Intra-Uterine Insemination (IUI) – using partner's sperm or donor sperm
IUI involves the injection of a sample of prepared sperm from the husband or partner(IUI-H) into the woman's uterine cavity around the time of ovulation.
Who is IUI suitable for?
IUI is recommended only if the woman has healthy fallopian tubes, preferably confirmed laparoscopically, and if the man's semen analysis is normal. It may be useful for women who have cervical mucus hostility and in some cases of unexplained infertility.
What does IUI involves?
The chance of success with IUI is enhanced if insemination is combined with ovulation induction using small doses of fertility drugs. These are taken by the woman, and the development of the follicles on the ovary is monitored with ultrasound. The insemination is timed to take place 36-40 hours after administration of another hormone injection which triggers ovulation.
On the day of the planned insemination, the partner provides a semen sample. A concentrated preparation of motile sperm is extracted from the semen sample in the laboratory. The sperm preparation is placed into the uterine cavity by the doctor / IVF nurse by means of a fine catheter inserted through the cervix. In general IUI is a painless procedure, which takes only a few minutes.
IUI using donor sperm?
IUI is also sometimes carried out using the sperm of an anonymous donor (IUI-D) in couples where there is a significant male factor involved.
Is IUI successful?
Yes, for some couples, IUI is a very effective form of treatment provided that the man's sperm and the woman's tubes are healthy.
In Vitro Fertilisation (IVF)
The term In Vitro Fertilisation (IVF) literally means fertilisation 'in glass' and it refers to the process where a woman's eggs are fertilised outside of her body in the laboratory. The resulting embryos are then transferred back into the uterus a few days later.
Who benefits from IVF?
IVF is specially recommended for women with absent, blocked or damaged fallopian tubes. It is also often used in cases of unexplained infertility and can be used in combination with ICSI (intracytoplasmic sperm injection) in cases of severe male factor infertility. ICSI is a variant of IVF and is where single live sperms are injected directly into oocytes (ripe eggs).
There are four steps involved in teh IVF cycle:
- Stimulation of the ovaries to encourage development and maturation of the eggs.
- Retrieval of the eggs
- Fertilisation of the eggs and culture of the embryos
- Transfer of the embryos back into the uterus
Stimulation of the ovaries to encourage development and maturation of the eggs
Under the care of a consultant gynaecologist, the woman is given fertlity medications to stimulate her ovaries to prodice many follicles. Follicles are the small fluid filled structures which develop on the ovaries, each of which hopefully contain eggs.
The number and size of the developing follicles is measured by trans-vaginal ultrasound scans. The exact number of follicles which develop varies between patients, but the average is about 10. the final preparation for egg retrieval involves a hormone injection which mimics the natural trigger for ovulation. Egg retrieval will take place 36-38 hours after this injection.
Retrieval of the eggs
Egg retrieval is a minor theatre procedure which is carried out on an outpatient basis under anaesthesia. The trans-vaginal ultrasound probe is used to visualise the ovaries and a needle attached to the probe is passed through the vaginal wall into the follicles. The fluid within each follicle is aspirated and then examined in the IVF laboratoryfor the presence of an egg. After identification, the eggs are washed and transferred into special culture medium in Petri dishes in an incubator.
Fertilisation of the eggs and culture of the embryos
While the egg retrieval is proceeding, the sperm is also prepared. A semen sample is provided by the male partner and, in the laboratory, a concentrated preparation of the best motile sperm is extracted from the semen sample. This sperm preparation (containing approximately 150,000 sperm) is added to the dishes containing the eggs, and they are incubated together overnight.
In some couples an alternative form of insemination is required called ICSI, which involves injecting a single sperm into each egg using a very fine neddle, rather than mixing the eggs and sperm in a dish.
Irrespective of the method of insemination used, on the moring after egg retrieval, the eggs are examined to see which have fertilised.
Fertilised eggs (zygotes) are then routinely cultured in the IVF laboratory until day 3, at which time the best 1-3 embryos are selected and transferred back into the woman's uterus. For some patients, a blastocyst cycle may have been recommended in which case embryo culture is extended to day 5.
