Microscopic insemination support device, microscopic insemination support system, microscopic insemination support program, and egg holding device
The ICSI support device simplifies the ICSI process by controlling stage movement based on acquired positional relationships, allowing precise sperm injection into eggs without complex sperm tool movement controls, thus addressing the complexity of existing ICSI technologies.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-09-08
- Publication Date
- 2026-03-12
AI Technical Summary
Current ICSI technologies require a long time to become proficient and often result in complex device configurations when attempting to automate sperm injection tools, necessitating a simpler and more efficient support system.
An ICSI support device and system that acquires the relative positional relationship between the sperm injection tool and the egg, controlling the stage movement to perform intracytoplasmic sperm injection without directly controlling the sperm injection tool, utilizing an egg holding device with a recess and suction port for precise sperm injection.
Facilitates a simpler device configuration for ICSI by enabling precise sperm injection into eggs based on acquired positional relationships, reducing the complexity of controlling the sperm injection tool movement.
Smart Images

Figure JP2025031718_12032026_PF_FP_ABST
Abstract
Description
Intracytoplasmic sperm injection support device, intracytoplasmic sperm injection support system, intracytoplasmic sperm injection support program, and egg retention device
[0001] The present disclosure relates to an intracytoplasmic sperm injection support apparatus, an intracytoplasmic sperm injection support system, an intracytoplasmic sperm injection support program, and an ovum holding device.
[0002] As one of the infertility treatments, intracytoplasmic sperm injection (ICSI), in which sperm are directly injected into the cytoplasm of an egg for fertilization, has been developed and put into practical use. In ICSI, sperm immobilization, sperm inhalation, and sperm injection into the egg are performed while observing the sperm and egg under a microscope, so ICSI is also called intracytoplasmic sperm injection.
[0003] Currently, ICSI is performed by embryologists, but since it takes a long time to become proficient in ICSI, there is a demand for technology to support ICSI. For example, Patent Document 1 discloses a control device for moving surgical tools manually operated by embryologists to desired positions.
[0004] Japanese Patent Application Laid-Open No. 2021-029453
[0005] However, currently, technology to support ICSI 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, the present disclosure provides an ICSI support device, ICSI support system, ICSI support program, or ovum holding device, etc., with a simple device configuration.
[0006] An intracytoplasmic sperm injection support device according to one aspect of the present disclosure is an intracytoplasmic sperm injection support device that supports intracytoplasmic sperm injection by injecting sperm held in a sperm injection tool into an egg held by an egg holding device, and includes 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 placed to inject sperm into the egg and perform intracytoplasmic sperm injection based on the information acquired by the acquisition unit.
[0007] This ICSI support device supports ICSI by moving the stage based on the acquired information including the relative positional relationship between the sperm injection tool and the egg. Therefore, unlike devices that support ICSI by controlling the movement of the sperm injection tool, such as those described in Patent Document 1, the ICSI system can be configured without a mechanism for controlling the movement of the sperm injection tool.
[0008] An ovum holding device according to one aspect of the present disclosure includes a recess for accommodating an ovum and a suction port for holding the ovum in the recess. Such an ovum holding device is disposed in the above-mentioned ICSI support apparatus for use.
[0009] Such an egg holding device allows the ICSI support device to fix and rotate the egg contained therein, so that, for example, the sperm injection tool can be inserted into the egg from an appropriate direction without controlling the movement of the sperm injection tool.
[0010] An intracytoplasmic sperm injection support system according to one aspect of the present disclosure includes an intracytoplasmic sperm injection support device according to one aspect of the present disclosure and a sperm injection tool.
[0011] An aspect of the present disclosure provides an ICSI support program that supports ICSI injecting sperm held in a sperm injection tool into an egg held by an egg holding device, and causes a computer to function 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, based on the information acquired by the acquisition unit, the movement of a stage on which the egg holding device is placed to inject sperm into the egg and perform ICSI.
[0012] The ICSI support system and ICSI support program support ICSI by moving the stage based on the acquired information including the relative positional relationship between the sperm injection tool and the egg. Therefore, unlike a device that supports ICSI by controlling the movement of the sperm injection tool, such as that described in Patent Document 1, the ICSI system can be configured without a mechanism for controlling the movement of the sperm injection tool.
[0013] In addition, the program according to one aspect of the present disclosure can be installed or loaded onto a computer and / or device through various recording media such as optical disks such as CD-ROMs, magnetic disks, and semiconductor memories, or by downloading via a communication network, etc.
[0014] Furthermore, in this specification, the term "unit" does not simply mean a physical component, but also includes cases where the functions of that component are realized by software. Furthermore, the functions of one component may be realized by two or more physical components, or the functions of two or more components may be realized by one physical component.
[0015] According to the present disclosure, it is possible to provide an ICSI support device, ICSI support system, ICSI support program, or ovum holding device, etc., having a simple device configuration.
[0016] FIG. 1 is an overall conceptual diagram of an intracytoplasmic sperm injection support system according to the present embodiment. FIG. 2 is an example of a functional block diagram of an intracytoplasmic sperm injection support device according to the present embodiment. FIG. 3 is an example of a physical configuration of an intracytoplasmic sperm injection support device according to the present embodiment. FIG. 4 is a schematic perspective view (A) and an enlarged plan view (B) of an ovum holding device according to the present embodiment. FIG. 5 is a flowchart showing an example of steps of an intracytoplasmic sperm injection method according to the present embodiment. FIG. 6 is a schematic perspective view of another example of an ovum holding device according to the present embodiment.
[0017] Hereinafter, an embodiment of the present invention (hereinafter referred to as "the present embodiment") will be described in detail with reference to the drawings. However, the present invention is not limited to this embodiment, and various modifications are possible without departing from the spirit of the present invention. 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 correspond to actual dimensions, proportions, etc. Parts in which the dimensional relationships and proportions differ from one another may be included.
[0018] [Intracytoplasmic sperm injection support system] An intracytoplasmic sperm injection support system 1 according to this embodiment will be described with reference to Fig. 1. Fig. 1 is an overall conceptual diagram of the intracytoplasmic sperm injection support system 1 according to this embodiment.
[0019] The ICSI support system 1 according to this embodiment includes an ICSI support device 2 according to this embodiment and a sperm injection tool 3. Details of the ICSI support device 2 according to this embodiment will be described later.
