Anovulation

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. In addition to the alteration of menstrual periods and infertility, chronic anovulation can cause or exacerbate other long-term problems, such as hyperandrogenism or osteopenia. It plays a central role in the multiple imbalances and dysfunctions of polycystic ovary syndrome. During the first two years after menarche 50% of the menstrual cycles could be anovulatory cycles. It is possible to restore ovulation using appropriate medication, and ovulation is successfully restored in approximately 90% of cases. The first step is the diagnosis of anovulation. The identification of anovulation is not easy; contrary to what is commonly believed, women undergoing anovulation still have (more or less) regular periods. In general, women only notice that there is a problem once they have started trying to conceive. Temperature charting is a useful way of providing early clues about anovulation, and can help gynaecologists in their diagnosis.

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. In addition to the alteration of menstrual periods and infertility, chronic anovulation can cause or exacerbate other long-term problems, such as hyperandrogenism or osteopenia. It plays a central role in the multiple imbalances and dysfunctions of polycystic ovary syndrome. During the first two years after menarche 50% of the menstrual cycles could be anovulatory cycles. It is possible to restore ovulation using appropriate medication, and ovulation is successfully restored in approximately 90% of cases. The first step is the diagnosis of anovulation. The identification of anovulation is not easy; contrary to what is commonly believed, women undergoing anovulation still have (more or less) regular periods. In general, women only notice that there is a problem once they have started trying to conceive. Temperature charting is a useful way of providing early clues about anovulation, and can help gynaecologists in their diagnosis.

Signs and symptoms

Anovulation is usually associated with specific symptoms. They are not necessarily all displayed simultaneously. Amenorrhea (absence of menstruation) occurs in about 20% of women with ovulatory dysfunction. Infrequent and light menstruation occurs in about 40% of women with ovulatory dysfunction. Another potential symptom is irregular menstruation, where five or more menstrual cycles a year are five or more days shorter or longer than the length of the average cycle. Absence of mastodynia (breast pain or tenderness) occurs in about 20% of women with ovulatory problems. Also possible is increased body mass and facial hair, which is relatively easy to treat, and is often associated with PCOS, or polycystic ovary syndrome.

Associated conditions

For most women, alteration of menstrual periods is the principal indication of chronic anovulation. Ovulatory menstrual periods tend to be regular and predictable in terms of cycle length, duration and heaviness of bleeding, and other symptoms. Ovulatory periods are often accompanied by midcycle symptoms such as mittelschmerz or premenstrual symptoms. In contrast, 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). Mittelschmerz and premenstrual symptoms tend to be absent or reduced when a woman is anovulatory.

Causes

Hormonal imbalance is the most common cause of anovulation and is thought to account for about 70% of all cases. About half the women with hormonal imbalances do not produce enough follicles to ensure the development of an ovule, possibly due to poor hormonal secretions from the pituitary gland or the hypothalamus. The pituitary gland controls most other hormonal glands in the human body. Therefore, any pituitary malfunctioning affects other glands under its influence, including the ovaries. This occurs in around 10% of cases. The pituitary gland is controlled by the hypothalamus. In 10% of cases, alterations in the chemical signals from the hypothalamus can easily seriously affect the ovaries. There are other hormonal anomalies with no direct link to the ones mentioned above that can affect ovulation. For instance, women with hyper- or hypothyroidism sometimes have ovulation problems. Thyroid dysfunction can halt ovulation by upsetting the balance of the body's natural reproductive hormones. Currently, the four main causes of ovulatory disorders are polyendocrine metabolic ovarian syndrome (PMOS), hypogonadotropic hypogonadism (HA), primary ovarian insufficiency (POI), and hyperprolactinemia.

Diagnosis

Fertility awareness and LH measurement

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 PMOS. 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.

Classification and testing

The World Health Organization criteria for classification of anovulation include the determination of oligomenorrhea (menstrual cycle >35 days) or amenorrea (menstrual cycle >6 months) in combination with concentration of prolactin, follicle stimulating hormone (FSH) and estradiol (E2). The patients are classified as WHO1 (15%)—hypo-gonadotropic, hypo-estrogenic, WHO2 (80%)—normo-gonadotropic, normo-estrogenic, and WHO3 (5%)—hyper-gonadotropic, hypo-estrogenic. The vast majority of anovulation patients belong to the WHO2 group and demonstrate very heterogeneous symptoms ranging from anovulation, obesity, biochemical or clinical hyperandrogenism and insulin resistance. This classification system does not include a separate category for anovulation caused by hyperprolactinemia, and experts do not consistently use this system. Diagnosis of anovulation cause involves hormone level tests, in conjunction with an assessment of associated symptoms. A patient history and physical exam should include history of onset and pattern of oligomenorrhea or amenorrhea, signs of PMOS such as hyperandrogenism and obesity, eating disorders, causes of excessive physical or mental stress, and breast secretions. Patients with symptoms of hyperandrogenism, such as hirsutism, can be tested for serum androgen levels as well as serum total testosterone levels. A 17-hydroprogesterone test may also be conducted if congenital adrenal hyperplasia is suspected. If the differential is broad, hormone serum levels of estradiol, follicle-stimulating hormone (FSH), gonadotropin-releasing hormone (GnRH), anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), and prolactin can be diagnostic since most causes of anovulation are hormonal imbalances. Transvaginal ultrasound may also be used to visualize polycystic ovaries.

Treatments

Treatment should be based on diagnosis of anovulation. Treatment varies based on the 4 most common causes of anovulation: polyendocrine metabolic ovarian syndrome (PMOS), hypogonadotropic hypogonadism (HA), primary ovarian insufficiency (POI), and hyperprolactinemia. Importantly, semen analysis should be carried out of the XY partner to exclude severe XY factors before managing anovulatory subfertility. Overall, in healthy individuals with anovulation, ovulatory disorders may be favorably influenced by a healthy diet such as a higher consumption of monounsaturated fats rather than trans fats, vegetable rather than animal protein sources, high fat dairy, multivitamins, and iron from plants and supplements.

Treatment for polycystic ovarian syndrome (PCOS)

Treatment for management of anovulation due to PCOS is multifaceted, including weight reduction, ovulation induction agents, insulin-sensitizing agents, gonadotrophins and ovarian drilling. In PCOS patients with overweight or obesity, weight loss is first line treatment. Studies show a reduction in weight as little of 5% by caloric restriction and increased physical activity can re-establish spontaneously ovulation and improve response to ovulation induction therapy if initiated. Weight loss also generally results in improved menstrual regularity and pregnancy rates in women with PCOS. It is well recognized that insulin resistance can be part of the sequelae of PCOS and if present, contribute to anovulation. Metformin, a biguanide, is a common insulin sensitizer often given to treat women with PCOS. No other insulin sensitizers have evidence of effective and safe use of fertility treatment. Previously, metformin was recommended as treatment for anovulation in polycystic ovary syndrome, but in the largest trial to date, comparing clomiphene with metformin, clomiphene was more effective than metformin alone. Following this study, the ESHRE/ASRM-sponsored A consensus workshop does not recommend metformin for ovulation stimulation. Subsequent randomized studies have confirmed the lack of evidence for adding metformin to clomiphene.

Other treatments

Corticosteroids (usually found in anti-inflammatory drugs) can be used to treat anovulation if it is caused by an overproduction of male hormones by the adrenal glands. Corticosteroids are usually used to reduce the production of testosterone.

References

Text derived from https://en.wikipedia.org/w/index.php?oldid=1363348909 under CC BY-SA 4.0; modifications have been made.