Forced lipophagy reveals that lipid droplets are required for early embryonic development in mouse.

Although autophagy is classically viewed as a non-selective degradation system, recent studies have revealed that various forms of selective autophagy also play crucial physiological roles. However, the induction of selective autophagy is not well understood. In this study, we established a forced selective autophagy system using a fusion of an autophagy adaptor and a substrate-binding protein. In both mammalian cells and fertilized mouse embryos, efficient forced lipophagy was induced by expression of a fusion of p62 (Sqstm1) and a lipid droplet (LD)-binding domain. In mouse embryos, induction of forced lipophagy caused a reduction in LD size and number, and decreased the triglyceride level throughout embryonic development, resulting in developmental retardation. Furthermore, lipophagy-induced embryos could eliminate excess LDs and were tolerant of lipotoxicity. Thus, by inducing forced lipophagy, expression of the p62 fusion protein generated LD-depleted cells, revealing an unexpected role of LD during preimplantation development.

Low Birth Weight and Prematurity Are Associated with Hypertensive Disorder of Pregnancy in Later Life: A Cross-Sectional Study in Japan.

OBJECTIVE: We previously reported that hypertensive disorder of pregnancy (HDP) was a risk factor for hypertension and hypercholesterolemia in later life. Additionally, the age-adjusted odds ratio (OR) of HDP was 2.72 for Japanese women whose mothers had a history of HDP versus those whose mothers did not. This study aimed to clarify the association of HDP with birth weight and gestational age. STUDY DESIGN: A self-administered baseline survey of the Japanese Nurses' Health Study (JNHS) cohort was conducted from 2001 to 2007. Data on 17,278 parous female nurses who knew their own birth weights were extracted from the JNHS baseline survey (n = 49,927) and subjected to cross-sectional, retrospective analysis. Data on weeks of gestation, birth weight, and history of HDP were collected. RESULTS: The age-adjusted ORs for HDP were 1.62 (95% confidence interval [CI]: 1.20-2.19) for birth weight <2,000 g, 1.24 (CI: 1.04-1.48) for 2,000 to 2,499 g, 1.11 (CI: 1.00-1.23) for 2,500 to 2,999 g, and 1.08 (CI: 0.94-1.24) for ≥3,500 g compared with 3,000 to 3,499 g. The age-adjusted ORs for HDP were 1.27 (95% CI: 1.04-1.54) for a gestational age < 37 weeks and 0.93 (0.70-1.23) for ≥42 weeks compared with 37-41 weeks. The age-adjusted OR of the birth weight score for HDP in later life was 0.98 (CI: 0.94-1.03; Cochran-Armitage trend test: z = 0.401, p = 0.688). CONCLUSION: Among women in Japan, a history of low birth weight and prematurity are risk factors for HDP in later life. The risk of HDP among women born with low birth weight and/or premature deserves attention.

Complementary Critical Functions of Zfy1 and Zfy2 in Mouse Spermatogenesis and Reproduction.

The mammalian Y chromosome plays a critical role in spermatogenesis. However, the exact functions of each gene in the Y chromosome have not been completely elucidated, partly owing to difficulties in gene targeting analysis of the Y chromosome. Zfy was first proposed to be a sex determination factor, but its function in spermatogenesis has been recently elucidated. Nevertheless, Zfy gene targeting analysis has not been performed thus far. Here, we adopted the highly efficient CRISPR/Cas9 system to generate individual Zfy1 or Zfy2 knockout (KO) mice and Zfy1 and Zfy2 double knockout (Zfy1/2-DKO) mice. While individual Zfy1 or Zfy2-KO mice did not show any significant phenotypic alterations in fertility, Zfy1/2-DKO mice were infertile and displayed abnormal sperm morphology, fertilization failure, and early embryonic development failure. Mass spectrometric screening, followed by confirmation with western blot analysis, showed that PLCZ1, PLCD4, PRSS21, and HTT protein expression were significantly deceased in spermatozoa of Zfy1/2-DKO mice compared with those of wild-type mice. These results are consistent with the phenotypic changes seen in the double-mutant mice. Collectively, our strategy and findings revealed that Zfy1 and Zfy2 have redundant functions in spermatogenesis, facilitating a better understanding of fertilization failure and early embryonic development failure.

