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The actual status of fertility preservation treatments in the startup phase in Japan was investigated as a basis for discussing future directions.This study was conducted as "Research project to promote support of children and parenting 2016" which was supported by Ministry of Health in Japan with the approval of the institutional review board at St. Marianna University. Subjects of the survey were facilities registered with the Japan Society of Obstetrics and Gynecology as fertility preservation facilities, and facilities belonging to the Japan Association of Private Assisted Reproductive Technology Clinics and Laboratories. We provided questionnaires to survey both the medical care system and cases for which fertility preservation was implemented between 2006 and 2016.Responses were obtained from 68 facilities (of the 64, 59 [92.2%] responded to the questionnaire and 9 clinics cooperated). Many facilities limited the cryopreservation of oocytes and ovaries to patients 40-41 years old and the use of eggs to patients 44-45 years old. In the patient survey, 812 cases of oocyte cryopreservation and 201 cases of ovarian tissue cryopreservation were performed during study period. Breast cancer was the most indicated disease, with oocyte cryopreservation in the late 30s and ovarian tissue cryopreservation in the early 30s. Very few babies were born from fertility preservation, and no live birth cases of ovarian tissue cryopreservation were identified.Even from the early days, fertility preservation was implemented according to certain standards in Japan, but was characterized by a large variety of facilities.

It has been shown that biotin, a water-soluble vitamin (B7), plays roles in reproductive functions, such as oocyte maturation and embryo development, in experimental animals. On the other hand, little is known about the clinical effects of biotin on human reproduction. In this study, serum and follicular fluid biotin levels were measured in patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), and their associations with reproductive outcomes were evaluated. As a result, biotin was detected in follicular fluid, as well as serum, and the biotin levels of follicular fluid were found to be positively correlated with those of serum. The biotin levels of serum were higher than those of follicular fluid, suggesting that biotin may be taken up into the follicular fluid from the blood. Although serum and follicular fluid biotin levels tended to be higher in pregnant patients than in non-pregnant patients, these data did not show the significant statistical difference. These findings indicate that biotin does not contribute to the maintenance of oocyte quality, and hence, it does not increase fertilization and pregnancy rates. J. Med. Invest. 69 : 65-69, February, 2022.

Taxanes are important chemotherapeutic agents used to manage breast cancer and gynaecological malignancies. However, ovarian toxicity induced by the taxane docetaxel (DOC) is of great concern. We investigated DOC-induced toxicity in the ovaries of female CD1 strain mice. The mice were divided into control (saline), DOC-5 (5 mg/kg DOC), and DOC-10 (10 mg/kg DOC) groups and administered saline or DOC on the first day of the study and two weeks later. Two weeks after the second dose, the ovaries were removed for analysis after inducing superovulation. Ovary weight, the number of secondary follicles, and the total number of follicles were reduced after DOC administration. Additionally, the expression levels of caspase-3 and the pro-apoptotic protein Bcl-2 interacting mediator of cell death (BIM) increased. Our findings suggest that high-dose DOC induces damage to growing follicles; however, it may not affect primordial follicles.Impact statement

In Japan, outcome measures for maternal and child health measures such as maternal, perinatal, and infant mortality have consistently shown a trend toward improvement. On the other hand, the problems of the declining birth rate, child abuse, and domestic violence have become evident since the 1990s. In terms of Japan's maternal and child health, it is necessary to take measures to preserve mental health of mothers and children, and also to respond to family issues such as abuse and violence. The services needed such as comprehensive support centers for families with children and new postpartum care programs have been established. It is necessary to further improve the competence of doctors, public health nurses, and midwives working in the maternal and child health field and to promptly construct a cooperation system in the community. J. Med. Invest. 69 : 159-164, August, 2022.

Many transgender men receive testosterone therapy to achieve virilization. The therapy is often mistaken for having a contraceptive effect because it causes amenorrhea. However, some treated patients become pregnant, which is not well known. A 25-year-old transgender man who had received testosterone for 3 years had an unplanned pregnancy during discontinuation of treatment. He was unaware of his pregnancy, resumed testosterone, and continued treatment until pregnancy was confirmed. His female child was exposed to androgens during the fetal period; thus, careful, long-term observation was required. He developed insomnia and depression during the postpartum, and giving birth made it difficult for him to change his family register to male. Transgender men can become pregnant through sexual intercourse with biological men, even during hormone replacement therapy, so correct contraception is necessary to avoid unwanted pregnancies. Transgender sex education is important to increase awareness of this issue among individuals and medical professionals.

