Ruth Stiller

Pregnancy complications in women with childhood sexual abuse experiences

OBJECTIVE Childhood sexual abuse (CSA) has an estimated prevalence of 20% and has a constantly growing list of known long-term consequences on physical as well as psychological health which may also influence obstetrical care attributed to it. However, scientific data on the association of CSA and pregnancy are sparse. Therefore, the study investigated pregnancy complications in women exposed to CSA. METHODS The study was designed as a cohort study comparing 85 women exposed to CSA with 170 matched unexposed women. CSA was identified by interview using modified questions from Wyatt [Child Abuse Negl 9 (1985) 507-519]. Data on pregnancy complications were collected by questionnaire and based on entries in a booklet (Mutterpass) in which all relevant data on pregnancy are documented at each prenatal consultation for any women attending prenatal care in Germany. Statistical analysis was performed with chi square, Fishers Exact Test, and multiple logistic regression analysis to control the association between CSA and pregnancy complications for confounders significant in univariate analysis, i.e., physical abuse, other adverse experiences during childhood, abuse during pregnancy, substance abuse, and occupation. RESULTS Women exposed to CSA were significantly more often hospitalized during pregnancy (41.2%/19.4%; OR 2.91, CI 1.64-5.17). They presented more often complications such as premature contractions (38.8%/20%; OR 2.54 CI 1.43-4.51), cervical insufficiency (25.9%/9.4%; OR 3.36, CI 1.65-6.82), and premature birth (18.8%/8.2%; OR 2.58, CI 1.19-5.59). CONCLUSION Therefore, health care providers should adapt prenatal care to the specific needs of women exposed to CSA.

Emotional stress and the risk to develop hypertensive diseases in pregnancy.

Objective: Cardiovascular diseases are strongly influenced by stress and do share several risk factors with hypertensive diseases in pregnancy (HDP). The aim of the study is to investigate the correlation between emotional stress during pregnancy and the risk for HDP. Methods: A self-administered questionnaire comprising obstetrical and psychosocial questions was completed by 725 patients and 880 controls matched for age, parity, nationality, and educational level. Results: Emotional stress during pregnancy was associated with a 1.6-fold increased risk for HDP. Conclusion: Psychosocial interventions to reduce emotional stress during pregnancy may help to decrease the risk to develop HDP.

Estradiol Stimulates Capillary Formation by Human Endothelial Progenitor Cells: Role of Estrogen Receptor-α/β, Heme Oxygenase 1, and Tyrosine Kinase

Endothelial progenitor cells (EPCs) repair damaged endothelium and promote capillary formation, processes involving receptor tyrosine kinases (RTKs) and heme oxygenase 1 (HO-1). Because estradiol augments vascular repair, we hypothesize that estradiol increases EPC proliferation and capillary formation via RTK activation and induction of HO-1. Physiological concentrations of estradiol (10 nmol/L) increased EPC-induced capillary sprout and lumen formation in matrigel/fibrin/collagen systems. Propyl-pyrazole-triol (PPT; 100 nmol/L; estrogen receptor [ER]-&agr; agonist), but not diarylpropionitrile (ER-&bgr; agonist), mimicked the stimulatory effects of estradiol on capillary formation, and methyl-piperidino-pyrazole (ER-&agr; antagonist) abolished the effects of estradiol and PPT. Three different RTK activators (vascular endothelial growth factor, hepatocyte growth factor, and stromal derived growth factor 1) mimicked the capillary-stimulating effects of estradiol and PPT. SU5416 (RTK inhibitor) blocked the stimulatory effects of estradiol and PPT on capillary formation. Estradiol increased HO-1 expression by 2- to 3-fold, an effect blocked by SU5416, and PPT mimicked the effects of estradiol on HO-1. The ability of estradiol to enhance capillary formation, increase expression of HO-1, and augment phosphorylation of extracellular signal–regulated kinase 1/2, Akt, and vascular endothelial growth factor receptor 2 was mimicked by its cell-impermeable analog BSA estradiol. Actinomycin (transcription inhibitor) did not alter the effects of estradiol on RTK activity or vascular endothelial growth factor secretion. We conclude that estradiol via ER-&agr; promotes EPC-mediated capillary formation by a mechanism that involves nongenomic activation of RTKs and HO-1 activation. Estradiol in particular and ER-&agr; agonists in general may promote healing of injured vascular beds by promoting EPC activity leading to more rapid endothelial recovery and capillary formation after injury.

