The process of "transition" from pediatric to adult health services in young adults with pediatric-onset chronic conditions become an issue these days. Many of these young adults continue to be cared for by their pediatrician at the current moment. However, a variety of gynecologic problems such as amenorrhea, abnormal uterine bleeding and menstrual disorders commonly occur in female patients. To meet the demands for gynecologic examinations of adolescent girls and young women with chronic diseases, we started a pediatric and adolescent gynecology clinic in the medical center for maternal and child health in 1997. We retrospectively studied 88 patients with intellectual and developmental disabilities, with a mean age of 16.4 (range 9-34) years. Among those, 15 (17%) patients had multiple malformation or malformation syndrome, 12 (14%) patients were associated with chromosomal abnormalities, such as trisomy 21, and 12 (14%) had seizure disorders. Eleven (13%) had no known cause for intellectual disabilities, and there were six patients with developmental disabilities. Reasons for consultation were menstrual cycle irregularity in 27 patients (31%), primary amenorrhea in 19 (22%), and dysmenorrhea including hypermenorrhea in 13 (15%). Eighty-two patients (93%) suffered from menstrual disorders. Medical therapy for menstrual disorders includes symptomatic treatment 13/82 (11%) and hormonal therapy 34/82 (41%). No treatment was needed in 31/82 (38%) patients. On the other hands, we needed to discontinue medical therapy in four patients. A number of adolescent and young adults with intellectual and developmental disabilities are increasing. Growing evidence demonstrates that these female patients are at risk for menstrual disorders. However, female patients with serious disabilities were unable to manage their menstruation. It was sometimes not appropriate to use the conventional hormone replacement therapy for these patients. Moreover, there was also a case of sexual abuse. As gynecologists, we need to pay careful attention to the various medical conditions in these patients. It is also noteworthy that female patients with disabilities have a higher risk for various forms of abuse including sexual ones, compared with those without disabilities. [Adv Obstet Gynecol, 69(3) : 245-252, 2017 (H29.8)]

Objective: Bevacizumab (BEV) was provided insurance coverage for ovarian cancer in 2014 in Japan. However, institutions differ in their indication of BEV. There are no large reports about adverse event in Japan. We performed a questionnaire survey to determine the actual usage of and adverse events associated with BEV. Method: Twenty-four institutions presented about chemotherapy with BEV in the 133rd OBSTETRICAL GYNECOLOGICAL SOCIETY OF KINKI DISTRICT JAPAN. This questionnaire survey targeted them. Result: We could receive answers from 18 institutions. The rate of valid response was 75%. The data of 232 cases were collected; 107 cases (46.1%) were primary advanced ovarian cancer and 125 cases (53.9%) were recurrent ovarian cancer. One institution (5.5%) used BEV for only primary advanced cases, three institutions (16.7%) used it for only recurrent cases, and 14 institutions (77.8%) used it for both kinds of cases. Paclitaxel+Carboplatin (TC) were used with BEV in 88 (82.2%) of primary advanced cases. Among cases of recurrent ovarian cancer, there were 14 (11.2%) that had not received any previous regimen, 62 (49.6%) that had received one previous regimen, 24 cases (19.2%) that had received two previous regimens, and 25 cases (20.0%) that had received more than three previous regimens. Among recurrent cases, TC was used in 26 cases (20.8%) with BEV, Gemcitabine+Carboplatin (GC) in 19 cases (15.2%), Pegylated Liposomal Doxorubicin (PLD) in 30 cases (24.0%), and Gemcitabine (GEM) in 19 cases (10.4%). The response rate was 52.4% for the cases which knows the effect. Grade 2 or higher hypertension occurred in 61 cases (26.2%). Grade 2 or higher neutropenia occurred in 36 cases (15.5%). Grade 3 or higher gastrointestinal perforation occurred in 6 cases (2.6%). Conclusion: We could show the actual usage of and adverse events associated with BEV in this questionnaire survey. The difference in the frequencies of adverse event was not admitted between past clinical trials and this questionnaire survey. This survey is limited because it was a questionnaire survey, therefore, large-scale trials and consideration of adverse events in Japan are warranted. [Adv Obstet Gynecol, 69(3) : 253-261, 2017 (H29.8)]

