JPS6058168A - Non-surgical method and apparatus for human embryo transplantation - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] [Summary of the invention] The present invention relates to a non-surgical method for human fetal transplantation.

This method allows non-surgical implantation of a embryo from a human female donor into a human female recipient. The methods of the invention include artificial conception methods.

Briefly, the present invention relates to a device for use in a non-surgical method of treating a human uterus. The device of the present invention, called a uterine catheter, has a non-rigid structure that allows the device to be inserted into the body by itself. It has sufficient stiffness to be inserted without the need for a quality stylent or rigid rond introduction means.

[Technical field to which the invention pertains]

The present author, Akira C., is concerned with non-surgical methods of human fetal transplantation. This method allows non-surgical pressure transfer of a pre-implantation belly from a human female donor to a human female recipient. The method of the present invention encompasses all methods of artificial fertilization in which a pre-implantation embryo is non-surgically removed from a human donor and the parenthesis f1 is non-surgically transferred to an infertile human recipient.

The invention further relates to an improved device for use in a non-surgical method for treating human children. The device of the present invention, called Child B Catheter, may be used in non-surgical retrieval processes in methods of human fetal implantation or artificial insemination, or in cleaning or testing Child H, introducing treatment substances into the uterus, or in diagnostic processes. I can do it. Preferably, the device is used for non-surgical human fetal retrieval in methods of human fetal implantation and artificial insemination.

[Prior art and its problems]

In Aikawa Province, America, it is estimated that the number of married couples is 10~
15% are infertile. Infertility in these couples is caused by both spouses. Approximately 40% of infertile couples are affected by noalopecia. however,
In either case, the infertile woman generally has a hormonally responsive uterus that can accept the fetus and hold it until birth.

Birth control and abortion have significantly reduced the population of children available for adoption by infertile couples. This decline, along with the lack of effective fertility treatments, has left many infertile couples childless.

Understanding the interrelated hormonal processes that regulate female fertility was particularly important in developing our method.

The main anatomical elements involved in the period of conception are the hypothalamus near the base of the brain, and the pituitary gland located just below the bedrock81).
Includes ovaries, fallopian tubes, uterus and vagina. During each normal conception period in a human female, one mII follicle is produced, matures, is expelled from the ovary, enters the enlarged end of the fallopian tube, and then travels to the uterus. If conception does not occur, this egg cell will disintegrate. This cycle is repeated at monthly intervals. If mating or fertilization occurs at the right time in the cycle, the egg cell will become an egg W.
It unites with sperm in the ampulla of the IC and fertilizes.

The fertilized egg then moves through the oviduct, feeding and dividing during this journey. Generally, the egg cells reach the uterus as a morula (ie, a spherical cluster of eight or more cells) after three days. The embryo attaches to and becomes embedded in the uterine wall within about 7 to 10 days after conception. Until that point, from the day the embryo enters the uterus until it attaches to the uterine wall, it floats in the free κ uterus.

Cell division continues in the uterus and produces an embryo: a blastula (i.e., a fluid-filled sphere with polar cell clusters called the internal substance on its 10,000 sides). This blastula develops and attaches to the endometrium (i.e., the lining of the uterus);
Through a complex implantation process, the blastula embeds itself into the uterine wall and becomes 1L.

The inner cellular material becomes the fetus, while the outer cells of the blastula, together with nearby uterine cells and blood vessels, form the placenta, the organ that exchanges material between the fetus and circulating materials. . It is said that the pregnancy has been confirmed from this transfer (C).
It can be detected by measuring hormones such as human chorionic gonadotropin (HCG) in the L1 maternal blood.

Phenomena related to conception and transfer are regulated by the interaction of hormones produced by the maternal thalamus F, pituitary gland, ovary, fallopian tubes, and offspring (tCb). Secreted from the pituitary gland.This FS
H stimulates the production and maturation of υ1j follicles containing the egg cell and its supporting 4'h'ittllll follicles. As this follicle develops, its cells secrete Esl-logonhormone C, mainly estodidiol)'L-, which acts on the pituitary gland to reduce FSII and at the same time , stimulates the growth of the endometrium.

When the follicle reaches a completed size of 1, the excretion of 1'SH decreases and the second pituitary hormone, progestin (1,H), decreases.
) is the main subject. This LH completes the maturation of rabbit cells,
and causes excretion of egg manure into the fallopian tubes. This excretion appears to occur approximately 1 day after the LH peak. One cell remaining after the discharge of the cell Ik'J is
The corpus luteum (i.e., the anatomical structure that secretes glogesterone) forms 1&L, and the uterus is fully developed.

If conception does not occur, the corpus luteum decreases and a new follicle tj'f
- is 1''} 6th grade. This decrease in estradiol/progesterone production subsides the regressive changes in the uterine wall and menstruation occurs.

After implantation into the uterine wall, the outer cells of the developing embryo secrete human chorionic gonata (HCG), a hormone with effects very similar to LH. This HCG! -1. Stimulates continued maintenance and hormone production by the corpus luteum.

Furthermore, this HCG acts to prevent the growth of new follicles in the ovary. After about 5 weeks, fetal whiskers develop and secrete sufficient amounts of glogesterone to maintain the pregnancy.

One technique for infertile couples to have children is to surgically remove egg cells from the woman, impregnate the egg cells in vitro, and surgically return the fertilized egg cells to the female donor child. be.

In vitro conception (IVF)/autotransplantation is a relatively new technique that consists of laparoscopic ovarian manipulation and surgical removal of non-fertilized eggs from the pre-ovulatory follicles of infertile women. It is based on culture of the clutch, laboratory (in vitro) conception of the egg cells, laboratory culture of the embryo for 2 to 6 days, and non-surgical reinstatement of the embryo into the offspring rB of the same woman.

The external maintenance of egg cells in such external therapy poses many problems. Egg cells are generally immersed in complex biological fluids. First of all, there is little information regarding what components of these fluids are essential for maintaining egg cell health.

A similar problem exists with the other component of normal conception, sperm K. During the first ejaculation, the vitreous is not made to penetrate the egg cell K. These litters must first undergo capacitation, a process commonly induced by conditions in the female reproductive tract. This ability must be provided externally if the sperm are to enter the egg cell 1c in an appropriate state.

Research on in vitro conception of non-human animals (primarily marine animals) dates back to 1893.

Twenty years ago, convincing evidence of successful external conception of rabbit egg cells was presented. Since that time, many other mammals (including humans) have used this method.

The first in vitro conception and embryo transfer in humans was reported in 1969 by British researchers R.G. Edsword, B.D. Babister, and B.C. Steptoe. The birth of Louis Joy Bujiun on July 25, 1978 was the first reported case of in vitro conception/autotransplantation, in which human egg cells were surgically removed from the wife's ovaries and fertilized in vitro. The baby was then placed back into the same woman's womb where it developed until birth. This type of technique does not allow non-surgical removal of non-conceived egg cells. Thus, these are complex procedures and involve surgical and anesthetic risks.

Embryo transfer, or removal of an in-vivo conceptus from a donor offspring and implantation into the uterus of another woman, where the recipient BBvβ is implanted and subsequently developed, has been performed in non-human animals. The first transplant of this kind was to Hepe, 91
It was reported in 890.

