Intracytoplasmic sperm injection (ICSI) support device, intracytoplasmic sperm injection (ICSI) support system, intracytoplasmic sperm injection (ICSI) support program, and egg retention device

Abstract

To provide an intracytoplasmic sperm injection support device with a simple device configuration. [Solution] An intracytoplasmic sperm injection (ICSI) support device 2 that assists in intracytoplasmic sperm injection (ICSI) in which sperm held by a sperm injection tool 3 is injected into an egg held by an egg holding device, comprising: an acquisition unit that acquires information including the relative positional relationship between the sperm injection tool 3 and the egg; and a control unit that controls the movement of a stage 11 on which an egg holding device is positioned to inject sperm into the egg and perform ICSI, based on the information acquired by the acquisition unit.

Description

Technical Field

[0001] The present invention relates to a micromanipulation-assisted device, a micromanipulation-assisted system, a micromanipulation-assisted program, and an egg holding device.

Background Art

[0002] As one of infertility treatments, intracytoplasmic sperm injection (ICSI), which involves directly injecting sperm into the egg cytoplasm to achieve fertilization, has been developed and put into practical use. In ICSI, operations such as sperm immobilization, sperm aspiration, and sperm injection into the egg are performed while observing the sperm and egg under a microscope, so ICSI is also called micromanipulation.

[0003] Currently, although micromanipulation is performed by embryologists, since it takes a very long time to master micromanipulation, there is a need for technology to assist micromanipulation. For example, Patent Document 1 discloses a control device for moving a surgical instrument manually operated by an embryologist to a desired position.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, at present, the technology for assisting micromanipulation is still under development. For example, when attempting to automate the movement of a sperm injection tool, the device configuration may become complicated as shown in Patent Document 1. Therefore, an object of the present invention is to provide a micromanipulation-assisted device, a micromanipulation-assisted system, a micromanipulation-assisted program, or an egg holding device having a simple device configuration.

Means for Solving the Problems

[0006] An intracytoplasmic sperm injection (ICSI) support device relating to one aspect of the present disclosure is an ICSI support device that assists in intracytoplasmic sperm injection in which sperm held by a sperm injection tool are injected into an egg held by an egg holding device, and comprises: an acquisition unit that acquires information including the relative positional relationship between the sperm injection tool and the egg; and a control unit that controls the movement of a stage on which the egg holding device is positioned to perform intracytoplasmic sperm injection by injecting sperm into the egg, based on the information acquired by the acquisition unit.

[0007] Such an intracytoplasmic sperm injection (ICSI) support device assists ICSI by moving a stage based on information including the relative positional relationship between the acquired sperm injection tool and the egg. Therefore, unlike devices that support ICSI by controlling the movement of the sperm injection tool, such as Patent Document 1, the ICSI system can be configured without a mechanism for controlling the movement of the sperm injection tool.

[0008] An egg retention device according to one aspect of this disclosure comprises a recess for containing an egg and a suction port for holding the egg in the recess. Such an egg retention device is used when placed in the above-mentioned intracytoplasmic sperm injection support device.

[0009] With such an egg retention device, the egg contained in the intracytoplasmic sperm injection support device can be fixed and rotated, so that, for example, the sperm injection tool can be inserted into the egg from the appropriate direction without controlling the movement of the sperm injection tool.

[0010] An intracytoplasmic sperm injection support system relating to one aspect of this disclosure comprises an intracytoplasmic sperm injection support device relating to one aspect of this disclosure and a sperm injection tool.

[0011] An intracytoplasmic sperm injection (ICSI) support program relating to one aspect of this disclosure is an ICSI support program that assists in intracytoplasmic sperm injection in which sperm held in a sperm injection tool are injected into an egg held by an egg holding device, wherein the computer functions as an acquisition unit that acquires information including the relative positional relationship between the sperm injection tool and the egg, and a control unit that controls the movement of a stage on which the egg holding device is positioned to perform ICSI by injecting sperm into the egg, based on the information acquired by the acquisition unit.

[0012] Such intracytoplasmic sperm injection (ICSI) support systems and ICSI support programs assist ICSI by moving stages based on information including the relative positional relationship between the acquired sperm injection tool and the egg. Therefore, unlike devices that support ICSI by controlling the movement of the sperm injection tool, such as Patent Document 1, the ICSI system can be configured without a mechanism for controlling the movement of the sperm injection tool.

[0013] Furthermore, the program relating to one aspect of this disclosure can be installed or loaded onto a computer and / or device by downloading it through various recording media such as optical discs like CD-ROMs, magnetic discs, or semiconductor memory, or via a communication network.

[0014] Furthermore, in this specification, "part" does not merely mean a physical configuration, but also includes cases where the functions of that configuration are realized by software. Also, even if the functions of one configuration are realized by two or more physical configurations, the functions of two or more configurations may be realized by one physical configuration. [Effects of the Invention]

[0015] According to the present invention, it is possible to provide an intracytoplasmic sperm injection (ICSI) support device, an ICSI support system, an ICSI support program, or an egg retention device, etc., having a simple device configuration. [Brief explanation of the drawing]

[0016] [Figure 1] It is an overall conceptual diagram of the micro-insemination support system according to this embodiment. [Figure 2] It is an example of a functional block diagram of the micro-insemination support device according to this embodiment. [Figure 3] It is an example of the physical configuration of the micro-insemination support device according to this embodiment. [Figure 4] It is a schematic perspective view (A) and an enlarged plan view (B) of the egg holding device according to this embodiment. [Figure 5] It is a flowchart showing an example of the steps of the micro-insemination method according to this embodiment. [Figure 6] It is a schematic perspective view of another example of the egg holding device according to this embodiment.

Embodiments for Carrying Out the Invention

[0017] Hereinafter, embodiments for carrying out the present invention (hereinafter referred to as "this embodiment") will be described in detail with reference to the drawings. However, the present invention is not limited to this, and various modifications are possible without departing from the gist thereof. In the following description of the drawings, the same or similar parts are denoted by the same or similar reference numerals. The drawings are schematic and do not necessarily match the actual dimensions, ratios, etc. There may be parts where the dimensional relationships and ratios are different between the drawings.

[0018] [Micro-insemination Support System] Referring to FIG. 1, the micro-insemination support system 1 according to this embodiment will be described. Here, FIG. 1 is an overall conceptual diagram of the micro-insemination support system 1 according to this embodiment.

[0019] The micro-insemination support system 1 according to this embodiment includes the micro-insemination support device 2 according to this embodiment and a sperm injection tool 3. Details of the micro-insemination support device 2 according to this embodiment will be described later.

[0020] As shown in FIG. 1, the micro-insemination support device 2 is connected to a sperm injection tool 3, a drive unit 12 for moving the stage 11, and an imaging unit 13 for imaging a sample placed on the stage 11. In FIG. 1, the micro-insemination support device 2 is shown as being wired-connected to other components, but the micro-insemination support device 2 may be wirelessly connected to other components or may be physically integrated with other components. Therefore, one or more of the stage 11, the drive unit 12, and the imaging unit 13 may be included in the micro-insemination support device 2 as part of the micro-insemination support device 2.

[0021] A container 14 containing a sample is placed on the stage 11. The container 14 is, for example, a dish made of glass or resin. In FIG. 1, the container 14 is provided with a sperm pool PS and an egg pool PO. The container 14 and / or the stage 11 may be provided with temperature control means for maintaining the sperm pool PS and / or the egg pool PO at a temperature suitable for micro-insemination. Examples of the temperature control means include a heater and a cooler. The temperature control means may have a function of measuring the temperature in the container 14. The temperature suitable for micro-insemination is, for example, around about 37° C., and may be 33 to 40° C., 35 to 38° C., 36 to 37° C., or 37° C.

