Maternal and fetal outcomes in multiparous women with Cystic Fibrosis.

BACKGROUND: Quality of life and survival in Cystic Fibrosis (CF) have improved dramatically, making family planning a feasible option. Maternal and perinatal outcomes in women with CF (wwCF) are similar to those seen in the general population. However, the effect of undergoing multiple pregnancies is unknown. METHODS: A multinational-multicenter retrospective cohort study. Data was obtained from 18 centers worldwide, anonymously, on wwCF 18-45 years old, including disease severity and outcome, as well as obstetric and newborn complications. Data were analyzed, within each individual patient to compare the outcomes of an initial pregnancy (1st or 2nd) with a multigravid pregnancy (≥3) as well as secondary analysis of grouped data to identify risk factors for disease progression or adverse neonatal outcomes. Three time periods were assessed - before, during, and after pregnancy. RESULTS: The study population included 141 wwCF of whom 41 (29%) had ≥3 pregnancies, "multiparous". Data were collected on 246 pregnancies, between 1973 and 2020, 69 (28%) were multiparous. A greater decline in ppFEV1 was seen in multiparous women, primarily in pancreatic insufficient (PI) wwCF and those with two severe (class I-III) mutations. Multigravid pregnancies were shorter, especially in wwCF over 30 years old, who had high rates of prematurity and newborn complications. There was no effect on pulmonary exacerbations or disease-related complications. CONCLUSIONS: Multiple pregnancies in wwCF are associated with accelerated respiratory deterioration and higher rates of preterm births. Therefore, strict follow-up by a multidisciplinary CF and obstetric team is needed in women who desire to carry multiple pregnancies.

The validity of oral glucose tolerance test after 36 weeks' gestation.

OBJECTIVE: Secretion of anti-insulin hormones plateaus near term, questioning the validity of OGTT (oral glucose tolerance test) during that period. We aimed at assessing the feasibility of OGTT near term as compared to OGTT at 26-32 weeks. PATIENTS AND METHODS: One thousand four hundred and eighty seven pregnant women were screened by GCT (glucose challenge test), and 282 (19%) of them performed an OGTT at 26th-32nd weeks ("early" OGTT) after meeting the threshold value for GCT. Forty-one women with abnormal and 16 with normal early OGTT underwent a repeated OGTT at 36-40 weeks' gestation ("late" OGTT). Blood glucose levels during GCT and OGTT were compared between women with early and late abnormal OGTT and women who converted from early abnormal to late normal OGTT. RESULTS: Thirty-six out of 41 participants (88%) with early abnormal OGTT had abnormal test near term as well (Group I). Five women with an early abnormal OGTT converted to normal according to a late OGTT (Group II). These women had lower glucose levels on both late and early OGTT as compared with Group I. All 16 women who tested normal on early OGTT had a consistently normal late OGTT. Glucose levels for all 57 women did not significantly differ between early and late OGTT. The sensitivity, specificity, and positive and negative predictive values of late OGTT were 88%, 100%, 100%, and 76%, respectively. CONCLUSION: The positive predictive value of late OGTT performed at 36-40 weeks' gestation is 100%. This test may be used to detect gestational diabetes in women near term.

Vaginal ring delivering estradiol and progesterone: a possible alternative to relieve climacteric symptoms.

BACKGROUND: Relief of climacteric symptoms is currently the main role of hormone therapy. However, vaginal bleeding complicating this therapy is among the leading causes for its early discontinuation. OBJECTIVES: To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms, produce an acceptable pattern of vaginal bleeding and control endometrial proliferation. METHODS: Twenty-nine postmenopausal women with an intact uterus were studied. All had climacteric symptoms. The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone (high dose progesterone) or 1.8 g (low dose progesterone), and were kept in place for 4-6 months. Serum progesterone, estradiol and estrone were measured and endometrial thickness determined. All women kept a daily diary of bleeding/spotting and completed a questionnaire on climacteric symptoms at monthly intervals. The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women. RESULTS: A total of 18 patients (9 in each group) completed the study. Mean levels of estradiol, estrone and progesterone were at their peak after 2 to 4 weeks. All rings were effective in alleviating vasomotor symptoms, although there was evidence of "escape from effect" in month 6. Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia. Of the 18 women who completed the study, 5 had amenorrhea throughout, 7 had amenorrhea after 3 months, and the remainder had one or two bleeding episodes after 3 months. Therapy was discontinued in 11 women. CONCLUSIONS: A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms, prevented endometrial proliferation, and provided an acceptable bleeding pattern. It should be viewed as a possible alternative for short-term estrogen-progesterone therapy.

[Female sexual dysfunction: classification, epidemiology, diagnosis and treatment].

