WO2002028311A1 - System of hysteroscopic insemination of mares - Google Patents
System of hysteroscopic insemination of mares Download PDFInfo
- Publication number
- WO2002028311A1 WO2002028311A1 PCT/US2001/002304 US0102304W WO0228311A1 WO 2002028311 A1 WO2002028311 A1 WO 2002028311A1 US 0102304 W US0102304 W US 0102304W WO 0228311 A1 WO0228311 A1 WO 0228311A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- mammal
- species
- female
- sperm
- artificial insemination
- Prior art date
Links
- 230000009027 insemination Effects 0.000 title claims abstract description 592
- 241000124008 Mammalia Species 0.000 claims abstract description 735
- 238000000034 method Methods 0.000 claims abstract description 431
- 241000282898 Sus scrofa Species 0.000 claims abstract description 54
- 241000282817 Bovidae Species 0.000 claims abstract description 39
- 201000010063 epididymitis Diseases 0.000 claims abstract description 16
- 241001465754 Metazoa Species 0.000 claims abstract description 7
- 241000894007 species Species 0.000 claims description 485
- 230000008569 process Effects 0.000 claims description 135
- 230000003287 optical effect Effects 0.000 claims description 76
- 238000000151 deposition Methods 0.000 claims description 30
- 210000004291 uterus Anatomy 0.000 claims description 28
- 241000283073 Equus caballus Species 0.000 claims description 26
- 210000001215 vagina Anatomy 0.000 claims description 19
- 230000001413 cellular effect Effects 0.000 claims description 17
- 238000007865 diluting Methods 0.000 claims description 15
- 230000001158 estrous effect Effects 0.000 claims description 12
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims description 10
- 239000007995 HEPES buffer Substances 0.000 claims description 10
- 230000012173 estrus Effects 0.000 claims description 10
- 238000007710 freezing Methods 0.000 claims description 9
- 230000008014 freezing Effects 0.000 claims description 9
- 235000020183 skimmed milk Nutrition 0.000 claims description 8
- 210000003679 cervix uteri Anatomy 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 238000005286 illumination Methods 0.000 claims description 6
- 230000000977 initiatory effect Effects 0.000 claims description 6
- WAHQVRCNDCHDIB-QZYSPNBYSA-N [(3s,8r,9s,10r,13s,14s,17r)-17-acetyl-17-acetyloxy-6,10,13-trimethyl-1,2,3,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-yl] 3-cyclopentylpropanoate Chemical compound O([C@@H]1C=C2C(C)=C[C@H]3[C@@H]4CC[C@]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)(OC(=O)C)C(C)=O)C(=O)CCC1CCCC1 WAHQVRCNDCHDIB-QZYSPNBYSA-N 0.000 claims description 5
- 239000000583 progesterone congener Substances 0.000 claims description 5
- 238000010257 thawing Methods 0.000 claims description 5
- VJGGHXVGBSZVMZ-QIZQQNKQSA-N Cloprostenol Chemical compound C([C@H](O)\C=C\[C@@H]1[C@H]([C@@H](O)C[C@H]1O)C\C=C/CCCC(O)=O)OC1=CC=CC(Cl)=C1 VJGGHXVGBSZVMZ-QIZQQNKQSA-N 0.000 claims description 4
- 229960004409 cloprostenol Drugs 0.000 claims description 4
- 238000001125 extrusion Methods 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 230000036760 body temperature Effects 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 abstract description 21
- 230000035558 fertility Effects 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 30
- 238000005516 engineering process Methods 0.000 description 11
- 230000035899 viability Effects 0.000 description 10
- 239000004606 Fillers/Extenders Substances 0.000 description 9
- 238000004321 preservation Methods 0.000 description 8
- 238000012545 processing Methods 0.000 description 8
- 238000009395 breeding Methods 0.000 description 7
- 230000001488 breeding effect Effects 0.000 description 7
- 230000004720 fertilization Effects 0.000 description 7
- 210000000582 semen Anatomy 0.000 description 7
- 230000008021 deposition Effects 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000009471 action Effects 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 230000035935 pregnancy Effects 0.000 description 5
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 230000004899 motility Effects 0.000 description 4
- 230000016087 ovulation Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 3
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 210000004696 endometrium Anatomy 0.000 description 3
- 210000000918 epididymis Anatomy 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000027758 ovulation cycle Effects 0.000 description 3
- 230000001360 synchronised effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001550 testis Anatomy 0.000 description 3
- VWAUPFMBXBWEQY-ANULTFPQSA-N Altrenogest Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@](CC3)(O)CC=C)C=C3)C3=C21 VWAUPFMBXBWEQY-ANULTFPQSA-N 0.000 description 2
- 229960000971 altrenogest Drugs 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 244000309465 heifer Species 0.000 description 2
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 2
- 210000000754 myometrium Anatomy 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000000624 ovulatory effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100457838 Caenorhabditis elegans mod-1 gene Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101150110972 ME1 gene Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- 210000002593 Y chromosome Anatomy 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940034629 chorulon Drugs 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 229940032383 estrumate Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000009399 inbreeding Methods 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 230000029860 luteolysis Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229940050570 regu-mate Drugs 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- IFEJLMHZNQJGQU-KXXGZHCCSA-M sodium;(z)-7-[(1r,2r,3r,5s)-2-[(e,3r)-4-(3-chlorophenoxy)-3-hydroxybut-1-enyl]-3,5-dihydroxycyclopentyl]hept-5-enoate Chemical compound [Na+].C([C@H](O)\C=C\[C@@H]1[C@H]([C@@H](O)C[C@H]1O)C\C=C/CCCC([O-])=O)OC1=CC=CC(Cl)=C1 IFEJLMHZNQJGQU-KXXGZHCCSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 210000001177 vas deferen Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D19/00—Instruments or methods for reproduction or fertilisation
- A61D19/02—Instruments or methods for reproduction or fertilisation for artificial insemination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D19/00—Instruments or methods for reproduction or fertilisation
- A61D19/02—Instruments or methods for reproduction or fertilisation for artificial insemination
- A61D19/027—Devices for injecting semen into animals, e.g. syringes, guns, probes
Definitions
- This invention relates generally to the field of insemination of mammals . Specifically, it relates to systems to achieve insemination which may be particularly applicable once sperm have been treated or processed in some manner, such as sorting the sperm through flow cytometry. More particularly, the invention may relate to systems to achieve insemination, with a low number of spermatozoa as compared to conventional artificial insemination, through hysteroscopic insemination techniques. The inventionmay be particularly applicable to systems for inseminating equids, bovids and swine. Furthermore, the invention may be particularly applicable to sex selection of offspring in mammals.
- Al Artificial insemination
- Traditional forms of Al include various in vivo technologies such as conventional intrauterine artificial insemination techniques, or more particularly, trans cervical artificial insemination.
- Natural insemination doses may typically be large.
- natural insemination may involve sperm numbers on the order of 2-20 x IO 9 sperm.
- conventional Al techniques in the same species may require sperm numbers on the order of 200-500 x IO 6 sperm. This can still be viewed as a large number of sperm, especially if the sperm are processed in some manner.
- High-speed sperm sorting using flow cytometry has been used successfully as a breeding technology to produce offspring in mammals, such as horses, cattle, sheep, rabbits, pigs and humans. It can potentially be used for several other species as well. Technologies have been developed to enhance or modify the pregnancy and resulting offspring of mammals, particularly with regard to the processing of sperm and insemination techniques.
