Maternal hCG concentrations in early IVF pregnancies: associations with number of cells in the Day 2 embryo and oocytes retrieved.

STUDY QUESTION: Do number of cells in the transferred cleavage stage embryo and number of oocytes retrieved for IVF influence maternal hCG concentrations in early pregnancies? SUMMARY ANSWER: Compared with transfer of a 2-cell embryo, transfer of a 4-cell embryo results in higher hCG concentrations on Day 12 after transfer, and more than 20 oocytes retrieved were associated with low hCG concentrations. WHAT IS KNOWN ALREADY: Maternal hCG concentration in very early pregnancy varies considerably among women, but is likely to be an indicator of time since implantation of the embryo into the endometrium, in addition to number and function of trophoblast cells. STUDY DESIGN, SIZE, DURATION: We followed 1047 pregnancies after IVF/ICSI from oocyte retrieval until Day 12 after embryo transfer. Women were recruited in Norway during the years 2005-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Successful pregnancies after transfer of one single embryo that had been cultured for 2 days were included. Maternal hCG was quantified on Day 12 after embryo transfer by chemiluminescence immunoassay, which measures intact hCG and the free ß-hCG chain. Information on a successful pregnancy, defined as birth after >16 weeks, was obtained by linkage to the Medical Birth Registry of Norway. MAIN RESULTS AND THE ROLE OF CHANCE: Transfer of a 4-cell embryo resulted in higher maternal hCG concentrations compared with transfer of a 2-cell embryo (134.8 versus 87.8 IU/l, P < 0.05). A high number of oocytes retrieved (>20) was associated with low hCG concentrations (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The factors studied explain a limited part of the total variation of hCG concentrations in early pregnancy. Although embryo transfer was performed at the same time after fertilization, we do not know the exact time of implantation. A further limitation to our study is that the number of pregnancies after transfer of a 2-cell embryo was small (27 cases). WIDER IMPLICATIONS OF THE FINDINGS: Number of cells in the transferred embryo and number of oocytes retrieved may influence the conditions and timing for embryo implantation in different ways and thereby influence maternal hCG concentrations. Such knowledge may be important for interpretation of hCG concentrations in early pregnancy.

Vulvovaginal photodynamic therapy vs. topical corticosteroids in genital erosive lichen planus: a randomized controlled trial.

BACKGROUND: Genital erosive lichen planus (GELP) in women is a chronic inflammatory disease characterized by painful vulval and vaginal erosions. Topical photodynamic therapy (PDT) is increasingly used in premalignant and malignant diseases and may have an effect in inflammatory diseases. OBJECTIVES: To assess the feasibility, efficacy and safety of hexyl 5-aminolevulinate-hydrocloride (HAL)-PDT in GELP. METHODS: Forty women, diagnosed with GELP at a specialized vulva clinic, were randomized to one session HAL-PDT in vulva and/or vagina (n = 20) or daily applications of clobetasol propionate 0·05% ointment in vulva and optional hydrocortisone acetate 1·0% foam in vagina for 6 weeks (n = 20). After 6 weeks, all patients were allowed to use topical corticosteroids as needed. Clinical examinations were performed at weeks 0, 6 and 24, using a clinical score developed for the study. All patients wrote a weekly log on pain, topical corticosteroid use and adverse events. RESULTS: Three patients, all in the corticosteroid group, withdrew from the study after 1-3 weeks. The mean reduction in clinical scores was similar in the PDT group and the corticosteroid group; 25% vs. 22% after 6 weeks (P = 0·787) and 35% vs. 38% after 24 weeks (P = 0·801). The mean reduction in pain visual analogue scale scores was 38% vs. 55% after 6 weeks (P = 0·286) and 39% vs. 12% after 24 weeks (P = 0·452). Patients in the PDT group reported significantly less topical corticosteroid use during weeks 7-24 than those in the corticosteroid group. No major adverse events were reported. CONCLUSIONS: Vulvovaginal HAL-PDT seems to be an effective and safe treatment for GELP.

