AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE Formerly The American Fertility Society OVULATION DETECTION A Guide for Patients PATIENT INFORMATION SERIES
Published by the American Society for Reproductive Medicine under the direction of the Patient Education Committee, the Publications Committee, and the Nurses Professional Group. No portion herein may be reproduced in any form without written permission. This booklet is in no way intended to replace, dictate, or fully define evaluation and treatment by a qualified specialist. It is intended solely as an aid for patients seeking general information on infertility evaluation, treatment, research, and related topics. Copyright 1995 by American Society for Reproductive Medicine.
AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE Formerly The American Fertility Society OVULATION DETECTION AGuide for Patients A glossary of italicized words is located at the end of this booklet. INTRODUCTION Ovulation, the release of an egg from its follicle in one of the two ovaries, is one of the most important factors in conceiving a child. In order for traditional conception to occur, the man must ejaculate his s e m e n, the fluid containing the sperm, into the woman s vagina near the time of ovulation. Once ovulated, the egg is picked up by one of the fallopian tubes and begins traveling toward the uterus (Figure 1). The man s sperm must be capable of swimming through the vagina and cervical mucus, up the cervical canal into the uterus, and up into the fallopian tube, where it must attach to and penetrate the egg in order to fertilize it. The fertilized egg continues traveling to the uterus and implants in the endometrium, where it grows and matures. If all goes well, a child is born approximately nine months later. Because a variety of problems can prevent or disrupt ovulation and result in i n f e r t i l i t y, it is often necessary to determine whether or not a woman i s ovulating. There are several ways to detect ovulation, including the basal body t e m p e r a t u re (BBT) chart, urine test kits to measure luteinizing hormone ( L H ) levels, vaginal u l t r a s o u n d, an endometrial biopsy, and blood tests to measure hormone levels. This booklet describes how ovulation occurs and methods of detecting ovulation. The Menstrual Cycle and Ovulation Ovulation is triggered by the LH surg e and occurs approximately 36 hours after the start of this surge. If the egg is fertilized and implants in the endometrium, a pregnancy is established. If a pregnancy is not established, the endometrial lining that develops in preparation for pregnancy is shed as the menstrual flow. 3
Uterus Fertilization Usually Occurs Here Fallopian Tube Ovary Endometrium Sperm Cervix Cervical Mucus Vagina Egg Released (ovulated) Figure 1. The female reproductive tract. Solid arrows indicate path sperm must travel to reach the egg. Dotted arrow indicates path of egg. The fertilized egg continues traveling through the fallopian tube to the uterus. Unlike men who continuously produce new sperm throughout their lives, a woman is born with all of the eggs that she will ever have. These eggs remain in an immature state within the ovary until they either underg o ovulation or a t re s i a (degeneration). Ovulation is a complex sequence of events involving hormones from the h y p o t h a l a m u s, p i t u i t a ry, and t h y ro i d g l a n d s, including g o n a d o t ropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and thyroid hormone. The hormones released by the egg s follicle in the ovary cause the endometrium to develop in anticipation of implantation. The coordination of this system is one of the most remarkable events in the body, resulting in the release of a mature egg at the exact time the cervical mucus is most receptive to sperm. Fertilization usually occurs in the fallopian tube 12 to 24 hours after ovulation. After this period of time, the egg loses its ability to be fertilized and begins to degenerate. If fertilized, the resulting embryo reaches the uterus about three to four days later and begins to implant in the endometrium. 4
