Abstract: The invention provides (1) a method for stabilizing an egg or embryo in the uterus of a female mammal, (2) eggs or embryos having improved stability in the uterus, and (3) a method for preparing these eggs or embryos. The invention involves the use of magnetic particles and a magnetic field.

Abstract: A device for the in vitro development of an embryo in a fluid. A method for the in vitro development of an embryo in a fluid is also provided.

Abstract: A method and apparatus of dispensing a radiopharmaceutical wherein a source of flushing fluid is connected to a first port of a fluid delivery set; a pressurizing unit of a powered injector system (including a powered injector and the pressurizing unit) is connected to a second port of the fluid delivery set; air is purged from the fluid delivery set; and, after purging air from the fluid delivery set, a third port of the fluid delivery set is connected to a source of the radiopharmaceutical. A valve system is included to control flow of fluid. A syringe is operatively connected with a powered injector. A radioactive shield encloses the syringe during operation to protect personnel from detrimental effects. A dose calibrator measure the radioactivity in the syringe.

Abstract: A catheter assembly for performing embryo implants in a female's uterus including an inner component having an echogenic soft distal tip for supporting the embryo to be implanted in the womb. A guide cannula receives the inner component which in combination with the rigid proximal portion facilitates insertion of the distal tip and embryo into the womb through the cervix. The guide cannula is a hollow tubular member attached to the hub, and a distal end which protects the embryo on the inner component during insertion. Markings indicate the position of the soft distal tip of the inner component with respect to the guide cannula as well as the overall length of the catheter assembly. During the implantation process, ultrasound imaging equipment is used to monitor the position of the echogenic distal tip.

Abstract: The invention provides (1) a method for stabilizing an egg or embryo in the uterus of a female mammal, (2) eggs or embryos having improved stability in the uterus, and (3) a method for preparing these eggs or embryos. The invention involves the use of magnetic particles and a magnetic field.

Abstract: A device for monitoring temperature generated by an ablation apparatus on organic tissue is provided. The device comprises a temperature sensing pad; and an output device to receive and display a representation of a lesion found on the ablated organic tissue. Ablation systems incorporating the device and methods of using the device are also provided.

Abstract: A method and apparatus for assisted embryo implantation using a specialized microcatheter to prepare an implantation site within the subject's endometrial lining and to transport and place an embryo into the implantation site.

Abstract: The present invention relates to the detection of HLA-G. Antibodies to both soluble and membrane bound HLA-G are disclosed. Exemplary antibodies include 2C/C8, 3C/G4, and 4H84. 2C/C8 and 4H84 antibodies bind to the same region of HLA-G, which is a different region than that bound by 3C/G4. Methods of detection and diagnosis are disclosed as well as kits, including a miniaturized assay suitable for a clinical setting. Further, a method of selecting an embryos for in vitro fertilization is disclosed. A sandwich ELISA test is provided using two antibodies that bind to HLA-G at different regions. The HLA-G test according to the invention is over 1000 times more selective in binding to HLA-G than to antigens HLA-A2, HLA-B4, HLA-C, or mixed WBC preparations.

Abstract: Described is a catheter system for implanting embryos into a woman's uterus. The catheter system utilizes a protective catheter sleeve for introducing a catheter into the uterus without mucus contamination of an inner catheter. Once the sleeve containing the inner catheter is introduced into the uterus, the protected inner catheter, carrying the embryos, is pushed through a swivelable distal end cap on the sleeve to a desired implanting location. The distal end of the inner catheter has a protective cap and a side opening for embryo release. Also, stiffness and indicia features of the outer sleeve and inner catheter assist in the physician's handling of the catheter system and in ensuring a desired uterus location for implanting.

Abstract: An embryo-transfer catheter has an extruded shaft with a gas-filled lumen that extends helically along the catheter to provide an ultrasound marker. The catheter has a side opening close to a closed rounded patient end.

