Elective Egg Freezing Information Package

PART-1: ELECTIVE EGG FREEZING INFORMATION PACKAGE

Welcome to Sameda Clinics Elective Egg Freezing Program. This package contains information about egg freezing that you are required to read before completing and signing your egg-freezing consent form. If you have further questions about the process, please speak to one of our nurses or book an appointment with your doctor.

Checklist

Before you are ready to begin an egg-freezing cycle, the following steps should be taken (though not all steps will apply to everyone). Please check with your doctor or nurses if you are unsure which investigations are required in your situation.

• Read this document.
• Complete blood tests. It is best to complete these at Sameda Clinics.
• Consent will be requested. Please sign the consent as soon as possible.
• To start your egg-freezing cycle, patients who have a regular menstrual cycle on their own are to call the clinic on the first day of a period. (First day of bleeding= Day 1).
• If you do not have a regular menstrual cycle, the clinic will provide you with additional information and instructions.
• Before filling your prescriptions, speak to one of our nurses to ensure you are only filling the prescriptions and amounts required.

Egg Freezing Overview

Sameda Clinics has been freezing eggs as a method of fertility preservation for a while. We use the process of vitrification, or ‘fast freeze’ of eggs, which is currently thought to offer the best chance of eggs surviving the freeze/thaw procedure intact.

To date, more than 5,000 babies have been born from frozen egg cycles around the world. Sameda clinics, as is true for most clinics, currently do not have much clinic-specific data on the freeze/thaw survival of frozen eggs and ongoing pregnancy rates resulting from embryos created with frozen eggs.

The option of freezing eggs has expanded beyond people hoping to preserve their fertility before cancer treatment. In fact, people are choosing to freeze eggs for several reasons including:

• A family history of infertility or early menopause
• A history of endometriosis
• Before ovarian surgery
• Before beginning medication that may impair fertility
• A wish to delay having a family for career or personal reasons such as financial stability or a lack of a partner.

For those who are delaying having children until later in life to find a good partner, establish a career, become financially secure, or for other reasons, the negative impact of age on fertility can be significant. Specifically, age negatively impacts the supply of eggs, with both quality and quantity rapidly declining after age 35. Elective egg freezing, also known as elective oocyte cryopreservation (EOC) or oocyte banking for anticipated gamete exhaustion (AGE) allows someone an option to freeze eggs to be used later in life when ready to start a family.

Before starting treatment, you will meet with one of our gynecologists or Nurse Practitioners for a consultation. We will discuss your goals for egg freezing, and the procedure, and advise you on your likelihood of successfully becoming pregnant in the future from frozen-thawed eggs. You will require a transvaginal pelvic ultrasound and bloodwork to test your ovarian function or reserve and screening bloodwork for infectious diseases.

Egg Freezing Procedure

Egg freezing involves the following:

1. Stimulation of ovaries to produce multiple eggs using injectable fertility medications,
2. Egg retrieval procedure to remove eggs from the ovaries, and
3. Vitrification

OvarianStimulation:

In a usual menstrual cycle, only one mature egg is produced each month. To increase the number of eggs to freeze during an egg-freezing cycle, hormonal medications are given to stimulate the ovaries to produce and grow more eggs, which can be removed for freezing. Fertility medications are injections that must be given daily for approximately 2 weeks. You will also be given an injection medication to prevent natural ovulation. You will be taught how to give the injections yourself or a support person can be taught to give them to you. While you are using the injectable medications, some blood tests and internal (transvaginal) ultrasounds are required to monitor the effects of the medications.

Egg Retrieval:

The egg retrieval is performed by a doctor. The doctor will use an ultrasound to see the follicles and place a needle through the top of the vagina into each ovary. All of the follicles will be drained, and the fluid will be sent to the embryology lab to identify the eggs. Shortly after the retrieval you will be told the number of eggs that were retrieved. The egg retrieval will be performed with sedation or short spinal anesthesia. Medications to relax you and provide pain relief may be given through an intravenous (IV) line during the procedure. You will not be completely unconscious but should be comfortable and able to tolerate the procedure.

Egg Freezing (Vitrification):

The mature eggs retrieved are frozen in the embryology lab on the day of egg retrieval using vitrification technology. If you choose to also freeze embryos (eggs fertilized with sperm), the eggs designated to be embryos will be fertilized the same day and the resulting embryos will be grown in the lab for 3-5 days before they are frozen. The cost of the egg-freezing procedure will be discussed with you as well as quarterly storage fees to keep eggs frozen. You may want to do multiple egg-freezing cycles to freeze a larger number of mature eggs to have a better chance of pregnancy in the future. You will be advised of the recommended number of eggs to freeze based on your age.

