Granulocyte colony-stimulating factor as a potential inducer of ovulation in infertile women with luteinized unruptured follicle syndrome.

Luteinized unruptured follicle (LUF) syndrome is one of the intractable ovulation disorders that are commonly observed during cycles of treatment with ovulation inducers, for which no effective therapy other than assisted reproductive technology is available. Here, we investigated whether granulocyte colony-stimulating factor (G-CSF) could prevent the onset of LUF syndrome. We analyzed the effects of G-CSF in 68 infertile women with LUF syndrome who received ovulation induction (clomiphene + human chorionic gonadotropin [hCG] therapy or follicle-stimulating hormone + hCG therapy). G-CSF (lenograstim, 100 µg) was administered subcutaneously. Onsets of LUF syndrome were compared between the cycle during which G-CSF was given in combination with the ovulation inducer (ie, the G-CSF treatment cycle) and the subsequent cycle during which only the ovulation inducer was given (ie, the G-CSF nontreatment control cycle). The results showed that LUF syndrome recurred in only 3 cycles during the G-CSF treatment cycle (4.4% [3/68 cycles]), whereas LUF syndrome recurred in 13 cycles during the subsequent G-CSF nontreatment control cycle (19.1% [13/68 cycles]). The additional use of G-CSF significantly prevented the onset of LUF syndrome during ovulation induction (P = 0.013, McNemar test). No serious adverse reactions because of the administration of G-CSF were observed. In conclusion, our findings indicate that G-CSF may become a useful therapy for LUF syndrome.

Prenatal diagnosis of fetal respiratory function: evaluation of fetal lung maturity using lung-to-liver signal intensity ratio at magnetic resonance imaging.

OBJECTIVE: The purpose of this retrospective study is to determine the fetal lung-to-liver signal intensity ratio (LLSIR) on T2-weighted images for the prediction of neonatal respiratory outcome. METHODS: One hundred ten fetuses who underwent magnetic resonance imaging (MRI) examination for various indications after 22 weeks of gestation participated in this study. LLSIR was measured as the ratio of signal intensities of the fetal lung and liver on T2-weighted images at MRI. We examined the changes of the ratio with advancing gestation and the relations between LLSIR and the presence of the severe respiratory disorder (SRD) after birth. The best cut-off value of the LLSIR to predict respiratory outcome after birth was calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: Lung-to-liver signal intensity ratio correlated significantly with advancing gestational age (R = 0.35, p < 0.001). The non-SRD group had higher LLSIR compared with the SRD group (2.15 ± 0.30 vs. 1.53 ± 0.40, p < 0.001). ROC curve analysis showed that fetuses with an LLSIR < 2.00 were more likely to develop SRD [sensitivity: 100%, 95% confidence interval (CI): 52-100%; specificity: 73%, 95% CI 54-88%]. CONCLUSION: The fetal LLSIR on T2-weighted images is an accurate marker to diagnose the fetal lung maturity.

Association between adolescent marriage and intimate partner violence: a study of young adult women in Bangladesh.

UNLABELLED: This study explores the association between adolescent marriage and intimate partner violence (IPV) among young adult women using 2007 Bangladesh Demographic Health Survey data. The analyses are restricted to young women 20 to 24 years old. Logistic regression analyses are constructed to estimate the odds ratios and 95% confidence intervals for the association between adolescent marriage and IPV in the past year. RESULTS: show that there is a strong significant relationship between adolescent marriage and experience of physical IPV in the past year among this population. Association between sexual IPV and adolescent marriage is insignificant. Adolescent marriage puts women at increased risk of physical IPV into their young adult period. Government agencies need to enforce existing law on the minimum age at marriage to reduce IPV among adolescent and young adult girls.

Detection of high-risk human papillomavirus subtypes in cervical glandular neoplasia by in situ hybridization.

In situ hybridization (ISH) was performed on paraffin-embedded tissues to detect multiple high-risk human papillomavirus (HPV) subtypes in 27 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma (CA) specimens. These results were compared with those of HPV detection by HPV-PCR genotyping and p16 immunohistochemistry in the same specimens. Of the 27 cases, 17 (63%) showed HPV-DNA by HPV-ISH, including 3 metastatic lesions. HPV-DNA was detected in 18 cases (67%) by PCR. The concordance rate between HPV-ISH and HPV-PCR genotyping was 74% with moderate agreement (Kappa value, 0.41). HPV-16 was identified in 5 cases, HPV-18 in 2 cases, and HPV-45 in 1 case. Combining the results of HPV-ISH and HPV-PCR/genotyping, 22 cases (81.5%) were considered HPV positive. Immunohistochemical staining of p16 indicated that 25 (93%) cases were positive; however, 4 of these cases were HPV-negative by both PCR and ISH. Combining HPV-ISH and HPV-PCR/genotyping techniques demonstrated a high sensitivity of HPV detection in FFPE tissues from cervical glandular neoplasias. In contrast, p16 immunohistochemistry seemed to have a low specificity for determining HPV status in cervical glandular neoplasia. HPV-ISH is useful for recognizing the distribution of HPV in AIS and CA tissues and visualizing signal patterns, and may be a useful tool to confirm the cervical origin of neoplasias and metastatic lesions.

Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer.

Human papillomavirus (HPV) is the most important etiological factor for cervical cancer. A recent study demonstrated that more than 20 HPV types were thought to be oncogenic for uterine cervical cancer. Notably, more than one-half of women show cervical HPV infections soon after their sexual debut, and about 90 % of such infections are cleared within 3 years. Immunity against HPV might be important for elimination of the virus. The innate immune responses involving macrophages, natural killer cells, and natural killer T cells may play a role in the first line of defense against HPV infection. In the second line of defense, adaptive immunity via cytotoxic T lymphocytes (CTLs) targeting HPV16 E2 and E6 proteins appears to eliminate cells infected with HPV16. However, HPV can evade host immune responses. First, HPV does not kill host cells during viral replication and therefore neither presents viral antigen nor induces inflammation. HPV16 E6 and E7 proteins downregulate the expression of type-1 interferons (IFNs) in host cells. The lack of co-stimulatory signals by inflammatory cytokines including IFNs during antigen recognition may induce immune tolerance rather than the appropriate responses. Moreover, HPV16 E5 protein downregulates the expression of HLA-class 1, and it facilitates evasion of CTL attack. These mechanisms of immune evasion may eventually support the establishment of persistent HPV infection, leading to the induction of cervical cancer. Considering such immunological events, prophylactic HPV16 and 18 vaccine appears to be the best way to prevent cervical cancer in women who are immunized in adolescence.

Intimate partner violence and unintended pregnancy among Bangladeshi women.

This study examined the relationship between intimate partner violence (IPV) and unintended pregnancy using data from women reporting IPV in the 2007 Bangladesh Demographic Health Survey. The analysis included 4,695 married women, aged 15 to 40 years, who had at least one birth in the last 5 years. Bivariate and multiple logistic regression analyses were performed to assess the relationship between IPV and pregnancy. About one third (30.4%) of women were abused physically and/or sexually and about one third (30.9%) of their births in the last 5 years were unintended. Compared with women who suffered no IPV, women who were abused sexually had a 1.64-fold increased risk of unintended pregnancy, which is higher than those who suffered physical abuse only (odds ratio: 1.35). The prevalence of unintended pregnancy among those who experienced severe physical violence was 1.60 times higher than those who reported no abuse. The findings indicate a significant relationship between IPV and unintended pregnancy among Bangladeshi women.

High prevalence of intermediate-risk human papillomavirus infection in uterine cervices of Kenyan women infected with human immunodeficiency virus.

The aim of this study was to investigate an association between certain human papillomavirus (HPV) types and human immunodeficiency virus (HIV) infections. Sexually active females (n = 487; 19-61 years old) were enrolled in the study. Subjects underwent Pap testing and evaluations of HIV and HPV infection status on uterine cervical cell samples. HPV genotyping was performed using a Kurabo GeneSQUARE DNA microarray test. Overall, 23 HPV genotypes were detected, and the most prevalent HPV genotype was HPV-52, followed by HPV-39, -54, -45, -56, -53, -31, -42, -16, -68, and -51. HPV-30, -53, -54, -61, and -66, which are associated with abnormal cytology, are categorized as intermediate-risk in this study. Detection of both high- and intermediate-risk HPV types was significantly associated with cervical abnormality and HIV infection. Multivariate analysis revealed that some high-risk HPV types (HPV-31, -45, -51, -56, and -59) and most intermediate-risk HPV types were associated with HIV infection, while the high-risk types (HPV-16, -18, -33, -35, -39, -52, -58, and -68) were not. The oncogenic effect of the most malignant HPV types (e.g., HPV-16 and -18) appear to be lower, while that of intermediate-risk types are greater, in areas with a high prevalence of HIV infection.

Regulation of amphiregulin, EGFR-like factor expression by hCG in cultured human granulosa cells.

BACKGROUND: It has long been suspected that the epidermal growth factor (EGF) receptor and some of its putative ligands may play an important role in ovarian function. Amphiregulin (AR) is the growth factor with an EGF-like motif, but its potential role in signalling in the ovary is still obscure. AR gene expression and its functional effect were evaluated in human granulosa cells from immature follicles. METHOD: Granulosa cells from immature follicles with early menstrual phase were cultured with or without 200 mIU/ml of FSH stimulation, following with or without 1 IU/ml of hCG. mRNA levels of AR and luteinising hormone replacement (LHR) were semi-quantified using RT-PCR. Progesterone (P) concentration in the medium was assayed. RESULTS: LHR mRNA was expressed 48 h after FSH stimulation without AR mRNA expression. AR mRNA was expressed 1 h after hCG stimulation, and increased the intensity in 6 h. P biosynthesis was increased by AR in a dose-dependent manner. AR mRNA was elevated by forskolin stimulation without FSH and hCG stimulation before LHR mRNA expression. When cultured with FSH for 15 h, followed by increasing doses of hCG stimulation for 6 h, the AR mRNA levels increased according to hCG concentration up to 1,000 mIU/ml. CONCLUSION: Occurrence of LHR gene expression following FSH stimulation was necessary for the AR gene expression in vivo, and the AR gene was induced by forskolin without LHR gene expression in vitro. P biosynthesis was stimulated, to some extent, by AR. This result suggests the differentiation effect of AR on granulosa cells. AR might be a mediator of LH signals before ovulation.

