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Evaluation of The Menstrual Cycle and Timing of Ovulation

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14 views11 pages

Evaluation of The Menstrual Cycle and Timing of Ovulation

Segundo artigo do pubmed sobre endocrinologia
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Official reprint from UpToDate®


www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Evaluation of the menstrual cycle and timing of ovulation


Author: Corrine K Welt, MD
Section Editors: Robert L Barbieri, MD, William F Crowley, Jr, MD
Deputy Editor: Kathryn A Martin, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2023. | This topic last updated: May 19, 2021.

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.

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 "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 in serum or urine kits, along with other
technologies, can be used to detect the timing of ovulation.

When to evaluate — Ovulation prediction is commonly used to time intercourse for pregnancy,
especially in women who are having trouble conceiving. Women with irregular cycles or heavy,
painful menses are appropriate candidates for evaluation/detection of ovulation (eg, is

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anovulation the underlying cause of their symptoms?) ( table 1). (See "Female infertility:
Causes", section on 'Ovulatory disorders' and "Abnormal uterine bleeding in nonpregnant
reproductive-age patients: Terminology, evaluation, and approach to diagnosis", section on
'Irregular bleeding'.)

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 molimina 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 postovulatory 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
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days before the next menses are expected (see "Normal menstrual cycle", section on 'Midcycle
surge and ovulation'). Normal mid-luteal phase progesterone levels are between 6 and 25
ng/mL. When a progesterone level is low (eg, 2 ng/mL), one option is to repeat the test in two to
three days. If it is not rising, it likely indicates a luteinized, unruptured follicle. These follicles are
partially luteinized and make progesterone, but they do not have a sufficient cell number or
synthetic ability to make adequate progesterone to support the luteal phase.

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) [1]. 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 3 months, 75 percent at 6 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
1 month and 100 percent at 7 months [2].

Identifying the fertile period — Calendar and basal body temperature 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 [2]. 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 (LH) and/or estrogen is more
expensive but also effective. Newer technologies include changes in saliva, vaginal mucous or
temperature. These methods are discussed here and outlined ( table 1).

Conventional methods

Measurement of LH surge and estradiol rise — The luteinizing hormone (LH) surge can
be detected in either urine or serum samples. Urinary LH kits are commercially available for

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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.

Digital and electronic monitors have been developed that monitor both the estradiol and LH
rise in urine to predict ovulation more precisely. These monitors identify more fertile days
before and including the ovulation day by detection of the estrogen rise before the LH surge as
well as the LH surge, which have been determined to be the fertile days.

The urinary LH 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 (PCOS), primary ovarian insufficiency, and menopause, can yield
false-positive results despite the absence of ovulation. Adding the estradiol rise to the
prediction may help decrease false-positive results. Patients should be instructed in correct use
of the kit as false-positive interpretation of the LH surge occurs in 7 percent of cycles
( table 1) [3].

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 [4]. In addition, there
are high amplitude LH pulses at the surge leading to considerable hour-to-hour variability.

Pelvic ultrasonography — Identification of a peri-ovulatory follicle on ultrasonography is


another important tool for evaluating the menstrual cycle and ovulation, although it is not used
routinely for timing of intercourse, given its expense. Ultrasonography can identify a large
follicle as a round cystic structure that reaches a diameter of 16 to 30 mm prior to rupture and
release of the oocyte.

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

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transabdominal approach is usually reserved for girls, sexually inactive women, and cases in
which a complete survey of the pelvis is important.

The average pre-ovulatory 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.

Additional approaches

Salivary ferning — Saliva forms a pattern that looks like a fern when the saliva dries
around the time of ovulation. Microscopes and slides can be purchased to look for salivary
ferning. The accuracy of salivary ferning is lower than for other methods ( table 1).

Temperature sensors — Vaginal and underarm temperature sensors that takes


thousands of measurements throughout the day and night and reports temperature data to a
server. The temperature data are used to predict ovulation ( table 1).

Smartphone-based detection — Smartphone apps can increase the chance of predicting


ovulation by combining data from temperature, urine, or salivary measurements, as described
above. New technology may even incorporate ultrasound to detect ovulation.

OVARIAN RESERVE

A final test in the evaluation of the menstrual cycle, especially in older or infertile women, is
assessment of ovarian reserve. This can include measurement of an early follicular phase (EFP)
serum follicle-stimulating hormone (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

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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 [5].

A more detailed discussion of ovarian reserve, including anti-müllerian hormone, inhibin B


concentrations, and ultrasound assessment of antral follicle count, are reviewed separately.
(See "Female infertility: Evaluation", section on 'Assessment of ovarian reserve' and "In vitro
fertilization: Procedure", section on 'Assessment of ovarian reserve' and "Evaluation and
management of infertility in females of advancing age", section on 'Diminished ovarian
reserve'.)

