ASSISTED REPRODUCTION THERAPY INSTRUCTIONS FOR IVF CYCLES (INCLUDES ICSI/AH)

ASSISTED REPRODUCTION THERAPY INSTRUCTIONS FOR IVF CYCLES (INCLUDES ICSI/AH)

TABLE OF CONTENTS INTRODUCTION... 1 TREATMENT... 1 DESCRIPTION OF MEDICINES... 2 SUPRESSION THERAPY... 2 BIRTHCONTROL PILLS (OCP)... 2 LUPRON... 2 GANIRELIX/CETROTIDE... 2 STIMULATION THERAPY... 2 MENOPUR/REPRONEX... 2 BRAVELLE/FOLLISTIM/GONAL-F... 2 PEPARE FOR EGG RETRIEVAL... 2 AFTER EGG RETRIEVAL THERAPY... 3 PROGESTERONE/CRINONE... 3 MEDROL... 3 ESTRACE... 3 PHARMACY INFORMATION... 3 MEDICATION PREPARATION... 4 LUPRON... 4 CETROTIDE... 4 GANIRELIX... 5 BRAVELLE/REPRONEX/MENOPUR/GONAL-F VIALS... 5 GONAL-F PEN... 5 GONAL-F MULTIDOSE... 6 FOLLISTIM PEN... 6 HCG MEDICATIONS... 7 PROGESTERONE... 7 CRINONE GEL... 8 MEDICATION ADMINISTRATION... 8 INJECTION SITES... 8 INJECTION TECHNIQUES... 8 SUBCUTANEOUS INJECTIONS... 8 INTRAMUSCULAR INJECTIONS... 9 HINTS TO MINIMIZE DISCOMFORT... 9

MONITORING INSTRUCTIONS... 10 BRIGHAM AND WOMEN'S HOSPITAL... 10 850 BOYLSTON ST... 12 PATRIOT'S PLACE... 13 PRE-OPERATIVE APPOINTMENT INSTRUCTIONS... 14 ANESTHESIA FOR EGG RETRIEVAL... 14 HCG/EGG RETRIEVAL INSTRUCTIONS... 15 DAY AFTER HCG (NIGHT BEFORE EGG RETRIEVAL)... 15 DAY OF EGG RETRIEVAL... 15 FRESH SPERM COLLECTION... 16 RETROGRADE EJACUALTION... 16 TESTICULAR BIOPSY... 16 EGG RETRIEVAL... 17 INSEMINATION... 17 INTRACYTOPLASMIC SPERM INJECTION (ICSI)... 17 DAY OF EMBRYO TRANSFER... 18 EMBRYO TRANSFER... 18 ASSISTED HATCHING (AH)... 18 EMBRYO FREEZING... 19 SUCCESS RATES... 19 STORAGE TIME... 19 FROZEN EMBRYO TRANSFER CYCLE... 19 CYCLE CANCELLATION... 19 POSSIBLE COMPLICATIONS... 20 PREGNANCY TEST AND MONITORING... 21 ADDITIONAL INFORMATION... 22 SPERM AVAILABILITY ISSUES... 22 ADDITIONAL MEDICINES... 22 RESEARCH... 22 AFTER THE CYCLE - CYCLE REVIEW... 22 EMERGENCIES... 22 INDEX... 23

INTRODUCTION Welcome to the Assisted Reproductive Technology (ART) program at Brigham and Women s Hospital (BWH). This booklet has been designed to help you better understand the process of ART. Please use it as a reference when you have questions regarding your treatment instructions. If you can't find answers to your questions in this booklet, please feel free to contact your nurse at the Center for Infertility and Reproductive Surgery. You have either been given or sent a folder (the Patient Packet) which contains most of the materials you will need to undergo an ART cycle with us. Included in this packet are the following: a Therapy Instruction Booklet, prescription information, start-up orders, blood test standing order, and other information. Make sure to bring the PATIENT PACKET with you for all of your ART appointments. During the course of ART, you will be monitored at either the Brigham and Women s Hospital or at an approved satellite facility. Regardless, you will undergo surgical procedures at the Center for Assisted Reproduction (located in the Tower Building, 5th floor, pod C) at Brigham and Women s Hospital. TREATMENT Most ART cycles are approximately 2 months in length. Frequently, ovulation is monitored in the month before the stimulated cycle and therapy (Lupron) is begun 1 week after ovulation. As an alternative, oral contraceptives followed by Cetrotide or Ganirelix or diluted Lupron may also be used. These medications are used to suppress the body's production of hormones. Once suppression is achieved, injectable medications are used to stimulate the ovaries to produce more than one mature egg for retrieval. When the physician has decided that your eggs are ready to be retrieved, you will be instructed to take a medication which causes the eggs to undergo their final maturing. Thirty-six hours later, eggs will be retrieved under anesthesia. Three to five days later, depending on your protocol, fertilized eggs (embryos) will be transferred to the uterus. Some patients may also have the following procedures added to their ART treatment plan: Intracytoplasmic Sperm Injection (ICSI), Assisted Hatching (AH), or Preimplantation Genetic Diagnosis (PGD). 1

