In a woman who ovulates normally, follicle-stimulating hormone (FSH) brings about the growth of a single follicle at the start of every menstrual cycle. Follicles are fluid filled sacs within the ovary, each of which contains an immature egg. Once the follicle reaches a certain size (usually 18mm) a sudden mid-cycle surge of luteinising hormone (LH) causes ovulation (rupture of the follicle, releasing the egg from the ovary). In some women ovulation does not occur regularly, making it difficult to conceive (most commonly in women with polycystic ovarian syndrome or PCOS).
Ovulation induction (the simplest form of fertility treatment) is recommended for women who are not ovulating. Clomid tablets or low dose FSH injections are administered with the aim of stimulating the growth of one or two follicles. Follicle tracking scans are carried out to make sure the treatment is working, i.e. that follicles are, in fact, growing and that not too many follicles are growing (if three follicles grow, a triplet pregnancy could result). Once the follicle is big enough ovulation is triggered with an injection of HCG, (this has the same biological action as LH). Ovulation will take place over the next thirty six hours and the couple are advised to have intercourse in this period.
Administration of clomid without follicle tracking scans and a HCG trigger is often inefficient (because follicles may or may not grow and may or may not rupture), and occasionally dangerous because triplet pregnancies can result. Follicle tracking by experienced fertility clinicians is important.
A typical OII cycle with clomid takes place as follows:
The woman takes Clomid daily for 5 days, starting on cycle day 2 (the second day of her period)
She attends for a follicle tracking trans-vaginal scan on cycle day 12
1 or more further follicle tracking scans may be necessary, depending on how quickly the follicles start growing
Once the follicle has reached a size of 18mm a hCG injection is given and the couple are advised to have intercourse the same evening and the following day
A pregnancy test is carried out two weeks later
IUI combines ovulation induction with introduction of purified semen into the uterus on the day of ovulation.
Ovulation induction involves low dose FSH injections (rather than Clomid) and follicle tracking scans and an hCG trigger are employed – exactly as in OII cycles. As in OII cycles is it not safe to proceed if more than 2 preovulatory follicles develop, due to the risk of multiple pregnancy.
IUI treatment is often recommended:
A typical IUI cycle takes place as follows:
The woman attends the clinic for a base line scan (on cycle day 1 or 2 or up to 10 days before the start of the period) to make sure that no temporary cysts are present which could interfere with treatment.
She starts low does FSH injections on cycle day 2 (1 injection per day) and continues these injections until advised to stop.
She attends for a follicle tracking scan on cycle day 9 - further scans may be necessary depending on how quickly the follicle(s) starts growing.
Once the follicle is 18mm in diameter a hCG trigger is administered.
The couple attend the unit the following day and the man produces a semen sample which is processed in order to produce a much smaller preparation of highly purified and motile sperms.
This sperm preparation is introduced into the uterus using a soft, flexible plastic catheter (fine tube); the experience for the woman is similar to that of a smear test.
Two weeks later, a pregnancy test is carried out.
Sometimes, if too many follicles grow in an IUI cycle (so that triplets are a risk) one or more eggs can be removed to avoid cancellation of the cycle. The eggs are removed by passing a long fine needle through the vaginal wall (under ultrasound guidance) and using suction to remove follicular fluid and egg from each unwanted follicle. The aspiration procedure may be slightly painful and can take between 2–5 minutes depending on the number of follicles to be aspirated.
In order for a pregnancy to occur naturally the ovary releases an egg at ovulation which travels through the Fallopian tube where it meets the sperm and is fertilised. The fertilised egg enters the uterine cavity where it implants in the thickened lining of the uterus (the endometrium). In IVF, the ovaries are stimulated to produce a number of eggs which are collected and mixed with sperm in the laboratory, allowing fertilisation to occur. The developing embryos are monitored closely and the healthiest embryos are then transferred into the uterus to allow implantation to occur.
IVF treatment is often recommended in the following cases:
There are several stages to an IVF cycle. The average treatment cycle takes approximately eight weeks from the start of medications until a pregnancy test is taken.
First Stage: Pituitary Gland Suppression (‘Down-Regulation’)
In the most commonly used treatment protocol (‘long protocol’) the woman takes the combined oral contraceptive pill for approximately three weeks, starting with the first day of her period. This prevents the development of ovarian cysts as the treatment cycle begins.
Following this she commences a daily injection of gonadotrophin-releasing hormone (GnRH) analogue (Buserelin) which temporarily makes the pituitary gland incapable of releasing LH, thus preventing early ovulation.
Some patients experience minor side effects such as hot flushes while taking Buserelin.
