What is the first choice for ovulation induction in most women?
Clomiphene citrate (Clomid, Serophene) is the first-line agent used in most women for ovulation induction. It became available in 1968 and is a good medication, given its safety profile, effectiveness and cost. Treatment with clomiphene improves the timing and frequency of ovulation and enhances the possibility of conception for the patient who ovulates only occasionally. It works by increasing the levels of FSH (follicle stimulation hormone) and LH (luteinizing hormone) secreted by the ovary to stimulate the maturation of follicles (which contain the eggs) in the ovary leading to ovulation and more predictable cycle length.
How is clomiphene given?
When you are planning a clomiphene cycle, we ask that you call our office on the first or second day of your menstrual cycle. If you start on a weekend, call on Monday morning. The nurse will talk with you about the cycle, schedule an ultrasound if needed and call your prescription to the pharmacy. The usual clomiphene dose is 100mg/day for 5 days beginning on cycle day 3, 4 or 5. Ovulation usually occurs approximately 7 days after the last pill is taken.
If you have no menstrual cycle, progesterone will be prescribed in order to induce a menses. After 5 days of progestin therapy, a period occurs, then clomiphene is started on the fifth day of bleeding. We usually start at a dose of 100mg/day taken cycle day 5 through 9.
How do I know when I am ovulating?
Ovulation can be predicted with the use of an ovulation predictor kit, which detects the surge of LH that occurs 1-2 days prior to ovulation. Alternatively, we use ultrasound to evaluate the growth of ovarian follicles, as well as to look at the endometrial thickness.When follicles measure 18-20 mm, and the endometrial thickness is adequate, we give an injection of hCG which triggers the ovary to release the eggs from the follicles. Intercourse and/or intrauterine insemination (IUI) can then be timed to coincide with ovulation. We obtain a progesterone level in the second half of the cycle to evaluate ovulation.
What specific findings are we looking for with ultrasound monitoring?
We are looking at the number and size of the follicles, as well as the pattern and thickness of the endometrium. Ultrasound monitoring is performed at all three locations Monday-Friday and on weekends in the Frisco office to evaluate your response to medications. We use ultrasound monitoring as the main indicator of how close you are to ovulating as it allows us to time, in a very precise way, when you are ovulating with either IUI or timed intercourse.
When can I tell if I am pregnant?
If you have not had a period 14-16 days after ovulation, you may do a home pregnancy test. (Performing the test before 14 days may result in a false positive.) Call the nurse with the results. If it is positive, we will have you come in for a blood pregnancy test. If it is negative, we will ask you to wait a few more days, then repeat the test. If it is still negative, your physician will prescribe Provera to induce a period.
How long do I stay on clomiphene?
Of the women who conceive on clomiphene, approximately 90% do so within the first 3-4 cycles of taking the medication. If you are not pregnant after this time, we will schedule a consultation with your physician to discuss further treatment options.
What side effects can I expect from clomiphene?
For most women side effects are minimal and transient, but this is variable. The most common side effect is hot flashes during the time you are taking the medication. Other side effects can include nausea, breast tenderness, mood changes, depression and vaginal dryness. Some complaints such as visual disturbances may require that clomiphene be stopped.
Does clomiphene decrease cervical mucus and uterine lining?
Estrogen is the hormone that causes the cervical mucous to increase and facilitate the passage of sperm through the cervix. It also causes the uterine lining (endometrium) to thicken in preparation for the implantation of a fertilized egg. For some women, clomiphene can have an anti-estrogenic effect on the cervical mucus and endometrium. The use of IUI provides a way to by-pass the cervical issue by placing the sperm directly into the uterine cavity with a small catheter.
The addition of estrogen either orally or with an estrogen patch has been shown to increase the endometrium, but whether this results in improved pregnancy rates is unknown. If the endometrium is less than 8mm at the time of ovulation, treatments other than clomiphene should be considered.
What alternatives to clomiphene are available?
