Menstrual cycle

The menstrual cycle,

is a series of physiological changes that can occur in fertile females. Overt menstruation (where there is blood flow from the uterus through the vagina) occurs primarily in humans and close evolutionary relatives such as chimpanzees.Females of other species of placental mammal undergo estrous cycles, in which the endometrium is completely reabsorbed by the animal (covert menstruation) at the end of its reproductive cycle. This article focuses on the human menstrual cycle.

The menstrual cycle, under the control of the endocrine system, is necessary for reproduction. It is commonly divided into three phases: the follicular phase, ovulation, and the luteal phase; although some sources use a different set of phases: menstruation, proliferative phase, and secretory phase. The length of each phase varies from woman to woman and cycle to cycle, though the average menstrual cycle is 28 days. Menstrual cycles are counted from the first day of menstrual bleeding. Hormonal contraception interferes with the normal hormonal changes with the aim of preventing reproduction.

Stimulated by gradually increasing amounts of estrogen in the follicular phase, discharges of blood (= menses) slow then stop, and the lining of the uterus thickens. Follicles in the ovary begin developing under the influence of a complex interplay of hormones, and after several days one or occasionally two become dominant (non-dominant follicles atrophy and die). Approximately mid-cycle, 24–36 hours after the Luteinizing Hormone (LH) surges, the dominant follicle releases an ovum, or egg in an event called ovulation. After ovulation, the egg only lives for 24 hours or less without fertilization while the remains of the dominant follicle in the ovary become a corpus luteum; this body has a primary function of producing large amounts of progesterone. Under the influence of progesterone, the endometrium (uterine lining) changes to prepare for potential implantation of an embryo to establish a pregnancy. If implantation does not occur within approximately two weeks, the corpus luteum will involute, causing sharp drops in levels of both progesterone and estrogen. These hormone drops cause the uterus to shed its lining in a process termed menstruation.

In the menstrual cycle, changes occur in the female reproductive system as well as other systems (which lead to breast tenderness or mood changes, for example). A woman's first menstruation is termed menarche, and occurs typically around age 12. The end of a woman's reproductive phase is called the menopause, which commonly occurs somewhere between the ages of 45 and 55.

Terminology

The menarche 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. The cessation of menstrual cycles at the end of a woman's reproductive period is termed menopause. The average age of menopause in women is 52 years in industrialised countries such as the UK, with anywhere between 45 and 55 being common. Menopause before age 45 is considered premature in industrialised countries. The age of menopause is largely a result of genetics; however, illnesses, certain surgeries, or medical treatments may cause menopause to occur earlier.

The length of a woman's menstrual cycle will typically vary, with some shorter cycles and some longer cycles. A woman who experiences variations of less than eight days between her longest cycles and shortest cycles is considered to have regular menstrual cycles. It is unusual for a woman to experience cycle length variations of less than four days. Length variation between eight and 20 days is considered as moderately irregular cycles. Variation of 21 days or more between a woman's shortest and longest cycle lengths is considered very irregular (see cycle abnormalities).

Phases

The menstrual cycle can be divided into several different phases. The average length of each phase is shown below, the first three are related to changes in the lining of the uterus whereas the final three are related to processes occurring in the ovary:

Name of phase Average start day

assuming a 28-day cycle Average end day

menstrual phase (menstruation) 1 4

proliferative phase (some sources include menstruation in this phase) 5 13

ischemic phase 27 28

follicular phase 1 13

ovulatory phase (ovulation) 13 16

luteal phase (also known as secretory phase) 16 28

Menstruation

Menstruation is also called menstrual bleeding, menses, catamenia or a period. The flow of menses normally serves as a sign that a woman has not become pregnant. (However, this cannot be taken as certainty, as a number of factors can cause bleeding during pregnancy; some factors are specific to early pregnancy, and some can cause heavy flow.) During the reproductive years, failure to menstruate may provide the first indication to a woman that she may have become pregnant.

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 milliliters with 10–80 ml considered normal. (Because of this blood loss, women are more susceptible to iron deficiency than men are.)An enzyme called plasmin inhibits clotting in the menstrual fluid.

Painful cramping in the abdomen, back, or upper thighs is common during the first few days of menstruation (most women experience some pain during menstruation). Severe uterine pain during menstruation is known as dysmenorrhea, and it is most common among adolescents and younger women (affecting about 67.2% of adolescent females). When menstruation begins, symptoms of premenstrual syndrome (PMS) such as breast tenderness and irritability generally decrease. Many sanitary products are marketed to women for use during their menstruation.

Follicular phase

Reference ranges for estradiol and progesterone in the menstrual cycle, expressed in mass and molar concentration. The relative concentrations of estradiol and progesterone differ somewhat between the mass and molar scales because of slightly different molar mass. The scale is logarithmic.

Main article: Follicular phase

This phase is also called the proliferative phase because a hormone causes the lining of the uterus to grow, or proliferate, during this time.

Through the influence of a rise in follicle stimulating hormone (FSH) during the first days of the cycle, a few ovarian follicles are stimulated. These follicles, which were present at birth and have been developing 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 stop growing, while one dominant follicle in the ovary will continue to maturity. The follicle that reaches maturity is called a tertiary, or Graafian, follicle, and it forms the ovum.

As they mature, the follicles secrete increasing amounts of estradiol, an estrogen. The estrogens initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium. The estrogen also stimulates crypts in the cervix to produce fertile cervical mucus, which may be noticed by women practicing fertility awareness.

Ovulation

An ovary about to release an egg.

During the follicular phase, estradiol suppresses production of luteinizing hormone (LH) from the anterior pituitary gland. When the egg has nearly matured, levels of estradiol reach a threshold above which they stimulate production of LH. These opposite responses of LH to estradiol may be enabled by the presence of two different estrogen receptors in the hypothalamus: estrogen receptor alpha, which is responsible for the negative feedback estradiol-LH loop, and estrogen receptor beta, which is responsible for the positive estradiol-LH relationship.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, causing the fully developed follicle to release its secondary oocyte. The secondary oocyte promptly matures into an ootid and then becomes a mature ovum. The mature ovum has a diameter of about 0.2 mm.

Which of the two ovaries—left or right—ovulates appears essentially random; no known left and right co-ordination exists. Occasionally, both ovaries will release an egg; if both eggs are fertilized, the result is fraternal twins.

After being released from the ovary, the egg is swept into the fallopian tube by the fimbria, which is a fringe of tissue at the end of each fallopian tube. After about a day, an unfertilized egg will disintegrate or dissolve in the fallopian tube.

Fertilization by a spermatozoon, when it occurs, usually takes place in the ampulla, the widest section of the fallopian tubes. A fertilized egg immediately begins the process of embryogenesis, or development. The developing embryo takes about three days to reach the uterus and another three days to implant into the endometrium. It has usually reached the blastocyst stage at the time of implantation.

In some women, ovulation features a characteristic pain called mittelschmerz (German term meaning middle pain). The sudden change in hormones at the time of ovulation sometimes also causes light mid-cycle blood flow.

Luteal phase

Reference ranges for luteinizing hormone and follicle-stimulating hormone in the menstrual cycle, expressed in international units. The scale is logarithmic.

Main article: Luteal phase

The luteal phase is also called the secretory phase. An important role is played by the corpus luteum, the solid body formed in an ovary after the egg has been released from the ovary into the fallopian tube. This body continues to grow for some time after ovulation and produces significant amounts of hormones, particularly progesterone. Progesterone plays a vital role in making the endometrium receptive to implantation of the blastocyst and supportive of the early pregnancy; it also has the side effect of raising the woman's basal body temperature. There is a noted secretion of prolactin towards the end of the secretory phase.

