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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Symptoms-based methods of fertility awareness may be used to detect ovulation or to determine that cycles are anovulatory. Charting of the menstrual cycle may be done by hand, or with the aid of various fertility monitors. Records of one of the primary fertility awareness signs—basal body temperature—can detect ovulation by identifying the shift in temperature which takes place after ovulation. It is said to be the most reliable way of confirming whether ovulation has occurred.
Women may also use ovulation predictor kits (OPKs) which detect the increase in luteinizing hormone (LH) levels that usually indicates imminent ovulation. For some women, these devices do not detect the LH surge, or high levels of LH are a poor predictor of ovulation; this is particularly common in women with PCOS. In such cases, OPKs and those fertility monitors which are based on LH may show false results, with an increased number of false positives or false negatives. Dr Freundl from the University of Heidelberg suggests that tests which use LH as a reference often lack sensitivity and specificity.
Perimenopause is a natural stage of life. It is not a disease or a disorder. Therefore, it does not automatically require any kind of medical treatment. However, in those cases where the physical, mental, and emotional effects of perimenopause are strong enough that they significantly disrupt the life of the woman experiencing them, palliative medical therapy may sometimes be appropriate.
Diagnosis is largely achieved by obtaining a complete medical history followed by physical exam and ultrasound. If need be, laboratory tests or hysteroscopy may be used. The following are a list of diagnostic procedures that medical professionals may use to identify the cause of the abnormal uterine bleeding.
- Pelvic and rectal examination to ensure that bleeding is not from lower reproductive tract (i.e. vagina, cervix) or rectum
- Pap smear to rule out cervical neoplasia
- Pelvic ultrasound scan is the first line diagnostic tool for identifying structural abnormalities.
- Endometrial biopsy to exclude endometrial cancer or atypical hyperplasia
- Hysteroscopy
- TSH and T4 dosage to rule out hypothyroidism
The European Society of Human Reproduction and Embryology (ESHRE) notes that the aim of ovulation induction should be mono-ovulation and not over-stimulation of the ovaries . The risks associated with multiple pregnancy are much higher than singleton pregnancy; incidences of perinatal death are seven times higher in triplet births and five times higher in twin births than the risks associated with a singleton pregnancy. It is therefore important to adapt the treatment to each individual patient.
Women with polycystic ovary syndrome may be particularly at risk. Multiple pregnancy occurs in approximately 15-20% of cases following cycles induced with gonadotrophins such as hMG and FSH induced ovulations.
During ovulation induction, it is recommended to start at a low dose and monitor the ovarian response with vaginal ultrasound, including discernment of the number of developing follicles. A cycle with supernumerary follicles is usually defined as one where there are more than two follicles >16 mm in diameter. It is generally recommended to have such cycles cancelled because of the risk of multiple pregnancy. In cancelled cycles, the woman or couple should be warned of the risks in case of supernumerary follicles, and should avoid sexual intercourse or use contraception until the next menstruation. Induction of final maturation (such as done with hCG) may need to be withheld because of increased risk of ovarian hyperstimulation syndrome(OHSS). The starting dose of the inducing drug should be reduced in the next cycle.
Alternatives to cancelling a cycle are mainly:
- Aspiration of supernumerary follicles until one or two remain.
- Converting the protocol to IVF treatment with embryo transfer of up to two embryos only.
- Selective fetal reduction. This alternative confers a high risk of complications.
- Proceeding with any multiple pregnancy without fetal reduction, with the ensuing risk of complications. This alternative is not recommended.
The term "postmenopausal" describes women who have not experienced any menstrual flow for a minimum of 12 months, assuming that they have a uterus and are not pregnant or lactating. In women without a uterus, menopause or postmenopause can be identified by a blood test showing a very high FSH level. Thus postmenopause is the time in a woman's life that takes place after her last period or, more accurately, after the point when her ovaries become inactive.
The reason for this delay in declaring postmenopause is because periods are usually erratic at this time of life. Therefore, a reasonably long stretch of time is necessary to be sure that the cycling has ceased. At this point a woman is considered infertile; however, the possibility of becoming pregnant has usually been very low (but not quite zero) for a number of years before this point is reached.
A woman's reproductive hormone levels continue to drop and fluctuate for some time into post-menopause, so hormone withdrawal effects such as hot flashes may take several years to disappear.
A period-like flow during postmenopause, even spotting, may be a sign of endometrial cancer.
Once a diagnosis of dysmenorrhea is made, further workup is required to search for any secondary underlying cause of it, in order to be able to treat it specifically and to avoid the aggravation of a perhaps serious underlying cause.
