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Unexplained Infertility

There is not enough evidence on the outcomes of IVF for unexplained infertility. Some of the studies showed no major benefit of IVF or GIFT over intrauterine insemination, with or without ovulation induction. The reviewers concluded that it is possible that IVF results in more pregnancies than other options for unexplained infertility, but this is not certain. More research is needed on birth rates, adverse outcomes and costs.

IVF also can give us clues as to the cause of the infertility. For example, we may see low fertilization rates per egg, or we may see slow embryo development, excessive fragmentation of the embryos, abnormal eggs, abnormal egg shells (zona pellucida), etc.

Tubal flushing (a procedure that may help by 'clearing the path' for eggs to move through the fallopian tubes).

Tubal flushing with oil-soluble contrast media might increase the chances of pregnancy Tubal flushing (also called hydrotubation) was originally used only as a test for blockages in the fallopian tubes that stop the egg from reaching the uterus.

The traditional methods of tubal flushing have involved using a blue dye and other water-soluble contrast media (WSCM) with laparoscopy, and oil-soluble contrast media (OSCM) for a hysterosalpingogram. The adverse effects of hysterosalpingograms have been reduced with availability of screening with fluoroscopy. Fluoroscopy involves using TV-type screens to view the flushing instead of needing to take x-ray films and develop them.

It was noticed that more women seemed to become pregnant after the test - without any other treatment. A Cochrane review has studied trials of tubal flushing to see if it is useful as a treatment for infertility. The review found that OSCM tubal flushing (particularly with lipidiol accompanied by hysterosalpingogram) increased the chances of pregnancy for couples with unexplained infertility.

Tubal flushing with OSCM also results in less pain for the woman than flushing with WSCM (perhaps because of less chemical irritation from the spread of the fluid into the body). It may be that OSCM is more effective at flushing out debris or dislodging plugs of material from otherwise undamaged tubes: that is, that the tubes are not actually blocked, but there is enough there to get in the way of eggs. However, many infertility specialists and clinics no longer use tubal flushing with hysterosalpingograms in their routine tests investigating infertility. The laparoscopic test with WSCM has become more frequently used instead, as that test can provide extra information. However, what is best as a diagnostic test may not be the best form of tubal flushing to try and increase the chances of pregnancy.

There is not enough evidence to be certain that tubal flushing with OSCM definitely increases the chances of pregnancy more than WSCM and laparoscopy. Overall, 13% of women having hysterosalpingogram with OSCM conceived within three months (compared with only 7% in a group having hysterosalpingogram with WSCM), but more research is needed to show if other people can expect similar results.

While it is not certain that tubal flushing with OSCM is an effective form of treatment, rather than just a useful test, the reviewers concluded that it was worthy of more research. They are currently running a trial of tubal flushing with OSCM as a treatment for infertility.

Ovulation induction with hormones ('fertility drugs') and other hormones

Clomiphene may lead to a small increase in pregnancies in women with unexplained infertility, but other drugs might not help.

For couples with unexplained infertility, ovulation induction is intended to increase the chances of pregnancy, by increasing the woman's fertility. This theoreticallly might overcome, or compensate for, a number of problems.

There are two types of hormones for ovulation induction. One type is synthetic (such as clomiphene) and hormones which are foreign to the body. The other type are gonadotrophins, which are also produced by the body.

The first type are more common, and are oral (by mouth) treatments. These are

clomiphene(clomifene) citrate, and tamoxifen (the same hormone used in breast cancer treatment). These drugs work by blocking the effects of the hormone oestrogen (estrogen), and stimulating other hormones with are involved in follicle development and ovulation. The follicle is the part of the ovary that produces the egg.

There is also concern that clomiphene may increase the chances of ovarian cancer. Some studies have found a strong link, while others have found none1. For this reason, use of clomiphene might be restricted by some doctors to six menstrual cycles, to lower any chance of longterm harm to the ovaries.

Review of clomiphene by women with unexplained infertility found that it does increase the chances of pregnancy, although not greatly.

These cover the main medical options for people with unexplained infertility. Another set of medical option is the area of immunotherapy generally (treatments that affect immune responses, such as corticosteroids).

One of the possible contributors to infertility is a woman's immune system. Some women develop antibodies which can prevent fertilisation or the establishment of pregnancy (for example, antibodies against sperm, or antibodies that might prevent an embryo implanting into the uterus).

Tests for one of these factors (antiphospholipid antibodies, or APL) is becoming more widely available to women with infertility . However, testing all women with unexplained infertility for APL or other antibodies remains controversial, and there is no strong evidence of benefit for having this test if there is no particular reason to look for antibodies.

Corticosteroid drugs are one of the possible immunotherapy treatments, and these drugs have been used for women with unexplained infertility. This and other forms of immunotherapy for people with unexplained infertility are controversial experimental treatments.

Some chemicals or lifestyle factors could, in some people, upset the delicate hormonal balance necessary for conception. However, this does not mean that exposure to these factors has 'caused' a person's infertility - or that removing these elements from someone's lifestyle will guarantee a pregnancy. Too much emphasis on poorly proven theories about risks and lifestyle changes has the potential to increase people's levels of guilt about infertility. This is not helpful, especially when there is no guarantee that a lifestyle factor would have changed the outcome.

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