treatments to become a mom last fall.

Transcription

1 September Newsletter 2018 IVF Medications and Protocols Most common fertility treatments: how they work and how much they cost - Patricia Kozicka Most common fertility treatments: how they work and how much they cost - Patricia Kozicka Fertility treatment: in vitro fertilization (IVF) - BabyCenter Preparation for an IVF Cycle - Regional Fertility Program IVF Nurses Corner - Melanie Mitchell, RN Don t forget to read our new blog this week: How CSC Provides a Unique Support System This is the latest article in a Global News investigation into fertility in Canada, and the emotional and financial impact infertility has on Canadians struggling to conceive. *** It took Rebecca Nielsen a lot of fertility treatments to become a mom last fall. The 41-year-old and her husband Kevin, who is a Global News employee, a met in In 2010, when she was 35, they stopped using birth control. A year later, ovulation trackers and scheduled intercourse became part of their lives. Your prime conception years physically are between 18 to 24, she acknowledged, when you re doing everything you can not to get pregnant. Then you re in debt. Then you break up with your long-term boyfriend and need to find yourself. Then you find the guy. By 2012, the two had tied the knot but were still struggling to make a baby. Some couples in this situation turn to naturopaths, acupuncturists or chiropractors who specialize in fertility. Others try to improve their chances of conception by making certain lifestyle changes (like healthier eating and cutting out certain vices), which sometimes works. Not for the Nielsens, though. Their family doctor suggested they reduce their stress levels and just keep trying. When a year of that didn t work, the couple got a referral to the big guns: the Hannam Fertility Clinic in Toronto. Nielsen estimates she had to go there every other day either for blood work, ultrasounds or procedures over the two years that followed. She thinks the parking alone cost her about $3,500. The whole process cost the couple roughly $100,000, since it was before Ontario introduced fertility funding. A lot of that was reimbursed through Nielsen s drug plan and tax credits. Family also helped. As is the protocol with all new

2 case to prevent breast cancer recurrence but has been shown to also help treat infertility.) At one point Nielsen was put on HGH (human growth hormone). 3. Injectable a range of gonadotropins like Gonal-F, Puregon and Menopur. The drugs taken (and in what dose) are dependent on the treatment, how many eggs a woman has to begin with, where she is in her cycle and what shows up in her blood work and ultrasounds. patients, the first step is a battery of fertility tests to try and figure out what the problem is. For example, if someone comes in and turns out their thyroid is unbalanced, we help them with their hormone level and they re more likely to get pregnant naturally, said Tom Hannam, the clinic s founder and one of its doctors. Everything s linked to everything else. In rare cases, if there s a problem with the uterus or fallopian tubes, surgery might be needed. In the Nielsen s case, the test results were inconclusive. So a series of chemical cocktails started off their treatment. A cocktail of fertility drugs I was taking at one point, a vitamin mix cocktail that was a combination of 13 pills, Nielsen said. I used to joke you d hear me walking down the hallways because I had so many pills in my stomach. That particular chemical concoction included prenatal vitamins, CoQ10, Omegas, iron, vitamins C, D and B12. Fertility doctor Ellen Greenblatt, who s the medical director of the Mount Sinai Fertility and IVF unit, explains there are three classes of fertility drugs: 1. Oral tablets like clomiphene citrate (aka Clomid or Serophene) 2. Off-label letrozole (a.k.a. Femara, which is similar to clomiphene but it s off label, meaning it s traditionally used for something else in this For instance, the tests might show the uterine lining needs to be thicker in order to create an optimal environment for embryo implantation. The prescription would be adjusted accordingly. Nielsen s drug cocktail would sometimes include a combination of pills, patches and injections. Each came with their own side-effects. You don t feel like yourself because you ve been so pumped of hormones, she admitted. You re tired, you re lethargic. IUI Sending in the marines Apart from fertility drugs, the first line of offence Nielsen s doctor recommended was intrauterine insemination (IUI). It s a common treatment for couples with unexplained infertility that can range in price from $1,500 to as high as $4,000 in Toronto, and is often paired with a $500 sperm wash. It s like sending in the marines, Nielsen said. They take the best, smartest, strongest and fastest the few, the proud, the brave and send them in on a covert mission and hope they re successful. Once the model swimmers are chosen, they re given a little boost and shipped into the uterus through a tiny catheter that Nielsen recalls being only slightly thicker than a strand of hair and feeling no worse than a pap smear. The hope is that the sperm will make it to the egg and fertilize it naturally. An ultrasound technician watches a monitor to ensure the catheter releases the marines at the right place, while the patient lays back with their feet in stirrups.

