So, what is IVF? What does the IVF process involve? Most people have a vague idea that it is something to do with helping couples with fertility issues but they do not know the details. Certainly, before my wife and I started treatment we did not know what it involved.
This lack of knowledge created uncertainty and the uncertainty gave rise to fear.
I’m sure we are not alone in feeling this way so this post aims to provide a thorough guide to help you take back control.
IVF process
There are variations on the theme but the IVF process typically involves several stages:
Let’s have a look at each of them.
Ovary stimulation
The first stage of treatment involves taking drugs to stimulate your body to produce eggs. To do this doctors use either “long protocol IVF” or “short protocol IVF”.
The main difference between the two is the point in your period when you start taking these drugs.
Long protocol IVF
The long protocol takes place over two periods and is the standard IVF protocol. It is called “long” because the treatment process lasts around 4-6 weeks.
Short protocol IVF
On the other hand, short protocol IVF works over just one menstrual cycle and only takes around 2 weeks.
It is used instead of a long protocol where there is a risk of Ovarian Hyperstimulation Syndrome (see Risks section below), a patient has responded poorly to a long protocol or where a patient is older than average.
Where possible the IVF process seeks to work in harmony with your normal monthly cycle and aims to enhance your ability to produce eggs. This being the case the long protocol starts on day 21 of your first period and the short protocol begins on day 1 (remember, short protocol IVF takes place over just one period).
In a natural cycle your ovaries grow fluid-filled pouches that each contain a single, immature egg (or “oocyte” to give it the medical name). These pouches are called “follicles”.
Without additional drug stimulation only one follicle each month will become mature enough to release its egg. In a natural cycle this happens when your body produces a surge of a hormone called “luteinising hormone” (LH).
Stages of each IVF protocol
1
With IVF the aim is to encourage multiple follicles to become mature enough to release eggs so a medication is given from day 21 of the first period (long protocol) or day 1 (short protocol) for around 14 days to temporarily switch off LH.
This is called “down-regulation”.
The medication is given as either a daily injection or a nasal spray. Without it the body’s natural production of LH would kick in when only one follicle had matured and cause the release to happen too early.
We want to wait until several eggs are mature before triggering the release.
2
Having switched off LH, in a long protocol another medicine (called, appropriately, “follicle stimulating hormone”) is given from day 3-5 of the second period for 10-12 days to help stimulate the development of multiple follicles.
In short IVF protocol the same medicine is given from day 1 in parallel with the down-regulation medicine, again for 10-12 days.
This drug is usually given as a daily injection under the skin (called “sub-cutaneous” by the doctors) using a special injection pen that makes it easy for patients to do themselves.
3
From this point the long and short protocols follow the same path.
During the stimulation stage the doctors will monitor progress using ultrasound scans and blood tests. They are looking for multiple follicles to reach a certain size before giving a final injection about 36 hours prior to egg collection.
This injection contains something called “human chorionic gonadotropin” which finishes the maturation process and loosens eggs from the follicles ready for collection.
Do success rates vary for different IVF protocols?
Of course, one of the most important considerations when deciding between long protocol and short protocol IVF is success rates.
Is one better than the other? Let’s have a look.
A large meta-analysis1 (a study looking at a collection of previous studies) of over 50 studies found that success rates for short protocol IVF were significantly lower.
The results are summarised in this table:
Outcome
Pregnancy
Live Birth
Short Protocol IVF
23.8%
21.2%
Long Protocol IVF
27.4%
24.1%
So, in general pregnancy rates in short protocol IVF are 13% lower and birth rates are 12% lower than using the long protocol.
However, these are general statistics and it may be that in your specific circumstances a short protocol is the best option for you.
1 GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017 Sep 1;23(5):560-579
Egg collection
Whichever IVF protocol you follow, the day of egg collection can be both exciting and daunting. Following the ultrasounds you should have a general idea of the number of eggs available for collection but it is not until they have been retrieved that you will know the exact number.
The procedure is carried out under sedation. A doctor uses an ultrasound scanner to help guide a microscopic needle through the vagina to the ovaries. The needle is then used to drain each follicle and collect the contents. Hopefully, this will include an egg. The contents are then examined under a microscope and the eggs are separated.