Second Stage: Superovulation
During this stage the ovaries are stimulated to produce a large number of mature eggs. A daily injection of FSH+/- LH is commenced which stimulates the growth of several follicles, generally between 10 and 20, each containing an egg.
Trans-vaginal ultrasound scans are used to monitor the growth of the follicles. When the follicles reach an appropriate size (approximately 18mm) the GnRH analogue and FSH+/- LH injections are stopped and an injection of hCG (human Chorionic Gonadotrophin) is given to bring about final maturation of the eggs.
Third Stage: Egg Collection
Approximately 36 hours after the hCG injection, egg collection takes place and usually occurs in the morning. This is a minor procedure carried out under light sedation in our theatre at CFC. A slim trans-vaginal ultrasound probe is used to guide a fine needle through the vaginal wall in order to drain the fluid from each follicle (which should contain an egg). The procedure takes 15-30 minutes patients are allowed home approximately one hour after the procedure.
Fourth Stage: Insemination
On the morning of the egg collection the male partner is asked to produce a semen sample which is then washed and prepared. The best quality sperm are then mixed with the retrieved eggs in a petri-dish containing a high quality culture medium and placed in an incubator to allow fertilisation to occur.
The embryologist examines the eggs microscopically the following day to check for fertilisation. Under normal circumstances 80% of eggs will fertilise.
Fifth Stage: Embryo Culture and Transfer
The embryologists examine each fertilised egg daily to monitor progress and development and communicate with the couple by telephone to keep them updated during this time. The best quality embryos are graded based on microscopic appearance and one or two of the best quality embryos are selected for transfer into the uterus. Embryo transfer usually occurs three or five days after egg collection.
Embryo transfer is a simple out-patient procedure and no sedation is necessary. Similar to a smear test, a speculum is used to visualise the cervix. The embryos are picked up, in a tiny drop of culture fluid, in the tip of a fine plastic transfer catheter. This catheter is passed carefully through the cervical canal and into the uterine cavity where the embryos are deposited.
The number of embryos transferred depends on the apparent quality of the embryos and the female partner’s age. The final decision as to whether to transfer one, two or (rarely) three embryos is made by the doctor and embryologist who try to maximise the chance of conception but minimise the chance of a multiple pregnancy (e.g. triplets).
Sixth Stage: Luteal Phase and Pregnancy Test
Eighteen days after egg collection the couple should perform a urine pregnancy test and inform the clinic of the result. The time between embryo transfer and pregnancy test is often the most stressful period of the treatment cycle.
In the week following embryo transfer, patients should avoid vigorous physical activity, swimming, baths and sexual intercourse. A number of medications are prescribed to help support the implantation process.
Two weeks after a positive pregnancy test a trans-vaginal ultrasound scan is performed to assess the pregnancy. At a follow-up ultrasound scan two weeks later the fetus should be visible and heart activity should be present.
ICSI is a variant of IVF carried out when semen quality appears poor.
The female partner’s treatment is carried out in exactly the same way as for ‘ordinary’ IVF until the eggs are collected. Then an additional laboratory procedure is necessary to help the sperms fertilise the egg.
This involves directly injecting a single moving sperm it into each of the collected eggs. Once the procedure is complete, the eggs injected with sperm are monitored over a 24 hour period to check if fertilisation has occurred. Click here for video clip.
The fertilised eggs are then transferred back into the female partner on either day 3 or day 5 following egg collection (as per IVF).
Surgical sperm retrieval is a technique for collecting sperm from men who have no sperm in the ejaculate, either congenital or acquired as a result of vasectomy. In this procedure, a fine needle is inserted through the skin of the scrotum to aspirate the sperm from the epididymis. The procedure is performed in the clinic under sedation and local anaesthesia.
TESE is generally performed when PESA is unsuccessful. In this procedure, a small incision is made in the scrotum and testis and a biopsy of testicular tissue is taken. This tissue is examined carefully under the microscope for motile sperm, which are extracted and then used in an ICSI cycle. The procedure is performed in the clinic under sedation and local anaesthesia.
Microsurgical Testicular Sperm Extraction (Micro-TESE)
Micro-TESE is a more advanced procedure for men whose basic problem is failure to produce sperm cells. The procedure involves carrying out targeted dissection of tiny tubes within the testicle, which are more likely to contain sperm. A high powered microscope is used during the procedure to distinguish between healthy and unhealthy tissue. The healthy tissue samples are then examined in the laboratory. If viable sperm is found, it is prepared and frozen for use in a subsequent IVF cycle.
For IVF and ICSI Success Rates at Cork Fertility please refer to Success Rates section here.