Any additional embryos that are not transferred on either day 3 or day 5 can be frozen.
Embryo Transfer
Embryo Transfer is a simple theatre procedure that does not routinely require anaesthesia. The embryos are placed into the uterine cavity by the doctor / IVF nurse by means of a fine catheter inserted through the cervix. The correct positioning of the embryos is confirmed by abdominal ultrasound, so the woman is required to have a full bladder for the procedure.
ICSI
ICSI is very similar to conventional IVF in that gamete (eggs and soerm) are collected from each partner. The difference between the two procedures is the method of achieving fertilisation.
In conventional IVF, the eggs and pserm are mixed together in a dish and the sperm fertilises the egg 'naturally'. However to have a chance that this will occur, large numbers of actively swimming normal sperm are required. For many couples, the number of suitable sperm available may be very limited or there may be other factors preventing fertilisation, so conventional IVF is not an option. ICSI has provided hope for these couples.
ICSI refers to the laboratory procedure where a single sperm is picked up with a fine glass needle and is injected directly into each egg. This is carried out in the laboratory by experienced embryologist using specialist equipment. Very few sperm are required and the ability of the sperm to penetrate the egg is no longer important as this has been assisted by the ICSI technique. ICSI does not guarantee that fertilisation will occur as the normal cellular events of fertlisation still need to occur once the sperm has been placed in the egg.
Who is ICSI suitable for?
From a patient perspecrive, undergoing an ICSI treatment cycle is exactly the same as a conventional IVF cycle, and the same steps are involved.
Circumstances in which ICSI may be appropriate include:
- When the sperm count is very low
- When the sperm cannot move properly or are in other ways abonormal
- When sperm has been retrieved surgically from the epididymis (MESA/PESA) or the testes
- (TESE/TESA), from urine or following electro-ejaculation
- When there are high levels of antibodies in the semen
- When there has been a previous fertilisation failure using conventional IVF
What does ICSI involve?
From a patient perspective, undergoing an ICSI treatment cycle is exactly the same as a conventional IVF cycle. Patients should however be aware of the risks associated with ICSI.
Circumstances in which ICSI may be appropriate include:
- Stimulation of the ovaries to encourage development and maturation of the eggs
- Retrieval of the eggs
- Fertilisation of the eggs and the culture of the embryos
- Transfer of the embryos back inot the uterus
Intracytoplasmic Morphologically-Selected Sperm Injection (IMSI)
IMSI is a new technique that allows a better selection of the sperm that is going to be micro-injected during an IVF or during egg donation.
TESE Sperm retrieval
What is TESE?
TESE is a surgical sperm retrieval produce used in fertility treatment for men who have no sperm in their ejaculate.
Who is TESE suitable for?
TESE is used for men with both obstructive and non-obsturctive azoospermia. These men have no sperm in their ejaculate because either there is a blockage in the route between the site of sperm production (the testes) and ejaculation or because there is a partial or complete failure in sperm production in the testes.
What does TESE involve?
Under the care of a consultant urologist, TESE is a minor theatre procedure carried out on an outpatient basis under local anaesthesia.
Sperm are retrieved from the testes and can be used to achieve fertilisation of eggs in the laboratory. However, because the nubers of sperm retrieved is often very low, it is necessary to combine TESE with ICSI.
When is TESE carried out?
In consultation with the urologist, the doctor may advise that TESE is carried out in advance of any fertility treatment to confirm that sperm production is occurring. If suitable numbers of sperm are identified on this occasion, it is sometimes possible to freeze the testicular extract and to thaw and use this sample for subsequent treatment. More commonly however, once it has been confirmed that sperm production is occurring, the TESE procedure is repeated on the day of the egg retrieval and the fresh sample used for ICSI.
Again, providing that there are suitable numbers of sperm present, the sample can sometimes be frozen for use in future treament cycles.
