> of the base <NUM> when the inner vessel <NUM> is in a closed configuration <NUM>.

The sealing member (not shown) can alternatively be formed of a variety of biocompatible polymers, biocompatible rubbers, or the like. Alternatively, the sealing member can be located on the upper rim <NUM> of the base <NUM>, or at any other suitable location whereby the sealing member will contact the base <NUM> and the lid <NUM> when the inner vessel <NUM> is in the closed configuration <NUM>.

Referring back to <FIG>, the first inner vessel <NUM> can be housed in the upper portion <NUM> and the second inner vessel <NUM> can be housed in the lower portion <NUM>. As was previously described, in this example the first inner vessel <NUM> and the second inner vessel <NUM> are identical and interchangeable; therefore, the first inner vessel <NUM> can be housed in the lower portion <NUM> and the first inner vessel <NUM> can be housed in the upper portion <NUM>. In this manner, a total of two internal vessels <NUM>, <NUM> can be housed within the outer vessel <NUM>.

The upper portion <NUM> of the outer vessel <NUM> includes a first receiving cavity <NUM>. A second receiving cavity <NUM> is located within the lower portion <NUM>. Each receiving cavity <NUM>, <NUM> houses a lower portion <NUM> of an inner vessel <NUM> therein. As such, the internal diameters <NUM>, <NUM> of the receiving cavities <NUM>,<NUM> are slightly larger than an external diameter <NUM> of the base <NUM> of the inner vessels <NUM>, <NUM>. Each receiving cavity <NUM>, <NUM> can include an internal fillet <NUM> configured to cooperate with the rounded lower edge <NUM> of the base <NUM>.

The receiving cavity <NUM> of the lower portion <NUM> is depicted as including a lip <NUM>. When the lower portion <NUM> of the inner vessel <NUM> is fully inserted into the receiving cavity <NUM>, a lower rim <NUM> of the lid <NUM> can rest upon the lip <NUM>. The receiving cavity <NUM> is depicted as including lip <NUM> upon which the lower rim <NUM> of the lid <NUM> of the inner vessel <NUM> can rest.

The lower portion <NUM> can include an enlarged inner diameter <NUM> located toward the rim <NUM>. The inner diameter <NUM> is depicted as being larger than the diameter <NUM>, to accommodate the lid <NUM> of the inner vessel <NUM>. The upper portion <NUM> can also include an enlarged inner diameter located toward lower rim <NUM> to accommodate a lid <NUM>.

In one preferable, non-limiting form, an external diameter <NUM> of the base <NUM> of the inner vessel <NUM> approximates an internal diameter of a <NUM>-well dish, as are standard in IVF labs in the United States. The external diameter <NUM> of the base <NUM> is for example slightly less than <NUM>, <NUM> being the internal diameter of each well of the <NUM>-well dish. Use of such a <NUM>-well dish can enable ease of handling of the inner vessels <NUM>, <NUM>, and significantly reduces the likelihood of spillage from the inner vessels <NUM>, <NUM>.

Another potential advantage of having the base <NUM> fit into a <NUM>-well dish is that such a configuration will have a flat bottom surface, which can then be placed upon a warmed microscope stage, as are common in IVF laboratories. The constant contact of the <NUM>-well dish with the microscope stage will permit the transfer of heat from the microscope stage, through the <NUM>-well dish, and into the base <NUM>. It has been discovered that the ability to utilize a warmed microscope stage can eliminate the necessity to purchase a large metal heating block, as are commonly utilized with intravaginal culture devices of the prior art.

Referring back to <FIG>, the upper portion <NUM> and the lower portion <NUM> of the outer vessel include gas permeable portions <NUM>, <NUM>, respectively. These gas permeable portions <NUM>, <NUM> permit the passage of CO<NUM> therethrough. Preferably, the upper portion <NUM> and the lower portion <NUM> are constructed of a gas permeable material <NUM>, thereby providing a large surface area for CO<NUM> to permeate through. In one non-limiting form, the gas permeable material <NUM> is medical grade general purpose polystyrene GPPS; however, it is contemplated that other gas permeable polymers could also be utilized. The gas permeable material <NUM> enables the passage of CO<NUM> between the vaginal canal and the interior cavity <NUM> of the outer vessel <NUM>.