[0022] The sperm pool PS contains sperm obtained from a patient or subject who wishes to undergo micro-insemination. The sperm pool PS may contain, in addition to sperm, a sperm culture medium or a highly viscous liquid that suppresses sperm motility (for example, a polyvinylpyrrolidone (PVP) solution). Further, the egg pool PO contains eggs obtained from a patient or subject who wishes to undergo micro-insemination.

[0023] The egg pool PO may contain, in addition to eggs, an egg culture medium or the like. The sperm and egg culture medium is not particularly limited, but examples include physiological saline (saline containing 0.9 w / v% sodium chloride). The egg pool PO is provided on or adjacent to an egg holding device so that the egg can be held by the egg holding device.

[0024] The stage 11 is equipped with a drive unit 12 for moving the stage. The drive unit 12 only needs to be able to move the stage 11 in the in-plane direction of the stage 11 (the x and y directions in Figure 1), but it is preferable that it can also move the stage 11 in a direction perpendicular to the plane of the stage 11 (the z direction in Figure 1). In other words, it is preferable that the stage 11 is a stage that is movable in three axial directions and is equipped with a drive unit 12. The drive unit 12 may rotate the stage around each axis x, y, and z. In this case, the drive unit 12 can control a total of six degrees of freedom of movement, including translational and rotational movement around the x, y, and z axes.

[0025] The drive unit 12 is not particularly limited as long as it can move the stage 11 under the control of the microinsemination support device 2, and may be, for example, an electrically controllable motor. The stage 11 and the drive unit 12 may be, for example, an electrically controllable automatic stage provided in a microscope.

[0026] The imaging unit 13 acquires image or video footage of the sample on the stage 11 and the sperm injection tool 3. In Figure 1, the imaging unit 13 is capturing images of the sample on the stage 11 from a vertically upward direction, in a plan view. The imaging unit 13 also captures images so that at least the portion of the sperm injection tool 3 used for sperm aspiration and injection is included in the field of view, in order to acquire positional information of that portion. The imaging unit 13 only needs to be able to acquire images or video footage that include the positional relationship between the sample on the stage 11 and the sperm injection tool 3, and does not necessarily need to be located vertically upward from the stage 11.

[0027] The imaging unit 13 may be composed of an imaging device equipped with, for example, a CCD camera or a CMOS sensor. The imaging unit 13 may also image the sample on the stage 11 and the sperm injection tool 3 via an optical microscope. The observation method using the optical microscope is not particularly limited, but examples include bright-field observation, dark-field observation, phase-contrast observation, polarization observation, spindle observation, differential interference contrast observation, and relief contrast observation. The magnification of the objective lens may also be adjusted as appropriate, for example, 20x, 40x, 60x, etc. The data captured by the imaging unit 13 may be a still image or a moving image. The following description will focus on the case where the imaging unit 13 acquires a moving image, but it goes without saying that the imaging unit 13 can similarly support intracytoplasmic sperm injection when it acquires multiple still images.

[0028] The sperm injection tool 3 is a tool for injecting specific sperm into the cytoplasm of an egg. The sperm injection tool 3 may be, for example, an injection pipette commonly used in intracytoplasmic sperm injection (ICSI). It is preferable that the sperm injection tool 3 can be brought into contact with the sperm pool PS to aspirate sperm. The sperm injection tool 3 may also be equipped with means for immobilizing the sperm in the sperm pool PS. Means for immobilizing sperm include means for applying weak vibrations such as a piezoelectric element, and means for irradiating with laser light. Alternatively, sperm may be immobilized by directly applying pressure to the sperm using the tip (e.g., inlet / outlet) of the sperm injection tool 3. Means for immobilizing sperm may be provided in the ICSI support system 1 as a mechanism different from that of the sperm injection tool 3.

[0029] The sperm injection tool 3 may be equipped with a pressure control mechanism for aspirating and injecting sperm. Based on the control of the intracytoplasmic sperm injection support device 2, the pressure control mechanism may adjust the output of a pump that is present in or attached to the sperm injection tool 3 to aspirate sperm present near the inlet and outlet of the sperm injection tool 3, or to discharge sperm that have been aspirated and held inside the sperm injection tool 3 from the inlet and outlet.

[0030] It is preferable that the sperm injection tool 3 is fixed in its relative position to the imaging unit 13. In this configuration, even if the stage 11 is moved, the position of the sperm injection tool 3 does not move within the imaging field of view of the imaging unit 13, so the relative positional relationship between the sample on the stage 11 and the sperm injection tool 3 can be easily adjusted.

[0031] The intracytoplasmic sperm injection (ICSI) support device 2 assists with ICSI based on the imaging motion images of the sample on the stage 11 and the sperm injection tool 3 acquired by the imaging unit 13. The ICSI support device 2 will be described in detail below.

[0032] (Microinsemination support device) Figure 2 is a functional block diagram of the intracytoplasmic sperm injection (ICSI) support device 2. The ICSI support device 2 comprises an acquisition unit 21, a control unit 22, and an analysis unit 23. The ICSI support device 2 assists in intracytoplasmic sperm injection (ICSI) by injecting sperm held by the sperm injection tool 3 into an egg held by the egg holding device.

[0033] The acquisition unit 21 acquires information including the relative positional relationship between the sperm injection tool 3 and the egg, which is obtained by the imaging unit 13 imaging the egg pool PO and sperm injection tool 3 on the stage 11. The acquisition unit 21 only needs to acquire information including the relative positional relationship between the sperm injection tool 3 and the egg based on the image or video footage captured by the imaging unit 13, and does not need to acquire the image or video footage itself captured by the imaging unit 13.

[0034] In one embodiment, the acquisition unit 21 may acquire an image or video image captured by the imaging unit 13, which includes the sperm injection tool 3 and the egg in the imaging field of view. In one embodiment, the acquisition unit 21 may acquire information indicating the relative positional relationship between the sperm injection tool 3 and the egg, obtained by analyzing the image or video image captured by the imaging unit 13. The information indicating the relative positional relationship between the sperm injection tool 3 and the egg may be, for example, the distance between the inlet / outlet of the sperm injection tool 3 and the egg, or the coordinates of the inlet / outlet of the sperm injection tool 3 and the egg. The information indicating the relative positional relationship between the sperm injection tool 3 and the egg may be estimated, for example, from the relative positional relationship between the sperm injection tool 3 and a marker provided around the portion of the egg-holding device that contains the egg. The coordinates of the inlet / outlet of the sperm injection tool 3 and the egg may be xy coordinates in the in-plane direction of the stage 11, and may also be xyz coordinates with the z direction perpendicular to the plane of the stage 11 added. The acquisition unit 21 may acquire the extension direction of the inlet and outlet of the sperm injection tool 3, that is, the insertion direction when inserting the sperm injection tool 3 into the egg.

[0035] The acquisition unit 21 may further acquire information including the position of the polar body of the oocyte. In intracytoplasmic sperm injection (ICSI), sperm is often injected into the cytoplasm of the oocyte while avoiding the polar body. This is because the spindle tends to be located near the polar body (first polar body) of the oocyte, and this is done to prevent damage to the spindle by inserting the sperm injection tool 3. Therefore, the acquisition unit 21 may further acquire information including the position of the spindle of the oocyte.

[0036] Since the position of the polar body of the oocyte can be obtained from an observation image of the oocyte, the acquisition unit 21 may acquire information including the position of the polar body of the oocyte by acquiring the image or video of the oocyte captured by the imaging unit 13. In one embodiment, the acquisition unit 21 may acquire information indicating the position of the polar body of the oocyte, obtained by analyzing the image or video of the oocyte captured by the imaging unit 13.

