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.

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.

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.

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.

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.

Urinary tract infections and asymptomatic bacteriuria after vaginal plastic surgery. A comparison of suprapubic and transurethral catheters.

In a prospective randomized study comprising 90 women undergoing vaginal plastic surgery, suprapubic and transurethral catheter drainage of the bladder were compared regarding urinary tract infection and asymptomatic bacteriuria. No statistically significant differences were found. The mean duration of catheterization was 4.9 days for suprapubic vs 3.3 days for transurethral catheter patients. Postoperative urinary tract infection was diagnosed in 23.7% of patients with suprapubic and in 27.5% of patients with transurethral catheters. Asymptomatic bacteriuria at catheter removal was found in 21.0% of suprapubic and in 12.5% of transurethral catheter patients. More mechanical complications were seen with SPCs than with TUCs. It is concluded that the two methods involve similar risks of infectious complications but that SPCs have a higher rate of mechanical complications.

The grand multipara--maternal and neonatal complications.

During the period of 1974-83 the records of all grand multiparous women were analysed and compared with an equally large control group consisting of second and third parae. Antenatal complications, the management of and complications in labor, complications in the puerperium, perinatal mortality and neonatal morbidity were recorded and compared with the control group. Although there was no statistically significant difference in the frequency of abruptio placentae and placenta praevia in the groups, the increased tendency in the grand multipara group resulted in a high frequency of induced preterm delivery. There was also an increased occurrence of abnormal presentations and positions. The perinatal mortality was high, 23.5% compared with none in the control group. Furthermore there was an increased incidence of neonatal morbidity. One mother in the grand multipara group died from dissecting aortic aneurysm during the puerperium.