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Ovulation Induction

Ovulation induction is a promising option for patients with polycystic ovarian syndrome, oligomenorrhea, endometriosis or male factor infertility. The technique involves the use of certain medications to stimulate a woman’s ovaries to produce one or more eggs, or oocytes. These medications also can be used to control when a woman ovulates, so that sexual intercourse, intrauterine insemination, and in vitro fertilization (IVF) procedures can be scheduled at an optimal time.

Medication regimens for ovulation induction vary by patient; while some patients may be prescribed a pill that can be taken orally, such as Clomid, others may be prescribed injectable hormone medications, like Gonal-F®.

Injectable medications are typically administered at home by the patient and her partner, between the hours of 6 and 11 p.m. Before being prescribed these medications, you and your partner will be taught all necessary administration techniques by our physicians and staff. Your progress will be monitored closely, via regular blood tests and ultrasounds, and your medication dosage will be adjusted accordingly. Blood test and ultrasound results are available from 1 to 4 p.m., Monday through Friday, and from 11 a.m. to 2 p.m., Saturday and Sunday.

It’s important to keep in mind that ALL ovulation-inducing medications carry the risk of side effects. However, these side effects are usually temporary. If any side effects become persistent or bothersome, please call our office at 215-887-2010.

Note: A recent study has raised the possibility of a link between ovulation-inducing agents and an increased risk of ovarian carcinoma. Other studies have not shown this association. If you have any concerns about this, please share them with your physician.



Medications Used in Ovulation Induction

Listed below are some of the medications we commonly prescribe to induce ovulation. For administration instructions and other important information, simply click on the name of the medication you have been prescribed.

If you’re prescribed ovulation-inducing medication that is NOT listed below, please contact our office at 215-887-2010.

Clomiphene Citrate

What is clomiphene citrate?

Clomiphene, or clomiphene citrate, is a synthetic drug that stimulates the ovaries, causing estrogen levels to rise and increasing the chances of ovulation. There are two trade names for clomiphene: Clomid (manufactured by Merrell-Dow) and Serophene (manufactured by Serono). These two brands are medically equivalent, although Serophene costs a little less. While there are several generic forms of clomiphene that cost substantially less, we have no data on their efficacy.

Why is clomiphene used?

Clomiphene is primarily used to induce ovulation. Many women who do not ovulate (produce an egg) will do so if given clomiphene.

Is clomiphene ever prescribed to women who ovulate naturally?

Yes. In this case, the drug is taken to increase the odds of achieving a pregnancy.

Can clomiphene impair fertility?

The anti-estrogenic effects of clomiphene can cause a thickening of the cervical mucus, which may make it difficult for the sperm to access to the egg(s). Treatment options for this problem include intrauterine insemination and estrogen administration.

Clomiphene also may cause a thinning of the uterine lining, making it difficult for embryo implantation. Ultrasound can be used to detect changes in the width of a patient’s uterine lining.

What is a typical clomiphene dosage?

Most patients are prescribed a daily clomiphene dosage of 50 mg (one tablet), taken each day for a total of five consecutive days. The medication is usually initiated at some point between day three and five of a patient’s menstrual cycle, with cycle day one being the first day of menstrual bleeding (continuous flow, not spotting).

If ovulation occurs, but pregnancy is not established in the first cycle, the treatment can be repeated at the same dosage for up to six cycles. If ovulation does not occur with a 50 mg dosage, the dosage may be doubled. Some patients may be prescribed as much as 150 mg (three tablets) per day for five days. In rare cases, as much as 200 mg (four tablets) per day may be prescribed.

How is ovulation determined?

There are several different ways to determine ovulation. Some of the most common methods include:

  • Basal body temperature detection
  • Urinary LH (luteinizing hormone) surge determination
  • Endometrial biopsy
  • Mid-luteal progesterone test
  • Office transvaginal ultrasound

While all of these methods are considered effective, only pregnancy can definitively prove ovulation.

When is a progesterone test performed?

To perform a progesterone test, a blood sample is obtained seven days after the probable date of ovulation. In women with 28-day cycles, the sample is taken on cycle day 21. In women with longer or shorter cycles, the sample is obtained seven days before the anticipated onset of the next period.

A progesterone test also can be timed at five to seven days after the increase in basal body temperature, seven to nine days after the color change in the urinary LH test kit or by using ultrasound.

For cases in which the calculated day of the progesterone test happens to fall on a Sunday or holiday, the test can be performed on the previous or subsequent day.

What constitutes a "good" progesterone test?

A progesterone value of ten or greater is usually considered adequate. If a patient’s progesterone value is low, it may be necessary to increase her clomiphene dosage, prescribe a different kind of ovulation-inducing drug or introduce progesterone suppositories.

How does a urine LH test kit work?

