Does i.v. albumin prevent ovarian hyperstimulation syndrome?

Toshimitsu Koike1, Shigeo Araki, Shuichi Ogawa, Hisanori Minakami and Ikuo Sato

Department of Obstetrics and Gynecology, Jichi Medical School, Minamikawachi-machi, Tochigi 329–04, Japan

Dear Sir,

I read with great interest the paper on i.v. albumin in the prevention of severe ovarian hyperstimulation syndrome (OHSS) (Orvieto and Ben-Rafael, 1998Go). Prophylactic administration of albumin for severe OHSS was initially introduced in 1993 (Asch et al., 1993Go), and supportive studies have subsequently been reported (Shalev, 1998Go). Therefore we have been evaluating the efficacy of albumin to prevent severe OHSS since 1996.

In our institute, >=20 oocytes were retrieved from 98 patients at high risk of severe OHSS between January 1996 and September 1997. The oestradiol in their serum was not measured. The patients were prospectively divided into two groups based on the presence or absence of the administration of albumin as a prophylaxis. Randomization was performed with use of a random-number table. All patients gave informed consent to participate. A total of 43 patients were administered electrolyte solution 1000 ml per day plus albumin 37.5 g per day, for 3 consecutive days from the day of oocyte retrieval (group A). A total of 55 patients were administered sole electrolyte solution 1000 ml per day for 3 consecutive days from the day of oocyte retrieval (group B). Gamete intra-fallopian transfer (GIFT), in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was performed in all patients. Furthermore, all subjects underwent embryo (gamete) transfer. The incidence of severe OHSS was compared in both groups to evaluate the efficacy of i.v. albumin in the primary prevention (Orvieto and Ben-Rafael, 1998Go) of severe OHSS. In this study, severe OHSS was defined by the presence of marked haemoconcentration (haematocrit >=45%) and/or hypoproteinaemia (serum total protein <6.0 g/dl) in addition to marked ascites on the upper abdomen at least 4 days after oocyte retrieval. Early and late OHSS were defined as previously described (Orvieto and Ben-Rafael, 1998Go). The protocols of ovarian stimulation and luteal support were the same in both groups (Sayama et al., 1996)Go).

The profiles and outcomes of both groups are shown in Table IGo. The incidence of severe OHSS was slightly lower in group A (30.2%) than in group B (38.1%). The frequency of the occurrence of early severe OHSS was similar in both groups (25.6% in group A and 27.3% in group B respectively). Late severe OHSS occurred slightly less frequently in group A (4.7%) compared with that in group B (10.9%). In patients who subsequently exhibited severe OHSS, i.v. albumin supplementation and restriction of water intake were used as the main protocol. Although some patients (five patients in group A and 11 patients in group B) required additional therapy (paracentesis, anticoagulant and dopamine), all patients recovered without critical conditions.


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Table I. The profiles and clinical outcomes of 98 patients at high risk of severe ovarian hyperstimulation syndrome (OHSS). Values are shown as mean ±SD, with range in parentheses
 
Our findings support the negative findings of studies of the efficacy of prophylactic i.v. albumin at the time of oocyte retrieval (i.e. in the primary prevention of OHSS). If i.v. albumin is administered in all patients at high risk for severe OHSS, ~60% (shown in group B) in whom severe OHSS would not have subsequently occurred, received unnecessary i.v. albumin. The chance of allergic reactions and viral infections caused by exogenous albumin may be increased. A high rate of late severe OHSS in group B compared with group A may be explained by a high pregnancy rate in group B. The incidence of late severe OHSS in conception cycles was similar in both groups (two out of 14, 14.3% in group A and four out of 24, 16.7% in group B). The late severe OHSS occurred in 6 (16%) of the 38 conception cycles whereas it occurred in two (3.3%) of 60 non-conception cycles (not statistically significant). Thus, late severe OHSS may be more likely to occur in conception cycles than in non-conception cycles. A low rate of late severe OHSS in group A may have reflected a low pregnancy rate rather than the use of i.v. albumin. Therefore, albumin should not be employed as a prophylactic treatment. Since we managed severe OHSS without critical complications, supplementation of albumin when severe OHSS is clinically apparent may be effective. However, the role of i.v. albumin at the time of oocyte retrieval for secondary prevention of severe OHSS (Orvieto and Ben-Rafael, 1998Go) is unclear.

In conclusion, we surmise that the efficacy of i.v. albumin in the primary prevention of severe OHSS is limited.

Notes

1 To whom correspondence should be addressed Back

References

Asch, R.H., Ivery, G., Goldsman, M. et al. (1993) The use of intravenous albumin in patients at high risk for severe ovarian hyperstimulation syndrome. Hum. Reprod., 8, 1015–1020.[Abstract]

Orvieto, R. and Ben-Rafael, Z. (1998) Role of intravenous albumin in the prevention of severe ovarian hyperstimulation syndrome. Hum. Reprod., 13, 3306–3309.[Free Full Text]

Sayama, M., Araki, S., Motoyama, M. et al. (1996) The clinical efficacy of gamete intrafallopian transfer by minilaparotomy versus in vitro fertilization and embryo transfer. J. Obstet. Gynaecol. Res., 22, 409–416.[Medline]

Shalev, E. (1998) The role of intravenous albumin in the prevention of ovarian hyperstimulation syndrome. In Filicori, M. and Flamigni, C. (eds), Ovulation Induction Update `98. Parthenon Press, London, UK, 177 pp.





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