Egg Thawing, Fertilization, and Embryo Transfer in the Future: When you come to use your frozen eggs in the future, the eggs will be thawed and fertilized the same day using ICSI (sperm injection). Fertilization is the process where the egg and sperm join to form an embryo. ICSI is a procedure in which a sperm is chosen and mechanically placed into an egg for fertilization. ICSI is required when eggs have been frozen. It is expected that approximately 85% of eggs will survive freezing and thawing and only approximately 70% of surviving eggs will fertilize.

The cost of egg thawing, fertilizing, embryo development, and transferring embryos in the future will depend on clinic costs at that time.

Embryos (fertilized eggs) will be placed in an incubator and checked by the embryology team. The embryo transfer will occur either on day 3 or day 5 after egg thawing and fertilization. The embryo transfer is performed by the doctor. An ultrasound is used to see the uterus, and the embryos are placed in the uterus using a small catheter (tube) through the cervix.

Outcomes

Sameda Clinics tracks the outcomes of all egg-freezing treatment cycles, including information about pregnancies and births. This information helps us to continue to improve our treatments and patient care. You may be contacted in the future and asked to provide information regarding pregnancy and outcomes.

Egg Freezing RisksMedicationRisks:

Most people will experience some bloating and fullness in the lower abdomen with medications. This is a normal reaction to the medications and often indicates the medications are stimulating egg development. Side effects of the medications may include bruising and soreness at the injection site, allergic reaction, gastrointestinal distress, headaches, or mood changes. It is important to discuss with your doctor if you experience any reactions to the medications.

Currently, there is no definite evidence directly linking fertility medications to breast or ovarian cancer. Those with infertility, regardless of exposure to fertility medications, have a higher risk for ovarian cancer. However, further long-term studies are needed to determine if there is an association between fertility treatments and breast or ovarian cancer.

OvarianHyperstimulation:

Ovarian hyperstimulation syndrome (OHSS) is a condition where there is an over-response to medications with the development of a large number of follicles and very high hormone (estrogen) levels’. In severe cases, people will have fluid (water) build up in their abdomen and lungs and develop blood clots. The fluid may need to be removed with a needle and there may be a need to be admitted to the hospital for management. Severe OHSS can occur in 1-3% of people undergoing ovarian stimulation but is less likely with egg freezing compared to IVF. Rarely, an ovary that has been stimulated may twist (ovarian torsion), which may require surgery (<1%).

ProcedureRisks:

Risks associated with egg retrieval include discomfort during the procedure, bleeding, infection, or puncture of the bowel. Infections are rare, but severe infections may require antibiotics or rarely surgery. The risks of sedation include being too sedated, breathing, and/or heart rate complications.

Cycle Cancellation:

In some situations, your egg-freezing cycle may be canceled before the egg retrieval. Reasons for canceling an egg-freezing cycle may include:

• The ovaries are not responding to medications (too few follicles developing)
• An unusual response to medications (follicles developing too quickly or too slowly)
• Hormone levels too high or too low
• Findings on ultrasound/blood tests that show a decreased chance of freezing eggs

When there are a low number of follicles developing, there is a very low chance of future pregnancy. Because of the risks and costs associated with egg retrieval and IVF procedure, a doctor may advise canceling the cycle if it is felt your chances of success are small. If your cycle is canceled, a review appointment will be booked with your primary physician. If your cycle is canceled, a portion of your costs will be refunded based on the treatments/procedures which have already occurred.

Pregnancy Risks:

There are no known specific increased risks to a baby that is born from IVF with previously frozen eggs compared with risks from standard IVF, although this remains a relatively new technology.

All pregnancies have a small risk that the babies can have a birth defect. The general risk for all pregnancies is approximately 3-5%. The risk of birth defects including cerebral palsy appears to be higher in people with infertility, even if they conceive without fertility treatment. The risk in babies born after IVF appears to be slightly increased (7%), but not statistically different from those with infertility who conceive without the use of fertility treatments. The risk is slightly higher after ICSI (10%). Certain rare conditions have been associated with IVF (Beckwith-Wideman syndrome and Angel man syndrome), although they still occur in less than 1% of babies born after IVF or IVF/ICSI. This is an issue that continues to be studied.

Other problems which can occur in pregnancy may also occur in an IVF pregnancy from frozen and thawed oocytes are Miscarriages (spontaneous abortions) occur in approximately 15%-30% of IVF pregnancies (depending on age) and ectopic pregnancies (pregnancy in the fallopian tube) will occur in about 2% of IVF pregnancies.

If you decide to use your frozen-thawed eggs for pregnancy at a later age in life, then you are more likely to have some pregnancy complications because you are older than if you had been pregnant at a younger age. Pregnancies at advanced reproductive ages are at higher risk for problems such as high blood pressure, gestational diabetes, preeclampsia, premature delivery, C-section, and low birth weight. Furthermore, pregnancies conceived through IVF are more likely to have some pregnancy complications including high blood pressure, premature delivery, operative delivery, and small babies. Studies looking specifically at pregnancies conceived from frozen-thawed eggs are limited but reassuring, showing no increased risk of pregnancy complications or birth defects compared with pregnancies from standard IVF.