Abstract: An embryo transfer catheter has a main lumen, which opens close to the patient end through a side opening. The catheter is extruded with a second, smaller lumen, which is closed at both ends. The second lumen is filled with air so that it reflects ultrasound energy and enhances the visibility of the catheter under ultrasound observation.

Abstract: An internal catheter has a flexible plastic inner tube with an integrally formed protruding head with an axial channel. The internal catheter extends through an axial channel in an exterior catheter. With the internal catheter head withdrawn within the foam or spiral tip of the exterior catheter, the assembly is advanced into a sow cervix, and the internal catheter is then advanced through the tip of the catheter and remaining portion of the cervix and into the uterine body and possibly into a uterine horn. Semen or embryos are then introduced through the axial cavity. The tip of the exterior catheter may have a protective flap which is not penetrated until the inner tube is advanced therethrough. The internal catheter axial channel may have a constricted portion within the head, to engage a semen or embryo containing straw.

Abstract: An internal catheter has a flexible plastic inner tube with an integrally formed protruding head with an axial channel. The internal catheter extends through an axial channel in an exterior catheter. With the internal catheter head withdrawn within the foam or spiral tip of the exterior catheter, the assembly is advanced into a sow cervix, and the internal catheter is then advanced through the tip of the catheter and remaining portion of the cervix and into the uterine body and possibly into a uterine horn. Semen or embryos are then introduced through the axial cavity. The tip of the exterior catheter may have a protective flap which is not penetrated until the inner tube is advanced therethrough. The internal catheter axial channel may have a constricted portion within the head, to engage a semen or embryo containing straw.

Abstract: A catheter including a shaft comprising a body with a proximal portion and a distal portion, the body defining an opening from the proximal portion to the distal portion, the distal portion having an end that is beveled in a first direction across an end opening, such that a length of the shaft to a first point on the end is a first length and a length of the shaft to a second point on the end is a second length longer than the first length. A method including placing at least one embryo near an open end of a catheter, inserting the open end of the catheter into an endometrial lining of a subject's uterus, using the catheter to open a flap of the endometrial lining, and transferring the at least one embryo from the catheter to the pocket site.

Abstract: A method and apparatus for assisted embryo implantation using a specialized microcatheter to prepare an implantation site within the subject's endometrial lining and to transport and place an embryo into the implantation site.

Abstract: An isolated and purified glycoprotein designated PUP-1 and functional analogs thereof are disclosed and characterized by being a progesterone induced and estradiol inhibited secretory glycoprotein from stromal cells of endometrial origin; having an N-terminal amino acid sequence as set forth in SEQ ID No:1; having a molecular weight of 70,000 daltons and an isoelectric point of 5.7; and synthesized by endometrium at the time of fertilization, early embryogenesis, and implantation. The present invention further provides a method of determining endometrial receptivity, monitoring placental physiology during gestation, and monitoring the effects of protocols to induce ovarian hyperstimulation or ovulation induction on uterine receptivity by monitoring the cyclic presence of PUP-1 in bodily fluid and tissue samples.

Abstract: The present invention is directed to compositions and apparatus to be used in methods of implantation of embryos for in vitro fertilization. The methods include insertion of embryos that have attached adhesives. Such methods, compositions and apparatus can be used with any mammals, including humans, farm animals and exotic or endangered animals.

Abstract: The present invention aims to provide a medium composition for in vitro fertilization, in particular, a composition usable in the culture of ova or early embryos which are fertilized eggs, the preparation or culture of sperm, and the pre-treatment of ova or sperm.The composition comprises, as its essential components, L-phenylalanine, L-tryptophan, L-lysine, L-threonine, L-valine, L-methionine, L-isoleucine, L-leucine, L-proline, glycine, L-alanine, L-tyrosine, L-histidine, L-arginine, L-taurine, L-aspartic acid, L-serine, L-asparagine, L-glutamic acid, L-glutamine and L-cystine, provided that at least a part of the L-cystine may be replaced by L-cysteine.