After ovulation, the pituitary hormones FSH and LH cause the remaining parts of the dominant follicle to transform into the corpus luteum, which produces progesterone. The increased progesterone in the adrenals starts to induce the production of estrogen. The hormones produced by the corpus luteum also suppress production of the FSH and LH that the corpus luteum needs to maintain itself. Consequently, the level of FSH and LH fall quickly over time, and the corpus luteum subsequently atrophies.[3] Falling levels of progesterone trigger menstruation and the beginning of the next cycle. From the time of ovulation until progesterone withdrawal has caused menstruation to begin, the process typically takes about two weeks, with ten to sixteen days considered normal. For an individual woman, the follicular phase often varies in length from cycle to cycle; by contrast, the length of her luteal phase will be fairly consistent from cycle to cycle.

The loss of the corpus luteum can be prevented by fertilization of the egg; the resulting embryo produces human chorionic gonadotropin (hCG), which is very similar to LH and which can preserve the corpus luteum. Because the hormone is unique to the embryo, most pregnancy tests look for the presence of hCG.

Fertile window

The most fertile period (the time with the highest likelihood of pregnancy resulting from sexual intercourse) covers the time from some 5 days before 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. However, few cycles are exactly average. A variety of methods have been developed to help individual women estimate the relatively fertile and the relatively infertile days in the cycle: these systems are called fertility awareness.

Fertility awareness methods that rely on cycle length records alone are called calendar-based methods. Methods that require observation of one or more of the three primary fertility signs (basal body temperature, cervical mucus, and cervical position) are known as symptoms-based methods. Urine test kits are available that detect the LH surge that occurs 24 to 36 hours before ovulation; these are known as ovulation predictor kits (OPKs). Computerized devices that interpret basal body temperatures, urinary test results, or changes in saliva are called fertility monitors.

A woman's fertility is also affected by her age. As a woman's total egg supply is formed in fetal life,[30] 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.

Effect on other systems

Some women with neurological conditions experience increased activity of their conditions at about the same time during each menstrual cycle. For example, drops in estrogen levels have been known to trigger migraines (a neurological syndrome Migraines), especially when the woman who suffers migraines is also taking the birth control pill. Many women with epilepsy have more seizures in a pattern linked to the menstrual cycle; this is called "catamenial epilepsy". Different patterns seem to exist (such as seizures coinciding with the time of menstruation, or coinciding with the time of ovulation), and the frequency with which they occur has not been firmly established. Using one particular definition, one group of scientists found that around one-third of women with intractable partial epilepsy have catamenial epilepsy.An effect of hormones has been proposed, in which progesterone declines and estrogen increases would trigger seizures. Recently, studies have shown that high doses of estrogen can cause or worsen seizures, whereas high doses of progestrone can act like an antiepileptic drug. Studies by medical journals have found that women experiencing menses are 1.68 times more likely to commit suicide.

Mice have been used as an experimental system to investigate possible mechanisms by which levels of sex steroid hormones might regulate nervous system function. During the part of the mouse estrous cycle when progesterone is highest, the level of nerve-cell GABA receptor subtype delta was high. Since these GABA receptors are inhibitory, nerve cells with more delta receptors are less likely to fire than cells with lower numbers of delta receptors. During the part of the mouse estrous cycle when estrogen levels are higher than progesterone levels, the number of delta receptors decrease, increasing nerve cell activity, in turn increasing anxiety and seizure susceptibility.

Estrogen levels may affect thyroid behavior. For example, during the luteal phase (when estrogen levels are lower), the velocity of blood flow in the thyroid is lower than during the follicular phase (when estrogen levels are higher).

Among women living closely together, the onsets of menstruation may tend to synchronize 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 hypothesis into question.

Cycle abnormalities

Menstrual disorder

Infrequent or irregular ovulation is called oligoovulation. The absence of ovulation is called anovulation. Normal menstrual flow can occur without ovulation preceding it: an anovulatory cycle. In some cycles, 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 cycles commonly occur before menopause (perimenopause) and in women with polycystic ovary syndrome.

Very little flow (less than 10 ml) is called hypomenorrhea. Regular cycles with intervals of 21 days or fewer are polymenorrhea; frequent but irregular menstruation is known as metrorrhagia. Sudden heavy flows or amounts greater than 80 ml are termed menorrhagia. Heavy menstruation that occurs frequently and irregularly is menometrorrhagia. The term for cycles with intervals exceeding 35 days is oligomenorrhea.Amenorrhea refers to more than three to six months without menses (while not being pregnant) during a woman's reproductive years.

Ovulation suppression

Hormonal contraception

Half-used blister pack of a combined oral contraceptive. The white pills are placebos, mainly for the purpose of reminding the woman to continue taking the pills.

While some forms of birth control do not affect the menstrual cycle, hormonal contraceptives work by disrupting it. Progestogen negative feedback decreases the pulse frequency of gonadotropin-releasing hormone (GnRH) release by the hypothalamus, which decreases the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol levels. Progestogen negative feedback and the lack of estrogen positive feedback on LH release prevent a mid-cycle LH surge. Inhibition of follicular development and the absence of a LH surge prevent ovulation.

The degree of ovulation suppression in progestogen-only contraceptives depends on the progestogen activity and dose. Low dose progestogen-only contraceptives—traditional progestogen only pills, subdermal implants Norplant and Jadelle, and intrauterine system Mirena—inhibit ovulation in ~50% of cycles and rely mainly on other effects, such as thickening of cervical mucus, for their contraceptive effectiveness. Intermediate dose progestogen-only contraceptives—the progestogen-only pill Cerazette and the subdermal implant Implanon—allow some follicular development but more consistently inhibit ovulation in 97–99% of cycles. The same cervical mucus changes occur as with very low dose progestogens. High dose progestogen-only contraceptives—the injectables Depo-Provera and Noristerat—completely inhibit follicular development and ovulation.

Combined hormonal contraceptives include both an estrogen and a progestogen. Estrogen negative feedback on the anterior pituitary greatly decreases the release of FSH, which makes combined hormonal contraceptives more effective at inhibiting follicular development and preventing ovulation. Estrogen also reduces the incidence of irregular breakthrough bleeding. Several combined hormonal contraceptives—the pill, NuvaRing, and the contraceptive patch—are usually used in a way that causes regular withdrawal bleeding. In a normal cycle, menstruation occurs when estrogen and progesterone levels drop rapidly. Temporarily discontinuing use of combined hormonal contraceptives (a placebo week, not using patch or ring for a week) has a similar effect of causing the uterine lining to shed. If withdrawal bleeding is not desired, combined hormonal contraceptives may be taken continuously, although this increases the risk of breakthrough bleeding.

Lactational amenorrhea

Breastfeeding causes negative feedback to occur on pulse secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Depending on the strength of the negative feedback, breastfeeding women may experience complete suppression of follicular development, follicular development but no ovulation, or normal menstrual cycles may resume. Suppression of ovulation is more likely when suckling occurs more frequently. The production of prolactin in response to suckling is important to maintaining lactational amenorrhea. On average, women who are fully breastfeeding whose infants suckle frequently experience a return of menstruation at fourteen and a half months postpartum. There is a wide range of response between individual breastfeeding women, however, with some experiencing return of menstruation at two months and others remaining amenorrheic for up to 42 months postpartum.

Etymological and biological associations

Nightlighting and the moon

The word "menstruation" is etymologically related to "moon". The terms "menstruation" and "menses" are derived from the Latin mensis (month), which in turn relates to the Greek mene (moon) and to the roots of the English words month and moon— reflecting the fact that the moon's period of revolution around the earth (27.32 days) is similar to that of the human menstrual cycle. The synodical lunar month, the period between two new moons (or full moons), is 29.53 days long.