- Pickett et al. recognized that apotential minimal recommended dose for conventional artificial insemination in the mare may be as high as 500 x IO 6 progressively motile sperm. With low sort rates of around 700 spermatozoa per second in some sperm sorting technologies, it may take several days to obtain the recommended dose of spermatozoa for artificial insemination. This may not only be impractical, but the viability of the spermatozoa may also be significantly reduced. Low-dose insemination techniques, therefore, may be a desirability to those skilled in the art to potentially reduce the number of spermatozoa needed for acceptable fertility rates.
- Fertility rates may be considered acceptable or statistically comparable, for example, if they are achievable over a high sample size, range or percentage of the fertility rates resulting from conventional Al. Low-dose insemination techniques, therefore, may be a desirability to those skilled in the art to potentially reduce the number of spermatozoa needed to maximize fertility.
- an additional concern regarding artificial insemination is the efficiency of the procedure as a whole with regard to the resulting numbers of pregnancies.
- a number of procedural steps may have been used in conventional Al procedures, such as the synchronization of estrus in breeding mares; the preparation of the insemination dose, more particularly the use of extenders for the dilution (Kenny et al., 1975) and resuspension of spermatozoa (using TALP or HEPES-buffered Tyrode's Medium, for example), centrifuging the sample through a density or viscosity gradient (using PERCOLL or the like); assessing viability or motility; and the particulars of the insemination procedure.
- references may have demonstrated conception rates of 33 % for 3.8 x 10 6 spermatozoa and 22% for 1.0 x 10 6 spermatozoa, respectively, which may be considered non-comparable conception rates relative to conventional Al for the species involved.
- a long felt but unsatisfied need for an efficient procedure for the hysteroscopic insemination of mammals has existed inbreeding technology.
- a need for efficient, low-dose hysteroscopic insemination has heretofore existed in current breeding technology.
- insemination procedure One important procedural step with regard to insemination procedure, generally, is the establishment of a insemination dose containing desirable numbers of viable and motile spermatozoa to potentially provide higher fertility rates.
- Procedures for the selection of motile spermatozoa may have been conducted with regard to conventional Al, for example in the reference Gr ⁇ ndahl et al, 1996 and in hysteroscopic insemination generally, by establishing a density or viscosity gradient utilizing, for example, PERCOLL (Sigma Chemical Co., St. Louis, MO) alone or in combination with other substances.
- a second potential issue with regard to insemination procedure is the establishment of a insemination dose containing desirable numbers of viable and motile spermatozoa to potentially provide higher fertility rates without a particular motility test, as described above.
- the introduction of a density or viscosity gradient may introduce a stress to the spermatozoa that may actually reduce the actual number of viable and motile spermatozoa available from a particular sample.
- the substantial efforts to fractionate viable or motile sperm have not particularly addressed the identified needs for an insemination technique providing for high fertility rates, high fertility rates for low insemination dosages, and insemination techniques to address issues of efficaciousness, particularly with regard to the hysteroscopic insemination technique.
- a third potential issue with regard to insemination procedure is the establishment of a compatible volume for the particular insemination technique.
- One recognized need as described above, is the desire to potentially provide higher fertility rates.
- a second recognized need also described above, is the ability to use low numbers of spermatozoa to potentially achieve high fertility rates.
- the insemination dose volume may be determined by the particular insemination technique. However, the dose volume may contain a desirable number of spermatozoa to potentially provide for a higher rate of fertility. Substantial attempts have been made to establish an appropriate insemination technique that would allow for the appropriate number of spermatozoa, given the potential volume requirements of the insemination technique, to potentially provide acceptable fertility rates.
- the sperm sample may be processed prior to the insemination procedure.
- Conventional Al may provide for the use of extenders for the dilution (Kenny et al., 1975) and resuspension of spermatozoa.
- the particular media used may not be compatible with the insemination procedure itself. Incompatibility of the sample media may result in lower deposition numbers of spermatozoa or dose volume or a lower fertility rate.
- the mode or form of the deposited insemination dose or the particular method of deposit during Al may further affect the number of deposited spermatozoa available for conception.
- Insemination timing may be an important factor, for example, to sperm viability and longevity and the timing of the estrous cycle of the mammal. Particularly at issue might be the distant location of sperm sample acquisition (i.e. the location of the male mammal) and ultimate location of the Al. Previous efforts may have been made in conventional Al to preserve the sperm sample prior to insemination and to coordinate the insemination with the estrous cycle.
- the source of the sperm sample may also be of importance to the resulting insemination.
- Epididymal acquisition of the sperm sample (obtaining sperm sample from the epididymis of the testis; ductules emerging posteriorly from the testis that holds sperm during maturation and that forms a tangled mass before uniting into a single coiled duct which is continuous with the vas deferens) may provide some inherent advantages as to timing of the insemination and viability of the sperm.
- embodiments of the present invention may provide for the production of a mammal through the use of artificial insemination that may address inadequacies of previous insemination techniques and systems.
- the invention may comprise, according to particular embodiments, a method of producing a mammal whereby potentially high fertility rates may be accomplished, fertility rates which may be statistically compatible with conventional Al results, and potentially high fertility rates with the use of low spermatozoa doses.
- embodiments of the present invention may provide for the production of a mammal through the use of hysteroscopic insemination techniques.
- the present invention may comprise embodiments particularly directed at mammals such as equids, bovids, and swine, among other mammals. Embodiments of the present invention, therefore, may even be considered development away from previous efforts of artificial insemination.
- One object of the present invention is to provide for the production of a mammal utilizing an efficacious procedure. Therefore, a goal of the present invention is to provide atechnique of artificial insemination for mammal production such that lower numbers of spermatozoa may be used in the insemination dose relative to conventional Al and other insemination techniques, while, in particular embodiments of the invention, at least statistically comparable success rates in fertility are maintained.
- Another object of the present invention is to provide for the production of a mammal utilizing an artificial insemination procedure that may potentially achieve high fertility rates consistent with lower spermatozoa production from breeding technologies such as sperm sorting.
- a goal of the present invention therefore, is to provide a technique of artificial insemination for mammal production that achieves statistically comparable success rates in fertility, compared to conventional Al and other insemination techniques, with lower-doses of spermatozoa.
- an obj ect of the invention is to provide for the production of a mammal utilizing an artificial insemination procedure that may enhance steps involved in the artificial insemination.
- one goal of the present invention is to provide a technique of artificial insemination for mammal production such that steps of esfrous cycle timing, spermatozoa source, viability, longevity and processing, insemination dose media and volume, and insemination timing may be optimized, particularly for low-dose insemination and potentially high fertility.
- An additional object of the present invention is to provide for the production of a mammal through hysteroscopic insemination.
- a goal of the present invention is to provide a technique of artificial insemination for mammal production such that the insertion of the insemination dose, guiding of the insemination dose to the deposition site, deposition of the insemination dose at the appropriate location, in an appropriate mode or form, may be accomplished to achieve other objects and goals as previously stated.
- blister insemination and bubble or froth insemination may be infroduced as preferred embodiments to optimize fertility rates.
- a particular goal of the present invention is to provide a technique of artificial insemination for mammal production utilizing a catheter comprising a videoendoscope for guiding and depositing the insemination dose.
- an object of the present invention in accordance with particular embodiments, is to provide for the production of various mammal species utilizing an artificial insemination procedure.
- a goal of the present invention therefore, is to provide atechnique of artificial insemination for mammals such as equids, bovids and swine, among other species.
- a further goal is to provide a technique of artificial insemination for various mammal species that additionally provides for low numbers of spermatozoa in the insemination dose and for potentially high fertility rates, particularly rates that may be statistically comparable to conventional AL
- Figure 1 is a partially exploded and perspective diagrammatic view of the optical element, cannula, catheter and syringe in accordance with one embodiment of the present invention.
