Embryo Transfer System

Abstract

A device (100) suitable for delivering a fertilized egg or embryo to the maternal endometrium of a human or any other mammalian species, the device (100) comprising a body (110) configured to fit within a lumen of the female reproductive system, the body (110) comprising one or more lumens extending from a proximal end (130) of the body (110) to a distal portion of the body (110) and having a distal opening (150) at the distal portion of the body (110), a first lumen (120) of the one or more lumens slidably receiving an inner body (160) having a distal end adapted to penetrate the endometrial epithelium, the inner body (160) comprising an inner lumen for receiving a fertilized egg, and an actuator (195) operable to expel the fertilized egg from the inner lumen. The covering layer (170a) at least partially covers the distal opening of at least one of the one or more lumens and at least partially covers the distal opening (150) of the first lumen (120), and the inner body (160) is configured to penetrate the covering layer (170a) when the inner body (160) is advanced from the distal opening (150) of the body (110).

Description

[Technical field]

[0001] The present disclosure relates to systems and methods for implanting a fertilized egg or embryo into the endometrial epithelium, and to devices for guiding such systems and engaging a speculum. [Background technology]

[0002] Human in vitro fertilization (IVF) and embryo transfer (ET), first successful in 1978, has become a widely practiced procedure to treat infertile couples after more conventional methods of treatment such as superovulation and intrauterine insemination have failed. The most common indication for IVF and related procedures includes women with blocked or damaged fallopian tubes, and includes poor sperm and / or egg quality, such as gamete in vitro fertilization or gamete intrafallopian tube transfer (GIFT). Associated factors include the woman's age and endometrial receptivity. This procedure can also be used in severe male factor cases where direct (intracytoplasmic) injection of sperm is an option.

[0003] IVF / ET procedures typically involve first suppressing a woman's ability to ovulate on her own, then hormonal stimulation to stimulate the development of ovarian follicles with fertility drugs. Mature eggs are retrieved from the ovaries transvaginally using a needle, preferably guided under ultrasound. After egg collection, the eggs are identified and sorted for maturity, then placed with a sperm sample from the male. Approximately 24 hours after fertilization, the eggs are tested to confirm fertilization, which occurs in approximately 65% ​​to 85% of collected eggs.

[0004] After a short developmental period, the embryo is transferred into the uterus with a certain amount of fluid using a delivery catheter. The delivery catheter is usually made of a soft plastic material to avoid damage to the endometrium. There are many potential difficulties in achieving successful transfer. Due to the soft nature of standard delivery catheters, the tip of the catheter can often bend on itself or curve away from the fundus of the uterus. The tip can also accidentally pass between the endometrial layer and the myometrium. Conversely, a stiffer catheter increases the risk of trauma to the uterus or cervix, the latter possibly resulting in the release of prostaglandins and the release of the egg from the endometrium.

[0005] One particular difficulty in achieving successful implantation is the difficulty the surgeon has in visualizing the uterus and endometrium into which the embryo will be implanted. In particular, mucus and other bodily fluids can make it difficult for the surgeon to determine whether the endometrial epithelium has been reached.

[0006] It has also been observed that the fertilized eggs may be released from the endometrial epithelium or expelled after the implantation procedure, thereby increasing the risk of failure of the procedure.Similarly, the fertilized eggs may remain attached to the implantation device after the medium containing the fertilized eggs has been injected into the endometrial epithelium.

[0007] Furthermore, a wide variety of specula are used in different shapes and sizes, making it difficult for the embryo transfer device to spatially lock onto the patient's anatomy to enhance precision of embryo delivery.

[0008] Therefore, there is a need for improved embryo transfer devices with increased reliability and methods for locking such embryo transfer devices into various speculum configurations. Summary of the Invention

[0009] According to a first aspect of the present invention, there is provided a system for delivering a fertilized egg or embryo to the maternal endometrium in a human or any other mammalian species, the system comprising a body having a distal end suitable for penetrating the endometrial epithelium, a plunger slidably received within the lumen of the body, an actuator operable to advance the plunger to expel the fertilized egg from the lumen of the body, a first injectable medium, and a second injectable medium for containing the fertilized egg, the first injectable medium having a higher viscosity than the second injectable medium.

[0010] According to a second aspect of the present invention there is provided a method of incorporating a system for delivering a fertilized egg or embryo to the maternal endometrium in a human or any other mammalian species, the system comprising a body having a distal end suitable for penetrating the endometrial epithelium, a plunger slidably received within a lumen of the body, and an actuator operable to advance the plunger to expel the fertilized egg from the lumen of the body, the method comprising the steps of drawing a first injectable medium into the lumen and thereafter drawing a second injectable medium containing the fertilized egg into the lumen, the first injectable medium having a higher viscosity than the second injectable medium.

[0011] According to a third aspect of the present invention there is provided a device suitable for delivering a fertilised egg or embryo to a maternal endometrium in a human or any other mammalian species, the device comprising: a body configured to fit within a lumen of the female reproductive system, the body comprising one or more lumens extending from a proximal end of the body to a distal portion of the body and having a distal opening at the distal portion of the body, a first of the one or more lumens slidably receiving an inner body having a distal end suitable for penetrating the endometrial epithelium, the inner body comprising an inner lumen for receiving the fertilised egg; an actuator operable to release the fertilised egg from the inner lumen; and a covering layer at least partially covering the distal opening of at least one of the one or more lumens.

[0012] According to a fourth aspect of the present invention there is provided a device for engaging a speculum, the device comprising two or more expandable engagement elements for externally engaging the speculum to secure the device to the speculum, the two or more expandable engagement elements having a plurality of expansion configurations for engaging a plurality of speculum sizes, and a guide for guiding an embryo delivery apparatus through the speculum between the expandable engagement elements when the device is secured to the speculum.

[0013] According to a fifth aspect of the present invention there is provided a device suitable for delivering a fertilised egg or embryo to a maternal endometrium in a human or any other mammalian species, comprising a body configured to fit within a lumen of the female reproductive system, the body comprising a lumen extending from a proximal end of the body to a distal portion of the body and having a distal opening at the distal portion of the body, the lumen slidably receiving an inner body having a distal end suitable for penetrating the endometrial epithelium, the device further comprising a first actuator operable to advance the inner body from the distal opening of the body and a second actuator operable to expel the fertilised egg from the inner lumen of the inner body, the inner body comprising a hydrophobic coating formed on the distal portion of the inner body. [Brief description of the drawings]

[0014] To enable a better understanding of the present disclosure and to show how it may be put into effect, reference will now be made, by way of example only, to the accompanying schematic drawings. [Figure 1A] FIG. 1 shows a perspective view of a device suitable for delivering a fertilized egg or embryo to the maternal endometrium according to one or more embodiments shown and described herein. [Figure 1B] FIG. 1 shows a perspective view of another device suitable for delivering a fertilized egg or embryo to the maternal endometrium according to one or more embodiments shown and described herein. [Figure 1C] FIG. 1 shows a perspective view of another device suitable for delivering a fertilized egg or embryo to the maternal endometrium according to one or more embodiments shown and described herein. [Figure 1D] FIG. 1D shows a side view of the distal portion of the device shown in FIG. 1C. [Figure 1E] FIG. 1D shows a front view of the device shown in FIG. 1C. [Figure 1F] FIG. 1 shows a perspective view of another device suitable for delivering a fertilized egg or embryo to the maternal endometrium according to one or more embodiments shown and described herein. [Figure 1G] FIG. 1 shows a perspective view of another device suitable for delivering a fertilized egg or embryo to the maternal endometrium according to one or more embodiments shown and described herein. [Figure 1H] FIG. 1 shows a perspective view of another device suitable for delivering a fertilized egg or embryo to the maternal endometrium according to one or more embodiments shown and described herein. [Figure 1J] FIG. 2 shows a schematic side view of a body for a device according to one or more embodiments shown and described herein. [Figure 1K] FIG. 2 shows a schematic side view of a stylet for a device according to one or more embodiments shown and described herein. [Figure 1L] 1C shows a schematic cross-sectional side view of the stylet of FIG. 1K inserted into a body for a device according to one or more embodiments. [Figure 2A] 1 shows a schematic perspective view of a system for delivering a fertilized egg or embryo to a maternal endometrium in a first configuration according to one or more embodiments shown and described herein. FIG. [Figure 2B] 2B is a schematic perspective view of the system of FIG. 2A in the second to fourth embodiments. [Figure 2C] 2B is a schematic perspective view of the system of FIG. 2A in the second to fourth embodiments. [Figure 2D] 2B is a schematic perspective view of the system of FIG. 2A in the second to fourth embodiments. [Figure 2E] FIG. 1 shows a schematic diagram of first, second and third media located in the endometrial epithelium. [Diagram 3] FIG. 2 shows a schematic diagram of a beveled tip according to one or more embodiments shown and described herein. [Figure 4] 1 shows a diagram of a pointing device according to one or more embodiments shown and described herein. [Diagram 5]FIG. 2 shows a diagram of a computer that may be used to control an apparatus according to one or more embodiments shown and described herein. [Figure 6A] 1 illustrates a cross-sectional perspective view of a connector according to one or more embodiments shown and described herein. [Figure 6B] 6B shows an enlarged view of a portion of the connector shown in FIG. 6A. [Figure 6C] 1 illustrates a perspective view of a proximal end of a connector according to one or more embodiments shown and described herein. [Figure 6D] FIG. 2 illustrates a perspective view of a distal end of a motion controller according to one or more embodiments shown and described herein. [Figure 6E] 6B shows an exploded view of the connector shown in FIG. 6A. [Figure 6F] FIG. 1 illustrates a perspective view of a connection between a body connector and a distal end of a motion controller according to one or more embodiments shown and described herein. [Figure 6G] FIG. 2 illustrates a perspective view of a proximal portion of a motion controller according to one or more embodiments shown and described herein. [Figure 6H] FIG. 1 illustrates a perspective view of a motion controller according to one or more embodiments shown and described herein. [Figure 7A] FIG. 1 illustrates a side cross-sectional view of a device for engaging a speculum according to one or more embodiments shown and described herein. [Figure 7B] FIG. 1 illustrates a side cross-sectional view of a device for engaging a speculum according to one or more embodiments shown and described herein. [Figure 7C] 7C shows the device of FIG. 7B in a second configuration. [Figure 8A] FIG. 2 shows a schematic perspective front view of a device for engaging a speculum in a first form according to one or more embodiments shown and described herein. [Figure 8B] FIG. 8B shows a schematic perspective side view of the device of FIG. 8A in a first configuration. [Figure 8C] 8B shows a schematic perspective front view of the device of FIG. 8A in a second configuration. [Figure 8D] FIG. 8B shows a schematic perspective front view of the device of FIG. 8A in a third configuration. [Figure 9A] FIG. 2 illustrates a side view of a steering mechanism according to some embodiments shown and described herein. [Figure 9B] FIG. 13 illustrates a side view of another steering mechanism according to some embodiments shown and described herein. [Figure 9C] FIG. 9C shows a plan view of the steering mechanism shown in FIG. 9A or FIG. 9B. [Figure 9D] FIG. 2 illustrates a side view of a steering mechanism with the cables in a retracted position according to one or more embodiments shown and described herein. [Figure 9E] FIG. 13 illustrates a perspective view of a third actuator according to certain embodiments shown and described herein. [Figure 9F] FIG. 8F shows a perspective view of the third actuator shown in FIG. 8E, with the outer shell shown as transparent. [Figure 9G] FIG. 2 illustrates a perspective view of an inner element of a steering mechanism according to some embodiments shown and described herein. [Figure 9H] FIG. 2 illustrates a perspective view of a steering mechanism according to some embodiments shown and described herein, with the outer shell shown as partially transparent. [Figure 10] FIG. 1 illustrates a perspective view of an apparatus according to one or more embodiments. [Figure 11] FIG. 1 shows a schematic perspective view of an apparatus according to one or more embodiments. [Figure 12A-12B] FIG. 1 shows a schematic side view of an apparatus according to one or more embodiments. [Figure 13] FIG. 1 shows a schematic side view of an apparatus according to one or more embodiments. [Figure 14A] FIG. 1 shows a schematic top view of an apparatus according to one or more embodiments. [Figure 14B] 14B shows a side cross-sectional view of the device shown in FIG. 14A taken along line AA. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Detailed Description FIG. 1A shows a perspective view of a device 100 suitable for delivering a fertilized egg or embryo to a maternal endometrium, the device 100 comprising a body 110 (e.g., a catheter also referred to as an outer body) configured to fit within a lumen of a female reproductive system. The body comprises one or more lumens including a lumen 120 extending from a proximal end 130 of the body 110 to a distal portion 140 of the body 110 and 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 penetrating the endometrial epithelium. The device 100 may also comprise a first actuator 190 operable to advance the inner body 160 from the distal opening 150 of the body 110, and a second actuator 195 operable to expel the fertilized egg or embryo from the inner body.

[0016] The device 100 may include a covering layer 170a at least partially covering the distal opening of one or more of the lumens (e.g., in the embodiment shown in FIG. 1A, the covering layer 170a covers the distal opening 150 of the lumen 120). Providing the covering layer 170a prevents mucus and other bodily fluids from entering the lumen 120 as the device is advanced through the female reproductive system. This prevents components slidably received within one or more of the covered lumens (e.g., the inner body 160 or the measurement assembly) from being exposed to the bodily fluids, and may allow the bodily fluids to be reused if they are extractable from the device 100. Furthermore, if a covering layer 170a is used for a lumen that includes a measurement assembly, it reduces variability in measurements made by the measurement assembly to provide a more reliable measurement for determining when the endometrial epithelium has been reached. For example, if the covering layer 170a is not provided, mucus and other body fluids may enter the lumen in an unpredictable manner, which may affect the measurements made by the measurement assembly and thus reduce the accuracy of determining when the endometrial epithelium has been reached. For example, if the measurement assembly includes a capacitance sensor configured to make electrical contact with the distal portion of the inner body, it has been observed that the presence of mucus in the lumen reduces the ability of the capacitance sensor to distinguish between a first state and a second state. Similarly, if the device includes a camera, mucus entering the lumen receiving the camera may partially or even completely obscure the camera's field of view.

