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1. Which procedures are available and what is the difference between procedures?
2. What tests are required prior to starting a cycle?
3. How much does medication cost?
4. Where can I purchase my medications?
5. What happens in an ART cycle?
6. Are there any restrictions on physical or personal activities during an ART cycle?
7. How much time will I need to take off work during an ART cycle?
8. What happens during an oocyte aspiration, GIFT, and embryo transfer? What risks are associated with these procedures?
9. How does the ART laboratory operate and what are the safety measures? What will happen to the eggs and sperm after retrieval?
10. When is the pregnancy test performed?
11. What happens if I become pregnant?
12. If I am not pregnant, when can we try again?
13. Will I need a high risk OB because I conceived with an ART procedure?
14. What restrictions will I have between embryo transfer and the pregnancy test?
15. Is there a higher miscarriage rate for ART patients?
16. What can be done to improve sperm quality?
17. How do we decide how many embryos to transfer?
18. Am I depleting my store of eggs by doing an ART cycle?
19. What are the long term effects of infertility treatments, i.e., ovarian cancer?

1. Which procedures are available and what are the differences between procedures?

The Reproductive Medicine Group was first to introduce virtually all prudent new assisted reproductive technology procedures to the Tampa and southwest Florida areas.

In Vitro Fertilization (IVF)-- IVF is a method of assisted reproduction where the woman’s egg and man’s sperm are combined outside of the body, in a laboratory, where fertilization occurs. The fertilized egg divides in an incubator for two to three days. The resulting embryo is transferred into the woman’s uterus. Embryo transfer is a relatively simple, but extremely important procedure. The embryos are placed in a catheter, threaded through the cervix and gently deposited into the uterus. It is similar in discomfort to a pap smear.

The basic steps in an IVF cycle are ovulation induction (utilizing injectable medications), oocyte aspiration, insemination and fertilization, and embryo transfer.

IVF is the treatment of first choice for a variety of infertility diagnosis. Initially, it was primarily for tubal factor infertility. IVF is now used to treat infertility caused by endometriosis, male factor, immunologic factor, and unexplained etiology. The use of IVF has increased because of dramatic improvement in success rates.

Gamete Intrafallopian Transfer (GIFT)-- In a GIFT procedure, the woman’s eggs are retrieved, mixed with the man’s sperm outside of the body, drawn into a catheter, and deposited into one or both Fallopian tubes by laparoscopy. These steps take place during a single surgical procedure. Fertilization then takes place in the Fallopian tube as it does in natural fertilization. After fertilization, the embryo travels to the uterus where implantation occurs.

A GIFT cycle, like an IVF cycle, begins with ovulation induction and proceeds to oocyte aspiration. The similarity to IVF ends at this point. In GIFT, eggs and sperm are transferred into the Fallopian tube while in IVF, embryos (the sperm has penetrated the egg and cell division has begun) are transferred to the uterus.

Patients who have at least one functioning Fallopian tube are candidates for GIFT. Couples whose diagnosis includes unexplained infertility, endometriosis, male, cervical, or immunologic factors may be eligible for GIFT.

GIFT offers no advantage over IVF. It was originally thought that fertilization in the Fallopian tube was more "natural" and therefore conception rates would be higher. Broad clinical experience has not confirmed this hypothesis. GIFT provides couples with the option of "fertilization within the body" which is sometimes more in line with their religious preferences.

The disadvantage of GIFT is that fertilization cannot be visualized and documented as it can in IVF. The GIFT/IVF combo approach allows the embryologist to document fertilization.

GIFT/IVF Combination (Combo)-- Combo is a combination of both the GIFT and IVF procedures. Ovulation induction is started to produce multiple eggs. At the time of oocyte aspiration the best eggs are chosen, mixed with the sperm, and placed in the Fallopian tube by laparoscopy. This is the same as a standard GIFT procedure.

The excess eggs are taken to the lab and inseminated with sperm. If fertilization occurs, the embryo is transferred into the uterus 2 to 3 days later. This is the same procedure used in standard IVF. In some cases, the eggs will be fertilized using intracytoplasmic sperm injection.

Combo is relatively new and has not been used by many programs in the United States, however, we have experienced good success rates. Combo is most often used in couples with severe male factor infertility, advanced maternal age, or those who have failed previous ART attempts. Combo may increase the likelihood of multiple gestation.

Zygote Intrafallopian Transfer (ZIFT)-- ZIFT is used to place fertilized oocytes within the Fallopian tubes.