The greatest number of embryo transfers were performed in cows. However, successful cases of embryo transfer have been reported in mice, rats, sheep, pigs, horses, rabbits,
It has also been reported in other types of suckling animals, including baboons, rhesus monkeys, and goats. Commission O Oz Fist The European ●Community=Nai'tc pants length 197b
The paper ``Egg Cell Transplantation in Cattle'' presented at the 2011 Agricultural Research Institute Seminar describes some of these embryo transfer methods. Further references are made to Theriogenology, Niens Magazine, Journal Opuli Production and Fadeility, and Biology of Reproduction, published by Keron-X Incorporated, Los Altos, California. can.

US 'l:'? 1'F Publication No. 3,854,470 and Colorado State University Animal Production Laboratory General Report, No. 97
No. 5 (1978.1980) "Cow Fetus Transplantation Method" also describes the transplantation of embryos other than humans, and specifically describes the use of cows. The above U.S. Patent No. 3,854,470 is
The removal of fertilized and non-fertilized ovaries in ungulate 1'nj mammals K by surgical removal followed by non-surgical implantation using a cervical cannula 2 is described.

U.S. Patent No. 4,32 (S,505) discloses that host animal c.
% of animals with uterine horns] describes a method for surgically implanting embryos. US Pat. Nos. 4,178,936 and 4,004,588 describe a method for non-surgical egg cell retrieval in animals, particularly cattle, using a catheter in combination with a rigid introducer.

Although fetal removal and transplantation has been performed in cows and other non-human animals, these known techniques have heretofore been either infeasible or impractical to perform in humans. This is because there are fundamental anatomical and physiological differences in the female reproductive system between humans and non-human mammals. Comparing the bovine and human uteri reveals critical differences, for example in size, shape and tissue quality.

For example, in cows the utero-tubal junction is sealed. Therefore, the fluid used for non-surgical bovine uterine irrigation is not lost outside the fallopian tubes. (In humans, however, the opening from the uterus to the fallopian tubes is generally unobstructed.) The use of bovine uterine irrigation techniques and tools in human patients results in the loss of lavage fluid into the fallopian tubes and peritoneal cavity. This is t
However, it may cause loss of the embryo or ectopic pregnancy in the female donor.

Methods of non-surgical embryo removal and non-surgical implantation in cattle also involve painful implantation and repositioning of internal organs and therefore require the administration of local or general anesthesia. 6) The anatomical manipulations performed on cattle are impossible on humans. Finally, the steps used in removal and transplantation methods in some animals may not necessarily be performed in other animals. This is because the size of the proliferative organs, the leakage of lavage fluid from the fallopian tubes, differences in the time of conception, as well as differences in the responsiveness of the receptor, donor or fetus to drugs, compounds and vehicles,
as well as differences in the effectiveness or safety of particular removal or implantation devices in different animals.

Currently available equipment designed for use in processing human uterus is typically the Mosquito 1K. This type of device causes discomfort to the patient and is difficult to penetrate internal tissues. be.

Additionally, the use of this type of rigid device requires dilation of the cervix, repositioning of the uterus, and use of stabilizing clangs. These operations are often painful and can induce uterine bleeding.

U.S. Pat. No. 5,527,203 describes a body cavity cleaning device that includes an inlet tube, an outlet tube, and a sealing member. These tubes are constructed from a hard plastic material and have rough edged openings designed to allow for complete collection of tissue samples.

U.S. Pat. No. 7,948,270 describes a uterine cannula for human uterine eminence, which includes a rigid tube that is placed inside a 7-Ory catheter. Because of its rigidity, this type of cannula can only adapt to the natural contours of the uterus.

US patent d'. Publication No. 3,095,871 describes a diagnostic tool for human uterus IC No. 1. This tool is
Includes a rigid rubber catheter for use in conjunction with a rigid stylet introducer.

The rigid uterine penetration device is also used in the field of animal husbandry. For example, U.S. Pat. No. 3,854,470 describes a rigid pichet containing a catheter for inserting rabbit cells into ungulates. U.S. Pat. No. 4,178,936 and its younger brother, U.S. Pat. No. 4,004,588, are particularly concerned with the use of cattle. ! 6 [Shi] are listed for each child bacade to be used in combination with a hard introducing device for invading the child gκ for taking out the child.

Non-rigid catheters have been developed to facilitate non-surgical methods for handling the human uterus.

This outfit? 6° causes little discomfort to the patient and does not require the use of external induction stages or anesthesia.

This device combines rigidity and flexibility making it extremely advantageous for non-surgical methods of this type.

Although this non-rigid catheter can be used for human fetal implantation, ie, the removal of pre-implantation embryos for artificial fertilization, this application has some drawbacks. This is because lavage fluid may be lost from the fallopian tube during the procedure or may become obstructed by fetal tissue or mucous membranes. Such obstruction may result in loss of lavage fluid from the cervix. be. Such loss of lavage fluid risks losing the fetus.

Additionally, ectopic pregnancies can occur if fluid loss occurs through the fallopian tubes. Additionally, this catheter cannot be manipulated within the glenoid cavity, making it difficult to clean the entire uterine surface. As a result, the abdomen of the 7-plaster AiJ cannot be removed as desired using this catheter.

Methods of non-surgical human embryo transfer and artificial fertilization Capabilities are not fully realized in i1.

[Eleventh Object of the Invention] Therefore, it is an object of the present invention to provide a non-alteric method of leech/fetus transplantation and an apparatus therefor. This method allows non-surgical removal of the embryo and non-surgical transfer from a human female donor to a human female recipient. The method of the present invention involves the non-surgical removal of a pre-implantation embryo (i.e., a conceptus) from a human donor and its non-surgical transfer into an infertile human recipient. do.

[Key points of the invention]

In a broad sense, the method of the present invention involves synchronizing the ovulation of both the donor and the recipient, artificially inseminating the donor,
The process consists of non-surgically removing the IJf from the donor's uterus, detecting the embryo in a washing medium, and non-surgically implanting the whole embryo into the recipient uterus.

Non-surgical transfer of human fetus according to the method of the present invention, 111
Synchronize the ovulation of a human female donor and a human female recipient, artificially fertilize the donor, and physically and non-surgically remove the resulting 7n pre-bed embryo from the donor's uterus. It consists of detecting the embryo in a recovery medium and physically and non-surgically implanting the embryo into the recipient's uterus.

Additionally, the present invention is directed to improved devices for use in non-surgical methods of treating the human uterus.

The limb rest of the present invention, designated as Child B Catheter, has a flexible semi-rigid structure. It is easily introduced through the cervix without clogging the busy mucosa or endometrial cells, can clean almost the entire surface of the uterus, and recovers a high percentage of the cleaning fluid without occlusion. This minimizes the loss of cleaning fluid through the pouch or the neck. Additionally, the collected lavage fluid is generally clear and free of p1 blood and cell debris, making detection of pre-implantation embryos easier.

[General description of the invention]

Implantation of a human fetus according to the present invention is a non-surgical and non-anesthetic transvaginal and transcervical method for both donor and recipient.