Uterine leiomyomata: a retrospective study of correlations with hypertension and diabetes mellitus from the Japan Nurses' Health Study.

We performed a scrutiny survey of self-reported uterine leiomyomata (UL) to investigate the associations of parental history with hypertension and personal history of hypertension in the UL cases in Japanese women. Questionnaires that included items on the sites of UL determined by imaging techniques and surgical procedure were mailed to 2015 women with a self-reported UL at a baseline survey of the Japan Nurses' Health Study (n = 15,019). We found that women with a past history and a maternal history of hypertension had an increase in their risk of UL. A maternal history of hypertension was significantly associated with an increase in the risk of UL in women without a past history of hypertension but not in the women with a past history of hypertension. A past history and a parental history of diabetes mellitus were not associated with an increase in the risk of UL. Women of reproductive age with a maternal history of hypertension may be at a higher risk for hypertension and UL. Impact Statement What is already known on this subject? A positive association of uterine leiomyomata (UL) with a past history of hypertension has been found but the association of a parental history of hypertension with UL has not yet been clarified. What do the results of this study add? Maternal hypertension, as well as a personal history of hypertension, was associated with an increased risk of UL and a past history and a parental history of diabetes mellitus were not associated with an increase in the risk of UL. What are the implications of these findings for clinical practice and/or further research? Women of a reproductive age with a maternal history of hypertension may be at a higher risk for hypertension and UL.

Advanced paternal age alone does not adversely affect pregnancy or live-birth rates or sperm parameters following intrauterine insemination.

PURPOSE: This study aimed to evaluate the effect of advanced paternal age on pregnancy outcomes and sperm parameters following intrauterine insemination (IUI). We used IUI data rather than assisted reproductive technology data, which might mask the effects of sperm impairments. METHODS: We retrospectively analyzed 1576 IUI cycles in women under 40 years old between April 2012 and May 2016 at the National Center for Child Health and Development in Japan. The main outcomes were clinical pregnancy and live birth. RESULTS: The mean male age was significantly lower in cycles that resulted in pregnancy compared with those without pregnancy (38.0 vs 39.1 years; P < 0.001), with a similar trend for live-birth cycles. However, there was no relationship between advanced paternal age and pregnancy outcomes after adjusting for confounding factors and correlations within patients using generalized estimating equations, and the age of the female partner was the only factor affecting pregnancy rate. Furthermore, advanced paternal age had no effect on sperm parameters. CONCLUSIONS: Advanced paternal age alone does not adversely affect pregnancy or live-birth rates or sperm parameters following IUI.

ArbAlign: A Tool for Optimal Alignment of Arbitrarily Ordered Isomers Using the Kuhn-Munkres Algorithm.

When assessing the similarity between two isomers whose atoms are ordered identically, one typically translates and rotates their Cartesian coordinates for best alignment and computes the pairwise root-mean-square distance (RMSD). However, if the atoms are ordered differently or the molecular axes are switched, it is necessary to find the best ordering of the atoms and check for optimal axes before calculating a meaningful pairwise RMSD. The factorial scaling of finding the best ordering by looking at all permutations is too expensive for any system with more than ten atoms. We report use of the Kuhn-Munkres matching algorithm to reduce the cost of finding the best ordering from factorial to polynomial scaling. That allows the application of this scheme to any arbitrary system efficiently. Its performance is demonstrated for a range of molecular clusters as well as rigid systems. The largely standalone tool is freely available for download and distribution under the GNU General Public License v3.0 (GNU_GPL_v3) agreement. An online implementation is also provided via a web server ( http://www.arbalign.org ) for convenient use.

Increased incidence of post-term delivery and Cesarean section after frozen-thawed embryo transfer during a hormone replacement cycle.

