CHAPTER 10

What to Expect from Infertility Treatment

Infertility treatment is like nothing you've ever experienced before. You'll see the doctor and clinic staff more than you'll see your best friends. You'll speak with the nurses on a daily basis and have frequent blood draws and ultrasound appointments. And then suddenly, you'll get a call one day that you may need to reschedule your plans for the next few days because you're ready for insemination or egg retrieval. Having an idea of what to expect can make the process much easier.

Process Overview

Undergoing infertility treatment is a unique process, to say the least. Once the doctor chooses a medication regimen for you, you will most likely sit down with a nurse, either in a group setting or individually, who will explain the protocol, the medications, and most importantly, how to administer them. She will also discuss the policies of the facility, including the hours that you can come in for monitoring, what phone numbers to call if you have a questions, and how you are supposed to handle medication emergencies after hours. If the nurse does not address these issues, they are important questions that you should ask during this appointment.

There are many different regimens and approaches to treatment. Your reproductive endocrinologist (RE) will start with the simplest treatment plan that gives you the best chance for pregnancy. This could mean an oral medication like Clomid, or even IVF.

Taking Medication

Whatever protocol is selected for you, you will follow the instructions given to you by the nursing staff. The nurses act as a liaison between you and your doctor during treatment, relaying instructions from the doctor to you. It is common for you to be in for monitoring on a regular basis, often every day if you are being treated with IVF. Don't worry; this frequent monitoring doesn't usually last more than two weeks.

Depending on what type of ovarian stimulation you're taking, you may need a final injection of a form of human chorionic gonadotropin (hCG), which will help your eggs complete their maturation. Once you take this injection, ovulation will occur approximately thirty-six hours later. Either your insemination or egg retrieval will be scheduled according to the time they tell you to take the injection. Sometimes, if your partner's semen analysis is normal, the doctor may just instruct you when you have sex. You may need additional hormonal support during the luteal phase of your cycle, i.e., after you ovulate.

When Will I Find Out If It Worked?

Finally, after about two weeks, you will need to take a pregnancy test. You may be able to test at home using a urine pregnancy test, or you may be asked to come back into the office for a blood test. It is really important to not take your pregnancy test earlier then recommended. Some of the medications, namely the trigger injection, will cause the test to read falsely positive.

If you are pregnant, most Res will follow your pregnancy through the first several weeks. Once a heartbeat can be seen on the ultrasound and your RE feels comfortable with the success of your pregnancy, usually around ten weeks, you will be discharged and sent to your regular ob/gyn for routine prenatal care.

What If It Doesn't Work?

If you are not pregnant, your doctor will analyze your entire cycle from your response to the medication to the results of your hormonal blood tests. A plan will be created for your next cycle. If it does not work the first, second, or even third time, it doesn't mean that you won't get pregnant. Don't lose hope!

Monitoring

Monitoring is an integral part of fertility treatment. Whether you are having IUIs, going through IVF, or even using donated eggs or sperm, the doctor will need to assess your ovaries, uterus, and hormone levels fairly frequently, sometimes every day.

Make sure that you have a voicemail system or answering machine set up so that you can receive your instructions when you are not available to answer the phone. Most likely, your instructions will be for later that night, so it is really important that you receive them in a timely fashion.

The doctor will make a decision on the basis of those results, and you'll get your instructions later in the day. This is why it's very important that the travel time to your clinic is reasonable; you'll be making the trip a lot.

Estradiol

Estradiol is a form of estrogen and is secreted by the developing egg follicle(s). As the follicle grows and the egg matures, your estradiol level increases as well. In the very beginning of your menstrual cycle, your estradiol levels are low, usually under 60ng/ml. By the time the egg has reached maturity, your estradiol level will be above 200ng/ml. This is true for every egg follicle on the ovary. So if you are being treated with IVF with the goal of producing many egg follicles, your estradiol level could easily be several thousand ng/ml. If you are taking medication before having insemination, your estradiol level will not be quite so high, but will still be several hundred ng/ml.

