Assessing the Medical Risks of Human Oocyte Donation for Stem Cell Research Workshop Report (2007) / Chapter Skim
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2 Potential Risks Associated with Hormone Treatment
2 Potential Risks Associated with Hormone Treatment
Pages 13-30
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From page 13... ...
At each stage, the process may be compromised, resulting in a small chance of success in each IVF cycle. For this reason, in the 1980s assisted reproduction specialists began treating the prospective mother -- or the egg donor, if the eggs are coming from a woman other than the mother -- with a series of hormone injections designed to increase the number of eggs that come to maturity in a given cycle.
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From page 14... ...
OOCYTE PRODUCTION To understand the potential risks associated with the hormone therapy used in egg donation, one must first understand the hormone therapy itself. And that, in turn, requires an understanding of how the body produces eggs, without outside intervention from administrated hormones.
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From page 15... ...
Once at the antral stage, the follicles require a certain level of FSH to survive and grow. In prepubertal girls and women taking birth control pills, without high enough levels of FSH to enable them to grow, the small antral follicles remain dominant.
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From page 16... ...
For example, pigs generally have litters of 6 to 12 piglets; and cows typically have 1 or, at most, 2 calves. OVARIAN STIMULATION Although only the dominant follicle survives to produce an oocyte in a normal monthly cycle, the other antral follicles can also survive and grow if there is enough circulating FSH.
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From page 17... ...
POTENTIAL RISK OF OVARIAN HYPERSTIMULATION SYNDROME The most common side effect of the use of fertility drugs is what is called ovarian hyperstimulation syndrome (OHSS)
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From page 18... ...
Since ovarian stimulation generally results in 10 or more follicles growing to a large size, it is not surprising that some women should feel pain as their ovarian capsule stretches to accommodate the multiple follicles that are growing. The mild cases generally have no serious complications, resolve themselves spontaneously, and are quite common in women after hormone treatment.
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From page 19... ...
A recent study from Finland, for example, found that kidney failure occurred in about 1.4 percent of patients who had severe ovarian hyperstimulation, or about 1 in 100,000 oocyte stimulation and retrieval cycles. Somewhere between 0.78 percent and 2.4 of patients with the severe form of the syndrome experience blood clots.
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From page 20... ...
It is particularly important for the issue of donating eggs for research purposes, since these donors will not become pregnant immediately after donating their eggs and thus will not be affected by the late-onset type of hyperstimulation syndrome. Doctors can use a number of strategies to help egg donors avoid hyperstimulation (see Box 2-3)
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From page 21... ...
Even women who don't have all the classic symptoms of PCOS -- they may have regular ovulatory cycles, for example -- but who have polycystic ovaries are still BOX 2-3 Ovarian Hyperstimulation Syndrome Strategies for Prevention Identification of the patient at risk ● Individualization of stimulation protocols ("gentle stimulation") ● Decreasing the pool of granulosa cells/follicles ● Using LH or GnRHa as ovulatory trigger ● Modify stimulation protocol ● -- Decrease gonadotropin dosage -- OCP/Lupron/Low dose gonadotropins Reduce the ovulatory dose of hCG ● Delay administration of hCG: "Coast" ● Cancellation of cycle eliminates the risk of OHSS ● Withhold hCG administration ●
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From page 22... ...
A strategy for doing that might include excluding women from donating their eggs who have irregular menstrual cycles, who have ovaries with a polycystic appearance, and perhaps even those with high levels of androgens, as well as modifying the hormone treatment regimen to minimize the factors that are known to make hyperstimulation more likely, such as a higher than normal egg follicle count. POTENTIAL RISK OF CANCER One of the most serious concerns about ovarian stimulation is that it may increase the chances that a woman will suffer certain types of cancer later in her life (see Figure 2-3)
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From page 23... ...
Endometrial cancer seems most affected by estrogen alone. And the risk of ovarian cancer may be increased by an increase in ovulation over a woman's lifetime and by exposure to gonadotropins -- i.e., mainly LH and FSH.
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From page 24... ...
Women who receive assisted reproduction therapy may be more likely than others to get pregnant, and since pregnancy lessens the risk of the cancers, that can have an effect in the opposite direction, making it seem as though ovarian stimulation is less risky than it really is. Different drugs may work via different mechanisms, Dr.
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From page 25... ...
A second meta-analysis of assisted reproductive technologies and ovarian cancers looked not only at case-control studies but also cohort studies. The advantage of the cohort studies, which followed groups of women over a period of time after they took the fertility drugs, is that they make it possible to determine the relationship over time between the hormone exposure and the cancer risk.
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From page 26... ...
And the final concern is that these effects may not be evident until a longer period of time has elapsed between the exposure, the assisted reproduction therapy, and the cancer." POTENTIAL LONG-TERM FERTILITY EFFECTS One of the major concerns that has been raised about the possible risks involved with hormone treatment is that the treatment may have some effect on a woman's long-term fertility. "We've heard a lot about ovarian stimulation as a route to achieving more eggs," Dr.
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From page 27... ...
Of those 1,000 per month, only 10 to 20 reach the stage of antral follicles; the rest die at various stages along the developmental path. Normally only one of the antral follicles completes its development and ovulates, with the rest dying and being absorbed by the body, but hormone treatment can rescue most of those.
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From page 28... ...
Cataldo said, "if you look at just the first 4 or 5 cycles, there appears to be absolutely no fall-off at all in terms of the ability to recruit roughly 15 or 16 oocytes per cycle from these donors in repeated use." So as far as either basic ovarian physiology or clinical experience indicates, there is no reason to think that repeated ovarian stimulation poses a risk to a woman's long-term fertility. Still, Dr.
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From page 29... ...
Its symptoms include increased ovarian size; nausea and vomiting; increased permeability of the blood vessels, leading to an accumulation of fluid in the abdomen; breathing difficulties; hemoconcentration, or an increased concentration of red blood cells; kidney and liver problems; and, in the most severe cases, blood clots or kidney failure. The severe cases affect only a very small percentage of women who undergo in vitro fertilization -- about 0.1 to 0.2 percent of all treatment cycles -- and the Class C severe, or the most dangerous, are an even smaller percentage.
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From page 30... ...
30 ASSESSING RISKS OF OOCYTE DONATION FOR STEM CELL RESEARCH The last concern is that fertility drugs may affect a woman's longterm fertility. However, there is no evidence, either from studies of women who have taken fertility drugs or from what is known about ovarian physiology, that this is the case.
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