leptin and Abortion--Spontaneous

Obesity is a growing worldwide problem and is associated with a wide range of adverse effects on the female reproductive system. The endocrinological changes in obesity that may cause these adverse effects are complex and include changes in circulating adipokines and sex steroids as well as insulin resistance. Considerable evidence suggests an adverse effect of obesity on the risk of miscarriage and other maternal and fetal complications. Obese patients are also more prone to infertility. The most important single method to improve reproductive performance in obese women is weight loss that can be achieved with lifestyle changes and diet. Antiobesity drugs may also be used and, in severe cases, bariatric surgery.

Topics: Abortion, Spontaneous; Adiponectin; Anti-Obesity Agents; Bariatric Surgery; Endocrinology; Female; Fertilization in Vitro; Ghrelin; Humans; Infertility, Female; Leptin; Obesity; Pregnancy; Resistin; Risk

Obese women who are able to attain pregnancy are at increased risk for early-pregnancy loss due, in part, to reduced oocyte quality. We and others have demonstrated that female Lethal Yellow (LY) mice and female C57BL/6 mice fed a high fat diet (B6-HFD) exhibit phenotypes consistent with human obesity. These studies also showed that zygotes collected from LY and B6-HFD females have reduced developmental competence. The current hypothesis is that LY and B6-HFD females exhibit an abnormal response to gonadotropin stimulation compared to C57BL/6 controls fed normal rodent chow (B6-ND), resulting in the ovulation of oocytes with an altered molecular phenotype which may contribute to its reduced developmental competence. To test this hypothesis, age-matched B6-ND, B6-HFD, and LY females were stimulated with exogenous gonadotropins, then circulating hormone levels and the phenotypes of ovulated oocytes were analyzed. There was no difference in ovulation rate or in the percentage of morphologically abnormal oocytes collected from the oviduct of any females. Progesterone and progesterone/estradiol ratios, however, were increased in B6-HFD and LY compared to B6-ND females 16 hr post-human chorionic gonadotropin treatment. The transcript abundance of several candidate oocyte genes was also increased in B6-HFD- and LY-derived oocytes compared to B6-ND-derived oocytes. These data suggest that increased insulin and leptin levels of obese females elevated circulating progesterone concentrations, altered transcriptional activity during oocyte growth, and/or impaired mechanisms of RNA translation and degradation during oocyte maturation. These changes in mRNA abundance likely contribute to reduced oocyte quality and the subsequent poor embryogenesis associated with obesity.

Topics: Abortion, Spontaneous; Analysis of Variance; Animals; DNA Primers; Estradiol; Female; Gene Expression Regulation, Developmental; Gonadotropins; Insulin; Leptin; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Oocytes; Ovulation; Phenotype; Polymerase Chain Reaction; Pregnancy; Progesterone; RNA, Messenger

The objective was to investigate whether the associations between leptin, adiponectin, andadiposity reported in classic polycystic ovary syndrome (PCOS) are also observed in elderly women with a novel putative postmenopausal PCOS phenotype. We studied 713 postmenopausal community-dwelling women. Diagnosis of the novel phenotype required the presence of ≥3 diagnostic features including: 1) a personal history of oligomenorrhea; 2) history of infertility or miscarriage; 3) current or past clinical or hormonal evidence of hyperandrogenism; 4) central obesity; 5) biochemical evidence of insulin resistance. Women in the control group had ≤2 of these components. Mean age (±SD) was 74±8 years for the study cohort. Sixty-six women (9.3%) had the putative PCOS phenotype. Serum leptin was higher (mean 25.70±15.67 vs 14.94+9.89 ng/mL, P<.01) and adiponectin lower (mean 11.72±4.80 vs 17.31±7.45 μg/mL, P<.01) in cases vs controls. Leptin was positively, and adiponectin inversely, associated with an increasing number of phenotype features (P<.01 for linearity). In age-adjusted regression analysis, adjustment for waist circumference eliminated the association between leptin and the PCOS phenotype, but not the association between adiponectin and the PCOS phenotype. In this novel postmenopausal PCOS phenotype, adipocytokine profiles and their associations with adiposity parallel those reported in younger women with classic PCOS. These results support our hypothesis that a putative phenotype analogous to PCOS can be identified in postmenopausal women using clinical and biochemical criteria. Use of this novel phenotype could provide a basis for studies of the delayed consequences of PCOS in older women.