- Figure 2 is a diagrammatic depiction of the reproductive organs of a female of a mammalian species and, in particular, a depiction of artificial insemination in accordance with one embodiment of the present invention.
- Figure 3 is a magnified diagrammatic view of an enshrouded insemination insertion embodiment of the present invention.
- the basic concepts of the invention may be embodied in many different ways.
- the inventive concept may involve the materials, elements, apparatus, device and methods for the production of a mammal through artificial insemination.
- one preferred embodiment of the invention may be particularly directed to the production of equids through artificial insemination
- the broad concept of the invention should be construed as a disclosure of the production of mammals in general, and as indicated, to other mammal species such as bovids and swine.
- the present invention includes a variety of aspects that may be used in various combinations depending upon the application's needs.
- the invention is intended to encompass a variety of embodiments of mammal production and combinations thereof. It involves both methods and devices to accomplish the various aspects explained.
- some methods and devices are disclosed, it should be understood that these may be varied.
- all aspects should be understood to be encompassed by this patent both independently and in combination as set forth in the claims now or later issued.
- one embodiment of the present invention may provide for the collection of sperm cells from a male of the species of interest.
- sperm cells are collected from one or more stallions of the equine species.
- semen may be collected, and in preferred embodiments, semen may be collected with a commercially available artificial vagina, perhaps from at least one stallion of known acceptable fertility.
- An artificial vagina such as one made available by Animal Reproduction Systems may be used with an in-line gel filter, and in preferred embodiments, used on alternate days throughout collection. After collection, the semen may be evaluated for gel-free volume, motility, and sperm concentration.
- sperm cells may be collected from other male species of mammal, particularly that of bovids, equids or swine.
- An alternative embodiment of the present invention may provide for the collecting of epididymal sperm cells obtained from the epididymis of the testis of the male species of the mammal.
- the alternative embodiment providing for the use of epididymal sperm may be incorporated with all other disclosed embodiments herein, either in single or in combination.
- the present invention provides particular embodiments a hysteroscopic insemination sample comprising a reservoir element, a catheter system to which the reservoir element is responsive, and a plurality of epididymal sperm cells contained within the reservoir element.
- an artificial insemination sample may be established for the insemination of the female species.
- the sample may be prepared as having a low number of sperm compared to a natural insemination dosage for the mammal.
- the sample may have a low number of sperm for particular breeding technologies, and in accordance with preferred embodiments, the sample may have a low number of sperm as the result of sorting the sperm for particular sexed sperm.
- the spermatozoa may be stained with Hoechst 33342 and sorted into X and Y chromosome-bearing populations based on DNA content using a commercially available SX MoFlo® sperm sorter.
- an artificial insemination sample may be established at volumes, in accordance with preferred embodiments, at volumes between about 30 and 150 ul, less than about 500 ul, about 230 ul, and about 100 ul.
- One embodiment of the present invention is directed to establishing a hysteroscopic insemination compatible volume, preferably an insemination sample at a volume selected from a group consisting of: between about 30 and 150 ul, less than about 500 ul, about 230 ul, and about 100 ul.
- the present invention is directed to a hysteroscopic insemination sample comprising a reservoir element a catheter system to which the reservoir element is responsive, and a hysteroscopic compatible volume of sperm contained within said reservoir element.
- the hysteroscopic compatible volume of sperm contained within said reservoir element may comprise a volume selected from a group consisting of: between about 30 and 150 ul, less than about 500 ul, about 230 ul, and about 100 ul.
- the artificial insemination sample may be placed within a catheter or catheter system.
- the sample may be placed within a reservoir element or other sample holding element responsive to the catheter or catheter system.
- a catheter or catheter system should be understood to define any device, system or method of insertion into canals, vessels, passageways, or body cavities to permit injection or withdrawal of fluids, and in accordance with preferred embodiments such injection or withdraw may provide the response of the reservoir element or sample holding element, or to keep a passage open.
- the catheter or catheter system may be used in conjunction with a guide element, and in preferred embodiments an optical element or device, and in preferred embodiments an illumination element, to provide guidance in the artificial insemination procedure, as more particularly described below.
- Preferred embodiments may provide the strobing of the illumination element.
- manual guidance may also be implemented.
- the insemination sample may be aspirated into an equine GIFT catheter (2) (Cook Neterinary
- the loaded catheter may be withdrawn into a tube, or preferably an outer polypropylene cannula (10), which may be responsive to an optical element (12), and in accordance with preferred embodiments, passed down a working channel of a Pentax EPM 3000 videoendoscope (Pentax UK Ltd, Slough, Bucks K).
- estrus may be induced to determine the estrous time and, for multiple mares, even synchronized. Estrus may be defined as a state in which the female mammal is capable of conceiving and estrous cycle may be defined as the correlated phenomena of the endocrine and generative systems of a female mammal, potentially from the beginning of one period of estrus to not later than the beginning of the next.
- estrus may be induced, and for multiple female mammals synchronized, by administering a substance such as aprogestagen, preferably for mares altrenogest, and preferably 10ml orally, potentially for 10 consecutive days, followed by 250 ⁇ g cloprostenol i.m., potentially on day 11.
- a female mammal may be induced into ovulation at the time of insemination.
- Ovulation may be induced, and in preferred embodiments, by the administration of 3000 iu human Chorionic Gonadotropin (hCG, Chorulon, Intervet, Inc., Millsboro, Holland), preferably administered intravenously at the time of insemination or up to approximately 8 hours previously.
- Ovulation may even be induced, in preferred embodiments, by the administration of from about 2000 to about 5000 iu human Chorionic Gonadotropin.
- esfrous cycles may be synchronized by administering a synthetic progestagen altrenogest (0.044mg/kg p.o., Regumate; Hoechst Roussel Net, Warren, New Jersey, USA) daily for 10 consecutive days.
- Luteolysis may be induced, in preferred embodiments with the prostaglandin analogue, cloprostenol (250 ⁇ g Estrumate, i.m. ; Bayer Corporation, Agriculture Division, Shawnee Mission, Kansas, USA) administered on the eleventh day.
- a time when the female mammal is appropriately fertile may be determined.
- the ovaries may be examined, and in preferred embodiments examined ultrasonographically, and preferably every second day until a follicle, and in accordance with preferred embodiments a dominant follicle, preferably of > 30mm diameter, is detected.
- the female may be examined until a follicle, preferably pre-ovulatory, of preferably > 35mm is detected.
- the female may be inseminated during the same day as esfrous inducement or synchronization, the same day as ovulation inducement or synchronization, or the same day as estrus and insemination inducement or sychronization.
- the guide element and in preferred embodiments the optical element (12), may be vaginally inserted into the female.
- the catheter (2) and in preferred embodiments the reservoir element, may be inserted into the female.
- the sequence of insertion of the optical element (12) and the catheter (12) may be sequential or coincidental in time.
- the guide element or optical element (12) and the catheter (2) may then be guided through the vagina (20) of the female, as depicted in Figure 2.
- the optical element (12) and catheter (2) may be manually guided.
- the catheter (2) may be manually guided without the optical element (12).
- accuracy in finding the UTJ and the potential result in increased fertility rates, particularly for low numbers of sperm and overall potential efficacy in the procedure may require a more accurate guidance procedure.
- the optical element or endoscope preferably a flexible endoscope, in preferred embodiments having dimensions of 1.6 m long with an outer diameter of 12 mm, may be guided through the cervix (22) and propelled forward through the uterine lumen (24), or in additional embodiments, through a uterine horn of the female of the species.
