2Female Reproductive Cycle The ovarian cycle is a series of events in the ovaries that occur during and after the maturation of the oocyte (egg or ovum). During their reproductive years, nonpregnant females usually experience a cyclical sequence of changes in their ovaries and uterus. Each cycle takes about one month and involves both oogenesis, the process of formation and development of oocyte, and preparation of the uterus to receive a fertilized ovum. Hormones secreted by the hypothalamus, anterior pituitary gland, and ovaries control the principal events.The uterine (menstrual) cycle is a concurrent series of changes in the endometrium of the uterus to prepare it for the arrival of a fertilized ovum that will develop in the uterus until birth. If fertilization does not occur, the lining (stratum functionalis) of the endometrium is shed during menstruation.FemaleReproductiveCycle
3The general term female reproductive cycle encompasses the ovarian and uterine cycles,
4Phases of the female reproductive cycle Name of phaseDaysmenstrual phase1–4follicular phase (also known as proliferative phase)5–13ovulation (not a phase, but an event dividing phases)14luteal phase (also known as secretory phase)15–26ischemic phase (some sources group this with secretory phase)27–28
5MenstruationMenstruation is also called menstrual bleeding, menses, a period or catamenia. The flow of menses normally serves as a sign that a woman has not become pregnant.A woman's first menstruation is termed menarche, and is one of the later stages of puberty in girls. The average age of menarche in humans is 12 years, but is normal anywhere between ages 8 and 16. Factors such as heredity, diet and overall health can accelerate or delay menarche
6The cessation of menstrual cycles at the end of a woman's reproductive life is termed menopause. The average age of menopause in women is 51 years, Eumenorrhea denotes normal, regular menstruation that lasts for a few days (usually 3 to 5 days, but anywhere from 2 to 7 days is considered normal). The average blood loss during menstruation is 35 millitres with 10–80 ml considered normal; many women also notice shedding of the endometrium lining that appears as tissue mixed with the blood. An enzyme called plasmin— contained in the endometrium — tends to inhibit the blood from clotting. Because of this blood loss, women have higher dietary requirements for iron than do males to prevent iron deficiency. Many women experience uterine cramps during this time (severe cramps or other symptoms are called dysmenorrhea).
8FollicularphaseThrough the influence of a rise in follicle stimulating hormone (FSH), five to seven tertiary-stage ovarian follicles are recruited for entry into the next menstrual cycle.These follicles, that have been growing for the better part of a year in a process known as folliculogenesis, compete with each other for dominance. Under the influence of several hormones, all but one of these follicles will undergo atresia, while one (or occasionally two) dominant follicles will continue to maturity. As they mature, the follicles secrete increasing amounts of estradiol , an estrogen.
9FollicularphaseThe estrogens that follicles secrete, initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium.During the follicular phase the lining of the uterus thickens, stimulated by gradually increasing amounts of estrogen.Follicles in the ovary begin developing under the influence of a complex interplay of hormones, and after several days one or occasionally two follicles become dominant (non-dominant follicles atrophy and die). The dominant follicle releases an ovum or egg in an event called ovulation.
10Ovulation. (An egg that is fertilized by a spermatozoon will become a zygote, taking one to two weeks to travel down the fallopian tubes to the uterus. If the egg is not fertilized within about a day of ovulation, it will die and be absorbed by the woman's body.)When the egg has matured, it secretes enough estradiol to trigger the acute release of luteinizing hormone (LH).In the average cycle this LH surge starts around cycle day 12 and may last 48 hours. The release of LH matures the egg and weakens the wall of the follicle in the ovary.
11OvulationThe egg is swept into the fallopian tube by the fimbria - a fringe of tissue at the end of each fallopian tube. If fertilization occurs, it will happen in the fallopian tube.In some women, ovulation features a characteristic pain called mittelschmerzThe sudden change in hormones at the time of ovulation also causes light mid-cycle bleeding for some women. An unfertilized egg will eventually disintegrate or dissolve.
