Letters to the editor |
Which is more counterproductive: a brief delay or ‘start anyway’?
ARGC, 13 Upper Wimpole Street, London WIM 7TD, UK
1 To whom correspondence should be addressed. E-mail: tarekeltoukhy{at}hotmail.com
Sir,
We read with interest the article entitled ‘Repeated testing of basal FSH levels has no predictive value for IVF outcome in women with elevated basal FSH’ by Abdalla and Thum (2006)
. Although we congratulate the authors on their work, we disagree with them that the study ‘...provides a specific answer to the question as to whether repeated testing of FSH for patients to bring their basal FSH levels down...would be beneficial for the patients’ treatment’ for the following reasons:
- The study refers to FSH levels that were generally measured in a menstrual cycle other than the actual cycle of IVF treatment. Given the well-documented phenomenon of inter-cycle FSH level variability (Brown et al., 1995; Buyalos et al., 1998; Jain et al., 2003), correlating IVF cycle parameters and outcome to an FSH level measured in a different cycle seems illogical and undermines the validity of the study results. Obtaining more than double the live birth rate in the high-FSH group somehow exposes the weakness of the study design (even though statistical significance was not reached because of the profoundly small number of patients involved).
- Even in IVF cycles where the FSH and estradiol (E2) levels were measured within the same cycle of treatment, the authors declared in the materials and methods section that ovarian stimulation in some of those cycles (actual proportion not provided) was carried out using the long luteal-phase down-regulation protocol. This meant that multifollicular stimulation was effectively started in the ovarian cycle subsequent to that when the FSH level was measured, further undermining the hypothesis behind group allocation.
- The authors claim in the abstract conclusion that delaying treatment for women with high FSH could be counterproductive, as they may wait for several months, during which time ‘they are getting older and closer to the menopause’. Yet in the discussion section, the authors justified the study design by stating that the study was limited to a 12-month period ‘to negate the effect of age’, implying that ovarian ageing is unlikely to have a significant impact within a period of 12 months or less. To our knowledge, there is no evidence to show that delaying treatment by up to 3 months is detrimental to cycle outcome. By the same token, if the authors’ assumption was true, then briefly delaying treatment to rectify a variety of gynaecological conditions (such as presence of fibroids, hydrosalpinges, endometriosis or infection) could also be counterproductive through ovarian ageing!
- The authors referred to the study of Bancsi et al. (2004), which did not use E2 measurement in conjunction with basal FSH levels, but did not include the studies showing the negative impact of high basal FSH level in a particular cycle on treatment outcome especially when a short (flare-up) or antagonist stimulation protocol is used (Martin et al., 1996; Gurgan et al., 1997; Jurema et al., 2003). The authors also provided no explanation for the cause or significance of basal FSH inter-cycle variability.
- Monitoring of basal (day 2) FSH and E2 levels with a view to starting ovarian stimulation using a short (flare-up) or antagonist protocol on day 3 of cycle in the presence of low hormone levels requires a 7-day-per-week clinical and laboratory services, which are not available in most UK IVF clinics, hence the unpopularity of this practice.
In conclusion, only a randomized controlled trial could specifically answer the question as to whether repeated testing of basal FSH level is beneficial. Acknowledging the difficulty in undertaking such study and until it is completed, we believe that, in the presence of a high basal FSH, a pragmatic approach of offering three consecutive day 2 FSH and E2 measurements is appropriate. If the FSH and/or E2 levels remain high, the patient is extensively counselled and subsequent management is strongly dictated by her choice.
References
Abdalla H and Thum MY. (2006) Repeated testing of basal FSH levels has no predictive value for IVF outcome in women with elevated basal FSH. Hum Reprod 21:1171–174.
Bancsi LF, Broekmans FJ, Looman CW, Habbema JD, te Velde ER. (2004) Predicting poor ovarian response in IVF: use of repeat basal FSH measurement. J Reprod Med 49:3187–194.[Web of Science][Medline]
Brown JR, Liu HC, Sewitch KF, Rosenwaks Z, Berkeley AS. (1995) Variability of day 3 follicle-stimulating hormone levels in eumenorrheic women. J Reprod Med 40:9620–624.[Web of Science][Medline]
Buyalos RP, Ghosh K, Daneshmand ST. (1998) Infertile women of advanced reproductive age. Variability of day 3 FSH and E2 levels. J Reprod Med 43:121023–1026.[Web of Science][Medline]
Gurgan T, Urman B, Yarali H, Duran HE. (1997) Follicle-stimulating hormone levels on cycle day 3 to predict ovarian response in women undergoing controlled ovarian hyperstimulation for in vitro fertilization using a flare-up protocol. Fertil Steril 68:3483–487.[CrossRef][Web of Science][Medline]
Jain T, Klein NA, Lee DM, Sluss PM, Soules MR. (2003) Endocrine assessment of relative reproductive age in normal eumenorrheic younger and older women across multiple cycles. Am J Obstet Gynecol 189:4 1084.
Jurema MW, Bracero NJ, Garcia JE. (2003) Fine tuning cycle day 3 hormonal assessment of ovarian reserve improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles. Fertil Steril 80:51156–1161.[CrossRef][Web of Science][Medline]
Martin JS, Nisker JA, Tummon IS, Daniel SA, Auckland JL, Feyles V. (1996) Future in vitro fertilization pregnancy potential of women with variably elevated day 3 follicle-stimulating hormone levels. Fertil Steril 65:61238–1240.[Web of Science][Medline]
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