Ovulation | |
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Identifiers | |
MeSH | D010060 |
TE | E1.0.0.0.0.0.7 |
Anatomical terminology |
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and after the follicular phase. Ovulation is stimulated by an increase in luteinizing hormone (LH). The ovarian follicles rupture and release the secondary oocyte ovarian cells. [1]
After ovulation, during the luteal phase, the egg will be available to be fertilized by sperm. If it is not, it will break down in less than a day. Meanwhile, the uterine lining (endometrium) continues to thicken to be able to receive a fertilized egg. If no conception occurs, the uterine lining will eventually break down and be shed from the body via the vagina during menstruation. [2]
Some people choose to track ovulation in order to improve or aid becoming pregnant by timing intercourse with the their ovulation. [3] The signs of ovulation may include cervical mucus changes, mild cramping in the abdominal area, and a small rise in basal body temperature. Medication is also sometimes required by those experiencing infertility to induce ovulation. [3]
Ovulation occurs about midway through the menstrual cycle, after the follicular phase. The days in which a woman is most fertile can be calculated based on the date of the last menstrual period and the length of a typical menstrual cycle. [4] The few days surrounding ovulation (from approximately days 10 to 18 of a 28-day cycle), constitute the most fertile phase. [5] [6] [7] [8] The time from the beginning of the last menstrual period (LMP) until ovulation is, on average, 14.6 days, but with substantial variation among females and between cycles in any single female, with an overall 95% prediction interval of 8.2 to 20.5 days. [9]
The process of ovulation is controlled by the hypothalamus of the brain and through the release of hormones secreted in the anterior lobe of the pituitary gland, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). [10] In the preovulatory phase of the menstrual cycle, the ovarian follicle will undergo a series of transformations called cumulus expansion, which is stimulated by FSH. After this is done, a hole called the stigma will form in the follicle, and the secondary oocyte will leave the follicle through this hole. Ovulation is triggered by a spike in the amount of FSH and LH released from the pituitary gland. During the luteal (post-ovulatory) phase, the secondary oocyte will travel through the fallopian tubes toward the uterus. If fertilized by a sperm, the fertilized secondary oocyte or ovum may implant there 6–12 days later. [11]
The follicular phase (or proliferative phase) is the phase of the menstrual cycle during which the ovarian follicles mature. The follicular phase lasts from the beginning of menstruation to the start of ovulation. [12] [13]
For ovulation to be successful, the ovum must be supported by the corona radiata and cumulus oophorous granulosa cells. [14] The latter undergo a period of proliferation and mucification known as cumulus expansion. Mucification is the secretion of a hyaluronic acid-rich cocktail that disperses and gathers the cumulus cell network in a sticky matrix around the ovum. This network stays with the ovum after ovulation and has been shown to be necessary for fertilization. [15] [16]
Estrogen levels peak towards the end of the follicular phase, around 12 and 24 hours. This, by positive feedback, causes a surge in levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This lasts from 24 to 36 hours, and results in the rupture of the ovarian follicles, causing the oocyte to be released from the ovary. [17]
Through a signal transduction cascade initiated by LH, which activates the pro-inflammatory genes through cAMP secondary messenger, proteolytic enzymes are secreted by the follicle that degrade the follicular tissue at the site of the blister, forming a hole called the stigma. The secondary oocyte leaves the ruptured follicle and moves out into the peritoneal cavity through the stigma, where it is caught by the fimbriae at the end of the fallopian tube. After entering the fallopian tube, the oocyte is pushed along by cilia, beginning its journey toward the uterus. [10]
By this time, the oocyte has completed meiosis I, yielding two cells: the larger secondary oocyte that contains all of the cytoplasmic material and a smaller, inactive first polar body. Meiosis II follows at once but will be arrested in the metaphase and will so remain until fertilization. The spindle apparatus of the second meiotic division appears at the time of ovulation. If no fertilization occurs, the oocyte will degenerate between 12 and 24 hours after ovulation. [18] Approximately 1–2% of ovulations release more than one oocyte. This tendency increases with maternal age. Fertilization of two different oocytes by two different spermatozoa results in fraternal twins. [10]
The precise moment of ovulation was captured on film for the first time in 2008, coincidentally, during a routine hysterectomy procedure. According to the attending gynecologist, the ovum's emergence and subsequent release from the ovarian follicle occurred within a 15-minute timeframe. [19]
The follicle proper has met the end of its lifespan. Without the oocyte, the follicle folds inward on itself, transforming into the corpus luteum (pl. corpora lutea), a steroidogenic cluster of cells that produces estrogen and progesterone. These hormones induce the endometrial glands to begin production of the proliferative endometrium and later into secretory endometrium, the site of embryonic growth if implantation occurs. The action of progesterone increases basal body temperature by one-quarter to one-half degree Celsius (one-half to one degree Fahrenheit). The corpus luteum continues this paracrine action for the remainder of the menstrual cycle, maintaining the endometrium, before disintegrating into scar tissue during menses. [20]
The start of ovulation may be detected by signs that are not readily discernible other than to the ovulating female herself, thus humans are said to have a concealed ovulation. [21] In many animal species there are distinctive signals indicating the period when the female is fertile. Several explanations have been proposed to explain concealed ovulation in humans.