[0017] The dimensions of body 110 are exaggerated in Figures 1A-1G for clarity, but in reality body 110 is a narrow, elongated body configured to extend into the uterus to the endometrial epithelium.

[0018] FIG. 1B illustrates an embodiment of the device 100 of FIG. 1A, further comprising an inner body 160 having a distal end adapted to penetrate the endometrial epithelium. In this embodiment, the inner body 160 is shown positioned in the lumen 120 of the body 110. The plunger 165 is housed within the inner body 160 and configured to advance toward the distal end of the inner body 160 when actuated by the second actuator 195 to release a fertilized egg located inside the inner body 160. The covering layer 170a may at least partially cover the distal opening 150, and the inner body 160 may be configured to penetrate the covering layer 170a when the inner body 160 is advanced from the distal opening of the body, such that the inner body 160 may be advanced from the distal opening 150 through the covering layer 170a to penetrate the endometrial epithelium. As used herein, the term "perforate" is understood to mean to pierce to form a hole in the covering layer 170a. In other words, the portion of the covering layer 170a to be perforated is free of holes, slits or gaps through which mucus or other fluids may enter prior to perforation.

[0019] FIG. 1C shows a perspective view of another device 100 suitable for delivering a fertilized egg or embryo to a maternal endometrium, comprising 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. FIG. 1D and FIG. 1E show a side view and a front view of a distal portion of the device 100 shown in FIG. 1C. The body 110 comprises one or more lumens, including a lumen 120 extending from a proximal end 130 of the body 110 to a distal portion 140 of the body 110 and 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 penetrating the endometrial epithelium. The device 100 further comprises a measurement assembly comprising a measurement portion 170 disposed at the distal portion 140 of the body 110 (i.e., proximal to the distal opening 150). The measuring 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., in the direction in which the inner body advances from the distal opening 150) or in 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 device 100 further comprises an indicating device 180 coupled to the measuring assembly 170 via a connection extending through the lumen 175 and configured to indicate that the measuring assembly 170 is in the first state or the second state. The measuring assembly may be removable from the body 110. In particular, the measuring portion 170 may be slidably received within a lumen of the body such that it can be extracted from the body 110 through the lumen, meaning that the measuring assembly may be reusable. The inner body 160 and the measuring assembly may be received in the same or different lumens. The device 100 also includes a first actuator 190 operable to advance the inner body 160 at least a predetermined distance from the distal opening 150 of the body 110, and a second actuator 195 operable to expel the fertilized egg from the inner body (e.g., advance the plunger 165). The covering layer 170a at least partially covers at least one of the distal openings of the lumen.When the covering layer 170a covers the distal opening of the lumen 175 and thus the measuring portion 170, the covering layer prevents exposure of the measuring portion 170 to mucus when the measuring assembly is removable from the device (i.e., in embodiments where the measuring assembly is not fixedly attached to the inner lumen 175 and is removable), and enhances its reusability.

[0020] In some embodiments, the measurement portion 170 is a camera proximal to the opening 150 and configured to view a portion of the endometrial epithelium.

[0021] Covering layer 170a preferably comprises a biocompatible transparent or translucent film, more preferably comprising or consisting of polyether block amide (PEBAX), polyolefin, PVC, paraffin, cellulose and derivatives, hyaluronic acid thin film, parylene C film, collagen, gelatin, vegetable casing, alginate or composites or combinations thereof. Covering layer 170a is expected to reduce the clarity of the image of the endometrial epithelium, but in practice provides a clearer image than would be possible if mucus entered lumen 175 and obscured the camera.

[0022] The predetermined distance may be, for example, less than 6 mm. The inner body may be slidable to extend from the distal opening any suitable distance determined by the predetermined distance to the endometrial epithelium and the desired implantation depth of the embryo. For example, the inner body 160 may be slidable to extend from 0 to 6 mm from the distal opening 150 of the body 110.

[0023] The body 110 may be an elongated body made of any suitable flexible and biocompatible material, such as PTFE, FEP, PEEK, or other flexible lubricious material. The elongated body 110 and lumen may be formed, for example, by extrusion using known methods. The outer diameter of the body 110 may be 1 mm to 1.6 mm, more preferably 1.2 mm to 1.4 mm, and even more preferably 1.3 mm. The overall length of the body 110 may be any length suitable for insertion into a location close to the endometrial epithelium. For example, the body 110 may have a length of 400 mm to 500 mm, for example 450 mm.

[0024] The inner body 160 can be made from any suitable biocompatible material, such as PEEK and PI (polyimide). Such materials allow the wall of the inner body 160 to be relatively thin while maintaining the necessary stiffness of the inner body 160 to penetrate the endometrial epithelium. The inner body 160 can have any suitable outer diameter that slidably fits within the lumen 120 of the body 110. For example, the lumen 120 can have an inner diameter greater than 0.45 mm, and the outer diameter of the inner body can be about 0.45 mm.

[0025] The plunger 165 can also be made from materials such as PTFE, FEP, PEEK, or other flexible lubricous materials. The plunger 165 can have an appropriate diameter that closely matches the inner diameter of the inner body 160 to effectively aspirate or expel fluid from the inner body 160. For example, the inner diameter of the inner body and the diameter of the plunger 165 can be about 0.28 mm.

[0026] The measurement assembly can be any suitable measurement assembly that allows for a determination to be made whether the distance between the distal opening 150 of the body 110 and the endometrial epithelium is greater or less than a predetermined distance. It should be noted that the measurement assembly can provide a qualitative measurement (e.g., the measurement assembly can transition between two states) or a quantitative measurement (e.g., actually measuring a parameter indicative of a value of the distance to the endometrial epithelium and comparing the parameter to a threshold indicative of a predetermined distance). The measurement portion 170 is the part of the measurement assembly that is configured to interact with the endometrial epithelium in order for the measurement assembly to make a determination and can comprise any suitable elements. The elements of the measurement portion 170 can be connected to components of the measurement assembly (not shown) and components of the proximal end of the device 100, such as the indication device 180, via connections that extend through one or more lumens 175 in the body 110. For example, the measurement portion can comprise components optically, acoustically, or electrically connected to the proximal components of the measurement assembly, such as light or sound emitters or receivers, electrical signal components, or power sources. The measurement assembly may be any of the measurement assemblies disclosed in PCT Application No. PCT / EP2021 / 078712, the entirety of which is incorporated herein by reference.

[0027] The indicating device 180 is coupled (i.e., operatively coupled) to the measurement assembly as long as it is capable of determining the difference between two states of the measurement assembly. The indicating device 180 may be any suitable device capable of indicating the difference between two states. For example, if the measurement assembly provides a qualitative visual difference between the two states, the indicating device 180 may be a display (e.g., a scope display or a digital display) configured to display the visual difference to a user of the apparatus, or may comprise suitable software and / or hardware for receiving data (such as image data) from the measurement assembly and performing an analysis of the data to determine the state of the measurement assembly (or displaying the image data). The results of the analysis may be displayed. Alternatively, the measurement assembly may comprise software / hardware and provide the results of the analysis to the indicating device 180.

[0028] The indication provided by the indicating device 180 may be provided to a user of the apparatus 100 (e.g., a visual indication on a display or an audio indication from a speaker) if the first actuator 190 is manually actuated by the user, or may be provided as a command signal to an electronic controller (such as a motion controller disclosed herein) if the first actuator 190 is automatically actuated by the electronic controller. The indication provides a means for an operator or controller to confirm that the distal opening is sufficiently close to the endometrial epithelium to deliver a fertilized egg through the body.

[0029] The first and second actuators 190, 195 may be any suitable actuators controllable to advance the inner body 160 and expel the fertilized eggs. For example, the first actuator 190 may be a pusher or other manual tool for advancing the inner body, or may comprise a motor system configured to advance the inner body. Similarly, the second actuator 195 may be configured to slide a movable plunger within the inner body to pressurize the fluid within the inner body distally and expel the eggs. The second actuator may comprise a lead screw for advancing the plunger, i.e., the second actuator may be actuated by applying a torque, and the resulting rotational motion is translated into linear motion of the plunger. Rotary actuation of the lead screw allows for high controllability of the linear motion and therefore the amount of liquid aspirated and dispensed. The first and second actuators 190, 195 may be contained within a housing connected to the proximal end of the inner body 160 and the plunger 165.

[0030] Although Fig. 1D shows the measurement portion 170 and distal opening 150 of the body 110 at the distal tip of the body 110, in other embodiments, the measurement portion 170 and the distal opening of one or more lumens, such as the distal opening 150, may be located on the side of the distal portion 140 of the body 110, as shown in Fig. 1G. The lumen 120 includes a gradually curving portion proximal to the distal opening 150 of the body 110 to guide the inner body 160 laterally. A covering layer 170a may be provided at least partially on the sidewall of the body 110 to cover the one or more distal openings of the one or more lumens on the sidewall of the body 110.

[0031] FIG. 1C shows a measurement assembly comprising a measurement portion 170 disposed at the distal portion 140 of the body 110. In other embodiments, the measurement portion 170 may be located at a different location (e.g., at the distal portion of the inner body 160) or the measurement assembly may be configured to interact with elements of the device 100 to provide qualitative or quantitative measurements and may comprise any suitable elements without the need to have a measurement portion in the measurement assembly. This is shown in the embodiment of FIG. 1F, where the device 100 comprises an inner body 160 having a distal portion 161 including a distal end suitable for penetrating the endometrial epithelium. The device 100 further comprises a body 110 (e.g., a catheter) configured to fit within a lumen of the female reproductive system. The body comprises a lumen 120 extending from a proximal end 130 of the body 110 to a distal portion 140 of the body 110 and having a distal opening 150 at the distal portion 140 of the body. The lumen 120 is configured to slidably receive the inner body 160. The apparatus 100 of FIG. 1F further comprises a measurement assembly 162. The measurement assembly 162 is configured to measure whether the apparatus 100 is in a first state indicating that the distance between the distal end of the inner body 160 and the endometrial epithelium is greater than a predetermined distance (i.e., in the direction in which the inner body advances from the distal opening 150 of the body 110) or in a second state indicating that the distance between the distal end of the inner body 160 and the endometrial epithelium is equal to or less than the predetermined distance. The apparatus 100 of FIG. 1F further comprises an indication device 180 coupled to the measurement assembly 162 and configured to indicate that the apparatus 100 is in the first state or the second state. The apparatus 100 also comprises a first actuator 190 operable to advance the inner body 160 from the distal opening 150 of the body 110 and a second actuator 195 operable to expel the fertilized egg from the inner body (e.g., advance the plunger 165).

[0032] In an embodiment, the distal portion 161 of the inner body 160 is electrically conductive, and the measurement assembly 162 is configured to be in electrical contact with such distal portion 161 of the inner body 160. The measurement assembly thus provides an indication of capacitance. In an embodiment, a first state is indicated by a capacitance measurement below a threshold, and a second state is indicated by a capacitance measurement above the threshold. The covering layer 170a may cover the distal opening 150 to prevent mucus from entering the lumen 120 and affecting the capacitance measurement of the distal portion 161 as the inner body 160 is moved towards the distal opening 150. The inner body 160 is configured to pierce the covering layer 170a so that the inner body 160 can extend distally from the device 100 to penetrate the endometrial epithelium and implant a fertilized egg.

[0033] In certain embodiments, the capacitance varies according to a change in distance between the distal portion 161 of the inner body 160 and the endometrial epithelium, i.e., the capacitance value varies depending on the proximity of the distal portion 161 of the inner body 160 to the endometrial epithelium. In an embodiment, the predetermined distance is zero (thus implying contact between the distal portion 161 of the inner body 160 and the endometrial epithelium). In an embodiment, the capacitance value is measured by a measurement assembly 162 comprising an electrical system electrically connected to the distal portion 161 of the inner body 160 for measuring capacitance.

[0034] Use of the measurement assembly in combination with the indicating device assists in determining when the distal portion of the device is within a predetermined distance so that it can be advanced within the body into the endometrial epithelium to deliver the fertilized egg. In embodiments where the indication provides information regarding the distance between the distal portion of the body 110 and the endometrial epithelium, this can assist in avoiding direct contact between the distal portion of the body 110 and the endometrial epithelium. Furthermore, premature extension of the inner body 160 into the uterus while the device is still in place can cause damage to the inner body 160. Thus, the indicating device assists in identifying when it is appropriate to extend the inner body 160 from the device.

[0035] In embodiments in which the indication provides information regarding the distance between the distal end of the inner body 160 and the endometrial epithelium, use of the measurement assembly in combination with the indicating device assists in determining when the distal end of the inner body is within a predetermined distance such that the inner body can advance further into the endometrial epithelium to deliver a fertilized egg and / or such that the inner body is in a position to deliver a fertilized egg. Thus, the indicating device assists in identifying when it is appropriate to deliver a fertilized egg.

[0036] In one embodiment, the device 100 of Figs. 1A-1F further comprises an imaging device, not shown, in particular a camera (i.e. in addition to or separate from the measurement assembly). In an embodiment, the camera is attached to the body 110 and moves with said body 110 as an integral device. In a particular embodiment, the camera is housed within the body 110. Fig. 1H shows a perspective view of a distal portion of the device 100 comprising a camera 171 and an inner body 160 slidably received within a single lumen 120. Thus, the camera 171 may be removable and sterilizable for multiple uses among multiple devices 100. The device of Fig. 1H may comprise all of the features shown in Fig. 1F with the addition of the camera 171 provided in the same lumen 120. It may comprise one or more light sources (not shown) for illuminating the area in front of the camera 171 to be imaged. The one or more light sources may be located proximal to the camera to avoid glare in the image captured by the camera 171. Covering layer 170a covers distal opening 150 of lumen 120. Camera 171 may be provided on elongated body 172 that includes a longitudinal recess for receiving inner body 160. Camera 171 may be connected to a display device (not shown) for displaying the field of view of camera 171 via an electrical connection extending through elongated body 172.

