In Vitro Fertilisation (IVF)
In-vitro fertilization is the fertilization of eggs by sperm outside the body. In IVF, eggs are removed from the woman’s ovaries and are fertilized with the man’s sperm in the laboratory to create embryos which can then be transferred to the woman’s uterus. IVF treatment is used when there is damage to the fallopian tubes, severe male factor infertility, severe endometriosis, or when other infertility treatments have failed or in older women who have been infertile for a long time.
IVF Medication
The hormone therapy that precedes the egg retrieval is more complex than the hormone therapy given before IUI (insemination) in basic treatment. With IVF, the goal of hormone therapy is twofold: to stimulate the ovaries to produce many mature eggs and, to prevent premature ovulation before egg collection.
There are different medications and strategies that can be used to stimulate the ovaries and control ovulation. The treatment plan and choice of medications is based on the couple's test results and unique medical history. Various types of medication such as oral contraceptives and gonadotropins (hormone injections) may be used during an IVF treatment. These medications can have some side effects such as fatigue, headaches, breast tenderness and mood changes; however, side effects are usually mild and of short duration.
Additional hormone therapy is given after the egg retrieval, in order to help implantation of the embryo and to support the possible pregnancy.
Monitoring
Women following hormone therapy prior to egg retrieval are carefully monitored by vaginal ultrasound and serum Estradiol (hormone blood test). A first ultrasound is performed prior to ovarian stimulation; a second one is done after a few days of stimulation, and then every 1-2 days until follicular maturation, for an average of three ultrasounds per treatment cycle.
The hormone injection dose is adjusted according to the results of the ultrasound scan and blood test. Cycle cancellation may be considered if response to hormone therapy is poor or, if ultrasound reveals an over response to medications and a significant risk of Ovarian Hyper Stimulation Syndrome (OHSS). Based on the patient's results, the physician decides on the best time to retrieve the eggs. One last injection (HCG or Ovidrel) is given 36 hours before the egg retrieval.
The eggs cannot be seen on the ultrasounds during the monitoring phase. Only after the egg retrieval, can we know the number of eggs retrieved and if they are mature. Only mature eggs can be fertilized by the man’s sperm.
Oocyte Retrieval "Egg Collection"
The oocyte retrieval (egg collection) is a procedure used to aspirate the eggs from the ovaries. Although the egg retrieval usually takes about 20-30 minutes, the time may vary depending on the number of follicles. On the day of the procedure, patients undergoing egg retrieval and their partners can expect to be at the clinic for a few hours as there is some preparation to be done before, and monitoring required after.
It is very important that our patients remain comfortable during the procedure and that their treatment remains a positive experience. We therefore administer a local analgesic into the vagina and supplement it with strong intravenous sedation and analgesics at regular intervals to reduce any discomfort during the procedure.
In Vitro Fertilization
Collected eggs are placed in Petri dishes that contain culture medium that provides nutrients necessary for growth, and partner’s sperm is added (about 100,000 sperm sample are added to each egg). Dishes are placed in incubators overnight. The next morning the laboratory staff will examine each egg under the microscope to see if they have been fertilized.
When there is concern that there are too few sperm to achieve fertilization, in vitro fertilization (IVF) can be done manually in the laboratory using Intra Cytoplasmic Sperm Injection (ICSI)
Embryo Transfer
The embryo transfer takes place two, three, or five days after the egg retrieval, depending on the development of the embryos. Every day the laboratory staff examines each embryo under the microscope to evaluate how well they are developing. The decision about when to transfer the embryo is made on an individual basis and depends on the number and quality of embryos.
The Centre is required to follow Quebec law in determining the number of embryos that can be transferred at each transfer. In most cases, this will be a single embryo. In special circumstances, such as in an older patient or after many failed attempts, the physician may decide to transfer more than one embryo, to a maximum of two. The goal is to maximize the chances of achieving a pregnancy without increasing too much the risk of having a multiple pregnancy (a pregnancy with more than one baby).
