Ultrasound evaluation of the normal menstrual cycle

INTRODUCTION — Transvaginal ultrasonography provides a direct and sensitive method of monitoring ovarian size and follicular development during the menstrual cycle and is superior to transabdominal ultrasonography in several ways. When a high-frequency transducer is placed in the vaginal fornix close to the organs of interest, image quality is greatly improved, particularly in obese women. There is no requirement for a full urinary bladder, so patient discomfort is minimized. As a result, transabdominal ultrasonography is now reserved for situations that require a complete pelvic survey or for examining children or women who have not yet been sexually active.

This topic will review the ultrasonographic findings during the normal menstrual cycle. The events that occur during the cycle are discussed in detail separately. (See "Normal menstrual cycle".)

OVARIAN CHANGES DURING THE NORMAL MENSTRUAL CYCLE — The ovaries can be seen by ultrasonography throughout the menstrual cycle in normal women. Ovarian volume is determined using a simplified formula for a prolate ellipse [1].

Ovarian volume is typically used to describe ovarian size. It is calculated by multiplying the longest dimension of the ovary (in cm) by the two orthogonal dimensions by a factor of 0.523:

Ovarian volume declines after menopause, as illustrated by a study of 13,963 women ages 25 to 91 years undergoing annual transvaginal ultrasonography for 1 to 11 years as part of an ovarian cancer screening program [2]. Mean ovarian volume decreased from 4.9±0.03 cm³ in premenopausal women to 2.2±0.01 cm³ in postmenopausal women. Based upon these data, the upper limit of ovarian volume (using a definition of two standard deviations above the mean [3]) was approximately 20 cm³ for premenopausal women and 10 cm³ for postmenopausal women (figure 1).

Ovarian follicles as small as 2 mm can be detected by transvaginal ultrasonography. They are easily visible as echo-free structures that are sharply demarcated from the surrounding ovarian tissue, which is more echogenic. The follicles are usually spherical but become more ovoid as they enlarge.

Follicular phase — The development of ovarian follicles can be documented by serial scanning throughout the menstrual cycle [4-8]. (See "Normal menstrual cycle".)

●Folliculogenesis begins in the late luteal phase of the previous cycle; the follicle destined to ovulate is derived from a cohort of developing antral follicles [9].

●By cycle days 5 to 7, a varying number of small follicles of 2 to 6 mm in diameter can be seen in both ovaries [8].

●By cycle day 8 (six to nine days before the midcycle luteinizing hormone [LH] surge) (image 1), one follicle (the dominant follicle) reaches 10 mm in diameter [10,11]. The others may enlarge somewhat but to a lesser extent [11].

Subsequently, as the dominant follicle develops, the follicles in that ovary decrease in size, which suggests that there may be active suppression of follicular growth by some intraovarian paracrine mechanism [11,12]. The side of the dominant follicle in subsequent cycles appears to be a random event that is not influenced by the preceding cycle [13]. In 5 to 11 percent of cycles, two dominant follicles develop and ovulate, usually in opposite ovaries [6].

The dominant follicle grows approximately 2 mm a day, usually reaching a diameter of 20 to 25 mm by the time of ovulation [6]. However, follicular size just before ovulation is quite variable, ranging from 18 to 30 mm [4-6], thereby limiting the value of measurement of follicle diameter alone as a predictor of ovulation [14].

The accuracy of ultrasonographic measurements has been confirmed at laparoscopy by direct measurements of follicle diameter and the volume of follicular fluid [5,6]. Serial measurements by a single observer are less variable than those performed by multiple observers, and the errors in size estimates are greater for larger follicles [15,16].

There is a linear correlation between the diameter of the dominant follicle and serum estradiol concentrations during the period of rapid follicular growth [5,6], supporting earlier conclusions that most of the estradiol in serum comes from the dominant follicle [11].

Ovulation — Attempts have been made to predict impending ovulation by documenting specific intrafollicular sonographic features in the periovulatory period. At the time of the LH surge (figure 2), the granulosa cell layer begins to separate from the theca cell layer, and it develops a crenulated appearance [17]. However, this sign may easily be missed because it occurs just a few hours before ovulation. Another sign of follicular maturity is detection of the dissociated cumulus oophorus, which appears as a small, triangular echogenic structure projecting into the follicle within 24 hours before ovulation (image 2) [6,7]. However, this sign is also not seen sufficiently often to be a reliable predictor of ovulation [6,14].

