A short guide to ovarian stimulation

A short guide to ovarian stimulation. HMG, HCG, FSH and LH recombinant or urinary, clomiphene citrate, GnRH pump … Behind these strange names and initials are hidden numerous drugs used for ovarian stimulation. Each has advantages and disadvantages. Effects of complications, discover everything you need to know about these allies of motherhood.

Of all the infertility treatments, the most common is to stimulate the ovaries for ovulation. Whether used alone, in combination with artificial insemination or done as part of an in vitro fertilization, ovarian stimulation such an act are common in gynecology. But they must be perfectly controlled to have the best chance of being effective and to avoid two risks: the ovarian hyperstimulation syndrome, often Benin, and multiple pregnancies.

Three floors for ovulation
Hormones called gonadotropins, LH and FSH, allow ovulation. This is the LH that triggers the process, but a balance between FSH and LH is required for the maturation of a “follicle” which will break at the time of ovulation to release an egg. The secretion of FSH and LH are influenced by other hormones.

Inducing ovulation induction Schematically female hormones are secreted in three stages:

The ovary produces estrogen and progesterone.
The pituitary gland at the base of the brain secretes gonadotrophins: LH and FSH.
The hypothalamus, above the pituitary secretes GnRH.

These three stories communicate, GnRH modulating the secretion of gonadotropins, which, in turn, regulate the secretion of sex hormones by the ovary. Estrogens inhibit the secretion back of GnRH, LH and FSH. Ovarian stimulation may be exercised over three floors. New drugs have been developed in recent years, including drugs known as “recombinant”, genetically engineered and experience to better tailor treatment to the biological profile of each woman.

An oral medication to stimulate ovulation
The simplest treatment to stimulate the ovary is to use an antiestrogen, mainly clomiphene citrate ( Clomid or Pergotime ), which binds to estrogen receptors in the hypothalamus and the pituitary gland and prevent and curb secretion of FSH and LH. Unlike other treatments, only specialists, clomiphene citrate may be prescribed by all physicians. It has the advantage to be taken orally and not require close monitoring than other treatments, because the risk of hyperstimulation and multiple pregnancy is lower. In return, it is less consistently effective. Ease of use that it is recommended as first choice for a few cycles when the infertility is associated with anovulation (no ovulation) or a dysovulation (irregular ovulation), the ovaries secrete estrogen and that pituitary gland is able to function.

Side effects of ovarian stimulation
In practice it is the drug most often prescribed (more than 300,000 cans redeemed in 2002). Rarely, minor side effects may occur, such as hot flashes, visual disturbances or headaches. Miscarriages (10 to 19% of cases, according to studies) and ectopic pregnancies are slightly more frequent than in the case of a natural pregnancy.

Although small, the risk of hyperstimulation leading to the maturation of several follicles are, however, especially in women with polycystic ovaries, abnormal frequent. It is therefore preferable to perform an ultrasound to check that the treatment is effective and no more than one mature follicle. If multiple follicles grew, reports must be protected during this cycle, to avoid conceiving twins, triplets or quadruplets.
The most potent gonadotropin

If after a few cycles there was no pregnancy, we must move on to other more powerful drugs. This is essentially going gonadotropins act directly on the ovaries to develop follicles. This treatment is given immediately for women with anovulation of hypothalamic or pituitary. It is also used for artificial insemination and in vitro fertilization. It is sometimes suggested to women with unexplained infertility, but their effectiveness is not established in this case.

Gonadotropins are more effective than clomiphene citrate, but the risk of ovarian hyperstimulation syndrome and multiple pregnancy are higher, which requires close monitoring by ultrasound and estradiol assays repeated to fine tune the doses each individual case and monitor the development of follicles. Treatment should be especially careful in women who have polycystic ovaries. As with clomiphene citrate, miscarriages (20% of cases) are slightly more frequent in cases of spontaneous pregnancy.

Stimulate ovulation
Different types of gonadotropins are marketed. The oldest are extracted from urine of postmenopausal women. This may be HMG ( Menopur ), which contains both FSH and LH, or FSH alone ( Fostimon ). No risk of infection was observed with these hormones. In addition to the stimulation of ovulation, the Menopur is also indicated for women with an insufficient mucus. In fact, in most cases is the fact that FSH is required. The HMG or pure FSH are used for the maturation of a follicle, ovulation is then triggered by another product. Some protocols combine the LH to FSH, but the interest of this association is well accepted that for women with a deficiency of these hormones. These gonadotropins from urine are injected intramuscularly or, for some, subcutaneous.

In recent years, gonadotropins are also available in recombinant form ( Puregon or Gonal F for FSH, Luveris for LH). These products have the advantage of being very pure and constant concentration of a preparation to another, thereby avoiding allergic reactions and allows for more precise dosages. Recombinant FSH is more potent than urinary FSH, allowing shorter treatments at lower doses. The reactions at the injection are rare. Finally, these products are administered subcutaneously, which allows for self-injections (self-injection).

Beware of hyperstimulation
Currently most of the stimuli (nine out of ten in IVF) are performed with these recombinant forms.
When the ultrasound shows the development of one or two follicles, and the results are correct dosages of estrogen, ovulation is triggered. Most often this is done using the HCG. This other gonadotropin is produced by the placenta. First extracted from the urine of pregnant women, it is also available in recombinant form since 2002 ( Ovitrelle ), with the same advantages with respect to the form of urine, as for other gonadotropins, including the injection subcutaneously which allows to inject the product itself.

Ovarian stimulation with a pump
Pulsatile GnRH or GnRH pump (Gonadorelin) is a portable syringe that injects regularly GnRH to mimic the effects of the hypothalamus. This process is especially suitable for women with anovulation of hypothalamic origin. It then allows to restore almost physiological cycles, with very low risks of hyperstimulation and multiple pregnancy. Monitoring is reduced. However we must accept the small inconvenience of wearing a micropump for several weeks. For women who refuse this method, the treatment must involve FSH and LH, but with closer monitoring by blood tests and ultrasounds, because the risk of hyperstimulation is more important.

Ovarian stimulation: what are the risks?
Ovarian stimulation can it increase the risk of ovarian cancer? Four studies published in 1993 had cast doubt. In reality it is difficult to conclude. Indeed, all published studies open to criticism and we know that infertility itself increases the risk of ovarian cancer, pregnancy exercise, in contrast, a protective effect. In addition to regular ultrasounds performed in women treated can lead to identify tumors that would otherwise go unnoticed. Studies are underway that will better answer this question.

No increased risk of fetal malformations have been observed to date with the drugs used. The harm to the child exist yet, but they are related to multiple pregnancies, well-known factor of fetal and neonatal complications. Hence the importance of being followed by experienced specialists. If multiple ovulation is to be feared, it is reasonable to “lose” a cycle by stopping the treatment and having sex. In vitro fertilization is a special case because it seeks to produce hyperstimulation to collect a large number of oocytes and obtain several embryos. It must be accepted in this case to limit the number of embryos implanted in the uterus, although this reduces the chances of pregnancy.