Medically Assisted Conception An Agenda for Research : Report of a Study (1989) / Chapter Skim
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ADVANCES IN THE PRACTICE AND SCIENCE BASE OF MEDICALLY ASSISTED CONCEPTION
ADVANCES IN THE PRACTICE AND SCIENCE BASE OF MEDICALLY ASSISTED CONCEPTION
Pages 25-65
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From page 25... ...
Eastern Virginia Medical School, one of the premier centers for the clinical practice of in vitro fertilization, has a pregnancy rate of 18.3 percent, based on the number of attempts used to stimulate the ovaries with either follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hfC)
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From page 26... ...
Nevertheless, basic science research is needed to assess the necessary parameters for successful Cryopreservation and the possible deleterious effects of freezing on the embryo. In cases of ovarian failure, failure of in vitro fertilization, poor quality of eggs, genetic abnormality, or inaccessible ovaries, the only option available to women wanting to bear a child is to use eggs from a donor to perform in vitro fertilization with the husband's sperm.
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From page 27... ...
All of these areas, if improved by increased knowledge of the cell biology of early reproductive events, should greatly increase the ability to identify couples with high probability of success and may increase the success rates of IVFET in human clinical practice. Developments in Assisted Conception in Food-Producing Animals [2]
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From page 28... ...
Embryo freezing, in concert with embryo transfer, has been generally successful in terms of pregnancy rates. Freezing embryos allows for the storage of rare breeds and preservation of a cattle surplus.
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From page 29... ...
However, as in human IVFET, the success of in vitro fertilization and embryo transfer in the cattle industry suffers from a lack of basic knowledge of the oetll biology and biochemistry of early gamete maturation and fertilization. Among the areas in which research is lacking is oocyte maturation.
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From page 30... ...
These are human menopausal gonadotropin, human FSH, pregnant mare's serum gonadotropin, or porcine FSH. However, monkeys sometimes produce antibodies that block the activity of hormones obtained from other species activity, and ovarian stimulation fails.
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From page 31... ...
Resolution of the problems associated with the use of non-human primates in this type of research could be facilitated by an increased ability to augment natural hormone and gonadotropin release, by improved resolution of ultrasound imaging to identify mature oocytes and guide their collection by non-surgical means, and by the development of cell lines that could produce larger quantities of non-human primate gonadotropins. Finally, it is important to note that many of the same questions remain unanswered regarding human ovarian stimulation and that particular non-human primate species serve as the best model for human reproductive physiology.
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From page 32... ...
Therefore, the need to increase the offspring from one individual, while helpful in certain circumstances, is not as compelling in pigs as in other domestic animals. Nevertheless, superovulation and embryo transfer may - 32
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From page 33... ...
As with monkeys, developing ways to bypass the use of exogenous agents like FMSG and porcine FSH would be of enormous use in domestic animals. One way of doing this may be by blocking inhibin as has been done in sheep.
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From page 34... ...
Mammalian Oocyte Mafotration In a normal follicle there is communication between the oocytes and the surrounding nurse cells, called granulosa cells, through specialized junctions (gap junctions) through which small molecules pass from one cell to another.
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From page 35... ...
It has been shown in vivo that administration of IH in origination with human menopausal gcnadotropin reduces cyclic AMP in the oocyte, but not in the surrounding nurse cells. This effect is puzzling since the gap junctions between the oocytes and the other cells still appear to be functional, so cyclic AMP should pass through these junctions easily.
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From page 36... ...
One degree to which data obtained from experiments with mouse oocytes can be applied to humans is not known. Therefore, for such applications to be realized in human IVFET, it is probably necessary that basic research be done using oocytes from human ovaries removed for justified clinical reasons and/or oocytes from non-human primates.
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From page 37... ...
The osmotic characteristics of particular solutions are important also. In the case of glyoerol, if one exposes a cell to a solution of water and glyoerol, glyoerol moves into the rail by osmosis, a process by which molecules in a high concentration will move across a semi-permeable barrier, such as a cell membrane, into a region of low concentration of that molecule.
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From page 38... ...
These new freezing procedures are still being developed, but they have the potential to increase the success rate of ova and embryo freezing. Improvements in cryobiology would have significant impact.
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From page 39... ...
Fibroblast growth factor stimulates replication of Sertoli cells by causing an increase in the number of receptors for follicle stimulating hormone (FSH)
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From page 40... ...
One such protein has been found in Sertoli cells, and its synthesis and secretion have been shown to be stage-specific. These experiments have also found that such proteins diffuse into the extracellular spaces of the seminiferous tubules, but because of the slow flow rate within the tubules, remain in spaces near developing sperm cells for quite a long time before being degraded by proteolytic enzymes.
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From page 41... ...
They seem to stimulate all kinds of effects in granulosa cells including increasing enzyme levels, cell numbers, protein synthesis, glucose utilization, and various secretions. Insulin itself and the IGFs seem essential for FSH induction of receptors for IH, for generation of cyclic AMP, and for FSH stimulation of steroids.
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From page 42... ...
In vitro, fibroblast growth factor has effects on OR! Is of the corpus luteum and it stimulates granulosa cells to divide.
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From page 43... ...
Thus, the possibility exists that the chromosome abnormality is simply an indicator of some other developmental problem. In addition, there are no data on the percentages of normal, unstimulated oocytes which are aneuploid, so how much of the observed abnormality is caused by hormonal stimulation is not known.
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From page 44... ...
Usually the membranes of the sperm form protrusions, called microvilli, which seem to be important for sperm binding to an egg. Sperm associated with these seemingly unfertilized eggs lack this structural feature.
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From page 45... ...
