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IVF-ET at C.A.R.S.

Before Starting the IVF cycle

The IVF-ET Process at C.A.R.S.
1. Ovarian Preparation and Stimulation
2. Follicle Aspiration
3. In Vitro Fertilization and Culture
4. Embryo Transfer
5. Implantation Support

IVF Model Cycle (requires Acrobat Reader)

Questions and Emergencies

Financial Arrangements

IVF success rates at C.A.R.S.


Before Starting the IVF Cycle

A complete medical history of both partners is taken on the first visit. Physical examination is usually postponed until a later visit. We may perform blood tests to exclude hormonal problems known to lower the response to ovarian stimulation and pregnancy rates. A pap smear should have been performed within the past year. You should have had a mammogram if you are over age 35. The screening process is usually performed one to several months before the first treatment cycle is scheduled. Screening always includes a "baseline" ultrasound to exclude pelvic pathology. Testing for AIDS and hepatitis should be current. Please advise us of any health issue, or past medical history you feel might impact on your therapy or chances of success. We make an earnest attempt to keep screening tests, and therefore cost, to a minimum. (Please review preconception-counseling recommendations) General information about the science and practice of IVF is available as an info sheet in The Learning Center

To the Male Partner - We encourage you to accompany your partner as much as possible during all visits and procedures at C.A.R.S. It is essential that you accompany your partner for at least one consultation because IVF is an important issue that affects both of you. This is an opportunity for us to answer questions you may have regarding the IVF procedure.

It may be necessary for you to learn the techniques to give injection(s) of the medicines used for ovarian stimulation. These injections are simple and safe procedures.

Please let us know of any changes in health or medications. Tobacco use is strongly discouraged.

An absolute requirement is a recent semen sample from you prior to the beginning of the IVF cycle. This sample permits a check on the number and movement (motility) of the sperm. If a problem is diagnosed or suspected, a more detailed examination may be in order before proceeding. We do not routinely perform more complex sperm function tests, such as hamster egg penetration or sperm antibody tests, due to the expense and their failure to alter course of therapy.

In some cases we may "bank" your sperm by freezing to provide convenience, or in select cases, a greater chance of fertilization. In cases of previous fertilization failure, we may suggest assisted fertilization (ICSI). where the oocyte coverings are manipulated and fertilization rate possibly improved. With advance notification and planning, donor sperm is also available through several certified sperm banks, all of which meet certification standards of the American Society of Reproductive Medicine. You may also want to read our information on male infertility in The Learning Center.

The science of IVF is presented in our IVF-ET INFO SHEET on this subject. Financial matters are discussed in IVF finances. Let’s now review how each of the steps of the IVF cycle is accomplished at C.A.R.S. You will also receive a copy of written instructions covering each step of the procedure. You will be given well in advance an informed consent form that outlines the risks that may be associated with the IVF and provided ample time to answer questions or address any concern.


STEP 1 – Ovarian Preparation and Stimulation

The objective of ovarian stimulation is to increase the possibility of successful initiation of pregnancy by synchronizing the ovary and increasing the number of eggs available for IVF. There are countless different regimens that have been tried and in fact, most are much more similar than different. At C.A.R.S., we do not have a fixed method. We do not believe that “one size fits all.” We try to design a treatment regimen that fosters the best egg quality and the greatest chance of pregnancy, remaining ever mindful of the inconvenience and cost of therapy. While we want to maximize the chances of pregnancy, we want to minimize the chances of over-stimulation of the ovaries and resulting cyst formation. All of this can be a tall order to fill.

In cases where there is a high probability of pregnancy, such as a woman under age 30 who has had previous tubal sterilization, fertility pills (clomiphene) rather than injections may be adequate. Some women may require very large dosages of medication and prolonged therapy to achieve an adequate number of eggs to fertilize. You have our guarantee that if a superior method for ovarian stimulation is found, we will use it.

An example of the most commonly used stimulation regimen has been included as an IVF cycle model (requires Adobe Acrobat Reader). While this is similar, if not identical, to the most commonly used regimen in the world today, individual response will still vary. The rationale and plans for your therapy will be presented in detail and please ask questions.

Traditionally we use A GnRH analog (the commonly recognized brand is Lupron) beginning around cycle day 21 of the in the cycle before IVF is anticipated. This helps synchronize egg/follicle development and helps prevent and unwanted ovulation before aspiration.

If your periods are irregular we often use oral contraceptives or progestins to help regulate and time bleeding.

Various regimens are used to stimulate the ovary to develop multiple follicles, but most involve the use of injectable fertility medications, gonadotropins. The purpose of these injections is to cause more than one follicle to advance toward ovulation. The injections are safe and easy to administer.

For time, cost and convenience, your partner will be taught how to give the injections when you are using an injectable form of therapy. In our experience, partners are the best of all “shot givers.” We have videotapes and written instructions to guide this process. It is important to know that there is very little chance for mistake if a few simple guidelines are followed. The risk of injury (other than an occasional bruise or complication of the injection procedure is very rare. If there are ever any problems or questions, please ask.

