Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Guideline for Gynecological Practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2020 edition.

Nine years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 4th Revised Edition was published in 2020. The 2020 Guidelines includes 4 additional clinical questions (CQ), which brings the total to 99 CQ (12 on infectious disease, 29 on oncology and benign tumors, 29 on endocrinology and infertility and 29 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Effects of prenatal maternal stress by repeated cold environment on behavioral and emotional development in the rat offspring.

It has been reported that many types of stresses, which caused physiological and psychological alterations in dams as prenatal maternal stress, affected behavioral and emotional traits of their offspring. However, effects of environmental temperature changes, which induce various stress responses in both animals and humans, have not been assessed as prenatal maternal stress. Repeated cold stress (RCS) is a type of chronic cold stress in which environmental temperature changes rapidly and frequently several times within a day. In the present study, to investigate effects of chronic maternal stress by the RCS on behavioral and emotional development of the rat offspring (prenatal RCS rats), the RCS stress was loaded to pregnant rats between day 9 and 19 after fertilization. The prenatal RCS rats showed similar locomotor activity in an open field to control rats that were borne by non-stressed pregnant rats. On the other hand, the prenatal RCS rats showed significantly higher startle responses than the control rats in a light enhanced startle paradigm. However, treatment of diazepam decreased the startle responses in the prenatal RCS rats to the same degree as those in the control rats. The results indicated that prenatal RCS affected emotional development of the rat offspring, but not locomotor activity. Comparison of the present results with the previous studies suggests that there might be unknown common mechanisms among different prenatal maternal stresses that induce similar behavioral developmental alteration.

Cadmium and nutritional intake in pregnant Japanese women.

A study to clarify the food composition and nutritional factors that contribute to the levels of blood and urinary cadmium (Cd) was conducted on 50 pregnant Japanese women with mean age of 29 years. The mean iron (Fe) intake of subjects was 9.2 mg, which is much lower than the recommended level of 20 mg for pregnant women. Cd in urine samples collected at 30-32 weeks of gestation were correlated (r = 0.354), but urinary Cd was related to age more than blood Cd. Urinary Cd and blood Cd levels were inversely related to total energy (rpartial = -0.325, and -0.334, respectively) and fat intake (rpartial = -0.419, and -0.379, respectively), even after adjustment for age. Blood Cd was also correlated to protein and iron intake (rpartial = -0.299, and -0.353, respectively). These results indicate that Cd exposure levels of pregnant women with low energy intake, especially less fat intake, were higher than those of women with more energy and fat intake. In particular, blood Cd may be affected by protein and iron intake in pregnant women with increased these nutrients demand.

Relationship between newborn size and mother's blood cadmium levels, Toyama, Japan.

The effect of blood cadmium (Cd), which reflects not only Cd body burden but also recent Cd exposure and communicates with fetal blood in the placenta, on newborn size at birth was investigated. Blood Cd of 55 mothers from Toyama, Japan, at 30-32 gestational weeks was measured using a flameless atomic absorption spectrophotometer. The relationship between blood Cd and newborn size was analyzed after adjustment for gestational age and maternal build. A significant inverse correlation was found between infant height and maternal blood Cd. After adjustment for gestational age and maternal weight at 30-32 gestational weeks, the significant inverse relationship between maternal blood Cd and infant height was shown using the multiple regression analysis. Newborn size might be influenced by maternal blood Cd levels to which infants may be exposed during gestation.

Cadmium exposure and trace elements in human breast milk.

The interrelations of the seven elements, calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), phosphorus (P), copper (Cu), zinc (Zn), and cadmium (Cd) in human breast milk were examined in Japanese mothers to clarify the effects of Cd exposure on these important elements for infant growth. Breast milk and urine samples were obtained from 68 mothers, aged 19-38 years, at 5-8 days postpartum. The concentrations were determined by inductively-coupled plasma atomic emission spectrometry for Ca, Mg, Na, K, P, by flame atomic absorption spectrophotometry for Cu and Zn, and by flameless atomic absorption spectrophotometry for Cd. Geometrical mean Cd concentrations were 0.28 (geometrical standard deviation=1.82) microg/l in breast milk and 1.00 (1.93) microg/g creatinine in urine. Among the above elements only Cd concentration in breast milk was significantly correlated with urinary Cd concentration (r=0.451, P<0.001). Significant positive correlations were found between Cu and Ca (r=0.500, P<0.001), Cu and Mg (r=0.378, P<0.01), and Zn and Mg (r=0.355, P<0.01) in breast milk. Cd concentration in breast milk showed an inverse relationship with Ca concentration in breast milk (r=-0.248, P<0.05). These results indicate that the Cd concentration in breast milk closely reflects Cd body burden, with increased Cd in breast milk possibly affecting Ca secretion in breast milk.

The preterm labor index and fetal fibronectin for prediction of preterm delivery with intact membranes.