The abnormal secretion of luteinizing hormone (LH) is one of the typical features of polycystic ovary syndrome (PCOS) and adopted in the diagnostic criteria of the Japan Society of Obstetrics and Gynecology (JSOG). We investigated cut-off values for LH and the LH/follicle-stimulating hormone (FSH) ratio in resent two measurement systems for the diagnosis of PCOS.Ninety-nine controls and 106 patients with PCOS were enrolled. Serum LH and FSH levels were measured using an electrochemiluminescence immunoassay (ARCHITECT) and chemiluminescence immunoassay (ECLusys). We examined the distribution of the measured levels, selected the conversion closest to the standard normal distribution in the control group, and calculated mean + 1 SD values for LH and the LH/FSH ratio as candidates. Cut-off values coincided with the medians of the candidates in the two assay systems using a regression equation. We calculated the endocrinological abnormality rate in PCOS according to the JSOG criteria by abnormal LH secretion and elevated T.Cut-off values for LH (mIU/mL) and the LH/FSH ratio were 7.1 and 1.21, respectively, in ARCHITECT, and 9.9 and 1.51, respectively, in ECLusys. The detection rates of endocrinological abnormalities in PCOS were 72.2% and 70.6% in the nonoverweight/obese PCOS group and overweight/obese PCOS group, respectively, in ARCHITECT, and 69.4% and 73.5%, respectively, in ECLusys.We obtained cut-off values of LH and the LH/FSH ratio for diagnostic criteria of JSOG criteria for PCOS, that were highly compatible between two major assay systems. These cut-off values will contribute to the diagnosis of PCOS in Japan and presumably in women of Asian ethnicities.

Imperforate anus (IA) requires urgent treatment after birth, which is dependent on the type of IA, and is also frequently associated with other congenital abnormalities. Most patients with IA have an accompanying fistula, whose location is strongly associated with the type of IA. The fistula location can be a key factor in defining appropriate treatment, especially in neonates presenting with severe associated abnormalities. Herein, we report three cases of IA in which fistulas were detected and localized prenatally. Examination of the fetal pelvis through the sagittal or coronal view, using high-frequency transducers, revealed the location of the fistulas. In particular, the sagittal view obtained using the fetal infracoccygeal or perineal approach allowed us to determine the precise anatomy of the fistulas. Neonatal assessment confirmed the fistula locations. We recommend using the sagittal view obtained using the fetal infracoccygeal or perineal approach with high-frequency transducers to assess fistulas in fetuses with IA.

Purpose We studied the influence of psychological stress during the early neonatal period on sexual maturation and sexual behavior in rats. Methods Neonatal male and female rats were divided into control (C) and maternal separation (MS) groups (n = 20‐24 per group). The pups in the MS groups were placed in isolation cages for 240 minutes/d from postnatal days 2‐11. Vaginal opening (VO) in females and preputial separation (PS) in males (indicators of sexual maturation) were monitored, as was the estrous cycle in females. Thereafter, sexual behavior was monitored twice at 13 and 15 weeks of age. Results As for sexual maturation, the onset of PS occurred significantly earlier in the MS group than in the C group, whereas the onset of VO did not differ between the groups. The length of the estrous cycle did not differ between the groups. The frequencies of sexual behaviors did not differ between the groups in either sex. Conclusions In conclusion, early‐life psychological stress induced by MS advanced sexual maturation in male rats, whereas it did not affect sexual maturation in female rats. On the other hand, early‐life psychological stress might not affect sexual behavior in adulthood in either sex.