The menstrual cycle is divided into three phases: the follicular phase, m i d - c y c l e, and the luteal phase. The follicular phase lasts 10 to 14 days, beginning with the onset of menstruation and lasting until the onset of the LH surge. During the follicular phase, the hormone FSH triggers the development of many follicles and encourages the egg in the d o m i n a n t f o l l i c l e to mature. The dominant follicle increases in size and secretes e s t ro g e n into the bloodstream. The increasing levels of estrogen cause the hypothalamus and pituitary to decrease the production of FSH, insuring the development of a single egg. As the egg matures during the mid-cycle, estrogen levels rise, triggering the pituitary gland to release a large amount of LH (the LH surge), which stimulates the release (ovulation) of the egg from its follicle in the ovary. The LH surge usually occurs 34 to 36 hours prior to ovulation. It can be measured in either the blood or the urine. The luteal phase, which generally lasts about 14 days, begins after ovulation, when the empty follicle collapses and becomes known as the corpus luteum. The corpus luteum secretes large amounts of progesterone, the hormone responsible for the rise in basal body temperature characteristic of the luteal phase. Progesterone also induces specific changes in the endometrium that make it receptive for embryo implantation. The highest levels of progesterone occur about one week after ovulation and then decline if a pregnancy does not result. Declining progesterone levels allow breakdown of the endometrium, which results in menstruation. A b n o r m a l progesterone secretion may be caused by poor follicular development, inadequate LH levels during the mid-cycle surge, or inadequate LH after ovulation. SIGNS OF OVULATION Cycle Length In most women aged 15 to 44, the average menstrual cycle length is 28 days. However, normal menstrual cycles may range from 21 to 35 days. The menstrual cycle starts on the first day of menstrual flow. Ovulation u s u a l l y occurs between the 13th and 15th day of a 28-day cycle. Keeping track o f menstrual cycle length can help determine the approximate time of ovulation. Abdominal Pain Mittelschmerz refers to a pain on one side of the abdomen near the time of ovulation. Mittelschmerz discomfort may begin prior to actual ovulation and is generally caused by nerve fibers that stretch as the follicle matures. Pain experienced after ovulation is usually due to irritation of the body lining (peritoneum) by the small amount of fluid or blood that leaks into the pelvis after ovulation. This pain may last for one to two days. 5
Cervical Mucus Test (Billings Method) Another indication of impending ovulation is an increase in cervical mucus discharged from the vagina and sometimes visible to the woman (Figure 2). This is due to the increasing estrogen secreted by the growing ovarian follicle. Early in the cycle, the cervix is closed and there is no mucus. When mucus production begins, the early mucus is thick, cloudy, and sticky. As the cycle progresses, the mucus becomes abundant, slippery, clear, and elastic; conditions favorable to sperm passage. These changes begin about two or three days before ovulation. After ovulation, the mucus becomes thick again. a. Early cycle the cerv i c a l mucus is sticky and does not s t re t c h. b. Nearing o v u l a t i o n t h e c e rvical mucus extends a little b e f o re bre a k i n g. c. Just before o v u l a t i o n t h e c e rvical mucus is v e ry thin, watery, and stre t c h a b l e. d. A f t e r o v u l a t i o n t h e c e rvical mucus becomes thick a g a i n. Figure 2. The cervical mucus test can provide information about ovulation. DETECTING OVULATION Basal Body Temperature (BBT) Chart The basal body temperature chart helps to monitor the duration of the different phases of the menstrual cycle and can help determine if and when ovulation has occurred. During the follicular phase, the woman s body temperature is relatively low. When progesterone production begins at ovulation, it produces a temperature rise with a minimum increase of 0.5 degrees Fahrenheit (Figure 3). An increased body temperature for several days indicates ovulation has occurred. BBT charts cannot predict when ovulation is going to occur; they only confirm that ovulation has occurred after the fact. The following are general instructions for keeping a basal body temperature chart: 6
1. The chart starts on the first day of menstrual flow. Record the date and place an x on the chart for each day of menstrual bleeding. 