The procedure usually takes less than 30 minutes.
Sperm collection
At the same time as the eggs are collected your partner will produce a sperm sample. Depending on the circumstances an operation may be required but, generally, the sample is produced “manually” using “traditional” methods!
Fertilisation
Ok, by this stage you will hopefully have a number of eggs and a sperm sample. The next stage of the IVF process is fertilisation.
The sperm sample is treated, concentrated and then combined with the eggs (this is where the phrase “test tube baby” comes from). The mixture is left overnight during which time the sperm will hopefully have fertilised some of the eggs.
If there have been or may be issues with fertilisation your doctor may recommend using a technique called ICSI (“intracytoplasmic sperm injection”).
ICSI involves the embryologist injecting a single sperm into an egg rather than just mixing the two together.
Fertilised eggs are called embryos. Any that are obtained are kept in laboratory conditions for up to 6 days to enable them to develop into something called “blastocysts”.
Blastocysts are simply 5-6 day old embryos. Transferring embryos at this stage has been shown to produce better results than transferring 3 day old embryos which used to be the standard practice.
Embryo transfer
If you have read our About page you will know that at this stage of the process my wife and I froze our embryos for future use so we could get on with beating leukaemia.
In a typical IVF procedure whilst your embryos are developing the thickness of your womb lining becomes the focus.
Whereas up to this point all the attention has been on the number and size of the follicles on your ovaries the thickness of the lining now becomes key. It is in the lining that an embryo will hopefully implant and develop into a pregnancy.
If you have had issues with the thickness of your womb lining in the past your doctor may recommend that you take estrogen (usually in the form of patches or injections) and progesterone (as a suppository) to help increase the thickness. If this is the case you will take the drugs in the days prior to the transfer.
A key question, of course, is how many embryos to transfer.
The UK’s National Institute for Health and Care Excellence (NICE), the body responsible for issuing guidance on health and social care, has made the following recommendations:
Note for women between 40 and 42 only 1 cycle is recommended by NICE.
A key part of NICE’s thinking is to reduce the number of multiple pregnancies.
The more embryos you transfer the greater the chance of a multiple pregnancy and multiple pregnancies pose risks to both the babies and the mother. As a result, in making their recommendations NICE are seeking to reduce the likelihood of them occurring.
They also have to factor in the budget constraints of the UK’s National Health Service (NHS) so their guidelines are not focused purely on what is best for patients.
In the US, the American Society for Reproductive Medicine (ASRM) has also issued guidelines on the number of embryos to transfer. ASRM does not have the same budgetary considerations so can focus solely on patients’ best interests. Because of this they give a better guide to the maximum number to transfer.
It’s recommendations are set out below:
Ultimately, it is a matter to discuss with your doctor. Everyone is different and there is no “one size fits all” approach. Don’t allow yourself to be pushed in a direction you are not comfortable with.
The transfer procedure itself is less invasive than the egg collection. It is similar to having a cervical smear test. Each embryo is delicately inserted into the womb using a fine plastic tube. The procedure takes a few minutes and should be painless.
If you are lucky enough to have produced a number of good quality embryos the remainder can be frozen for future use.
Post-transfer follow-up
The next step of the IVF process is known as the “two week wait” and, I’ll be honest, it can be quite a tense time.
On leaving the fertility clinic you will be given a pregnancy test kit to be used 10-14 days after embryo transfer. This is crunch time where you will find out whether the treatment has worked or not. You will likely experience a whirlwind of emotions and I hope they culminate in joy.
If the test is positive you will then be asked to have an ultrasound scan in the following weeks to check that your baby is developing properly.
As we saw in Real IVF Success Rates (What Your Clinic isn’t Telling You) this is an important time.
Assuming all is ok following the scan your care will be transferred to the antenatal team at your local hospital and you will be treated the same as other pregnant women.
