Infertility is not uncommon and challenges one out of every six couples.
There are many causes of infertility, due either to a male factor, a female factor, or a combination of the two.
When traditional treatments fail, in-vitro fertilization (IVF) may offer the chance of achieving a pregnancy.
IVF is a procedure in which egg(s) are removed from ripe follicles in the ovary and then fertilized by sperm outside the body more
Each fertilized egg is allowed to divide in a special growth environment for three to five days and then inserted back into the uterus, usually one at a time.
In general, the chance of achieving pregnancy through IVF, for women 35 and under) is approximately 40 percent for a complete treatment cycle (national average), although the rate declines with increasing age. This is higher than the expected conception rate per monthly menstrual cycle for any normal fertile couple (20%).
There is no guarantee that an IVF cycle will result in a successful pregnancy but it does increase the statistical probability.
In normal reproduction, a woman’s ovary releases one egg (oocyte) per month. In IVF, medication is given in order to encourage the development of a number of mature eggs.
Eggs develop in small fluid spaces (follicles) in the ovary. As follicles grow, the hormone estradiol is produced. When estradiol reaches a certain level and the follicles reach an appropriate size, another hormone, luteinizing hormone (LH) is released which is the driving force necessary for final maturation and release of the egg.
This process is known as ovulation.
During IVF treatment, human chorionic gonadotropin (hCG) is given as an injection which works in a similar way to LH, and the eggs are collected before ovulation can take place. When a couple chooses IVF, the medical team helps them proceed through this sequence of biologic events.
THE IVF PROCEDURE
There are 7 steps involved
a) Blood Tests more
Blood tests (Female and Partner) are done to determine your blood type and to screen for certain viruses; one of these is the HIV test. If appropriate, we also perform an analysis of cervical and vaginal secretions to determine the presence of microorganism which may interfere with fertility.
b) Male Factor Assessment more
It is important that a sperm functional assessment be obtained prior to your IVF treatment cycle. A separate leaflet is available which explains the details and rationale of this investigation.
Patients with low sperm numbers or other sperm abnormalities on this test may be suitable candidates for Intracytoplasmic sperm injection (ICSI). Please note the fee for this test is not included in the basic cost of IVF. See Male InfertilityAssessment
c) Hysterosonogram more
A hysterosonogram allows assessment of the uterine cavity to exclude irregularities that may impair embryo implantation and to assess patency of the tubes. Blocked tubes would be an absolute indication for IVF for example.
In traditional IVF, fertility medication (gonadotrophins) are used for approximately 10 days to stimulate the ovaries to produce multiple mature, eggs (oocytes). The medications used will include some of the following
a) Gonadotropins which may include Bravelle, Gonal-F, Puregon and Menopur more
These hormones which are self-injected beneath the skin daily, stimulate the follicles to grow.
Gonal-F and Puregon are pure forms of FSH (follicle stimulating hormone) which have been synthetically produced.
Menopur is a mixture of FSH and LH.
Side effects from gonadotropins may include local irritation at the injection site, and with hormone changes, mood swings, and hot flashes occasionally. Overstimulation of the ovaries (hyperstimulation) may also occur. If the ovaries become overstimulated, treatment with gonadotropins may have to be stopped and the cycle cancelled or what is more common now, for the embryos to be frozen and transferred at a later date.
b) GnRH Agonists – Synarel (Nafarelin) Suprefact (Buserelin Acetate) or Lupron (Leuprolide Acetate) more
These medications cause suppression of ovarian function by turning off the release of FSH and LH by the pituitary gland. This occurs usually within two weeks after starting treatment. Synarel is administered as a nasal spray. Women who require Lupron can be taught to self-inject this medication subcutaneously while Suprefact can be administered by either route.
Side effects associated with these medications are uncommon. Occasionally women experience hot flushes, a decrease in libido (sex drive), or local reaction at the injection sites. Rarely, a rash may be associated with the use of these drugs.
c) GnRH Antagonists – Orgalutran (ganirelix acetate) or Citrotide (cetrorelix acetate) more
These medications similarly suppress the release of LH from the pituitary gland and therefore prevent hormonal changes leading to the release of the eggs until more follicles (hence, eggs) can mature during gonadotropin stimulation.
d) Human Chorionic Gonadotropin (hCG) is one form of “trigger shot” given and is carefully timed and used to act as the final follicle maturing step more
HCG is a hormone that acts in the same way as the natural hormone LH which is normally produced by the pituitary gland and acts as a final “driving mechanism” to mature the eggs.