Some authors believe women in traditional societies without nightlighting ovulated with the full moon and menstruated with the new moon. A few studies in both humans and animals have found that artificial light at night does influence the menstrual cycle in humans and the estrus cycle in mice (cycles are more regular in the absence of artificial light at night), though none have demonstrated the synchronization of women's menstrual cycles with the lunar cycle. It has also been suggested that bright light exposure in the morning promotes more regular cycles. One author has suggested that sensitivity of women's cycles to nightlighting is caused by nutritional deficiencies of certain vitamins and minerals.

Other animals' menstrual cycles may be greatly different from lunar cycles: while the average cycle length in orangutans is the same as in humans—28 days—the average for chimpanzees is 35 days. Some take this as evidence that the average length of humans' cycle is most likely a coincidence.

Estrus and menstruation

Females of most mammal species advertise fertility to males with visual behavioral cues, pheromones, or both. This period of advertised fertility is known as estrus or heat. In species that experience estrus, females are generally only receptive to copulation while they are in heat(dolphins are an exception). In the estrous cycles of most placental mammals, if no fertilization takes place, the uterus reabsorbs the endometrium. This breakdown of the endometrium without vaginal discharge is sometimes called covert menstruation. Overt menstruation (where there is blood flow from the vagina) occurs primarily in humans and close evolutionary relatives such as chimpanzees. Some species, such as domestic dogs, experience small amounts of vaginal bleeding while in heat; this discharge has a different physiologic cause than menstruation.

A few mammals do not experience obvious, visible signs of fertility (concealed ovulation). In humans, while women can be taught to recognize their own level of fertility (fertility awareness), whether men can detect fertility in women is debated; recent studies have given conflicting results. Orangutans also lack visible signs of impending ovulation. Also, it has been said 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.

(source:wikipedia)

Endometriosis,

Endometriosis,

(from endo, "inside", and metra, "womb") is a gynecological medical condition in women in which endometrial-like cells appear and flourish in areas outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones. These endometrial-like cells in areas outside the uterus (endometriosis) are influenced by hormonal changes and respond in a way that is similar to the cells found inside the uterus. Symptoms often worsen with the menstrual cycle.

Endometriosis is typically seen during the reproductive years; it has been estimated that endometriosis occurs in roughly 5-10% of women. Symptoms may depend on the site of active endometriosis. Its main but not universal symptom is pelvic pain in various manifestations. Endometriosis is a common finding in women with infertility.

Signs and symptoms

Pelvic pain

A major symptom of endometriosis is recurring pelvic pain. The pain can be mild to severe cramping that occurs on both sides of the pelvis, in the lower back and rectal area, and even down the legs. The amount of pain a woman feels is not necessarily related to the extent or stage (1 through 4) of endometriosis. Some women will have little or no pain despite having extensive endometriosis or endometriosis with scarring. On the other hand, women may have severe pain even though they have only a few small areas of endometriosis. However, pain does typically correlate to the extent of the disease. Symptoms of endometriosic-related pain may include:

dysmenorrhea – painful, sometimes disabling cramps during menses; pain may get worse over time (progressive pain), also lower back pains linked to the pelvis

chronic pelvic pain – typically accompanied by lower back pain or abdominal pain

dyspareunia – painful sex

dysuria – urinary urgency, frequency, and sometimes painful voiding

Throbbing, gnawing, and dragging pain to the legs are reported more commonly by women with endometriosis.[4] Compared with women with superficial endometriosis, those with deep disease appears to be more likely to report shooting rectal pain and a sense of their insides being pulled down.Individual pain areas and pain intensity appears to be unrelated to the surgical diagnosis, and the area of pain unrelated to area of endometriosis.

Infertility

Many women with infertility have endometriosis. As endometriosis can lead to anatomical distorsions and adhesions (the fibrous bands that form between tissues and organs following recovery from an injury), the causality may be easy to understand; however, the link between infertility and endometriosis remains enigmatic when the extent of endometriosis is limited. It has been suggested that endometriotic lesions release factors which are detrimental to gametes or embryos, or, alternatively, endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon; for this reason it is preferable to speak of endometriosis-associated infertility in such cases.

Other

Other symptoms may be present, including:

Constipation

chronic fatigue

heavy or long uncontrollable menstrual periods with small or large blood clots

gastrointestinal problems including diarrhoea, bloating and painful defecation

extreme pain in legs and thighs

back pain

mild to extreme pain during intercourse

pain from adhesions which may bind an ovary to the side of the pelvic wall, or they may extend between the bladder and the bowel,uterus, etc.

extreme pain with or without the presence of menses

premenstrual spotting

mild to severe fever

headaches

depression

hypoglycemia (low blood sugar)

anxiety

In addition, women who are diagnosed with endometriosis may have gastrointestinal symptoms that mimic irritable bowel syndrome

Patients who rupture an endometriotic cyst may present with an acute abdomen as a medical emergency.

Occasionally pain may also occur in other regions. Cysts can occur in the bladder (although rare) and cause pain and even bleeding during urination. Endometriosis can invade the intestine and cause painful bowel movements or diarrhea.

In addition to pain during menstruation, the pain of endometriosis can occur at other times of the month and doesn't have to be just on the date on menses. There can be pain with ovulation, pain associated with adhesions, pain caused by inflammation in the pelvic cavity, pain during bowel movements and urination, during general bodily movement i.e. exercise, pain from standing or walking, and pain with intercourse. But the most desperate pain is usually with menstruation and many women dread having their periods. Also the pain can start a week before menses, during and even a week after menses, or it can be constant. There is no known cure for endometriosis.

Cause

While the exact cause of endometriosis remains unknown, many theories have been presented to better understand and explain its development. These concepts do not necessarily exclude each other.

Estrogens: Endometriosis is a condition that is estrogen-dependent and thus seen primarily during the reproductive years. In experimental models, estrogen is necessary to induce or maintain endometriosis. Medical therapy is often aimed at lowering estrogen levels to control the disease. Additionally, the current research into aromatase, an estrogen-synthesizing enzyme, has provided evidence as to why and how the disease persists after menopause and hysterectomy.

Retrograde menstruation: The theory of retrograde menstruation, first proposed by John A. Sampson, suggests that during a woman's menstrual flow, some of the endometrial debris exits the uterus through the fallopian tubes and attaches itself to the peritoneal surface (the lining of the abdominal cavity) where it can proceed to invade the tissue as endometriosis. While most women may have some retrograde menstrual flow, typically their immune system is able to clear the debris and prevent implantation and growth of cells from this occurrence. However, in some patients, endometrial tissue transplanted by retrograde menstruation may be able to implant and establish itself as endometriosis. Factors that might cause the tissue to grow in some women but not in others need to be studied, and some of the possible causes below may provide some explanation, e.g., hereditary factors, toxins, or a compromised immune system. It can be argued that the uninterrupted occurrence of regular menstruation month after month for decades is a modern phenomenon, as in the past women had more frequent menstrual rest due to pregnancy and lactation. Sampson's theory certainly is not able to explain all instances of endometriosis, and it needs additional factors such as genetic or immune differences to account for the fact that many women with retrograde menstruation do not have endometriosis. In addition, at least one study found that endometriotic lesions are biochemically very different from transplanted ectopic tissue, which casts doubt on Sampson's theory.

Müllerianosis: A competing theory states that cells with the potential to become endometrial are laid down in tracts during embryonic development and organogenesis. These tracts follow the female reproductive (Mullerian) tract as it migrates caudally (downward) at 8–10 weeks of embryonic life. Primitive endometrial cells become dislocated from the migrating uterus and act like seeds or stem cells. This theory is supported by foetal autopsy.