Risks
As is the case with any type of medical treatment there are risks associated with undergoing IVF. The first risk is that it may not be successful but aside from that you should be aware of the following:
Medicine side effects
As we have seen, various drugs are given during the IVF process and these may cause a number of side effects:
- skin bruising and soreness at injection sites
- swelling and tenderness in the abdomen
- breast tenderness
- nausea
- mood swings/irritability
- headaches
- hot flushes
- vaginal dryness
- ovarian cysts
- ovarian hyperstimulation syndrome caused by over stimulation of the ovaries which in rare cases can be serious
It is important to keep these side effects in context. When you read information about any drug you will usually find a long list of potential side effects. They often sound scary. Keep in mind that the likelihood of serious side effects occurring is low.
Multiple pregnancy
As the aim of the IVF process is to have a baby it is slightly counter-intuitive to refer to multiple pregnancies as a risk. The reason for including it here is that multiple pregnancies increase the chances of complications for both the mother and babies. For example, it has been shown that:
- around 60% of twins are born prematurely and the risk increases further with triplets, etc. Premature babies may not have developed fully by the time of birth and so may need help breathing, eating and fighting infections. Babies born before 28 weeks are especially vulnerable and may need intensive care
- low birth weight is more common and this is in turn associated with a greater chance of long term health issues
- women are twice as likely to suffer from high blood pressure which in some cases may increase the chance of early separation of the placenta from the womb. This can lead to serious complications for both mother and babies
- anaemia is twice as common in women with multiple pregnancies
- the placenta may not be able to cope with the growth of the babies (called “intrauterine growth retardation”) which can hamper their development
- birth defects are twice as likely in multiple pregnancies
- the chances of miscarriage increase
- “twin to twin transfusion syndrome” can occur which causes one foetus to receive too much blood and the other to receive too little. In rare cases this can be extremely serious
As you can see some of these complications can be serious.
Fortunately the really serious issues are relatively rare. When you consider that many IVF cycles result in multiple pregnancies the potential complications help to explain why health authorities around the world are implementing measures to reduce the likelihood of them occurring.
If you do have a multiple pregnancy please try not to worry. The majority pass successfully and without any problems. Your medical team will monitor you very closely so that they can act quickly to address any issues at an early stage
Adnexal torsion
In very rare cases it is possible for an ovary to become twisted, cutting off its blood supply. If not treated promptly the ovary can, in extreme cases, die. This occurs more frequently in women with ovarian hyperstimulation syndrome.
Egg collection
Like other minor surgery, the egg collection procedure can cause issues. These are, again, rare but include bleeding, damage to adjoining tissue and infection together with the potential to react adversely to the sedative given.
Cost
The cost of undergoing IVF treatment can be significant. It is not typically covered by health insurance in the UK but cover is sometimes available in the US and other countries. Because of the unique way healthcare in the UK is funded we’ll look at that separately below.
Of course, in an ideal world, cost should not be the only criteria you consider when choosing an IVF clinic.
Take a look at our Choose the Best Fertility Clinic (That is Right for You) post. In it you will find all the things that are relevant when choosing a clinic. There’s also a free comparison tool you can download to rate several clinics based on the things that are most important to you.
What's included?
Estimates vary depending on location and specific treatment protocols but a single cycle typically costs between £4,000 ($6,000) and £7,000 ($10,500) but can go up to £20,000 ($30,000). When you are quoted prices by a clinic the key thing to look out for is the total cost of treatment.
Fertility clinics have been criticised for charging for additional things that were not expected at the start of treatment. Frequently, for example, the drugs will not be included in the price given. You can use the following checklist to establish what is included:
- medicines
- ultrasound scans, blood and other tests
- egg and sperm collection
- embryology services such as fertilisation
- storage for any embryos to be frozen
- embryo transfer
- pregnancy test kit
- doctor's appointments
- nurse co-ordination appointments
- counselling
Insurance
Whilst your health insurance is unlikely to cover IVF if you live in the UK the position is better in the US… if you live in certain states… but even then it is confusing.
Some states have laws that require insurance companies to cover IVF treatment but not all costs are covered; that depends on the plan. These states are: Arkansas, Connecticut, Hawaii, Illinois, Louisiana, Maryland, Massachusetts, Montana, New Jersey, New York, Ohio, Rhode Island and West Virginia.
