Boston IVF

IVF TREATMENT GUIDE________________________

WHAT EVERY PATIENT SHOULD KNOW

BOSTON IVF The Boston Center One Brookline Place Brookline, MA 02445 Tel. (617) 735-9000

BOSTON IVF The South Shore Center 2300 Crown Colony Drive Quincy, MA 02169 Tel. (617) 793-1100

BOSTON IVF The Waltham Center 40 Second Avenue Waltham, MA 02451 Tel. (781) 434-6500 www.bostonivf.com/documents

TABLE OF CONTENTS____________________________________

INTRODUCTION .......................................................................................................................................................3 BEFORE STARTING TREATMENT ......................................................................................................................3 IN-VITRO FERTILIZATION (IVF) PROCEDURE...............................................................................................4 MEDICATIONS USED FOR OVARIAN STIMULATION ....................................................................................4 MEDICATION PROTOCOLS DURING AN IVF TREATMENT CYCLE .........................................................9 TELEPHONE CONTACT DURING TREATMENT:............................................................................................10 PRE-EGG RETRIEVAL INSTRUCTIONS ...........................................................................................................11 DAY OF EGG RETRIEVAL ...................................................................................................................................11 MALE PARTNER INSTRUCTIONS.....................................................................................................................12 POST-EGG RETREVIAL INSTRUCTIONS.........................................................................................................12 EMBRYO TRANSFER.............................................................................................................................................13 FREQUENTLY ASKED QUESTIONS ABOUT EMBRYOS ..............................................................................14 CAN EMBRYOS UNDERGO GENETIC TESTS TO DETERMINE IF THEY ARE NORMAL?....................................................16 EMBRYO FREEZING .............................................................................................................................................17 THE PREGNANCY TEST .......................................................................................................................................17 POST-OPERATIVE APPOINTMENTS.................................................................................................................17 THAWED EMBRYO SUCCESS RATES ...............................................................................................................17 THAWED EMBRYO REPLACEMENT................................................................................................................18 COUNSELING AND SUPPORT: WHEN AND WHERE TO FIND IT..............................................................20 EMOTIONAL SUPPORT SERVICES AT BOSTON IVF:....................................................................................20 SUPPORT GROUPS ..............................................................................................................................................21 SIDE EFFECTS OF IVF TREATMENT................................................................................................................21 OVARIAN HYPERSTIMULATION .....................................................................................................................21 MULTIFETAL PREGNANCY ..............................................................................................................................22 OVARIAN CANCER AND FERTILITY DRUGS ................................................................................................25 BOSTON IVF LOCATIONS AND HOURS OF SERVICE ..................................................................................25 LOCATION INFORMATION ...............................................................................................................................25 HOLIDAYS OBSERVED AT BOSTON IVF .........................................................................................................27 WALTHAM HOTEL LISTING ..............................................................................................................................27 HOW TO GET STARTED:......................................................................................................................................28 QUICK PRE-TREATMENT CHECKLIST:..........................................................................................................28 TIPS FROM BOSTON IVF ON MEDICATIONS AND TREATMENT CYCLES............................................28

INTRODUCTION Over the years, the expansion of knowledge and the improvement of techniques in reproductive technology have increased the variety, availability and simplicity of procedures designed to assist infertile couples in attaining pregnancy. This handbook is the how-to of IVF at Boston IVF. Other factors such as patient age, ovarian reserve sperm status, and the conditions of the fallopian tubes are taken into consideration when designing a patients individual treatment protocol. BEFORE STARTING TREATMENT 1. Completed Medical Evaluation Prior to starting treatment, all testing ordered by the physician must be completed. During a consultation, the physician will review the treatment in detail. 2. IVF Orientation / Patient Educational Services Please contact Boston IVF Patient Educational Services at 781-434-6524 several weeks before you plan to start treatment. Our Patient Liaisons, Paula Benson and Heather Todd, RN will guide you through the orientation process. If you need to learn about injectable medications, Paula and Heather will facilitate your education. Even if you have used injectable medication in other types of fertility therapy, your treatment will be enhanced by speaking with Paula or Heather. 3. Consent At least two consent forms must be signed prior to the initiation of treatment. All Boston IVF patients are required to provide a signed copy of the IVF Consent Form and the Embryo Freezing Consent Form. A member of your medical team will inform you if your treatment protocol requires additional consent forms. You can obtain a copy of any of our consent forms at your Boston IVF physicians office or on our web site at www.bostonivf.com/documents. It is vitally important that you read, sign and return the appropriate consent forms to us prior to starting treatment. 4. Pap Smear and Mammogram Dont forget your routine health maintenance examinations during fertility therapy! These include annual physical examinations, a pap smear and, if appropriate, a mammogram. These exams and tests should be scheduled with your gynecologist or primary care physician. 5. Financial Authorization You must have financial arrangements in place prior to beginning treatment. Your Boston IVF financial counselor will find out exactly what insurance benefits you have and will tell you what

you need to do to apply for them. Different forms of treatment require different levels of insurance company authorization. This is in addition to and separate from any referrals that are issued by your primary care physician. Your insurance company may require specific information or additional testing prior to authorizing treatment. Applying for treatment authorization from your insurance carrier does not mean it will be granted. If your insurance company denies you coverage you may need to file an appeal directly with your insurer. Your Boston IVF financial counselor can discuss this topic with you if needed. Please realize that obtaining insurance company authorization takes time. Once we submit a request for coverage to your insurance company, we like you, must wait for their reply. A little pre-planning on your part can help avoid frustrating delays in treatment. If you change insurance plans during your time as a patient at Boston IVF it is critical that you notify our financial counselors immediately. Sometimes a change in insurance policies will delay initiation of treatment. Fortunately, you can minimize and often avoid these delays entirely by giving a copy of your insurance card (both sides) to our financial counselors and your Boston IVF doctor's secretary. A more comprehensive discussion about insurance and fertility treatment can be found in the Boston IVF publication "Guide to Infertility Insurance Coverage" on-line at www.bostonivf.com/documents. IN-VITRO FERTILIZATION (IVF) PROCEDURE IVF involves removing eggs from the ovaries, fertilizing them in the laboratory and transferring the resulting fertilized egg (embryo) into the uterus through the cervix. The egg retrieval technique most frequently used at Boston IVF is ultrasound-guided needle aspiration. A vaginal probe, similar to that used for follicle ultrasound, is placed into the vagina and a fine needle is guided toward the ovary as the physician visualizes the follicles on ultrasound. Fluid from the follicles is then collected through a needle connected to a test tube. A scientist standing by in the adjoining room examines the follicular fluid, identifies the microscopic eggs and places them in a special culture fluid. Later that day, sperm which has been treated to remove seminal fluid and to isolate the most healthy and active sperm, are mixed with the eggs and put into an incubator overnight. Usually performed under light general anesthesia (asleep), the egg retrieval takes less then 20 minutes and requires only a short recovery period of about one hour. The husband or partner may accompany the patient in the recovery room during this period. MEDICATIONS USED FOR OVARIAN STIMULATION SYNOPSIS: Medications are prescribed to increase the number of eggs that are retrieved during an IVF treatment cycle. There are several types of medications which are described below. Clomiphene Citrate Clomiphene citrate is an oral medication that is available under the trade names of Serophene or Clomid. Clomiphene citrate (Serophene, Clomid) is an oral medication that has been available for more than 40 years. It is rarely used in IVF treatment.

