In Vitro Fertilisation (IVF)
What is In Vitro Fertilisation (IVF)
‘Vitro’ is derived from the Latin, ‘vitrum’, which means glass. ‘In-vitro fertilisation’ (IVF) literally means ‘fertilised in glass’, which is why children resulting from this treatment are often referred to as ‘test tube babies’. It was developed more than 30 years ago for the treatment of women with damaged Fallopian tubes, and this remains an important reason for treatment today.
The world’s first IVF baby Louise Brown was born in 1978 in the United Kingdom and IVF became a standard treatment for infertility since 1983. Since then, over 5 million babies have been born worldwide and IVF success rates are now comparable and even superior to those of nature. Dr. Johan Van Schouwenburg of Medfem Fertility Clinic performed the first IVF in South Africa with Professor Kruger at Tygerberg hospital in 1983.
IVF refers to a technique of assisted reproduction where the egg and sperm are fertilised outside of the body to form an embryo. This embryo is then transferred to the uterus to hopefully implant and become a pregnancy.
All IVF treatments begin with a course of hormone therapy to stimulate the development of several follicles in the ovary. These are then punctured with a specialised needle under ultrasound guidance to retrieve eggs, which are then fertilised in a petri dish (‘in vitro’) to create several embryos. After between three and five days in an incubator, one or two of these embryos are transferred through the vagina to the uterus, where implantation occurs and pregnancy begins. However, in IVF as in natural conception, not every embryo implants to become a pregnancy, which is why surplus embryos are frozen – so that a subsequent transfer might be tried if the first one fails. Freezing is now an essential part of every clinic’s IVF programme.
Medfem Fertility Clinic implements individualised IVF stimulation protocols which are customised to each patient according to a multitude of factors (infertility diagnosis, age, weight/height, prior cycle outcome, prior reproductive history). Our IVF clinic treats over a thousand patients each year with success rates that have consistently remained high and well above the national averages.
Low Dose IVF
Low Dose IVF, a minimal stimulation IVF, is a relatively new and advanced reproductive technology (ART) that offers a gentle alternative of ovarian stimulation to traditional in vitro fertilisation (IVF). In Low Dose IVF the ovaries of a woman are minimally stimulated, using oral ovulation induction agents and/or low doses of gonadotropins (follicle stimulating hormone and luteinizing hormone), in order to induce the growth of a small number of eggs.
The process is identical to traditional IVF, except that the goal is to create only a few but high quality embryos for transfer. Low Dose IVF answers two major concerns for both patient and doctor — cost and overmedication. Recent trends in the fertility field prefer an ovulation induction that uses fewer medications and produces fewer but better quality embryos than an ovulation induction that uses significantly higher doses of medications. In other words, Low Dose IVF is a useful method that can be used to help women get pregnant with minimal risks and low cost.
Low Dose IVF is an excellent ART tool which bridges the gap between Natural Cycle IVF and traditional IVF. While in Natural cycle IVF no ovarian stimulation is performed (no oral and/or injectable medications are taken), typically yielding only 1-2 naturally grown eggs and one embryo, in Low Dose IVF a “gentle” ovarian stimulation yields 3-4 eggs and 2-3 embryos, increasing the cycle efficiency significantly. Whereas in traditional IVF a high dose of gonadotropins is often used to maximise eggs/embryos from a single cycle, in Low Dose IVF it is egg and embryo quality which is maximised rather than number.
When is IVF Used?
IVF was originally developed for women with blocked fallopian tubes or missing tubes and is still used to treat these conditions. It is also used when infertility cannot be explained and with the following ovulatory or structural causes:
- Cervical problems
- Failure of IUI
- Male factor infertility
- Ovulation problems
- Polycystic ovarian syndrome
- Unexplained infertility
The stages of IVF
Starting IVF can be a very exciting time – it is another step closer to becoming parents. Naturally you will feel hopeful about a successful outcome but you also need to prepare yourself for around two months of medications, several procedures and testing. The success rate of IVF is high, but for the majority of couples multiple treatment cycles may be necessary.