The method of artificial fertilization described in the present invention A'lllMJ is a non-surgical method for removing a fertilized rabbit or implantation eye embryo from a human female donor and non-surgically transplanting it into a human female recipient. Remove by surgical method. Artificial fertilization is a process in which the pre-implantation abdomen is artificially fertilized with sperm from the infertile woman's husband, the fertilized egg is removed from a human woman, and the embryo is transferred to the infertile woman's uterus. This is a method to

The uterine catheter of the present invention is used in non-surgical human fetal transplantation and artificial fertilization methods to remove embryos before implantation.
Useful. In human fetal transplantation and artificial endowment methods, the Δcatheter of the present invention is used as a cleaning tool. This introduces and collects the wash solution containing the pre-implantation embryo. Positive fluid pressure is used to direct the lavage fluid into the uterus, and negative pressure is used to remove the lavage fluid and the embryo.

The uterus catheter can be used for many non-surgical methods of treating the uterus. For example, the uterine catheter can be used for uterine examination, non-surgical methods of treating pre-implantation embryos. It can be used for target extraction, washing the uterus, testing tube opening, introducing treatment substances into the uterus and sampling endometrium or 10 gm tissue.

Alternatively, the improved catheter of the present invention can also be used in methods of irrigating the uterine cavity with various solutions as a method of birth control.

The improved catheter of the present invention facilitates a non-surgical method of treating the uterus with minimal discomfort to the patient. The catheter is constructed from a semi-rigid, smooth material that allows it to move smoothly and freely pass through the child's head, while also being flexible enough to conform to the contours of the child's head. .

The method of the invention begins by synchronizing the ovulation of the donor and recipient to ensure a similar fertile and hormonal environment for the embryo. The donor is then artificially inseminated using any method known in the art. Particularly commonly, the sperm of the recipient's husband is used. The fertilized egg or pre-implantation embryo is then physically and non-surgically removed from the K donor's uterus;
detection and then physically and non-externally implantation into the recipient's uterus.

Non-surgical removal of embryos from flj [according to recipient 81'7 eggs or implantation r11] is carried out during pup cleaning p1
This is done by inserting a thin, open-ended device, or catheter, through the head of the uterus into the uterine wall of the donor with the unembedded fetus. It is performed by inserting it into the uterus. Then, the tissue culture medium is poured into the offspring B via the catheter, and the embryo is expelled through the extraction channel of the U-reck.

The abdomen is then detected in the medium using a single-purpose optical microscope. Embryos are then transferred to fresh media, washed and carefully VC examined for conception, cell division, cell structure and organization under a high-resolution single-image microscope. Preferably, the ideal embryo to be transferred is one that has developed to about 50-100 cells stage. Implantation of embryos at developmental stages below 50 cells is also contemplated by the method of the present invention. However, in the case of embryos that have not matured to about 50 cells before implantation,
It should be understood that porting is not efficient.

The embryos are then non-surgically transferred into nine receptor bodies.

This transfer is performed by inserting the embryo into the recipient offspring B through the cervix using a non-surgical insertion catheter. The embryo is then expelled into the uterus along with a small mouse tissue culture medium.

As much as possible, the embryo is kept in the same environment as the recipient so that it is only outside the donor for a short period of time. This is carried out using an incubator in which the humidity, acidity and vapor pressure of carbon dioxide and nitrogen are all carefully controlled. Preferably Q,
Embryos can be kept outside the human body for up to about 30 minutes, but are capable of IJf for longer periods of time. For longer periods of time, it is preferable to use the culture method described above. Alternatively, the embryos can be cryopreserved until transplanted into whole recipients.

Human fetal transplantation involving artificial insemination as described in Suimei J is advantageous because it is a bureaucratic procedure for both donor and recipient. No surgery is performed on either the donor or the recipient. Therefore, anesthesia is necessary and both donor and acceptor tolerate these procedures well.

The artificial insemination method of the present invention is used when the donor is a fertile human female and the recipient is an infertile human female. A fertile donor is artificially inseminated with sperm from the husband of an infertile recipient. Then, by the method of the present invention, kl
E. is transplanted into an infertile recipient offspring. The fetus that will be sacrificed will not have any of the genes of the recipient, but the child will have the genes of both the husband and the donor. Additionally, the recipient retains the fetus throughout the entire gestation period, including a pre-implantation period of approximately 5 days.

Alternatively, the method according to the invention allows for full fetus or antenatal adoption in which couples accept fetuses from other men and women. This fetus is then implanted into Lou's uterus. In this case, the fetus has neither the wife's genes nor the husband's genes, and neither the husband nor the wife requires fertility.

Thus, fetal transplantation provides an infertile woman with the opportunity to raise a child, providing her with a biological rhythm and a chance of success. Many people consider this pregnancy and birth process to be a powerful experience that allows the receptor to fulfill their desire to become a mother.

Although the child T does not carry the gene for the receptor and is not technically related to her genetically, the giving birth mother carries and carries the child for almost the entire pregnancy and gives birth to the child.

Furthermore, the methods of the present invention can also be used in cases where the recipient has a family history of genetic disease.

Furthermore, the human fetal transplantation method of the present inventor can also be used in cases where the donor produces a viable fetus but is unable to maintain it until delivery. In this case, the h6 baby can be implanted into a female surrogate who will serve as a surrogate mother who will be retained until fetal tube delivery. This method is therefore suitable for donors who have an incapacitated cervix, or due to disease or paralysis:
It is also useful for those who have been informed that their pregnancy is dangerous or abnormal.

Advantageously, the method of the present invention is a non-surgical method that generally requires neither dilation of the cervix nor clamping of the cervix with support hooks. This method generally renders the natural cervical position 11 capable of +EJ rather than artificial apex repositioning, and thus causes minimal discomfort and pain to both donor and recipient.

In all of the above methods, the new and improved fetal catheter of the present invention can be inserted in the natural state of the child's cervix and uterus, and without the use of clamps or any type of device. There's no need. These processes are explained in Process If. It causes almost no pain to the patient.

Retrieval of the fetus by the non-external cleaning method of the present invention, rather than the external method, is almost painless and, in many cases,
More effective than surgical methods.

The non-surgical, almost external vortex-free fetal retrieval method of the present invention lv4 can be repeated for any donor 1c. / In short, 3 days 2! The removal process can then be reversed by washing the donor pellet several times to increase the chances of successful fetal removal.

The techniques described herein may be particularly useful for the treatment of certain types of human infertility without in vitro fertilization, and for recovery of uterus and pregnancy material to improve pregnancy testing and medical diagnosis. and believed to be effective.

Furthermore, using the method of the present invention, embryonic cells from a woman who has decided to carry a child in the future can be taken and stored in liquid nitrogen in exactly the same way that sperm are stored in a sperm bank.

This "fetal bank" is for people who want to postpone having a child for professional reasons, or if they change their mind after undergoing basic pregnancy procedures, and it is convenient to preserve the fetus. I think it is preferable especially for -1f for 9 women.