Mechanism of Action Clomiphene citrate binds to specific receptors in the brain, which stimulates the pituitary gland to release higher amounts of follicle stimulating hormone (FSH). FSH is the main hormone that stimulates the follicles (the fluid-filled cysts which contain the eggs) to develop in the ovaries. The increased levels of FSH in turn have a beneficial effect on the ovary to allow a follicle or sometimes more than one follicle to develop. Dosage Clomiphene citrate comes in 50-mg tablets. The usual starting dose is one to two tablets a day for five days that can be started beginning on day 2, 3, 4 or 5 of the cycle. The dosage may be increased up to 4 tablets daily in certain cases. Side Effects Clomiphene can cause some unusual side effects that you should be aware of, including hot flashes, visual spots in front of the eyes, headaches and mood changes. However, it should be pointed out that most patients tolerate clomiphene very well. Gonadotropins Gonadotropins are injectable medications that stimulate the ovaries to produce eggs. Some gonadotropins contain the hormone FSH (Follistim, Gonal-F, Multi-dose Gonal F) and other medications contain a combination of FSH and LH (luteinizing hormone) (Pergonal, Bravelle, Repronex). Gonadotropins must be administered by injection. The medication can be administered by the patient herself or someone who has received instruction on injections. If you have access to the internet on-line instruction incorporating streaming video is available to you. Go to www.bostonivf.com/documents and download the information sheet "e-lessons on Healthbanks.com". Office based injection teaching and telephone review of on-line lessons can be arranged by calling our Patient Liaisons, Paula Benson or Heather Todd, at 781-434-6524. Please arrange to have an orientation/injection lesson before therapy is to begin. Dosage Gonadotropins generally come in packages that contain glass ampules or vials. Some of the ampules contain the medication in powder form. Other ampules contain water or sodium chloride, which is used to dissolve the powder for injection. Each ampule of the powder contains the active medication and is measured in units as indicated on the package. You will be given instructions on the exact dosage of gonadotropins to take (i.e., the number of ampules or units per day) before you begin treatment. In order to help you remember the timing and dosages of medications that you will take in your treatment cycle go to www.bostonivf.com/documents and download the appropriate "cycle calendar". This will allow you to organize the information you need to successfully complete treatment. Gonadotropins are usually taken between 5:00 and 10:00 p.m. however taking the medication somewhat earlier or later on a single day is not usually a problem. New Packaging and Gonadotropin Dosing

There are several new developments on the horizon regarding how gonadotropins are delivered to patients. A new multidose vial of Gonal-F is currently available. Looking to the future it is likely that other innovative methods will appear that make the use and administration of gonadotropins even easier than it is today. Side Effects In IVF treatment the important side effect is excessive enlargement of the ovaries, often called ovarian hyperstimulation. This side effect results in fluid retention and abdominal discomfort. Side effects with gonadotropins include some local discomfort at the injection site. Rare bruising and soreness may result. Careful massage at the site of the injection will help to alleviate most of the discomfort. Changes in mood, abdominal discomfort, bloating and cramping are some other potential side effects. Studies have raised a possible link between fertility drugs and ovarian cancer (discussed later), although this has not been proven in any large retrospective analysis. Human Chorionic Gonadotropin (HCG) Human chorionic gonadotropin or hCG mimics the natural LH surge that leads to ovulation. Some women will use this single subcutaneous injectable medication during treatment. HCG is available as a urinary extract under the brand names Choron, Novarel, Pregnyl or Profasi or in recombinant form, Ovidrel. HCG is bottled as 10,000 units of powder accompanied by a 10-ml vial of water or sterile saline. Unless otherwise directed, you should dissolve the 10,000 units of powder in only 1 ml of water or saline. Then, administer the medication via subcutaneous injection. We are aware that the packaging says "for intramuscular use". The safety and efficacy of HCG is not affected when given subcutaneously. Occasional redness at the injection site may be noted and should disappear within 24 hours. Ovidrel is recombinant hCG. It is packaged differently than other forms of hCG. Ovidrel comes in vials of 250 mcg. Some women will use one vial and others will be instructed to use two vial of this medication.

GnRH Agonists These medications are used to help get better control of the cycle and prevent premature ovulation. Two forms of the medication are Lupron (given by injection) and Synarel (given by nasal spray). The GnRH agonist medications first stimulate the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and then suppress the pituitary gland's secretion of LH and FSH. Normally, LH is secreted in high amounts by the pituitary gland just before ovulation. In fact, it is this rapid release of LH (the "LH surge") which triggers ovulation. Therefore, Lupron and Synarel suppress the LH surge and prevent ovulation. They are especially advantageous when used in conjunction with gonadotropin therapy since premature unsuspected ovulation may interfere with cycle completion.

There are several protocols for taking Lupron. 1. The long or luteal protocol: a. the first dose of Lupron is started a week after ovulation (often day 21 of the cycle) in the preceding menstrual cycle. Contraception must be used during this cycle. b. With the long protocol your period may be delayed; notify your IVF nurse if your period is delayed more than one week. 2. The microdose protocol: a. Sometimes the doctor may request that you take a smaller than standard dose twice daily, the so-called micro dose regimen. This may be prescribed for the entire cycle or for a limited time only (5 days). Please call your IVF nurse to notify them when you start your Lupron. Lupron is given by subcutaneous injection, which means just under the skin. The usual dose is between 0.05cc (5 units) and 0.1cc (10 units) (note cc and ml are the same). The instructions within the Lupron kit are very good in explaining how to do the injections. If you are using insulin syringes, 10 units is 0.1 ml and 5 units is 0.05 ml. Synarel is given by nasal spray, one or two sniffs once or twice daily. Side Effects Some women using GnRH agonists get hot flashes, mood changes, nasal stuffiness, and headaches. Other more rare and uncommon side effects have been reported. If you experience any untoward symptoms while using a GnRH agonist, please call your doctor. GnRH Antagonists A new class of medications is now available to prevent premature ovulation. Cetrotide (Cetrorelix) is available both as a 3-mg single subcutaneous injection that lasts for 4 days and 0.25 mg meant for daily subcutaneous injection. Antagon (Ganirelix) is available at a dose of 0.25 mg for daily subcutaneous administration. GnRH antagonists are also used to prevent the premature release of luteinizing hormone (LH). Therefore, Cetrotide and Antagon are designed to prevent premature ovulation. These medications are most commonly used in assisted reproductive technologies such as in vitro fertilization where the timing of egg release is critical. Dosing Cetrotide is available as a 3-mg single subcutaneous injection that lasts for 4 days. Cetrotide also is available in the form of a 0.25 mg dose that is given daily. Antagon is available as a 0.25 mg daily dose. The medication if frequently administered once gonadotropin therapy has started. Often, an ultrasound measurement of ovarian follicles cues the start of GnRH antagonist administration. At other times, the medication is begun on a preset day of stimulation. Side Effects Side effects are uncommon. However, among side effects seen the most common ones include headache; injection site bruising, itching, swelling, or redness; nausea. Less common side effects include abdominal or stomach pain; continuing or severe nausea, vomiting or diarrhea; decreased

amount of urine; feeling of indigestion; moderate to severe bloating; pelvic pain, rapid weight gain; shortness of breath; swelling of lower legs.