Letrozole (Femara) works in much the same way as clomiphene, but may have less of an adverse effect on the cervical mucus and endometrium. If these medications are not successful, the next form of treatment is the use of injectable medications called gonadotropins.
What is the incidence of twins with clomiphene?
Approximately 8% of pregnancies conceived with clomiphene result in twins. Triplets, though rare, can occur. There is no increase in the incidence of congenital anomalies.
Letrozole is used frequently as an infertility treatment. It is a recent addition to the drugs that are currently used for fertility treatment. This medication is a helpful aid to induce an egg to develop and be released in women who are not ovulating naturally; this is known as ovulation induction. Fertility drugs can also be utilized to increase the probability of pregnancy in women who are already ovulating.
Pregnancy rates with letrozole are similar to those seen with clomid and are lower than the pregnancy rates seen with gonadotropins. Older patients will have a reduced chance of success than younger patients.
Treatment with letrozole may still be successful even if other treatments have failed. Some data has shown that in women who did not ovulate with clomiphene citrate, may ovulate with letrozole.
Letrozole has also been shown to improve outcomes in cycles combining injectable FSH with oral ovulation induction. Recent studies report that the combination of letrozole and FSH enhances follicular recruitment while reducing the amount of FSH needed for optimal stimulation, thus reducing the cost of the cycle. This method has also been useful in patients who previously responded poorly to superovulation treatment protocols.
Letrozole works by reducing estrogen levels. Low estrogen levels may cause a woman to have symptoms. The data on side effects is from women who have been utilizing letrozole for an extended period of time as a means of treating breast cancer. The treatment duration for letrozole is only 5 days. In our practice, we have seen side effects that are comparable to those seen with clomid:
- Hot flashes
- Breast tenderness
Human Menopausal Gonadotropins (hMGs) are the hormones that your pituitary gland normally secretes to stimulate the ovulation of one egg from your ovary. These hormones are Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). When given by injection hMGs serve to stimulate or enhance the maturation of several eggs within the ovaries. The following are types of hMGs that your physician may prescribe: Follistim, Gonal F, Repronex and Menopur. In addition, an hCG product such as Ovidrel or Novarel will be used to complete the maturation of the eggs and allow them to be released from the ovaries for fertilization.
Patients often have concerns about the use of needles and syringes to administer fertility medications. The prefilled cartridges arrive with ready-to-use medication, so there’s no mixing or preparation. These are 2 of the pens that are used to give injectable medications.
How do I know if I need gonadotropins instead of Clomid?
Each patient is treated based on age, prior history and individual fertility problems. Patients under the age of 35 often start with Clomid for 3-4 months. If no pregnancy occurs, consideration is given to moving on to gonadotropins. If a patient is over 35 she may begin treatment with gonadotropins. Both options are discussed in a consultation with your doctor.
You will need to have had a basic fertility workup, including lab, HSG and a semen analysis for your partner. You will be asked to call the office on day 1-2 of your menstrual cycle to arrange a baseline estradiol blood test and an ultrasound. These tests must be done on day 2 or 3; if you start your period on a Saturday, please call the office early Monday morning to schedule a same-day appointment. The injections typically begin on day 3 of your cycle and should be given at approximately the same time every day, usually between 6 pm and 10 pm. Injections are given for about 10-12 days or until you are close to ovulation.
You or your partner will administer the injections at home; one of our nurses will carefully review the injection process with you before you leave the office. Current design of gonadotropin injections is user-friendly and causes minimal discomfort.
Your cycle will be monitored carefully with ultrasound and blood estradiol (estrogen) levels. Ultrasounds are performed with a vaginal probe, which enables us to evaluate the size and number of follicles present. Follicles are the fluid-filled sacs within the ovary that contain the eggs. Eggs are too small to see on ultrasound, but measuring the follicle gives information about the maturity of the egg inside. Ultrasounds are usually scheduled after you have been on medication for 5 days and may be required every 1-2 days until your follicles are mature.