[0037] The acquisition unit 21 may further acquire information including the relative positional relationship between the sperm injection tool 3 and the sperm contained in the sperm pool PS located in the stage 11.

[0038] In one embodiment, the acquisition unit 21 may acquire an image or video image captured by the imaging unit 13, which includes the sperm injection tool 3 and sperm in the imaging field. In one embodiment, the acquisition unit 21 may acquire information indicating the relative positional relationship between the sperm injection tool 3 and sperm, obtained by analyzing the image or video image captured by the imaging unit 13. The information indicating the relative positional relationship between the sperm injection tool 3 and sperm may be, for example, the distance between the inlet / outlet of the sperm injection tool 3 and the sperm, or the coordinates of the inlet / outlet of the sperm injection tool 3 and the sperm.

[0039] The acquisition unit 21 may be implemented by the communication unit 2d described later.

[0040] Based on the information acquired by the acquisition unit 21, the control unit 22 controls the movement of the stage 11 where the egg holding device is positioned to perform intracytoplasmic sperm injection (ICSI) by injecting sperm into the egg. The control unit 22 may also control the movement of the stage 11 to hold immobilized sperm in the sperm injection tool 3 based on the information acquired by the acquisition unit 21.

[0041] The control unit 22 may include an imaging control unit 221, a drive control unit 222, a sperm injection tool control unit 223, a suction device control unit 224, and a water supply device control unit 225 in order to hold sperm in the sperm injection tool 3 and inject the held sperm into the egg to perform intracytoplasmic sperm injection (ICSI).

[0042] The imaging control unit 221 controls the imaging unit 13 and adjusts the imaging area of ​​the imaging unit 13. The imaging control unit 221 may adjust the imaging area by adjusting the imaging field of view of the imaging unit 13. When the imaging unit 13 performs imaging via a microscope system, the imaging control unit 221 may adjust the settings of the microscope system attached to the imaging unit 13 in order to image sperm and / or eggs with high resolution. This adjustment may be performed by the person performing the intracytoplasmic sperm injection.

[0043] The drive control unit 222 controls the drive unit 12 to move the stage 11. The drive control unit 222 may move the stage 11 via the electrical mechanism provided by the drive unit 12.

[0044] The sperm injection tool control unit 223 controls the sperm injection tool 3 to aspirate and expel sperm. The sperm injection tool control unit 223 may control the pressure control mechanism of the sperm injection tool 3 to adjust the output of the pump that the sperm injection tool 3 has or that is attached to the sperm injection tool 3. If the sperm injection tool 3 is equipped with means for immobilizing sperm, the sperm injection tool control unit 223 may activate the means for immobilizing sperm and control the sperm injection tool 3 to immobilize the sperm.

[0045] The suction device control unit 224 and the water supply device control unit 225 control the suction device and water supply device, respectively, which may be connected to the egg holding device. Details of the egg holding device will be described later, but the suction device holds the egg in the egg holding device. The water supply device may also rotate the egg held or contained in the egg holding device.

[0046] The suction device control unit 224 and the water supply device control unit 225 control the suction device and the water supply device, respectively, to perform oocyte suction and rotation. Based on the information about the oocyte acquired by the acquisition unit 21, the suction device control unit 224 and the water supply device control unit 225 suction the oocyte and supply water to the oocyte.

[0047] The water supply device control unit 225 may control the water supply device to rotate the egg in order to inject sperm using a sperm injection tool from a direction in which the polar body of the egg is not located, based on information including the position of the polar body of the egg acquired by the acquisition unit 21. To this end, the water supply device control unit 225 may rotate the egg by controlling the water supply device to deliver water to the egg so that the polar body of the egg is located approximately at 12 o'clock or 6 o'clock, with the direction in which the sperm injection tool 3 is located being 3 o'clock. The water supply device control unit 225 may control the temperature of the fluid supplied from the water supply device so that the temperature in the container 14 is maintained at a temperature suitable for intracytoplasmic sperm injection. Temperature control of the fluid is performed, for example, by temperature control means that may be provided in the water supply device. Examples of temperature control means include heaters and coolers. The temperature control means may have a function to measure the temperature of the fluid supplied from the water supply device.

[0048] The suction device is not particularly limited as long as it is connected to the egg holding device and is capable of aspirating eggs located near the suction port of the egg holding device. The suction device may be, for example, a pump whose pressure can be controlled by the suction device control unit 224.

[0049] Furthermore, the water supply device is not particularly limited as long as it is connected to the egg holding device and capable of supplying fluid from the water inlet of the egg holding device. The water supply device may be, for example, a pump capable of controlling the flow rate of the supplied fluid by the water supply device control unit 225. The water supply device may be equipped with temperature control means for maintaining the temperature of the supplied fluid within a certain range. Examples of temperature control means include heaters and coolers. The temperature control means may have a function to measure the temperature of the fluid supplied from the water supply device. The temperature of the fluid is preferably maintained at a temperature suitable for intracytoplasmic sperm injection (ICSI), which is, for example, around 37°C, and may be 33-40°C, 35-38°C, 36-37°C, or 37°C. The temperature control means may control the temperature of the supplied fluid so that the temperature in the container 14 is maintained at a temperature suitable for ICSI.

[0050] The control unit 22 may be implemented by a program stored in the RAM 2b or ROM 2c (described later) and executed by the CPU 2a. Instructions from the control unit 22 are transmitted to each unit and device via the communication unit 2d.

[0051] The analysis unit 23 analyzes the information acquired by the acquisition unit 21 and assists the control unit 22 in its operation. In this embodiment, the analysis unit 23 is provided in the intracytoplasmic sperm injection support device 2, but it may be provided in a unit or device other than the intracytoplasmic sperm injection support device 2, for example, in the imaging unit 13 or a computer connected to the imaging unit 13. The analysis unit 23 may include, for example, a sperm recognition unit 231, an egg recognition unit 232, a sperm evaluation unit 233, and an egg evaluation unit 234.

[0052] The sperm recognition unit 231 analyzes the information acquired by the acquisition unit 21 and recognizes sperm. When the acquisition unit 21 acquires an image or video, methods for recognizing sperm from the image or video include preparing multiple representative images that show the typical shape of sperm and using the representative images for pattern matching for each frame in the image or video, or using a learning model that has been trained using observed sperm images as training data.

[0053] The egg recognition unit 232 analyzes the information acquired by the acquisition unit 21 and recognizes the egg. When the acquisition unit 21 acquires an image or video, methods for recognizing the egg from the image or video include preparing multiple representative images that show the typical shape of the egg and using the representative images for pattern matching for each frame in the image or video, or using a learning model that has been trained using observed images of the egg as training data. Alternatively, the egg may be recognized based on a marker attached to the egg holding device.

[0054] The sperm evaluation unit 233 analyzes the information acquired by the acquisition unit 21 and evaluates the quality of each sperm. Sperm quality refers to the properties of each sperm related to the fertilization success rate, blastocyst formation rate, implantation rate, and / or live birth success rate when used in intracytoplasmic sperm injection (ICSI). High sperm quality means that the fertilization success rate, blastocyst formation rate, implantation rate, and / or live birth success rate when used in ICSI are relatively high. The sperm evaluation unit 233 may quantify sperm quality by calculating at least one indicator related to sperm quality.

[0055] At least one indicator related to sperm quality is, but is not limited to, the indicators described in the WHO Laboratory Manual for the Examination and Processing of Human Semen, Sixth Edition, published by the World Health Organization (WHO). Such indicators may include, for example, at least one of sperm motility, sperm morphology, and the degree of sperm DNA fragmentation, or a calculation based on two or more of these.