Abstract: A system for controlling a plurality of ophthalmic microsurgical instruments connected thereto. The microsurgical instruments are for use by a user such as a surgeon in performing ophthalmic surgical procedures. The system includes a data communications bus and a user interface connected to the data communications bus. The user interface provides information to the user and receives information from the user which is representative of operating parameters of the microsurgical instruments. The system also includes surgical modules connected to and controlling the microsurgical instruments as a function of at least one of the operating parameters. The surgical modules are also connected to the data communications bus. The data communications bus provides communication of data representative of the operating parameters between the user interface and the surgical modules.

Abstract: Improved insemination systems particularly adapted to use for sex-selected sperm sorting include systems which achieve superovulation and then multiple embryo production with sexed embryos. These systems combine with other techniques, including techniques for enhanced sheath fluid and other strategies which minimize stress on the sperm cells, and, potentially, a 2.9 percent sodium citrate sheath solution for bovine species and a hepes bovine gamete media for equine species. Improved collection systems and techniques for the process are described so that commercial application of sperms samples as well as the resulting animals may be achieved.

Abstract: The present invention comprises a method and apparatus for implantation of an embryo by a flexible delivery catheter onto a pre-selected optimum site on the endometrium of a female uterus. The method comprises the steps of securing the embryo onto the endometrium of the uterus with an adhesive carried by a distal end of the flexible catheter, and depositing the embryo in a medium of Hyaluronic Acid prior to its disposition onto the endometrium of the uterus. The method also includes the steps of positioning the flexible delivery catheter within the uterus, under the guidance of a flexible visualization device carried by the catheter, and arranging a plurality of lumens within the catheter to permit the introduction of the adhesive medium through one lumen, and the visualization device through another of the lumens, to permit the delivery site selection.

Abstract: The present invention covers a method for the emplacement of an embryo against an endometrium wall of a uterus. The method comprises the steps of: placing the embryo onto a balloon; inserting the balloon into a uterus; inflating the balloon in the uterus, so as to expand the balloon and the embryo thereon against the endometrium for implantation in the uterus. The invention also includes an apparatus for the emplacement of that embryo against an endometrium wall of a uterus. The apparatus includes a balloon having an outer surface for the receipt of an embryo thereon, a hollow inserter tube having a proximal and a distal end, and an optical fiber viewing device movably arranged within the hollow inserter tube. The balloon is arranged on the distal end of the inserter tube. A cavity is arranged adjacent the distal end of the inserter tube, for receipt of a portion of the balloon during insertion of the balloon on the inserter tube into a uterus.

Abstract: This invention relates to a system for penetrating the uterus of an animal during a non-surgical procudure, the uterus having a cervix leading to a uterus body. The system comprises a probe having a long tubular body with a central longitudinal axis, open forward and rearward ends, and a probing member projecting forward and laterally outward beyond the forward end of the probe body. The probe is inserted, forward end first, inside the cervix of said animal, and the probe body is manipulated to gently maneuver the probing member in a forward direction through the cervix to a position in which the probing member and the forward open end of the probe body are adjacent the body of the uterus.

Abstract: The present invention provides a human embryo co-culture system comprising a suspension of cultured human tubal epithelial cells. Also provided is a method of method of improving the pregnancy rate of a female undergoing in vitro fertilization, comprising the steps of: contacting an oocyte from said female with a monolayer of cultured human tubal epithelial cells; inseminating the oocyte; and transferring an embryo back to said female.

Abstract: The present invention includes a closed sterile in-vitro fertilization system to provide incubation for an oocyte. The system comprises a pouch having a flexible front and a flexible back wall joined at their outer peripheries. The pouch is divided into a first and a second segregated chamber. An entry port is arranged in each of the chambers through the wall of the pouch. A vacuum means is arranged in the first chamber, to permit direct aspiration of an oocyte from an ovary into that chamber, and an entry conduit is arranged between the first and the second chambers, to permit an oocyte to be transferred therebetween.

