Arizona Reproductive Medicine Specialists Assisted Reproductive Technology Patient Guide
Welcome All of us at Arizona Reproductive Medicine Specialists are pleased to welcome you to our program. We know that the beginning of this phase of your treatment means a lot to you. Every person that we treat is different and their clinical and emotional needs are unique. We want you to know that we are always available to address your concerns and to help you through this process. This guide provides you with a general outline of the treatment you will be receiving over the next several weeks. After treating many patients, however, it is clear to us that each person has a unique set of circumstances requiring an individual treatment plan and personalized care. In this guide therefore, we attempt to provide a framework of understanding that can then be added upon so that your experience here is comfortable, familiar and informed. Please review the contents of this guide and feel free to ask any questions that arise. Specific teaching visits will take place to assure that you understand the process and have enough time to have all your questions answered. We look forward to participating with you in this important step toward your goal of parenthood. The Staff 2
PROGRAM OVERVIEW Assisted reproduction technologies (ART) involve the removal of eggs from the ovary, their combination with sperm, and the return of the eggs and sperm or the fertilized egg to the patient. There are many variations of this general strategy. After discussions with your physician a specific plan will be formulated. It will usually involve the following components: MEDICATIONS Most patients will be placed on an oral contraceptive pill (OCPs) before starting any other medications. The purpose of this medication is to decrease cyst formation and to allow for easier initiation of the following medications. Medications are typically given to cause the production of many follicles. Follicles are the supporting structure for the egg. They are a hollow structure full of fluid that nourishes the egg that resides within the follicle. The most common medications given for the purpose of multiple follicular development are called GONADOTROPINS. Many patients have already received these medications in the form of Repronex, Follistim, or Gonal-F. These medications contain the hormones Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH), which are involved in the stimulation of follicle production. All of these medications are given with a short insulin needle. In order to safely administer these medications, frequent blood draws to check hormone levels and frequent ultrasounds to check follicular growth are necessary. This information allows us to tailor your treatment to your individual needs. There are other combinations of medications that can be used to achieve multiple follicular growth. Your physician will discuss these protocols with you if you are an appropriate candidate. Some patients will also be treated with a medication called GnRH-Agonist commonly referred to as Lupron. Other medications are called GnRH-Antagonists. These medications are used to suppress your own natural hormone production so that your stimulation is more controlled. HORMONE MONITORING Before your treatment cycle starts, we will need to measure FSH, LH and estrogen levels on day three of your cycle. You will then be prescribed 100mg of clomiphene citrate for five days starting cycle day 5 and then your blood will be redrawn on cycle day 10 for FSH. This is called a Clomiphene Citrate Challenge Test. This will help us plan and individualize a dose of medication for you to start on. Once your treatment is underway, we will check your estrogen level to determine how you are stimulating and your medication needs. 3
ULTRASOUND MONITORING At various times throughout your cycle an ultrasound will need to be performed to determine the condition of the ovaries and their response to medication. During these examinations we determine if the ovaries are normal and determine the size and number of any developing follicles. HCG Trigger Once many follicles have developed to the appropriate stage, another medication is used to make the developing eggs mature enough to be removed from the ovary and successfully fertilized. This medication to cause this is called Human Chorionic Gonadotropin or hcg. In special cases, a GnRH-Agonist may be used for this same purpose. This medication is administered before the anticipated time of the removal of the eggs from the ovary (retrieval). This has been found to be the time needed for the eggs to mature in the ovary. Since the retrieval procedure is frequently performed in the morning this means that the medication is given in the evening. EGG RETRIEVAL The eggs are removed from the follicles using a special needle placed through the vagina and into the follicle. The same kind of ultrasound system used to monitor the follicles throughout your cycle is used to guide the needle into the follicle. No incisions are made and only local anesthesia with intravenous sedation is usually needed. The procedure is performed in the procedure room at ARMS. LABORATORY PROCEDURES Once the