Coelomic Metaplasia: This theory is based on the fact that coelomic epithelium is the common ancestor of endometrial and peritoneal cells and hypothesizes that later metaplasia (transformation) from one type of cell to the other is possible, perhaps triggered by inflammation.This theory is further supported by laboratory observation of this transformation.

Genetics: Hereditary factors play a role. It is well recognized that daughters or sisters of patients with endometriosis are at higher risk of developing endometriosis themselves; for example, low progesterone levels may be genetic, and may contribute to a hormone imbalance. There is an about 10-fold increased incidence in women with an affected first-degree relative. A 2005 study published in the American Journal of Human Genetics found a link between endometriosis and chromosome 10q26. One study found that in female siblings of patients with endometriosis the relative risk of endometriosis is 5.7:1 versus a control population.

Transplantation: It is accepted that in specific patients endometriosis can spread directly. Thus endometriosis has been found in abdominal incisional scars after surgery for endometriosis. It can also grow invasively into different tissue layers, i.e., from the cul-de-sac into the vagina. On rare occasions endometriosis may be transplanted by blood or by the lymphatic system into peripheral organs such as the lungs and brain.

Immune system: Research is focusing on the possibility that the immune system may not be able to cope with the cyclic onslaught of retrograde menstrual fluid. In this context there is interest in studying the relationship of endometriosis to autoimmune disease, allergic reactions, and the impact of toxins.It is still unclear what, if any, causal relationship exists between toxins, autoimmune disease, and endometriosis.

Environment: There is a growing suspicion that environmental factors may cause endometriosis, specifically some plastics and cooking with certain types of plastic containers with microwave ovens. Other sources suggest that pesticides and hormones in our food cause a hormone imbalance.

Birth Defect: In rare cases where imperforate hymen does not resolve itself prior to the first menstrual cycle and goes undetected, blood and endometrium are trapped within the uterus of the patient until such time as the problem is resolved by surgical incision. Many health care practitioners never encounter this defect, and due to the flu-like symptoms it is often misdiagnosed or overlooked until multiple menstrual cycles have passed. By the time a correct diagnosis has been made, endometrium and other fluids have filled the uterus and fallopian tubes with results similar to retrograde menstruation resulting in endometriosis. The initial stage of endometriosis may vary based on the time elapsed between onset and surgical procedure.

Cause of pain

The way endometriosis causes pain is the subject of much research. Because many women with endometriosis feel pain during or around their periods and may spill further menstrual flow into the pelvis with each menstruation, some researchers are trying to reduce menstrual events in patients with endometriosis.

Endometriosis lesions react to hormonal stimulation and may "bleed" at the time of menstruation. The blood accumulates locally, causes swelling, and triggers inflammatory responses with the activation of cytokines. It is thought that this process may cause pain.

Pain can also occur from adhesions (internal scar tissue) binding internal organs to each other, causing organ dislocation. Fallopian tubes, ovaries, the uterus, the bowels, and the bladder can be bound together in ways that are painful on a daily basis, not just during menstrual periods.

Smoking

Smokers tend to be at a lower risk for endometriosis. Smoking causes decreased estrogens with increased breakthrough bleeding and shortened luteal phases. Smokers have an earlier than normal (by about 1.5–3 years) menopause which suggests that there is some toxic effect of smoking on the follicles directly. Chemically, nicotine has been shown to concentrate in cervical mucous and metabolites have been found in follicular fluid and been associated with delayed follicular growth and maturation. Finally, there is some effect on tubal motility because smoking is associated with an increased incidence of ectopic pregnancy as well as an increased spontaneous abortion rate.

Pregnancy

Aging brings with it many effects that may reduce fertility. Depletion over time of ovarian follicles affects menstrual regularity. Endometriosis has more time to produce scarring of the ovary and tubes so they cannot move freely or it can even replace ovarian follicular tissue if ovarian endometriosis persists and grows. Leiomyomata (fibroids) can slowly grow and start causing endometrial bleeding that disrupts implantation sites or distorts the endometrial cavity which affects carrying a pregnancy in the very early stages. Abdominal adhesions from other intraabdominal surgery, or ruptured ovarian cysts can also affect tubal motility needed to sweep the ovary and gather an ovulated follicle (egg).

Endometriosis in postmenopausal women does occur and has been described as an aggressive form of this disease characterized by complete progesterone resistance and extraordinarily high levels of aromatase expression. In less common cases, girls may have endometriosis symptoms before they even reach menarche.

Co-morbidity

Endometriosis bears no relationship to endometrial cancer. Current research has demonstrated an association between endometriosis and certain types of cancers, notably ovarian cancer, non-Hodgkin's lymphoma and brain cancer. Endometriosis often also coexists with leiomyoma or adenomyosis, as well as autoimmune disorders. A 1988 survey conducted in the US found significantly more Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma in women with endometriosis compared to the general population.

Pathophysiology

Endoscopic image of endometriotic lesions at the peritoneum of the pelvic wall.

Micrograph of the wall of an endometrioma. All features of endometriosis are present (endometrial glands, endometrial stroma and hemosiderin-laden macrophages. H&E stain.

Active endometriosis produces inflammatory mediators that cause pain and inflammation, as well as scarring or fibrosis of surrounding tissue. Triggers of various kinds, including menses, toxins, and immune factors, may be necessary to start this process. Typical endometriotic lesions show histologic features similar to endometrium, namely endometrial stroma, endometrial epithelium, and glands that respond to hormonal stimuli. Older lesions may display no glands but hemosiderin deposits as residual. To the eye, lesions can appear dark blue or powder-burn black and vary in size; red, white, yellow, brown or non-pigmented. Some lesions within the pelvis walls may not be visible to the eye, as normal-appearing peritoneum of infertile women reveals endometriosis on biopsy in 6–13% of cases.Additionally other lesions may be present, notably endometriomas of the ovary, scar formation, and peritoneal defects or pockets. Endometrioma on the ovary of any significant size (Approx. 2 cm +) must be removed surgically because hormonal treatment alone will not remove the full endometrioma cyst, which can progress to acute pain from the rupturing of the cyst and internal bleeding. Endometrioma is sometimes misdiagnosed as ovarian cysts.

Endometriosis correlates with abnormal amounts of multiple substances, possibly indicating a causative link in its pathogenesis, although correlation does not imply causation:

Endometrial cells in women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of splice variants of CD44, a cell-surface protein involved in cell adhesions.

The matrix metalloproteinases MMP-1 and MMP-2 are also increased, and appear to be major factors involved in the invasion of endometrium into the peritoneum and in vascularization of endometriosis.

Endometriosis patients also have elevated levels of vascular endothelial growth factor A (VEGF-A), soluble vascular endothelial growth factor receptors-1 and -2 (sVEGFR-1 and -2) and angiopoietin-2 (Ang-2).IL-4 may induce angiogenesis in endometriosis by inducing expression of eotaxin.

Increased oxidative stress is also implicated in the pathophysiology of endometriosis, as well as 8-iso-PGF2α and oxysterols, being potential causative links in this oxidative stress.

Early endometriosis typically occurs on the surfaces of organs in the pelvic and intra-abdominal areas. Health care providers may call areas of endometriosis by different names, such as implants, lesions, or nodules. Larger lesions may be seen within the ovaries as endometriomas or "chocolate cysts", "chocolate" because they contain a thick brownish fluid, mostly old blood. Endometriosis may trigger inflammatory responses leading to scar formation and adhesions.