The basic stages involved in the IVF procedure are detailed below. The whole process from commencement of ovarian stimulation up to the embryo transfer stage usually takes just under three weeks.
- Stage 1: Ovarian stimulation and monitoring
- Stage 2: Egg (oocyte) retrieval
- Stage 3: Fertilisation and Embryo development
- Stage 4: Embryo Transfer
- Stage 5: Luteal phase support
How Stressful is IVF
IVF is not a single event but rather a series of stages that each need to be completed before tackling the next. This can make it a very time consuming process. Couples may go through a range of intense emotions. Moods can swing from hope to fear, from joy to disappointment. Many women describe the experience of coping with infertility and IVF treatment as an “emotional rollercoaster.” You may feel periods of intense sadness, anger or isolation during this time. Your experience and how you cope will depend on a large number of individual factors including your own personality, your support network, the relationship you have with your partner, how you react to the fertility medications and the length and number of cycles of IVF you undergo.
It is normal to feel overwhelmed, but you can do many things to take care of your emotional well-being. It is important to give yourself time to relax and recover from each cycle of treatment. You will need to accept the changes that IVF brings to your body, the changes in your energy levels, and you should try to cut back or prioritise your activities accordingly.
Medfem Fertility Clinic offers infertility counselling services through our partner Dr. Mandy Rodrigues. We highly recommend that anyone commencing an IVF cycle seeks the support of an experienced and sympathetic infertility psychologist. Lowered stress levels and a good support system are noted to increase a positive pregnancy outcome.
The most widely reported ‘side effect’ associated with IVF is a multiple pregnancy. There is also a very small risk that some women (1-2%) will over-react to the hormone drugs used to stimulate the ovaries, but ultrasound and hormone monitoring during this drug treatment phase usually ensures that any over-reaction is foreseen and any risk avoided. Egg collection can be uncomfortable, and is performed with conscious sedation. Suitable pain killers are prescribed to all should the need arise to take.
Ovarian Hyperstimulation Syndrome (OHSS) is a rare but potentially life-threatening medical condition which may occur when your ovaries have been overly stimulated by fertility medications. The ovaries may increase in size and produce large amounts of fluid. It is characterized by pain and bloating in your abdomen and if sever can cause problems with breathing or urinating. Contact a member of your healthcare team immediately if you believe you have any of these symptoms.
Optimising Your Chances
Weight: It is important to be at a healthy weight for your height. Women with a body mass index under 19 or over 32 have a lower chance of getting pregnant and an increased risk of miscarriage.
Smoking: Women who smoke have a lower chance of becoming pregnant and a higher rate of miscarriage.
Supplements: We recommend that you take a multivitamin containing folic acid (0.4 to 1.0 mg daily). This B vitamin reduces the risk of some serious defects of the brain and spinal cord in the foetus.
As with other type of fertility treatment, success rates in IVF decline once patients reach the age of 35 or so. Before that, IVF pregnancy rates at Medfem Fertility Clinic are around 50%. It is important to understand what success means and commonly now the “livebirth” rate is used, the chance of delivering a healthy baby. Medfem Fertility Clinic has success rates consistent with the highest reported amongst clinics worldwide.
Intracytoplasmic sperm injection (ICSI) is a technique in which a single sperm is placed into an egg. ICSI is the biggest advancement in fertility treatment since in vitro fertilization (IVF) and has allowed many men to have genetically-related children. Since ICSI requires very few sperm, it can be an effective treatment for men with severe sperm abnormalities. Typically, ICSI uses ejaculated sperm, but surgically retrieved sperm can also be used. ICSI is performed as part of an IVF cycle.
Laser Assisted Hatching: In the normal process of implantation the embryo has to break through its gel-like outer covering called the zona pellucida prior to attaching to the endometrium. Some embryos may have a tougher zona pellucida than others. It is possible to make a small opening in the zona pellucida using a laser, just before the embryo transfer. This technique is called laser assisted hatching. It is routine at Medfem Clinic in patients over the age of 38.