Although endometrial cancer is extremely rare during pregnancy, the placental metastasis of endometrial cancer is even rarer. The current study presents a case of endometrial carcinoma that was diagnosed through the pathological examination of the placenta. A 35-year-old primipara woman who underwent frozen-thawed embryo transfer at the Keiai Ladies Clinic in Tokushima prefecture (Japan) received regular prenatal check-ups. She was transferred to Tokushima University Hospital for perinatal management due to the preterm premature rupture of membranes at 21 weeks and 6 days gestation. The administration of antibiotics and tocolytic agents was continued; however, labor pain occurred at 23 weeks and 3 days gestation, and a female fetus weighing 524 g was delivered vaginally. The placenta weighed 262 g and had no macroscopic abnormalities. It was submitted for pathological examination, which revealed metastatic adenocarcinoma (clear cell carcinoma suspected). The patient was subsequently diagnosed with endometrial cancer (stage I suspected), and underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and pelvic lymph node dissection. The final diagnosis was stage IA endometrial cancer (endometrioid carcinoma, G2). At 1 year after surgery, there was no evidence of disease. The present case highlights the importance of considering the emergence of endometrial cancer during pregnancy.

The metabolic effects of androgens and their underlying mechanisms in females have been revealed by recent studies. An excess of androgens can have adverse effects on feeding behavior and metabolic functions and induce metabolic disorders / diseases, such as obesity, insulin resistance, and diabetes, in women and experimental animals of reproductive age. Interestingly, these effects of androgens are not observed in ovariectomized animals, indicating that their effects might be dependent on the estrogen milieu. Central and peripheral mechanisms, such as alterations in the activity of hypothalamic factors, reductions in energy expenditure, skeletal muscle insulin resistance, and β-cell dysfunction, might be related to these androgens' effects. J. Med. Invest. 68 : 228-231, August, 2021.

Background Although animal models of PCOS have been used in many studies, none of them can reproduce both the reproductive and metabolic phenotypes of PCOS. In addition, behavioral parameters have not been evaluated in PCOS animal models. Purpose We tried to produce an improved rat model of PCOS, and the reproductive, metabolic, and behavioral phenotypes of the model rats were evaluated. Methods Female rats were implanted with silicon tubes containing oil‐dissolved dihydrotestosterone (Oil‐DHT) as a new PCOS model. Their phenotypes were compared with those of conventional PCOS model rats (DHT), into which tubes containing crystalline DHT were implanted, and non‐DHT‐treated rats (control). Results Both the Oil‐DHT and DHT rats showed greater body weight gain, food intake, and fat depot weight than the control rats. Furthermore, these groups showed fewer estrous stages and increased numbers of cystic follicles. The DHT rats exhibited lower ovarian and uterine weights than the control rats, whereas no such changes were observed in the Oil‐DHT rats. The Oil‐DHT and DHT rats showed less locomotor activity in the light phase than the control rats. Conclusions Our proposed PCOS model reproduced both the reproductive and metabolic phenotypes of PCOS and may have potential for PCOS research.

The Japan Society of Obstetrics and Gynecology Reproductive Endocrinology Committee summarizes the activities of each subcommittee below from April 2017 to March 2019. Current important issues regarding reproductive medicine were examined and discussed from social, political, ethical and scientific viewpoints. A nation-wide survey targeted at OB/GYN facilities revealed the usual procedure in diagnosis and management of fertility-desiring POI patients and fertility outcomes of the patients. How to introduce and adapt FIGO AUB systems to obstetric and gynecologic practices in Japan was examined and discussed.

STUDY QUESTION What were the risks with regard to the pregnancy outcomes of patients who conceived by frozen-thawed embryo transfer (FET) during a hormone replacement cycle (HRC-FET)? SUMMARY ANSWER The patients who conceived by HRC-FET had increased risks of hypertensive disorders of pregnancy (HDP) and placenta accreta and a reduced risk of gestational diabetes mellitus (GDM) in comparison to those who conceived by FET during a natural ovulatory cycle (NC-FET). WHAT IS KNOWN ALREADY Previous studies have shown that pregnancy and live-birth rates after HRC-FET and NC-FET are comparable. Little has been clarified regarding the association between endometrium preparation and other pregnancy outcomes. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of patients who conceived after HRC-FET and those who conceived after NC-FET was performed based on the Japanese assisted reproductive technology registry in 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS The pregnancy outcomes were compared between NC-FET (n = 29 760) and HRC-FET (n = 75 474) cycles. Multiple logistic regression analyses were performed to investigate the potential confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE The pregnancy rate (32.1% vs 36.1%) and the live birth rate among pregnancies (67.1% vs 71.9%) in HRC-FET cycles were significantly lower than those in NC-FET cycles. A multiple logistic regression analysis showed that pregnancies after HRC-FET had increased odds of HDPs [adjusted odds ratio, 1.43; 95% confidence interval (CI), 1.14–1.80] and placenta accreta (adjusted odds ratio, 6.91; 95% CI, 2.87–16.66) and decreased odds for GDM (adjusted odds ratio, 0.52; 95% CI, 0.40–0.68) in comparison to pregnancies after NC-FET. LIMITATIONS, REASONS FOR CAUTION Our study was retrospective in nature, and some cases were excluded due to missing data. The implication of bias and residual confounding factors such as body mass index, alcohol consumption, and smoking habits should be considered in other observational studies. WIDER IMPLICATIONS OF THE FINDINGS Pregnancies following HRC-FET are associated with higher risks of HDPs and placenta accreta and a lower risk of GDM. The association between the endometrium preparation method and obstetrical complication merits further attention. STUDY FUNDING/COMPETING INTEREST(S) No funding was obtained for this work. The authors declare no conflicts of interest in association with the present study. TRIAL REGISTRATION NUMBER Not applicable.