DESCRIPTION OF MEDICATIONS USED Some of the following medicines will be ordered for you. Consult your individual treatment plan to determine which ones. Additional medications may be necessary. SUPPRESSION THERAPY BIRTH CONTROL PILLS (Oral Contraceptive Pills - OCPs) OCPs are sometimes used the month before the stimulated cycle to suppress hormones. They can also be used for women who do not get regular periods or in egg donation/gestational carrier cycles to coordinate two women s cycles. LUPRON (Leuprolide Acetate GnRh agonist) Lupron is an injectable medication used to suppress follicular stimulating hormone (FSH) and luteinizing hormone (LH). It is used in some cycles to prevent premature ovulation. It is used once or twice a day. It is important that you do not get pregnant while taking it. Therefore we ask that you use condoms or a diaphragm the month you are starting lupron. GANIRELIX/CETROTIDE (GnRh antagonist) Ganirelix and Cetrotide are injectable medications used to suppress the hormones FSH and LH. They are used in some cycles to prevent premature ovulation. They are used once a day. STIMULATION THERAPY MENOPUR/REPRONEX (Human Menopausal Gonadotropin - hmg) Menopur and Repronex are injectable medications containing the two hormones, FSH and LH, which stimulate egg and ovarian follicle growth. They are used once or twice a day. BRAVELLE/FOLLISTIM/GONAL-F (Follicular Stimulating Hormone FSH) Bravelle, Follistim, and Gonal-f are injectable medications containing FSH which stimulates egg and ovarian follicle growth. They are used once or twice a day. PREPARE FOR EGG RETRIEVAL PREGNYL/ NOVAREL OR GENERIC (Human Chorionic Gonadotropin - HCG) Pregnyl, Novarel or generic HCG are injectable medications which cause the final maturing of the egg. They are given when the follicles have reached sufficient size after stimulation therapy. Most patients will be instructed to administer HCG between 8:30pm and 3:00am (you will be given an exact time). It is given only once. The egg retrieval is usually performed 36 hours after HCG is given. Please make sure that the injection is given on time. 2

AFTER EGG RETRIEVAL THERAPY PROGESTERONE/CRINONE (Progesterone) - a hormone normally secreted by the ovary after ovulation to thicken and maintain the lining of the uterus. Because of the way eggs are retrieved (i.e. a needle placed in the ovary) it is thought that the body's normal production of progesterone could be reduced. Progesterone (injection or vaginal suppository) and Crinone (vaginal gel) provide progesterone. Injections are given once a day; vaginal suppositories are used three times a day; and the gel is used once a day in the morning. MEDROL (methylprednisolone) an anti-inflammatory medication started the evening of the egg retrieval then once a day for three more days to minimize the inflammatory response to manipulated embryos in the case of ICSI, AH, or PGD. ESTRACE (estradiol) a hormone started twice a day beginning the day after the egg retrieval to aid implantation of manipulated embryos in the case of ICSI, AH, or PGD. PHARMACY INFORMATION We will be happy to assist you in obtaining your medications and will send orders to the pharmacy of your choice. If you have a specific drug plan, please notify your nurse and the order will be sent. MAIL ORDER: If you choose to purchase your medications through an infertility mail order pharmacy, please notify your nurse and the order will be sent. Major infertility pharmacies are: Freedom Fertility Pharmacy 800-660-4283 Village Fertility Pharmacy 877-334-1610 Walgreens Specialty Pharmacy 800-424-9002 press #1 and #1 again 3

MEDICATION PREPARATION LUPRON (Premixed, multidose bottle, refrigerate after opening) It is important that you NOT be pregnant while taking Lupron. To avoid this possibility, we ask that you use a condom or diaphragm starting the period before Lupron starts. Please note: When drawing up Lupron, dosages will be measured differently based on the syringe used. We require the use of low dose insulin syringes. Directions and instructions are solely for use with these syringes and no others. 1. Wash hands thoroughly with soap and water. 2. Remove plastic cover from the vial and clean the rubber top with an alcohol wipe. 3. Remove the sterile insulin syringe from the wrapper. 4. Remove the protective cap from the needle and pull back the plunger to the required dose. The syringe will fill with air. 5. Push the needle through the rubber stopper and inject the air into the vial. 6. Keep the needle in the vial and turn it upside down so that the fluid level is over the needle tip. Pull back on the plunger so that the fluid flows into the syringe to the dose. 7. If there is air in the syringe, gently tap the syringe. If this doesn't move the air bubbles, push the fluid back into the vial and repeat step #6. MAKE SURE THAT THE SYRINGE IS FILLED TO THE PROPER LEVEL WITH FLUID, NOT AIR. Remove the syringe from the vial. 8. Perform a subcutaneous injection (refer to the Administration of Medications section). CETROTIDE (Needs mixing, single-dose preparation, refrigerate) 1. Wash hands thoroughly with soap and water. 2. Remove plastic cover from the vial and clean the rubber top with an alcohol wipe. 3. Remove sterile syringe, which is pre-filled with sterile diluent (water), from the wrapper. 4. Remove the protective cap from the needle, push the needle through the rubber stopper, and inject the fluid into the vial. 5. Keep the needle in the vial. When medication dissolves, turn the vial upside down so that the fluid level is over the needle tip. Pull back on the plunger so that the fluid flows into the syringe. 6. If there is air in the syringe, gently tap the syringe. If this doesn't move the air bubbles, push the fluid back into the vial and repeat step #5. MAKE SURE THAT THE SYRINGE IS FILLED TO THE PROPER LEVEL WITH FLUID, NOT AIR. 7. Remove the syringe from vial and carefully put the needle cover over the needle. 8. Cover the needle and remove it from the syringe, then put the ½ inch needle on it. 9. Perform a subcutaneous injection (refer to the Administration of Medications section). 4