- An added benefit of the use of the videoendoscope can be lack of a need to rectally guide the insemination process, as may have been required in past efforts by those of skill in the art.
- the uterotubal junction (UTJ) (30) of the female mammal may then be located, preferably optically with the optical element (12).
- the catheter (2) may then be positioned in the vicinity of or proximate to the uterotubal junction.
- the endoscope may be directed under visual control along the uterine horn (26) ipsilateral to the ovary containing the pre-ovulatory follicle (28).
- the tip of the endoscope may be directed proximate to, and in preferred embodiments within about 3 -5cm of said uterotubal junction, and in preferred embodiments within about 3-5 cm of the papilla (32) of the uterotubal junction.
- At least a portion of the artificial insemination sample may then be extruded from the catheter (2).
- the outer cannula (10), followed by the inner GIFT catheter (2) containing the sperm suspension may be extruded from the working channel of the endoscope until the tip of the GIFT catheter touches the uterotubal junction, and in preferred embodiments, touches the papilla.
- a portion or at least a portion of the artificial insemination sample may be aspirated during extrusion from the catheter, thereby potentially creating an aspirated sample.
- Such aspirated samples should be understood to include bubbled samples and frothed samples.
- an aspirated sample may not only provide better adherence to a surface in the vicinity of the UTJ, but may further allow for improved fertility rates.
- an embodiment of the present invention provides a hysteroscopic insemination element comprising a uterus of a female species of a mammal, a plurality of sperm cells contained within said uterus, and an aspirated volume of media surrounding or interspersed with the sperm cells and to which the sperm cells are responsive.
- Such alternative embodiments should be construed as disclosed with regard to all embodiments of the present invention, either in single or in combination, and should be construed to be disclosed as such.
- a low number of sperm may be deposited in the vicinity of the uterotubal junction.
- a plunger of the syringe (4) may be depressed to deposit the sample, and in particular embodiments, a small volume (preferably perhaps ⁇ 1 OO ⁇ l) of the sample, preferably onto the surface of the papilla.
- the guide element, and in preferred embodiments the optical element (12), and the catheter (2) may be withdrawn from the uterus of the female mammal.
- filtered air may be introduced within the uterus of the female to facilitate passage of the instruments through the uterine lumen.
- the filtered air may be evacuated from the uterus, preferably simultaneous to the withdrawal of the optical element (12) and catheter (2).
- the placing of a low number of sperm may be accomplished, in one preferred embodiment of the invention, by placing with the catheter (2) a number of sperm, preferably numbers selected from: less than about ten million sperm, less than about five million sperm, less than about two million sperm, less than about one million sperm, less than about five hundred thousand sperm, and less than about one hundred thousand sperm.
- success levels of fertilization may be statistically comparable to a conventional uterine body artificial insemination process.
- Statistically comparable success levels may be defined as fertilization rates of at least about 75% success rates, at least about 65% success rates, at least about 60% success rates, at least about 50% success rates, at least about 45% success rates, and at least about 90% of a success rate practically experienced with conventional Al for any particular species.
- success levels for the present invention may be statistically comparable to a conventional uterine body artificial insemination process over a sample of cumulative fertilizations which is greater than about 100, which is greater than about 500, and which is greater than about 1000. Success rates may further statistically provide for at least a confidence level of at least about 95 percent confidence (potentially expressed as P> or equal to about 0.05), therefore potentially being statistically comparable with conventional Al. Additionally, success rates for the present invention may potentially have the same P value over a range of differing sperm numbers, potentially such as 1 , 5 or 10 x 10 6 sperm for equine.
- a success level or rate may be expressed in terms of sample size, whereby the present invention may provide, in preferred embodiments, any of the aforementioned success rates over a power calculation ( ⁇ ) of at least about 80 percent.
- the success rates in preferred embodiments, given particular insemination doses for sex-sorted stallion spermatozoa, may even apply to a low number of spermatozoa and may routinely produce fertility rates of at least about 90% of those rates resulting from conventional artificial insemination for a species.
- the previous success rates may even be achieved for species of mammal such as bovids, equids, and swine.
- the present invention may provide for establishing an artificial insemination sample utilizing fresh sperm.
- fresh sperm may be broadly defined as sperm that has not been treated, processed or preserved in any manner such that the sperm viability, longevity and/or mobility might be compromised.
- treatment, processing or preserving may include, for example, the sorting of sperm, the freezing and subsequent thawing of sperm, the dilution and resuspension of sperm, and motility and viability testing or separation, generally, and in particular, Percoll gradient processing.
- the use of fresh sperm in accordance with embodiments of the present invention herein may permit the use of low numbers of sperm for insemination even, for example, when using poor quality collected semen.
- Alternative embodiments of the present invention may broadly provide for freatment, processing and preserving of insemination sperm.
- Alternative embodiments of the present invention may provide, for example, for the selection of the collected sperm cells more likely to achieve insemination.
- the selection of desired sperm cells or sperm cells more likely to achieve insemination may comprise concentrating the more motile sperm collected.
- Additional embodiments may provide the step of centrifuging the sperm through density gradients, and in preferred embodiments a Percoll gradient.
- a potentially preferred embodiment may use a 90:45% Percoll gradient.
- An additional embodiment may comprise limiting the concentration to less than about twice the starting concentration.
- the Percoll gradient procedure may be used with "fresh sperm.”
- the sample established from the desired or selected sperm cells may be used to establish the artificial insemination sample, potentially increasing the fertility rates due, at least in part, to the potentially higher rate of viability of the sample.
- the Percoll gradient procedure in accordance with the present invention may be conducted in conjunction with the use of lower numbers of sperm placed within the depositing catheter, as more particularly described supra.
- an artificial insemination sample may be provided by establishing a sample having hysteroscopic compatible media, thereby providing for potentially increased fertility rates and an efficacious insemination procedure. More particularly, an embodiment of the invention may provide establishing an artificial insemination sample, and in preferred embodiments having a low number sperm compared to natural insemination doses, and providing for the establishment of an artificial insemination sample compatible media, for example extender, and in preferred embodiments, a skim milk medium, such as EZ- Mixin CST® (Animal Reproduction Systems, Chino, CA), preferably as a diluting media, potentially prior to additional processing.
- EZ- Mixin CST® EZ- Mixin CST®
- dilution may occur to no more than a 2 : 1 ratio, to no more than a 5 : 1 ratio, and to no more than a 10:1 ratio, to potentially achieve at least a hysteroscopic compatible volume or media with appropriate concentrations.
- embodiments of the present invention may provide for the use of an extender, potentially a second extender provided after sperm processing and potentially in conjunction with a first extender, as previously mentioned, to establish the sample utilizing hysteroscopic compatible media.
- the second extender may serve to resuspend the sperm sample after processing, and more particularly, provide for a sample utilizing hysteroscopic compatible media.
- the medium or second extender may comprise a TALP medium, a HEPES-buffered Tyrode's medium, and an Androhep medium.
- dilution may be performed with a skim milk medium such as EZ-Mixin CST®, with a TALP medium, with a HEPES-buffered Tyrode' s medium, and with an Androhep medium, either single or in combination, to potentially achieve at least a hysteroscopic compatible volume or media with appropriate concentrations.
- An additional embodiment of the present invention may also provide for an artificial insemination sample utilizing ahy steroscopic compatible media or medium having a catheter coordinated viscosity.
- the viscosity may, for example, potentially facilitate the steps of extruding and depositing the sample.
