Device for delivering fertilized eggs or embryos

Abstract

The present invention relates to a device suitable for delivering a fertilized egg or embryo into a maternal endometrium. The device includes an elongate body with a distal tip and a lumen extending therethrough to an opening located at the distal tip. The lumen is configured to receive and expel the fertilized egg or embryo through the opening. A plunger is configured to be slidably received within the lumen. The distal tip includes a piercing portion for piercing the maternal endometrium, and the opening has a concave shape.

Description

[Technical Field]

[0001] The present invention relates to the field of devices for delivering a fertilized egg or embryo to the maternal endometrium, and in particular to the field of devices configured to pierce the maternal endometrium and deliver a fertilized egg or embryo. [Background technology]

[0002] Since its first successful performance in 1978, human in vitro fertilization (IVF) and embryo transfer (ET) have become widely practiced therapies for treating infertile couples who have failed more conventional treatments, such as superovulation induction and intrauterine insemination. The most common indications for IVF and related therapies, such as gamete in vitro fertilization or gamete intrafallopian tube transfer (GIFT), include women with blocked or damaged fallopian tubes and poor sperm and / or egg quality. Associated factors include the woman's age and the degree of endometrial receptivity. Furthermore, this treatment can also be used in severe male factor infertility, where direct sperm injection (intracytoplasmic sperm injection) is an option.

[0003] IVF / ET treatments typically involve hormonal stimulation of the female, first suppressing her own ovulatory ability and then stimulating the development of follicles within the ovaries with ovulation-inducing drugs. Mature eggs are collected transvaginally from the ovaries using a needle, preferably under ultrasound guidance. After collection, the eggs are identified and sorted based on maturity and then mixed with the man's sperm sample. Approximately 24 hours after fertilization, the eggs are tested to confirm fertilization. Fertilization occurs in approximately 65% ​​to 85% of the collected eggs.

[0004] After a short development period, the embryo is transferred to the uterus with a certain volume of fluid using a delivery catheter. To increase the success rate of this procedure, the embryo needs to be implanted into the endometrium using a needle tip to penetrate the endometrium. By applying pressure to the fluid in the needle tip, the embryo can be expelled onto the endometrium.

[0005] It has been observed that the embryo may attach to the distal tip of the needle, and depending on the attachment location, fluid may flow out of the needle and miss the embryo. In such cases, the embryo may remain attached to the tip of the needle even after all the fluid has been expelled, as the expelled fluid may not capture the embryo. This can result in the embryo becoming dislodged or even detached from the endometrium when the needle is withdrawn. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] PCT / EP2021 / 078712 Summary of the Invention [Problem to be solved by the invention]

[0007] Therefore, there is a need to provide an improved device for delivering embryos or fertilized eggs into the endometrium that more effectively expels the embryos or fertilized eggs from the device. [Means for solving the problem]

[0008] A first aspect of the present invention provides a device suitable for delivering a fertilized egg or embryo into a maternal endometrium, the device comprising: an elongate body having a distal tip and a lumen extending therethrough to an opening located at the distal tip, the lumen being configured to receive and expel the fertilized egg or embryo through the opening; and a plunger configured to be slidably received within the lumen, the distal tip including a piercing portion for piercing the maternal endometrium, the opening having a concave shape.

[0009] In order that the present disclosure may be better understood and to show how the same may be carried into effect, reference will now be made, by way of example only, to the accompanying schematic drawings. [Brief explanation of the drawings]

