Selhání IVF 1.část

IVF FAILURE WITH GOOD QUALITY EMBRYOS:“UNEXPLAINED” OR UNDIAGNOSED?

Currently, with few exceptions, practitioners of Assisted Reproduction tend to attribute “unexplained and/or repeated” IVF failure(s), almost exclusively to poor embryo quality, advocating adjusted protocols for ovarian stimulation and/or gamete and embryo preparation as a potential remedy. The idea that having failed IVF, all that it takes to ultimately succeed is to keep trying over and over using the same recipe is over simplistic. There are numerous non-embryologic factors such as, the woman’s age, poor endometrial receptivity leading to implantation failure, and sub-optimal embryo transfer technique, that are just as likely to be responsible for failed IVF. The considerable emotional, physical and financial burden associated with infertility treatment in general and with IVF in specific, demand that factors known to affect outcome be identified and regulated prior to initiating treatment. This presentation addresses those clinical (non-embryologic) factors that affect IVF outcome, which often fail to be given the required amount of consideration:

• 1.The Woman's Age, Egg Quality and "Ovarian Reserve":

The onset of the climacteric is heralded by gradually increasing blood concentrations of FSH and/decreasing Inhibin B levels, as measured on the 3rd day of a spontaneous menstrual cycle and continue for a number of years (approximately 4-6 years) until virtually all remaining eggs have been used up, at which time ovulation and menstruation ceases altogether, i.e.; the menopause has arrived. The timing of the onset of the climacteric varies from person to person. Genetic factors, exposure to environmental toxins and radiation, disease, drugs and pelvic disease associated with severe peri-ovarian adhesions that compromise blood flow to the ovaries, can all influence the timing of the onset of both the climacteric and the menopause. Most American women will enter the climacteric in their early to mid forties and go into menopause around 45-52yrs.

As a woman advances beyond 30 years of age, her eggs become progressively less likely to be “normal” such that with every advancing year, upon fertilization, her eggs, are less likely to produce embryos with a normal chromosome number and/or structure. Such abnormal embryos are referred to as being aneuploidic. For instance, at age 35 approximately 1 in 4 fertilized eggs will develop into embryos with an abnormal chromosome make-up. About 50% of the embryos derived from a 40-year old woman’s eggs are likely to be aneuploidic. At 43 years, roughly 2 out of 3 embryos are so affected and at 45years the incidence of embryo aneuploidy could be as high as 70-80%. Since it is nature’s intent to preserve the integrity of the species through natural selection, abnormal embryos usually either fail to implant (attach to the uterine lining (in which case the woman would probably not even be aware that she was actually pregnant for a very brief period of time), or it may attach for a period of days or weeks and then be rejected in the first three months of pregnancy as a miscarriage. Infrequently nature will make a mistake and allow a chromosomally defective fetus to continue on to delivery, resulting in a birth (e.g. Down’s syndrome).

The risk of embryo aneuploidy increases with advancing age. This explains why there is a progressive increase in the incidence of infertility, miscarriage, and birth defects that occurs as the age of conception increases progressively as the woman’s age advances beyond 35 years. It also serves to explain why treatment of infertility (regardless of the chosen method) becomes progressively less successful with advancing maternal age.

Since the onset of the advent of the climacteric usually takes place after age 40 years, many physicians erroneously attribute poor egg/embryo quality to a reduction of ovarian responsivity to fertility drugs as evidenced by rising blood levels of FSH. Simply a woman over 40 years, who has entered the climacteric would not only be far more likely to produce fewer follicles/eggs even following the administration of relatively high doses of fertility drugs but because of her age, a higher percentage of her eggs/embryos would be chromosomally abnormal. Accordingly her chances of having a baby using her own eggs would be reduced. Conversely, a woman over 40 years undergoing in vitro fertilization, who has not yet entered the climacteric, might yield many more eggs/embryos, thus allowing for increased availability of eggs/embryos and thereby, the opportunity to select out more and better quality embryos or blastocysts (advanced embryos grown for 5-6 days) for embryo transfer (ET) to her uterus. It should be pointed out that it is embryo/blastocyst quality rather than simply the number transferred to the uterus that influences the incidence of multiple pregnancies. Accordingly, the further the woman’s age has advanced beyond 40 years...the greater the number of embryos or blastocysts (advanced embryos) that could likely be safely transferred to her uterus, without a significant risk of high-order multiple pregnancies (triplets or greater number). It is important to be aware that the only way to optimize IVF birthrates in older women is to increase the number of embryos/blastocysts transferred.

For women whose advancing age and/or ovarian resistance makes having a baby with their own eggs unappealing or unlikely, ovum donation (using donated eggs from a young donor (usually compatible and anonymous) is an excellent option.