IVF Centre, Maternity Hospital, Kuwait Department of Obstetrics and Gynaecology, St Bartholomew's and The Royal London School of Medicine and Dentistry, Royal London Hospital, London E1 1BB, UK
Dear Sir,
Ovarian hyperstimulation syndrome (OHSS) is the most severe complication associated with controlled ovarian stimulation (COH) for fertility treatment. The fact that this life-threatening condition is iatrogenic makes it all the more important to develop strategies and prevent its occurrence. Since the aetiology remains unknown and the pathophysiology is poorly understood, it is not surprising that no strategy has yet been shown to completely prevent the occurrence of severe OHSS, short of cancelling the cycle, prior to administration of the trigger human chorionic gonadotrophin (HCG) (Navot et al., 1992). Consequently, clinicians and researchers continue to explore clinical practices aimed at preventing this condition thus leading to publications in peer-reviewed medical journals of proposed novel strategies to prevent severe OHSS (Grudzinzkas and Egbase, 1998).
The adoption of any of such novel strategies (Sher et al., 1995; Tomazevic and Meden-Vrtovec, 1996
; Rimington et al., 1997
) in clinical practice, in the absence of other collaborative reports or randomized prospective trials that have validated their benefits, is a contentious area as the clinician has to make decisions during a treatment cycle. In these circumstances, it is appropriate that the senior clinicians of the team (the clinical review committee), charged with reviewing the clinical practice and protocols in a unit, should examine carefully the medical evidence in detail in these publications and decide on the risk/benefits of the novel strategies vis-à-vis existing practice (typically cancellation of the treatment cycle). Thus, couples are provided with information on the novel nature of the strategies and given detailed counselling on the risks/purported benefits of the treatment procedures vis-à-vis the risk of severe OHSS or cancellation of the controlled ovarian stimulation cycle.
In our IVF centre in Kuwait, we have chosen to explore two strategies which have been considered to be effective in peer-reviewed publications, i.e. early timed follicular aspiration (EUFA) (Tomazevic and Meden-Vrtovec, 1996) and `prolonged coasting' (Sher et al., 1995
). These two strategies were considered to be the most relevant in our population given firstly that cryopreservation of gametes and embryos is culturally not acceptable in our community and secondly the high incidence of women with polycystic ovarian syndrome (PCOS). We had already explored and adopted pre-treatment unilateral ovarian diathermy in women with a previous history of OHSS, but were left with the challenge of women who had not yet been exposed to controlled ovarian hyperstimulation (COH), who declined ovarian diathermy or in whom laparoscopy treatment was contraindicated because of obesity. Thus, the clinical review committee of the centre decided upon a clinical strategy which attempted to provide safe, effective, controlled ovarian stimulation to women by offering either EUFA or prolonged coasting. The women were informed and counselled about four possible outcomes of their proposed treatment cycle: (i) successful conclusion of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer without OHSS; (ii) EUFA; (iii) prolonged coasting; or (iv) cancellation of the treatment cycles, once a risk of OHSS was identified (Egbase et al., 1999
).
Despite the careful identification of patients at risk of severe OHSS, utilization of low threshold dosages of gonadotrophin or modification of the trigger dose of HCG, patients with severe PCOS with gross obesity, at risk of severe OHSS or repeated cycle cancellations in the course of advanced COH because of the risk of the condition, continued to present to our centre for treatment. Our patients are treated with assisted reproduction technology which is free to all citizens without a limit on the number of treatment cycles. Of the 37 women described in our report, 30 women enrolled in the study after obtaining informed consent, while seven women opted for cancellation of the cycle (Egbase et al., 1999).
In clinical practice, decisions are required on a daily basis to modify therapy to minimize complications from iatrogenic disease; controlled ovarian stimulation with the attendant risk of OHSS is a prime example of this. Should every aspect of care be scrutinized by ethics committees? The answer is clearly affirmative if untried strategies are considered. In the circumstances described here, we chose to inform and counsel couples on the basis of the experience of other centres validated by international peer review, and our own clinical review committee in accordance with the Code of Good Practice.
Notes
1 To whom correspondence should be addressed
References
Egbase, P.E., Al Sharhan, M. and Grudzinskas, J.G. (1999) Early unilateral follicular aspiration compared to coasting for the prevention of severe ovarian hyperstimulation syndrome: a prospective randomized study. Hum. Reprod., 14, 14211425.
Grudzinskas, J.G. and Egbase, P.E. (1998) Prevention of ovarian hyperstimulation syndrome: novel strategies. Hum. Reprod., 13, 20432045.
Navot, D., Bergh, P.A. and Laufer, N. (1992) Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil. Steril., 58, 249261.[ISI][Medline]
Rimington, M.R., Walker, S.M. and Shaw, R.W. (1997) The use of laparoscopic ovarian electrocautery in preventing cancellation of in-vitro fertilization treatment cycles due to risk of ovarian hyperstimulation syndrome in women with polycystic ovaries. Hum. Reprod., 12, 14431447.[Abstract]
Sher, G., Zouves, C., Feinman, M. and Maassarani, G. (1995) `Prolonged coasting': an effective method of preventing severe ovarian hyperstimulation syndrome in patients undergoing in-vitro fertilization. Hum. Reprod., 10, 31073109.[Abstract]
Tomazevic, T. and Meden-Vrtovec, H. (1996) Early times follicular aspiration prevents severe ovarian hyperstimulation syndrome. J. Assist. Reprod. Genet., 13, 282286.[ISI][Medline]