eggs are removed, they are taken to the embryology laboratory where they are identified. At this point, they are placed in an incubator and cultured for later combination with sperm in order to achieve fertilization in the laboratory (In Vitro Fertilization, IVF, or sperm injection into the egg: ICSI). TRANSFER Once an appropriate stage is reached, the embryos are transferred to the patient. There are several different approaches to the timing of this step. Embryos are transferred after three or five days of culture. The number of embryos to be transferred depends on several factors including: developmental stage of the embryos, embryo quality, female s age, patient s willingness to undergo selective reduction. In most cases 3 to 4 day 3 embryos or 1 to 2 blastocysts (day 5 embryos) are transferred. 4
LUTEAL PHASE SUPPORT The luteal phase is the second half of the cycle. It is important that adequate levels of progesterone are present during the luteal phase. To ensure this, progesterone is routinely added to your treatment after the egg retrieval. There are many ways to administer this medication. We use the less painful and more convenient forms of vaginal gel, capsules and melt-in-your-mouth lozenges. GENERAL INSTRUCTIONS The following information describes the nuts and bolts of the program. Though each patient may have a unique treatment plan, the general steps of treatment are quite similar. Please review this material before your teaching visit. We will refer to it frequently. You will be instructed on what to do next at each phase of your cycle, but this guide will help you to know what to expect. Our program is designed to allow us to carefully keep track of each patient. Our staff is invaluable in this process. If however, at any time you desire to review your progress with your physician, please feel free to ask for a meeting or a phone call and we will accommodate you as quickly as possible. THE DIAGNOSTIC EVALUATION By the time most patients come to ART, they have already gone through numerous tests. As a result, there are usually very few things that need to be checked before starting a cycle. 1. A visit with the physician will be required to review your history and make sure we have obtained all appropriate records of your prior treatment. A physical exam will also be required to make sure you are healthy enough to undergo treatment. If your body mass index is over 29, or you have a history of respiratory disease, you will need a visit with one of our anesthesiologists. This is to ensure the safe administration of anesthetic during your egg retrieval. 2. We require that each patient have a clomiphene citrate challenge test. The purpose of this test is to evaluate your ovarian responsiveness and plan your treatment. This involves having blood drawn on cycle day 2, 3 or 4 for FSH, LH and an estrogen level. You will then be prescribed Clomiphene Citrate 50 mg, two tablets once a day for cycle days 5-9. Your blood will then be redrawn for a repeat FSH on CD 10. These blood tests need to be performed at our laboratory, and need to have been performed within the last year. We may also need results of other labs depending on your individual circumstances. 3. The American Society for Reproductive Medicine provides guidelines for infectious disease screening for patients undergoing ART procedures. We require that the husband and the wife have these blood tests done within 1 year of the proposed date of the procedure. 5
4. All couples are treated with a course of antibiotics (Zithromax) in order to treat organisms that are not always accurately cultured. 5. Studies of the semen need to have been performed within the last six months. We require analysis of the count, motility, and morphology. An adequate semen analysis includes a morphological evaluation of the sperm using a method called a strict criteria. This is called a KSM. Other more specialized studies of the sperm might also be ordered. 6. A trial embryo transfer is performed. This will involve passing a small tube through the cervix and measuring the depth of the uterus. We also inject fluid into your uterus and perform an ultrasound to make sure you do not have any subtle abnormalities in the uterine cavity. This study is called a sonohysterogram or SHG with a mock embryo transfer or Sono-Mock. 7. Smoking has been shown to significantly compromise fertility in the male and the female. We require that both partners stop smoking completely at least three months before starting medication. 8. Caffeine has also been shown to compromise fertility in the female. We require that the woman stop caffeine intake at least one month before starting treatment. Though it is not required that the man stop caffeine intake, it is often easier for the woman if her partner also stop to support her in her efforts. If all of these studies are complete and appropriate, you can begin treatment in the next available series. 6