3 Donor eggs can alternatively be used if needed. However, it s important to note you cannot pay anyone to be an egg donor in Canada. So any exchange would have to be altruistic. The donor would have to undergo a round of IVF for the eggs to be harvested, so it s also not cheap. Fortunately, Nielsen didn t have problems producing eggs. That first round she whipped out 18 of them. The ultrasounds showed her ovaries, which are typically the size of a walnut, grow to the size of chicken eggs. She compares it to having swollen glands when you re sick. You could physically feel them. They feel really heavy and sore. In IVF, eggs are extracted with a needle from a woman s body. Nielsen remembers being in more of an operating theater rather than an exam room for this procedure. Then you go home and you cross your legs and you hope it takes. The other alternative, if there s male factor infertility or in the case of a female same-sex couple, is to use donor sperm. Sperm is ordered from sperm banks in the U.S., that offer profiles of the donors, and then shipped to a fertility clinic. While the effectiveness of any treatment always goes down with age, IUI s average success rate is said to be 12 to 15 per cent per cycle. It drops to about five per cent per cycle for women around 40, according to Greenblatt. Nielsen, then 37, tried four rounds of IUI within six months in They were all unsuccessful. They sedate you but you re not completely out of it. She recalls a lady with a light on her head talking to me, saying, everything is good. The exciting part for her was finding out how many eggs were retrieved. Of the 18 she produced, 14 got fertilized right away. There are two fertilization options in IVF. One is for the eggs to be put into a dish and sprinkled with some 100,000 sperm in hopes they ll fertilize the egg naturally. The other, which comes at an additional cost of about $1,500 and the one which Nielsen opted for, is called IVF, the final frontier Nielsen hoped for a better prognosis with in vitro fertilization (IVF). It s the most expensive fertility treatment but also has the best odds. IVF is paired with the injectable gonadotropins that stimulate the ovaries to produce, on average, eight to 15 eggs (compared to the standard one egg that s released a month).

4 intracytoplasmic sperm injection, or ICSI (pronounced ick-see ) for short. As its name suggests, fertilization occurs by injecting the sperm into the egg to guarantee fertilization. At this point, Nielsen didn t see the point of leaving that to chance. But fertilization doesn t mean pregnancy. The embryos need to make it to Day 5 or 6 before being transferred to the uterus (called a fresh transfer) or frozen (called a frozen embryo transfer). Only four of her 14 embryos reached any of those benchmarks. Two were put on ice (to be thawed and transferred later), and two were put in fresh. None of them took. And there were no answers why. The cells may not divide and it may just not work, Nielsen said. You don t know why it doesn t work it just doesn t work. After that, the Nielsens decided to try one more round of IVF, but this time, they paired it with something called pre-implantation genetic screening (PGS) also known as comprehensive chromosome screening (CCS). It cost about $5,000, on top of the $23,000 the couple was already paying for the second round of IVF. However it increased their chances of conception to 72 per cent. Other couples may see an average success rate of 60 to 70 per cent with the screening, according to fertility doctor Caitlin Dunne of the Pacific Centre for Reproductive Medicine in Vancouver. At the time (in 2014, when Nielsen was 39), the test was not recommended as an add-on for genetically healthy couples. Dunne says it s now considered to be most helpful for women over 38 who make more than two embryos through IVF. It involves a small biopsy of cells from what would become the placenta in each embryo. The samples are then sent to a lab, where they re analyzed for a variety of chromosomal and genetic defects. What came back three weeks later, Nielsen said, freakin blows my mind. Of the eight embryos they had analyzed, all but one had chromosomal problems that would have either resulted in a failed implantation, a miscarriage or a baby with Down Syndrome. The test saved them potentially multiple rounds of heartbreak. Nielsen got emotional when she spoke about the day that one genetically perfect embryo was transferred. This is the magical part for me, she said before taking a big breath. They put you on the gurney and wheel all the equipment into this room. There s an incubator and on top of it there s a flat screen TV. As she held her husband s hand, an image of the embryo they were about to put inside her was put on the screen. I may have just seen the first picture of my daughter and she hasn t been born yet, she recalls thinking. Nine months later, her beautiful baby Margaret was born healthy, happy and chatty. Nielsen says the past 14 months with her now super funny toddler made the emotional roller-coaster and huge financial cost all worth it. The crazy part? I want to do it again, Nielsen said. Don t tell my husband. Global News

