IVF

Hello everyone, and huge apologies for this piece being slightly later than anticipated. Life has just got in the way in the last few weeks as we’ve just bought our first home as a couple. Thank you to all those who messaged me privately and also those who commented publically following my last blog piece.

Today I am discussing In vitro fertilisation, more commonly known as ‘IVF’. I’ll also talk a little about some other fertility treatments and medications. Grab a drink because this is a long one!

The vast majority of couples will never reach this point. As I explained in my last piece, approximately 95% of couples will conceive within 2 years of trying without any medical intervention. The statistics are useful when you’re starting out on your trying to conceive (TTC) journey but if you end up being one of the 5% of couples that have not conceived in those 2 years, that can be a scary place.

Before we get into the science of it, can we just have a moment to discuss the emotional impact of this process? From the patients I see, and the friends I have who have been through the process, it is the emotional impact that is the hardest to try and get through.

Through this process it is imperative you are kind to yourself and your partner.

In terms of what I suggest to the couples I see who are going through the process, these are my top 5 tips:

1. Be present – this means try as hard as you possibly can to live in the present and not look back on things you cannot change or look forward and worry about things that may or may not happen. This is the hardest one of the lot but is very important to ensure you are still enjoying the beautiful parts of life – your friends, your family and funny things you see.
2. Eat well and exercise – When life is stressful, food and regular exercise can be the first things to suffer. Eating well and exercising will improve your overall wellbeing. Exercise does not necessarily mean running marathons, but it can mean regular yoga or even jumping jacks every day!
3. Consider mindfulness – the headspace app is my personal favourite. Personally mindfulness changed my ability to handle the stress that comes with my job. If you can consider using mindfulness as a coping strategy, then you may find being present (tip 1) easier to achieve.
4. Start writing things down – this may be journal writing or free writing. Whatever makes you feel like you’ve got it out. I have a notebook next to my bed so I can jot things down before I sleep. I also practice free writing – that is giving myself 5 minutes a day to write things down about how I’m feeling. Sometimes that just says “I have nothing to say” over and over again but it helps! There are lots of tips online about writing for stress so have a look and see what you think.
5. Connect with others – you may feel like you’re in a lonely place, but there are others who are going through what you are. Using support groups to connect with people can be a great way of feeling supported. Your GP or Obstetrician should be able to point you to a fertility group near you.

Clearly there are plenty of other things you can do to keep your mind healthy through this tough time, but hopefully these tips are a start.

Right, so firstly IVF is talked about so much but for clarity I thought it would be helpful to explain what it actually means.

It’s helpful to think about the physiology of the process in couples that conceive without medical assistance.

In a normal menstrual cycle there are a variety of hormones at play. Normally when we discuss the normal menstrual cycle we split it into 2 phases – the follicular phase and the luteal phase.

FSH (follicle stimulating hormone) is released by the pituitary gland – a tiny pea sized gland at the base of the brain. It’s a hormone that is tested frequently in the peri-menopausal time of life, as it is an indicator of ovarian reserve (egg supply). High levels depict a reduction in ovarian reserve. It spikes at ovulation.

The ovaries secrete the hormone Oestrogen. Oestrogen is a clever hormone as it makes two important things happen; it stops FSH being produced to ensure that only one egg will mature in a cycle, and it also stimulates the pituitary gland to release LH (Luteinising hormone).

LH is also produced by the pituitary gland and it causes the mature egg to be released from the ovary. If you test for ovulation then this is what you’re testing for. The surge in the LH levels means your egg will be in prime position to be ovulated in the 24 hours following the surge. Confused yet? We’re almost there so bear with me!

You also have progesterone. Progesterone is the hormone that maintains the lining of your womb. So, the level of progesterone is low on day 1-14 (if you have a 28 day cycle) and then steadily builds up in the second stage of your cycle so the lining of your uterus builds.

Trying to explain in a coherent way how these hormones work together is really difficult so hopefully this illustration should help put it all together, and also clarify why you have different hormones tested at different stages in your cycle.

– Normal hormone menstrual cycle –

Ah, we’re complicated creatures aren’t we?