[0020] As shown in Fig. 1, the ICSI support device 2 is connected to a sperm injection tool 3, a drive unit 12 for moving a stage 11, and an imaging unit 13 for imaging a sample placed on the stage 11. Although the ICSI support device 2 is connected to other components by wire in Fig. 1, the ICSI support device 2 may be connected to other components wirelessly or may be physically integrated with other components. Therefore, one or more of the stage 11, drive unit 12, and imaging unit 13 may be included in the ICSI support device 2 as part of the ICSI support device 2.
[0021] A container 14 containing a sample is placed on the stage 11. The container 14 is, for example, a glass or resin dish. 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 equipped with a temperature control means for maintaining the sperm pool PS and / or the egg pool PO at a temperature suitable for ICSI. Examples of the temperature control means include a heater and a cooler. The temperature control means may have a function for measuring the temperature inside the container 14. The temperature suitable for ICSI is, for example, around 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 patients or subjects wishing to undergo ICSI. In addition to sperm, the sperm pool PS may contain a sperm culture medium or a highly viscous liquid that inhibits sperm motility (e.g., a polyvinylpyrrolidone (PVP) solution). The egg pool PO contains eggs obtained from patients or subjects wishing to undergo ICSI.
[0023] The egg pool PO may contain eggs as well as an egg culture medium. Examples of culture medium for sperm and eggs include, but are not limited to, physiological saline (salt containing 0.9 w / v% sodium chloride). The egg pool PO is provided on or adjacent to the egg holding device so that the egg can be held by the egg holding device.
[0024] The stage 11 includes a driver 12 for moving the stage. The driver 12 is only required to be able to move the stage 11 in the in-plane direction of the stage 11 (x and y directions in FIG. 1 ), but it is preferable that the driver 12 can also move the stage 11 in the direction perpendicular to the plane of the stage 11 (z direction in FIG. 1 ). In other words, the stage 11 is preferably a stage equipped with the driver 12 and capable of movement in three axial directions. The driver 12 may rotate the stage around each of the x, y, and z axes. In this case, the driver 12 can control movement with a total of six degrees of freedom, including translational movement and rotational movement about the x, y, and z axes.
[0025] The driving unit 12 is not particularly limited as long as it can move the stage 11 under the control of the ICSI supporting device 2, and may be, for example, an electrically controllable motor. The stage 11 and the driving unit 12 may be, for example, an electrically controllable automatic stage provided in a microscope.
[0026] The imaging unit 13 acquires captured images or captured video images of the sample on the stage 11 and the sperm injection tool 3. In Fig. 1, the imaging unit 13 captures a planar image of the sample on the stage 11 from a vertically upward direction of the stage 11. The imaging unit 13 also captures images so that the viewing angle includes at least the portion of the sperm injection tool 3 used for suctioning and injecting sperm, so that positional information of this portion can be acquired. Note that the imaging unit 13 does not necessarily have to be provided vertically upward of the stage 11, as long as it can acquire images or video images including the positional relationship between the sample on the stage 11 and the sperm injection tool 3.
[0027] The imaging unit 13 may be configured, for example, by an imaging device equipped with a CCD camera or a CMOS sensor. The imaging unit 13 may capture images of the sample on the stage 11 and the sperm injection tool 3 via an optical microscope. Observation methods using an optical microscope include, but are not limited to, bright-field observation, dark-field observation, phase-contrast observation, polarized light observation, spindle observation, differential interference observation, and relief contrast observation. The magnification of the objective lens may also be adjusted appropriately, and may be, 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 describes the case where the imaging unit 13 acquires a moving image; however, it goes without saying that ICSI can also be supported when the imaging unit 13 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 ICSI. The sperm injection tool 3 is preferably capable of contacting the sperm pool PS and aspirating sperm. The sperm injection tool 3 may also be equipped with a means for immobilizing sperm in the sperm pool PS. Examples of means for immobilizing sperm include a means for applying weak vibrations, such as a piezoelectric element, and a laser light irradiation means. Alternatively, the sperm may be immobilized by applying pressure directly to the sperm using the tip (e.g., the inlet / outlet) of the sperm injection tool 3. The means for immobilizing sperm may be provided in the ICSI support system 1 as a mechanism separate from the sperm injection tool 3.
[0029] The sperm injection tool 3 may be equipped with a pressure control mechanism for aspirating and injecting sperm. The pressure control mechanism may adjust the output of a pump included in or attached to the sperm injection tool 3 based on the control of the ICSI support device 2, and may aspirate sperm present near the inlet / outlet of the sperm injection tool 3, or expel sperm aspirated and held in the sperm injection tool 3 from the inlet / outlet.
[0030] It is preferable that the sperm injection tool 3 is provided at a fixed position relative to the imaging unit 13. According to this embodiment, even if the stage 11 is moved, the position of the sperm injection tool 3 does not move in the imaging field 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 ICSI support device 2 supports ICSI based on the captured moving 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] (Intracytoplasmic sperm injection support device) Figure 2 is a functional block diagram of the intracytoplasmic sperm injection support device 2. The intracytoplasmic sperm injection support device 2 includes an acquisition unit 21, a control unit 22, and an analysis unit 23. The intracytoplasmic sperm injection support device 2 supports intracytoplasmic sperm injection, which injects sperm held in a sperm injection tool 3 into an egg held by an 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 acquired by the imaging unit 13 capturing images of the egg pool PO and the 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 captured image or captured video captured by the imaging unit 13, and does not need to acquire the captured image or captured video itself captured by the imaging unit 13.
[0034] In one embodiment, the acquisition unit 21 may acquire a captured image or a captured video captured by the imaging unit 13, the image capturing field including the sperm injection tool 3 and the egg. 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 captured image or the captured video 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 entrance / exit of the sperm injection tool 3 and the egg, or the coordinates of the entrance / exit 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 accommodates the egg. The coordinates of the entrance / exit of the sperm injection tool 3 and the egg may be xy coordinates in the in-plane direction of the stage 11, or may be xyz coordinates that further include the z direction perpendicular to the plane of the stage 11. The acquisition unit 21 may acquire the extension direction of the entrance / exit of the sperm injection tool 3, that is, the insertion direction when inserting the sperm injection tool 3 into an egg.