PURPOSE: This study aimed to clarify the risks of adverse pregnancy outcomes in patients who conceive singletons after frozen embryo transfer (FET) during a hormone replacement cycle and their offspring. METHODS: A retrospective cohort study was conducted in patients who conceived after FET, based on the Japanese-assisted reproductive technology registry for 2013. The perinatal outcomes in cases with live-born singletons achieved through natural ovulatory cycle FET (NC-FET) (n = 6287) or hormone replacement cycle FET (HRC-FET) (n = 10,235) were compared. Multiple logistic regression analyses were performed to determine the potential confounding factors. RESULTS: The frequencies of macrosomia (1.1% in NC-FET and 1.4% in HRC-FET; P = 0.058) were comparable between patients after NC-FET and HRC-FET. The proportions of post-term delivery (0.2% in NC-FET and 1.3% in HRC-FET; P < 0.001) and Cesarean section (33.6% in NC-FET and 43.0% in HRC-FET; P < 0.001) were higher in patients after HRC-FET than in patients after NC-FET. The risks of post-term delivery (adjusted odds ratio (AOR) 5.68, 95% confidence interval (CI) 3.30-9.80) and Cesarean section (AOR 1.64, 95% CI 1.52-1.76) were also higher in patients after HRC-FET than in patients after NC-FET. CONCLUSIONS: Patients who conceived singletons after HRC-FET were at increased risk of post-term delivery and Cesarean section compared with those who conceived after NC-FET.

SLUG expression is an indicator of tumour recurrence in high-grade endometrial carcinomas.

AIMS: To investigate how SNAIL and SLUG were involved in the nature of high-grade endometrial carcinomas (grade 3 endometrioid carcinoma, serous carcinoma and clear cell carcinoma), we analysed the correlation of their expression status with clinicopathological characteristics and evaluated their prognostic significance. METHODS AND RESULTS: We performed immunohistochemical staining in 52 high-grade endometrial carcinomas. Expression status of SNAIL and SLUG was classified into a high expression (positive in more than 50% of the tumour cells) and a low expression. Thirteen cases (25%) showed a high expression of SLUG, whereas all 52 cases showed a low expression of SNAIL. High expression of SLUG was correlated significantly with tumour recurrence (P = 0.0203) and aberrant p53 expression (P = 0.000559). Overall survival was worse in patients with high SLUG expression at all stages (P = 0.0327) and in those who underwent adjuvant therapy (P = 0.00963). Among the patients with complete tumour resection, high SLUG expression was associated with worse recurrence-free survival (RFS) in the patients at all stages (P = 0.00264), at stages III/IV (P = 0.0146), and who underwent adjuvant therapy (P = 0.000743). SLUG expression was identified as an independent factor of RFS by multivariate analysis (hazard ratio 5.938, 95% confidence interval 1.251-28.18, P = 0.025). CONCLUSIONS: SLUG expression could be correlated with TP53 mutational status and could be involved in therapeutic resistance resulting in tumour recurrence. A high expression level of SLUG can be an indicator of recurrence and a therapeutic target for long-term remission in high-grade endometrial carcinomas.

Obstetrical management of patients with extra-anatomic vascular bypass grafts due to Takayasu arteritis.

Little is known about the obstetrical management of patients with Takayasu arteritis (TA) who have undergone extra-anatomic vascular bypass (EAVB). We describe two cases of EAVB. Case 1 underwent EAVB due to renovascular hypertension associated with stenosis of the abdominal aorta, and Case 2 due to amaurosis fugax episodes associated with stenosis of the brachiocephalic and left common carotid arteries. Pregnancy outcomes were favorable for both cases, though the original symptoms recurred during the third trimester in each case, possibly due to increased blood flow to the pregnant uterus. Neither bypass occlusion nor anastomotic aneurysm formation was observed. Pregnancy outcomes of patients with EAVB due to TA are favorable, although pregnancies of patients with TA who have cardiovascular complications are associated with an increased risk of maternal and fetal morbidity. The obstetrical management of these patients, however, should include monitoring for complications related to the EAVB.

Vanishing intravenous leiomyomatosis after hysterectomy: Assessment of the need to perform complete resection.

Intravenous leiomyomatosis (IVL) is a rare smooth muscle tumor that may extend into extrauterine veins. A high IVL recurrence rate has been reported after hysterectomy. A 44-year-old woman underwent total hysterectomy as a result of uterine leiomyoma, and IVL within the left uterine vein was incidentally found during the surgery. A residual tumor within the right ovarian vein was detected on contrast-enhanced computed tomography (CT) two days postoperatively. The tumor was diagnosed as IVL because it showed contrast enhancement on preoperative magnetic resonance imaging by retrospective re-interpretation. However, the tumor completely disappeared on contrast-enhanced CT without any medical treatment five months postoperatively. This is the first report of spontaneous regression of IVL. Postsurgical imaging was important to determine the residual extrauterine extension of IVL when it was incidentally found during gynecologic surgery. A hysterectomy alone may be adequate in selected cases, but long-term follow-up imaging is strongly recommended in all cases.

