Baseline non-fasting serum leptin concentration to body mass index ratio is predictive of IVF outcomes.

BACKGROUND: The present study was designed to determine whether circulating leptin concentrations and/or body mass index (BMI) in women undergoing IVF are predictive of outcomes. METHODS: IVF cycle outcomes, e.g. fertilization, embryo development, implantation, pregnancy, were analysed relative to baseline (i.e. day gonadotrophin stimulation was initiated) non-fasting serum leptin concentrations and BMI. RESULTS: Serum leptin concentrations correlated with BMI (r = 0.739, P < 0.0001) as expected. Multiple logistic regression analyses showed correlation between serum leptin and pregnancy success (likelihood ratio = 5.198, P < 0.05), but there was no association between pregnancy and BMI. However, the serum leptin to BMI ratio was more strongly correlated (likelihood ratio = 7.258, P < 0.01) with pregnancy success than was leptin alone. Moreover, women with a low leptin:BMI ratio (< or =0.3) had significantly more superior quality embryos on day 3 post-retrieval (2.5 versus 1.4, P < 0.05, Kruskal-Wallis) and a greater implantation rate (26.7 versus 13.2%, P < 0.025, chi(2)) than women with a high leptin:BMI ratio (> or =0.7). CONCLUSIONS: The leptin:BMI ratio appears to be highly predictive of IVF success. Elevated leptin concentrations, particularly relative to BMI, may negatively impact fertility by assisted reproduction, possibly through direct ovarian actions resulting in impaired oocyte quality and/or early embryo development.

Chromatin structure in globozoospermia: a case report.

Sperm nuclear abnormalities in patients with globozoospermia have not been well characterized and may lead to the high rates of fertilization failure and embryo loss reported in patients with this form of teratozoospermia. This study used transmission electron microscopy (TEM), the sperm chromatin structure assay (SCSA), and single cell gel eletrophoresis assay (COMET) to assess if globozoospermia is associated with sperm chromatin structure abnormalities, DNA fragmentation, or both. The flow cytometric SCSA measures abnormal chromatin structure based on the susceptibility of sperm nuclear DNA to acid-induced denaturation in situ. COMET measures DNA fragmentation in individual sperm nuclei based upon gel electrophoretic patterns. Although sperm concentration (113 million/mL) and motility (66%) were normal in the patient, there was complete acrosome deficiency. TEM and SCSA data confirmed light microscopic examination that showed that sperm populations included a mixture of round and elongated sperm heads. Even though 100% of sperm had abnormal head morphology, only 13% demonstrated DNA denaturation (COMPalpha(t)), which is below our threshold of 15% COMPalpha(t), and consistent with high-fertility patients. Of interest, 13% of the sperm were also positive in the COMET assay, supporting our previous observations that SCSA-positive cells are also positive for DNA fragmentation. It was unexpected but of great interest that a human sperm population with 100% sperm morphology abnormalities had a chromatin integrity at the molecular level that is equivalent to sperm populations shown in previous studies to be highly fertile. These data are the first reported using SCSA and COMET assays to evaluate a patient with globozoospermia and support previous reports that intracytoplasmic sperm injection of globozoospermia may result in fertility/pregnancy. Lower success rates seen in some patients may be due to unrelated factors.

Serum leptin concentrations in women during gonadotropin stimulation cycles.

OBJECTIVE: To determine whether elevated follicular steroid levels during gonadotropin stimulation cycles are associated with altered circulating leptin concentrations. STUDY DESIGN: Sequential serum samples were collected from women (N = 37) undergoing luteal phase GnRH agonist + FSH treatment cycles prior to oocyte retrieval for in vitro fertilization. Leptin concentrations in serum were measured by radioimmunoassay and compared with serum estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) levels. RESULTS: Serum leptin concentrations during stimulated cycles were variable between patients and correlated positively (r = .556, P < .01) with body mass index. Serum leptin levels correlated positively (r = .185, P < .05) with estradiol concentrations across all days. Mean serum leptin concentrations on the day gonadotropin treatment began (baseline, 12.9 +/- 2.0 ng/mL) were lower (P < .0001) than on the day peak estradiol levels were reached (18.4 +/- 2.3 ng/mL). Serum leptin concentrations also correlated with DHEAS levels (r = .214, P < .05) but did not correlate with testosterone or the estradiol:testosterone ratio. CONCLUSION: Gonadotropin stimulation in women is associated with elevated leptin levels, consistent with an interaction between the reproductive axis and leptin secretion and/or clearance.

Is the free androgen index a useful clinical marker in male patients?

The clinical relevance of the free androgen index (FAI), a ratio of total testosterone (T) to sex-hormone binding globulin (SHBG), was investigated in a regional population of men (n = 40) and women (n = 30). The FAI correlated well with free testosterone (T) in both men (r = 0.551, p < 0.001) and women (r = 0.454, p < 0.01). However, there was considerable variability among individual patients. Moreover, the FAI showed no association with sperm parameters in male patients, although total T and free T showed weak associations. The FAI may be a cost-effective alternative to free T measurement in the diagnosis of oligomenorrhea and hirsutism in women as previously shown, but may have little relevance in men.

Effect of follicular size on oocyte retrieval, fertilization, cleavage, and embryo quality in in vitro fertilization cycles: a 6-year data collection.

OBJECTIVE: To determine the effect of follicular size, including the size of the leading follicle, on oocyte retrieval, fertilization, cleavage, and embryo quality in IVF cycles based on a large data collection. DESIGN: Retrospective analysis of 1,109 IVF cycles between 1987 and 1993 at the Hospital of the University of Pennsylvania including 606 patients ranging in age from 23 to 49 years. RESULTS: Follicles with a volume < or = 1 mL show a significantly lower oocyte recovery rate than follicles with a volume of > 1 mL. The highest recovery rate (83.5%) was found in follicles with a volume of 3 to 4 mL. Above a follicular volume of 7 mL, the oocyte recovery drops below that observed for follicles between 1 and 7 mL. Fertilization and cleavage rates were also higher in oocytes obtained from follicles > 1 mL compared with follicles < or = 1 mL. Although fertilization rates were fairly stable above volumes of 1 mL, cleavage rates continued to rise to a peak percentage of 92% with volumes between 6 and 7 mL. Leading follicle size did not have an effect on fertilization and cleavage rates of cohort oocytes. Embryo quality was not influenced significantly by follicular volume. CONCLUSION: Based on this evaluation of a large number of follicles, follicular size is a useful indicator of oocyte recovery, fertilization, and cleavage in IVF cycles. For optimal results, the follicular fluid volume in gonadotropin- and hCG-stimulated cycles should be > 1 mL, which corresponds to a follicle diameter of > 12 mm, and not larger than 7 mL (24 mm). For timing of hCG administration, the number of adequate size follicles appears to be more important than the size of the leading follicle(s).

Digital blunt dissection technique to assist laparoscopic gonadectomy in inguinally located/adhered gonads.

Laparoscopic gonadal removal in two patients, one with XY gonadal dysgenesis and the other with complete androgen insensitivity is described. In both cases, the gonads were either located deep in the inguinal canal or adherent in that area. Digital blunt dissection using a finger passed through the lateral lower abdominal trocar incision site (12 mm) at the mid-clavicular line of the lower abdomen, combined with external palpation/elevation of the inguinal ring, allowed rapid dissection and isolation of the desired structures and vascular pedicles.