As shown in <FIG>, the inner vessels <NUM>, <NUM> include gas permeable portion <NUM>. The gas permeable portion <NUM> enables the passage of CO<NUM> therethrough. Preferably, the base <NUM> can be constructed of a CO<NUM> gas permeable material <NUM>. Such a construction provides a large surface area for CO<NUM> to permeate from the interior cavity <NUM> into and out of the receiving chamber <NUM>. One exemplary gas permeable material <NUM> is medical grade general purpose polystyrene GPPS; however, the use of other CO<NUM> permeable polymers is contemplated herein.

The gas permeable portions <NUM>, <NUM> and <NUM> enable the passage of CO<NUM> between the vaginal canal and the receiving chamber <NUM>, in which the embryos and/or gametes are contained. The gas permeable construction of the outer vessel <NUM> and inner vessels <NUM>, <NUM> permits passage of CO<NUM> between the vaginal canal and the receiving chamber <NUM>. As such, a CO<NUM> concentration within the receiving chamber <NUM> will reach equilibrium with a CO<NUM> concentration of the vaginal canal, thereby subjecting the embryos and/or gametes housed within the receiving chamber <NUM> to the natural conditions of embryonic development.

Additionally, the free permeation of CO<NUM> between the receiving chamber <NUM> and the vaginal canal will regulate the pH of the culture medium contained within the receiving chamber <NUM>. As is known to a person of skill in the art, the concentration of CO<NUM> present within the culture medium affects the pH of the culture medium. The free permeation of CO<NUM> between the receiving chamber <NUM> and the vagina will provide a suitable pH for embryonic development within the receiving chamber <NUM>, assuming the vagina of the patient has a suitable pH for embryonic development.

It has been discovered that the CO<NUM> permeable construction of the outer vessel <NUM> and inner vessels <NUM>, <NUM> eliminates the need for a CO<NUM> enriched buffer chamber from the intravaginal culture device <NUM> (e.g. the CO<NUM> in the enriched buffer chamber would merely permeate out of intravaginal culture device <NUM> into the vagina). As the intravaginal culture device <NUM> is devoid of a CO<NUM> enriched buffer chamber, a standard IVF incubator may be utilized to prepare the culture medium to be inserted into the present intravaginal culture device <NUM>. This has been discovered to be highly advantageous as the present intravaginal culture device <NUM> does not require a costly IVF chamber to load.

Construction of the outer vessel <NUM> and inner vessels <NUM>, <NUM> from general purpose polystyrene GPPS, which is a crystal polystyrene, can additionally be advantageous as such a construction can be transparent. The ability to see within the inner vessels <NUM>, <NUM> without opening the lid <NUM> can reduce temperature fluctuations within the receiving chamber <NUM>.

Referring now to <FIG>, an alternative inner vessel <NUM>, <NUM> construction will now be described. The inner vessels <NUM>, <NUM> are depicted as being placed in a <NUM>-well dish <NUM>, as was previously described with inner vessels <NUM>, <NUM>. The inner vessels <NUM>, <NUM> include a substantially cylindrical shape <NUM>. The inner vessels <NUM>, <NUM> can include an outer diameter <NUM> of approximately <NUM>, which is approximately the internal diameter <NUM> of each well <NUM> of the <NUM>-well dish <NUM>.

A primary difference between inner vessels <NUM>, <NUM> and inner vessels <NUM>,<NUM> is the closure mechanism. While inner vessels <NUM>, <NUM> included a twist-lock closure mechanism <NUM>, inner vessels <NUM>, <NUM> are depicted as closing through a press-lock closure mechanism.

As in this example the inner vessels <NUM> and <NUM> are identical and interchangeable, only the closure mechanism of the first inner vessel <NUM> will be described. A base <NUM> of the inner vessel <NUM> is depicted as including an outwardly extending lip <NUM>. A lid <NUM> includes an inwardly extending lip receiving channel <NUM>. When the lid <NUM> is depressed onto the base <NUM>, the outwardly extending lip <NUM> is forced into the lip receiving channel <NUM> which securely receives and retains the outwardly extending lip <NUM> therein, thereby removably coupling the lid <NUM> onto the base <NUM>. A sealing member <NUM> can be located on an interior surface <NUM> of the lid <NUM> to sealingly contact with the base <NUM>; thereby preventing the egress of culture medium from the inner vessel <NUM>. However, it is also contemplated that the lid <NUM> can securely fasten to the base <NUM> through a threaded screw-on type closure mechanism.

