Ovulation Induction

Ovulation Induction (OI) is a fertility treatment which uses hormonal medication to induce or regulate ovulation, and/or increase the number of eggs produced during your menstrual cycle. Because these powerful medications produce significant changes in your system, their effects are tracked by blood tests and ultrasound.

Please notify the nurses if you need to take any medication during your OI cycle. Some medications such as aspirin, antihistamines, and non-steroidal anti-inflammatory drugs can block ovulation. It is advised that you avoid these medications as you approach ovulation during your cycle.

If you are given any prescriptions by your family doctor or any other physician, remember to inform them of your intent to get pregnant so that they can order a pregnancy safe medication.

Oral drugs used to induce ovulation include clomiphene citrate (Clomid), aromatase inhibitors (Letrozole, Femara), and insulin-lowering drugs (Metformin). While taking these drugs, you will be monitored to see if and when ovulation occurs. This can be done by tracking your menstrual cycle or with an ovulation-predictor kit (an at-home urine test). You will be required to visit our office for blood tests  and ultrasound exams.

If clomiphene citrate or other drugs are not successful, drugs called gonadotropins may be tried to induce ovulation. Gonadotropins also are used when many eggs are needed for infertility treatments. 

Gonadotropins are given in a series of shots early in the menstrual cycle. Blood tests and ultrasound exams are used to track the development of the follicles. When test results show that the follicles have reached a certain size, another drug may be given to signal a follicle to release its matured egg.

Ovulation induction medications are available at various pharmacies; however, they may not have it on hand for immediate purchase and require notice to order it. Please check with your local pharmacy for details. Specialty pharmacies may mail your order directly to your home.

We will authorize refills on your medication; however, you need to be aware of when you are going to need more medication. Please remember, we can estimate, but cannot predict the exact number of vials you will use each cycle; this depends upon your response. Be certain to have enough medication on hand.

Attention: While taking fertility drugs do not take Advil®, Motrin®, or anything containing ibuprofen (except during menstrual periods).

Gonadotropin Prerequisites
There are prerequisites for starting gonadotropin therapy. The most important of these is having an open and functioning fallopian tube. This can be confirmed by performing an Sono-HSG or a laparoscopy. In addition, sperm must be present in such a quantity as to provide a reasonable chance of obtaining a pregnancy (for example, at least 5 to 10 million motile sperm after being prepared for intrauterine insemination). These prerequisites are justified because gonadotropin therapy is a demanding experience that involves considerable time and expense.

Gonadotropin Protocol
Gonadotropins that are prescribed and can be given by intramuscular (IM) or subcutaneous (SQ) injection. Now, SQ appears to be easier and just as effective. After the fertility drug is absorbed into the blood stream, it is carried down to the ovaries, where it stimulates the eggs to develop and mature. Typically, three to eight eggs will mature when gonadotropins are administered, but ovulation of these mature eggs will not occur unless another fertility drug is given, which is referred to as human chorionic gonadotropin (hCG). This medication has multiple trade names: Ovidrel®, Profasi®, Novarel®, and Pregnyl®, and is administered when we determine that the eggs are mature and ready to be ovulated. This is determined by monitoring estrogen blood levels as well as the size of the follicles by ultrasound. When the estrogen levels and ultrasound show that two or more follicles are properly developed, hCG is administered. It is well known that ovulation will occur approximately 36 hours after the hCG injection, and therefore inseminations are timed accordingly.

After the hCG injection, the patient will notice a rise in her basal body temperature chart and possibly abdominal bloating and discomfort. This is due to enlargement of the ovaries caused by both gonadotropins and hCG administration. Once ovulation is confirmed by ultrasound, progesterone levels are checked 5 and 8 days post ovulation, and a pregnancy test is obtained 12 days post ovulation. A progesterone level is obtained to ensure adequate ovarian progesterone production, which is important in supporting an early pregnancy. If the cycle is unsuccessful, menstruation will occur approximately 14 days from the time of the hCG injection.

Gonadotropin Cycle Cancellation
Gonadotropin cycles may be canceled for a variety of reasons. On menstrual cycle day 3, we perform a “baseline” blood estradiol test and ultrasound. If the estradiol level is too high, and/or there are several large cysts on the ovaries, we will delay the administration of the fertility drugs until the beginning of the next menstrual cycle. In addition, if gonadotropins are begun and the response to the fertility drug is poor, the cycle will be canceled and restarted after the next menstrual period. Similarly, one can have a good response, but find that after six or seven days of gonadotropin injections, the estradiol levels begin to drop. This is due to either a premature “LH surge” or premature ovulation. In these situations, the eggs have not matured properly so it best to stop the cycle at this time.

Another reason to stop the cycle will be a situation where too many follicles have developed. This may put you at high risk for a multiple gestation pregnancy. If this occurs, your cycle may either be stopped, or if possible, converted to an IVF cycle.

