Preparation for an IVF Cycle
Achieving the best chances for a successful IVF cycle involves many factors including additional testing and personal lifestyle changes. The following video was developed to help patients prepare for their IVF cycle. Further information is available from your physician.
Check out our frequently asked questions (FAQ’s) for further information regarding your IVF cycle.
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 waitlist 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.
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.
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.
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.
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.
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 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.
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.
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 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 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.
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 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.
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).
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.