Polycystic ovary syndrome (PCOS) is commonly associated with metabolic disorders, which are exacerbated by obesity. Recent studies have revealed that oxytocin contributes to metabolic, appetite, and body weight regulation. In the present study, we evaluated the effects of chronic administration of oxytocin on body weight, food intake, and fat mass in a dihydrotestosterone-induced rat model of PCOS. Body weight, body weight change, and relative cumulative food intake were significantly lower in the oxytocin-treated PCOS rats than in the vehicle-treated control PCOS rats. Similarly, visceral adipocyte size was significantly smaller in the oxytocin-treated PCOS rats than in the vehicle-treated control PCOS rats. On the other hand, the numbers of cystic follicles in the ovary did not differ between the two groups. The chronic administration of oxytocin did not affect the rats' serum aspartate aminotransferase, alanine aminotransferase, or lactate dehydrogenase levels, indicating that it does not have adverse effects on hepatic function. These findings suggest that oxytocin could be a candidate drug for preventing the onset of obesity-related metabolic disorders in PCOS patients.

Recent studies have shown that oxytocin reduces food intake and body weight gain and promotes lipolysis in some species, including humans. Interestingly, these effects of oxytocin are more marked in obese individuals. Although the menopausal loss of ovarian function induces increased visceral adiposity and some metabolic disorders, no safe medical interventions for these conditions have been established. In this study, we evaluated the effects of oxytocin on appetite, body weight, and fat mass in ovariectomized rats. Six-day oxytocin treatment attenuated cumulative food intake and body weight gain, and reduced visceral and subcutaneous fat weight and adipocyte cell area in ovariectomized rats. Blood examinations indicated that 6-day oxytocin treatment did not alter renal or hepatic functions. Instead, it might prevent ovariectomy-induced liver damage. In addition, acute oxytocin treatment did not affect body temperature or locomotor activity. These results indicate that oxytocin might be useful for treating or preventing menopause-induced metabolic disorders, without causing any adverse effects.

Background Children born after intracytoplasmic sperm injection (ICSI) are at increased risk of specific major birth defects compared with children born after in vitro fertilization (IVF). However, whether this risk is due to the treatment itself (i.e., IVF or ICSI) or underlying male subfertility is unknown. This study investigated the associations between male subfertility and the risk of major birth defects in children born after IVF and ICSI. Methods We conducted a retrospective cohort study using data from the Japanese assisted reproductive technology registry between 2007 and 2014. Fresh embryo transfer cycles registered from 2007 to 2014 that resulted in singleton live births, still births, or selective terminations were included (n = 59,971). Major birth defects were defined by the US Centers for Disease Control and Prevention guidelines, excluding chromosomal abnormalities. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using generalized estimating equations adjusting for potential confounders. Results Major birth defects were reported in 626/59,971 (1.04%) cases. Among IVF cycles, male subfertility was associated with significantly greater risks of hypospadias (3/3163 [0.09%] vs 4/28,671 [0.01%], adjusted OR = 6.85, 95% CI 2.05–22.9, P = 0.002) and atrial septal defects (4/3163 [0.13%] vs 9/28,671 [0.03%], adjusted OR = 3.98, 95% CI 1.12–14.1, P = 0.03) compared with fertile men. Subgroup analysis using sperm parameters showed that oligozoospermia (i.e., sperm concentrations

