Anovulation - Treatments

Treatments

Treatments available to induce ovulation are usually quite efficient. 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 pregnancies 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.

The medication which is most commonly used to treat anovulation is clomifene citrate (or clomid). It is relatively easy and convenient to use. Clomifene appears to inhibit estrogen receptors in hypothalamus, thereby inhibiting negative feedback of estrogen on gonadotropin production. It may also result in direct stimulation of the hypothalamic-pituitary axis. It also has an effect on cervical mucus quality and uterine mucosa, which might affect sperm penetration and survival, hence its early administration during the menstrual cycle. Clomifene citrate is a very efficient ovulation inductor, and has a success rate of 67%. Nevertheless, it only has a 37% success rate in inducing pregnancy. This difference may be due to the anti-estrogenic effect which clomifene citrate has on the endometrium, cervical mucus, uterine blood flow, as well as the resulting decrease in the motility of the fallopian tubes and the maturation of the oocytes.
Another anti-estrogenic molecule called tamoxifen is often used in the prevention and treatment of breast cancer. It can therefore also be used to treat patients that have a reaction to clomifene citrate.
Human chorionic gonadotropin (hCG) is 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. The results associated with this method have been described as "quite encouraging". HCG should only be administered at certain points in the cycle, around the time of ovulation, and only if the infertility diagnostic has indicated that the problem is related to the release of the egg.
Human menopausal gonadotropin (hMG) is a very powerful treatment for infertility. It consists of a combination of LH and FSH. 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.
Follicle-stimulating hormone (FSH or recombinant FSH) is now used as a replacement for hMG. Although hMG is a combination of FSH and LH, 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.
The gonadotropin-releasing hormone (GnRH) pump is used to release doses of GnRH in a pulsatile fashion. This hormone is synthesised by the hypothalamus and induces the secretion of LH and FSH by the pituitary. GnRH must be delivered in a pulsatile fashion to imitate the random secretion of the hypothalamus in order to fool the pituitary into secreting LH and FSH. The GnRH pump is the size of a cigarette box and has a small catheter. Unlike other treatments, using the GnRH pump doesn’t usually lead to multiple pregnancies. Dr. Filicori from the University of Bologna suggests that this might be because gonadotrophins are absent when the treatment is initiated, and therefore the hormones released by the pituitary (LH and FSH) can still take part in the retro-control of gonadotrophin secretion, mimicking the natural cycle. This treatment can also be used for underweight and/or anorexic patients; it has also been used in certain cases of hyperprolactimenia.
Bromocriptine acts in a completely different manner to the other treatments mentioned above. It does not induce ovulation, but reduces the production of prolactin by the pituitary. Bromocriptine is only prescribed in cases of overproduction of prolactin (hyperprolactinemia).
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.
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 women 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). However, it is widely acknowledged by doctors that it is usually very difficult for PCOS patients to lose weight.

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 Consensus workshop do not recommend metformin for ovulation stimulation. Subsequent randomized studies have confirmed the lack of evidence for adding metformin to clomiphene.