GANIRELIX (Premixed, single-dose syringe, store at room temperature) 1. Wash hands thoroughly with soap and water. 2. Remove the cover from the needle and perform a subcutaneous injection (refer to the Administration of Medications section). BRAVELLE/REPRONEX/MENOPUR/GONAL-F (Needs mixing, single-dose preparation, store at room temperature) 1. Wash hands thoroughly with soap and water. 2. Line up the number of vials prescribed and 1 vial of diluent (water). 3. Remove the plastic covers from the vials and clean the rubber tops with an alcohol wipe. 4. Remove a 3cc(ml) syringe with a 1 ½ inch needle from the wrapper, tighten the needle on the syringe 5. Remove the protective cap from the needle. Push the needle into the diluent vial and pull back to the 1cc (ml) mark on the syringe. 6. Push the needle through the rubber stopper of the first medication vial and inject the diluent. Keep the needle in the vial and gently swirl it until the fluid looks clear. Do not shake. 7. Turn the vial upside down so that the fluid level is over the needle tip. Pull back on the plunger so that the fluid flows into the syringe. MAKE SURE THAT THE SYRINGE IS FILLED TO THE PROPER LEVEL WITH FLUID AND NOT AIR. Remove the syringe from the vial. 8. If multiple vials are prescribed repeat #6 and #7 with the same diluent filled syringe. Remove the syringe from vial and carefully put the needle cover over the needle. 9. If there is air in the syringe, remove it by holding the syringe with the needle straight up. Gently tap the syringe until the air is at the top. Carefully push the plunger in to remove the air. 10. Cover the needle and remove it from the syringe, then put the ½ inch needle on it. 11. Perform a subcutaneous injection (refer to the Administration of Medications section). GONAL-F PEN (Premixed pen, store at room temperature, store extra pens in the refrigerator) 1. Wash hands thoroughly with soap and water. 2. Remove the pen cap and clean the rubber stopper at the end of the pen with an alcohol wipe. Attach a needle by twisting clockwise. 3. Dial your required dose to the black arrow. 4. Load the dose by pulling out the plunger as far as it will go. (Number on the last visible triangular red mark should match the dose number. If the dose number does not appear in red, there is not enough medication in the pen for the required dose. Either use a new pen or inject as much as is in the pen and use a new pen to get the rest.) 5. Perform a subcutaneous injection (refer to the Administration of Medications section). 6. After the injection, carefully cap the needle and remove it. If there is more medication in the pen replace the pen cap and store it in the refrigerator. 5

GONAL-F MULTIDOSE (Needs mixing, multi-dose bottle, refrigerate after mixing) 1. Wash hands thoroughly with soap and water. 2. Remove plastic cover from the vial and clean the rubber top with an alcohol wipe. 3. Remove sterile syringe, which is pre-filled with sterile bacteriostatic water, from the wrapper. 4. Remove the protective cap from the needle and push the needle through the rubber stopper. Inject the fluid into the vial. Remove the syringe and gently swirl the vial until the fluid looks clear. Refrigerate after mixing. Preparing the dose: 1. Wash hands thoroughly with soap and water. 2. Clean the rubber top of the Gonal-f multidose vial with an alcohol wipe. 3. Remove the sterile syringe from the wrapper. Remove the protective cap from the needle and pull back the plunger to the required dose. The syringe will fill with air. Do not touch the needle, it must remain sterile. 4. Push the needle through the rubber stopper and inject the air into the vial. 5. Keep the needle in the vial and turn it upside down so that the fluid level is over the needle tip. Pull back on the plunger so that the fluid flows into the syringe to the dose. 6. If there is air in the syringe, gently tap the syringe. If this doesn't move the air bubbles, push the fluid back into the bottle and repeat step #5. MAKE SURE THAT THE SYRINGE IS FILLED TO THE PROPER LEVEL WITH FLUID, NOT AIR. Remove the syringe from the vial. 7. Perform a subcutaneous injection (refer to the Administration of Medications section). FOLLISTIM PEN (Multi dose cartridge, store at room temperature, store extra cartridges in the refrigerator) 1. Wash hands thoroughly with soap and water. 2. Place a cartridge in the pen with the rubber stopper end going in first. 3. Clean the rubber stopper at the end of the cartridge with an alcohol wipe. Attach a needle by twisting clockwise. 4. Dial your required dose to the window. If you go past your dose do not dial backwards. Dial to the highest dose and push the plunger in, then redial. 5. Perform a subcutaneous injection (refer to the Administration of Medications section). 6. After the injection, check that the dose window shows 0. If it doesn t, the number in the window is the amount of medicine still needed. Insert a new cartridge and repeat #3,4,5. 7. After the injection, carefully cap the needle and remove it. If there is more medication in the pen replace the pen cap and store in the refrigerator. 6

HCG MEDICATIONS (Pregnyl, Novarel, generic) (Needs mixing, single-dose preparation, store at room temperature) Two vials: The first contains 10,000 International Units of HCG powder and the second contains 10cc (ml) of diluent (water). 1. Wash hands thoroughly with soap and water. 2. Remove the plastic covers from the vials and clean the rubber tops with an alcohol wipe. 3. Remove a 3cc (ml) syringe with a 1 ½ inch needle from the wrapper and tighten the needle on the syringe. 4. Remove the protective cap from the needle. Push the needle into the diluent vial and pull back to the 1cc (ml) mark on the syringe. 5. Push the needle through the rubber stopper of the medication vial and inject the diluent. Keep the needle in the vial and gently swirl it until the fluid looks clear. 6. Turn the vial upside down so that the fluid level is over the needle tip. Pull back on the plunger so that the fluid flows into the syringe. MAKE SURE THAT THE SYRINGE IS FILLED TO THE PROPER LEVEL WITH FLUID AND NOT AIR. Remove the syringe from the vial. 7. If there is air in the syringe, remove it by holding the syringe with the needle straight up. Gently tap the syringe until the air is at the top. Carefully push the plunger in to remove the air. 8. Perform an intramuscular injection (see Administration of Medications section). PROGESTERONE injection (Premixed, multidose vial preparation, store at room temperature) 1. Wash hands thoroughly with soap and water. 2. Remove plastic cover from the vial and clean the rubber top with an alcohol wipe. 3. Remove the 3cc (ml) syringe from the wrapper and tighten the needle on the syringe. 4. Remove the protective cap from the needle and pull back the plunger to the required dose. The syringe will fill with air. 5. Push the needle through the rubber stopper and inject the air into the vial. 6. Keep the needle in the vial and turn it upside down so that the fluid level is over the needle tip. Pull back on the plunger so that the fluid flows into the syringe to the dose. 7. If there is air in the syringe, gently tap the syringe. If this doesn't move the air bubbles, push the fluid back into the vial and repeat step #6. MAKE SURE THAT THE SYRINGE IS FILLED TO THE PROPER LEVEL WITH FLUID, NOT AIR. Remove the syringe from the vial. 8. Perform an intramuscular injection (see Administration of Medications section). PROGESTERONE SUPPOSITORIES (Store at room temperature) 1. Remove the suppository from the packaging. 2. Insert in the vagina approximately 1 ½ inches with your finger. 3. Recline for 20-30 minutes after insertion. 4. It is suggested to wear a mini pad due to leakage of the wax base. 7

