Ovulation Induction

Ovulation induction or Controlled Ovulation Hyper-stimulation or Super-ovulation means using fertility medications to stimulate the ovary to produce one or more eggs.

OVULATION INDUCTION may be done in one of two particular situations.

Female infertility is often a result of woman’s failure to ovulate, failure to ovulate regularly, or failure to ovulate healthy eggs. The cells around the egg that secrete female hormones into a woman’s bloodstream as the egg matures may not always function properly. Sometimes the amount of hormones secreted may not be sufficient to properly prepare the uterine lining so that it will be receptive to a fertilized egg, or embryo. This can result in repeated pregnancy loss. Ovulation induction is often used to correct this cause of infertility when other reasons for recurrent miscarriage are not identified.

Abnormal ovulatory cycles are among the most common causes of infertility. The causes of these types of disorders are quite diverse, and may include problems with the central nervous system or pituitary gland, problems within the developing follicles or ovary, or both. Polycystic Ovary Syndrome is the diagnosis for the vast majority of women who fail to ovulate regularly. Central nervous system problems, thyroid problems, and premature ovarian failure are first ruled out with blood tests. These women usually have plenty of egg-containing follicles in their ovaries, but for hormonal reasons, are unable to release eggs on a regular basis. This syndrome is often quite amenable to treatment with ovulation inducing drugs.

Ovulation induction is also used in circumstances where the exact cause of infertility is not known even if a woman is ovulating regularly on her own . Endometriosis-associated infertility, not associated with anatomical damage to the fallopian tubes or surrounding structures, can also treated by ovulation induction. In such cases, the woman uses ovulation inducing agents to “superovulate” the ovaries, or cause multiple eggs to mature, instead of the one egg that usually matures per menstrual cycle. By combining superovulation with Intrauterine Insemination (IUI) timed to coincide with ovulation, the sperm are given more “targets.” It is hoped that pregnancy will result because multiple, mature, and, perhaps, healthier eggs are available after superovulation. Though superovulation combined with timed intrauterine insemination does not guarantee that a woman with unexplained, mild male factor, or endometriosis-associated infertility will conceive in a given treatment cycle, the chance for pregnancy to occur is higher than the infertile woman’s background rate of conception.
 
OVULATION INDUCTION is often used in conjunction with another treatment called Intrauterine Insemination (IUI). Intrauterine Insemination (IUI) is an office procedure in which the sperm is carefully placed in the woman’s uterus, bypassing the cervix and allowing more sperm to reach the egg.  The process involves the use of a very thin flexible catheter that facilitates passage of sperm. The procedure takes just a few minutes, and patients are able to return to regular activities immediately after the procedure. IUI may be recommended to increase the probability of pregnancy if a patient has unexplained infertility, male factor infertility (low sperm), problems with cervical mucous, or difficulty with intercourse.
Various IUI treatment options include the following:
•    Natural Cycle (using no medications)
•    Oral Medication for ovulation induction (e.g.Clomiphene or Letrozole)
•    Injectable Gonadotropin Medications for ovulation induction (Follistim, Gonal-F, Menopur, Bravelle)
Your physician will recommend the treatment cycle most appropriate for you. The doctor might recommend adjunctive therapy when using gonadotropins, such as ovarian “down-regulation” with a drug called Lupron to get a better response from the ovaries. Patients using clomiphene may be pretreated with medication to lower insulin levels in the blood (Metformin, Glucophase). This helps certain patients with polycystic ovaries better respond to ovulation induction. Weight loss is helpful for some patients who are obese and not ovulating regularly. The use of all these medications carry certain risks and benefits that vary with each case.
 
1. Natural Cycle
During a Natural Cycle, no fertility drugs are taken. The patient will begin treatment by calling us on your first day of menstruation (Cycle Day 1) On Cycle Day 10 (CD 10), you will be instructed to begin checking for ovulation using an over-the-counter Ovulation Predictor Kit. When ovulation is detected, you must call to schedule the IUI. Generally the IUI is scheduled the day after a positive ovulation. A pregnancy test is done two weeks later to determine if the IUI was successful.