The successful pharmacological treatment of erectile dysfunction in males has led to increasing interest in the sexual problems of women. Yet in recent years there has been growing consensus regarding the differences between male and female sexuality. William Masters and Virginia Johnson's model of sexual response, revised by Helen Singer Kaplan, has been generally accepted for many decades. This model consists of 4 successive phases: desire, excitement (arousal), orgasm and resolution. Rosemary Basson has suggested a different model, valid especially in long-term relationships. According to Basson, a woman may decide to seek a stimuli necessary to ignite sexual desire, for reasons which are not sexual (such as the need for intimacy or emotional bonding). The desire develops at a latter stage, as a consequence and not as a cause. As the understanding of the sexual response grows, new methods of classification and treatment are being developed. Female sexual dysfunction is common, frequently neglected and has a significant impact on the lives of women. It has a diverse etiology including anatomical, physiological, medical as well as psychological and social factors. The assessment of these disorders incorporates both medical and psychological evaluation. The treatment includes education, improvement of inter-personal communication, behavioral treatment and the solution of medical problems. Different medications are being developed but most have yet to be proven effective. This review presents the female sexual response as it is understood today and the different methods of classification, diagnosis and treatment of female sexual dysfunction.

Pesticide exposure among pregnant women in Jerusalem, Israel: results of a pilot study.

BACKGROUND: Pesticides have been shown to disrupt neurodevelopment in laboratory animals and in human populations. To date, there have been no studies on exposure to pesticides in pregnant women in Israel, despite reports of widespread exposure in other populations of pregnant women and the importance of evaluating exposure in this susceptible sub-population. METHODS: We measured urinary concentrations of organophosphorus (OP) insecticide metabolites and plasma concentrations of OP and other pesticides in 20 pregnant women, recruited in Jerusalem, Israel in 2006, and collected questionnaire data on demographic factors and consumer habits from these women. We compared geometric mean concentrations in subgroups using the Mann-Whitney U-test for independent samples. We compared creatinine-adjusted OP pesticide metabolite concentrations, as well as plasma pesticide concentrations, with other populations of pregnant women. RESULTS: Creatinine-adjusted total dimethyl (DM) metabolite concentrations were between 4 and 6 times higher in this population compared to other populations of pregnant women in the United States while total diethyl (DE) metabolite concentrations were lower. Dimethylphosphate (DMP) was detected in 74% of the urine samples whereas dimethylthiophosphate (DMTP) was detected in 90% of the urine samples. The carbamate bendiocarb was detected in 89% of the plasma samples, while the OP insecticide chlorpyrifos was detected in 42% of the samples. Mean plasma concentrations of bendiocarb and chlorpyrifos in our sample were 4.4 and 3.9 times higher, respectively, than that of an urban minority cohort from New York City. Twelve women (63%) reported using some form of household pest control during their pregnancy and five (26%) reported using household pest control during the past month. Women with a graduate degree had significantly higher geometric mean concentrations of total urinary DM metabolite concentrations compared to other women (P=0.006). Finally, one woman in the study had exceptionally high concentrations of DMP, DMTP, DMDTP compared to the other women in the study, despite reporting no current occupational exposure to OP pesticides and no other significant exposure sources. CONCLUSIONS: Pregnant women in the Jerusalem area are exposed to OP pesticides and to the carbamate pesticide bendiocarb. It is unclear why total DM metabolites concentrations were much higher in this population compared to other populations of pregnant women in the United States and Netherlands. Finally, the finding of very high DM metabolite concentrations in one woman who reported being moved from her regular laboratory work to administrative work upon becoming pregnant, raises questions about the adequacy of measures to protect pregnant women from pesticide exposures during pregnancy.

Sexual function and quality of life for women with mild-to-moderate stress urinary incontinence.

INTRODUCTION: Sexual function is affected by stress urinary incontinence with or without pelvic organ prolapse. The aim of the study was to describe the sexual function of women with mild-to-moderate stress urinary incontinence, with or without pelvic organ prolapse (up to stage 2) and examine correlations with symptoms and quality of life. This investigation was part of a large, randomized, clinical trial of women with stress urinary incontinence who participated in an exercise intervention. METHODS: Women included in the study suffered from stress urinary incontinence as measured by a pad test and were interested in an exercise intervention. All participants underwent assessment for prolapse staging. Instruments included: the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Incontinence Quality of Life Questionnaire (I-QOL), and a health and urinary leakage questionnaire. RESULTS: One hundred and eighty-seven ambulatory women, aged 20 to 65 years, had a mean sexual function score of 36.9 (standard deviation [SD] 5.9). No significant correlation was found between the sexual function scores and quantity of urinary leakage. A significant correlation existed between the sexual function and I-QOL scores (P < .001). An additional finding was that women with urgency symptoms were older (P= .04) and had significantly lower sexual function scores (mean 35.7; SD 6.4) than those who did not report urgency (mean 38.7; SD 4.6; P < .001). DISCUSSION: Women with mild-to-moderate stress urinary incontinence, without or with lower stages of pelvic organ prolapse, demonstrated good sexual function, which correlated with physical and psychosocial factors. Health professionals need to perform multifaceted intake assessments on women with urinary leakage to customize their health promotion regimen.

Massive bleeding from ectopic varices in the postpartum period: rare but serious complication in women with portal hypertension.