At the 12-16 cell stage, some normally fertilized eggs develop multiple nuclei. Finally, during the first mitotic division of the zygote to form two cells, a chromosome pair sometimes does not separate or disjoin.
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From page 46... ...
The proteins that participate in this cascade of reactions associated with oocyte maturation are not known, but are a subject of great research interest. In addition, it must be emphasized that, in addition to cyclic AMP, other types of molecules present in the follicle are likely to participate in maintenance of meiotic arrest.
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From page 47... ...
Enveloping the egg directly is a jelly-like covering, called the zona pellucida, which is surrounded itself by a cellular layer, called the cumulus. The zona plays a major role during fertilization and many of its molecular features have been defined.
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From page 48... ...
peptide as a vaccine may have wide spread application. This method of contraception is desirable because it would prevent fertilization, not implantation, and would avoid the dangers and side effects of the hormones administered in birth control pills.
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From page 49... ...
Once the sperm has fused with the egg, mnll packages called cortical granules, which contain enzymes that modify the zona pellucida, move to the egg membrane, fuse with it, and release their contents into the space between the egg and the zona pellucida. The released enzymes modify the ZP2 protein so that acxosome-reacted sperm can no longer bind to ZF2.
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From page 50... ...
Blastulation begins about the fourth day after fertilization, just as the developing embryo reaches the uterus. At blastulaticn, cavities form in the cell mass and the cells separate into two regions, an inner cell mass, from which the fetus and some extra embryonic membranes will form, and an outer cell layer, called the tzophectoderm.
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From page 51... ...
through the middle, the blastocyst would look lite a ring of nells with a clunp of other cells stuck to one part of the inside of that ring. mis polarization is important for implantation later since the pole of the blastocyst containing the inner cell mass will first touch the lining of the uterus in preparation for implantation in sane species (in others, the opposite is true)
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From page 52... ...
reactions. In glyoogen synthesis, the G-6-P is converted to glycogen, which is the way cells store glucose for later use.
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From page 53... ...
In contrast, the levels of fructose 1,6, biphosphate (an intermediate molecule formed in glycolysis) do not change with starvation of glucose at any embryonic stage.
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From page 54... ...
In theory, one cell from a multicelled embryo could be removed, analyzed for disease and, if found to be affected, a decision could be made not to implant that embryo. As an alternative, naturally fertilized eggs could be removed from the uterus by flushing, biopsied, and then returned via embryo transfer.
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From page 55... ...
In another experiment, when chemicals, which blocked transcription of messenger FNA, were added to the culture medium, they had no effect on unfertilized oocytes or early embryos and development proceeded normally. However, the blockade of FNA, or protein synthesis, from the 4-cell stage caused the embryos to stop developing.
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From page 56... ...
pattern of proteins preocnt in early and late embryos and found that the pattern changed quite clearly, the protein patterns were measured with and without the blockade of messenger RNA. These results demonstrated that, when FNA synthesis was blocked, the changes in protein pattern characteristic of the 8-oell stage and beyond did not occur, but the pattern remained in the early state.
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From page 57... ...
While 65 percent of half embryos survive from the 2-cell stage, only about 45 percent survive from later stages. The success at later stages may not mean that all the cells are totipotent; rather, it may mean that each half embryo contained the required number and type of cell to complete development.
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From page 58... ...
Embryos with a low cell number at blastulation had a lower inner cell mass ratio and exhibited a lower viability than embryos with a higher cell number at blastulation. These experiments further showed that maintaining the half embryos in vivo, even in a nonpregnant uterus, increased the formation of the inner cell mass, resulting in a higher inner cell mass ratio and higher viability than that achieved in vitro.
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From page 59... ...
The understanding of the biology of implantation has far-reaching implications for human and non-human reproduction. Both in the natural reproductive process and in the practice of medically assisted conception, there is a huge gap between the number of successfully fertilized eggs and the number of offspring born.
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From page 60... ...
This makes sense if one considers that, following ovulation, the corpus luteum in the ovary begins to produce progesterone, which acts to prepare the uterus for pregnancy.If the corpus luteum degenerates, the drop in progesterone causes the uterine lining to be shed resulting in menstruation. A hormone secreted by the txophectcderm, chorionic gonadotropin, prevents the degeneration of the corpus luteum and, thus, maintains the progesterone secretion.
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From page 61... ...
Two other proteins -- plasmin and trypsin inhibitors -- protect the uterine cells from destruction by embryonic enzymes, and lysozyme protects against infection. In summary, many classes of proteins are produced and secreted by endometrial cells in response to estrogen, progesterone, or eridryD-prcduced factors.
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From page 62... ...
Extracellular matrix is simply the intercellular space and its component molecules, which are usually synthesized by the surrounding cells and secreted into the extracellular space. The exact composition of the matrix varies from tissue to tissue, but it is important in the uterus since interactions between it and the blastocyst occur during implantation.
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From page 63... ...
The trophoblastic cells dislodge the endometrial cells and penetrate beneath them in a process resembling intrusive implantation. These experiments suggest that the extracellular matrix always permits attachment and differentiation of the syncytiotrophoblast.
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From page 64... ...
Such findings could be of great use in understanding rtififwre states like tmcpmiii in which abnormal invasion of trophoblastic cells is suspected to be a cause. Finally, investigators see a real need for the institution of a national or international registry of IVFET programs to track the incidence of abnormal implantation and correlate those data with the types of ovarian stimulation protocols used and hormone replacement therapy given.
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From page 65... ...
For additional detail see Weitlauf, H.M. and Suda-Hartman, M., Changes in secreted uterine proteins associated with embryo implantation in the mouse.
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