CRINONE 8% GEL (Store at room temperature) 1. Remove the applicator from the packaging. 2. Twist off the tip to create an opening. 3. Insert the thin end into the vagina. 4. Squeeze the box to deposit the medicine. Remove the applicator. 5. It is suggested to wear a mini pad due to leakage of the gel. Lupron Ganirelix/Cetrotide Menopur/Repronex Gonal-F Bravelle/Folllistim MEDICATION ADMINISTRATION Subcutaneous (SC) 1. Injection sites should be rotated daily. INJECTION SITES Intramuscular (IM) hcg Progesterone Progesterone injections should only be given in the buttocks TECHNIQUES 2. Wash hands thoroughly with soap and water before preparing and giving the medicine. 3. Never touch the needles, they must remain sterile. If it is touched, remove the needle and replace it with a new needle. 4. Make sure that the syringe is filled with medicine and not air (a tiny bubble of air is acceptable and will not cause problems). 5. Use syringes only one time, then throw away in a "sharps" container. When the container is full, either bring it back to the pharmacy or call your town waste disposal department and ask how to dispose of medical waste. 6. It is safe to administer as much as 2cc (ml) per IM injection and 1cc (ml) per SC injection. GIVING SUBCUTANEOUS (SC) INJECTIONS 1. Clean the injection site with an alcohol wipe by rubbing in a circular motion. Remove the needle cap. 2. Pinch the injection site with one hand. Using the other hand, quickly insert the needle straight in as far as it will go. Inject the medication by pushing the plunger down to empty the syringe. 3. Remove the needle. Rub the area in a circular motion to massage the medication. Dispose of the syringe in a sharps container. If you see blood or a small amount of fluid at the injection site, simply wipe the site with the alcohol wipe and apply light pressure. 8

GIVING INTRAMUSCULAR (IM) INJECTIONS 1. Clean the injection site with an alcohol wipe by rubbing in a circular motion. Remove the needle cap. 2. Stretch the injection site with one hand and using the other hand, quickly insert the needle straight in as far as it will go. 3. Release the skin. With that hand draw back very gently on plunger; if no blood is immediately visible, inject the medication by steady pressure. If blood is seen when drawing the plunger up, the needle is probably in a vein - you must remove the needle and apply pressure to the needle site for 5 minutes. The injection can then be attempted at another site after putting on a new needle (repeat 1-3). 4. Remove the needle. Rub the area in a circular motion to massage the medication. Dispose of the syringe in a sharps container. If you see blood or a small amount of fluid at the injection site, simply wipe the site with the alcohol wipe and apply light pressure. HINTS TO MINIMIZE DISCOMFORT 1. Push the needle quickly through the skin. 2. Use room temperature diluent (water). 3. Put ice on the site for one minute before the injection. 4. Put a warm, wet washcloth on the site for 10 minutes after the injection. 9

MONITORING INSTRUCTIONS Women will have both vaginal ultrasound scans and blood tests. Please be on time as same day results are needed for physicians to evaluate the cycle. Please follow these instructions during your monitoring phase: 1. Ultrasound exams will be done with a vaginal probe. This is done with an empty bladder. If you prefer a female ultrasound technician you may request it and if possible a female will perform the test (you may have a longer waiting period). 2. No appointments are needed during the week at BWH, 850 Boylston Street or Foxboro. Patients are taken on a first come first serve basis. Waiting times vary depending on how many patients are testing in a day. 3. On weekends/holidays you will be given a specific time to arrive in groups of 6-8. Patients are taken on a first come first serve basis. ULTRASOUND 1. Ultrasound hours MONITORING AT BWH a. Weekdays: Arrive in ultrasound between 6:45am - 7:30am. b. Weekends and holidays: Come in at your assigned time between 7am-8:30am. 2. Ultrasound location - Ultrasound Department, level L-1 From the main lobby at 75 Francis Street, take the elevators next to the revolving door down to L-1. Take a right off the elevator and see the sign for Ultrasound half way down the corridor on the left. 3. Ultrasound requisitions You will receive requisitions in the ultrasound department the first time you test. Hand one in each time you test. When you run low on requisitions inform your secretary or nurse to order more. BLOOD TESTS 1. Blood test hours a. Weekdays: 7a 9a if only blood test is ordered. b. Weekdays: 7a - 8a in the ultrasound department if both blood and ultrasound are ordered. c. Weekend and holidays: at your assigned time. 2. Blood drawing location a. Ultrasound department, see above. 10

b. Weekday blood drawing only: from the main lobby at 75 Francis Street, take the elevators next to the revolving door up to the 3 rd floor. Take a right off the elevator and follow signs to the OB/GYN clinics. The blood drawing lab is to the right of the OB/GYN reception desk. 3. Blood test requisition SIGN-IN You will be provided with a Standing Order Blood Test requisition. Show it to the phlebotomist on the first testing day. It will be good for a year. Always bring a copy of the standing order to the lab and tell the phlebotomist what test you are having. Patients are responsible for signing in either in CIRS or the ultrasound department every day of testing. It is important to complete all the information on the sign-in sheet: your name, hospital number, phone number, physician s name, and whether a voice message can be left. If you forget to sign-in, call your nurse with this information. DAILY INSTRUCTIONS 1. At approximately 2pm each day physicians evaluate each individual patient s response to the medications. Decisions are made about medication dosages and further testing. 2. Patients are then called with the results of the day and their new orders. Phone calls are usually finished by 5:30p. If you have not received a call by 5:30p call the F&E doctor on call at (617) 732-6660. 11