Your doctor will want to monitor your estradiol very closely. Each clinic will have its own criteria for how they want the estradiol level to rise, and will adjust your medication based on the result of your testing accordingly. Your risk for serious complications increases if your estradiol gets too high, so it is extremely important that you follow your clinic's instructions very closely.

LH

As you now know, a rise in your luteinizing hormone (LH) levels precedes ovulation. So if your doctor sees that your LH level is suddenly starting to rise, it may indicate that your body is getting ready to ovulate. Once an egg follicle starts to reach maturity, it will trigger the LH surge. This isn't such a big deal if you are undergoing insemination or will be having intercourse because you don't want a high number of eggs released. But if you are going through IVF, the goal is to produce many eggs. These eggs will be at different levels of maturity, so you don't want the lead follicle to trigger ovulation when the remainder of the eggs isn't quite mature yet. This is why you'll be taking a suppressive medication to prevent you from ovulating.

Progesterone

Just as the LH surge can predict ovulation, your progesterone level will also start to increase just prior to ovulation. So if your blood results show that your ovulation is approaching 3ng/ml (usually the point where ovulation is presumed to occur), they can prepare you for retrieval or insemination if you are ready.

Your physician may also check your progesterone periodically during the diagnostic phase to determine if you are ovulating on your own.

If your progesterone level indicates that you've ovulated and you're going through IVF, your cycle will likely need to be cancelled. Once eggs are released from the ovary, it is not possible to retrieve them from the abdomen or Fallopian tube. No further treatment is possible at that point.

Ultrasound

Ultrasound is often thought of as being beneficial for pregnancy, but you may not know that ultrasound plays a large part in most fertility treatment programs. You will get to know the ultrasound technicians at your fertility clinic very well.

A follicular ultrasound

By using mostly transvaginal ultrasound, meaning that a probe is inserted into the vagina for better views of your reproductive organs, doctors can see the cervix, your uterus, ovaries, endometrial (uterine) lining, and even down to the fine detail of follicle production.

During different phases of your cycle, ultrasound can be used to monitor what is going on inside your body. Your fertility team can monitor how your follicles grow in relation to your hormonal production or in reaction to medications given. This can help your doctor adjust medications as needed to help you to maximize your response. Using ultrasound in this manner can also help prevent overmedication and risking your health.

The endometrial or uterine lining can also be looked at in great detail. Your uterine lining will be monitored for thickness at various points in your cycle. Since it responds to various hormones to build a secure place for implantation of your fertilized egg, it is a vital component on the road to pregnancy. You may need to take hormone supplements to help you build a thicker lining that will support a pregnancy.

Lastly, ultrasound can be used to help diagnose any abnormalities of the uterus, ovaries, or Fallopian tubes. This may be something like endometriosis, cysts, fibroids, and any structural abnormality. It can also help suggest that further testing is needed based on suspicious information revealed.

Hormone Supplementation

Supplemental medications can be nearly anything that addresses an issue you need help with during your fertility treatment. Some medications might be used to help you correct certain hormonal imbalances, while others are prescribed to manage blood-clotting issues found during testing.

Remember that these medications can affect urine and blood pregnancy tests. When undergoing assisted reproductive technology like superovulation and IVF, don't be tempted to take a pregnancy test without your doctor's okay. You may get inaccurate results.

During the course of your treatment, you and your reproductive specialty team will decide on a medication protocol. This protocol will go along with your known fertility issues. Except in a few rare instances, you will start at the lowest dose, strength, and type of medication possible in order to minimize the risk of complications with any given medication.

Your team may decide from the beginning of treatment that supplemental medication is required for a successful cycle, or it may not be until midcycle that your team makes a change or addition to your medications to help ensure a successful and safe cycle. Which medications, if any, are used for supplementation depend on many factors.