Referring now to <FIG>, another form of an intravaginal culture device <NUM> will now be described. The intravaginal culture device <NUM> includes an outer container <NUM>. The outer container <NUM> includes an upper portion <NUM> and a lower portion <NUM>. The upper portion <NUM> is configured to removably attach to the lower portion <NUM>. The outer container <NUM> is depicted in a closed configuration <NUM> in <FIG>, in which the upper portion <NUM> is securely attached to the lower portion <NUM>.

The outer container <NUM> extends between an upper surface <NUM> and a lower surface <NUM>. The upper surface <NUM> is depicted as including a flattened surface <NUM>, and the lower surface <NUM> is depicted as including a flattened surface <NUM>. The flattened surfaces <NUM> and <NUM> enable the outer container <NUM> to remain upright when placed on a flat surface, such as a laboratory table. When the upper portion <NUM> is detached from the lower portion <NUM>, the upper portion <NUM> can be stood upright upon the flattened surface <NUM> and the lower portion <NUM> can be stood upright upon the flattened surface <NUM>.

The outer container <NUM> is structured to be inserted into the vaginal canal of a patient, and will remain in the vaginal canal for a period of several days. To provide for ease of insertion and to maximize patient comfort, the outer container <NUM> is devoid of sharp edges. Transitional areas <NUM> and <NUM> of the outer container <NUM> are rounded and smooth. Portions <NUM> of the outer container <NUM> can have a substantially cylindrical form.

<FIG> depicts a sectional view of the intravaginal culture device <NUM>. In this example, the upper portion <NUM> is removably attached to the lower portion <NUM> through a threaded connection <NUM>. As is illustrated, the upper portion <NUM> of the outer container <NUM> includes an outward flare <NUM>. A vertically oriented sidewall <NUM> extends downwardly from the outward flare <NUM>. An inner surface <NUM> of the vertically oriented sidewall <NUM> includes internal threads <NUM>.

The lower portion <NUM> of the outer container <NUM> is depicted as including an outward flare <NUM>. A vertically oriented sidewall <NUM> extends upwardly from the outward flare <NUM>. An outer surface <NUM> of the vertically oriented sidewall <NUM> includes external threads <NUM>.

The external threads <NUM> of the lower portion <NUM> threadingly engage with the internal threads <NUM> of the upper portion <NUM> to removably couple the upper portion <NUM> and the lower portion <NUM>. To close the outer container <NUM>, the external threads <NUM> are aligned with the internal threads <NUM> and the lower portion <NUM> is rotated relative the upper portion <NUM>, thereby screwing the lower portion <NUM> into the upper portion <NUM>.

The upper portion <NUM> sealingly engages with the lower portion <NUM> to prevent the ingress of liquids therein. An interference seal <NUM> can be formed between the upper portion <NUM> and the lower portion <NUM>. This interference seal <NUM> is a sealing engagement between the upper portion <NUM> and the lower portion <NUM> in which the material of the upper portion <NUM> is firmly pressed against the material of the lower portion <NUM> in a manner sufficient to prevent the passage of liquids therethrough.

An exemplary interference seal <NUM> will now be described. The upper portion <NUM> includes a downward extension <NUM> which is located radially inward from the sidewall <NUM>. This downward extension <NUM> includes an outward taper <NUM>. The vertically oriented sidewall <NUM> of the lower portion <NUM> extends to an upper lip <NUM>. An inward taper <NUM> extends downwardly from the upper lip <NUM>. When the lower portion <NUM> is screwed into the upper portion <NUM>, the outward taper <NUM> is firmly pressed against inward taper <NUM> and the interference seal <NUM> is formed therebetween, which prevents the ingress of vaginal liquids into the outer container <NUM>.