- the use of compatible media or medium may create an artificial insemination sample having a viscosity of preferably greater than about that of the blood of said mammal or greater than about that of a saline solution.
- additional embodiments may provide for compatible media having a viscosity of greater than about 1 OOcp, a media having a viscosity of greater than about 3 OOcp, a media having a viscosity of greater than about lOOOcp, a media having a viscosity of greater than about 3000cp, and a media having a viscosity of greater than about 6000cp, each at about the mammal's average body temperature.
- an embodiment of the present invention may provide a hysteroscopic insemination sample comprising a reservoir element, a catheter system to which said reservoir element is responsive, a plurality of sperm cells contained within said reservoir element; and hysteroscopic compatible media contained within said reservoir element and to which said sperm cells are responsive.
- an insemination containment wherein said plurality of sperm cells are contained within said reservoir element may include a low number of sperm cells as compared to the number of sperm cells typically found in a natural insemination.
- Altering a property of the insemination specimen or sperm cell sample may be conducted according to the present invention, and in accordance with preferred embodiments, determining an estrous time for a female of a species of said mammal and then altering a property of said insemination specimen to establish an artificial insemination sample at about said estrous time.
- Alternative embodiments may provide altering a property of the sample at about the time determined for the female of said species to be appropriately fertile, as previously defined.
- the present invention may also provide initiation of the altering of a property of the insemination specimen within a time selected from: within about twenty-four hours of said time determined for said female of said species of said mammal to be appropriately fertile, within about twelve hours of said time determined for said female of said species of said mammal to be appropriately fertile, within about eight hours of said time determined for said female of said species of said mammal to be appropriately fertile, within about three hours of said time determined for said female of said species of said mammal to be appropriately fertile, and within about one hour of said time determined for said female of said species of said mammal to be appropriately fertile.
- This alteration may consist of preparing the sample, sorting the sperm, thawing the sperm, or the like.
- One particular embodiment of the present invention may provide for establishing a hysteroscopic compatible media and the concentration of sperm to select sperm more likely to achieve insemination.
- one potentially preferred embodiment of the invention may provide preparation of the semen through centrifugation.
- the semen may be diluted to provide, for example, 100 x IO 6 spermatozoa/ml in preferably a commercial skim milk extender (EZ-Mixin CST®, Animal Reproduction Systems, Chino, CA).
- the sperm suspension may be protected from light and maintained for preferably 6 hours at room (20 - 25°c) temperature to simulate the potential time needed to sort the spermatozoa, if so desired.
- the sperm suspension may then be centrifuged through a 90:45% Percoll (Sigma Chemical Co., St. Louis, MO, USA) discontinuous density gradient with the goal of reconcentrating the cells and to potentially select a highly motile fraction of spermatozoa.
- the 90% Percoll may be diluted at a ratio of 1:1 (v/v) with HEPES-buffered Tyrode's medium (Gr ⁇ ndahl et al, 1996) to make a 45% solution.
- a preferably 15-mL cenfrifuge tube preferably 1 mL of 45% Percoll may be carefully layered on top of preferably 1 mL of 90% Percoll.
- sperm suspension 100 x 10 6 sperm/mL in EZ-Mixin, CST
- the tube may be centrifuged at 800 x g for a preferred period of 12 minutes. After centrifugation, the supernatant may be completely removed and the pellet may be resuspended in preferably 600 ⁇ l HEPES-buffered Tyrode's Medium.
- the sperm concentration may be determined, in accordance with one embodiment, using a Densimeter (534B MOD-1, Animal Reproduction Systems, Chino, CA) and the potential volume to deliver 5 million spermatozoa (potentially of a preferred ⁇ 100 ⁇ l) may be calculated and prepared for insemination.
- a Densimeter 534B MOD-1, Animal Reproduction Systems, Chino, CA
- the potential volume to deliver 5 million spermatozoa potentially of a preferred ⁇ 100 ⁇ l
- one embodiment thereof may provide for the positioning of the catheter near the UTJ of the female species of mammal whereby the catheter is inserted under a surface in the vicinity of the uterotubal junction. At least a portion of the sample may be extruded or deposited in the vicinity of the UTJ under the surface.
- One embodiment of the present invention may provide for the collecting of sperm cells from the male species of mammal, establishing an artificial insemination sample utilizing at least some of the sperm cells collected, and placing the artificial insemination sample in a catheter.
- a determination of a time when the female is appropriately fertile may be determined, as described above.
- the optical element (12) and the catheter (2) may be inserted vaginally and guided through the vagina, as depicted in Figure 2.
- the UTJ may be optically located with optical element (12).
- the catheter may be inserted under a surface (34) in the vicinity of the UTJ (30), as depicted in Figure 3. At least a portion of said artificial insemination sample may be extruded under the surface within the vicinity of the UTJ, thus creating a "blister" with the sample enshrouded between layers. Deposition of at least a portion of the artificial insemination sample may be provided under the surface (34) in the vicinity of the UTJ.
- the surface (34) may comprise the endometrium or other portion of the uterus or the uterine lining.
- the catheter may be inserted such that a particular portion of the uterus is not pierced, and in accordance with one embodiment, such that a vascularized portion of the uterus is not pierced.
- a vascularized portion of the uterus that may not be pierced may include, for example, the mesomefrium or the myometrium portion of the uterus or other vascularized portions.
- An embodiment of the present invention may also provide a potentially corresponding insemination catheter having a guide element, or in preferred embodiments a videoendoscope or a cannula, a reservoir element responsive to the guide element, an extrusion element, or in preferred embodiments a syringe to which said reservoir element is responsive, and a cellular piercing tip (36) positioned in front of the reservoir element.
- the catheter may further provide a pierce depth control element, such as an adjustment element or a stop on the piercing tip (36) positioned in the vicinity of the tip.
- a pierce depth control element such as an adjustment element or a stop on the piercing tip (36) positioned in the vicinity of the tip.
- a number of steps of producing a mammal may be performed.
- a low number of sperm may be placed in the catheter (2), and in preferred embodiments, preferably numbers selected from: less than about ten million sperm, less than about five million sperm, less than about two million sperm, less than about one million sperm, less than about five hundred thousand sperm, and less than about one hundred thousand sperm.
- the fertilization of an egg may be performed in accordance with the preferred embodiments of the invention wherein success levels success levels of fertilization may be statistically comparable to a conventional uterine body artificial insemination process. Statistically comparable success levels may be defined as previously mentioned.
- the sperm cells may be collected from a male species of mammal, in alternative embodiments of the invention, comprising bovids, equids, or swine. In accordance with alternative embodiments of the invention, sperm cells may be selected from collected cells for those cells that may be more likely to achieve insemination, as previously described.
- an insemination containment element may be provided, in accordance with embodiments of the invention, preferably comprising a cellular base surface, and in particular embodiments a uterine lining or, in accordance with preferred embodiments, a nonvascularized portion of the uterus, such as the mesomefrium or the myometrium, a cellular cover surface adjacent to the cellular base surface, and in particular embodiments, the endometrium or uterine lining, a substantial enshrouded volume between the cellular base and the cover surface, and in preferred embodiments located in the vicinity of the UTJ, and sperm cells from the male of the species.
- Preferred embodiments may also utilize low numbers of sperm relative to natural insemination, located within the volume and a sperm emission element adjacent the volume through which sperm may pass.
- the sperm may be collected, selected, of an inseminate volume, perhaps even of an epididymis origin, or of any other limitation previously discussed.