[0056] The sperm evaluation unit 233 may calculate at least one index related to sperm quality using various methods. For example, sperm motility can be indexed by the speed of movement and the linearity of the movement trajectory at predetermined time intervals. The sperm evaluation unit 233 can track sperm at predetermined time intervals and calculate the speed of movement and the linearity of the movement trajectory based on the positional information of the sperm in each frame. Sperm motility may also be calculated using a learning model that has been trained using sperm quality and movement as training data.

[0057] Sperm morphology can be indexed based on the morphology of sperm captured in each frame of an image or video. The sperm evaluation unit 233 may index the morphology of a single sperm based on multiple frames and calculate a single index by averaging these values. Sperm morphology can be indexed based, for example, on the shape of the sperm head, the shape of the tail, and the balance of defects and sizes thereof. Sperm motility may be calculated using a learning model that has been trained using sperm quality and morphology as training data.

[0058] The degree of sperm DNA fragmentation can be indexed by comprehensively considering sperm motility, such as the speed of movement and the linearity of the movement trajectory at predetermined time intervals, as well as the morphology of sperm captured in each frame of an image or video. The degree of sperm DNA fragmentation may also be calculated using a learning model trained with the degree of sperm DNA fragmentation and sperm motility and / or morphology as training data. Furthermore, the degree of sperm DNA fragmentation can be measured using stained images obtained by selectively staining sperm that have undergone DNA fragmentation.

[0059] The sperm evaluation unit 233 may calculate an index that comprehensively evaluates sperm quality by considering two or more of the above-mentioned indicators. The sperm evaluation unit 233 may calculate an index by arbitrarily weighting and averaging indicators related to sperm motility, sperm morphology, and the degree of sperm DNA fragmentation. In this case, if any of the indicators fall below a threshold, a penalty may be imposed by deducting a certain number from the calculated index.

[0060] The egg evaluation unit 234 analyzes the information acquired by the acquisition unit 21 and evaluates the quality of each egg. Egg quality refers to the properties of each egg related to the fertilization success rate, blastocyst formation rate, implantation rate, and / or birth success rate when used in intracytoplasmic sperm injection (ICSI). High egg quality means that the fertilization success rate, blastocyst formation rate, implantation rate, and / or birth success rate when used in ICSI are relatively high. The egg evaluation unit 234 may quantify egg quality by calculating at least one indicator related to egg quality.

[0061] The oocyte evaluation unit 234 may evaluate the quality of the oocyte based, for example, on the position, shape, and size of the polar body, spindle, and smooth endoplasmic reticulum, as well as the degree of cytoplasmic turbidity. The oocyte evaluation unit 234 may also evaluate the quality of the oocyte using a learning model that has been trained using the quality and morphology of the oocyte as training data.

[0062] The analysis unit 23 may be implemented by a program stored in RAM 2b or ROM 2c (described later) and executed by CPU 2a. The analysis results from the analysis unit 23 may be used by the control unit 22, transmitted to each unit and device via the communication unit 2d, or displayed on the display unit 2f.

[0063] Next, the physical configuration of the intracytoplasmic sperm injection support device 2 will be described with reference to Figure 3. Figure 3 is a diagram showing an example of the physical configuration of the intracytoplasmic sperm injection support device 2. The intracytoplasmic sperm injection support device 2 includes a CPU (Central Processing Unit) 2a, which corresponds to a processor, RAM (Random Access Memory) 2b and ROM (Read-only Memory) 2c, which correspond to storage units, a communication unit 2d, an input unit 2e, and a display unit 2f. Each of these components is connected to each other via a bus so that data can be sent and received from each other. In this example, the case in which the functions of the intracytoplasmic sperm injection support device 2 are configured on a single computer is described, but the functions of the intracytoplasmic sperm injection support device 2 may be realized by combining multiple computers. Also, the configuration shown in Figure 3 is just an example, and the intracytoplasmic sperm injection support device 2 may have other components, or may not have some of these components.

[0064] The CPU 2a controls the execution of programs stored in RAM 2b or ROM 2c, and performs calculations and processing of data. The CPU 2a is a calculation unit that executes a program that makes the computer function as an acquisition unit 21, a control unit 22, and an analysis unit 23. The CPU 2a receives various data from the input unit 2e and the communication unit 2d, and displays the calculation results of the data on the display unit 2f or stores them in RAM 2b or ROM 2c.

[0065] RAM2b is a memory unit that allows data to be rewritten, and may be composed of, for example, semiconductor memory elements. RAM2b may store the program executed by CPU2a. Note that these are examples, and RAM2b may store other types of data.

[0066] ROM2c is a data readable portion of the storage unit and may be composed of, for example, semiconductor memory elements. ROM2c may store, for example, data that is not rewritten.

[0067] The communication unit 2d is an interface that connects the intracytoplasmic sperm injection support device 2 to other units and devices, such as the sperm injection tool 3, the drive unit 12, the imaging unit 13, the aspiration device, and the water supply device. The communication unit 2d may be connected to a network by wire or wireless.

[0068] The input unit 2e receives data input from the user and may include, for example, a keyboard and a touch panel.

[0069] The display unit 2f visually displays the calculation results by the CPU 2a and may be configured as an LCD (Liquid Crystal Display), for example. The display unit 2f may display information acquired by the acquisition unit 21, for example, an image or video acquired by the imaging unit 13.

[0070] The intracytoplasmic sperm injection (ICSI) support program according to this embodiment may be stored and provided on a computer-readable storage medium such as RAM2b or ROM2c, or it may be provided via a communication network connected by the communication unit 2d. In the ICSI support device 2, the CPU 2a executes the program according to this embodiment, thereby realizing the functions described with reference to Figure 2. These physical configurations are illustrative and do not necessarily have to be independent. For example, the ICSI support device 2 may include a Large-Scale Integration (LSI) in which the CPU 2a and RAM2b and / or ROM2c are integrated.

[0071] (Egg retention device) Next, with reference to Figure 4, an egg retention device for use in the intracytoplasmic sperm injection support system 1 will be described. The egg retention device according to this embodiment is used to efficiently implement control by the intracytoplasmic sperm injection support device 2 according to this embodiment. The egg retention device according to this embodiment may be made of, for example, resin.

[0072] Figure 4 is a schematic perspective view (Figure 4(A)) and an enlarged plan view (Figure 4(B)) of the egg holding device D1 according to this embodiment. As shown in Figures 4(A) and (B), the egg holding device D1 comprises recesses 151a, 151b, and 151c for accommodating egg cells O1, O2, and O3, respectively, and suction ports 154a, 154b, and 154c for holding egg cells O1, O2, and O3 in the recesses 151a, 151b, and 151c, respectively. Figure 4(B) is an enlarged plan view relating to egg cell O1 held in recess 151a. The egg holding device D1 further comprises water inlets 153a, 153b, and 153c for rotating egg cells O1, O2, and O3 in the recesses 151a, 151b, and 151c.

[0073] In Figure 4(A), three oocytes O1, O2, and O3 are housed in three recesses 151a, 151b, and 151c, respectively. However, the oocyte holding device D1 only needs to have a structure for housing and holding one or more oocytes. The following description will focus on the case where three oocytes O1, O2, and O3 are housed in three recesses 151a, 151b, and 151c, respectively, as shown in Figure 4(A). However, the number of oocytes housed and held in the oocyte holding device D1 is not particularly limited.

[0074] Furthermore, in the following, if it is not necessary to distinguish between the three oocytes O1, O2, and O3, they will be collectively referred to as oocyte O. The same applies to the other components. In Figure 4(A), the symbols a, b, and c are assigned to each component of the oocyte holding device D1, corresponding to the three oocytes O1, O2, and O3. However, if it is not necessary to distinguish between the components corresponding to the three oocytes O1, O2, and O3, the symbols a, b, and c will be omitted. For example, the three recesses 151a, 151b, and 151c corresponding to the three oocytes O1, O2, and O3 may be collectively referred to as recess 151.