ADJUNCT MEDICATIONS Some women may benefit from other medications given during the stimulation phase of treatment while others may require supplementary medications after ovulation. The following list covers the most common adjunct medications prescribed during ovulation induction therapy. Insulin Sensitizers The most common insulin sensitizers available today include Glucophage (Metformin), Avandia (Rosiglitazone) and Actos (Pioglitazone). Of these three, Glucophage has the longest track record of success and is the most highly prescribed. A small fraction of women, often those with irregular or infrequent menstrual periods, may not use the hormone insulin efficiently. The inefficient use of insulin can cause or make worse menstrual cycle irregularity. Some women may benefit from the addition of insulin sensitizing medications like Glucophage (Metformin), Avandia (Rosiglitazone) and Actos (Pioglitazone). The insulin sensitizers were developed for the treatment of non-insulin dependent diabetes; however over the past 5 years there has been increased use of these compounds, particularly Metformin, in women with irregular or infrequent menstrual periods who do not have diabetes to improve their chance for spontaneous ovulation. Dosing Metformin is often given at a dose of 500 1000 mg two or three times daily. Typically, gastrointestinal side effects (gas, bloating, nausea and diarrhea) are experienced when initiating metformin therapy. In order to minimize the side effects we generally recommend starting with a dose of 500 mg daily for one week. Then increase the dose to 500 mg twice daily for another week, then to 500 mg three times daily for another week and then to 850 or 1000 mg twice daily thereafter. It is also available in a slow release form (Glucophage XR) which may decrease the side effects. Side effects Gastrointestinal symptoms (diarrhea, nausea, vomiting, abdominal bloating, flatulence, and anorexia) are the most common reactions to metformin and are approximately 30% more frequent in patients on metformin monotherapy than in placebo-treated patients, particularly during initiation of metformin therapy. These symptoms are generally transient and resolve spontaneously during continued treatment. Occasionally, temporary dose reduction may be useful. In controlled trials, metformin was discontinued due to gastrointestinal reactions in approximately 4% of patients. Oral Contraceptives The birth control pill may be used in conjunction with any number of ovulation induction protocols. Progesterone

Progesterone is an important hormone that helps to prepare the lining of the uterus for implantation of the fertilized egg. Supplemental progesterone is used routinely in IVF. Progesterone can be administered vaginally (Crinone, Prometrium, pharmacy compounded suppositories) or by intramuscular injection. Progesterone may be given by vaginal gel, tablets, capsules or suppositories or by intramuscular injection. The dose and route of administration of the progesterone will be determined by your doctor. If progesterone is prescribed, it should be taken up to the time of the pregnancy test. In some cases progesterone is continued if pregnancy is detected. Also, please be aware that the progesterone suppositories must be made up by the pharmacist. Therefore, many pharmacies do not carry this medication. Please note that some forms of progesterone routinely used to support pregnancy carry a warning against their use in pregnancy. The progesterone that is prescribed during your treatment is a natural preparation. Natural progesterone has been used to support pregnancy for years and is a well accepted form of therapy. We have had many years of experience using this medication and when we feel that it would be beneficial to you we feel comfortable recommending it as part of your therapy. Occasionally, women will complain about an itchy discharge with progesterone use. It is possible to develop a yeast infection while using this hormone. This is not a serious complication and it will not affect fertility. If you are bothered by increased discharge accompanied by an itch or raw feeling, then please let us know. Natural progesterone may also be accompanied by sleepiness. Progesterone Side Effects The majority of patients report no side effects. However, progesterone may delay the onset of menstruation; therefore there may be a need to do a pregnancy test to rule out pregnancy. Progesterone may improve premenstrual symptoms in some women but create premenstrual symptoms, breast sensitivity, feeling bloated and irritability in others. Nodules (small, hard bumps) in the skin can occur with injectable progesterone. Allergic reaction to the progesterone but more commonly to the particular oil used (peanut or sesame) is sometimes seen. Fever, rash or prolonged painful red nodules are rare. MEDICATION PROTOCOLS DURING AN IVF TREATMENT CYCLE The choice of which medications are right for you will be determined by your doctor. Many different ways of using these medications have been described over the years. The timing and combination of medications are chosen by your doctor after considering your medical history. Treatment Timelines that describe typical combinations of medications as well as cycle calendars that allow you to record your specific combinations in an orderly way are available on www.bostonivf.com/documents. Your IVF coordinator can provide you with these materials if you lack internet access.

CYCLE MONITORING In order to monitor the response of the ovaries to medications, ultrasound examination of the ovaries and/or measurement of blood hormone levels are performed. The number of ultrasound examinations and blood tests varies considerably from cycle to cycle and patient to patient. Some women will be able to successfully complete their cycle monitoring with ultrasound measurement of follicles alone. The average number of monitoring tests per cycle is 3. You will be given instructions on when to have your first test(s) performed. The ultrasound examination is done using the vaginal ultrasound technique. A vaginal probe is placed into the vagina and visualization of the ovaries is obtained. Follicles are fluid-filled areas on the ovaries in which the egg develops. The number and size of the follicles are recorded by ultrasound. The objective is to obtain a number of follicles of sufficient diameter to result in a mature egg. A mature follicle is between 15-23 mm in diameter. The results of the examinations are available in the afternoon at approximately 2:00 p.m. or later. Please note that you should not expect to have an egg recovered from every single follicle seen on ultrasound exam. Typically, only follicles in 15-23 mm range on the day of hCG are likely to have recoverable eggs. When the monitoring data suggests a reasonable cohort of eggs may be available, you will be given specific instructions to take a single injection of the medication HCG. Your egg retrieval will be scheduled to occur 36 hours after the HCG injection. Actual release of the egg from your ovaries is unlikely to occur less than 41 hours after an HCG injection, therefore we are building in a time buffer. Important Monitoring Note: Boston IVF offers ultrasound and blood testing during the week at all of our sites and in Waltham only on holidays and weekends. There may be alternative locations available to you. However, use of some non-Boston IVF locations may result in charges not covered by your insurance company or your IVF cycle authorization. It is imperative that you speak with a Boston IVF financial coordinator if you plan to use any monitoring site other than a Boston IVF office. TELEPHONE CONTACT DURING TREATMENT: You will receive a call between 2:00 to 4:00 p.m. with instructions as to the dose of medication required that evening. Please make arrangements to be available for that phone call. If you have not heard from the office by 4:00 p.m., please be certain to contact the office. The dose of gonadotropins may be reduced, increased or maintained at the same level. Please be sure to have at least a two day supply of medications available should you be told to take that dose or a slightly increased dose. This avoids you having to rush to the pharmacy late in the afternoon for your evening dose of gonadotropins. CYCLE CANCELLATION About 15 percent of patients who begin taking medication are canceled prior to the procedure. Some of the reasons for cycle cancellation are follicles not developing properly, inadequate blood hormone levels, premature ovulation, and less than three follicles maturing simultaneously. If a cycle is cancelled, medication may be modified in subsequent cycles in an