Low-dose isoflavone aglycone alleviates psychological symptoms of menopause in Japanese women: a randomized, double-blind, placebo-controlled study.

PURPOSE: Many studies have demonstrated the effectiveness of isoflavones on menopausal symptoms; however, these mostly used high dosages. Because high-dose isoflavone may result in endometrial hyperplasia, we investigated whether low-dose isoflavone aglycone alleviates menopausal symptoms similarly to high dosages. METHODS: We conducted a randomized, double-blind, placebo-controlled study in 90 healthy women aged 40-60 years who had at least one menopausal symptom on the Menopausal Symptom Scale (MSS). The participants were randomized to receive active tablets containing ultralow-dose (12.5 mg/day; n = 30) or low-dose (25 mg/day; n = 30) isoflavone aglycone, or placebo (n = 30) tablets, for 8 weeks. Their menopausal symptoms were evaluated using MSS, Hospital Anxiety and Depression Scale (HADS), and Athens Insomnia Scale (AIS) before, and 4 and 8 weeks after treatment. RESULTS: Eighty-seven women (97 %) completed the 8-week treatment. In the low-dose group, significant improvement was observed from baseline, in the following parameters: (1) HADS-depression subscale score, (2) AIS score, (3) MSS-somatic symptom score after 4 and 8 weeks of treatment, and (4) MSS-vasomotor symptom score after 8 weeks of treatment. The changes in scores on HADS-depression subscale and AIS from baseline to 8 weeks were significantly higher in the low-dose group than in the placebo group. CONCLUSIONS: Low-dose (25 mg/day) isoflavone aglycone significantly alleviated symptoms of depression and insomnia in Japanese middle-aged women. Clinical Trial Registration UMIN-CTR UMIN000011876.

Copy-number variations in Y-chromosomal azoospermia factor regions identified by multiplex ligation-dependent probe amplification.

Although copy-number variations (CNVs) in Y-chromosomal azoospermia factor (AZF) regions have been associated with the risk of spermatogenic failure (SF), the precise frequency, genomic basis and clinical consequences of these CNVs remain unclear. Here we performed multiplex ligation-dependent probe amplification (MLPA) analysis of 56 Japanese SF patients and 65 control individuals. We compared the results of MLPA with those of conventional sequence-tagged site PCR analyses. Eleven simple and complex CNVs, including three hitherto unreported variations, were identified by MLPA. Seven of the 11 CNVs were undetectable by conventional analyses. CNVs were widely distributed in AZF regions and shared by ~60% of the patients and ~40% of the controls. Most breakpoints resided within locus-specific repeats. The majority of CNVs, including the most common gr/gr deletion, were identified in the patient and control groups at similar frequencies, whereas simple duplications were observed exclusively in the patient group. The results imply that AZF-linked CNVs are more frequent and heterogeneous than previously reported. Non-allelic homologous recombination likely underlies these CNVs. Our data confirm the functional neutrality of the gr/gr deletion in the Japanese population. We also found a possible association between AZF-linked simple duplications and SF, which needs to be evaluated in future studies.

S-equol Partially Restored Endothelial Nitric Oxide Production in Isoflavone-deficient Ovariectomized Rats.

BACKGROUND: S-equol is known as an estrogenic substance, but its ability to restore vascular endothelial function is unknown. The aim of this study was to investigate the impact of S-equol on endothelial function and intimal thickening under isoflavone- and estrogen-deficient circumstances. METHODS: Twelve-week-old female Sprague-Dawley rats were bilaterally ovariectomized and assigned to one of the 3 groups: control, isoflavone-deficient (ID), or ID plus equol (n = 12, respectively). The control group received a normal diet containing isoflavones, while ID and ID plus equol groups received isoflavones-free diet. At 16th week, subcutaneous administration of S-equol (200 µg/d) started in the ID plus equol group. At 18th week, endothelial denudation of the left common carotid artery was performed in all groups, and thoracic and carotid arteries were collected at 20th week. RESULTS: In thoracic artery, endothelium-dependent relaxation, cyclic guanosine monophosphate levels in the tissue, and endothelial nitric oxide (NO) synthase expression and phosphorylation were significantly higher in the groups of ID plus equol and control than in the ID. The ratio of intima to media of the injured carotid artery in the control group was the lowest. CONCLUSIONS: Removal of dietary soy isoflavones decreased endothelium-derived NO level in ovariectomized rats. S-equol supplementation partially improved NO-related endothelial function.

