Methods and kits for reducing the likelihood of implantation failure and pregnancy-related disorders in recipients of artificial insemination

a technology of artificial insemination and kits, which is applied in the field of methods and kits to reduce the likelihood of implantation failure and pregnancy-related disorders in recipients of artificial insemination, can solve the problems of recipients failing repeatedly, theories have yet to be substantiated, and require an intricate and delicate interplay of physiology and anatomy, so as to prevent miscarriage or implantation failure

Inactive Publication Date: 2011-04-28
NORA THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

One objective of the present invention is to provide methods, compositions and kits comprising a granulocyte colony stimulating factor (G-CSF) in an amount effective to prevent miscarriage or implantation failure in an artificial insemination procedure.

Problems solved by technology

Conception, pregnancy and delivery require an intricate and delicate interplay of physiology and anatomy.
Although pregnancy rates following six cycles of AI or one cycle of IVF can be as high as 60%, some recipients fail repeatedly.
Various uterine pathologies, such as thin endometrium, altered expression of adhesive molecules and immunological factors, may be the causes for repeated failure.
It has been theorized that spontaneous abortions are a natural rejection of a fetus with abnormalities incompatible with life; however, this theory has yet to be substantiated.
As families are planned later and later in life, the frequency of spontaneous abortion will only increase without effective methods of prevention.
This conservative treatment provides palliative care for the mother but does little to alter the outcome.
The use of hormones is generally contraindicated due to the risk of congenital anomalies, including malformation of the vessels of the heart of the embryo and possible genital abnormalities in female offspring.
Preeclampsia and other hypertensive disorders of pregnancy are a leading global cause of maternal and infant illness and death.
Preeclampsia can prevent the placenta from getting enough blood which can cause low birth weight and other problems for the baby.
Although most women with preeclampsia still deliver healthy babies, some develop eclampsia, a serious condition that threatens the life of the mother and the fetus.
In addition to the physical toll of these disorders, the loss of a desired pregnancy takes a tremendous emotional toll on hopeful and expectant parents.
Loss of a pregnancy can lead to feelings of inadequacy, hopelessness and guilt which can have a devastating effect on individuals and on a marriage.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

G-CSF Prevents Embryotoxic Effects of Cells from Women with Recurrent Spontaneous Abortion In Vitro

G-CSF is effective in preventing the death of mouse embryos in an in vitro clinical assay for spontaneous abortion. Mouse bioassays have widely been used to detect embryotoxic effects of sera from subjects having reproductive difficulty. (See, Cameo, et al., 1999, Human Reprod. 14(4): 959-63, Oksenberg and Brautbar 1986, Am. J. Reprod Immunol. Microbiol 11(4): 118-24, Roussev et al., 1995, Am. Reprod. Immunol. 33(2): 171-175 and Thomason et al., 1995, Am. J. Reprod. Immunol. 34(6): 338-41.).

In the in vitro clinical assay, mononuclear leukocytes are isolated from women suffering from recurrent spontaneous abortion. The leukocytes are cultured, and the culture medium is removed from the leukocytes. This culture medium is then contacted with murine embryos. Toxic factors in the culture medium typically kill the murine embryos in this assay.

The mononuclear leukocytes are incubated with G-C...

example 2

G-CSF Prevents Spontaneous Abortion in a Mouse Model In Vitro

G-CSF effectively inhibits a well-known in vivo model for spontaneous abortion.

The murine mating pair CBA×DBA / 2 (see e.g., Yabuki et al., 2003, Exp. Anim. 52(2)159-63) results in a spontaneous abortion rate of approximately 40%. In this example, female CBA mice are treated according to the methods of the invention. They are treated with G-CSF prior to mating, at the time of mating and immediately after mating. A reduction of the rate of spontaneous abortion in mice treated with G-CSF relative to control mice indicates that G-CSF effectively prevents spontaneous abortion in this in vivo model.

example 3

G-CSF Prevents Habitual Abortion In Vivo

Thirty-one women with habitual abortion, having more than three abortions, were recruited in the study (Scarpellini & Sbracia, 2004, Am. J. Repro. Imm. 51(6)433-4). The cytogenetic studies, hysterosalpingography, ultrasound, endometrial biopsy, hormonal assays (estradiol, progesterone, prolactin, thyroid hormones, etc.) diabetes workup and autoantibody tests (ACA, AND, AMA, SMA and anti-lupus Ab) were unremarkable. All of the women failed a previous treatment with Igs, or corticosteroid and aspirin in the former pregnancy. Sixteen women were randomly chosen and treated with filgrastim at 100 mg / day SC, which was started the sixth day after ovulation and continued through the 35th day after ovulation. The other fifteen women received a placebo and progesterone.

In the group receiving filgrastim, 14 of 16 became pregnant and maintained pregnancy during the recording period. The karyotype of the fetuses was normal. In the control group, only four ...

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Abstract

Methods and kits for preventing or reducing the likelihood of implantation failure and pregnancy-related disorders in a recipient of artificial insemination are provided. The methods include administering into a recipient of artificial insemination in need of such treatment an effective amount of granulocyte colony stimulating factor (G-CSF).

Description

FIELDThe present invention generally relates to methods of preventing implantation failure or miscarriage during assisted reproduction and, in particular, to methods for reducing the likelihood of or preventing implantation failure or miscarriage in recipients of intravaginal insemination, intracervical insemination, intratubal insemination, and intrauterine insemination.BACKGROUNDAccompanying the rising age of hopeful parents is the increasing use of assisted reproductive techniques such as artificial insemination, in vitro fertilization (IVF), gamete intrafallopian tube transfer (GIFT), and the like. Artificial insemination (AI) is the process by which sperm is placed into the reproductive tract of a female for the purpose of impregnating the female by using means other than sexual intercourse. In humans, it is used as assisted reproductive technology, primarily to treat infertility but is also increasingly used to enable women without a male partner to produce children by using s...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/19A61K9/00A61P15/06
CPCG01N33/6893G01N2800/368A61K31/593A61K31/573G01N33/689A61K45/06A61K38/21A61K38/20A61K38/193A61K38/1841A61K38/1816A61K2300/00A61P9/12A61P15/00A61P15/06
Inventor CARTER, DARRYL L.
Owner NORA THERAPEUTICS
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