2. What tests are required prior to starting a cycle?

Tests are ordered based upon on the individual needs of each patient. In general, all patients will receive: semen analysis, hysteroscopy or hysterosalpingogram, pap smear, and hormone assays. See the section entitled Common Tests for Infertility.

3. How much does medication cost?

The average cost of medication an ART cycle is between $2,000 and $2,500. The majority of this cost is attributable to FSH administered as Follistim, Fertinex, or Gonal-F. Repronex is a generic version of Pergonal currently available in the United States. The cost of Repronex is roughly ½ that of the other preparations. Some patients respond better to pure FSH than Repronex. You and your physician will decide which medication best suits your particular situation.

4. Where can I purchase my medications?

Medication can be purchased at most pharmacies, however, it is best to choose a store that routinely supplies fertility products. There are wide variations in price and it is best to obtain quotes from several stores in your area. Do not assume that all pharmacies will have the fertility medications you will need.

It is also very important to purchase hCG (human chorionic gonadotropin: Pregnyl, Profasi) well in advance of when you will need it. We recommend that you keep an additional vial on hand in the event you break the first. The injection of hCG must be given at the precise time prescribed or an entire ART cycle could be lost. Again, explain clearly to your pharmacist what your treatment regimen will involve. Many pharmacists are not familiar with infertility treatment protocols. Our nurse will be happy to speak with your pharmacist if necessary. The most important factor is that the medication be available on the day needed in the appropriate quantities.

Recently, there has been discussion about purchasing products from outside of the United States. While these products can be less expensive, they are not subject to the same rigorous quality control standards as US product. There is little control over their storage and distribution and quality can vary significantly from vial to vial. Radical changes in temperature can alter the pharmacology of fertility medications rendering them inactive. For these and other reasons, We strongly recommend US approved products.

5. What happens in an ART cycle?

The goal of ovulation induction is to produce multiple follicles on the ovaries from which eggs are retrieved. In an ART cycle it is optimal to retrieve and fertilize as many eggs as possible to increase the chance of pregnancy.

Most of the medications used are for the female, however, the male is asked to comply with a regimen of antibiotic therapy to prevent and treat certain organisms in the semen.

Transvaginal ultrasound examinations and blood hormone levels are used to monitor egg development. Ultrasound allows the physician to visualize the ovaries and ascertain follicle size.

Blood is drawn numerous times during a stimulation cycle. As the follicles in the ovaries begin to grow, they produce estrogen. The physician compares the estrogen level with the ultrasound results to determine how much medication to prescribe prior to egg aspiration.

A baseline ultrasound and estrogen level are obtained prior to beginning any stimulation medications. A repeat ultrasound and estrogen level will be obtained approximately six days after medication has begun. Eventually, ultrasound examinations and blood tests may be necessary on a daily basis.

Ovulation induction ends when the physician estimates an appropriate number of eggs are likely to be mature and of good quality. This determination is made by follicle size and estrogen level. All fertility drugs will be discontinued at this time. An hCG (Profasi or Pregnyl) injection will be administered at the time specified by the ART nurse. Oocyte (egg) aspiration will be scheduled 34 hours from the hCG injection.

About 10 to 15% of patients who begin taking medications for ovulation are canceled before any procedures are done. The reasons for this can include an insufficient number of mature follicles, an inadequate blood level of estrogen, an exaggerated response leading to hyperstimulation syndrome. If an ART cycle is canceled medications may be modified in subsequent attempts in order to try to improve the response.

6. Are there any restrictions on physical or personal activities during an ART cycle?

A. Smoking- Stop smoking before ovulation induction begins. If you cannot stop "cold turkey," make an effort to stop at least two weeks before the egg aspiration or laparoscopy. The GIFT and ZIFT procedures, and sometimes aspiration, require general anesthesia. General anesthesia temporarily changes the normal function of the lungs. Smoking cessation insures that the lungs are in the best possible shape for surgery, and it also insures better tolerance of anesthesia.

B. Drinking- Alcohol is a drug and, in general, should be avoided during infertility treatment and pregnancy. There is no reason to consume alcohol and it can introduce another "unknown" factor into treatment. If you drink socially, you may continue to do so during ovulation induction. Two to three alcoholic beverages per week is acceptable. Please do not drink alcoholic beverages from approximately 4 days before egg aspiration unit the pregnancy test.

C. Medications- If you are taking any medication, prescribed or over the counter, please inform your physician. Some medication should not be taken before an operation, some may interfere with those prescribed during your cycle, and others may interfere with ovulation or pregnancy implantation.