Estrogen Supplementation

During the course of your fertility treatment, your blood work will be monitored as well as your uterine lining. If it is determined that you need to boost your estrogen levels, you may be asked to take supplemental estrogen. This is usually, and thankfully, done in patch form. This means you simply wear a small piece of plastic tape that has the estrogen imbedded in it. The medication is absorbed through your skin. No muss, no fuss!

Some people have an allergy to the tape or adhesive on the patch. Make sure to let your clinic know if you have any irritation, itchiness, redness, or swelling. They will need to switch you to a different form of estrogen.

In addition to the patch, you can also take estrogen supplementation in pill form. These are taken either orally or inserted into the vagina. It is the same pill, but just taken via a different route.

Progesterone Supplementation

Progesterone supplementation can be used in high-level fertility procedures like IVF and superovulation. It can also be used to help supplement some other women and is commonly used in cases of frequent or recurrent pregnancy loss and for unexplained infertility. This is most often done as an injectable form or as a vaginal suppository. The injectables are usually suspended in oil and are given intramuscularly.

Mixing Your Medication

You will want to follow the specific directions for each medication when you actually draw up or mix your drugs. This will be given to you before you start your medication therapy. It may be gone over in a class setting as well.

Drawing Back a Premixed Medication

Start with a clean surface and clean hands. Wipe off the tops of any vials of medication with alcohol swabs. Inject the vial with your needle, and invert the vial so that it is upside down. With the needle completely covered in the fluid, draw the exact amount of medication you need. Remove the needle from the vial and, with needle pointed in the air, flick the syringe to move air bubbles to the top. Squeeze slightly on the plunge to remove excess air. Now you'll recap your needle in preparation to inject the medications.

Mixing Powdered Medication

If your medication doesn't come premixed, you will actually need to mix the diluents, or liquid, into the powder. It is very important to only use the recommended or included liquid when mixing your medication — if you don't, the medication may not work properly.

First, prepare all of your supplies:

• Alcohol wipes

• Needle and syringe

• Bottle of medication (the powder)

• Diluent (liquid)

Next, remove all of the caps from the bottles and swab with an alcohol pad. Put the needle into the rubber stopper of the bottle of diluent. Turn the bottle upside down so the tip of the needle is facing upward and is in the liquid solution. Draw back the amount of solution necessary to mix your medication, usually 1ml to 2ml. Remove the needle from the bottle of diluent, and push the needle into the bottle of powder. Depress the plunger to inject the liquid into the powder and watch it dissolve. You can shake the bottle a little bit to make sure everything dissolves. Turn the bottle back upside down, and pull back the plunger to remove the mixed medication.

Some medications, like Bravelle and Menopur, require that you mix several vials of powder into 1ml of solution. When doing so you may not be able to retrieve every drop from the vial. This is fine; do not panic.

You can change the actual needle and put a fresh one on once you've mixed the medication. A sharper needle will make the injection a little easier and less painful.

Subcutaneous Injections

A subcutaneous injection is given just under the surface of the skin. These can be given in the thigh or abdomen and are therefore easier to give yourself than intramuscular injections.

Again, you should always begin by washing your hands. Choose a location to give your injection where you have plenty of room and quiet time. Then gather your supplies. You will need:

• Alcohol wipes

• Medications

• Syringes

• Sharps container

Once you have your medications ready and drawn up, you will select a site.

The best bets for subcutaneous injection sites are the abdomen (belly) and thigh. These work well for most people. You can also give yourself these injections easily.

Example of a subcutaneous injection site

Select a site and wipe it with the alcohol swab — remember not to get closer than two inches around the belly button or navel. Pinch the area of skin you intend to use. Holding the syringe like a pencil, press the needle quickly into your skin at a 90 degree angle. Hold the syringe firmly to prevent the needle from bouncing off your skin. Depress the plunger and administer all of the medication. Remember to always discard your used needles into your sharps container — a special plastic container that prevents the needles from poking out of the container, thereby preventing accidental punctures from used needles — and never into the garbage. Hold or massage the site for pain relief.