[0010] [Figure 1] 1 is a perspective view of a device according to the prior art; [Figure 2] 1 is a schematic perspective view of an apparatus according to one or more embodiments. [Figure 3A] 1 is a schematic side view of an apparatus according to one or more embodiments. [Figure 3B] 1 is a schematic side view of an apparatus according to one or more embodiments. [Figure 4] 1 is a schematic side view of an apparatus according to one or more embodiments. [Figure 5A] 1 is a schematic top view of an apparatus according to one or more embodiments. [Figure 5B] 5B is a side cross-sectional view of the device shown in FIG. 5A taken along line AA. [Figure 6] 1 is a schematic diagram of an apparatus according to one or more embodiments. [Figure 7] 1 is a schematic diagram of an apparatus according to one or more embodiments. [Figure 8] 1 is a schematic diagram of an apparatus according to one or more embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0011] FIG. 1 shows a perspective view of a prior art device 1. The device 1 includes an elongate body 2 (e.g., a needle) having a distal tip 4 and a lumen 3 extending therethrough to an opening 6 located at the distal tip 4. The lumen 3 is configured to receive and expel a fertilized egg or embryo 5 (hereinafter, simply referred to as "fertilized egg, etc.") through the opening 6. A plunger (not shown) is slidably received within the lumen 3. The distal tip 4 is configured to perforate the maternal endometrium and includes a first surface 4a inclined relative to the longitudinal axis of the elongate body 2. The distal tip 4 further includes a perforating portion at its most distal end, which is a double-bevel perforating portion including a first surface 4b and a second surface 4c. The first surface 4b and the second surface 4c are inclined relative to the first surface 4a to form a sharp tip at the distal end of the distal tip 4. In use, the plunger can be retracted proximally away from the distal tip 4. This retraction can be used to generate suction at the distal tip 4 and position the embryo 5 within the lumen 3. The embryo 5 is typically positioned within the lumen 3 with fluid positioned proximal to the embryo 5. To implant the embryo 5 within the endometrium, the elongate body 2 penetrates the endometrium using the distal piercing tip, and the plunger is advanced distally to expel the fluid and the embryo 5 from the lumen 3. The embryo 5 is typically pushed distally by pressure transmitted through the fluid by the plunger. However, when the embryo 5 reaches the most distal end of the elongate body 2, a gap is formed at the opening 6, as shown in FIG. 1 . This allows fluid contained within the lumen 3 to leak out of the lumen via fluid path F, but the fluid is expelled without exerting pressure on the embryo 5. Thus, in some cases, even after the plunger has been fully advanced and the fluid has been fully expelled, the embryo 5 may remain attached to the distal tip 4. This reduces the success rate of implantation, as the embryo 5 may become displaced or even detached from the endometrium when the elongate body 2 is removed.

[0012] FIG. 2 shows a schematic perspective view of a device 10 suitable for delivering a fertilized egg or embryo 50 (hereinafter referred to simply as "zygote") into the maternal endometrium, according to one or more embodiments. The device 10 comprises an elongate body 20 having a distal tip 40 and a lumen 30 extending therethrough to an opening 60 located at the distal tip 40. The lumen 30 is configured to receive and expel the fertilized egg or embryo 50 through the opening 60. The device 10 further comprises a plunger 44 configured to be slidably received within the lumen 30. The distal tip 40 comprises a piercing portion 70 for piercing the maternal endometrium, and the opening 60 has a concave shape. The piercing portion may have any shape and sharpness suitable for piercing the endometrium. In some embodiments, the piercing portion may comprise a tip or edge having an edge radius of less than 2 μm, preferably less than 1 μm. This concave shape of the opening 60 reduces or eliminates the amount of fluid that leaks out of the lumen 30 without exerting pressure on the embryo 50 at the distal end of the distal tip 40, thereby reducing the likelihood that the embryo 50 will remain lodged in the distal tip 40 when the fluid is completely expelled, thereby increasing the success rate of implantation.

[0013] 3A and 3B show different schematic side views of the device 10 shown in FIG. 2. In FIG. 3A, the concave shape of opening 60 is shown in contrast to the shape of opening 6 of device 1. It can be seen that the available fluid path F shown in FIG. 1 is blocked by the concave shape of opening 60. As shown in FIG. 3B, piercing portion 70 may comprise a double-bevel tip with a back-cut bevel for piercing the maternal endometrium. In particular, piercing portion 70 may comprise first and second surfaces 72 and 74 that are inclined relative to the outer surface of elongate body 20, and these inclined surfaces 72 and 74 form a sharp tip 75 at the distal end of distal tip 40.

