Letter to the editor |
Is 250 µg rHCG always better and safer than 500 µg rHCG?
Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China
1 To whom correspondence should be addressed. E-mail: cwcchan{at}graduate.hku.hk
Sir,
We read with interest the recent article written by Al-Inany et al. (2005)
. Amongst the four trials included in this meta-analysis, only one compared the effect of two different doses of recombinant (r)HCG (Chang et al., 2001). Ovarian hyperstimulation syndrome (OHSS) was more commonly reported in patients treated with 500 mg rHCG (9.0%) as compared to the group receiving 250 mg rHCG (3.2%), although this was not statistically significant. A recommendation was made by Al-Inany et al. (2005) that ‘increasing the dose of rHCG (single 500 mg dose of rHCG) may lead to a higher rate of OHSS compared with a 250 mg dose, with no significant improvement in pregnancy rate. As both safety and efficacy are required for any medication, the dose of 250 mg seems the dose of choice for triggering ovulation.’ While we agree that a dose of 250 mg is sufficient to achieve ovulation trigger for the majority, we have some reservations in condemning the use of 500 mg rHCG completely.
We have recently published a randomized controlled trial which further confirmed the equivalence of 250 mg and 500 mg rHCG on inducing final oocyte maturity (Chan et al., 2005). In our study, the incidence of mild to moderate OHSS was less in the 500 mg rHCG group (7%), when compared to the 13% in the 250 mg rHCG group, although the difference was not statistically significant. We have deliberately excluded patients who were at risk of OHSS from recruitment into the study, which may explain the seemingly paradoxical observation and that no severe OHSS was recorded. The data from either study did not support the notion that a higher dose of rHCG is associated with a higher incidence of OHSS.
There is little controversy in the effectiveness of the two difference doses of rHCG in ovulation trigger, either defined by the mean number of oocytes retrieved per patient (Chang et al., 2001) or the percentage of metaphase II oocytes per patient (Chan et al., 2005). Nevertheless, there are some subtle differences between the two groups of patients. For example, the numbers of two-pronuclear fertilized oocytes and cleaved embryos were significantly higher in the 500 mg rHCG group (Chang et al., 2001). In our study, the serum and follicular fluid HCG levels on day HCG +2 as well as the follicular fluid:serum HCG ratio were significantly higher in the 500 mg rHCG group, indicating a better delivery of HCG from the serum to the follicle (Chan et al., 2005). The serum estradiol and progesterone levels were significantly higher in the 500 mg rHCG group in the luteal phase in both studies. Whether such differences in the embryo variables and hormone profiles confer a better environment for successful implantation is unknown. Although the implantation rate did not differ in both studies, neither of them was powered to detect this difference.
The problem of high body mass index (BMI) and the poor response in obese patients to a standard amount of HCG are well recognized. Indeed, we have shown that the absorption of HCG in the obese women was only half of that of women with normal BMI (Chan et al., 2003). Both studies comparing the two different doses of rHCG excluded obese women (Chang et al., 2001; Chan et al., 2005). For those with a higher BMI, a higher dose of rHCG may be required to achieve the same ovulation trigger. We therefore recommend that the higher dose should be considered in selected patients who have a high BMI and a low risk of OHSS.
References
Al-Inany H, Aboulghar MA, Mansour RT and Proctor M (2005) Recombinant versus urinary gonadotrophins for triggering ovulation in assisted conception. Hum Reprod 20,2061–2073.
Chan CCW, Ng EHY, MMY Chan, Tang OS, Yeung WSB, Lau EYL and Ho PC (2003) Bioavailability of human chorionic gonadotrophin after intramuscular and subcutaneous injections in obese and non-obese women. Hum Reprod 18,2294–2297.
Chan CCW, Ng EHY, Tang OS, Yeung WSB, Lau EYL and Ho PC (2005) A prospective, randomized, double-blind study to compare two doses of recombinant human chorionic gonadotrophin in inducing final oocyte maturity and the hormonal profile during the luteal phase. J Clin Endocrinol Metab 90,3933–3938.
Chang P, Kenley S, Burns T, Denton G, Currie K, De Vane G and O’Dea L (2001) Recombinant human chorionic gonadotrophin (rhCG) in assisted reproductive technology: results of a clinical trial comparing two doses of rhCG (Ovidrel®) to urinary hCG (Profasi®) for induction of final follicular maturation in in vitro fertilization-embryo transfer. Fertil Steril 76,67–74.[CrossRef][ISI][Medline]
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