- the sperm emission element may comprise a breach in the endometrium surface of the uterus, as depicted in Figure 3, or may simply occur by diffusion or the like.
- Such procedures may include sorting the sperm cells by a sex characteristic, thereby establishing a sex-sorted artificial insemination sample, and in preferred embodiments having a low number of sperm compared to a natural insemination dosage for said mammal, may include establishing a low dose sex-selected artificial insemination sample.
- preserving or freezing, and the subsequent thawing of, sperm sells may be accomplished in particular embodiments, particularly in regard to various mammals such as equid, bovid and swine.
- Deposition of the insemination sample may be processed or aspirated in any way, may be deposited with the crypts or folds of the UTJ, and may provide some type of preservation of the sperm for subsequent insemination.
- Establishment of an insemination specimen or insemination sample at a hysteroscopic compatible volume and utilizing compatible media may further provide for allowing cooling of the specimen or sample at room temperature.
- Centrifugation may preferably be performed through a Percoll gradient for about five minutes at about 200g and for about ten minutes at about 800g.
- concentrating the more motile sperm may be limited to concentrating to less than about twice the starting concentration.
- the broad and narrow concepts embodied in the present invention should be construed as applying to other species of mammal, including equids, bovids and swine.
- the present invention directed in part to the producing of an offspring mammal, may further be considered to disclose an embodiment of an animal produced utilizing a process as described in any of the foregoing method claims.
- Sorting in accordance with embodiments of the present invention, may particularly provide for collecting sperm cells from a male of a species of mammal, sorting the sperm cells according to a sex-specific characteristic, establishing a sorted, sex-specific artificial insemination sample, placing the sorted, sex-specific artificial insemination sample in a catheter; among the various other aspects of the invention disclosed herein that might be incorporated in method of producing a mammal.
- the basic concepts of the present invention may be embodied in a variety of ways. It involves both insemination techniques as well as apparatus to accomplish appropriate insemination.
- the insemination techniques are disclosed as part of the results shown to be achieved by the various devices described and as steps which are inherent to utilization. They are simply the natural result of utilizing the devices as intended and described.
- the devices are disclosed, it should be understood that these not only accomplish certain methods but also can be varied in a number of ways.
- all of these facets should be understood to be encompassed by this disclosure.
- each of the various elements of the invention and claims may also be achieved in a variety of manners.
- This disclosure should be understood to encompass each such variation, be it a variation of an embodiment of any apparatus embodiment, a method or process embodiment, or even merely a variation of any element of these.
- the words for each element may be expressed by equivalent apparatus terms or method terms ⁇ even if only the function or result is the same.
- Such equivalent, broader, or even more generic terms should be considered to be encompassed in the description of each element or action. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled.
- each of the insemination devices as herein disclosed and described, ii) the related methods disclosed and described, iii) similar, equivalent, and even implicit variations of each of these devices and methods, iv) those alternative designs which accomplish each of the functions shown as are disclosed and described, v) those alternative designs and methods which accomplish each of the functions shown as are implicit to accomplish that which is disclosed and described, vi) each feature, component, and step shown as separate and independent inventions, vii) the applications enhanced by the various systems or components disclosed, viii) the resulting products produced by such systems or components, and ix) methods and apparatuses substantially as described hereinbefore and with reference to any of the accompanying examples, and x) the various combinations and permutations of each of the elements disclosed.
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MXPA03002710A MXPA03002710A (en) | 2000-10-05 | 2001-01-24 | System of hysteroscopic insemination of mares. |
JP2002531941A JP2004510423A (en) | 2000-10-05 | 2001-01-24 | Female hysteroscope insemination system |
BR0114442-1A BR0114442A (en) | 2000-10-05 | 2001-01-24 | Hysteroscopic Mares Insemination System |
NZ525667A NZ525667A (en) | 2000-10-05 | 2001-01-24 | System of hysteroscopic insemination of mammals especially mares |
AU3651701A AU3651701A (en) | 2000-10-05 | 2001-01-24 | System of hysteroscopic insemination of mares |
GB0309041A GB2383543B (en) | 2000-10-05 | 2001-01-24 | System of hysteroscopic insemination of mares |
AU2001236517A AU2001236517A2 (en) | 2000-10-05 | 2001-01-24 | System of hysteroscopic insemination of mares |
CA002424115A CA2424115A1 (en) | 2000-10-05 | 2001-01-24 | System of hysteroscopic insemination of animals |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US23829400P | 2000-10-05 | 2000-10-05 | |
US60/238,294 | 2000-10-05 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US23829400P Continuation | 2000-10-05 | 2000-10-05 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10398796 A-371-Of-International | 2003-04-03 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002028311A1 true WO2002028311A1 (en) | 2002-04-11 |
Family
ID=22897281
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2001/002304 WO2002028311A1 (en) | 2000-10-05 | 2001-01-24 | System of hysteroscopic insemination of mares |
Country Status (10)
Country | Link |
---|---|
JP (2) | JP2004510423A (en) |
CN (1) | CN1473026A (en) |
AR (1) | AR029030A1 (en) |
AU (2) | AU3651701A (en) |
BR (1) | BR0114442A (en) |
CA (1) | CA2424115A1 (en) |
GB (1) | GB2383543B (en) |
MX (1) | MXPA03002710A (en) |
NZ (2) | NZ525667A (en) |
WO (1) | WO2002028311A1 (en) |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7713687B2 (en) | 2000-11-29 | 2010-05-11 | Xy, Inc. | System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations |
US7758811B2 (en) | 2003-03-28 | 2010-07-20 | Inguran, Llc | System for analyzing particles using multiple flow cytometry units |
US7820425B2 (en) | 1999-11-24 | 2010-10-26 | Xy, Llc | Method of cryopreserving selected sperm cells |
US7833147B2 (en) | 2004-07-22 | 2010-11-16 | Inguran, LLC. | Process for enriching a population of sperm cells |
US7838210B2 (en) | 2004-03-29 | 2010-11-23 | Inguran, LLC. | Sperm suspensions for sorting into X or Y chromosome-bearing enriched populations |
US7855078B2 (en) | 2002-08-15 | 2010-12-21 | Xy, Llc | High resolution flow cytometer |
US7929137B2 (en) | 1997-01-31 | 2011-04-19 | Xy, Llc | Optical apparatus |
US8137967B2 (en) | 2000-11-29 | 2012-03-20 | Xy, Llc | In-vitro fertilization systems with spermatozoa separated into X-chromosome and Y-chromosome bearing populations |
US8211629B2 (en) | 2002-08-01 | 2012-07-03 | Xy, Llc | Low pressure sperm cell separation system |