[0014] 3A and 3B, the distal surface 84 of the distal tip 40 defining the opening 60 may have a curved, concave shape with a radius of curvature R, such that the opening 60 has a curved, concave shape with a radius of curvature R. A curved, concave shape with a radius of curvature is preferred because the opening 60 generally conforms to the spherical shape of the fertilized egg 50, and therefore conforms to the shape of the fertilized egg 50 when the fertilized egg 50 is positioned at the distal end of the distal tip 40, preventing the formation of a fluid path F. In a preferred embodiment, the radius of curvature R is between 1.5 and 4 times the outer diameter D of the elongate body 20, which is believed to be optimal for preventing the formation of a fluid path F for typical fertilized egg and embryo sizes.

[0015] 3A, preferably, this curved concave portion extends between the perforated portion 70 and the lowest portion of the distal tip 40. This lowest portion of the distal tip 40 extends perpendicular to the longitudinal axis of the elongate body 20. This ensures that when an embryo or the like 50 is placed at the distal end of the elongate body 20, contact between the distal tip 40 and the embryo or the like 50 is maintained while minimizing the fluid path.

[0016] In a preferred embodiment, the height of the distal tip 40, measured from the lowest portion 77 of the distal tip 40 to the distal end 75 of the perforated portion 70, is between 0.25 and 1.25 times the outer diameter D of the elongate body 20, and more preferably between 0.5 and 1.25 times the outer diameter D of the elongate body 20.

[0017] The distal tip may be made from a biocompatible metal, such as stainless steel.

[0018] In a preferred embodiment, the distal tip 40 includes a hydrophobic coating. This hydrophobic coating may be provided on one or more of the inner surface 82 of the distal tip 40, the outer surface 86 of the distal tip 40, and the distally facing surface 84 of the distal tip 40. The hydrophobic coating may include or consist of a polymer or polymer composite, preferably parylene, acrylic, polyethylene, polyurethane, polytetrafluoroethylene, and composites thereof. The hydrophobic coating further reduces the likelihood that the embryo or the like 50 will remain in place at the distal tip 40 after the fluid has been expelled.

[0019] FIG. 4 shows a schematic side view of another device 10′ according to one or more embodiments. This device may include any of the features disclosed with reference to FIGS. 2, 3A, and 3B, but the opening 60 of device 10′ does not include a curved concave portion. As an alternative to the curved concave portion shown in FIGS. 2, 3A, and 3B, the opening 60 can employ a concave portion formed by a plurality of flat surfaces. In the illustrated embodiment, the concave portion is formed by two flat surfaces, but it will be appreciated that the concave portion can be formed by any number of flat surfaces. Again, the concave portion of opening 60 is shown for comparison with the shape of opening 6 of device 1. It will be appreciated that the available fluid path F shown in FIG. 1 is blocked by the concave portion of opening 60 of device 10′.

[0020] FIG. 5A shows a schematic top view of device 200 according to one or more embodiments. FIG. 5B shows a side cross-sectional view of device 200 shown in FIG. 5A taken along line AA. Device 200 may include any feature of the devices described herein (e.g., device 10 or 10′). Perforating portion 70 has first and second surfaces 72 and 74, which are inclined relative to the outer surface of elongate body 20. These inclined surfaces 72 and 74 form a sharp tip 75 (double bevel tip) at the distal end of distal tip 40. Inclined surface 72 is defined by a bevel angle α in a plane perpendicular to the longitudinal axis of elongate body 20 and a draft angle β relative to the longitudinal axis of elongate body 20. Bevel angle α is defined as the angle formed by a plane containing inclined surface 72 and a tangent to the surface of elongate body 20 located at tip 75. Draft angle β is defined as the angle formed by a plane containing inclined surface 72 and the longitudinal axis of elongate body 20. The bevel angle and draft angle of inclined surface 74 are similarly defined. The bevel angle of inclined surfaces 72 and 74 is preferably between 20° and 40°. The draft angle of inclined surfaces 72 and 74 is preferably between 1° and 20°. The bevel angle and draft angle of inclined surfaces 72 and 74 may be the same (as shown) or different.

[0021] In a preferred embodiment, the diameter of the lumen 30 is between 1 and 2 times the outer diameter of the fertilized egg or the like to be transplanted, and more preferably between 1 and 1.5 times the outer diameter of the fertilized egg or the like to be transplanted.

