The endocrinology of normal pregnancy is complex. Because spontaneous pregnancy is critically dependent on appropriately timed endocrinologic changes of the menstrual cycle, it is not surprising that those endocrine abnormalities that ultimately alter pregnancy maintenance may mediate their effects during the follicular phase of the cycle in which conception occurs, or even earlier. Modifications in follicular development and ovulation, in turn, may be reﬂected in abnormalities of blastocyst transport and development, alterations in uterine receptivity to the implanting blastocyst, and improper functioning of the corpus luteum. Beginning with ovulation and lasting until approximately 7 to 9 weeks of gestation, maintenance of early pregnancy depends on the production of progesterone by the corpus luteum. Normal pregnancies are characterized by a luteal–placental shift at about 7 to 9 weeks gestation, during which the developing placental trophoblast cells take over progesterone production and pregnancy maintenance (87). Spontaneous pregnancy losses occurring before 10 weeks of gestation may result from a number of alterations in normal progesterone production or utilization. These include failure of the corpus luteum to produce sufficient quantities of progesterone, impaired delivery of progesterone to the uterus, or inappropriate utilization of progesterone by the uterine decidua. Pregnancy failures may also occur near the time of the expected luteal– placental shift if the trophoblast is unable to produce biologically active progesterone following demise of the corpus luteum.
Endocrinologic factors associated with recurrent abortion include luteal phase insufficiency, diabetes mellitus, hypersecretion of luteinizing hormone (LH), thyroid disease, and, potentially, insulin resistance and polycystic ovarian syndrome, hyperprolactinemia and decreased ovarian reserve. Luteal phase insufficiency or luteal phase defects (LPD) are characterized by inadequate luteal milestones and most likely relate to adverse pregnancy outcome via inadequate or improperly timed endometrial development at potential implantation sites. An elegant description of abnormalities at the site of implantation, which may be responsible for some cases of recurrent pregnancy loss, describes impaired decidualization of the endometrium as a mechanism for natural selection of human embryos (88). LPD has many causes, some of which are associated with hypersecretion of luteinizing hormone. Although the mechanism underlying the association of elevated LH levels with recurrent pregnancy loss is incompletely understood, abnormal LH secretion may have direct effects on the developing oocyte (premature aging), on the endometrium (dyssynchronous maturation), or both. Many patients with elevated LH levels also display physical, endocrinologic, and metabolic characteristics of polycystic ovarian syndrome (PCOS). Some studies report ovarian radiologic evidence of PCOS in as many as 40% to 80% of recurrent pregnancy loss patients (89,90). In addition to inappropriately elevated LH levels, PCOS patients are frequently obese and often have elevated circulating androgen levels. Although not undisputed, both changes have been linked to recurrent pregnancy loss, and elevated androgen levels have been shown to adversely affect markers of uterine receptivity in women with a history of recurrent pregnancy loss (89–92).