Where the cause of infertility is a failure to ovulate, drug treatment is usually highly effective. Except in women with an early menopause, this can result in ovulation in about 80 per cent of women ovulating. At least 65 per cent of couples succeed in getting pregnant with these treatments.
This is the standard ‘fertility pill’, usually marketed as Clomid or Serophene. It is a good first-time treatment. It is cheap and free from major side-effects. It rarely causes multiple births because it is only a weak stimulant. It promotes ovulation by stimulating the natural release of FSH from the pituitary. This makes the ovaries work harder to produce follicles. But its use requires supervision because it is an anti-oestrogen: it can thicken cervical mucus, making the cervix unresponsive to sperm; it can interfere with the growth of the uterine lining, and possibly prevent the embryo from implanting; and overstimulation can cause ovarian cysts.
An article published in the late 1990s suggested the possibility of a slightly increased risk of ovarian cancer in women who had taken clomiphene for a very long time. There was no definite evidence of this increased cancer risk unless a woman had been taking it for at least a year.
Usually, one tablet (25– 50 mg) is taken every day for five days, starting on the first or second day of menstruation. If the woman’s cycle is much longer than 28 days, clomiphene may be given from the fifth day. The dose may be increased if there is no positive response.
Symptoms that indicate ovulation are:
None of these are conclusive proof of ovulation, so tests to check that ovulation really is occurring should be done. The best method is ultrasound as this will not only confirm ovulation but will also detect any cysts.
A blood progesterone test is often used but is less reliable because Clomiphene can stimulate the production of more than one follicle, without ovulation occurring. The combined amounts of progesterone that these follicles produce together may raise the blood progesterone to an ovulatory value (30nmols or more) even although an egg has not been shed.
Clomiphene should be discontinued if a pregnancy has not occurred within six to nine months.
Clomiphene may cause hot flushes. A few women get frequent or irregular periods, and if this happens they may need to stop the drug. Cysts that may develop are not serious, but the drug should be stopped to give the ovaries a chance to recover. Some people just feel unwell while taking Clomiphene. There are drugs similar to clomiphene that can be taken instead, including tamoxifen and cyclofenil. But they less effective and more expensive.
Biologically derived Human menopausal gonadotrophin (hMG), was the first mixture of hormones to be used to help fertility, although it is the FSH that is the active ingredient. Genetically engineered FSH (or so-called recombinant FSH/recFSH) has now virtually entirely replaced hMG as it is safer and less likely to have the side-effects associated with skin reactions and other reactions to foreign proteins. This treatment is often reserved for cases where clomiphene has failed, but for some women they may be used as an initial treatment.
FSH is usually injected daily from the early part of the menstrual cycle until ovulation is imminent – usually about five to ten days later. When ovulation is about to occur, a triggering injection of human chorionic gonadotrophin (hCG) is given. It is usual to conduct regular ultrasound measurements of the ovarian follicles and often to measure the level of oestrogen in the blood as well during the course of FSH and hyperstimulation syndrome (OHSS) is the main risk. Multiple ovulation can also result in multiple birth. If there are too many follicles the triggering dose of hCG can be withheld. Most clinics offer treatment for only three months at a time. If conception does not follow after six cycles in which ovulation has occurred, treatment should be stopped.
In normally fertile women the pituitary gland releases FSH and LH in pulses every 60 to 90 minutes. Consequently, some doctors have tried to mimic nature. Pulsatile injections of FS and LH can be delivered at appropriate intervals via a small electric pump attached to a syringe worn by the patient. ‘Pump therapy’ can be helpful, particularly in cases of polycystic ovary disease, and for women who are producing very small amounts of FSH and LH of their own.
The hypothalamus in the brain secretes the releasing hormones that trigger the pituitary gland to produce of LH and FSH (see page 000). Injection of LH-releasing hormone (LHRH) at regular intervals has been shown to be a particularly effective treatment in rare cases where the communication between the hypothalamus and the pituitary gland is not working properly. LHRH therapy is less likely to result in multiple pregnancies as it merely stimulates the pituitary gland to release LH and FSH in the quantities naturally required. If indicated, this treatment can be continued for at least six months to a year before considering IVF.
When drug treatment fails in cases of polycystic ovaries POS (see page 000) it may possible to stimulate ovulation by removing a piece of ovarian tissue. The operation can be performed using laparoscopy and microsurgery without the risk of adhesion formation, which can damage the tubes. The ovarian capsule can be drilled during a laparoscopy or burning or drilling can be done with an electric needle or with a fine laser beam. If pregnancy has not occurred within one year of this treatment, IVF should certainly be considered.
These drugs are chemically similar LHRH, above, initially encouraging the pituitary gland to produce more FSH and LH. After several days of use, they suppress it. They are taken in the form of a nasal spray, usually up to four hourly during the day. Buserelin is not generally used on its own as a fertility treatment, but its ability to stop ovarian function helps suppress hormonally dependent conditions like endometriosis or fibroids. Once the ovaries are suppressed, endometriosis tends to disappear and fibroids to shrink. As soon as these drugs are stopped this temporary menopause ceases but it often means the return of endometriosis and the regrowth of fibroids.
Buserelin is chiefly used with drugs like FSH to stimulate the ovaries. In women with polycystic ovaries, it can be more effective to give Buserelin initially to suppress pituitary function and then to follow this up with FSH. This principle is used during IVF treatment, but it can be used simply to induce ovulation. The approach has many disadvantages as it may cause too much stimulation with too many eggs.
In some cases, the endometrium seems too thin for an embryo to implant, perhaps because the ovary has not produced enough progesterone. It can be useful to try to make up for this deficiency by giving extra progesterone in the form of an injection or vaginal pessary. Injections of hCG which encourage the ovaries to produce their own progesterone may have the same effect.
Despite countless breakthroughs in medical science, we still do not understand why some pregnancies will end in tragedy. For most of us, having a child of our own is the most fulfilling experience of our lives. All of us can imagine the desperation and sadness of parents who lose a baby, and the life-shattering impact that a disabled or seriously ill child has on a family.
Professor Robert Winston’s Genesis Research Trust raises money for the largest UK-based collection of scientists and clinicians who are researching the causes and cures for conditions that affect the health of women and babies.
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