Controlled Ovarian Hyperstimulation in Patients with Anovulatory Infertility Participating in In Vitro Fertilization Programs: the Less the Better?
Study Objective: To compare the effectiveness of conventional and low-dose protocols for controlled ovarian hyperstimulation in treating anovulatory infertility in patients with chronic anovulation (World Health Organization [WHO] Group II) participating in in vitro fertilization (IVF) programs. Study Design: This was an open-label, prospective, non-controlled study. Materials and Methods: Fifty-seven women with chronic anovulation (WHO Group II) receiving treatment for infertility in IVF programs were included in the study. These patients were stratified into two groups by the dose of gonadotropin used for controlled ovarian hyperstimulation. Hyperstimulation was induced by gonadotropins given at a total dose of 1,000-1,250 units/cycle in Group I (n = 32) and 300-525 units/cycle in Group II (n = 25). A "short" protocol was used to achieve ovarian hyperstimulation. Transvaginal pelvic ultrasound examination was performed to confirm pregnancy, to locate the implanted embryos, and determine their number. The statistical significance of the differences between the study parameters was analyzed using the Student t-test, the x<sup>2</sup> test, and the Wilcoxon-Mann-Whitney test. Statistically significant differences were defined as values of p<0.05. Study Results: In Group I, 11 to 21 oocytes were collected after hyperstimulation with gonadotropins. The ratio of mature to immature oocytes was 6.5:3.5. Normal zygotes were selected and cultured to the blastocyst stage, with the mean number of blatocysts varying from five to seven. In Group II, two to five oocytes were obtained, with a 9:1 ratio of mature to immature oocytes. The number of blastocysts obtained was two to five. The mean number of oocytes retrieved during follicular aspiration was 17.8 ± 3.1 in Group I and 2.8 ± 2.2 in Group II (p < 0.05). While Group I patients had a large number of mature oocytes (p < 0.05), almost one out of three of their oocytes (31%) was immature. When low-dose gonadotropin protocols were used, the number of immature oocytes was 10% lower (p < 0.05). Comparison of the number of blastocysts showed that Group I patients had significantly more blastocysts (5.1 ± 1.4 in Group I vs. 2.8 ± 1.0 in Group II, p < 0.05), which was an expected result. In the low-dose gonadotropin protocols, however, embryo transfer was performed during the same treatment cycle in 100% of the cases studied; while in 68.75% of the women undergoing treatment with conventional protocols, the fresh embryo transfer was cancelled, and a frozen transfer performed instead, because of a high risk of ovarian hyperstimulation syndrome (OHSS). The rate of biochemical pregnancy in the study population as a whole was 42.1%, and the rate of clinical pregnancy was 31.6%, with no differences between Groups I and II (p < 0.05). Conclusion: In patients with chronic anovulation (WHO Group II), the efficacy of the ovarian stimulation strategy designed for this study, using low-dose gonadotropins, is the same as that of the strategies generally accepted for use in IVF programs. Nevertheless, it is associated with a higher ratio of mature to immature oocytes (90% vs. 65%, p < 0.05), and is safer because it carries a lower risk of OHSS (p < 0.05). Another significant advantage of this strategy is its obvious reduction of the total cost of the stimulation protocols and duration of the IVF programs.