2. After your period is over, or on about the fifth day of bleeding, begin taking your temperature every morning before getting out of bed and before eating, drinking, or smoking. Record your temperature on the chart every day, noting any unusual circumstances such as insomnia, illness, or alcohol consumption. Also note on the chart each time you have sexual intercourse or have a test for infertility. When your next period begins, start a new chart. Figure 3. The basal body temperature (BBT) chart. Blood Tests Elevated progesterone levels in the blood are usually associated with ovulation. A blood test to measure progesterone can be performed about one week before the anticipated onset of the next menstrual period. The LH s u rge occurs just before ovulation. LH levels in the blood or urine can be measured to predict when the follicle is mature and ready for ovulation. Estrogen is secreted by the growing follicle and rises rapidly prior to ovulation. If ovulation is being induced with fertility drugs, frequent estrogen level measurements may be needed to determine follicular growth. Common hormonal problems such as thyroid gland disorders or excessive secretion of the hormone prolactin can cause ovulatory disturbances. Levels of these hormones can also be measured by blood tests. In women with excess hair growth or acne, the physician may suggest measuring the male hormones (a n d ro g e n s), since increases in these hormones are associated with adrenal gland and ovarian disorders which can also prevent ovulation. 7
Ultrasound Follicular growth can be measured with ultrasound, a technique which uses soundwaves to produce an image on a monitor screen. This is a painless procedure that can be done using either a vaginal probe or an abdominal scanning device. Prior to ovulation, the follicle is thin-walled and filled with fluid. As the egg inside the follicle develops, the follicle increases in size. Ovulation generally occurs when the follicle measures about 1.8 to 2.5 centimeters. Ultrasound is especially useful for timing intercourse or insemination. In women taking fertility drugs, ultrasound may be performed on several different days during the menstrual cycle so that each follicle can be carefully measured and monitored. Ovulation Prediction Kits Several ovulation prediction tests are available at drug stores. These kits use paper dip sticks that show changes in the level of LH in the urine. Once the LH surge has occurred, ovulation usually takes place within 12 to 44 hours. Urine testing usually begins two days prior to the expected day of ovulation. For women with 28-day cycles, ovulation usually occurs on days 13 to 15. For women with irregular menstrual cycles, urine testing should be timed according to the earliest and latest possible dates of ovulation. If the cycle ranges between 27 and 34 days, ovulation usually occurs between days 13 and 20. Therefore, testing should begin on day 11 and continue until ovulation is indicated or through day 20. There is an 80 percent chance of detecting ovulation with five days of testing and a 95 percent chance with ten days of testing. Once ovulation is documented, it is no longer necessary to continue testing. Occasionally, ovulation may not occur in a particular cycle. If ovulation is not detected in two or more consecutive cycles, an ovulatory problem may be present. The following are general guidelines for ovulation prediction tests that are based on detecting LH in the urine: 1. The manufacturer s instructions should be followed precisely. 2. Urine that is very dilute (light) may not have an adequate concentration of LH for detection. Therefore, women should avoid food and liquids for two to four hours before obtaining urine for testing so as to have an adequately concentrated (dark) urine sample. 3. False positive results in urinary LH detection may occur if the woman is currently pregnant, has recently been pregnant, or is close to menopause. Fertility medications such as human menopausal gonadotropin (hmg), human chorionic gonadotropin (hcg), or clomiphene citrate may also cause inaccurate results. Women taking any of these drugs should consult their physician before using a urinary ovulation prediction test and ask the manufacturer about the medication s effect on the test kit. 8
Endometrial Biopsy Progesterone helps prepare the endometrium (lining of the uterus) to receive an embryo. An endometrial biopsy can determine if a woman has ovulated and if the endometrium has been adequately stimulated with progesterone. During this office procedure, a small amount of endometrial tissue from inside the uterine cavity is removed and examined under a microscope. This test is performed just before menstruation is expected to begin. In order to interpret the endometrial biopsy, the physician will need to know the day that menstruation begins after the biopsy. Maintaining a BBT chart and/or using an ovulation prediction test kit is generally helpful in determining the best day to perform an endometrial biopsy and also in interpreting the result. If the degree of progesterone-induced changes in the endometrium i s l e s s than what is expected, a luteal phase defect may be diagnosed. Asecond