[0035] The acquisition unit 21 may further acquire information including the position of the polar body of the egg. In ICSI, sperm injection into the cytoplasm of the egg is often performed while avoiding the polar body of the egg. This is because the spindle tends to be located near the polar body (first polar body) of the egg, and damage to the spindle due to insertion of the sperm injection tool 3 is prevented. Therefore, the acquisition unit 21 may further acquire information including the position of the spindle of the egg.
[0036] The position of the polar body of the ovum can be acquired from an observation image of the ovum, and therefore the acquisition unit 21 may acquire information including the position of the polar body of the ovum by acquiring the captured image or the captured video of the ovum 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 ovum, which is obtained by analyzing the captured image or the captured video 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 placed on the stage 11.
[0038] In one embodiment, the acquisition unit 21 may acquire a captured image or a captured video image captured by the imaging unit 13, the image including the sperm injection tool 3 and the sperm 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 sperm, obtained by analyzing the captured image or the captured video image captured by the imaging unit 13. The information indicating the relative positional relationship between the sperm injection tool 3 and the sperm may be, for example, the distance between the entrance / exit of the sperm injection tool 3 and the sperm, or the coordinates of the entrance / exit of the sperm injection tool 3 and the sperm.
[0039] The acquisition unit 21 may be realized by a communication unit 2d described later.
[0040] The control unit 22 controls the movement of the stage 11 on which the egg holding device is placed to inject sperm into eggs and perform ICSI, based on the information acquired by the acquisition unit 21. 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 (fluid supply device control unit) 225 in order to hold sperm in the sperm injection tool 3 and inject the held sperm into an egg to perform intracytoplasmic sperm injection.
[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 ICSI.
[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 an electrical mechanism included in the drive unit 12.
[0044] The sperm injection tool control unit 223 controls the sperm injection tool 3 to aspirate and eject 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 a pump included in or attached to the sperm injection tool 3. If the sperm injection tool 3 is equipped with a means for immobilizing sperm, the sperm injection tool control unit 223 may control the sperm injection tool 3 to operate the means for immobilizing sperm and immobilize the sperm.
[0045] The suction device control unit 224 and the fluid supply device control unit 225 respectively control a suction device and a water supply device (fluid supply device) that may be connected to the egg holding device. Details of the egg holding device will be described later, but the suction device holds the eggs in the egg holding device. In addition, the fluid supply device may rotate the eggs held or housed in the egg holding device.
[0046] The suction device control unit 224 and the fluid supply device control unit 225 respectively control the suction device and the fluid supply device to suck and rotate the ovum. The suction device control unit 224 and the fluid supply device control unit 225 suck the ovum and supply water (supply fluid) to the ovum based on the information about the ovum acquired by the acquisition unit 21.
[0047] Based on information including the position of the polar body of the ovum acquired by the acquisition unit 21, the fluid supplying device control unit 225 may control the fluid supplying device to rotate the ovum so that sperm can be injected by the sperm injection tool from a direction in which the polar body is not located. To this end, the fluid supplying device control unit 225 may rotate the ovum by controlling the fluid supplying device to supply fluid to the ovum so that the polar body of the ovum is positioned approximately at 12 o'clock or 6 o'clock, with the direction in which the sperm injection tool 3 is located being the 3 o'clock direction. The fluid supplying device control unit 225 may control the temperature of the fluid supplied from the fluid supplying device so that the temperature in the container 14 is maintained at a temperature suitable for ICSI. The temperature of the fluid is controlled, for example, by a temperature control unit that may be provided in the fluid supplying device. Examples of the temperature control unit include a heater and a cooler. The temperature control unit may have a function of measuring the temperature of the fluid supplied from the fluid supplying device.
[0048] The suction device is not particularly limited as long as it is connected to the ovum holding device and can suck up ova located near the suction port of the ovum 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 fluid supplying device is not particularly limited as long as it is connected to the ovum holding device and can supply fluid from the fluid supply port of the ovum holding device. The fluid supplying device may be, for example, a pump capable of controlling the flow rate of the supplied fluid by the fluid supplying device control unit 225. The fluid supplying device may be equipped with a temperature control means for maintaining the temperature of the supplied fluid within a certain range. Examples of the temperature control means include a heater and a cooler. The temperature control means may have a function for measuring the temperature of the fluid supplied from the fluid supplying device. The temperature of the fluid is preferably maintained at a temperature suitable for ICSI, which is, for example, around 37°C, and may be 33 to 40°C, 35 to 38°C, 36 to 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 realized by a program stored in a RAM 2b or a ROM 2c (described later) and executed by the CPU 2a. Instructions from the control unit 22 are sent 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 by the control unit 22. In this embodiment, the analysis unit 23 is provided in the ICSI support device 2, but may be provided in a unit or device other than the ICSI support device 2, for example, 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 ovum recognition unit 232, a sperm evaluation unit 233, and an ovum evaluation unit 234.
[0052] The sperm recognition unit 231 recognizes sperm by analyzing the information acquired by the acquisition unit 21. When the acquisition unit 21 acquires a captured image or a captured video, methods for recognizing sperm from the image or video include a method of preparing multiple representative images showing typical shapes of sperm and performing pattern matching using the representative images for each frame in the image or video, and a method of using a learning model trained using sperm observation images as training data.
[0053] The ovum recognition unit 232 analyzes the information acquired by the acquisition unit 21 and recognizes the ovum. When the acquisition unit 21 acquires captured images or captured video, methods for recognizing the ovum from the images or video include a method of preparing multiple representative images showing typical shapes of the ovum and performing pattern matching using the representative images for each frame in the image or video, and a method of using a learning model trained using observed images of the ovum as training data. Alternatively, the ovum may be recognized based on markers attached to the ovum 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 birth success rate when used in ICSI. High sperm 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 sperm evaluation unit 233 may quantify the sperm quality by calculating at least one index related to sperm quality.
[0055] The at least one index related to sperm quality is not particularly limited, but may include, for example, an index described in the WHO Laboratory Manual for the Examination and Processing of Human Semen (Sixth Edition) published by the World Health Organization (WHO). Such an index may include, for example, at least one of sperm motility, sperm morphology, and the degree of sperm DNA fragmentation, or an index calculated from 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 over a predetermined time interval, the linearity of the movement trajectory, etc. The sperm evaluation unit 233 can track sperm over a predetermined time interval and calculate the speed of movement, the linearity of the movement trajectory, etc. based on the position information of the sperm in each frame. Sperm motility may also be calculated using a learning model trained using sperm quality and movement as training data.