attempt to improve your response. Such issues are discussed by the physician during the postoperative visit. Ordinarily, the month after a cancelled treatment plan is used to allow a medication washout. It is during that month when you will meet with your physician to plan future therapy. Occasionally, the estradiol (E2) level is too high and the risk of hyperstimulation may be aggravated if a pregnancy does occur. In such cases, we may recommend that all the embryos be frozen, and possibly transferred a month or two later. If it is necessary to freeze all embryos because of the high risk of hyperstimulation, we would also recommend avoiding intercourse as well. PRE-EGG RETRIEVAL INSTRUCTIONS The following instructions are important to remember in preparing for your egg retrieval: 1. Do not take products such as Ibuprofen (Motrin), Advil, Aleve and Naproxen since they can interfere with blood clotting. You may take Acetaminophen (Tylenol). 2. Complete the on-line medical history at www.onemedicalpassport.com 3. Do not eat or drink after midnight the night before the egg retrieval. 4. Arrange for a ride home after egg retrieval in the company of a responsible adult. 5. A responsible adult should be with you for 24 hours after egg retrieval. 6. Leave valuables such as jewelry, money, eyeglasses and credit cards at home. A wedding band may be worn. 7. If you have any piercing jewelry it must be removed prior to egg retrieval. 8. Bring a small bag for personal belongings. 9. Arrive at Boston IVF, The Surgery Center of Waltham, 40 Second Avenue, Suite 200, Waltham, MA at the specified time. DAY OF EGG RETRIEVAL Arrive at Boston IVF at the designated time and check in with the second floor receptionist. Boston IVF loves children but if you have any we politely request that you refrain from bringing them to your surgical procedure as a courtesy to other patients. We thank you for your understanding and cooperation. A nurse will soon call you to take your vital signs and help prepare you for the procedure. Next, the anesthesiologist explains the anesthesia to be used and answers any questions. Lastly, you meet with the surgeon who will perform the procedure. When you are ready to be escorted into the operating room, an intravenous (IV) will be started to administer anesthesia to you. Please remember to bring the completed and signed consent forms (IVF/GIFT consent forms, cryopreservation forms, or ICSI consent forms) if you have not already signed and returned them. (Please note: The Boston IVF physician performing procedures on the day of your egg retrieval may not be your own personal physician. The attending physician will be able to answer

questions of a general nature but we recommend that you thoroughly discuss your treatment plan with your own doctor well in advance of the procedure.) MALE PARTNER INSTRUCTIONS There are no restrictions on sexual relations prior to your partners hCG (Profasi, Pregnyl, or Novarel) injection. Please abstain from ejaculation between the time of hCG administration and specimen collection on the day of egg retrieval. Abstinence for more than one week prior to the day of your egg retrieval is discouraged. In general, on the day of egg retrieval, the male partner is asked to provide a fresh semen sample between 8:30 and 9:30 am; if you are undergoing ICSI, the specimen is requested at 7:30 a.m. Specific instructions as to when the sample must be delivered to our laboratory in Suite 200 will be given in advance by a Coordinator. If you live within a 1 hour drive of our Waltham location you may collect the specimen at home in a sterile specimen container available at Boston IVF. The semen sample should be at room temperature and should not be exposed to excessive heat or cold. (Please note: If travel time to Boston IVF is greater than one hour, the male partner should plan on using one of our exam rooms to collect the semen sample as it is required within one hour after collection. He then must wait 20 minutes after giving the sample in the unlikely event that our lab scientists determine a second sample is needed.) Important note: Some men find that the stress of producing a fresh specimen on the day of egg retrieval prevents collection. For other men, the collection process is unreliable when a specific day or hour is assigned. If this is even a remote possibility, discuss it with your doctor in advance. It may be possible to make arrangements to freeze sperm in advance of the IVF procedure. There are financial implications to sperm freezing so plan to speak with your Boston IVF financial counselor. POST-EGG RETREVIAL INSTRUCTIONS Following egg retrieval, a patient usually spends about an hour in the recovery room before being discharged. Prior arrangements for a ride home are mandatory as the woman must be accompanied by a responsible adult upon discharge and for the first 24 hours after egg retrieval. The following instructions are important to remember: 1. Do not drive a car or return to work for 24 hours. 2. Relax at home for the remainder of the day; activity as tolerated. Do not stay alone for the first 24 hours after receiving anesthetics. 3. Diet and fluid as tolerated, but no alcohol. 4. Bath or showers are permitted after 24 hours. 5. Plain or extra-strength Tylenol for any discomfort. 6. You will start your progesterone the day after your egg retrieval and take it as prescribed by your physician. Progesterone is continued until the day you receive the results of your

blood pregnancy test and you will be instructed at this time as to whether to continue your progesterone or not. 7. A physician is available (on-call 24 hours) for emergencies. If any of the following occur, call the office or the Boston IVF on-call physician at (781) 434-6400: a. Fever over 99.5, orally b. Unusually heavy bleeding c. Persistent pain d. Inability to urinate within 8-10 hours after procedure, with increasing pain. FERTILIZATION The morning after retrieval, the eggs are studied for evidence of fertilization. To allow further cell division, eggs are cultured for another 48 hours or more before the resulting embryos are considered ready for transfer. The afternoon following the egg retrieval, a Coordinator will call with information about fertilization. If fertilization has occurred, clear instructions about embryo transfer will be given at that time. The embryos are assessed again just before transfer and although rare, a transfer may be canceled when no viable embryos exist. EMBRYO TRANSFER Fertilized eggs are called embryos. Embryos are routinely returned to a womans uterus 3 days after the eggs have been retrieved. For some patients, the embryos may be grown in culture for an additional 2 or 3 days (day 5 or 6 after egg retrieval). Those embryos are called blastocysts. Your doctor will discuss which technique is best for your individual circumstance. A specific time for the embryo transfer will be assigned. Although no special preparation is required, a light breakfast is suggested that morning. On rare occasion, the embryos will not survive the development process and the embryo transfer will be cancelled. We also strongly recommend that you leave an accurate contact phone number in case we need to call you on the day of embryo transfer prior to your arrival. Embryo transfer is usually a minor procedure requiring no anesthesia and takes about 5 minutes. Your partner is welcome to be with you at the time of your embryo transfer. First, a speculum is placed into the vagina and the cervix cleansed. Then, a fine plastic catheter is guided through the cervix into the uterus where the embryos are placed. Although usually a painless procedure, some mild cramping may occur. Post-Embryo Transfer Instructions The following post-embryo transfer instructions are important to remember: 1. Rest until the morning after the transfer. Keep activities to a minimum. 2. Diet and fluids as tolerated. 3. You may shower as usual. 4. Take your progesterone as instructed by your physician.

FREQUENTLY ASKED QUESTIONS ABOUT EMBRYOS Can you tell if it's a good embryo? Each patient who comes to the point of an embryo transfer asks this question. The purpose of this section is to explain how we describe embryos at Boston IVF. By reading through this information now, you will be better prepared to discuss your embryos with the doctor when it comes time for your embryo transfer. Numbers and Letters: How we used to describe embryos Until January 2001 we described embryos using system of numbers and letters. For example, 6A, 8B, 5C, 3D, etc. Many patients found the descriptions confusing and complex. In order to clarify the grading scheme, we now report cell number and degree of fragmentation. Numbers and Fragmentation: What does it all mean? The numbers An egg is a single cell (Fig. 1). When an egg is fertilized by a single sperm cell it forms an embryo. We can tell that a sperm has fertilized an egg when we observe the presence of two pronuclei (Fig. 2). One pronucleus contains the genetic information from the sperm and the other pronucleus contains the genetic information from the egg. This early embryo is still a single cell. Using our numbering system the early embryo at this point can be assigned the number 1. The one cell embryo then begins the process of cell division (Mitosis). The single cell embryo divides from one cell to two. Using our numbering system the early embryo at this point can be assigned the number 2. At the 2-cell stage, the individual cells begin another round of cell division. Interestingly, the two cells dont divide at exactly the same time. If both cells have divided when the laboratory scientist examines the embryo she or he will see a 4-cell embryo (Fig 3). Using our numbering system the embryo at this point would be assigned the number 4. If only one of the two cells of a 2-cell embryo has divided when the scientist observes it, she or he will see a 3-cell embryo. Using our numbering system the embryo at this point would be assigned the number 3. The embryos cells continue to divide and that is why, on average, we see numbers that range from 1 to 8. Occasionally several cells of an 8-cell embryo will divide and when observed, and may result in an even greater number of cells. What is a normal number?