MONITORING AT 850 BOYLSTON ST, ROUTE 9, CHESTNUT HILL NOTE: It is necessary to have testing on Pre-Op day done at Brigham & Women's Hospital. 850 Boylston Street is only available for monitoring Monday Friday. Testing on weekends and holidays will be done at BWH. RT 128 850 BOYLSTON ST RESERVOIR PARK BROOKLINE VILLAGE RT 9 x x CHESTNUT HILL MALL FIRE STATION BROOKLINE AVE x BEACON ST CLEAVELAND CIRCLE JAMAICA WAY-RT 1 ULTRASOUND 1. Ultrasound hours: Arrive in ultrasound 7a 8a. 2. Ultrasound location: 5 th floor 3. Ultrasound requisitions You will receive requisitions in the ultrasound department the first time you test. Hand one in each time you test. When you run low on requisitions inform your secretary or nurse to order more. BLOOD TESTS 1. Blood test hours: 7a 8:30a 2. Blood drawing location: 1 st floor 3. Blood test requisition SIGN-IN You will be provided with a Standing Order Blood Test requisition. Give it to the phlebotomist on the first testing day. It will be kept on file for a year. Always bring a copy of the standing order to the lab and tell the phlebotomist what test you are having. There are sign-in sheets for blood tests and/or ultrasounds in the Ultrasound Department at 850 Boylston Street, but not in the lab. It is important to complete all the information on the sign-in sheet: your name, hospital number, phone number, physician s name, and whether a voice message can be left. If you forget to sign-in, call your nurse with this information. DAILY INSTRUCTIONS 1. At approximately 2pm each day physicians evaluate each individual patient s response to the medications. Decisions are made about medication dosages and further testing. 2. Patients are then called with the results of the day and their new orders. Phone calls are usually finished by 5:30p. If you have not received a call by 5:30p call the F&E doctor on call at (617) 732-6660. 12

MONITORING AT PATRIOT S PLACE, FOXBORO NOTE: It is necessary to have testing on Pre-Op day done at Brigham & Women's Hospital. Patriot s Place is only available for monitoring Monday Friday. Testing on weekends and holidays will be done at BWH. Directions from the south: Interstate 95 North to Interstate 495 North; Exit 14A onto Route 1 North. Follow Route 1 approximately 4 miles to Patriot Place (on the right). Directions from the north: Interstate 93 South (S.E. Expressway) to Interstate 95 South to Exit 9 (Wrentham) onto Route 1 South. Follow Route 1 South approximately 3 miles to Patriot Place (on the left). ULTRASOUND 1. Ultrasound hours: Arrive in the radiology department at 7:30a. 2. Ultrasound location: 1 st floor 3. Ultrasound requisitions: You will receive requisitions in the ultrasound department the first time you test. Hand one in each time you test. When you run low on requisitions inform your BWH secretary or nurse to order more. BLOOD TESTS 1. Blood test hours: 7a 7:30a 2. Blood drawing location: 1 st floor 3. Blood test requisition: You will be provided with a Standing Order Blood Test requisition. Give it to the phlebotomist on the first testing day. It will be kept on file for a year. Always bring a copy of the standing order to the lab and tell the phlebotomist what test you are having. SIGN-IN There are sign-in sheets in the blood drawing area. It is important to complete all the information on the sign-in sheet: your name, hospital number, phone number, physician s name, and whether a voice message can be left. If you forget to sign-in, call your nurse with this information. DAILY INSTRUCTIONS 1. At approximately 2pm each day physicians evaluate each individual patient s response to the medications. Decisions are made about medication dosages and further testing. 2. Patients are then called with the results of the day and their new orders. Phone calls are usually finished by 5:30p. If you have not received a call by 5:30p call the F&E doctor on call at (617) 732-6660. 13

PRE-OPERATIVE APPOINTMENT INSTRUCTIONS Pre-operative (pre-op) visits for new IVF patients, or those with medical problems, particular concerns, or questions, take place at BWH during the cycle, before the egg retrieval. Patients will meet with a physician to sign a surgical consent form and with an anesthesiologist to discuss anesthesia and sign an anesthesia consent form. The visit takes place in the morning. You will be told what day to report to the receptionist at CIRS at 8:15 am. Patients should expect to be at the hospital approximately an hour on the pre-op day. Every effort will be made to make it as convenient as possible. (Please note: patients undergoing repeat cycles may have their pre-op appointment on the phone or the morning of the egg retrieval in the IVF suite). Patients with complicated medical conditions may have their pre-op appointment scheduled before the cycle starts. ANESTHESIA FOR ART Due to the surgical manipulation that occurs during an Egg Retrieval (ER), anesthesia (the loss of sensation) is provided. Before the ER, an anesthesiologist will review a person s medical history, specifically: prior operations, type of anesthesia used, any problems encountered, and any other medical conditions that might impact on the form of anesthesia used. A brief physical examination may be done looking in your mouth and listening to your heart and lungs, followed by a discussion of the type of anesthesia. The type of anesthesia depends on the procedure and any medical conditions. INTRAVENOUS GENERAL ANESTHESIA (IVGA) IVGA is most commonly used for ER. This is accomplished by a combination of short-acting medications given through an intravenous line. The amount of medicine depends on sensitivity to these medicines and the length of the surgery. You will be completely asleep during the ER when IVGA is used. Recovery time from IVGA is generally 1-2 hours. REGIONAL ANESTHESIA Occasionally spinal anesthesia is used for ER. In the operating room the patient either lies on her side or sits up. After the lower back is washed with a cleansing solution and the skin made numb with a local anesthetic, a small needle is placed through the skin into the column of fluid that lies below the spinal cord. A mixture of medicines is injected and the needle removed. The medicines quickly produce numbness from the waist to the toes. With this technique, one is aware but relaxed during the procedure and awake in the recovery room. Recovery time from a spinal is 2-3 hours. The anesthesiologist monitors vital signs and remains in the operating room at all times during the procedure. Following the ER the recovery room nurse and the anesthesiologist monitor recovery and are available if there is any pain or nausea. 14

