Ovarian Superstimulation

Background information:

If a female patient is having regular menstrual cycles, she most likely is ovulating or releasing an egg each month. Ordinarily, women only release one egg in a given menstrual cycle. With superstimulation, medicines are given to achieve ovulation or to increase the number of eggs that are released thereby increasing the chance for pregnancy within that superstimulated cycle. The hormonal environment around these superstimulated eggs is also improved significantly further increasing the chances for pregnancy. Patients suffering from recurrent miscarriages may benefit from superstimulation due to this improved hormonal environment. 

What medicines are used?

  1. Bravelle, Gonal F, or Follistim – These drugs contain only concentrated follicular-stimulating hormone (FSH). All three are given by subcutaneous injections with short needles. Bravelle contains highly purified FSH from traditional sources, while Gonal F and Follistim are recombinant DNA products. There are certain situations where these FSH only drugs may work better such as in polycystic ovarian disease or recurrent pregnancy loss.
  2. Pergonal, Humegon, or Repronex – These drugs contain concentrated FSH and luteinizing hormone (LH). These two hormones are normally released by the pituitary gland within the brain to control the menstrual cycle and ovulation. When given to female patients, the effect is to increase the number of eggs that are ovulated in a given cycle. These drugs also achieve ovulation in most patients who have not ovulated on previous therapies.
  3. Novarel, Profasi or Pregnyl – These drugs contain human chorionic gonadotropin (hCG). They are typically given at the end of the superovulatory cycle to assure adequate ovulation. The hCG mimics a LH surge. Approximately one-third of patients undergoing superovulation therapy will not ovulate adequately without hCG.

How are the medicines given?

All of the medicines listed above are only available by injection. Typically, the husbands or friends are taught to give the intramuscular (IM) injections. Patients can be taught to give their own subcutaneous (just under the skin) injections. The injections are usually given nightly for 7 to 12 days.

How are the doses of the medicines adjusted?

All of these medications need to be dosed according to response. In other words, there is no standard dose of these drugs. The amount used is adjusted based on the level of blood estrogen along with the growth of ovarian follicles (which contain the eggs) as seen on vaginal ultrasound. In an average cycle, a patient can expect to be seen 4-5 times for blood estrogen determination and vaginal ultrasound measurements over a two-week period.

How effective are these therapies?

The chance for pregnancy each month with these drugs depends on the patient’s diagnosis. Patients with certain problems do better than others. In general, if this therapy is going to work, it will do so in the first 3 cycles. If pregnancy has not occurred within the first 3 cycles of superstimulation, it generally is more cost effective to switch to the next level of treatment, in vitro fertilization (IVF). The table below lists various diagnoses and the chances for pregnancy in each month with superstimulation.

Unexplained Infertility
Ovulation Disorder

*The chance for pregnancy each month in a completely normal couple with two children having timed intercourse is only 20%.

Does addition of intrauterine insemination (IUI) with the husband's sperm improve the odds for pregnancy with superstimulation?

Intrauterine insemination (IUI) places a higher concentration of motile sperm closer to the eggs. This results in roughly a 5% increase for the chance of pregnancy within that superstimulated cycle. There is a small risk of infection of about 1 per 500 from this procedure.

What is the cost of a superstimulation cycle?

Each daily injection of medicine may cost between $80 and $180 depending on the amount and type of medication used. After allowing for the blood estrogen levels, sonograms and insemination, the total cost of a super-stimulated cycle can be $1500 to $2500 each month. A few insurance policies cover the entire cost of the super-stimulated cycle. Other insurance policies will only cover the sonograms and the blood estrogen levels, while remaining insurance policies may pay for nothing. It is important for you to check with your particular insurance plan. If pre-certification for the cycle is needed, we need at least one week to work on the pre-certification process, since insurance companies frequently leave us on hold for hours and are often slow to respond to the pre-certification requests. 

What are the possible risks involved with superstimulation?

  1. Multiple gestation – If a pregnancy is achieved, about 70% of the time there is only 1 baby, however, about 24% of the time there are twins, about 5% of the time there are triplets, and less than 1% of the time quadruplets or more are present. While many couples are happy to have twins, the complications of pregnancy increase with the number of babies present. The most serious complication of multiple gestation is preterm labor with delivery of premature infants. Severe pre-maturity can result in the death or brain damage of a child. With proper prenatal care, the risks of premature labor can be lessened but not eliminated. Every effort is made to increase the chances for pregnancy while minimizing the chances for multiple births.
  2. Ovarian Hyperstimulation Syndrome – Approximately 1-2% of patients undergoing super-stimulation therapy will develop ovarian hyperstimulation syndrome. This occurs when the ovaries are extremely sensitive to the fertility medication and become quite enlarged and swollen. If this occurs, most patients are successfully treated at home on bed rest, but rare patients have to be hospitalized. One value of the blood estrogen testing and vaginal sonograms is that individuals at high risk of developing this hyperstimulation syndrome can be identified and precautions taken. Very rarely, an ovary has to be surgically removed due to complications from ovarian hyperstimulation such as ovarian torsion.
  3. Ovarian cancer – A study in the early 1990’s suggested that Pergonal use may increase the chances for developing ovarian cancer later in life. However, many more recent studies do not agree. Patients who suffer from infertility already have a higher chance of getting ovarian cancer on the basis of the infertility alone. Pregnancy somehow has a protective effect against developing ovarian cancer. Women with a history of Pergonal use who successfully conceived, do not have a higher risk of developing ovarian cancer over the general population.

What are the reasons for cancellation of a superstimulation cycle?

  1. If the patient is at significant risk of developing the ovarian hyperstimulation syndrome, the ovulatory dose of hCG will not be given and the patient will be instructed to avoid pregnancy for that cycle. In the absence of hCG the ovarian hyperstimulation syndrome does not occur. If the patient becomes pregnant without the hCG injection, the pregnancy will make hCG and the ovarian hyperstimulation syndrome will still occur and can be more severe.
  2. If there are too many mature follicles on the day the hCG injection is needed, the cycle may be canceled because the risks of multiple births may be too high. Rarely, we proceed with the ovulatory dose of hCG if the patient is willing to accept the increased risk for multiples. Selective reduction of extra embryos is possible and some patients will choose to have this procedure while others do not. Selective reduction is not presently done in Kentucky and patients will have to travel to have this procedure performed.
  3. A rare patient will not respond to the medication and the cycle will simply be stopped.

How do I get started?

  1. Typically, the medication is started on the third day of the menses. Please phone (859) 260-1515 the first, second or third day of your period. You will need to be seen for a vaginal sonogram and have your blood drawn for an estrogen level.
  2. If it is your first time, you or your husband will be instructed on mixing the medicine and giving the injection by one of the nurses. If you or your husband can not give the injections, other arrangements will be made.
  3. Some patients obtain their medication directly from a local pharmacy while others need a prescription to mail off for the medication. Please check with your insurance to see which would apply for you. Also, if precertification for the cycle needs to be done, please arrange this at least a week ahead of time as the precertification process can be slow.
  4. Times for follow-up visits are decided based on dosage of medication, blood estrogen levels and ultrasound findings.