Purpose : The aims of this study were to clarify the effects of lipopolysaccharide (LPS) on the early development of endometriosis and on the production of cytokines and chemokines in the murine peritoneal cavity. Methods : Endometriotic lesions were induced in C57BL/6J adult female mice by intraperitoneal injection of endometrial fragments plus blood or endometrial fragments plus blood with LPS. On day 7, endometriotic lesions were assessed by gross and microscopic evaluations. Time-dependent changes in the secretion of TNF-α, IL-6, and CXCL2/MIP-2 in peritoneal lavage fluid after the intraperitoneal injection of LPS (50 µg/body) were measured by their respective enzyme-linked immunosorbent assays. Results : The areas of endometriotic lesions in the LPS group (10.8±8.6 mm2) were significantly larger than those in the control group (3.1±3.7 mm2). The levels of TNF-α and IL-6 peaked within 2 hours and the level of MIP-2 reached a maximum on day 1 after the injection of LPS. Conclusions : LPS promotes development of the early stages of murine endometriotic lesions.

As the follicular environment transits from being activin dominant to inhibin dominant during folliculogenesis, it is assumed that activin plays an important role in the early stage of follicular growth. We examined the effects of activin on morphological, biochemical and molecular changes in isolated preantral follicles. Preantral follicles were mechanically isolated from 14-day old female C57BL/6 mice. Each follicle was cultured and observed for 14 days usingan in vitro follicle culture system containing FSH, FSH + activin A and FSH + inhibin in the culture medium. We subsequently examined FSH receptor (FSH-R) mRNA expression in isolated follicle cultures with or without activin on days 0 and 2. Activin was observed to significantly stimulate follicle enlargement on days 2, 4, 6 and 8, accelerate morphological changes and increase estradiollevels in culture medium on days 4, 12 and 14. In contrast, inhibin did not alter follicular growth. Additionally, activin stimulated the expression of FSH-R mRNA in isolated granulosa cells. It was demonstrated that activin stimulated the growth of preantral follicles, mainly during the early stage of folliculogenesis, by inducing FSH-R expression, in an isolated follicle culture system. J. Med. Invest. 66 : 165-171, February, 2019.

Objective : We aimed to demonstrate the effect of prolonged hospitalization on fetal growth in cases of threatened preterm labor (TPL). Methods : In this retrospective cohort study, we included women who received prenatal care for TPL but delivered their child after 36 weeks of gestation. These were compared with a control group of healthy pregnant women and fetuses delivered at term. Fetal growth was compared using biparietal diameter, abdominal circumference (AC), femur length, and estimated fetal weight (EFW) assessed using ultrasonography at 18, 26, 30, and 36 weeks of gestation. Neonatal parameters at birth were also compared. Results : In total, we enrolled 228 control women and 114 women with TPL who were treated with hospitalization, including bed rest. The AC at 30 and 36 weeks of gestation and EFW at 36 weeks of gestation were smaller in women treated with bed rest than for normal pregnant women. The mean duration of pregnancy was shorter in the hospitalization group than in the control group. Neonatal weight, length, head circumference, and chest circumference at birth were smaller after prolonged hospitalization for TPL than after normal pregnancy. Conclusion : Prolonged hospitalization for threatened preterm labor is associated with impaired fetal growth, particularly AC.

The purpose of this study was to compare digit lengths and proximal phalanx lengths in newborn infants by using ultrasonography (USG) and to examine sex differences between the ratio of the second digit (2D) and fourth digit (4D) of digit length and that of proximal phalanx length and the associations of digit length and proximal phalanx length with birth weight and birth height. Sixty newborn infants (28 males and 32 females) were recruited. Digit lengths were measured by using a transparent ruler and proximal phalanx lengths were measured by using USG. There were significant correlations between digit length and proximal phalanx length in the left and right hands. There was no significant correlation between 2D:4D ratios of digit lengths and 2D:4D ratios of proximal phalanx lengths measured by using USG. In males, birth height was significantly associated with right fourth proximal phalanx length and with left second and fourth proximal phalanx lengths. Birth weight was significantly associated with proximal phalanx length in males. Proximal phalanx length measured by using USG was significantly associated with digit length in newborn infants. Hormonal exposure before birth may be involved in the associations of proximal phalanx length with birth weight and height in males.Impact statement