When an embryo is observed 3 days after fertilization we expect to see between 6 and 8 cells. Using our numbering system the embryos at this point would be assigned the numbers 6, 7 or 8. When an embryo has 3 cells or fewer 3 days after fertilization it represents an abnormally slow rate of growth. We do not believe that these embryos can cause a pregnancy. Embryos with 4 or 5 cells are growing at a slightly slower rate but we have seen pregnancies from embryos with 4 or 5 cells 3 days after fertilization. Fragmentation Cell division is not a neat, crisp and clean process. At the cellular level, there is a tremendous amount of activity going on within the cell. Large amounts of cellular matter are being pulled and pushed around in a process orchestrated by the cells internal machinery. As the cells divide, some of the cellular cytoplasm is commonly ejected in the form of small chips or fragments. We refer to the quantity of chips or fragments as the degree of fragmentation. We have three descriptive categories for fragmentation: No significant fragmentation, Fragmented and Excessively Fragmented. When an embryo is observed 3 days after fertilization some degree of fragmentation is normal.

(Fig. 4, 5). An embryo that is excessively fragmented 3 days after fertilization is abnormal (Fig. 7). We do not believe that excessively fragmented embryos can result in a normal pregnancy. What is a good embryo? The appearance of an embryo, its cell number and fragmentation, does not tell us whether the embryo will implant and become a baby. If the appearance of the embryo alone predicted success, we would able to transfer a single embryo, unfortunately however, the cell number and assessment of fragmentation alone do not predict success. That is why we currently need to transfer more than a single embryo during most IVF treatment cycles. Some embryos that have lots of cells and no significant fragmentation may not result in a pregnancy while other embryos with fewer cells and fragmentation may result in a pregnancy. Are my embryos HIP? Boston IVF scientists have described a method of assessing the implantation potential of individual embryos. Embryos with High Implantation Potential (HIP) typically have 4 cells on Day 2 and 7-8 cells on Day 3 after egg retrieval. In addition, HIP embryos have no significant fragmentation. When one or more developing embryos are HIP we often advise placing fewer total embryos, and under select circumstances a single embryo, back in the uterus.

Can embryos undergo genetic tests to determine if they are normal?

There is a technique known as preimplantation genetic diagnosis (PGD) from which one can learn about the genetic content of individual embryos. This technique is available through Boston IVF for patients with specific medical conditions. How do you decide how many embryos to transfer? Your doctor will make a recommendation to you regarding the maximum number of embryos to transfer. Frequently your doctor will leave instructions with the laboratory to put back one embryo fewer if the embryo appearance is superb. What about freezing embryos? In our experience, embryos that have not yet reached the 6 cell stage and embryos that are fragmented or excessively fragmented are less likely to freeze and thaw successfully. If at least one embryo meets freezing criteria, 6 cells and no significant fragmentation, we will freeze that embryo. You will learn how many embryos, if any, were frozen for you at the time of your post operative appointment with your doctor. Evaluating Blastocysts Blastocysts are embryos with cells that have divided many times. Blastocysts generally reach this stage 5 to 6 days after fertilization and contain 60 to 160 cells. The cells of a blastocyst surround a small fluid pocket (Fig. 7). A small group of cells in the blastocyst called the inner cell mass is the portion that might develop into a baby if the embryo is capable of reaching its potential. The remaining cells of the blastocyst become the placenta (commonly called the afterbirth). Do you assign numbers and letters to blastocysts? Blastocysts are more complex structures than are embryos on day 3. We do not assign numbers and letters to blastocysts; rather we note the size of the fluid pocket and general appearance of the group of inner cells among other things. Are blastocysts better? No. An embryo that has gotten to the blastocyst stage is a survivor. Therefore, no more than 2 blastocysts are transferred. Unfortunately, many normal embryos might not survive the growth conditions in the laboratory to get to the blastocyst stage. Likewise, growth to the blastocyst stage does not mean that the embryo is genetically capable of becoming a baby. How do you choose whether or not to try blastocyst transfer? The decision is made by the patient and her doctor taking into account a number of factors. How many embryos the patient is likely to produce? What about freezing spare embryos? What is the likelihood of a triplet pregnancy or more It is important to understand that an embryo that makes it to blastocyst was just as likely to produce a pregnancy had it been transferred two days earlier. Therefore, it's the embryo (and the patient), not the fact that an embryo has become a blastocyst, that determines whether pregnancy can occur.

EMBRYO FREEZING Excess good quality embryos from an IVF or GIFT cycle can be frozen (cryopreserved) for use in a later cycle. These embryos may be stored for several years, thawed at a specific time in the menstrual cycle, and transferred to the uterus. To date, over 500 pregnancies have been established from frozen embryos at Boston IVF. Disposition of Frozen Embryos All couples are asked to carefully consider a variety of options for disposition of stored frozen embryos, select those best for them under a number of unforeseen circumstances and sign a disposition form. The consent form must be signed before embryos can be frozen. This gives Boston IVF specific instructions as to how to dispose of frozen embryos in the event of a divorce or the death of a spouse. Unless a couple clearly states their wishes regarding excess embryos, they will be discarded. Couples who wish to change their decision at any time should do so by making the request in writing to Boston IVF, only if both partners agree to the change. Frozen embryos will be stored at Boston IVF for a maximum of three years, after which time they will be transferred to another facility or discarded, depending on the couples prior decision, as selected on the consent form. THE PREGNANCY TEST A blood pregnancy test is performed 14 days after the egg retrieval. Even if what may be considered a menstrual period occurs, blood pregnancy testing still is recommended as implantation bleeding is often mistaken for menses. If the date for the pregnancy test day falls on a weekend, the blood can be drawn on the weekend or it can wait until Monday, but in either case the results will not be available until Monday afternoon. POST-OPERATIVE APPOINTMENTS We strongly recommend calling your physicians office the day after the procedure, or as soon as possible, to schedule the post-operative appointment. An appointment with your Boston IVF physician should be scheduled for 1 to 2 weeks after the pregnancy test. The post-operative appointment is a critical part of the cycle as it gives the physician and couple an excellent opportunity to review the cycle and discuss possible recommendations for future cycles, including thaw cycles if necessary. If you are pregnant from your IVF cycle, schedule an ultrasound to coincide with your consultation. Under special circumstances, the post-operative appointment may be done by telephone. Since the doctor will not have all the cycle information until the post-operative visit, we recommend saving your questions until then. Plan to have a one month break from fertility therapy following your pregnancy test. THAWED EMBRYO SUCCESS RATES Typically, thaw cycles result in pregnancy slightly more than half as often as from fresh cycles. However, there is no surgery involved in the treatment and medications are often kept to a minimum. Furthermore, we think of thaw cycles as a way of extending the opportunity to

become pregnant from the fresh cycle without putting you at risk for a high order multiple pregnancy (triplets or more). THAWED EMBRYO REPLACEMENT The transfer of thawed embryos is the same as that performed in a routine IVF cycle. Embryos are introduced through the cervix into the uterus using a soft, plastic catheter. The procedure takes about 10 minutes and requires no anesthesia. A Thaw Cycle Consent Form that is valid for 6 months and an Supplemental Thaw Cycle Consent form valid for 30 days must be signed by both partners prior to the embryo thaw. KNOWING WHEN TO TRANSFER THE THAWED FROZEN EMBRYOS There are several different methods available to time the transfer of thawed embryos. The embryos can be thawed at the proper point in a natural menstrual cycle, when the uterine lining is ideally suited to implantation. Alternatively, medications can be administered in a relatively simple fashion to prepare the uterine lining for receiving an embryo. Most medicated thaw cycles employ oral and or transdermal estrogen and vaginal progesterone without any injections. Your doctor will discuss which method best suits you. FINANCES There is a one-time charge for the cryopreservation procedure that covers the first three years of storage. If you have insurance coverage for your IVF cycle, it often includes the cost of cryopreservation and the first three years of storage. Check with your Boston IVF financial counselor to see if your coverage includes this service. After three years, there is an annual storage fee. The annual storage fee is most commonly not covered by insurance. There is a separate charge for the thaw procedure and its attendant cycle management. Some insurance policies cover thaw cycles while others do not. Check with your Boston IVF financial counselor to see if your coverage includes this service