Pregnancy Testing
After the embryo transfer, patients should continue their medication until the pregnancy test (blood test) is scheduled 16 days after the egg retrieval. When the pregnancy test is positive, patients are advised to continue their medication until twelve weeks of pregnancy (ten weeks after embryo transfer).
An ultrasound scan is usually scheduled two weeks after a positive pregnancy test to confirm a healthy pregnancy. An ultrasound scan is safe to perform in early pregnancy. Once the pregnancy is confirmed patients are referred to their obstetrician for follow-up throughout the pregnancy.
Risks Associated with IVF Treatment
IVF treatment is generally considered safe however there are some risks that need to be considered. Egg retrieval carries a very low risk of complications, but may be associated with pelvic infection in 1/500 cases and with significant bleeding in 1/1000 cases.
Ovarian Hyper Stimulation Syndrome (OHSS)
A rare risk (about 1% of patients) of hormone therapy is the risk of Ovarian Hyper Stimulation Syndrome (OHSS). OHSS is a complication that occurs when the ovaries over respond to stimulation and an excessive number of eggs has grown. OHSS is more often seen in younger women and women with polycystic ovaries. Symptoms range from mild to severe and may include nausea and/or vomiting, abdominal distension and discomfort/pain, shortness of breath, edema (swollen feet), and blood changes. OHSS can last for a few days or for a few weeks and usually resolves on its own, but is considered serious and requires close monitoring and treatment of symptoms. Some women with OHSS need to be admitted to the hospital and may need drainage of fluid that collects in the abdomen. During treatment, every effort is made to limit the risk of OHSS – if present, the gonadotropin (hormone) dosage may be lowered or the treatment may be cancelled, in order to reduce the risk of OHSS.
Multiple Pregnancy
When more than one embryo is transferred, there is a risk of having a multiple pregnancy (a pregnancy with more than one baby). When two or more embryos are transferred in IVF treatment, there is a risk that both or all will implant. Multiple pregnancies present health risk to both the mother and unborn children (this applies to all multiple pregnancies and equally those that are naturally conceived). Maternal risks associated with multiple pregnancy include increased risk of gestational diabetes (diabetes in pregnancy), hypertension (high blood pressure), and haemorrhage. Fetal complications include increase risk for prematurity and fetal death, cerebral palsy and low birth weight. If there is a triplet pregnancy, we strongly recommend fetal reduction to singleton or twins.
Ectopic Pregnancy
There is also risk of ectopic pregnancy with IVF. An ectopic pregnancy is one in which the embryo begins to grow outside the uterus. In an ectopic pregnancy, the embryo is located in the fallopian tube but can sometimes be found in the ovary, cervix, or elsewhere in the abdomen. The risk of an ectopic pregnancy is slightly higher after IVF (5%) compared with spontaneously conceived pregnancies (1.6%) because women having IVF have a higher chance of having blocked or damaged tubes.
Finally, there is a slightly higher risk of problems during pregnancy following IVF compared with spontaneously conceived pregnancies – although the reasons are unclear and may be due to many factors, such as the age of the mother, the cause of infertility and the infertility status of the patient itself. These concerns should be discussed with the physician.
Other In Vitro Treatments
In Vitro Maturation (IVM)
The MUHC Reproductive Centre is a pioneer in the application of In Vitro Maturation treatment. With this treatment no hormone therapy is taken to produce large numbers of mature eggs at egg retrieval; instead, immature oocytes are retrieved from the ovary and matured in the laboratory for 24-48 hours. Once the eggs have matured, fertilization is performed and then, one fertilized egg is transferred to the uterus as in conventional treatment.
IVM treatment is an option for women who want to avoid the inconvenience, cost and risks of ovarian stimulation. In general, the best candidates for IVM are women under the age of 38 who have a large number of ovarian follicles seen on ultrasound, and also, women who are at increased risk of ovarian hyperstimulation syndrome (OHSS) or have indeed had OHSS before.
