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Small Alterations in Gonadotropin-Releasing Hormone Antagonist Protocols May Increase Assisted Pregnancy Rates: Presented at ASRM

By Amanda Strong

MONTREAL, QC -- October 19, 2005 -- Switching to a fixed start protocol of gonadotropin-releasing hormone (GnRH) antagonist, in which the agent is given as early as day 5 of ovarian stimulation, might improve the rates of success after assisted pregnancy procedures, suggests a retrospective review of in vitro fertilization (IVF) protocols.

Investigators led by Myvanwy McIlveen, MD, Clinical Research Fellow, Jessop Wing Assisted Contraception Unit, Sheffield Hospital, Sheffield, United Kingdom, reviewed pregnancy and implantation rates for more than 595 cycles.

The four protocols used in the study cohort were the following: a fixed start protocol using the GnRH antagonist ganirelix on day 6 of ovarian stimulation; flexible-start ganirelix commenced between days 5 to 9 of stimulation, when the lead follicle was at least 14 mm in diameter and/or peak estradiol levels were greater than 1000 pmol/L; a flexible-start ganirelix as a morning injection; fixed start ganirelix as a morning dose given on day 5 of ovarian stimulation.

Dr. McIlveen presented the outcomes with each of these protocols here on October 18^th at the 2005 annual meeting of the American Society of Reproductive Medicine (ASRM).

"What we found when we switched to the morning dosing schedule of the third protocol was that 90% of our patients were starting the antagonist on day 5 based on the criteria of lead follicles and peak estradiol levels," Dr. McIlveen said. The day 5, fixed-start protocol is the one that is currently being used at Sheffield Hospital.

With each successive protocol, pregnancy and implantation rates improved significantly. During the first protocol, 20.8% of transplanted embryos resulted in successful pregnancy, compared with 26.8% and 36.1% in protocols two and three, respectively (P < .001). The rate for the fourth protocol was similar to the third, at about 37%.

Pregnancies were determined by the presence a foetal heartbeat during an ultrasound scan.

Implantation rates followed a similar pattern: 10.3% for protocol 1, 16.3% for protocol 2, and 24.8% for protocol 3 (P < .001). Protocol 4 was similar to protocol 3, with implantation rates around 25%.

Luteinising hormone (LH) levels were measured for protocols 1 through 3. Premature LH surges were seen in 13.2% of cycles in the first protocol but were uncommon in subsequent protocols. As expected, women with higher LH levels (>10 IU/L) on the day that GnRH antagonist was started had lower pregnancy rates than those with lower LH levels; however, the difference was not statistically significant.

"I think what this tells us is that we can play with things and improve pregnancy rates for our patients," Dr. McIlveen said. "We should be considering starting antagonists earlier rather than later."

The results of the study also support findings from other studies from Europe that suggest there is little benefit to a flexible approach and that early commencement with GnRH antagonists can improve assisted pregnancy rates by controlling LH levels, she said. Nonetheless, large, multicentre, randomised, controlled trials are needed to confirm these findings.


[Presentation title: Alterations in the GnRH Antagonist Protocol Used Can Improve Pregnancy Rates. O-97]

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