In IUI, better quality sperm are separated from sperm that are sluggish, non-moving or abnormally shaped. These sperm are then injected directly into the womb. This may be performed with your partner’s sperm or donor sperm (known as donor insemination). It may be used in the treatment of:

· Couples who are unable (or would find it very difficult) to have vaginal intercourse, for example, because of a physical disability or psychosexual problem.

· People who need donor sperm but have no female fertility problems, including single women and same-sex couples.

· Those who have a condition which means they need specific help to achieve pregnancy safely (for example, men who are HIV positive and have had sperm washing to reduce the risk of passing on the disease to their partner and potential child).

· You may be offered IUI with your partner’ sperm if you have unexplained infertility, but the National Institute for Health and Care Excellence (NICE) advise against this, and, as a result, it is generally not funded by the NHS. If you have unexplained infertility and would prefer IUI rather than IVF you are likely to have to pay privately.

IUI allows the body to do more on its own than IVF, so it’s a more natural but also less successful form of treatment.

In IUI, the highest quality sperm is selected and injected into the uterus where they are left to fertilise the eggs naturally. In IVF, the eggs are removed from the body and fertilised in the lab. This means that IUI is a less invasive procedure which involves fewer drugs than IVF. It’s also considerably less expensive – one cycle of IUI is typically a quarter of the price of one IVF cycle.

However, IUI is also less successful than IVF. Once you’ve injected the sperm, you’re allowing the body’s natural processes to take over whereas in IVF you have more control – you can check the egg has fertilised and select the best embryo(s) to put back into the womb. Success rates for IUI are generally around a third of that for IVF.

As with any fertility treatment, the younger the woman is the higher her chances of getting pregnant. You’re also more likely to get pregnant if you have fertility drugs to stimulate your natural cycle.

For women aged under 35, about 18% of IUI cycles result in a healthy baby being born. Women aged 35 to 37 have a 14% success rate and the birth rate for women aged 38-39 is 12%. For women over 40, your chances are lower (5% for women aged 40 to 42 and 1% for women aged over 42).

Many women will have several cycles of IUI before they have a successful pregnancy so it’s worth considering that when you’re thinking about the costs of treatment.

Ovarian hyperstimulation syndrome affects women taking injectable hormone medications to stimulate the development of eggs in the ovaries. Ovarian hyperstimulation syndrome is a potentially serious complication of fertility treatment, particularly of in vitro fertilisation (IVF).

Too much hormone medication in your system can lead to ovarian hyperstimulation syndrome (OHSS), in which your ovaries become swollen and painful. A small number of women may develop severe OHSS, which can cause rapid weight gain, abdominal pain, vomiting and shortness of breath.

Occasionally it may occur after oral medications such as clomiphene.

It is normal to have some mild discomfort after egg collection. If you are worried or develop any of the symptoms below, you should seek medical advice. OHSS can range from mild to severe:

• Mild OHSS – mild abdominal swelling, discomfort and nausea.

• Moderate OHSS – symptoms of mild OHSS, but the swelling is worse because of fluid build-up in the abdomen. This can cause abdominal pain and vomiting.

• Severe OHSS – symptoms of moderate OHSS with extreme thirst and dehydration. You may only pass small amounts of urine which are dark in colour and/or you may experience difficulty breathing because of a build-up of fluid in your chest. A serious, but rare, the complication is the formation of a blood clot (thrombosis) in the legs or lungs. The symptoms of this are a swollen, tender leg or pain in your chest and breathlessness. You should report any unusual symptoms to your doctor.

Fertility drugs, usual gonadotrophins, are used to stimulate the ovaries during IVF treatment to make eggs grow. Sometimes there is an excessive response to these drugs, leading to OHSS. Overstimulated ovaries enlarge and release chemicals into the bloodstream. Fluid from the blood vessels leaks into your abdomen and in severe cases into the space around the heart and lungs. OHSS can affect the kidneys, liver and lungs. A very small number of deaths due to OHSS have been reported.

