Risks of IVF Therapy

Introduction

In vitro fertilization and embryo transfer (IVF-ET) was first successfully used in humans over 25 years ago; since then, more than one million children have been conceived using this technology. IVF is a procedure designed to enhance the likelihood of conception in couples for whom other fertility therapies have been unsuccessful or are not possible. It is a complex process and involves multiple steps resulting in the insemination and fertilization of oocytes (eggs) in our laboratory. The embryos created in this process are then placed into the uterus for potential implantation. Each stage of the procedure is associated with specific risks, as outlined below. IVF is an elective medical treatment. IVF may provide a couple who has been otherwise unable to conceive with a chance to establish a pregnancy.

Risks of Therapy

Risks associated with the medications may include, but are not limited to, allergic reactions, hyperstimulation of the ovaries (mild, moderate or severe), and failure of the ovaries to respond and cancellation of the treatment cycle.

There are situations that can occur during a stimulation that may necessitate canceling your IVF cycle and stopping treatment for a period of time. This occurs because the ovaries produce either too many or too few eggs in response to drug stimulation protocol. Although we realize that this can be a big disappointment, at times it is necessary to discontinue the use of the medications to avoid the possibility of complications and to afford you the best chance of future success. If canceling the cycle becomes necessary, you will be told to stop your injections. No hCG injection will be given and no egg retrieval will occur. You will be asked to schedule an appointment with your physician to make decisions regarding future treatment cycles.

When ovulation induction medications are used in fertility therapy, the ovaries are coaxed to produce more than one egg to the point of maturity. Consequently, hormone levels of estrogen and progesterone reach much higher than normal values. When the estrogen level becomes mildly to moderately elevated, side effects that may be experienced include, but are not limited to, fluid retention with slight transient weight gain, nausea, and diarrhea, pelvic discomfort due to enlarged cystic ovaries, breast tenderness, mood swings, headache and fatigue.

Ovarian Hyperstimulation Syndrome (OHSS)

If the estrogen level rises excessively and hCG is administered to trigger final maturation of the eggs, the following more serious complications may result:

Excessive fluid retention with fluid in the abdomen and/or chest cavity;
Thrombosis of arteries and/or veins (formation of blood clots) which may lead to stroke, embolus, or potentially fatal complications; Abnormally enlarged ovaries, which have the possibility of rupturing or twisting (a surgical emergency);
The medications used to stimulate your ovaries may cause side effects. These side effects can range from mild to severe. Excessive stimulation of the ovaries is called ovarian hyperstimulation. This may require removing some of the fluid in our office and/or a hospital stay in approximately 1 % of the patients. Be aware of body changes and ask your primary nurse if you have any questions or concerns. She will contact the physician if necessary. You may have symptoms of mild hyperstimulation during your treatment cycle, however, moderate and severe symptoms usually occur 6-8 days after treatment ends.

Facts about Ovarian Hyperstimulation Syndrome (OHSS)

SIGNS AND SYMPTOMS	WHY IT HAPPENS	WHAT TO DO
Mild You may experience: - Abdominal bloating and feeling of fullness - Nausea - Diarrhea - Slight weight gain	This may be due to: - Ovaries are larger than normal, tender and fragile - High level so estrogen (E2) and progesterone in the bloodstream may upset your digestive system and fluid balance causing bloating.	Recommended treatment: - Avoid sexual intercourse - Do not have a vaginal (pelvic) exam other than by one of our physicians - Reduce activities, no heavy lifting, straining or exercise - Drink clear fluids, flat coke, ginger ale, cranberry juice, Gatorade or Ensure
Moderate You may also experience: - Weight gain of greater than 2 lbs. per day (excessive weight gain) - Increased abdominal measurement causing clothes to feel tight - Vomiting & diarrhea - Urine is darker and amount is less - Skin/hair may feel dry - Thirst	This may be due to: - High levels of hormones in the bloodstream upset the digestive system - Fluid imbalance causes dehydration because body fluids collect in the abdomen and other tissues - This fluid collection causes severe bloating	As noted above plus: - Call our nurses - You may need to be seen by a physician who will do an ultrasound - Record your weight twice daily - Record the number of times you urinate each day - Contact our office if you note a five pound weight gain over the previous 24 hours, note a drop in the frequency of urination (~50%), or increasing pelvic pain
Severe You may also experience: - Fullness/bloating up above the belly button - Shortness of breath - Urination has reduced or stopped and become darker - Calf pains and chest pains - Marked abdominal bloating or distention - Lower abdominal pain	This may be due to: - Extremely large ovaries - Fluid collects in lungs and/or abdominal cavity, as well as in tissues - The risk of abnormal blood clotting increases	As noted above plus: -This is life threatening situation. Do not wait! - Notify the physician on call - You may need to be assessed at the hospital or our clinic - Excess fluid may need to be removed from your abdominal cavity