HCG/EGG RETRIEVAL (ER) INSTRUCTIONS 1. Take HCG medication IM (the big needle) at the time you are instructed because the retrieval will usually be 36 hours later. 2. Stop taking the injectable medicines. 3. Men are asked to ejaculate or have intercourse within 3 days of the HCG injection and abstain from ejaculation thereafter until asked to provide a specimen on the day of the ER. If more than 3 days has elapsed since last ejaculation, intercourse with a condom early the evening of HCG is acceptable, unless the partner is known to have an extremely low sperm count. 4. No intercourse from the time of HCG through 48 hours after the ER. DAY AFTER HCG (NIGHT BEFORE ER) 1. Do not eat anything after midnight the night before the ER. 2. Clear fluids (water, apple juice, plain tea, etc.) are allowed up to 4 hours before the ER. 3. If you take non-ivf medicines regularly, the anesthesiologist will give you specific instructions about whether to take them the morning of the ER. DAY OF EGG RETRIEVAL 1. Arrive at the Center for Assisted Reproduction (Tower 5C) 1 hour before your ER. 2. Bring your blue hospital card. 3. Be aware that children are not allowed on 5C no exceptions. 4. If applicable, the partner must bring a picture ID. 5. 5C is a strict fragrance free area no perfumes, hair spray, after shave, etc. 6. Do not wear fingernail polish or dangling jewelry. 7. Bring a container for contact lenses for removal before surgery, or wear glasses. 8. Couples can be together before and after the ER. 9. Recovery from the ER is 1-2 hours. 10. Before discharge an embryologist will give information about the number of eggs retrieved and the numbers of the sperm specimen. 11. After recovering in the recovery room, women will be discharged home. Please be aware that when you are discharged you will need someone to drive you home and you should rest until the next day. 12. The staff at the Center for Assisted Reproduction has been instructed not to accept left over medicines or containers of used and unused needles. Contact your local waste disposal department for information about disposing used and unused needles. 15

FRESH SPERM COLLECTION 1. If the semen specimen is being collected away from the Center for Assisted Reproduction (CAR) it must have been produced within an hour of arrival, collected in an approved sterile container, and kept at body temperature. Containers can be picked up ahead of time at the CAR. 2. Fresh sperm is collected during the ER. 3. The collection lounge is located just outside the double doors of the CAR. 4. Lock the door after entering the room 5. Inside the room there are: collection instructions, specimen cups, biohazard bags, small brown bags, and specimen release forms. 6. The room is equipped with a toilet, sink, recliner chair, and a DVD player with videos. 7. Follow the instructions for collecting the specimen, then: a. Cap the specimen tightly and label it with your name and medical record number or social security number, partner s name, and date and time of collection. b. Put the container in a biohazard bag and place it upright in a brown bag. 8. Fill out the BWH SEMEN Verification/Requisition for ART Therapy form (SVR). 9. Bring the SVR form and the specimen to the preop/recovery room. A staff member will verify your picture ID and take the specimen from you. 10. In rare cases a second semen specimen may be needed on the day of the ER. RETROGRADE EJACULATION PATIENTS Please note: we require that you abstain for at least 48 hours prior to ejaculation. 1. One hour before sample collection, adjust the ph of your urine by taking 4 Alka-Seltzer tablets. 2. One-half hour before sample collection, drink a full glass of water and empty your bladder. 3. Perform sample collection. 4. After ejaculation, collect urine into a separate container and submit both samples to the staff. 5. Label the containers; see FRESH SPERM COLLECTION #7 - #10. TESTICULAR BIOPSY FOR SPERM RETRIEVAL 1. Men having testicular biopsies on the day of the ER should follow the instructions above under DAY AFTER HCG. 2. If both partners have received general anesthesia, a third person will need to take the couple home. 16

EGG RETRIEVAL & INSEMINATION or INTRACYTOPLASMIC SPERM INJECTION (ICSI) Eggs are usually retrieved 36 hours after taking HCG. The patient will be anesthetized and eggs will be retrieved through a needle using vaginal ultrasound guidance (see to the right). The needle will enter each follicle and drain the fluid and the egg. The fluid collected from the ovaries is examined under a microscope and the eggs are put into culture dishes (labeled with patient's name) which are then placed in an incubator. (Reprinted with permission of the American Society for Reproductive Medicine) Each patient's eggs are placed on a different shelf. If fresh sperm is being used, partners will produce a semen specimen during or after the ER. Insemination patients: the sperm is placed with the eggs 3-6 hours after the ER. Granul osa Cells (from the follicle) Sperm fem ale + male pronuc lei Egg inc ubate ov er night Fertilization Egg m atur ity c an v ar y when r etr iev ed Not all eggs w ill fertilize ICSI patients: the eggs will be evaluated 3-5 hours after the ER. An enzyme (hyaluronidase) is used to separate the eggs from their surrounding cells and the mature eggs are injected with sperm. Granul osa Cells (from the follicle) Egg Remove Granulosa Cells Separate Mature Eggs Inject sperm pipet containing a single sperm incubate overnight Not all eggs will fertilize female + male pronuclei Fertilization The following day, the eggs will be examined for fertilization and the patient will be called with the results. 17