[0057] Sperm morphology can be indexed based on the morphology of the sperm captured in each frame of a captured image or video. The sperm evaluation unit 233 may index the morphology of one sperm based on multiple frames and calculate a single index by averaging these values. Sperm morphology can be indexed based on, for example, the shape of the sperm head, the shape of the sperm tail, and the balance of their defects and sizes. Sperm motility may be calculated using a learning model trained using sperm quality and morphology as training data.
[0058] The degree of sperm DNA fragmentation can be indexed by comprehensively considering the sperm's movement, such as the speed of movement over a predetermined time interval and the linearity of the movement trajectory, as well as the morphology of the sperm captured in each frame of the captured image or video. The degree of sperm DNA fragmentation can also be calculated using a learning model trained using the degree of sperm DNA fragmentation and the sperm's movement and / or morphology as training data. The degree of sperm DNA fragmentation can be measured using stained images in which sperm with DNA fragmentation are selectively stained.
[0059] The sperm evaluation unit 233 may calculate an index that comprehensively evaluates sperm quality by taking into consideration two or more of the above-mentioned indices. The sperm evaluation unit 233 may calculate an index by optionally weighting the indices related to sperm motility, sperm morphology, and the degree of occurrence of sperm DNA fragmentation, and then averaging the weighted indices. In this case, if any of the indices is below a threshold, a penalty may be imposed by subtracting 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 achievement rate, implantation rate, and / or birth success rate when used in ICSI. High egg quality means that the fertilization success rate, blastocyst achievement rate, implantation rate, and / or birth success rate when used in ICSI are relatively high. The egg evaluation unit 234 may quantify the egg quality by calculating at least one index related to egg quality.
[0061] The ovum evaluation unit 234 may evaluate the quality of the ovum based on, for example, the positions, shapes, and sizes of the polar bodies, spindles, and smooth endoplasmic reticulum, the degree of turbidity of the cytoplasm, etc. The ovum evaluation unit 234 may evaluate the quality of the ovum using a learning model that is trained using the quality and morphology of the ovum as training data.
[0062] The analysis unit 23 may be realized by a program stored in the RAM 2 b or the ROM 2 c described below and executed by the CPU 2 a. The analysis results by the analysis unit 23 may be used by the control unit 22, may be transmitted to each unit and device via the communication unit 2 d, or may be displayed on the display unit 2 f.
[0063] Next, the physical configuration of the ICSI 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 ICSI support device 2. The ICSI support device 2 has a CPU (Central Processing Unit) 2a equivalent to a processor, a RAM (Random Access Memory) 2b and a ROM (Read only Memory) 2c equivalent to a storage unit, a communication unit 2d, an input unit 2e, and a display unit 2f. These components are connected to each other via a bus so that data can be transmitted and received. In this example, the function of the ICSI support device 2 is described as being configured by a single computer, but the function of the ICSI support device 2 may be realized by combining multiple computers. Furthermore, the configuration shown in Figure 3 is an example, and the ICSI support device 2 may have components other than these, or may not have some of these components.
[0064] The CPU 2a controls the execution of programs stored in the RAM 2b or the ROM 2c and calculates and processes data. The CPU 2a is a calculation unit that executes programs that cause the computer to function as the acquisition unit 21, the control unit 22, and the 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 the RAM 2b or the ROM 2c.
[0065] The RAM 2b is a rewritable storage device and may be implemented as a semiconductor memory device. The RAM 2b may store programs executed by the CPU 2a. Note that these are merely examples, and the RAM 2b may store other data.
[0066] The ROM 2c is a memory from which data can be read, and may be configured with, for example, a semiconductor memory element. The ROM 2c may store, for example, data that is not rewritten.
[0067] The communication unit 2d is an interface that connects the ICSI support device 2 to other units and devices, such as the sperm injection tool 3, the drive unit 12, the imaging unit 13, the suction device, and the fluid supply device. The communication unit 2d may be connected to a network by wire or wirelessly.
[0068] The input unit 2e receives data input from a user and may include, for example, a keyboard and a touch panel.
[0069] The display unit 2f visually displays the results of calculations performed by the CPU 2a and may be configured with, for example, an LCD (Liquid Crystal Display). The display unit 2f may display information acquired by the acquisition unit 21, such as captured images or captured video images acquired by the imaging unit 13.
[0070] The ICSI support program according to this embodiment may be provided by being stored in a computer-readable storage medium such as RAM 2b or ROM 2c, or 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 using FIG. 2. Note that these physical configurations are merely examples and do not necessarily have to be independent configurations. For example, the ICSI support device 2 may be provided with an LSI (Large-Scale Integration) in which the CPU 2a and the RAM 2b and / or ROM 2c are integrated.
[0071] (Egg holding device) Next, an egg holding device for use in the ICSI support system 1 will be described with reference to Fig. 4. The egg holding device according to this embodiment is used to efficiently carry out control by the ICSI support apparatus 2 according to this embodiment. The egg holding device according to this embodiment may be made of, for example, resin.
[0072] 4A and 4B are a schematic perspective view and an enlarged plan view, respectively, of an ovum holding device D1 according to this embodiment. As shown in FIGS. 4A and 4B, the ovum holding device D1 includes recesses 151a, 151b, and 151c for accommodating ovum O1, O2, and O3, respectively, and suction ports 154a, 154b, and 154c for holding the ovum O1, O2, and O3 in the recesses 151a, 151b, and 151c, respectively. FIG. 4B is an enlarged plan view of the ovum O1 held in the recess 151a. The ovum holding device D1 further includes water supply ports (fluid supply ports) 153a, 153b, and 153c for rotating the ovum O1, O2, and O3 in the recesses 151a, 151b, and 151c.
[0073] 4(A), three eggs O1, O2, and O3 are respectively contained in three recesses 151a, 151b, and 151c, but the egg holding device D1 only needs to have a structure for containing and holding one or more eggs. Below, we will explain the case where three eggs O1, O2, and O3 are respectively contained in three recesses 151a, 151b, and 151c as shown in FIG. 4(A), but the number of eggs contained and held in the egg holding device D1 is not particularly limited.
[0074] Furthermore, in the following, when there is no need to distinguish between the three ova O1, O2, and O3, they will be collectively referred to as ova O. The same applies to other configurations; in Fig. 4(A), the symbols a, b, and c are assigned to the components of the ova holding device D1 corresponding to the three ova O1, O2, and O3, respectively, but when there is no need to distinguish between the components corresponding to the three ova 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 ova O1, O2, and O3 may be collectively referred to as recess 151.
