IUI for Unexplained infertility

Two meta-analysis published recently comparing oral medication like Clomiphene and Letrozole versus Gonadotrophins (FSH injections) to stimulate ovaries during IUI treatment for Unexplained Infertility, coming up with contradictory conclusions:

The first paper published in Human Reproduction Update in Jan2020, says that the

Gonadotropins (FSH injections) are better than oral drugs (clomiphene/letrozole) in achieving a higher live birth rate. However, it should be used with strict cancellation criteria to keep the multiple pregnancy rates low.

On the other hand, the second paper published in Fertility and Sterility Journal in February 2020, concludes that it does not support the use of gonadotropins (FSH injections) over oral agents (clomiphene/letrozole) for ovarian stimulation during IUI for unexplained infertility as the live birth rate for gonadotrophins are same as that of oral agents when used with the strict cancellation policy.

What is IUI?

Intra-Uterine Insemination (IUI) is frequently used treatment for couples with unexplained infertility when washed sperm is placed in the uterine cavity around the time of ovulation.

It can be done in a natural cycle, where no medications are given to the woman and insemination is done at the time of natural ovulation.

However, the success rate is higher when it is combined with ovarian stimulation, which increases the number of eggs released to 2-3. This increases the chances of success by increasing the number of eggs available for fertilisation.

However, increasing the number of eggs increases the risk of multiple pregnancies like twins or triplets, which are considered high-risk pregnancies.

Ovarian stimulation can be done with oral drugs like clomiphene or letrozole or gonadotropins (FSH injections).

What do the guidelines say?

Management of Unexplained infertility is full of controversies. There is no universal agreement on treatment policies. Since there are no definite identifiable causes for these patients, their treatment remains empirical.

UK, NICE guideline recommends not to routinely offer IUI for couples with unexplained subfertility but to proceed directly to IVF after two years infertility.

American Society for reproductive medicine suggests 3-4 cycles of IUI with oral medications before moving to IVF. They recommend against using gonadotrophins for IUI for these patients.

Where we stand now?

Management of couples with unexplained infertility should be individualised, taking into consideration the age of the women, duration of infertility, previous pregnancies, patient’s preference and cost implications.

3-4 cycles of IUI before moving to IVF is a valid option for young women <37 years and trying for 2-3 years. However, for women >37 years or for those trying for a longer duration, IVF should be considered sooner.

Oral agents for IUI makes the treatment more patient-friendly while keeping the success almost similar to that of gonadotrophins, without overtly increasing the multiple pregnancy rate.

Written by: Dr Anupa Nandi