As for men, sperm is created (spermatogenesis) on an on-going basis. Women are born with all the eggs they will ever have, and every month following puberty an egg is lost. That’s why women talk about the “biological clock” and men do not have such a time pressure.

Testicles produce sperm and testosterone so they have some sperm producing cells, some nursing cells (the cells that help the sperm develop and grow) and the testosterone producing cells.

Anyway, sperm take almost 2.5 months to reach maturity. They’re formed in tiny microscopic tubes called seminiferous tubules.

That clever little pituitary gland also has a role for men. It is what produces the impulse for the testicle to produce testosterone and sperm. FSH and LH are both produced by the pituitary gland to trigger sperm and testosterone development respectively. Testosterone is released into the bloodstream immediately. Once the FSH has triggered the testicles to produce sperm, this sperm will take 72 days to reach maturity. The reason this is an important point is that men who make lifestyle changes for fertility reasons (less alcohol, weight loss, stop smoking) will see improvements in the quality of their sperm in as little as 12 weeks.

As sperm mature they work their way through the seminiferous tubules into the epididymis. The epididymis becomes the vas deferens and then the sperm is carried out of the scrotum up into the pelvis and through the prostate gland. The prostate gland and seminal vesicles produce the fluid (semen) that is released during ejaculation.

In fertilisation the sperm needs to meet the egg and be implanted into the lining of the womb. This has to be a perfectly timed process as the sperm needs to reach the egg whilst the egg is still in the fallopian tube. This is usually in the 24 hours after ovulation. During intercourse a man will normally ejaculate releasing up to 150 million sperm in a single ejaculation. About 85% of the sperm will not be properly structured for the journey to reach the egg. So the 15% that remain race off to try and fertilise the egg. Once the sperm make it through the uterus into the fallopian tube they will hopefully reach an egg! The process from ejaculation to meeting the egg takes less than 30 minutes. At this point probably a few dozen sperm will have actually made it to the egg. But hey, you only need one to break through and fertilise.

Fertility medications

Now you know about the physiology of the menstrual cycle, let’s talk about some medications you may be prescribed if your cycle is a little problematic. A large group who may require some fertility medications are women who suffer with Polycystic Ovary Syndrome. Other groups that may be offered medication include those with an irregular cycle or very unpredictable ovulation, people with pituitary gland issues, men who produce small numbers of sperm or low motility sperm, and men with certain infections.

Metformin

This is probably the most common drug prescribed in women with polycystic ovaries. It isn’t technically a fertility medication, it’s actually a drug used in the treatment of diabetes. In terms of fertility it is helpful in women with polycystic ovaries who are not ovulating regularly because of abnormal insulin levels in the body. The reason it helps is that women with polycystic ovaries can develop insulin resistance and that means the body stops reacting to normal insulin levels. Now, the body likes hormones to be at a consistent level and in response to this it starts releasing more insulin to try and evoke a reaction. This high insulin can lead to high male hormones (androgens) which subsequently affects ovulation. Metformin reduces insulin to normal levels and therefore can help ovulation return to normal.

Clomifene

Clomifene (also called Clomid) is a really effective treatment that is used to stimulate ovaries to produce more eggs. Women who have polycystic ovaries may be prescribed this if they are having difficulty conceiving. Women who have irregular periods can also use it.

Gonadotropins

We will come to this later, but women with polycystic ovaries who have not responded to Clomid can use these injections. They’re injectable hormones that stimulate the ovaries to produce eggs.

Bromocriptine and Cabergoline

You may not have read much about these previously as they’re not particularly common. They’re used by women who have problems with their pituitary gland.

In Vitro Fertilisation (IVF)

Finally, we reach IVF. I hope you’ve found the previous information useful. The reason I felt it necessary to discuss it is because frequently the lack of understanding of the normal physiological process of conception can lead to lots of confusion about IVF.

In vitro fertilisation is when we engineer this process to take place outside the body.  As I said previously, it is a very small percentage of TTC couples who end up at this point, but if it happens to be you, or someone you know, then hopefully I can offer a bit of an explanation for you.