[0075] Furthermore, the oocyte retention device D1 according to this embodiment may be provided as the oocyte pool PO in Figure 1, or it may be provided adjacent to the oocyte pool PO. That is, each recess of the oocyte retention device D1 may be used as the oocyte pool PO, or a separate oocyte pool PO containing oocytes may be provided separately from the recesses of the oocyte retention device D1. Therefore, the oocyte retention device D1 according to this embodiment may move in accordance with the stage 11. When the sperm injection tool 3 is fixed to the imaging unit 13, by moving the stage 11, the sperm injection tool 3 is substantially fixed in the imaging field of view of the imaging unit 13, and only the oocyte retention device D1 can be moved. This makes it possible to perform intracytoplasmic sperm injection with high precision by moving the stage 11.

[0076] Returning to Figure 4, the oocyte O is contained in the recess 151 of the oocyte holding device D1. The recess 151 is not particularly limited as long as it can accommodate the oocyte O in a predetermined area. The recess 151 may have a width and length of, for example, 100 to 1000 μm, preferably 150 to 500 μm, in a plan view. The recess 151 may have a depth of, for example, 100 to 1000 μm, preferably 150 to 500 μm.

[0077] The recess 151 may be a recess enclosed on the bottom and all four sides, with an opening at the top. One of the four enclosures forming the recess 151 may be partially removed. By partially removing one of the four enclosures forming the recess 151 in this way, it is possible to facilitate contact between the egg O and the sperm injection tool 3.

[0078] In one embodiment, the recess 151 may be formed by being surrounded by a bottom surface and a wall portion extending upward from the bottom surface, and at least a portion of the wall portion may be configured to be lower in height than other portions of the wall portion. For example, a portion of the wall portion may have a height of, for example, 100 to 1000 μm, preferably 150 to 500 μm, and a portion of the wall portion that is relatively low in height may have a height of, for example, 20 to 200 μm, preferably 50 to 150 μm. The portion of the wall portion that is relatively low in height may be located on the opposite side of the wall portion from which the suction port described later is provided.

[0079] A suction port 154 is provided in the wall portion forming the recess 151 of the egg holding device D1. By aspirating the egg O through the suction port 154, the egg O can be held in the egg holding device D1. With the egg O aspirated through the suction port 154, sperm can be injected into the egg O by bringing the inlet and outlet of the sperm injection tool 3 into contact with the egg O. In other words, the suction port 154 serves the role of a holding pipette in conventional intracytoplasmic sperm injection procedures.

[0080] Therefore, the suction port 154 may have a shape similar to that of a holding pipette. For example, as shown in Figure 4(B), the suction port 154 may have a substantially tapered shape, with its diameter decreasing as it approaches the recess 151. The shape of the opening of the suction port 154 is not particularly limited, but may be, for example, substantially circular, substantially elliptical, or a rounded rectangle. By using such a shape, the damage inflicted on the oocyte O when aspirating the oocyte O can be reduced. The equivalent circle diameter d of the opening of the suction port 154 is, for example, 10 to 150 μm, preferably 15 to 100 μm. The equivalent circle diameter refers to the diameter of a circle having the same area as the shape of the opening.

[0081] The suction port 154 is connected to a suction device for aspirating oocytes O through a suction port 158. The suction port 154 and the suction port 158 ​​are connected by a flow path inside the oocyte holding device D1. Multiple suction ports 158 may be provided corresponding to multiple suction ports 154a, 154b, 154c, or one or more suction ports 158 may be provided connected to each of the multiple suction ports 154a, 154b, 154c. In Figure 4(A), one suction port 158 ​​is provided connected to each of the multiple suction ports 154a, 154b, 154c. Therefore, in Figure 4(A), when the suction device connected to the suction port 158 ​​is operated and oocytes O are aspirated, all of the oocytes O1, O2, and O3 contained in the recesses 151a, 151b, 151c will be aspirated simultaneously.

[0082] As shown in Figure 4(B), when the oocyte O is aspirated through the suction port 158, a fluid flow F1 is generated from the opening of the suction port 154 toward the suction port 158, causing the oocyte O to be attracted to the opening of the suction port 154 and come into contact with it. By maintaining suction in this state of contact with the opening, the oocyte O can be held in the opening of the suction port 154.

[0083] A water inlet 153 is provided in the wall portion forming the recess 151 of the egg-holding device D1. By supplying fluid from the water inlet 153, the egg contained in the recess 151 can be moved or rotated within the recess 151.

[0084] As described above, in intracytoplasmic sperm injection (ICSI), it is preferable to avoid the polar bodies when inserting the sperm injection tool into the egg in order to avoid damaging the spindle. As shown in Figure 4(B), the acquisition unit 21 acquires the positional information of the polar bodies PB of the egg O, and water is supplied to the egg O from the water supply port 153, thereby moving the polar bodies to an appropriate position and holding them in this state at the opening of the suction port 154.

[0085] In the embodiment shown in Figure 4(B), since the sperm injection tool 3 is inserted from the opposite direction of the suction port 154, i.e., from below in Figure 4(B), it is preferable that the polar body PB is positioned in the direction of the water inlet 153 or the drain port 155, i.e., to the left or right in Figure 4(B).

[0086] The shape of the water inlet 153 is not particularly limited as long as it can supply fluid to the recess 151. Furthermore, while the fluid supplied from the water inlet 153 is typically a liquid such as water or culture medium, a gas such as air may also be supplied to the recess 151.

[0087] The water inlet 153 is connected to a water supply device for supplying water to the oocyte O through the water supply port 157. The water inlet 153 and the water supply port 157 are connected by a flow path inside the oocyte holding device D1. Multiple water supply ports 157 may be provided corresponding to multiple water inlets 153a, 153b, 153c, or one or more water supply ports 157 may be provided connected to each of the multiple water inlets 153a, 153b, 153c. In Figure 4(A), one water supply port 157 is provided connected to each of the multiple water inlets 153a, 153b, 153c. Therefore, in Figure 4(A), when the water supply device connected to the water supply port 157 is operated and the oocyte O is aspirated, water will be supplied to the recesses 151a, 151b, 151c.

[0088] As shown in Figure 4(B), when water is supplied to the recess 151 through the water supply port 157, a fluid flow F2 is generated from the water supply port 157 toward the opening of the water outlet 153.

[0089] A drain port 155 may be provided in the wall portion forming the recess 151 of the egg-holding device D1. The drain port 155 is provided as a discharge path for the fluid supplied from the water inlet 153. If the upper part of the recess 151 is an opening as shown in Figure 4(A), the drain port 155 can be omitted.

[0090] The drain port 155 may be connected to a drainage device through a drain port 159. The drain port 155 and the drain port 159 are connected by a flow path inside the egg holding device D1. Multiple drain ports 159 may be provided corresponding to multiple drain ports 155a, 155b, 155c, or one or more drain ports 159 may be provided connected to each of the multiple drain ports 155a, 155b, 155c. As shown in Figure 4(B), when draining through the drain port 159, a fluid flow F3 is generated from the opening of the drain port 155 toward the drain port 159.

[0091] A marker 152 may be provided around the recess 151 of the egg-holding device D1 to assist in the recognition of the recess 151 and the egg O. There may be one or more markers 152. It is preferable that the marker 152 be provided on the wall opposite the wall where the suction port 154 is provided, in order to facilitate contact between the egg O and the sperm injection tool 3. In this case, the control unit 22 can recognize the marker 152 and control the sperm injection tool 3 to be inserted into the egg O from the direction of the marker 152. The marker 152 may be provided around the recess 151, in which case the analysis unit 23 can recognize the marker 152 and recognize the approximate location of the egg O.