Maternal age and emergency operative deliveries at term: a population-based registry study among low-risk primiparous women.

OBJECTIVE: To study the association between maternal age and emergency operative delivery. The roles of in-labour indications, and birthweight ≥ 4000 g, gestational age ≥ 42 weeks, induction of labour, and epidural use, according to maternal age were explored. DESIGN: Population-based study. SETTING: Medical Birth Registry of Norway and Statistics Norway. POPULATION: We studied 169 583 low-risk primiparous mothers with singleton, cephalic labours, at ≥37 weeks of gestation, from 1999 to 2009. METHODS: The associations between maternal age and mode of delivery were analysed using multinomial regression analyses, adjusting for sociodemographic factors. MAIN OUTCOME MEASURES: Emergency caesarean section and operative vaginal delivery. RESULTS: Of women aged ≥40 years, 22% had emergency caesarean sections and 24% had operative vaginal deliveries, giving adjusted relative risk ratios (RRRs) of 6.60 (95% confidence interval, 95% CI 5.53-7.87) and 3.30 (95% CI 2.79-3.90), respectively, when compared with women aged 20-24 years. Adjustments for sociodemographic factors only slightly changed the estimates. Dystocia was the main indication, followed by fetal distress. All of the listed factors increased the level of emergency operative deliveries, mainly because of an increase in dystocia. The increase in risk for emergency caesarean section by all factors, and for operative vaginal deliveries by epidural, were greater in older than in younger women, but were significant for epidural only. CONCLUSIONS: We found a close association between maternal age and emergency operative delivery in low-risk primiparas. Contributory factors increased the risk for both emergency operative delivery and epidural more in older than in younger women.

Is unilateral oophorectomy associated with age at menopause? A population study (the HUNT2 Survey).

STUDY QUESTION: Is unilateral oophorectomy associated with age at menopause? SUMMARY ANSWER: Women who had undergone unilateral oophorectomy entered menopause 1 year earlier than women with two ovaries intact. WHAT IS ALREADY KNOWN: There is substantial variation in age at natural menopause. Unilateral oophorectomy implies a significant reduction of the ovarian follicular reserve. Thus, one might expect that the time to menopause is shortened by several years in women who have undergone unilateral oophorectomy. STUDY DESIGN, SIZE AND DURATION: A retrospective cohort study of 23 580 Norwegian women who were included in the population-based HUNT2 Survey during the years 1995-1997. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained by two self-administered questionnaires at study inclusion. Cox proportional hazard models were used to estimate relative risks of menopause according to unilateral oophorectomy status with and without adjustment for birth cohort, parity, smoking, body mass index (BMI) and age at menarche. MAIN RESULTS AND THE ROLE OF CHANCE: Women who had undergone unilateral oophorectomy were younger at menopause [mean 49.6 years; 95% confidence interval (CI): 49.2-50.0] than women without unilateral oophorectomy (mean 50.7 years; 95% CI: 50.6-50.8) (P < 0.001). The crude relative risk of menopause was 1.28 (95% CI: 1.15-1.42) and remained similar after adjustment for the study factors above (adjusted relative risk 1.27; 95% CI: 1.14-1.41). In addition, recent birth cohort and high BMI were associated with higher age at menopause. LIMITATIONS, REASONS FOR CAUTION: Information on unilateral oophorectomy was based on self-reports. Some women may therefore have been misclassified. WIDER IMPLICATIONS OF THE FINDINGS: Although the effect of unilateral oophorectomy on the age at menopause is similar to that of smoking, it is weaker than anticipated from the loss of ovarian follicular reserve. Thus, compensatory mechanisms may occur in the remaining ovary.

Concentrations of human chorionic gonadotrophin in very early pregnancy and subsequent pre-eclampsia: a cohort study.