[0037] 1J shows a schematic side view of body 110, which may be the body 110 described above in connection with FIGS. 1A-1H and may form part of device 100 as described above. Body 110 may include a covering layer 170a that partially or completely covers a distal end of body 110, including one or more distal openings. Lumen 120 (see FIG. 1L) extends through body 110, which may be configured to slidably or fixably receive a camera, such as camera 171 and inner body 160 described in connection with FIG. 1H. At the proximal end of body 110, body 110 may include first and second branches 109a, 109b, each having a proximal opening. The lumen 120 branches towards the proximal end of the body 110 to form two lumens, one extending along the first branch 109a and the other extending along the second branch 109a, such that the lumen 120 can be accessed through a proximal opening of either the first or second branch 109a, 109b. The body 110 may be made of any suitable material and have any suitable length, particularly those materials and lengths described above in relation to Figures 1A-1H. The body 110 may be a single piece or may be formed from several pieces connected by any suitable method, such as adhesive or welding. In some embodiments, the body 110 may comprise a distal portion 110b and a proximal portion 110a, each formed separately and joined together by welding or adhesive to form a unitary body defining the lumen 120 and the branches 109a, 109b.

[0038] The lumen of branch 109b may be configured to receive camera 171 as described in connection with FIG. 1H. In some embodiments, the lumen of branch 109b may include a guide, such as a protrusion, such that camera 171 may only be inserted into lumen 120 via branch 109a, such that elongated body 172 with a longitudinal recess is oriented in a predetermined direction within lumen 120. The proximal end of branch 109b may include a connector, such as a thread for connecting to a corresponding thread or luer lock on a housing at the proximal end of the camera, the housing including an electrical connection for connecting to an electronic cable for controlling camera 171 (e.g., for providing power to an imaging device and one or more light sources of camera 171 and receiving image data from camera 171). The lumen of branch 109a may be configured to receive inner body 160 as described in connection with FIGS. 1A-1H. The proximal end of the branch 109a may include a connector for connecting to a housing that houses the actuators 190 and 195. For example, the proximal end of the branch 109a may include threads configured to mate with corresponding threads on the housing or a luer lock. Thus, the inner body 160 and plunger 165 may be inserted into the body 110 via the branch 109a and secured to the body 110 by the housing that houses the actuators 190 and 195. The inner body 160 and plunger 165 may be advanced and retracted relative to the body 110 by actuating the actuators 190 and 195 as described herein.

[0039] FIG. 1K illustrates a schematic side view of a stylet 121 for one or more embodiments of a device, such as the device 100 described in connection with FIGS. 1A-1J. The stylet comprises an elastic elongate element 123 (e.g., a wire or ribbon) configured to slidably extend through the body 110. The elongate element 123 is made of an elastically deformable material that can provide stiffness to the body 110 when it is initially inserted through the cervix during an embryo transfer procedure. For example, the elongate element 123 can be made of a material such as Nitinol or stainless steel. The elongate element 123 can have a rounded tip 123a to reduce damage or breakage of the inner wall of the body 110 that defines the lumen 120 when the stylet 121 is inserted into the body 110. In some embodiments, the stylet can comprise a handle 122 adapted to be gripped by a user during insertion into the body 110. The handle 122 may be connected at its distal end to the elongate element 123, for example, by adhesive, welding, or a friction fit. The handle may include a connector 122a at its distal end for connecting to the proximal end of the body 110. For example, the connector 122a may include threads configured to mesh with threads on the proximal end of the body 110 (e.g., the proximal end of one of the branches 109a, 109b) and may include a luer lock or other suitable mechanism (such as a friction fit). Thus, the stylet 121 may be secured to the body 110 during insertion through the cervix and then detached from the body 110.

[0040] 1L shows a schematic cross-sectional side view of stylet 121 inserted into lumen 120 of body 110. Elongate element 123 may have a length that is less than the length of lumen 120 such that distal tip 123a of stylet 121 does not reach the distal end of body 110 when stylet 121 is fully inserted into body 110 and fixedly connected to body 110 (e.g., by threads, luer lock, or friction fit). In embodiments in which body 110 includes covering layer 170a, this prevents covering layer 170a from being punctured by stylet 121 as body 110 is advanced through the cervix. For example, in some embodiments, the length of elongate body 123 may be such that distal tip 123a is at least 5 mm proximal of the distal end of body 110 when fully inserted.

[0041] FIG. 2A illustrates a system 101 for delivering a fertilized egg or embryo to the maternal endometrium in a human or any other mammalian species. The system 101 comprises a body 160 having a distal end 162 adapted to penetrate the endometrial epithelium. The system 101 further comprises a plunger 165 slidably received in the lumen of the body 160 and an actuator 195 operable to advance the plunger 165 to expel the fertilized egg from the lumen of the body 160. The actuator 195 may be any suitable actuator for advancing and retracting the plunger 165, or may be a manual actuator, such as a proximal end of the plunger 165 that remains accessible to a user when the system 101 is inserted into a lumen of the female reproductive system. The actuator 195 may be any of the actuators disclosed herein, or may be a lead screw rotatable to advance and retract the plunger 165 as disclosed in connection with FIGS. 6A-6H. The system 101 further comprises a first injectable medium 111 and a second injectable medium 112 for containing the fertilized eggs. The first injectable medium 111 has a higher viscosity than the second injectable medium 112.

[0042] The first injectable medium 111 may be any suitable biocompatible injectable medium having a higher viscosity than the second injectable medium 112. The second injectable medium 112 may be any injectable medium that is biocompatible and non-toxic to the fertilized egg, as known in the art. It may be appreciated that the lower limit of the viscosity of the first injectable medium 111 depends on the viscosity of the selected second injectable medium 112. In some embodiments, the first injectable medium 111 includes or consists of one or more of hyaluronic acid, salts of hyaluronic acid, biocompatible hydrogels, poloxamers, collagen, fibrinogen, gelatin, sodium hyaluronate, and combinations thereof. The use of hyaluronic acid may promote repair of the endometrial epithelium at the site of perforation of the endometrial epithelium by the body 160.

[0043] In some embodiments, a third injectable medium 113 is also provided that also has a higher viscosity than the second injectable medium 112. The third injectable medium 113 may be of the same or different viscosity as the first injectable medium 111 and may include or consist of the same or different substances as the first injectable medium 111. In some embodiments, the third injectable medium 113 includes or consists of one or more of hyaluronic acid, salts of hyaluronic acid, biocompatible hydrogels, poloxamers, collagen, gelatin, fibrinogen, sodium hyaluronate, and combinations thereof.

[0044] The first infusible medium 111 and the second infusible medium 112 (and optionally the third infusible medium 113) may be provided in a medium reservoir (e.g., a vial or the like), and a user may manually load the infusible medium into the system 101 by inserting the body 160 into the reservoir and retracting the plunger 165 to draw each infusible medium into the lumen of the body 160. In some embodiments, the infusible medium may be pre-loaded into the body 160.

[0045] In one embodiment, the first injectable medium 111 and the second injectable medium 112 are received (i.e., pre-loaded) within the lumen of the body 160, with the second injectable medium 112 positioned forward of the first injectable medium 111 relative to the distal end 162 of the body 160 such that the second injectable medium 111 is released before the first injectable medium 112 when the actuator 195 is actuated to release the fertilized egg. Figure 2C illustrates such an arrangement. As will be described in more detail below in connection with Figure 2E, the first injectable medium 111 acts as a plug to prevent the second injectable medium from being released from the endometrial epithelium E.

[0046] In one embodiment, the first injectable medium 111, the second injectable medium 112, and the third injectable medium 113 are received (i.e., preloaded) within the lumen of the body 160, and the second injectable medium 112 is received between the first and third injectable mediums 111, 113 such that when the actuator 195 is actuated to release the fertilized eggs, the second medium 112 is released before one of the first and third injectable mediums 111, 113 and after the other of the first and third injectable mediums 111, 113. Figure 2D illustrates such a configuration. As will be described in more detail below in connection with Figure 2E, the first injectable medium 111 acts as a plug to prevent the second injectable medium from being released from the endometrial epithelium E, and the third injectable medium 113 provides additional structural support to maintain the second injectable medium 112 containing the fertilized eggs at the desired injection location within the endometrial epithelium E.

[0047] The system 101 shown in FIG. 2A (and in any of the configurations shown in any of FIG. 2A-2D) may be provided as shown in FIG. 2A or may be incorporated into any suitable embryo transfer system. For example, the body 160 may be slidably received through a delivery catheter positionable within a lumen of the female reproductive system. The system 101 may optionally be incorporated into any of the embryo transfer systems disclosed herein. In particular, the body 160 shown in FIG. 2A-2D may be the inner body 160 shown in any of FIG. 1B-1H and may further comprise a body 110 (also referred to as an outer body) configured to fit within a lumen of the female reproductive system, the body 110 comprising an outer lumen 120 extending from a proximal end 130 of the body 110 to a distal portion 140 of the body 110 and having a distal opening 150 at the distal portion 140 of the body 110, the lumen 120 configured to slidably receive the body 160 (also referred to as an inner body). The system may further include an actuator 190 operable to advance the inner body 160 out of the distal opening 150 of the outer body 110 .

[0048] A method of incorporating the system 101 of FIG. 2A (whether incorporated into the system described in connection with FIGS. 1B-1H or any other embryo transfer system) may be as follows: In a first step, a first injectable medium 111 may be drawn into the lumen of the body 160. In particular, the body 160 may be inserted into a reservoir containing the first injectable medium 111, and the actuator 195 may be actuated to retract the plunger 165 to draw the first injectable medium 111 into the lumen of the body 160 (FIGS. 2A-2B). In a second step following the first step, a second injectable medium 112 may be drawn into the lumen of the body 160. In particular, the body 160 may be inserted into a reservoir housing the second injectable medium 112, and the actuator 195 may be actuated to retract the plunger 165 to draw the second injectable medium 112 into the lumen of the body 160 (FIGS. 2B-2C). In some embodiments, in a third step following the second step, the third injectable medium 113 may be drawn into the lumen of the body 160. In particular, the body 160 may be inserted into a reservoir housing the third injectable medium 113, and the actuator 195 may be actuated to retract the plunger 165 to draw the third injectable medium 113 into the lumen of the body 160 (FIGS. 2C-2D).

[0049] It should be noted that the system 101 may be delivered to the endometrial epithelium E in either of the uptake states shown in Figures 2C and 2D and the actuator 195 may be actuated to deliver the first and second injectable medium 111 and 112 to the endometrial epithelium E. Figure 2E shows the injectable medium 111, 112 and optionally the injectable medium 113 inside the endometrial epithelium E after injection by the system 101. It has been found that if the system is removed from the endometrial epithelium E after injection, the endometrial epithelium E exerts an expulsion force F on the injected material and there is a risk that the injectable medium 112 will be released from the endometrial epithelium E immediately after injection, risking failure of the fertility treatment procedure. By providing the first injectable medium 111 at the location shown in Figure 2B, the first injectable medium 111 can become the outermost portion of the injected material in the endometrial epithelium E, as shown in Figure 2E, and provides a high viscosity plug that better resists the ejection force F, thus reducing the risk of the endometrial epithelium E expelling the second injectable medium 112 from the endometrial epithelium E. In an embodiment in which a third injectable medium 113 is used, by providing the third injectable medium 113 at the location shown in Figure 2D, the third injectable medium 112 can become the innermost portion of the injected material in the endometrial epithelium E, as shown in Figure 2E. Thus, the first and third injectable media 111, 113 provide a pocket within the endometrial epithelium E within which the second injectable medium 112 is positioned, and the first and third injectable media 111, 113 provide structural support on either side of the pocket to prevent the transmission of forces such as the ejection force F or any inward pressure from the surrounding tissue to be transmitted to the second injectable medium 112, thereby further enhancing the stability of the injected material when positioned within the endometrial epithelium E.

[0050] 1A-2E, the inner body 160 may include a hydrophobic coating formed on a distal portion of the inner body 160. The hydrophobic coating may be formed on one, both, or all of the inner surface 164 of the distal portion of the inner body 160, the distal tip 163 of the inner body 160, and the outer surface 166 of the distal portion of the inner body 160. Alternatively or additionally, the inner body 160 may include a beveled tip 163.

[0051] The beveled tip 163 aids in piercing the covering layer if one is provided covering the distal opening of the lumen that contains the inner body 160. Additionally, the beveled tip 163 reduces the force required to penetrate the endometrial epithelium.

[0052] The hydrophobic coating may include or consist of a polymer or polymer composite, preferably parylene, acrylic, polyethylene, polyurethane, and polytetrafluoroethylene, and any of their composites. The hydrophobic coating prevents the attachment of a fertilized egg or embryo to the distal portion of inner body 160 (e.g., causing the embryo or egg to not be released in the first place or to be removed from the endometrial epithelium along with inner body 160), thus reducing the risk of failure of the egg or embryo implantation procedure.

[0053] FIG. 4 shows a diagram of an indication device 180 that may be used in any of the apparatuses disclosed herein that include a measurement assembly when the output of the measurement assembly is a signal (e.g., when the measurement assembly includes a distance measuring probe such as a camera and / or a capacitance sensor). The indication device includes a device interface 1100 configured to communicate with the measurement assembly (i.e., to send and receive signals). The indication device further includes a memory 1110, a processor 1120, and an indicator 1130. It can be understood that any suitable computing system may be used for the indication device 180, and the device shown in FIG. 4 is one of many devices that may be used. For example, a distributed computer system may be used, for example including one or more server or client computing systems, using any known distributed computing technique. In some examples, a general purpose computer or any other processing system may be used to implement the methods disclosed herein. Furthermore, the steps disclosed below may be implemented in software, hardware, or any combination thereof to accomplish the same steps.

[0054] It may be understood by those skilled in the art that the pointing device of Fig. 4 may be powered by any suitable power supply means. The memory 1110 may include one or more volatile or non-volatile memory devices, such as DRAM, SRAM, flash memory, read-only memory, ferroelectric RAM, hard disk drive, floppy disk, magnetic tape, optical disk, etc. Similarly, the processor 1120 may comprise one or more processing units, such as a microprocessor, GPU, CPU, multi-core processor, etc. The device interface 1100 may include a wired connection, such as optical, fiber optic, Ethernet, or any suitable wireless communication.