Remember that different medications, while administered with the same technique, will feel differently when you inject them. The same may be said of other medications given by someone else, like your partner. Practicing will help with any fear and anxiety you or your partner may have.

Remember to put the needle in — long or short — quickly. This will make the injection portion nearly painless if you do it rapidly enough. Also, depress the plunger slowly. This can be difficult if you are nervous, but the more slowly you inject the liquids, the less pain you will feel. By doing it slowly you allow time for the tissues to stretch.

You should always mix your medications before cleansing your medication site. Have the syringe ready to give the injection so that you have that part out of way.

A subcutaneous injection

Intramuscular Injections

An intramuscular (IM) injection means that you will be giving an injection into a muscle. This is used for a variety of medications, including progesterone and human chorionic gonadotrophin.

You should always begin by washing your hands. Choose a location to give your injection where you have plenty of room and quiet time. Be sure that the location is clean as well. Then gather your supplies. You will need:

• Alcohol wipes

• Medications

• Syringes

• Sharps container

You will choose a spot for the injection to be given. Divide each buttock into four quadrants. You will want to inject into the upper, outer quadrant of your buttocks, almost toward the hipbone. If you choose the buttocks, you will probably want someone else to help you. Pinch a hunk of the muscle between your thumb and forefinger to test your location, making certain the spot isn't already sore from a previous injection.

Once you have decided on a spot, open your alcohol wipe and cleanse the area to be injected, as well as the top of the vial. Allow this area to dry, or the injection will be more painful.

Example of an intramuscular injection site

When the area is dry, take your weight off the side you've chosen as your injection site by either lying down or taking the weight off that foot — this makes it easier to give the injection. Stretch the area of skin between your fingers, and hold it tightly enough that it doesn't move.

Take your needle and insert it all the way until none of the needle is showing. Pull back slightly on the plunger of the syringe. You should not see blood. If you do see blood, you have hit a blood vessel and must remove the needle entirely and start over.

If there is no blood returned in the syringe, depress the plunger and inject the medications. When you are done, pull the needle straight out. If you experience a bit of bleeding, and there should not be much of it, use the alcohol pad to put a bit of pressure on the spot until the bleeding has stopped. You can also massage the injection site gently for pain relief and apply a heating pad for a few minutes. The heat and massage will help the medication be absorbed into the muscle.

You should rotate which side you use for injections. This will help prevent you from getting too sore from the daily injections. You should also rotate the spot where the needle enters. This is easier to do if someone else is helping you with the injections.

When you are done with the needle it needs to go into a sharps container. Your fertility clinic or pharmacy may provide one for you, or you can purchase one yourself. You might also use something handy from home, like a detergent bottle with a screw cap lid or other heavy plastic bottle or container. Return any sharps containers or other used needles to your doctor or pharmacy for proper disposal.

Complications and Risks

Infertility treatment isn't inherently dangerous or life threatening, but it can cause serious complications if your cycle isn't monitored properly. It is really important to keep track of how you are feeling and ask your nurse if you are concerned about anything. Some of the medications can cause alarming side effects, like visual problems, that need to be addressed. Don't ever hesitate to mention anything you are concerned about — even seemingly minor complaints may be important.

Ovarian Torsion

This is one of the rarest complications resulting from infertility treatment. As you progress through a medicated cycle, your ovaries tend to enlarge slightly. Of course, with IVF your ovaries will get significantly larger than if you are going through an insemination cycle. If the ovaries get large and heavy enough, it could cause one of the ligaments holding it in place to twist over on itself. If that were to happen, blood flow to the ovary would be cut off, causing the ovary to die if the ovarian ligament were not untwisted quickly.