12Luteal phaseThe corpus luteum is the solid body formed in the ovaries after the egg has been released into the fallopian tube which continues to grow and divide for a while.After ovulation, the residual follicle transforms into the corpus luteum under the support of the pituitary hormones. This corpus luteum will produce progesterone in addition to estrogens for approximately the next 2 weeks. Progesterone plays a vital role in converting the proliferative endometrium into a secretory lining receptive for implantation and supportive of the early pregnancy.It raises the body temperature by one-half to one degree Fahrenheit
13If fertilization of an egg has occurred, it will travel as an early blastocyst through the fallopian tube to the uterine cavity and implant itself 6 to 12 days after ovulationOne very early signal consists of human chorionic gonadotropin (hCG), a hormone that pregnancy tests can measure. This signal has an important role in maintaining the corpus luteum and enabling it to continue to produce progesterone.In the absence of a pregnancy and without hCG, the corpus luteum demises and inhibin and progesterone levels fall. This will set the stage for the next cycle. Progesterone withdrawal leads to menstrual shedding (progesterone withdrawal bleeding), and falling inhibin levels allow FSH levels to rise to raise a new crop of follicles.Luteal phase
15Two sex hormones play a role in the control of the menstrual cycle: estrogen and progesterone: Estradiol peaks twice, during follicular growth and during the luteal phase.Progesterone remains virtually absent prior to ovulation, but becomes critical in the luteal phase and during pregnancy. Many tests for ovulation check for the presence of progesterone.After ovulation the corpus luteum — which develops from the burst follicle and remains in the ovary — secretes both estradiol and progesterone. Only if pregnancy occurs do hormones appear in order to suspend the menstrual cycle, while production of estradiol and progesterone continues. Abnormal hormonal regulation leads to disturbance in the menstrual cycleGonadal
17Hypothalamus pituitary & These sex hormones come under the influence of the pituitary gland, and both FSH and LH play necessary roles:FSH stimulates immature follicles in the ovaries to grow.LH triggers ovulation.The gonadotropin-releasing hormone of the hypothalamus controls the pituitary, yet both the pituitary and the hypothalamus receive feedback from the follicle.Hypothalamus&pituitary
19Unlike almost all other species, the external physical changes of a human female near ovulation are very subtle. In contrast, other species often signal receptivity through heat, swellings, and/or changes in color in the genital area. Humans are the only mammal to lack obvious, visible manifestations of ovulation, although some argue that the extended estrus period of the bonobo (reproductive-age females are in heat for 75% of their menstrual cycle) has a similar effect to the lack of a "heat" in human females. While women can be taught to recognize their own ovulation (fertility awareness), whether men can detect ovulation in women is highly debated. At least one recent study has argued that men are more likely to initiate sex with fertile women, while another has found male-initiated sex to occur at a constant rate throughout the menstrual cycle.Hidden ovulation
20The ovary as an egg-bank Evidence suggests that eggs are formed from germ cells early in fetal life. The number is reduced to an estimated 400,000 to 450,000 immature ova residing in each ovary at puberty. The menstrual cycle, as a biologic event, allows for ovulation of one egg typically each month. Thus over her reproductive lifetime a woman will ovulate approximately 400 to 450 times. All the other eggs dissolve by a process called atresia. As a woman's total egg supply is formed in fetal life, to be ovulated decades later, it has been suggested that this long lifetime may make the chromatin of eggs more vulnerable to division problems, breakage, and mutation than the chromatin of sperm, which are produced continuously during a man's reproductive life.The ovary as an egg-bank
21ovarian volume and antral follicle countsHigh ovarian volume and high antral follicle countsUltrasound image of an ovary at the beginning of a menstrual cycle. No medications are being given. The ovary is outlined in blue. There are numerous antral follicles visible - marked with red spots 16 are seen in this image, this ovary had a total of 35 antrals (only 1 plane is shown above) This is a polycystic ovary, with a higher than average antral count and volume (ovary = 37 by 19.5mm) This woman had very irregular periods and was a "high responder" to injectable FSH medication