IVF can be useful for a whole range of people such as:

• Women with blocked or damaged fallopian tunes
• People who have unexplained fertility problems or who have had unsuccessful tries with other treatments
• Men with low sperm counts
• Men who have high numbers of sperm with an abnormal shape or movement
• Women with difficulty ovulating
• Older women who are deemed less likely to be successful with less invasive treatments but it is still felt there is a good chance of conception

IVF is not suitable for everyone trying to conceive and it may not be offered as an option to some couples. Success rates vary from clinic to clinic.

The following figures give the average success rate for IVF and Intracytoplasmic Sperm Injection (ICSI) treatment using a woman’s own fresh eggs in the UK in 2010.

• 32.2% for women under 35
• 27.7% for women aged 35-37
• 20.8% for women aged 38-39
• 13.5% for women aged 40-42
• 5% for women aged 43-44
• 1.9% for women aged 45+

So, getting back to what IVF is. IVF involves five basic steps – suppressing the normal cycle, stimulating the ovaries, taking the eggs, insemination and fertilisation, and then embryo transfer.

From experience with couples going through IVF starting treatment is  a very stressful and upsetting time. Some couples comment that it’s the first time they feel “medicated” for their fertility troubles and this brings lots of emotions. Excitement, of course, but lots of trepidation. Another comment some couples make is that there is an overwhelming fear that the response to the medication will not be adequate. Just remember that you can and should ask as many questions as you need to along the way.

Cycle suppression

To allow a controlled process, medication is given to suppress the hormones you would normally be producing naturally through your cycle. This is in the form of injections and usually it’s a 2 week course.

Ovarian stimulation

As we discussed previously, in a normal menstrual cycle, hormones will ensure that a single follicle containing a single egg will develop to maturity. In IVF the aim is to create the best possible chance of success. To do that, the ovaries are stimulated to produce multiple eggs. Drugs called Gonadotropins are given. Gonadotropins are two hormones we’ve come across before; LH and FSH. To recap, these are the hormones that are normally produced by the pituitary gland and encourage the ovaries to produce a follicle (which contains an egg). In IVF the gonadotropins are made in a laboratory and are called recombinant preparations. They need to be injected under the skin. The majority of women will have an injection that just contains FSH. Some women who do not have regular cycles and who have particularly low levels of FSH and LH may be advised to have a preparation that contains both FSH and LH.

Gonadotropin treatment for most couples going through IVF involves daily subcutaneous injections.

Gonadatropin protocols differ but in general on day one of the menstrual cycle (the first day of a period) most women will have blood tests and an ultrasound done. Then on day 3 to 5 some women may have more blood tests to measure hormone levels and also another ultrasound to make sure there are no large cysts on the ovaries. It’s at this point that you’re normally given the timing of when to start your Gonadotropin injections.

Once the daily gonadotropin injections start you will have more ultrasounds and blood tests. This is so the doctors can assess if the dose of the injections is correct or not. All women will respond differently to FSH, some needing more to stimulate follicle growth than others. The scans will help the doctors work out the best time to move on to egg collection.

The main risk of the gonadotropin injections is ovarian hyperstimulation. This is when there is an excessive response to the drugs. Women with polycystic ovarian syndrome are at greater risk of this. This condition is rare but is discussed at length prior to the start of IVF treatment.

36 hours or so before the eggs are collected a new injection; human chorionic gonadotropin (hCG) is given to start the final process of egg maturation. This needs to be precisely timed because the eggs will be suitable to be collected 34-36 hours after the injection.

Egg collection

This part of the process happens under sedation or general anaesthetic. A needle is inserted through the top of the vagina into the ovary. To make sure this is done correctly the doctor will do this under ultrasound guidance. A little suction device is used to draw the fluid out of each of the follicles.

Insemination and fertilisation

The male partner will produce a semen sample by masturbation and the sperm are harvested from that. Sperm are combined with the collected eggs and placed in an incubator.

If male factor infertility is an issue then ICSI (Intracytoplasmic sperm injection) will probably be advised. This is true for about half the couples that have IVF. I won’t go into too much detail but it’s the process of taking individual sperm and fertilising an egg. The sperm are sorted through and the best ones are chosen for fertilisation. For some men who have semen tests that show no, or very little sperm, surgical retrieval of sperm may be required.