Similar to the intravaginal culture device <NUM>, the outer container <NUM> of the intravaginal culture device <NUM> houses a first inner vessel <NUM> and a second inner vessel <NUM>. The first inner vessel <NUM> is depicted as being located within the upper portion <NUM>, and the second inner vessel <NUM> is depicted as being located within the lower portion <NUM>.

A first receiving cavity <NUM> is located in the upper portion <NUM>. A second receiving cavity <NUM> is located in the lower portion <NUM>. A base <NUM> of the first inner vessel <NUM> is removably positioned into the receiving cavity <NUM> in the upper portion <NUM>. A base <NUM> of the second inner vessel <NUM> is removably positioned into the receiving cavity <NUM> of the lower portion <NUM>. When the upper portion <NUM> is unscrewed from the lower portion <NUM>, the inner vessels <NUM> and <NUM> can be completely removed from the outer container <NUM>. The receiving cavities <NUM>, <NUM> are depicted as taking a substantially cylindrical form. The bases <NUM>, <NUM> of the inner vessels <NUM>, <NUM> are closely received within, and substantially fill, the receiving cavities <NUM>, <NUM>.

The first inner vessel <NUM> is preferably identical to the second inner vessel <NUM>, and includes similar features thereto. The first inner vessel <NUM> includes a base <NUM> and a lid <NUM>. An interior chamber <NUM> is defined within the first inner vessel <NUM>. The second inner vessel <NUM> includes a base <NUM> and a lid <NUM>. An interior chamber <NUM> is defined within the second inner vessel <NUM>.

When the outer container <NUM> is placed in a closed configuration <NUM>, the lid <NUM> of the first inner vessel <NUM> may contact the lid <NUM> of the second inner vessel <NUM> as is shown at <NUM>. The outward flare <NUM> of the upper portion <NUM> can be located radially outwardly from the lid <NUM> to provide clearance for the lid <NUM>. The outward flare <NUM> of the lower portion <NUM> can be located radially outwardly from the lid <NUM> to provide clearance for the lid <NUM>. A lower rim <NUM> of the lid <NUM> may contact an inner surface <NUM> of the flare <NUM> of the upper portion <NUM>. A lower rim <NUM> of the lid <NUM> may contact an inner surface <NUM> of the flare <NUM> of the lower portion <NUM>.

The first inner vessel <NUM> and the second inner vessel <NUM> each enclose and contain gametes and/or embryos and a suitable culture medium. In one non-limiting form, each inner vessel <NUM>, <NUM> can house between one and ten embryos (e.g. up to twenty embryos can be housed in the intravaginal culture device <NUM>). However, it is also contemplated that the sizing of the inner vessels <NUM>, <NUM> and the outer container <NUM> can be increased or decreased depending upon the specific application and number of embryos desired to be housed therein.

Referring now to <FIG>, the first inner vessel <NUM> will now be described. As was previously discussed, the second inner vessel <NUM> is preferably identical to the first inner vessel <NUM>. The base <NUM> of the first inner vessel <NUM> includes a sidewall <NUM> which extends upwardly from a closed lower portion <NUM>. An inner lower edge <NUM> is located where the sidewall <NUM> abuts the closed lower portion <NUM>. This inner lower edge <NUM> can include a fillet. The base <NUM> includes an open top <NUM>. The base <NUM> is depicted as taking a cylindrical form <NUM>, and the base <NUM> is preferably sized to fit within a well of a <NUM>-well IVF laboratory dish.

A lid <NUM> threadingly engages with the base <NUM> to close the open top <NUM>, thereby sealing the culture medium and embryos within the interior chamber <NUM>. An outer surface <NUM> of the sidewall <NUM> includes threads <NUM>. These threads <NUM> are located near an upper portion <NUM> of the base <NUM>. The lid <NUM> includes a downwardly extending wall <NUM>. An inner surface <NUM> of the downwardly extending wall <NUM> includes threads <NUM>. The threads <NUM> of the base <NUM> cooperate with the threads <NUM> of the lid <NUM> to rotatably attach the lid <NUM> to the base <NUM>. To close the first inner vessel <NUM>, the lid <NUM> is rotated relative the base <NUM> and the lid <NUM> is screwed onto the base <NUM>.