[0055] If the measurement assembly performs quantitative measurements (e.g., comprises a distance detection probe), the memory 1110 may include appropriate instructions for performing a comparison of the received signal to a predetermined distance, and the processor 1120 may be configured to execute the instructions. For example, the indication device 180 may receive the raw data signal via the device interface 1110, and the processor 1120 may convert the raw data to a numerical value of the predetermined distance, which may be compared to the predetermined distance. If the numerical value is equal to or less than the predetermined distance, the processor 1120 may instruct the indicator 1130 to indicate that the predetermined distance has been reached. For example, the indicator 1130 may provide an audio or visual signal to an operator, or may comprise an electronic controller configured to provide a command signal to an electronic motion controller to perform the operation of advancing the needle and expelling the embryo (the memory 1110 includes appropriate instructions for providing a control signal to the actuator). The indication device 180 may also be configured to further indicate to the user when the automated procedure of advancing the needle and expelling the embryo is completed (e.g., audio or visual signal). Alternatively, the indicator 1130 may comprise a display that displays the measured distance along a predetermined distance.

[0056] For a measurement assembly with a camera, where the measurement is a qualitative measurement, the indication device may be a display for displaying a real-time image captured by the camera, and may optionally display a comparison overlay on the display. Alternatively, the memory 1110 may store instructions for performing image analysis of the image data to automatically determine whether the image indicates that a predetermined distance has been reached. The processor 1120 may be configured to execute the instructions. The processor 1120 may then instruct the indicator 1130 to indicate that the predetermined distance has been reached. For example, the indicator 1130 may provide an audio or visual signal to the operator, or may provide a command signal to an electronic control motion controller to perform the action of advancing the needle to release the embryo.

[0057] 4 shows the motion controller and pointing device as separate devices, the pointing device and the motion controller may be incorporated into a single device, and alternatively, the measurement assembly may be indirectly connected to the pointing device via a device interface of the motion controller.

[0058] FIG. 5 shows a diagram of a computer 1200 that may be used to control one or more of the actuators disclosed herein. The computer 1200 may comprise one or more of a controller 1210, a processor 1220, a user interface 1230, a display 1240, a network connection 1245, a device interface 1250, and a memory 1255 that stores instructions for a program 1260 and a data repository 1270. Any suitable computing system may be used for the computer 1200, and it may be understood that the device shown in FIG. 5 is one of many devices that may be used. For example, a distributed computer system may be used, for example comprising one or more server or client computing systems, using any known distributed computing technique. In some examples, a general purpose computer or any other processing system may be used to implement the methods disclosed herein. Furthermore, the steps disclosed below may be implemented in software, hardware, or any combination thereof to accomplish the same steps.

[0059] It may be understood by those skilled in the art that the pointing device of Fig. 5 may be powered by any suitable power supply means. The memory 1255 may include one or more volatile or non-volatile memory devices, such as DRAM, SRAM, flash memory, read-only memory, ferroelectric RAM, hard disk drive, floppy disk, magnetic tape, optical disk, etc. Similarly, the processor 1220 may comprise one or more processing units, such as a microprocessor, GPU, CPU, multi-core processor, etc. The device interface 1250 may include a wired connection, such as optical, fiber optic, Ethernet, or any suitable wireless communication.

[0060] The device interface 1250 is configured to communicate (i.e., send and receive control information) with one or more electronically controlled actuators. Any of the actuators disclosed herein can be electronically controlled. The device interface 1250 may also be configured to communicate with a pointing device 180. Alternatively, the computer 1200 may comprise all the features of the pointing device shown in FIG. 4 and may itself be considered as the pointing device 180.

[0061] The computer 1200 provides manual control of the electronically controlled actuators by a user of the device. For example, the memory 1255 may include instructions for a program 1260 that, when executed by the processor 1220, causes a graphical user interface (GUI) to be displayed on the display 1240 or remotely via a network connection 1245. The GUI may include appropriate inputs that allow a user to actuate one or more of the actuators. For example, a user may select a function from the GUI, which causes the controller 1210 to send corresponding control signals to one or more actuators to perform that function.

[0062] For example, the user may select a command from the GUI to advance the body a certain distance or at a certain constant speed. The user may select one or more commands to operate the steering mechanism. The user may select one or more commands to advance the inner body and / or the plunger. The commands may correspond to a sequence of commands, such that several commands are executed in sequence. For example, the memory 1255 may store instructions to advance the body 110 until a predetermined distance is reached (i.e., until the indicating device indicates that the predetermined distance has been reached), and then advance the inner body and plunger to expel the embryo. It is possible that all actuators are actuated via such an automated process, or that only some are actuated automatically and the rest are actuated manually (i.e., by user control via the GUI).

[0063] The computer 1200 can be configured to receive data from the measurement assembly directly or via the pointing device 180 and display the data in a GUI along with command options. For example, the display 1240 can display real-time image data received from the measurement assembly. The GUI can also display an indication to the user that a predetermined distance has been reached.

[0064] In some embodiments, the device may further comprise a motion controller configured to connect to a proximal portion of the body 100, the controller configured to actuate the first actuator, the second actuator, and / or the fourth actuator to advance the body relative to the motion controller. Any suitable motion controller may be used. For example, the motion controller may comprise one or more linear or rotary mechanisms for actuating the first actuator, the second actuator, and / or the fourth actuator. In some embodiments, one or more of the first, second, and fourth actuators may comprise a lead screw, each lead screw rotatable to advance the body 110, the inner body 160, or the plunger 165, and the motion controller may be configured to actuate the one or more lead screws. The motion controller may be manually or electronically controlled. The motion controller may be configured to connect to the body via a connector.

[0065] 6A shows a cross-sectional perspective view of the connector 1300 configured to connect to a motion controller 1350. FIG 6E shows an exploded view of the connector 1300. The connector 1300 comprises a connector housing 1310 insertable into a distal end of the motion controller 1350. The connector 1300 also comprises a body connector 1314 that fixedly receives a proximal portion of the body 110 (e.g., by friction fit or by adhesive), an inner body connector 1324 that fixedly receives a proximal portion of the inner body 160 (e.g., by friction fit or by adhesive), and a plunger connector 1332 that fixedly receives a proximal portion of the plunger 165 (e.g., by friction fit or by adhesive).

[0066] The body connector 1314 is received by the connector housing 1310 and is slidable relative to the connector housing 1310 in a fixed rotational orientation. For example, the connector housing 1310 may include a longitudinally extending protrusion or recess, and the body connector 1314 may include a corresponding recess or protrusion such that the body connector 1314 is receivable into the connector housing 1310 in only a single rotational orientation. The connector 1300 further includes a body lead screw 1316 having male threads 1320 that correspond to the female threads 1312 of the connector housing 1310. The body lead screw 1316 abuts the body connector such that rotating the body lead screw 1316 to advance the body connector 1314 distally also advances the body connector 1314 distally (but in a fixed orientation). In the illustrated embodiment, the body lead screw 1316 is connected to the body connector 1314 by one or more protrusions 1318 that are received by corresponding recesses 1322 in the body connector. The interaction between the protrusions 1318 and the recesses 1322 means that the body lead screw 1316 abuts the body connector 1314 as it slides both distally and proximally, meaning that the body lead screw 1316 can advance and retract the body connector 1314 and therefore the body 110. In some embodiments, the protrusions 1318 may instead be located in recesses in the body connector 1314 and body lead screw 1316.

[0067] The inner body connector 1324 is received in the body connector 1314 and is slidable relative to the connector housing 1310 and the body connector 1314. In some embodiments, the inner body connector 1324 may be slidable relative to the connector housing 1310 and the body connector 1314 in a fixed rotational orientation (e.g., using corresponding protrusions and recesses in the body connector 1314 and the inner body connector 1324 as previously disclosed).

[0068] 6B shows a close-up view of the inner body connector 1324 and plunger connector 1332 shown in FIG. 6A. The connector further comprises an inner body lead screw 1328 having external threads 1326 that correspond to the internal threads 1327 of the body connector 1314. The inner body lead screw 1328 abuts the inner body connector 1324 such that rotating the inner body lead screw 1328 to advance the inner body lead screw 1328 distally also advances the inner body connector 1324 distally. In the illustrated embodiment, the inner body lead screw 1328 is connected to the inner body connector 1325 by one or more protrusions 1325 that are received by corresponding recesses in the inner body connector 1324. The interaction between the protrusions 1325 and the recesses means that the inner body lead screw 1328 abuts the inner body connector 1324 as it slides both distally and proximally, meaning that the inner body lead screw 1328 can advance and retract the inner body connector 1324 and therefore the inner body 160. In some embodiments, the protrusions 1325 may instead be located in recesses in the inner body connector 1324 and the inner body lead screw 1328. In some embodiments, the inner body connector 1324 and the inner body lead screw 1328 may be a single unitary body.

[0069] The plunger connector 1332 is received in the inner body connector 1324 and is slidable relative to the connector housing 1310, the body connector 1314, and the inner body connector 1324. In some embodiments, the plunger connector 1332 may be slidable relative to the connector housing 1310, the body connector 1324, and the inner body connector 1332 in a fixed rotational orientation (e.g., using corresponding protrusions and recesses in the inner body connector 1324 and the plunger connector 1332 as previously disclosed). The connector further comprises a plunger lead screw 1336 having external threads 1333 that correspond to the internal threads 1334 of the inner body connector 1324. When the plunger lead screw 1336 abuts the plunger connector 1332 and rotating the plunger lead screw 1336 to advance the plunger lead screw 1336 distally also advances the plunger connector 1332 distally. In the illustrated embodiment, the plunger lead screw 1336 is connected to the plunger connector 1336 by one or more protrusions 1335 in the plunger connector 1332 that are received by corresponding recesses in the plunger connector 1332. The interaction between the protrusions 1335 and the recesses means that the plunger lead screw 1336 abuts the plunger connector 1332 when sliding in both distal and proximal directions, which means that the plunger lead screw 1336 can advance and retract the plunger connector 1332, and therefore the plunger 165. In some embodiments, the protrusions 1335 may instead be located in recesses in the plunger lead screw 1336 and the plunger connector 1332. In some embodiments, the plunger connector 1332 and the plunger lead screw 1336 may be a single unitary body.

[0070] The connector 1300 may include an interlocking mechanism 1340, such as a luer lock, at its distal end to secure the distal end of the connector 1300 to the next distal component of the device.

[0071] 6C shows a perspective view of the proximal end of the connector 1300. FIG. 6D shows a perspective view of the distal end of the motion controller 1350. The proximal end of the connector 1300 is configured to connect with the distal end of the motion controller 1350. The body lead screw 1316 includes a toothed proximal end 1360 configured to engage with a body lead screw drive 1352 of the motion controller 1350. The inner body lead screw 1328 includes a toothed proximal end 1362 configured to engage with an inner body lead screw drive 1354 of the motion controller 1350. The plunger lead screw includes a toothed proximal end (not shown) configured to engage with a plunger lead screw drive 1356 of the motion controller 1350. The proximal end of the connector housing 1310 may further include a locking mechanism, such as a protrusion 1364 configured to be received by a recess in a distal end of a motion controller (not shown) to prevent relative rotation between the distal end of the motion controller 1350 and the connector housing 1310. The connector 1300 may be connected to the motion controller 1350 by a push-fit, click-fit, friction fit, or similar mechanism. The lead screw drives 1352, 1354, and 1356 may be biased distally by a spring 1358 (see FIG. 6A ) to ensure engagement with the proximal ends of the lead screws during rotation.

[0072] While the illustrated embodiment shows a connector that actuates the body connector, inner body connector, and plunger connector by a lead screw mechanism, it can be understood that in other embodiments, the connector only actuates one or more of the body connector, inner body connector, and plunger connector by a lead screw mechanism. For example, the connector may only include a body connector 1314 that is actuated by a body lead screw 1316 as described above, and the needle and plunger may be actuated differently (i.e., by a linear motion mechanism). It can also be understood that the outermost threads of a given embodiment engage with the inner threads 1312 of the connector housing 1310. For example, in an embodiment where the connector 1300 only actuates the inner body 160 and plunger 165 by the disclosed thread mechanism, the outer threads 1326 of the inner body lead screw 1328 engage with the inner threads 1312 of the connector housing 1310, but not with the inner threads of the body connector 1314.

[0073] The connector housing 1310, the connectors 1314, 1324, and 1332, and the lead screws 1316, 1328, and 1336 may be made from any suitable material, such as plastic, and may be molded or 3D printed. Similarly, the lead screw drives 1352, 1354, and 1356 may be made from any suitable material, such as plastic.

[0074] The electrical wiring and / or optical fiber extending from the measuring portion 170 through the body 110 from the distal end of the device may terminate in the connector 1300. In particular, a proximal portion of the electrical wiring extending from the distal end of the device through the body 110 may be electrically connected to an electrical terminal of the connector. The motion controller may comprise a corresponding electrical terminal biased toward the electrical terminal of the connector to maintain contact with the electrical terminal of the connector. Similarly, a proximal portion of the optical fiber may be optically connected to an optical terminal of the connector 1300, and the motion controller may comprise an optical terminal configured to form a face seal with the optical terminal of the connector 1300 and biased toward the optical terminal of the connector 1300 to maintain a face seal with the first optical terminal.

[0075] 6F shows a perspective view of the connection between the body connector 1314 and the distal end of the motion controller 1350. The illustrated embodiment shows a proximal portion of the electrical cable 312 extending from the measurement portion (e.g., the camera 171) through the body 110 to the connector 1300. The cable 312 is electrically connected (e.g., by soldering) to an electrical terminal (such as a printed circuit board) on the body connector 1314. The electrical terminal comprises an electrical connection configured to engage an electrical pin 1374 of the motion controller 1350. The electrical pin 1374 is biased distally such that an electrical connection between the pin 1374 and the electrical terminal of the body connector 1314 is maintained as the body connector 1314 advances through the connector housing 1300. It can be appreciated that an optical connection between the connector 1300 and the motion controller 1350 can be established and maintained as well.