Estradiol levels are monitored along with ultrasounds to help evaluate the developing follicles. Estradiol is a form of estrogen, which should increase as the follicles mature. Estradiol levels are drawn in our offices between 8-10 am.
Throughout your cycle one of our physicians will review the results of your ultrasound and estradiol levels and adjust your medication dosage accordingly. When the follicles reach a state of maturity as evidenced by your ultrasounds and estradiol results, your physician will have you take your hCG injection to trigger the release of the eggs from your ovaries. Most patients will ovulate 36-40 hours after the injection.
On days you have had an ultrasound, and/or estradiol test, you will receive a call from a nurse with medication instructions and your next appointment. We ask that you be available by phone to speak with our staff on the days you have had ultrasound or blood work monitoring so we can verbally confirm your medication dose and schedule your follow-up appointment.
We recommend that you have intercourse every 2-5 days during the first half of your cycle. Intrauterine insemination (IUI) will be scheduled as close to ovulation as possible, which is approximately 36 hours after your hCG injection. We ask that you abstain from intercourse for 24 hours prior to insemination to maximize the sperm count. You may have intercourse as desired after the IUI.
If you are not having IUI, we recommend intercourse the day of hCG and well as the following 2 days. It is possible to ovulate spontaneously without hCG and this is the reason regular intercourse is suggested.
Gonadotropins stimulate the ovaries and cause mild ovarian enlargement. Well-established exercise programs may be continued prior to ovulation but may need to be limited afterward. Due to increased ovarian size, activities which may be jarring to the pelvis should be avoided. Limit yourself to routine activities that are not strenuous. Jogging, aerobics, horseback riding and heavy lifting (>25 lbs) may increase ovarian discomfort.
If you have not started your period 14 days after IUI or timed intercourse, you may do a home pregnancy test. Testing earlier than 14 days may yield a false positive due to residual hCG (which is a pregnancy hormone) in your urine. If you have a positive home test, please call the office to schedule a blood pregnancy test. If your test is negative and you still have not started your period, please let us know.
Because your ovaries have produced a higher number of eggs than they usually do, they may become enlarged causing you to have symptoms of mild hyperstimulation such as abdominal bloating and weight gain of 2-3 pounds. Mild symptoms may be treated with decreased activity and observation at home. Moderate to severe hyperstimulation occurs rarely (<2%) and causes fluid to accumulate in the abdomen making you feel very distended and bloated. If you experience symptoms of pelvic pain, bloating, weight gain of more than 8 pounds, vomiting, difficulty breathing or decreased urine output, please report this to our physicians or staff immediately. In very rare cases, this can lead to a salt/water imbalance, temporary kidney or heart failure and blood clots. These major symptoms require hospitalization until resolution occurs.
Even more uncommon (<1%) are ovarian rupture or twisting (torsion). These complications also may require hospitalization.
The other major risk of gonadotropin therapy is multiple gestation, which is approximately 30% in contrast to a rate of 1% in the general population. Even with careful monitoring, the risk of multiples cannot be eliminated. While most of these pregnancies are twins, triplet or higher numbers do occur. Multiple gestation is associated with increased risk of pregnancy loss, premature delivery, pregnancy induced hypertension and post-partum hemorrhage. If multiple gestation does occur, you will be counseled regarding the risks/benefits of continuing the pregnancy with multiples versus undergoing pregnancy reduction (reducing the fetal number). The decision, of course, is ultimately yours.
Yes. If the estradiol levels are not rising appropriately or if there is inadequate follicular development, the cycle may need to be canceled. Conversely, if the estradiol level rises too high or if there are too many follicles present, the doctor may counsel you to discontinue the cycle and not take hCG. It is always difficult for patients to be told the cycle needs to be canceled, but your safety comes first. When hyperstimulation is present and the risk of multiples is high, it is usually the best approach. Even if the cycle is canceled and no hCG is given, there is a 15% chance that spontaneous ovulation may occur. Therefore you will be advised not to have intercourse until your menstrual period begins.