Factors affecting success rates in two concurrent clinical IVF trials: an examination of potential explanations for the difference in pregnancy rates between the United States and Europe.

OBJECTIVE: To compare a US clinical trial of gonadotropin therapy for IVF with a similar European trial to determine what factors may explain the higher clinical pregnancy rate in the US trial. DESIGN: Comparison of baseline, treatment, and outcome variables in the United States (US) and European trials. SETTING: IVF practices in the US (n=4) and Europe (n=6). PATIENT(S): 297 women undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Clinical pregnancy rates were 43.4% in the US compared with 29.7% in Europe (p=0.016), with a live birth rate of 38.2% versus 27.6% (p=0.064). This difference in clinical pregnancy rate could not be explained by differences in the US versus Europe for number of embryos transferred (2.3 vs. 2.6) or female age (34.6 vs. 30.4). Although the starting dose of gonadotropin was higher in the US trial compared with the European trial (300 versus 225 IU), the total dose of gonadotropin was only slightly higher in the US. In multiple logistic regression analysis of 81 pretransfer variables on clinical pregnancy, the only two found to be significant predictors of outcome were baseline endometrial thickness following down-regulation and number of days of gonadotropin treatment. CONCLUSION(S): This study suggests the possibility that US pregnancy rates may be higher in part because of differences in down-regulation or gonadotropin dosing. Other factors not assessed in these studies or in national datasets likely also contribute to the difference in pregnancy rates.

Clinical efficacy of highly purified urinary FSH versus recombinant FSH in volunteers undergoing controlled ovarian stimulation for in vitro fertilization: a randomized, multicenter, investigator-blind trial.

OBJECTIVE: To compare the efficacy of highly purified human urinary follicle stimulating hormone (HP-hFSH) versus human recombinant follitropin-alpha (rFSH) in volunteers undergoing controlled ovarian stimulation for IVF. DESIGN: A randomized, controlled, investigator-blind trial. SETTING: Four assisted reproductive technology centers. PATIENT(S): One hundred fifty-two IVF patients. INTERVENTION(S): Volunteers, aged 18-39, were randomized to HP-hFSH (n = 76) versus rFSH (n = 76) at a starting dose of 300 IU in down-regulated cycles. MAIN OUTCOME MEASURE(S): Number of oocytes, clinical pregnancy rate, and live birth rate with HP-hFSH versus rFSH. RESULT(S): The total IU of gonadotropin used did not differ between the two groups. There was no difference in number of oocytes retrieved with HP-hFSH (mean = 16.3) compared with rFSH (mean = 17.1), confidence interval (CI) of difference = -3.79 to +2.18. Clinical pregnancy rate, as defined by the presence of a gestational sac, was 48.7% (CI = 37.0%-60.4%) with HP-hFSH versus 44.7% (CI = 33.3%-56.6%) with rFSH (CI of difference = -11.9% to +19.8%). Live birth rate was 38.2% (29 of 76) in both groups (CI = 27.2%-50.0%), for a difference between groups of 0.0% (CI of the difference = -15.4% to +15.4%). CONCLUSION(S): There were no statistically significant differences in mean oocyte number, clinical pregnancy rate, or live birth rate between HP-hFSH versus rFSH.

Effects of lacrimal occlusion with collagen and silicone plugs on patients with conjunctivitis associated with dry eye.

PURPOSE: To determine whether canalicular occlusion with collagen and silicone plugs reduces the severity of symptoms in patients with conjunctivitis secondary to dry eye. METHODS: This was a prospective, randomized, double-masked study conducted at a single center in Mexico, in which 61 patients with dry eye/conjunctivitis were assigned to progressive lacrimal occlusion with collagen and silicone plugs or a sham procedural group. Outcome variables included total and individual dry eye and conjunctivitis symptom scores, moisturizing agent usage, best-corrected visual acuity, ocular comfort level, visual performance, corneal/conjunctival fluorescein staining, and incidence of adverse events. RESULTS: Total dry eye and conjunctival symptom scores were reduced by 43.7 and 33.7%, respectively 2 weeks after occlusion of all four lacrimal canaliculi with collagen plugs, increasing to 77.4 and 72.1% 2 weeks later following superior canalicular occlusion of both eyes with silicone plugs and inferior placement of collagen plugs. At the 8-week visit (4 weeks after silicone plug implantation of the inferior canaliculi of both eyes), the reduction in total dry eye and conjunctival symptom scores further increased to 94.2 and 93.0%, respectively, accompanied by a marked decline in each of the seven individual symptom scores (dryness, watery eyes, itching, burning, foreign body, fluctuating vision, and light sensitivity). In concert with these changes, moisturizing agent usage and corneal/conjunctival fluorescein staining decreased in a progressive fashion over the 8-week study period, and best-corrected visual acuity, ocular comfort, and visual performance improved in the absence of any treatment-related adverse events except for one case of epiphora. The response of patients to lacrimal occlusion can be sharply contrasted with the sham procedure group, which remained relatively unchanged from baseline at each of the study visits. CONCLUSIONS: Progressive lacrimal occlusion with collagen and silicone plugs was of clinical benefit to patients with dry eye and conjunctivitis.

Retrospective safety study of the herrick lacrimal plug: a device used to occlude the lacrimal canaliculus.

PURPOSE: The purpose of this study was to evaluate the safety of the Herrick Lacrimal Plug (HLP) (Lacrimedics, Eastsound, WA) by reviewing medical records obtained from patients in whom the HLP was implanted. METHODS: A total of 228, primarily dry-eye, patients who had received one or more HLP implants at 19 centers during 1994 were included in the review; both centers and patients were randomly selected for inclusion. Medical records were examined for evidence of adverse events, which were characterized by presumed relationship to treatment, time of occurrence, severity, treatment required, and clinical outcome. Patients were contacted by phone whenever possible to verify the accuracy of the information extracted from their medical records. RESULTS: A total of 35 adverse events likely, or definitively related to treatment, were recorded for 25 (11.0%) of 227 evaluable patients who were followed for 0 to 4.6 years (mean, 0.9 years). The most common adverse event was epiphora (21), followed by plug displacement (7), ocular irritation (5), ocular pain (1), and headache (1). Sixteen (7.0%) patients (15 epiphora, 1 headache) had one or more plugs removed using a perfusion technique, with symptoms resolving for 13 patients, reduced for one but persisting for the remaining two. None of the baseline or treatment variables were found to be predictors of the occurrence of an adverse event following plug implantation. DISCUSSION: Approximately 10% of the patients who underwent implantation with the HLP in this series presented with a device-related adverse event, most commonly epiphora, which usually resolved following plug removal with a saline perfusion method. For the two patients (0.9%) whose epiphora did not resolve following plug removal, both had the same symptom before plug implantation, so it is unclear if persistence was the result of plug retention in the lacrimal drainage system or merely continuation of a preexisting condition.