Topics: Abortion, Spontaneous; Adiponectin; Aged; Biomarkers; Body Mass Index; Female; Humans; Hyperandrogenism; Infertility, Female; Insulin Resistance; Leptin; Medical History Taking; Middle Aged; Obesity; Obesity, Abdominal; Oligomenorrhea; Phenotype; Polycystic Ovary Syndrome; Postmenopause; Premenopause

To determine whether maternal serum leptin levels can predict pregnancy outcome in cases of threatened miscarriage.. Observational study.. Fifty-seven women with normal pregnancy (group A), 19 women with threatened miscarriage who delivered at term (group B), 22 women with threatened miscarriage with subsequent miscarriage (group C) and 27 women with delayed miscarriage (group D).. Maternal serum leptin was determined using a commercial radioimmunoassay (RIA) kit.. Serum leptin levels were not significantly different among groups A, B and C [median (range) 17.6 (10.1-26.5), 18.2 (12.5-25.6) and 17.3 (11.2-27.6) microg/l, respectively]. Women in group D showed significantly lower serum leptin levels in comparison with other groups [14 (6.7-21.3) microg/l; P < 0.05].. Serum leptin levels in the first trimester of pregnancy may not be the primary indicator of miscarriage in cases of threatened abortion.

Topics: Abortion, Spontaneous; Abortion, Threatened; Adult; Analysis of Variance; Biomarkers; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Statistics, Nonparametric

Prevalence of uterine progesterone receptors over estrogen ones, high uterine cAMP level, and low uterine prostaglandin level are necessary conditions of normal pregnancy. In cases of spontaneous and antiprogestin RU486-induced abortions, estrogen receptors prevail over progesterone ones, cAMP level decreases, and prostaglandin concentration in decidual tissue increases. Porcine and bovine beta-lipotropines were the first proteins, whose correct amino acid sequence was first determined in Russia. Several research centers carried out collaborative studies of the nucleotide sequences of human and animal proopiomelanocortin (lipotropin precursor) and prolactin cDNA. Researchers constructed genetic engineering producers of human pre-proinsulin and somatostatin, identified structural genes expressed in pancreatic beta-cells, studied antigenic properties of glutamic acid decarboxylase (GAD), which determine insulin-dependent diabetes, and identified the cholesterase determinant. They revealed mutations in the genes of proopiomelanocortin and melanocortin receptors (MC4-P), which inhibit leptin regulation of appetite and are associated with human obesity.

Topics: Abortifacient Agents, Steroidal; Abortion, Induced; Abortion, Spontaneous; Animals; Appetite; beta-Lipotropin; Cattle; Diabetes Mellitus, Type 1; Female; Genetic Engineering; Glutamate Decarboxylase; Humans; Leptin; Lipid Metabolism; Male; Mifepristone; Mutation; Obesity; Pregnancy; Receptors, Estrogen; Receptors, Melanocortin; Receptors, Progesterone; Reproduction; Research; RNA, Messenger; Sterol Esterase; Swine; Uterus

To establish whether initial screening characteristics of normogonadotropic anovulatory infertile women can aid in predicting live birth after induction of ovulation with clomiphene citrate (CC).. Prospective longitudinal single-center study.. Specialist academic fertility unit.. Two hundred fifty-nine couples with a history of infertility, oligoamenorrhea, and normal follicle-stimulating hormone (FSH) concentrations who have not been previously treated with any ovulation-induction medication.. 50, 100, or 150 mg of oral CC per day, for 5 subsequent days per cycle.. Conception leading to live birth after CC administration.. After receiving CC, 98 (38%) women conceived, leading to live birth. The cumulative live birth rate within 12 months was 42% for the total study population and 56% for the ovulatory women who had received CC. Factors predicting the chances for live birth included free androgen index (testosterone/sex hormone-binding globulin ratio), body mass index, cycle history (oligomenorrhea versus amenorrhea), and the woman's age.. It is possible to predict the individual chances of live birth after CC administration using two distinct prediction models combined in a nomogram. Applying this nomogram in the clinic may be a step forward in optimizing the decision-making process in the treatment of normogonadotropic anovulatory infertility. Alternative first line of treatment options could be considered for some women who have limited chances for success.