[0022] In a preferred embodiment, the outer diameter of elongate body 20 is between 1.5 and 3 times the diameter of lumen 30, and more preferably between 1.5 and 2 times the diameter of lumen 30.

[0023] FIG. 6 shows a schematic diagram of a device 100 suitable for delivering a fertilized egg or embryo into the maternal endometrium, according to one or more embodiments. The device 100 includes a body 110 (e.g., a catheter, also referred to as an outer body) configured to fit within a lumen of the female reproductive system. The body includes one or more lumens, including a lumen 120 extending from a proximal end 130 to a distal portion 140 of the body 110, the lumen 120 having a distal opening 150 at the distal portion 140 of the body. The lumen 120 is configured to slidably receive an inner body 160 having a distal end suitable for piercing the endometrial epithelium. The inner body 160 can be any of the elongate bodies 20 disclosed herein and can include features of any of the devices disclosed with reference to the preceding figures. Additionally, the device 100 may include a first actuator 190 that can advance the inner body 160 outward from the distal opening 150 of the main body 110, and a second actuator 195 that can eject the fertilized egg or embryo from the inner body.

[0024] Device 100 may include a cover layer (not shown) that at least partially covers the distal opening of one or more lumens (e.g., in the embodiment shown in FIG. 6, the cover layer may cover distal opening 150 of lumen 120). The inclusion of a cover layer prevents mucus and other bodily fluids from entering lumen 120 as the device is advanced through the female reproductive system.

[0025] In FIG. 6, the dimensions of body 110 are shown exaggerated for clarity, but in reality body 110 is a thin elongated body configured to extend within the uterus down to the endometrial epithelium.

[0026] As described above, inner body 160 has a distal end (e.g., piercing portion 70) suitable for piercing the endometrial epithelium. In this embodiment, inner body 160 is shown disposed within lumen 120 of body 110. A plunger 165, which may be plunger 44, is housed within inner body 160 and configured to advance toward the distal end of inner body 160 upon actuation by second actuator 195 to expel a fertilized egg located within inner body 160. If a cover layer is provided, the cover layer may at least partially cover distal opening 150, and inner body 160 may be configured to pierce the cover layer when inner body 160 is advanced outward from the distal opening of the body, thereby allowing inner body 160 to penetrate cover layer 170a and advance outward from distal opening 150 to pierce the endometrial epithelium.

[0027] FIG. 7 shows a schematic diagram of another device 100′ according to one or more embodiments. The device 100′ can include any of the features described with reference to FIG. 6. The inner body 160 can be any of the devices 10, 10′ disclosed with reference to FIGS. 2-5B. The device 100′ can further include a measurement assembly including a measurement portion 170 disposed at the distal portion 140 of the body 110 (i.e., proximal to the distal opening 150). The measurement assembly 170 is configured to measure whether the device is in a first state indicating that the distance between the distal opening 150 of the body 110 and the endometrial epithelium is greater than a predetermined distance (i.e., the distance in the direction in which the inner body advances from the distal opening 150) or a second state indicating that the distance between the distal opening 150 of the body 110 and the endometrial epithelium is equal to or less than the predetermined distance. The apparatus 100′ further includes an indicator device 180 coupled to the measurement assembly 170 via a connection extending through the lumen 175 and configured to indicate whether the measurement assembly 170 is in the first state or the second state. The measurement assembly is removable from the body 110. In particular, the measuring portion 170 may be slidably housed within the body lumen so that it can be withdrawn from the body 110 through the lumen, thereby making the measurement assembly reusable. The inner body 160 and the measurement assembly may be housed within the same lumen or different lumens. The apparatus 100′ further includes a first actuator 190 that can advance the inner body 160 outward at least a predetermined distance from the distal opening 150 of the body 110, and a second actuator 195 that can expel a fertilized egg from the inner body (e.g., by advancing the plunger 165). As shown, the cover layer 170a can at least partially cover one of the distal openings of the lumens.When the cover layer 170a covers the distal opening of the lumen 175, and therefore the measurement portion 170, the cover layer prevents the measurement portion 170 from being exposed to mucus and improves the reusability of the measurement assembly when it can be removed from the device (i.e., in embodiments where the measurement assembly is not permanently attached to the inner lumen 175 and is removable).