Risk profiles for endometriosis in Japanese women: results from a repeated survey of self-reports.

BACKGROUND: The prevalence and risk factors for endometriosis may differ according to diagnosis methodologies, such as study populations and diagnostic accuracy. We examined risk profiles in imaging-diagnosed endometriosis with and without surgical confirmation in a large population of Japanese women, as well as the differences in risk profiles of endometriosis based on history of infertility. METHODS: Questionnaires that included items on sites of endometriosis determined by imaging techniques and surgical procedure were mailed to 1025 women who self-reported endometriosis in a baseline survey of the Japan Nurses' Health Study (n = 15 019). RESULTS: Two hundred and ten women had surgically confirmed endometriosis (Group A), 120 had imaging-diagnosed endometriosis without a surgical procedure (Group B), and 264 had adenomyosis (Group C). A short menstrual cycle at 18-22 years of age and cigarette smoking at 30 years of age were associated with significantly increased risk of endometriosis (Group A plus Group B), while older age was associated with risk of adenomyosis (Group C). In women with a history of infertility, a short menstrual cycle was associated with a significantly increased risk of endometriosis in both Group A and Group B, but risk profiles of endometriosis were different between Group A and Group B in women without a history of infertility. CONCLUSIONS: Women with surgically confirmed endometriosis and those with imaging-diagnosed endometriosis without surgery have basically common risk profiles, but these risk profiles are different from those with adenomyosis. The presence of a history of infertility should be taken into consideration for evaluation of risk profiles.

Dkk-3 induces apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer cells.

OBJECTIVE: Dkk-3 is a Wnt signaling inhibitor that is frequently inactivated in human cancers. Dkk-3 possesses an antiproliferative activity and induces apoptosis in tumor cells, suggesting that it functions as a tumor suppressor. In this study, we investigated the molecular function of Dkk-3 in human ovarian cancer cells. METHODS: We assessed the levels of Dkk-3 protein expression in human mucinous and clear cell ovarian cancer cells, and compared cell viabilities between cell lines that expressed Dkk-3 and those that did not, as well as between cells that expressed Dkk-3 and those whose expression of Dkk-3 was reduced by small interfering RNA. We also evaluated the characteristic fragmentation of DNA to detect apoptosis in Dkk-3-deficient cells. To further investigate the molecular mechanisms of apoptosis, we assessed the expression of molecules involved in apoptosis signaling pathways in Dkk-3-deficient cells. RESULTS: The expression of the Dkk-3 protein was observed in most of the ovarian cancer cell lines tested. Dkk-3-deficient cells showed faster growth than Dkk-3-replete cells. The characteristic fragmentation of DNA was not observed in Dkk-3-deficient cells, which showed decreased levels of expression in caspase-3, activated caspase-9, Bax, p53, activated caspase-8, and Fas/CD95, as well as an increase in Bcl-2 expression. CONCLUSIONS: Although Dkk-3 expression was observed in most of human ovarian cancer cell lines, Dkk-3 has a tumor-suppressive function and a proapoptotic effect, inducing apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer MCAS cells.

Tomato juice intake increases resting energy expenditure and improves hypertriglyceridemia in middle-aged women: an open-label, single-arm study.

