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A Guide to PGD
In a woman’s normal monthly menstrual cycle a single egg (called an oocyte) is released from a follicle that has been developed in one of the ovaries as a result of a complex interaction between the body’s hormones. Dependent upon the timing and frequency of sexual activity the egg will may be fertilised by her partner’s sperm.
The PGD cycle is quite different than this natural process. It is made up of seven stages:
1. Downregulation and stimulation of the ovaries
2. Egg collection
3. Insemination
4. Fertilisation
5. Embryo biopsy
6. Embryo transfer
7. Pregnancy test
Stage 1 – Stimulation of the ovaries with hormones to produce eggs
To maximise the chance of a successful pregnancy we need to transfer up to two embryos into the womb, which in turn normally requires around four to eight embryos to have been cultivated. To achieve this number of embryos, our scientific team would aim to collect 10 or more oocytes. This means that we need to stimulate the female’s ovaries to produce many more than the usual single oocyte, and we do this by means of hormonal stimulation of the ovaries, using drugs which mimic the hormones you naturally produce.
These hormones are given to you both as a nasal spray and an injection under the skin on the tummy. A detailed treatment schedule (in the form of a calendar) indicating the dates and medication to be used will be given to you the treatment starts. This of course will be designed taking your travel and period dates into account.
Buserelin/ Nafarelin medication This is the medication you will be given. This part of the treatment is known as ‘downregulation’ which:-
Temporarily stops your ovaries from working
Prevents you from releasing the eggs before we have time to collect them
This medication continues throughout the treatment. It is only stopped following your final scan in Cyprus. Instructions to stop this medication will be given by the Cyprus IVF Centre once a decision for egg collection is made.
We perform an internal ultrasound scan after two weeks of downregulation, to check that your ovaries are inactive and contain no large follicles or cysts and that the lining of the uterus (endometrium) is thin.
Please note: It is normal to have a period during this time. It does not mean that the medication is not working, so please do not stop the Buserelin/Nafarelin. If you stop the medication too soon, your eggs could be released before we have a chance to collect them.
In some patients, there may be temporary side effects from this medication. The potential side effects are hot flushes, night sweats and mood swings.
FSH injections
Follicle Stimulating Hormone (FSH) injections are given to you as a daily injection over 10 to 14 days to stimulate egg development in the ovaries. We will teach you or your partner to do this or you can arrange to have the injections at your GP surgery or local hospital.
We will explain the potential side-effects of these injections and monitor your response using internal scans. The first scan is usually done nine days after starting the injections.
Deciding the day of your egg collection
Cyprus IVF Centre (CIC) team of doctors, embryologists and nurses decide the best day for your egg collection. The cycle may be cancelled before egg collection if you under or over respond to the medication.
Late at night and about 36 hours before the egg collection, an injection of hCG hormone is given as a ‘one off’ injection. This medication causes the final stages of egg ripening to take place. The time you need to give yourself this injection at home is very important and will be explained very clearly to you.
Stage 2 – Collection of eggs from the ovaries You are deeply sedated and monitored throughout the egg collection procedure, which usually takes about 15 minutes. Using an ultrasound probe to guide, a fine needle is passed inside the vagina and through the vaginal wall into each follicle, until we have emptied all the follicles in one ovary. The needle is then removed and the procedure is repeated in the other ovary.
Each egg is placed in special fluid and transferred to an incubator. Not every follicle will contain an egg and sometimes no eggs will be found during an egg collection. We will discuss this with you before the procedure.
After the procedure you will rest on a bed in your private room for about one or two hours.
You will be prescribed the hormone progesterone for 17 days following the egg collection to help the lining of your uterus be as receptive as possible to the embryos.
Stage 3 – Insemination / injection of sperm
Your semen sample is prepared by separating the normal and active sperm from the ejaculated fluid. Fertilisation during pre-implantation genetic diagnosis (PGD) treatment will be done by Intracytoplasmic Sperm Injection (ICSI). ICSI involves injecting a single sperm into the centre of each egg to help achieve fertilisation.
Stage 4 – Fertilisation
The morning after injection / insemination of the sperm, the embryologist carefully examines each egg to see if fertilisation has occurred. We will then call you to tell you how many eggs have fertilised.
Rarely, about one in 100 times, none of the eggs fertilise and there are no embryos to be replaced. This is obviously very disappointing. We will offer you the earliest available appointment to see a PGD team doctor and an appointment to see one of our counsellors if this happens.
Stage 5- Embryo biopsy Three to four days after fertilisation the embryos will usually have reached the stage of development where gender selection can take place, normally involving a complex and expensive scientific process called Pre-implantation Genetic Diagnosis (PGD). This involves removing one or two cells from each embryo and analysing the chromosomes in carefully controlled laboratory conditions, during which the ‘X’ and ‘Y’ chromosomes are clearly identified. The removal of up to two cells does not damage the embryo’s development in any way, and each embryo will continue to grow normally. Our aim is to reach this stage with a minimum of two good, healthy embryos of the chosen sex available for the fourth and final stage of your treatment – the transfer of the embryos to the female’s uterus.