[0092] [Intracytoplasmic sperm injection (ICSI) method] The following describes a method for performing intracytoplasmic sperm injection (ICSI) using the ICSI support system according to this embodiment. Because the ICSI method according to this embodiment uses the ICSI support system according to this embodiment, at least some of the steps of ICSI can be automated. In particular, since the step of injecting sperm into the egg can be automated, ICSI can be performed efficiently and with a high success rate, regardless of the individual skills of the embryologist.

[0093] Figure 5 is a flowchart showing an example of the steps of the intracytoplasmic sperm injection (ICSI) method according to this embodiment. Although not shown in Figure 5, the person performing the ICSI (typically an embryologist) places the container 14 containing the sample on the stage 11 of the ICSI support system 1 according to this embodiment, and sets it up so that the entry and exit points for the sample and sperm injection tool 3 are within the imaging field of view of the imaging unit 13.

[0094] The following describes how the intracytoplasmic sperm injection (ICSI) support system 1 automatically performs ICSI without requiring any processing from the person performing the ICSI. However, some or all of the following steps can also be performed manually by the person performing the ICSI.

[0095] As shown in Figure 5, in the intracytoplasmic sperm injection method according to this embodiment, first, the imaging field of view of the imaging unit 13 is moved to the sperm pool PS (hereinafter also referred to as "step S1"). Step S1 is performed by the imaging control unit 221 controlling the imaging unit 13 and / or the drive control unit 222 controlling the drive unit 12 to move the stage 11, so that the imaging unit 13 images the sperm pool PS on the stage 11.

[0096] In step S1, the position of the sperm pool PS may be stored in the intracytoplasmic sperm injection support device 2, and the stored position of the sperm pool PS may be recalled, and the imaging area of ​​the imaging unit 13 may be moved to the sperm pool PS. Alternatively, a marker indicating the position of the sperm pool PS may be placed around the sperm pool PS, and the analysis unit 23 may recognize the marker, thereby moving the imaging area of ​​the imaging unit 13 to the sperm pool PS.

[0097] Next, sperm to be used for intracytoplasmic sperm injection (ICSI) are selected and immobilized (hereinafter also referred to as "Step S2"). In Step S2, first, good quality sperm suitable for use in ICSI are selected. Specifically, the sperm recognition unit 231 recognizes each sperm in the sperm pool PS, and the sperm evaluation unit 233 evaluates the quality of each sperm. The sperm evaluation unit 233 selects good quality sperm from among the sperm whose quality has been evaluated. The sperm evaluation unit 233 may select sperm that are evaluated as being of relatively high quality from among the sperm whose quality has been evaluated, or it may select sperm that exceed a predetermined threshold.

[0098] In step S2, the selected sperm are then immobilized. Sperm immobilization may be performed by the sperm injection tool control unit 223 controlling the immobilization means provided on the sperm injection tool 3, or by the control unit 22 controlling an immobilization device different from the sperm injection tool 3. When the sperm injection tool control unit 223 immobilizes the sperm by controlling the immobilization means provided on the sperm injection tool 3, the drive control unit 222 may control the drive unit 12 and move the stage 11 in order to position the selected sperm and the immobilization means provided on the sperm injection tool 3 in an appropriate position for immobilization. When the inlet and outlet of the sperm injection tool 3 are pressed directly against the sperm to immobilize them, the drive control unit 222 may control the drive unit 12 and move the stage 11 in order to properly contact the inlet and outlet of the sperm injection tool 3 with the sperm.

[0099] Next, the sperm selected and immobilized in step S2 are aspirated (hereinafter also referred to as "step S3"). In step S3, the drive control unit 222 controls the drive unit 12 to move the stage 11 in order to bring the sperm to be aspirated close to the inlet and outlet of the sperm injection tool 3. Then, the sperm injection tool control unit 223 controls the sperm injection tool 3 to aspirate the sperm from the inlet and outlet and hold the sperm in the sperm injection tool 3.

[0100] Next, the imaging field of view of the imaging unit 13 is moved to the oocyte pool (hereinafter also referred to as "step S4"). In step S4, the imaging control unit 221 controls the imaging unit 13 and / or the drive control unit 222 controls the drive unit 12 to move the stage 11, so that the imaging unit 13 images the oocyte pool PO on the stage 11.

[0101] In step S4, the position of the oocyte pool PO may be stored in the intracytoplasmic sperm injection support device 2, and the stored position of the oocyte pool PO may be recalled, and the imaging area of ​​the imaging unit 13 may be moved to the oocyte pool PO. Alternatively, a marker indicating the position of the oocyte pool PO may be placed around the oocyte pool PO, and the analysis unit 23 may recognize the marker, thereby moving the imaging area of ​​the imaging unit 13 to the oocyte pool PO. The analysis unit 23 may recognize the oocyte holding device, or it may recognize the marker attached to the oocyte holding device.

[0102] Next, the oocytes to be used for intracytoplasmic sperm injection (ICSI) are recognized and selected (hereinafter also referred to as "Step S5"). In Step S5, good quality oocytes suitable for use in ICSI are selected. Specifically, the oocyte recognition unit 232 recognizes each oocyte in the oocyte pool PO, and the oocyte evaluation unit 234 evaluates the quality of each oocyte. The oocyte evaluation unit 234 selects good quality oocytes from among the oocytes whose quality has been evaluated. The oocyte evaluation unit 234 may select oocytes that are evaluated as being of relatively high quality from among the oocytes whose quality has been evaluated, or it may select oocytes that exceed a predetermined threshold.

[0103] In intracytoplasmic sperm injection (ICSI), the number of egg cells prepared is often less than the number of sperm cells. Therefore, it is preferable to inject high-quality sperm into high-quality eggs to further increase the fertilization success rate. In Figure 5, steps S4 and S5 may be performed before step S1 to adjust the quality of the sperm selected in step S2 according to the quality of the selected egg.

[0104] For example, if high-quality eggs are selected in step S5, then relatively high-quality sperm may be selected in step S2, or the threshold for selecting sperm may be set higher than the normal setting to select high-quality sperm.

[0105] Alternatively, in intracytoplasmic sperm injection (ICSI), sperm is often injected into all prepared eggs, so the evaluation of egg quality can be omitted.

[0106] Alternatively, if an egg of inferior quality is selected in step S5, for example, if an egg whose quality indicator falls below a threshold is selected, the automation of sperm injection may be discontinued, the person performing the intracytoplasmic sperm injection may be notified, and the person performing the injection may be encouraged to perform it manually.

[0107] Next, the orientation of the egg selected in step S5 is adjusted (hereinafter also referred to as "step S6"). In step S6, first, the analysis unit 23 determines a preferred orientation of the egg based on the positional relationship between the sperm injection tool 3 and the egg acquired by the acquisition unit 21. For example, the analysis unit 23 recognizes the position of the polar body of the egg acquired by the acquisition unit 21 and determines the orientation of the egg so that the polar body of the egg is positioned perpendicular to the direction in which the sperm injection tool 3 is inserted.

[0108] Next, the egg oriented in the direction determined in step S5 is held in the egg holding device (hereinafter also referred to as "step S7"). In step S7, the water supply device control unit 225 controls the water supply device while the suction device control unit 224 controls the suction device, thereby holding the egg oriented in the appropriate direction in the egg holding device.