D. The physician will prescribe a multivitamin.

E. Inform your physician of any changes in your health even minor colds or infections. This is especially important prior to surgery.

F. Any kind of surgery, or ART cycle, can be stressful physically and emotionally. Avoid becoming tired in the days before and after a procedure. Eating correctly, and getting proper rest and exercise, become even more important before an operative procedure.

G. An ART cycle can be an emotional and stressful time for you and your partner. You need to consider supportive relationships; For example; friends, clergy, family members, and psychologists.

H. Heavy exercise such as aerobics, jogging, weight lifting, roller blading, etc. will be prohibited during ovarian stimulation and until the pregnancy test.

7. How much time will I need to take off work during an ART cycle?

You will have 4-7 early morning appointments for ultrasound monitoring and blood work. Each of these visits will require approximately 1 hour. For an IVF cycle, 1-2 days off are needed for the egg aspiration and 24 hours of bed rest is mandatory after an embryo transfer. A laparoscopy is done in the GIFT procedure and 2-3 days off work is needed after the surgery.

8. What happens during an oocyte aspiration, GIFT, and embryo transfer? What are the risks associated with these procedures?

See Virtual IVF. Oocyte aspiration, or egg retrieval, is a procedure performed on an outpatient basis. You can expect same day surgery, recovery, and discharge on the day of aspiration.

Approximately one hour before the procedure the patient is taken to the preoperative holding area where an IV is started and the anesthesiologist consult takes place. He or she will take a medical history of any previous surgeries, reactions to anesthesia, and address any patient concerns. Anesthetic agents are administered when the physician is ready to begin the procedure since we want to minimize any possible effects of the anesthesia on the eggs. If you are feeling excessively anxious please let the anesthesiologist know.

During the egg retrieval, the oocytes are collected by ultrasound guided needle aspiration.

The aspiration is performed under epidural or general anesthesia so little or no discomfort is experienced.

After anesthesia has been administered, the physician places a speculum in the vagina and prepares for the removal of the eggs. A catheter is placed into the bladder so urine does not collect and prevent visualization of the ovaries.

The speculum is removed and an ultrasound probe equipped with a needle guide is placed into the vagina. The probe emits high frequency sound waves that are translated into images of the ovaries that are shown on a monitor screen.

An aspiration needle is passed through the needle guide on the ultrasound probe and through the upper vaginal wall. When a mature ovarian follicle is visualized on the screen, the physician guides the needle into the follicle and applies suction. The fluid contents of the follicle are aspirated into small tubes and passed to the embryologist who examines the fluid to locate the egg.

Transvaginal aspiration usually takes 30-45 minutes and the recovery time is about 2 hours. After the aspiration is complete the patient is taken to the recovery room. The length of stay in the recovery room varies dependent upon the type of anesthesia received.

The patient is released from the recovery room and transferred to a general room for monitoring by a nurse until discharged. Some discomfort is to be expected after a surgical procedure. Medication for pain or nausea is given, if necessary.

Ice chips and liquids are given. The IV will be removed when liquids can be taken without becoming nauseated. Urination must occur prior to discharge. The patient must be alert enough to dress and walk without assistance.

There may be a small amount of vaginal bleeding the day of aspiration and the day following. A responsible adult must drive the patient home. A patient cannot operate dangerous equipment, or sign legal documents, for 24 hours after anesthesia.

Oocyte aspiration has a low complication rate, however, please be aware the following may occur: Allergic or adverse reactions to anesthesia or pain medications, pain from the IVF site, urinary tract infection from bladder cauterization, possible injury to the vagina, uterus or ovaries, bleeding, and in rare cases bowel or bladder injury.

In rare cases, the eggs will be retrieved via laparoscopy. This is done when the ovaries are not accessible by transvaginal aspiration. In the operation room, the physician inserts a laparoscope, a long thin tube like a telescope, through an incision in or below the navel.

The ovaries are visible through the laparoscope. While looking through the laparoscope, the physician inserts a needle in a separate incision in the abdominal wall and then into the ovaries to aspirate the follicular fluid. The fluid contents of the follicle are aspirated into small tubes and passed to the embryologist as in a transvaginal retrieval.

In IVF, the patient returns in three days for the embryo transfer. In a GIFT procedure, the physician will most likely aspirate the eggs transvaginally. After aspiration, the eggs and sperm will be placed into the Fallopian tubes by laparoscopy.

