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Fruit of the Womb
Fruit of the Womb

Recurrent Early Pregnancy Loss - 1 - Implantation

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In our last post we discussed the high frequency of early pregnancy losses in first conceptions that probably results from a naive maternal immune response to the fetal tissues; and also the high frequency of chromosomal abnormalities as the most common cause of sporadic early pregnancy losses in otherwise healthy women who have successfully carried a pregnancy. But, what about the scenario our patient had concerns about – the patient who has or is at risk for repetitive early pregnancy losses?

Although uncommon, about one out of every 100-200 women will have recurrent early losses without a successful pregnancy and another small percentage will have recurrent losses only after initially having successful outcomes (these women have been termed ‘secondary aborters’). A woman who has had one clinically recognized miscarriage is probably at no greater risk than any woman in the general population for having another (15-20%). However, if she has had two spontaneous losses in a row, the risk rises to about 35% for a third; and, if she has three consecutive losses, the risk is about 50%. Before looking at some factors that can contribute to early pregnancy loss, let’s review the ‘normal’ sequence of events that lead to a ‘successful’ pregnancy.

Under ideal circumstances, a woman with regular menstrual cycles (every 28 days) produces an egg (ovulates) around day 14 (counting from the first day of the last menstrual bleeding). The egg contains 23 ‘normal’ chromosomes and begins the trip down the fallopian tube where it becomes fertilized (ideally within less than 24 hours of being ‘hatched’) by a sperm, also containing 23 ‘normal’ chromosomes, producing a ‘fertilized’ egg, or zygote, with 46 chromosomes. Over the next two days, the zygote undergoes rapid cell divisions, entering the uterine cavity as a relatively homogeneous mass of about 16 cells called the morula. Once in the uterus, the cell mass begins to ‘differentiate’ (separate into cells that will eventually form the baby and those that will eventually form the placenta) into a structure called the blastocyst which must then attach to a favorable location on the inner lining of the uterus (the endometrium) within about 48 hours. Over the next week (and prior to the time of the next expected menstrual period), the blastocyst solidifies its attachments to the endometrium and, while continuing to differentiate into tissues that will eventually form the placenta or the baby, literally buries itself in the endometrial lining.

The cells (trophoblasts) that will develop into the placenta first anchor the blastocyst to the endometrium, eventually burrowing further into maternal tissues in which there are lakes of blood, an early source of nutrients for the developing pregnancy. Over the next 6 weeks (the embryonic period), not only will all major internal and external structures of the baby develop, but the trophoblasts will begin an extremely important 'second wave’ of invasion that involves a dangerous journey through the relatively ‘hostile’ environment of the maternal endometrial tissues where they are exposed to both nonspecific and specific mediators of the mother’s immune response. At the end of this long journey, under 'normal' circumstances, the trophoblasts will have successfully invaded and replaced (remodeled) the lining and muscular wall of the endometrial portion of the mother’s ‘spiral arterioles’ assuring the developing placenta of a continuous source of maternal blood in which to ‘bathe’ and, thereby, providing the placenta (and hence the baby) a source of oxygen and nutrients to continue its growth.

Factors that contribute to recurrent early pregnancy loss can result from problems occuring at ANY of the stages (and more that haven’t been mentioned) detailed above; and in our next post, we will begin the discussion of specific areas of concern to which evaluation and treatment might be directed.
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