Further work-up includes a specific medical history of symptoms and menstrual cycles and a pelvic exam. Based on results from these, additional exams and tests may be motivated, such as:
- Laboratory tests
- Gynecologic ultrasonography
- Laparoscopy may be required.
In terms of ovarian reserve, a typical woman has 12% of her reserve at age 30 and has only 3% at age 40. 81% of variation in ovarian reserve is due to age alone, making age the most important factor in female infertility.
The most common methods of checking the status of the ovarian reserve is to perform a blood test on day 3 of the menstrual cycle to measure serum FSH level, alternatively a blood test to measure the serum AMH level can give similar information. Transvaginal ultrasound can also be used to “count the number of follicles” and this procedure is called Antral Follicle Count.
The American College of Obstetricians and Gynecologists recommends ovarian reserve testing should be performed for women older than 35 years who have not conceived after 6 months of attempting pregnancy and women at higher risk of diminished ovarian reserve, such as those with a history of cancer treated with gonadotoxic therapy, pelvic irradiation, or both; those with medical conditions who were treated with gonadotoxic therapies; or those who had ovarian surgery for endometriomas.
It is important to recognize that a poor result from ovarian reserve testing does not signify an absolute inability to conceive and should not be the sole criterion considered to limit or deny access to infertility treatment.
The diagnosis of dysmenorrhea is usually made simply on a medical history of menstrual pain that interferes with daily activities. However, there is no universally accepted gold standard technique for quantifying the severity of menstrual pains. Yet, there are quantification models, called "menstrual symptometrics", that can be used to estimate the severity of menstrual pains as well as correlate them with pain in other parts of the body, menstrual bleeding and degree of interference with daily activities.
The most common pain scale for quantification of endometriosis-related pain is the visual analogue scale (VAS); VAS and numerical rating scale (NRS) were the best adapted pain scales for pain measurement in endometriosis. For research purposes, and for more detailed pain measurement in clinical practice, VAS or NRS for each type of typical pain related to endometriosis (dysmenorrhea, deep dyspareunia and non-menstrual chronic pelvic pain), combined with the clinical global impression (CGI) and a quality of life scale, are used.
An area of research is the search for endometriosis markers.
In 2010 essentially all proposed biomarkers for endometriosis were of unclear medical use, although some appear to be promising. The one biomarker that has been in use over the last 20 years is CA-125. A 2016 review found that in those with symptoms of endometriosis and once ovarian cancer has been ruled out, a positive CA-125 may confirm the diagnosis. Its performance in ruling out endometriosis; however, is low. CA-125 levels appear to fall during endometriosis treatment, but has not shown a correlation with disease response.
Another review in 2011 identified several putative biomarkers upon biopsy, including findings of small sensory nerve fibers or defectively expressed β3 integrin subunit. It has been postulated a future diagnostic tool for endometriosis will consist of a panel of several specific and sensitive biomarkers, including both substance concentrations and genetic predisposition.
Women charting with some form of fertility awareness may find mittelschmerz to be a helpful secondary sign in detecting ovulation. Because normal sperm life is up to five days, however, mittelschmerz alone does not provide sufficient advance warning to avoid pregnancy. Because other causes of minor abdominal pain are common, mittelschmerz alone also cannot be used to confirm the beginning of the post-ovulatory infertile period.
Secondary amenorrhea's most common and most easily diagnosable causes are pregnancy, thyroid disease, and hyperprolactinemia. A pregnancy test is a common first step for diagnosis. Hyperprolactinemia, characterized by high levels of the hormone prolactin, is often associated with a pituitary tumor. A dopamine agonist can often help relieve symptoms. The subsiding of the causal syndrome is usually enough to restore menses after a few months. Secondary amenorrhea may also be caused by outflow tract obstruction, often related to Asherman's Syndrome. Polycystic ovary syndrome can cause secondary amenorrhea, although the link between the two is not well understood. Ovarian failure related to early onset menopause can cause secondary amenorrhea, and although the condition can usually be treated, it is not always reversible. Secondary amenorrhea is also caused by stress, extreme weight loss, or excessive exercise. Young athletes are particularly vulnerable, although normal menses usually return with healthy body weight. Causes of secondary amenorrhea can also result in primary amenorrhea, especially if present before onset of menarche.
Diagnosis of mittelschmerz is generally made if a woman is mid-cycle and a pelvic examination shows no abnormalities. If the pain is prolonged and/or severe, other diagnostic procedures such as an abdominal ultrasound may be performed to rule out other causes of abdominal pain.
The pain of mittelschmerz is sometimes mistaken for appendicitis and is one of the differential diagnoses for appendicitis in women of child-bearing age.