STUDY QUESTION: Are low serum concentrations of human chorionic gonadotrophin (hCG) in very early pregnancy associated with pre-eclampsia risk? SUMMARY ANSWER: Low hCG concentrations in very early pregnancy are associated with increased risk of severe pre-eclampsia. WHAT IS KNOWN ALREADY: Low maternal serum concentrations of hCG early in pregnancy may indicate impaired proliferation or invasion of trophoblast cells, and thus low hCG concentrations may serve as a marker for impaired placental development. Impaired placental development is assumed to be a cause of pre-eclampsia, but there is little prospective evidence to support this hypothesis. STUDY DESIGN, SIZE, DURATION: We performed a prospective cohort study of pregnancies after IVF at Oslo University Hospital 1996-2010 with linkage to the Medical Birth Registry of Norway to obtain information on pre-eclampsia development. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 2405 consecutive singleton pregnancies and examined the association of maternal serum hCG concentrations (measured using Elecsys, Roche) on Day 12 after embryo transfer with the risk of any pre-eclampsia and of mild and severe pre-eclampsia. MAIN RESULTS AND THE ROLE OF CHANCE: HCG concentrations were inversely associated with pre-eclampsia risk in a dose-dependent manner (Ptrend 0.02). Compared with women with hCG ≥150 IU/l, women with hCG <50 IU/l were at 2-fold higher overall risk of pre-eclampsia [absolute risk 6.4 versus 2.8%; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2-4.7]. The inverse association was restricted to severe pre-eclampsia (Ptrend 0.01), thus, women with hCG <50 IU/l were at 4-fold higher risk of severe pre-eclampsia than women with hCG ≥150 IU/l (absolute risk 3.6 versus 0.9%; OR 4.2, 95% CI 1.4-12.2). For mild pre-eclampsia, there was no corresponding association (Ptrend 0.36). LIMITATIONS, REASONS FOR CAUTION: Results for IVF pregnancies may not be generalizable to spontaneously conceived pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: Plausible causes of low maternal hCG concentrations very early in pregnancy include impaired placental development and delayed implantation. Thus, these results provide prospective evidence to support the hypothesis that impaired placental development may be associated with subsequent development of severe pre-eclampsia. STUDY FUNDING/COMPETING INTEREST: The study was financially supported by the Research Council of Norway. None of the authors has any conflict of interest to declare.

Paternal age, placental weight and placental to birthweight ratio: a population-based study of 590,835 pregnancies.

STUDY QUESTION: Is the age of the father associated with placental weight or the ratio of placental weight to birthweight? SUMMARY ANSWER: Placental weight and placental to birthweight ratio increased according to increasing paternal age, also after adjustment for maternal age. WHAT IS KNOWN ALREADY: High paternal age and also high placental to birthweight ratio have been associated with adverse pregnancy outcome. STUDY DESIGN, SIZE AND DURATION: We performed a population-based study and included all singleton births after 22 weeks of gestation in the Medical Birth Registry of Norway (n = 590,835) during the years 1999-2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: We compared mean placental weight and placental to birthweight ratio between paternal age groups. The association of paternal age with placental weight was estimated by linear regression analyses, and adjustments were made for maternal age, birthweight, parity, offspring sex, gestational age at birth, maternal smoking, pre-eclampsia, maternal diabetes mellitus and pregnancy after assisted reproductive technology (ART). MAIN RESULTS AND THE ROLE OF CHANCE: In pregnancies with fathers aged 20-24 years old, the mean placental weight was 656.2 g [standard deviation (SD) 142.8], whereas it was 677.8 g (SD 160.0) in pregnancies with fathers aged 50 years or older (P < 0.001). The mean offspring birthweight in pregnancies with fathers aged 20-24 year old was 3465.0 g (SD 583.8), and it was 3498.9 g (SD 621.8) when the father was 50 years or older (P < 0.001). The placental to birthweight ratio in the corresponding paternal age groups were 0.191 (SD 0.039) and 0.196 (SD 0.044) (P < 0.001). In multivariable linear regression analysis the placentas in pregnancies fathered by a man of 50 years or older were estimated to weigh 13.99 g [95% confidence interval (CI) 10.88-17.10] more than in pregnancies with a 20-24-year-old father (P < 0.001) after adjustment for maternal age, birthweight, parity, offspring sex, gestational age at birth, maternal smoking, pre-eclampsia, maternal diabetes mellitus and pregnancy after ART. LIMITATIONS, REASONS FOR CAUTION: Paternal age explains only a small proportion of the total variation in placental weight. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may increase the understanding of the father's role in human pregnancy. STUDY FUNDING/ COMPETING INTEREST(S): Norwegian Resource Centre for Women's Health, Norway. No conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Placental weight in singleton pregnancies with and without assisted reproductive technology: a population study of 536,567 pregnancies.