5 Fertility treatment: in vitro fertilization (IVF) - BabyCenter IVF is the process by which eggs are removed from your ovaries and mixed with sperm in a laboratory culture dish. Fertilization takes place in this dish in vitro, which means in glass. Thousands of IVF babies have been born since the first in The number of babies born using IVF is rising each year. Who might be recommended for IVF? IVF is likely to be recommended for same-sex or single women wishing to conceive using a sperm donor, and for the following fertility problems: If you have blocked or damaged fallopian tubes. If your partner has a minor problem with his sperm. Major problems are better treated using ICSI. If you have tried fertility drugs, such as clomiphene, or another fertility treatment such as IUI, without success. If you have been trying to conceive for at least two years, or less if you are 40 years or more. This is if a cause hasn t been found to explain why you have not become pregnant. Is IVF paid for by Medicare? A single cycle of IVF treatment costs around $10,000, and whether the costs of one or multiple IVF cycles are paid for by Medicare depends on your provincial health plan. There is wide provincial and territorial variation in who and what is covered. Quebec does pay for a certain number of IVF treatments through the provincial health plan. Ontario does pay for a single IVF cycle, but there are restrictions on who qualifies. Saskatchewan and Manitoba offer some financial help in the form of tax credits. Other provinces are considering some form of coverage but in most places there is still no provincial help. What is covered for whom is changing across Canada, though, so the best place to start looking for up to date information on Medicare and IVF is your province s Ministry of Health website. How is IVF done? IVF follows a series of steps, starting with fertility drugs to help you produce as many eggs as possible. Fertility drugs You will probably need to take fertility drugs to stimulate your ovaries to develop mature eggs ready for fertilization. During your normal menstrual cycle you release one egg per month. You can choose not to take drugs to stimulate your ovaries, but your odds of getting pregnant will be better with more eggs. Your fertility specialist will offer treatment to control your menstrual cycle. Drugs called gonadotrophin-releasing hormone (GnRH) analogues (pituitary agonists) suppress or stop your cycle. You take these daily for about two weeks in pill form or by an injection. If you have endometriosis you may take Cetrotide to control

6 your cycle and improve your chances of success. Hormone injections You will then have daily hormone injections for 12 days. These stimulate your ovaries to release a greater number of mature eggs than usual (ovulation induction). The hormones used are gonadotrophins follicle stimulating hormone (FSH) and luteinizing hormone (LH). Women respond to these fertility drugs in different ways, and they may have strong side-effects. Your doctor will closely monitor you to make sure that you are cared for if this happens. By monitoring your blood hormone levels, your doctor can detect when your eggs are mature. An injection of human chorionic gonadotrophin (hcg) will trigger the release of your eggs between 34 hours and 38 hours before they are collected. Egg retrieval and sperm collection An ultrasound will show when your eggs are ready to be retrieved. You ll be given an anesthetic that will make you drowsy but still conscious. Your doctor will then remove the eggs from your ovaries. Your doctor will use a fine, hollow needle attached to an ultrasound probe. The probe helps to locate the follicles that contain the eggs. You may feel mild discomfort during the procedure, but if you feel pain later on your specialist will prescribe painkillers. While your eggs are being collected, your partner will need to provide a fresh sample of semen. If donated sperm or frozen sperm are being used, the sample is taken from the freezer. The sperm is washed and the best-quality sperm extracted ready to fertilize the eggs. The sperm is then combined with the eggs in a dish and left to culture in an incubator. Fertilization and embryo transfer Within one day of combining the eggs and sperm, the dish is checked to see if any eggs have been fertilized. If they have, they ll be kept for between two days and five days before being transferred back into your uterus. Any fertilized eggs will each have