Primary amenorrhoea can be diagnosed in female children by age 14 if no secondary sex characteristics, such as enlarged breasts and body hair, are present. In the absence of secondary sex characteristics, the most common cause of amenorrhoea is low levels of FSH and LH caused by a delay in puberty. Gonadal dysgenesis, often associated with Turner's Syndrome, or premature ovarian failure may also be to blame. If secondary sex characteristics are present, but menstruation is not, primary amenorrhoea can be diagnosed by age 16. A reason for this occurrence may be that a person phenotypically female but genetically male, a situation known as androgen insensitivity syndrome. If undescended testes are present, they are often removed after puberty (~21 years of age) due to the increased risk of testicular cancer. In the absence of undescended testes, an MRI can be used to determine whether or not a uterus is present. Müllerian agenesis causes around 15% of primary amenorrhoea cases. If a uterus is present, outflow track obstruction may be to blame for primary amenorrhoea.
Where an underlying cause can be identified, treatment may be directed at this. Clearly heavy periods at menarche and menopause may settle spontaneously (the menarche being the start and menopause being the cessation of periods).
If the degree of bleeding is mild, all that may be sought by the woman is the reassurance that there is no sinister underlying cause. If anemia occurs due to bleeding then iron tablets may be used to help restore normal hemoglobin levels.
The condition is often treated with hormones, particularly as abnormal uterine bleeding commonly occurs in the early and late menstrual years when contraception is also sought. Usually, oral combined contraceptive or progesterone only pills may be taken for a few months, but for longer-term treatment the alternatives of injected Depo Provera or the more recent progesterone releasing IntraUterine System (IUS) may be used. Fibroids may respond to hormonal treatment, and if they do not, then surgical removal may be required.
Tranexamic acid tablets that may also reduce loss by up to 50%. This may be combined with hormonal medication previously mentioned.
Anti-inflammatory medication like NSAIDs may also be used. NSAIDs are the first-line medications in ovulatory menorrhagia, resulting in an average reduction of 20-46% in menstrual blood flow. For this purpose, NSAIDs are ingested for only 5 days of the menstrual cycle, limiting their most common adverse effect of dyspepsia.
A definitive treatment for menorrhagia is to perform hysterectomy (removal of the uterus). The risks of the procedure have been reduced with measures to reduce the risk of deep vein thrombosis after surgery, and the switch from the front abdominal to vaginal approach greatly minimizing the discomfort and recuperation time for the patient; however extensive fibroids may make the womb too large for removal by the vaginal approach. Small fibroids may be dealt with by local removal (myomectomy). A further surgical technique is endometrial ablation (destruction) by the use of applied heat (thermoablation).
In the UK the use of hysterectomy for menorrhagia has been almost halved between 1989 and 2003. This has a number of causes: better medical management, endometrial ablation and particularly the introduction of IUS which may be inserted in the community and avoid the need for specialist referral; in one study up to 64% of women cancelled surgery.
Some other blood tests are suggestive but not diagnostic. The ratio of LH (Luteinizing hormone) to FSH (Follicle-stimulating hormone), when measured in international units, is elevated in women with PCOS. Common cut-offs to designate abnormally high LH/FSH ratios are 2:1 or 3:1 as tested on Day 3 of the menstrual cycle. The pattern is not very sensitive; a ratio of 2:1 or higher was present in less than 50% of women with PCOS in one study. There are often low levels of sex hormone-binding globulin, in particular among obese or overweight women.
Anti-Müllerian hormone (AMH) is increased in PCOS, and may become part of its diagnostic criteria.
Other causes of irregular or absent menstruation and hirsutism, such as hypothyroidism, congenital adrenal hyperplasia (21-hydroxylase deficiency), Cushing's syndrome, hyperprolactinemia, androgen secreting neoplasms, and other pituitary or adrenal disorders, should be investigated.
A study of a population of French women from 1670 and 1789 shows that those who married at age 20–24 had 7.0 children on average and 3.7% remained childless. Women who married at age 25–29 years had a mean of 5.7 children and 5.0% remained childless. Women who married at 30–34 years had a mean of 4.0 children and 8.2% remained childless. The average age at last birth in natural fertility populations that have been studied is around 40.
In 1957, a study was done on a large population (American Hutterites) that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. (Infertility rates today are believed to be higher in the general population than for the population in this study from the 1950s.)
This 1957 study found that:
- By age 30, 7% of couples were infertile
- By age 35, 11% of couples were infertile
- By age 40, 33% of couples were infertile
- At age 45, 87% of couples were infertile
Drug of choice is progesterone.
Management of dysfunctional uterine bleeding predominantly consists of reassurance, though mid-cycle estrogen and late-cycle progestin can be used for mid- and late-cycle bleeding respectively.
