Ovulation induction at a glance
- Ovulation induction is the use of medications, often called fertility drugs, to stimulate the ovaries to produce and release mature eggs for fertilization.
- Primarily we utilize ovulation induction in two cases: (1) for those who do not ovulate regularly or at all (anovulation) and (2) to stimulate the production of multiple eggs rather than the single egg that is naturally produced during a menstrual cycle.
- The production of multiple eggs increases the number of chances for fertilization in treatments such as in vitro fertilization (IVF) and attaining pregnancy through intrauterine insemination (IUI); it is also routinely used for the same reason in egg freezing for later use and in egg donation.
- Ovulation induction is frequently used in treating female infertility, as about 25% of such cases are due to ovulation problems. These can be due to various causes including polycystic ovary syndrome (PCOS) and can often be an underlying cause in a diagnosis of unexplained infertility.
- Our physicians generally first try oral medications for ovulation induction, depending on the individual’s circumstances, and may include injectable drugs if necessary.
- Ovulation induction is a cost-effective treatment for many with ovulation-related infertility and is often a first step taken in fertility treatments.
What is the ovulation induction treatment for infertility?
When ovulation difficulties prevent spontaneous pregnancy, we can perform ovulation induction, which uses medications to stimulate the ovaries to produce and release mature eggs for fertilization.
In 25% of women who experience infertility, the cause is a problem with ovulation, or the release of a mature egg on a monthly basis, according to the American Society for Reproductive Medicine. Ovulation occurs when a woman’s reproductive system and hormones are properly balanced to result in regular ovulation needed for sperm and egg to meet.
Anovulation and infertility
When ovulation does not occur, which is called anovulation, pregnancy can’t occur. Anovulation in some menstrual cycles is not necessarily abnormal, but on a chronic basis it can result in infertility. Ovulation that is infrequent or unpredictable is called oligoovulation, which can also prevent pregnancy.
Ovulation induction can work around these problems by helping a woman ovulate more regularly, increasing the chance of an egg being released and available for fertilization. When the cause of ovulation difficulties is an underlying condition, such as polycystic ovary syndrome (PCOS), treating that condition can remove the barrier to pregnancy brought on by the irregular ovulation.
This medication-induced stimulation of the production and release of mature eggs (oocytes) is also part of IVF, in which having more eggs increases the chances of fertilization in the lab and a pregnancy. This is called superovulation, which may also be used in a less stimulating fashion in IUI. For the same reason, we use ovulation induction in egg freezing for later use and in egg donation.
Who can benefit from ovulation induction?
Ovulation induction is an option for many individuals for various reasons.
- Those who do not ovulate or have infrequent or irregular ovulation that limit opportunities for pregnancy.
- Those undergoing IVF.
- Individuals with ovulation difficulties who might need additional eggs to increase the chance of conception or conception through IUI.
- Those with PCOS.
- Patients with a diagnosis of unexplained infertility, which means we can’t pinpoint a cause for infertility.
- Individuals who are freezing their eggs for later use or who are donating their eggs.
After discussing health and reproductive history, as well as menstrual cycle, we may perform blood tests to evaluate numerous hormone levels that may help us to determine why oligoovulation or anovulation may be occurring. These may include androgens, like testosterone, thyroid levels, estrogen, FSH (follicle-stimulating hormone), LH (luteinizing hormone), prolactin and anti-müllerian hormone, among others.
A transvaginal ultrasound can show if the follicles (egg sacs) are in a certain pattern indicative of possible PCOS, and potentially if the woman is developing an ovulatory follicle. At times, we can also see that ovulation has occurred, based on the presence of a corpus luteum in the ovary and changes in the uterine lining.
Using the fertility drugs Clomid, letrozole and gonadotropins
Oral fertility drugs
Oral drugs we use at Fertility Medical Specialists Group are clomiphene citrate (brand name Clomid and Serophene) and letrozole (Femara). Clomid is approved by the Food and Drug Administration for ovulation induction. Letrozole is a drug to treat breast cancer but it also promotes ovulation, so fertility specialists use it for this purpose.
Clomid works by blocking estrogen’s function in the brain, causing it to signal the pituitary gland to produce more FSH and LH, resulting in ovulation. Letrozole causes the ovary to make less estrogen, which has the same effect in increasing FSH and LH.
We generally begin with the lowest dose of these fertility drugs that will result in ovulation and increase the dose as needed. With Clomid, the dose begins at 50-100 mg given for five consecutive days, starting on the second to fifth day of the menstrual cycle. If ovulation is not occurring, the dose can be increased in increments, generally topping out at 200 mg. Other fertility drugs may be used in conjunction with Clomid.
Letrozole is usually given in 2.5-5 mg doses for five days, beginning on the second to fifth day of the menstrual cycle. Patients with PCOS who have diabetes or prediabetes may be given the insulin-sensitizing medication metformin.
About 80% of women who are screened as good candidates and who are not ovulating will ovulate taking clomiphene citrate (Clomid), according to ASRM. Letrozole and Clomid have similar pregnancy success rates. Letrozole has been shown to be more effective in helping women with PCOS.
Injectable fertility drugs
Typically, about 30%of those who use oral fertility drugs do not ovulate, and injectable medications are often used. Gonadotropin medications contain FSH or LH or both together. Brand names for gonadotropins are Follistim, Menopur and Gonal-F. Gonadotropins are often used for women who don’t respond to Clomid or letrozole. These also are used to generate multiple eggs for IVF and egg freezing.
Gonadotropin injections for patients with ovulation problems usually begin on day two or three of menstruation and are self-administered by the patient daily for seven to twelve days. The dose can be extended, with the goal of attaining a mature follicle. A fertility specialist will monitor the follicle development with ultrasound and measure estrogen levels in the blood.
If the follicle develops properly, an injection of human chorionic gonadotropin (hCG) is given. The hCG is chemically similar to LH and imitates the natural LH surge that causes the follicle to release its mature egg.
OHSS and other ovulation induction risks
Oral fertility drugs
The side effects from these oral fertility drugs are usually mild and go away quickly, though they are also relatively common. These include:
- Hot flashes
- Mood swings
- Breast tenderness
- Ovarian cysts
Additionally, the chance of a pregnancy with twins if conceiving with Clomid or letrozole is 5%-8%, according to ASRM. This is slightly higher than the natural multiple pregnancy rate of 1%-2%.
Gonadotropins and OHSS
These ovulation-inducing drugs can sometimes cause ovulation hyperstimulation syndrome (OHSS), though it is exceptionally rare with close monitoring and the use of additional medications to reduce risk and symptoms. With OHSS the ovaries become enlarged and fluid may accumulate in the abdomen, causing bloating and discomfort.
A mild form of these symptoms may occur in anyone using gonadotropins and is not necessarily an indication of OHSS. Severe cases are rare, occurring in <1% of cycles. These cases may require further evaluation and medical treatment.
Due to the higher number of eggs stimulated or the number of embryos transferred, there is an increase in the chances of a multiple pregnancy (twins or more) with gonadotropins. The risk is dependent on the number of eggs released and the age of the woman. Multiple pregnancies carry risks for the mother and the resulting child.
Other risks include ectopic pregnancy and ovarian torsion (twisting), though these occur rarely. Soreness at the injection site is another typical side effect.