Topics: Abortion, Spontaneous; Amenorrhea; Clomiphene; Ejaculation; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Infant, Newborn; Infertility, Female; Insulin-Like Growth Factor I; Leptin; Male; Odds Ratio; Oligomenorrhea; Ovulation; Ovulation Induction; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Probability; Retrospective Studies; Sperm Count; Treatment Outcome

Previous studies in humans and mice have suggested the importance of leptin in fetal growth. Recurrent miscarriage may be a result of abnormal placental and/or fetal development and therefore abnormal leptin levels may be associated with this form of pregnancy loss.. Leptin and leptin-binding activity (LBA) were measured in blood obtained from women who had a history of recurrent miscarriage (n = 53) during weeks 5-6 and 7-8 of pregnancy, and the concentrations were correlated with subsequent pregnancy outcome.. Concentrations of leptin ranged from 1.4-62.8 ng/ml, but there was a strong correlation (r = 0.825, P < 0.001) between leptin values at weeks 5-6 and 7-8 in the same woman. Women who subsequently miscarried had significantly lower plasma leptin concentrations on both weeks 5-6 (13.34 +/- 2.1 ng/ml) (P < 0.05) and 7-8 (13.71 +/- 2.4 ng/ml) (P < 0.01) of pregnancy, than women who subsequently had a term birth (22.04 +/- 2.43 ng/ml week 5-6, 24.76 +/- 3.66 ng/ml week 7-8). LBA values ranged from 1-8.5% but there was no significant difference in LBA in blood obtained from women who subsequently miscarried or had a live birth.. The significantly lower concentrations of leptin in women who subsequently miscarried suggest that leptin may play a role in preventing miscarriage. However, as there was a considerable overlap between the values of leptin in women who subsequently miscarried, and those that had a live birth, these measurements are of limited use in the prediction of pregnancy outcome in these women.

Topics: Abortion, Habitual; Abortion, Spontaneous; Adult; Carrier Proteins; Female; Humans; Labor, Obstetric; Leptin; Osmolar Concentration; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Receptors, Cell Surface; Receptors, Leptin

In pregnancy, important changes occur in the body weight of the mother, caused by sodium and water retention and by an increase in body fat tissue, but the mechanisms that regulate maternal and foetal changes in fat mass are poorly understood. Leptin is a hormone produced by adipocytes in order to regulate food intake and energy expenditure at the hypothalamic level in man. In order to verify whether leptin participates in the changes in body composition during pregnancy and postpartum, 630 healthy women were studied at specific time periods and leptin and auxological parameters were determined.. A cross-sectional study in which leptin levels were measured in women at specific time periods related to pregnancy. Each woman was assessed only once.. 630 women participated in the study, and were divided into categories as follows: Group A, 29 internal controls, with no previous or current pregnancy; Group B, 73 women in the first trimester of pregnancy; Group C, 60 women in the 24 h before delivery; Group D, 212 women in the 24 h postpartum; Group E, 93 women in the eightH postpartum week (2 months group); Group F, 71 women in the sixteenth postpartum week (4 months group); Group G, 20 women in the sixth month postpartum; Group H, 23 women one year postpartum; Group I, 20 women two years postpartum; finally Group J, of 29 women who had suffered spontaneous abortion in the first trimester of pregnancy and were studied in the 24 h after the stillborn delivery.. Serum leptin levels were measured in duplicate by radioimmunoassay using commercial kits. Height and weight was measured and BMI (kg/m2) calculated.. Compared with serum leptin in the control group (11.7 +/- 1.0 micrograms/l), a non significant (NS) increase was observed in the first trimester of pregnancy (14.3 +/- 1.4 micrograms/l), with no parallel changes in body weight. A reduction in leptin occurred in the 24 h after delivery (9.4 +/- 1.4 micrograms/l, P = 0.02). After delivery a progressive increase in leptin concentrations was observed, 13.3 +/- 1.5 micrograms/l at two months (NS) and 17.4 +/- 2.6 micrograms/l at four months (P = 0.035 vs controls). Afterwards leptin values decreased towards normal values at 6, 12 and 24 months after delivery 14.4 +/- 1.8 micrograms/l; 12.9 +/- 1.6 micrograms/l; and 10.1 +/- 1.1 micrograms/l respectively (all NS). With the exception of the postpartum group, a significant correlation was observed between leptin concentrations and body weight or BMI in each group of women studied. In the women who suffered spontaneous abortion in the first trimester of pregnancy a reduction in leptin levels occurred (8.8 +/- 1.0 micrograms/l, P = 0.001 vs first trimester group).. Serum leptin concentrations rose slightly during pregnancy, fell following delivery and subsequently increased during the first six months postpartum. These variations were unrelated to changes in body composition, and may be responsible for the postpartum weight gain observed in some women. Abnormally low serum leptin levels were observed in women suffering spontaneous abortion in the first trimester of pregnancy.

Topics: Abortion, Spontaneous; Adolescent; Adult; Analysis of Variance; Cross-Sectional Studies; Female; Humans; Leptin; Middle Aged; Postpartum Period; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Third; Proteins; Statistics, Nonparametric