All forms of IVF are relatively inefficient and not guaranteed to produce a successful pregnancy. At best, the chance of a successful pregnancy after a cycle of IVF is only 50%. The chance for some couples will be far less than 50% (where the female is older than 35, and/or has poor ovarian reserve, and/or has severe endometriosis).
Sometimes good quality embryos are transferred and there is no obvious reason for implantation failure. In these cases, the couple would be encouraged to try again.
If you do not achieve pregnancy on the first attempt, your treatment cycle will be reviewed with you at a post treatment consultation and your treatment regime may be modified for the next cycle. The age of the female partner is a critical factor in determining your chances of success with IVF and you will be given an indication of your individual chance of success at consultation.
Risk of multiple pregnancy
Assisted conception treatments are associated with an increased risk of multiple pregnancy. At Cork Fertility, about 22% of IVF cycles result in twin pregnancies and less than 0.5% in triplet pregnancy. Multiple pregnancy carries a significant risk to the mother and babies. Multiple pregnancies frequently deliver early (often by caesarean section) with the newborns being cared for in the neonatal care unit.
At Cork Fertility, for those we feel are at high risk, we try to reduce the risk by culturing embryos to blastocyst stage and selecting the embryo for transfer that is most likely to result in a healthy baby. Our Elective Single Embryo Transfer programme (e-SET) has success rates of 62% live birth rate.
Nevertheless, multiple pregnancies do occur. For some, delivery of healthy twin babies is a welcome bonus but for others it is stressful and exhausting. The clinicians will discuss with each couple whether one or two embryos will be transferred. Our aim is to give each couple the best chance of achieving a viable pregnancy, but preferably resulting in the delivery of a single healthy baby.
Risk of Ovarian Hyperstimulation Syndrome (OHSS)
OHSS is a serious complication of IVF and ICSI and tends to affect women who have developed a large number of follicles during the treatment cycle. Fluid accumulates in the ovaries (which become swollen) and in the abdominal cavity leading to abdominal swelling and discomfort. If OHSS is very severe, blood clotting problems can develop which can cause stroke and very rarely, death.
Patients who become unwell with OHSS may require hospitalisation for approximately one week. Pregnancy exacerbates OHSS and patients at risk (those who have produced a large number of follicles and eggs), may have an egg collection with no embryo transfer – all viable embryos being cryopreserved so that they can be transferred safely at a later time.
Risk of Egg Collection
There is a very small risk of pelvic infection from egg collection. The vagina is cleaned before the procedure but it is possible for bacteria to be introduced by the needle as it passes into the ovary. Antibiotics are administered on the day of egg collection to further reduce this risk.
It is also possible that the egg collection needle could cause internal bleeding that would, in rare circumstances, necessitate an operation.
Pre-implantation genetic diagnosis (PGD) is diagnosis of a genetic condition prior to achievement of a pregnancy. It is a technique that enables couples who are known to be at risk of or have a specific inherited condition to avoid passing it on to their children. The PGD process involves generating a number of pre-implantation embryos through IVF treatment and checking the genes of those embryos for the condition involved before transferring them to the uterus of the female partner.
Genetic testing of embryos may be recommended where:
Couples already have a child with a serious genetic condition
Couples have a family history of a serious genetic condition or have the condition themselves
Couples have found out that they are both carriers for the condition
Performing PGD prior to implantation of embryos will reduce the risk of having an affected pregnancy. Cork Fertility offers PGD to couples at high risk of producing a child with a genetic disorder. We can carry out PGD for single gene disorders including; cystic fibrosis, fragile X syndrome, Duchenne muscular dystrophy and myotonic dystrophy, Tay-Sachs disease, beta-thalassemia, hemophilia A, and sickle cell disease.
PGD involves one extra step within an IVF cycle. Following egg collection, the eggs are fertilized with prepared sperm to create embryos. These embryos are cultured and monitored for progression. After either three or five days, embryos which appear to be developing normally are suitable for PGD embryo biopsy and genetic analysis.
Embryo biopsy involves making a small opening in the zona (shell) which surrounds the pre-implantation embryo using a laser. On day 3 there are usually 5-8 cells present and biopsy on day 3 involves removing one of these cells (occasionally a second cell may need to be removed); the remaining cells are capable of developing normally and forming a complete and normal pregnancy. Biopsy on day 5 involves removing several cells from the more than 100 that are present at that (blastocyst) stage.
The genetic analysis of each removed cell takes place at a specialist genetic centre in the UK. The biopsied cells are analysed for the presence of specific changes in the genetic code that causes the disease and the results are sent to Cork Fertility prior to embryo transfer. Embryos which are diagnosed to be free from the specific genetic disorder are safe to be used. Undiagnosed embryos are not transferred.