BACKGROUND: Tomato-based food products have health-promoting and disease-preventing effects. Some tomato juice ingredients may have health benefits for middle-aged women, including women with menopausal symptoms and cardiovascular diseases. We investigated the net effect of tomato juice intake on several health parameters in women in this age group. METHODS: An open-label, single-arm study was conducted, involving 95 women (40-60-years-old) who had at least one menopausal symptom. The participants refrained from foods and drinks rich in tomato and tomato-based products for 2 weeks prior to the study and during the 8 weeks of tomato juice consumption. After the run-in period, the women were asked to consume 200 mL of unsalted tomato juice, twice daily for 8 weeks. Their menopausal symptoms were evaluated using the Menopausal Symptom Scale (MSS), Hospital Anxiety and Depression Scale (HADS), and Athens Insomnia Scale (AIS) before the study, and at 4 and 8 weeks after study commencement. At the same times, body composition; blood pressure; heart rate; resting energy expenditures (REEs); and serum levels of triglyceride (TG), cholesterol, glucose, and hemoglobin A1c were measured. RESULTS: Ninety-three women (98%) completed the study. The following parameters showed significant changes, compared with baseline, at study weeks 4 and 8 (mean ± standard deviation at baseline, week 4, and week 8): (1) the MSS score improved (9.9 ± 5.2, 8.5 ± 5.0, 8.3 ± 5.0; P < 0.0001, repeated measures analysis of variance(ANOVA)), (2) the HADS-anxiety subscale score improved (5.3 ± 2.7, 4.8 ± 2.4, 4.9 ± 2.9; P = 0.041, Friedman test), (3) heart rate increased (62.6 ± 9.4 bpm, 64.4 ± 8.6 bpm, 63.8 ± 8.2 bpm; P = 0.028, Friedman test), (4) REE increased (1980 ± 368 kcal/day, 2108 ± 440 kcal/day, 2149 ± 470 kcal/day; P = 0.0030, repeated measures ANOVA), (5) serum TG level decreased in the subgroup of women (n = 22) who had high TG (150 mg/dL or higher) at baseline (237.8 ± 88.9 mg/dL, 166.7 ± 86.1 mg/dL, 170.9 ± 109.7 mg/dL; P = 0.0002, Friedman test). CONCLUSIONS: Tomato juice intake alleviated menopausal symptoms, including anxiety, increased REEs and heart rate, and lowered high baseline serum TG levels in middle-aged women. TRIAL REGISTRATION: UMIN-CTR UMIN000011877 .

Relationship between autonomic nervous system activity and bone mineral density in non-medicated perimenopausal women.

The autonomic nervous system (ANS) has attracted attention as a regulator of bone remodeling and the effects of beta-blockers on the prevention of osteoporosis have been studied. However, results are as yet inconclusive and the physiological role of the ANS in bone metabolism has not been clarified. Thus, we investigated the relationship between bone mineral density (BMD) and ANS activity in non-medicated perimenopausal women. ANS activity was evaluated by power spectral analysis of heart rate variability, and overall ANS activity and the balance between sympathetic and parasympathetic nervous activities (SNS and PNS) were quantified. Pre- and postmenopausal subjects were divided into higher or lower overall ANS activity groups, and were also divided into SNS- and PNS-dominant groups. BMD (percentage of young adult mean) was significantly higher in the higher overall ANS group than in the lower group (112.2 ± 16.2 % vs 99.7 ± 14.8 %, p < 0.05) of premenopausal subjects, but not in postmenopausal subjects (91.5 ± 15.9 % vs 91.0 ± 14.9 %). BMD was significantly higher in the SNS-dominant group than in the PNS-dominant group (94.1 ± 16.3 % vs 88.4 ± 18.8 %, p < 0.05) of postmenopausal subjects, but not in the premenopausal subjects (103.5 ± 18.4 % vs. 107.2 ± 14.6 %). Our study revealed that ANS influences bone metabolism under physiological conditions. Thus, it appears to be worthwhile to introduce ANS activity evaluation into the management of bone health in perimenopausal women.

Subgrouping of Japanese middle-aged women attending a menopause clinic using physical and psychological symptom profiles: a cross-sectional study.