THE MONTH BEFORE The month before you plan to have treatment, we will arrange a teaching visit with you. During this visit we will review in detail all of the procedures for your upcoming cycle. Before coming to this meeting you should review this guide and also our IVF video so that you have a good understanding of the process and are prepared to ask any questions that you might have. At this time you will also be asked to finalize all financial arrangements (See the Financial Arrangements Information Sheet). You will also be required to turn in completed consent forms. Payment and consent forms must be finalized at your teaching visit. If it is not, we will need to release the slot we have reserved for you to make room for another patient who is ready to proceed. Many patients will be treated with Lupron. This medication will be started in the cycle just before your egg retrieval. The dose of Lupron will vary depending on your situation. Most patients will start birth control pills prior to starting Lupron. If you are still smoking, you must not take birth control pills!! This allows us to control the timing of the Lupron start and prevents ovulation in the cycle before treatment begins. If you are taking Lupron it will be started on a Thursday. All birth control pills are stopped on a Sunday. This means that the last pill you will take will be on a Sunday. You will not take a pill on Monday. Lupron is later either decreased in dosage or stopped. This also occurs on a Thursday. Your physician will let you know if this protocol is appropriate for you. Those patients not receiving Lupron will receive specific instructions regarding their cycles at the time of their teaching visit. CYCLE DAY 1 The first day of your menstrual cycle is defined as the first day of full flow starting prior to midnight. Spotting is not considered menstrual flow. Please call the cycle day 1 line and leave a message including your first and last name and your phone number. It is not essential to start a period or stop a period before the medications begin. PRE-START EVALUATION You will be called on the Wednesday before your start date with an appointment for Thursday or Friday for blood work and an ultrasound. On the morning of your office visit, the nurse will review your treatment plan for the rest of your IVF cycle. You should have already obtained all of your medications and you should bring all of those medications with you. 7
1. Appointments are scheduled between 7:30a.m. and 8:30a.m. Blood will be drawn for hormonal analysis. You should arrive 10 minutes early to allow for a blood draw before your ultrasound. Early morning visits are needed to allow us to initiate the analysis of your blood in the morning so that we can have the results before our afternoon meeting. 2. You will be given the Med-Voice phone number. (480-423-7125). This is our patient communication voicemail system. You access your mailbox by entering you social security number. Please double check with the nurse that the social security number we are using is the correct one. If it is not, you will not be able to access the important information we leave for you. 3. The ART team meets each day to review all patients undergoing treatment and to select the appropriate medication dose or treatment action for that day. In the afternoons, you will call Med-Voice to receive your instructions for the evening medication. EVERY DAY THAT YOU COME TO THE OFFICE FOR ULTRASOUND AND BLOOD WORK, THERE WILL BE A MESSAGE FOR YOU IN THE MEDVOICE SYSTEM. YOU MUST CHECK IT BETWEEN 3 AND 5 PM EVERY TIME YOU COME IN. IF THERE IS NOT A MESSAGE THERE BY 5 PM, YOU ARE TO PAGE THE CLINICIAN ON CALL AND FIND OUT WHAT MESSAGE WAS LEFT. THIS IS VERY IMPORTANT! If at any time you have questions or concerns that you wish to direct to your physician, please feel free to ask a nurse to put you in contact with them. 4. Depending on your response to the medications, your dose may be increased to as many as 450 units a day. This is done to try to increase the number of follicles growing. If your dose is increased, please contact the pharmacy to obtain more medications. GONADOTROPIN START DAY (GSD)* *The day gonadotropins are started is designated as cycle day three. This may not actually be cycle day three for you since the medications you are on allow us to coordinate your start time. The gonadotropin start day is Saturday except for patients doing preimplantation genetic diagnosis (PGD). 1. That evening you will start your medication. It will include either FSH, hmg or a combination of the two. We request that you take your medication between 6 pm and 8 pm each night. If you are ever unable to take your medication during that time, you should let the Nursing staff know. Late dosing could affect the hormonal values obtained the next morning. You may also receive a morning dose. Morning doses should be administered before coming to the office for monitoring. 2. Start one low-dose aspirin (81 mg) today. 8