Recent studies have revealed that the administration of oxytocin has beneficial effects on the regulation of body weight, food intake, and metabolic functions, especially in obese individuals. Obesity is common in women after the menopause and drives many components of metabolic syndrome. Weight gain in menopausal women has been frequently reported. Although obesity and associated metabolic disorders are frequently observed in peri- and postmenopausal women, there are few medical interventions for these conditions. In this study, we evaluated the effects of chronic oxytocin administration on appetite, body weight, and fat mass in peri- and postmenopausal female rats. Sixteen naturally premenopausal or menopausal rats were intraperitoneally injected with oxytocin (1,000 μg/day) for 12 days. The daily changes in their body weight and food intake were measured at the same time as the oxytocin and vehicle injections. Intraperitoneally administering oxytocin for 12 days significantly reduced food intake, body weight, and visceral adipocyte size. In addition, oxytocin administration caused reductions in serum triglyceride and low-density lipoprotein-cholesterol levels, while it did not disturb hepatic or renal functions or locomotor activity. This is the first study to show the effects of oxytocin on the metabolic and feeding functions of peri- and postmenopausal female rats. Oxytocin might be a useful treatment for metabolic disorders caused by the menopause or aging.

Infectious, psychological and metabolic stresses in the prenatal and early neonatal period induce long-lasting effects in physiological function and increase the risk of metabolic disorders later in life. We examined the sexual behavior of female rats that were subjected to undernutrition in the prenatal period. Eight pregnant rats were divided into two groups: a maternal normal nutrition group (mNN; n = 4) and a maternal undernutrition group (mUN; n = 4), which received 50% of the daily food intake amount of the mNN group from gestation day 13 to delivery. Nine and seven female offspring were randomly selected from the mNN and mUN groups, respectively. Vaginal opening (VO), estrous cycle length, sexual behavior and mRNA expression levels of the factors that regulate sexual behavior were observed. In the mUN group, VO day was later, the estrous cycle was longer, and the lordosis quotient and lordosis rating were lower than in the mNN group; such differences were not seen in other sexual performances, such as ear wiggles, darts, kick bouts and box. The hypothalamic mRNA expression level of progesterone receptor (PR) A + B and oxytocin (OT) were significantly lower in the mUN group than in the mNN group. These findings indicated that prenatal undernutrition disrupted puberty onset, the estrous cycle, sexual behavior and hypothalamic mRNA expression of PR and OT in female rat pups.

Although polycystic ovary syndrome (PCOS) is among the most common endocrine disorders in women of reproductive age, its etiology remains poorly understood. From the perspective of developmental origins of health and disease, some studies have investigated the relationship between low birth weight and the prevalence of PCOS and/or PCOS phenotypes in humans; however, the results of these studies were inconclusive. Here, we evaluated the effects of prenatal undernutrition on the metabolic and reproductive phenotypes of dihydrotestosterone-induced PCOS model rats. The PCOS model rats showed increased body weight, food intake, fat weight, adipocyte size and upregulation of inflammatory cytokines in adipose tissue; prenatal undernutrition exacerbated these metabolic changes. Prenatal undernutrition also increased the gene expression of hypothalamic orexigenic factor and decreased the gene expression of anorexigenic factor in the PCOS model rats. In addition, the PCOS model rats exhibited irregular cyclicity, polycystic ovaries and disrupted gene expression of ovarian steroidogenic enzymes. Interestingly, prenatal undernutrition attenuated these reproductive changes in the PCOS model rats. Our results suggest that in dihydrotestosterone-induced PCOS model rats, prenatal undernutrition exacerbates the metabolic phenotypes, whereas it improves the reproductive phenotypes and that such phenotypic changes may be induced by the alteration of some peripheral and central factors.