About 12 hours after the eggs have been fertilised they start to divide. When they form a blastocyst (an advanced stage of an embryo) then they are at the point they can be transferred.

Embryo transfer

This happens 2-3 days after collection for most people. It may differ in individual cases but the laboratory will decide this, based on how the embryos are developing.

Transfer is done under ultrasound and for most women a single embryo is transferred. There may be specific reasons for 2 embryos to be transferred but your doctor will discuss this. The transfer procedure is painless for most.

After transfer some women may be prescribed hormones  to support the womb lining. This can be progesterone pessaries, gel or injections and in some cases hCG injections are used; hCG injections are not normally offered in the UK.

The waiting game

As if all of the time off work, the injections, appointments, scans and blood tests weren’t stressful enough you then just have to wait. For most couples this is the time to truly treat yourself with kindness. The anxiety during the 2 weeks can be overwhelming and all consuming. Meditation, mindfulness and all the things that allow you to live in the moment are really important here. The majority of fertility centres have counsellors attached to them – use them.

If all goes to plan, 2 weeks down the line you’re pregnant.

But what if you’re not?

Oh this is one of the hardest times. The first thing is you really mustn’t blame yourself. This is just biology – it is not your fault and no one could have predicted it. It doesn’t mean another attempt won’t be successful, it doesn’t mean you’re just not meant to carry a child.

Please, please allow yourself and your relationship to heal. I have some couples that tell me IVF wasn’t as bad as they thought it would be, and others who tell me it was harrowing for them. Regardless of how you found the actual process, the emotions you will have gone through should not be pushed under the carpet. Talk to each other, talk to people who have experienced IVF, talk to medics if you want to. Don’t if you don’t.

When you’re ready you can begin to make a plan. That plan may involve more cycles and that will depend on your financial situation. Talk of finances leads me neatly to the elephant in the room that is the postcode lottery of NHS IVF availability.

The postcode lottery

The National institute of Clinical Excellence (NICE) produces guidelines of best practice. The guidelines for IVF are clear but I am unaware of a single area in the country that follows them. NICE recommend that in women under 40 years of age who have not conceived after 2 years of regular unprotected intercourse, 3 cycles of IVF should be offered on the NHS, with or without ICSI. Interestingly, if a couple have paid cycles privately then NICE advise that should be counted as one of the cycles that can be offered.

In women who are 40-42 years old NICE recommends the NHS should fund 1 cycle of IVF providing they have never had previous IVF treatment and there is no issue with ovarian reserve.

As a GP it can be really hard knowing what NICE guidelines say and what I can offer my patients. In my area of Bristol, there is a form that must be filled in for every fertility referral. If there is any part of the criteria that are not fulfilled then the referral is not accepted. I am unable to refer anyone over the ago of 40, even though NICE state women up to the age of 42 should be offered a cycle. I cannot refer anyone who has a BMI over 30.

This is not uncommon and when I see my friends who are GPs in other parts of the country, our criteria are not considered harsh. You may find your area has an earlier cut off for maternal age for IVF. It is certainly worth researching what the situation is in your area. The reason this is important is that most people will try to have another cycle of IVF if they have a failed attempt. This can cost £5,000-£7,000, depending on where in the country you are. It’s a huge expense for most people so should be considered prior to starting the journey. It can be devastating if an NHS cycle is unsuccessful and there is no possibility of another cycle privately.

In my area, there are plans to restrict the access to IVF even further.

They are proposing to

1. Drastically reduce the female age criteria, so that only women aged between 30-35 will be able to access NHS fertility treatment.
2. Introduce new restriction criteria barring access to NHS treatment if one partner has a child from a previous relationship.
3. Amend the age criteria for the prospective father or female partner in a same sex couple; the new proposal is that the prospective father or female partner in a same sex couple should be younger than 52 years.

I really worry about the implication this will have on my patients and have sent multiple letters and emails to the commissioners in our area. Obviously money is not infinite in the NHS but drastically reducing the age that women can access IVF will devastate many.

So, there we are. I’m sorry the piece is so long but there were bits I really didn’t want to gloss over. This is a huge and emotive topic and although it won’t be relevant to most of you, some of you I know will be going through the journey right at this moment – this piece is for you and those that will support you.