Occasionally, the corpus luteum will not produce sufficient progesterone to maintain pregnancy during its very early stages. Initial signs of early spontaneous pregnancy termination include pelvic cramping and the detection of blood, similar to indications of menstruation. If the corpus luteum is truly deficient, then fertilization may occur around the idealized day 14 (ovulation), pregnancy will terminate during the deficient luteal phase, and menses will start on schedule. Without measuring levels of hCG, the pregnancy detection hormone, the woman would not know that she is pregnant because of the continuation of regular menstrual cycles. Luteal insufficiency is a common cause of infertility. Women are advised to see their physician if pregnancy does not result after 6 months of unprotected intercourse.
Analysis of the regulation of progesterone secretion by the corpus luteum provides insights into this clinical problem. There are several reasons for luteal insufficiency. First, the number of luteinized granulosa cells in the corpus luteum may be insufficient because of the ovulation of a small follicle or the premature ovulation of a follicle that was not fully developed. Second, the number of LH receptors on the luteinized granulosa cells in the graafian follicle and developing corpus luteum may be insufficient. LH re ceptors mediate the action of LH, which stimulates progesterone secretion. An insufficient number of LH receptors could be due to insufficient priming of the developing follicle with FSH. It is well known that FSH increases the number of LH receptors in the follicle. Third, the LH surge could have been inadequate in inducing full luteinization of the corpus luteum, yet there was sufficient LH to induce ovulation. It has been estimated that only 10% of the LH surge is required for ovulation, but the amount required for full luteinization and adequate progesterone secretion to maintain pregnancy is not known.
If progesterone values are low in consecutive cycles at the midluteal phase and do not match endometrial biopsies, exogenous progesterone may be administered in order to prevent early pregnancy termination during a fertile cycle. Other options include the induction of follicular development and ovulation with clomiphene and hCG. This treatment would likely produce a large, healthy, estrogen-secreting graafian follicle with sufficient LH receptors for luteinization. The exogenous hCG is given to supplement the endogenous LH surge and to ensure full stimulation of the graafian follicle, ovulation, adequate progesterone, and luteinization of the developing corpus luteum.
Phase: Menstrual Follicular Ovulatory Luteal
Phase: Menstrual Follicular Ovulatory Luteal
Day of menstrual cycle
^FnflfflRBIBBI^fc Hormonal and ovarian events during the menstrual cycle. P, progesterone,- E2P, estra-17-OH P, 17-hydroxyprogesterone.
The average menstrual cycle length in adult women is 28 days, with a range of 25 to 35 days. The interval from ovulation to the onset of menstruation is relatively constant, averaging 14 days in most women and is dictated by the fixed life span of the corpus luteum. In contrast, the interval from the onset of menses to ovulation (the follicular phase) is more variable and accounts for differences in cycle lengths among ovulating women.
The menstrual cycle is divided into four phases (Fig. 38.6). The menstrual phase, also called menses or menstruation, is the bleeding phase and lasts about 5 days. The ovarian follicular phase lasts about 10 to 16 days,- follicle development occurs, estradiol secretion increases, and the uterine endometrium undergoes proliferation in response to rising estrogen levels. The ovulatory phase lasts 24 to 48 hours, and the luteal phase lasts 14 days. In the luteal phase, progesterone is produced, and the en-dometrium secretes numerous proteins in preparation for implantation of an embryo.
The cycles become irregular as menopause approaches around age 50, and cycles cease thereafter. During the reproductive years, menstrual cycling is interrupted by con ception and lactation and is subjected to modulation by physiological, psychological, and social factors.
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