COMMONLY ASKED QUESTIONS REGARDING TREATMENT Q. A. Q. A. Q. A. Q. A. Q. Can I swim after my egg retrieval or embryo transfer? Yes, 48 hours after procedure. Can I use a hot tub, auna, or acuzzi? Yes, after 48 hours but not above 100 Fahrenheit. Can I get a massage? Yes Can I have a glass of wine or alcohol during the cycle up until the pregnancy test? No alcohol after procedure. Can I travel more than 4-6 hours in a car after my embryo transfer? Fly in an airplane?

A. Q. A. Q. A. Q. A. Q. A. Q. A. Q. A. Q. A.

Yes What length of time should I spend on modified bed rest after an egg retrieval? 24 hours How much exercise can I do after hCG? After embryo transfer? No vigorous exercise until after negative pregnancy test. How soon after my procedure (egg retrieval/ embryo transfer) can I have intercourse? 48 hours after egg retrieval or embryo transfer. Can I get my hair colored or permed? No Can I use Monistat for yeast infections? Yes Can I have electrical stimulation i.e. TENS? Yes What medications can I take during my treatment cycle and after my Embryo Transfer? Please refer to the following list of medications during your treatment cycle and after your E.T.

Medication type Prednisone Cold medications (Sudafed, Robitussen) Anaprox, Motrin, Aleve, Advil Amoxicillin, Ampicillin Bactrim Flagyl Doxcycline Erythromycin Nasal spray decongestants Tylenol Cold or PM Claritin D Valium Prozac Xanax Ativan Benadryl GI Meds: MOM, Colace, Senekot, Kaopectate, Imodium, Pepcid Headache meds: Fioricet, Fiorinal Other: Echinacea, St. John Wart, G. Biloba

Can I take this? Yes Yes No Yes Yes before pregnancy test Yes before pregnancy test, No after test. Yes before pregnancy test Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No

Q. What medical injections can I get during my treatment cycle? A. The following list details which injections you may receive during treatment. Injection Flu Shot Hepatitis Vaccine Chicken pox immunoglobulin TB Test, PPD Tetanus Allergy Shots Novocaine, dental procedures Can I have this injection? Yes Yes, vaccine and immunoglobulin Yes Yes Yes Yes Yes

COUNSELING AND SUPPORT: WHEN AND WHERE TO FIND IT. Boston IVF offers individual and couples counseling with social workers who specialize in fertility issues and well as group programs run through the Mind/Body Center for Womens Health at Boston IVF. Few situations in life are as challenging, demanding and stressful as infertility and its treatment. Patients often express a sense of loss of control over their lives when pregnancy does not come quickly. Multiple tests and office visits can compound this anxiety for some patients. Boston IVF is committed to providing complete care for the whole patient. In an effort to meet the diverse emotional needs of our patient population, Boston IVF provides a variety of support services. Patients are encouraged to attend monthly seminars, led by the staff of the Mind/Body Center, which are designed to teach patients about coping with the emotional side-effects of infertility. Additional patient forums on topics of interest are held on a quarterly basis. Our goal is to help patient's sort out their feelings, identify coping strategies and to feel better about themselves in the midst of the fertility ordeal.
EMOTIONAL SUPPORT SERVICES AT BOSTON IVF:

The Mind/Body Center Staff: Dr. Alice Domar, Director 781-434-6578* April Seibring, Program Leader 781-434-6578 *

Liz Milovanovic, Program Manager 781-434-6578* April Prewitt, Program Leader 781-434-6578*

(* Please note, all inquiries should be directed to Liz Milovanovic)

Counseling Staff: Jeanne Ungerleider, Director of Counseling Services at Boston IVF, LICSW 617-739-9000 ext. 201 Terry Chen Rothchild, LICSW 617-964-6626 SUPPORT GROUPS The American Infertility Association 666 Fifth Avenue, Suite 278 New York, NY 10103 Tel: (888) 917-3777 www.americaninfertility.org Resolve P.O. Box 541553 Waltham, MA 02454 Tel:781-647-1614 www.resolveofthebaystate.org American Society for Reproductive Medicine Formerly The American Fertility Society 1209 Montgomery Highway Birmingham, Alabama 35216 Tel: 205-978-5000 www.asrm.org Lynn Nichols, LICSW 978-369-2390

SIDE EFFECTS OF IVF TREATMENT

OVARIAN HYPERSTIMULATION

Gonadotropins and rarely clomiphene citrate can occasionally cause hyperstimulation of the ovaries. This means that the ovaries are especially sensitive to the medication and enlarge more than is desired. To decrease the risk, your physician prescribes the lowest possible dose of medication. When taking gonadotropins, your response is monitored with ultrasound and/or estradiol blood tests. Even with careful monitoring, occasionally some women do develop hyperstimulation. Usually, this problem will reverse itself without treatment in 2-3 weeks. Please check for the following signs and symptoms, which may indicate hyperstimulation. If you develop any of the following symptoms, please call your physician as soon as possible.

Abdominal Pain: While mild bloating and cramping may be normal, watch for excessive bloating, or unusual tenderness or pain in your abdomen. Sometimes abdominal pain is accompanied by nausea, vomiting and/or diarrhea. These symptoms may indicate hyperstimulation and must be reported as soon as possible. If symptoms persist or worsen, please call your physician. Urine Output: Please let us know right away if you notice any obvious change in urine output, either an increase or decrease. At the same time, check for signs of bladder infection (burning, painful or frequent urination). Shortness of Breath: If you have any difficulty breathing, either at rest or during activity, please report this at once. Significant Weight Gain: A weight gain of two pounds or more for two days in a row along with any of the symptoms listed above may be a warning sign. Please weigh yourself daily and report any sudden or rapid weight gain. Weight gain as an isolated finding is rarely indicative of OHSS. If you notice any of the above symptoms, call your physician as soon as possible. A simple physical exam is sometimes all that is needed to check for hyperstimulation. In some cases, a pelvic ultrasound and/or blood tests are also necessary. Hyperstimulation usually occurs 5 or more days after ovulation or after the hCG injection. If the warning signs are noticed early in the cycle, your physician may choose to withhold the hCG injection to substantially reduce the chances of hyperstimulation. These signs include: increased size of ovaries, excessive rise in estradiol and an excessive number of follicles. If hyperstimulation is mild to moderate, you may be asked to return to the office within the week for another exam and possibly an ultrasound. You will be asked to continue to check your weight every morning to be sure you are drinking and urinating properly. If hyperstimulation is severe, your doctor may advise you to have an outpatient procedure to drain some of the excess fluid that can collect inside the abdominal cavity that causes bloating and pain. This procedure may allow the hyperstimulation to resolve more quickly and usually improves your symptoms. In rare cases, hospitalization is necessary. There is a remote chance of severe illness, such as bleeding from the ovary, blood clots, kidney failure, etc. With current experience with these medications such effects are extremely remote. In the presence of hyperstimulation, it is important to avoid strenuous activities, either work or sports related. In addition, heavy housework that involves pushing or lifting (e.g., vacuuming) should he avoided. Intercourse is not advised in cases of moderate to severe ovarian hyperstimulation. MULTIFETAL PREGNANCY The advent of modern fertility treatments has lead to a substantial increase in the frequency of twins, triplets, quadruplets, quintuplets and even higher order multiples as shown by the birth of septuplets in Iowa in 1997. Multifetal pregnancy refers to a pregnancy in which two or more fetuses are present in the womb.