Other Risks

Egg freezing can be costly and sometimes may not be necessary. Many people who freeze eggs never use them, either because they are able to get pregnant in the future without any fertility treatment, or because they decide not to use them for various reasons. It is important to think about what you would choose to do with frozen eggs that you may never use in the future, the options being discarding them, donating them for ethically approved research, or to your partner or another individual who needs eggs to conceive.

While unlikely, it is possible that our clinic will stop operating, requiring the transfer of eggs to another facility, or that an accident could occur in the laboratory during the time your eggs are frozen, but before you are ready to use the eggs, resulting in no viable eggs available for use. Only about 85% of eggs will survive freezing and thawing and only approximately 70% of surviving eggs will fertilize. It is possible that there could be no surviving embryos (fertilized eggs) to implant, and even if there are, there is no guarantee of pregnancy from egg freezing. There is a risk that you may decide to put off having a family even longer, when fertility is even less likely because you feel reassured that you will be able to get pregnant from your previously frozen eggs, even though this is not a guarantee.

BenefitsofEggFreezing

If you anticipate having a pregnancy later in life, you may benefit from planning to conceive using frozen-thawed eggs from an egg-freezing cycle when you were younger than trying to conceive at an older age when egg quality is reduced, and pregnancy rates are lower. Freezing eggs can allow you an opportunity to focus on obtaining a good career, financial stability, or a stable

relationship with less worry about the effect of age on fertility, and gives you a potential opportunity to be genetically related to your future child. Furthermore, egg freezing could benefit you if you have a medical condition that is known to reduce fertility over time, such as endometriosis or a family history of early menopause. By freezing eggs at a younger age, when pregnancy rates are higher, there is a better chance of being able to have a family later in life when you are ready.

Egg freezing can also reduce the risk of some pregnancy complications. Individuals who

become pregnant at an older age are more likely to have a miscarriage or a pregnancy with a chromosomal abnormality due to problems with separating chromosomes in older eggs. In contrast, if you decide to become pregnant at an older age with frozen-thawed eggs stored when you were younger, you will be at a lower risk for these problems in pregnancy.

Alternatives To Egg Freezing

One alternative to egg freezing is to wait until the right time to try for pregnancy, and if this does not work, then try fertility treatment such as IVF or using donor eggs in an IVF cycle. Another alternative is to try for pregnancy now instead of delaying pregnancy. If you are single or do not have a partner with sperm, this could mean using donor sperm either with intrauterine insemination (JUI) or IVF. Adoption is also an option, as well as not pursuing pregnancy at all.

Chance Of Success With Egg Freezing

Optimal Timing for Egg Freezing:

Studies on egg freezing show a better chance of live birth compared with waiting to become pregnant later in life, particularly when done before age 35, but is cost-effective up to about age 38.

For most people, there is little benefit to freezing eggs before age 30 over waiting, although there may be some exceptions to this.

Chance of Successful Pregnancy with Egg Freezing:

The chance of pregnancy in the future depends on the age that a person freezes eggs, the number of eggs frozen, and the stage of development of the embryo after fertilization.” The chance of pregnancy per frozen-thawed egg has been quoted at approximately 6.4%. Studies have shown that approximately 8-20 mature eggs are required to be frozen to have a good chance of pregnancy, and this number varies with age and ovarian reserve. Therefore, you may need to do multiple egg-freezing cycles in order to have an adequate number of eggs frozen to provide a

reasonable chance of pregnancy upon thawing. This is particularly true if doing egg freezing at an older age when the number and quality of eggs in the ovaries are already reduced. The average ongoing pregnancy rate reported per egg-freezing cycle in studies is 25%. Pregnancy rates range from less than 5% up to as high as 60% depending on the age that a person freezes eggs and the number of eggs frozen.

If you would like to discuss any of the information listed above, please book a review appointment with us at Sameda Clinics.

PART-2: PREPARING FOR TREATMENT

Ovarian Reserve Testing:

These tests can be completed any day of your menstrual cycle. The internal (transvaginal) ultrasound will be used to count the number of resting follicles in your ovary. The Anti-Mullerian Hormone (AMH) blood work drawn, along with the ultrasound results, will give us an idea of your fertility potential.

Prediction Of Fertility Potential (Ovarian Reserve)

Fertility potential declines with age due to declining egg quality and numbers. This is reflected in the decreased ability to become pregnant and the increased rate of miscarriage with age. Although the ability to achieve a live birth decreases with age, the precise age when someone can no longer conceive varies among individuals. Several tests may be useful in assessing fertility potential (ovarian reserve).