[0076] 6G shows a perspective view of a proximal portion of the motion controller 1350. The motion controller 1350 comprises a first motor 1381, a second motor 1383, and a third motor 1385. In one embodiment, the first motor 1381 may be configured to drive the body lead screw drive 1352, the second motor 1383 may be configured to drive the inner body lead screw drive 1354, and the third motor may be configured to drive the plunger lead screw drive 1356. The motion controller 1350 may be configured to advance / retract the body 110, inner body 160, and plunger 165 at the same speed by actuating the first, second, and third motors 1381, 1383, 1385 in unison at speeds corresponding to the same advancement speeds of the body 110, inner body 160, and plunger 165. The motion controller 1350 may also be configured to advance / retract the inner body 160 and plunger 165 at the same speed relative to the body 110 by actuating the second and third motors 1383, 1385 in unison at speeds that correspond to the same advancement speed of the inner body 160 and plunger 165. The motion controller 1350 may also be configured to advance / retract the plunger 165 relative to the inner body 160 by actuating only the third motor 1385.

[0077] Alternatively, the first motor 1381 may be configured to rotate each lead screw drive 1352, 1354, 1356 (e.g., via a first threaded rod) to advance the lead screws 1316, 1328, 1336 at the same speed (to advance the body 110, inner body 160, and plunger 165 at the same speed). The second motor 1383 may be configured to rotate the inner body lead screw drive 1354 and the plunger lead screw drive 1356 (e.g., via a second threaded rod) to advance the inner body lead screw 1328 and the plunger lead screw 1336 at the same speed (to advance the inner body 160 and plunger 165 at the same speed). The third motor 1386 may be configured to rotate the plunger lead screw drive 1356 (e.g., via a threaded rod) to advance the plunger 165.

[0078] The motion controller 1350 may further include an axial motor (not shown) for retracting the plunger lead screw drive 1352 before connecting or disconnecting the connector 1300 to prevent damage to the plunger lead screw drive 1352 during connecting or disconnecting the connector 1300.

[0079] The connector 1300 can be assembled in the following steps (the steps are not necessarily performed chronologically in the order described): A proximal portion of the plunger 165 can be secured to the plunger connector 1332. The plunger connector 1332 can be connected to the plunger lead screw 1336 (e.g., the connector and lead screw are pressed together until a protrusion drops into a recess to secure the connector and lead screw together). A proximal portion of the inner body 160 can be connected to the inner body connector 1324. The inner body connector 1324 can be connected to the inner body lead screw 1328 (e.g., by pressing the connector and lead screw together until a protrusion drops into a recess to secure the connector and lead screw together). A proximal portion of the body 110 can be connected to the body connector 1314. The body connector 1314 can be connected to the body lead screw 1316 (e.g., by pressing the connector and lead screw together until a protrusion drops into a recess to secure the connector and lead screw together). The distal end of the plunger 165 can pass through the inner body 160 from the proximal end through the inner body connector 1324. The plunger lead screw 1336 can be threaded into the inner body connector 1324. The distal end of the inner body 160 can pass through the body connector 1314 from the proximal end into the body 110. The inner body lead screw 1328 can be threaded into the body connector 1314. The distal end of the body can pass through the connector housing 1310 from the proximal end. The body lead screw 1316 can be threaded into the connector housing 1310. The lead screws can then be actuated to move the body 110, inner body 160, and plunger 165 into the correct relative positions.

[0080] Once the connector 1300 is assembled, the plunger lead screw 1336 can be actuated to aspirate the fluid containing the embryos. The connector 1300 is then connected to a motion controller 1350.

[0081] The length from the proximal end of the body connector 1314 to the distal tip of the body 110 can be about 300mm to 400mm, preferably 325mm to 375mm, e.g., 358mm. The maximum length of the connector 1300 from the proximal end to the distal tip of the body 110 can be about 400mm to 500mm, preferably 425mm to 475mm, e.g., 450mm.

[0082] FIG. 6H shows a perspective view of a motion controller 1350 according to an embodiment. The motion controller 1350 is configured to connect to a proximal portion of the body 110 and act on said body 110. In the embodiment shown in FIG. 6H, the motion controller 1350 comprises two lead screws 1351, 1353 configured to advance / retract the body 110 and, in an embodiment, to rotate and advance / retract an outer catheter that houses the body 110. In the embodiment shown, the motion controller 1350 further comprises three actuation mechanisms 1357, 1359, 1361, each actuation mechanism configured to act on one of the lead screws 1351, 1353. Actuation of the lead screws 1351, 1353 may be manual or motorized. In this embodiment, two lead screws 1351, 1353 are shown, but in other embodiments, there may be only one lead screw depending on the element intended to be moved by the motion controller 1350. The motion controller 1350 allows for precise and accurate control of the movement of the body 110 and the outer catheter that houses it, as well as fixing the outer catheter in a required position. In an embodiment, the motion controller 1350 can be actuated based on real-time images captured by an imaging device, such as a camera, present in the apparatus 100.

[0083] 7A shows a side cross-sectional view of a device 700a for engaging a speculum (also referred to as a speculum lock). The device 700a comprises two or more expandable engagement elements 710 for externally engaging a speculum to secure the device to the speculum, the two or more expandable engagement elements 710 comprising multiple extension configurations for engaging multiple speculum sizes. The device 700a comprises a guide 705 for guiding an embryo delivery device through the speculum between the engagement elements 710 when the device 700a is secured to the speculum. In particular, the guide 705 at least partially conforms to an outer surface of the embryo delivery device to allow longitudinal (i.e., x-direction) movement of the embryo delivery device through the guide and prevent lateral (i.e., y-direction) movement of the embryo delivery device within the guide. The guide 705 may comprise a tubular body 701 having a tubular wall 702 defining a lumen 705 for slidably receiving the embryo delivery device, the cross-sectional shape of the inner surface of the tubular wall 702 at least partially conforming to the outer surface of the embryo delivery device to allow longitudinal movement of the embryo delivery device through the guide and prevent lateral movement of the embryo delivery device within the guide. The embryo delivery device may be a body 110 incorporated into any of the apparatus for delivering a fertilized egg described in connection with Figures 1A-6H.

[0084] The expandable engaging element 710 may be coupled to the tubular body 701. The engaging element 710 may be expandable using any suitable mechanism. For example, the device 700a may include one or more biasing elements, such as springs, connected between the tubular body 701 and the engaging element 710 to bias the engaging element 710 to the expanded configuration. The engaging element 710 may be maintained in the collapsed configuration by a sheath or cover that covers the engaging element 710. The engaging element 710 may be inserted into the speculum, and the sheath or cover may be removed (e.g., retracted) from the engaging element 710, thereby biasing the engaging element 710 to the expanded configuration and engaging both sides of the speculum, and the device 700a is secured to the speculum. Other mechanisms, such as a motor connected to the engaging element 710, may be used to move the engaging element between the collapsed configuration and one or more expanded configurations. In some embodiments, the engaging elements 710 may be attached to the guides 705 via respective scissor lifts 745. The scissor lift 745 may comprise one or more pairs of struts pivotally connected to one another, with one strut pivotally mounted to the guide 705 (e.g., tubular body 701) and respective engagement element 710, and the other strut slidably mounted to the guide 705 (e.g., tubular body 701) and respective engagement element. Longitudinal compression of the scissor lift 745 translates to lateral movement of the engagement element 710 to move to the expanded configuration. The device 100 may comprise one ratchet actuator 746 slidably mounted to the guide 705 and configured to move the scissor lift 745 between a plurality of positions corresponding to a plurality of expanded configurations of the expandable engagement element 710. The ratchet actuator 746 comprises a plurality of teeth (not shown) that mesh with respective teeth on the guide 705 to allow movement in the distal direction D but not in the opposite direction. The device 700a may further include a release mechanism (not shown) for releasing the ratchet mechanism (i.e., disengaging the teeth) and allowing movement in a proximal direction opposite the distal direction D, and thus movement from the extended configuration to the collapsed configuration.

[0085] In some embodiments, guide 705 may include a first bifurcated guide 725 and a second bifurcated guide 730 at its proximal end that define respective lumens 707, 708 that branch off from lumen 706. Bifurcated guides 725 and 730 allow separable components of the embryo transfer device (e.g., the measurement assembly and inner body) to be inserted separately through device 700a or 700b while moving as a unit when device 700a or 700b is moved to position the embryo transfer device within the uterus.

[0086] The expandable engagement element 710 of FIG. 7A may be straight, as shown, or may include any of the features of the engagement element 710 disclosed in connection with FIGS. 7B and 7C.

[0087] FIG. 7B shows a perspective view of another device 700b (also referred to as a speculum lock) for engaging a speculum in a collapsed configuration. FIG. 7C shows the device 700b of FIG. 7B in an expanded configuration. Again, the device 700b comprises two or more expandable engagement elements 710 for externally engaging a speculum to secure the device 700b to the speculum, the two or more expandable engagement elements 710 comprising multiple expanded configurations for engaging multiple speculum sizes. The device further comprises a guide 705 for guiding an embryo delivery device through the speculum between the expandable engagement elements 710 when the device 700b is secured to the speculum. The guide 705 may comprise a tubular body 701 having a tubular wall defining a lumen for slidably receiving the embryo delivery device, the cross-sectional shape of the inner surface of the tubular wall 702 at least partially conforming to the outer surface of the embryo delivery device to allow longitudinal movement of the embryo delivery device through the guide and prevent lateral movement of the embryo delivery device within the guide.

[0088] The engaging elements 710 may be expandable using any suitable mechanism such as those described in connection with FIG. 7A. In the illustrated embodiment, the engaging elements 710 may be attached to the guide 705 via respective scissor lifts 745. The scissor lifts 745 may comprise one or more pairs of struts pivotally connected to one another, one strut pivotally attached to the guide 705 (e.g., tubular body 701) and respective engaging elements 710, and the other strut slidably attached to the guide 705 (e.g., tubular body 701) and respective engaging elements. The device 700b comprises a proximal portion 735 and a distal portion 740 that are slidably connected. In the illustrated embodiment, the proximal portion 735 is slidably received within a lumen of the distal portion 740. One strut of each scissor lift 745 is pivotally attached to the proximal portion 735, and the other strut is pivotally attached to the distal portion 740. As the proximal and distal portions 735, 740 are moved relative to one another, the scissor lift is actuated to move the expandable engagement element between various expanded configurations. The device 700b also includes a ratchet actuator 750 that includes a plurality of teeth on the proximal portion 740 that engage with respective teeth on the distal portion 740 to allow relative movement of the proximal portion 735 relative to the distal portion 740 in one direction but not in the opposite direction. The device 700a may further include a release mechanism (not shown) to release the ratchet mechanism (i.e., disengage the teeth) and allow opposite movement of the proximal portion 735 relative to the distal portion 740, and thus from the expanded configuration to the folded configuration. It can be appreciated that the direction of relative movement of the proximal and distal portions 735, 740 that moves the engagement element 710 to the expanded position depends on which struts are pivotally attached to which portions. In the illustrated embodiment, the struts are attached such that movement of the proximal portion 735 in the distal direction D causes the engagement elements to move outwardly to the expanded configuration.

[0089] In some embodiments, one or more of the expandable engagement elements 710 comprise struts 712 movable between a folded configuration (as shown in FIG. 7A) and a plurality of expanded configurations (as shown in FIG. 7B). The struts 712 may be straight as shown in FIG. 7A and may have an outer portion 711, an inner portion 713 having a smaller radial extent than the outer portion 711, and a middle portion 712 connecting the outer portion 711 and the inner portion 713. The struts of the scissor lift 745 are rotatably / slidably attached to the inner surface of the outer portion 711. In any of the embodiments, the expandable engagement element 710 may further comprise a friction layer 715 attached to the struts 712 and made of a material having a higher coefficient of friction than the struts 712. The struts 712 provide structural support for the engagement element while the friction layer provides a contact area for the speculum. Struts 712 may be made of, for example, metal, and friction layer 715 may be made of any suitable material having higher friction. As seen in FIG. 7B, the use of outer portion 711 and inner portion 713 allows the components of device 700b outside of the speculum to be more compact, while reducing the radial profile of the distal end of device 700b ready for insertion into the speculum.

[0090] Device 700b may include one or more branches at its proximal end. In the illustrated embodiment, device 700b includes first and second branch guides 725 and 730 at its proximal end that define respective lumens branching from the lumen of tubular body 701.

[0091] The device 700b may also include a connection mechanism 724, such as a luer lock or stub fit connection, at the distal end of the guide 705 for connection to the proximal end of other components of the embryo delivery apparatus, such as the steering mechanism disclosed in Figures 9A-H. The device 700b may further include a handle 720 secured to the distal portion 740.

[0092] In use, a speculum may be inserted into the vagina to dilate the vagina. The embryo delivery device may pass through the device 700a or 700b, through the speculum, and through the cervix. The engagement element 710 may be expanded to an expanded configuration such that the device 700a or 700b is secured to the speculum. As a result, the embryo delivery device limits movement relative to the patient's anatomy, allowing for greater control of the embryo delivery device.

[0093] FIG. 8A shows a device 700c for engaging with a speculum. The device 700c comprises two or more expandable engagement elements 710 for externally engaging a speculum to secure the device to the speculum, the two or more expandable engagement elements 710 comprising multiple extension configurations for engaging multiple speculum sizes. The device 700c comprises a guide 705 for guiding an embryo delivery device through the speculum between the engagement elements 710 when the device 700c is secured to the speculum. In particular, the guide 705 has a configuration that at least partially conforms to an outer surface of the embryo delivery device to allow longitudinal (i.e., x-direction) movement of the embryo delivery device through the guide and prevent lateral (i.e., y-direction) movement of the embryo delivery device within the guide. In some embodiments, the guide 705 has an open configuration in which the embryo delivery device is released, as shown in FIG. 8A. FIG. 8B shows a side view of the device 700c in the same configuration as shown in FIG. 8A.