Abstract: Invitro incubation of primate embryos in the presence of gonadotrophin releasor hormone (GnRH) results in enhanced chorionic gonadotrophin production associated with increased survival and attachment of the embryos. Treatment of invitro fertilized embryos with GnRH can be used to improve implantation. Agonists of GnRH reduce attachment competence of embryos and are thereby useful as post-fertilization contraceptives.

Abstract: Cryopreservation of primordial germ cells and germ cells, in which primordial germ cells or germ cells are separated from bird embryos before meiosis and are then suspended and frozen in a freezing medium containing a cryoprotective agent is useful for the conservation of species of birds, for the protection of rare species which are in danger of extinction and also for the production of transgenic animals, the production of novel animals having gene markers on a cellular level, the production of animals useful as disease models, the production of useful substances by genetic engineering, and the development of test methods for toxicity to germ-line cells.

Abstract: A method of directly freezing porcine embryos which includes adding a solution to be frozen including ethylene glycol, propylene glycol, bovine serum and dextran in the presence of basic medium to porcine embryos and freezing the resulting mixture.

Abstract: Therapeutic and diagnostic methods of use for the growth factor transforming growth factor .beta., are provided by this invention. In accordance with preferred embodiments, methods of determining competence of a conceptus toward uterine implantation are provided as are methods for determining female infertility in mammals.

Abstract: The invention involves a system for effecting the nonsurgical transplant of embryos into the uterus of an animal. The system comprises (1) a long tubular gripping instrument having an open forward end configured for gripping the walls of the cervix of the uterus when the instrument is inserted to a position inside the cervix, and (2) a probe having a long tubular body which extends through the tubular gripping instrument, the probe being manipulatable to effect movement of the probe relative to the gripping instrument to facilitate passage of the probe and the gripping instrument through the cervix to a position generally adjacent the body of the uterus, and (3) an embryo carrier for carrying one or more embryos to be placed in the uterus of the animal. The embryo carrier is sized for insertion in and through the tubular probe to an embryo release position for release of the embryos into the uterus.

Abstract: This invention relates to a method and apparatus for concentrating motile erm from a sperm sample, including concentrating sperm in the vicinity of one or more oocytes for in vitro fertilization. The method comprises placing a volume of fertilization medium in a container, said container having at least one microchamber and being shaped such that the fertilization medium, when placed in the container, fills the microchamber and a portion of the container outside of the microchamber, such that when a sperm sample is placed in the medium outside the chamber motile sperm swim into the microchamber, where they may be harvested or, if an oocyte is in the microchamber, in vitro fertilization occurs.

Abstract: A method is provided for increasing the fertilization potential of oocytes comprising culturing oocytes in vitro with an effective amount of inhibin, activin, or a combination of inhibin and activin. Preferably the oocytes being cultured are immature. After the culturing step, the oocytes can be fertilized. The oocytes are suitably cryopreserved and thawed before the culturing step.

Abstract: This invention is directed to a method of effecting the non-surgical transplant of embryos into the uterus of an animal. The method involves the use of a long tubular gripping instrument having an open forward end and an external gripping formation generally adjacent its forward end. A probe with a long tubular body having an open forward end extends axially inside the gripping instrument. A probing member projects in a generally non-axial direction from the probe body generally adjacent its forward end. The method comprises the steps of inserting the gripping instrument, forward end first, into a cervix of the uterus, and establishing a grip between the walls of the cervix and the external gripping formation on the gripping instrument. While maintaining said grip, the gripping instrument is pulled in a rearward direction to straighten the cervix.