BACKGROUND: Pregnancies conceived by assisted reproductive technology (ART) are at increased risk of adverse outcomes. Previous studies have suggested increased placental weight and increased placental weight/birthweight ratio in pregnancies associated with adverse outcomes. We therefore studied the association of ART with placental weight and placental weight/birthweight ratio. METHODS: We included all singleton births in the Medical Birth Registry of Norway during the period 1999-2008 (n = 536 567, including 8259 after ART). We divided placental weight and placental weight/birthweight ratio into quartiles, and calculated the proportions of ART and spontaneous pregnancies in the lowest and the highest quartile by length of gestation. Thereafter, we estimated crude and adjusted odds ratios (ORs) for being in each quartile of placental weight for ART pregnancies with spontaneous pregnancies as the reference. The analyses were repeated with ART pregnancies subgrouped into IVF or ICSI. RESULTS: Mean placental weight was 678.9 g in pregnancies conceived by ART, and 673.0 g in pregnancies after spontaneous conception. ART pregnancies were overrepresented in the highest quartile of placental weight and underrepresented in the highest quartile of birthweight, independent of length of gestation at delivery. Thus, placental weight/birthweight ratio was higher in ART pregnancies. For ART pregnancies, the OR for being in the highest quartile of placental weight was 1.37 (95% confidence interval 1.30-1.45) after adjustment for length of gestation, offspring birthweight, parity, fetal sex, maternal age, pre-eclampsia and diabetes. There was no difference in placental weight/birthweight ratio between IVF and ICSI pregnancies. CONCLUSIONS: We found larger placentas and a higher placental weight/birthweight ratio among pregnancies conceived by ART compared with spontaneous pregnancies, and the difference was independent of length of gestation at delivery and ART method.

Complete surgical removal of minimal and mild endometriosis improves outcome of subsequent IVF/ICSI treatment.

Surgical eradication of minimal and mild endometriosis has been shown to increase the birth rate both spontaneously and after intrauterine insemination. This study from a reproductive medicine unit at a referral university hospital examined whether surgical eradication of minimal and mild endometriosis prior to IVF improved the treatment outcome. Records of infertile patients with minimal and mild endometriosis (American Society for Reproductive Medicine stages I and II) with no prior IVF/intracytoplasmic sperm injection (ICSI) treatments were analysed. During the first treatment cycle, women who had undergone complete removal (n=399) of endometriotic lesions experienced, compared with women with diagnostic laparoscopy only (n=262), a significantly improved implantation rate (30.9% versus 23.9%, P=0.02), pregnancy rate (40.1% versus 29.4%, P=0.004) and live-birth rate per ovum retrieval (27.7% versus 20.6%, P=0.04). Surgical removal of minimal and mild endometriotic lesions also gave shorter time to first pregnancy and a higher cumulative pregnancy rate. The study shows that women with stages I and II endometriosis undergoing IVF/ICSI have significantly shorter time to pregnancy and higher live-birth rate if all visible endometriosis is completely eliminated at the time of diagnostic surgery. Surgical elimination of minimal and mild endometriosis has been shown to increase the birth rate both spontaneously and after intrauterine insemination. In this study from a reproductive medicine unit at a referral university hospital, we examined whether surgical elimination of minimal and mild endometriosis prior to IVF improved the outcome of this treatment as well. During the first IVF treatment cycle, women who had undergone complete surgical removal of endometriosis experienced, compared with women who still had their endometriosis, an improved rate of embryo implantation, pregnancy rate and live birth rate per ovum retrieval. Surgical removal of minimal and mild endometriotic lesions also gave shorter time to first pregnancy and a higher cumulative pregnancy rate. In summary, our study shows that women with minimal and mild endometriosis undergoing IVF have shorter time to pregnancy and higher live-birth rate if all visible endometriosis is completely eliminated before the start of treatment.