22ovarian volume and antral follicle countsNormal ovarian volume and "normal" antral follicle countsUltrasound image of an ovary at the beginning of a menstrual cycle. No medications are being given. The ovary is outlined in blue. 9 antral follicles are seen - marked with red spots The ovary has normal volume (cursors measuring ovary = 30 by 17.8mm) This woman had regular periods and a normal response to injectable FSH drugs
23ovarian volume and antral follicle countsLow ovarian volume and low antral follicle countsThe left ovary is outlined in blue and is small (low volume) Only 1 antral follicle is seen This woman had regular periods and a normal day 3 FSH testThe right ovary from the same woman This ovary is also small with only 2 antral follicles She only had 3 antrals total - from both ovaries Attempts to stimulate her ovaries for IVF were not successfu
24Cycle abnormalities Anovulation Apparently normal menstrual flow can occur without ovulation preceding it.In some women, follicular development may start but not be completed; nevertheless, estrogens will form and will stimulate the uterine lining.Anovulatory flow resulting from a very thick endometrium caused by prolonged, continued high estrogen levels is called estrogen breakthrough bleeding.Anovulatory bleeding triggered by a sudden drop in estrogen levels is called estrogen withdrawal bleeding.Anovulatory flow commonly occurs prior to menopause (premenopause) or in women with polycystic ovary syndrome
26Cycle abnormalities Flow Sudden heavy flows or amounts in excess of 80 ml (hypermenorrhea or menorrhagia) are not normal.Very little flow (less than 10ml) is called hypomenorrheaProlonged flow (metrorrhagia, also meno-metrorrhagia) no longer shows a clear interval pattern. Dysfunctional uterine bleeding refers to hormonally caused flow abnormalities, typically anovulation.All bleeding abnormalities need medical attention; they may indicate hormone imbalances, uterine fibroids, or other problems. As pregnant patients may bleed, a pregnancy test forms part of the evaluation of abnormalAmenorrhea refers to a prolonged absence of menses during the reproductive years of a woman. For example, women with very low body fat, such as athletes, may cease to menstruate. Amenorrhea also occurs during pregancy.
27Cycle abnormalities Early menarche The condition precocious puberty has caused menstruation to occur in girls as young as eight months old.
29Diseases An ovarian cyst is any collection of fluid, surrounded by a very thin wall, within an ovary. Any ovarian follicle that is larger than about two centimeters is termed an ovarian cyst. An ovarian cyst can be as small as a pea, or as large as a grapefruit.
30Diseases Ovarian cancer Ovarian cancer cellis a malignant tumor, of any histology, on or within an ovary.
31Polycystic Ovary Syndrome DiseasesPolycystic Ovary Syndrome(abbreviated PCOS or PCO), also known clinically as Stein-Leventhal syndrome, is an endocrine disorder that affects approximately one in ten women. It occurs amongst all races and nationalities, is the most common hormonal disorder among women of reproductive age, and is a leading cause of infertility. The principal features are weight problems, lack of regular ovulation and/or menstruation, and excessive amounts or effects of androgenic (masculinizing) hormones
32Endocrine, nutritional and metabolic diseases Diseases of thegenitourinary systemEndocrine, nutritionaland metabolic diseases
33Laparoscopic oophorectomy DiseasesOophorectomyLaparoscopic oophorectomyIn the case of humans, oophorectomies are most often performed due to diseases such as ovarian cysts or cancer; prophylactially to reduce the chances of developing ovarian cancer or breast cancer; or in conjunction with removal of the uterus.
34Preimplantation genetic diagnosis DiseasesPreimplantation genetic diagnosisIn medicine and (clinical) genetics preimplantation genetic diagnosis (PGD) (or also known as Embryo Screening) refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes prior to fertilization. PGD is considered an alternative to prenatal diagnosis. Its main advantage is that it avoids selective pregnancy termination as the method makes it highly likely that the baby will be free of the disease under consideration.
35Preimplantation genetic diagnosis DiseasesPreimplantation genetic diagnosisPGD thus is an adjunct to assisted reproductive technology, and requires in vitro fertilization (IVF) to obtain oocytes or embryos for evaluation. The term preimplantation genetic screening (PGS) is used to denote procedures that do not look for a specific disease but use PGD techniques to identify embryos at risk. PGD is a poorly chosen phrase because, in medicine, to "diagnose" means to identify an illness or determine its cause. An oocyte or early-stage embryo has no symptoms of disease. They are not ill. Rather, they may have a genetic condition that could lead to disease. To "screen" means to test for anatomical, physiological, or genetic conditions in the absence of symptoms of disease. So, both PGD and PGS should, be referred to as types of embryo screening.