Purpose: Aids for infertility couples by the government are limited for women under 42 years old after April 2016. However, pregnancy of women older than 43 years old is not uncommon in infertility treatment. Therefore, it is an urgent issue to consider the treatment options for these women. In this study, we examined women who were over 43 years old and achieved pregnancy by infertility treatment to be of some help toward this issue. Materials and Methods: There were 3743 women who became pregnant after infertility treatment between January 2011 and December 2013 at our infertility center. Among these, we selected 118 patients older than 43 years old and examined their background, history, treatment and outcome of pregnancy retrospectively. Results: The patients were diagnosed as pregnancy at the age of 44.2 on average, and the oldest was at the age of 48.7. The duration of the treatment is 508 days on average (27-2260 days), which is significantly longer than that of the patients younger than 40 years old. 69% of cases (81 patients) had no history of treatment at other hospitals or clinics and 71% of cases (84 patients) had history of pregnancy including spontaneous abortion. Most of the patients (85%, 100 patients) achieved pregnancy by assisted reproductive technology (ART), and 13% of cases (15 patients) by timed intercourse, 3% (3 patients) by intrauterine insemination (IUI). 95% of women who had been treated previously and 94% of those who had no history of pregnancy achieved pregnancy by ART. In ART, although about half of cases (54 patients) used clomiphene citrate for ovarian stimulation because of ovarian dysfunction from advanced maternal age, 36 patients used short protocol, and frozen embryos were transferred in 49 patients. Only 34% of cases (40 patients) resulted in live birth, in which 26 patients gave birth by cesarean section. Among the rest, 68 patients (58% of all cases) ended in spontaneous abortion, 3 patients in ectopic pregnancy and five patients in artificial abortion. Conclusion: ART attained pregnancy in 85% of cases, especially, in almost of women who had been treated previously and those who had no history of pregnancy. Thus, history of previous treatment and pregnancy are important factors in choosing treatment options. Although clomiphene citrate was used most in ovarian stimulation for ART, short protocol achieved pregnancy in many cases and it would be a positive option in patients with appropriate ovarian reserve. The outcome of pregnancy is unfavorable in these patients, in which more than half of cases resulted in abortion. In addition to that, artificial abortion was chosen in five cases. Thorough information including outcome of pregnancy should be offered to patients when commencing treatments for infertility. [Adv Obstet Gynecol, 69(3) : 262-268, 2017 (H29.8)]

Between posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), there are similar clinical features and images. We experienced a case that had a diagnosis of PRES and RCVS complicated with HELLP syndrome by magnetic resonance imaging. She was 35-year-old with gravida 4 para 3. At 40 weeks pregnant, she came to the hospital because of diarrhea for two days and epigastric pain. After 155 minutes, she had thunderclap headache and after 215 minutes, she had tonic convulsions. The blood test suggested HELLP syndrome (T-bil 0.89 mg/dl, LDH 1788 IU/l, AST 699 IU/l, Plt 85000 /mm³). Computed tomography showed the subarachnoid hemorrhage (high absorbance in the left sylvian fissure, right high fornix of the frontal lobe, and fissure interhemispheric). We performed cesarean section under general anesthesia for maternal safety first. We gave a diagnosis of PRES just after the operation because magnetic resonance angiography (MRI) showed high-signal foci in the cortex and subcortical of left caudate nucleus, bilateral putamen, and bilateral occipital lobe in FLAIR. We also suspected RCVS on day three after operation because MR angiography showed multifocal vasoconstrictions toward bilateral anterior and middle cerebral arteries. On day seven after operation, the high-signal foci were reduced, and the multifocal vasoconstrictions were improved. On day 21 after operation, her general condition became better and left the hospital with though she complained of mild headache and defect of memory. [Adv Obstet Gynecol, 69 (3) : 269-276, 2017 (H29.8)]

The intrauterine contraceptive device (IUD) is the effective methods of reversible contraception. Recently, a levonorgestrel-releasing intrauterine system (LNG-IUS) for hypermenorrhea and dysmenorrhea has been included under insurance coverage. As users of IUDs increase, further attention should be paid to complication such as expulsion, missing strings, uterine perforation, and pelvic infection. The patient was a 41 years old woman, gravida 3 para 3, who received a copper coated IUD three months after vaginal delivery two years earlier. She presented for annual gynecological check-up, and the IUD could not be detected in uterine cavity on ultrasonography. The patient was referred to our hospital to confirm the missing IUD. Plain radiography revealed that the IUD had entered the peritoneal cavity. After the localization of the displaced IUD near the sigmoid colon by using computed tomography, we performed the endoscopic inspection of colon to ensure that the colon had no injury. The IUD was successfully removed with laparoscopic surgery regardless of firm adhesion to omentum. To prevent complications of IUD insertion, it is important to evaluate the risks of each patient, to consider the best timing of insertion, to check the patients regularly after insertion, and to make the correct diagnosis of missing IUD. [Adv Obstet Gynecol, 69 (3) : 277-281, 2017 (H29.8)]