Blastocyst culture is used to sustain embryo growth in the lab beyond three days. After five days in culture, embryos reach the blastocyst stage, where they have more than 80 cells surrounding a central fluid-filled cavity. This longer period of embryo culture permits an improved ability to choose the healthiest embryos for transfer and is associated with a higher pregnancy rate, while transferring fewer embryos.
Embryo Vitrification: Excess embryos may remain after your in vitro fertilization (IVF) cycle and fresh embryo transfer. These embryos may be suitable for cryopreservation or freezing. Embryo cryopreservation provides the opportunity for additional attempts at pregnancy from a single IVF cycle. Vitrification is a specialised freezing technique whereby embryos are cryopreserved using an ultra-rapid cooling technique, turning them into a glassy solid instead of ice, and by doing so avoiding ice-crystal formation which can be very detrimental to their survival.
Stages of IVF
Stage 1: Ovarian stimulation and monitoring
At the beginning of your menstrual cycle the hypothalamus releases a hormone called gonadtrophin-releasing hormone (GnRH). GnRH in turn causes the pituitary gland to release a hormone called follicle stimulating hormone (FSH) to prepare an egg for release. When the egg is mature the pituitary gland produces another hormone called luteinising hormone (LH). This promotes the follicle to release the egg into the fallopian tube in the process known as ovulation. Follicles are fluid filled sacs in which eggs grow to maturity.
With IVF, certain medications are used to prevent an early release of eggs while other medications, which are synthetic versions of FSH, are used to stimulate the ovaries to develop more ovarian follicles. By having several mature eggs available for attempted fertilisation and transfer it is hoped that at least one will result in pregnancy.
In the ovarian stimulation phase, your ovaries are stimulated to produce more eggs than usual. You will take daily injections of luteinizing hormone (LH) and follicle stimulating hormone (FSH) for about 8 to 10 days. These hormone injections will stimulate your ovaries to produce several follicles, each of which may contain an egg. One of our nurses will teach you how to give the injections to yourself.
Two types of medication are used during this stage to suppress ovulation:
- Cetrotide is added in as a subcutaneous injection once the follicles reach about 14mm in size in the most popular protocol. This is known as the antagonist protocol and begins on the third day of menstruation.
- In the Long Course Protocol a medication called Lucrin is commenced subcutaneously from the twenty first day of the menstrual cycle to prevent ovulation of the stimulated follicles. Once the period begins the FSH and LH are commenced to stimulate follicle growth as in the other protocol.
During ovarian stimulation we use ultrasound to monitor your ovaries, and blood tests to measure your estrogen levels. Ultrasound scans are performed after five days of hormone injections to determine the number of follicles and the follicle size. Not all follicles contain eggs and the size of the follicle determines the maturity of the eggs. Usually the follicles are small at the first scan, subsequent scans and hormone injections will continue until the leading follicle reaches 18mm or more in size.
Ovulation Injection (Ovitrelle or Lucrin) – This injection is usually given at a specific time in the evening. Egg retrieval will then take place 36 hours or so after the ovulation injection.
You will have your ultrasounds and blood tests done at Medfem Fertility Clinic between 7:00 am and 9:30 am Monday to Friday, and between 7:30 am and 9:00 am on weekends.
Stage 2: Egg (oocyte) retrieval
Once the ultrasounds and blood tests show that you have a reasonable size and number of follicles, you will take an injection of hCG (human Chorionic Gonadotropin) to trigger final maturation of the eggs. Egg retrieval is arranged just prior to expected ovulation, usually 36 hours after the administration of the ovulation inducing drugs. Your doctor will try to retrieve as many mature eggs as possible.