The Japan Society of Reproductive Medicine (JSRM) issued the guideline for cryopreservation of unfertilized eggs and ovarian tissue in 2013. The Japan Society of Obstetrics and Gynecology also announced the society opinions concerning cryopreservation of unfertilized/fertilized eggs and ovarian tissue in 2016, independently. To integrate these statements and to reflect the development of current therapeutic modalities in Japan, ethics committee of JSRM revised the guideline for cryopreservation of unfertilized eggs and ovarian tissues. First, considering that medical interventions for the treatment of malignancies might cause iatrogenic ovarian dysfunction, medical indication for cryopreservation of unfertilized eggs and ovarian tissues was specified. Second, the guideline of cryopreservation of unfertilized eggs and ovarian tissues for women that do not apparently possess malignancies and hope to preserve probable future fecundity was also described. Furthermore, requirements to be obeyed by facilities of reproductive medicine were raised to avoid the easy execution of these treatments. We hope that this new guideline could help the specialists of reproductive medicine in their daily practice and also would be helpful for women that definitely desire to preserve future fecundity.

Objective To compare physical and cognitive development of babies born after round spermatid injection (ROSI) with those born after natural conception. Design Comparison of efficiencies of ROSI and ICSI using testicular spermatozoa, performed in the St. Mother Clinic. Physical and cognitive development of ROSI babies recorded by parents in the government-issued Mother-Child Handbook was checked and verified by attending pediatricians. Data included baby's weight gain and response to parents' voice/gesture. Setting Assisted reproduction technology practice. Patient(s) A total of 721 men participated in ROSI; 90 ROSI babies were followed for 2 years for their physical and cognitive development. Control subjects were 1,818 naturally born babies. Intervention(s) Surgical retrieval of spermatogenic cells from testes; selection and injection of round spermatids into oocytes; oocyte activation, in vitro culture of fertilized eggs, and embryo transfer to mothers. Main Outcome Measure(s) Physical and cognitive development of ROSI babies (e.g., body weight increase, response to parents, and understanding and speaking simple language) compared with naturally born babies. Result(s) Of 90 ROSI babies, three had congenital aberrations at birth, which corrected spontaneously (ventricular septa) or after surgery (cleft lip and omphalocele). Physical and cognitive development of ROSI babies was similar to those of naturally born babies. Conclusion(s) There were no significant differences between ROSI and naturally conceived babies in either physical or cognitive development during the first 2 years after birth. Clinical Trial Registration Number UMIN Clinical Trials Registry UMIN000006117.

Case Approximately 3%‐25% of cases of endometrial carcinoma (EC) or atypical endometrial hyperplasia (AH) occur in women aged

Purpose To evaluate the optimized protocol of low dose follicle‐stimulating hormone (FSH) therapy that has a starting dose of 50 IU/62.5 IU with a small increment dose (12.5 IU) for women with World Health Organization (WHO) II ovulatory disorder and unexplained infertility. Methods Anovulatory women with WHO group II ovulatory disorder (ovulation induction [OI] patients, n = 29), and with an unexplained infertility (ovarian stimulation [OS] patients, n = 21) were enrolled. The protocol of low dose step‐up FSH therapy was optimized for the starting dose as 50 IU (body mass index [BMI]

Aim: We aimed to evaluate the effect of prolonged hospitalization for threatened preterm labor on maternal and fetal vitamin D status. Methods: This was a retrospective cohort study, spanning 4 years, including 18 women with threatened preterm labor and 36 women with normal pregnancy, who received prenatal care for a singleton pregnancy at our center. Threatened preterm labor cases were women who were admitted to our hospital after the second trimester test, for at least 28 days, during which, the third trimester test was also performed. Controls were randomly sampled from women matched for age as well as the season during which the third trimester test was performed. Serum 25-hydroxyvitamin D concentration in maternal blood was compared between the two groups at second trimester, third trimester and in the umbilical cord blood at delivery. Results: The mean±SD of maternal serum 25-hydroxyvitamin D concentration in the threatened preterm labor group (14.0±3.0 ng/mL) was significantly lower than that in the control group (17.8±5.9 ng/mL) (p