Females near ovulation experience changes in the cervical mucus, and in basal body temperature. Furthermore, many females experience secondary fertility signs including Mittelschmerz (pain associated with ovulation) and a heightened sense of smell, and can sense the precise moment of ovulation. [22] [23] However, midcycle pain may also not be due to Mittelschmerz, but due to other factors such as cysts, endometriosis, sexually transmitted infections, or an ectopic pregnancy. [24] Other possible signs of ovulation include tender breasts, bloating, and cramps, although these symptoms are not a guarantee that ovulation is taking place. [25] [26]
Many females experience heightened sexual desire in the several days immediately before ovulation. [27] One study concluded that females subtly improve their facial attractiveness during ovulation. [28]
Symptoms related to the onset of ovulation, the moment of ovulation and the body's process of beginning and ending the menstrual cycle vary in intensity with each female but are fundamentally the same. The charting of such symptoms — primarily basal body temperature, mittelschmerz and cervical position — is referred to as the sympto-thermal method of fertility awareness, which allow auto-diagnosis by a female of her state of ovulation. Once training has been given by a suitable authority, fertility charts can be completed on a cycle-by-cycle basis to show ovulation. This gives the possibility of using the data to predict fertility for natural contraception and pregnancy planning.
Urine levels of the hormone pregnanediol 3-glucuronide of over 5 μg/mL has been used to confirm ovulation. This test has a 100% specificity over 107 women. [30]
Disorders of ovulation, also known as ovulatory disorders are classified as menstrual disorders and include oligoovulation (infrequent or irregular ovulation) and anovulation (absence of ovulation): [31]
The World Health Organization (WHO) has developed the following classification of ovulatory disorders: [32]
Menstrual disorders can often indicate ovulatory disorder. [34]
Ovulation induction is a promising assisted reproductive technology for patients with conditions such as polycystic ovary syndrome (PCOS) and oligomenorrhea. It is also used in in vitro fertilization to make the follicles mature before egg retrieval. Usually, ovarian stimulation is used in conjunction with ovulation induction to stimulate the formation of multiple oocytes. [35] Some sources [35] include ovulation induction in the definition of ovarian stimulation.
A low dose of human chorionic gonadotropin (HCG) may be injected after completed ovarian stimulation. Ovulation will occur between 24 and 36 hours after the HCG injection. [35]
By contrast, induced ovulation in some animal species occurs naturally, ovulation can be stimulated by coitus. [36]
Combined hormonal contraceptives inhibit follicular development and prevent ovulation as a primary mechanism of action. [37] The ovulation-inhibiting dose (OID) of an estrogen or progestogen refers to the dose required to consistently inhibit ovulation in women. [38] Ovulation inhibition is an antigonadotropic effect and is mediated by inhibition of the secretion of the gonadotropins, LH and FSH, from the pituitary gland.
In assisted reproductive technology including in vitro fertilization, cycles where a transvaginal oocyte retrieval is planned generally necessitates ovulation suppression, because it is not practically feasible to collect oocytes after ovulation. For this purpose, ovulation can be suppressed by either a GnRH agonist or a GnRH antagonist, with different protocols depending on which substance is used.
Most women who are able to conceive are fertile for an estimated five days before ovulation and one day after ovulation. [39] There is some evidence that for couples who have been trying to conceive a child for less than 12 months, and the female is under 40 years old, practicing timed intercourse (timing intercourse with ovulation using urine tests that predict ovulation) may help improve the rate of pregnancy and live births. [39] The role that stress plays in ovulation, fertility, and understanding the biological basis for stress-induced anovulation and the role of cortisol is not entirely clear. [40]
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eggs and the cyclic release of estrogen and progesterone. The uterine cycle governs the preparation and maintenance of the lining of the uterus (womb) to receive an embryo. These cycles are concurrent and coordinated, normally last between 21 and 35 days, with a median length of 28 days. Menarche usually occurs around the age of 12 years; menstrual cycles continue for about 30–45 years.
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and luteinizing hormone (LH) work together in the reproductive system.