Egg retrieval is done under local anaesthetic, most commonly by ultrasound guided fine needle. The mature follicles are identified using ultrasound, and then a needle is passed through the vaginal wall into the follicle and the fluid withdrawn from the mature follicle with gentle suction. The fluid is immediately examined under a microscope to see if an egg has been retrieved. The process is repeated for each mature follicle in both ovaries.
Not every follicle contains an egg so don’t be surprised if the number of eggs retrieved is less than the number of follicles you’ve been watching develop on ultrasound. The average number of eggs retrieved is between eight and nice and the retrieval process lasts approximately 20-30 minutes.
Most commonly, men will provide an ejaculated sperm sample for use, just before the egg retrieval procedure. In other situations, previously cryopreserved sperm, donor sperm or surgically retrieved sperm will be used for fertilisation.
How might you feel?
After the procedure some women may feel a little tender in their abdomen – a hot water bottle may help. You may also feel tired because of the anaesthetic. You will be monitored for a couple of hours before being allowed to go home. Following the procedure you may notice some light vaginal spotting. This is normal and nothing to worry about. It is recommended that someone drives you home from the clinic and you may need to take the following day off work because o of minor pain and fatigue.
Stage 3: Fertilisation and Embryo Development
About two hours before egg retrieval, a semen sample is collected from the male partner. Two to three days abstinence from intercourse is preferred prior to the sample collection day. The sperm is then processed to select the strongest and most active sperm. This is called sperm washing.
Extensive infection tests on both male and female are necessary before the IVF procedure to prevent the growth medium being contaminated. The dish with eggs and sperm are placed in an incubator, fertilisation will occur naturally.
The eggs are placed into a dish that has a highly specialised growth medium in place. The medium allows the eggs and later embryos to continue developing as they would in the fallopian tubes. The sperm are then placed with the eggs in an incubator set to the same temperature as a woman’s body.
One of our embryologists examines the eggs the next day for fertilisation. The eggs are examined under a microscope to determine whether fertilisation has occurred and you will be phoned about how many of your eggs have been fertilised. The resulting embryos will be ready to transfer to the uterus two to five days later.
If undergoing ICSI, the eggs are prepared for injection and their maturity confirmed. A single sperm is then placed directly into the cytoplasm of the egg – hence the name intra-cytoplasmic sperm injection. Fertilisation can then be identified in a similar fashion to IVF after about 24 hours.
If the sperm sample looks normal, we expect about 70% to 80% of the eggs to be fertilised. It is important to know that not every follicle will contain an egg, not every egg will be fertilised, and not every egg that is fertilised will go on to form a good-quality embryo.
During IVF, your embryos are cultured for up to six days in a temperature-controlled incubator. Every other day the embryos are evaluated for quality and development. This information is shared with the doctors to help determine the appropriate day for embryo transfer, which is typically day three or day five of embryo culture. Our embryologists will call you after each examination of the embryos to update you on the embryo quality and to answer any questions that you may have.
The Stages of Development
Zygote: A single sperm penetrates the egg and the resulting cell is called a zygote. The zygote contains all of the genetic information (DNA) necessary to become a child. half of the genetic information comes from the mother’s egg and half from the father’s sperm. the zygote spends the next few days dividing to form a ball of cells. The term cleavage is used to describe this cell division.
Morula: When the zygote reaches 16 or more cells it is called a morula. The morula is no larger than the zygote, but keeps producing smaller and smaller cells through cleavage.
Blastocyst: the morula continues to divide, creating an inner group of cells with an outer shell. This stage is called a blastocyst and consists of approximately 100 cells. The inner group of cells will become the embryo, while the outer group of cells will become the membranes that nourish and protect it.
Embryo: The blastocyst reaches the uterus around day five, and implants into the uterine wall on about day six. The cells of the embryo now multiply and begin to take on specific functions resulting in the various cell types that make up a human being e.g. blood cells, kidney cells and nerve cells.
One of the most common reasons for an IVF cycle to fail is because the embryo/s have failed to implant. An embryo must hatch out of its shell in order to implant into the lining of the uterus. This usually occurs five days after fertilisation.