2. Oral Medicated Cycle
This is the common initial treatment for couples with unexplained infertility, or those who failed the Natural Cycle. These medications are in the form of tablets which are taken daily by mouth for five days. Clomiphene and Letrozole are the two more commonly used oral medications. Your physician will determine the medication most suitable for you.
Baseline ultrasound is performed before starting oral medications. Occasionally there may be an ovarian cyst detected at this time. If a cyst is detected, you will be instructed not begin treatment. If there are no cysts present, you will be asked to take your medication.

A decision making ultrasound will be performed mid-cycle to check for follicular development. When the ultrasound examination suggests that the eggs are mature (usually when the lead follicle average size is about 18 mm or greater in diameter), you will be instructed to take an injection of human chorionic gonadotropin (HCG). The timing of the HCG is critical, so it is crucial that you take it at the time instructed. This injection is administered subcutaneously similar to the one used to administer insulin.  Approximately 36 to 40 hours after the HCG injection, an IUI will be performed.
Two weeks following the IUI a pregnancy test is performed to determine if the IUI was successful.

Most women do not suffer any side effects with these medications. However, some women may have side effects such as mood changes, bloating, breast tenderness, or hot flashes. Risk of multiple pregnancies depends on the number of oocytes released (which can be predicted by ultrasound) and age.
Often, a patient is switched to injections if the pill form of ovulation induction fails. The patient should expect to try a certain medication about three times, before trying the next form of treatment.  

3. Injectable Gonadotropin Medication Cycle
Injectable gonadotropin (FSH) may be the third treatment option recommended by your doctor. To begin this treatment patient contacts us on the first day of full menstrual flow (cycle day 1). A baseline ultrasound must be scheduled by cycle day 3 to check for possible ovarian cysts in the ovaries. If there are no cysts detected on ultrasound, you will be instructed to begin your gonadotropin injections the evening of CD3. We will teach you to administer these medications yourself or you may choose to have your partner administer them to you. The medications are to be injected subcutaneously (into fatty tissue injection sites) every night until instructed to discontinue.
The next ultrasound performed will usually fall on cycle day 7; this is to monitor the response of the ovaries to the first few days of injections. The physicians will then determine if the dose is appropriate based on the number and size of the follicles seen on ultrasound. The dose may be increased, decreased or maintained. Too great a response can be dangerous and may result in high-order multiple pregnancy or excessive swelling of the ovaries. Too little a response usually does not end up in pregnancy. An ultrasound may be performed every 2-3 days later, along with blood tests to monitor the growth of the follicles. Once the lead follicle(s) measure at least 16-18 mm in diameter, another set of instructions will be provided as to the timing of the HCG injection to coordinate ovulation induction and the IUI. Ovulation typically occurs 40 hours after administration of the HCG injection.

Similar to oral medications, most women do not suffer any side effects. But it is possible to have bloating, breast tenderness, and other side effects commonly associated with the oral medications. Risk of multiple pregnancies depends on the number of oocytes developing and your age. 

Success rates

Success rates are contingent upon the procedure being performed:
1. For the correct indications.
2. Avoiding doing this when contraindications exist (such as blocked tubes, poor sperm quality).
3. Whether the woman is ovulating normally on her own.
4. The age of the woman.

An approximation of the pregnancy rates per cycle of superovulation/IUI performed for the correct indications are as follows:

1. 20% for women under the age of 30.
2. 15 % - 18% for women aged between 30 and 35.
3. 10 - 15% for women aged 35 to 39.
4. 5 - 10% for women over the age of 40.

However, the projected success rates really need to be individualized. It does depend largely on age and the choice of medication. Using gonadotropins improves pregnancy rates over using an oral agent like clomiphene. For instance, in the couple under the age of 30 with normal sperm parameters and using gonadotropins to stimulate ovulation, the success rate may be as high as 25% per cycle. At the other extreme, in the woman who is over 40, using only Clomiphene to stimulate the ovaries, the success rate for ovulation induction with Clomiphene and IUI would only be about 2 – 5 % per cycle.