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Fertility testing | |
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Purpose | assess fertility |
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.
Healthy women are fertile from puberty until menopause, although fertility is typically much reduced towards the extremes of this period. The onset of puberty is typically identified by menarche and the presence of secondary sexual characteristics such as breast development, the appearance of pubic hair and changes to body fat distribution. The end of fertility typically comes somewhat before menopause, as fertility declines to a point where establishing a viable pregnancy is very unlikely.
Various methods of predicting the timing of ovulation exist, some of which may be performed at home or in a clinical setting. Knowing the timing of ovulation can help a woman to determine the days of the menstrual cycle that are most likely to result in conception.
The cervix is a structure between the vaginal canal and the uterus. The cervical cells secrete mucus that changes its consistency over different parts of the menstrual cycle. During the fertile window, the mucus increases in quantity and becomes clear and stretchy and is known as "egg-white cervical mucus." This mucus allows sperm to survive in and travel through it. In contrast, when outside of the fertile window, the mucus does not stretch, is sticky, and is not clear.
The stretch test can be performed prior to and immediately after urination. Mucus can be sampled with by either wiping with toilet paper or inserting a clean finger into the vagina. The mucus quality can then be observed by stretching the mucus between the finger and thumb as shown in the image. [2]
Urinary ovulation prediction kits are typically found over-the-counter and there are many brands to choose from. This test measures the amount of luteinizing hormone, a hormone that increases just before ovulation, that is in the urine. Before ovulation, the luteinizing hormone levels dramatically increase; this is known as the "LH surge". This test can recognize the LH surge about 1-1.5 days prior to ovulation. Additionally, some ovulation prediction kits detect estrone-3-glucuronide. This is a breakdown product of estrogen and will have increased levels in the urine around the time of ovulation. This test is able to detect luteinizing hormone and estrone-3-glucuronide 90% of the time.
This test can be used in multiple ways. A few drops of urine can be added to the test device tip. Alternatively, the test device tip can be held in the urine stream. Finally, the test device tip can be dipped into a cup of urine. The test will indicate positive or negative results in about five minutes. [3]
A fertility monitor is an electronic device which may use various methods to assist the user with fertility awareness. A fertility monitor may analyze changes in hormone levels in urine, basal body temperature, electrical resistance of saliva and vaginal fluids, or a combination of these methods. These devices may assist in pregnancy achievement. An updated 2023 Cochrane review has found that the use of urine ovulation test probably improves life births in women under 40 but that further study on risk and benefits is needed on timed intercourse via the use of these test. [4]
Daily ultrasounds are used to follow the development of follicles which can help predict ovulation. The ultrasounds can predict ovulation with a 24-hour overlap to actual ovulation. [5]
Serum progesterone level is measured during the mid-luteal phase of the menstrual cycle. In women who are experiencing infertility, this test is only somewhat helpful for predicting ovulation. [6]
The cervix becomes soft, high, open and wet during the fertile window.
Basal body temperature changes during the menstrual cycle. Higher levels of progesterone released during the menstrual cycle causes an abrupt increase in basal body temperature by 0.5 °C to 1 °C at the time of ovulation. [7] This enables identification of the fertile window through the use of commercial thermometers. This test can also indicate if there are issues with ovulation. [8]
In women who have regular menstrual cycles, the fertile window occurs at approximately the same time every month. If the first day of menses is considered day 1, then ovulation occurs around day 14. In regular cycles that are 26–32 days long, the fertile window occurs on days 8–19. [9]
Women who are of fertile age may be infertile for a number of reasons. Various diagnostic tests are available to establish reasons. Several diagnostic procedures and clinical instruments are used for to evaluate anatomical causes of infertility. Some use a combination of imaging such as an X-ray or ultrasound with a contrast agent to visualize anatomic structures within the uterus and fallopian tubes. An electronic, flexible scope with a camera can also be inserted through the cervix to display live images. A variety of hormones can be tested at different times in the menstrual cycle to determine the likelihood of different responses to stimulation for In vitro fertilization (IVF).
