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Assisted conception

If simpler infertility treatments are unsuccessful or inappropriate, your doctor may suggest that you consider some form of assisted conception. These techniques won’t treat the cause of your infertility, but will bypass it to increase your chance of conceiving. They include in vitro fertilisation (IVF), which is the original ‘test tube baby’
treatment, intrauterine insemi­nation (IUI) and intracytoplasmic sperm injection (ICSI).

STAGES OF TREATMENT

Assisted conception involves several similar procedures. The first is the stimulation of the woman’s ovaries to develop a number of eggs using high doses of fertility hormone injections. This is referred to as superovulation. The second is the monitoring of the development of the woman’s eggs by ultrasound scans and, in some clinics, measuring the oestrogen levels in her blood to know when the eggs are mature and ready to be fertilised. The third is the collection of sperm. These stages of treatment are all arranged as an outpatient. For IVF and ICSI, the woman will need to be admitted to hospital as a day-case for collection of her eggs. For surgical sperm recovery, the man will usually be admitted as a day-case.

Superovulation

Several hormones are used to stimulate the woman’s ovaries to produce additional mature eggs. Two methods of treatment are in use, the first more common than the second.
In the first, the woman’s own hormones will be suppressed temporarily using a drug called a gonadotrophin-releasing hormone agonist (GnRHa). This is usually started about seven to ten days before she is due to start her period, in the cycle before assisted conception is planned.
The GnRHa is usually given as a nasal spray or a daily or monthly injection, and the woman will need to continue taking this until shortly before her eggs are mature. In some clinics, she may be given a seven-day course of progestogen tablets as well, to make sure that she sheds the lining of her uterus completely when she has her period.

In the second, the daily injections of gonadotrophin are started just after the woman’s own natural period. Six or seven days into these injections, the woman’s own hormones will be suppressed using a drug called a gonadotrophin-releasing hormone antagonist (GnRHant). Compared with the agonist, the action of this drug is maximal within six to eight hours and this is then continued, by injection daily or every few days, until egg collection is imminent.
Daily injections of FSH as human menopausal gonadotrophin (hMG) or genetically engineered pure FSH (recFSH) are used to stimulate the development of follicles in the ovaries. The developing follicles are monitored as they mature by several ultrasound scans. In some clinics, blood samples are taken to monitor the levels of oestrogen produced by the ovaries.
When the follicles are mature, a single injection of human chorionic gonadotrophin (hCG) is given to trigger the final stages of egg development and ovulation about 38 to 42 hours later. Once the hCG injection has been given, the woman stops using the GnRH agonist or antagonist. However, because this has been suppressing her own hormones, she will need some additional treatment to keep the lining of her uterus stable and receptive for a pregnancy over the following eight to ten days. This may be with one or two lower-dose hCG injections or with progestogen hormone injections or vaginal pessaries. Some clinics are using GnRHant extensively. Although these were thought to be likely to lead to lower requirements for FSH injections, this has not transpired and the success rates from IVF have not been better or, in some cases, have been slightly worse than with GnRHa use.

Sperm collection

The man will be asked to produce a semen sample early on the day of the woman’s egg collection or ovulation. This may be into a pot containing culture fluid, or into two pots (a ‘split’ ejaculate), depending on the assessment of previous semen samples. The semen is left for a short time to liquefy and then forced through some filtration fluid at high speed (a process called centrifugation). Any debris and abnormal sperm are separated out and healthy, intact sperm collect at the bottom. These are transferred to a test tube of fresh culture fluid. The number of sperm are counted and prepared for the appropriate treatment.

SSR

If the man is releasing no sperm in his ejaculate (azoospermia), surgical sperm recovery (SSR) techniques may be necessary. For men with obstructive azoospermia (where the tubes taking sperm from the testes are blocked), sperm may be collected by passing a needle through the skin of the scrotum into the testis itself, or into the coiled tubules on the surface of the testis, the epididymis. The sperm may be collected on the day the woman’s eggs are collected or one or two days beforehand. Any extra sperm collected may be frozen and stored for future use to avoid the need for repeated SSR.
If the tubes are not blocked (non-obstructive azoospermia), the inside of the testis is thoroughly examined. This can be done as a day-case procedure under general anaesthetic. Several matchhead­sized pieces of tissue may be removed for examination under a microscope, as sperm production may be occurring only in small areas. The chance of collecting sperm is lower for men with non-obstructive azoospermia (50 to 60 per cent) than for men with obstructive azoospermia (about 95 per cent).
After SSR, the man will be advised to wear a firm support for 48 hours, and may need to take some simple pain-killers, such as aspirin or paracetamol. If SSR has been done as an open operation, he may need to rest for three to five days before returning to work.

