Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tiqva 49 100 and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Email: orvieto{at}clalit.org.il
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Abstract |
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Key words: controlled ovarian stimulation/ovarian hyperstimulation syndrome/prevention
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Introduction |
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The syndrome almost always presents either 37 days after hCG administration in susceptible patients (early onset) or during early pregnancy, 1217 days after hCG administration (late onset). Early OHSS can to some extent be predicted by pre-ovulatory indices of ovarian response, in time to institute preventive measures such as cancellation (Hancock et al., 1970). Late OHSS does not relate strongly to pre-ovulatory ovarian response, making it difficult for clinicians to identify the cycles in which it is likely to occur (Mathur et al., 1997
). In the original description of OHSS, the late form was observed only in cycles with multiple gestations (Lyons et al., 1994
), with a trend toward an increase in the severity of disease with an increase in the number of gestational sacs (Mathur et al., 1995
).
Several articles have reviewed the epidemiological, hormonal and ultrasonographic characteristics of patients susceptible to OHSS (Blankstein et al., 1987; Asch et al., 1991
; Navot et al., 1992
, 1996
; Morris et al., 1995
; Zalel et al., 1995
; Levy et al., 1996
; Delvigne and Rozenberg, 2002
). Despite the many years of clinical experience, however, the pathophysiology of OHSS remains poorly understood, and there is no reliable test to predict which patients will develop severe OHSS (American Society for Reproductive Medicine Practice Committee, 2004
). When all the accepted predictive variables were combined, the prevalence of severe OHSS in the ostensibly high-risk patients was only
20% (Delvigne and Rozenberg, 2002
; Orvieto and Ben-Rafael, 1998
)an extremely low value for reliable prediction.
With the introduction in 1987 of GnRH agonists to the controlled ovarian stimulation (COS) protocols, clinicians initiated treatment with higher doses of gonadotrophins for retrieval of a higher number of mature oocytes. These protocols came into widespread use because of their higher conception and lower cancellation rates (Fleming et al., 1985). Unfortunately, they were also associated with an increased occurrence of OHSS (Forman et al., 1990
).
Alternatively, GnRH agonist can induce a sustained release of LH and FSH from the pituitary (flare effect), which effectively triggers oocyte maturation and ovulation, making it a potential alternative to hCG. However, the use of this approach was limited by its inapplicability in GnRH agonist-induced pituitary down-regulation-based protocols. Recently, some authors have suggested that replacing hCG with GnRH agonist can reduce the occurrence of OHSS (Balasch et al., 1994, reviewed by Kol, 2004
).
Morris et al. (1995) studied assisted reproduction cycles by oocyte donor and classical IVF patients, in which E2 (>4000 pg/ml) or oocyte number (>25) or both were elevated. While there were no cases of severe OHSS in the oocyte donor group, six cases of severe OHSS were observed in the classical IVF group. The calculated relative risk of OHSS with pregnancy was 12-fold higher. The authors concluded that the risk of OHSS even at high levels of stimulation is lower than previously believed and that donors have a very low risk of OHSS, probably because of the absence of pregnancy. As such, cryopreservation of all oocytes in IVF cycles is a reasonable alternative. Their findings were supported by Mathur et al. (1995)
who observed that OHSS may be more likely if multiple pregnancy occurs following assisted conception. However, other studies showed that when there is serious risk of severe OHSS, cryopreservation of all resulting embryos may prevent pregnancy-associated late OHSS, but not early-onset OHSS, which is precipitated with the trigger hCG dose (Lyons et al., 1994
; Queenan et al., 1997
).
The best means of prevention is individualization. Based on the aforementioned clinical observations and our personal experience, the occurrence of severe OHSS has been eliminated by strict adherence to the following triage (Figure 1).
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Elimination of OHSS |
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In patients with <20 oocytes, the number of embryos transferred and the time of transfer should adhere to the standard practice of the specific IVF unit.
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References |
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Submitted on June 24, 2004; resubmitted on August 31, 2004; accepted on October 21, 2004.