Embryo Grading
After insemination by IVF or ICSI, fertilised eggs are then routinely cultured in the laboratory for 3 days before being transferred back into the woman's uterus.
Before embryo transfer, the embryos are graded by a specially trained embryologist in order to select the embryos with the best chance of implanting in the uterus and forming a healthy baby.
The main criteria used to grade embryos on day 3 are:
The number of cells which the embryo has.
Embryos showing good development will generally have 6 to 8 cells after 3 days of growth. Embryos with fewer cells may still be good, but they are less likely to continue normal development.
The amount of 'fragmentation' that the embryos show.
Fragmentation describes the way that cells of an embryo spilt off into fragments. A small amount of fragmentation is normal, but excessive fragmentation suggests that the embryo will have a lower chance of continuing normal development.
Blastocyst Culture and Trasfer
What is a blastocyst?
The term 'blastocyst' refers to the human embryo 5-6 days after fertilisation.It is the stage of development that the embryo must reach before it can implant in the uterus.The structure of the blastocyst is more complex than earlier embryo stages because as well as increasing in cell number, the cells have become organised into 2 types, the trophectoderm, whose main role is in the implantation into the uterine lining and the inner cell mass which will give rise to the foetus itself.
The egg is fertilised following ovulation from the ovary and the embryo goes on to divide (cleave) as it travles along the fallopian tube. Blastocyst formation occurs asthe embryo reaches the uterus.
What's so special about blastocyst culture in an IVF setting?
Standard practice in IVF involves the replacement of embryos into the uterus after 3 days when the embryos are at the cleavage stage of development.Blastocyst transfer however involves extending the period that the embryos are cultured in the laboratory to 5 or 6 days.
Why extended the time that the embryos are cultured in the laboratory?
It is known that a lot of embros are destined to arrest at early stages so extended culture allows the embryologist to identify which (if any) of a group of embryos have the best potential for implantation by identifying those which form a normal blastocyst in culture.
Transferring embryos at the blastocyst stage also provides a better co-ordination between the embryo back in the right place (the uterus) at the right time(blastocyst stage).
What are the benefits of blastocyst culture?
Overall, if you have a normal blastocyst for transfer on day 5, the chances of pregnancy are higher (in our hands) than if you have embryos transferred on day 3.However, the chances of having no embryos for transfer at all are also higher.
Semen Freezing
Semen freezing is useful for the man who finds it difficult to ejaculate on demand and where it may result in an inability to produce a sample on the day of egg collection.However, the quality of the semen is reduced after freezing, so if possible fresh samples are preferred on the day required.
Embryo Freezing and replacement
In a typical IVF or ICSI treament cycle, the woman's ovaries are stimulated to produce many eggs. Following fertilisation and embryo culture, the best embryos are selected for embryo transfer. For about 50% of couples, there will also be good embryos which are surplus to those required for embryo transfer. These embryo can be frozen at this point for future use.
Embryo freezing (cryopreservation) is a method of preserving the viability of embryos by carefully cooling them to very low temperatures (-196. c). This is carried out in the laboratory using specialised freezing equipment and the embryos can then be safely stored in liquid nitrogen for extended periods.
What are the benefits of embryo freezing?
The main benefit of embryo freezing is the option to have frozen embryos thawed and transferred to the woman's uterus in the future without having to undergo stimulation of the ovaries or egg retrieval. It is also possible that there may be enough frozen embryos for more than one subsequent cycle.
What does a frozen embryo transfer cycle actually involve?
Frozen embryo transfer cycles are relatively simple. In some cases, the woman's natural cycle will be monitored by ultrasound to assess the development of the lining of the uterus and to determine the timing of ovulation and hence embryo transfer. In other cases, depending on the woman's history a more hormonally controlled cycle may be warranted.
The decision regarding the most appropriate treatment will be made in consultation with the clinician.
Are there any disadvantages to embryo freezing?
Approximately 70% of the embryos that are frozen will survive the thawing process. This does however vary between patients and it is possible that none of a couple's embryos will survive the freezing and thawing process.
