Inversion Ratio of Gonadotropins Activity in Ovulation Induction in Women at Risk of Developing Ovarian Hyperstimulation Syndrome: Preliminary Results

Abstract

Ovarian hyperstimulation syndrome (OHSS) is a potential life-threatening complication of treatment for infertility. The purpose of this study was to evaluate a protocol of ovarian stimulation in women at risk of developing OHSS, performing the inversion ratio of FSH/LH activity in the mid-follicular phase, through the use of LH activity in the form of low-dose hCG. Case series in a tertiary care center. Seven patients having their first cycle of in-vitro fertilization cancelled because of high risk at developing OHSS (> 30 follicles, E2 > 5,000 pg/mL) were included in this study. Ovarian stimulation was performed with recombinant FSH, 150 IU daily, commencing on day 2 after spontaneous or progestagen-induced withdrawal bleeding. Ovarian response was monitored by pelvic ultrasonography and daily blood samples. When the leading follicle had a size of at least 13 mm, we performed the inversion ratio of FSH/LH activity, by switching the stimulation from recombinant FSH to hCG alone, at the dose of 200 IU intramuscularly daily. At this moment the GnRH antagonist, 0.25 mg cetrotide subcutaneously once daily, was added to the stimulation regimen. When at least three follicles > 17 mm had developed, final oocyte maturation was triggered with 5,000 IU of hCG intramuscularly. Follicular aspiration was performed 35-36 hours later. The outcomes were evaluated in terms of cancellation rate, estradiol concentrations on the day of hCG injection to trigger oocyte maturation, number of mature oocytes retrieved, fertilization rate and pregnancy rate. The age of the women ranged from 27 to 37 years (mean: 33.7). In all patients, risk factors for OHSS were not observed during ovarian stimulation. All treatment cycles produced developing embryos, and there were no cycles cancelled. In all cases, cetrotide and hCG administration began on day 6 of ovarian stimulation, so that the total dose of recombinant FSH administered was 750 IU for each patient. Low-dose hCG was administered for 3 days in 6 women (total dose of hCG: 600 IU, 8 days of stimulation) and for 4 days in 1 woman (total dose of hCG: 800 IU, 9 days of stimulation). Number of mature oocytes (MII) retrieved ranged from 7 to 16 (mean: 11). Estradiol concentrations on the day of hCG administration to trigger oocyte maturation ranged from 2200.5 to 3531.2 pg/mL (mean: 2984.1 pg/mL). Overall fertilization rate was 78,6%. Clinical pregnancy was observed in 2 patients (pregnancy rate: 28.5%). All of these pregnancies are ongoing. Our preliminary results suggest that an ovarian stimulation protocol with low-dose hCG to produce inversion ratio of FSH/LH activity in the mid-follicular phase, associated to a GnRH antagonist, may be an efficient, non-expensive and safe option for women at risk of developing OHSS. The reduction in the development of small follicles induced by this protocol of ovarian stimulation, may play an important role in the prevention of the syndrome. To our knowledge, this is the first report using the inversion ratio of gonadotropins activity and a GnRH antagonist to diminish the likelihood of OHSS in high-risk patients. Nevertheless, comparative and randomized clinical trials are needed to confirm our preliminary observations.