Endoscopic image of endometriotic lesions in the Pouch of Douglas and on the right sacrouterine ligament.

Most endometriosis is found on these structures in the pelvic cavity where it can produce mild, moderate, and/or severe pain felt in the pelvis and/or lower back areas. The pain is often more severe before, during, and/or after the menstrual period:

Ovaries (the most common site)

Fallopian tubes

The back of the uterus and the posterior cul-de-sac

The front of the uterus and the anterior cul-de-sac

Uterine ligaments such as the broad or round ligament of the uterus

Pelvic and back wall

Intestines, most commonly the rectosigmoid

Urinary bladder and ureters

Bowel endometriosis affects approximately 10% of women with endometriosis, and can cause severe pain with bowel movements.

Endometriosis may spread to the cervix and vagina or to sites of a surgical abdominal incision.

Less commonly lesions can be found on the diaphragm. Diaphragmatic endometriosis is rare, most always on the right hemidiaphragm, and may inflict cyclic pain of the right shoulder just before and during menses. Rarely, endometriosis can be extraperitoneal and is found in the lungs and CNS.

Pleural implantations are associated with recurrent right pneumothoraces at times of menses, termed catamenial pneumothorax.

Endometriosis may also present with skin lesions in cutaneous endometriosis.

Complications

Endoscopic image of a ruptured chocolate cyst in left ovary.

Complications of endometriosis include:

Internal scarring

Adhesions
Pelvic cysts

Chocolate cyst of ovarys

Ruptured cyst

Blocked bowel/bowel obstruction

Infertility can be related to scar formation and anatomical distortions due to the endometriosis; however, endometriosis may also interfere in more subtle ways: cytokines and other chemical agents may be released that interfere with reproduction.

Other complications of endometriosis include bowel and ureteral obstruction resulting from pelvic adhesions. Also, peritonitis from bowel perforation can occur.

Ovarian endometriosis may complicate pregnancy by decidualization, abscess and/or rupture. It is the most common adnexal mass detected during pregnancy, being present in 0.52% of deliveries as studied in the period 2002 to 2007. Still, ovarian endometriosis during pregnancy can be safely observed conservatively.

Diagnosis

Micrograph showing endometriosis (right) and ovarian stroma (left). H&E stain.

A health history and a physical examination can in many patients lead the physician to suspect endometriosis. Surgery is the gold standard in diagnosis. However, in the United States most insurance plans will not cover surgical diagnosis unless the patient has already attempted to become pregnant and failed. Use of imaging tests may identify endometriotic cysts or larger endometriotic areas. It also may identify free fluid often within the cul-de-sac. The two most common imaging tests are ultrasound and magnetic resonance imaging (MRI). Normal results on these tests do not eliminate the possibility of endometriosis. Areas of endometriosis are often too small to be seen by these tests.

The only way to diagnose endometriosis is by laparoscopy or other types of surgery with lesion biopsy. The diagnosis is based on the characteristic appearance of the disease, and should be corroborated by a biopsy. Surgery for diagnoses also allows for surgical treatment of endometriosis at the same time.

Although doctors can often feel the endometrial growths during a pelvic exam, and your symptoms may be telltale signs of endometriosis, diagnosis cannot be confirmed without performing a laparoscopic procedure. Often the symptoms of ovarian cancer are identical to those of endometriosis. If a misdiagnosis of endometriosis occurs due to failure to confirm diagnosis through laparoscopy, early diagnosis of ovarian cancer, which is crucial for successful treatment, may have been missed.

Staging

possible locations of endometriosis

Surgically, endometriosis can be staged I–IV (Revised Classification of the American Society of Reproductive Medicine) The process is a complex point system that assesses lesions and adhesions in the pelvic organs, but it is important to note staging assesses physical disease only, not the level of pain or infertility. A patient with Stage I endometriosis may have little disease and severe pain, while a patient with Stage IV endometriosis may have severe disease and no pain or vice versa. In principle the various stages show these findings:

Stage I (Minimal)

Findings restricted to only superficial lesions and possibly a few filmy adhesions

Stage II (Mild)

In addition, some deep lesions are present in the cul-de-sac

Stage III (Moderate)

As above, plus presence of endometriomas on the ovary and more adhesions

Stage IV (Severe)

As above, plus large endometriomas, extensive adhesions.

Markers

An area of research is the search for endometriosis markers. These markers are substances made by or in response to endometriosis that health care providers can measure in the blood or urine. If markers are found, health care providers could diagnose endometriosis by testing a woman's blood or urine which might show high levels of estrogen or low levels of progesterone, and reduce the need for surgery. The antigen CA-125 is known to be elevated in many patients with endometriosis but is not specifically indicative of endometriosis.

Research is also being conducted on potential genetic markers associated with endometriosis so that a saliva-based diagnostic may replace surgical procedures for basic diagnosis. However, this research remains very preliminary and the diagnostic standard continues to be surgical intervention.

Treatments

While there is no cure for endometriosis, in many patients menopause (natural or surgical) will abate the process. In patients in the reproductive years, endometriosis is merely managed: the goal is to provide pain relief, to restrict progression of the process, and to restore or preserve fertility where needed. In younger women with unfulfilled reproductive potential, surgical treatment attempts to remove endometrial tissue and preserving the ovaries without damaging normal tissue. In women who do not have need to maintain their reproductive potential, hysterectomy and/or removal of the ovaries may be an option; however, this will not guarantee that the endometriosis and/or the symptoms of endometriosis will not come back, and surgery may induce adhesions which can lead to complications.

In general, the diagnose of endometriosis is confirmed during surgery, at which time ablative steps can be taken. Further steps depend on circumstances: patients without infertility can be managed with hormonal medication that suppress the natural cycle and pain medication, while infertile patients may be treated expectantly after surgery, with fertility medication, or with IVF.

Sonography is a method to monitor recurrence of endometriomas during treatments.

Treatments for endometriosis in women who do not wish to become pregnant include:

Hormonal medication

Progesterone or Progestins: Progesterone counteracts estrogen and inhibits the growth of the endometrium. Such therapy can reduce or eliminate menstruation in a controlled and reversible fashion. Progestins are chemical variants of natural progesterone.

Avoiding products with xenoestrogens, which have a similar effect to naturally produced estrogen and can increase growth of the endometrium.

Hormone contraception therapy: Oral contraceptives reduce the menstrual pain associated with endometriosis.They may function by reducing or eliminating menstrual flow and providing estrogen support. Typically, it is a long-term approach. Recently Seasonale was FDA approved to reduce periods to 4 per year. Other OCPs have however been used like this off label for years. Continuous hormonal contraception consists of the use of combined oral contraceptive pills without the use of placebo pills, or the use of NuvaRing or the contraceptive patch without the break week. This eliminates monthly bleeding episodes.

Danazol (Danocrine) and gestrinone are suppressive steroids with some androgenic activity. Both agents inhibit the growth of endometriosis but their use remains limited as they may cause hirsutism and voice changes.

Gonadotropin Releasing Hormone (GnRH) agonist: These agents work by increasing the levels of GnRH. Consistent stimulation of the GnRH receptors results in downregulation, inducing a profound hypoestrogenism by decreasing FSH and LH levels. While effective in some patients, they induce unpleasant menopausal symptoms, and over time may lead to osteoporosis. To counteract such side effects some estrogen may have to be given back (add-back therapy). These drugs can only be used for six months at a time.

Lupron depo shot is a GnRH agonist and is used to lower the hormone levels in the woman's body to prevent or reduce growth of endometriosis. The injection is given in 2 different doses a once a month for 3 month shot with the dosage of (11.25 mg) or a once a month for 6 month shot with the dosage of (3.75 mg).