How successful are cycles involving the transfer of frozen / thawed embryos?
Overall, frozen embryos have a slightly lower chance of implanting than fresh embryos. This is mainly because in general the best embryos in a group will already have been trasferred on the fresh embryo transfer.
Our DOP Programme is an option for women who have:
- Primary ovarian failure
- Premature menopause (before the age of 40)
- Ovarian damage following surgery, radiation or chemotheraphy
- An inheritable genetic disorder like haemophilia
- Repeated failure to respond to ovarian stimulation in an IVF programme
- History of recurrent miscarriage.
Women who do not produce eggs or those with poor quality eggs may be advised to seek treatment with donated eggs. Our standard policy is to offer donation to women less than 50 years of age.
Egg donation has become an increasingly popular option because it has higher success rates than IVF cycles using the woman's own eggs. Egg donation also allows for strong biological and developmental relationships within the family because donor eggs are fertilised with the male partner's own sperm through ICSI, matured to the embryonic stage and then placed in the partner's uterus, providing her with the same experience of pregnancy as natural conception.
Factors Affecting the Outcome of Treatment
Age
As with natural conception the chances of success following any fertility treatment decline with the age of the woman. There is much documentaion to show a significant drop in the pregnancy rate for women over the age of 40. Unfortunately the risk of miscarriage in this group is higher; therefore the percentage of women having a live birth decreases.
Number of Eggs Collected and Embryo Quality
The number of healthy eggs collected and the number of normally fertilised eggs also affect the outcome. The number of embryos available affects the chances of success for transfer and the number transferred. If only one embryo is available for transfer the chance of success are lower. The possible disadvantage of transferring more than one embryo is a multiple pregnancy. Approximately 20% of pregnancies following assisted conception are twins.
Ovarian Reserve
In a woman with normal menstrual periods, apart from her age the second most important element that affects IVF outcome is the ovarian reserve – the number of potential eggs available in the ovary – which is usually measured by checking the AMH.
How successful are cycles involving the transfer of frozen / thawed embryos?
AMH operates on a scale from low to high. Women with reduced ovarian reserve have a lower, but reasonable chance, of achieving live birth.
Complications in Fertility Treatment
Multiple Pregnancy
One of the complications of assisted reproduction is the increased incidence of multiple pregnancy. Concerns about multiple pregnancy arise because it is associated with a great incidence of complications.
Problems are more commonly seen in triplet or higher order multiple pregnancies but may also occur with twin pregnancies. Because of the greater chance of pre-term labour and delivery, there is an increased risk of the babies being born before they are mature enough to survive and a greater risk of complications associated with prematurity if they do.
The maximum number of embryos transferred is generally three and therefore high order multiple pregnancies are not common. Women aged 37 years or under are usually advised to have two embryos transferred.
When 3 embryos are transferred in this younger group of patients, the overall chances of success are not significantly increased but the chances of multiple pregnancy are greater.
In women over 37 the implantation rate is lower which accounts for the reduced pregnancy rate. In an attempt to improve the overall chances of a pregnancy most women over 37 are usually advised to have 3 embryos transferred, if they are available on day 3. We would not generally recommend this to women of all ages if the embryos are grown to blastocyst stage.If a woman conceives with multiple pregnancy, careful antenatal management is advised.
Miscarriage
The incidence of misccarriage in women who conceive naturally is approximately 25%. With assisted reproduction treatment this statistic is not significantly different, although in women over 40 there is an increased risk. Pregnancies should be monitored to ensure that the pregnancy is proceeding normally.
Ectopic pregnancy
An ectopic pregnancy is a pregnancy that occurs somewhere other than in the uterus, most commonly in the fallopian tubes. The incidence of ectopic pregnancy with assisted conception treatment is approximately 2.5%. It is potentially a serious condition but will often be detected very early in the pregnancy by ultrasound scan. It is recommended that a detailed vaginal ultrasound scan be carried out 3 weeks after confirmation of pregnancy.