36In vitro fertilisation DiseasesIn vitro fertilisation(IVF) is a technique in which egg cells are fertilised by sperm outside the woman's womb
37The fertile windowThe most fertile period (the time with the highest likelihood of pregnancy resulting from sexual intercourse) covers the time from some 5 days before ovulation until 1–2 days after ovulation. In an average 28 day cycle with a 14-day luteal phase, this corresponds to the second and the beginning of the third week of the cycle. Fertility awareness methods of birth control attempt to determine the precise time of ovulation in order to find the relatively fertile and the relatively infertile days in the cycle.
38The fertile windowIf a woman wants to conceive, the most fertile time occurs between 19 and 10 days prior to the expected menses. Many women use ovulation detection kits that detect the presence of the LH surge in the urine to indicate the most fertile time. Other ovulation detection systems rely on observation of one or more of the three primary fertility signs (basal body temperature, cervical fluid, and cervical position).
39The fertile windowAmong women living closely together, the onsets of menstruation may tend to synchronise somewhat. This McClintock effect was first described in 1971, and possibly explained by the action of pheromones in 1998. However, subsequent research has called this conclusion into question.
40Contraception and menstruation Hormonal optionsEstrogens and progesterone-like hormones make up the main active ingredients of hormonal birth control methods such as the pill. Typically they cause regular monthly flow that roughly mimics a menstrual cycle in appearance, but suppresses ovulation.With most pills, a woman takes hormone pills for 21 days, followed by 7 days of non-functional placebo pills or no pills at all, then the cycle starts again.
41Contraception and menstruation Hormonal optionsDuring the 7 placebo days, a withdrawal bleeding occurs; this differs from ordinary menstruation, and skipping the placebos and continuing with the next batch of hormone pills maysuppress it. (There are two main versions of the pill: monophasic and triphasic. With triphasic pills, skipping placebos and continuing with the next month's dose can make a woman more likely to experience spotting or breakthrough bleeding.) In 2003, the U.S. Food and Drug Administration (FDA) approved low-dose monophasic birth control pills that induce withdrawal bleeding every 3 months. Yet another version of the pill is the Loestrin Fe, which has only a four-day placebo "week" (the placebos are actually iron supplements intended to replenish iron lost by uterine shedding); the other three placebos are replaced with active hormone pills. This system is intended to help shorten periods. Mircette contains several days of estrogen-only pills in addition to the usual combination estrogen/progestin pills, in the case of women who may have problems with low estrogen during the placebo days with other pills.
42Contraception and menstruation Hormonal optionsOther types of hormonal birth control which affect menstruation include the vaginal Nuvaring and the transdermal patch (like the standard pill pack, active hormones are given for three weeks, followed by a one-week break for bleeding) and the injection (which can eliminate all flow as long as the injections are taken every twelve weeks, although spotting is a common side effect).
43Contraception and menstruation Effects on menstruation All such methods are designed to regulate monthly bleeding. Because of this, they are often chosen by females who wish to regulate the frequency and length of their period, often for basic convenience and especially when such factors are irregular and problematic on their own. Hormonal contraception has also been shown to improve menstrual factors such as cramping, heavy flow, and other bothersome physical and emotional issues related to periods.
44Contraception and menstruation Control and flexibility Hormonal methods which are controlled by the user day-to-day, including pills, the ring, and the patch, need not always be used according to the standard cycle/calendar. Their use can be rescheduled and altered in various ways to postpone or skip periods when desired for reasons of convenience (e.g., traveling or scheduled gynecological exams), personal enjoyment (such as expected sexual encounters or events like a wedding or dance), or health (including very painful periods or sensitivity to hormone fluctuations). Similarly, abrupt cessation of use can induce a breakthrough period mid-cycle.
45ResourcesBooksAdashi, E.Y. Ovulation: Evolving Scientific and Clinical Concepts. New York: Springer Verlag, 2000.Grudzinskas, J.G., and J. Yovich, eds. Gametes: The Oocyte. Cambridge: Cambridge University Press, 1995.Heffner, Linda G. Human Reproduction at a Glance. Oxford: Blackwell Science, 2001