It is clear that for the implantation of an externally fertilized embryo to be successful in a recipient, the maturation of the embryo must be closely matched to the condition of the recipient's calf wall. The synchronization of the ovulatory period determined by the LH peak, which is the first step in the method of the present invention, is the synchronization between the donor and the recipient during normal ovulation, fertilization, oviductal transport, uterine maintenance, and transplantation. provides the necessary hormonal adaptation. Advantageously, the cycles of donor and acceptor are synchronized with respect to the timing of ovulation within ±3 days, particularly preferably within ±2 days. This synchronization is the ovulation day fc
(by pharmacological methods of regulation) or by using pools of donors and recipients that are tracked with hormonal measurements to select for natural ovulatory compatibility. C, detailed menstrual cycle of each donor and acceptor) jifi
F3 is generally obtained.

Preferably, synchronization takes place during the preconception period, which advantageously provides a normal hormonal environment for conception to take place.
I can do it. Preferably, administering to the donor, acceptor, or both an effective amount of an oral estrogen-glogesterone mixture (oral fertility regulator) or an intravenous groggesterone insert (50 mg, once or twice a day). to delay the onset of menstruation and achieve synchronization. This treatment is started at least 3 days before the cycle of decrease in basal body temperature. Menstruation begins 24-36 hours after stopping estrogen-glogesterone, and cycles are normal thereafter. Alternatively, glogestin may be administered to the donor, acceptor, or both, eg, orally, topically, or non-deliciously, to ensure coincidence of ovulation dates.

The support vehicle will vary depending on the route of administration, and any known vehicle can be used. For example, synchronization is the donor, acceptor, or both. K progestin, estrogen, human chorionic gonadotropin (I{CG), human menopausal gonadotropin (HMG), citrate, clomihuene, follicle-stimulating hormone (FS{) An effective amount of a compound selected from the group consisting of gonadotobin-releasing hormone (GN-H), gonadotobin-releasing hormone (GN-H), and mixtures thereof can be achieved or adjusted by co-administration with a suitable supporting vehicle. Alternatively, a suitable donor and acceptor can be matched using a natural synchronous gold standard.

After 7L of proper synchronization, the embryo donor is artificially inseminated with sperm from, for example, the husband of the infertile recipient. Preferably, the monoclonal fertilization technique is used, as described in J. On the day of Il Beak, TC reception will be held! L is ±1 of J and H peaks.
It is also possible to perform the reception within one day.

After fertilization, the embryo moves along the rabbit's axis and divides during each movement. Generally, the embryo becomes an eastern body after 03-4 days of fertilization.
That is, it reaches the uterus as a spherical cluster consisting of cells of 8 fW or more. Atomic follicle division continues in the offspring, and the embryo (i.e.
One capsule's proboscis produces a liquid-filled sphere with 111θK. This blastula is surrounded by a transparent proteinaceous substance called the ``zona pellucida''. The blastula floats freely within the offspring. Approximately 7 to 9 days later, 1001 solid A1 cells develop from the transparent tube. The grown 14 capsules jjh can then be transplanted, which takes place within about 48 hours after 0}1 day q.

In the book '1G Akira's method IC, non-surgical embryo retrieval is
Includes uterine irrigation of the embryo prior to implantation into a collection channel or suction lumen of an instrument or catheter.

Irrigation of the donor's uterus is preferably carried out at L1. ．． After 1 beak, it will begin to crawl within about 3 to 7 days. Since the embryo has not yet implanted, it can be recovered by washing. Next, 11. 9 can be transferred to the recipient during normal pre-implantation steps.

The improver H catheter of the present invention includes (a) at least two lumens at the distal anterior end defined by an outer tube and at least one inner tube that are coaxial with each other; and (b) a human calf catheter. a distal anterior end suitable for insertion into the canal and ascillary endothelial cavity and having a rounded closure tip adjoining the distal t4:J end of the medial augus; The most distal end of the inner tube is mounted positionally relative to the distal end and proximally to the distal end of the outer tube, surrounding the coaxially oriented distal end of the inner tube; the proximal posterior end with means for supplying the uterine cavity to the uterine cavity; When inserted into the uterine cavity, it has an open ocean of approximately 7-16 French p1, and when inserted into the uterine cavity, 6 (1 per .711).
A corner ek of 0 to 30 is formed to conform to the contour of the child I and +. An improved uterine catheter for use in non-external removal for the treatment of human uteruses having a combination of flexibility and hardness sufficient to produce It consists of This catheter is
The shape, size, position, and interlocking of the gods that adapt to the contours of the uterus and are seen in the shape of the human uterus (one ship L7, a semi-rigid structure t1: J do.

The catheter may be made of a material such as polyvinyl chloride, polyethylene or Deflon® (tetranoroethylene). The preferred catheter is 9 transparent so that fluid content and its transport 411 can be observed during use of this child 8 catheter. Furthermore, it is preferable to cover it with a smooth 45J resin such as Teflon or 7licorn.

The female catheter of the present invention has a small straight tip that can be easily positioned into the catheter through the cervical canal. Preferably, the catheter is a double lumen device, with one lumen introducing irrigation fluid into the uterus and the other lumen removing irrigation fluid and fluid from the uterus. The outer diameter of the catheter is preferably about 7 to 16 French, particularly preferably 11 French. In general, child! The catheter is approximately 3 Qix in length.

The relative flow rate of fluid through the catheter lumen at operating pressure is important. The supply lumen must not provide flow at a rate substantially greater than the flow rate removed by the supply lumen. Also, the suction lumen may not withdraw liquid at a rate substantially greater than the rate at which it is dispensed by the supply lumen. Preferably, L< is such that the feed rate and recovery rate are approximately the same. To achieve this uniformity of supply and withdrawal, the pressure of the shallow flow and the dimensions of the lumen are adjusted. In a preferred embodiment of the invention, the flow has a ratio of suction lumen diameter to supply lumen diameter of 5:1 to 11.
: Adjust so that it becomes 1.

The tube defining the lumen should be made of a resilient, flexible, smooth abrasive material such as Teflon, polyvinyl chloride, and polyethylene. Inside and outside 1] {The inner surface of the suction lumen defined by the tubes is smooth and smooth to allow the liquid to flow freely without obstruction, and to prevent loss of embryos due to sticking to the tube surface. It must be something that can be used. This can be done by treating the tube wall with a silicone spray, or by other methods known in the art. J″M. Nabe has shown that any catheter construction having at least two lumens may be used within the scope of the present invention, provided that at the distal end of the catheter these lumens are
defined by a tube and at least one inner tube.

The rounded closure tip is rigid. It can be made of high impact resistant glass or resin, or metal. It should be rounded υ, preferably bullet-shaped. In one preferred embodiment of the invention,
This tip is attached to the distal front end of the inner tube.

The cage is designed such that the space defined by this cage is not obstructed by the mucous membrane and/or the uterine lining 4 during the treatment of the uterine cavity with liquid and the withdrawal of this liquid.
It can be of any design or material sufficient to protect it. For example, the cage may be of a helical or lipped design and preferably made of a non-corrosive hard material, such as stainless steel.

