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Friday, November 16, 2012

Infertility and assisted conception


Many couples believe that it is easy to have a child and are often surprised when the woman does not fall pregnant as soon as they start trying for a baby. The chance of getting pregnant in each menstrual cycle (each month) is calculated to be one in four for an average fertile couple. However, it may take a long time to conceive, even if everything is normal. Eight out of every ten women trying for a baby will fall pregnant within the first year. Women who do become pregnant without any medical assistance generally do so within two years of trying. It is common for couples to seek help and advice if there is difficulty conceiving. Overall, around 15 per cent (one in six) of all couples will seek help. The point at which they may want to seek help will depend on various factors. For example, if they are over 35 years of age or if they have any worrying symptoms, such as infrequent periods, the couple should seek help after about six months of trying.

What happens during normal conception?

1. The woman

Ovulation is the end of a complicated series of events leading to the release of an egg from the ovary. If that egg is fertilized by a sperm and implants in the lining of the womb (endometrium), a pregnancy has started. All of a woman's eggs will already be present when she is born. From the early years of childhood, she starts to lose eggs, but it is calculated that a woman aged 50 still has about 1000 of her eggs left.

A woman's cycle begins with a hormonal signal from the pituitary gland at the base of the brain. It releases a follicle stimulating hormone (FSH), which stimulates the ovaries. FSH stimulates a group of about 20 follicles on the surface of the ovary to grow. Within the follicles are the developing eggs. Another hormone, estrogen, is produced by the ovary and in response to increasing oestrogen levels, the largest follicle continues to develop. This is why most pregnancies result in only a single baby. Another hormone, luteinizing hormone (LH), also produced by the pituitary gland, causes the follicle in the ovary to release the egg. This release of the egg (or ovum) is called ovulation.

After ovulation, the empty follicle forms a structure called the corpus luteum which produces a hormone called progesterone. Levels of progesterone rise after ovulation and prepare the womb to receive a fertilized egg (embryo). Fertilization by a sperm, if this occurs, takes place in the Fallopian tube, which then moves the early embryo along towards the womb itself. If the egg is not fertilized, or the embryo does not implant in the womb, the progesterone levels fall and a period starts. The whole cycle then begins again.

2. The man

The man's role in conception is the production and ejaculation of sperm cells. To fertilize an egg, a man must be capable of producing adequate numbers of swimming (motile) sperm. Only a few of these sperm cells will in the end reach the egg, and only one will actually enter and fertilize it.

During puberty, the testes become active and start to produce sperm. From his teens until about the age of 70, a man will typically produce 5,000 sperm cells every minute. Ejaculation produces semen, which is a mixture of two per cent sperm cells and 98 per cent liquid produced by the glands in the testes. Production of sperm is under the control of FSH and LH, the same hormones that control the woman's fertility.

When are the chances of fertilization and conception greatest?

  • Fertilization only happens if intercourse takes place almost around the time of ovulation. Ovulation only takes place once in every menstrual cycle, which means that there are only a few days each month when a woman can fall pregnant. However, intercourse and ovulation don't need to be at exactly the same time as healthy sperm can survive for about 48 to 72 hours inside a woman's body and a woman's egg lives for about 12 to 24 hours after ovulation.
  • Fertility is therefore a result of sperm and egg meeting each other almost immediately after ovulation. Ovulation occurs 14 days before the onset of a period. This is reasonably predictable if the cycle is regular, but may be very unpredictable if the cycle is irregular.

What does fertility depend upon?

The hormone balance must be correct to ensure an egg develops and ovulates normally. Intercourse must take place during the fertile part of the cycle. There must be an adequate number of motile sperm and no mechanical barrier such as blocked Fallopian tubes, which may prevent sperm reaching the egg.

Infertility investigations

Infertility investigations will vary according to the couple's particular problem. It is sensible to ensure immunity to rubella (German Measles) before attempting to become pregnant. This involves a simple blood test. Also, it is advisable that the woman is taking a daily dose of folic acid to prevent spina bifida in her baby if she falls pregnant.

Other investigations are described below

Tests to predict ovulation

Ovulation raises the body temperature slightly, so for many years women were advised to take their temperature every morning to find out when they were ovulating. It is also possible to test a sample of urine for LH (luteinizing hormone) and ovulation predictor kits can be purchased from most chemists. The advantage of testing urine, rather than taking the temperature, is that the sample reveals LH before actual ovulation takes place. Since examination of urine samples is expensive, the temperature method can still be used as a supplement.

Semen analysis

This will give information about the number of sperm per milliliter, the percentage of sperm swimming normally (motility), and the percentage of abnormal sperm. There can be considerable variation in the results between different samples, which is why a reduced semen analysis will always be checked with one or two repeat tests.