Mild OHSS is common in women having IVF treatment; affecting as many as 33 in 100 women (33%). However, just over 1 in 100 women (1%) will develop moderate or severe OHSS.

The risk is higher in women who:

• have polycystic ovaries

• are under 30 years old

• have had OHSS previously

• get pregnant in the same IVF cycle as they get their symptoms, particularly if this is multiple pregnancies (more than one baby).

At p4 fertility, predictive and preventive care are two vital pillars to avoid any complications. To minimize the risk of developing OHSS, we predict the risk very carefully. The stimulation protocol and dosage of medications are chosen to minimize the risk of OHSS. However, despite the personalising protocol, to balance the success and risks, there is a small chance that ovaries will be hyper-stimulated. When we suspect the risk during monitoring of cycle, we use various evidence-based strategies to reduce the risk without compromising the chances of success. Freezing all embryos and use of agnostic (Buserline ) trigger injection are commonly used strategies to reduce OHSS risk.

Most of your symptoms should resolve in 7–10 days. If your fertility treatment does not result in a pregnancy, OHSS usually gets better by the time your next period starts. If you become pregnant, OHSS can get worse and last up to a few weeks or longer. What should I do if I have mild OHSS? If you have mild OHSS, you can be looked after at home. Ensure that you drink fluids at regular intervals depending on how thirsty you feel. If you have pain, take paracetamol or codeine (no more than the maximum dose). You should avoid anti-inflammatory drugs (aspirin or aspirin-like drugs such as ibuprofen), which can affect your kidneys. It is advisable to remain active to reduce the risk of thrombosis.

Ovarian hyperstimulation syndrome (OHSS) in IVF/ICSI cycles may occur either as an early (early-onset) or a late pattern (late-onset). When OHSS develops more than 10 days after egg collection in a cycle which had embryo transfer is called late-onset OHSS. This type of OHSS is difficult to predict, therefore, hard to prevent. Late-onset OHSS may indicate embryo implantation. Late OHSS nearly always occurs with pregnancy. OHSS develops as the hormones released by implanting embryo stimulates the ovaries. Late OHSS tends to be more prolonged and severe than the early form as there is ongoing hormonal stimulation from pregnancy.

Call for medical help if you develop any of the symptoms of OHSS, particularly if the pain is not getting any better or if you start to vomit, have urinary problems or chest pain or have difficulty breathing.

You should have the details of your fertility unit to call for help and advice.

If you are unable to contact your fertility clinic, contact:

• The A&E department at your local hospital or

• Your general practice or

• The NHS on 111.

Your doctor will ask you to describe your symptoms and will examine you. Besides, your doctor may:

• Ask about how much urine you are passing and whether it is darker than normal (concentrated)

• Measure your blood pressure, pulse rate and breathing rate

• Take an initial measurement of your waistline and check your weight to see whether the fluid is building up or reducing

• Arrange an ultrasound scan to measure the size of your ovaries and to check whether there is any fluid build-up in your abdomen

• Take blood tests to measure how concentrated your blood is and how well your kidneys are working. A diagnosis is made based on your symptoms, the examination findings and the results of your tests. If you are well enough to go home, you may be advised to attend for regular check-ups.

Many women can be managed as outpatients, but you may need admission if:

• your pain is not helped by pain-relieving medications

• you have severe nausea and vomiting

• your condition is not getting better

• you will be unable to attend hospital easily for monitoring and follow-up.

If you are vomiting, you may need a drip to replace the fluids you have lost. The fluid will help to keep you hydrated and may contain sugar and carbohydrates (for energy), and minerals and chemical elements (for regulating and maintaining the organs in your body). It is important that, if you are admitted to a hospital which is not the one where you had your fertility treatment, your care is discussed and coordinated with a specialist in this condition.

Although no treatment can reverse OHSS, it will usually get better with time. Treatment is to help symptoms and prevent complications. This includes:

• pain relief such as paracetamol or codeine

• anti-sickness drugs to help reduce nausea and vomiting

• an intravenous drip to replace fluids

• support stockings and heparin injections to prevent thrombosis (a blood clot in the leg or lungs).