In a preferred embodiment of the invention, the ten stages for supplying the irrigating fluid to the uterine gear are secured by a cage.
Radial spray hole at the distal-most end of the ull chew. These radial spray holes are approximately 0.00
It has a diameter of 3 to 0.02Q inches. Although they can be placed randomly along the tip of the inner tube, they are preferably placed near the point where the distal end of the inner tube joins the rounded tip. . It is believed that cleaning the larva and removing the embryo are most effective for this individual. These holes are self-positioned to prevent the Kohiko Washing Sugrey from directly impacting the structural members defining the cage.

The catheter is inserted into the uterine cavity.
6f to accommodate the K contour and operate within the child B cavity? It should have a combination of stiffness and flexibility sufficient to form an angle of 10 to 30 degrees. Preferably, for retrieving pre-implantation embryos, the free end is 0.2 inches in displacement under a load in the range of 0.5 to 2.5 oz. A catheter such as that defined as a fixed 2 inch catheter is used. Preferably, a catheter is used that forms an angle of 10 to 30 degrees per 6 m, more preferably 15 degrees, before insertion into the uterine cavity.

The improved catheter of the present invention can be used with or without an attached guide or catheter sleeve. Preferably, when using the catheter for embryo retrieval, use the guide section. The guide has four main functions: (1) stabilizes the catheter when it is applied to the cervix; (2) provides a shield for the coiled spring tip of the catheter when inserted into the cervix; Prevents the tip from becoming obstructed by head secretions; (3) Easily measures the gag depth to prevent the catheter from penetrating too deeply into the uterine cavity and causing damage. and (4) transmitting a rotational motion to the catheter to enable the operator to sweep substantially the entire uterine surface.

This optional guide or catheter sleeve has an inner diameter of about 8 to 177 mm. It is made of a hard material such as copper, brass, stainless steel or hard plastic. This is about 10~14c
Determine the length of m. Additionally, the guide has a locating plunger located about 2 to 2.5 pins from the distal front end of the guide. This 72 inch, which is generally perpendicular to the sleeve IC, allows the guide to penetrate 2 to 2.5 cy into the cervical canal.
The position is determined to be placed outside the head so that it penetrates by n and does not enter the uterus.

The guide section of the catheter is connected to the catheter κ from the outside.
Insert it into the guide part so that it is positioned accurately! Sill.

The space between the interior and the catheter is sufficiently fluid-tight and rounded to prevent irrigation fluid from escaping from the cavity between the sleeve and the catheter. I wanted to-
C, the inclination between the catheter and the sleeve fits perfectly so that there is almost no gap. However, the catheter is free to swivel inside the sleeve. The guide features a positioning flange that is inserted into the gag-head tube, and the guide protrudes no more than about 2-2.5 cm at an angle of about 0-6o0.

1. Therefore, the sleeve or guide never enters the baby's chest.

The introduction of the catheter and guide according to the present invention into the canal of the fetus is such that (1) the uterine catheter has a blunt end, preferably a bullet-shaped nose; Segmented 141 for benefits catheter
This is simplified because the unisexuality is increased by J-1.

or without guides or sleeves and of length approximately 4
Vertical ff at 15 points without cvi bending
iffl and further 1 at intervals of 1,Q to 3,QCm.
It is also possible to use a cleaning tool that is sufficiently hard to bend the horizontal direction M amount r times the length 4- of the horizontal direction. The outer surface of this type of tool is between 0.03 and 0.1
It has a J-mechanism coefficient of 5.

This type of device penetrates the human uterus without the need for extraneous means, and yet accommodates the various shapes, shapes, and irregularities that are present in today's female reproductive system.

Furthermore, the cleaning device can also include an inflatable root bladder for maintaining and blocking the flow of cleaning fluid. When using,
This device does not constantly cleanse the uterus. The bulb is temporarily sealed with a small balloon inflated with irrigation fluid, and then the fluid is removed by negative pressure.

In operation, the improved catheter of the present invention delivers fluid under positive pressure from a source to the child cavity. Preferably, positive pressure is provided by a syringe or gravity feed. Sarakappa
, the catheter is capable of withdrawing nearly all fluid from the uterine capitium under positive pressure or JR force. Preferably, the negative pressure is generated by a motor pump.

An advantageous feature of the method according to the invention is that it is possible to wash the donor pups each time and to recover embryos;
It does not cause any pain, and the donor does not hesitate to undergo the washing process more than once. This allows for continuous washing for up to three days, for example, to ensure removal of viable fetuses.

Preferably, lavage is performed using an intravenous stand. For example, a cleaning liquid container or a cleaning liquid system! 1. Place the device on a stand, connect the irrigator or catheter to the container using the tube, and adjust the height of the container using the up and down buttons to obtain the desired fluid pressure. Thus, adjusting the height of the trough relative to the patient places 61 degrees of fluid pressure into the catheter. A 1m long tube can exert approximately -5 atmospheres on the liquid force ram. Furthermore, the syringe or syringe may be used with an outlet that provides a negative pressure on the outlet fluid by varying the pressure, for example by using a vacuum pump. Preferably, a combination of these force methods is used.

Alternatively, the liquid can be delivered by an assistant with a manual syringe.

Adjustment of the inlet and outlet pressures, in combination with suction of the uterine wall through the helical tip, can prevent the risk of tubal pregnancy that could result from backwashing of the embryo into the fallopian tubes.

Tissue culture fluids that increase body temperature are commonly used for cleaning. The fertilized rabbit or embryo is flushed out into the liquid in the irrigating suction channel. Typically, the volume of cleaning fluid is about 5-15 Qm/, preferably 30-60 Qm/each for each treatment.
is within the range of Particularly preferably, the uterus of the donor is irrigated by applying a 6Qmt lavage solution for about 5 minutes.

The liquid used can be one of several packages suitable for tissue culture. For example, Japur ● Ob Tei Experimental Fist Meteisun, Volume 98, No. 167.
Calcium chloride, potassium chloride, potassium dihydrogen phosphorus, magnesium monosilicate, sodium chloride, and sodium hydrogen phosphate IJ. Gigcomedium 199 as described in the Society of Experimental Biology and Medicine, Vol. 73, No. 1 (1950) or TCM-19
9, calcium chloride, ferric nitrate, potassium chloride, potassium dihydrogen phosphate, magnesium chloride, sodium chloride,
j (including aqueous solutions of sodium carbonate and sodium hydrogen phosphate. These media have pI-I7.0 to
7.5, preferably pf {7.3 to 7.40 range.

Additives to the basic tissue culture medium include human serum albumin (up to 20%), antibiotics, antibacterial agents and energy sources such as glucose and vitamins.

After the embryo is washed from the donor's uterus, it is detected using a liquid culture medium microscopic inspection button. Unlike cow or mouse embryos, which have the largest number of implants, the human embryos are almost transparent and are therefore more difficult to detect. After detecting the embryo, it is transferred to fresh medium, washed, and carefully examined under a high-resolution microscope for conception, division, cell structure, and organization. The preferred stage of embryonic development for the present invention is the 50-100 cell stage.

After the embryo has been detected and examined, it is removed with the transfer catheter and inserted into the recipient's sterilization chamber.

As mentioned above, K1 embryos are preferably maintained externally for <Vi30 minutes, although longer times are possible.

