Landscape of somatic mutated genes and inherited susceptibility genes in gynecological cancer.

Traditionally, gynecological cancers have been classified based on histology. Since remarkable advancements in next-generation sequencing technology have enabled the exploration of somatic mutations in various cancer types, comprehensive sequencing efforts have revealed the genomic landscapes of some common forms of human cancer. The genomic features of various gynecological malignancies have been reported by several studies of large-scale genomic cohorts, including The Cancer Genome Atlas. Although recent comprehensive genomic profiling tests, which can detect hundreds of genetic mutations at a time from cancer tissues or blood samples, have been increasingly used as diagnostic clinical biomarkers and in therapeutic management decisions, germline pathogenic variants associated with hereditary cancers can also be detected using this test. Gynecological cancers are closely related to genetic factors, with approximately 5% of endometrial cancer cases and 20% of ovarian cancer cases being caused by germline pathogenic variants. Hereditary breast and ovarian cancer syndrome and Lynch syndrome are the two major cancer susceptibility syndromes among gynecological cancers. In addition, several other hereditary syndromes have been reported to be associated with gynecological cancers. In this review, we highlight the genes for somatic mutation and germline pathogenic variants commonly seen in gynecological cancers. We first describe the relationship between clinicopathological attributes and somatic mutated genes. Subsequently, we discuss the characteristics and clinical management of inherited cancer syndromes resulting from pathogenic germline variants in gynecological malignancies.

Association between Preconception Dietary Fiber Intake and Preterm Birth: The Japan Environment and Children's Study.

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. Therefore, this study aimed to determine whether preconception dietary fiber intake is associated with PTB. This was a prospective cohort Japan Environmental and Children's Study (JECS). The study population comprised 85,116 singleton live-birth pregnancies from the JECS database delivered between 2011 and 2014. The participants were categorized into five groups based on their preconception dietary fiber intake quintiles (Q1 and Q5 were the lowest and highest groups, respectively). Multiple logistic regression analysis was performed to determine the association between preconception dietary fiber intake and PTB. Multiple logistic regression analysis revealed that the risk for PTB before 34 weeks was lower in the Q3, Q4, and Q5 groups than in the Q1 group (Q3: adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.62-0.997; Q4: aOR 0.74, 95% CI 0.57-0.95; Q5: aOR 0.68, 95% CI 0.50-0.92). However, there was no significant difference between preconception dietary fiber intake and PTB before 37 weeks. In conclusion, higher preconception dietary fiber intake correlated with a reduced the risk for PTB before 34 weeks. Therefore, new recommendations on dietary fiber intake as part of preconception care should be considered.

Association between preconception dietary fiber intake and hypertensive disorders of pregnancy: The Japan Environment and Children's Study.

OBJECTIVES: Hypertensive disorders of pregnancy (HDP) are a significant cause of morbidity and mortality. This study aimed to investigate whether preconception dietary fiber intake is associated with new-onset HDP. STUDY DESIGN: We identified 84,873 (primipara, 33,712; multipara, 51,161) normotensive participants from the Japan Environmental Children's Study database who delivered between 2011 and 2014. The participants were subsequently categorized into five groups based on their preconception dietary fiber intake quintiles (Q1-Q5). MAIN OUTCOME MEASURES: The main obstetric outcome was HDP, and the secondary obstetric outcomes included early-onset (Eo, <34 weeks)-HDP, late-onset (Lo, ≥34 weeks)-HDP, small for gestational age (SGA) births, and HDP with/without SGA. RESULTS: Multiple logistic regression analysis showed that in primiparas, the risks of HDP, Lo-HDP, and HDP without SGA were lower in the Q5 group compared with the Q3 group (HDP: adjusted odds ratio [aOR] = 0.73, 95 % confidence intervals [95 % CI] = 0.58-0.93; Lo-HDP: aOR = 0.72, 95 % CI = 0.55-0.94; and HDP without SGA: aOR = 0.68, 95 % CI = 0.53-0.88). However, the risks of Eo-HDP and HDP with SGA were higher in the Q1 group compared with the Q3 group (Eo-HDP: aOR = 1.66, 95 % CI = 1.02-2.70; and HDP with SGA: aOR = 1.81, 95 % CI = 1.04-3.17). In multiparas, the risks of Lo-HDP and SGA were higher in the Q1 group compared with the Q3 group (Lo-HDP: aOR = 1.47, 95 % CI = 1.10-1.97; SGA: aOR = 1.17, 95 % CI = 1.02-1.35). CONCLUSIONS: Preconception dietary fiber intake is beneficial in preventing HDP onset. Therefore, new recommendations should be considered to encourage higher dietary fiber intake as part of preconception care.

Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.

CONTEXT: Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). OBJECTIVE: To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. DESIGN: Prospective observational study using data from the Japan Environment and Children's Study (JECS). PARTICIPANTS: Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded. MAIN OUTCOME MEASURES: Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model. RESULTS: We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07). CONCLUSIONS: The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.

