Letter to the editor |
Reply: Luteal support post GnRH agonist trigger: do not stop too soon
The Fertility Clinic, Viborg Hospital (Skive), Resenvej 25, DK-7800 Skive, Denmark
E- mail: peter.humaidan{at}sygehusviborg.dk
Sir,
We wish to thank Dr Kol for his letter regarding the length of the luteal support given in GnRH antagonist IVF/ICSI cycles in which ovulation was induced with a single bolus of a GnRH agonist. In our study (Humaidan et al., 2005
) we showed that patients who were treated with a GnRH agonist for final oocyte maturation had a significantly lower implantation rate and clinical pregnancy rate as compared to patients treated with hCG for final oocyte maturation. At the same time the rate of early pregnancy loss was significantly higher. This occurred despite luteal support with micronized progesterone vaginally, 90 mg/day, and estradiol, 4 mg/day per os, administered from the day following oocyte aspiration and continuing until the day of the pregnancy test, i.e. a total of 13–14 days. We concluded that this protocol is not clinically acceptable in its present design.
Of course we cannot totally exclude that the length of the luteal phase support in the present set up could have an impact on the poor clinical results, as a prospective randomized study regarding this issue, according to our knowledge, has not been performed. But several factors support the results of our study.
First of all, Griesinger et al. (2004) in a study with a design similar to ours has obtained equally poor reproductive outcome results, despite luteal support with micronized progesterone and estradiol orally until 7 weeks of gestation.
Secondly, Dr Kol is one of the co-authors of a study by Itskovitz et al. (2000), including few patients, in which a low pregnancy rate per transfer (14.3%) was found in a non-randomized group of high-responder IVF/ICSI patients treated with a GnRH agonist to trigger ovulation. The low pregnancy rate was obtained despite luteal support until 9 weeks of gestation.
Thirdly, in the study by Fauser et al. (2002) pregnancy rates remained low and rates of early pregnancy loss high despite luteal support for >2 weeks in the two arms of the study in which ovulation was triggered with a GnRH agonist.
Finally, in the present study the mean plasma 
-hCG levels on the day of the pregnancy test (day 12 after embryo transfer) were already significantly lower in the GnRH agonist group as compared to the hCG group, indicative of an early malfunction of the trophoblast, irrespective of the length of the luteal support given.
In conclusion, our present knowledge does not support the notion that the length of the luteal support, >12 days, has a major impact on the reproductive outcome when regarding the use of GnRH agonists to trigger ovulation. Other factors seem to play a key role. Given the fact that significantly more metaphase II oocytes (16%) were harvested in the GnRH agonist group, we are currently developing new strategies in an attempt to improve this protocol.
References
Fauser BC, de Jong D, Olivennes F, Wramsby H, Tay C, Itskovitz-Eldor J and van Hooren HG (2002) Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. J Clin Endocrinol Metab 87,709–715.
Griesinger G, Schultze-Mosgau A, Schroer A, van Steirteghem A, Devroey P, Diedrich K and Kolibianakis E (2005) GnRH_agonist instead of hCG for final ooyte maturation in GnRH-antagonist cycles. Hum Reprod vol 20, supplement 1, i92, O-247.
Humaidan P, Ejdrup Bredkjaer H, Bungum L, Bungum M, Grondahl ML, Westergaard L and Yding Andersen C (2005) GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod 20,1213–1220.
Itskovitz-Eldor J, Kol S and Mannaerts B (2000) Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyperstimulation syndrome: preliminary report. Hum Reprod 9,1965–1968.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||