HCG is given by subcutaneous injection to the abdomen or thigh. Following the administration of HCG, aspiration of follicles to retrieve the eggs is performed approximately 34 to 36 hours later.
Side effects associated with hCG include mild fatigue, depression, or some discomfort in the area of the injection. Lower abdominal bloating or pressure may also occur.
(ii) MONITORING OF THE OVARIAN STIMULATION
a) Blood Tests when indicated are done in the early morning at Lifelabs. Blood tests are now limited to obtaining initial baseline levels, and occasionally at the end of the cycle.
b) Ultrasound Examination
Vaginal ultrasound is performed in the early morning on approximately alternate days and is used to monitor, count and measure the development of ovarian follicles (fluid-filled sacs which contain the eggs). This frequent monitoring, has effectively eliminated the need for second daily blood draws. more
Ultrasound examinations are performed, by Dr Cheung, as indicated, once monitoring of follicle development begins. Occasionally, unscheduled ultrasound examinations may be necessary. Therefore, women need to be available almost daily once monitoring begins except perhaps for the first 3-4 days.
An ultrasound probe is inserted into the vagina which most women find to be less uncomfortable than a pap test.
The developing follicles are recorded in terms of size and number . Unlike an abdominal pelvic ultrasound, an empty bladder is required. A feeling of pressure may be associated with this procedure, but it is otherwise painless.
It is important to know that not all follicles will necessarily contain a mature egg (oocyte) although this is rare and the more likely issue is that not all eggs may be mature at the time of retrieval. In the stimulation stage , what is aimed for is the maximum number of mature follicles and hence mature eggs
c) Egg retrieval will occur approximately 36 hours after the “trigger shot” of HCG (or alternate medication) which is given when the follicles are considered of optimal size
Cancellation may be indicated if the ovaries do not respond sufficiently to stimulation more
Not all couples proceed through the monitoring phase successfully. Cancellation may be necessary if the ovaries do not respond enough to the medications or if they respond too much. Cancellation occurs in approximately 10 percent or less of cycles.
When the ovarian follicles are mature (correct size as seen on the ultrasound or appropriate hormone levels according to the blood tests), ovulation is triggered by an injection of human chorionic gonadotropin hormone (hCG) in the late evening.
This is an ultrasound guided procedure done under light sedation and local anaesthetic. The fluid removed from the follicles is examined by the embryologist to identify and collect the eggs more
Women are admitted to Grace Fertility Centre as outpatients in the morning one hour prior to oocyte pickup (oocyte retrieval).
You must be fasting for at least 6 hours. An intravenous infusion (IV) is started before this procedure and sedatives are given.
Your partner may be present for this procedure. The amount of discomfort that can usually be anticipated is similar to that experience during a dental procedure under local anesthetic.
To retrieve oocytes (eggs), a vaginal ultrasound probe is used to guide the aspiration needle. Oocytes are removed from the follicles by suction. This technique is known as follicle aspiration.
After sedation and pain relief has been given, the aspiration needle is inserted into each follicle. Suction is used to drain the fluid from follicles into a test tube. A laboratory scientist examines the fluid under a microscope to identify the eggs (oocytes).
The follicle numbers on ultrasound will roughly correspond to the number of eggs retrieved, but all of these may not be mature and therefore suitable for IVF or ICSI
a) Progesterone is used following retrieval to support the lining of the uterus and must be continued when pregnant more
Progesterone is produced naturally in a normal ovulatory cycle but in a controlled stimulated cycle this has to be provided by medication. Thus, when fertilization does occur, the developing embryo will find the lining of the uterus receptive to implantation and growth.
Progesterone is usually given by the vaginal route although it can also be administered by daily intramuscular injection. Women are given progesterone vaginal pessaries commencing the day after the oocyte (“egg”) retrieval procedure.
Side effects associated with progesterone include fatigue, dizziness, bloating, and breast tenderness. Progesterone is continued every day until the end of 10 weeks of pregnancy or the result of a negative pregnancy test.
b) Estradiol (Estrace) more
Estradiol is a hormone which continues to be produced after natural ovulation and then during the developing pregnancy.