Your brain secretes a hormone called LH (luteinizing hormone) in order to trigger ovulation. A "surge" in LH levels usually occurs between cycle days 12 and 16. LH can be detected using commercially available kits. We recommend Assure by Conception Technology or Ovuquick® by Quidel Corporation; mail order information is available through our office. You may be asked to test your urine each morning, starting on cycle day nine (i.e. two or three days before the anticipated day of the LH surge). Ovulation should occur 12 to 36 hours after the color change is detected. "False" or premature surges usually generate a fainter color than genuine surges.

Will I need an ultrasound examination?

An ultrasound examination may be scheduled between cycle days 10 and 12 (or later) to measure the thickness of your uterine lining or follicles.Follicles are temporary ovarian cysts that contain an egg. Once your follicles reach an adequate size, you may be given an injection hormone (e.g. Profasi®, Pregnyl®, Novarel, Ovidrel) to trigger ovulation.

When should patients taking clomiphene have intercourse?

You should have intercourse every one to three days, unless instructed otherwise by your physician. Having intercourse near the time of ovulation, however, greatly increases your chances of conceiving.

What are my chances of conceiving while on clomiphene?

The chances of conceiving while taking clomiphene range from ten to 13 percent for each treatment cycle, depending on your age, the cause of your infertility, your response to treatment and any concurrent treatments you are receiving. This compares to a 20 to 25 percent pregnancy rate per cycle in the normally fertile population. Your overall chances of conceiving following six cycles of clomiphene range from 30 to 60 percent.

What are the chances of multiple births while taking clomiphene?

About five to ten percent of clomiphene-induced pregnancies result in the delivery of twins, and less than one percent result in deliveries of triplets or more. This compares to a 1.2 percent rate of twin pregnancies in those not taking clomiphene.

What side effects can occur while taking clomiphene?

Side effects, which are usually temporary, may include hot flashes, ovarian cysts, ovarian discomfort or pain, breast tenderness, headache, nervousness, moodiness, irritability, dizziness, nausea, vomiting, fatigue, and visual disturbances. Your menstrual period may also be heavier or lighter than usual, and your cycles may be shorter or longer than usual. You should contact our office at 215-887-2010 if you experience visual disturbances or any unusual symptoms.

Does clomiphene cause ovarian cancer?

In women with a consecutive exposure of fewer than 12 cycles of clomiphene, there is no evidence of increased ovarian cancer risk. If you have undergone 12 or more cycles of clomiphene, your risk of ovarian cancer may increase.

For women who have never taken fertility drugs, their lifetime risk of developing ovarian cancer is about 1.7 percent. In women who have had less than 12 cycles of clomiphene, their risk of ovarian cancer may actually be slightly less. There is one study that suggests for women who have undergone 12 or more cycles of clomiphene, their lifetime risk of ovarian cancer may be increase 7 to 11-fold. It should be noted the studies examining occurrences of ovarian cancer following clomiphene use are limited by small patient numbers.

When considering cancer risk, remember that a woman's lifetime risk of developing breast cancer, for example, is 12 percent, even if she has never used clomiphene. In fact, since pregnancy reduces the risk of ovarian, breast, and endometrial (uterine) cancer, women who become pregnant due to clomiphene use may actually derive health benefits from the medication.

Does clomiphene cause any anomalies in the offspring conceived?

Clomiphene has been safely used in the U.S. since 1967. To date, there is no evidence that clomiphene causes an increase in birth defects or developmental problems.

Are there any alternatives to clomiphene?

Most women who do not become pregnant using clomiphene can be treated with gonadotropins—injectable medications such as Follistim, Gonal-F®, Repronex, Bravelle and Menopur—that work directly on the ovary to stimulate egg maturation.

On rare occasions, your physician may prescribe a drug called Tamoxifen. While this drug is similar to clomiphene and may have fewer side effects, it can be less effective in stimulating ovulation. Whereas patients who take high doses of Tamoxifen for long periods of time (usually for the suppressive treatment of certain cancers) may be at a slightly increased risk for developing other cancers, the dosages and treatment durations used for infertility purposes are unlikely to cause any lasting, adverse effects.

Gonal-F and Follistim

Part of a family of injectable hormone medications called gonadotropins, Gonal-F® and Follistim AQ work directly on the ovaries to stimulate egg maturation. They can be administered as subcutaneous (SQ)injections and should be administered around the same time every evening.