An interference seal <NUM> can be created between the base <NUM> and the lid <NUM>. An inner surface <NUM> of the lid <NUM> includes a curvature <NUM>. An upper rim <NUM> of the sidewall <NUM> can include a curvature <NUM> which is configured to abut the curvature <NUM>. When the lid <NUM> is firmly screwed onto the base <NUM>, the curvature <NUM> abuts the curvature <NUM>, and the material <NUM> of the lid <NUM> presses against the material <NUM> of the base <NUM> creating interference seal <NUM>. This interference seal <NUM> prevents the egress of the culture medium and embryos from within the interior chamber <NUM> of the inner vessel <NUM>.

Preferably, the outer container <NUM> is formed of a CO<NUM> permeable material <NUM>. The inner vessels <NUM> and <NUM> are preferably formed of a CO<NUM> permeable material <NUM>. The materials <NUM> and <NUM> can be medical grade general purpose polystyrene, which is commonly referred to as GPPS; however, the use of other CO<NUM> permeable polymers is also contemplated herein. GPPS is a crystal polystyrene which is has insulative properties and can be transparent in nature. The ability to view inside the inner chambers <NUM>, <NUM> without removing the lids <NUM>, <NUM> can be beneficial as removal of the lids <NUM>, <NUM> can cause the temperature within the inner chambers <NUM>, <NUM> to fluctuate.

The lids <NUM> and <NUM> can be constructed of a polymeric material <NUM>. The lids can be formed of a formed of a CO<NUM> permeable material <NUM>, such as GPPS. However, the lids <NUM> and <NUM> can also be formed of polyethylene, thermoplastic elastomers, or other polymers.

The polystyrene construction of the outer container <NUM> and the bases <NUM>, <NUM> permits CO<NUM> to pass between the vaginal cavity and the interior chambers <NUM>, <NUM>, but prevents the passage of liquids therethrough. As such, the outer container <NUM> prevents the ingress of vaginal fluids therein. The inner vessels <NUM>, <NUM> prevent the egress of the culture medium fluid such that the culture medium fluid and embryos are confined within the interior chambers <NUM>, <NUM>. It is believed that the polystyrene construction of the outer container <NUM> and the bases <NUM>, <NUM> will also serve as an insulator, thereby reducing temperature fluctuations with the embryos and/or gametes confined within the interior chambers <NUM>, <NUM>.

The passage of CO<NUM> between the vaginal canal and the interior chambers <NUM>, <NUM>, combined with a culture medium having a high initial CO<NUM> concentration (e.g. as can be achieved by leaving culture medium in a typical IVF lab incubator), has been discovered to sufficiently regulate the pH of the culture medium and thereby provide a suitable environment for the embryos and/or gametes. The intravaginal culture device <NUM> is devoid of a CO<NUM> enriched buffer chamber (i.e. a CO<NUM> enriched buffer chamber is absent from the intravaginal culture device <NUM>). An IVF chamber is not required to load the intravaginal culture device <NUM>.

One exemplary, non-limiting method of use of the intravaginal culture device <NUM> will now be described. On the day prior to oocyte retrieval, the intravaginal culture device <NUM> can be removed from its packaging and placed in an IVF lab incubator at <NUM>, <NUM>% CO<NUM> to warm overnight. <NUM> of culture media and <NUM> of oil can be placed in a <NUM> triple gas IVF lab incubator to pre-equilibrate overnight.

On the day of oocyte retrieval, ICSI can be performed on the oocytes. The inner vessels <NUM>, <NUM> can be removed from the IVF lab incubator and placed into a warmed <NUM>-well dish on a heated microscope stage to be prepared. The lids <NUM>, <NUM> are removed from the bases <NUM>, <NUM> of the inner vessels <NUM>, <NUM>. The interior chambers <NUM>, <NUM> of the inner vessels <NUM>, <NUM> can each be filled with 500µL culture media with a 500µL oil overlay.