US8486618B2 (en) | 2002-08-01 | 2013-07-16 | Xy, Llc | Heterogeneous inseminate system |
US9145590B2 (en) | 2000-05-09 | 2015-09-29 | Xy, Llc | Methods and apparatus for high purity X-chromosome bearing and Y-chromosome bearing populations of spermatozoa |
US9277981B2 (en) | 2008-09-26 | 2016-03-08 | Universidad De Murcia | Device and method for inserting or obtaining a fluid with gametes, embryos or any other type of solution in the oviduct of a sow |
US9365822B2 (en) | 1997-12-31 | 2016-06-14 | Xy, Llc | System and method for sorting cells |
US11230695B2 (en) | 2002-09-13 | 2022-01-25 | Xy, Llc | Sperm cell processing and preservation systems |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2424115A1 (en) * | 2000-10-05 | 2002-04-11 | Xy, Inc. | System of hysteroscopic insemination of animals |
US9433195B2 (en) * | 2012-06-06 | 2016-09-06 | Inguran, Llc | Methods for increasing genetic progress in a line or breed of swine using sex-selected sperm cells |
CN104195104B (en) * | 2014-07-04 | 2019-04-09 | 扬州大学 | A kind of new method of Chicken Semen purifying |
EP3232986A1 (en) * | 2014-12-18 | 2017-10-25 | Li-Nom Management Ltd. | Split balloon catheter for intra uterine insemination (iui) and slow release insemination (sri) |
CN105248368B (en) * | 2015-10-15 | 2018-08-10 | 内蒙古自治区农牧业科学院 | A method of promoting the double calves of beef cattle production |
BR112021003722A2 (en) * | 2018-08-31 | 2021-05-25 | Inguran, Llc | devices and methods for artificial insemination. |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0214043A1 (en) * | 1985-08-19 | 1987-03-11 | Etablissement public dit: INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE | Instrument and process for artificial insemination, in utero embryo transplants or taking follicular liquid by transperitoneal means in animals |
US4846785A (en) * | 1987-01-22 | 1989-07-11 | Robert Cassou | Instrument for artificial insemination, embryo transfer or sampling follicular liquids in mammals |
US5135759A (en) | 1989-05-10 | 1992-08-04 | The United States Of America As Represented By The Secretary Of Agriculture | Method to preselect the sex of offspring |
EP0570102A1 (en) * | 1992-05-12 | 1993-11-18 | Ovamed Corporation | Delivery catheter |
WO1998034094A1 (en) | 1997-01-31 | 1998-08-06 | The Horticulture & Food Research Institute Of New Zealand Ltd. | Optical apparatus |
WO1999033956A1 (en) | 1997-12-31 | 1999-07-08 | Xy, Inc. | Sex-specific insemination of mammals with low number of sperm cells |
WO1999038883A1 (en) | 1998-02-03 | 1999-08-05 | Xy, Inc. | Specific oligonucleotide primers for detection of bovine male chromosome presence by polymerase chain reaction and method |
WO1999042810A1 (en) | 1998-02-20 | 1999-08-26 | Xy, Inc. | A vibratory system for a sorting flow cytometer |
WO2000006193A1 (en) | 1998-07-30 | 2000-02-10 | Xy, Inc. | Equine system for non-surgical artificial insemination |
US6117068A (en) * | 1995-10-19 | 2000-09-12 | Elite Genetics, Inc | Artificial insemination system |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997014785A2 (en) * | 1995-10-19 | 1997-04-24 | Advanced Reproduction Technologies, Inc. | Methods and compositions to improve germ cell and embryo survival and function |
CA2424115A1 (en) * | 2000-10-05 | 2002-04-11 | Xy, Inc. | System of hysteroscopic insemination of animals |
-
2001
- 2001-01-24 CA CA002424115A patent/CA2424115A1/en not_active Abandoned
- 2001-01-24 JP JP2002531941A patent/JP2004510423A/en active Pending
- 2001-01-24 BR BR0114442-1A patent/BR0114442A/en not_active Application Discontinuation
- 2001-01-24 AU AU3651701A patent/AU3651701A/en active Pending
- 2001-01-24 GB GB0309041A patent/GB2383543B/en not_active Expired - Fee Related
- 2001-01-24 NZ NZ525667A patent/NZ525667A/en unknown
- 2001-01-24 WO PCT/US2001/002304 patent/WO2002028311A1/en not_active Application Discontinuation
- 2001-01-24 CN CNA018185584A patent/CN1473026A/en active Pending
- 2001-01-24 AR ARP010100293A patent/AR029030A1/en not_active Application Discontinuation
- 2001-01-24 MX MXPA03002710A patent/MXPA03002710A/en not_active Application Discontinuation
- 2001-01-24 AU AU2001236517A patent/AU2001236517A2/en not_active Abandoned
- 2001-01-24 NZ NZ53768001A patent/NZ537680A/en unknown
-
2008
- 2008-01-11 JP JP2008005039A patent/JP2008093483A/en active Pending
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0214043A1 (en) * | 1985-08-19 | 1987-03-11 | Etablissement public dit: INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE | Instrument and process for artificial insemination, in utero embryo transplants or taking follicular liquid by transperitoneal means in animals |
US4846785A (en) * | 1987-01-22 | 1989-07-11 | Robert Cassou | Instrument for artificial insemination, embryo transfer or sampling follicular liquids in mammals |
US5135759A (en) | 1989-05-10 | 1992-08-04 | The United States Of America As Represented By The Secretary Of Agriculture | Method to preselect the sex of offspring |
EP0570102A1 (en) * | 1992-05-12 | 1993-11-18 | Ovamed Corporation | Delivery catheter |
US6117068A (en) * | 1995-10-19 | 2000-09-12 | Elite Genetics, Inc | Artificial insemination system |
WO1998034094A1 (en) | 1997-01-31 | 1998-08-06 | The Horticulture & Food Research Institute Of New Zealand Ltd. | Optical apparatus |
WO1999033956A1 (en) | 1997-12-31 | 1999-07-08 | Xy, Inc. | Sex-specific insemination of mammals with low number of sperm cells |
US6071689A (en) | 1997-12-31 | 2000-06-06 | Xy, Inc. | System for improving yield of sexed embryos in mammals |
WO1999038883A1 (en) | 1998-02-03 | 1999-08-05 | Xy, Inc. | Specific oligonucleotide primers for detection of bovine male chromosome presence by polymerase chain reaction and method |
WO1999042810A1 (en) | 1998-02-20 | 1999-08-26 | Xy, Inc. | A vibratory system for a sorting flow cytometer |
WO2000006193A1 (en) | 1998-07-30 | 2000-02-10 | Xy, Inc. | Equine system for non-surgical artificial insemination |
Cited By (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7929137B2 (en) | 1997-01-31 | 2011-04-19 | Xy, Llc | Optical apparatus |
US9422523B2 (en) | 1997-12-31 | 2016-08-23 | Xy, Llc | System and method for sorting cells |
US9365822B2 (en) | 1997-12-31 | 2016-06-14 | Xy, Llc | System and method for sorting cells |
US7820425B2 (en) | 1999-11-24 | 2010-10-26 | Xy, Llc | Method of cryopreserving selected sperm cells |
US10208345B2 (en) | 2000-05-09 | 2019-02-19 | Xy, Llc | Method for producing high purity X-chromosome bearing and Y-chromosome bearing populations of spermatozoa |
US9145590B2 (en) | 2000-05-09 | 2015-09-29 | Xy, Llc | Methods and apparatus for high purity X-chromosome bearing and Y-chromosome bearing populations of spermatozoa |
US8137967B2 (en) | 2000-11-29 | 2012-03-20 | Xy, Llc | In-vitro fertilization systems with spermatozoa separated into X-chromosome and Y-chromosome bearing populations |
US9879221B2 (en) | 2000-11-29 | 2018-01-30 | Xy, Llc | Method of in-vitro fertilization with spermatozoa separated into X-chromosome and Y-chromosome bearing populations |
US8652769B2 (en) | 2000-11-29 | 2014-02-18 | Xy, Llc | Methods for separating frozen-thawed spermatozoa into X-chromosome bearing and Y-chromosome bearing populations |
US7771921B2 (en) | 2000-11-29 | 2010-08-10 | Xy, Llc | Separation systems of frozen-thawed spermatozoa into X-chromosome bearing and Y-chromosome bearing populations |