Heparin injections for blood thinning should be continued for 7 days from the cure of your symptoms if you are not pregnant or until the end of the 12th week of your pregnancy. If your abdomen is tense and swollen because of fluid build-up, you may be offered a procedure known as paracentesis. This is when a thin needle or tube is inserted under ultrasound guidance into your abdomen to remove the fluid. You may be offered a local anaesthetic for this procedure. This treatment helps relieve discomfort and improve kidney function and breathing. Rarely, advice may be sought from a more specialist team which may involve anaesthetists and/or intensive care doctors.

• To lower the risk of developing a blood clot in your legs or lungs, you will be advised to continue wearing support stockings and taking heparin (blood-thinning) injections until 12 weeks of your pregnancy.

• You may be at increased risk of developing pre-eclampsia or giving birth to your baby prematurely. However, there are no known risks to your baby’s development as a result of OHSS.

It is a good question, as technically, one egg one sperm can make one baby. It is possible to have a baby with one good quality egg. However, recent research showed, there is a strong association between the number of eggs and chances of a baby; chances of having a baby at end of IVF cycle rise with an increasing number of eggs up to 15 (https://academic.oup.com/humrep/article/26/7/1768/2913935).

An average number of eggs collected per cycle is 9. But the rise in quantity does not mean a rise in quality. Therefore the balance of quality and quantity is important which is what we aim for at p4 fertility.

Ovarian reserve tests are developed by IVF clinics to predict how a woman having IVF treatment would respond to the drugs used to stimulate the ovaries and ultimately how many eggs she may produce. Ovarian reserve can be assessed through blood tests to measure two important hormones: follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) or by an ultrasound scan that counts the growing follicles within each ovary. As all of these ovarian reserve marker tests have some limitations, P4 fertility, with its personalised and predictive approach, advice on appropriate ovarian reserve marker tests and its personalised interpretation. Every test, if not done correctly or not interpreted correctly may result in misinformation. Age is a golden predictor for the success of fertility treatment. The ovarian reserve markers should be combined for personalised prediction. We first time proposed the approach of combing age and AMH together for prediction. (Link to paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963310/ )

There are three stages of eggs in the ovary at any given time for a fertile woman.

The first stage is eggs which are in sleeping stage- these eggs do not respond to any stimulation and there is no test to find the number of these eggs.

The second stage is eggs which are started to wake up but not ready to get stimulated in the cycle. During this stage, eggs may have some activity but they are not seen on an ultrasound scan as their follicle is small. Some of these follicles release AMH.

The third stage is Antral follicle which could be seen on an ultrasound scan. Commonly called as AFC or antral follicle count. This stage follicles release AMH. These eggs are ready to get stimulated in the cycle.

Therefore, useful ovarian reserve over the period of time is estimated by AMH. AFC explains the estimated eggs which can come out in the given cycle.

FSH measurement is an indirect measure of the reserve, high FSH means low reserve. But being indirect measure and changing values during the menstrual cycle, FSH is not a reliable marker of the reserve.

AMH levels are stable over a period of time and very slowly change. AFC may be different from cycle to cycle, depending upon a pool of eggs coming out from the first two stages.

At P4 fertility, we personalise the reserve testing and when and how to stimulate.

AMH test is a blood test which can be done at any time during the cycle. AMH is a hormone produced by the growing follicles in the ovaries and is a direct marker of the number of follicles. Therefore, it is used as an ovarian reserve marker. AMH varies with age. Normal levels are interpreted with age. AMH <5pmol/ml is considered as a poor ovarian reserve. Lower levels are indicative of poor reserve and higher levels associated with, but not diagnostic of, polycystic ovaries. AMH varies less through the period cycle and so can be measured at any time. AMH should not be measured with long term use of contraceptive pills, it may show lower levels than normal.

No. AMH is not a good predictor for chances of natural conception.

AMH gives an idea of a number of eggs in the ovary.