[0075] Furthermore, the egg holding device D1 according to this embodiment may be provided as the egg pool PO in FIG. 1 or adjacent to the egg pool PO. That is, each recess of the egg holding device D1 may be used as an egg pool PO, or an egg pool PO containing eggs may be provided separately from the recesses of the egg holding device D1. Therefore, the egg holding device D1 according to this embodiment may move following 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 the imaging unit 13, and only the egg holding device D1 can be moved. As a result, by moving the stage 11, ICSI can be performed with high accuracy.
[0076] Returning to Figure 4, an egg O is held in the recess 151 of the egg holding device D1. The recess 151 is not particularly limited as long as it can hold the egg O in a predetermined area. The recess 151 may have a horizontal width and a vertical width 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 surrounded on the bottom and all four sides and having an opening at the top. One of the four surroundings forming the recess 151 may be partially removed. By partially removing one of the surroundings on the four sides forming the recess 151 in this way, it is possible to make it easier for the egg O to come into contact with the sperm injection tool 3.
[0078] In one embodiment, 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 the other wall portions. 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 the relatively lower portion of the wall portion may have a height of, for example, 20 to 200 μm, preferably 50 to 150 μm. The relatively lower portion of the wall portion may be located on the opposite side of the wall portion in which the suction port described below is provided.
[0079] A suction port 154 is provided on the wall forming the recess 151 of the egg holding device D1. By sucking the egg O through the suction port 154, the egg O can be held in the egg holding device D1. With the egg O sucked through the suction port 154, sperm can be injected into the egg O by bringing the entrance / exit of the sperm injection tool 3 into contact with the egg O. In other words, the suction port 154 plays the role of a holding pipette in a conventional ICSI operation.
[0080] Therefore, the suction port 154 may have a shape similar to that of the suction port of the holding pipette. For example, as shown in FIG. 4B, the suction port 154 may have a generally tapered shape whose diameter decreases 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, a generally circular, generally elliptical, or rounded rectangular shape. Such a shape can reduce damage to the ovum O when it is sucked in. The circle-equivalent diameter d of the opening of the suction port 154 is, for example, 10 to 150 μm, preferably 15 to 100 μm. The circle-equivalent 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 sucking the ovum O through the suction port 158. The suction port 154 and the suction port 158 are connected by a flow path inside the ovum holding device D1. A plurality of suction ports 158 may be provided corresponding to the plurality of suction ports 154a, 154b, and 154c, or one or a plurality of suction ports 158 connected to each of the plurality of suction ports 154a, 154b, and 154c may be provided. In FIG. 4(A), one suction port 158 is provided connected to each of the plurality of suction ports 154a, 154b, and 154c. Therefore, in FIG. 4(A), when the suction device connected to the suction port 158 is operated to suck the ovum O, all of the ovum O1, O2, and O3 contained in the recesses 151a, 151b, and 151c are sucked in simultaneously.
[0082] 4(B), when the ovum O is sucked through the suction port 158, a fluid flow F1 is generated from the opening of the suction port 154 toward the suction port 158, and the ovum O is drawn to and comes into contact with the opening of the suction port 154. By maintaining suction in this state of contact with the opening, the ovum O can be held at the opening of the suction port 154.
[0083] The wall portion that forms the recess 151 of the ovum holding device D1 is further provided with a fluid supply port 153. By supplying a fluid from the fluid supply port 153, the ovum held in the recess 151 can be moved or rotated within the recess 151.
[0084] As mentioned above, in ICSI, it is preferable to avoid the polar body when inserting the sperm injection tool into the oocyte in order to avoid damaging the spindle. As shown in Figure 4(B) , by supplying fluid to the oocyte O from the fluid supply port 153 while the acquisition unit 21 acquires positional information of the polar body PB of the oocyte O, the polar body can be moved to an appropriate position and held at the opening of the suction port 154 in this state.
[0085] In the embodiment shown in Figure 4(B), since the sperm injection tool 3 is inserted in the opposite direction to the suction port 154, i.e., from the bottom of Figure 4(B), it is preferable that the polar body PB is positioned in the direction of the fluid supply port 153 or the drain port 155, i.e., on the left or right side of Figure 4(B).
[0086] The shape of the fluid supply port 153 is not particularly limited as long as it can supply a fluid to the recess 151. The fluid supplied from the fluid supply port 153 is typically a liquid such as water or culture solution, but a gas such as air may also be supplied to the recess 151.
[0087] The fluid supply port 153 is connected to a fluid supply device that supplies fluid to the ova O through a water supply port (fluid supply port) 157. The fluid supply port 153 and the fluid supply port 157 are connected by a flow path inside the ovum holding device D1. A plurality of fluid supply ports 157 may be provided corresponding to the plurality of fluid supply ports 153a, 153b, and 153c, or one or a plurality of fluid supply ports 157 connected to each of the plurality of fluid supply ports 153a, 153b, and 153c may be provided. In FIG. 4(A), one fluid supply port 157 is provided that is connected to each of the plurality of fluid supply ports 153a, 153b, and 153c. Therefore, in FIG. 4(A), when the fluid supply device connected to the fluid supply port 157 is operated and the ova O is suctioned, fluid is supplied to the recesses 151a, 151b, and 151c.
[0088] As shown in FIG. 4B, when fluid is supplied to the recess 151 through the fluid supply port 157, a flow F2 of fluid is generated from the fluid supply port 157 toward the opening of the fluid supply port 153.
[0089] A drain port 155 may be provided in the wall portion forming the recess 151 of the ovum holding device D1. The drain port 155 is provided as a discharge path for the fluid supplied from the fluid supply port 153. When the upper portion of the recess 151 is an opening as in Fig. 4(A), the drain port 155 can be omitted.
[0090] The drain outlet 155 may be connected to a drainage device through a drainage port 159. The drain outlet 155 and the drainage port 159 are connected by a flow path inside the ovum holding device D1. A plurality of drainage ports 159 may be provided corresponding to the plurality of drainage ports 155a, 155b, and 155c, or one or a plurality of drainage ports 159 connected to each of the plurality of drainage ports 155a, 155b, and 155c may be provided. As shown in FIG. 4(B) , when draining through the drainage port 159, a fluid flow F3 is generated from the opening of the drainage outlet 155 toward the drainage port 159.