If you develop ovarian torsion, you would feel sudden and extreme abdominal pain. It would likely worsen over time and you may become nauseated or even vomit. Anytime you have a lot of abdominal or pelvic pain, you should call your doctor, or the on-call service if there is one available.

If the doctor suspects that you have ovarian torsion and recommends that you go to the hospital, it is better that you go to the one where your doctor is licensed to practice. Your doctor will be able to expedite your care through the emergency room and into surgery much quicker than if you are in a hospital where he doesn't have privileges. That being said, if that hospital is several hours away, you should proceed to the nearest emergency room instead.

The best way to prevent this is to rest as much as you can while you are cycling, especially once you are finished with your medication and waiting to take your pregnancy test. This is when your ovaries are at their largest and you are at the greatest risk.

Ovarian Hyperstimulation Syndrome

Stimulation of the ovaries can cause ovarian hyperstimulation syndrome (OHSS), a situation in which your ovaries enlarge drastically and leak fluid into the abdomen. This can cause pain, bloating, weight gain, shortness of breath, dizziness, nausea, and vomiting. The first sign is significant weight gain and bloating in a short amount of time. Make sure to call your doctor if you have any symptoms.

You are at the greatest risk for OHSS right after ovulation (or egg retrieval) up until your pregnancy test. Young, thin women with a high response to the stimulant medication have a slightly higher tendency to become hyperstimulated, but it can affect women of all ages and sizes.

Pregnancy can actually make this problem worse because your hormone levels stay high, instead of declining as they normally would once you would get your period.

Treatment varies according to the severity of the syndrome. Most mild to moderate cases are treated simply with bed rest for a short period of time until your ovaries return to their normal size. If it progresses to the severe form, you may require hospitalization or intravenous medication.

Weighing yourself every day once you start cycling can be an easy way to monitor for OHSS, as you will likely see this weight gain much sooner than if you hadn't kept track of your weight. Weigh yourself, undressed, at the same time each morning. Make sure to report significant weight gain in a twenty-four hour period.

Multi-Fetal Pregnancy

The rate of multiple pregnancies is on the rise. Some of this is due to the rates of assisted reproductive technology and other fertility treatments. Of course, it is still possible to get pregnant with multiples using any fertility treatment. The rate of twinning is about one in every eighty-nine pregnancies.

What if you find out that you are having more than one baby? Twins are the most common form of multiple pregnancy. While there are increased risks if you are having twins, many practitioners still consider you a candidate for a normal birth while being more closely monitored. If you are having higher order multiples — triplets or more — you will probably wish to seek out the care of a perinatologist who specializes in multiple pregnancy.

You will want to ask questions about how your practitioner handles multiple pregnancies.

• What type of extra monitoring, if any, will I have?

• What considerations will be made at the birth?

• What is your Cesarean rate for multiples?

• When would you consider doing a Cesarean delivery?

• What type of routine interventions do you use in multiple births?

• Will I be able to breastfeed my babies right away?

It is worth having a discussion with you partner about how you feel about having multiples. If that is something you don't feel comfortable with, you need to convey this to your RE. He can proceed much more conservatively with your treatment or even recommend only transferring a single embryo during IVF, instead of the usual two or three.

Do Fertility Drugs Cause Cancer?

Some initial studies did point to a possible connection between infertility drugs and cancer. It is important to know, however, that certain causes of infertility can increase your risk for cancer as well. For example, PCOS can increase your risk for endometrial cancer. In fact, never giving birth can also increase your risk for certain types of cancer. These early studies did not take that fact into account. So it is unclear whether the observed cancer risk is a result of the infertility drugs, or the cause of the infertility itself. Current studies do not show any link between taking fertility drugs and your risk for developing breast, uterine, or ovarian cancer. However, more studies are definitely needed to confirm this.

After all of this, there are still more questions to ask! You can never ask too many questions. Don't worry about being annoying or causing trouble; these practices and the people who staff them understand that you are investing your emotional and fertile future with them. They are willing to answer questions to help you make a choice.