biopsy may be needed to confirm this problem. Medication may be recommended to help correct the situation. Progesterone given either orally, vaginally, or by injection after ovulation may help to correct a luteal phase defect by exerting a direct effect on the endometrium. Clomiphene citrate, an ovulation-inducing medication, may act indirectly on the endometrium by improving ovulation. It is not known which treatment is best for luteal phase defect. IRREGULAR OVULATION Abnormal ovulation may appear in several ways. Menstrual cycles that are shorter than 21 days or longer than 35 days are often associated with anovulation. Lack of a menstrual period for three months or more is called oligomenorrhea. The complete absence of menstrual periods is referred to as amenorrhea. Many hormonal systems work together to produce regular menstrual periods, and the hormones that make up these systems are often evaluated to determine the cause of ovulatory disorders. Therefore, in order to prescribe the appropriate therapy, physicians may require additional tests to determine why ovulation is not taking place. Common conditions that may cause irregular ovulation or anovulation include disorders of the hypothalamus. Hypothalamic disorders are usually caused by subtle changes in the signal sent from the hypothalamus to the pituitary gland. This may result in changes in the secretion of FSH and LH and may cause ovulatory disturbances. Acute stress as well as rapid weight loss or weight gain can alter the function of the hypothalamus and pituitary glands and cause anovulation. An elevation of the pituitary hormone 9
prolactin may also lead to absence of menstrual periods and anovulation. Disturbances involving the thyroid gland can affect ovulation. Although less common, disorders of the adrenal gland may also be associated with anovulation. Blood tests are usually needed to confirm the diagnosis of these disorders. Polycystic ovary syndrome (PCOS), a condition which is frequently associated with weight gain, excess hair growth on the face and body, and irregular menstrual periods, can cause irregular ovulation or anovulation. Women with PCOS frequently have an increased LH level relative to the FSH level, which can be detected by a blood test. Increased androgens are also frequently present. In most cases, medical therapy with fertility drugs is successful in restoring ovulation. A thorough evaluation, including hormonal studies and appropriate medical therapy, may be required if these disorders are suspected. For more information on PCOS, consult the ASRM patient information booklet entitled Hirsutism and Polycystic Ovarian Syndrome. DRUGS USED TO REGULATE OVULATION Clomiphene citrate, the most commonly prescribed ovulation drug, is an oral medication often used to regulate ovulation or to induce ovulation in women who are not ovulating or do not have normal menstrual cycles. Clomiphene citrate is also used to time ovulation for patients who plan to undergo insemination. Human menopausal gonadotropins (hmg) are injectable medications that stimulate multiple follicle development. Physicians may prescribe these medications for patients who do not respond well to oral therapy such as clomiphene citrate. Gonadotropin releasing hormone (GnRH), a hormone secreted by the hypothalamus which prompts the pituitary gland to release FSH and LH, is released from the hypothalamus in small amounts approximately every hour or so. Synthetic GnRH can be administered by a pump to stimulate the pituitary to secrete LH and FSH. This medication is only useful for women who are anovulatory due to abnormalities in FSH and LH release. GnRH analogs may be used as adjunctive therapy to enhance induction of ovulation with other drugs. These analogs are prescribed to women whose hormonal patterns interfere with normal follicular development or with the administration of hmg. For a complete listing of ovulation drugs and more information on regulating ovulation, consult the ASRM patient information booklet entitled Ovulation Drugs. 1 0
SUMMARY Although determining if and when ovulation is occurring may seem frustrating and time consuming, it is often an essential step toward achieving pregnancy. It is important that women work with their physicians to decide which method of ovulation detection is best for them. If these tests indicate that the woman is not ovulating, has irregular cycles, or has a luteal phase defect, several treatments are available to correct the problem and increase the chances of a successful pregnancy. 1 1