Following laparoscopy it is not uncommon to experience mild to moderate abdominal or shoulder pain. Possible complications of the laparoscopy include bleeding, infection, embolism, and possible damage to the intestines or other pelvic or abdominal organs. Complications are more likely to occur if there has been previous pelvic surgery or infection.

All patients are requested to schedule a post operative appointment with their physician. This is an important part of the treatment cycle as it gives the physician and the couple an opportunity to review the cycle and discuss recommendations for future cycles. At this visit a physical and emotional assessment will be performed.

9. How does the ART laboratory operate and what safety measures are taken? What will happen to the eggs and sperm after retrieval?

On the day before the oocyte retrieval, oocyte culture dishes are carefully labeled with the patient's name, date of birth, and ART identification number.

The dishes are then placed in the embryology incubator for warming to body temperature. The incubator also adjusts the pH of the culture media to that of the human body.

A large amount of rinsing media is equilibrated in the incubator. This fluid is used by the physician to wash the oocyte from the ovarian follicle if it is not found in the initial aspirations. Media is also equilibrated in the andrology laboratory for processing of the sperm.

One of the more important and useful IVF laboratory instruments is the mobile IVF chamber. It is a pediatric isolette (incubator) on wheels that has been modified to contain a scanning microscope.

Prior to the egg retrieval it is warmed to body temperature and put at the neutral pH of the culture dish media. These conditions avoid any abrupt changes the eggs might encounter outside the body. The chamber has two small doors on each side.

The embryologist places his or her hands on one side to identify eggs and move dishes. The OR nurse uses the opposite doors to pass test tubes containing the follicular fluid to the embryologist.

Upon arrival in the operating room the patient identity is verified by the embryologist, physician, and safety nurse. The also verify that the culture dishes are correctly labeled.

At the time of surgery the mobile chamber is loaded with the equilibrated, large dishes for receiving the follicular fluids, and a sterile pipette (similar to a long eye dropper) for picking up the eggs. It is then moved from the embryology laboratory to the adjoining operating room.

The physician aspirates the fluid from the ovarian follicles into a test tube. A nurse passes the test tube, through the IVF chamber door, to the embryologist. The embryologist dispenses the fluid into a large dish and rapidly scans it under the microscope.

The egg complex is usually visible to the naked eye, but microscopic verification of the presence of the eggs is always done. The oocyte is removed from the large dish by pipette, rinsed in the outer well of the culture dish and placed in the center well for culture and the addition of sperm (insemination).

The presence of an egg in the follicular fluid is immediately reported to the physician. The physician will then discontinue washing that particular follicle.

After all the eggs have been aspirated, the mobile chamber is moved to the embryology laboratory for a more critical assessment of the oocytes, insemination with sperm, and culture. The embryologist uses fine needles to spread the cumulus mass that obscures the oocytes.

The maturity and health of oocytes can be more accurately assessed by thinning this mass. Oocytes are graded as mature, intermediate, immature, post mature or degenerate. Oocytes judged mature are incubated 1 to 4 hours before insemination.

Less mature oocytes are incubated until they reach maturity, and then inseminated. 100,000 motile sperm are added to the media surrounding each oocyte in the center well of the culture dish. Dishes containing eggs and sperm are then returned to the main embryology incubators for culture.

The male will be asked to collect a semen sample by masturbation after the oocyte aspiration. In the GIFT procedure he is asked to collect 2 hours prior to the aspiration. The andrologist escorting him to the collection room will identify your partner from his identification bracelet prior to collection and write both of your names on the outside of the specimen container after collection. Your partner will be asked to verify that both names are correct.

Approximately 30 minutes after collection, when the semen liquefies, a semen analysis is performed. The sperm is prepared for insemination, usually by "swim- up." The swim-up procedure begins with two centrifugal washings of the semen to remove the seminal fluid. The seminal fluid is an excellent media for the sperm, but extended exposure is detrimental.

The concentrated sperm is then covered by a layer of the equilibrated sperm preparation media and placed in an incubator. The sperm are allowed to swim-up into the upper layer for one to two hours.

For those patients undergoing a GIFT procedure, the embryologist will select the best mature eggs and pool them into a single culture dish. The number of eggs to be pooled and transferred will have been previously documented on the consent forms by the couple and their physician.

The embryologist loads a GIFT catheter with prepared sperm and eggs. The loaded catheter is carefully given to the physician who will catherize the Fallopian tube and inject the sperm and eggs. After the transfer is complete the catheter is given back to the embryologist for rinsing with fresh medium and examination for the presence of retained eggs.