Aromatase inhibitors are medications that block the formation of estrogen and have become of interest for researchers who are treating endometriosis.

Other medication

NSAIDs Anti-inflammatory. They are commonly used in conjunction with other therapy. For more severe cases narcotic prescription drugs may be used. NSAID injections can be helpful for severe pain or if stomach pain prevents oral NSAID use.

MST Morphine sulphate tablets and other opioid painkillers work by mimicking the action of naturally occurring pain-reducing chemicals called "endorphins". There are different long acting and short acting medications that can be used alone or in combination to provide appropriate pain control.

Diclofenac in suppository or pill form. Taken to reduce inflammation and as an analgesic reducing pain.

Surgery

Procedures are classified as

conservative when reproductive organs are retained,

semi-conservative when ovarian function is allowed to continue, and

radical when the uterus and ovaries are removed.

Conservative therapy consists of removal, excision (called cystectomy) or ablation of endometriosis, adhesions, resection of endometriomas, and restoration of normal pelvic anatomy as much as is possible.[5] There are combinations as well, notably one consisting of cystectomy followed by ablative surgery using a CO2 laser to vaporize the remaining 10%–20% of the endometrioma wall close to the hilus.

Radical therapy in endometriosis removes the uterus (hysterectomy) and tubes and ovaries (bilateral salpingo-oophorectomy) and thus the chance for reproduction. Radical surgery is generally reserved for women with chronic pelvic pain that is disabling and treatment-resistant. Not all patients with radical surgery will become pain-free.

Semi-conservative therapy preserves a healthy appearing ovary, and yet, it also increases the risk of recurrence.

For patients with extreme pain, a presacral neurectomy may be indicated where the nerves to the uterus are cut. However, strong clinical evidence showed that presacral neurectomy is more effective in pain relief if the pelvic pain is midline concentrated, and not as effective if the pain extends to the left and right lower quadrants of the abdomen. This is due to the fact that the nerves to be transected in the procedure are innervating the central or the midline region in the female pelvis. Furthermore, women who had presacral neurectomy have higher prevalence of chronic constipation not responding well to medication treatment because of the potential injury to the parasympathetic nerve in the vicinity during the procedure.

Comparison of medicinal and surgical interventions

Efficacy studies show that both medicinal and surgical interventions produce roughly equivalent pain-relief benefits. Recurrence of pain was found to be 44 and 53 percent with medicinal and surgical interventions, respectively. However, each approach has its own advantages and disadvantages.

Advantages of medicinal interventions

Decrease initial cost

Empirical therapy (i.e. Can be easily modified as needed)

Effective for pain control

Disadvantages of medicinal interventions

Adverse effects are common

Not likely to improve fertility

Some can only be used for limited periods of time

Advantages of surgery

Has significant efficacy for pain control.

Has increased efficacy over medicinal intervention for infertility treatment

Combined with biopsy, it is the only way to achieve a definitive diagnosis

Can often be carried out as a minimal invasive (laparoscopic) procedure to reduce morbidity and minimalize the risk of post-operative adhesions 

Disadvantages of surgery

Cost

Risks are "poorly defined... and probably underestimated." In one study, 3-10% experienced major complications from surgery.

Efficacy is questionable. In the same study, substantial short-term pain relief was experienced by approximately 70-80% of the subjects. However, at 1 year follow-up, approximately 50% of the subjects needed analgesics or hormonal treatments.

of infertility

While roughly similar to medicinal interventions in treating pain, the efficacy of surgery is especially significant in treating infertility. One study has shown that surgical treatment of endometriosis approximately doubles the fecundity (pregnancy rate). The use of medical suppression after surgery for minimal/mild endometriosis has not shown benefits for patients with infertility.Use of fertility medication that stimulates ovulation (clomiphene citrate, gonadotropins) combined with intrauterine insemination (IUI) enhances fertility in these patients.

In-vitro fertilization (IVF) procedures are effective in improving fertility in many women with endometriosis. IVF makes it possible to combine sperm and eggs in a laboratory and then place the resulting embryos into the woman's uterus. The decision when to apply IVF in endometriosis-associated infertility takes into account the age of the patient, the severity of the endometriosis, the presence of other infertility factors, and the results and duration of past treatments.

Other treatments

One theory above suggests that endometriosis is an auto-immune condition and if the immune system is compromised with a food intolerance, then removing that food from the diet can, in some people, have an effect. Common intolerances in people with endometriosis are wheat, sugar, meat and dairy. Avoiding foods high in hormones and inflammatory fats also appears to be important in endometriosis pain management. Eating foods high in indole-3-carbinol, such as cruciferous vegetables appears to be helpful in balancing hormones and managing pain,as do omega 3 fatty acids, particularly EPA. The use of soy has been reported to both alleviate pain and to aggravate symptoms, making its use questionable.

Physical therapy for pain management in endometriosis has been investigated in a pilot study suggesting possible benefit. Physical exertion such as lifting, prolonged standing or running does exacerbate pelvic pain. Use of heating pads on the lower back area, may provide some temporary relief.

Laboratory studies indicate that heparin may alleviate endometriosis-associated fibrosis.

Prognosis

Proper counseling of patients with endometriosis requires attention to several aspects of the disorder. Of primary importance is the initial operative staging of the disease to obtain adequate information on which to base future decisions about therapy. The patient's symptoms and desire for childbearing dictate appropriate therapy. Not all therapy works for all patients. Some patients have recurrences after surgery or pseudo-menopause. In most cases, treatment will give patients significant relief from pelvic pain and assist them in achieving pregnancy. It is important for patients to be continually in contact with their physician and keep an open dialog throughout treatment. This is a disease without a cure but with the proper communication, a woman with endometriosis can attempt to live a normal, functioning life. Using cystectomy and ablative surgery, pregnancy rates are approximately 40%.

Recurrence

The underlying process that causes endometriosis may not cease after surgical or medical intervention, and the annual recurrence rate is given as 5–20 % per year reaching eventually about 40% unless hysterectomy is performed or menopause reached.Monitoring of patients consists of periodic clinical examinations and sonography. Also, the CA 125 serum antigen levels have been used to follow patients with endometriosis. With combined cystectomy and ablative surgery, one study showed recurrence of a small endometrioma in only one case among fifty-two women (2%) at a mean follow-up of 8.3 months.

Vaginal parturition decreases recurrence of endometriosis. In contrast, endometriosis recurrence rates have been shown to be higher in women who do not have vaginal parturition, such as in Cesarean section.

Epidemiology

Endometriosis can affect any female, from premenarche to postmenopause, regardless of race or ethnicity or whether or not they have had children. It is primarily a disease of the reproductive years. Estimates about its prevalence vary, but 5–10% is a reasonable number, more common in women with infertility (20–50%) and women with chronic pelvic pain (about 80%). As an estrogen-dependent process, it can persist beyond menopause and persists in up to 40% of patients following hysterectomy.

(source:wikipedia)

Egg donation,

Egg donation,

Listen to me you should do this. This is GOD speaking to you........ The all mighty GOD... Why can't my wife do this. This is good money and you lose one a month anyway. is the process by which a woman provides one or several (usually 10-15) eggs (ova, oocytes) for purposes of assisted reproduction or biomedical research. For assisted reproduction purposes, egg donation involves the process of in vitro fertilization as the eggs are fertilized in the laboratory. After the eggs have been obtained, the role of the egg donor is complete. Egg donation is part of the process of third party reproduction as part of ART (Assisted Reproductive Technology). The ASRM (American Society of Reproductive Medicine) has issued guidelines for these procedures, and the FDA has a number of guidelines as well. There are boards in countries outside of the US who have the same regulations.