If your period starts, you will likely begin to feel better. Pregnancy may prolong or exaggerate these side effects. It may take up to 10 weeks for the symptoms to resolve if you are pregnant. Remember: The fact sheet is only a guide and not intended as a substitute for medical care. Given the potential for such severe complications, it is important that we carefully monitor your response to these medications. This monitoring also allows your physician to determine when the eggs are ready for the next stage, oocyte (egg) retrieval. Monitoring includes frequent blood drawing for estradiol (estrogen) and possibly progesterone, LH and FSH levels. These blood tests will take place over approximately a twelve-day period. Risks associated with blood drawing may include, but are not limited to:

1.- Pain at the site of needle stick
2.- Tenderness or infection of the skin
3.- Bruising or scarring of the site of blood draw
4.- Development of a blood clot in the vein (thrombosis, thrombophlebitis)

The second portion of the monitoring phase in IVF involves the use of intravaginal ultrasound to track follicular growth. The eggs develop inside fluid-filled cysts of the ovaries called follicles, which enlarge as the eggs mature. Ultrasound studies usually begin after an estrogen response has been measured and continue on a frequent basis until oocyte (egg) retrieval. The ultrasound studies are performed using a vaginal probe. Vaginal sonograms carry no appreciable risk but may cause slight discomfort, particularly as you near the point of ovulation.

Ovarian stimulation with the fertility medications causes multiple follicles to develop. This is desirable in IVF because as the number of eggs increases, the chance for success increases. Multiple embryos can also increase the risk of a multiple pregnancy. Approximately 20-25% of pregnancies with IVF will be multiple. Most of these will be twins, but triplets, quadruplets or even greater multiple pregnancies can occur. A procedure called "selective reduction of pregnancy" has been performed in several medical centers across the country in selected cases of triplets or more. Selective reduction is not offered on site or by SEMERT staff. More information on this procedure and recommended centers is available on request.

Other Concerns:

Unfortunately, neither conception nor a successful outcome of pregnancy is guaranteed by the IVF-ET procedure. There are many reasons why pregnancy may not occur with the IVF-ET procedure. In fact, there are complex and largely unknown factors that limit pregnancy rates following assisted reproductive techniques. Some of the known reasons for failure may include, but are not limited to:

1.- There may be a failure to recover an egg because:
- follicles that contain mature eggs may not develop in the treatment cycle
- ovulation has occurred before time of egg recovery
- one or more eggs cannot be recovered
- pre-existing pelvic scarring and/or technical difficulties prevent safe egg recovery

2.- The eggs that are recovered may not be normal;

3.- There may be insufficient semen to attempt fertilization of the recovered eggs because the man is unable to produce a semen specimen, because the specimen contains an insufficient number of sperm to attempt fertilization, because the laboratory is unable to adequately process the specimen provided, or because the option to use a donor sperm as a "backup" was declined;

4.- Fertilization of the eggs to form embryos may fail even when the egg(s) and sperm are normal;

5.- The embryos may not develop normally or may not develop at all. Embryos that display any abnormal development will not be transferred;

6.- Embryo transfer into the uterus may be difficult/impossible, or implantation(s) may not occur after transfer, or the embryo(s) may not grow or develop normally after implantation;

7.- Any step in the IVF-ET process may be complicated by unforeseen events, such as hazardous or catastrophic weather, equipment failure, laboratory conditions, infection, human error and the like.

8.- Complications of pregnancy. When pregnancy occurs following IVF, it will typically be a normal pregnancy. However, there is always a risk of abnormal pregnancy, miscarriage, blighted ovum, ectopic pregnancy or premature delivery. Older women with multiple pregnancies have a higher risk of complicated pregnancies, which may include the following: toxemia, pre-eclampsia, miscarriage, premature labor and delivery, stillbirth, and other complications.

9.- Congenital abnormalities. Congenital abnormalities, genetic abnormalities, mental retardation or other birth defects which occur in approximately 3% of spontaneously-conceived pregnancies may still occur in children born following assisted reproductive techniques. A large review of a subset of children born following assisted reproductive procedures found the incidence of developmental anomalies similar to a control group of children spontaneously conceived. The process of IVF-ET does not protect against such normal occurrences.

10.- Emotional Stress. Any assisted reproduction process or technique can be psychologically stressful. Significant anxiety and disappointment may occur. We encourage you to consider short-term supportive counseling during this time and we are happy to provide you with a list of psychiatrists, psychologists, counselors and social workers who may help you through this difficult time.

11.- Time commitment. A substantial time commitment is required by both partners to complete an entire course of IVF therapy. It will be necessary for couples to adjust their schedules to undergo the required testing and therapies associated with IVF-ET. It is the responsibility of the woman to report to our office as scheduled for repeated ultrasound examinations and blood tests over several days or weeks before and after the expected time of egg collection. It is the responsibility of the man to be available at the time identified by the physician to provide sperm.