GLOSSARY Adrenal glands. Glands located above each kidney that secrete hormones (cortisol, adrenaline, and other hormones) that help the body withstand stress and regulate metabolism. Altered function of these glands can disrupt menstruation. A n d r o g e n s. In men, androgens are the male hormones produced by the testes which are responsible for encouraging masculine characteristics. In women, androgens are produced in small amounts by the adrenal glands and ovaries. Excess amounts of androgens can lead to irregular menstrual periods, obesity, excessive growth of body hair (hirsutism), and infertility. Amenorrhea. Absence of menstrual cycles. Anovulation. Failure or absence of ovulation. May or may not be associated with amenorrhea. Atresia. The normal degeneration of eggs and follicles in the ovaries. Basal body temperature (BBT) chart. A temperature record designed to detect ovulation by measuring basal (resting) body temperature. Cervical canal. The passageway leading from the vagina into the uterus. Cervical mucus. The substance through which sperm must swim in order to pass the cervical canal and enter the uterus. Clomiphene citrate. An anti-estrogen drug used to induce ovulation. Brand names are Clomid and Serophene. Corpus luteum. Tissue formed in the ovary from a mature follicle that has released its egg at ovulation. The corpus luteum secretes progesterone and estrogen. The progesterone prepares the lining of the uterus (endometrium) to support a pregnancy. Dominant follicle. The largest follicle among the developing follicles in the ovary. Endometrial biopsy. A small piece of tissue extracted from the endometrium for microscopic examination. Endometrium. The lining of the uterus. E s t r o g e n. The female sex hormone produced by the ovaries which is responsible for the development of female sex characteristics. Estrogen is l a rgely responsible for stimulating the uterine lining to thicken during the first part of the menstrual cycle in preparation for ovulation and possible pregnancy. It is also important for healthy bones and overall health. A small amount of this hormone is also produced in the male when testosterone is converted to estrogen in fat cells. Fallopian tubes. The two tubular structures, located one on each side of the uterus, which pick up the ovulated egg. Sperm and egg usually meet and fertilize in the tube in normal conception. 1 2
F o l l i c l e. Located in the ovary, the follicle contains an egg, the cells that nourish the egg (granulosa cells), and the fluid secreted by these cells. The granulosa cells produce estrogen, which in turn acts on the uterus, hypothalamus, and pituitary gland. Estrogen levels rise until the follicle reaches a mature size, at which time ovulation occurs and the follicle ruptures and releases its egg. The empty follicle is known as the corpus luteum. Follicle stimulating hormone (FSH). The pituitary hormone responsible for egg development. FSH can also be given as a medication. Metrodin is a brand name. Follicular phase. The first phase of the menstrual cycle (beginning on the first day of bleeding) when the developing follicle secretes increasing amounts of estrogen. Gonadotropin releasing hormone (GnRH). A hormone secreted in a pulsatile manner by the hypothalamus that prompts the pituitary gland to synthesize and release follicle stimulating hormone (FSH) and luteinizing hormone (LH). Brand names are Factrel and Lutrepulse. GnRH analogs. Synthetic, long-acting hormones similar to the naturally occurring gonadotropin releasing hormone (GnRH). Brand names are Lupron, Synarel, and Zoladex. Human chorionic gonadotropin (hcg). A hormone produced by the placenta during pregnancy that is often used as a surrogate LH surge with clomiphene citrate or hmg for the treatment of ovulation disorders. Brand names are A.P.L., Pregnyl, and Profasi. Human menopausal gonadotropin (hmg). A drug used to stimulate egg development and follicle growth. It contains follicle stimulating hormone (FSH) and luteinizing hormone (LH), derived from the urine of postmenopausal women. Pergonal and Humegon are brand names. Hypothalamus. A thumb-sized area in the base of the brain that controls many body functions, regulates the pituitary gland, and releases GnRH. I n s e m i n a t i o n. Placement of sperm via a syringe into a female's uterus or cervix for the purpose of producing a pregnancy. LH surge. The surge of luteinizing hormone (LH) that the pituitary gland releases to trigger ovulation. Luteal phase. The third phase of the menstrual cycle that follows ovulation and is characterized by the production of large amounts of progesterone and estrogen by the corpus luteum. Luteal phase defect. Abnormality of the luteal phase resulting in inadequate development of the endometrium. Luteinizing hormone (LH). A hormone produced by the pituitary gland that triggers ovulation and stimulates the corpus luteum to secrete progesterone. Mid-cycle. The second phase of the menstrual cycle in which the LH surge occurs. 1 3
