Parental aging synergistically decreases offspring sex ratio.

OBJECTIVE: The aim of this study was to investigate the effect of parental age as a factor in the observed decline in the male to female birth ratio expressed as the offspring sex ratio (OSR). STUDY DESIGN: A prospective multicenter study was conducted from August 2005 to February 2007 at five community-based hospitals in Osaka, Japan. Pregnant women in the first trimester were recruited at their first prenatal care visit and followed until delivery. Multiple pregnancies and assisted conceptions were excluded. Periconceptional parental ages were recorded. Neonatal information was obtained at the time of delivery. Proportional distribution of categorical variables was studied using the chi(2) or Fisher's exact tests (two-tailed). RESULTS: Data on 3,049 deliveries were available for review. OSR for the largest paternal and maternal subgroup (both, age 30-34) were male dominant (1.17 and 1.12, respectively). Paternal age > or =40 showed a smaller OSR (0.75 vs 1.17, P = 0.001). Advanced maternal age was associated with smaller OSR: age 35-39, 0.87 versus 1.12, P = 0.02; and age > or =40, 0.63 versus 1.12, P = 0.047. Synergistic effects of increasing paternal and maternal age on the OSR were observed. OSR for parental ages > or =40 were significantly smaller than ages 30-34 (0.52 vs 1.17, P = 0.029). CONCLUSIONS: Increasing paternal ages synergistically decrease the male to female birth ratio.

Estrogen stimulates the human endometrium to express a factor(s) that promotes vascular smooth muscle cell migration as an early step in microvessel remodeling.

Vascular smooth muscle cell (VSMC) migration is a pivotal early step in blood vessel remodeling; however, very little is known about the regulation of this process in the human endometrium during the menstrual cycle. In this study, explants of human endometrium were incubated with estradiol and/or progesterone and the conditioned medium (CM) applied to cultures of VSMC to test the hypothesis that estrogen and progesterone stimulate endometrial cells to secrete a factor(s) that promotes VSMC migration. Endometrial explants were composed of highly organized glands and stroma. VSMC migration (cells migrated in 21 h/mm(2) fibronectin-coated semipermeable membrane) in the presence of CM from human endometrial explants obtained in the proliferative phase of the menstrual cycle and incubated for 24 h with estradiol was approximately threefold greater (P < 0.001) than with medium alone and greater (P < 0.05) than with CM from explants treated with estradiol plus progesterone or progesterone. It is concluded, therefore, that estrogen stimulates endometrial secretion of a factor(s) that promotes VSMC migration as an early step in vessel remodeling within the endometrium.

Use of outcomes-based data in reducing high-order multiple pregnancies: the role of age, diagnosis, and embryo score.

OBJECTIVE: To identify high-risk categories for high-order multiple pregnancy (HMP) in in vitro fertilization (IVF), establish clinic-specific HMP risk data for counseling use, and verify their utility in reducing HMP. DESIGN: Before and after intervention study. SETTING: Two IVF programs using the same embryology laboratory and IVF protocols. PATIENT(S): All IVF patients undergoing fresh embryo transfers. INTERVENTION(S): Use of clinic-specific age, diagnosis, and embryo score (ES) risk data in assessing individual HMP risk during informed consent. MAIN OUTCOME MEASURE(S): HMP and pregnancy outcomes. RESULT(S): In determining clinic-specific high risk categories and developing outcomes-based HMP risk data for counseling, the good outcome rate (GR) was defined as the percentage of singleton or twin deliveries per cycle and the bad outcome rate included no pregnancy or nondelivered pregnancies (miscarriages, multifetal reduction) and HMP per cycle. During 1995 to 1999, age <35 years, calculated morphologic ES, and donor egg (DE) cycles were factors shown by logistic regression to statistically significantly affect the GR. The optimal GRs for DE <35 and >or=35 years (donor age), and non-DE cycles <35 years were achieved with two (57.7%), three (43.2%), and three (43.2%) embryos transferred, respectively. A DE <35 years with >or=3 embryos transferred had the highest risk for HMP. The GR correlated (0.91) with the ES according to the formula: GR = 3.3 + 2.0 ES, when ES range was between 4 and 26. Clinic-specific risks for HMP based on age, diagnosis, and ES were developed and considered while counseling for ET during 2004. The clinic-specific HMP risk data made for a reduction in the HMP rate of 90.9% for DE-IVF (11.8% to 1%) and 53.8% for all IVF (9.1% to 4.2%), without decreases in clinical pregnancy or delivery rates. Physicians showing the greatest decline (64%) in HMP had no reduction in pregnancy or delivery rates. CONCLUSION(S): The use of clinic-specific HMP risk data in counseling based on age, diagnosis, and ES provided a 53% to 64% reduction in HMP without affecting rates of pregnancy or delivery. The clinic-specific ES system correlated closely with good outcomes. A standardized ES system may provide useful information for counseling during ET informed consent.

Regulation of granulosa cell-derived insulin-like growth factor binding proteins (IGFBPs): role for protein kinase-C in the pre- and posttranslational modulation of IGFBP-4 and IGFBP-5.

A growing body of information suggests antigonadotropic and atretogenic roles for granulosa cell-derived insulin-like growth factor binding proteins (IGFBPs) 4 and 5 during ovarian folliculogenesis. Activation of protein kinase-A (PKA) in rat granulosa cells has been shown to modulate the relative expression of IGFBP-4 and -5 transcripts and proteins. In this article, we assess the role of protein kinase-C (PKC) in this regard. Provision of granulosa cells with phorbol 12-myristate 13-acetate (PMA) (but not 4alphaPMA, an inert analogue), a tumor-promoting phorbol ester and an established activator of PKC, was without significant effect on the expression of IGFBP-4 transcripts but resulted in biphasic dose-dependent alterations in IGFBP-5 transcripts and in the accumulation of the IGFBP-4 and -5 proteins. Comparable effects were noted for GnRH, an established PKC agonist. Provision of staurosporine, a potent inhibitor of the catalytic subunit of PKC, produced significant dose-dependent decrements in the relative expression of IGFBP-5 transcripts. Treatment with FSH (presumptively PKA-mediated) markedly attenuated the ability of PMA or GnRH to upregulate the accumulation of the IGFBP-5 (but not IGFBP-4) protein. Taken together, our present findings indicate that the modulation of rat ovarian IGFBP-4 and -5 is PKC as well as PKA dependent and that these two signaling pathways interact in a diametrically opposed and antagonistic fashion.