Test | Method | Invasiveness |
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Anti-Müllerian hormone testing | Lab test | Blood draw |
Cycle-day-three follicle-stimulating hormone (FSH) testing | Lab test | Blood draw |
Clomiphene citrate challenge test (CCCT) | Lab test | Blood draw |
Antral follicle count | Ultrasound imaging | Non-invasive |
X-ray hysterosalpingography | X-ray imaging | Minimally invasive |
Hystero contrast sonography (HyCoSy) | Ultrasound with contrast dye | Minimally invasive |
Saline infusion sonohysterography (SHG) | Ultrasound with saline | Minimally invasive |
Hystero foam sonography (HyFoSy) | Ultrasound with foam | Minimally invasive |
Ovarian ultrasound | Ultrasound | Minimally invasive |
Three-dimensional sonography | Ultrasound with 3D imaging | Minimally invasive |
Hysteroscopy | Transvaginal endoscope | Invasive |
Laparoscopy with chromotubation | Abdominal laparoscope | Invasive |
Anti-Müllerian hormone (AMH) is a glycoprotein hormone produced by granulosa cells in preantral and small antral follicles of the ovaries. [11] Testing for plasma levels of AMH allows physicians to estimate ovarian reserve. Estimations of ovarian reserve help to determine the likelihood of pregnancy by In vitro fertilization (IVF). AMH testing is considered to be one of the most accurate estimates of ovarian reserve, can be used for assessment at any point in the menstrual cycle, and is non-invasive. [12]
Follicle-stimulating hormone (FSH) is a peptide hormone which causes the primordial follicles in the ovaries to develop and to produce estrogen. [13] FSH levels are elevated early in the cycle of women who have lower ovarian reserve, because their follicles do not produce enough estrogen to inhibit FSH production, [14] therefore high levels early on in a woman's menstrual cycle can indicate lower ovarian reserve and lower likelihood of retrieving eggs for IVF. To test for ovarian reserve in women with infertility, FSH levels are measured from blood samples taken on day three of the menstrual cycle and compared to standards to determine the likelihood of pregnancy after IVF treatment.
The clomifene citrate challenge test is similar to cycle-day-three FSH testing. To perform this test blood samples are taken on day three of the menstrual cycle to obtain FSH and estradiol levels, then 100 mg of clomiphene citrate are given orally once a day on days 5 through 9 of the menstrual cycle, and finally on day 10 of the menstrual cycle a second blood sample is taken to measure FSH levels. CCCT is not better at predicting ovarian response in IVF patients than baseline FSH on day 3. [15]
Antral follicles are cells early in the process of developing from an oogonium into a mature oocyte. A physician may use a transvaginal ultrasound to visualize and count the number of antral follicles in each of a woman's ovaries in order to determine her ovarian reserve; however AFC is not predictive of embryo quality. [12] A higher number of antral follicles indicates a higher likelihood of pregnancy by IVF.
Hysterosalpingography (HSG) is an invasive x-ray imaging technique used to evaluate the shape and size of the uterus and openness of the fallopian tubes. It is a diagnostic test used in the investigation of infertility from genetic or infectious causes such as uterine fibroids, uterine polyps, uterine anomalies, scarring or tumors. [16]
A HSG is performed after menses and before ovulation during the first half of a menstrual cycle. It is not performed if the patient is pregnant, has a pelvic infection, or heavy bleeding at the time of the test. [17]
The procedure usually takes 30 minutes and often takes place in an outpatient setting such as a hospital or clinic. The patient is draped and positioned on her back as if for a pelvic exam with feet elevated. A speculum is used to visualize the cervix. The cervix is cleaned with an antiseptic and injected with a local anesthetic to minimize discomfort and pain. A small catheter is used to fill the uterus with an iodinated contrast dye. X-ray images are taken as the contrast dye makes its way through the uterus and fallopian tubes. After images have been captured, the catheter is removed and contrast dye may either spill outside of the vagina or become absorbed. [16] [17]
Risks associated with HSG are rare and include exposure to radiation, infection, allergic reactions to the contrast dye or antiseptic. It is normal for patients to experience mild to moderate abdominal cramping, pain and vaginal spotting for a few days after the procedure. [16]
Hystero contrast sonography (HyCoSy) is a transvaginal ultrasound imaging technique used to evaluate the uterus, fallopian tubes and ovaries. It is a screening test used to determine the need for a diagnostic laparoscopy. [18]
A HyCoSy is typically performed after menses and before ovulation during the first half of a menstrual cycle. Unlike a HSG, a HyCoSy can be used to investigate causes of heavy bleeding. [19]
The procedure usually takes 15–20 minutes and often takes place in an outpatient setting such as a hospital or clinic. The patient is draped and positioned on her back as if for a pelvic exam with feet elevate. A speculum is used to visualize the cervix. The cervix is cleaned with an antiseptic such as iodine and injected with a local anesthetic to minimize discomfort and pain. A small catheter is used to fill the uterus and fallopian tubes with a contrast agent consisting of a galactose solution called Echovist to enhance visibility. A transvaginal ultrasound is inserted into the vagina and manually positioned to visualize the uterus, fallopian tubes, and ovaries. Once images have been captured, the ultrasound probe and catheter are removed. The contrast agent used during the study may either spill outside of the vagina or become absorbed. [18]
HyCoSy does not carry the same risks as X-ray hysterosalpingography because it does not use radiation or iodinated contrast dye.
