Corrine K Welt, MD
Robert L Barbieri, MD
William F Crowley, Jr, MD
Kathryn A Martin, MD
INTRODUCTION — There are a number of settings in which evaluation of the menstrual cycle may be important. A common question is whether a particular woman ovulates, an issue that can arise in a number of different settings.
- Some women have irregular cycles (oligomenorrhea) and wish to determine how abnormal they are.
- Other women have heavy and painful menstrual periods (hypermenorrhea and dysmenorrhea) that may be associated with anovulatory cycles.
- Some women with apparently normal cycles fail to conceive and wish to know both whether they ovulate and, if so, how to optimize the timing of intercourse.
The detection and timing of ovulation will be reviewed here. The sequence of events occurring in the normal menstrual cycle, with a detailed description of the different phases, is discussed separately. (See “Physiology of the normal menstrual cycle”.) A discussion of female infertility is found elsewhere. (See “Overview of infertility”.)
DETECTION OF OVULATION — There are several ways to evaluate the function of the hypothalamic-pituitary-ovarian axis in women, each with different costs and time frames. They also address different issues such as detection of the presence of ovulation and detection of the timing of ovulation. Menstrual cycle charting, basal body temperature monitoring, and measurement of the serum progesterone concentration can be used to answer whether ovulation has occurred while measurement of follicle size and the luteinizing hormone (LH) surge can be used to detect the timing of ovulation.
Menstrual cycle charting — The simplest and least expensive method is menstrual cycle charting. This involves recording the days of onset and cessation of menses for several months in succession. Menstrual cycles between 25 and 35 days are generally ovulatory. Shorter cycles may occur owing to a shortening of the follicular phase, as occurs in aging, or with a short (inadequate) luteal phase, which means that the endometrium is not appropriately prepared to receive a fertilized embryo. Longer and shorter cycles may also indicate anovulation.
The patient should also note moliminal symptoms, which can be a useful clinical indicator of normal reproductive hormone cycling. These symptoms include an increase in thin cervical mucus secretions noted at mid-cycle and typical premenstrual symptoms such as menstrual cramps, breast tenderness, fluid retention, and appetite or mood changes.
Basal body temperature monitoring — Progesterone released from the corpus luteum after ovulation (figure 1) has potent effects on the hypothalamus, one of which is to increase body temperature. As a result, daily temperature monitoring can be used to document progesterone production and therefore ovulation.
This technique requires the use of a special basal body temperature thermometer, which typically has units from 96 to 100 degrees, so that each one-tenth of a degree is easily distinguishable. We recommend the use of a mercury thermometer, obtainable from any pharmacy. In our experience, current electronic thermometers are not sufficiently accurate for detection of the post-ovulatory temperature rise.
The woman takes her temperature by putting the thermometer under her tongue every morning while she is still in the basal state. This means before she gets out of bed, uses the bathroom, or has anything to eat or drink. Although there is an expected amount of variability with daily use of the thermometer, an approximately 0.5°F rise in body temperature can be detected in the luteal phase of the menstrual cycle compared with the follicular phase. In a normal cycle, the temperature rise begins one or two days after the LH surge and persists for at least 10 days. Thus, temperature changes are sufficient to retrospectively identify ovulation, but they occur too late to be useful for timing sexual intercourse to conceive. The subsequent fall in basal body temperature can be used as an indicator of the imminent onset of menses.
Serum progesterone concentration — Another simple test is measurement of the serum progesterone level in the mid-luteal phase, 18 to 24 days after the onset of menses or seven days before the next menses are expected. (See “Physiology of the normal menstrual cycle”, section on ‘Luteal phase: Mid-cycle surge and ovulation’.) A progesterone concentration above 2.0 ng/mL is consistent with luteinization but values this low may not correspond to a normal luteal phase. Normal mid-luteal phase progesterone levels are between 6 and 25 ng/mL.
However, there is considerable variability in single blood samples for progesterone because progesterone levels can increase in response to LH pulsations occurring after ovulation (figure 2) . Thus, a single low value cannot reliably detect an abnormal luteal phase, since it may be obtained between LH pulses. In comparison, a single level above 6 ng/mL is usually indicative of normal corpus luteum function.
TIMING OF OVULATION — For couples pursuing pregnancy, the highest probability of conception appears to be with intercourse one to two days prior to ovulation (see “Unexplained infertility”). Therefore, attempting to identify the fertile period and timing intercourse during this interval maximizes the probability of conception. This can be inferred by comparing the results of the following studies: the first series consisted of 100 fertile couples who conceived without timed intercourse and reported pregnancy rates of 50 percent at three months, 75 percent at six months, and over 90 percent at 12 months, whereas a second series of similar couples who used a method of fertility awareness with timed intercourse observed pregnancy rates of 76 percent at one month and 100 percent at seven months .
Identifying the fertile period — Calendar and basal body temperature (BBT) methods are not very reliable for identifying the fertile period because of normal variation in cycle length and because the temperature rise associated with ovulation occurs too late to be useful . Better alternatives are methods that have the woman examine her vaginal discharge for changes suggestive of a preovulatory estrogen effect, such as an increased volume of clear, stretchy, slippery mucus. Measurement of urinary luteinizing hormone is more expensive, but also effective.