Gonadotropin Success Rate
The success with gonadotropin therapy depends on the individual patient’s clinical diagnosis. For patients who do not ovulate or ovulate infrequently, almost all will be able to ovulate using gonadotropins. The pregnancy rate per fertility drug cycle is approximately 25 percent, and over 60 percent of patients will become pregnant within 5 to 6 cycles. These success rates will differ, however, when there are additional factors affecting a couple’s fertility. These factors may include endometriosis, cervical factor, luteal phase defect, male factor, or unexplained infertility. Success rates for these patients will range from approximately 15 percent to 25 percent per gonadotropin treatment cycle.

  • Cycle Day 1 (first day of menses) – Call the office to schedule “Baseline” labs and ultrasound for cycle day 2/3.
  • Cycle Days 2-3 – Baseline labs and ultrasound to determine medication start.
  • Cycle Days 3-8 – Medication administration as prescribed.
    • As you continue to administer your medication each evening, your estradiol level will rise as ovarian follicular development increases.
    • The number of follicles you develop depends on your individual response to the medication, your age, and your ovarian physiology.
  • Cycle Days 8-12 – Ovulation monitoring with labs and ultrasound, schedule as instructed.
  • Cycle Days 12-16 – hCG administration & timed intercourse and/or intrauterine insemination.
    • Once the follicles are mature in size, instructions for hCG administration and IUI and/or Intercourse will be given.
    • hCG is a hormone which promotes the final maturation of the follicles, resulting in ovulation.
  • Cycle Days 16-18 – Ultrasound to confirm ovulation is performed approximately 48 hours after the hCG injection.
  • Cycle Days 18-26 – Luteal phase monitoring and progesterone instructions will be given after the ultrasound is completed.
  • Cycle Days 26-28 – Pregnancy test (blood draw), which is typically performed approximately 12-14 days after ovulation.

Twins occur in 5–8% of women treated with clomiphene citrate and aromatase inhibitors. Triplets or more are rare. The risk of multiple pregnancy is higher when gonadotropins are used. Up to 30% of pregnancies achieved using gonadotropins are multiple. If too many eggs are developing, your health care professional may postpone the cycle to reduce the possibility of a multiple pregnancy.

Ovulation induction, especially with gonadotropins, can lead to ovarian hyperstimulation syndrome. Women undergoing ovulation induction are monitored for this condition.

Another risk of using gonadotropins is ectopic pregnancy. This is a pregnancy that begins to grow in a place other than the uterus, usually in one of the fallopian tubes. Ectopic pregnancy requires treatment with medication or surgery.

There are potential side effects and complications that can occur when stimulating the ovaries with gonadotropins. The major side effects with OI (ovulation induction) medications relate to the stimulation of the ovary. Stimulation of the ovary is required to produce the desired follicular development and subsequent ovulation; however, two problems can be observed when the ovary is stimulated excessively.

The first side effect is that ovulating multiple eggs can result in a multiple gestation pregnancy. In gonadotropin stimulated cycles, up to 30% of pregnancies are a multiple gestation (American Society for Reproductive Medicine, 2006). Careful monitoring of ultrasound scans during the cycle will help us determine if you are at risk for a multiple gestation pregnancy.

The second problem that occasionally occurs is ovarian hyperstimulation syndrome (OHSS). OHSS was first encountered in patients who were not having their estrogen levels and ultrasounds monitored closely. With careful estrogen monitoring and adjustments in the doses of medications prior to ovulation we can reduce, but not eliminate, OHSS. When it does occur, the ovaries enlarge and there is an increase in the vascular permeability causing an accumulation of fluid in the peritoneal cavity (abdomen) along with characteristic weight gain. If this syndrome occurs, it is usually 2 to 5 days after the HCG injection.

Patients with OHSS are rarely hospitalized. Treatment for OHSS includes bed rest and an increase in fluids by mouth to prevent dehydration. Occasionally, patients must undergo a procedure called “culdocentesis” in which the fluid is drained from the peritoneal cavity. This procedure is done in our office. You must weigh yourself every day after hCG for approximately 10 days. You will need to inform us if you gain more than 5 pounds in one week or feel severely bloated and/or uncomfortable. Dr. Russell will need to see you in the office for evaluation of OHSS by ultrasound scan. The first line of treatment for OHSS is bed rest. If you become hyperstimulated you may remain on bed rest for up to two weeks. It is important to remember that the best way to decrease the possibility of OHSS is to stop the gonadotropin injections and delay or reduce the amount of hCG injection. The only way to prevent OHSS in a susceptible patient is to withhold hCG. These medication decisions would be made by Dr. Russell and discussed with you in a consult appointment.

Our goal is to assist you in becoming pregnant with one healthy baby. If Dr. Russell feels you are producing too many eggs he may decide to withhold hCG on the last evening of your stimulation. Ten percent of patients will go on to ovulate 1-2 follicles on their own. You will be given instructions and offered to consult with Dr. Russell at that time. If you do not conceive, you will start stimulation with your next menses. If a patient does not conceive within 3 cycles of OI we request they schedule a consult with Dr. Russell to discuss how to proceed in treatment.
It is important to discuss these side effects with Dr. Russell prior to your first cycle so you are fully informed and any questions you have are addressed.