There is some evidence that additional support may increase success in an IVF cycle and there is no evidence of any detrimental effects. Estradiol (Estrace), if applicable, is taken orally or dermal Estogen patches applied before and after oocyte retrieval.
Just after egg retrieval the male partner provides an ejaculatory sperm sample that will be prepared by the lab staff for the subsequent fertilization process. In the afternoon of the same day the sperm preparation is used to either directly fertilize the eggs, or in the case of intracytoplasmic sperm injection (ICSI) to inject or introduce a single sperm into the egg under high power microscope with the use of robotic arms. See IVF Lab Section
The following morning the eggs are examined under the microscope to confirm normal fertilization more
All men involved in an IVF cycle are advised to refrain from ejaculation (“save up”) for three days prior to the expected day of egg pickup. This is to ensure that enough sperm will be available for fertilization of the eggs.
The semen sample is normally supplied shortly after the oocyte pickup. Sperm from the specimen are washed by an IVF scientist and then placed into the culture dishes along with the oocytes. These dishes are kept in an incubator in the IVF laboratory. If intracytoplasmic sperm injection (ICSI) is being used or has been recommended as part of your treatment, then you will have been provided with a separate explanatory leaflet on that topic and asked to sign a consent form for that laboratory procedure.
Occasionally, a man’s sperm sample provided on the day of oocyte retrieval is substantially worse than expected, and the IVF treatment plan must be revised and ICSI recommended. In this unfortunate situation, the laboratory or medical staff will endeavor to contact the couple to fully explain the situation, answer all questions and concerns, and obtain a duly informed consent without coercion. The timing of ICSI in relation to fertilization success is crucial and if the couple cannot be contacted in a timely manner, then the laboratory staff has the discretion to proceed with ICSI. The procedure will be done in this unusual situation without prior payment; however payment for ICSI must be made in full prior to embryo transfer. This situation is outlined in the consent document “Consent to undergo a treatment cycle of In Vitro Fertilization (IVF) section 9.. Not all eggs become fertilized and/or grow to the expected cell stage (embryo) at this time. Refer to Fertilization and Development under LAB
If the embryos develop and divide properly, transfer is usually performed either on the third day or the fifth day after oocyte pickup. Patients that have many high score embryos usually will proceed to embryo transfer on day five after “oocyte pickup” This blastocyst stage is a better predictor of the most viable embryos for transfer short of doing PGS. more
After Day 3 the embryonic genome ‘switches on’ so it means the embryos have progressed through this stage.
Whether done on Day 3 or Day 5, the embryo transfer procedure is performed by the same technique. Embryos are placed in a fine plastic tube called a transfer catheter by a laboratory scientist. The doctor then passes this catheter through the woman’s cervix into the uterine cavity.
Gentle pressure is applied to the end of the catheter and the embryos are transferred into the uterus in a drop of fluid. Following this procedure, the woman rests for a short time (half an hour to an hour).
No anesthetic or medication is required for this procedure. Usually transfers are painless. The partner is encouraged to be present. The maximum number of embryos transferred is usually three with female age as a major deciding factor.
is available to couples who have surplus Day 5 embryos(blastocysts). With the recognised risks of multiple pregnancy, single embryo transfer (SET) is the preferred approach but is dictated by the woman’s age, the absence of a history of previous failed cycles and whether there are remaining blastocysts for freezing Approximately 50 percent of couples would be expected to have embryos available for freezing more
It is important to note that not all embryos are suitable for freezing.
Assisted hatching is a procedure of creating a small opening in the embryo’s shell, called the zona pellucida. The purpose is to assist the embryo to escape from the zona (hatching), which is needed for the embryo to implant. The procedure is done now more as a preparation for PGS.
GUIDELINES FOLLOWING EMBRYO TRANSFER more
A clear, pinkish discharge or spotting may appear following embryo transfer for 24 to 48 hours. This is quite normal. Spotting occurs when the cervical canal has been touched by the transfer catheter. Excessive bleeding should be reported to the IVF team.
Couples are advised to refrain from intercourse for at least one week following transfer. Bouncing activities such as horseback riding or aerobics should be avoided until the outcome of the IVF cycle is known. Otherwise, you may resume normal activities.
