Efficacy, safety, and immunogenicity of a biosimilar recombinant human follicle-stimulating hormone (Folitime®) vs. Gonal-f® in women undergoing ovarian stimulation for IVF: A randomized, multicenter, evaluator-blinded, non-inferiority study.

OBJECTIVE: We compared the efficacy, safety, and immunogenicity of a biosimilar recombinant human follicle-stimulating hormone (Folitime®) with Gonal-f® in women undergoing ovarian stimulation for in-vitro fertilization. METHODS: This randomized (1:1), multicenter, assessor-blinded, non-inferiority, parallel-group, controlled study conducted at four infertility clinics in Argentina included infertile normogonadotropic women with ages below 39 years, with menstrual cycles of 25/35 days and a body mass index of 18-32 kg/m2 undergoing assisted reproductive technology therapy. During a 5-day fixed-dose phase, the women received 225 IU/day of Folitime® (n=49) or Gonal-f® (n=44), followed by a dose-adaptation phase up to a maximum of 450 IU/day. The non-inferiority margin for oocyte retrieval was estimated at -4 oocytes (one-sided test). Immunogenicity was investigated on days 9 and 84, following the start of treatment. RESULTS: The mean number of oocytes retrieved was 12.6 (SD 7.4) in the Folitime® group and 13.4 (SD 6.9) in the Gonal-f® group (per protocol analysis, 95% confidence interval = -3.82; 2.33), within the non-inferiority margin. Pregnancy rate at week 10 was 24.4% among subjects treated with Folitime® and 19.5% for subjects treated with Gonal-f®. One serious adverse drug reaction-late mild ovarian hyper stimulation syndrome and deep venous thrombosis in the left deep jugular vein-occurred in a subject treated with Folitime®. None of the subjects developed antibodies against the study drugs. There were no unexpected safety findings. CONCLUSIONS: Folitime® is non-inferior to Gonal-f®, with no differences in the safety profile and has been approved as a biosimilar in Argentina.

Overweight and seminal quality: a study of 794 patients.

OBJECTIVES: To evaluate sperm quality, levels of markers of epididymal and accessory gland function, and T in semen from men grouped according to their body mass index (BMI). DESIGN: Blind prospective study. SETTING: Andrology and reproduction laboratory in Cordoba, Argentina (2006-2007). PATIENT(S): Seven hundred ninety-four men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): In semen samples, sperm quality (volume, density, motility, morphology, viability, hypoosmotic swell test, and nuclear maturity) and levels of neutral alpha-glucosidase, fructose, citric acid and T. RESULT(S): Multivariate analysis showed a negative association between BMI and motility, rapid motility and neutral alpha-glucosidase levels, and a positive association between BMI and seminal fructose levels. No associations were found among BMI and sperm concentration, the other parameters evaluated, or seminal T levels. CONCLUSION(S): Results found in our study support a deleterious effect of obesity on seminal quality, probably by alterations in the function of the epididymis (i.e., in epididymal maturation).

Improving the predictive value of the hypoosmotic swelling test in humans.

Using a combined hypoosmotic swelling-eosin (HOS-E) technique in human semen samples, we evaluated the frequency of dead swollen spermatozoa (dHOS) after 10 and 30 minutes of incubation, the correlation between total HOS-reactive (tHOS) and viable HOS-reactive (vHOS) spermatozoa with other seminal parameters, and the possibility that dead spermatozoa react to HOS. We obtained the following results: [1] some dead spermatozoa swell under hypoosmotic conditions and [2] HOS-E results correlate strongly with other seminal parameters. We recommend that HOS be performed after 10 minutes of incubation because [1] the increase in the incubation time enhances the percentage of dHOS, [2] there are no differences in vHOS percentages between 10 and 30 minutes, and [3] correlation coefficients between vHOS and tHOS with other parameters are very similar at 10 or 30 minutes of incubation.

Determination of human sperm calcium uptake mediated by progesterone may be useful for evaluating unexplained sterility.

Sperm samples from couples who underwent assisted reproduction were classified according to the World Health Organization (WHO) criteria of concentration, motility, and morphology, in normal and subnormal cases (oligozoospermic, asthenozoospermic, and teratozoospermic). The percentage of spermatozoa that increased [Ca(2+)](i) in response to progesterone (P) was determined by means of flow cytometry. The evaluation of the P-mediated intracellular calcium increase by flow cytometry may be a fast and objective tool for the diagnosis of human sperm samples, especially in cases of unexplained sterility.

Effects of alcohol and cigarette consumption on human seminal quality.

OBJECTIVE: To evaluate the effects of alcohol or cigarette consumption on seminal parameters in a large population of men attending an andrology laboratory. DESIGN: Analysis of ten years of data (1990-1999). SETTING: Andrology and Reproduction Laboratory (Córdoba, Argentina). PATIENT(S): Patients (3,976) were grouped according to nonsmokers; <==20 cigarettes/day; >20 cigarettes/day; nonalcohol consumers; <==500 mL of wine ( approximately 52 g of ethanol) or equivalent/day; and >500 mL of wine or equivalent/day. Patients who drank alcohol and smoked were also considered. INTERVENTION(S): A questionnaire was voluntarily filled out by patients. It provided data on drug consumption and genitourinary diseases. MAIN OUTCOME MEASURE(S): Seminal volume, sperm concentration, motility, viability, and morphology. RESULTS: No statistical differences in seminal parameters were found between the degrees of alcohol or tobacco consumption; so, independently of the degree of consumption patients were considered as smokers or alcohol consumers. CONCLUSION(S): Alcohol or cigarette consumption did not alter the seminal parameters. Nevertheless, when the patients with these two habits were compared to those without these habits, a significant reduction in seminal volume, sperm concentration, percentage of motile spermatozoa, and a significant increase of the nonmotile viable gametes were detected. The synergic or additive effect of these two toxic habits is discussed.