Abstract: High efficiency in vitro fertilization is achieved when the oocytes to be fertilized are placed in individual, low volume oocyte chambers disposed about the periphery of a microdrop of fertilization medium. A sperm sample, particularly an unfractionated sperm sample, is then placed in the center of the microdrop. Motile sperm tend to move rapidly toward the periphery of the microdrop, thus resulting in an in situ separation of motile from non-motile sperm. Once at the periphery, fertilization by sperm that enter the oocyte chambers is quite facile because of the low volume of the chamber. This method of fertilization can be performed in a culture dish having a plurality of oocyte chambers formed on the interior surface of the base portion of the dish. Each oocyte chamber has a volume which exceeds the volume of an oocyte to be fertilized but is small enough to provide for facile fertilization. In general, the oocyte chamber will have a volume which exceeds the volume of the oocyte by from 800% to 2000%.

Abstract: An embryo collection dish has a cylindrical sidewall with an inlet tube which communicates with an animal uterus from which the embryos are flushed. A lid is engaged with the dish and clamps a sheet of filter material therebetween. In use the filter is disposed vertically and the embryo cattier fluid is discharged from the device through an outlet tube which extends from the lid. The vertical distance between the inlet and outlet tubes is adjustable to control the volume of liquid retained in the dish along with the embryos. The dish together with its contents may be placed directly under a microscope for selection and extraction of the collected embryos. The device is sufficiently compact and fluid tight that it may be placed within a users clothing during collection to keep the embryos warm. Alternatively, an intermediate ring may be provided which joins a reusable lid to a disposable dish.

Abstract: A method for freezing bovine embryos with a composition which includes 4% ethylene glycol and 4% propanediol and in addition 4% bovine serum albumin containing a high lipid content is disclosed. The mixture is subjected to freezing and used in a method for reproducing cattle by transferring to a cow recipient directly after thawing the preserved embryos. Further, a high lipid content is disclosed as 2.5 ug or more of lipid/mg of bovine serum albumin. The bovine embryos are obtained by in vivo fertilization or by in vitro fertilization for use in the disclosed methods.

Abstract: Therapeutic and diagnostic methods of use for the growth factor transforming growth factor .beta., are provided by this invention. In accordance with preferred embodiments, methods of determining and improving competence of a conceptus toward uterine implantation are provided as are methods for determining female infertility in mammals.

Abstract: The present invention relates to the use of leukemia inhibitory factor (LIF) in the enhancement of development and maintenance of mammalian embryos, particularly sheep embryos. It has been observed that following the introduction into foster mothers of embryos cultured in vitro in the presence of LIF, the maintenance of pregnancy is enhanced relative to that seen following introduction of embryos that had not been cultured with LIF prior to introduction into foster mothers.

Abstract: The invention provides methods for implantation of an embryo into a mammal comprising placing the embryo in a catheter, admitting the catheter through the mammal's cervical os into the endometrial cavity, directing a distal tip of the catheter into the mammal's uterine tissue, and depositing the embryo into the uterine tissue beneath the surface of or within the endometrial lining. Flushing the catheter with a physiologic solution assists in deposition of the embryo. Fiberoptic guidance can facilitate direction of the catheter tip and deposition of the embryo.

Abstract: An artificial zona pellucida is provided for implantation in the peritoneal cavities of small laboratory animals. The assembly includes a hydrogel cartridge for containing one or more nude isolated blastomeres which can be cultured therein to an implant stage in the peritoneal cavity of a small animal such as a mouse. The combination is particularly advantageous for culturing of nude isolated blastomeres of a species different from the host small laboratory animal, such as blastomeres of domestic animals.

Abstract: A method for both disposing an agent in a body organ, preferably a sexual organ, of a human or animal and retrieving a fluid sample containing the agent from the body organ of the human or animal, utilizing a percutaneous access port. A portion of the percutaneous access port is implanted in a body organ of the human or animal and connected to the body organ so that fluid communication exists between the body organ and the fluid chamber of the percutaneous access port, wherein the fluid chamber is not percutaneously implanted. An agent is disposed in the fluid chamber of the percutaneous access port, and flushed to the organ. At a later time, a fluid sample containing the agent is withdrawn from the fluid chamber, and the amount of the agent in the sample is determined.