US7713687B2 (en) | 2000-11-29 | 2010-05-11 | Xy, Inc. | System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations |
US8486618B2 (en) | 2002-08-01 | 2013-07-16 | Xy, Llc | Heterogeneous inseminate system |
US8211629B2 (en) | 2002-08-01 | 2012-07-03 | Xy, Llc | Low pressure sperm cell separation system |
US8497063B2 (en) | 2002-08-01 | 2013-07-30 | Xy, Llc | Sex selected equine embryo production system |
US7855078B2 (en) | 2002-08-15 | 2010-12-21 | Xy, Llc | High resolution flow cytometer |
US11230695B2 (en) | 2002-09-13 | 2022-01-25 | Xy, Llc | Sperm cell processing and preservation systems |
US11261424B2 (en) | 2002-09-13 | 2022-03-01 | Xy, Llc | Sperm cell processing systems |
US9377390B2 (en) | 2003-03-28 | 2016-06-28 | Inguran, Llc | Apparatus, methods and processes for sorting particles and for providing sex-sorted animal sperm |
US7943384B2 (en) | 2003-03-28 | 2011-05-17 | Inguran Llc | Apparatus and methods for sorting particles |
US8748183B2 (en) | 2003-03-28 | 2014-06-10 | Inguran, Llc | Method and apparatus for calibrating a flow cytometer |
US9040304B2 (en) | 2003-03-28 | 2015-05-26 | Inguran, Llc | Multi-channel system and methods for sorting particles |
US8709825B2 (en) | 2003-03-28 | 2014-04-29 | Inguran, Llc | Flow cytometer method and apparatus |
US11718826B2 (en) | 2003-03-28 | 2023-08-08 | Inguran, Llc | System and method for sorting particles |
US8664006B2 (en) | 2003-03-28 | 2014-03-04 | Inguran, Llc | Flow cytometer apparatus and method |
US8709817B2 (en) | 2003-03-28 | 2014-04-29 | Inguran, Llc | Systems and methods for sorting particles |
US7758811B2 (en) | 2003-03-28 | 2010-07-20 | Inguran, Llc | System for analyzing particles using multiple flow cytometry units |
US7799569B2 (en) | 2003-03-28 | 2010-09-21 | Inguran, Llc | Process for evaluating staining conditions of cells for sorting |
US10100278B2 (en) | 2003-03-28 | 2018-10-16 | Inguran, Llc | Multi-channel system and methods for sorting particles |
US11104880B2 (en) | 2003-03-28 | 2021-08-31 | Inguran, Llc | Photo-damage system for sorting particles |
US7838210B2 (en) | 2004-03-29 | 2010-11-23 | Inguran, LLC. | Sperm suspensions for sorting into X or Y chromosome-bearing enriched populations |
US7892725B2 (en) | 2004-03-29 | 2011-02-22 | Inguran, Llc | Process for storing a sperm dispersion |
US7833147B2 (en) | 2004-07-22 | 2010-11-16 | Inguran, LLC. | Process for enriching a population of sperm cells |
US9277981B2 (en) | 2008-09-26 | 2016-03-08 | Universidad De Murcia | Device and method for inserting or obtaining a fluid with gametes, embryos or any other type of solution in the oviduct of a sow |
Also Published As
Publication number | Publication date |
---|---|
NZ537680A (en) | 2007-01-26 |
AU3651701A (en) | 2002-04-15 |
NZ525667A (en) | 2005-07-29 |
MXPA03002710A (en) | 2004-01-26 |
GB2383543B (en) | 2005-03-09 |
CN1473026A (en) | 2004-02-04 |
GB0309041D0 (en) | 2003-05-28 |
JP2004510423A (en) | 2004-04-08 |
GB2383543A (en) | 2003-07-02 |
JP2008093483A (en) | 2008-04-24 |
BR0114442A (en) | 2004-02-17 |
AR029030A1 (en) | 2003-06-04 |
CA2424115A1 (en) | 2002-04-11 |
AU2001236517A2 (en) | 2002-04-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20040031071A1 (en) | System of hysteroscopic insemination of mares | |
Lindsey et al. | Hysteroscopic insemination of low numbers of flow sorted fresh and frozen/thawed stallion spermatozoa | |
WO2002028311A1 (en) | System of hysteroscopic insemination of mares | |
Buchanan et al. | Insemination of mares with low numbers of either unsexed or sexed spermatozoa | |
AU2011201281B2 (en) | System to separate frozen-thawed spermatozoa into X-chromosome bearing and Y-chromosome bearing populations | |
Hollinshead et al. | In vitro and in vivo assessment of functional capacity of flow cytometrically sorted ram spermatozoa after freezing and thawing | |
Hollinshead et al. | Production of lambs of predetermined sex after the insemination of ewes with low numbers of frozen–thawed sorted X-or Y-chromosome-bearing spermatozoa | |
Lindsey et al. | Hysteroscopic insemination of mares with low numbers of nonsorted or flow sorted spermatozoa | |
King et al. | Lambing rates and litter sizes following intrauterine or cervical insemination of frozen/thawed semen with or without oxytocin administration | |
Lindsey et al. | Low dose insemination of mares using non-sorted and sex-sorted sperm | |
CA2538118C (en) | Sperm cell preservation and processing systems | |
Miró et al. | Effect of donkey seminal plasma on sperm movement and sperm–polymorphonuclear neutrophils attachment in vitro | |
Jainudeen et al. | Ovulation induction, embryo production and transfer | |
Sá Filho et al. | Sex-sorted sperm for artificial insemination and embryo transfer programs in cattle | |
Clulow et al. | Field fertility of sex-sorted and non-sorted frozen–thawed stallion spermatozoa | |
Farstad | Artificial insemination in dogs | |
Cazales et al. | Sperm transport and endometrial inflammatory response in mares after artificial insemination with cryopreserved spermatozoa | |
Sanchez et al. | ARTIFICIAL INSEMINATION WITH 15 FROZEN SEMEN | |
Squires et al. | Simplified strategy for insemination of mares with frozen semen. | |
Kurykin et al. | Low semen dose intracornual insemination of cows at fixed time after PGF2α treatment or at spontaneous estrus | |
GB2399272A (en) | An insemination sample | |
Skidmore et al. | Comparison of two closed vitrification methods for vitrifying dromedary camel (Camelus dromedarius) embryos | |
Arakaki | The Atelids | |
Turner et al. | Use of alkaline phosphatase activity as a diagnostic tool in stallions with azoospermia and oligospermia | |
Hasler | Embryo transfer and in vitro fertilization |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
ENP | Entry into the national phase |
Ref document number: 0309041 Country of ref document: GB Kind code of ref document: A Free format text: PCT FILING DATE = 20010124 Format of ref document f/p: F |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2002531941 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2003/002710 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2424115 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10398796 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: 200350019 Country of ref document: ES Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: P200350019 Country of ref document: ES |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2001236517 Country of ref document: AU Ref document number: 525667 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 018185584 Country of ref document: CN |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
122 | Ep: pct application non-entry in european phase | ||
ENP | Entry into the national phase |
Ref document number: 200550008 Country of ref document: ES Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: P200550008 Country of ref document: ES |
|
WWR | Wipo information: refused in national office |
Ref document number: 200350019 Country of ref document: ES Kind code of ref document: A |
|
WWP | Wipo information: published in national office |
Ref document number: 525667 Country of ref document: NZ |
|
WWG | Wipo information: grant in national office |
Ref document number: 525667 Country of ref document: NZ |
|
WWR | Wipo information: refused in national office |
Ref document number: 200550008 Country of ref document: ES Kind code of ref document: A Ref document number: 200350019 Country of ref document: ES Kind code of ref document: A |