FOLLISTIM AQ

Equipment:

• Follistim Pen device
• Follistim AQ cartridge (300 IU, 600 IU or 900 IU)
The cartridges should be stored refrigerated. They may be stored refrigerated for 3 months or until expiration date, whichever occurs first. Once rubber stopper on Follistim AQ cartridge has been pierced by a needle, the cartridge may be stored at room temperature for a maximum of 28 days.
• BD Micro-fine Pen Needles
• Alcohol swabs or rubbing alcohol and cotton

To prepare medication:

1. Remove protective cap from pen device; set aside.
2. Unscrew pen device.
3. Take a Follistim AQ cartride out of its package, clean stopper with alcohol and insert cartridge into yellow part of pen device by placing the metal-rimmed cap end first. Screw pen device back together, lining the arrow with the yellow rectangle.
4. Clean open end of the pen device with alcohol pad. After dialing dose, apply needle. Peel off protective paper seal on BD Micro-Fine Pen needle. Push the yellow end of the pen device onto the needle and screw them together tightly.

Follistim administration:

  1. For doses of 50 IU up to 450 IU, turn the dosage knob until the dot beside the correct number on the dosage scale is sitting in the middle of the dosage window.
  2. If by mistake you dial past the correct number, do not try to turn the dosage knob backward to fix the mistake. Continue to turn the dosage knob in the same directrion past the 450 IU mark, as far as it will turn. The dosage scale must move freely. Push the injection button in all the way. Start to dial again, starting from "0" upwards.
  3. Needle: Wipe the injection site with alcohol (back of arm, abdomen, or outer thigh), pinch swabbed area between two fingers. With other hand, insert entire needle straight into the skin. Press the injection button all the way to make sure you give full injection. Wait for 5 seconds before pulling the needle out of skin. You should see "0" in the middle of the injection window. If the number is not "0" this means there was not enough medication in the cartridge to give entire dose. The number in the window is the amount of medication still needed to be administered. Write down this number. Replace cartridge and needle - dial up remaining dose and follow procedure to administration.
  4. Recap the needle, pushing the needle into the cap while the cap is on a flat surface. Push down firmly. The outer needle shield should now be attached to the cartridge holder and cover the needle.
  5. Grip the outer needle shield and use it to unscrew the needle from the cartridge holder. Dispose of needle in a sharps container. Replace cap to pen device for storage.

GONAL-F/RFF PEN

Equipment:

• Gonal -F Pen (300 IU, 450 IU or 900 IU). The pens maybe stored refrigerated for 3 months or until expiration date, whichever occurs first.
• Needles
• Alcohol swabs or rubbing alcohol and cotton

To Prepare Medication:

  1. Wipe threaded end with alcohol.
  2. Remove the peel tab from the outer needle cap.
  3. Press the outer needle cap to the tip.
  4. Twist cap onto end of pen until tight.
  5. Remove outer needle cap.

To Prime Pen: This is required only prior to first use of each new pen.

  1. Turn dosage dial to align dose of 37.5 with black arrow.
  2. Pull out injection button as far as it will go.
  3. Remove the inner needle cap.
  4. Hold the inj with needles pointing toward ceiling. Tap barrel to dislodge any air bubbles. Push injection button in and watch for drop of medication. 

GONAL-F Administration:

  1. Turn the dosage dial so your prescribed dose is in front of the dose arrow. Carefully check the dosage dial before proceeding to the next stop.
  2. Pull out the injection button as far as it will go. Confirm the dose with the closest red arrow. If the loaded dose is lower than the set dose, the quantity of drug left in the pen is not enough to complete dose. You need to start a new pen.
  3. Wipe injection site (back of arm, abdomen, outer thigh) with alcohol. Pinch swabbed area between two fingers. With other hand, insert entire needle straight into skin and push the injection button in as far as it will go. Wait 5seconds then remove needle from skin. Apply pressure with gauze or tissue.
  4. Replace outer needle cap over needle.
  5. Twist needle and needle cap off as one unit. Dispose of needle in sharps container. Replace pen cap. Gonal-F may be stored at room temperature for a maximum of 28 days once used.

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Metformin

Patient Information

Metformin is a typically prescribed to patients with Polycystic Ovarian Syndrome (PCOS), a common cause of infertility. PCOS patients are at increased risk of developing Type II diabetes, hypertension, dyslipidemia and coronary heart disease. Metformin is an oral antihyperglycemic agent that has been shown to improve the body's use of insulin (patients with PCOS typically have hyperinsulinemia, meaning their pancreas produces large amounts of insulin), decrease androgen levels and restore normal ovulatory function.

During Treatment

It is very important to maintain a proper diet while taking Metformin. Weight loss has been demonstrated to decrease androgen levels and increase insulin sensitivity. We can refer you to a nutritional counselor if you need guidance in this area.

We also advise you to initiate or continue a daily exercise routine (20 minutes per day is ideal), avoid excessive alcohol intake (alcohol increases your risk of lactic acidosis) and discontinue drug use.

How to Take Metformin

You will begin by taking one 500 mg tablet of Metformin daily for one week. Your dosage will be increased each subsequent week until you are taking 1,500 mg (three 500 mg tablets taken separately) of Metformin each day.