[0094] The device 700c comprises a first half 760a and a second half 760b pivotally connected by a pivot joint 761 about which the halves 760a and 760b articulate. Each half 760a, 760 comprises a handle 762a, 762b and an expandable engagement element 710 for externally engaging a speculum, with each respective handle 762a, 762b connected to a respective expandable engagement element 710 via a lever 770a, 770b. In the illustrated embodiment, the expandable engagement element 710 is connected to the handles 762a, 762b and the pivot joint 761 such that when the handles 762a, 762b move together the expandable engagement element 710 moves apart and when the handles 762a, 762b move apart the expandable engagement element 710 moves together. In other embodiments, the expandable engagement element 710 may be connected to the handles 762a, 762b in a scissor arrangement, such that when the handles 762a, 762b move together the expandable engagement element 710 moves together and when the handles 762a, 762b move apart the expandable engagement element 710 moves apart. Although the handles 762a, 762b are shown as loops, the handles may take any suitable shape without departing from the scope of the invention.

[0095] The device 700c may include a ratchet mechanism 763 configured to allow the handles 762a, 762b to move in a direction that moves the engagement elements 710 apart and prevents the handles 762a, 762b from moving in the opposite direction. In the illustrated embodiment, the ratchet mechanism 763 includes sets of teeth 764a, 764b on each half 760a, 760b configured to engage with one another such that movement of the handles 762a, 762b together engages the sets of teeth to prevent movement of the handles 762a, 762b apart. The teeth 764a, 764b may be disengaged by displacing the handles 762a, 762b in distal and proximal directions, respectively (i.e., in a direction perpendicular to the teeth 764a, 764b) to allow the handles 762a, 762b to move apart.

[0096] In the embodiment of Fig. 8A, the guide 705 comprises opposing side walls 765a, 765b each shaped to at least partially conform to an exterior surface of an embryo delivery device. The side wall 765a is connected to one of the halves 760b via a flexible arm 766a, and the side wall 765b is connected to the other of the halves 760a via a flexible arm 766b. The side wall 765a is connected to the halves 760a, 760b such that the side walls 766a and 766b move towards each other when the engagement element 710 moves away from each other. The flexible arms 766a, 766b may be made of any suitable elastically deformable material such that the flexible arms 766a, 766b are configured to bend when the side walls 765a, 765b abut each other. This allows the expandable engagement element 710 to move through a range of positions even when side walls 765a, 765b abut one another, thereby allowing a wider range of speculum sizes to be engaged by device 700c.

[0097] The device 700c may further comprise a guide locking mechanism 767 having a first configuration in which the guide locking mechanism 767 disengages from the guide 705 and a second configuration in which the guide locking mechanism 767 engages and grips the guide 705. In the illustrated embodiment, the guide locking mechanism 767 comprises a grip pivotally connected to one of the side walls 765a, 765b. The grip is movable to a closed configuration that covers both side walls 765a, 765b and exerts a compressive force on the guide 705 such that the embryo delivery device is securely gripped. The guide 705 may be provided proximal to the expandable engagement element 710 such that movement of the grip is not impeded by the expandable engagement element 710 (see FIG. 8B). In the illustrated embodiment, the guide locking mechanism 767 is a rotatable grip, however, in other embodiments, the guide locking mechanism 767 may be any suitable mechanism operable to apply a compressive force to the guide 705, such as a clip, clamp, or screw mechanism configured to compress the guide 705.

[0098] The device 700c can generally be made of any suitable material, such as a resilient plastic (e.g., a thermoplastic polymer, such as polycarbonate, or the like) or a metal (e.g., stainless steel, brass) or a combination thereof. The engaging element 710 may be provided with a frictional coating having a higher coefficient of friction than the material of the device 700c, such as silicone rubber, to increase the frictional force exerted by the engaging element 710 on the speculum. Similarly, the inner wall of the guide 705 (i.e., the radially inner surface of the side walls 766a, 766b) may be provided with a frictional coating having a higher coefficient of friction than the material of the device 700c, such as silicone rubber, to increase the friction between the embryo delivery device and the guide 705. In the case of a deformable material, such as silicone rubber, the coating may further provide flexibility to conform to the particular shape of the speculum and embryo transfer device.

[0099] 8C shows the device 700c in a second configuration in which the expandable engagement element 710 is moved to an expanded configuration to engage a speculum. The side walls 765a, 765b are moved to a closed configuration forming a lumen for engagement with an embryo delivery device. The guide lock mechanism 767 is in a disengaged configuration to allow sliding movement of the embryo delivery device in a proximal or distal direction (i.e., toward or away from the endometrial wall).

[0100] 8D illustrates the device 700c in a third configuration in which the expandable engagement element 710 remains in the expanded configuration and engages the speculum, and further in which the guide locking mechanism 767 engages the guide 705 and applies a compressive force to the guide 705. In this configuration, sliding movement of the embryo delivery device is prevented by the compressive force applied by the guide locking mechanism 767.

[0101] In use, a speculum may be inserted into the vagina to dilate the vagina. The device 700c in the first configuration of FIG. 8A may be positioned such that the expandable engagement element 710 is inserted into the speculum and the body 110 (e.g., the body shown in FIG. 1J) is positioned approximately within the side walls 765a, 765b. The device 700c may then be moved to the second configuration shown in FIG. 8C. In the second configuration, the expandable engagement element 710 engages the inside of the speculum such that the device 700c is secured to the speculum. Furthermore, the side walls 765a, 765b abut each other to form a lumen for receiving and fitting the body 110, thus forming a guide 705 that prevents lateral movement of the body 110 but allows sliding movement of the body 110. A device such as the body 110, optionally with a stylet 121 inserted therein, may then be inserted through the guide 705 and through the cervix to a preliminary position.

[0102] Note that in some embodiments, body 110 (with or without stylet 121) may be initially inserted through the vagina and into the uterus through the cervix after a speculum has been inserted through the vagina, but before device 700c is inserted into the speculum. After successful insertion of body 110, device 700c may be inserted into the speculum in a first configuration shown in FIG. 8A. Device 700c may then be moved to a second configuration shown in FIG. 8C, with body 100 held between sidewalls 765a, 765b, until device 700c engages the speculum and body 100.

[0103] Once the device 700a is locked to the speculum and the body 110 is correctly positioned within the uterus, the guide lock mechanism 767 may then be moved to a closed position to prevent further sliding movement of the body 110. The stylet 121 may be removed from the body 110. A camera 171 may be inserted into the body 110 and connected to a display device and power source so that a user can view a real-time image of the distal end of the body 110. If necessary, the guide lock mechanism 767 may be released to adjust the insertion depth of the body 110 until the tip of the body 110 is determined to be close to the fundus, and then the guide lock mechanism 767 may be closed again to prevent sliding movement of the body 110. The inner body 160 loaded with the fertilized egg or embryo may then be inserted into the body 110, and the actuator 190 may advance the inner body 160 into the endometrial epithelium. Once it is determined that the inner body 160 has reached the endometrial epithelium (e.g., by observing a change in capacitance measured by a capacitance sensor electrically connected to the inner body 160), the inner body 160 is advanced a predetermined distance into the endometrial epithelium and the plunger is advanced to deploy the fertilized egg or embryo.

[0104] It should be noted that devices 700a, 700b and 700c may be used in conjunction with any suitable tertiary device for insertion into the body through a speculum, in addition to an embryo transfer device.

[0105] FIG. 9A illustrates a side view of a steering mechanism configured to manipulate a distal portion of the body 110, according to some embodiments. The steering mechanism comprises a plurality of connected rings 910 forming a tube wall configured to at least partially surround a portion of the body 110. Specifically, the rings 910 are sized to receive the body 110 inside the tube wall and can slidably receive the body 110. The mechanism further comprises at least one cable 920 extending longitudinally along the tube wall and attached to a distal end 930 of the tube wall. For example, the at least one cable may extend longitudinally along the inside or outside of the tube wall or may extend longitudinally through the tube wall. The mechanism can comprise a plurality of said cables disposed at different circumferential positions around the tube wall. The connected rings 910 may be connected only by the cable 920. The connected rings 910 may be further configured to maintain a predetermined alignment by comprising a set of interlocking mechanisms that prevent the rings 910 from rotating about the longitudinal axis. The steering mechanism shown in FIG. 9A comprises a number of connected rings 910 that can rotate about each other. In other words, the connected rings are undulating such that adjacent rings abut at tangential contact points. This allows the rings 910 to rotate relative to each other to steer the body 110 when one of the cables 920 is retracted by a third actuator (not shown). The circumferential positions of the tangential contact points about which the rings 910 roll may vary along the length of the steering mechanism. For example, successive circumferential contact points may be offset by 90 degrees to accommodate rotation in two perpendicular directions by the multiple cables. Preferably, the steering mechanism comprises two pairs of said cables, each pair comprising diametrically opposed cables to provide steering in multiple directions. Such an arrangement is shown in FIG. 9C, which is a plan view of such a steering mechanism.

[0106] The connected rings shown in FIG. 9A can be made from any suitable material, such as medical grade injection moldable or 3D printed plastic resins, such as ABS, PET, DELRIN or PTFE. The cables 920 can be made, for example, from stainless steel and threaded through holes formed in the walls of the connected rings that form the tube wall. The cables 920 each extend through a pair of holes in the connected rings and may be looped at the distal end 930 as shown in FIGS. 9A and 9C. The third actuator can be any suitable actuator for contracting one or more cables.

[0107] FIG. 9B shows a side view of a steering mechanism according to another embodiment. The steering mechanism comprises a plurality of connected rings 915 forming a tube wall configured to at least partially surround a portion of the body 110. Specifically, the rings 915 are sized to receive the body 110 inside the tube wall and can slidably receive the body 110. The mechanism further comprises at least one cable 920 extending longitudinally through the tube wall and attached to a distal end 930 of the tube wall. The plurality of connected rings 910 are rings of compressible tubes or springs. When one of the cables is retracted by a third actuator (not shown), the tube or spring is compressed on the side of the retracted cable, thereby manipulating the steering mechanism towards the contracted side. Because the tubes are compressible, tension is partially counteracted, so that the resulting curvature of the mechanism shown in FIG. 9B can be smaller than the embodiment shown in FIG. 9A for a given tension. Again, preferably the steering mechanism comprises two pairs of said cables, each pair comprising diametrically opposed cables, to provide steering in multiple directions, as shown in FIG. 9C.

[0108] The connected rings shown in Figure 9B may be compressible tubes or springs made of any suitable material, such as FEP, PTFE, etc. The cables may be made of any suitable material, such as stainless steel and threaded through holes formed in the walls of the connected rings that form the tube walls. The cables 920 each extend through a pair of holes in the connected rings and may be looped at the distal end 930 as shown in Figures 9A and 9C. The third actuator may be any suitable actuator for contracting one or more cables.

[0109] FIG. 9D shows a side view of the steering mechanism when one of the cables is retracted such that the steering mechanism is steered in the direction indicated by arrow 925.

[0110] FIG. 9E shows a perspective view of a third actuator according to some embodiments. FIG. 9F shows a perspective view of the third actuator shown in FIG. 9E, with the outer shell 950 shown as transparent. The third actuator comprises an inner element 940 and an outer shell 950 that houses the inner element 940. Each of the at least one cable 920 is fixed to the outer shell at a proximal portion 960, for example by welding, adhesive, or around a fixed winch. The inner element 940 is fixedly connected to the tube wall 910, either directly or indirectly through one or more intermediate components. The outer shell 950 is rotatable relative to the inner element 940. Optionally, a handle 970 may be fixed to the inner element 940 via the outer shell 950. Rotating the outer shell 950 around the inner element 940 retracts one of the cables 920, manipulating the tube wall in a particular direction as previously described. The body can extend through the handle 970 and inner element 940 so that it can be advanced through a steering mechanism.

[0111] FIG. 9G shows a perspective view of the inner element according to some embodiments. The inner element 940 can comprise one or more components biased to abut against the outer shell 950. For example, the inner element 940 can comprise two hemispheres 942a, 942b biased away from each other to abut against the inner surface of the outer shell 950. The bias creates a friction fit between the inner element 940 and the outer shell 950 so that they can only slide relative to each other when sufficient force is applied, which means that once the desired orientation of the steering mechanism is achieved, it can be maintained in place by a third actuator. The inner element can be connected to the handle via a handle connector 946 and to the tube wall via an intermediate section 948. The intermediate section 948 can be incompressible and the cable 920 can be threaded through the intermediate section to the tube wall.

[0112] FIG. 9H shows a perspective view of the steering mechanism according to some embodiments, with the outer shell 950 shown as partially transparent. The steering mechanism of FIG. 9H also comprises an inner element 940 and an outer shell 950 housing the inner element 940 and rotatable relative to the inner element 940, as previously described. The steering mechanism may also comprise a handle 970. Furthermore, each of the cables 920 is fixedly connected to the outer shell via a winch 952 (i.e., the cables are wound on the winch). The winch can be wound or unwound using an adjuster 954 (e.g., a flat head adjuster) accessible from the outside of the outer shell 950, which means that the default tension of each cable 920 can be calibrated after assembly of the steering mechanism. The ring 910 forming the tube wall may be fixedly connected to the inner element 940 via a non-flexible tubular intermediate body 958. The tubular intermediate body 958 may be of any suitable length. For example, in embodiments in which an outer catheter is used, the tubular intermediate body 958 may be configured to extend through any inflexible portion of the outer catheter.

[0113] The cables 920 can extend through channels 956 formed in the inner surface of the outer shell 950, thus avoiding contact with the inner element 940 and avoiding damage to the cables as the outer shell rotates relative to the inner shell 940. The cables 920 may extend from the channels 956, through lumens formed in the wall of the tubular intermediate body 958, and to the tube wall.

[0114] The outer shell 950, inner element 940, handle 970, winch 952 and tubular intermediate body 958 can be made from medical grade injection moldable or 3D printed plastic resins such as ABS, PET, DELRIN or PTFE.