OBJECTIVE: To compare the preterm labor index with the biochemical marker fetal fibronectin in predicting preterm delivery. METHODS: In 185 women with preterm labor and intact membranes, the preterm labor index was determined based on clinical findings of uterine contractions, bleeding, and cervical dilatation. An immunosorbent assay was used to measure oncofetal fibronectin. RESULTS: A significant negative correlation was noted between the preterm labor index and the interval from hospitalization to delivery. Based on a receiver operating characteristic curve, a preterm labor index 4 or higher was defined as positive. Rates of preterm delivery overall and of delivery within 1 week in the preterm labor index-negative group were 55.2% and 13.8%, respectively. Those in the preterm labor index-positive group were significantly higher (88.4% and 56.5%). With respect to predicting when a delivery would occur during the first week of hospitalization, the preterm labor index and fetal fibronectin did not differ in sensitivity (77.7% and 73.8%, respectively), specificity (79.5% and 74.2%), positive predictive value (66.7% and 60.8%), or negative predictive value (84.5% and 83.9%). However, within the preterm labor index-negative group, the rates of preterm delivery (68.4%), delivery within 1 week (28.9%), and neonatal treatment in an intensive care unit (36.8%) were significantly higher in fetal fibronectin-positive than in fibronectin-negative cases (46.2%, 9.0%, and 10.3%, respectively). CONCLUSION: The preterm labor index was similar to the fetal fibronectin assay in its ability to predict preterm delivery.

A Th2 chemokine, TARC, produced by trophoblasts and endometrial gland cells, regulates the infiltration of CCR4+ T lymphocytes into human decidua at early pregnancy.

PROBLEM: A chemokine receptor, CCR4 preferentially expressed on type 2 helper T (Th2-type) cells, and its ligand, thymus and activation regulated chemokine--(TARC/CCL)--play important roles in the recruitment of Th2-type cells. We examined the distribution of CCR4 expressing CD4+ and CD8+-T cells in human decidua at early pregnancy, and localized TARC in the decidual tissue and chorionic tissue. METHOD OF STUDY: Decidual tissue was obtained by legal abortion. The percentages of CCR4 expressing CD4+ and CD8+-T cells were analyzed by flow cytometry. Localization of TARC protein was evaluated by immunofluorescence staining. The expression of TARC mRNA in the choriocarcinoma cell line and endometrial cell line was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT: The percentages of CCR4+ cells in CD4+-T cells and CD8+-T cells were significantly increased in human early pregnancy decidua compared with those in peripheral blood. An another marker of human Th2 and Tc2 cells, CRTH2 molecules was also expressed on CCR4+ CD4+-T cells and CCR4+ CD8+-T cells. In addition, we found that trophoblasts, uterine epithelial cells and endometrial gland cells produce TARC by immunohistochemical staining and the RT-PCR method. CONCLUSION: Our findings imply that TARC secreted in decidua mediates the infiltration of CCR4+ T-cell migration into the fetomaternal interface, decidua, resulting in the maintenance of pregnancy.

Interleukin 2 receptor gamma chain (gamma(c)) knockout mice show less regularity in estrous cycle but achieve normal pregnancy without fetal compromise.

PROBLEM: Implication of cytokines in pregnancy suggested but remains to be established. We studied the effect of cytokines on reproductive functions such as ovulation and pregnancy, with mutant mice lacking interleukin 2 receptor gamma (IL-2Rgamma), the so-called common gamma chain (gamma(c)), which is shared among receptors for multiple cytokines such as IL-2, IL-4, IL-7, IL-9 and IL-15. METHOD OF STUDY: Regularities of estrous cycles were observed by vaginal smear. Ovaries stimulated with postmenopausal serum gonadotropin (PMSG) were examined for the ovarian capacities. The uteri at 13 days of gestation were used for histological analysis of the maternal-fetal interface. RESULTS: The estrous cycles in gamma(c) knockout (gamma(c) KO) mice were irregular compared with wild-type mice, although, the mutants could become pregnant. No uterine natural killer (uNK) cell was found in the uterus at 13 days of pregnancy, and poor decidual formation and thickness of blood vessel walls were observed. Apparent differences were not seen in the numbers and weight of the fetuses between wild type and mutant animals, and fetuses were not compromised throughout pregnancy. CONCLUSIONS: The gamma(c) KO mice showed irregular estrous cycle but they could carry out normal pregnancy despite lacking uNK and cytokines actions of IL-2, 4, 7, 9 and 15.

Interleukin-12 secretion by peripheral blood mononuclear cells is decreased in normal pregnant subjects and increased in preeclamptic patients.

PROBLEM: It has been reported that T-helper (Th) 2 dominance in normal pregnancy shifts to Th1 dominance in preeclampsia. Peripheral blood mononuclear cell (PBMC) production of interleukin (IL)-12, which induce Th1 responses, has not been compared between these clinical states. METHOD OF STUDY: Peripheral blood mononuclear cell from 35 non-pregnant women, 35 healthy pregnant women, 12 mildly preeclamptic patients, and 15 severely preeclamptic patients were cultured for 24 hr. IL-12 secretion was determined by enzyme-linked immunosorbent assay (ELISA). Th1/Th2 ratios in PBMC were determined flow-cytometrically, and the amounts of HLA-DR and CD14 expression on the monocytes were obtained by flow cytometry. RESULTS: Peripheral blood mononuclear cell from healthy pregnant subjects secreted less IL-12 than non-pregnant women. PBMC from severely preeclamptic patients secreted more IL-12 than those from healthy pregnant subjects, while IL-12 secretion in mild preeclampsia resembled secretion in normal pregnancy. Th1/Th2 ratios correlated were positively with IL-12. Increased HLA-DR antigens and reduced CD14 expression, suggesting monocyte activation, were observed in preeclamptic patients, although monocyte counts were unchanged. CONCLUSION: Decreased IL-12 secretion by PBMC may cause Th2 dominance in normal pregnancy, while increased IL-12 secretion by activated monocytes may cause Th1 dominance in preeclampsia.