Free days! Enjoy, but continue medications. CYCLE DAYS 4 AND 5 CYCLE DAY 6 Appointments are scheduled between 7:30a.m. and 8:30a.m. Blood will be drawn for hormonal analysis. You should arrive 10 minutes early to allow for a blood draw before your ultrasound. This examination is done using vaginal ultrasound. We will need to you to empty your bladder before the examination to improve visualization. The size of each follicle will be recorded. CYCLE DAY 7 Free day! Usually no studies need to be performed this day. Rare circumstances may require blood or an ultrasound to be done today, but if not, enjoy! Remember to take your medications! CYCLE DAY 8 TO DAY OF hcg TRIGGER Please report as usual for blood and an ultrasound. As before, this information will be used to decide when you are ready to go for retrieval. Semen quality is best when three to five days of abstinence precede the collection. In order to coordinate an appropriate period of abstinence before the day of retrieval, you should have intercourse at least twice during this time. DAY OF TRIGGER The day you are triggered, you will get a live call in the afternoon. Please be sure there are no mistakes in the administration of this medication. This is your most important shot! It is also your last one: YEAH!! THE DAY AFTER TRIGGER The day after your trigger, you will come to ARMS for a final blood draw and a pre-op visit. You will also have a teaching visit to review all the details about the retrieval and what to expect afterwards. Please bring all of your remaining medications. You will be given detailed instructions about what you are to take the rest of your treatment. You should not eat or drink anything after midnight. This means you should not put anything in your mouth after midnight. 9
Retrievals are performed at ARMS. THE DAY OF RETRIEVAL 1. Please follow the instructions listed below: If you are scheduled at 7:30 for your egg retrieval, please arrive by 7:00. If your case is not the first case, then please arrive 60 minutes before your scheduled procedure time. Your husband will collect during your egg retrieval. *If you or your husband anticipate a problem in providing the semen specimen, please inform a nurse no later than your initial IVF teaching visit. 2. An anesthesiologist will meet with you to review your situation and determine your preferences. We work with board certified anesthesiologists in order to provide an added degree of safety and greater flexibility for patient comfort. The anesthesiologist can usually titrate your level of anesthesia from being slightly sedated to being completely asleep. 3. During the retrieval, there will be several staff personnel assisting in the procedure. The retrieval will only be performed by Dr. Moffitt, Dr. Johnson, or Dr. Faber. 4. After the retrieval, the eggs will be cultured and then combined with sperm. 5. An antibiotic will be prescribed for you to help prevent infection. You will be given specific instructions at your pre-op visit. 6. You will remain at the facility, recovering from the retrieval, for about one hour. Since you had anesthesia, you will not be able to drive, you should make arrangements for your return trip home. 7. You should eat as soon as you feel able and drink as many fluids as possible. 8. Your husband should remain available by phone until 5:00 p.m. on the day of the retrieval in case the lab needs a second sample. 9. A prescription for a pain medication will be given to you. If it does not control your pain, you should contact the office and explain your symptoms to us. 10
ADDITIONAL LABORATORY PROCEDURES ICSI (Intracytoplasmic Sperm Injection) This procedure involves injecting sperm into the egg to facilitate fertilization. This procedure is performed in the afternoon to evening of the day the eggs are retrieved. This is only utilized when there is a significant risk of no fertilization due to poor quality sperm. This risk is based on a review of your semen analysis and your Kruger s Strict Morphology (KSM) test. Some people who had this test earlier and were allowed to do inseminations wonder why ICSI would be recommended if they were allowed to do inseminations before. This is done because there are results of these tests that are in a gray area where a trial of insemination is recommended. If the trial of insemination is unsuccessful, then these patients are at risk for failed fertilization. When the lab recommends conventional insemination of the eggs for IVF, (meaning they do not recommend ICSI, there is still a chance <10%) that very few or no eggs will fertilize. When this occurs, we attempt to fertilize the eggs with ICSI the day after the egg retrieval when this is first recognized. This procedure, called rescue ICSI is controversial in that the true success rates of this procedure are not clear. We do have live births from this procedure so we feel it is worth a try. Otherwise no embryos would be created and the cycle would be over without even a chance of obtaining a pregnancy. There is no question that ICSI, when used the day of the egg retrieval, is more successful than rescue ICSI. There is also no question that if you do not need to do ICSI you should not do it. This is because conventional IVF yields more embryos per egg retrieved than does ICSI when ICSI is not needed. EXAMPLE: The Smiths decide to go along with conventional IVF and 10 eggs are obtained from the egg retrieval process. They are all inseminated and 7 fertilize. (Normal fertilization rates are 70% at our clinic). They now have 7 embryos. The Jones decide to do ICSI even though they have a normal semen analysis and KSM. 10 eggs are obtained from the egg retrieval process. Only mature eggs can be injected and only 7 mature eggs are identified by the embryologist. (Mature egg rates are 70% at out clinic). The 7 eggs are injected and 4 fertilize. (Normal fertilization rates are 60% at our clinic). They now have 4 embryos. You can see from this example that the couple that chose to do ICSI when they didn t really need it, had three fewer embryos. The problem is that before the case is actually done, you don t really know if you are one of the 93% of patients who don t need ICSI, or one of the 7% who do. We have chosen not to make 93% of our patients have a procedure that they don t really need, will cost them more money, and will result in them 11