Saline infusion sonohysterography is identical in procedure to hystero contrast sonography (HyCoSy) but uses saline instead of a contrast agent. [18]
An alternative to saline and Echovist, the galactose solution used to enhance visualization of anatomic features via ultrasound in HyCoSy, was needed because of limitations and high costs. [18] A sterile gel foam designed for gynecological use paved the entry for a new technique called hystero foam sonography (HyFoSy). The gel offers more stability than saline and patients may experience less discomfort and fluid leakage. [18]
Ultrasound scans of the ovaries (optimally by transvaginal ultrasonography) may be conducted to establish the development of ovarian follicles. This can be useful particularly in the diagnosis of polycystic ovary syndrome.
Three-dimension sonography is a 3D ultrasound technique that uses a series of 2D images to render 3D images of the uterus and fallopian tubes.
Hysteroscopy is used to visualize the inside of the uterus using a thin, lighted, flexible camera that is inserted vaginally and through the cervix. The camera projects live images on an external screen. It is used to evaluate intrauterine causes of infertility.
Laparoscopy is a minimally-invasive surgical procedure in which a camera is inserted into the abdominal cavity via a small (0.5 - 1.5 cm) incision. It is often used to diagnose endometriosis. Chromopertubation is a combined laparoscopic procedure commonly referred to as a "laparoscopy and dye" test. It uses the injection of a blue dye solution (methylene blue or indigo carmine) into the uterus to help determine the openness of the fallopian tubes. Though considered to be a "gold standard" for diagnosing disorders of fallopian tube patency, it is an invasive procedure requiring general anesthesia. [20]
Men who have gone through puberty should be fertile throughout life. The semen in ejaculate contains sex cells called sperm. After intercourse, sperm travel to the egg through the female reproductive tract, typically causing fertilisation to occur in the fallopian tubes.
Fertility testing for men involves semen testing and genetic testing, as other factors such as impotence are obvious. Semen can be tested for sperm count, sperm motility, sperm morphology, pH, volume, fructose content, and acrosome activity. Checks are also made to identify undescended testicles and retrograde ejaculation, along with medical history, such as cancer treatment, radiation, drug use, etc. In some cases the hamster zona-free ovum test may also be used to diagnose fertility. Genetic testing and chromosomal analysis can rule out some other causes of male infertility, such as Klinefelter syndrome.
A recent study identified epigenetic patterns in male sperm that may contribute to infertility. [21]
Fertility awareness (FA) refers to a set of practices used to determine the fertile and infertile phases of a woman's menstrual cycle. Fertility awareness methods may be used to avoid pregnancy, to achieve pregnancy, or as a way to monitor gynecological health.
The ovary is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocrine glands, secreting various hormones that play a role in the menstrual cycle and fertility. The ovary progresses through many stages beginning in the prenatal period through menopause.
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.
Ovulation is the release of egg cells from the ovaries as part of the ovarian cycle for most vertebrates. In women, this event occurs at the end of the follicular phase, when the ovarian follicles rupture and release the secondary oocyte ovarian cells.
Mittelschmerz is a term for pain due to ovulation. It occurs mid-cycle and can last minutes to up to several days. The pain affects one side of the lower abdomen and may be dull or sharp in nature. Other symptoms may include spotting. Often it occurs monthly and may alternate sides.
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.
The human female reproductive system is made up of the internal and external sex organs that function in the reproduction of new offspring. The reproductive system is immature at birth and develops at puberty to be able to release matured ova from the ovaries, facilitate their fertilization, and create a protective environment for the developing fetus during pregnancy. The female reproductive tract is made of several connected internal sex organs—the vagina, uterus, and fallopian tubes—and is prone to infections. The vagina allows for sexual intercourse, and is connected to the uterus at the cervix. The uterus accommodates the embryo by developing the uterine lining.
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.
Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options available for men.
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.
Ovarian reserve is a term that is used to determine the capacity of the ovary to provide egg cells that are capable of fertilization resulting in a healthy and successful pregnancy. With advanced maternal age, the number of egg cell that can be successfully recruited for a possible pregnancy declines, constituting a major factor in the inverse correlation between age and female fertility.
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. Unlike the follicular phase which can vary in length among individuals, the luteal phase is typically fixed at approximately 14 days and 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.
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.
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.
The fallopian tubes, also known as uterine tubes, oviducts or salpinges, are paired tubular sex organs in the human female body that stretch from the ovaries to the uterus. The fallopian tubes are part of the female reproductive system. In other vertebrates, they are only called oviducts.
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.