become a ball of cells called an embryo. They may also be referred to by your specialist as blastocysts if the embryos are being transferred at the later blastocyst stage, at about day five. The healthiest embryos are chosen to be inserted into your uterus. Some clinics offer a pre-implantation test called comprehensive chromosome screening (CCS). This screens embryos before they are transferred at the blastocyst stage. Only the embryos that are predicted to have a full set of chromosomes are selected. CCS may boost your chances of getting pregnant and may also reduce your risk of miscarriage when a single embryo is transferred. This is especially the case if you are an older mom-to-be, using your own eggs. By now you will have been helping your uterus (womb) to prepare for the embryo by taking progesterone, which helps thicken its lining. You receive this by injection, pessary or gel. If your uterus lining (endometrium) is too thin, the embryos are unlikely to implant. If this is the case, the IVF cycle will unfortunately be abandoned. Usually, one or two embryos are transferred with a thin catheter (tube) through your cervix into your uterus. Your fertility specialist may use ultrasound to guide him. To avoid the risk of a high order multiple pregnancy, The Society of Gynaecologists and Obstetritians Canada recommends transferring the fewest number of embryos possible. The number of embryos that are transferred will depend on your age and your chances of success. This in turn depends on your particular fertility problem. If you are under 35 you will likely have a maximum of two embryos transferred to your uterus per IVF cycle. If you are 35 to 37, and a suitable candidate, the SOGC recommends a maximum transfer of two embryos at one time. For women aged 38 to 39 the SOGC recommends the transfer of two or possibly three embryos during an IVF cycle. If you are over 40, the SOGC recommends the maximum transfer of four embryos during one cycle. The SOGC does recommend adjusting these recommendations depending on the quality of the embryos and the prognosis for each woman. If you are using donated eggs then the recommended number of embryos will be determined based on the age of the donor.

7 Repeated cycles If there are any extra embryos, these may be frozen for future use. This is in case the first cycle doesn t succeed, or you want another baby after your successful treatment. IVF normally involves transferring embryos at about two to three days after fertilization. Another option is to wait until about five days after fertilization when the ball of cells has developed into a blastocyst. Only the healthiest embryos will reach the blastocyst stage in vitro. You may have a better chance of having a healthy pregnancy after blastocyst transfer. Most clinics offer blastocyst transfer to all patients depending on quality and number of embryos available. However some clinics offer blastocyst transfer only if: You have had previous normal IVF with healthy embryos but they have not implanted You are under 40 Your clinic will probably advise you to rest for about 30 minutes immediately after your treatment. Though there s no evidence to suggest this increases your chances of becoming pregnant. In a successful cycle, one or more embryos will implant in your uterine wall and will continue to grow. You can take a pregnancy test in about two weeks. Once your pregnancy has been confirmed following IVF, you should have an early ultrasound at about six weeks. This is to check that the embryo has implanted in your uterus. How long will IVF treatment last? One cycle of IVF takes between four weeks and six weeks to complete. You and your partner can expect to spend about half a day at your clinic for the egg retrieval and fertilization procedures. You ll go back between two days and three days later for the embryos to be transferred to your uterus, or between five days and six days with blastocyst transfer. What s the success rate of IVF? You can find results for Canadian fertility clinic success rates through the Canadian Assisted Reproductive Technologies Register (CARTR). This organization collects data on IVF at Canadian fertility clinics. They publish the results of their research each year. You will not find specific clinic success rates. The success rates depends on your particular fertility problem and your age. The younger you are, and the healthier your eggs are, the higher your chances of success. If you have been pregnant or have had a baby before, you have an increased chance of success. If you are within a healthy weight range, with a body mass index (BMI) of between 18.5 and 25, you are more likely to be successful. If you are overweight or underweight you may increase your chance of success by getting nearer to your ideal weight for your height before you start treatment.

