Anovulation affects between 6% and 15% of all women of childbearing age. During the first two years after menarche 50% of the menstrual cycles could be anovulatories. In addition to the alteration of menstrual periods and infertility, chronic anovulation can cause or exacerbate other long term problems, such as polycystic ovary syndrome.

It is in fact 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. Temperature charting is a useful way of providing early clues about anovulation, and can help gynaecologists in their diagnosis. 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, patients only notice that there is a problem once they have started trying to conceive.

Hormonal or chemical 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 mammary glands are also controlled by the pituitary gland, so lactation can also be affected. 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 hypo-thyroidism sometimes have ovulation problems. Thyroid dysfunction can halt ovulation by upsetting the balance of the body’s natural reproductive hormones. Polycystic ovary syndrome (also known as Stein-Leventhal syndrome) and hyperprolactinemia can also cause anovulatory cycles through hormonal imbalances.

Classification

According the World Health Organization (WHO) criteria for classification of anovulation, (which include the determination of oligomenorrhea or amenorrea in combination with concentration of prolactin, follicle stimulating hormone and estradiol) the patients are classified as:

  • WHO1 (15%) - hypo-gonadotropic, hypo-estrogenic
  • WHO2 (80%) - normo-gonadotropic, normo-estrogenic
  • 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.

Associated diseases

  • Polycystic ovary syndrome (a set of symptoms due to a hormone imbalance in women)
  • pituitary gland malfunction
  • hypothalamus malfunction
  • hyperthyroidism (the condition that occurs due to excessive production of thyroid hormone by the thyroid gland)
  • hypothyroidism (a common disorder of the endocrine system in which the thyroid gland does not produce enough thyroid    hormone)
  • hyperprolactinemia (the presence of abnormally high levels of prolactin in the blood)
  • luteinised unruptured follicle syndrome 
  • anorexia
  • obesity
  • premature ovarian failure  

Complications

Anovulation can result in a number of health complications, especially if it is left untreated.

Functional problem

This accounts for around 10-15% of all cases of anovulation. The ovaries can stop working in about 5% of cases. This may be because the ovaries do not contain eggs. However, a complete blockage of the ovaries is rarely a cause of infertility.

Risk factors

An anovulatory cycle is a menstrual cycle during which the ovaries do not release an oocyte. When a woman is anovulatory, she can't get pregnant because there is no egg to be fertilized. Women who are anovulatory have irregular, few or no periods.
This is common in women from their mid-thirties, but research has found that increasingly younger women are also suffering from these cycles.  In fact, about 40 % of infertility in women is related to cycles that don't ovulate.

Several studies indicate that in some cases, a simple change in lifestyle could help patients suffering from anovulation. Consulting a nutritionist, for example, could help a young woman suffering from anorexia to put on some weight, which might restart her menstrual cycle. Conversely, a young overweight woman who manages to lose weight could also relieve the problem of anovulation (losing just 5% of body mass could be enough to restart ovulation).

Anovulation is usually associated with specific symptoms.

Some cases of anovulation can be treated by lifestyle change or diet.

Chinese/East Asian medicine

Acupuncture and other modalities of Chinese/East Asian medicine have been used to treat women's health for many centuries. Gynecology specialties focus particularly on menstrual and reproductive disorders. Acupuncture may positively influence ovulation and fertility.

Pharmacotherapy

Ovulation stimulators

Clomid (Clomiphene citrate)

Clomifene is useful in those who are infertile due to anovulation or oligoovulation. Evidence is lacking for the use of clomifene in those who are infertile without a known reason. In such cases, studies have observed a clinical pregnancy rate 5.6% per cycle with clomifene treatment vs. 1.3%–4.2% per cycle without treatment. Clomifene has also been used with other assisted reproductive technology to increase success rates of these other modalities.

Oral antidiabetic agents

Metformin 

Metformin was recommended as treatment for anovulation in polycystic ovary syndrome.

