To begin our discussion of actual causes of recurrent early pregnancy loss, let’s start with the one that is probably the most commonly touted, though still the least well-understood (and to me the MOST confusing) – HORMONAL CAUSES. Now, let me also begin by saying, we will not be addressing the most severe hormonal abnormalities that lead to primary infertility problems. I will leave that discussion to the real experts in that area – the specialists in Reproductive Endocrinology. Instead, let’s focus the discussion today on more subtle abnormalities that are associated with decreased likelihood of a successful pregnancy once conception has taken place.
If you look back at my second post about the young couple who had an early pregnancy loss (technically given the unflattering terminology of a ‘missed abortion’), I asked her a series of questions upon which to direct my later discussion of potential causes. One of first issues I tried to sort out was the normalcy of her menstrual cycles in terms of regularity, timing, and bleeding. She reported that she always had regular menstrual cycles with bleeding beginning about every 28-29 days and she had had these from the age of 13 when she first started having periods. Without doing a mega workup for hormonal abnormalities, it is highly likely that she has none, if what she reported to me is true. She is probably ovulating regularly and in midcycle and the second part of the cycle, the ‘luteal phase’, is probably characterized by normal production of and response to the hormone progesterone. Progesterone is necessary for the final preparation of the uterine lining (the endometrium) to accept and nurture the early growth of the fertilized egg. On the otherhand, it is also likely that the woman who reports irregular cycles, or cycles that are unusually short or long in duration DOES have some degree of hormonal imbalance.
The simplest way of thinking about this in terms of its negative effects on a successful pregnancy is that the abnormal cycles indicate that the patient is either not ovulating at the appropriate time (around day 14, counting from the first day of the last period) or, if she is, she has inappropriate production or action (in terms of timing, amount, or effect) of the hormone progesterone that is made by the ovary (the corpus luteum at the site from which the egg was hatched) during the second half of the menstrual cycle and the early weeks of pregnancy. Unusually long cycles usually reflect a delay in ovulation and are more common in women with thyroid disorders, excess amounts of the pituitary hormone prolactin (hyperprolactinemia) from any cause, and women who have ‘polycystic ovary syndrome’ that may be accompanied by hyperandrogenemia (increased levels of male hormones), elevated levels of luteinizing hormone (LH, another pituitary hormone that stimulates androgen production in the ovary), and insulin resistance. Unusually short cycles usually indicate an inadequate progesterone effect on the endometrium (often called “luteal phase defects’) and may result from too little progesterone production or from an endometrium that is less responsive to the hormone.
In any individual, one or more of these hormonal imbalances may exist. And, regardless of the specific contribution of each to early pregnancy loss, the common thread is that they disrupt the 'window of receptivity' by impairing the successful attachment, implantation, or early growth of a fertilized egg in the endometrium. There is only a very limited period of time in its development during which the fertilized egg (at this point the ‘blastocyst’) can attach to the endometrium and if the timing is off, or the endometrial response to progesterone is inadequate, and it is not ready to receive the blastocyst, hold onto it, and allow it to invade, and grow, then the pregnancy will not be successful. Hormones can influence every step of this process by their effects on the production and types of adhesion molecules present in the endometrium (necessary for attachment), regulation of the maternal immune response (permitting and promoting trohpblastic invasion), and by the production of growth factors that facilitate invasion and differentiation of the early embryonic and placental tissues.