Prenatal care in adult women exposed to childhood sexual abuse

Abstract Aims: Several case reports show a negative impact of childhood sexual abuse (CSA) on prenatal care. The study aimed to systematically investigate this association in a larger study group. Methods: CSA was investigated by face-to-face interviews and by a modified questionnaire developed by Wyatt. All study participants completed a self-administered questionnaire designed to investigate the consequences of CSA on prenatal care during adulthood. Data from 85 women after CSA were compared to those of 170 matched women without such experiences. Results: Women exposed to CSA had fewer than five prenatal consultations more often than unexposed women (26%/7%; P<0.0001). Of the 85 women with a positive history for CSA, 9.4% had been asked for such antecedents, 36.5% had intense memories on original abuse situations during pregnancy, 56.6% mentioned specific consequences of CSA on prenatal care and 61.2% were satisfied with obstetrical support. Exposed women (62.4%) felt significantly less prepared for labor than unexposed women (75.9%) (P<0.0001). Conclusions: CSA experiences are associated with impaired prenatal care. These results underscore the compelling need to improve prenatal care in women exposed to CSA through better education of obstetricians regarding the effects of CSA and in their ability to provide empathetic professional support.

Estradiol stimulates capillary formation by human endothelial progenitor cells: role of estrogen receptor-{alpha}/{beta}, heme oxygenase 1, and tyrosine kinase.

Endothelial progenitor cells (EPCs) repair damaged endothelium and promote capillary formation, processes involving receptor tyrosine kinases (RTKs) and heme oxygenase 1 (HO-1). Because estradiol augments vascular repair, we hypothesize that estradiol increases EPC proliferation and capillary formation via RTK activation and induction of HO-1. Physiological concentrations of estradiol (10 nmol/L) increased EPC-induced capillary sprout and lumen formation in matrigel/fibrin/collagen systems. Propyl-pyrazole-triol (PPT; 100 nmol/L; estrogen receptor [ER]-&agr; agonist), but not diarylpropionitrile (ER-&bgr; agonist), mimicked the stimulatory effects of estradiol on capillary formation, and methyl-piperidino-pyrazole (ER-&agr; antagonist) abolished the effects of estradiol and PPT. Three different RTK activators (vascular endothelial growth factor, hepatocyte growth factor, and stromal derived growth factor 1) mimicked the capillary-stimulating effects of estradiol and PPT. SU5416 (RTK inhibitor) blocked the stimulatory effects of estradiol and PPT on capillary formation. Estradiol increased HO-1 expression by 2- to 3-fold, an effect blocked by SU5416, and PPT mimicked the effects of estradiol on HO-1. The ability of estradiol to enhance capillary formation, increase expression of HO-1, and augment phosphorylation of extracellular signal–regulated kinase 1/2, Akt, and vascular endothelial growth factor receptor 2 was mimicked by its cell-impermeable analog BSA estradiol. Actinomycin (transcription inhibitor) did not alter the effects of estradiol on RTK activity or vascular endothelial growth factor secretion. We conclude that estradiol via ER-&agr; promotes EPC-mediated capillary formation by a mechanism that involves nongenomic activation of RTKs and HO-1 activation. Estradiol in particular and ER-&agr; agonists in general may promote healing of injured vascular beds by promoting EPC activity leading to more rapid endothelial recovery and capillary formation after injury.

Vitrification of human single pronuclear oocytes following two approaches to polar body biopsy

The purpose of the present study was to investigate whether the size of the opening in the zona pellucida (ZP) of human single pronuclear (1PN) oocytes made by laser and partial zona dissection (PZD) techniques might interfere with the survival and subsequent development to blastocyst stage upon vitrification and warming. Moreover, the viability of these blastocysts was evaluated by comparing their total cell number (TCN) to the TCN of blastocysts developed from control non-vitrified zona-intact 1PN oocytes. Prior to vitrification, a total of 97 and 88 1PN oocytes were subjected to polar body biopsy using laser-assisted and PZD techniques, respectively. The size of ZP opening made by laser and PZD techniques did not interfere with survival (94.8% and 95.4%) or development to the blastocyst stage (27.8% and 26.1%). However, the TCN of laser-derived blastocysts was significantly lower than the TCN of blastocysts developed from non-vitrified control 1PN oocytes (48.7 ± 3.4 versus 70.8 ± 7.1, P < 0.028). The vitrification protocol used here is thus revealed to be an effective method for cryopreservation of 1PN oocytes following polar body biopsy. However, the viability of blastocysts developed from laser-treated 1PN oocytes seems to be negatively affected by this method of biopsy.