Abstract: An improved cryopreservation of embryos has been developed. After freezing in a cryoprotective solution of ethylene glycol, glycerol or a combination thereof, the embryos can be thawed and transferred directly to the recipient animal without serial rehydration. The transfer can be made directly from the cryoprotective container to the recipient animal.

Abstract: The fertilization process comprises the following steps: a) a container (15) which can be introduced into, and lodged in, the uterine cavity of the mammal is provided; b) the container (15) is filled with a culture medium, at least one ovocyte of the mammal, and spermatozoa; c) the filled container (15) is inserted in the uterine cavity; d) the container (15) is left for a given length of time to allow fertilization of the ovocyte(s) to take place; e) the contents of the container (15) are released into the uterine cavity. The container may be made from a tube of biodegradable or non-biodegradable material. In the latter case, it is associated with a stiffening device. A biodegradable container (15) filled with gametes and a culture medium is placed in the uterine cavity using an implantation device (20) which is then withdrawn from the mammal's genital tract.

Abstract: A system for embryo retrieval from a uterine cavity may employ apparatus comprising a container of liquid medium, a syringe and a filter interconnected by a plurality of valved conduits connected in a closed loop to circulate the liquid medium into and out of the container, syringe, filter and cavity cyclically. The circulation cycle can be repeated many times with a minimum amount of liquid medium to collect a maximum number of embryos in the filter.

Abstract: A container for biological liquids such as a culture medium comprises a hollow body of elastomeric material including a tubular intermediate part, rounded ends and a portion perforable by a cannula for introducing the biological liquid and hermetically resealing itself once the cannula is removed. The interior and exterior surfaces of the hollow body are smooth and curved throughout and the portion perforable by the cannula is thick walled and is preferably provided at one or both ends of the hollow body. The container may comprise two half shells joined together or a blow extruded member. The interior surface is advantageously coated to eliminate asperities.

Abstract: The invention relates to a container for fertilization of human ovocytes in the absence of CO.sub.2 which may be done in an incubuator at 37.degree. C. or in the vaginal cavity. The container of cylindrical shape has smooth and rounded walls 1 whose thickness is 2 mm in the body 2 of the cylinder but only 1 mm at the neck 3. On the outer wall of the neck is seen a screwthread 4 permitting external screwing on of the plug 12 whose sides are smooth and rounded. The blind end 5 of the container is rounded, the other 6 is flat and has a round orifice 7, which orifice is closed by a fine membrane 9 permitting hermeticity of the tube in order to avoid disorders of the culture medium 8 present in the container as of manufacture. Above the liquid remains about 200 .mu.l of gas 10. The inner walls 11 are smooth and rounded.

Abstract: An instrument of artificial insemination or embryo transfer by a transperitoneal and/or cervical route or for sampling follicular liquids in mammals especially horses, pigs, sheep, goats, deer and carnivores is of the type constituted by a syringe formed by a sheath in which slides in fluid-tight manner a piston movable in translation. The sheath is externally protected by a rigid cover and is immobilized in a manipulator sleeve comprising a rotary member adapted to actuate the piston. The anterior end of the sheath is fitted with a needle. The cover protecting the sheath is covered by and guides a palpator the length of which is greater than that of the cover but less than that of the sheath (including the needle). Thus the needle of the syringe is selectively covered or exposed in whole or in part by axial sliding movement of the cover.

Abstract: A method and apparatus for artificial fertilization in which an ovum or embryonic implant is inserted in the uterine cavity by means of tubing which communicates with the outside and passes through the uterine wall. The tubing comprises a flexible but relatively incompressible silicone elastomer tube having, and bulges are provided on the outer surface of the tube. In some embodiments the tube includes a spiral reenforcement of stainless steel wire.

Abstract: A method for producing, in a functionally agonadal human female body, an environment suitable for the implantation, nutrition, and development of an embryo, comprising the placement of at least one carrier containing at least one releasable steroid hormone into the vagina of the human female.