Is this the time when the embryo should be kept outside for more than 30 minutes? The incubator is maintained inside the incubator, and in this condition the atmosphere is preferably about 0.5 to 5% CO2, up to 95% humidity, about 5 to 15% oxygen, and residual elements. contained at biological temperatures to avoid temperature shock during introduction and removal.

Embryo transfer is performed by inserting the embryo into the recipient's womb using a non-surgical insertion catheter or catheter, and the embryo is 5 to 50 μt in size. Inhibition culture 欣K@make. This type of insertion catheter includes the 1-mukat catheter and other tit insertion head catheters. This catheter is inserted into the body of the pup H through the head of the pup and releases the embryo along with a small amount of tissue culture fluid. This catheter is inserted into the dome of the uterus.
One embryo can be delivered either through the side hole or through the open tip of the catheter. Alternatively, the catheter can be passed 26' or less above the internal os of the cervix.

As mentioned above, the removed embryos can be frozen and stored for long periods of time prior to thawing and implantation. Problems with embryo freezing and storage include mechanical and biochemical destruction of cells due to water expansion during freezing. Therefore, it is reconnaissance to use cryopreservatives that perform several functions = (
1) Decrease Ii: of water in cells without killing cells; Q) Decrease swelling IAI during freezing; t3》
Number 417! (4) produces K uniformly distributed microcrystalline gold instead of large macrocrystals; and (4) is not itself toxic.

Freezing is done slowly to suit the cells. Final assimilation often does not occur until -60 or -80°C for many cryoprotectants and cellular components. These conditions can be achieved by using stepwise sequential cryoprotectant concentrations in combination with temperature reduction or vice versa before freezing.
During thawing and heating, adjust the temperature of the cryopreservative in stages.
It can then be diluted to a total of 1 cf or 4 cf as needed. Cryoprotectants include DMSO (dimethyl sulfoxide) and glycerin buds.

Is surgical removal of the anus more likely to lead to unwanted pregnancy in humans? It can also be used as a means of prevention. Liquid gold is introduced and the embryos are washed and removed prior to implantation, thus preventing implantation and pregnancy. Preferably, the liquid contains estrogens (the group consisting of estondiol-17βκ hyperosmolar compounds s+i%'ffl/l/:7-s), propylene glycol glucose, crosstagnondine, lactic alkali and urea and mixtures thereof. Contains an effective amount of embryo killing agents selected from iL. These embryo killing agents are generally mixed with normal saline washings. This treatment is useful if unwanted conception is to be avoided, at least 31 days after sexual intercourse. Alternatively, it may be carried out after 4 days, and 11 or more counterattacks may be made over 3 consecutive days.

[Hatsumoe'-k example]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The improved double lumen catheter (1) of the present invention will be described in a front view with Embodiment K with reference to WrJ1 and FIG.

κ, catheter (1) as shown in Figures 1 and 2
consists of an outer tube (16) and an inner tube (17) and two lumens (4 and 7 in FIG. 2) defined by κ. These tubes are coaxial with each other.

The distal front end of the catheter (1) is suitable for insertion into the cervical canal and endometrial cavity. It has a rounded closed tip (10) which is attached to the distal front end K of the inner tube (17). The catheter (1) further comprises a cage (9) mounted distally to the rounded tip (10) and proximally to the distal end of the outer tube (16). This cage 1 has an inner tube (17) coaxially arranged inside it.
surrounding the distal end of. The most distal end of the inner tube (17) has a number of radial spray holes (14) arranged so that the uterine irrigation spray does not impinge on structural members defining the cage.

The catheter further comprises a proximal rear end suitable for connecting the inner tube (17) and the outer tube (16) separately to a liquid supply and collection reservoir (12).

The catheter shown in Figure 1 is inserted into a metal sleeve or guide (5), which has a positioning flange (5) that is suspended above the sleeve so that it rests on the outside of the neck. 6).At this position κ,
The guide part protrudes into the uterus 9'9AW by about 2 to 2.5α or less. This guide does not enter the uterus. As shown in FIG. 1, the guide part further has an angle of 0 to 300 to facilitate manipulation of the catheter within the uterus by rotation.

As shown in Figure 1, the catheter further has a handle (15) and a slide (2) to facilitate determining the insertion depth of the catheter into the uterine cavity and to provide a fluid supply and reservoir 4. '! The catheter shown in FIG. For example 8
and 11), making it possible to separately connect the tubes to said supply container and collection container. Furthermore, the embodiment of FIG. 1 allows the supply of the uterine cavity via the hole (14) under positive pressure and the withdrawal of almost the entire fluid into the collection container (12) under negative pressure.

As shown in Figures 1 and 2, the cage (9) in the illustrated A-body example is formed by a helical spring-like arrangement located around the distal-most end of the inner tube (17). stipulated. As shown in FIG. 2K, the structural members defining the hole (14) and the cage (9) are arranged relative to each other so that the cleaning spray from the hole (14) does not spill directly onto the structural member. to snatch

EXAMPLE The following example fully illustrates the human fetal transfer method according to the present invention. These examples are presented for illustrative purposes and are not intended to limit the scope of the invention in any way.

These embodiments can be used to synchronize the ovulation period with that of the recipient, either naturally or artificially (using an oral pregnancy regulator), and to synchronize the ovulation period of the recipient's husband with the artificial receptor. f
Shows the results of 12 trials in which embryos of ffL donors (4-5 donors) were recovered. In these trials, 3 +1 s were removed (Example 1. 2 and 3), three transplants were performed in the recipient's uterus (Examples 1, 2 and 3) and one case of pregnancy was detected (Example 2).

Example 1 Example 1t illustrates the non-surgical removal of fertilized eggs or embryos from donor pups in the artificial insemination method of the present invention. This further indicates expulsion of t)11 rh into the lavage fluid and non-surgical transfer into the receptor df. However, no proof of embryo transfer, {1a, or pregnancy} could be obtained.

This lack of kCrdl pregnancy is not statistically unexpected. Because it's natural. 'j results in spontaneous miscarriage. Furthermore, the relative maturity of the removed embryos in this example b1μ (114 vacuoles) further differs from l in this example.
a'Causes pregnancy failure.

In this example, a 2-year-old woman had two failed pregnancies (one spontaneous miscarriage and one extracardiac pregnancy) prior to her pregnancy. . She had a history of infertility for 6.5 years and had complications from intestinal and pelvic infections.
was infected.

In addition, she has undergone 6 laparoscopy procedures and 4 laparotomy surgeries. Her fallopian tubes and uterus were not present on the pressure side, and the appendages on the stone side had severe complications. However, she had normal ovulatory periods. Receptor's husband is 35
He was a talented and extremely healthy man.

Donor Q is a 26-year-old woman who has had three pregnancies (all resulting in voluntary abortions). This donor had normal ovulatory periods.

The recipient, her husband, and the donor were examined with a detailed medical history, physical examination, laboratory screening, psychological testing, and interview with a clinical psychiatrist. Pedigree analysis and blood type Ic were also investigated for the human race and the donor. In addition, the donor and acceptor may have specific characteristics and predominant blood type, although this is not necessary in the method of the present invention. All parties must individually sign a consent form:
Name and research Jj. Er, we have approval from the top.