Mittelschmerz. A pain in the lower abdomen that is associated with ovulation. It is usually related to the rupture of the follicle as the egg is released. Oligomenorrhea. An abnormally infrequent or light menstrual flow. O v a r i e s. The two female sex glands in the pelvis, located one on each side of the uterus, that produce eggs and hormones including estrogen, progesterone, and androgens. Ovulation. The release of a mature egg from its follicle in the ovary, usually occurring on approximately day 14 of a 28-day cycle. Peritoneum. The smooth transparent membrane that lines the abdominal and pelvic cavities. Pituitary gland. The small gland just beneath the hypothalamus in the brain that stimulates ovarian function by secreting follicle stimulating hormone (FSH) and luteinizing hormone (LH). Disorders of this gland may lead to irregular or absent ovulation. Polycystic ovary syndrome (PCOS). A condition in which the ovaries contain many small follicles or cysts that are associated with anovulation and increased secretion of androgens. Symptoms can include irregular or absent menstrual periods, obesity, and excessive growth of body hair in a male pattern. Progesterone. A female hormone secreted by the corpus luteum during the third phase of the menstrual cycle. It prepares the lining of the uterus (endometrium) for implantation of an embryo and also allows for complete shedding of the endometrium at the time of menstruation. Prolactin. A protein hormone secreted by the pituitary gland into the blood. When elevated, it may lead to absence of menstrual periods and anovulation as well as the secretion of a milk-like substance from the breasts. Semen. The sperm and glandular fluid that comes out of the urethra when a man ejaculates. Sperm. The male reproductive cells that fertilize a woman s egg. The sperm head carries genetic material (chromosomes), the midpiece produces energy for movement, and the long, thin tail wiggles to propel the sperm. Thyroid gland. A large, two-lobed, ductless gland located in front of and on either side of the trachea (windpipe) in the neck that secretes a hormone that maintains normal body growth and metabolism. Thyroid hormone. A hormone produced by the thyroid gland that regulates growth and metabolism. Ultrasound. A picture of internal organs produced by high frequency sound waves and viewed as an image on a monitor screen. U t e r u s. The hollow muscular organ in the female where a fertilized egg implants and matures. Vagina. The canal in the female that leads to the cervix, which leads to the uterus. 1 4
L e t U s K n o w W h a t Yo u T h i n k This booklet was written by members of the American Society for Reproductive Medicine Nurses Professional Group and reviewed by members of the ASRM Patient Education Committee. Please take a few moments to fill out the following information and return this card. I found the Ovulation Detection b o o k l e t : very helpful h e l p f u l not helpful I would have liked the booklet to include: The booklet's readability was: just right too elementary too complicated I would like to see other booklets of this type about:
Booklets available for purchase through the American Society for Reproductive Medicine include: Abnormal Uterine Bleeding Adoption Age and Fert i l i t y B i rth Defects of the Female Reproductive System Donor Insemination Early Menopause (Pre m a t u re Ovarian Failure) Ectopic Pre g n a n c y Endometriosis (Also available in Spanish) F e rtility After Cancer Treatment Hirsutism and Polycystic Ovarian Syndrome Husband Insemination I n f e rtility: An Overview (Also available in Spanish) I n f e rtility: Coping and Decision Making IVF & GIFT: A Guide to Assisted Reproductive Technologies (Also available in Spanish) L a p a roscopy and Hysteroscopy Male Infertility and Vasectomy Reversal Menopause M i s c a rriage Ovulation Detection Ovulation Drugs P regnancy After Infert i l i t y P re m e n s t rual Syndrome (PMS) T h i rd Party Reproduction (Donor Eggs, Donor Sperm, Donor Embryos, & Surrogacy) Tubal Factor Infertility Uterine Fibroids For copies, ask your physician or contact the ASRM at the address below. AM E R I C A N SO C I E T Y F O R RE P R O D U C T I V E ME D I C I N E Formerly The American Fertility Society 1209 Montgomery Highway Birmingham, Alabama 35216-2809 (205) 978-5000