Portal hypertension (PHT) often leads to collateralization of blood flow through variceal vessels that shunt blood from the portal to the systemic circulation. Life-threatening bleeding from esophageal and ectopic varices often complicates severe PHT. Increase in PHT occurs during the last stages of the second trimester of pregnancy and is associated with increased risk of PHT bleeding in the later stages of pregnancy. In this report, we present two rare cases of pregnant women with PHT, who had postpartum bleeding from very uncommon sites. The first had a rupture of an intra-abdominal varix and the second had two episodes of bleeding from abdominal wall varices, after two emergent cesarean sections, in two consecutive pregnancies. On the basis of a literature review, we constructed an algorithm that includes instructions on how to handle women with PHT during the various stages of pregnancy and labor.

Phthalate exposure among pregnant women in Jerusalem, Israel: results of a pilot study.

BACKGROUND: Phthalates can disrupt endocrine function and induce reproductive and developmental toxicity in laboratory animals. Few studies have evaluated exposure to phthalates in pregnant women, despite the potential sensitivity of the developing fetus to adverse effects of phthalates. METHODS: We measured urinary concentrations of 11 phthalate metabolites in 19 pregnant women, recruited in Jerusalem, Israel in 2006, and collected questionnaire data on demographic factors and consumer habits from these women. We compared geometric mean concentrations in subgroups and used the Mann-Whitney U-test for independent samples to determine significant differences between groups. RESULTS: Nine metabolites were detected in at least 95% of the samples: mono(2-ethyl-5-carboxypentyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(n-butyl) phthalate, monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), mono(2-ethylhexyl) phthalate and monoisobutyl phthalate. Phthalate metabolite concentrations in these pregnant women were remarkably similar to those in the general United States female population. MBzP geometric mean concentrations were higher in women living in buildings existing 40 years or more (P=0.04). In women who used four or more personal care products (perfume, deodorant, lipstick, nail polish, or hand/face cream) in the 48 h prior to providing the urine sample, geometric mean MEP concentrations were more than 4 times higher than concentrations in women using only two or three of the aforementioned products (P=0.07). CONCLUSIONS: Pregnant women in Jerusalem are exposed to a wide range of phthalates. Building materials used in old constructions may be a source of exposure to benzylbutyl phthalate, the parent compound of MBzP. Personal care products may be sources of exposure to diethyl phthalate, the parent compound of MEP.

Ethnic gap in coronary artery disease: comparison of the extent, severity, and risk factors in Arab and Jewish middle-aged women.

The authors examined risk factors and extent of coronary artery disease (CAD) among Jewish and Arab women in Jerusalem, where Arab women were found to have worse outcome. All angiographically confirmed cases of CAD among women aged 45 to 65 years who were hospitalized during 1990 to 1995 consisted of 40 Arab and 179 Jewish patients. Arab women had more atypical clinical presentations (P<.0001) and more extensive CAD (P=.0016) despite younger age (53+/-3 vs 55+/-5 years; P<.0003) and lesser smoking (P<.0006). The Arab women, however, were more likely to be obese (80% vs 46%; P=.0002), be physically inactive (100% vs 89%; P=.0285), and have diabetes mellitus (73% vs 40%; P=.0004). Moreover, they were more likely to have 3 or more risk factors (45% vs 23%; P=.036). Thus, a combination of an atypical presentation and higher risk (ie, diabetes mellitus combined with hypertension and other risk factors) and much more extensive disease readily explains their worse outcome.

FGF 10 and Sprouty 2 modulate trophoblast invasion and branching morphogenesis.

Branching morphogenesis (BM) of the chorionic villous tree is a crucial component of early placental formation. Fibroblast growth factors (FGFs), their receptor tyrosine kinase (RTK) and negative regulators like Sprouty (Spry) proteins are pivotal factors in the development of diverse branching organ systems. The aim of this study was to examine the effect of FGF10 and Sprouty 2 on BM of the chorionic villi in vitro. Villous explants of first trimester placentas were cultured and their outgrowths were monitored. The effect of FGF10 was tested on matrigel migration/invasion assay, collagenolytic activity of single cell trophoblasts and on villous explants outgrowths. siRNA of Spry2 was used to reduce its expression and to investigate the role of Sprouty 2 in villous explants outgrowths. Quantitative RT-PCR and immunohistochemistry were performed to determine Sprouty 2 and HLA-G (a marker of invasion) expression. FGF 10 stimulated by 8-fold the migration/invasion of single cell trophoblast enhanced their collagenolytic activity. Reduction of Spry2 expression in villous explants showed a marked increase in villous outgrowths. This was accompanied by enhanced staining for HLA-G and by the reduction of Spry2 expression that was confirmed by immunohistochemistry and by quantitative RT-PCR. We conclude that trophoblast outgrowth and invasion (part of placental villi sprouting) at the fetal maternal interface is in part under delicate control of FGF 10 and Sprouty 2. FGF 10 promotes invasion and outgrowth of trophoblasts. In addition, it increases Spry2 expression, which attenuates trophoblast sprouting.