The injected oocytes (e.g. fertilized oocytes) can then be loaded into the interior chambers <NUM>, <NUM> of the inner vessels <NUM>, <NUM>. As was previously discussed, it is contemplated that up to <NUM> embryos can be inserted into each inner vessel <NUM>, <NUM>, and a total of <NUM> embryos can be housed within the intravaginal culture device <NUM>. After the oocytes are placed in the interior chambers <NUM>, <NUM>, the lids <NUM>, <NUM> can be screwed onto the bases <NUM>, <NUM> sealing the embryos and culture media within the interior chambers <NUM>, <NUM>.

The outer container <NUM> can be removed from the IVF lab incubator and unscrewed, separating the upper portion <NUM> from the lower portion <NUM>. The first inner vessel <NUM> is placed in the upper portion <NUM> and the second inner vessel <NUM> is placed in the lower portion <NUM>. With the inner vessels <NUM>, <NUM> in place, the lower portion <NUM> is screwed into the upper portion <NUM>, thereby sealing the outer container <NUM>.

The loaded intravaginal culture device <NUM> can then be placed into the <NUM>, <NUM>% CO<NUM> IVF lab incubator until the patient is ready for device placement. The intravaginal culture device <NUM> can be removed from the IVF lab incubator to be inserted into the upper vaginal canal of the patient. Depending upon the specific patient, or upon the preferences of the fertility provider, a diaphragm (not shown) may be inserted into the vaginal canal below the intravaginal culture device <NUM> to securely retain the intravaginal culture device <NUM> in the upper vaginal canal.

The intravaginal culture device <NUM> can remain in the upper vaginal canal of the patient for a predetermined time, such as <NUM> days to the blastocyst stage. After the predetermined time, the patient can return to the fertility provider. The fertility provider can remove the intravaginal culture device <NUM> from the vaginal canal of the patient. Once removed from the patient, the upper portion <NUM> can be unscrewed from the lower portion <NUM>. The inner vessels <NUM>, <NUM> are then removed from the outer container <NUM>. The inner vessels <NUM>, <NUM> can then be placed into a pre-warmed <NUM>-well dish, which can be placed onto a heated microscope stage. The lids <NUM>, <NUM> can be unscrewed from the bases <NUM>, <NUM>, and the embryos can be removed from the interior chambers <NUM>, <NUM> to then be evaluated, graded, and eventually transferred, biopsied, or cryopreserved.

Referring now to both intravaginal culture devices <NUM> and <NUM>, the intravaginal culture devices <NUM>, <NUM> can be individually packaged, and can be sterilized by gamma irradiation. It is also contemplated that the intravaginal culture devices <NUM>, <NUM> can be single use devices; therefore, all components can be discarded after any embryos and/or gametes have been removed.

The intravaginal culture devices <NUM> and <NUM> can be manufactured through injection molding; however, other construction techniques such as milling and vacuum forming are contemplated herein. It is contemplated that metallic inserts (not shown) can be integrated into the devices <NUM>, <NUM> during the molding process for added strength. For example, it may be desirable to utilize metallic inserts for the tabs <NUM> in the intravaginal culture device <NUM>, and may be desirable to utilize metallic inserts for the threads <NUM>, <NUM>, <NUM>, and <NUM> in the intravaginal culture device <NUM>.

It is also contemplated that the tabs <NUM> can be integrally formed with the base <NUM> from polystyrene. The threads <NUM> can be integrally formed or machined in the upper portion <NUM> from polystyrene, and the threads <NUM> can be integrally formed or machined in the lower portion <NUM> from polystyrene. The threads <NUM> can be integrally formed or machined in the base <NUM> from polystyrene.

Claim 1:
An intravaginal culture apparatus, (<NUM>) comprising:
an outer container (<NUM>) configured for insertion into a vaginal canal, wherein the outer container includes an upper portion (<NUM>) that removably couples with a lower portion (<NUM>);
a receiving cavity (<NUM>) located in the upper portion;
an inner vessel (<NUM>) received in the receiving cavity, wherein the inner vessel includes an interior chamber (<NUM>) configured to house an embryo;
a second receiving cavity (<NUM>) located in the lower portion;
a second inner vessel (<NUM>) received in the second receiving cavity,<NUM> wherein the second inner vessel is configured to house an embryo; and
wherein the outer container, the inner vessel, and the second inner vessel include a CO<NUM> permeable construction<NUM>.