DAY OF EMBRYO TRANSFER 1. Arrive at the Center for Assisted Reproduction (Tower 5C) 1 hour before your embryo transfer (ET). 2. Bring your blue hospital card. 3. Be aware that children are not allowed on 5C no exceptions. 4. If applicable, the partner must bring a picture ID. 5. 5C is a strict fragrance free area no perfumes, hair spray, after shave, etc. 6. Your bladder should be filling. 7. Before the ET the transferring physician will discuss the embryos with you; what they look like and how many are recommended to transfer. 8. Partner may be in the room for the ET. 9. After the ET, relax in a recliner for 10 minutes. EMBRYO TRANSFER Embryo transfer (ET) takes place 3 to 5 days after the ER. STANDARD IVF CULTURE: Fertilized Egg Fertilized eggs do not always divide Cleavage Stage Embryo Embryos can vary in cell number and quality ASSISTED HATCHING: If Assisted Hatching (AH) is planned, the embryos will be evaluated before the transfer and the best ones will have a small hole made in their outer membrane (zona pellucida) using a slightly acidic buffer or laser. Fertilized Egg Cr eate a hole in the z ona 72 hours after egg retrieval 1-3 hour s after AH The ET procedure takes 15 minutes. A thin tube (catheter) is loaded with the embryos selected. The catheter is placed in the uterus (through the cervix) and a syringe on the outer end is pushed to place the embryos in the uterus. The catheter is examined under a microscope to ensure that all the embryos were transferred into the uterus. If requested, embryos of good quality will be frozen for future use. (Reprinted with permission of the American Society for Reproductive Medicine) 18

EMBRYO FREEZING Excess embryos of good quality may be frozen. Various factors affect the success of the freezing process, therefore only good quality embryos will be frozen. The best quality embryos will be transferred fresh into the uterus. Any remaining embryos may be allowed to grow for 2 more days. If the embryos are of good quality they will be frozen. SUCCESS RATE Take-home baby rates following the transfer of frozen embryos are slightly lower than that of transfers with fresh embryos. No increase in fetal abnormalities has been found after freezing and thawing human embryos. STORAGE TIME FOR FROZEN EMBRYOS Frozen embryos can be stored in liquid nitrogen for many years without risk of degeneration. We suggest that frozen embryo transfer cycles not be scheduled unless there are at least 3-4 embryos frozen. Frozen embryos should be used in a timely manner. Embryos will be kept by the Center for Assisted Reproduction for up to 3 years, then arrangements will need to be made to transfer them to a long term embryo banking facility. FROZEN EMBRYO TRANSFER CYCLE Frozen embryo transfer cycle generally requires the use of a form of estrogen (pills or patches). Progesterone (usually intramuscular, but in some cases suppositories or gel) is started several days before the transfer. Women taking estrogen pills will take them twice per day. Women using estrogen patches will replace them every other day, taking care to only place them on the abdomen, upper buttocks or upper legs. Blood work and transvaginal ultrasounds will be done during the cycle to check the uterine lining growth. The embryo transfer will usually occur after 17-23 days of estrogen. CANCELLATION WHY AN ART CYCLE MAY NEED TO BE STOPPED 1. Poor response to the medication or there are too few follicles. 2. The estrogen level and the follicle development are not in line. 3. You have missed testing or instructions regarding your medication dose. 4. Ovulation occurs before the egg retrieval. 5. Fertilization failure. 6. Poor growth of the embryo(s). 19

POSSIBLE COMPLICATIONS OF ART If you have concerns or any unusual symptoms, call your nurse Monday to Friday 8a-4:15 pm All other times call the F&E Fellow on call at 617-732-6660 MULTIPLE PREGNANCY Usually more than one embryo is transferred. Thus multiple implantation of embryo can occur. Usually, the number of fetuses can be determined by ultrasound at 7-8 weeks gestation (5-6 weeks after the embryo transfer). Fetal reduction may be possible in high order multiple gestation pregnancies. OVARIAN HYPERSTIMULATION SYNDROME (OHSS) After the ER, the follicles, which have been drained, can fill up with fluid and form cysts. This results in ovarian enlargement and can lead to lower abdominal discomfort and bloating. Other symptoms may include: nausea and vomiting, shortness of breath, weight increase 2-3 pounds a day, decreased urine output. These symptoms can occur within two weeks after the egg retrieval. The symptoms usually resolve within 1-2 weeks without treatment. Pregnancy can worsen the symptoms of OHSS and make it last longer. Treatment may include cancelling the cycle before the HCG and egg retrieval, cancelling the ET by freezing all the embryo, and/or hospitalization for fluid management. INFECTION AT THE INJECTION OR OPERATIVE SITE Symptoms of injection or operative site infection can include redness and/or extreme tenderness at the site and fever (rare). You may be instructed to apply warm soaks to the site and/or be given antibiotic treatment. ECTOPIC PREGNANCY (TUBAL PREGNANCY) The Center for Infertility and Reproductive Surgery will have you undergo 3 pregnancy tests 48 hours apart to rule out ectopic pregnancy. Approximately 3% of Assisted Reproduction pregnancies become ectopic and resolve on their own or are treated with medication or surgery. Symptoms may include abdominal pain and/or irregular bleeding. OVARIAN TORSION (TWISTING) In less than 1% of cases, the enlarged ovary can twist on itself. This can decrease the blood supply to the ovary and result in significant lower abdominal pain. Surgery may be required to untwist or possibly remove the ovary. MEDICATION SIDE EFFECTS Read the package inserts of your medications and discuss any possible side effects with your physician. 20