In women with periovulatory pain, the pain is on the side of the dominant follicle and may occur before ovulation, due to local effects from the enlarging ovary [18,19], or at the time of follicle rupture secondary to peritoneal irritation from blood and follicular fluid.

Development of the corpus luteum — Follicular rupture occurs within 24 to 48 hours after the onset of the LH surge. It can be seen on ultrasonography, with complete follicular emptying taking from 1 to 45 minutes [8,20-22]. The corpus hemorrhagicum develops within one hour after ovulation; it is recognized as a small, irregular cyst with echogenic walls and multiple echoes, which originate from clotted blood [8].

Thereafter, the corpus luteum varies in size and echo pattern [4,5,22]. It can remain as a 1 to 2 cm cyst with thick crenulated walls (image 3) [7], or a predominantly cystic structure with strands of solid material; a predominantly solid structure with no cystic component, or a 3 to 4 cm hemorrhagic corpus luteum cyst with a reticular "spider web" internal echo pattern. The most frequent finding is a small, irregular, thick-walled cyst with low-level echoes (image 3) [7]. This usually slowly decreases in size during the luteal phase but it may first increase transiently.

The corpus luteum is a very vascular structure, and color Doppler shows low resistance blood flow around the cyst known as a "ring of fire." This flow persists throughout the first trimester of pregnancy. The relationship between the structure and function of the corpus luteum is unclear. Early reports that morphologic features of the corpus luteum (such as echogenicity and wall thickness) reflected function [23] could not be reproduced in a later study, which did, however, note a good correlation between vascularity and volume of the corpus luteum and serum progesterone concentrations [24]. However, the sonographic and Doppler characteristics of the corpus luteum do not appear to correlate with first trimester pregnancy outcome [25].

After ovulation, there is an increase in the volume of free fluid in the posterior cul-de-sac (pouch of Douglas), which can be detected by ultrasonography [26,27]. This peritoneal fluid is probably an exudate from the ovary because the quantity measured by laparoscopic aspiration (approximately 15 to 25 mL) greatly exceeds that released by the dominant follicle (4 to 6 mL) [20].

ENDOMETRIAL CHANGES DURING THE NORMAL MENSTRUAL CYCLE — The changes in thickness and texture of the endometrium that occur during the menstrual cycle can be detected by ultrasonography [28,29], and they are correlated with those determined by serial endometrial biopsies [30]. Endometrial thickness is measured from the echogenic interface at the junction of endometrium and myometrium at the level of the maximum anteroposterior diameter in the sagittal plane.

The use of transvaginal ultrasound in the evaluation of women with abnormal vaginal bleeding is reviewed separately. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis", section on 'Imaging: Choice of modality'.)

Follicular phase — After menses, the endometrium appears as a thin hyperechoic line, as a result of shedding of the functional layer (image 4). Proliferation from the basal layer begins soon thereafter and continues throughout the follicular phase under the influence of increasing estradiol secretion (figure 2) [29,31]. This proliferation results in a "triple-line" appearance on ultrasonography, with the endometrium appearing hypoechoic compared with the bright lines of the central and outer basalis layers (image 5).

By the end of the follicular phase, the endometrium measures between 8 and 12 mm [30,32]. At midcycle, the cervical canal may be dilated with mucus, which appears as an anechoic stripe within the cervix and is a sign of impending ovulation.

Luteal phase — After ovulation, the "triple-line" disappears and is replaced by a hyperechoic stripe, 10 to 14 mm in thickness (image 6). The brightness of this stripe appears to be related to increasing length and tortuosity of endometrial glands with mucin and glycogen storage within the functionalis layer.

The clinical importance of these changes is unclear. Many studies have attempted to relate endometrial thickness and texture to the outcome of pregnancy, but the results are conflicting. Most have focused on stimulated cycles in preparation for in vitro fertilization and are discussed separately (see "Overview of ovulation induction"). However, a study evaluated the relationship between endometrial thickness and echogenicity and the rates of pregnancy in women with natural cycles treated for luteal phase defects; in contrast to most of the findings in stimulated cycles for in vitro fertilization, the thickness and echo pattern of the endometrium at the time of ovulation did not predict the outcome of pregnancy [33].