During fertilisation the sperm must penetrate the hard shell surrounding the egg. This hard shell is called the zona pellucida. Once the sperm has penetrated the egg, the zona hardens again to prevent any additional sperm from entering the egg. During the following days the embryo undergoes a series of development stages, from zygote to morula to blastocyst. In nature this development occurs in the fallopian tubes and when the embryos reach the blastocyst stage they leave the fallopian tube and enter the uterine cavity.
In order to implant into the uterine lining, the embryo must hatch out of its shell, the zona pellucida. If hatching does not occur the embryo cannot implant and pregnancy will not occur. A common cause of difficulties with hatching is that the shell is too thick or too hard.
In assisted hatching a small break is made in the zona pellucida to weaken it just prior to blastocyst transfer. In specific cases this results in increased implantation of the blastocyst into the endometrium and increased pregnancy rates.
At Medfem we employ assisted hatching in cases such as advanced reproductive age, elevated FSH, decreased ovarian reserve, thickened zona, and prior implantation failure.
Preimplantation Genetic Diagnosis
PGD is a screening process that enables us to test the embryos of a couple who carry a known genetic marker for a specific inherited disorder so that only healthy embryos are selected to be replaced/transferred to the woman’s uterus in order to attempt to achieve a pregnancy. Read more
Stage 4: Embryo Transfer
The embryo transfer is a very special experience. Three to five days following egg retrieval, the embryo is placed in a catheter and transferred to the uterus via the vagina opening. The number of embryos transferred depends on a woman’s age, cause of infertility, pregnancy history, and other factors. Generally one to two of the healthiest embryos will be transferred to the uterus. It is important to note that the risk of multiple pregnancies increases with the number of good quality embryos transferred. If there are any addition embryos that are of good quality, they may be frozen for later use. You also will receive pictures of your embryos being transferred for your records.
This procedure only takes a few minutes and most women do not find it uncomfortable. Following the procedure you will rest for 30 minutes in our recovery room and will then be released to return home. We suggest that you take it easy for 24 hours after your embryo transfer. You can resume light, non-aerobic activity over the next few days. Many women return to work the next day if their jobs are not that strenuous.
Stage 5: Luteal phase support
The Luteal phase is the two week period between the embryo transfer and the pregnancy test. Starting the day of the egg retrieval process you will be prescribed progesterone in order to support a developing pregnancy. The progesterone will either be in the form of pessaries or injections. A pregnancy test is performed 14 days after embryo transfer. To confirm the positive pregnancy test, we will schedule an ultrasound two weeks following these pregnancy tests. At this visit we will be looking for implantation of embryos and fetal heart motion.
Emotionally this is a very taxing time. Hormone levels are high and there is not much that can be or cannot be done to influence the outcome of the treatment. Whether there is a pregnancy has been determined physiologically soon after the embryo transfer. It is recommended to resume normal activities in this period.
In the event of a pregnancy it is essential that you continue on the medications that were prescribed at the time of embryo transfer. If there is no pregnancy it is important to communicate with your doctor. Even though it will be extremely disappointing – remember your doctor has gained valuable diagnostic information throughout the procedure that will guide him in planning future treatment.
How might you feel?
Some of us find that starting treatment is a positive experience because you have something to focus on. However, others may fear the physical intervention or feel very disappointed that they have to face intervention.
In addition to dealing with feelings of uncertainty and trepidation, as well as hope, you will be dealing with the impact of hormonal changes on your body. Responses to the medications used vary enormously. Some women have no symptoms while others feel emotional and much more prone to tears, anxiety and irritability. Others feel uncomfortable with bloating, headaches, tiredness and other symptoms. While you cannot help the way you feel, with the help of a counsellor, you may be able to find a way to better manage your feelings and reactions during these times.
Initially women may fear the actual process, but waiting for results is often the most difficult part of treatment. Days seem to pass very slowly and it can be a time of acute vulnerability and sensitivity, making it difficult to concentrate on ordinary life.