Hormone-responsive adenylyl cyclase in the human fallopian tube.

Hormone-responsive adenylyl cyclase (AC) activity in biopsies from normal human Fallopian tubes was studied. Enzyme activity with a Km of 0.15 mmol/L and a maximum velocity of 13.8 pmol/mg.min in the basal condition was demonstrated. The addition of prostaglandin E1 (PGE1), PGE2, PGF2a, vasoactive intestinal polypeptide, isoproterenol, and terbutaline increased enzyme activity, with no change in the Km. Maximum stimulation of AC activity was obtained with PGE1, resulting in a 2- to 8-fold increase in AC activity. The response of AC to PGE1 revealed a possible topographical variation, with lowest responses to PGE1 in the isthmus. No such segmental variation in AC activity and response was seen after stimulation with PGF2a, vasoactive intestinal polypeptide, or isoproterenol.

Obstetric outcome in singleton pregnancies after assisted reproduction.

OBJECTIVE: To compare the obstetric outcome of singleton pregnancies after various procedures of assisted reproduction with a control group. METHODS: Maternal and perinatal outcome in 355 assisted-reproduction singleton pregnancies (study group) with a duration of 140 days or more were compared retrospectively with a control group matched for age and parity. All assisted-reproduction pregnancies resulted from treatment in one university hospital, and all control subjects delivered in the obstetric department of the same hospital. The controls consisted of 643 women, also with singleton pregnancies, who were matched for age and parity. RESULTS: In the study group, the frequencies of pregnancy-induced hypertension and placenta previa were increased. More patients in the study group were delivered by elective cesarean. Pregnancies after assisted reproduction were of shorter duration, with an increased incidence of preterm birth. Infants in the study group had a lower mean birth weight than did those in the control group and were more frequently referred to a neonatal care unit. CONCLUSION: Singleton pregnancies resulting from assisted reproduction represent obstetric risk cases, and the patients should be offered special attention during the pregnancy, which will probably be their only one.

Pregnancy after transfer of cryopreserved embryos in clomiphene citrate resistant polycystic ovarian syndrome.

Transfer of cryopreserved embryos in PCOS patients resistant to CC stimulation is an intriguing problem. Ovarian stimulation with hMG/hCG to create a secretory endometrium, will entail an unnecessary risk of OHSS. In this case study, we report the accomplishment of a successful pregnancy after transfer of cryopreserved embryos after secretory transformation of the endometrium by E2/P substitution in the absence of corpus luteum formation. However, the success rate of this treatment modality in terms of pregnancy per embryo transfer has still to be evaluated in an ongoing study.

Stimulation with human menopausal gonadotropin versus follicle-stimulating hormone after pituitary suppression in polycystic ovarian syndrome.

Stimulation with human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) was compared in 34 patients with polycystic ovarian syndrome after pituitary gonadotrope suppression with buserelin acetate. No differences were seen in the hormone parameters observed. Also, the duration of the stimulation period and the dose of gonadotropin used were the same. In both groups a multifollicular response was seen. Oocyte retrieval and in vitro fertilization resulted in identical ratios of mature to total oocytes and cleavage rates. Nine pregnancies occurred, four in the hMG group and five in the FSH group. Of the nine pregnancies, two were the result of transfer of frozen-thawed embryos in estradiol and progesterone substituted cycles.

Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations.

OBJECTIVE: To investigate the impact of body weight (BW) and insulin levels on gonadotropin and androgen levels in women with the polycystic ovarian syndrome (PCOS). DESIGN: Comparative study of endocrinologic parameters in PCOS women. SETTING: University Hospital Reproductive Endocrinology Unit. PATIENTS: Thirty obese and 19 nonobese women with PCOS. Seven obese and 7 nonobese normal women. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone. Serum LH response to gonadotropin-releasing hormone (GnRH) administration and assessment of insulin resistance by the continuous infusion of glucose with model assessment (CIGMA) test. RESULTS: Fasting insulin levels correlated with body mass index (BMI). Basal LH levels correlated inversely with BMI. Nonobese women with PCOS had a higher LH response to GnRH than obese women with PCOS. Only obese women with PCOS showed insulin resistance and fasting hyperinsulinemia. CONCLUSIONS: The data suggest that women with PCOS may be divided into two subgroups: those with obesity, insulin resistance, hyperinsulinemia, and normal/minimally elevated LH levels and those with normal BW, elevated LH levels, and normoinsulinemia.

Prediction of response to controlled ovarian hyperstimulation: a comparison of basal and clomiphene citrate-stimulated follicle-stimulating hormone levels.

OBJECTIVE: To test the ovarian reserve in a high-risk population before controlled ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN: A prospective study comparing the outcome of a clomiphene citrate (CC) challenge test to the outcome of subsequent IVF cycles. SETTING: Unit for assisted reproductive technology in a university hospital. PATIENTS, PARTICIPANTS: Ninety-one infertile women with an age of 35 years or more, who had previous ovarian surgery or who had been diagnosed with ovarian endometriosis. MAIN OUTCOME MEASURE: Relate follicle-stimulating hormone (FSH) levels before and after CC to frequency of cancellation of an IVF cycle because of a poor follicular response. RESULTS: Twenty-one patients had elevated basal levels of FSH. Thirty-seven patients, including 20 with high basal levels, showed an excessive FSH response to CC with an FSH level after CC above the 95% confidence limit. Clomiphene citrate-stimulated FSH levels correlated better than basal levels with response to controlled ovarian hyperstimulation. An excessive FSH response to CC predicted a poor response outcome of subsequent controlled ovarian hyperstimulation for IVF with 85% accuracy. CONCLUSION: Follicle-stimulating hormone response to CC predicts subsequent follicular response to controlled ovarian hyperstimulation.

The first attempt at IVF treatment. Results and requirements for a satisfactory success rate.

The purpose of this study was to report the success rate of the first IVF treatment in 161 patients who attended our department in 1988. The indications for IVF were tubal damage in 84 couples (52.1%), unexplained infertility and endometriosis (with patent tubes) in 61 couples (37.9%), and polycystic ovarian syndrome in 16 couples (10%). Clinical pregnancies were diagnosed in 40 patients, giving an overall clinical pregnancy rate of 35.4% per embryo transfer. In the group of patients with unexplained infertility or endometriosis one in three of the embryo transfer cycles will predictably result in a birth, one in four in the group of patients with tubal damage or polycystic ovarian syndrome. These results invite discussion of the possible reasons for the success of our IVF program.

Duration of the latency period in preterm premature rupture of the membranes. Maternal and neonatal consequences of expectant management.