The donor and acceptor had natural ovulatory synchronization in cycles without the need for external synchronization. Shigashi/Yogara, as described in the earth record, the donor, the uke body, or both are expelled υI
Delaying or accelerating JJUJ νC. l:j
), it should also be understood that external or artificial synchronization can be achieved. Both the donor and acceptor t″f are simultaneously excreting estradiol at the same time!:) II + 'hu begins to show an increase (donor = 2401) i'/rnl; acceptor: 235!) j' /tA!) and showed the same IISI-like progesterone (LH) peak after 3FIJ (donor e>100111IU/at; reception time: 98m
LU/ml).

For the donor, sperm samples 3, Od (li'j sperm analysis, number 11
Artificial fertilization was carried out by transplanting 4×10 mice (having good motility) into the canal. Before artificial conception, there were no spermatozoa in the donor Succan mucus + Xκ.

Five days after fertilization, donor offspring were washed at υ°C with 60 g of tissue culture medium (Hums F-103, supplemented with 5% H1 serum albumin and glucose, and then washed with 5% H1 serum albumin and glucose.
C embryo was removed. Is the uterus cleansing the above-mentioned guideline? It was performed using an R-4 semi-rigid catheter.

More than 98% of cleaning bath Y was recovered.71. Ta. The donor was found to have sufficient capacity for the +JAI1 shellfish of this group. No anesthesia was used.

Next, I recovered under the theory of imitation and confirmed the purple color of the embryo of 14th scale thinning. The embryos were washed with medium, cultured and transferred into the recipient offspring H via the uterine head via a catheter with a lateral hole. This transplant requires 2.5 hours of cleaning.
I did it after jJ. Receptor i-1: It remains supine for 2 hours on the examination table and is able to withstand this treatment. +tl: +伜 was not used.

Two weeks after the LH peak, a child with normal lunate I-jμ1↑γ was born. The receptor is a strong 4X4cIn stone.
I saw some serious pregnancy bleeding. However, the serial serum ml concentration of human chorionic gonadotrocopine (HCG) is 5,000 m
Receptor menstruation began 13L'' after the LH peak.

Example 2 Example 2 demonstrates the non-surgical removal of fertilized eggs or embryos from donor offspring in the artificial fertilization method of the present invention. In addition, this is the detection of the embryo in the cleaning chamber, the reception Buddha d
The gestation I'i is now in its 9th week.

In this example, the hands 11, T.
j was used. However, in this example, the Lf{peak of the Uke body is 2 days ri1f of the LH peak of the donor.
(same donor as in Example 1).

Again, the donor has an L11 peak]](66m
I[J/m/) has the receptor's husband's hyaline (2.51117,
33x1o/IlIl, good motility) was artificially inseminated.

The donor litter was washed 5 days after artificial insemination using the same tissue culture solution at 601d in much the same manner as in Example 1.

Here too, the cleaning solution was almost completely collected. Furthermore, recovery was well tolerated by the donor.

Embryos (50 cells) were detected in whole lavage fluid, washed with additional medium, cultured and cultured using a conventional Tomcut catheter for 55 minutes.
Recipients were transplanted in medium supplemented with 0% cord serum gold. The implants were implanted 1.5 hours after washing. Again, the recipients were kept supine, 1 l, on the examination table for 2 hours after implantation. Straight grafts were well tolerated by the recipients.

Twenty days after transplantation, the recipient's uterus becomes soft and tender.
Hypertrophy and I{CG increases &. 6. 33rd day of translocation Kuyu,
Kyushu Ukitani's uterus was fully developed, and this was revealed by HIE results from ultra-B wave examinations. The fetal heartbeat was not known until now. Ukitani suffered from Tsuwaji. Seven weeks after the transfer, Ukitani still suffered from morning sickness, but had no other symptoms of syndrome.

Example 3 This Example t'' shows the non-surgical removal of fertilized eggs or embryos from fertile egg whites in the artificial fertilization method of the present inventor. This indicates the expulsion of the embryo into the washing solution and its transfer to the fetus. However, if the embryo were to be placed in the lavage solution, no pregnancy was detected.

Again, the lack of implantation and pregnancy is not statistically unexpected (see above). Sarak is recovered! tatasu (
6jll'u's? The relative immaturity of the 1n1i1flJ('C) is also responsible for the failure of this fruit's pregnancy.

Furthermore, the procedure used in this Run M is substantially the same as that used in Examples 1 and 2.

In this example, the donor I,H peak occurred one day earlier than the acceptor LH peak.

One day after the LH peak, Donor K artificially inseminated 3.3 ml of the embryo from the recipient's husband and placed it in her uterus. C. Washed 5 days later in the same manner as above. Six κIII cells were detected in the lavage fluid, and 3 hours after lavage, this fL was implanted into the uterus of a K recipient using a 1.mukat catheter.

In this case as well, both the donor and acceptor are
Although it was able to withstand the test well, the recipient showed slight sagging.

This recipient resumed menstruation.

Although the original author has been described above with reference to preferred specific examples, it is our understanding that various changes may be made without departing from the original idea and scope of the original author.

〔Effect of the invention〕

Thanks to the above-mentioned assistance from Brother X, we will be able to carry out artificial insemination more safely and reliably.

[Brief explanation of drawings]

FIG. 1 is a front view of a specific example of the improved double lumen catheter (Kihatsu RiJLJ), and FIG. 2 is an enlarged front view of the front end of the catheter shown in FIG. 1 in a prostrate position. 1... Catheter 2... Slide 3... Manifold 4... Lumen 5... Guide part 6... Flange 8... Mounting part 9... Cage 10... Tip part 11. ... Pick up section 12... Supply section 14... Hole section 15... Handle 16.17... Tube two hands one eyebrow k7 city j1self'iFE (homin) 11-i II. '． r
! j year 8 sword 2. }1 JPO Commissioner Shify Gakuden 1. 1159'15l! 'f'#fr+! 1200
8L: No. 2. Name of the invention: Transfer {1(c) Non-Edit 4.7'l Method O6j, Hi Apparatus 3, 冫di+[Two-over person q+I!1shi no Seki 176 'I;) Sode1pi ('jri[
America i7, jlij country, 1'ri, Neu River t5Of-
i1) 3; Nokago, Rius-Noshiru Kari-ri-113
5 dr.
7, 1, Inox Aso So Koshi Itsuiri-r + No-J゛-1・-1 So-1 No 1 (Nationality)
United States), 1, pIB people! IilifritWi--j1.07--! '11
Tokoroku・Iξ/iM-ku north i'fi1i2-J't17-2
No. 2 Suzuki 1 Nil, April} So ζ {is L+, W+iP1+high X5fl, {), L piece. 7G,9,j”1(6(ra4f
lI)I. l. 'l! -h? j＜Ill7! ．． :”05
．． ? ili positive sentence J elephant, ≦′te゛＼＼ (1) request old 1 wholesale'I outll'J-like Iffl,, ℃,, 1, 7 condolence (2) committee Ij one letter《j9 Hoo, J; translation (3) 明jl
ll2t collar (4th E'jlli+jlg'riIFj' (Mukumoto, j,
Yo. Translation, 2 copies, 47--Contents of the original IF (11'15 supplemented with the name of the representative ministry of the fraudulent applicant.・[. (3} Type 'a") Hahiki JF attached sheet (there are no changes to the contents). (J no yo) 11,
of! f'llll+! Nl'. ! I sword/Ll: 1 Secretary of the Ship License Agency, i: Q studies L {ri■. ．． ￥jili display Akikawa 5941 old; t, Tsuyoshi j 1200ifG-shi 2. Name of the invention f++, Hi1/fetus r. ``The eighth Jl of t+fi, tflf self-no.1, rest, ↓ O-equipment: I, t3.?+lW-, skip U thing {'] with {thread, l'+'j'l'f .l111 nail people 11 nori i7%lnoka,'7izumi1sho1'ri,7-lkawa(iil(i(i(13,sosojgo,sau4-71no'-rus1・ri-1l:u 5th grade'1 t'JF-Noryoichi-Lairity upper 1.・A;,,-1 Inons "ノ' Sono Eights Representative Fj'Vf-Ya l Sono-1 (Nationalization) (America,: 1j1i) Country) 4, Agent! IIli (II1 υI (]?-!冫II}) li 1 East East/il le Iy. North 11j Mountain 2J'l-+No. 7+271
,; Suzu 1, Shi-zuki Telephone East 5; Possible (404) 57 ((8・
．． 'l76if mountain (mailing lY1,, bundle 8dlilL' scratched red jj God 11 post office +1, カ゛: box; {゛j7dSノ》
Generation (401) Noix {! l! I1': mil. +10
5. Sodemasa's elephant (1) 1 drawing