having fewer embryos. This does mean that on average, 7 8% of our patients will have a fertilization outcome which is not what we or they hoped for. In some cases we may recommend a split ICSI case. This is usually for patients that are borderline ICSI. In these cases, the decision will be made by the embryologist regarding whether to do a split case and how many eggs to allocate to either ICSI or traditional IVF. For most patients (but not all), you must have at least 8 eggs to be considered for a split ICSI case. We perform split cases because 1) traditional IVF embryos produce on average better embryos and higher pregnancy rates, 2) when ICSI is recommended to avoid fertilization failure, only a relatively low percent (maybe 50%) of patients will actually have fertilization failure and 3) doing both hedges against complete fertilization failure (which may still occur in ICSI, but is rarer). When a patient signs the consent form for our IVF process, (ASSISTED REPRODUCTION INFORMED CONSENT FORM ) I understand that there is no guarantee of successful fertilization or of a successful pregnancy as a result of this treatment. I agree to follow the course of treatment recommended by ARMS physicians, Laboratory, and support staff. I understand that any treatment that I desire that is different than this must be specifically requested by me in writing and signed by ARMS staff as received. Oral requests will not be accepted and are not binding. I understand that unexpected laboratory circumstances might require procedures such as assisted hatching or sperm injection which will need to be initiated before I can be contacted, and that I will be responsible for the cost of these procedures. if they have not been given a written plan from us indicating that ICSI is recommended, this means that they are willing to take the 7 to 8% chance that they will have few or no eggs fertilize. If a couple does not want to take this risk, they must indicate this to us in writing and obtain from us a written plan, which indicates that we have ordered ICSI. ASSISTED HATCHING This is performed on embryos two or three days after the egg retrieval. It is performed on embryos from patients with prior IVF failures, poor ovarian response, poor quality embryos, embryos with thick shells, or women greater than 38 years old. It involves making a small hole in the shell of the embryo so it can break out of the shell more easily. BLASTOCYST CULTURE Blastocyst culture involves the culturing of human embryos for five, instead of the traditional 3 days. This procedure involves the use of new media for culturing and new freezing and thawing protocols. Blastocyst culture is a new technique that reduces the 12
probability for high order multiple gestations (triplets or greater) when only one or two blastocysts are transferred to the uterus. High order pregnancies have significant complications such as premature delivery leading to permanent damage to the infant. We feel that these should be avoided. Blastocyst culture is an effective way to maintain high pregnancy rates but lower high order multiple pregnancy rates. Blastocyst culture may enhance the implantation rate of embryos. Implantation rates of 50% have been reported. Higher implantation rates do not necessarily mean higher overall pregnancy rates. The main reason to do the blastocyst culture is to be able to select fewer embryos to transfer and therefore have a lower chance of a multiple pregnancy. On average, 30 to 50% of embryos will progress to the blastocyst stage. This means that if a patient has 10 embryos on day three, they should expect to have only 3 to 5 blastocysts on day five. (Not all of these blastocysts will be of a good enough quality to transfer or freeze.) Some women electing to have blastocyst culture may not have any embryos for transfer because all of them have failed to progress to the blastocyst stage. This occurs in only a very small minority of cases. We feel that in these cases, the embryos if transferred on day 3 would most likely not have developed to the blastocyst stage. There is some evidence that blastocyst culture increases the incidence of identical twins. This could result in more fetuses than embryos transferred. The identical twinning could be such that the two pregnancies are in the same gestational sac. This has been associated with miscarriages and pregnancy complications and loss at more advanced stages of pregnancy. This rate is estimated to be up to 5 to 8%. This occurs in nature in only about 0.5% of pregnancies. Blastocyst culture may decrease the number of embryos available for freezing. The full potential and risks of blastocyst culture and blastocyst freezing is unknown. Not all patients will qualify for blastocyst culture. You must meet criteria defined in A.R.M.S. Blastocyst Culture protocol in order to participate. In general though, only embryos that reach the blastocyst stage will be frozen. THE DAY AFTER RETRIEVAL 1. If you are having IVF, today is the day that we check for fertilization. You will be contacted in the afternoon regarding the outcome of the fertilization process. Your husband should be available in the morning until 10:00 a.m. to provide an additional semen specimen if one is needed. 2. You may experience any of the following symptoms: 13