111 pregnancies complicated with premature rupture of the membranes (PROM) at a gestational age between 20 and 34 weeks, were observed prospectively with expectant management. Median duration of the latency period was 7 (0-109) days. The duration of the latency period was inversely related to the gestational age at PROM. Intra-uterine death ensued in 9.9% of the pregnancies. Clinical chorioamnionitis ensued in 12.6% of the pregnancies. Eight (7.6%) neonates developed sepsis. None of the babies died as a consequence of sepsis alone. Of the 43 (41.0%) neonates who developed idiopathic respiratory distress syndrome (IRDS), 8 (7.6%) babies died. The perinatal mortality rate was 18.6%. The study seems to justify the expectant management of PROM pregnancies of less than 34 weeks of gestation.

The interplay of human chorionic gonadotropin (hCG) with basic fibroblast growth factor and adipokines on angiogenesis in vitro.

INTRODUCTION: Human chorionic gonadotropin (hCG) is suggested to regulate placental angiogenesis, however, its role is incompletely understood. hCG may directly stimulate angiogenesis or influence the effect of other angiogenic factors. We examined the effect of hCG and the interplay of hCG with basic fibroblast growth factor (bFGF) and with various adipokines on proliferation of vascular endothelial cells in vitro. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated for 2 days with combinations of hCG, bFGF, leptin, resistin, adiponectin, IL6 and TNFα. Incorporation of radiolabelled thymidine was used to assess cell proliferation. Immunofluorescence and flow cytometry were used to examine activation of p44/42 mitogen-activated kinase (MAPK). RESULTS: hCG induced proliferation of HUVEC alone and in combination with bFGF. Cells exposed to both hCG and bFGF displayed increased activation of p44/42 MAPK as compared to hCG or bFGF alone. Increased HUVEC proliferation was observed in the presence of increasing concentrations of leptin, resistin, adiponectin, and IL6, whereas HUVEC proliferation decreased in the presence of TNFα. hCG in combination with leptin, resistin, adiponectin or IL6 stimulated HUVEC proliferation beyond the effect of hCG alone. DISCUSSION: An interplay of hCG with adipose tissue-derived factors with angiogenic properties is plausible. Thus, maternal obesity may affect placental angiogenesis in pregnancy. CONCLUSIONS: hCG may directly stimulate angiogenesis. Also, hCG may indirectly stimulate angiogenesis through interplay with bFGF and adipokines.

Impact of gender on vitamin D deficiency in morbidly obese patients: a cross-sectional study.

BACKGROUND/OBJECTIVE: Obesity is associated with vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) <50 nmol/l). We aimed to examine the effect of gender on vitamin D status in severe obesity. SUBJECTS/METHODS: Cross-sectional study of 2026 morbidly obese patients examined consecutively at a tertiary care centre between November 2005 and June 2010. Serum 25(OH)D concentration and use of vitamin D supplements were registered in all patients. Total vitamin D intake (µg/day) was assessed in a subgroup of 154 patients using a validated food frequency questionnaire. RESULTS: The male (n=690) and female (n=1336) patients had a mean (s.d.) age of 45.0 (12.1) years and 42.2 (12.2) years (P<0.001), body mass index (BMI) of 44.6 (6.0) kg/m(2) and 44.3 (5.9) kg/m(2) (P=0.30) and waist circumference (WC) of 140 (13) cm and 127 (13) cm (P<0.001), respectively. Male patients had significantly lower mean 25(OH)D concentrations than female patients 50.0 (22.0) nmol/l versus 53.6 (22.4) nmol/l (P=0.001) and a higher rate of vitamin D deficiency (56% versus 47%; P<0.001). Obese men had significantly higher odds of vitamin D deficiency than women (odds ratio=1.41; 95% confidence interval: 1.17-1.70, P<0.001), also after adjustment for season, age, current smoking, intake of vitamin D supplements, BMI and WC (odds ratio=1.39; 95% confidence interval: 1.10-1.76). CONCLUSIONS: Morbidly obese Norwegian men seeking weight loss treatment have significantly higher odds of vitamin D deficiency than women. Monitoring of 25(OH)D concentrations in obese patients should therefore take gender into account.

IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression.

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.