Also, non-specific hormonal therapy such as combined high-dose estrogen and high-dose progestin can be given. Ormeloxifene is a non-hormonal medication that treats DUB but is only legally available in India.
The goal of therapy should be to arrest bleeding, replace lost iron to avoid anemia, and prevent future bleeding.
Excessive movement before any treatments or surgeries will cause excessive bleeding.
A hysterectomy may be performed in some cases.
A menstrual disorder is an abnormal condition in a woman's menstrual cycle.
Disorders of ovulation include oligoovulation and anovulation:
- Oligoovulation is infrequent or irregular ovulation (usually defined as cycles of ≥36 days or <8 cycles a year)
- Anovulation is absence of ovulation when it would be normally expected (in a post-menarchal, premenopausal woman). Anovulation usually manifests itself as irregularity of menstrual periods, that is, unpredictable variability of intervals, duration, or bleeding. Anovulation can also cause cessation of periods (secondary amenorrhea) or excessive bleeding (dysfunctional uterine bleeding).
Irregular menstruation is a menstrual disorder whose manifestations include irregular cycle lengths as well as metrorrhagia (vaginal bleeding between expected periods).
Female patients may show symptoms of hyperandrogenism in their early life, but physicians become more concerned when the patient is in her late teens or older.
Hyperandrogenism is most often diagnosed by checking for signs of hirsutism according to a standardized method that scores the range of excess hair growth.
Checking medical history and a physical examination of symptoms are used for an initial diagnosis. Patient history assessed includes age at thelarche, adrenarche, and menarche; patterns of menstruation; obesity; reproductive history; and the start and advancement of hyperandrogenism symptoms. Patterns of menstruation are examined since irregular patterns may appear with hirsutism. Family history is also assessed for occurrences of hyperandrogenism symptoms or obesity in other family members.
A laboratory test can also be done on the patient to evaluate levels of FSH, LH, DHEAS, prolactin, 17OHP, and total and free testosterone in the patient's blood. Abnormally high levels of any of these hormones help in diagnosing hyperandrogenism.
Excessive menstruation between puberty and 19 years of age is called puberty menorrhagia. Excessive menstruation is defined as bleeding over 80 ml per menstrual period or lasting more than 7 days. The most common cause for puberty menorrhagia is dysfunctional uterine bleeding. The other reasons are idiopathic thrombocytopenic purpura, hypothyroidism, genital tuberculosis, polycystic ovarian disease, leukemia and coagulation disorders. The most common physiological reason for puberty menorrhagia is the immaturity of hypothalamic-pituitary-ovarian axis, leading to inadequate positive feedback and sustained high estrogen levels. Most patients present with anemia due to excessive blood loss.
The patient is assessed with a thorough medical history, physical examination (to look for features of anemia), gynaecological examination (to rule out local causes) and laboratory investigations (to rule out coagulopathies and malignancy). It is mandatory to exclude pregnancy. The treatment is determined based on the cause of menorrhagia. In case of puberty menorrhagia due to immaturity of hypothalamic axis, hormonal therapy is beneficial. Treatment for blood loss should be done simultaneously with iron therapy in mild to moderate blood loss and blood transfusion in severe blood loss.
Oligomenorrhea can be a result of prolactinomas (adenomas of the anterior pituitary). It may be caused by thyrotoxicosis, hormonal changes in perimenopause, Prader–Willi syndrome, and Graves disease.
"Endurance exercises such as running or swimming can affect the reproductive physiology of women athletes. Female runners, swimmers and ballet dancers menstruate infrequently in comparison to nonatheletic women of comparable age or not at all (amenorrhea). The degree of menstrual abnormality is directly proportional to the intensity of the exercise. For example, Malina et al., (1978) have shown menstrual irregularity is more common, and more severe among tennis players than among golfers" (modified by a student paper written by A. Lord)
Breastfeeding has been linked to irregularity of menstrual cycles due to hormones that delay ovulation.
Women with polycystic ovary syndrome (PCOS) are also likely to suffer from oligomenorrhea. PCOS is a condition in which excessive androgens (male sex hormones) are released by the ovaries. Women with PCOS show menstrual irregularities that range from oligomenorrhea and amenorrhea, to very heavy, irregular periods. The condition affects about 6% of premenopausal women.
Eating disorders can result in oligomenorrhea. Although menstrual disorders are most strongly associated with Anorexia nervosa, Bulimia nervosa may also result in oligomenorrhea or amenorrhea. There is some controversy regarding the mechanism for the menstrual dysregulation, since amenorrhea may sometimes precede substantial weight loss in some anorexics. Some researchers hypothesize that some as-yet unrecognized neuroendocrine phenomenon may be involved; the menstrual irregularities may be related to the biological undergirding of the disorders, rather than a result of nutritional deficiencies.