The types of tests we perform on the embryos will depend upon the reason behind you having PGD. Apart from sex selection, we are able to screen for any genetic disease that can be tested for.
Stage 6 – Embryo transfer
During embryo transfer we place the best quality embryos into your uterus. This is a much simpler procedure than egg collection and there is no need for an anaesthetic. Ultrasound scan is used through your tummy to help us to transfer the embryos where they would have the highest chance of implanting. A speculum, which is the instrument also used during a smear test, is placed in your vagina to clearly see your cervix (neck of the womb). The outside of your cervix is cleaned and any mucus from inside your cervical canal is removed. This mucus might prevent the embryos getting to where we want them to be in the womb.
The soft catheter, which holds the embryo(s), is inserted the neck of your womb. When we are happy that the catheter is in the best position, the embryos are gently dropped off. The catheter is then removed and checked to make sure all of the embryo(s) have been replaced. This process takes about 5 minutes. It is generally painless although some discomfort comes from the scan probe that pushes down on your bladder which needs to be full for the procedure as well as the speculum in the vagina.
How many embryos will be transferred?
Current HFEA guidelines allow us to transfer a maximum of two embryos in women who are under 40 years of age. Transferring two embryos has been shown to maximise your chances of a successful implantation, while presenting minimal risks of more than a singleton pregnancy. It is important to note that the risk of a triplet pregnancy, however small, is not completely excluded despite the transfer of a maximum of two embryos.
The number of embryos transferred is limited to lower the risk of a multiple pregnancy. Triplet pregnancies have a significantly increased risk of complications including miscarriage, high blood pressure and premature birth and even twins have more problems with delivery and at birth. Premature babies have an increased risk of complications, such as a weakened immune system, physical and mental disability and feeding and breathing difficulties.
What happens after embryo transfer? You will know if the treatment has been successful 10-12 days after embryo transfer.
We appreciate that this wait can be difficult for many people. Please do not be tempted to perform a pregnancy test earlier than advised. The hCG injection can stay in your blood stream for eight to 10 days and this will make the test positive, even if you are not pregnant. Please continue to take progesterone vaginally twice a day.
Unfortunately, there is no evidence that anything you do at this stage will increase the chance of you becoming pregnant. We encourage you to return to work but you may prefer to have a few days off around the time of transfer. Having a bath or sexual intercourse is not known to affect the chances of pregnancy.
What happens if there are spare normal embryos?
It is possible to freeze embryos from a PGD cycle for later use. A frozen embryo, which has been thawed, is less likely to implant into the lining of the uterus than a fresh embryo, especially when it has been biopsied. We are selective about the embryos we choose to freeze but we will attempt to freeze any embryos that are suitable. Embryos are frozen at an extremely low temperature, which makes sure they do not deteriorate over the number of years they are stored. Even if you get pregnant in your initial attempt at treatment, you may wish to use frozen embryos, if possible, to expand your family at a later date. If you have frozen embryos, it is essential that you keep in touch with us to let us know what you wish to do with them and tell us of any changes of address.
Frozen embryo cycle
In a Frozen Embryo Transfer Cycle (FET) we thaw your frozen embryos and transfer any that are suitable into your uterus. Our survival rate is good following thawing, but not all embryos will survive this process. An advantage of a frozen cycle is that we do not need to use hormone injections to stimulate the ovaries nor do any further genetic testing of the embryos.
Stage 7 – Pregnancy test
All women should perform a pregnancy test 12 days after the embryo transfer, even if they bleed before this time. This is essential because some patients could miscarry one of a twin pregnancy or have an ectopic pregnancy. This is an uncommon but potentially serious complication. Please inform us about the results of the pregnancy test whatever the outcome.
A positive pregnancy test
This means that one or more embryos have implanted, but we will not be able to see this on a scan until you are about six weeks pregnant (four weeks after embryo transfer). We will usually scan you to:
See how many embryos have implanted
Have they developed a heartbeat?
Sadly, we sometimes diagnose miscarriages and ectopic pregnancies at this stage.
If you are pregnant we will refer you back to your GP to arrange antenatal care at your local hospital. Unfortunately, a number of pregnancies can still miscarry even if these early scans are encouraging.
A negative pregnancy test
Sadly, this means that the treatment has been unsuccessful. If you have not already started bleeding, a period will come in the next few days. This might be heavier than normal due to the medications you have taken.
We know this can be a very disappointing time and will offer you an appointment to discuss the cycle and possible treatment options for the future. You might also find it helpful to speak to one of our counsellors.