8 If you haven t become pregnant after your third attempt at IVF, you may need to accept that it isn t going to work for you. This may be hard to come to terms with, but there are organizations that can support you through it. Ask your doctor or staff at your fertility clinic for details. What are the advantages of IVF? For most children conceived by IVF there are no longterm problems. IVF can offer you a chance of having a baby if you are unable to conceive naturally, for example if you have blocked, damaged or missing fallopian tubes. What are the disadvantages of IVF? IVF increases your risk of certain complications, such as: A multiple birth, when more than one embryo is transferred to your uterus. Many couples consider twins to be a blessing, but a multiple pregnancy increases your risk of having a premature baby or a baby with a low birth weight. Side-effects from fertility drugs are usually mild, and include hot flushes, headaches, and nausea. However, you will need to be closely monitored for signs of ovarian hyperstimulation syndrome (OHSS). Having this may mean a stay in hospital while your over-stimulated ovaries settle down. An increased risk of ectopic pregnancy, where an embryo implants in a fallopian tube or in your abdominal cavity. This is more likely if you have previously had problems affecting your fallopian tubes. You may be more likely to have a baby with a birth defect such as spina bifida if you conceive with IVF. One study showed an increase in birth defects from about three per cent in naturally conceived babies to about six per cent after IVF. However, this increased risk could also be due to the parents age, or other fertility problems. Despite these risks, many parents still go on to give birth to much-wanted, much-loved babies through IVF. You can talk to other women having IVF treatment in our BabyCenter Canada community.

9 Preparation for an IVF Cycle - Regional Fertility Program Achieving the best chances for a successful IVF cycle involves many factors including additional testing and personal lifestyle changes. The following video ( ivf-2/steps/ ) was developed to help patients prepare for their IVF cycle. Further information is available from your physician. Ovarian Suppression Downregulation GnRH Agonist In order to optimize pregnancy rates, medications are given to increase the number of eggs produced in an IVF cycle. To prevent premature egg release (ovulation) and control the timing of retrieving mature eggs a GnRH agonist is given. These medications cause a temporary state of menopause and are administered as either an intranasal spray, or subcutaneous (needle under the skin) injection. In some circumstance the birth control pill may be used in combination with these medications. Your physician will determine which protocol is used based on your individual medical history. The nursing staff will start your medications on set days of your menstrual cycle. Once a patient is on the IVF waiting list she will phone in her last menstrual period on the first day of full flow. As the wait-list for IVF is short you will most likely be offered treatment within one to two months of registering for treatment. Suppression Check Pelvic Ultrasound After a patient has had approximately 2 weeks of GnRH agonist, or just prior to completing a package of birth control pills, a pelvic ultrasound is performed. This ultrasound is necessary to confirm ovarian suppression and to ensure that no new findings (such as an ovarian cyst) have developed that may interfere with treatment. The transvaginal ultrasound is usually done at the clinic; however, for patients who live a long distance away, alternative arrangements may be made. Medications/Side Effects GnRH agonists are commonly known as Suprefact or Lupron. These medications may occasionally cause nausea, vomiting, hot flashes, night sweats, and headache. You should notify your doctor if you develop rapid heartbeat, chest pain, breathing difficulties, fever, chills, severe headache, or visual changes. GnRH Antagonist In some circumstances, an alternative to GnRH Agonist downregulation may be required or preferred. A GnRH antagonist prevents premature release (ovulation) of eggs by producing a rapid, reversible suppression of pituitary LH secretion. This medication is administered by subcutaneous (under the skin) injection. This is started during the controlled ovarian stimulation phase of the cycle. The specific protocol used will be determined according to your medical history and stimulation response. Suppression Check Pelvic Ultrasound The patient is not suppressed during an antagonist cycle. However, a pelvic ultrasound is required within a day or two of starting menses and prior to stimulation medication to ensure that no new findings (such as an ovarian cyst) have developed that may interfere with treatment.