[0028] In some embodiments, measurement portion 170 is a camera positioned proximal to opening 150 and configured to observe a portion of the endometrial epithelium.

[0029] The measurement assembly may be any suitable measurement assembly capable of determining whether the distance between the distal opening 150 of the body 110 and the endometrial epithelium is above or below a predetermined distance. It will be appreciated that the measurement assembly may provide either a qualitative measurement (e.g., the measurement assembly may transition between two states) or a quantitative measurement (e.g., whereby a parameter indicative of the distance to the endometrial epithelium is actually measured and the parameter is compared to a threshold value indicative of the predetermined distance). The measurement portion 170 is the portion of the measurement assembly configured to interact with the endometrial epithelium to cause the measurement assembly to perform the determination and may include any suitable elements. These elements of the measurement portion 170 may be connected to components at the proximal end of the apparatus 100, such as components of the measurement assembly (not shown) and indicator device 180, via connections extending through one or more lumens 175 within the body 110. For example, the measurement portion may include components optically, acoustically, or electrically connected to the proximal components of the measurement assembly, such as a light or sound emitter or receiver, an electrical signal component, or a power source. The measurement assembly may be any of the measurement assemblies disclosed in PCT Application No. PCT / EP2021 / 078712, which is incorporated herein by reference in its entirety.

[0030] FIG. 8 shows a schematic diagram of device 100″ according to one or more embodiments. Device 100″ may include any of the features of the devices disclosed with reference to FIGS. 6 and 7, and inner body 160 may include any of the features of elongate bodies 10, 10′ disclosed herein. In the embodiment of FIG. 8, measurement assembly 162 includes a capacitance sensor configured to be in electrical contact with a distal portion of the inner body. Measurement assembly 162 is configured to measure whether device 100 is in a first state indicating that the distance between the distal end of inner body 160 and the endometrial epithelium is greater than a predetermined distance (i.e., the distance in the direction in which the inner body advances from distal opening 150 of body 110), or a second state indicating that the distance between the distal end of inner body 160 and the endometrial epithelium is equal to or less than the predetermined distance. In one embodiment, distal portion 161 of inner body 160 is electrically conductive, and measurement assembly 162 is configured to be in electrical contact with said distal portion 161 of inner body 160. The measurement assembly thereby provides an indication of capacitance. In one embodiment, a first condition is indicated by a capacitance measurement below a threshold, and a second condition is indicated by a capacitance measurement above the threshold. If provided, cover layer 170a may cover distal opening 150 to prevent mucus from entering lumen 120 and affecting the capacitance measurement of distal portion 161 when inner body 160 is moved toward distal opening 150. Inner body 160 is configured to penetrate cover layer 170a, thereby allowing inner body 160 to extend distally from device 100 and penetrate the endometrial epithelium for implantation of a fertilized egg.

[0031] In one particular embodiment, the capacitance changes with changes in the distance between the distal portion 161 of the inner body 160 and the endometrial epithelium. That is, the capacitance value changes with the proximity of the distal portion 161 of the inner body 160 to the endometrial epithelium. In one embodiment, the predetermined distance is zero (thus meaning that there is contact between the distal portion 161 of the inner body 160 and the endometrial epithelium). In one embodiment, the capacitance value is measured by a measurement assembly 162, which comprises an electrical system electrically connected to the distal portion 161 of the inner body 160 for measuring capacitance.

[0032] Any of the foregoing is considered to form the basis of alternative embodiments which fall fully within the scope of the present disclosure and in which one or more combinations of the above features are applied, without being limited to the specific combinations disclosed above.