Claims (1)

[Claims] (1) (a) Synchronize the ovulation of a human female donor and a human female recipient, and (a) artificially fertilize the donor and donate the preimplantation embryo A human body characterized by physically and non-surgically removing the embryo from the uterus of the body, detecting the embryo in a retrieval medium, and physically and non-surgically implanting the embryo into the recipient's uterus. A non-surgical method of transplanting a fetus. (2) Ovulation between the donor and recipient is induced by glogestin
p-gen, human chorionic gonadotropin, human menopausal gonadotropin, clomiphene citrate, follicle-stimulating hormone,
6. The method of claim 1 nC, wherein the synchronization is effected by administering an effective amount of a compound selected from the group consisting of gonadotrobin-releasing hormone and mixtures thereof. (3) Ovulation between donor and recipient
2. The method according to claim 1, wherein the method is synchronized to a time period of l. (4) The method according to claim 1, in which the ovulation of the donor body and the recipient body is synchronized within three days or less than e. (5) The method described in Paragraph 4 of the patent application for synchronizing the ovulation of a donor and a recipient within two days or less. (6) The method according to claim 1, wherein the pre-implantation embryo is removed non-surgically by washing the donor's uterus. {The method according to claim 1, wherein the uterine washing of the force donor's uterus is carried out by supplying a washing liquid 6 (Jrnl) for about 5 minutes. (8) The donor's uterus The method according to claim 1, wherein the uterine washing is carried out within about 3 to 7 days after the L1-1 peak. The method according to claim 1, d1, which is in the fertile stage. A donor is artificially inseminated with sperm from a good person, and the obtained pre-implantation embryo is physically and non-surgically removed from the donor's uterus, and the embryo is detected in the recovered culture medium. death. A method for artificial conception in human Ic, characterized by physically and non-surgically transferring a fel embryo into the uterus of a recipient. (11) Ovulation between donor and acceptor is controlled by progestin, estacene, human chorionic gonadotrophin, human menopausal gonadotrophin, clomiphen citrate, follicle-stimulating hormone,
11. The method of claim 10, wherein the synchronization is effected by administering an effective amount of a compound selected from the group consisting of: gokadotopin-releasing hormone and mixtures thereof. (12) The method according to claim 10, in which the ovulation of the donor and the recipient is synchronized in the preconception period. (13) The ovulation of the donor and the recipient is synchronized for 3 days or less. The method according to claim 10, which synchronizes the ovulation of the donor and the recipient within two days or less. (15) The method according to claim 13, which synchronizes the ovulation of the donor and the recipient within two days or less. The method according to claim @Claim 10 for non-surgically removing the uterine washing force from the donor's uterus. (17) The method according to claim 10, wherein the uterine washing of donor child B is carried out within about 3 to 7 days after L1 peak. The method according to claim 10. (18) The method according to claim 10, wherein the embryo to be transplanted into the recipient is about 50 to 100 a follicle stage 1. (19) Donating an implanted ah embryo that is ial1q. physically and non-surgically removing the embryo from the body's uterus, detecting and examining the embryo in a retrieval medium, and physically and non-surgically implanting the embryo into the uterus of a human female. j) A method of non-surgical transplantation of a human embryo, which is characterized in that: 1
The method described in Section 9. (21) Physically and non-surgically remove the pre-bedded embryos from the recipient's uterus after uterine washing, detect fblIff in the recovery medium, and cryopreserve the embryos. A method for extraneous recovery of human HFJ infants that specifically exhibit I'a. (22) Thaw embryos frozen in IDL
22. The method of claim 21, further comprising physically and non-surgically transferring the embryo into a human female. (231Ia) at least two lumens at the distal anterior end coaxial with each other and defined by an outer tube and at least one inner tube;
)) a distal anterior end suitable for insertion into the human cervical canal and endometrial cavity and having a rounded closed tip adjacent the distal anterior end of the inner tube;
(C) mounted distally to the closed tip K and proximally to the distal end of the outer dupe and encircling the most proximal end of the inner tube; The distal-most end of the inner tube has a cage with means for supplying irrigating fluid to the child's cavity, and the proximal inner and outer tubes can be connected separately to the fluid supply and collection trough. Rear end and length, approximately 7-16
When inserted into the uterine cavity and having the outer diameter of 1. It is characterized by forming an angle of 1 to 3 cm and having a combination of stiffness and hardness sufficient to conform to the contours of the uterus and to be maneuverable within the uterine cavity.
A non-surgical method for treating the human uterus is used. (24) One outer tube and one inner tube define sr+. (25) A catheter according to claim 23, in which two lumens exist, (25) a li'-5'ff distal front end of the distal end r inner tube, and a catheter according to claim 11123; fre1no. 26. The catheter of claim 23, wherein the distal-most end of the inner tube has a plurality of radial spray holes having a diameter of 0.003 to 0.020 inches. (27) The catheter according to claim 23, wherein the curve in the catheter forms an angle of 15° per 6 cm. (28) The catheter according to claim 23, wherein the catheter is curved before being inserted into the uterine cavity, and this curve forms an angle of J15 to 60 degrees per 6cIn. (29) Claim 2 whose outer diameter is 117 wrench
The catheter according to item 3. [30] The improved catheter according to claim 23 and a rigid sleeve, wherein the catheter is inserted into the sleeve, the sleeve is coaxially positioned with respect to the catheter from the outside, and the sleeve is (e) A combination body characterized in that it is provided with an installation plunger and is positioned so as to be placed outside the head canal so that the sleeve can protrude into the head canal by about 2 to 2.5 degrees.