All obstetricians should be aware of the basic reproductive biological processes required for women to successfully achieve pregnancy. A number of abnormalities can affect each of these processes and lead to infertility or pregnancy loss. In most women, spontaneous, cyclical ovulation at 25- to 35-day intervals continues during almost 40 years between menarche and menopause. Without contraception, there are approximately 400 opportunities for pregnancy, which may occur with intercourse on any of 1200 days—the day of ovulation and its two preceding days. This narrow window for fertilization is controlled by tightly regulated production of ovarian steroids. These hormones promote optimal regeneration of endometrium after menstruation ends in preparation for the next implantation window.
Should fertilization occur, the events that unfold after initial implantation of the blastocyst onto the endometrium and through to parturition result from a unique interaction between fetal trophoblasts and maternal endometrium-decidua. The ability of mother and fetus to coexist as two distinct immunological systems results from endocrine, paracrine, and immunological modification of fetal and maternal tissues in a manner not seen elsewhere. The placenta mediates a unique fetal–maternal communication system, which creates a hormonal environment that helps initially to maintain pregnancy and eventually initiates the events leading to parturition. The following sections address the physiology of the ovarian-endometrial cycle, implantation, placenta, and fetal membranes, and specialized endocrine arrangements between fetus and mother.
The endometrium-decidua is the anatomical site of blastocyst apposition, implantation, and placental development. From an evolutionary perspective, the human endometrium is highly developed to accommodate endometrial implantation and a hemochorial type of placentation. Endometrial development of a magnitude similar to that observed in women—that is, with special spiral (or coiling) arteries—is restricted to only a few primates, such as humans, great apes, and Old World monkeys. Trophoblasts of the blastocyst invade these endometrial arteries during implantation and placentation to establish uteroplacental vessels.
These primates are the only mammals that menstruate, which is a process of endometrial tissue shedding with hemorrhage and is dependent on sex steroid hormone-directed changes in blood flow in the spiral arteries. With nonfertile, but ovulatory, ovarian cycles, menstruation effects endometrial desquamation. New growth and development must be initiated with each cycle so that endometrial maturation corresponds rather precisely with the next opportunity for implantation and pregnancy. There seems to be a narrow window of endometrial receptivity to blastocyst implantation that corresponds approximately to menstrual cycle days 20 to 24.
The development of predictable, regular, cyclical, and spontaneous ovulatory menstrual cycles is regulated by complex interactions of the hypothalamic-pituitary axis, the ovaries, and the genital tract (Fig. 3-1). The average cycle duration is approximately 28 days, with a range of 25 to 32 days. The sequence of hormonal events leading to ovulation directs the menstrual cycle. The cyclical changes in endometrial histology are faithfully reproduced during each ovulatory cycle.
Gonadotropin control of the ovarian and endometrial cycles. The ovarian-endometrial cycle has been structured as a 28-day cycle. The follicular phase (days 1 to 14) is characterized by rising levels of estrogen, thickening of the endometrium, 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 blastocysts will begin to produce human chorionic gonadotropin (hCG) and rescue the corpus luteum, thus maintaining progesterone production. FSH = follicle-stimulating hormone; LH-luteinizing hormone.
In 1937, Rock and Bartlett suggested that endometrial histological features were sufficiently characteristic to permit “dating” of the cycle. These changes are illustrated in Figure 3-2. The follicular—proliferative—phase and the postovulatory-luteal or secretory—phase of the cycle are customarily divided into early and late stages.
Photomicrographs illustrating endometrial changes during the menstrual cycle. A. Proliferative phase: straight to slightly coiled, tubular glands are lined by pseudostratified columnar epithelium with scattered mitoses. B. Early secretory phase: coiled glands with a slightly widened diameter are lined by simple columnar epithelium that contains clear subnuclear vacuoles. Luminal secretions are seen. C. Late secretory phase: serrated, dilated glands with intraluminal secretion are lined by short columnar cells. D. Menstrual phase: fragmented endometrium with condensed stroma and glands with secretory vacuoles are seen in a background of blood. (Courtesy of Dr. Kelley Carrick.) E. Early pregnancy: a hypersecretory effect demonstrated by cell clearing and cytoplasmic blebs is seen. (Courtesy of Dr. Raheela Ashfaq.)
Follicular or Preovulatory Ovarian Phase
There are 2 million oocytes in the human ovary at birth, and about 400,000 follicles are present at the onset of puberty (Baker, 1963). The remaining follicles are depleted at a rate of approximately 1000 follicles per month until age 35, when this rate accelerates (Faddy and colleagues, 1992). Only 400 follicles are normally released during female reproductive life. Therefore, more than 99.9 percent of follicles undergo atresia through a process of cell death termed apoptosis (Gougeon, 1996; Kaipia and Hsueh, 1997).
Follicular development consists of several stages, which include the gonadotropin-independent recruitment of primordial follicles from the resting pool and their growth to the antral stage. This appears to be under the control of locally produced growth factors. Two members of the transforming growth factor-β family—growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP-15)—regulate proliferation and differentiation of granulosa cells as ...