BACKGROUND: Women in the menopausal transition and the postmenopausal period are affected with vasomotor symptoms, urogenital atrophy, sexual dysfunction, somatic symptoms, cognitive difficulty, sleep disturbance, and psychological problems. It is important to gain a better understanding of the complexity and diversity of climacteric disturbance in order to optimize treatments for individual patients. The aim of this study was to identify subgroups of Japanese perimenopausal and postmenopausal women attending a menopause clinic based on their physical and psychological symptom profiles. METHODS: We administered the Menopausal Health-Related Quality of Life questionnaire to 491 Japanese women aged 40-64 years who had enrolled in the Systematic Health and Nutrition Education Program at the Menopause Clinic of the Tokyo Medical and Dental University Hospital between 2005 and 2012. We performed a principal component analysis followed by a hierarchical cluster analysis of the responses to 9 physical and 12 psychological items on the questionnaire. RESULTS: The first analysis extracted 3 principal components that defined the variance of physical and psychological symptom profiles: depression, somatic, and vasomotor/sleep. A subsequent cluster analysis was performed based on the 3 principal components to generate 4 clusters, CL8 (N = 162; 33.0%), CL6 (N = 111; 22.6%), CL5 (N = 102; 20.8%), and CL4 (N = 116; 23.6%). CL8 included women who only had mild-to-moderate musculoskeletal pains and tiredness. All women in CL6, CL5, and CL4 described their musculoskeletal pains and tiredness as moderate to severe. The women in CL5 also had moderate-to-severe vasomotor symptoms, while the women in CL4 also suffered from moderate-to-severe psychological symptoms, such as depression, anxiety, and insomnia. CONCLUSIONS: Distinct subgroups of Japanese perimenopausal and postmenopausal women were identified based on their symptom profiles. Menopausal symptoms were shown to accumulate in this population in the order of musculoskeletal pains and tiredness, vasomotor symptoms, and psychological symptoms.

Validity for assisted hatching on pregnancy rate in assisted reproductive technology: analysis based on results of Japan Assisted Reproductive Technology Registry System 2010.

AIM: The aim of this study was to assess the efficacy of assisted hatching (AH) in assisted reproductive technology (ART) treatment. MATERIAL AND METHODS: In this retrospective observational study, the data of patients who were registered in the National ART Registry System of Japan between January and December 2010 were analyzed. The descriptive statistics and validity of AH in fresh embryo transfer (ET) and frozen-thawed ET were assessed by using multiple logistic regression analyses. RESULTS: From a total of 105,450 single ET, 46,029 (43.7%) cycles underwent AH. A total of 9737 (21.3%) and 36,292 (60.9%) cycles underwent AH from 45,818 fresh single ET and 59,632 frozen-thawed single ET, respectively. In the fresh ET patients that underwent AH, the clinical pregnancy and live birth rate were significantly decreased in patients of all ages compared with that of the non-AH group. In the frozen-thawed ET patients, there was no significant difference in pregnancy and live birth rate between the AH group and the non-AH group. CONCLUSION: AH treatment was more frequently performed in frozen-thawed ET patients than in fresh ET patients, and in the blastocyst stage than in the early cleavage stage. A significantly decreased pregnancy and live birth rate was observed in the fresh ET patients who underwent AH. In the frozen-thawed ET patients who underwent AH, improvement in the clinical pregnancy and live birth rate was not observed. Further studies on the indication and application of AH in ART treatment are required.

The incidence of monozygotic twinning in assisted reproductive technology: analysis based on results from the 2010 Japanese ART national registry.

PURPOSE: To assess the incidence of monozygotic twinning (MZT) among cases undergoing assisted reproductive technology (ART) treatment. METHODS: We performed a retrospective observational study and analyzed the data of patients who were registered in the national ART registry system of Japan from January to December 2010; only the data of patients with single embryo transfer (ET) were included. RESULTS: Of 30,405 pregnancies, 425 resulted in MZT following fresh and frozenthawed ET. The MZT incidence among women undergoing ART was 1.4 %. Multiple logistic regression analysis indicated that cases undergoing fresh and frozen-thawed ET, blastocyst transfer had a significantly increased MZT rate (P < 0.01). Assisted hatching (AH) and frozen-thawed ET and maternal age did not significantly affect the MZT incidence. Of 8510 fresh ET pregnancies, 104 resulted in MZT. Multiple logistic regression analysis indicated that blastocyst transfer significantly increased the MZT rate in cases undergoing fresh ET. Ovarian stimulation, intracytoplasmic sperm injection, AH, and maternal age did not significantly affect the MZT incidence. CONCLUSIONS: Blastocyst transfer was associated with an increased MZT incidence. We have to be aware of the potential risk of MZT caused by blastocyst transfer. However, further studies are required to assess the correlation among specific AH types, embryo culture conditions, and MZT incidence.