A case of delayed postoperative bleeding after excision of endometrial polyp using resectoscope in an infertile woman with von Willebrand disease:a case report and literature review.

Von Willebrand disease (VWD) is a bleeding disorder caused by a congenital quantitative reduction, deficiency, or qualitative abnormality of the von Willebrand factor (VWF). Here, we report a case of delayed postoperative bleeding in an infertile woman with endometrial polyps complicated by VWD. The patient was a 39-year-old infertile woman with type 2A VWD. At 38 years of age, she was referred to our hospital for infertility and heavy menstrual bleeding. Hysteroscopy revealed a 15-mm polyp lesion in the uterus. The patient was scheduled for transcervical resection (TCR) of the endometrial polyp. Gonadotropin-releasing hormone agonists were preoperatively administered to prevent menstruation. The VWF-containing concentrate was administered for 3 days according to guidelines. The patient was discharged on postoperative day 3 after confirming the absence of uterine bleeding. Uterine bleeding began on postoperative day 6. The patient was readmitted on postoperative day 7 and treated with VWF-containing concentrate for 5 days, after which hemostasis was confirmed. TCR surgery for endometrial lesions is classified as a minor surgery, and guidelines recommend short-term VWF-containing concentrate replacement. However, it should be kept in mind that only short-term VWF-containing concentrate replacement may cause rebleeding postoperatively.

Successful pregnancy and delivery after a vitrified-warmed embryo transfer in a woman with Kallmann syndrome: A case report and literature review.

Kallmann syndrome, a congenital disorder of idiopathic hypogonadotropic hypogonadism associated with anosmia, results in infertility because of anovulation. Assisted reproductive technology (ART) is considered when optimal ovulation induction therapy is difficult or when several cycles of ovulation induction therapy do not result in pregnancy. However, evidence is lacking regarding the optimal ART treatment for Kallmann syndrome. We report the case of a 33-year-old woman who successfully achieved pregnancy and delivery after ART treatment. At 29 years old, she was diagnosed with Kallmann syndrome due to hypothalamic amenorrhea and anosmia. At 33 years old, she revisited the hospital, desiring a child after one year of infertility. Due to anovulation, she was treated with gonadotropin therapy, but controlling follicular development was difficult, and thus ART treatment was initiated. The controlled ovarian stimulation (COS) protocol for ART treatment employed gonadotropins, recombinant follicular stimulating hormone/human menopausal gonadotropin plus human chorionic gonadotropin, to promote follicular growth. Four oocytes were retrieved, and two cleaved embryos were vitrified and cryopreserved. After vitrified-warmed embryo transfer of a morula stage embryo in a hormone replacement cycle, pregnancy was achieved but resulted in a miscarriage. A second oocyte retrieval was performed under the same COS; four oocytes were retrieved, and two cleaved embryos were vitrified and cryopreserved. Further, a pregnancy was achieved through the vitrified warmed embryo transfer. At 40 weeks and 6 days of gestation, a baby boy weighing 3,344 g with an Apgar score of 7/8 was delivered vaginally. The mother's postpartum course and neonate were free from adverse events. For women with Kallmann syndrome, ART treatment and selective embryo cryopreservation may be a reasonable and safe option.

Severe Hemoperitoneum After Oocyte Retrieval Due to Ovarian Hemorrhage Possibly Caused by Violent Cough Under General Anesthesia With Propofol and Pentazocine: A Case Report and Literature Review.

Oocyte retrieval is an invasive procedure for patients undergoing assisted reproductive technology (ART). Complications regarding oocyte retrieval are rare; however, once they occur, patients often require hospitalization and, could in some cases, lead to life-threatening situations. We report a case of severe hemoperitoneum due to ovarian hemorrhage after oocyte retrieval. A 39-year-old patient wanted to have a second child and received ART treatment because of severe male infertility. Oocyte aspiration was performed under intravenous anesthesia with propofol and pentazocine. She suddenly coughed and violently moved her body while the puncture needle was inside the ovary. After increasing the propofol dose, the coughing subsided and oocyte retrieval continued. Five hours following oocyte retrieval, she revisited the clinic with severe abdominal pain. Transvaginal ultrasonography revealed echogenic findings in the Douglas' pouch; 300 mL of blood was aspirated by puncture of the Douglas pouch. She was transferred to our hospital because of suspected severe hemoperitoneum. Contrast-enhanced computed tomography revealed hematoma formation in the right ovary with a small amount of extravasation. Laparoscopic surgery revealed extensive hemoperitoneum due to right ovarian hemorrhage. The right ovary was enlarged to the size of a fist and contained a clot; the bleeding was due to a tear in the cortex of the ovary. The partially torn ovarian tissue was excised; hemostasis was performed using a bipolar device. The body movement caused by violent coughing during oocyte retrieval may have led to increased laceration at the ovarian puncture site. Although cough during general anesthesia using propofol and pentazocine is very rare, physicians and staff should be aware of the high risk of intra-abdominal hemorrhage when such complications occur.