Monitoring of in vitro fertilization-embryo transfer cycles by ultrasound versus by ultrasound and hormonal levels: a prospective, multicenter, randomized study. Ultrasonic control without hormone determination for ovulation induction in in-vitro fertilization/embryo transfer with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin.
To determine whether cycle monitoring using both serum E(2) and ultrasound findings yields superior clinical pregnancy rates during IVF-embryo transfer (ET) compared to monitoring with ultrasound alone.
                Prospective, randomized, multicenter, patient-blinded study.
                Four assisted conception units in the United Kingdom.
                Two hundred ninety-seven women believed to be normal responders undergoing IVF treatment.
                Patients were randomly allocated on day 7 of stimulation to one of the two hCG administration criteria: [1] the E(2)-to-follicle > or =11 mm ratio was between 250 and 500 pmol/L/follicle and at least 2 follicles reached a mean diameter of 18 mm or [2] at least 2 follicles reached a mean diameter of 18 mm and the endometrium thickness was > or =8 mm.
                Duration and cumulative dose of recombinant human FSH, total number of growing follicles, oocytes retrieved, number and quality of embryos, pregnancy rates, and ovarian hyperstimulation syndrome (OHSS) rates.
                Two hundred ninety-seven patients were randomized to one of the two criteria groups. Of these, 288 (97%) received urinary (u)-hCG (143 in group A and 145 in group B). One hundred three women in group A (72%) met both criteria for hCG administration. Pregnancy and OHSS rates were similar (34.3% vs. 31.4% and 4.9% vs. 4.1%, respectively).
                The addition of E(2)/follicle criteria to ultrasound monitoring of IVF cycles in normal responders seldom changes the timing of hCG, and does not increase pregnancy rates or the risk of OHSS. A total of 114 patients admitted to an in-vitro fertilization-embryo transfer programme for the first time, were randomly assigned to the study group or controls. Gonadotrophin-releasing hormone analogue (GnRHa) and human menopausal gonadotrophin (HMG) were used for ovulation induction. The study patients were followed up merely by ultrasonography and the controls by ultrasonography and serum determinations of oestradiol, progesterone and luteinizing hormone (LH). There was no significant difference in the duration and total amount of HMG used for ovulation induction (10.9 versus 11.5 days and 34.8 versus 37.9 ampoules, respectively). The number of oocytes retrieved (11.7 versus 13.4) and the numbers of embryos replaced (2.6 versus 2.8) and cryopreserved (1.9 versus 3.3) were also similar. Pregnancy rates were similar. Pregnancy rate per ovum retrieval was 22.2 versus 25% and per embryo transfer 27.2 versus 26.5%. Oestradiol patterns were also similar. The rate and severity of ovarian hyperstimulation syndrome were virtually identical. We conclude that 'ultrasound-only' monitoring of ovulation induction in IVF cycles treated by GnRHa-HMG in the long protocol is as effective and safe as the conventional ultrasound and hormone determination, but far simpler, swifter and more cost-effective.
There is no evidence from randomised trials to support cycle monitoring by ultrasound plus serum estradiol as more efficacious than cycle monitoring by ultrasound only on outcomes of live birth and pregnancy rates. A large well-designed randomised controlled trial is needed that reports on live birth rates and pregnancy, with economic evaluation of the costs involved and the views of the women undergoing cycle monitoring. A randomised trial with sufficiently large sample size to test the effects of different monitoring protocols on OHSS, a rare outcome, will pose a great challenge. Until such a trial is considered feasible, cycle monitoring by transvaginal ultrasound plus serum estradiol may need to be retained as a precautionary good practice point.