Hormone measurements

Tests to check whether the fallopian tubes are patent or blocked.
Hormones involved in ovulation are LH, FSH, oestrogen and progesterone. Another hormone, prolactin is also important, as are problems with the thyroid gland. LH, FSH, prolactin and thyroid hormones may be measured at the beginning of the cycle. Progesterone may be measured at the mid-point between ovulation and the next period as at this point its level in the blood will be highest and will indicate whether ovulation has occurred or not.

Hysterosalpingography (HSG)

This is an X-ray examination of the womb and Fallopian tubes and involves injecting a dye through the cervix into the womb. It does not usually require a general anaesthetic, but there may be associated discomfort.

Laparoscopy and dye examination

This involves admission to hospital and is performed under a general anaesthetic. A small incision is made in the abdomen and a needle inserted. Gas is passed through the needle to distend the abdomen then a telescope called a laparoscope is inserted into the abdomen. The womb, tubes and ovaries are then inspected. Dye is passed through the cervix into the womb and the tubes can be observed directly to see whether they are damaged or not.

How is infertility treated?

Clomifene tablets

These tablets prescribed for women who are not ovulating and who have normal levels of oestrogen. The tablets are taken for five days at the beginning of the cycle. There is a slightly increased chance of having twins with clomifene treatment.

Ovulation induction using gonadotrophins

Gonadotrophin (FSH, LH, and human chorionic gonadotrophin) is used for women who have a problem with ovulation that either has not responded to clomifene, or that is not suitable for clomifene treatment. It may also be used for couples in whom the infertility has no obvious cause (unexplained infertility).

FSH as follitropin alfa (Gonal-F) or follitropin beta (Puregon), or a combination of LH and FSH (Menopur) are given by daily injections. The response is monitored by ultrasound scans and blood tests. When the follicles have developed appropriately, another injection called human chorionic gonadotrophin (HCG) is given. This causes ovulation to happen. The couple are then advised to have intercourse or intrauterine insemination (IUI) of the partner's sperm is performed at a pre-determined time after the HCG injection.

The success rate of this treatment depends in part on the cause of the problem, but is generally approximately 20 per cent per cycle. Anxieties associated with this treatment are over stimulation of the ovaries, which occurs in about 0.5 per cent of cycles. Also the rate of multiple pregnancies is increased compared to spontaneous conception. The chance of twins is approximately 20 to 25 per cent.

In vitro fertilization (IVF)

This is the test tube method, more correctly known as in vitro (in glass) fertilization (IVF). Fertilization takes place outside the woman's body. Most clinics suppress the action of the woman's own LH and FSH by using an injection or a nasal spray (down-regulation). The ovaries are then stimulated with daily injections in the same way as ovulation induction with gonadotrophins .

Monitoring is again by ultrasound and blood tests. Once there are sufficient follicles of the correct size, an injection of HCG is given. The eggs are removed from the ovary 36 to 40 hours later. This is done using a fine needle placed into the vagina and is performed under sedation. The eggs are fertilized with sperm in a laboratory.

After a few days, when fertilization is confirmed, the fertilized egg (embryo) is returned to the womb. The chance of a positive pregnancy test after a fresh cycle of IVF varies, but is approximately 20 to 30 per cent. To maximize the chances of a pregnancy, two embryos are usually returned at the same time, which is why there is an increased chance of twin pregnancies.

If sufficient embryos of good quality develop there may be an option to freeze them and replace them, after thawing, in a subsequent cycle. The success of a frozen embryo transfer is slightly less than that of a fresh cycle.

The availability of IVF on the National Health Service varies considerably from one part of the country to the other. Couples often have to be prepared to pay to have their treatment at a private hospital.

Intra-cytoplasmic sperm injection (ICSI)

This is a technique used for male infertility, or for those patients where poor or no fertilization has been achieved after a cycle of IVF. The procedure is very similar to IVF. However, with ICSI a single sperm is injected into a single egg in the laboratory. The success rates are similar to those with IVF.Normally sperm is obtained by masturbation. Under certain circumstances sperm may be obtained directly from the testis by a minor operation.

Other treatments

Donor insemination

If the man has no sperm at all (azoospermia) or very few sperm present (severe oligospermia) donor insemination may be the only option open to them. Sperm is inseminated into the womb after ovulation has been precisely timed.

Egg donation

This may be offered to women who have undergone a premature menopause, which may occur for a variety of reasons, or to women who consistently respond poorly to ovarian stimulation in IVF.

The donor must be prepared to undergo stimulation of the ovaries with drugs and egg collection as if she were undergoing IVF herself. The eggs are then fertilized with sperm from the infertile woman's partner and the embryos replaced in the infertile woman's womb.



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