[0109] Next, the sperm aspirated in step S3 is injected into the egg held in step S7 (hereinafter also referred to as "step S8"). In step S8, first, the egg is brought close to the inlet and outlet of the sperm injection tool 3 in order to inject sperm into the egg and perform intracytoplasmic sperm injection. At this time, the drive control unit 222 controls the drive unit 12 and moves the stage 11. Next, the sperm injection tool control unit 223 controls the sperm injection tool 3 and injects sperm into the egg from the inlet and outlet. After the injection is complete, the sperm injection tool 3 is withdrawn from the egg, and the intracytoplasmic sperm injection is completed.

[0110] Next, it is determined whether sperm injection has been completed for all eggs (hereinafter also referred to as "step S9"). Step S9 only needs to be performed if the number of prepared egg cells is small, and can be omitted if a very large number of eggs have been prepared. The intracytoplasmic sperm injection support device 2 stores the eggs into which sperm has been injected, and if it determines that there are eggs into which sperm has not been injected (step S9: No), it returns to step S1. At this time, the number of eggs into which sperm has not been injected may be displayed on the display unit 2f. If it is determined that sperm injection has been completed for all eggs (step S9: Yes), the process is terminated.

[0111] In each of the above steps, the acquisition unit 21 may optionally acquire information including the relative positional relationship between the inlet / outlet of the sperm injection tool 3 and the egg, and / or information including the relative positional relationship between the inlet / outlet of the sperm injection tool 3 and the sperm. For example, in step S3, information including the relative positional relationship between the sperm injection tool 3 and the sperm is acquired, and based on this, the sperm is aspirated using the sperm injection tool 3. Also, in step S8, information including the relative positional relationship between the inlet / outlet of the sperm injection tool 3 and the egg is acquired, and based on this, the sperm injection tool 3 is inserted into the egg. Also, in step S6, the acquisition unit 21 further acquires information including the position of the polar body or spindle of the egg. Furthermore, when the acquisition unit 21 acquires an image or video from the imaging unit 13, in each step, if the imaging field of view includes at least one of the sperm injection tool 3, the egg, and the sperm, the coordinates of at least one of the sperm injection tool 3, the egg, and the sperm may be acquired based on the image or video.

[0112] [Differentiation] Although an example of this embodiment has been described above, the present invention is not limited to the above. For example, unless otherwise specified, the examples and / or preferred embodiments, etc. (preferred, more preferred, even more preferred, even more preferred embodiments, etc.) in the description of each component and step can be arbitrarily combined to form this embodiment. For example, for each embodiment, an embodiment described as a preferred embodiment may be combined with another embodiment described as a preferred embodiment, or an embodiment described as a preferred embodiment, etc. may be combined with a configuration described as a more preferred embodiment (or even more preferred embodiment, etc.). Furthermore, each component and step may be omitted as appropriate, as long as it does not hinder the effects of this embodiment.

[0113] For example, in the intracytoplasmic sperm injection (ICSI) support system 1 shown in Figure 1, the egg pool PO and sperm pool PS are located in the same container 14, but the egg pool PO and sperm pool PS may be located in different containers. Also, if the ICSI support system 1 is used only for injecting sperm into eggs, a sperm pool may not be provided in stage 11. In this case, the user of the ICSI support system 1 (typically an embryologist) can perform ICSI using a sperm injection tool 3 that holds sperm. In this case, steps S1 to S3 of the flowchart shown in Figure 5 can be omitted.

[0114] Furthermore, although the sperm injection tool 3 is fixed to the imaging unit 13 in the above description, this does not prevent the addition of a mechanism for moving the sperm injection tool 3. Therefore, in the intracytoplasmic sperm injection support device 2 according to this embodiment, the movement of the sperm injection tool 3 may be controlled by the sperm injection tool control unit 223. In this case, the movement of the stage 11 may be used as the primary means of movement (for example, a means for aligning the translational position between the egg and the inlet / outlet of the sperm injection tool 3), and the movement of the sperm injection tool 3 may be used as an auxiliary means of movement (for example, a means for aligning the rotational position to adjust the direction in which the inlet / outlet of the sperm injection tool 3 is inserted into the egg).

[0115] Furthermore, in the intracytoplasmic sperm injection (ICSI) method according to this embodiment, processing by the person performing the ICSI may be accepted before, after, or during each step. For example, in step S2, the person performing the ICSI may select the sperm to be aspirated, or the person performing the ICSI may immobilize the sperm.

[0116] Furthermore, in step S3, the person performing the intracytoplasmic sperm injection (ICSI) may specify the method of sperm aspiration. For example, the person performing the ICSI may choose whether to aspiration the sperm from the head end or from the tail end.

[0117] Furthermore, in step S5, the person performing the intracytoplasmic sperm injection may select the egg into which the sperm will be injected.

[0118] Furthermore, the person performing the intracytoplasmic sperm injection (ICSI) may make adjustments during the sperm injection into the egg in steps S6 to S8. For example, the person performing the ICSI may specify which part of the egg the sperm injection tool 3 should be inserted into, from which direction to insert it, and to what extent to insert it.

[0119] Furthermore, in the preceding or during-step process, the imaging control unit 221 may adjust the settings of the imaging unit 13 and / or the microscope system attached to the imaging unit 13 in order to image sperm and / or eggs with high resolution. This adjustment may be performed by the person performing the intracytoplasmic sperm injection. For example, the observation method and magnification of the optical microscope may be adjusted according to the imaging target and purpose of each step to ensure that each step is performed appropriately.

[0120] Furthermore, each step may include a confirmation step to ask the person performing the intracytoplasmic sperm injection (ICSI) whether to proceed to the next step. Also, if an abnormality is detected at any step, it is possible to switch to processing by the person performing the ICSI. Such abnormalities include, for example, when the oocyte is in an abnormal state, such as when the perivitelline space is filled and the cytoplasm cannot be seen, or when there is an abnormality in the shape of the zona pellucida. Additionally, if an abnormality is detected, a notification may be displayed to the person performing the ICSI, prompting them to check the setup of the ICSI support system 1.

[0121] Furthermore, in addition to the embodiment shown in Figure 4, the egg retention device may also be the embodiment shown in Figure 6. The egg retention device D2 shown in Figure 6 differs from the egg retention device D1 shown in Figure 4 in that the roles of the first recess 251a, the second recess 251b, and the third recess 251c are different.

[0122] In other words, the egg retention device D1 shown in Figure 4 has equivalent configurations, with the three recesses 151a, 151b, and 151c being equivalent. On the other hand, in the egg retention device D2 shown in Figure 6, the first recess 251a serves as a pool of eggs that have not yet been injected with sperm (i.e., the egg pool PO), the second recess 251b serves as a recess that holds eggs during sperm injection (i.e., the recess 151 of the egg retention device D1 shown in Figure 4), and the third recess 251c serves as a pool of eggs that have completed sperm injection.

[0123] The egg retention device D2 makes it easy to distinguish between eggs that have not been injected with sperm and eggs that have been injected with sperm, and makes the decision in step S9 of the flowchart shown in Figure 5 easier.

[0124] The egg holding device D2 shown in Figure 6 comprises a first recess 251a, a second recess 251b, and a third recess 251c for accommodating egg cells O1, O2, and O3, respectively; a suction port 254 for holding egg cell O2 in the second recess 251b; and a second water inlet 253b for rotating egg cell O2 in the second recess 251b.

[0125] In Figure 6, egg O1 is an egg that has not yet been injected with sperm, egg O2 is an egg that is about to be injected with sperm, and egg O3 is an egg that has completed sperm injection.

[0126] The egg retention device D2 further includes a first water inlet 253a for transferring the egg O1 contained in the first recess 251a to the second recess 251b. In the egg retention device D2, the egg O1 contained in the first recess 251a can be transferred to the second recess 251b by supplying fluid from the first water inlet 253a. This allows sperm injection into egg O1 to be performed after sperm injection into egg O2 has been completed.