Hemodynamic analysis of cephalothoracopagus by the color doppler method. A comparison to normal fetuses via a longitudinal study.

In a case of cephalothoracopagus, the umbilical artery (UA) was observed with color Doppler method, and the findings were compared with the hemodynamics of 46 normal fetuses. The patient was a 25-year-old primigravida who had appeared for routine prenatal visits since her 6th week of pregnancy. At a later time, the patient was examined after an interval of 4 weeks. Although an ultrasonography was also conducted, unfortunately, any findings of cephalothoracopagus were not detected. In the 25th week of gestation, we hospitalized her for marked polyhydramnios (amniotic fluid index: 280 mm), at which time an ultrasound examination revealed cephalothoracopagus. In the UA, the V(max) was 30.3 cm/s (normal fetus at 25-28 weeks: 33.5 +/- 3.9 cm/s). The UA hemodynamics fell below the normal range. At 26 weeks, the UA V(max) was 56.5 cm/sec, a level which significantly exceeded the normal range. The patient underwent a cesarean section at 27 weeks of gestation; the indication was fetal distress. This is caused by the condition in which the fetal heart beats decreases to 90 beats per minute 3 times during a 10-min period as measured on the cardiotocograms. She delivered a 1,392-gram female with an Apgar score of 2 points (respiratory 1 point and heart rate 1 point). The infant was a cephalothoracopagus, with one head, two hearts, four upper limbs, and four lower limbs. The neonate died from circulatory failure 56 min after birth.

Hemodynamics of the renal artery and descending aorta in fetuses with renal disease using color Doppler ultrasound--longitudinal comparison to normal fetuses.

OBJECTIVE: To examine the hemodynamic values of the renal artery (RA) and descending aorta (DA) in normal fetuses, and to compare these values to those of fetuses with renal disease, thus evaluating the usefulness of hemodynamic analysis for the diagnosis of fetal renal disease. MATERIALS AND METHODS: We examined 46 normal fetuses and 15 fetuses with renal disease (six cases of polycystic kidney (PCK) and nine cases of hydronephrosis). We measured the maximum systolic velocity (Vmax ) of the RA and DA using color Doppler. Measurements were made five times, from the 20th to the 40th week, in both the control and the renal disease group. RESULTS: In the fetuses with PCK (Potter's syndrome) that died postpartum from non-functional kidneys, the Vmax of the RA and DA in the 35th week were 13 cm/s and 25.4 cm/s, respectively. In the fetus with PCK (Trisomy 9) that died due to non-functional kidneys in the 34th week, the values were 13.3 cm/s and 29.6 cm/s, respectively. These values were well below those of the normal group: more than 1.5 SD below the mean. In two fetuses from the nine with hydronephrosis that had a unilateral non-functional kidney, the RA did not clearly show identifiable blood flow. CONCLUSIONS: The V max of the RA and DA in fetuses with renal disease correlates with fetal kidney function, particularly the RA Vmax.Vmax of 1.5 SD below the mean should be the lower normal limit.

Analysis of renal artery hemodynamics in normal fetuses using the color Doppler method.

OBJECTIVE: From analysis of fetal renal artery hemodynamics, we attempted to reveal renal glomerular and tubular function in normal fetuses during pregnancy. DESIGN: The study included 36 cases of normal fetuses from the 20th to the 40th week of gestation; V(max) (the systolic peak velocity of main renal artery), V(mean) (time averages of trace of peak velocity) blood flow were initially measured between 20 and 24 weeks of gestation and every 4 weeks thereafter. The measurement was performed a total of five times in a longitudinal study. In addition, the blood flow waveform was concurrently examined. RESULTS: The V(max) was 22.02 +/- 0.50 cm/s at 20-24 weeks of gestation. This standard value (100%) was found to increase for each group as follows: 125.2, 149.1, 156.1, and 181.5%. Furthermore, using 20-24()weeks of gestation as the standard, the V(mean) increased after the 37th week of gestation: 186.7%, respectively. At 20-24 weeks of gestation, the blood flow wave forms consisted of 43.2% type I (only systolic waveforms), and 56.8% type II (both systolic and diastolic waveforms). Type III waveforms (waveforms that extended beyond the diastolic to the next systolic component) were not recognized. In the 33- to 36-week group, 82.6% of the waveforms were type II, and in the 37- to 40-week group, 76.2% of the waveforms were type III. CONCLUSIONS: The V(max) and V(mean) of the renal artery in normal fetuses exhibit a similar rate increase when 20-24 weeks of gestation is compared to 37-40 weeks of gestation. The blood flow waveforms changed as pregnancy progresses; thus, it was inferred that this finding was related to the development of the renal glomerular and renal tubular function.