If you miss a dose, take it as soon as you remember. If you miss a dose and remember near the time of your next dose, skip the missed dose and resume your usual dosing schedule. Do not "double up."

Side Effects

Common side effects of Metformin include nausea, vomiting, diarrhea, loss of appetite, stomach fullness, constipation and heartburn. If you experience any unusual or bothersome side effects while taking Metformin, please contact our office at 215-887-2010.

Pregnancy

Metformin is pregnancy category "B," meaning there are no apparent fetal risks based on animal reproductive studies nor are there any risks associated with use of this drug during the late trimesters of pregnancy. PCOS patients should be screened for glucose tolerance in the first trimester (by 12 weeks) rather than during the typical screening period of 24 to 28 weeks. You will remain on Metformin until your visit with your OB/GYN. Your OB/GYN will then determine whether you should continue the Metformin.

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Bravelle, Menopur, Repromex

Bravelle is the newest highly purified human-derived FSH.Menopur and Repronex contain follicle stimulating hormones (FSH) and luteinizing hormones (LH). All of these medicationscan help stimulate the ovaries to produce and release eggs. The medication can be administered as a subcutaneous (SQ) or intramuscular (IM) injection according to your physician’s instructions. Note: IM administration requires assistance from your partner. If you have ANY questions about the following instructions or experience unusual, bothersome side effects while taking Repronex, please contact our office at 215-887-2010.

Equipment:

  • Medication (powder)
  • 3 cc 22 g 1 1/2” syringe
  • 27 g 1/2” needle tip for subcutaneous (SQ) administration or 22 g 1 1/2” needle tip for intramuscular (IM) administration
  • Diluent (saline)
  • Alcohol swab
  • Gauze pad or tissue
  • Rubbing alcohol

Note: Your injection materials MUST be sterile and MAY NOT be reused

To prepare medication:

  1. Remove the syringe from the package.
  2. Flip off the seals from the top of the medication and the diluent.
  3. Wipe the rubber stoppers with rubbing alcohol.
  4. Remove the cap from the syringe.
  5. Draw air into the syringe by pulling the plunger out to the 1 cc (l ml) mark. Inject the 1 cc air into the vial of diluent (saline).
  6. Push the syringe to the bottom of the vial. Pull back on the plunger to fill the syringe with 1 cc (l ml) of diluent.
  7. Slowly inject all the diluent from the syringe into the vial of medication (powder). The medication will dissolve readily. Swirl gently (do not shake).
  8. Push the syringe to the bottom of the vial and withdraw the entire 1cc of dissolved medication. For doses greater than 1 vial, take the dissolved medication and inject it into the next vial of powder until the correct dose is reached. Up to 4 powders can be mixed in 1 cc of diluent.

Subcutaneous (SQ)administration:

Twist off the needle tip of the syringe and replace with a new 27 g 1/2” needle tip. Make sure the new needle tip is twisted securely in place.

Choose the injection site: back of upper arms, abdomen or outer top of thigh.

Clean the injection site with rubbing alcohol and let dry.

Pinch the injection site with your non-dominant hand.

Use your dominant hand to insert the needle at a 45-degree angle with a quick, dart-like motion. Slowly, steadily depress the plunger to inject the medication.

Withdraw the needle and discard the syringe. Use a gauze pad or tissue to apply pressure at the injection site.

Note: SQ administration of Repronex may cause a raised red area at the injection site that should improve within 24 hours. If little or no improvement occurs, switch to intramuscular administration and contact our office at 215-887-2010.

Intramuscular (IM) Administration:

  1. Twist the needle tip of the syringe off and replace with a new 22 g 1 1/2” needle tip. Make sure the new needle tip is twisted securely in place.
  2. Choose injection site: upper outer quadrant of the buttock, right or lift side.
  3. Clean the injection site with rubbing alcohol and let dry.
  4. Lie on your side with your knee slightly bent.
    THE FOLLOWING STEPS (5-8) SHOULD BE COMPLETED BY YOUR PARTNER:
  5. Use the thumb and first two fingers of your dominant hand to hold the skin in position. Use your dominant hand to hold the syringe like a pencil and with a dart-like motion, insert the entire needle at a 90-degree angle. Once the needle is in place, release your grasp of the skin.
  6. Slowly pull back on the plunger with your non-dominant hand (the hand that just let go of the skin). If blood enters the syringe at this time, pull the needle out of the skin slightly and test again.
  7. If no blood appears, depress plunger in a slow, steady motion until all medication is injected.
  8. Withdraw the needle and discard the syringe. Use a gauze pad or tissue to apply pressure at the injection site.

Note: Rotate injection sites daily. For example, if you gave the first injection in the right buttock last night, you should give the second injection in the left buttock tonight.

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