High survival and developmental rates of vitrified mouse zygotes following polar body biopsy

The effect of two different methods of polar body biopsy followed by vitrification on the survival and development to blastocyst stage of mouse zygotes was examined. Prior to vitrification, a total of 119 and 124 mouse zygotes were subjected to polar body biopsy using either laser-assisted or partial zona dissection (PZD) techniques, respectively. Vitrification was also applied to 122 zona-intact zygotes that served as a control group. Following vitrification, no differences in the rate of zygote survival (95.8%, 91.9% and 94.3%) or in the rate of development to expanded blastocyst stage (82.3%, 79.8% and 82.0%) were observed between the two groups of biopsied zygotes, or between the biopsied zygotes and control zygotes. The mean total number of cells comprising the blastocysts of controls (77.1 +/- 4.7) was comparable to the mean cell number recorded in the laser (66.4 +/- 4.7) and PZD (69.7 +/- 5.3) groups. Blastocysts developed from laser-treated zygotes hatched much earlier than blastocysts developed from the control and PZD groups of zygotes (P < 0.001). The data obtained in the present study demonstrate that, irrespective of the biopsy method used prior to vitrification, mouse zygotes survive and develop to blastocysts upon warming in proportions similar to those of non-biopsied zygotes.

Calibration of a reflectance pulse oximeter in fetal lambs for arterial oxygen saturations below 70

Objective: To calibrate a reflectance pulse oximeter developed at the Division of Perinatal Physiology, University Hospital of Zurich, for monitoring of oxygen saturations below 70%. Methods: Oxygen saturation measured monivasively with the reflectance pulse oximeter in fetal sheep was compared with oxygen saturation of arterial blood samples measured by a conventional two-wavelength oximeter. Oxygen saturation was varied by stepwise reduction of the inspired oxygen concentration of the ewe. Results: A total of 58 data pairs was obtained from five fetuses, with a range of 10.9-73.5% for the reference method and 6.8-69.2% for the pulse oximetry oxygen saturation values. There was good correlation between the results obtained by the two methods (r2 = .89, P < .0001), with a 95% confidence interval of ± 12.5%. The pulse oximeter showed a precision of 6.2% oxygen saturation. Conclusion: The Zurich reflectance pulse oximeter offers valid measurements of oxygen saturation levels down to 10% oxygen saturation, and is therefore suitable for monitoring the fetus during delivery.

The relevance of age in female human reproduction – Current situation in Switzerland and pathophysiological background from a comparative perspective

During recent years women tend to postpone childbirth to ages when fertility declines. Consequently, an increasing number of women experiences reproductive difficulties and seeks help by assisted reproductive techniques (ART). To investigate the dynamics of age-related fertility in Switzerland we evaluated data from the nationwide FIVNAT-CH statistics on ART as well as from a subsample receiving ART at the Division of Reproductive Endocrinology, University Hospital Zurich. Since 2000 the average age of women receiving ART increased from 34.9 to 36.3 years in Switzerland and since 2006 numbers of annual ART cycles augmented steadily. The percentage of women ≥40 increased from 17.2% in 2007 to 19.6% in 2011. In the Zurich cohort AMH, the number of oocytes retrieved, the number of fertilized oocytes with two pronuclei, the number of embryos with an adequate cell number, clinical pregnancy rates as well as life birth/ongoing pregnancy rates were lower in the age group ≥40 years, especially when compared to 33 year-old women. In the nationwide sample pregnancy rates decreased from about 45% at the age of 30 to less than 3% at the age of 45; delivery rates declined from about 38% to nearly 0%. In the Zurich cohort percentages of clinical pregnancies declined from 46% in women ≤34 years to 21% in women ≥40 years. In the national sample as well as in the Zurich cohort the percentage of miscarriages increased dramatically from 15.4% and 22% in women ≤34 years to 38.6% and 33% in women ≥40 years, respectively. Even in a country with high health standards such as Switzerland fertility is declining with age and ART does not succeed to improve reduced fertility. Rodent and primate models enrich our knowledge on the pathophysiological mechanisms underlying reproductive senescence. As non-infertility specialist physicians as well as the general public are not sufficiently aware of the dramatic reduction of chances for life births in women ≥40 years, medical counseling as well as schools and media should support the distribution of information future parents need for successful family planning.

Evaluation of the use and handling of three different pen systems considered for in vitro fertilization treatment

Objective: The objective of this study was to assess and compare the features of the Bemfola, Gonal-f and Puregon injection pens. Methods: Females who intended to undergo hormonal treatment received the three different pens in a randomized, consecutive sequence. For each of the pens, the potential patients completed an Injection Pen Assessment Questionnaire, as well as a questionnaire comparing the handling, convenience and preference among the three pens. Results: The mean score on the visual analogue scale (VAS) for the Bemfola pen (BP) was 77.8 ± 14.0; for the Puregon pen (PP), 72.1 ± 12.4; and for the Gonal-f pen (GP), 68.6 ± 16.4. The BP was superior to both competitor devices in pen size, inconspicuousness, ease of use and dose changing; no significant differences to both competitor pens were observed in the way the pen looks, the way the pen feels and the ease of injection of the volume. The ‘overall’ assessment was significantly better for the BP when compared to the GP (p = 0.0019), while no significant difference was observed between the BP and the PP. Conclusions: This study demonstrated significantly higher ratings for pen size, inconspicuousness, ease of use and dose adjustment for the BP compared to other marketed pens.