[0033] In light of the above, there will be many alternatives that embody the teachings of the present disclosure. It is expected that those skilled in the art, in light of their general knowledge in the art, will be able to modify and adapt the above disclosure to suit their own circumstances and requirements within the scope of the present disclosure, while retaining some or all of the technical effects of the present disclosure disclosed in or derivable from the above. All such equivalents, modifications, or adaptations are included within the scope of the present disclosure. [Explanation of symbols]

[0034] 1 device 2 Elongated body 3 lumens 4 Distal tip 4a First surface 4b First surface 4c Second Surface 5 Fertilized eggs etc. 6 Opening 10 Device, elongated body 10' device, elongated body 20 Elongated body 30 lumens 40 Distal tip 44 Plunger 50 Fertilized eggs, etc., embryos 60 Opening 70 Perforated part 72 First surface, inclined surface 74 Second Surface, Inclined Surface 75 Sharp tip, distal end 77 Bottom part 82 Inner surface 84 Distal Surface 86 External surface 100 devices 100' equipment 100'' equipment 110 Main Unit 120 lumens 130 proximal end 140 Distal part 150 distal opening 160 Inner body 161 Distal portion 162 Measuring Assembly 165 Plunger 170 Measuring part, measuring assembly 170a cover layer 175 lumens, inner lumen 180 indicator device 190 First Actuator 195 Second Actuator 200 equipment F fluid path D Outer diameter

Claims

1. 1. A device suitable for delivering a fertilized egg or embryo into the maternal endometrium, comprising: an elongate body having a distal tip and a lumen extending therethrough to an opening at the distal tip, the lumen configured to receive and expel the fertilized egg or embryo through the opening; a plunger configured to be slidably received within the lumen; Equipped with The device, wherein the distal tip comprises a piercing portion for piercing the maternal endometrium, and the opening has a concave shape.

2. 10. The device of claim 1, wherein the piercing portion comprises a double-bevel tip for piercing the maternal endometrium.

3. 3. The device of claim 2, wherein the double bevel tip comprises two beveled surfaces having a bevel angle between 20° and 40° and a draft angle between 1° and 20°.

4. 4. The device of claim 1, wherein the opening has a curved concave portion with a radius of curvature.

5. 5. The device of claim 4, wherein the elongate body has an outer diameter and the curved concave portion of the opening has a radius of curvature that is between 1.5 and 4 times the outer diameter of the elongate body.

6. 6. The device of claim 4 or 5, wherein the curved concave portion extends between the perforated portion and a lowermost portion of the distal tip, the lowermost portion of the distal tip extending perpendicular to a longitudinal axis of the elongate body.

7. 7. The device of claim 6, wherein the elongate body has an outer diameter and the height of the distal tip, measured from the bottom portion to the distal end of the perforated portion, is between 0.5 and 1.25 times the outer diameter of the elongate body.

8. 8. The device of claim 1, wherein the distal tip is made from a biocompatible metal, preferably stainless steel.

9. The device of claim 1 , wherein the distal tip comprises a hydrophobic coating.

10. 10. The device of claim 9, wherein the hydrophobic coating is formed on at least one of an inner surface of the distal tip, an outer surface of the distal tip, and a distally facing surface of the distal tip.

11. 11. The device of claim 9 or 10, wherein the hydrophobic coating comprises or consists of a polymer or polymer composite, preferably any of parylene, acrylic, polyethylene, polyurethane, polytetrafluoroethylene, and composites thereof.

12. 12. The device according to claim 1, wherein the diameter of the lumen is between 1 and 1.5 times the outer diameter of the fertilized egg to be implanted.

13. The elongate body is an inner body, and the device further comprises an outer body configured to fit within a lumen of the female reproductive system, the outer body comprising: a lumen extending from a proximal end of the outer body to a distal portion of the outer body and having a distal opening at the distal portion of the outer body, the lumen slidably receiving the inner body; Equipped with The device comprises: a first actuator operable to advance the inner body outwardly from the distal opening of the outer body; a second actuator capable of advancing the plunger to expel a fertilized egg from the lumen of the inner body; and 13. The apparatus of claim 1, further comprising:

14. 14. The device of claim 13, further comprising a measurement assembly extending through one of the one or more lumens of the outer body and comprising a measurement portion proximal to a distal opening of the one or more lumens, the measurement portion configured to measure whether the device is in a first state indicating that the distance between the distal end of the outer body or the inner body and the endometrial epithelium is greater than a predetermined distance, or a second state indicating that the distance between the distal end of the outer body or the inner body and the endometrial epithelium is equal to or less than a predetermined distance.

15. The device of claim 14 , wherein the measurement assembly comprises a capacitance sensor configured to be in electrical contact with a distal portion of the inner body.

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