Anti-Mullerian Hormone (AMH) Blood Test

AMH is a protein that is produced from immature follicles within the ovary. AMH is secreted into the bloodstream and can therefore be measured by a lab test. The concentration of AMH measured in blood is a marker for the number of follicles and eggs remaining in the ovary. AMH decreases with age, as well as with damage to the ovaries due to radiation or chemotherapy and surgery on the ovaries. AMH is undetectable in individuals who are menopausal. AMH is a test that is not covered by OHIP.

Antral Follicle Count

An internal (transvaginal) ultrasound will be performed in the early part of the menstrual cycle to count the number of small (2mm-10mm) follicles in the ovary. The number of these follicles reflects the underlying egg supply and response to gonadotropins.

These tests are useful to qualitatively predict response to fertility treatment and the likelihood of success compared to others of the same age. In younger individuals, abnormal test results suggest that fertility potential is declining, but they do not identify who will or who will not conceive. It is also important to remember that some younger individuals with normal test results have difficulty conceiving. Those older than 40 years with abnormal test results have poor chances of achieving pregnancy naturally and after ovulation induction, and in these people the use of donor eggs or embryos can be considered because the chances of pregnancy are primarily related to the quality of the donated eggs. Unfortunately, even with a normal ovarian reserve test, older individuals may have difficulty achieving a pregnancy. Moreover, the results may vary from cycle to cycle. Any single abnormal test, however, generally indicates that fertility potential has diminished.

Before Your Gynaecologist Appointment:

1. Review medication with your nurse:
2. Write down any questions you may have.
3. Complete any consent given to you.

During Your Doctor/Nursing Appointment:

1. The doctor/nurse will review your planned egg-freezing cycle
2. You will be given a calendar with timelines and instructions.
3. Injection/Medication teaching and practice will take place.
4. You will have an opportunity to ask questions.

S) Medication may be dispensed at Sameda Clinics.

PART-3: DURING TREATMENT

Cycle Monitoring

Please review the following regarding morning monitoring: When to call:

To report your Day 1 (first full day of bleeding) is very important.

please inform us at Sameda Clinics OR go to your nearest Emergency Department if you are experiencing any of the following: Shortness of Breath, chest pain, severe abdominal pain, or heavy bleeding (bleeding through one pad or more an hour).

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Sameda Clinics

3a Yeye Olofin Street, Off Onikepo Akande Street (Beside Access Bank), off admiralty way, Lekki Phase-1. Lagos. Nigeria

Tel: 08096751790

Email: info@samedaclinics.com

Location: https://maps.app.goo.gl/22S5VrSDCZsp7sjW6

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REFERENCES

1. Fact sheet: Ovarian hyperstimulation syndrome (OHSS). Birmingham (AL): American Society for Reproductive Medicine; 2014. Available: www.asrm.org/uploadedFiles/ASRM Content/Resources/Patient Resources/Fact Sheets and Info Booklets/OHSS final 1-5-12.pdf

2. Petropanagos A., Cattapan A., Baylis F., and Leader A. Social egg freezing: risk, benefits and other considerations. CMAJ. 2015: accessessed online

3. Risks of in vitro fertilization {IVF). Birmingham (AL): American Society for Reproductive Medicine; 2014. Available: www.asrm.org/uploadedFiles/ASRM Content/Resources/Patient Resources/Fact Shee ts and Info Booklets/risksofivf.pdf.

4. Cobo A., Garcia-Valasco J.A., Coello A. et al. Oocyte vitrification as an efficient option for elective fertility preservation. Fertility and Sterility. 2016:105(3);755-764.

5. Doyle J.O., Richter K.S., Lim J. et al. Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval. Fertility and Sterility. 2016:105;459-466.

6. Liu K., and Case A. Advanced reproductive age and fertility. Journal of Obstetrics and Gynaecology Canada. 2011:33,1165-1175.

7. Noyes N., Porcu E., and Borini A. Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies. Reprod Biomed Online 2009; 18:769-76.

8. Chi an R.C., Huang J.Y., Gilbert L., et al. Obstetric outcomes following vitrification of in vitro and in vivo matured oocytes. Fertil Steril 2009; 91:2391-2398.
9. Tur-Kaspa I. et al. Genetics and health of children born from cryopreserved oocytes. Fertility and Sterility. 2007:88; suppl: S14

10. Mezen T.B., Mersereau J.E., Kane J.B. et al. Optimal timing for elective egg freezing. Fertility and Sterility. 2015:103(6);1551-1556.

11. Devine K., Mumford S.L, Goldman K.N. et al. Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth. Fertility and Sterility.

2015:103(6);1446-1453.

12. Rienzi L., Cobo A., Paffoni A. et al. Consistent and predictable delivery rates after oocyte vitrification: an observational longitudinal cohort multicentric study. Human Reproduction. 2012:27,1606-1612.