Monitoring of Follicle Growth - An initial screening ultrasound scan is usually scheduled on day 2 or 3 of the cycle in which IVF will be attempted. Ultrasound examinations are painless and are usually performed vaginally. This early screening is to ensure that the ovary and uterus are at the necessary low level of stimulation and that there are no ovarian cysts. Cysts, while generally not serious, may cause the ovary to respond less well and lessen the chance of pregnancy. If cysts are found, it may be necessary to postpone your IVF cycle.

Follicular growth will be monitored using ultrasound scans and blood samples. Monitoring is performed in either our Johnson City or Asheville offices or in any one of our several satellite offices. Careful monitoring of response to stimulation helps to ensure that adequate stimulation is occurring and over- and under-stimulation is avoided. With ultrasound scans, the number of follicles can be determined and their growth followed. Blood samples measure the level of estradiol, the principle hormone produced by the growing follicle, and possibly LH, luteinizing hormone, and progesterone. This ensures that ovulation has not occurred. Together these tests help to determine the number, size and quality of developing follicles.

Follicle Maturation - When the follicle(s) is judged to be mature, both by size (usually 16-22 mm) and estradiol level (above 400 pg/ml or 200 pg/ml per preovulatory follicle), you will receive an injection of human chorionic gonadotropin (hCG) to ensure the final maturation of the oocyte. The injection of hCG also sets the time for follicular aspiration. This injection is usually given in the evening between days 10 and 13 of the stimulation cycle. Follicle aspiration is scheduled 35-37 hours after this injection. If left alone you would probably ovulate at about 40 hours after the hCG injection. It is common to worry about ovulation occurring before the eggs can be removed. Ovulation is certainly not impossible, but very unlikely because of the medications discussed above used to block ovulation. It is common to feel considerable pressure and have a large amount of cervical mucus in the last several days, especially right before, the aspiration procedure.


STEP 2 – Follicle Aspiration

Follicle aspiration is performed at our Johnson City office. We know this is much less convenient for some, but it offers considerable cost savings and improved quality control to have a “central” laboratory. Before the aspiration procedure, a speculum is placed and the vagina cleansed with large amounts of sterile water. It is impossible to completely disinfect the vagina and we do not want to use strong antiseptic agents as that might kill the eggs. As a safeguard, you will be given an injectable antibiotic to reduce the chance of infection. Please let us know if you have any drug allergies.

Since this is an outpatient office procedure and we are trying to minimize intervention, complications and cost. We do not routinely start an intravenous infusion (IV). We use mild oral sedation (Valium or Ativan)/pain medication (usually a combination of Demerol and phenergan. Most patients are interested and like to see the eggs as they are isolated form the follicular fluid be the embryologist. Your partner is strongly encouraged to be with you during the procedure. The procedure is not painless, but is quick and generally well tolerated. The pain is often described as pressure, or a severe menstrual cramp or ovulation pain. After several thousand procedures using this method we are convinced that it is superior to all others.

An ultrasound scan, just like those used in monitoring is performed, but this time a needle will be attached to the ultrasound probe (transvaginal approach). The ovary, which is naturally positioned very close to the top of the vagina and the tip of the ultrasound probe, is usually easily accessible. In the procedure of follicle aspiration, the needle is passed through the upper vaginal wall and while watching on the ultrasound screen the follicle is entered and fluid removed with gentle suction.

With the fluid comes the egg, which is often floating freely in the follicle fluid at the time of the aspiration. The nurse who will be assisting passes the fluid into the adjacent mobile incubator (we call it the “egg mobile”). All culture dishes will have your name on them. The attending embryologist will empty the fluid into a small dish where the egg and its associated follicle cells can be seen through the microscope. He will move then move the egg into a culture medium and later the sperm will be introduced. Each culture dish is carefully labeled with your name.

We aspirate all follicles possible. Some follicles, especially small ones, may not have eggs capable of collection. All eggs may not be healthy eggs capable of being fertilized; some of fertilized eggs will not continue their development into embryos capable of establishing a pregnancy.

The procedure may last from several to about 10 minutes, with few exceptions. You will be in the procedure room for another 10-15 minutes before and after the procedure;. Immediately after aspiration of a follicle, the oocyte is isolated from the follicular fluid and placed in a culture dish containing nutrient media and transferred to the incubator. Each culture dish is carefully labeled with your name.

After the aspirations are completed, we let you rest a short while and usually permit you to go home within one hour.

For the Male Partner

Shortly before or after the aspiration procedure, the sperm are isolated from the semen obtained earlier. During this procedure, the most active sperm are selected and transferred to a culture dish for completion of the changes necessary for fertilization.

All specimen and culture containers are carefully labeled with the couple's name and isolated from all other patient material.

You must be available to give a semen specimen on the day of the follicle aspiration. You should abstain from ejaculation for at least 2 days, but no more than 7 days prior to the aspiration procedure. This timing has been judged to produce an optimal specimen. Too long or too short period of abstinence can be detrimental to sperm quality.