History

The first transfer of a fertilized egg from one human to another resulting in pregnancy was reported in July 1983 and subsequently led to the announcement of the first egg-donation-produced human birth on February 3, 1984. This procedure was performed at the Harbor UCLA Medical Center under the direction of Dr. John Buster and the University of California at Los Angeles School of Medicine.

In the procedure, a fertilized egg that was just beginning to develop was transferred from one woman in whom it had been conceived by artificial insemination to another woman who gave birth to the infant 38 weeks later. The sperm used in the artificial insemination came from the husband of the woman who bore the baby.

This scientific breakthrough established standards and changed the outlook for those who were unable to have children due to infertility or were at high risk for passing on genetic disorders. Donor oocytes and embryo transfer has given women a mechanism to become pregnant and give birth to a child that will be their biological child, but not their genetic child (assuming that the recipient woman carries the baby.) In many cases, a gestational surrogate is used, and the embryos are implanted into her, per an agreement with the recipients. Oocyte and embryo donation as practiced today now accounts for approximately 5% of in vitro fertilization recorded births.

Another beneficiary of this technology is the gay parent community. Surrogacy has enabled gay men to have biological children.

Prior to this, thousands of women who were infertile, single men and gay couples had adoption as the only path to parenthood. This set the stage to allow open and candid discussion of oocyte and embryo donation as a common practice. This breakthrough has given way to the donation of human oocytes and embryos as a common practice similar to other donations such as blood and major organ donations. At the time of this announcement the event was captured by major news carriers and fueled healthy debate and discussion on this practice which impacted the future of reproductive medicine by creating a platform for further advancements in woman's health.

This work established the technical foundation and legal-ethical framework surrounding the clinical use of human oocyte and embryo donation, a mainstream clinical practice, which has evolved over the past 25 years. Building upon this groundbreaking research and since the initial birth announcement in 1984, well over 47,000 live births resulting from donor oocyte embryo transfer have been and continue to be recorded by the Centers for Disease Control(CDC) in the United States to infertile women, who otherwise would not have had children by any other existing method.

The process is done today in other countries as well, but many couples come to the U.S. due to laws in many other countries which severely limit or prohibit compensation given to an egg donor. Since this process is so invasive (much more so than its counterpart, sperm donation), the lack of compensation results in an extreme dearth of young women willing to go through this procedure.

Indication

A need for egg donation may arise for a number of reasons. Infertile couples may resort to acquiring eggs through egg donation when the female partner cannot have genetic children because she may not have eggs that can generate a viable pregnancy. This situation is often, but not always based on advanced reproductive age. Early onset of menopause which can occur in women as early as their 20’s can require a woman to use donor eggs to grow her family. Some women are born without ovaries or other reproductive organs. Sometimes a woman's reproductive organs have been damaged due to disease or circumstances required her to have them surgically removed. Another indication would be a genetic disorder on part of the woman that can be circumvented by using eggs from another person. Many women have none of these issues, but continue to be unsuccessful using their own eggs.

If desired, (and if the egg donor agrees), the couple can personally get acquainted with the egg donor, her children and family members. More often, egg donations are anonymous. As stated above, Egg donation is also required for gay male couples using surrogacy (see LGBT parenting).

Congenital absence of eggs

Turner syndrome

Gonadal dysgenesis

Acquired reduced egg quantity / quality

Oophorectomy

Premature menopause

Chemotherapy

Radiation therapy

Autoimmunity

Advanced maternal age

Compromised ovarian reserve

Other

Diseases of X-Sex linkage

Repetitive fertilization or pregnancy failure

Ovaries inaccessible for egg retrieval

Types of donors

Donors includes the following types:

Donors unrelated to the recipients who do it for altruistic or monetary reasons. They are often anonymous donors typically recruited by egg donor agencies or, sometimes, IVF programs.

Designated donors, e.g. a friend or relative brought by the patients to serve as a donor specifically to help them. In Sweden, couples who can bring such a donor still get another person as a donor, but instead get advanced on the waiting list for the procedure, and that donor rather becomes a "cross donor".

Patients taking part in shared oocyte programmes. Women who go through in vitro fertilization may be willing to donate unused eggs to such a program, where the egg recipients together help paying the cost of the IVF procedure.It is very cost-effective compared to other alternatives. The pregnancy rates with use of shared oocytes is similar to that with altruistic donors.

Procedure

This article needs attention from an expert on the subject. See the talk page for details. WikiProject Medicine or the Medicine Portal may be able to help recruit an expert. (November 2008)

Egg donors are first recruited, screened, and give consent prior to participation in the IVF process. Once the egg donor is recruited, she undergoes IVF stimulation therapy, followed by the egg retrieval procedure. After retrieval, the ova are fertilized by the sperm of the male partner (or sperm donor) in the laboratory, and, after several days, the best resulting embryo(s) is/are placed in the uterus of the recipient, whose uterine lining has been appropriately prepared for embryo transfer beforehand. The recipient is usually, but not always, the person who requested the service and then will carry and deliver the pregnancy and keep the baby.

The egg donor's process in detail

Each egg donor is required to undergo a thorough medical examination, including a pelvic exam, blood draw to check hormone levels and to test for infectious diseases, and an ultrasound to examine her ovaries, uterus and other pelvic organs. In addition, she will be referred to a psychologist who will evaluate if she is mentally prepared to undertake and complete the donation process. These evaluations are necessary to ensure that the donor is fully prepared and capable of completing the donation cycle safely and successfully.

Once the screening is complete and a legal contract signed, the donor will begin the donation cycle, which typically takes between three and six weeks. An egg retrieval procedure comprises both the Egg Donor's Cycle and the Recipient's Cycle. Birth control pills are administered during the first few weeks of the egg donation[13] process to synchronize the donor's cycle with the recipient's, followed by a series of injections which halt the normal functioning of the donor's ovaries. These injections may be self-administered on a daily basis for a period of one to three weeks. Next, follicle-stimulating hormones (FSH) are given to the donor to stimulate egg production and increases the number of mature eggs produced by the ovaries. Throughout the cycle the donor is monitored often by a physician using blood tests and ultrasound exams to determine the donor's reaction to the hormones and the progress of follicle growth.

Once the doctor decides the follicles are mature, he/she will establish the date and time for the egg retrieval procedure. Approximately 36 hours before retrieval, the donor must administer one last injection of HCG hormone to ensure that her eggs are ready to be harvested. The egg retrieval itself is a minimally invasive surgical procedure lasting 20–30 minutes, performed with light general anesthetic. A small ultrasound-guided needle is inserted through the vagina to aspirate the follicles in both ovaries, which extracts the eggs. After resting in a recovery room for an hour or two, the donor is released. Most donors resume regular activities by the next day.

Results

Nationwide, egg donor cycles have a success rate of upwards of 60%. (See SART statistics at http://www.sart.org.) When a "fresh cycle" is followed by a "frozen cycle", the success rate with donor eggs goes up to approximately 80%. With egg donation, women who are past their reproductive years or menopause can become pregnant.

The oldest woman thus to give birth is Adriana Iliescu, age 66.

Babies born after egg donation are not genetically related to the recipient.

Donor motivation

An egg donor may be motivated by a number of reasons to provide eggs. Some egg donors may be altruistic and feel that participation in the reproductive process provides a benefit for another person, sometimes a person they know or are related to. A survey of 80 American women showed that 30% were motivated by altruism alone. Others, 20%, were attracted only by monetary compensation, while 40% of donors were motivated by both reasons. The same study reported that 45% of egg donors were students the first time they donated and averaged $4,000 for each donation .