AIM We conducted a self-administered survey on the perception of teachers toward human papillomavirus (HPV) vaccine to determine the ways to increase their willingness to encourage its use. METHODS Answers were obtained both prior to and after having the teachers read five brief information articles: (i) cervical cancer knowledge, (ii) vaccine knowledge, (iii) result of a survey in Nagoya, (iv) news report of the World Health Organization statement and (v) articles written by Dr Muranaka, a journalist. RESULTS Most of the respondents (180/247) did not know about the natural history of cervical cancer. Only 36% knew that HPV is the cause of cervical cancer, although 63% knew that HPV vaccine would prevent cervical cancer. Few respondents had knowledge regarding adverse events following immunization and the survey results from Nagoya. Among those who were initially negative for the HPV vaccine, only 43% revealed that they fully understood its safety and only 29% reversed their opinion to recommend vaccination to their daughters and/or students, even after reading our informational material. The most useful information for changing their attitudes was to increase their understanding of vaccines and informing them about Nagoya city survey results. They mostly wanted a proof of the preventive effects of the vaccine on cervical cancer in Japan. CONCLUSION Gynecologists and pediatricians must proactively communicate accurate scientific information to the government and the media to spread awareness among people in Japan. Also, we must try to demonstrate the capabilities of this vaccine to prevent cervical cancer and/or its precancerous lesions.

The objective of this study was to identify pathological indicators that could be used to identify a subgroup of patients with apparent stage I endometrial cancer who do require retroperitoneal lymphadenectomy. 188 T1 endometrial cancer patients underwent primary surgery at Tokushima University Hospital. We retrospectively evaluated their clinical records and histopathological factors. Systematic lymphadenectomy was performed for 149 patients, and 39 patients (grade 1 with < 5 mm of myometrial invasion) were treated without lymphadenectomy. Lymph node metastases were found in 19 (12.8%) of the lymphadenectomy cases. Twenty-four patients with a T1a endometrium-limited lesion did not exhibit lymph node metastasis. Three (3.1%) of the 95 patients with a T1a lesion exhibited lymph node metastasis, and these 3 cases exhibited approximately 50% myometrial invasion. The 39 low-risk patients who did not undergo systematic lymphadenectomy remain alive without recurrence. Systematic lymphadenectomy could be omitted for patients with a grade 1 tumor and minor myometrial invasion of less than 5mm. J. Med. Invest. 65:221-224, August, 2018.

Several kinds of stress suppress the hypothalamic-pituitary-gonadal (HPG) axis and reproductive behavior in humans and animals. These changes can eventually cause diseases and disorders, such as amenorrhea and infertility. In previous studies, it has been shown that stress-related factors, e.g., corticotropin-releasing hormone, cortisol, and pro-inflammatory cytokines, promote the stress-induced suppression of the HPG axis. However, these mechanisms are not sufficient to explain how stress suppresses HPG axis activity, and it has been suggested that some other factors might also be involved. In the early 21st century, novel neuroendocrine peptides, kisspeptin and gonadotropin inhibitory hormone (GnIH)/RFamide-related peptide 3 (RFRP-3), which directly regulate GnRH/gonadotropin synthesis and secretion, were newly discovered. Growing evidence indicates that kisspeptin and GnIH/RFRP-3 play pivotal roles in the stress-induced disruption of the HPG axis and reproductive behavior in addition to their physiological functions. This review summarizes what is currently known about the roles of kisspeptin and GnIH/RFRP-3 in stress-induced reproductive disorders.

Oxytocin (OT) and its receptor (OTR) play various roles in the central and peripheral regulation of appetite and body weight. Previously, we have shown that the administration of OT markedly decreased appetite and body weight gain in ovariectomized (OVX) obese rats. In addition, recent studies have shown that the endogenous OT system is also affected by endogenous or exogenous estrogen. In this study, we showed that ovariectomy decreased rats' hypothalamic OT/OTR mRNA and serum OT levels, but did not affect their visceral fat OTR mRNA levels. The chronic administration of estradiol (E2) abrogated these ovariectomy-induced changes; i.e., it increased the rats' hypothalamic OT/OTR mRNA and serum OT levels, and may be associated with reductions in food intake and body weight gain. In addition, acute E2 administration increased the rats' hypothalamic OTR mRNA and serum OT levels, but did not affect their hypothalamic OT mRNA levels. Taken together, these results suggest that endogenous OT and/or OTR expression might be positively regulated by E2 and that the suppressive effects of E2 on appetite and body weight gain might be mediated, at least in part, by the OT system. Thus, we consider that OT might be a target hormone to pursue subsequent interventions of menopause for menopause-induced metabolic disorders.