Progesterone suppositories may delay a menstrual period even if pregnancy does not result from an IVF treatment cycle. Thus, a delayed period does not necessarily mean that a pregnancy has occurred. Progesterone suppositories should be discontinued only when the pregnancy test is negative. If a pregnancy is diagnosed, women should continue to use these suppositories for the first 10 weeks of pregnancy. There is no known adverse effect of this medication on the developing fetus since it is a natural hormone of early pregnancy.
A blood test known as a beta hCG is performed 14 days after egg retrieval. This measures the level of pregnancy hormone and when positive is repeated three days later to look for a rise in the level.
An ultrasound examination is scheduled approximately 6 weeks after the transfer which confirm the location of the pregnancy in the uterus, the presence of a fetal sac and or heart beat
Note: If you are pregnant, it is important to keep on taking progesterone and Estrace (if prescribed) until the end of the 10th week of pregnancy.
RISKS ASSOCIATED WITH IVF
There are risks with an IVF procedure as with any medical procedure but these are minimal more
- Mild discomfort and bruising of the arm may result from blood tests.
- The drugs used to stimulate the ovaries may cause overstimulation in one to three percent of cases. Ovarian hyperstimulation syndrome (OHSS) may cause degrees of distress from mild lower abdominal / pelvic pain or cramping, spotting to more severe symptoms including, extreme bloating and difficulties in breathing.. This discomfort is due to the formation of excessively large ovarian follicles or cysts with fluid accumulating in the abdomen. These changes invariably occur only if hCG is administered; rarely, IVF treatment may be interrupted to prevent this from happening or embryo transfer being delayed to a later time by freezing the embryos. Although very uncommon, hospitalization and other therapies may be necessary to treat this condition.
- The technique of vaginal ultrasound-guided oocyte pickup (OPU) is usually associated with some discomfort. If it is significant, additional medication may be given during or after the procedure. In less than one percent of cases, bleeding or a pelvic infection can also occur after oocyte pickup.
- If more than one embryo is transferred, a multiple pregnancy may occur about 25-29% of cases (majority twins). In addition, an embryo may implant in the fallopian tube (1 – 3% of cases). The resulting tubal pregnancy requires medical or surgical removal since it cannot remain in the tube nor be transferred back into the uterus. 10 percent of cycles may be cancelled before oocyte retrieval. This can be for a variety of reasons, and does not necessarily mean that IVF cannot be offered in the future. Rarely, no eggs are obtained from an oocyte retrieval procedure although in instances where their are only one or two follicles this risk of course is higher.
- There are controversies on whether the rate of birth defects is higher in infants conceived through IVF than that of infants conceived naturally, and in addition, whether these concerns are associated directly with IVF and related procedures or related to the characteristics of couples with infertility. As with any pregnancy, no guarantee can be given that the fetus (child) will be normal. NIPT is now offered (>10weeks gestation) which does allow early screening of the common trisomy’s and in addition PGS and PGD are available, where indicated, prior to embryo transfer.
- The stress impact of infertility has been likened to that of receiving a diagnosis of cancer. Calming the mind and body aids in maintaining a positive mental attitude and allaying fear. Mind Body programs, yoga, acupuncture and tai chi are all valid and safe means of reducing stress
- Anxiety is inevitable particularly so in the two weeks after embryo transfer waiting for the pregnancy test. Couples are encouraged to contact GFRM for counseling or appropriate referral for coping with this and with IVF failure should this unfortunately occur.
- GFRM works with a number of qualified and trained personnel who can provide:
A fertility counselling session (3rd party counselling) is required by law for people using donor eggs, donor sperm, or surrogacy. This is to discuss and inform of the many issues that may be socially and legally relevant and that many of us might not think of in the present but that may be relevant in the future.
ASSESSMENT FOLLOWING AN UNSUCCESSFUL CYCLE more
All IVF cycles are reviewed by the IVF team regardless of outcome. A consultation (in person or by telephone) is arranged with you after the review to discuss all issues, concerns, treatment adjustments and future treatment
CONFIDENTIALITY AND PUBLICITY more
All patient information is confidential. However, the program must keep the medical and public communities informed about the status of the program. Any information released about the IVF program and its results is presented only in general terms. Patients’ names are never released. Specific details may appear in professional publications; however, patient identities are not revealed. Complete anonymity is maintained. No information about a patient’s progress or outcome in an IVF cycle is revealed to any other patient in the program.