In the general population, multifetal pregnancies occur in approximately 1 to 2 percent of all pregnancies. However, with the use of fertility drugs such as clomiphene citrate or gonadotropins (FSH) and high-tech procedures such as in vitro fertilization (IVF), multiple gestations are much more common. The vast majority of these pregnancies are twins, but triplets, quadruplets and higher numbers can occur. Triplets and higher order multifetal pregnancies occur in 3% to 4% of couples undergoing IVF, and in 7% to 8% of patients undergoing ovulation induction with injectable FSH preparations. Almost 1% are even greater multiples. In 1995, nearly 5,000 babies born in the United States were triplets or higher. Fetal and Maternal Risks Although the newspapers are full of stories of triumph and joy, often illustrated by pictures of adorable triplets and quadruplets, there is a less pleasant and painful side to high order multiple births. Fetal risks of multiple gestation include an increased chance of miscarriage, birth defects, premature birth and the mental and/or physical problems that can result from a premature delivery. The average length of pregnancy is 40 weeks for a single gestation; 37 weeks for twins; 33 weeks for triplets; and 29 weeks for quadruplets. 10% of triplets die at or about the time of birth, a mortality rate 12 times higher than that of singletons. All women with quadruplet and higher order gestations deliver prematurely and of those that reach 24 weeks' gestation, approximately 25% will die at or about the time of birth. They are far more likely to be handicapped by cerebral palsy, kidney failure, blindness and mental retardation. In addition, a recent study found the average cost for care of a mother and newborn triplets was $190,000. or 21 times that of a singleton birth. Maternal risks due to multiple gestation include premature labor, premature delivery, pregnancyinduced high blood pressure or pre-ecclampsia (toxemia), diabetes and vaginal or uterine hemorrhage. Reasons for Increased Risks The uterus can normally increase its blood supply to nourish about 10 pounds worth of baby or babies. The uterus usually accommodates twins well but twin pregnancy is still associated with greater risk to the mother and babies than is a singleton pregnancy. However, more than two babies can be problematic. As stated above, studies and surveys indicate that, on average, triplets are born seven weeks early, weighing 3.5 to 4 pounds. Quadruplets tend to be born 11 weeks early, weighing 2.8 to 3.5 pounds. Their prematurity is almost certain even though most of their mothers rest in bed for months, wear home monitors to count contractions and take drugs to ward off early labor. Multifetal Pregnancy Reduction Multifetal pregnancy reduction (MFPR) is a technique that reduces the number of fetuses in an effort to increase the likelihood that the pregnancy will continue safely. Consequently, the risks

to the mother and remaining fetuses are reduced. The first multifetal pregnancy reductions were performed between 1986 and 1988, and since then, thousands of patients have had the procedure performed successfully. The procedure is more likely to be performed when there are four or more fetuses present. The number of fetuses is usually reduced to two although in some circumstances they may be reduced to one. Because triplets and twins generally do better than higher order multiples, reduction in these cases is more individually determined and may be considered. Timing and Technique for MFPR Multifetal pregnancy reduction, is usually performed between nine and twelve weeks gestation but it has been performed as late as 24 weeks gestation. The procedure is most successful when performed early in pregnancy on an outpatient basis. Anesthesia is usually administered and includes a mild sedative along with local skin infiltration. According to some studies, the optimal number of fetuses following the MFPR procedure appears to be twins, since the outcome with twin pregnancies is generally good, and appears to be similar to the outcome for pregnancies reduced to singletons. The risk of an induced miscarriage related to MFPR is 8% to 9%. Although this is a significant risk and must be considered before undertaking the procedure, the risk is not higher than the 10% fetal loss rate found in twin gestations following assisted reproductive technology. Maternal infection rarely occurs and injury to a surviving (non-reduced) fetus is considered to be highly unlikely. Counseling The best time to consider MFPR is prior to starting treatment. Dealing with the decision of whether or not to undergo multifetal pregnancy reduction can be an emotionally traumatic experience. Couples who have invested a great deal of time, energy and money in pursuing pregnancy are often unprepared to make this decision. It is usually helpful for couples considering multifetal reduction to undergo professional counseling prior to undergoing the procedure. Both partners need to be comfortable with their decision and may need emotional support prior to and immediately following the procedure. The decision to proceed with MFPR is made with the intent to give a better chance of survival for babies resulting from high order multiple gestations and reduce the likelihood of significant mortality and morbidity associated with these pregnancies. Conclusion MFPR has become an accepted procedure that can be performed safely with technical success. In select patients with higher order gestations, it provides an intervention that increases the chance of achieving the desired outcome (taking home a healthy newborn) while minimizing the associated risks of multifetal pregnancy.

OVARIAN CANCER AND FERTILITY DRUGS Some studies have suggested a possible link between ovarian cancer and the use of fertility drugs (such as clomiphene citrate and gonadotropins). The association is by no means conclusive since the studies to date are potentially flawed by their design, leading to uncertain results. If these studies are indeed correct, there would be about a threefold increased risk of ovarian cancer which would translate to a risk of about 3% compared to 1% for the general population. Until further studies are available, it is unknown as to what, if any, increased risk exists. Other known risk factors for ovarian cancer that may be more important than fertility drugs include a family history of ovarian cancer and no prior delivery of a child. Further information on this important topic is available to the public on the website of the American Society for Reproductive Medicine (www.asrm.org). BOSTON IVF LOCATIONS AND HOURS OF SERVICE Aspects of your treatment can be provided at any of our centers. Service Ultrasounds & Blood Drawing Boston Center Monday-Friday 7:00-9:30 a.m. South Shore Monday-Friday 7:00-9:30 a.m. Waltham Center Performed every day 7:00-9:30 a.m.

Note: All services needed on the weekend and holidays will be provided at the Waltham office. All services must be coordinated through your doctor's office.
LOCATION INFORMATION

Boston IVF-The Boston Center One Brookline Place, Suite 602, Brookline, MA 02445 (617) 735-9000 Physicians Dr. Merle J. Berger Dr. Selwyn P. Oskowitz Directions to The Boston Center From Route 128 North and South Take Exit 20A Brookline/Boston Route 9 East. Continue on Route 9 East for approximately 5-6 miles into Brookline. Boston IVF is located on the left at One Brookline Place (red brick medical building) at a set of lights on the corner of Route 9 and Brookline Avenue. Other landmarks are the Brook House (large tan brick apartment complex with a waterfall in front) on your right and a Gulf gas station on the corner. Make a left turn onto Brookline Avenue then another left at the traffic light onto Pearl Street. There are street meters and a parking garage next to our building on Pearl Street. MBTA There is a T Stop behind One Brookline Place. Green Line: Take the Riverside D train, Brookline Village T Stop. We are located across the street, past Bertucci's, follow walkway.