[0091] Markers 152 may be attached around the recess 151 of the egg holding device D1 to assist in identifying the recess 151 and the egg O. There may be one or more markers 152. To facilitate contact between the egg O and the sperm injection tool 3, it is preferable that the marker 152 be provided on the wall opposite the wall on which the suction port 154 is provided. In this case, the control unit 22 can recognize the marker 152 and perform control so that the sperm injection tool 3 is inserted into the egg O from the direction of the marker 152. The markers 152 may be provided around the recess 151, and in this case, the analysis unit 23 can recognize the marker 152 and recognize the approximate position of the egg O.
[0092] [Intracytoplasmic sperm injection method] A method for performing intracytoplasmic sperm injection using the intracytoplasmic sperm injection support system according to this embodiment will be described below. The intracytoplasmic sperm injection method according to this embodiment uses the intracytoplasmic sperm injection support system according to this embodiment, so at least a portion of the steps of intracytoplasmic sperm injection can be automated. In particular, since the step of injecting sperm into eggs can be automated, intracytoplasmic sperm injection can be performed efficiently and with a high success rate without relying on the individual skills of the embryologist.
[0093] Fig. 5 is a flow chart showing an example of the steps of the ICSI method according to this embodiment. Although not shown in Fig. 5, the person who performs 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 sample and the entrance and exit for the sperm injection tool 3 are located within the imaging field of the imaging unit 13.
[0094] Below, we will explain how the ICSI support system 1 automatically performs ICSI without the intervention of the ICSI practitioner, but some or all of the following steps can also be performed manually by the ICSI practitioner.
[0095] 5, in the ICSI 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"). In step S1, 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 sperm pool PS on the stage 11.
[0096] In step S1, the position of the sperm pool PS may be stored in the ICSI support device 2, and the stored position of the sperm pool PS may be called up 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 provided around the sperm pool PS, and the analysis unit 23 may recognize the marker and move the imaging area of the imaging unit 13 to the sperm pool PS.
[0097] Next, sperm to be used in ICSI are selected and immobilized (hereinafter also referred to as "Step S2"). In Step S2, first, good 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 sperm from the sperm whose quality has been evaluated. The sperm evaluation unit 233 may select sperm that have been evaluated as having relatively high quality from the sperm whose quality has been evaluated, or may select sperm that exceed a predetermined threshold.
[0098] In step S2, the selected sperm are then immobilized. The sperm immobilization may be performed by the sperm injection tool control unit 223 controlling the immobilization means provided in 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 controls the immobilization means provided in the sperm injection tool 3 to immobilize the sperm, the drive control unit 222 may control the drive unit 12 to move the stage 11 so that the selected sperm and the immobilization means provided in the sperm injection tool 3 are in a positional relationship appropriate for immobilization. When immobilizing the sperm by directly pressing the entrance / exit of the sperm injection tool 3 against the sperm, the drive control unit 222 may control the drive unit 12 to move the stage 11 so that the entrance / exit of the sperm injection tool 3 is appropriately brought into contact with the sperm.
[0099] Next, the immobilized sperm selected in step S2 are sucked in (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 so that the sperm to be sucked in approaches the entrance / exit of the sperm injection tool 3. Next, the sperm injection tool control unit 223 controls the sperm injection tool 3 to suck in the sperm from the entrance / exit 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 ovum 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 ovum pool PO on the stage 11.
[0101] In step S4, the position of the egg pool PO may be stored in the ICSI support device 2, and the stored position of the egg pool PO may be called up and the imaging area of the imaging unit 13 may be moved to the egg pool PO. Alternatively, markers indicating the position of the egg pool PO may be provided around the egg pool PO, and the markers may be recognized by the analysis unit 23, and the imaging area of the imaging unit 13 may be moved to the egg pool PO. The analysis unit 23 may recognize the egg holding device or may recognize a marker attached to the egg holding device.
[0102] Next, eggs to be used for ICSI are recognized and selected (hereinafter also referred to as "step S5"). In step S5, good eggs suitable for use in ICSI are selected. Specifically, the egg recognition unit 232 recognizes each egg in the egg pool PO, and the egg evaluation unit 234 evaluates the quality of each egg. The egg evaluation unit 234 selects good eggs from the eggs whose quality has been evaluated. The egg evaluation unit 234 may select eggs that have been evaluated as having relatively high quality from the eggs whose quality has been evaluated, or may select eggs that exceed a predetermined threshold.
[0103] In ICSI, the number of egg cells prepared is often smaller 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 depending on the quality of the selected egg.
[0104] For example, if high-quality eggs are selected in step S5, sperm of relatively high quality may be selected in step S2, or the threshold for sperm to be selected may be set higher than the normal setting to select high-quality sperm.
[0105] Alternatively, in ICSI, sperm are often injected into all of the prepared eggs, so evaluation of egg quality may be omitted.
[0106] Alternatively, if an egg of poor quality is selected in step S5, for example an egg with a quality index below a threshold, the automation of sperm injection may be canceled and the person performing the ICSI may be notified and prompted to perform manual injection.
[0107] Next, the orientation of the ovum 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 ovum based on the positional relationship between the sperm injection tool 3 and the ovum acquired by the acquisition unit 21. For example, the analysis unit 23 recognizes the position of the polar body of the ovum acquired by the acquisition unit 21, and determines the orientation of the ovum so that the polar body of the ovum is positioned perpendicular to the direction in which the sperm injection tool 3 is inserted.
[0108] Next, the ovum oriented in the direction determined in step S5 is held in the ovum holding device (hereinafter also referred to as "step S7"). In step S7, the fluid supply device control unit 225 controls the fluid supply device while the suction device control unit 224 controls the suction device, thereby holding the ovum oriented in the appropriate direction in the ovum holding device.
[0109] Next, the sperm sucked in step S3 are injected into the egg held in step S7 (hereinafter also referred to as "step S8"). In step S8, first, in order to inject the sperm into the egg and perform ICSI, the egg is brought close to the entrance / exit of the sperm injection tool 3. At this time, the drive control unit 222 controls the drive unit 12 to move the stage 11. Next, the sperm injection tool control unit 223 controls the sperm injection tool 3 to inject the sperm into the egg from the entrance / exit. After injection is complete, the sperm injection tool 3 is removed from the egg, completing ICSI.