Twenty to twenty-four hours after retrieval, the oocytes are transferred to fresh dishes that were equilibrated on the day of retrieval. This pipette procedure and all future transfers to fresh dishes are done in the mobile IVF chamber.

Oocytes are then microscopically examined for pronuclei formation, the sign of fertilization. The pronuclei are the decondensed DNA of sperm and egg nuclei. They appear microscopically as two light spheres within the egg. Polyspermic oocytes, those possessing more than two sperm pronuclei, are discarded. These abnormal fertilizations are typically naturally aborted.

Fertilized oocytes in excess of those needed may be cryopreserved at this time or in the next two days of culture. Fertilized oocytes for uterine transfer are returned to the main embryology incubator for 24 hours.

At that time the embryos are transferred to fresh dishes where the cell stage and overall health of the embryos are microscopically evaluated. The embryos are returned to the main embryology incubator for the final 24 hour culture before uterine transfer.

10. When is the pregnancy test performed?

The blood pregnancy test is performed 14 days after the embryo transfer of 16 days after GIFT.

11. What happens if I become pregnant?

If pregnant, the patient is asked to return to the office for repeat blood tests and ultrasounds to insure an ongoing successful pregnancy. After 8-9 weeks she is referred to an obstetrician for the remainder of the pregnancy.

12. If I am not pregnant, when can we try again?

Usually we ask the patient to wait one or two complete menstrual cycles before beginning another ART cycle. Sometimes tests are required that can delay subsequent cycles.

13. Will I need a high risk OB because I conceived with an ART procedure?

A high risk OB is only needed when there are complications that put the mother or baby at increased risk, or in the case of multiple births. Other than a higher incidence of multiple births, ART does not increase the risk to the mother or fetus.

14. What restrictions will I have between embryo transfer and the pregnancy test?

Patients are asked to avoid strenuous activity that would strain the pelvic area, such as climbing stairs and lifting objects heavier than 15 pounds. Any formal exercise program such as weight lifting aerobics, jogging, etc. should be discussed with the physician.

15. Is there a higher miscarriage rate for ART patients?

The miscarriage rate is about the same for ART as the general population. Many times older females undergo ART and their miscarriage rates are naturally higher.

16. What can be done to improve sperm quality?

Sperm quality on the day of egg retrieval is often related to what happened in the male’s body 3 months ago. This is because sperm development takes almost 3 months.

1. A fever of 101 degrees Fahrenheit or higher within 3 months prior to ART treatment may adversely affect sperm quality. Sperm count and motility may appear normal, but fertilization may not occur. If you become sick before or during the ART cycle, please notify the ART nurse, and take Tylenol to keep the temperature below 101 degrees F.

2. Keep the use of alcohol and cigarettes to a minimum before and during ART treatment. Do not use any "recreational" drugs.

3. If any prescription medication has been taken during the last 3 months, notify the ART nurse.

4. Do not sit in hot tubs, spas, Jacuzis, or saunas during or 3 months prior to the ART cycle.

5. Don not begin any new form of endurance exercise during the 3 months prior to the ART cycle. Physical activity at a moderate level is acceptable and encouraged.

6. Do not wear tight pants or underwear during or 3 months before the ART cycle.

7. Tell your infertility physician if you have ever had genital herpes or suspect you may have been exposed to genital herpes in the past. Also tell your physician if you have pre lesion symptoms, develop a lesion, or have healing lesions before or during the ART cycle.

8 . Refrain from ejaculation for 2-3 days, but not more than 5 days, before collecting the semen sample for the ART cycle. The ART nurse will have your specific instructions from the andrologist.

17. How do we decide how many embryos to transfer?

Your physician will discuss this with you but we usually follow the American Society for Reproductive Medicine Guidelines:

30-35 years old- 3 embryos

35-40 years old- 3-4 embryos

The number varied may also vary dependent on each individual clinical circumstance.

18. Am I depleting my store of eggs by doing an ART cycle?

A woman is born with a full complement of eggs. There are far more eggs than will ever be used during a normal lifetime and ART has no measurable "lowering" effect.

19. What are the long term effects of infertility treatments, i.e., ovarian cancer?

There is no reliable study to support the claim that infertility treatment causes ovarian cancer. One highly publicized study suggested a link between ovarian cancer in women who had received ovulation induction drugs.

The Center for Disease Control is in the process of conducting a double blind study on this topic and the results will probably be available within the next 2 years.