Lower chance of pregnancy with repeated cycles with in vitro fertilization.

OBJECTIVE: To evaluate pregnancy outcomes in initial and replicate IVF cycles. STUDY DESIGN: A retrospective analysis of 2,167 fresh, nondonor IVF cycles performed in a large private practice from January 1, 2005, to March 1, 2006. Standard controlled ovarian hyperstimulation and laboratory protocols were followed. RESULTS: Patients undergoing multiple treatment cycles were significantly older. There was no difference in body mass index or percentage of cancelled cycles with increasing number of IVF attempts. The number of retrieved, mature and fertilized oocytes progressively declined as the number of treatment cycles increased. The number of embryos transferred increased with increasing number of treatment cycles. Implantation, pregnancy and clinical pregnancy rates decreased significantly with the second treatment cycle and more markedly with 3-5 treatment cycles. CONCLUSION: The likelihood of a successful outcome declined with each additional treatment cycle. The most notable decrease in clinical pregnancy rates occurred after the third cycle. Patients who fail to conceive after 3 cycles of IVF should be counseled to begin considering other options.

Body mass index: impact on IVF success appears age-related.

BACKGROUND: The objective of this study was to examine the effect of BMI on IVF outcomes. METHODS: This was a retrospective analysis of all patients undergoing IVF from 1st January 2005 to 1st March 2006 in a large private practice using a single IVF laboratory. The patients underwent standard protocols for controlled ovarian hyperstimulation and embryology parameters. The main outcome measure was clinical pregnancy rate. RESULTS: A total of 2167 fresh, non-donor IVF cycles were queried, but to minimize bias, only the first treatment cycle for each patient was analyzed (n = 1273). The data were examined by multiple regression models that included BMI and Age as main effects plus a BMI x Age interaction. When examined as a main effect, BMI did not appear to have a major effect on IVF outcome, but there was a significant BMI x Age interaction. At younger ages, a high BMI had a pronounced negative influence on fertility, but this effect diminished as the patient age increased. Clinical pregnancy rates decreased with increasing BMI and increasing Age. CONCLUSIONS: In younger patients undergoing IVF, BMI has a significant negative impact on fertility that diminishes as patients reach their mid thirties. After Age 36, BMI has a minimal impact on fertility.

Adding human menopausal gonadotrophin to antagonist protocols - is there a benefit?

The objective of this retrospective analysis was to compare the clinical outcomes of recombinant FSH (r-FSH) with combination r-FSH plus human menopausal gonadotrophin (HMG) protocols in a large private practice using a single IVF laboratory, from 2001 to 2003. Patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) antagonist protocol using r-FSH or combination r-FSH plus HMG. When two or more follicles had attained a minimum mean diameter of 20 mm, follicular triggering was achieved with either recombinant HCG (r-HCG; Ovidrel, 250 microg s.c.) or urinary HCG (u-HCG; 10,000 IU i.m.). The main outcome measures were number of oocytes retrieved and clinical pregnancy rate. There was a lower percentage of cancelled cycles and an increased number of oocytes retrieved, mature oocytes, oocytes that fertilized, embryo that cleaved and a tendency towards higher clinical pregnancy rates in patients treated with r-FSH alone compared with those treated with r-FSH plus HMG. Patients treated with r-FSH plus HMG had lower miscarriage rates and the live birth rate was similar in both treatment groups. In conclusion, irrespective of age, using a treatment regimen consisting of a combination of HMG plus r-FSH was not beneficial compared with r-FSH alone in patients using a GnRH antagonist protocol.

Age-matched comparison of recombinant and urinary HCG for final follicular maturation.

This age-matched retrospective analysis compared the clinical outcomes of recombinant human chorionic gonadotrophin (rHCG) and urinary HCG (uHCG) in patients undergoing fresh, nondonor IVF cycles. The patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) agonist down-regulation or a GnRH antagonist protocol using recombinant FSH (rFSH) alone or in combination with human menopausal gonadotrophin. When two or more follicles had attained a mean diameter of 20 mm, follicular triggering was achieved with either Ovidrel (rHCG) 250 mug SC or uHCG 10,000 IU IM. Patients receiving rHCG were considered subjects, and they were age-matched in a 1:2 ratio to patients receiving uHCG, who were designated as controls. The main outcome measures were number of oocytes retrieved, number of mature oocytes obtained, number of oocytes fertilized and clinical pregnancy rates. A total of 273 subjects were age-matched and compared with 546 controls. Recombinant HCG had a minimal effect on the number of oocytes retrieved (13.4 versus 13.2), mature oocytes (10.5 versus 10.3) and oocytes fertilized (8.2 versus 7.8) compared with uHCG. Pregnancy (46.0 versus 45.2%) and clinical pregnancy rates (38.1 versus 36.8%) were similar for rHCG and uHCG. Recombinant HCG was as effective as uHCG for final follicular maturation in IVF cycles.

The LHbeta gene of several mammals embeds a carboxyl-terminal peptide-like sequence revealing a critical role for mucin oligosaccharides in the evolution of lutropin to chorionic gonadotropin in the animal phyla.

The expression of a previously untranslated carboxylterminal sequence is associated with the ancestral lutropin (LH) beta to the beta-subunit gene evolution of choriogonadotropins (CG). The peptide extension (denoted as CTP) is rich in mucin-type O-glycans and confers new hormonal properties on CG relative to the LH. Although the LHbeta gene is conserved among mammals and only a few frameshift mutations account for the extension, it is merely seen in primates and equids. Bioinformatics identified a CTP-like sequence that is encrypted in the LHbeta gene of several mammalian species but not in birds, amphibians, or fish. We then examined whether or not decoding of the cryptic CTP in the bovine LHbeta gene (boCTP) would be sufficient to generate the LHbeta species of a ruminant with properties typical to the CGbeta subunit. The mutated bovine LHbeta-boCTP subunit was expressed and N-glycosylated in transfected Chinese hamster ovary cells. However, unlike human (h) CGbeta CTP, the cryptic boCTP was devoid of mucin O-glycans. This deficiency was further confirmed when the boCTP domain was substituted for the natural CTP in the human CGbeta subunit. Moreover, when expressed in polarized Madin-Darby canine kidney cells, this hCGbeta-boCTP chimera was secreted basolaterally rather than from the apical compartment, which is the route of the wild type hCGbeta subunit, a sorting function attributed to the O-glycans attached to the CTP. This result shows that the cryptic peptide does not orientate CG to the apical face of the placenta, to the maternal circulation as seen in primates. The absence of this function, which distinguishes CG from LH, provides an explanation as to why the LHbeta to CGbeta evolution did not occur in ruminants. We propose that in primates and equids, further natural mutations in the progenitor LHbeta gene resulted in the efficient O-glycosylation of the CTP, thus favoring the retention of an elongated reading frame.