California and Texas, on the other hand, have laws which mean insurance companies only have to offer coverage.
In other states no such requirements exist but you may find that certain elements of treatment, eg diagnosis, are covered, depending on your plan.
Resolve, the US National Infertility Association, has a great resource on its website summarising the different state requirements.
For IVF, coverage can broadly be split into 5 categories:
- no coverage
- coverage for diagnosis only
- coverage for diagnosis and limited treatment
- medication only coverage
- full coverage
But it all depends on the terms of your plan… and they differ massively. The best advice is to speak to your plan provider before you commit to treatment.
UK & the NHS
In theory, IVF is provided on the NHS but with the budget cuts of recent years it seems to be something of a lottery depending on where in the country you live. A recent report by the campaign group Fertility Fairness found that 4 out of 5 NHS Trusts did not offer the cycles recommended by NICE so the chances are that you may need to look elsewhere.
Currently, NICE recommends that:
Women under 40 should be offered 3 cycles of IVF if she:
- has not become pregnant after 2 years of trying or
- suffers from a condition that means she will not be able to get pregnant without IVF
Women between 40 and 42 should be offered 1 cycle if she:
- has not become pregnant after 2 years of trying
- has not had IVF before
- does not have low egg reserve
- has been informed of the increased risk of pregnancy at this age
Women over 42:
should not be offered IVF at all
So in theory, if you meet the criteria, you will be offered treatment. However, as noted above, NHS funding has been squeezed a great deal in recent years and NHS Trusts have to choose where they spend their budget. Unfortunately, IVF treatment has often been the target for some of the biggest cuts. As a result many Trusts impose stricter criteria. These vary but may include requirements around:
- not having any other children
- being under 35
- not smoking
- having a certain body mass index (BMI)
They may also further limit the number of cycles offered.
As you can see it is something of a postcode lottery but if you are based in the UK it is certainly worth checking to see if your local NHS Trust provides treatment.
Refund insurance
Some insurance providers offer policies that cover the costs of IVF failed cycles. The exact details of the policies vary but generally if you give birth you will pay the clinic’s fees but if you don’t they will be covered by the policy. Providers frequently cover the cost of up to 3 cycles.
Obviously, they will only cover good IVF candidates so there are a number of eligibility criteria but if you meet them these policies can provide some peace of mind.
One of the largest providers is called Access Fertility and for more information have a look at their website.
Payment plans
Some clinics also offer the ability to spread the cost of treatment over a period of time. Rather than having to pay a large lump sum at the beginning the cost can be paid in instalments each month. This is the same as other forms of credit/payment arrangement so you should ensure that you will be able to meet the payments. It can, however, offer a solution for patients who do not have the funds to pay up front.
IVF abroad
Another option where cost is an issue is to go abroad to have treatment. The cost of treatment in certain countries is lower than in the US and UK, for example.
However, it is worth repeating that any decision to undergo IVF should not be taken on price alone. In an effort to ensure the safety of patients and a high quality of care some systems (such as the UK) are heavily regulated but this is not the same in all countries.
This is not to discourage anyone from seeking treatment abroad but if you take this route it would be wise to carry out checks to ensure the clinic will provide good quality care. Our post Choose the Best Fertility Clinic (That is Right for You) will help you do this.
For instance, a lack of regulation often means that there is no central body that checks success rates published by clinics. You should therefore ask lots of questions and establish the facts rather than rely on anything that has been influenced by marketing spin. Have a look at Real IVF Success Rates (What your Clinic isn’t Telling You) for details of how to approach this.
You should also look into the following:
- safety record and standards
- frequency of visits required
- cost of travel and accommodation
- English skills
It may not be easy to gather information on certain clinics and if that is the case it may be better to choose a clinic that has a larger digital footprint. Online forums are a good starting point here but don’t just listen to one or two people’s opinions, try to build up a broad picture.
Frequently Asked Questions
What is the IVF process step by step?
There are different protocols but typically the IVF process involves six stages:
1. Ovary stimulation
2. Egg collection
3. Sperm collection
4. Fertilisation
5. Embryo transfer
6. Post-transfer follow-up (also know as the “two week wait”).
How much does IVF cost?