A Guide to PGD
In a woman’s normal monthly menstrual cycle a single egg (called an oocyte) is released from a follicle that has been developed in one of the ovaries as a result of a complex interaction between the body’s hormones. Dependent upon the timing and frequency of sexual activity the egg will may be fertilised by her partner’s sperm.
The PGD cycle is quite different than this natural process. It is made up of seven stages:
1. Downregulation and stimulation of the ovaries
2. Egg collection
3. Insemination
4. Fertilisation
5. Embryo biopsy
6. Embryo transfer
7. Pregnancy test
Stage 1 – Stimulation of the ovaries with hormones to produce eggs
To maximise the chance of a successful pregnancy we need to transfer up to two embryos into the womb, which in turn normally requires around four to eight embryos to have been cultivated. To achieve this number of embryos, our scientific team would aim to collect 10 or more oocytes. This means that we need to stimulate the female’s ovaries to produce many more than the usual single oocyte, and we do this by means of hormonal stimulation of the ovaries, using drugs which mimic the hormones you naturally produce.
These hormones are given to you both as a nasal spray and an injection under the skin on the tummy. A detailed treatment schedule (in the form of a calendar) indicating the dates and medication to be used will be given to you the treatment starts. This of course will be designed taking your travel and period dates into account.
Buserelin/ Nafarelin medication
This is the medication you will be given. This part of the treatment is known as ‘downregulation’ which:-
Temporarily stops your ovaries from working
Prevents you from releasing the eggs before we have time to collect them
This medication continues throughout the treatment. It is only stopped following your final scan in Cyprus. Instructions to stop this medication will be given by the Cyprus IVF Centre once a decision for egg collection is made.
We perform an internal ultrasound scan after two weeks of downregulation, to check that your ovaries are inactive and contain no large follicles or cysts and that the lining of the uterus (endometrium) is thin.
Please note: It is normal to have a period during this time. It does not mean that the medication is not working, so please do not stop the Buserelin/Nafarelin. If you stop the medication too soon, your eggs could be released before we have a chance to collect them.
In some patients, there may be temporary side effects from this medication. The potential side effects are hot flushes, night sweats and mood swings.
FSH injections
Follicle Stimulating Hormone (FSH) injections are given to you as a daily injection over 10 to 14 days to stimulate egg development in the ovaries. We will teach you or your partner to do this or you can arrange to have the injections at your GP surgery or local hospital.
We will explain the potential side-effects of these injections and monitor your response using internal scans. The first scan is usually done nine days after starting the injections.
Deciding the day of your egg collection
Cyprus IVF Centre (CIC) team of doctors, embryologists and nurses decide the best day for your egg collection. The cycle may be cancelled before egg collection if you under or over respond to the medication.
Late at night and about 36 hours before the egg collection, an injection of hCG hormone is given as a ‘one off’ injection. This medication causes the final stages of egg ripening to take place. The time you need to give yourself this injection at home is very important and will be explained very clearly to you.
Stage 2 – Collection of eggs from the ovaries
You are deeply sedated and monitored throughout the egg collection procedure, which usually takes about 15 minutes. Using an ultrasound probe to guide, a fine needle is passed inside the vagina and through the vaginal wall into each follicle, until we have emptied all the follicles in one ovary. The needle is then removed and the procedure is repeated in the other ovary.
Each egg is placed in special fluid and transferred to an incubator. Not every follicle will contain an egg and sometimes no eggs will be found during an egg collection. We will discuss this with you before the procedure.
After the procedure you will rest on a bed in your private room for about one or two hours.
You will be prescribed the hormone progesterone for 17 days following the egg collection to help the lining of your uterus be as receptive as possible to the embryos.
Stage 3 – Insemination / injection of sperm
Your semen sample is prepared by separating the normal and active sperm from the ejaculated fluid. Fertilisation during pre-implantation genetic diagnosis (PGD) treatment will be done by Intracytoplasmic Sperm Injection (ICSI). ICSI involves injecting a single sperm into the centre of each egg to help achieve fertilisation.
Stage 4 – Fertilisation
The morning after injection / insemination of the sperm, the embryologist carefully examines each egg to see if fertilisation has occurred. We will then call you to tell you how many eggs have fertilised.
Rarely, about one in 100 times, none of the eggs fertilise and there are no embryos to be replaced. This is obviously very disappointing. We will offer you the earliest available appointment to see a PGD team doctor and an appointment to see one of our counsellors if this happens.
Stage 5- Embryo biopsy
Three to four days after fertilisation the embryos will usually have reached the stage of development where gender selection can take place, normally involving a complex and expensive scientific process called Pre-implantation Genetic Diagnosis (PGD). This involves removing one or two cells from each embryo and analysing the chromosomes in carefully controlled laboratory conditions, during which the ‘X’ and ‘Y’ chromosomes are clearly identified. The removal of up to two cells does not damage the embryo’s development in any way, and each embryo will continue to grow normally. Our aim is to reach this stage with a minimum of two good, healthy embryos of the chosen sex available for the fourth and final stage of your treatment – the transfer of the embryos to the female’s uterus.
