Unexplained infertility

In the absence of a specific diagnosis, any form of treatment for unexplained infertility is speculative. While planning treatment, the likelihood of a spontaneous pregnancy must be taken into account, as even relatively invasive assisted reproduction techniques offer fairly modest pregnancy rates. A period of 3 years of unexplained infertility is generally accepted as a minimum duration before active intervention is considered. The decision to initiate treatment also needs to take the woman's age into consideration. Successful communication with the couple is vital at this point and the importance of detailed discussion, supported, where necessary, by written information sheets, cannot be overstated. Many couples feel frustrated by the apparent refusal to accede to their request for early treatment and need careful counselling.

EMPIRICAL CLOMIFENE

Clomifene citrate has been shown to increase the number of follicles produced per cycle, thus increasing the odds of a fertilized embryo reaching the uterine cavity. Its use in unexplained infertility is still open to debate. A meta-analysis has demonstrated a statistically significant benefit following the use of clomifene in unexplained infertility (Hughes et al. 2000). The combined odds ratio (OR) for clinical pregnancy per patient was 2.37 (CI 1.433.94). The small sample sizes of the trials included in this review inevitably means that the present conclusions are likely to be affected by the outcome of future studies. Traditionally, clomifene has been viewed as an inexpensive and relatively innocuous drug and its empirical use preferred by many to the more invasive assisted reproduction techniques. Concerns about clomifene induced multiple pregnancy and inability to rule out a potential link with ovarian cancer underline the need to weigh the risk-benefit ratio carefully. The approach to the use of clomifene in unexplained infertility differs from that in anovulatory women. A starting dose of 50 mg is used and a day-12 scan performed to assess ovarian follicular response. If the ovarian response is very brisk, the dose should be cut down to 25 mg. The aim is to achieve no more than two preovulatory follicles over 17 mm.

INTRAUTERINE INSEMINATION WITH OR WITHOUT SUPEROVULATION

Intrauterine insemination in natural (unstimulated) cycles as well as in combination with superovulation (SO/IUI) have been used to treat unexplained infertility. Neither treatment has been evaluated in comparison with expectant management. IUI with SO is the more commonly used intervention. Data to support its effectiveness come from a systematic review showing that gonadotrophins along with IUI led to higher pregnancy rates compared to gonadotrophins along with timed intercourse (OR 2.37,

95% CI 1.43-3.90) (Hughes 1997). A single randomized trial (Goverde et al. 2000) showed that pregnancy rates in women treated by IUI alone were comparable to those in women treated by SO/IUI or IVF. A much larger multicentre American trial (Guzick et al. 1999) found SO/IUI to be more effective than IUI alone in terms of live-birth rates (OR 1.7,95% CI 1.2-2.6) but associated with an appreciably higher risk of multiple pregnancy. IUI in an unstimu-lated cycle thus offers the safer option, while SO/IUI may enhance success rates at the cost of a higher multiple pregnancy rate.

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