Selective estrogen receptor modulator (SERM)

Tamoxifen

Tamoxifen may be used an alternative to clomiphene citrate for ovulation induction in women with anovulatory infertility. A dose of 10–40 mg per day is administered in days 3–7 of a woman's cycle.

Gonadotropins

  1. Human chorionic gonadotropin (hCG)

A molecule which is structurally similar to luteinizing hormone (LH). LH is secreted by the pituitary just before ovulation occurs, whereas hCG is released during pregnancy. On its own, hCG is not very effective in inducing ovulation, but when combined with clomifene citrate, it is much more effective. 

        2.  Human menopausal gonadotropin (hMG)

A very powerful treatment for infertility. It consists of a combination of LH (luteinizing hormone) and FSH (follicle-stimulating hormone). From menopause onwards, the body starts secreting LH and FSH in large quantities due to the slowing down of the ovarian function. This excess of hormones is not used by the body and is expelled in the urine. HMG is therefore collected from the urine of menopausal women. The urine then undergoes purification and a chemical treatment. The resulting hMG induces the stimulation of several ovarian follicles. This increases the risk of producing several oocytes during the same cycle, and thus the risk of multiple pregnancies.

        3.  Follicle-stimulating hormone (FSH or recombinant FSH)

Now used as a replacement for hMG (human menopausal gonadotropin). Although hMG is a combination of FSH and LH (luteinizing hormone), FSH is the only active component that has an effect on ovulation. However, until recently, it was not possible to produce pure FSH. FSH is now administered in a similar way as hMG, at a specific point during the cycle, and it requires medical monitoring. It is therefore important to fully understand a woman’s cycle, and to be able to accurately anticipate menstruation and ovulation dates. FSH is also sometimes useful for women who are suffering from PCOS (Polycystic ovary syndrome).

Surgical therapy

Surgical therapy is usually indicated to resolve the underlying cause for the anovulation (e.g. fallopian tube obstruction), typically when medical therapy has failed. Surgical treatment is also needed in uncommon cases, such as a macroadenoma of the pituitary with unrelenting growth eliciting acute symptoms (eg, headaches, bitemporal hemianopsia, diplopia). 

Surgery can be attempted in case of inefficient result with medications for ovulation induction. Though surgery is not commonly performed, the polycystic ovaries can be treated with a laparoscopic procedure called "ovarian drilling"(puncture of 4-10 small follicles with electrocautery), which often results in either resumption of spontaneous ovulations or ovulations after adjuvant treatment with clomiphene or FSH.

For patients who do not respond to diet, lifestyle modification and clomiphene, in vitro fertilisation (IVF-ICSI) can be performed. This usually includes controlled ovarian hyperstimulation with FSH (follicle-stimulating hormone) injections, and oocyte release triggering with human chorionic gonadotropin (hCG) or a GnRH (gonadotropin-releasing hormone) agonist.

Find more about related issues

Sources

Polycystic ovary syndrome ―sourced from Wikipedia licensed under CC BY-SA 3.0
Anovulation ―sourced from Wikipedia licensed under CC BY-SA 3.0
Anovulatory cycle ―sourced from Wikidoc licensed under CC BY-SA 3.0
Anovulatory ―sourced from World Heritage Encyclopedia licensed under CC BY-SA 3.0
Hypothyroidism ―sourced from Wikipedia licensed under CC BY-SA 3.0
Hyperthyroidism ―sourced from Wikipedia licensed under CC BY-SA 3.0
Hyperprolactinaemia ―sourced from Wikipedia licensed under CC BY-SA 3.0
Anovulation ―sourced from World Heritage Encyclopedia licensed under CC BY-SA 3.0
Ovulation ―sourced from Wikipedia licensed under CC BY-SA 3.0
Signs of infertility ―sourced from Progesterone Therapy licensed under CC BY 3.0
Infertility in polycystic ovary syndrome ―sourced from Wikipedia licensed under CC BY-SA 3.0
Clomifene ―sourced from Wikipedia licensed under CC BY-SA 3.0
Tamoxifen ―sourced from Wikipedia licensed under CC BY-SA 3.0
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