10 Medications/Side Effects GnRH antagonists are commonly known as Orgalutran or Cetrotide. These medications may cause skin reactions such as redness, with or without swelling at the injection site, or occasionally headache, nausea, dizziness, lack of energy or strength (asthenia) and malaise. Controlled Ovarian Stimulation (Superovulation) In a normal menstrual cycle, the ovaries typically produce a single mature egg. In order to maximize pregnancy opportunities, medications are administered to stimulate the ovaries to produce many eggs in an IVF cycle. These medications are called follicle stimulation hormone (FSH) and are administered by subcutaneous (SC) injection. These medications are required for 9-14 days (on average 12) and are self administered by the patient. The follicular development is monitored by serial transvaginal ultrasound examinations and estradiol (E2) levels. Once the monitoring results indicate mature eggs (appropriate follicle size and estrogen levels), another hormone called Human Chorionic Gonadotrophin (hcg) is given to complete the final maturation process and the egg retrieval is scheduled for 35 hours later. These medications rescue eggs that would otherwise be discarded naturally in a normal menstrual cycle. A typical IVF cycle will require an ultrasound examination and estradiol levels prior to starting superovulation (suppression check). Repeat testing of estradiol and ultrasound will be arranged on Day 4, Day 7 and about every second day after day 7 while on the FSH medication. The monitoring process is individualized and patients that are at high risk for ovarian hyperstimulation syndrome (OHSS) may require daily monitoring. All monitoring with estradiol blood tests and ultrasounds are done at the Regional Fertility Program during treatment. The IVF team including physicians, nursing staff and the embryology staff meet daily and discuss patients results in order to ensure the best decisions are made with regard to medication dosage, timing of hcg and number of embryos to transfer. Side Effects The active medication used to stimulate the ovaries is follicle stimulating hormone (FSH). These medications are commonly known as Gonal F, Puregon and Menopur. These medications act directly upon the ovary to stimulate multiple follicular development. Common side effects include bloating, enlarged ovaries, nausea, diarrhea, and tender breasts. Serious side effects can occur as a result of ovarian hyperstimulation syndrome (OHSS). This may cause ovarian enlargement, fluid in the abdomen (ascites), difficulty breathing, kidney failure and blood clots which in rare and extreme circumstances may even result in death. Over Response If over response to ovarian stimulation occurs this can be potentially very serious. However, several options exist. These options will be discussed and individualized accordingly. In general, options include: continuing with the cycle including embryo transfer and monitoring for ovarian hyperstimulation syndrome (OHSS), continuing with egg retrieval and freezing all embryos for use in a Frozen Embryo Transfer cycle later canceling the cycle and restarting at a lower dose of stimulation medication or different protocol. Suboptimal Response to Ovarian Stimulation The age of the female partner and day 3 FSH level will generally help to predict the ovarian response to ovarian stimulation. The stimulation regimen and dosage used will depend on these factors. If suboptimal response is evidenced by low levels of estradiol or low egg numbers (less than 4 eggs) these issues will be discussed individually with the couple and recommendations made. There are a number of options: The IVF cycle may be converted to Superovulation/ IUI if the semen analysis is normal and tubes are patent, The cycle may continue to egg retrieval albeit with

11 a lesser chance of success The cycle may be discontinued and a more aggressive stimulatory protocol used in a subsequent cycle. If these more aggressive stimulatory protocols fail to produce an appropriate ovulatory response consideration should then be given to egg donation. Egg (Oocyte) Retrieval Egg retrieval is performed while under narcotic conscious sedation. The patient receives intravenous medication to help with discomfort (Fentanyl ) and relaxation Midazolam (Versed ) prior to the procedure. The patient is awake but relaxed, drowsy and comfortable. Egg retrieval is accomplished by inserting the vaginal ultrasound probe (same probe as in the monitoring process) with a hollow bore aspiration needle attached into the vagina. The ovaries and follicles are visualized on ultrasound, and the needle is then passed through the wall of the vagina to access each ovary. The follicle contents (follicular fluid, cells and egg) are aspirated and drained into a test tube. The test tube is then collected by the embryology staff who examine the contents and collect the eggs under microscopic examination. The microscopic image of the eggs can be observed by the patient as the image is displayed on the TV monitor in the retrieval room. The technique of egg retrieval carries a small risk of damage to the internal organs, possible bleeding and infection. Insemination A semen sample is usually collected 1-3 hours following egg retrieval. Once the embryologist has assessed