The types of tests we perform on the embryos will depend upon the reason behind you having PGD. Apart from sex selection, we are able to screen for any genetic disease that can be tested for.
Stage 6 – Embryo transfer
During embryo transfer we place the best quality embryos into your uterus. This is a much simpler procedure than egg collection and there is no need for an anaesthetic. Ultrasound scan is used through your tummy to help us to transfer the embryos where they would have the highest chance of implanting. A speculum, which is the instrument also used during a smear test, is placed in your vagina to clearly see your cervix (neck of the womb). The outside of your cervix is cleaned and any mucus from inside your cervical canal is removed. This mucus might prevent the embryos getting to where we want them to be in the womb.
The soft catheter, which holds the embryo(s), is inserted the neck of your womb. When we are happy that the catheter is in the best position, the embryos are gently dropped off. The catheter is then removed and checked to make sure all of the embryo(s) have been replaced. This process takes about 5 minutes. It is generally painless although some discomfort comes from the scan probe that pushes down on your bladder which needs to be full for the procedure as well as the speculum in the vagina.
How many embryos will be transferred?
Current HFEA guidelines allow us to transfer a maximum of two embryos in women who are under 40 years of age. Transferring two embryos has been shown to maximise your chances of a successful implantation, while presenting minimal risks of more than a singleton pregnancy. It is important to note that the risk of a triplet pregnancy, however small, is not completely excluded despite the transfer of a maximum of two embryos.
The number of embryos transferred is limited to lower the risk of a multiple pregnancy. Triplet pregnancies have a significantly increased risk of complications including miscarriage, high blood pressure and premature birth and even twins have more problems with delivery and at birth. Premature babies have an increased risk of complications, such as a weakened immune system, physical and mental disability and feeding and breathing difficulties.
What happens after embryo transfer?
You will know if the treatment has been successful 10-12 days after embryo transfer.
We appreciate that this wait can be difficult for many people. Please do not be tempted to perform a pregnancy test earlier than advised. The hCG injection can stay in your blood stream for eight to 10 days and this will make the test positive, even if you are not pregnant. Please continue to take progesterone vaginally twice a day.
Unfortunately, there is no evidence that anything you do at this stage will increase the chance of you becoming pregnant. We encourage you to return to work but you may prefer to have a few days off around the time of transfer. Having a bath or sexual intercourse is not known to affect the chances of pregnancy.
What happens if there are spare normal embryos?
It is possible to freeze embryos from a PGD cycle for later use. A frozen embryo, which has been thawed, is less likely to implant into the lining of the uterus than a fresh embryo, especially when it has been biopsied. We are selective about the embryos we choose to freeze but we will attempt to freeze any embryos that are suitable. Embryos are frozen at an extremely low temperature, which makes sure they do not deteriorate over the number of years they are stored. Even if you get pregnant in your initial attempt at treatment, you may wish to use frozen embryos, if possible, to expand your family at a later date. If you have frozen embryos, it is essential that you keep in touch with us to let us know what you wish to do with them and tell us of any changes of address.
Frozen embryo cycle
In a Frozen Embryo Transfer Cycle (FET) we thaw your frozen embryos and transfer any that are suitable into your uterus. Our survival rate is good following thawing, but not all embryos will survive this process. An advantage of a frozen cycle is that we do not need to use hormone injections to stimulate the ovaries nor do any further genetic testing of the embryos.
Stage 7 – Pregnancy test
All women should perform a pregnancy test 12 days after the embryo transfer, even if they bleed before this time. This is essential because some patients could miscarry one of a twin pregnancy or have an ectopic pregnancy. This is an uncommon but potentially serious complication. Please inform us about the results of the pregnancy test whatever the outcome.
A positive pregnancy test
This means that one or more embryos have implanted, but we will not be able to see this on a scan until you are about six weeks pregnant (four weeks after embryo transfer). We will usually scan you to:
See how many embryos have implanted
Have they developed a heartbeat?
Sadly, we sometimes diagnose miscarriages and ectopic pregnancies at this stage.
If you are pregnant we will refer you back to your GP to arrange antenatal care at your local hospital. Unfortunately, a number of pregnancies can still miscarry even if these early scans are encouraging.
A negative pregnancy test
Sadly, this means that the treatment has been unsuccessful. If you have not already started bleeding, a period will come in the next few days. This might be heavier than normal due to the medications you have taken.
We know this can be a very disappointing time and will offer you an appointment to discuss the cycle and possible treatment options for the future. You might also find it helpful to speak to one of our counsellors.