Muscular dystrophy is a hereditary disease that causes progressive weakness, mainly by degeneration and necrosis of the muscle fibers. We experienced the perinatal management of two different types of dystrophy; myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD). The patient with DM presented with polyhydramnios. An emergent Cesarean section was performed at 34 weeks and two days of gestation due to non-reassuring fetal status. The newborn had respiratory and hemodynamic difficulties and died on the 123rd day after birth. The patient with FSHD showed fetal growth restriction and oligohydramnios. Labor onset developed at 39 weeks and one day of gestation, but an emergent Caesarean section was performed due to arrest of labor. Although it has not yet been confirmed whether the newborn carries genes for FSHD, he was discharged from our hospital in a good state. In the perinatal management of these two cases, both needed tocolytic therapy for threatened preterm labor. We chose isoxsuprine hydrochloride for tocolytic therapy to lower the risk of rhabdomyolysis, which is a known side effect of ritodrine hydrochloride. We described the perinatal management of two pregnancies complicated by muscular dystrophy without severe exacerbation of the primary disease.[Adv Obstet Gynecol, 69 (3) : 282-287, 2017 (H29.8)]

Idiopathic thrombocytopenic purpura (ITP) is prevalent in young women, occurring in 0.3 to 0.4% of pregnant women. We a case of intractable ITP in pregnancy that was not cured by corticosteroid therapy or intravenous immunoglobulin, but was cured with difficulty, using thrombopoietin receptor agonist (TPO-RA) . The patient was a 30-year-old woman (gravida 0), who was admitted with thrombocytopenia (platelet count of 75000 /μl) after previously visiting a doctor for infertility treatment . It was suspected that autoimmune disease was the cause. She visited our hospital six months later, in her eighth week of pregnancy, and was admitted with thrombocytopenia (platelet count of 53000 /μl). The thrombocytopenia progressed gradually and her illness was diagnosed by bone marrow puncture as ITP. The thrombocytopenia was not cured by corticosteroid therapy or intravenous immunoglobulin, therefore we administered a thrombopoietin receptor agonist, as well as platelet transfusions over several days. The patient had a cesarean section at 36 weeks five days of gestation when the platelet count increased to 63000 /μl). The platelet count promptly rose after the operation. In this case, it was difficult to cure the ITP and a thrombopoietin receptor agonist was used. It is important to make a thorough treatment plan, cognizant of the delivery date, and considering the effect of each treatment on intractable ITP. [Adv Obstet Gynecol, 69 (3) : 288-292, 2017 (H29.8)]

Malignant transformation of a mature cystic teratoma of the ovary is uncommon, and transformation to adenocarcinoma is especially rare. The current authors encountered a case of an ovarian mature cystic teratoma with spontaneous rupture, which was suspect of malignant transformation to adenocarcinoma. This case involved a 46-year-old woman, gravida 0, who was seen at a clinic for epigastric pain, a stomachache, a fever, and diarrhea. The woman was diagnosed with acute enterocolitis and she was given medication, but her condition failed to improve. Two days later, the woman was seen by internal medicine at a general hospital. Rupture of an ovarian tumor was suspected, and the women was referred to this department in the same day. A computed tomography (CT) scan revealed a multilocular cystic mass 8 cm in diameter with a solid component located in the lower abdomen and ascites around the liver. The patient was diagnosed with spontaneous rupture of an ovarian mature cystic teratoma, and she underwent laparoscopic right salpingo-oophorectomy. After surgery, histopathology indicated that the solid component was an admixture of endometrioid and clear cell adenocarcinoma, and the patient was diagnosed with suspicious of malignant transformation to adenocarcinoma of ovarian mature cystic teratoma. The patient underwent a staging laparotomy, and ovarian cancer was FIGO stage IC2 (pT1c, N0, M0). The patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, and the cancer had not recurred two years postoperatively. [Adv Obstet Gynecol, 69 (3) : 293-299 , 2017 (H29.8)]

The patient was a 28-year-old nulliparous woman who had no past or family medical history. She had a regular prenatal checkup from five weeks gestation and had a vaginal delivery at 35 weeks. There was no postpartum problem and she was discharged on postpartum day six. No abnormality was found in random blood glucose level, glucose urine test during pregnancy, blood glucose level immediately before delivery, and glucose urine test on postpartum day four. On postpartum day 23, she had flu-like symptoms and lower abdominal pain. The next day she felt worse and was aware of tachypnea, and thus she was referred to our hospital. At the time of admission, laboratory results were blood glucose 549 mg/dl, arterial blood gas pH 6.955, HCO₃^- 1.5 mmol/l and base excess -31.8 mmol/l. Remarkable metabolic acidosis was observed and diagnosed as diabetic ketoacidosis. Blood glucose level was normalized by administration of insulin and transfusion. Blood and urinary C-peptides were low and islet-related autoantibodies were negative. Although the patient was considered to have fulminant type 1 diabetes from the onset pattern, HbA1c was 9.2% (NGSP value), which did not meet the diagnostic criteria for fulminant type 1 diabetes. Her HLA typing and rapid beta cell destruction were consistent with the clinical course associated with pregnancy related fulminant type 1 diabetes, but only the HbA1c did not meet the diagnostic criteria. This case is important because it increases our understanding of the pathology of fulminant type 1 diabetes and pregnancy related fulminant type 1 diabetes. [Adv Obstet Gynecol, 69 (3) : 300-305, 2017 (H29.8)]