Costs can vary depending on the protocol, the fertility issue being treated and the drugs prescribed. Generally, a single cycle costs between $6,000 (£4,000) and $10,500 (£7,000) but can go up to $30,000 (£20,000).
Is IVF a painful procedure?
Aspects of the process can be painful. In particular, you will require regular injections during your cycle and egg collection is a surgical procedure. Whilst it will be done under sedation women tend to feel discomfort in the following days. This can be effectively treated with over the counter pain medication.
Is IVF covered by insurance?
In the UK it isn’t covered.
In the US coverage varies. Usually IVF isn’t covered, but sometimes elements of treatment may be covered, for example diagnosis and drugs. But it all depends on the terms of your plan and they differ massively. The best advice is to speak to your plan provider before you commit to treatment.
What is a short protocol in IVF?
The first stage of the IVF process involves taking drugs to stimulate your body to produce eggs. To do this, doctors use either a “short protocol” or a “long protocol”.
The main difference between the two is the point in your menstrual cycle when you start taking the drugs. The long protocol takes place over two cycles whereas the short protocol works over one period.
As the name suggests the “short protocol” is quicker and is used where there is a risk of Ovarian Hyperstimulation Syndrome. This is a potentially serious condition caused by over stimulation of the ovaries.
What are the different IVF protocols?
There are many variations, with each clinic taking slightly different approaches.
Generally, patients are treated using with a “long protocol” or a “short protocol”. These protocols are basically the length of time stimulation and down-regulation drugs are given.
In the long protocol treatment lasts for 4-6 weeks and takes place over two periods. In the short protocol treatment takes place over just 2 weeks during one menstrual cycle.
What is long protocol IVF?
Long protocol IVF is the standard IVF treatment. It refers to the length of time a patient is given stimulation and down-regulation drugs.
The long protocol takes place over two periods and lasts for around 4-6 weeks. After this phase any eggs which have developed will be collected, ready for fertilisation.
What is antagonist protocol IVF?
Antagonist protocol IVF is generally used as another name for short protocol IVF. For details of this please refer to the questions above.
Is IVF a painful procedure?
Aspects of the process can be painful. In particular, you will require regular injections during your cycle and egg collection is a surgical procedure. Whilst it will be done under sedation women tend to feel discomfort in the following days. This can be effectively treated with over the counter pain medication.
How do I prevent OHSS during IVF?
OHSS, or Ovarian Hyperstimulation Syndrome, is a potentially dangerous condition caused by a patient over-responding to stimulation drugs.
There are a few treatment options. Firstly, using a short protocol has been shown to reduce the likelihood of OHSS by around 40% (GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017 Sep 1;23(5):560-579).
A drug called cabergoline (brand name Dostinex) is also proven to reduce the likelihood of OHSS by around 60% (Cabergoline for preventing ovarian hyperstimulation syndrome in women at risk undergoing in vitro fertilization/intracytoplasmic sperm injection treatment cycles: A randomized controlled study. Avicenna J Med. 2015 Oct-Dec; 5(4): 123–127).
Hydroxyethyl starch (brand name Voluven) is another effective drug treatment, reducing the likelihood of OHSS occurring by 56% (Intravenous plasma expanders for preventing ovarian hyperstimulation syndrome (OHSS). Cochrane. 31 August 2016).
What does down-regulation mean in IVF?
Down-regulation is the process of switching off the natural egg production in your ovaries. It may seem strange to stop your ovaries producing eggs but doing this has been shown to make them more responsive to stimulation drugs. This in turn leads to better results overall.
What is the IVF short protocol success rate?
A large review of over 50 studies found that success rates for the IVF short protocol are significantly lower than for the standard long protocol.
The researchers reported that pregnancy rates were 23.8% compared to 27.4% and birth rates were 21.2% compared to 24.1% ( GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017 Sep 1;23(5):560-579).
IVF process: wrap-up
I hope that this guide has been useful and answers any questions you have. Please feel free to leave a comment or ask a question (either below or using the Contact page).
I will do all I can to help.