Limitations of PGD
Couples are advised that pre-implantation analysis is not yet considered to be a standard technique and consequently we highly recommend that patients who have successfully undergone PGD have prenatal testing using CVS or amniocentesis. Prenatal testing will reveal whether or not the PGD testing analysis was correct and confirm whether or not the fetus has been affected by the genetic disease tested.
PGD is aimed at reducing your chances of having a child with a genetic disease, however it does not test for all birth defects. It is not possible to obtain a diagnostic result from every cell tested. Approximately 10% will be undiagnosed after PGD. Of those embryos diagnosed, PGD for a single gene disorder detects about 95% of affected embryos. This means that misdiagnoses can occur. PGD is not a substitute for prenatal testing.
Download PGD Information Booklet here.
For further information about the PGD programme at Cork Fertility, please contact us.
Pre-implantation genetic screening (PGS) is a complex form of IVF treatment which is recommended for couples who have experienced recurrent miscarriages or repeated unsuccessful IVF cycles. Screening embryos for genetic defects before transferring them significantly increases the chance of a successful pregnancy and decreases the chance of miscarriage. It also considerably reduces the chance of having a baby with genetic problems.
With PGS, embryos are generated using a form of IVF treatment known as intracytoplasmic sperm injection (ICSI). They are then screened to find out if they have the correct number of chromosomes. Embryos with a normal number of chromosomes are then transferred into the woman’s uterus.
PGS can be recommended in the following situations:
Download PGS Information Booklet here.
The success of an IVF laboratory depends critically on the training and skill of the staff employed and the conditions present during the processing of gametes and embryos.
Cork Fertility employs highly trained scientists enabling the centre to offer the highest standards and latest techniques in Assisted Reproductive Technology.
We employ strict quality control measures, monitoring our equipment, consumables and processes daily. The laboratory air quality is monitored to ensure we maintain the right culture conditions for the embryos, which are sensitive to fluctuations in temperature/light/ph. We have invested in k-systems bench-top incubators which allow for culturing of embryos in individual compartments for maximum security and environmental control.
Laboratory details for each treatment cycle are recorded in a comprehensive database; this allows for a quick and thorough analysis of specific lab performance indicators and ensures we assess our successes and failures quickly and reliably. We are aware of the investment couples make in their endeavours to have a child and do our utmost to help them achieve this goal.
Conventional IVF involves culturing embryos for 3 days after egg collection, with embryo transfer on day three. Blastocyst culture involves growing embryos in media for a further two to three days longer than average to allow their cells to divide many more times. The embryologist examines each stage of development and selects the embryo(s) which are most likely to result in a pregnancy, for transfer. This extended culture allows the trained eye of the embryologist to choose the very best in order to maximise the chance of pregnancy.
Cryopreservation is a term used to indicate the freezing of embryos in order to preserve them for future use. Our cryopreservation programme allows us to preserve additional embryos or sperm that have not been required in a fresh cycle. For patients, this means an extra opportunity to return for treatment without having to undergo ovarian stimulation.
At Cork Fertility, we use a technique known as vitrification to freeze embryos. This involves freezing the embryo about 600 times faster than in conventional slow rate freezing. This ultra-rapid process is so fast that it allows no time for intracellular ice to form. As a result, vitrification avoids trauma to the embryo. In conventional (slow-rate) freezing, 20-30% of embryos do not survive the freeze-thaw, and those that do survive have less than half the likelihood of generating a pregnancy as fresh embryos. In contrast, vitrified embryos have a greater than 80% freeze-thaw survival rate, and a pregnancy generating potential that is comparable to fresh embryos.
Cork Fertility was the first to introduce a successful Blastocyst Programme to Ireland where embryos are cultured for 5-6 days in the laboratory before transfer. This has lead to Cork Fertility actively promoting blastocyst culture with elective Single Embryo Transfer (e-SET).
The e-SET programme at Cork Fertility is highly successful. Currently the live birth rate for first time IVF/ICSI treatment is 63% for women aged 40 and under.
Extended culture allows the scientist to choose the embryo with the best potential to achieve a pregnancy for transfer. Additional good quality embryos that are not transferred in a fresh cycle will be vitrified (frozen) and stored for future use.
These advances have made it possible to reduce the incidence of IVF twin pregnancies for couples without reducing their chance of success. Thus, e-SET is an effective and safe way to build families, one healthy baby at a time minimising risks of pregnancy while maintaining high pregnancy rates.