Ovulation Induction (OI)

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.

Patient Responsibilities

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 (Category B classification).

The Ovulation Induction Cycle Overview

You need to begin your ovulation induction cycle by calling the office when your period begins (cycle day 1) to schedule a cycle day 2 or 3 ultrasound and blood work (this is called a “baseline” appointment). The injectable medications need to be administered between 7pm-9pm starting on the 2nd or 3rd day of your period. You will be expected to return to our office for frequent ultrasounds and blood work until approximately cycle day 10-12. 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. Once the follicles are mature in size, instructions for hCG administration will be given. hCG is a hormone which promotes the final maturation of the follicles, resulting in ovulation. When hCG instructions are given, you will also be instructed on what to schedule next, such as a post-coital test, IUI, or given intercourse instructions. hCG is administered between 9-10pm unless otherwise instructed. An ultrasound to confirm ovulation is performed approximately 48 hours after the hCG injection. Luteal (progesterone) instructions will be given after the ultrasound is completed. The pregnancy test is done approximately 12 days after ovulation.

Please be advised, we will give you intercourse instructions on cycle day 8 in preparation for your post coital test or IUIs.

Gonadotropin Therapy

Gonadotropins are fertility medications that are used to stimulate follicular growth and induce ovulation. These medications contain follicle stimulating hormone (FSH) and luteinizing hormone (LH) either alone or in combination. These medications must be given by injection since it is a natural protein hormone and would be digested if taken orally. Gonadotropins are produced under the trade names Menopur, Bravelle, Follistim, Gonal-F, and hCG.

Human Menopausal Gonadotropins: Menopur is a medication used to stimulate ovulation. It is a natural product which contains 75 units of FSH (follicle stimulating hormone) and 75 units of LH (luteinizing hormone). Once injected, these two hormones circulating in the blood will stimulate the follicles, which contain the eggs in the ovary, to grow and mature. Menopur is a natural product made from the urine of newly post-menopausal women. These hormones are extracted from the urine, purified, and then freeze dried. Bravelle is another product similar to Menopur; however Bravelle contains FSH and only a very small amount of LH. Because of this extraction and purification process, these medications are costly. These mediations come in powder form and require mixing (reconstitution) prior to injection.

Recombinant Gonadotropins : Follistim and Gonal-F. These medications are also used to stimulate the ovary. These medications are made synthetically through recombinant DNA technology and contain only pure “FSH.” Follistim and Gonal-F work by stimulating follicles in the ovary to grow and mature the same way the urinary products do, but without any LH. New delivery systems allow for easy measuring and injection of FSH. It is no longer necessary to mix the medication prior to the injection. The “pen” device comes either pre-filled or with medication cartridges that are easily inserted into the device. This new delivery system is capable of variable dosing which allows for more specific and individualized medication protocols.

Lupron Depot®, Cetrotide, and Ganarelix

These medications are very similar to a brain hormone known as gonadotropin releasing hormone (GnRH). GnRH is responsible for the release of the pituitary gonadotropins. One of those hormones, LH, is responsible for triggering ovulation. We want to prevent the release of LH and avoid ovulation of the eggs prior to egg retrieval. By administering “GnRH-like” medications, we can suppress the release of LH and prevent premature ovulation. These fertility drugs are administered subcutaneously (SQ).

The choice of a particular gonadotropin or GnRH-like medication depends on many factors. Every patient and fertility drug is unique, and Dr. Russell will recommend a course of therapy that is considered best for you.

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 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. At the present time, 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 problems. For patients who do not ovulate or ovulate infrequently, close to 100 percent 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 five to six 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.

Ovulation Induction Side Effects

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.

Summary of the Gonadotropin Treatment Cycle – Ovulation Induction (OI)

Day 2-3 of Menses

Come in for an ultrasound and blood test. Appointments are necessary except on Sundays. We will use your assigned mailbox to provide you with instructions during your cycle. Blood tests and ultrasounds are performed from 7:30-10:00 a.m. weekdays and 7:30-9:30 a.m. on Saturdays and holidays. If the ultrasound and blood estradiol (E2) are normal, gonadotropins (OI) will be started.

Day 5-6

Blood E2 levels. If E2 is rising as expected, the gonadotropin dose will not be changed. If the E2 level is too high, the amount of gonadotropin will be decreased; if it is too low, an increase the gonadotropin dose will be needed.

Day 8

Blood E2 levels and possibly an ultrasound to check for enlargement of follicles (egg sacs). Please check your mailbox every time you have an ultrasound and blood work.

Day 10-11

Blood E2 levels and ultrasound. At this point, the E2 levels and size of the follicles may indicate that the eggs are ready for ovulation (release from the follicle). If so, you will administer hCG, at a specific time. If you are having an IUI, this will normally be done the day after hCG and the following day. If having intercourse and not IUIs, begin the evening of hCG and continue daily or every other day until at least the second day after hCG.

7 Days After hCG Administration

Blood progesterone level is determined to confirm ovulation. Progesterone may be prescribed.

Approximately 14 Days After hCG Injection

A pregnancy test will be performed. If conception has not taken place, the menstrual period will begin on or about this time. When you are three to five days late for your period, please come to the office to have a pregnancy test.

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

Regarding your medications:

Ovulation induction medications are available at various pharmacies; however, they may not have it on hand and require one to two days notice to order it. Our office sells each of these medications; however, we do not accept insurance plan cards at this time. Our medication prices at the office are very reasonable. Please check with the receptionist for current prices. Our prices will always be lower than retail pharmacies. If you are paying out-of-pocket consider purchasing your medication at our office.

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 do not know the total number of vials you will use each cycle. This depends upon your particular response. Be certain to have enough medication on hand.

If you have any questions after reviewing the tape and written information, please do not hesitate to call and talk to one of the nurses.