The specimen used for fertilization should be obtained in as clean a manner as possible. Wash the genital areas thoroughly with soap and water on the morning the sample is required. Use no lubricants in production of the specimen. A sterile container will be given to you. The specimen must be obtained by masturbation. A quiet and isolated room is provided for production of the sample. Your partner may accompany you. If you think there may be any problem in producing a specimen, please discuss this well in advance.


STEP 3 – In Vitro Fertilization and Culture

Oocytes and sperm are placed together in a culture dish, which is placed in a controlled environment inside an incubator. There they are left undisturbed until the next day when they are examined. If fertilization has occurred, you will be notified and the transfer time confirmed. If fertilization cannot be determined the eggs may be re-inseminated, or reexamined, before a decision to cancel the cycle is made. If there are more than four embryos after fertilization, you will be notified and given the option of cryopreservation for future embryo transfer cycles.


STEP 4 – Embryo Transfer

Usually on the third day following follicular aspiration, you will return to the clinic to receive the conceptuses ("embryo[s]"), which have developed in culture to the 2-12 cell stage. The transfer takes only a few minutes. This procedure involves placing a speculum into the vagina and transferring the embryo(s) through a small plastic tube placed through the cervix into the uterine cavity. No anesthesia is required and usually only minimal, if any, discomfort is felt.

You will remain in one of our procedure lounges for 1-2 hours after the transfer. During that period you will be lying down as a possible aid in retention and implantation of the embryos. If you want, bring something to read or music.


STEP 5 – Implantation Support

It is unknown when implantation takes place or what can be done to ensure the best chance of implantation. Common sense should prevail. Avoid guilt in deciding on activities.

In some cases either progesterone (suppositories or injections) or hCG injections may be given to help prepare and possibly support, the uterus. Whether or not they are prescribed depends on the type of ovarian stimulation and your response to this stimulation.

As the embryo attaches to the uterine wall, it produces hCG. This hormone can be measured in maternal blood and urine and is the basis of pregnancy tests. The hormone may be detected as early as 10 days after transfer by sensitive quantitative blood testing and should be seen by 12 days after transfer by home testing of urine. A rising level of ß-hCG indicates successful implantation and pregnancy. We do not routinely do blood testing, but wait for a missed menses. Early testing can possibly be misleading, but more importantly, the results will not change or therapeutic course or intervention. Normally, all residual hCG for injections has been cleared by 7-10 days after the last injection but it is possible, that there may be a very small amount that could falsely affect pregnancy test. Generally, if a pregnancy test is positive 10 days from hCG, you are pregnant, regardless of what future testing might show.

A large number of pregnancies, both normal and after IVF-ET, are lost very early. Generally, hCG and progesterone levels are followed until an intrauterine pregnancy can be identified. If progesterone is used for luteal support, it is tapered relatively quickly depending on blood levels. Ultrasound scans are performed weekly until fetal heart activity and the number of embryos has been determined. If there is spotting during this time--rest and call. If a pregnancy does not occur, menses will usually start 10 to 14 days after embryo transfer.


Specific charges for each portion of the IVF cycle are presented in IVF Cycle Fees.


Who to call in case of emergency, or if questions arise

You should feel free to ask any questions as you progress through your IVF cycle. You will be given time during your office visits to discuss your concerns. If you have additional questions or should problems arise, you may contact us at 423-461-8880; in Asheville, 828-285-8881. When calling our office please identify yourself as an IVF patient. If a nurse is not available, leave a message. Please call again if your call has not been returned in a reasonable length of time.

If it is before regular office hours, at night, or during the weekend, please leave a message on our voice mail at the above number. If it is a question that needs to be addressed immediately, please page your primary C.A.R.S. physician. If the call is not returned within 15 minutes page again. If the after the second try there has been no answer, page one of the other C.A.R.S. physicians. You may page Dr. Thatcher at 412-8880, or Dr. Kennedy at 412-8888. Asheville patients may call the Asheville office where pager numbers will be given (828-285-8881). If the call is not returned within a reasonable time, page Dr. Thatcher or one of the Johnson City physicians.

If there is a true medical emergency and you have been unable to reach your C.A.R.S. physician or you feel that you cannot wait for a return call, go directly to the nearest emergency room. In Johnson City, go to Johnson City Medical Center and identify yourself as a patient of your primary C.A.R.S. physician. In Asheville, go to Mission emergency room and identify yourself as a patient of Dr. Holman.

If you have an obstetrician or gynecologist, or live a considerable distance away, you may use this person for calls when your C.A.R.S. physician is not available.

We are very interested in your medical care and please keep us informed of any significant health changes.

Do not let a question go unanswered.

Also see C.A.R.S. IVF success rates and Dr. Thatcher's article on interpreting success rates.

 

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C.A.R.S. Center for Applied Reproductive Science - Johnson City,TN: (423) 461-8880 : Asheville,NC: (828) 285-8881