Measurement of LH surge — The LH surge can be detected in either urine or serum samples. Urinary LH kits are now commercially available for home use and are helpful for many women. The LH surge appears in the urine within 12 hours after it appears in the serum; as a result, it can accurately predict ovulation and therefore the optimal time for intercourse. The rise in serum LH typically occurs approximately 36 hours before the oocyte is released from the follicle into the fallopian tube. Women typically begin testing their urine one or two days before the expected surge, so that the increase over baseline levels can be clearly observed. Electronic monitors have been developed that monitor both the estradiol and LH rise in urine to predict ovulation more precisely.
The kit instructions must be followed precisely, as different kits are standardized to different times of the day. In addition, the urine kit should probably be used only after ovulation has previously been documented. Any condition associated with elevated LH levels, such as polycystic ovary syndrome, premature ovarian failure, and menopause, can yield false positive results despite the absence of ovulation. Patients should be instructed in correct use of the kit as false positive interpretation of the LH surge occurs in seven percent of cycles .
In contrast, there is little utility for serum LH measurements in conventional practice, except for women preparing for in vitro fertilization. Use of serum measurement requires very precise knowledge of normal LH ranges in the immunoassay used and there is considerable variability in assay results depending upon antibodies, standards, and techniques . In addition, there are high amplitude LH pulses at the surge leading to considerable hour-to-hour variability.
Pelvic ultrasonography —
There are two methods currently in use. The transabdominal approach requires a full urinary bladder as an echo-free window through which to observe the complete pelvis and its organs. The transvaginal approach uses a vaginal probe transducer. Due to its closer proximity to the internal organs, the vaginal probe achieves a higher resolution and avoids the requirement for a full bladder. Therefore, the transvaginal approach is generally preferred by women while the transabdominal approach is usually reserved for girls, sexually inactive women, and cases in which a complete survey of the pelvis is important.
The average preovulatory follicle is between 20 and 25 mm in diameter before rupture, depending partly upon the observer’s technique. Ultrasound is most useful when performed serially. The detection of a large cyst at any one time is insufficient to establish that it is a normal dominant follicle, unless preceded one week earlier with a scan demonstrating no large follicles, associated concurrently with an appropriately elevated serum estradiol level, or followed one week later with a scan showing a collapsed follicle in the same location with internal echoes consistent with its transformation to a corpus luteum. The last option may be preferable in women in whom there is a suggestion of low luteal phase progesterone levels, raising the possibility of anovulation with luteinization of the unruptured follicle.
The simultaneous appearance of the endometrium may also be useful in establishing the functionality of an observed cyst. A thick proliferative endometrium suggests active estradiol secretion and a brightly echogenic endometrium (due to changes in gland structure) suggests appropriate progesterone production in the luteal phase.
OVARIAN RESERVE — A final test in the evaluation of the menstrual cycle, especially in older or infertile women, is the measurement of an early follicular phase (EFP) serum FSH and estradiol level. The utility of this test derives from the gradual changes in gonadotropin levels that occur across the menstrual cycle as women age. (See “Ovarian development and failure (menopause) in normal women”.) In particular, as the follicular phase shortens prior to menopause, EFP FSH levels increase before any detectable fall in peak estradiol, or progesterone levels, or in luteal phase length . Thus, EFP FSH levels have been used as a marker of ovarian reserve. If follicle development occurs very rapidly, as in aging, it is useful to check a concomitant estradiol level because early follicle development and a high estradiol will suppress FSH levels into an apparently normal range.
This concept has been extended to in vitro fertilization procedures. An elevation of day three FSH above a particular level is highly correlated with a poor response to ovulation induction and poor pregnancy rates. (See “In vitro fertilization”, section on ‘Patient selection’.)
Of note, there is as much as a threefold difference between FSH measurements on the same serum samples with different FSH assays . Extensive normative data must be collected to improve the utility of FSH assays for predicting ovarian reserve in each institution.
Other tests to evaluate ovarian reserve, including serum estradiol, antimüllerian hormone, and inhibin B concentrations, and ultrasound assessment of antral follicle count are reviewed separately. (See “In vitro fertilization”, section on ‘Adequate ovarian reserve’.)
- In women with irregular menstrual cycles, excessive bleeding, or infertility, it is important to determine whether she is ovulating.
- Menstrual cycles between 25 and 35 days are generally ovulatory.
- A rise in basal body temperature of 0.5°F can be detected when the progesterone rises after ovulation.
- A serum progesterone level of 6 to 25 ng/mL drawn seven days before menses is a reliable indicator of ovulation.
- The day of ovulation can be determined in the fertile period (approximately 14 days before the expected day of menses) using an ovulation predictor kit or ultrasound measurement of follicle size.
- An early follicular phase FSH level, paired with an estradiol level, can help predict ovarian reserve if the assay used has been validated at the facility where it is used.
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