1 Department of Obstetrics and Gynecology, Rambam Medical Center, and 2 Faculty of Medicine, Technion Israel Institute of Technology, Haifa, 31096, Israel
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Abstract |
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Key words: GnRH agonist/OHSS/ovulation induction
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Introduction |
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These authors (as well as others) have ignored a strategy that prevents severe OHSS, i.e. triggering ovulation using gonadotrophin-releasing hormone (GnRH) agonists instead of human chorionic gonadotrophin (HCG). This strategy was first introduced by Itskovitz et al. (Itskovitz et al., 1988, 1991
), and has been used ever since with excellent results in terms of OHSS prevention. Our group has accumulated experience with this strategy with hundreds of patients (both induction of ovulation and IVF cycles), and some of this experience has been published (Itskovitz et al., 1991
; Lewit et al., 1995
, 1996
). This strategy is not applicable in ovarian stimulation cycles before which pituitary down-regulation is induced by GnRH agonists. However, in non-down-regulated or in GnRH antagonist-based cycles this approach prevents any clinically significant OHSS.
The few cases that described possible failures of this strategy were the focus of a previous debate published 4 years ago (Kol et al., 1996). Of note is one paper (van der Meer et al., 1993
), which describes three cases in which this strategy supposedly failed to prevent OHSS. While the three patients presented developed mild to moderate OHSS after receiving nasal GnRH agonist (instead of the injectable preparation), this paper is cited repeatedly, given its impressive and decisive title. This unfortunate situation undoubtedly denied a valuable treatment to many patients. We are not aware of any reports of failures during the last 4 years. On the contrary, a group from Saudi Arabia has presented its large and impressive experience with this strategy (Imoedemhe et al., 1999
). Ovulation was effectively triggered with GnRH agonist in 682 (96%) of 708 high responder IVF patients with polycystic ovarian syndrome (mean concentration of oestradiol on the day of ovulation triggering = 7817 pg/ml). One patient (0.1%) developed severe OHSS. Significantly, this patient was treated with HCG-based luteal support, probably by mistake, as the protocol dictated progesterone-only luteal support. Also of note is that in 26 patients, the GnRH agonist-induced LH surge was judged to be `inadequate'. In 18 of these patients, HCG was used, resulting in 11 (61%) cases of severe OHSS. This last figure may reflect the large number of severe OHSS cases in this series that were prevented by this strategy. The reason(s) for inadequate LH surge may have to do with dose (too low) or route (intranasal) of the GnRH agonist administration. A key point in this strategy is the ability of an adequate single dose of GnRH agonist to bring about an effective LH surge, and subsequently to induce early luteal phase relative pituitary down-regulation. Luteolysis could be induced by diminished early luteal phase LH pulsatility, leading to prevention of OHSS. Our protocol calls for a single s.c. injection of 0.2 mg triptorelin (Decapeptyl®; Ferring, Malmo, Sweden). We recorded no LH surge failures with this protocol, and of course, no clinically significant OHSS thus far.
As mentioned above, in a previous debate (Kol et al., 1996), we took a closer look at the reported cases where this strategy `failed'. In short, the cases reported in the literature do not represent severe OHSS (severe ascites, hypovolaemia, electrolyte imbalance, etc.) but rather a milder condition characterized mainly by enlarged ovaries (which is an integral part of ovarian stimulation). Given the impressive observational data compiled thus far, a randomized prospective study, with comparison with HCG, would be unethical to conduct at this point.
Importantly, this strategy does not work if the GnRH agonist is used before ovarian stimulation to down-regulate the pituitary (as the pituitary will not respond to the triggering dose of GnRH agonist). This limited the application of the proposed strategy, since pituitary down-regulation is the routine approach in most IVF cycles. A major advantage of the recently introduced GnRH antagonists is that the pituitary maintains its responsiveness to GnRH agonist. Therefore, triggering ovulation using GnRH agonists in high responders is an excellent way to prevent OHSS. In fact, we have used this strategy with complete prevention of OHSS (Kol et al., 2000). In addition, the clinical introduction of recombinant LH (expected in the near future), may also prove beneficial in terms of curbing the occurrence of OHSS, even when pituitary down-regulation is used, although the full impact of recombinant LH must await further clinical experience.
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Notes |
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This debate was previously published on Webtrack, July 31, 2000
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References |
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Imoedemhe, D., Chan, R., Pacpaco, E. et al. (1999) Preventing OHSS in at-risk patients: evidence from a long-term prospective study. [Abstr. no. O-185] Hum. Reprod., 14 (Abstr. Book 1), 102103.
Itskovitz, J., Boldes, R., Barlev, A. et al. (1988) The induction of LH surge and oocyte maturation by GnRH analogue (buserelin) in women undergoing ovarian stimulation for in vitro fertilization. Gynecol. Endocrinol., 2 (Suppl. 2), 165.[ISI][Medline]
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