-Lower abdominal bloating, pain, or discomfort -Vaginal Discharge -Vaginal Spotting -Low grade fever (less than 100 o F) These are to be expected. If these symptoms become severe, or you experience other significant symptoms not listed, you should contact the Nursing staff. 3. Remember to take the prescribed antibiotic as directed. TWO DAYS AFTER THE EGG RETRIEVAL Start your progesterone medication this day as directed. THE DAY OF TRANSFER 1. Your transfer will take place at ARMS. Please come prepared to spend approximately 1 1/2 to 2 hours. 2. You will need a full bladder for this procedure. You should plan your fluid intake and urinating schedule so as to have a bladder that is as full as you were told it needed to be at the time of your mock embryo transfer. 3. You will be given detailed instructions regarding your post transfer care including when to have a pregnancy test drawn. 4. The embryology lab will report to you on the outcome of the culture procedure. This will detail the number of embryos you are to have transferred, their stage of development, and the number that you have cryopreserved. 5. The transfer procedure is relatively simple. It will be very similar to your mock embryo transfer. A speculum exam is performed like you are used to for a PAP smear. The cervix is cleaned and a small flexible tube containing the embryos is passed through the opening of the cervix into the uterus. If you have had intrauterine inseminations, the process is essentially the same. An ultrasound is usually done on your belly to observe this process. 6. After the transfer you will rest for approximately 1 hour. Plan on bringing a video, music or something to read to help you pass the time. You should make arrangements so that you can rest and will be uninterrupted during this time. 7. You should make arrangements to be driven home after your transfer. 8. Once you return home, plan to remain at bed rest until the next day. You should get up only to go to the bathroom. Try to keep this a quiet time. POST TRANSFER The period after the transfer process can be the most difficult part of your treatment. We are all aware of how anxiety-provoking it can be. You should try to return to a normal routine as soon as possible. If you need help with any aspect of your care, please feel free to contact us. 14
1. Please continue your hormones as directed until otherwise notified by a staff member. If you experience unexpected bleeding or other symptoms, please notify the Nursing staff. Do not stop your hormone medication! 2. Most patients will be started on a pill called Estrace seven days after the transfer. 3. You will be scheduled to have your blood drawn for a pregnancy test on the first weekday, 14 days after your retrieval. If it is positive, a repeat level will be drawn 2-3 days later. Please stay on your hormones if you are pregnant. 4. During this time you may experience spotting, cramping, or a dark brown, or whitish clumpy discharge from the gel. These symptoms are not unusual and do not indicate that you are not pregnant. Please do not use a home pregnancy test as they are not very sensitive to the low hormone levels we expect to see at this time in a pregnancy. 5. You will be abstaining from sexual relations for the 2 weeks following the egg retrieval. This is done to protect the ovaries, not because it causes problems in early pregnancy. 6. Dr. Moffitt, Dr. Johnson or Dr. Faber will call you in the late afternoon on the day your pregnancy test is run with the results. Please be available at the phone number you indicated and keep the line open if possible. All of us at Arizona Reproductive Medicine Specialists hope that your news is good. 7. In case of emergency (after hours), call (602) 343-2767 and leave a message for the person on call. They will promptly return your call. Pregnancy Management If you are pregnant, you will need to continue your hormones until directed to stop. An early pregnancy ultrasound is performed between week 6 and week 7 (30 to 37 days after embryo transfer). Don't forget to continue taking your prenatal vitamins. Now is the most important time!!! We hope that this information has been useful to you. Please be assured that we are going to work closely with you to make sure everything goes smoothly. If you have any questions about this information, please feel free to ask. We are looking forward to seeing you soon! T:\ARMS\Packets\PATIENT GUIDE.doc 15