BASICS OF THE TECHNIQUES

IUI (intrauterine insemination)

IUI is only suitable if the woman has healthy fallopian tubes, for example, if there is unexplained infertility or endometriosis-associated infertility. It raises the chance of pregnancy by increasing the number of eggs and sperm coming into contact with each other in the fallopian tubes. Occasionally, it may be used for minor degrees of male infertility, for women with impaired cervical mucus production or quality, and for rare situations where normal sexual intercourse is not possible.
The prepared sperm are concentrated into a small volume of culture fluid, less than a quarter of a teaspoonful. The procedure should not be painful, and no sedation or anaesthetic is required. An instru­ment called a speculum is inserted into the woman’s vagina to allow a clear view of her cervix. The sperm are drawn up into a long, soft, narrow plastic straw with a syringe. The plastic straw is gently passed through the cervix to the top of her uterus where the sperm are released. The plastic straw is slowly withdrawn and, after a few minutes’ rest, to allow the woman’s cervical mucus to seal off the passage through her cervix, the woman can get up and return home.

Egg collection

For IVF or ICSI, the woman’s eggs are collected just before they are ready to be ovulated, usually about 32 to 36 hours after she has had her single injection of hCG. Almost all egg collection procedures are done through the woman’s vagina using an ultrasound scanner to guide a needle into each of the follicles and draw off the fluid and eggs. The needle passes down a hollow guide tube, which is clipped to the side of the ultrasound probe, and through the top of her vagina into her ovaries. The egg collection is carried out as a day-case procedure under sedation or a light general anaes­thetic, and usually takes about 20 to 40 minutes. As each follicle is drained, the test tube of fluid collected is passed to an embry­ologist, who examines it under a microscope to identify the egg. The eggs are transferred to carefully labelled tubes containing nutrient-rich culture fluid and placed in an incubator.
Rarely, the eggs will be collected at a laparoscopy operation under general anaesthetic. The laparoscope is a narrow telescope-like instrument that is inserted through a ‘keyhole’ incision at the woman’s navel. A needle is passed through the abdominal wall to collect the eggs under the direct vision of the surgeon through the laparoscope.

IVF (in vitro fertilisation)

In addition to being suitable for the problems outlined on page 48, women with damaged fallopian tubes in particular require IVF. About one to six hours after egg collection, 50,000 to 200,000 sperm are added to the small quantity of culture fluid around each egg. This mixture is then transferred to an incubator.
The eggs are inspected under a microscope 18 to 24 hours later. If fertilisation has occurred, the early embryos (called zygotes) are transferred to fresh culture fluid and then returned to the incubator for 24 to 48 hours to allow them to develop further. In the case of women under 40, only two embryos are selected for transfer back to the woman’s uterus, whereas women aged over 40 can choose three if they wish. Any additional embryos can be freeze–stored for later use if they are of sufficiently good quality.
The embryo transfer procedure is virtually identical to intrauterine insemination. However, a slightly narrower catheter is used and the embryos are transferred in a much smaller volume of culture fluid – literally a tiny drop. The woman’s cervix is viewed with a speculum. The embryo transfer catheter is carefully passed through the cervix to the upper end of the uterus where the embryos are injected. The catheter is then gently withdrawn and checked under a microscope to confirm that the embryos have been released. After a couple of minutes’ rest, the woman can get up and return home.

ICSI (intracytoplasmic sperm injection)

ICSI is used when there is severe male factor infertility. This may be the result of a very low sperm count or severely impaired sperm function. It is also necessary when sperm have been collected surgically, because the number of sperm will be low and their swimming ability reduced. ICSI may also be advised for some couples who have had failed fertilisation with previous standard IVF treatment.
ICSI involves the direct injection of a selected individual sperm into each egg in the laboratory under a high-power microscope. It is appropriate only for completely mature eggs. An individual sperm is selected from the man’s sample. It is immobilised (usually by fracturing its tail) so that it can’t swim back out of the egg after it has been injected. The sperm is then carefully loaded backwards into an ultra-fine glass injection needle.
Under the microscope, the egg is held firmly in position by suction onto the end of a thin, blunt, glass tube. The glass needle containing the single sperm approaches the egg slowly until it has pierced and entered the nucleus of the egg. The sperm is then injected. Even with an experienced embryologist, about one in 20 eggs will be damaged by the injection procedure. About 50 to 65 per cent of the mature eggs injected will fertilise after ICSI.