[0127] In the egg retention device D2, the second water inlet 253b not only plays a role in rotating the egg O2 in the second recess 251b, but also in transferring the egg O2 to the third recess 251c after sperm injection into the egg O2 is complete. By adjusting the amount and speed of the fluid supplied from the second water inlet 253b, it is possible to differentiate between rotating the egg O2 in the second recess 251b and transferring the egg O2 to the third recess 251c.

[0128] The first water inlet 253a and the second water inlet 253b are connected to the water supply device via the water supply port 257, similar to the egg holding device D1. Similar to the egg holding device D1, the first water inlet 253a and the second water inlet 253b may be connected to the same water supply port 257 or to different water supply ports 257.

[0129] Furthermore, the egg retention device D2 includes a marker 252, a suction port 254, a drain port 255, a suction port 258, and a drain port 259, and its configuration may be the same as that of the marker 152, suction port 154, drain port 155, suction port 158, and drain port 159 of the egg retention device D1.

[0130] [Note] This disclosure includes the following embodiments. [1] An intracytoplasmic sperm injection (ICSI) support device that assists in intracytoplasmic sperm injection by injecting sperm held in a sperm injection tool into an egg held in an egg holding device, An acquisition unit that acquires information including the relative positional relationship between the sperm injection tool and the egg, A control unit controls the movement of the stage on which the egg-holding device is positioned to perform intracytoplasmic sperm injection by injecting the sperm into the egg, based on the information acquired by the acquisition unit. An intracytoplasmic sperm injection support device equipped with the following features. [2] The acquisition unit further acquires information including the relative positional relationship between the sperm injection tool and the sperm contained in the sperm pool placed on the stage. The control unit further controls the movement of the stage to hold the immobilized sperm in the sperm injection tool based on the information acquired by the acquisition unit. [1] The intracytoplasmic sperm injection support device described above. [3] An imaging unit for imaging the egg, the sperm, and the sperm injection tool, A drive unit for moving the stage based on instructions from the control unit, Furthermore, The intracytoplasmic sperm injection support device described in [1] or [2]. [4] The egg-holding device is connected to an aspiration device for holding the egg in the egg-holding device. The control unit further controls the suction device. An intracytoplasmic sperm injection support device described in any one of [1] to [3]. [5] The egg-holding device is connected to a water supply device for rotating the egg within the egg-holding device. The control unit further controls the water supply device. An intracytoplasmic sperm injection support device described in any one of [1] to [4]. [6] The acquisition unit further acquires information including the position of the polar body of the egg, The control unit controls the water delivery device to rotate the egg in order to inject the sperm with the sperm injection tool from a direction in which the polar body is not located. [5] The intracytoplasmic sperm injection support device described below. [7] The water supply device includes temperature control means for maintaining the temperature of the water being supplied within a certain range. The intracytoplasmic sperm injection support device described in [5] or [6]. [8] The sperm injection tool is fixedly mounted to the imaging unit. An intracytoplasmic sperm injection support device as described in any one of [3] to [7]. [9] An egg retention device for placement in an intracytoplasmic sperm injection support device described in any one of [1] to [8], A recess for containing the egg, A suction port for holding the egg in the recess, Equipped with, Egg retention device.

[10] The device further includes a water inlet for rotating the egg in the recess. The egg retention device described in [9].

[11] A microinsemination support device described in any one of [1] to [8], The aforementioned sperm injection tool, Equipped with, Intracytoplasmic sperm injection (ICSI) support system.

[12] An intracytoplasmic sperm injection (ICSI) support program that assists in intracytoplasmic sperm injection by injecting sperm held in a sperm injection tool into an egg held in an egg holding device, Computers, An acquisition unit that acquires information including the relative positional relationship between the sperm injection tool and the egg, A control unit controls the movement of the stage on which the egg-holding device is positioned to perform intracytoplasmic sperm injection by injecting the sperm into the egg, based on the information acquired by the acquisition unit. To make it function as program. [Explanation of Symbols]

[0131] 1... Intracytoplasmic sperm injection support system, 2... Intracytoplasmic sperm injection support device, 3... Sperm injection tool, 11... Stage, 12... Drive unit, 13... Imaging unit, 14... Container, 21... Acquisition unit, 22... Control unit, 23... Analysis unit, 151, 251... Recess, 152, 252... Marker, 153, 253... Water inlet, 154, 254... Suction port, 155, 255... Drain port, 157, 257... Water supply port, 158, 258...Suction port, 159, 259...Drainage port, 221...Imaging control unit, 222...Drive control unit, 223...Sperm injection tool control unit, 224...Suction device control unit, 225...Water supply device control unit, 231...Sperm recognition unit, 232...Egg recognition unit, 233...Sperm evaluation unit, 234...Egg evaluation unit, D1, D2...Egg holding device, O...Egg, PO...Egg pool, PS...Sperm pool.

Claims

1. An intracytoplasmic sperm injection (ICSI) support device that assists in intracytoplasmic sperm injection by injecting sperm held in a sperm injection tool into an egg held in an egg holding device, An acquisition unit that acquires information including the relative positional relationship between the sperm injection tool and the egg, A control unit controls the movement of the stage on which the egg-holding device is positioned to perform intracytoplasmic sperm injection by injecting the sperm into the egg, based on the information acquired by the acquisition unit. An intracytoplasmic sperm injection support device equipped with the following features.

2. The acquisition unit further acquires information including the relative positional relationship between the sperm injection tool and the sperm contained in the sperm pool placed on the stage. The control unit further controls the movement of the stage to hold the immobilized sperm in the sperm injection tool based on the information acquired by the acquisition unit. The intracytoplasmic sperm injection support device according to claim 1.

3. An imaging unit for imaging the egg, the sperm, and the sperm injection tool, A drive unit for moving the stage based on instructions from the control unit, Furthermore, The intracytoplasmic sperm injection support device according to claim 1.

4. The egg-holding device is connected to an aspiration device for holding the egg in the egg-holding device. The control unit further controls the suction device. The intracytoplasmic sperm injection support device according to claim 1.

5. The egg-holding device is connected to a water supply device for rotating the egg within the egg-holding device. The control unit further controls the water supply device. The intracytoplasmic sperm injection support device according to claim 1.

6. The acquisition unit further acquires information including the position of the polar body of the egg, The control unit controls the water delivery device to rotate the egg in order to inject the sperm with the sperm injection tool from a direction in which the polar body is not located. The intracytoplasmic sperm injection support device according to claim 5.

7. The water supply device includes temperature control means for maintaining the temperature of the water being supplied within a certain range. The intracytoplasmic sperm injection support device according to claim 5.

8. The sperm injection tool is fixedly mounted to the imaging unit. The intracytoplasmic sperm injection support device according to claim 3.

9. An egg retention device for placement in an intracytoplasmic sperm injection support device according to any one of claims 1 to 8, A recess for containing the egg, A suction port for holding the egg in the recess, Equipped with, Egg retention device.

10. The device further includes a water inlet for rotating the egg in the recess. The egg retention device according to claim 9.

11. An intracytoplasmic sperm injection support device according to any one of claims 1 to 8, The aforementioned sperm injection tool, Equipped with, Intracytoplasmic sperm injection (ICSI) support system.

12. An intracytoplasmic sperm injection (ICSI) support program that assists in intracytoplasmic sperm injection by injecting sperm held in a sperm injection tool into an egg held in an egg holding device, Computers, An acquisition unit that acquires information including the relative positional relationship between the sperm injection tool and the egg, A control unit controls the movement of the stage on which the egg-holding device is positioned to perform intracytoplasmic sperm injection by injecting the sperm into the egg, based on the information acquired by the acquisition unit. To make it function as program.

Images