Department for Reproductive Medicine, Division of Perinatology and Gynecology, University Medical Center, Utrecht 3508 GA, The Netherlands
Address correspondence to: F. J. Broekmans, M.D., University Medical Centre, Department for Reproductive Medicine, Division of Perinatology and Gynecology, Huispostnummer F 05.829, Postbus 85500, Utrecht 3508 GA, The Netherlands. E-mail: f.broekmans{at}azu.nl.
To the editor:
In the study by Hohmann et al. (1), a new approach to ovarian stimulation for in vitro fertilization (IVF) is presented. The long agonist suppression protocol is compared with antagonist schemes in which initiation of FSH stimulation is in the early or mid-follicular phase. The authors hypothesize that this relatively late interference into normal cohort development will lead to a more modest ovarian response. The results show that per started cycle pregnancy rates are comparable among the three study groups, despite the fact that with the mild stimulation schemes a much higher cancellation rate due to poor response is obtained. With a comparable number of oocytes obtained at oocyte retrieval, in the mild stimulation protocols a higher rate of embryo transfer per pickup and a better embryo quality is observed. The authors claim that mild stimulation leads to a selection of good quality oocytes.
In our opinion the results may well be explained by selection of good quality patients rather than good quality oocytes. Poor or moderate responders to IVF due to ovarian ageing often show advancement of the dominant follicle maturation in a spontaneous cycle (2, 3). Attempts to stimulate the whole cohort from d 5 onward may become ineffective in those ovarian-aged patients due to early dominance of the leading follicle in the cohort. The group that is cancelled due to poor response in the mild stimulation protocols is exactly the category of patients with diminished ovarian reserve, as evidenced by "a significant difference in age and baseline FSH between the canceled patients and those who met the criteria for oocyte retrieval." In agonist cycles, stimulation of the entire cohort in such patients is much more likely to occur, and more patients will reach the criteria for follicle aspiration. It seems that in applying the mild stimulation scheme, good prognosis-normal responders are shifted into good prognosis-mild (or even poor) responders, and poor prognosis-poor responders turn into non responder-cancels. As such, the increased presence of patients with a poor prognosis reaching ovum pickup in the agonist group is sufficient explanation for the poorer embryo quality observed in the laboratory, leading to a lower rate of embryo transfer per aspiration.
Mild stimulation protocols may offer a unique improvement in the management of the IVF patient, with increased safety for both the woman and the offspring. However, it should be suggested that mild stimulation leads to the selection of "high quality" patients at the expense of the elimination of the prospects for lower prognosis patients in that cycle. This implies that mild stimulation may not be the first choice treatment in approximately 30% of our patients.
Received May 8, 2003.
References