[0115] The steering mechanism may alternatively be electronically controlled. For example, the steering mechanism shown in FIG. 9H may comprise an electronic controller secured to the inner element 940 and comprising a motor for actuating movement of the outer shell 950 relative to the inner element 940. Alternatively, the steering mechanism may comprise a plurality of connected rings forming a tube wall configured to at least partially surround a portion of the body, and at least two opposing cables extending longitudinally through the tube wall and attached to a distal end of the tube wall, the cables being connected to a motor configured to retract the cables to steer the steering mechanism.

[0116] The tube wall of the steering mechanism is sized to slidably receive the body 110. The outer diameter of the tube wall can be about 1.4 mm to 1.8 mm, or about 1.5 mm to 1.7 mm, e.g., 1.6 mm. In embodiments where a steering mechanism is used, the body 110 may be configured to advance about 20 mm to 40 mm, e.g., about 30 mm, beyond the end of the steering mechanism.

[0117] The proximal end of the steering mechanism may be configured to connect with a distal end of the speculum lock 700a or 700b. For example, the steering mechanism may include a connection mechanism configured to connect with a corresponding connection mechanism on the speculum lock 700a or 700b, such that the guide 705 and the steering mechanism define a continuous lumen through which the body 110 slidably extends.

[0118] FIG. 10 shows a perspective view of the device 1 comprising an elongate body, which may be the inner body 160 in any of the embodiments disclosed herein. The device 1 comprises an elongate body 2 (e.g., a needle) comprising a distal tip 4 and a lumen 3 extending therethrough to an opening 6 at the distal tip 4, the lumen 3 being configured to receive and expel a fertilized egg or embryo 5 (hereafter referred to as an "egg" for brevity) through the opening 6. A plunger (not shown) is slidably received within the lumen 3. The distal tip 4 is configured to puncture the maternal endometrium and comprises a first surface 4a that is inclined relative to a longitudinal axis of the elongate body 2. The distal tip 4 further comprises a puncturing portion at its most distal end, which is a double-beveled puncturing portion comprising first and second surfaces 4b and 4c that are inclined relative to the first surface 4a to form a sharp edge at the distal end of the distal tip 4. In use, the plunger can be retracted in a proximal direction opposite the distal tip 4, thereby creating a suction force on the distal tip 4, which can be used to position the egg 5 in the lumen 3. The egg 5 is typically positioned in the lumen with fluid in the lumen 3 proximal to the egg 5. To implant the egg 5 in the endometrium, the elongated body 2 is advanced distally to penetrate the endometrium using the piercing distal tip and expel the fluid and egg 5 in the lumen 3. The egg 5 is generally pushed distally by pressure transmitted from the plunger via the fluid. However, when the egg 5 reaches the most distal portion of the elongated body 2, a gap is formed at the opening 6 as shown in FIG. 10, which means that the fluid contained in the lumen 3 can escape the lumen via the fluid path F so that the fluid is expelled without applying pressure to the egg 5. Thus, in some cases, the egg 5 may remain attached to the distal tip 4 even after the plunger has been fully advanced and the fluid has been fully expelled. This reduces the chances of successful implantation as the egg 5 may be expelled or removed from the endometrium when the elongate body 2 is removed.

[0119] FIG. 11 shows a schematic perspective view of a device 10 suitable for delivering a fertilized egg or embryo 50 (hereinafter referred to as "egg" for brevity) to a maternal endometrium, according to one or more embodiments. The device 10 comprises an elongate body 20 comprising a distal tip 40 and a lumen 30 extending therethrough to an opening 60 at the distal tip 40, which may be the inner body 160 in any of the embodiments disclosed herein. The lumen 30 is configured to receive and expel the egg 50 through the opening 60. The device 10 also 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, the opening 60 having a concave shape. The piercing portion may take any suitable shape and sharpness suitable for piercing the endometrium. In some embodiments, the piercing portion may comprise a point or edge having an edge radius of less than 2 μm, preferably less than 1 μm. The concave shape of the opening 60 reduces or eliminates the amount of fluid that can escape the lumen 30 without exerting pressure on the egg 50 at the distal end of the distal tip 40, thereby reducing the likelihood that the egg 50 will remain at the distal tip 40 when the fluid is fully expelled, which increases the likelihood of successful implantation.

[0120] 12A and 12B show different schematic side views of the device 10 shown in FIG. 11. In FIG. 12A, the concave shape of the opening 60 is shown relative to the shape of the opening 6 of the device 1. It can be seen that the available fluid path F shown in FIG. 10 is prevented by the concave shape of the opening 60. As shown in FIG. 12B, the piercing portion 70 may comprise a dual beveled tip with back-cut bevels for piercing the maternal endometrium. In particular, the piercing portion 70 may comprise first and second surfaces 72, 74 that are beveled relative to the outer surface of the elongated body 20, the beveled surfaces 72 and 74 forming a sharp edge 75 at the distal end of the distal tip 40.

[0121] 12A and 12B, the distally facing surface 84 of the distal tip 40 that defines 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 follows the spherical shape of the egg 50 when the egg 50 is at the distal end of the distal tip 40 such that the opening conforms to the shape of the egg 50 to prevent fluid path F from occurring. In a preferred embodiment, the radius of curvature R is 1.5 to 4 times the outer diameter D of the elongated body 20, which is believed to be optimal to prevent fluid path F from occurring for typical egg and embryo sizes.

[0122] 12A , preferably the curved concave shape extends between the piercing portion 70 and the lowest portion of the distal tip 40, which extends perpendicular to the longitudinal axis of the elongate body 20. This ensures that when the distal tip 40 is positioned at the distal end of the elongate body 20, the fluid path is minimized while maintaining contact between the distal tip and the egg 50.

[0123] 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 puncture portion 70 is 0.25 to 1.25 times the outer diameter D of the elongated main body 20, more preferably 0.5 to 1.25 times the outer diameter D of the elongated main body 20.

[0124] The distal tip may be made of a biocompatible metal, such as stainless steel.

[0125] In a preferred embodiment, the distal tip 40 includes a hydrophobic coating. The 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 any of parylene, acrylic, polyethylene, polyurethane, and polytetrafluoroethylene and composites thereof. The hydrophobic coating further reduces the likelihood that an egg 50 will remain on the distal tip 40 after the fluid has been expelled.

[0126] FIG. 13 shows a schematic side view of another device 10' according to one or more embodiments. The device may have any of the features disclosed in connection with FIGS. 11, 12A and 12B, except that the opening 60 of the device 10' does not have a curved concave shape. Instead of the curved concave shape shown in FIGS. 11, 12A and 11B, the opening 60 may have a concave shape formed by multiple planes. In the illustrated embodiment, the concave shape is formed by two planes, but it can be understood that the concave shape may be formed by any number of multiple planes. The concave shape of the opening 60 is again shown relative to the shape of the opening 6 of the device 1. It can be seen that the available fluid path F shown in FIG. 10 is prevented by the concave shape of the opening 60 of the device 10'.

[0127] FIG. 14A shows a schematic top view of device 200 according to one or more embodiments. FIG. 14B shows a side cross-sectional view of device 200 shown in FIG. 14A along line AA. Device 200 may include any of the features of devices (e.g., device 10 or 10') described herein. Piercing portion 70 includes first and second surfaces 72, 74 inclined relative to the outer surface of elongate body 20, where inclined surfaces 72 and 74 form a sharp edge 75 (double inclined tip) at the distal end of distal tip 40. Inclined surface 72 is defined by an inclination angle a 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. Inclination angle a is defined as the angle that a plane containing inclined surface 72 makes with a tangent to the surface of elongate body 20 at point 75. Draft angle β is defined as the angle that a plane containing inclined surface 72 makes with the longitudinal axis of elongated body 20. The inclination angle and draft angle of inclined surface 74 are similarly defined. The inclination 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 inclination angle and draft angle of inclined surfaces 72 and 74 may be the same (as shown) or different.

[0128] In a preferred embodiment, the diameter of the lumen 30 is 1 to 2 times the outer diameter of the egg to be implanted, and more preferably 1 to 1.5 times the outer diameter of the egg to be implanted.

[0129] In a preferred embodiment, the outer diameter of the elongated main body 20 is 1.5 to 3 times the diameter of the lumen 30, and more preferably 1.5 to 2 times the diameter of the lumen 30.

[0130] The following sections also form part of this disclosure:

[0131] 1. A system for delivering a fertilized egg or embryo to the maternal endometrium in humans or any other mammalian species, comprising: a body having a distal end adapted to penetrate the endometrial epithelium; a plunger slidably received within the lumen of the body; an actuator operable to advance the plunger to expel a fertilized egg from the lumen of the body; a first injectable medium; and a second injectable medium for containing the fertilized eggs; Equipped with A system in which the first injectable medium has a higher viscosity than the second injectable medium.

[0132] 2. The system of paragraph 1, wherein the first injectable medium comprises or consists of one or more of hyaluronic acid, a salt of hyaluronic acid, a biocompatible hydrogel, a poloxamer, collagen, fibrinogen, gelatin, sodium hyaluronate, and combinations thereof.

[0133] 3. The system of paragraphs 1 or 2, wherein the first injectable medium and the second injectable medium are received within a lumen of the body, and the second injectable medium is positioned forward of the first injectable medium relative to the distal end of the body such that when the actuator is actuated to release the fertilized egg, the second injectable medium is released before the first injectable medium.

[0134] 4. The system of any of paragraphs 1 to 3, further comprising a third injectable medium having a higher viscosity than the second medium, optionally the third injectable medium comprising or consisting of one or more of hyaluronic acid, a salt of hyaluronic acid, a biocompatible hydrogel, a poloxamer, collagen, fibrinogen, gelatin, sodium hyaluronate, and combinations thereof.

[0135] 5. The system of paragraph 4, wherein the first, second and third injectable media are all received within a lumen of the body, and the second injectable medium is received between the first and third injectable media such that when the actuator is actuated to release the fertilized egg, the second medium is released before one of the first and third injectable media and after the other of the first and third injectable media.

[0136] 6. The actuator operable to advance the plunger is a first actuator, the body is an inner body, and the system includes: an outer body configured to fit within a lumen of the female reproductive system, the outer body including an outer 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 outer lumen configured to slidably receive the body; a second actuator operable to advance the inner body out of the distal opening of the outer body; 6. The system of any one of items 1 to 5, further comprising:

[0137] 7. A method incorporating a system for delivering a fertilized egg or embryo to the maternal endometrium in a human or any other mammalian species, the system comprising: a body having a distal end adapted to penetrate the endometrial epithelium; a plunger slidably received within the lumen of the body; an actuator operable to advance the plunger to expel the fertilized egg from the lumen of the body; Equipped with The method is: Drawing a first infusible medium into the lumen; Thereafter, drawing a second injectable medium containing the fertilized eggs into the lumen; Including, A method wherein the first injectable medium has a higher viscosity than the second injectable medium.

[0138] 8. The method of paragraph 7, wherein the first injectable medium comprises or consists of one or more of hyaluronic acid, a salt of hyaluronic acid, a biocompatible hydrogel, a poloxamer, collagen, fibrinogen, gelatin, sodium hyaluronate, and combinations thereof.

[0139] 9. The method of paragraphs 7 or 8, further comprising the step of subsequently drawing a third injectable medium into the inner lumen of the inner body after the second injectable medium has been drawn into the inner lumen of the inner body.

[0140] 10. The method of paragraph 9, wherein the third injectable medium comprises or consists of one or more of hyaluronic acid, a salt of hyaluronic acid, a biocompatible hydrogel, a poloxamer, collagen, fibrinogen, gelatin, sodium hyaluronate, and combinations thereof.

[0141] 11. The actuator operable to advance the plunger is a first actuator, the body is an inner body, and the system includes: an outer body configured to fit within a lumen of the female reproductive system, the outer body including an outer 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 outer lumen configured to slidably receive the body; a second actuator operable to advance the inner body out of the distal opening of the outer body; 11. The method of any one of paragraphs 7 to 10, further comprising:

[0142] 12. A device suitable for delivering a fertilized egg or embryo to the maternal endometrium in a human or any other mammalian species, comprising a body configured to fit within a lumen of the female reproductive system, the body comprising: one or more lumens extending from a proximal end of the body to a distal portion of the body and having a distal opening at the distal portion of the body, a first lumen of the one or more lumens slidably receiving an inner body having a distal end adapted to penetrate an endometrial epithelium, the inner body comprising an inner lumen for receiving a fertilized egg; an actuator operable to release the fertilized eggs from the inner lumen; a covering layer at least partially covering a distal opening of at least one of the one or more lumens; An apparatus comprising:

[0143] 13. The device of paragraph 12, wherein the covering layer at least partially covers the distal opening of the first lumen, and the inner body is configured to perforate the covering layer when the inner body is advanced from the distal opening of the body.

[0144] 14. The device of paragraph 12 or 13, further comprising a measurement assembly, the measurement assembly extending through one of the one or more lumens 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 body or inner body and the endometrial epithelium is greater than a predetermined distance, or in a second state indicating that the distance between the distal end of the body or inner body and the endometrial epithelium is equal to or less than a predetermined distance, and the measurement portion is at least partially covered by a coating layer.

[0145] 15. The device of paragraph 14, wherein the measurement assembly includes a capacitance sensor in electrical contact with a distal portion of the inner body that is conductive and configured to provide an indication of capacitance, wherein a first state is indicated by a capacitance measurement value below a threshold and a second state is indicated by a capacitance measurement value above the threshold.

[0146] 16. The device of any of paragraphs 12 to 15, further comprising a camera proximal to the distal opening and configured to view a portion of the endometrial epithelium.

[0147] 17. The device of paragraph 16, wherein the covering layer covers the camera so that the camera is not exposed to mucus when the distal portion of the device is positioned within a lumen of the female reproductive system.

[0148] 18. The device of any of paragraphs 12 to 17, wherein the covering layer comprises a biocompatible transparent or translucent film, preferably the covering layer is a transparent or translucent film comprising or consisting of any of polyether block amides, polyolefins, PVC, paraffin, cellulose and derivatives, hyaluronic acid thin film, parylene C film, collagen, gelatin, vegetable casing, alginate, and complexes or combinations thereof.