Comparisons have been made between conventional, 2-dimensional (2-D) images of the endometrium and 3-dimensional (3-D), reconstructed images in the coronal plane [34]. When the 2-D images were normal, additional information was obtained in only 2 of 42 patients, compared with 50 percent of patients who had abnormal findings on 2-D imaging. This included improved definition of the endometrium, delineation of endometrial polyps, and leiomyomas.

Subtle, wavelike, subendometrial contractions have been noted on ultrasound [35-37]. These are best seen when a magnified view of the endometrial canal is recorded on videotape and viewed at five times the regular speed [35,36]. These contractions propagate from the cervix toward the fundus in the follicular phase and increase in frequency and amplitude throughout the follicular and periovulatory phases. The direction of contractions is essentially reversed during the luteal phase and menstruation [37]. The direction of the follicular phase waves may assist sperm transport, and the reversed pattern in the luteal phase may help to maintain the blastocyst within the uterine fundus.

The myometrium also demonstrates contractile activity throughout the cycle, peaking before ovulation [38]. Peristalsis during the luteal phase is controlled by systemic and local hormone secretion from the corpus luteum and facilitates fundal implantation of the blastocyst, predominantly on the side of the dominant ovary.

OVARIAN AND UTERINE DOPPLER STUDIES — Transvaginal color flow Doppler ultrasonography has been used to investigate cyclic changes in ovarian and uterine blood flow during the menstrual cycle [39-43].

Uterine blood flow — In the follicular phase of the cycle, the blood flow in the uterine arteries is characterized by a high-resistance pattern that starts to decrease the day before ovulation, reaches a nadir approximately two days after ovulation, and then remains at that level for the rest of the cycle [39-43]. These changes do not occur during anovulatory cycles.

Similar changes have been noted using 3-dimensional power Doppler angiography (3D-PDA) [44]. The endometrial and subendometrial vascularization index (VI) and vascularization flow index (VFI) increased during the proliferative phase, peaked three days before ovulation, decreased to a nadir five days after ovulation, then gradually increased during the early to mid-secretory phase.

Ovarian blood flow — Resistance to ovarian artery blood flow begins to decline in the dominant ovary during the phase of rapid follicular growth, in association with rising serum estradiol concentrations, and reaches a nadir at the time of ovulation. Thereafter, it does not change for four to five days, and then gradually increases to a level slightly lower than that in the early follicular phase [40,41,43].

Angiogenesis has been demonstrated in the granulosa cell layer of the dominant follicle at the time of the ovulatory surge in luteinizing hormone (LH) secretion, a sign that could indicate impending ovulation [21,45].

Midcycle alterations in pelvic blood flow have been noted on the side of the nondominant as well as the dominant ovary. However, resistance in the uterine artery in the midluteal phase of the cycle is lower on the side of the corpus luteum than on the opposite side, which may optimize endometrial perfusion on the side of possible implantation [42].

Function of the corpus luteum — There is a close correlation between serum progesterone concentrations and peak systolic blood flow velocity surrounding the corpus luteum in spontaneous cycles [24]. Women with luteal phase defects have a higher resistance to corpus luteum blood flow, in association with significantly lower serum progesterone concentrations, when compared with women with normal cycles.

The resistance index (RI) in the corpus luteum of women with luteinized unruptured follicles (LUF) is high throughout the luteal phase in comparison with normal luteal function characterized by a decrease in RI from ovulation to the mid-luteal phase, followed by an increase in the late luteal phase [46]. In conception cycles, the RI remains at mid-luteal phase levels until seven weeks of gestation, thereafter rising significantly.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Menstruation (The Basics)")

SUMMARY — Transvaginal ultrasonography provides a direct and sensitive method of monitoring ovarian size and follicular development during the menstrual cycle. Information obtained from ultrasound includes:

●Measurement of ovarian volume. (See 'Ovarian changes during the normal menstrual cycle' above.)

●Monitoring of ovarian follicle development (ovarian follicles as small as 2 mm can be detected) (image 1). (See 'Follicular phase' above.)

●After ovulation, a corpus luteum is recognized as a small, irregular cyst with echogenic crenulated walls and multiple echoes, which originate from clotted blood (image 3). (See 'Development of the corpus luteum' above.)

In addition, ultrasound can be used to monitor the changes in thickness and texture of the endometrium that occur during the menstrual cycle. (See 'Endometrial changes during the normal menstrual cycle' above.)