IVM treatment is very easy and requires less time commitment compared to conventional IVF. Full treatment consists of two or three ultrasounds followed by an injection of HCG (Human Chorionic Gonadotropin) to mature the eggs 38 hours prior to egg retrieval.
Following egg retrieval, immature eggs (see illustration) are cultured in a maturation medium for 24 to 48 hours and then mature eggs (not all eggs will mature) will be fertilized using the ICSI technique. The transfer is scheduled two to five days after fertilization.
We reported the first IVM baby birth in Canada in 1999 and today we have one of the highest pregnancy rates in the world, with more than 100 IVM babies born from our program.
Medications
As with conventional IVF treatment, medications are given following egg retrieval in order to make implantation easier and to support the endometrium for pregnancy. Support of pregnancy is especially important in IVM treatment because the follicles that yield eggs (and would normally support pregnancy) are immature in IVM treatment. Medications taken following IVM egg retrieval include:
Estrogen
Estrogen helps develop and support the endometrium (lining of the uterus). Estrogen is taken as an oral medication on a daily basis through the first trimester of pregnancy. Side effects are rare but may include breast tenderness, mood changes, fatigue.
Progesterone
Progesterone plays an important role in supporting the endometrium in pregnancy. Progesterone is taken on a daily basis by intramuscular injection or by vaginal suppository through the first trimester of pregnancy. Side effects are rare but include mood changes and reactions at the site of injection.
Medrol
Medrol is a steroid that has been shown to help prepare the endometrium for implantation. Medrol is taken by mouth and is begun prior to embryo transfer. Medrol is taken for a short duration and has not been associated with side effects.
Doxycycline
Doxycycline is an antibiotic that is begun prior to embryo transfer, to help create a favourable environment for implantation. Doxycycline is taken orally.
Embryo Transfer
Embryo transfer takes place two, three, or five days after the fertilization of mature oocytes depending on their development (or growth).
The Clinic is required to follow Quebec law in determining the number of embryos that can be transferred at each transfer. In most cases, this will be a single embryo. In special circumstances, such as in an older patient or after many failed attempts, the physician may decide to transfer more than one embryo, to a maximum of three. The goal is to maximize the chances of achieving a pregnancy without increasing too much the risk of having a multiple pregnancy (a pregnancy with more than one baby).
Patients should continue their medication until the pregnancy blood test is done.
Pregnancy Testing
Following the embryo transfer, patients should continue their medication until the pregnancy test (blood test) is scheduled 16 days after the egg retrieval. When the pregnancy test is positive, patients are advised to continue their medication until twelve weeks of pregnancy (ten weeks after embryo transfer).
An ultrasound scan is usually scheduled two weeks after a positive pregnancy test to confirm a healthy pregnancy. An ultrasound scan is safe to perform in early pregnancy. Once the pregnancy is confirmed patients are referred to their obstetrician for follow up during pregnancy.
When there is concern that there are too few sperm to achieve fertilization, in vitro fertilization (IVF) can be done manually in the laboratory using Intra Cytoplasmic Sperm Injection (ICSI). With ICSI, highly sophisticated micromanipulation equipment is used to inject a single selected sperm into each egg in order to achieve fertilization. ICSI is routinely carried out in patients who have extremely low sperm counts, very low sperm motility, undergone a vasectomy, surgical sperm retrieval or for whom conventional IVF has failed because of low or absent fertilization. ICSI is also undertaken as part of IVM or frozen eggs treatment cycles.
Some observations of the ICSI procedure indicate a higher risk of sex chromosome abnormalities in offspring born following ICSI however, this is probably due to the underlying sperm abnormality rather than to the procedure itself - men who have very abnormal sperm are more likely to have a genetic defect that causes this, and that may be transmitted to offspring.These genetic defects can sometimes be detected by technology known as Pre-Implantation Genetic Diagnosis (PGD) which allows some genetic defects in embryos to be detected before they are transferred to the uterus.