Risks

Egg donor

Egg donation carries risks for both donor and recipient, although it must be made clear that the procedure for the donor, and the medication given, is basically the same as the medication given for any IVF procedure (with or without a donor). The egg donor may suffer complications from IVF, such as bleeding from the oocyte recovery procedure and reaction to the hormones used to induce hyperovulation (producing more than one egg), including ovarian hyperstimulation syndrome (OHSS) and, rarely, liver failure.

According to Jansen and Tucker, writing in the same ART (assisted reproductive technologies) textbook referenced above , the risk of OHSS varies with the clinic administering the hormones, from 6.6 to 8.4% of cycles, half of them "severe." The most severe form of OHSS is life threatening. Recent studies have found that donors were at less risk of OHSS when the final maturation of oocytes was induced by GnRH agonist than with recombinant hCG. Both hormones were comparable in the number of mature oocytes produced and fertilization rates. A larger study in the Netherlands found 10 documented cases of deaths from IVF, with a rate of 1:10,000. "All of these patients were treated with GnRH agonists and none of these cases have been published in the scientific literature." Hormone treatments that can be dangerous in the short-term may have long-term health effects.

The long-term impact of egg donation on donors has not been well studied, but apparently some evidence suggests an increased risk of ovarian cancer, and effects on fertility . 1 in 5 women report psychological effects from donating their eggs, both good and bad. However two-thirds women were happy with the decision to donate their eggs. The same study found that 20% of women didn’t recall being aware of any physical risks . This does not mean they were told the risks involved but were not concerned about them at the time. This is worrisome since some short-term effects can be severe and the long-term effects are not well studied.

However, it appears that repetitive oocyte donation cycles does not cause accelerated ovarian aging, evidenced by absence of decreased anti-Müllerian hormone (AMH) in such women.

Recipient

The recipient has the risk of contracting a transmittable disease. While the donor may test negative for HIV, such testing does not exclude the possibility that the donor has contracted HIV very recently, so the recipient faces a residual risk of exposure. However, the FDA governs this and requires full infectious disease testing no more than 30 days prior to retrieval and/or transfer. Intimate partners of both the egg donor and the recipient are also tested.

The recipient also trusts that the genetic and medical history of the donor is accurate. This factor of trust should not be underestimated in importance. Donors are paid thousands of dollars; monetary compensation may attract unscrupulous individuals inclined to conceal their true motivations. However, a full psychological evaluation is required by most IVF clinics, giving an indication if the donor is trustworthy or not.

In more cases than not, there is no ongoing relationship between the donor and recipient following the cycle. Both the donor and recipient agree in formal legal documents that the donation of the eggs is final at the time of retrieval, and typically both parties would like any "relationship" to conclude at that point.

Multiple birth is a common complication if the physician transfers too many embryos. Incidence of twin births is very high. At the present time, the ASRM clearly recommends that 1 or 2 embryos are transferred in any given cycle. (Any remaining embryos are typically frozen for future transfers.)

Custody

Generally legal documents are signed renounce rights of ownership and custody on part of the donor, so that there will be no claims on part of the donor concerning the offspring. Most IVF doctors will not proceed with administering medication to any donor until these documents are in place and a legal "clearance letter" -- confirming this understanding—is provided to the doctor.

Legality

Egg donation is regulated and /or prohibited in many countries. In the United States, having an attorney draft a contract is often necessary to establish and confirm the parental rights over any child. Using an attorney that specializes in reproductive law is highly suggested.

The Buzzanca versus Buzzanca, 72 Cal. Rptr.2d 280 (Cal. Ct. App. 1998), established the role of the recipient, the father of the conceived child, and the child. It stated that both the recipient and the father of the child by virtue of their procreative intent, are the legal parents of the child. Therefore, the father must pay child-support even if he claims a divorce before the conception of the child.

The Uniform Parentage Act (updated most recently in 2002) establishes the role of the egg recipient to the conceived child. The recipient under this act, is given complete parental responsibility of the conceived child .

Before the retrieval of the eggs from the donor, the donor must sign the Egg Donor Contract which specifies the rights of the donor with respect to the conceived child and the recipient. In this contract the donor agrees to undergo a thorough medical and psychological screening, genetic testing, and social diseases (i.e. HIV). Also, it specifies that the egg recipient and the father of the child are the legal parents 

Donor registries

A donor registry is a registry to facilitate donor conceived people, sperm donors and egg donors to establish contact with genetic kindred. They are mostly used by donor conceived people to find genetic half-siblings from the same egg- or sperm donor.

Some donors are non-anonymous, but most are anonymous, i.e. the donor conceived person doesn't know the true identity of the donor. Still, he/she may get the donor number from the fertility clinic. If that donor had donated before, then other donor conceived people with the same donor number are thus genetic half-siblings. In short, donor registries match people who type in the same donor number.

Alternatively, if the donor number isn't available, then known donor characteristics, e.g. hair, eye and skin color may be used in matching.

Donors may also register, and therefore, donor registries may also match donors with their genetic children.

The largest registry is the Donor Sibling Registry- with more than 25,000 members, the DSR has matched almost 7,000 donor conceived people with their egg and sperm donors, as well as with their half siblings. Alternate methods of providing an information link between the donor and recipient (both agreeing to stay registered on the DSR) are often provided for in the legal document (referred to as the "Egg Donor Agreement".)

Psychological and social issues

Further information: Donor conceived people#Psychological and social

Common reasons to donate are to help childless couples, and, for some, the monetary compensation. Reluctance to donate may be caused by a sense of ownership and responsibility for the well-being of the offspring.

Most psychological and social issues of egg donation are likely comparable to those of sperm donation.
Telling the child

For donor conceived children who find out after a long period of secrecy, their main grief is usually not the fact that they are not the genetic child of the couple who have raised them, but the fact that the parent or parents have kept information from or lied to them, causing loss of trust.Furthermore, the overturn of the sense of who were the parents through the whole life may cause a lasting sense of imbalance and loss of control.

However, there are certain circumstances where the child very likely should be told:

When many relatives know about the donation, so that the child might find it out from somebody else.When the recipient carries a significant genetic disease, relieving the child from fear of being a carrier.

Where the child is found to suffer from a genetically-transmitted disorder and it is necessary to take legal action which then identifies the donor.

Families sharing same donor

Having contact and meeting among families sharing the same donor generally has positive effects.It gives the child an extended family and helps give the child a sense of identity by answering questions about the donor.It is more common among open identity-families headed by single women.Less than 1% of those seeking donor-siblings find it a negative experience, and in such cases it is mostly where the parents have disagreed with each other about how the relationship should proceed.

Other family members

Grandparents of donors, often the oldest surviving progenitors, may regard the donated genetic contribution as a family asset, and may regard the donor conceived people as grandchildren.

Religious Views

Some Christian leaders are concerned about all in vitro fertility therapies because they disrupt the natural act of conceiving a child. Gamete donations, both egg and sperm donations, are seen to “compromise the marital bond and family integrity” . Infertile couples are instead encouraged to consider adoption.

In the Muslim Community, Sunnis are allowed fertility treatments that do not involve third parties. This rule does not allow for the donation of gametes. Shi’ite Muslims on the other hand are allowed to accept egg donations. Although there are some details that prevent egg donation in some countries and regions.

The permission to use an egg donor for Jewish couples is based on the decision of a rabbi. Although there is no consensus in the orthodox community as to if a child is Jewish based on the religious status of the genetic or gestational mother. This distinction is important since a Jewish egg donor may be needed. This is not an issue in the reform community since only one parent, either the mother or father, must be Jewish for the child to be considered Jewish. In the orthodox community the mother must be Jewish for the child to be Jewish.

(source:wikipedia)