[0110] Next, it is determined whether sperm injection into all eggs has been completed (hereinafter also referred to as "Step S9"). Step S9 only needs to be performed when a small number of egg cells have been prepared, and can be omitted when a large number of eggs have been prepared. The ICSI support device 2 stores the eggs into which sperm have been injected, and if it determines that there are eggs into which sperm have not been injected (Step S9: No), it returns to Step S1. At this time, the number of eggs into which sperm have not been injected may be displayed on the display unit 2f. If it determines that sperm injection into all eggs has been completed (Step S9: Yes), the process ends.
[0111] In each of the above steps, the acquisition unit 21 may optionally acquire information including the relative positional relationship between the entrance / exit of the sperm injection tool 3 and the egg, and / or information including the relative positional relationship between the entrance / exit 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 sperm is aspirated by the sperm injection tool 3 based on this information. In addition, in step S8, information including the relative positional relationship between the entrance / exit of the sperm injection tool 3 and the egg is acquired, and the sperm injection tool 3 is inserted into the egg based on this information. In addition, in step S6, the acquisition unit 21 further acquires information including the position of the polar body or spindle of the egg. In addition, when the acquisition unit 21 acquires captured images or captured video from the imaging unit 13, in each step, if at least one of the sperm injection tool 3, the egg, and the sperm is included in the imaging field of view, the acquisition unit 21 may acquire coordinates of at least one of the sperm injection tool 3, the egg, and the sperm based on the captured images or captured video.
[0112] [Modifications] Although an example of this embodiment has been described above, the present invention is not limited to the above. For example, unless otherwise specified, examples and / or preferred aspects (preferred, more preferred, even more preferred, even more preferred, 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 aspect may be combined with an embodiment described as a preferred aspect, or an embodiment described as a preferred aspect may be combined with a configuration described as a more preferred embodiment (or even more preferred embodiment, etc.). Furthermore, each component and step can be omitted as appropriate as long as it does not impair the effects of this embodiment.
[0113] For example, in the ICSI support system 1 shown in Figure 1, the egg pool PO and sperm pool PS are placed in the same container 14, but the egg pool PO and sperm pool PS may be placed in different containers. Also, if the ICSI support system 1 is used only for injecting sperm into eggs, a sperm pool does not need to be provided on the stage 11. In this case, the user of the ICSI support system 1 (typically, an embryologist) can perform ICSI using the sperm injection tool 3 holding sperm. In this case, steps S1 to S3 of the flowchart shown in Figure 5 can be omitted.
[0114] Furthermore, in the above description, the sperm injection tool 3 is fixed to the imaging unit 13, but this does not prevent the addition of a mechanism for moving the sperm injection tool 3. Therefore, the ICSI support device 2 according to this embodiment may control the movement of the sperm injection tool 3 in the sperm injection tool control unit 223. In this case, the movement of the stage 11 may be used as a primary movement means (e.g., a translational positioning means between the egg and the entrance / exit of the sperm injection tool 3), and the movement of the sperm injection tool 3 may be used as a secondary movement means (e.g., a rotational positioning means for adjusting the direction in which the entrance / exit of the sperm injection tool 3 is inserted into the egg).
[0115] In addition, in the ICSI method according to this embodiment, before, after, or during each step, the ICSI practitioner may accept processing. For example, in step S2, the ICSI practitioner may select sperm to be aspirated, or may immobilize sperm.
[0116] In step S3, the practitioner of ICSI may specify a method for aspirating sperm. For example, the practitioner of ICSI may select whether to aspirate sperm from the head side or the tail side.
[0117] In addition, in step S5, the person performing the ICSI may select an egg into which sperm will be injected.
[0118] Furthermore, the practitioner of ICSI may make adjustments during the injection of sperm into the ovum in steps S6 to S8. For example, the practitioner of ICSI may specify which part of the ovum the sperm injection tool 3 should be inserted into, the direction from which it should be inserted, and how far it should be inserted.
[0119] Furthermore, before or during each step, in order to capture high-resolution images of sperm and / or eggs, 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. Such adjustments may be performed by the person performing the ICSI. For example, the observation method and magnification of the optical microscope may be adjusted depending on the imaging target and purpose of each step, so that each step is performed appropriately.
[0120] Furthermore, a confirmation step may be included before each step, in which the ICSI practitioner is asked whether or not to proceed to the next step. Furthermore, if an abnormality is detected in each step, it is possible to switch to processing by the ICSI practitioner. Such abnormalities include, for example, when the state of the ovum is different from normal, such as when the perivitelline space is filled and the cytoplasm cannot be confirmed, or when there is an abnormality in the shape of the zona pellucida. Furthermore, when an abnormality is detected, a notice may be displayed to the ICSI practitioner to check the setup of the ICSI support system 1.
[0121] Furthermore, the ovum holding device may be the embodiment shown in Fig. 6 in addition to the embodiment shown in Fig. 4. The ovum holding device D2 shown in Fig. 6 differs from the ovum holding device D1 shown in Fig. 4 in that the first recess 251a, the second recess 251b, and the third recess 251c each have a different role.
[0122] That is, in the egg holding device D1 shown in Fig. 4, the three recesses 151a, 151b, and 151c are equivalent and have the same configuration. On the other hand, in the egg holding device D2 shown in Fig. 6, the first recess 251a serves as a pool of eggs that have not yet been injected with sperm (i.e., egg pool PO), the second recess 251b serves as a recess for holding eggs when sperm are injected (i.e., recess 151 of the egg holding device D1 shown in Fig. 4), and the third recess 251c serves as a pool of eggs that have completed sperm injection.
[0123] The ovum holding device D2 makes it easy to distinguish between ovum that have not been injected with sperm and ovum that have already been injected with sperm, facilitating the decision in step S9 in the flowchart shown in FIG.
[0124] The egg holding device D2 shown in Figure 6 includes a first recess 251a, a second recess 251b, and a third recess 251c for accommodating eggs O1, O2, and O3, respectively, a suction port 254 for holding the egg O2 in the second recess 251b, and a second water supply port (second fluid supply port) 253b for rotating the egg O2 in the second recess 251b.
[0125] In FIG. 6, egg O1 is an egg into which sperm has not yet been injected, egg O2 is an egg into which sperm is about to be injected, and egg O3 is an egg into which sperm has already been injected.