SURGICAL RISKS Possible surgical injuries or complications are outlined in the IVF consent book. Please read it carefully. OVARIAN CANCER Some research has suggested that the risk of ovarian cancer may increase in women who take any fertility drugs over a long period of time. These studies had significant flaws. More recent studies have not confirmed this risk. A major risk factor for ovarian cancer is infertility itself, suggesting that early studies may have incorrectly attributed the risk associated with infertility to the use of medications. PREGNANCY TEST MONITORING Waiting to take the pregnancy is a difficult time. If you need extra support call your nurse or one of our social workers at 617-732-5500 x32214 or x31565. Pregnancy tests are scheduled approximately 16 days after the ER. If bleeding starts before the pregnancy test, continue your medications. If the test is positive, monitoring continues with at least 2 repeat pregnancy tests, then an ultrasound at 7-8 weeks of the pregnancy. If the test is negative, the CIRS physicians and embryologists will review the cycle and make recommendations. Meet with your physician after a failed cycle. 21

ADDITIONAL INFORMATION SPERM AVAILABILITY ISSUES If the male partner is unavailable due to travel or is concerned about the ability to produce a sample on the day of egg retrieval, precycle sperm banking is available. This should be scheduled well in advance of the cycle start. Speak with your nurse and call the Reproductive Endocrine Lab at 617-732-7505 to arrange for sperm banking. Be aware that this is not always covered by insurance. OTHER MEDICATIONS Please check with your physician prior to taking any additional medication during the cycle. RESEARCH Brigham & Women's Hospital is always seeking to better understand and improve the therapies we offer. Therefore, we encourage patients to enroll in our research studies. We hope these studies will help us increase the chance of success in Assisted Reproduction therapies. Whether or not you choose to consent to be a participant will not affect the quality of the care that you are given in any way. AFTER THE CYCLE - CYCLE REVIEW Following the completion of your therapy, the entire Center for Infertility and Reproductive Surgery team will meet to discuss your cycle. Your CIRS physician will then send you a letter detailing their recommendations. Additional Assisted Reproduction cycles can be scheduled after you receive your review letter or hear from our office regarding insurance approval. You are encouraged to meet with your physician after your treatment cycle. You should have heard from the office staff within 2 weeks after a cycle to help you arrange further treatment; please call your CIRS managed care coordinator if you do not. PLEASE NOTE: You must have insurance approval prior to additional cycles. EMERGENCIES If an emergency arises, please call the Page Operator at 617-732-6660 and ask for the F&E Doctor on call. Stay on the line or leave a call back number and the physician will speak with you. EGG DONORS: Please be certain to call immediately if there are any problems after your retrieval. 22

INDEX After egg retrieval medications 3 Gonal-f 2 Mix: Picture identification 16 After the cycle-cycle review 22 Gonal-f vials 5 Post egg retrieval medications 3 Anesthesia 14 Gonal-f pen 5 Pregnancy test 21 Assisted Hatching (AH) 18 Gonal-f multidose 6 Pregnyl 3 mix 7 Birth Control Pills 2 HCG 3 Mix 7 Pre-operative appointment 14 Blood drawing: HCG/egg retrieval instructions 15 Medication to prepare for egg retrieval 3 850 Boylston Street 12 Hints to minimize injection discomfort 9 Progesterone 3 BWH 10 ICSI diagram 17 Injection Mix 7 Foxboro 13 Infection 20 Suppositories Use 7 Bravelle 2 Mix 5 Injection site diagram 8 Regional anesthesia (spinal) 14 Cetrotide 2 Mix 4 Injection techniques 8 Repronex 2 Mix 5 Complications 20 Insemination 17 Research 22 Crinone 8% gel 3 Use 8 Instruction for egg retrieval 15 Retrograde ejaculation 16 Cycle cancellation 19 Instructions for embryo transfer 18 Satellite monitoring 12, 13 Daily instructions: Intracytoplasmic sperm injection (ICSI) 17 Semen specimen from home 16 850 Boylston Street 12 Intramuscular injection (IM) 9 Sign-in/call back sheets: BWH 11 Introduction 1 850 Boylston Street 12 Foxboro 13 Intravenous general anesthesia 14 BWH 11 Day of egg retrieval 15 Lupron 2 Mix 4 Foxboro 13 Day of embryo transfer 18 Medication administration: 8 Stimulation therapy 2 Ectopic pregnancy 20 Medication side effects 20 Sperm: Egg retrieval 17 Medrol 3 Availability issues 22 Embryo freezing 19 Menopur 2 Mix 5 Fresh sperm 16 Embryo transfer 18 Monitoring instructions: 10 Retrograde ejaculation 16 Embryo transfer instructions 18 850 Boylston Street 12 Testicular biopsy 16 Emergencies 22 BWH 10 Storage time of frozen embryos 19 Estrace 3 Foxboro 13 Subcutaneous injection (SC) 8 Fertilization results 17 Multiple pregnancy 20 Suppression therapy 2 Follistim 2 Mix 6 Novarel 3 Mix 7 Surgical risks 21 Freezing embryos 19 Other medications 22 Testicular biopsy 16 Freezing success rates 19 Ovarian cancer 21 Treatment 1 Fresh sperm collection 16 Ovarian hyperstimulation syndrome (OHSS) 20 Ultrasound: Frozen embryo transfer cycle 19 Ovarian torsion (twisting) 20 850 Boylston Street 12 Ganirelix 2 Mix 5 Patient packet 1 BWH 10 General anesthesia (IVGA) 14 Pharmacy information 3 Foxboro 13 23

Notes 24