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All obstetricians should understand the basic biological steps required for women to achieve pregnancy. Moreover, abnormalities affecting these steps can lead to infertility or pregnancy loss. The biological and molecular changes involved in human zygote implantation and subsequent fetal and placental development are intricate. In the past 50 years, researchers have delineated many of these molecular and physiological events. Yet, much work remains in the continual challenge to improve clinical outcomes.

OVARIAN-ENDOMETRIAL CYCLE

In most women, cyclical ovulation continues during the almost 40 years between menarche and menopause. Thus, without contraception, approximately 400 opportunities for pregnancy exist, and these are tightly regulated by complex interactions of the hypothalamic-pituitary-ovarian axis. Concurrently, endometrium undergoes faithfully reproduced cyclical changes to prepare for pregnancy (Fig. 5-1). Essential contributors in this process include gonadotropin-releasing hormone (GnRH), the gonadotropin hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and the ovarian sex steroid hormones estrogen and progesterone. For a detailed description of menstrual cycle physiology, the reader is referred to Chapter 16 in Williams Gynecology, 4th edition (Halvorson, 2020).

FIGURE 5-1

Gonadotropin control of the ovarian and endometrial cycles. The ovarian-endometrial cycle is structured as a 28-day cycle. The follicular phase (days 1 to 14) is characterized by rising estrogen levels, endometrial thickening, and selection of the dominant “ovulatory” follicle. During the luteal phase (days 14 to 21), the corpus luteum (CL) produces estrogen and progesterone, which prepare the endometrium for implantation. If implantation occurs, the developing blastocyst begins to produce human chorionic gonadotropin (hCG) and rescues the corpus luteum, thus maintaining progesterone production. FSH = follicle-stimulating hormone; LH = luteinizing hormone.

Ovulation

This defining event separates the follicular and luteal phases of the menstrual cycle. Following ovulation, the corpus luteum develops from the remains of the graafian follicle in a process referred to as luteinization. The basement membrane separating the granulosa-lutein and theca-lutein cells breaks down, and by day 2 postovulation, blood vessels and capillaries invade the granulosa cell layer. During luteinization, these cells undergo hypertrophy and increase their capacity to synthesize hormones. LH is the primary luteotropic factor responsible for corpus luteum maintenance (Vande Wiele, 1970).

The hormone secretion pattern of the corpus luteum differs from that of the follicle. First, the greater capacity of granulosa-lutein cells to produce progesterone results from enhanced access to blood-borne, low-density lipoprotein (LDL)-derived cholesterol, which is a steroidogenic precursor (Carr, 1981). Ovarian progesterone production peaks at 25 to 50 mg/d during the midluteal phase. With pregnancy, the corpus luteum continues progesterone production in response to placental human chorionic gonadotropin (hCG). LH and hCG both act via the same LH-hCG receptor.

The human corpus luteum is a transient endocrine organ. In the absence of pregnancy, it rapidly undergoes apoptosis 9 to 11 ...

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