Examining the timing and administration of GnRH antagonists during IVF

This study examined the timing of gonadotropin-releasing hormone (GnRH) antagonists during in vitro fertilization (IVF) treatments. Authors concluded that a modified early GnRH protocol achieves similar outcomes to the GnRH agonist protocol with a shorter overall treatment duration.

IVF is a complex process which requires medical control over the ovulation (egg release) cycle. The most commonly used protocol for IVF involves first suppressing the woman’s natural hormones. This allows better control of the timing of ovulation. Common drugs used to achieve this suppression include GnRH antagonists, such as cetrorelix (Cetrotide). They are administered when the follicle size has reached 12 to 14 mm during ovarian stimulation treatment (usually around Day 6). The follicle is the structure that holds the egg before it is released into the uterus. Larger follicles improve the chances of pregnancy.

There are two GnRH analogues (agonists and antagonists) that can predictably control ovulation. GnRH antagonists work immediately, while GnRH agonists take several days of treatment. However, GnRH agonists have been associated with better pregnancy rates. It has been argued that adjusting the timing of GnRH antagonists may improve treatment outcomes. 

This study examined whether starting GnRH antagonists early can lead to improved ovulation and pregnancy rates during IVF. A total of 218 women undergoing their first IVF cycle were included.

The first analysis divided 68 women according to two GnRH protocols. 34 women received the conventional protocol: GnRH administered when follicle size has reached 12 to 14 mm (Day 6 to 7). 34 women received the early protocol: GnRH administered on Day 2 before follicle size of 18 mm is reached.

The average number of mature eggs was 11.9 for women undergoing the early protocol. This was significantly higher than 8.2 for women undergoing the conventional protocol. 82.6% of eggs retrieved were mature with the early protocol, compared to 71.9% of eggs with the conventional protocol. However, no differences in pregnancy rates were noted between the early (23.5%) and the conventional GnRH protocol (26.5%).

The second analysis compared three GnRH protocols in 150 women. 43 women received the conventional protocol. 34 women received a modified early protocol: GnRH administered on Day 2, then switched to another gonadotropin-based hormone once follicle size of 18 mm was reached. 73 women received the GnRH agonist long protocol, started several days before ovarian stimulation.

The average number of mature eggs was higher with the modified early protocol (average 10.7) than with the conventional protocol (average 8.8). This difference was not statistically significant. However, the pregnancy rate was significantly higher with the modified early protocol (41.2%) compared to the conventional protocol (30.2%). The pregnancy rate of the GnRH long protocol was 39.7% and therefore similar to that of the modified early protocol.

Authors concluded that a modified early GnRH protocol achieves similar treatment outcomes to the GnRH agonist protocol with a shorter treatment duration.