egg maturity, the male partner will be given specific instructions as to the timing of collection. Samples are produced on site at the Regional Fertility Program in the Diagnostic Semen Laboratory. The male partner must present government issued identification(with photo and signature) at the time of collection. The sample cannot be accepted without identification. Sometimes in stressful situations men find it difficult to produce a semen sample. If there is any possibility that the male partner will be unable to provide a sample to inseminate the eggs on the day of the egg retrieval it is highly advisable that a sperm sample be frozen well in advance of starting the IVF cycle. There is a charge for freezing and storing the sperm sample but is well worthwhile to prevent this unfortunate situation. The eggs have to be fertilized shortly after retrieval and if there is no sperm sample available the eggs will have to be frozen. This results in extra charges and a reduced chance of having a pregnancy from that IVF cycle. If there is even a remote possibility that the male partner may experience difficulty producing a semen sample, it is important that you speak with your fertility physician well in advance of the IVF cycle so arrangements can be made to freeze a semen sample as a backup. Once the eggs and sperm have been collected, either conventional or ICSI insemination is carried out. The determination of suitability of conventional insemination or ICSI will be decided in consultation with your physician prior to the procedure. In conventional insemination, several thousand sperm are placed with each egg in a Petri dish containing nutrient media. These dishes are then incubated for approximately 16 hours (overnight) and assessed the following morning for fertilization. Fertilization Check The morning following egg retrieval, the embryologist will assess the number and quality of fertilized eggs which are now called zygotes. The embryologist will speak with each couple personally to discuss the results. The male partner must remain in Calgary until fertilization is confirmed. In cases of failed or poor fertilization, a second semen sample may be required the morning following retrieval. Embryo Assessment and Development Each day the embryologist will assess the quality of the embryos by examining factors such as: cell division number timing of division cell size cellular components spatial arrangement, and degree of fragmentation, if any. Poor quality embryos include those with improper cell division, high degree of fragmentation, or intracellular inclusions such as vacuoles. Laser assisted embryo hatching may be recommended if there is poor embryo quality or if the embryo shell (zona pellucida) is excessively thick. By the third day after egg retrieval, a

12 healthy embryo should have approximately eight cells, and by the fifth day after egg retrieval it is termed a blastocyst, which contains over 100 cells. Embryo Transfer Embryo transfer usually occurs on the third or fifth day following egg retrieval. Many couples may benefit from a day 5 blastocyst transfer also known as blastocyst transfer. Blastocyst transfer involves growing embryos to the blastocyst stage (usually day 5), which allows for more accurate assessment of the embryos implantation potential. One of the benefits of blastocyst transfer is that it allows for transfer of fewer embryos (usually one embryo), minimizing the multiple pregnancy rate while maximizing the opportunity for a singleton pregnancy. This will be individualized based on discussion with your physician. As multiple pregnancies are higher risk pregnancies, every effort will be made to maximize singleton pregnancies. Several patient specific considerations determine the number including: age of female partner stimulation cycle quality of embryos number of embryos suitable for cryopreservation and previous fertility history. Individual recommendations will be made. The procedure of embryo transfer is comfortable and does not require sedation (comparable to a pap smear). The patient is requested to have a full bladder so that transfer may be visualized using ultrasound guidance using an abdominal probe. The embryos are loaded into a fine catheter and passed though the cervix, into the uterus. Gentle pressure is applied to the catheter syringe and the embryos are released into the uterus. The female partner is asked to rest for approximately one half hour and is then discharged home. If the patient lives a significant drive or flight from Calgary they are advised to stay overnight post transfer. support following embryo transfer. These medications are commonly known as Prometrium, Endometrin and Crinone. Progesterone can be given as a vaginal suppository, gel, capsules or intramuscular injection. If the pregnancy test is positive, progesterone is continued until the tenth week of pregnancy. Medications/Side Effects Some common side effects may include vaginal dryness, vaginal itching, nausea, headache, depression, changes in vaginal secretions, breast tenderness, and fluid retention. Please notify your doctor at the RFP if you experience severe headache, vomiting, dizziness, trouble breathing, pain/swelling/warmth or redness in the lower legs, fainting, chest pain or visual changes as this could