The FSH containing fertility drugs, the gonadotropins including Repronex, Bravelle, Follistim, Menopur and Gonal F are used to stimulate ovulation in IVF patients and those undergoing stimulated IUI. Gonal-F and Follistim are composed of pure FSH identical to the humans’. These fertility drugs are manufactured using “recombinant genetic technologies” and contain no impurities. Fertility drugs like Repronex are composed of two hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH). Repronex is a “natural fertility drug” being derived from the urine of post menopausal women.
Gonal-F, Follistim, and several other fertility drugs in this class, are administered as a subcutaneous injection starting on the 3rd, 4th or 5th day of the menstrual cycle. Whether to use FSH or HMG depends on the underlying problem to be corrected. The dose of FSH or HMG, and the length of treatment, is determined by the patient’s response. FSH fertility drugs are also used to stimulate egg recruitment and development in egg donors.
In order to properly monitor the response to these fertility drugs, blood tests for estrogen and ultrasound examinations for detection of ovarian follicles are performed during treatment. Usually, two visits to our Charlottesville, VA fertility clinic are necessary for these tests with each monthly treatment. The first visit is usually sometime between cycle days 7 and 9 and the second test is 1 to 3 days later and varies depending upon the patient’s response. These tests are usually performed between 8:00 and 10:00 a.m. at our office location. Results of the blood test will be available by mid-afternoon (between 1:00 - 3:00 p.m.) and they help determine the dose of fertility drugs and reduce the possibility of side effects.
Once the appropriate number of mature follicles has been reached, FSH administration ceases and a second hormone injection of 10,000 units of human chorionic gonadotropin (hCG) is given (also subcutaneous). hCG is a fertility drug available as a natural product, Pregnyl, being derived from placental tissue Ovidrel is a relatively new pure form of hCG derived using genetic recombinant technologies. Several new fertility drugs use this same manufacturing technology.
The injection of Pregnyl, or Ovidrel, establishes the exact timing for egg release allowing couples to time intercourse or for the physician to schedule the artificial (intrauterine) inseminations. Rarely ovulation will occur prior to hCG administration (very rare if the patient is taking the fertility drugs Lupron or Cetrotide or Antagon) and thus interfere with the timing of the insemination or intercourse. For this reason we suggest most patients have intercourse every other day beginning on cycle day 9. We provide each couple with an individualized treatment protocol/schedule.
FSH (the fertility drugs Gonal-F, Follistim, Bravelle, Repronex, etc.) is highly effective in stimulating follicular recruitment and development. Approximately 80% of women treated with HMG/FSH will ovulate. Pregnancy rates vary depending on the presence of other contributing infertility factors and numerous “couple specific factors”. For all-comers, FSH combined with IUI has a pregnancy rate of 18-19% per cycle. The cumulative pregnancy rate is about 30% for 3 completed treatment cycles using these fertility drugs. Pregnancy rates are about half that if timed intercourse is chosen instead of IUI.
Treatment with the fertility drug FSH or HMG does not usually cause significant side effects but occasionally it causes headaches and/or mood changes. There are three main risks of FSH/HMG treatment: ovarian cyst formation, multiple pregnancy, and ovarian hyperstimulation syndrome (OHSS).
The development of small ovarian cysts during fertility drug treatment is not uncommon and does not usually pose a significant medical problem. The cysts go away on their own, usually within a month. There is a rare risk of massive ovarian enlargement (OHSS) and in this condition, the ovaries enlarge and may create a significant medical illness with loss of body fluid into the abdomen or chest and associated increased risk of vascular thrombosis (blood clot forming in a vein or artery). OHSS requires hospitalization and is potentially serious.
The blood test for estrogen, which is described above, is a routine part of patient management when these fertility drugs are administered. It is intended to help prevent the development of massive ovarian enlargement by closely monitoring follicular development. The fertility drugs dose is adjusted according to estradiol measurements, ultrasound evaluation and the clinician’s clinical impression. If the blood estrogen level rises above the safety zone, treatment will be terminated. Ovarian enlargement (OHSS) will only occur if ovulation takes place. Usually, ovulation will not take place unless a second hormone fertility drug, human chorionic gonadotropin (hCG), is administered. The overall risk of massive ovarian enlargement as a result of these fertility drugs is less than 1%.
Patients must come to our office for a “baseline ultrasound examination” at the end of each treatment cycle. An appointment should be made near the time the period is due. This exam will evaluate the ovaries to make certain there is no enlargement (ovarian cyst) and is essential prior to another treatment cycle with FSH/HMG.
The risk of multiple pregnancies with these FSH containing fertility drugs is approximately 20% but varies significantly depending on patient response. Most of these multiple pregnancies are twins. Multiple pregnancy increases the risk of premature birth and neonatal complications or neonatal death. Occasionally, the ultrasound may detect the presence of a high number of eggs during a treatment cycle. A decision may be made to terminate treatment based on this finding in an effort to reduce the risk of multiple pregnancies.
There may be a slight increase in the risk of tubal pregnancy with FSH/HMG therapy. If ovarian enlargement occurs, there is a somewhat increased, but quite uncommon, risk of ovarian torsion (the ovary twisting and cutting off its blood supply). In addition, there have been a variety of serious illnesses reported in association with HMG fertility drug treatment. Their frequency is rare, or extremely rare, and in some cases a proven link to HMG treatment as the cause is not clear. These fertility drugs have been around for decades and are commonplace and FDA-approved for inducing ovulation.
There are at least two medical publications in the ‘90s suggesting that these fertility drugs may increase the long-term risk of developing ovarian cancer. There are now recent, more powerful studies suggesting no increase in cancer risk. This issue is new and is evolving and we do not have clear and conclusive evidence one way or the other at this point.
FSH containing fertility drugs are expensive and the related blood and ultrasound monitoring make each cycle costly, between $1,000 and $2,200. The reason there is such a range in cost is due to the variability in the amount of fertility drug required for each woman and the number of visits required to properly supervise the stimulation cycle. If intrauterine insemination is to be utilized there is an additional cost of $315.
Follow up visits during HMG (FSH or FSH/LH products) treatment to evaluate follicle (egg) development is called “Gonadotropin ultrasounds (GNT scans)”. Follow up at the end of the cycle to check for ovarian enlargement is called a “baseline ultrasound” appointment. By using these terms, the office staff will clearly understand the purpose of the appointment.
HMG and hCG are mixed and injected in the same way. One cc (or milliliter) of fluid from the bottle of liquid is injected into the powder. By gently mixing, the powder will dissolve. Then withdraw the liquid and it is ready for “subq” injection. If you are using more than one vial of gonadotropin, withdraw the dissolved fluid from the first vial (after the powder is dissolved) and inject it into the second. Some newer fertility drugs, such as Gonal-F and Follistim, are supplied in a convenient “pen injection” system.
Both HMG, FSH and hCG are given subcutaneous (“subq”). The hCG bottle says it is only given intramuscularly but this is “dated information” and it should be given subq. Do not give the hCG until instructed. It causes ovulation and timing is key.