Assisted hatching

One recent addition to the technology involved in assisted conception is the technique of assisted hatching. The fertilised egg grows and divides within a dense protective layer of tissue called the ‘zona pellucida’. This layer remains intact after fertilisation until the embryo is ready to implant into the lining of the uterus. Occasionally, it is believed that this tissue layer remains too hard for the embryo to hatch and implant. Using a variety of chemical techniques or laser technology, a small section of the zona pellucida can be removed under an operating microscope in the laboratory, before embryo transfer. This is assisted hatching. It may give rise to better success rates following embryo replacement in certain circumstances.

Assisted hatching may be of particular value for older women (over the age of 38 years) and when freeze–stored embryos are being replaced, because the zona pellucida is sometimes more dense in these situations. It may also be advised when a couple have had several unsuccessful attempts at IVF, despite having good numbers of embryos transferred. The technique is expensive and does not give increased pregnancy rates other than for the situations mentioned above, and the authors would not advise its routine use in other circumstances.

POSSIBLE COMPLICATIONS

Complications are uncommon with assisted conception techniques.

However, sometimes the treatment is discontinued because the woman’s ovaries respond exces­sively or inadequately to hormone stimulation. The hormone treatment can sometimes cause side effects (such as headaches with GnRHa, or tenderness and localised redness at the site of the daily hMG injections). Other potential problems are that fewer eggs are collected than ex­pected, there may be slight vaginal bleeding after egg collection, the eggs do not fertilise at IVF or there are technical difficulties with embryo transfer (which may then require a short general anaesthetic).
Two major complications are ovarian hyperstimulation syndrome and multiple pregnancy. Ovarian hyperstimulation syndrome (OHSS) occurs when the woman’s ovaries enlarge with fluid-filled cysts. It occurs in about three to five per cent of IVF treatments and is a complication that occurs only after embryos have been transferred back to the woman’s uterus. It is more common if the woman’s ovaries have responded particularly well to hormone stimulation or if she has polycystic ovarian syndrome. Mild symptoms include lower abdominal discomfort, bloating and nausea. More severe – and rarer – symptoms include abdominal swelling and pain, vomiting, shortness of breath (particularly when lying down) and reduced urine production.
A multiple pregnancy (twins, triplets or more) is more likely with assisted conception, as up to a maximum of three embryos are returned to the fallopian tubes. About a third of the multiple births in the UK are now thought to result from assisted conception treat­ments.
The risk of multiple pregnancy will vary depending on the individual clinic and the couple’s circumstances (particularly the woman’s age and whether she has had previous pregnancies). As a rough guide, transferring three embryos, about 65 to 75 per cent of pregnancies will be singleton, 20 to 30 per cent twins and 3 to 5 per cent triplets (90, 10 and less than 1 per cent, respectively, with two embryos). Multiple pregnancies carry an increased risk of complications for the mother and babies, and increased emotional and financial pressures for the couple. To minimise the risk of multiple pregnancy – particularly triplets – some couples have only two embryos transferred during IVF treatment, unless they are aged 40 or more.

TREATMENTS THROUGH THE NHS

The extent of NHS funding for assisted conception treatments varies in different parts of the UK.
The range and extent of treatments available may also change from year to year, and you should ask your GP for advice. You may also get useful information from the local branch of one of the national patient support groups, whose addresses are given at the end of this book.
The guidelines produced by the National Institute for Health and Clinical Excellence (NICE) on infertility in April 2004 have led to expectations that IVF will be more widely available on the NHS. Some primary care trusts (the bodies currently responsible for paying for IVF on the NHS) have begun to put systems into place to provide IVF for their patients through NHS or private clinics. It is likely that there may be restrictions on couples who are eligible for NHS treatment, often based on the woman’s age, the type of fertility problem and whether the couple already have one or more children. If treatment is available, there is likely to be a waiting list initially, varying from several months to two or three years, although this is likely to improve with time. Simpler and cheaper (although also less successful) treatments, such as IUI, may be more readily available. Recent speculation suggests that it will be more readily available, but the barriers and restrictions to treatment may be considerable and it is unlikely to be available to everyone.

THE COST OF PRIVATE TREATMENT
Treatment costs vary between fertility clinics. Most clinics charge separately for an initial consultation and any preliminary investigations. However, your GP may be willing to organise some of these initial tests.
If you have private health insurance, this may cover the cost of your initial consultation and assessment (although not your treatment), as this is essentially an investigation of whether assisted conception is appropriate.

Most clinics do not include drug and hormone costs in their treat­ment charges, as the dosages needed will vary for different women. These are usually paid separately. In some cases, your family doctor may be prepared to prescribe the necessary drugs, even if only for the first cycle of treatment.