indicate the development of ovarian hyperstimulation syndrome (OHSS). Pregnancy A laboratory blood test for pregnancy (hcg) will be arranged for day 16 post embryo transfer if a transfer was done on day 3, or 14 days post embryo transfer if the transfer was done on day 5. A clinic nurse will phone the patient the next day when the result is available to inform the patient of the result. Following a positive pregnancy test, an early ultrasound (6-8 weeks gestation) is recommended. Luteal Phase Support with Progesterone is continued until 10 weeks gestation. As the Regional Fertility Program is exclusively devoted to fertility treatment, the clinic does not provide prenatal care or obstetrical care. Patients should arrange obstetrical follow-up with their family doctor or obstetrician. Following a negative outcome, all medications are stopped and a follow-up appointment should be booked to discuss cycle outcome and future treatment options. Luteal Phase Support / Early Pregnancy Follow-Up In order to support the endometrial lining at time of implantation and early pregnancy, supplemental progesterone is given. Progesterone supplementation is usually started the day after oocyte retrieval for luteal phase

13 IVF Nurses Corner - Melanie Mitchell, RN IVF Medications and Protocols Families Building Families Be a surrogate and join hands against infertility Support for every unique journey Find us on Facebook Check out our new edition in September Please send me your stories or ideas to: info@surrogacycommunity.ca or call me at: (519) When the next step is IVF, there are may things to consider; most of which should be explained to you by your Reproductive Endocrinologist &/or team of Healthcare providers. IVF protocols can be similar with some tweaks that are individualize to your specific needs. It is important to remember that everyone responds differently to the medications; as what works for one person, may not yield the same results for another. During your protocol the use of ultrasound; to measure the size of the follicles, and blood test to assess hormone levels of estradiol, luteinizing hormone and progesterone are done throughout the cycle so that your doctor can make adjustments to the medication doses; and determine time of trigger/ egg retrieval. There are 2 types of protocols which can have may variations. Antagonist protocols are commonly used as this is considered a short protocol, this may involve taking birth control pills (for timing purposes, when an ovum donor is involved); prior to starting the IVF injections. The average stimulation phase (number of days of injections) can be approximately 9-12 days. This is completely dependent on your body s response to the medications. Patients are considered a poor responder would hopefully respond better to this type of protocol as there is no suppression from an agonist (lupron) or BCP. Antagonist protocols involve daily injections of follicle stimulating hormone (FSH; commonly known as Gonal F or Puregon), possibly a second injection of Luteinizing hormone (commonly known as Menopur/ Repronex or Luveris) and about mid cycle (day 6) an antagonist (Orgulatran/ Cetrotide) is introduced to prevent ovulation. The antagonist sends a message to the brain to stop the brain from thinking that your ovaries are ready for ovulation; as the goal is to have the follicles grow to 18mm-24mm. For those that are at risk for Ovarian Hyper Stimulation Syndrome (OHSS), instructions for management will be provided post egg retrieval. Agonist protocols are commonly used in many variations. A Long lupron protocol; which involves a synthetic medication used to suppress/downregulate the hormones; usually starting on day 21 of the preceding cycle (just prior to the IVF cycle). Once menses has begun the introductions of FSH (Gonal F or Puregon) and LH (Menopur/ Repronex or Luveris) are introduced and the Agonist dose is usually decreased for the duration of the cycle. Micro dose flare with lupron is used similarly, however injections are started with day 1 of menses with the injections of FSH & LH. The agonist is only used in the beginning of the cycle for the first 5 days, as it is known to have suppressive effects on ovulation, up to 15 days from the last agonist injection. Agonist protocols are generally longer in duration approximately days of injections depending on the specific protocol. This particular protocol can be used in egg donor cycles as well as those with a diagnosis of Poly Cystic Cvarian Syndrome (PCOS) and/or a risk or history of Ovarian Hyper Stimulation Syndrome (OHSS). Side Effects of medications used during an IVF stimulation cycle: FSH, LH medications: headaches, nausea &/ vomiting, feeling more emotional /mood swings, lightheadedness, breast tenderness, pelvic discomfort, abdominal bloating, extremely rare; thromboembolism (blood clots) Agonist medications: Hot flashes, changes in sleep patterns, Joint discomfort Side effects noted at the injection site(s) can include: rash, swelling, local stinging/burning/ itching, redness, bruising. Despite some side effects being common, they can vary in severity from person to person, so it is always recommended to notify your healthcare provider. For further information on specific protocols feel free to contact me at: yourivfnurse@gmail.com