[0149] 18a. The device of any of paragraphs 12 to 18, further comprising a stylet insertable into one or more lumens of the body, the stylet comprising a resilient elongate element configured to slidably extend through the body and provide increased rigidity to the body.

[0150] 18b. The device of paragraph 18a, wherein the stylet has a rounded distal tip.

[0151] 18c. The device of paragraphs 18a or 18b, wherein the stylet has a length that is shorter than the length of the body such that when the stylet is fully inserted into the body, the distal tip of the stylet is proximal to the covering layer.

[0152] 19. A device for engaging a speculum, comprising: two or more expandable engagement elements for externally engaging the speculum to secure the device to the speculum, the two or more expandable engagement elements having multiple expansion configurations for engaging multiple speculum sizes; a guide for guiding the tertiary device through the speculum between the expandable engagement elements when the device is secured to the speculum; 16. A device comprising:

[0153] 20. The device of paragraph 19, further comprising a tertiary device, the guide conforming at least partially to an outer surface of the tertiary device to allow longitudinal movement of the tertiary device through the guide and to prevent lateral movement of the tertiary device within the guide, and optionally, the tertiary device is an embryo delivery device.

[0154] 21. The device of paragraphs 19 or 20, further comprising first and second handles respectively connected to the first and second engagement elements, the handles being pivotally connected to one another such that movement of the handles in a direction about a pivot axis moves the engagement elements apart to the extended configuration.

[0155] 22. The device of clause 21, wherein the guide comprises a first side wall connected to the first handle and an opposing second side wall connected to the second handle, the side walls being connected such that movement of the handle in a direction about the pivot axis moves both of the engagement elements apart to an extended configuration and moves the side walls towards each other.

[0156] 23. The device of paragraphs 21 or 22, further comprising a ratchet mechanism configured to allow the handle to move in a direction to move the engagement elements apart and to prevent the handle from moving in the opposite direction.

[0157] 24. The device of any of paragraphs 19 to 23, further comprising a guide locking mechanism having a first configuration in which the guide locking mechanism is disengaged from the guide and a second configuration in which the guide locking mechanism grips the guide and applies a compressive force to the guide, thereby preventing longitudinal movement of the tertiary device through the guide.

[0158] 24a. Any of the devices of paragraphs 19 to 24, wherein an inner surface of the guide is at least partially coated with a frictional coating having a higher coefficient of friction than the inner surface of the guide, and / or one or more surfaces of the engagement element configured to engage with the speculum are at least partially coated with a frictional coating having a higher coefficient of friction than the outer surface.

[0159] 24b. The device of paragraph 24, wherein the friction coating is a deformable material, preferably silicone rubber.

[0160] 25. A device suitable for delivering a fertilized egg or embryo to the maternal endometrium in a human or any other mammalian species, comprising a body configured to fit within a lumen of the female reproductive system, the body comprising: a lumen extending from a proximal end of the body to a distal portion of the body and having a distal opening at the distal portion of the body, the lumen slidably receiving an inner body having a distal end adapted to penetrate the endometrial epithelium; Equipped with The device is a first actuator operable to advance the inner body from a distal opening of the body; a second actuator operable to expel the fertilized egg from the inner lumen of the inner body; Further comprising: The device, wherein the inner body includes a hydrophobic coating formed on a distal portion of the inner body.

[0161] 26. The device of paragraph 25, wherein the hydrophobic coating is provided on at least a distal portion of the inner surface of the inner body that defines the inner lumen.

[0162] 27. The device of paragraphs 25 or 26, wherein the hydrophobic coating is provided on the outer surface of the inner body and / or the distal tip.

[0163] 28. The device of any of paragraphs 25 to 27, wherein the inner body has a beveled tip.

[0164] 29. The device of any of paragraphs 25 to 28, wherein the hydrophobic coating comprises or consists of a polymer or polymer composite, preferably any of parylene, acrylic, polyethylene, polyurethane and polytetrafluoroethylene and composites thereof.

[0165] 30. The device of any of paragraphs 25 to 29, wherein the inner body has a distal tip, the inner lumen extends through the distal tip to an opening at the distal tip, the distal tip has a puncturing portion for puncturing the maternal endometrium, and the opening has a concave shape.

[0166] 31. The device of paragraph 30, wherein the opening has a curved concave shape having a radius of curvature.

[0167] 32. The device described in item 31, wherein the elongated body has an outer diameter, and the curved concave shape of the opening has a radius of curvature that is 1.5 to 4 times the outer diameter of the elongated body.

[0168] 33. The device of paragraph 31 or 32, wherein the curved concave shape extends between the puncturing portion and the lowest portion of the distal tip, and the lowest portion of the distal tip extends perpendicular to the longitudinal axis of the elongated body.

[0169] 34. A device suitable for delivering a fertilized egg or embryo to the maternal endometrium, comprising: an elongate body having a distal tip and a lumen extending through the distal tip to an opening at the distal tip, the lumen configured to receive and expel a fertilized egg or embryo through the opening; a plunger configured to be slidably received within the lumen; Equipped with A device wherein the distal tip comprises a piercing portion for piercing the maternal endometrium, the opening having a concave shape.

[0170] 35. The device described in clause 34, wherein the puncturing portion is equipped with a double beveled tip for puncturing the maternal endometrium.

[0171] 36. The device described in paragraph 35, wherein the double beveled tip has two beveled surfaces having a bevel angle of 20° to 40° and a draft angle of 1° to 20°.

[0172] 37. The device of any one of clauses 34 to 36, wherein the opening has a curved concave shape with a radius of curvature.

[0173] 38. The device described in item 37, wherein the elongated body has an outer diameter, and the curved concave shape of the opening has a radius of curvature that is 1.5 to 4 times the outer diameter of the elongated body.

[0174] 39. The device of paragraphs 37 or 38, wherein the curved concave shape extends between the puncturing portion and the lowest portion of the distal tip, and the lowest portion of the distal tip extends perpendicular to the longitudinal axis of the elongated body.

[0175] 40. The device described in paragraph 39, wherein the elongated body has an outer diameter, and the height of the distal tip measured from the lowest portion to the distal end of the puncture portion is between 0.5 and 1.25 times the outer diameter of the elongated body.

[0176] 41. The device of any one of clauses 34 to 40, wherein the distal tip is formed from a biocompatible metal, preferably stainless steel.

[0177] 42. The device of any one of clauses 34 to 40, wherein the distal tip is provided with a hydrophobic coating.

[0178] 43. The device of claim 42, wherein a hydrophobic coating is provided on at least one of the inner surface of the distal tip, the outer surface of the distal tip, and the distal-facing surface of the distal tip.

[0179] 44. The device according to paragraph 42 or 43, wherein the hydrophobic coating comprises or consists of a polymer or polymer composite, preferably parylene, acrylic, polyethylene, polyurethane and polytetrafluoroethylene, and any of their composites.

[0180] 45. The device according to any one of paragraphs 34 to 44, wherein the diameter of the lumen is 1 to 1.5 times the outer diameter of the egg to be implanted.

[0181] 46. ​​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 the proximal end of the body to a distal portion of the body and having a distal opening at the distal portion of the body, the lumen slidably receiving the inner body; Equipped with The device is a first actuator operable to advance the inner body from a distal opening of the body; a second actuator operable to advance the plunger to expel the fertilized eggs from the lumen of the inner body; 46. ​​The device of any one of claims 34 to 45, further comprising:

[0182] 47. The device described in clause 46, 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 being configured to measure whether the device is in a first state indicating that the distance between the distal end of the body or inner body and the endometrial epithelium is greater than a predetermined distance, or in a second state indicating that the distance between the distal end of the body or inner body and the endometrial epithelium is less than or equal to a predetermined distance.

[0183] 48. The device of clause 47, wherein the measurement assembly includes a capacitance sensor configured to be in electrical contact with the distal portion of the inner body.

[0184] All of the above are fully within the scope of the present disclosure and are not limited to the specific combinations disclosed above, but are considered to form the basis of alternative embodiments in which one or more combinations of the above features are applied.

[0185] In light of this, there are many alternatives for implementing the teachings of the present disclosure. It is expected that those skilled in the art can modify and adapt the above disclosure to suit their own circumstances and requirements within the scope of the present disclosure, while retaining part or all of the above disclosure or the technical effects derivable therefrom in light of the common general knowledge of those skilled in the art in the art. All such equivalents, modifications or adaptations are included within the scope of the present disclosure.

Claims

1. A device suitable for delivering a fertilized egg or embryo to the maternal endometrium in a human or any other mammalian species, comprising a body configured to fit into the lumen of the female reproductive system, the body being One or more lumens extending from the proximal end to the distal portion of the main body and having a distal opening in the distal portion of the main body, wherein the first lumen of the one or more lumens slidably receives an inner body having a distal end suitable for penetrating the endometrial epithelium, and the inner body comprises an inner lumen for receiving a fertilized egg, An actuator capable of releasing the fertilized egg from the inner lumen, A covering layer that at least partially covers the distal opening of at least one of the one or more lumens, Equipped with, The apparatus wherein the covering layer at least partially covers the distal opening of the first lumen, and the inner body is configured to perforate the covering layer when the inner body advances from the distal opening of the body.

2. The apparatus according to claim 1, further comprising a measuring assembly, the measuring assembly extending through one of the one or more lumens and having a measuring portion located proximal to the distal opening of the one or more lumens, the measuring portion being configured to measure whether the apparatus is in a first state indicating that the distance between the distal end of the main body or the inner body and the endometrial epithelium is greater than a predetermined distance, or in a second state indicating that the distance between the distal end of the main body or the inner body and the endometrial epithelium is less than or equal to a predetermined distance, and the measuring portion being at least partially covered by the covering layer.

3. The apparatus according to claim 2, wherein the measuring assembly comprises a capacitance sensor configured to electrically contact a distal portion of the conductive inner body and to provide an indication of capacitance, the first state being indicated by a capacitance measurement below a threshold, and the second state being indicated by a capacitance measurement above the threshold.

4. The apparatus according to claim 1, further comprising a camera located proximal to the distal opening and configured to view a portion of the endometrial epithelium.

5. The apparatus according to claim 4, wherein the covering layer covers the camera so that the camera is not exposed to mucus when the distal portion of the apparatus is positioned within the lumen of the female reproductive system.

6. The apparatus according to claim 1, wherein the coating layer comprises a biocompatible transparent or translucent film, preferably the coating layer is a transparent or translucent film comprising or composed of any of the following: polyolefin, PVC, paraffin, cellulose and derivatives, hyaluronic acid thin film, parylene C film, collagen, gelatin, plant casing, alginate and composites thereof.

7. A first actuator that can be operated to advance the inner body from the distal opening of the main body, A second actuator capable of releasing a fertilized egg from the inner lumen of the inner body, Furthermore, The apparatus according to claim 1, wherein the inner body is provided with a hydrophobic coating formed on the distal portion of the inner body.

8. The apparatus according to claim 7, wherein the hydrophobic coating is provided on at least the distal portion of the inner surface of the inner body that defines the inner lumen.

9. The apparatus according to claim 7, wherein the hydrophobic coating is provided on the outer surface and / or distal tip of the inner body.

10. The apparatus according to claim 7, wherein the inner body is provided with an inclined tip.

11. The apparatus according to claim 7, wherein the hydrophobic coating comprises or consists of a polymer or polymer composite, preferably parylene, acrylic, polyethylene, polyurethane, and polytetrafluoroethylene or composites thereof.

12. The apparatus according to claim 7, wherein the inner body has a distal tip, the inner lumen extends through the distal tip to the opening of the distal tip, the distal tip has a puncture portion for puncturing the maternal endometrium, and the opening has a concave shape.

13. The apparatus according to claim 12, wherein the opening has a curved concave shape having a radius of curvature.

14. The apparatus according to claim 13, wherein the elongated body has an outer diameter, and the curved concave shape of the opening has a radius of curvature of 1.5 to 4 times the outer diameter of the elongated body.

15. The apparatus according to claim 13, wherein the curved concave shape extends between the puncture portion and the lowest portion of the distal tip, and the lowest portion of the distal tip extends perpendicular to the longitudinal axis of the elongated body.

16. A system comprising the apparatus according to any one of claims 1 to 15 and a device for engaging with a microscope, Two or more expandable engagement elements for engaging with a microscope from the outside and securing the device to the microscope, the two or more expandable engagement elements having multiple expansion forms for engaging with multiple microscope sizes, When the device is fixed to the microscope, a guide for guiding the main body through the microscope between the expandable engaging elements, A system equipped with these features.

17. The system according to claim 16, wherein the guide fits at least partially to the outer surface of the body, enabling longitudinal movement of the body through the guide and preventing lateral movement of the body within the guide.

18. The system according to claim 16, further comprising first and second handles connected to first and second engaging elements, respectively, wherein the handles are rotatably connected to each other such that movement of the handles in the direction of a pivot causes the engaging elements to move apart to the extended form.

19. The system according to claim 18, wherein the guide comprises a first side wall connected to the first handle and an opposing second side wall connected to the second handle, the side walls being connected such that movement of the handle in the direction of the pivot causes both of the engaging elements to move apart to the extended form and the side walls to move toward each other.

20. The system according to claim 18, further comprising a ratchet mechanism configured to allow the handle to move in a direction that moves the engaging element apart and to prevent the handle from moving in the opposite direction.

21. The system according to claim 16, further comprising a guide lock mechanism, the guide lock mechanism having a first mode in which engagement with the guide is released, and a second mode in which the guide lock mechanism grips the guide and applies a compressive force to the guide, thereby preventing longitudinal movement of the main body through the guide.

22. The system according to claim 16, wherein the inner surface of the guide is at least partially coated with a friction coating having a higher coefficient of friction than the inner surface of the guide, and / or one or more surfaces of an engaging element configured to engage with the microscope are at least partially coated with a friction coating having a higher coefficient of friction than the outer surface.

23. The system according to claim 16, wherein the friction coating is made of a deformable material, preferably silicone rubber.

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