Oogenesis or ovogenesis is the differentiation of the ovum into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated in the embryonic stage.
Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulation is a common cause of infertility.
An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with the potential to release an egg cell (ovum) at ovulation for fertilization. These eggs are developed once every menstrual cycle with around 450–500 being ovulated during a woman's reproductive lifetime.
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete in the ovary of mammals.
In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains an immature oocyte. Folliculogenesis describes the progression of a number of small primordial follicles into large preovulatory follicles that occurs in part during the menstrual cycle.
The hypothalamic–pituitary–gonadal axis refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. Because these glands often act in concert, physiologists and endocrinologists find it convenient and descriptive to speak of them as a single system.
The menstrual cycle is on average 28 days in length. It begins with menses during the follicular phase, followed by ovulation and ending with the luteal phase. while historically, medical experts believed the luteal phase to be relatively fixed at approximately 14 days, recent research suggests that there can be wide variability in luteal phase lengths not just from person to person, but from cycle to cycle within one person. The luteal phase is characterized by changes to hormone levels, such as an increase in progesterone and estrogen levels, decrease in gonadotropins such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), changes to the endometrial lining to promote implantation of the fertilized egg, and development of the corpus luteum. In the absence of fertilization by sperm, the corpus luteum degenerates leading to a decrease in progesterone and estrogen, an increase in FSH and LH, and shedding of the endometrial lining (menses) to begin the menstrual cycle again.
The follicular phase, also known as the preovulatory phase or proliferative phase, is the phase of the estrous cycle during which follicles in the ovary mature from primary follicle to a fully mature graafian follicle. It ends with ovulation. The main hormones controlling this stage are secretion of gonadotropin-releasing hormones, which are follicle-stimulating hormones and luteinising hormones. They are released by pulsatile secretion. The duration of the follicular phase can differ depending on the length of the menstrual cycle, while the luteal phase is usually stable, does not really change and lasts 14 days.
Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation.
An antral or secondary follicle, also known as Graafian follicle and tertiary follicle, is an ovarian follicle during a certain latter stage of folliculogenesis.
Controlled ovarian hyperstimulation is a technique used in assisted reproduction involving the use of fertility medications to induce ovulation by multiple ovarian follicles. These multiple follicles can be taken out by oocyte retrieval for use in in vitro fertilisation (IVF), or be given time to ovulate, resulting in superovulation which is the ovulation of a larger-than-normal number of eggs, generally in the sense of at least two. When ovulated follicles are fertilised in vivo, whether by natural or artificial insemination, there is a very high risk of a multiple pregnancy.
In vitro maturation (IVM) is the technique of letting the contents of ovarian follicles and the oocytes inside mature in vitro. It can be offered to women with infertility problems, combined with In Vitro Fertilization (IVF), offering women pregnancy without ovarian stimulation.
Poor ovarian reserve is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment. Recent research suggests that premature ovarian aging and premature ovarian failure may represent a continuum of premature ovarian senescence. It is usually accompanied by high FSH levels.
Fertility testing is the process by which fertility is assessed, both generally and also to find the "fertile window" in the menstrual cycle. General health affects fertility, and STI testing is an important related field.
Infertility in polycystic ovary disease (PCOS) is a hormonal imbalance in women that is thought to be one of the leading causes of female infertility. Polycystic ovary syndrome causes more than 75% of cases of anovulatory infertility.
Gonadotropin surge-attenuating factor (GnSAF) is a nonsteroidal ovarian hormone produced by the granulosa cells of small antral ovarian follicles in females. GnSAF is involved in regulating the secretion of luteinizing hormone (LH) from the anterior pituitary and the ovarian cycle. During the early to mid-follicular phase of the ovarian cycle, GnSAF acts on the anterior pituitary to attenuate LH release, limiting the secretion of LH to only basal levels. At the transition between follicular and luteal phase, GnSAF bioactivity declines sufficiently to permit LH secretion above basal levels, resulting in the mid-cycle LH surge that initiates ovulation. In normally ovulating women, the LH surge only occurs when the oocyte is mature and ready for extrusion. GnSAF bioactivity is responsible for the synchronised, biphasic nature of LH secretion.
Ovarian follicle dominance is the process where one or more follicles are selected per cycle to ovulate.
Female fertility agents are medications that improve female’s ability to conceive pregnancy. These agents are prescribed for infertile female who fails to conceive pregnancy after 1-year of regular and unprotected sexual intercourse. The following will cover the advancements of female fertility agents, major causes of female infertility. Next, it emphasizes on common female fertility agents in terms of their mechanism of action, side effects, fetal consideration and clinical application and ended up by the introduction of supplements and herbal medicines for female infertility.