Broadly speaking AMH = quantity of eggs in the ovary (high value of AMH, a high number of eggs)

Age= quality of eggs. (Higher the age, lower is the quality)

The stimulation protocols are based on age and AMH results. At p4 fertility, we analyse all factors including AMH and age to personalise the IVF protocols.

AMH action in the ovary is like a double edge sword. On one hand, it suggests a high reserve. On the other hand, it holds the follicles in the ovary and not let it come out. High levels of AMH suggests a high number of eggs are ready to come out, however, during the treatment cycle, few eggs come out. This happens when AMH is higher than the dose of stimulation medication (FSH) could make follicles free from AMH action. AMH holds follicles like someone holding the bunch of balloons. If FSH doses is not sufficient (which happens due to clinicians’ fear of OHSS), or cycle is coasted, the result is poor quality and less quantity of eggs. When the stimulation dose is higher than AMH negative effect, the risk of hyperstimulation (OHSS) is higher as all balloons get released at once.

Stimulation protocols for women with high AMH require true personalisation and use of multiple tricks to strike a right balance of quantity and quality. P4 fertility offers a truly personalised plan for their IVF patients.

Low AMH does not mean anything more than the low ovarian reserve. It does not mean simply that there are low chances of success. As explained above, AMH measures pool of eggs including those not ready to get stimulated. Age predicts the quality and AMH predict the quantity.

Therefore, at p4 fertility, the focus is on when to stimulate, how to stimulate and how to get maximum eggs which are ready to get stimulated for this group of women (low AMH). Low AMH tells clinician to personalise the strategy 9 rather than using standard approach) to get a good number of eggs out.

Our truly personalised protocols help to get this right. We focus on the cycle to get a good number of eggs out with pre-treatment optimisation.

We have good success rates for this group with AMH<5 pmol/l. We do not advise against treatment based on AMH alone.

We have done extensive research on poor ovarian response. You may see the research paper ….. Personalised IVF protocols and pre-treatment is the key as one size does not fit all. At p4 fertility, our focus is on personalised poor responder protocols- when, how, what doses, which medications for women with low egg count are low due to low DHEAS (adrenal origin) it may make sense to add DHEA supplement.

Your body naturally produces the hormone dehydroepiandrosterone (DHEA) in the adrenal gland. In turn, DHEA helps produce other hormones, including testosterone and estrogen. Natural DHEA levels peak in early adulthood and then slowly fall as you age.

These hormones present in both sexes. These hormones are present in ovary and helpful for the production and development of eggs. In an infertility setting, particularly in conjunction with IVF, DHEA is thought to be useful to treat women with reduced ovarian reserve. However, research so far did not show any significant benefit.

DHEA supplementation helps women with low reserve by increasing the androgen levels within their ovarian environments to a normal range. As their immature eggs develop to the ovulation-ready stage in the androgen-enhanced ovarian environment, it is claimed that these eggs mature into better-quality eggs. High-quality, healthy eggs develop into high-quality embryos, which have better chances of implantation and lower risks of miscarriage.

No. It is not licenced in the UK. There is no research evidence to support its use. It is available as a food supplement on the internet.

All women over 40 and younger women with the low ovarian reserve are advised to take at least 6-8 weeks of DHEA supplementation before starting IVF. DHEA dosage for fertility is 75mg daily, which is split into three 25mg doses. Peak effect is seen after 12 weeks of supplementation. As mentioned above there is no evidence to support DHEA in poor responders.

It is important to note that alone, DHEA for fertility is unlikely to be effective for women with a reduced ovarian reserve who are trying to conceive. Not all women have reduced androgen levels in the ovary. The individualisation of the protocols is the key. It is advisable to measure androgen levels and DHEAS levels to find out the origin of low androgen in ovary if at all it is present. If androgens in ovarian micro-environment are low due to low DHEAS (adrenal origin) it may make sense to add DHEA supplement.

Negative side effects of DHEA are possible but rare, include:

· Oily skin

· Acne

· Hair loss

· Stomach upset

Do not take DHEA when you are pregnant. Close monitoring of androgen and SHBG is necessary during DHEA supplementation. We strongly discourage women from DHEA self-supplementation.