[0126] The egg holding device D2 further includes a first water supply port (first fluid supply port) 253a for transferring the egg O1 held in the first recess 251a to the second recess 251b. In the egg holding device D2, the egg O1 held in the first recess 251a can be transferred to the second recess 251b by supplying fluid from the first fluid supply port 253a. This allows sperm injection into the egg O1 to be performed subsequently after sperm injection into the egg O2 has been completed.
[0127] In the egg holding device D2, the second fluid supply port 253b not only serves to rotate the egg O2 in the second recess 251b but also to transfer the egg O2 to the third recess 251c after sperm injection into the egg O2 is completed. By adjusting the amount and speed of the fluid supplied from the second fluid supply port 253b, it is possible to distinguish between rotating the egg O2 in the second recess 251b and transferring the egg O2 to the third recess 251c.
[0128] Similar to the ovum holding device D1, the first fluid supply port 253a and the second fluid supply port 253b are connected to a fluid supply device via a fluid supply port 257. Similar to the ovum holding device D1, the first fluid supply port 253a and the second fluid supply port 253b may be connected to the same fluid supply port 257 or different fluid supply ports 257.
[0129] The egg holding device D2 also has a marker 252, a suction port 254, a drain port 255, a suction port 258, and a drain port 259, but the configuration may be similar to the marker 152, the suction port 154, the drain port 155, the suction port 158, and the drain port 159 of the egg holding device D1.
[0130] [Additional Notes] The present disclosure includes the following embodiments. [1] An ICSI support device that supports ICSI by injecting sperm held in a sperm injection tool into an egg held in an egg holding device, comprising: 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, based on the information acquired by the acquisition unit, movement of a stage on which the egg holding device is placed to inject the sperm into the egg for ICSI. [2] The ICSI support device described in [1], wherein the acquisition unit further acquires information including the relative positional relationship between the sperm injection tool and sperm held in a sperm pool placed on the stage, and the control unit further controls movement of the stage to hold the immobilized sperm in the sperm injection tool, based on the information acquired by the acquisition unit. [3] The ICSI support device according to [1] or [2], further comprising: an imaging unit that images the ovum, the sperm, and the sperm injection tool; and a drive unit that moves the stage based on instructions from the control unit. [4] The ICSI support device according to any one of [1] to [3], wherein the ovum holding device is connected to a suction device that holds the ovum in the ovum holding device, and the control unit further controls the suction device. [5] The ICSI support device according to any one of [1] to [4], wherein the ovum holding device is connected to a fluid supply device that rotates the ovum in the ovum holding device, and the control unit further controls the fluid supply device. [6] The ICSI support device according to [5], wherein the acquisition unit further acquires information including the position of the polar body of the ovum, and the control unit controls the fluid supply device to rotate the ovum so that the sperm can be injected by the sperm injection tool from a direction in which the polar body is not located. [7] The ICSI support device according to [5] or [6], wherein the fluid supply device is provided with a temperature control means for maintaining the temperature of the supplied fluid within a certain range. [8] The ICSI support device according to any one of [3] to [7], wherein the sperm injection tool is fixed to the imaging unit.[9] An egg holding device to be placed in the ICSI support apparatus described in any one of [1] to [8], comprising: a recess for accommodating an egg; and a suction port for holding the egg in the recess.
[10] An egg holding device described in [9], further comprising a fluid supply port for rotating the egg in the recess.
[11] An ICSI support system comprising: the ICSI support apparatus described in any one of [1] to [8]; and the sperm injection tool.
[12] An ICSI support program for supporting ICSI injecting sperm held in a sperm injection tool into an egg held by an egg holding device, the program causing a computer to function 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, based on the information acquired by the acquisition unit, movement of a stage on which the egg holding device is placed to inject the sperm into the egg and perform ICSI.
[0131] 1... ICSI support system, 2... ICSI 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... fluid supply port, 154, 254... suction port, 155, 255... drain port, 157, 257... fluid 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...fluid 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 ICSI support device that supports ICSI by injecting sperm held in a sperm injection tool 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 and the egg; and a control unit that controls the movement of a stage on which the egg holding device is placed, based on the information acquired by the acquisition unit, in order to inject the sperm into the egg and perform ICSI.
2. The ICSI support device of claim 1, wherein the acquisition unit further acquires information including the relative positional relationship between the sperm injection tool and the sperm contained in a sperm pool placed on the stage, and 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.
3. The ICSI support device according to claim 1, further comprising: an imaging unit that images the egg, the sperm, and the sperm injection tool; and a drive unit that moves the stage based on instructions from the control unit.
4. The ICSI assistance device according to claim 1, wherein the egg holding device is connected to a suction device for holding the egg in the egg holding device, and the control unit further controls the suction device.
5. The ICSI assistance device according to claim 1, wherein the egg holding device is connected to a fluid supplying device for rotating the egg in the egg holding device, and the control unit further controls the fluid supplying device.
6. The ICSI assistance device according to claim 5, wherein the acquisition unit further acquires information including the position of the polar body of the ovum, and the control unit controls the fluid supply device to rotate the ovum so that the sperm injection tool can inject the sperm from a direction in which the polar body is not located.
7. The ICSI assistance device according to claim 5, wherein the fluid supply device is provided with temperature control means for maintaining the temperature of the supplied fluid within a certain range.
8. The ICSI assistance device according to claim 3, wherein the sperm injection tool is fixed to the imaging unit.
9. An egg holding device to be placed in the ICSI assistance device according to any one of claims 1 to 8, comprising: a recess for accommodating an egg; and a suction port for holding the egg in the recess.
10. The egg holding device according to claim 9, further comprising a fluid supply port for rotating the egg in the recess.
11. An ICSI support system comprising: the ICSI support device according to any one of claims 1 to 8; and the sperm injection tool.
12. An ICSI support program that supports ICSI injecting sperm held in a sperm injection tool into an egg held by an egg holding device, the program causing a computer to function 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, based on the information acquired by the acquisition unit, the movement of a stage on which the egg holding device is placed in order to inject the sperm into the egg and perform ICSI.
Citation Information
Patent Citations
Micromanipulator
JP2001330781A
Stage device and minute manipulation equipment
JP2020126126A
Intracytoplasmic sperm injection training device
JP2020185007A
Micro-insemination apparatus and position control method of micro-insemination surgical instrument
JP2021029453A
Manipulator system and method for manipulating microscopic object to be manipulated
WO2012018136A1