SUMMARY

● In women with irregular menstrual cycles, excessive bleeding, or infertility, it is important


to determine whether she is ovulating. (See 'Detection of ovulation' above.)

● Menstrual cycles between 25 and 35 days are generally ovulatory. (See 'Detection of
ovulation' above.)

● A rise in basal body temperature of 0.5°F can be detected when the progesterone rises
after ovulation. (See 'Detection of ovulation' above.)

● A serum progesterone level of 6 to 25 ng/mL drawn seven days before menses is a reliable
indicator of ovulation. (See 'Detection of ovulation' above.)

● 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. (See 'Timing of ovulation' above.)

● An early follicular phase (EFP) follicle-stimulating hormone (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. (See 'Ovarian reserve' above.)

Use of UpToDate is subject to the Terms of Use.

REFERENCES

1. Filicori M, Butler JP, Crowley WF Jr. Neuroendocrine regulation of the corpus luteum in the
human. Evidence for pulsatile progesterone secretion. J Clin Invest 1984; 73:1638.

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2. Stanford JB, White GL, Hatasaka H. Timing intercourse to achieve pregnancy: current
evidence. Obstet Gynecol 2002; 100:1333.

3. McGovern PG, Myers ER, Silva S, et al. Absence of secretory endometrium after false-
positive home urine luteinizing hormone testing. Fertil Steril 2004; 82:1273.

4. Taylor AE, Khoury RH, Crowley WF Jr. A comparison of 13 different immunometric assay kits
for gonadotropins: implications for clinical investigation. J Clin Endocrinol Metab 1994;
79:240.

5. Sherman BM, West JH, Korenman SG. The menopausal transition: analysis of LH, FSH,
estradiol, and progesterone concentrations during menstrual cycles of older women. J Clin
Endocrinol Metab 1976; 42:629.
Topic 7437 Version 14.0

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GRAPHICS

Commercially available methods to detect ovulation

Test Description Brands Accuracy*

Urinary LH Detection of high LH in Many 97%


urine

Urinary LH and Detects rising estrogen Clearblue easy fertility 95 to 97% for fertile
estrone-3-glucuronide and high LH in urine monitor and Clearblue days
digital

Underarm Constant body DuoFertility 100% sensitive to


temperature temperature detect ovulation
measurement measurement

Vaginal temperature Vaginal temperature OvuSense 99% for ovulation, 89%


measurement measurement for ovulation
prediction

Salivary ferning Microscope to look for KNOWHEN ovulation 42 to 53%


salivary ferning monitoring system,
Geratherm

LH: luteinizing hormone.

* Detection of ovulation, a review of currently available methods.

Adapted from: Su HW, Yi YC, Wei TY, et al. Detection of ovulation, a review of currently available methods. Bioeng Transl Med
2017; 2:238.

Graphic 121117 Version 1.0

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Hormonal changes during normal menstrual cycle

Sequential changes in the serum concentrations of the hormones released from the
pituitary gland (FSH and LH; left panel) and from the ovaries (estrogen and
progesterone; right panel) during the normal menstrual cycle. By convention, the first
day of menses is day 1 of the cycle (shown here as day -14). The cycle is then divided
into two phases: the follicular phase is from the onset of menses until ovulation, and
the luteal phase is from ovulation until the next menses. To convert serum estradiol
values to pmol/L, multiply by 3.67, and to convert serum progesterone values to
nmol/L, multiply by 3.18.

LH: luteinizing hormone; IU: international units; FSH: follicle-stimulating hormone.

Graphic 72415 Version 5.0

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LH pulses stimulate progesterone release in mid-


luteal phase

Serum concentrations of luteinizing hormone and progesterone


during 24 hours of blood sampling at 10-minute intervals in a typical
female studied during the mid-luteal phase. There is a significant
correlation between LH pulses and increased serum progesterone
concentrations. To convert serum progesterone values to nmol/L,
multiply by 3.18.

LH: luteinizing hormone.

Data from: Filicori M, Butler JP, Crowley WF Jr. Neuroendocrine regulation of the
corpus luteum in the human. Evidence for pulsatile progesterone secretion. J Clin
Invest 1984; 73:1638.

Graphic 68311 Version 4.0

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Contributor Disclosures
Corrine K Welt, MD No relevant financial relationship(s) with ineligible companies to disclose. Robert L
Barbieri, MD No relevant financial relationship(s) with ineligible companies to disclose. William F
Crowley, Jr, MD Equity Ownership/Stock Options: Dare Bioscience [Endocrinology]. Consultant/Advisory
Boards: Dare Bioscience [Endocrinology]. All of the relevant financial relationships listed have been
mitigated. Kathryn A Martin, MD No relevant financial relationship(s) with ineligible companies to
disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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