Boston IVF-The South Shore Center 2300 Crown Colony Drive, Quincy MA 02169 (617) 793-1100 Physicians Dr. Brian M. Berger Dr. Richard H. Reindollar

Directions to the South Shore Center From Boston Take Route 93 South to Exit 7. Take Exit 7 to MA- 3 (Route 3) South. Follow MA-3 S to Exit 18, Burgin/ Washington Street (Exit 18 is the first exit on Route 3). Bear left and follow the Quincy Center/ T Station Signs. At the first set of lights, turn left onto Center Street. At the next set of lights, turn left again to enter Crown Colony Office Park (Dunkin Donuts will be on your right). Follow Crown Colony Drive to #2300. The entrance to Boston IVF is located on the right side of the building. From Cape Cod Take Rte 3 North to Exit 19. Follow the same directions as above from Burgin Parkway. From Dedham/Milton Take Route 128 South (93 N) towards the South Shore Plaza. Take Rte 3 South to Exit 18 and follow the directions from Burgin Parkway. Boston IVF-The Waltham Center 40 Second Avenue, Suite 300, Waltham, MA 02451 (781) 434-6500 Physicians Dr. Michael M. Alper Dr. Steven R. Bayer Dr. Alan S. Penzias Dr. Kim L. Thornton Dr. Robert Weiss Directions to the Waltham Center From the East and West: Follow the Mass. Pike to Exit 14 (Rte. 95/128). Follow signs for 95 North/128 North, proceeding to Exit 27B Waltham (Winter St./ Wyman St. exit). Bear right off of exit and bear right again to continue over overpass. Go straight through first set of lights and left through second set of lights. See Second Avenue directions. From the North: Take Route 93 South to Route 95 South/128 South. Take Exit 27B and follow signs for Second Ave./Bear Hill Road. See Second Avenue directions.

From the South: Take Route 95 North/128 North to Exit 27B Waltham (Winter St/Wyman St.). Bear right off exit and bear right again to continue over overpass. Go straight through first set of lights and left through second set of lights. See Second Avenue directions. Second Avenue Directions: Keep in right lane to take a right onto Second Avenue/Bear Hill Road and left into the first parking garage on the left (across the street from the Costco Parking lot) A sign on top of the building says Mass General West and is visible from Route 128.

The Surgery Center of Waltham A Division of Boston IVF 40 Second Ave., Suite 200, Waltham, MA 02451 (781) 434-6400 The Surgery Center is located on the 2nd floor of the building in Suite 200. HOLIDAYS OBSERVED AT BOSTON IVF The following are holidays observed by Boston IVF. Please call the office on the next day if you need to schedule an appointment with a secretary. However, be aware that the Boston IVFWaltham office is open in the morning on holidays for IUI appointments and monitoring. The Surgery Center is open for IVF Cases. New Year's Day Columbus Day Thanksgiving Day Day after Thanksgiving Christmas Day WALTHAM HOTEL LISTING Best Western 477 Totten Pond Rd Waltham, MA 781-290-5600 Wyndham Garden Hotel 420 Totten Pond Road Waltham, MA 781-890-0100 Labor Day Presidents Day Patriots Day Memorial Day Independence Day

Westin Hotel 70 Third Avenue Waltham, MA

Double Tree Guest Suites 550 Winter St Waltham, MA 781-890-6767

QUICK PRE-TREATMENT CHECKLIST: HOW TO GET STARTED 1. Check with your financial coordinator to obtain the necessary financial clearance. This can take several weeks in some cases. Further information about insurance authorization is available on line at www.bostonivf.com/documents in our booklet entitled "Guide to Infertility Insurance Coverage" 2. Download the "cycle calendar" that matches your treatment as well as the Orientation to Treatment entitled "IVF Orientation" and "e-lessons on Healthbanks.com" They are available on line at www.bostonivf.com/documents 3. Log on to www.healthbanks.com using the instructions in the sheet downloaded from our website. 4. Call your nurse for prescriptions for ALL medications that you will use during the treatment cycle. 5. Call Patient Educational Services (781- 434-6524) and speak with one of our patient liaisons, Paula Benson or Heather Todd, RN to arrange for an IVF orientation with injection teaching as needed. 6. Treatment generally can begin after you met all prerequisites and insurance authorization has been obtained. Please check that you have received all of the medications and supplies that you will need during the treatment cycle 1-2 weeks prior to your anticipated menses. 7. You should call on the first day of your menstrual period to start a cycle. If your period starts after 5 p.m., then you should call the following morning. Tips from Boston IVF on Medications and Treatment Cycles The amount of information presented to you prior to and during your treatment is enormous. This section contains information addressing the most frequent issues that arise during treatment. Calling to start a cycle When you get your period, call the office during business hours, 9 am to 4 pm only. Example: Your period begins at 6pm and your information says to start medication on cycle day. Call the following day, the next day will be defined as cycle day 1. Please do not page the doctor on call to report the onset of menstruation. Medication supplies When you get your medications and supplies home from the pharmacy, take everything out of the box or bag. Lay everything out on a counter or table. Make sure that you have every medication and all the supplies that you are going to use during treatment.

Example: Lupron, FSH, hCG, Progesterone, 3cc syringes, 1 cc syringes, 1 inch needles, inch needles, alcohol wipes, gauze pads, bandaids. Dont wait until the day you need something to look for it in the box or bag. Searching for an open pharmacy at 11:30 on a Sunday night looking for hCG isnt any fun at all! HCG (Profasi, Pregnyl, Novarel) Perhaps the most confusion occurs with this medication. Many manufacturers package a 10 ml (ten) bottle of water (diluent) with a bottle of 10,000 units of powder. Withdraw ONLY 1 ml (one) of water and throw away the other 9 ml (nine). All 10,000 units of powder will dissolve in the 1 ml (one). HCG (Ovidrel) If you are using Ovidrel hCG, look at the vials of powder and diluent. You will dilute TWO VIALS of Ovidrel powder in a single 1.0 ml of diluent and withdraw 0.7 ml for injection. Reconstituting Medications and Injection Techniques It is best to review the techniques during office hours prior to starting medications. Boston IVF provides web based resources on www.bostonivf.com/documents in our Treatment Guides and E-lessons on Healthbanks.com (complete with on line video). Additional after hours resources may be available from your fertility specialty pharmacies including: 1. Village Pharmacy (www.villagepharmacy.com ; 617-735-9090) 2. Freedom Drug (www.freedomdrug.com 978-499-4500). Test results and further instructions When you have a blood test and expect results and instructions that same day: If you havent yet received your message by 4 pm its vital that you call your nurse immediately. Otherwise, you might not be able to get the results until the following day. Your Phone Service and Accessibility 1. If you have call intercept our phone system will be blocked from contacting you directly. Please disable this feature when you expect a telephone call from us. 2. Please leave an identifying outgoing message on your answering machine or voice mail so we can confirm that we are indeed leaving the correct message for the correct individual. Sperm Collection for IUI or IVF The stress of being asked for a semen specimen on a specific day at a specific time causes some men to be unable to produce. If there is any chance that specimen collection will be difficult, please speak with your doctor well in advance. There are several possible solutions to this problem but we must know about this possibility before the day of a scheduled procedure. The Doctor on call For your safety, there is a Boston IVF doctor on call 24 hours a day for medical emergencies only. Please address all routine questions including test results and cycle starts with the office staff during business hours (9 am to 4 pm) Mon Fri. Nurses are also available for questions 9 am to 3 pm on weekends and holidays.