Study of uterine kinetics in nonpregnant women using cine-mode magnetic resonance imaging.

PURPOSE: To evaluate the uterine kinetics in each phase of the menstrual cycle when observed in detail using cine-mode magnetic resonance imaging (MRI) of sagittal and transverse plane images. METHODS: Seven volunteers with a history of multiple natural pregnancies and deliveries were enrolled from January 2017 to May 2017. The kinetic parameters (depth, frequency, and direction) of uterine muscle contractions were evaluated in cine-mode MRI. RESULTS: Strong contractions from the uterine cornua to cervix were detected during menstruation. In the late follicular phase, the frequency of opposing contractions from the cervix and uterine cornua increased. Immediately before ovulation, contractions from the cervix reached the uterine fundus. After ovulation, opposing contractions returned. These contractions gradually decreased in the mid-luteal phase, while fine contractions from the cervix to the middle of the uterine body were frequently observed until 7 days after ovulation. Few contractions were observed in the implantation phase. CONCLUSIONS: Our data suggest that the uterine kinetics change in each phase of the menstrual cycle in accordance with the purpose of the uterus in each phase. Further, cine-mode MRI studies of each phase are needed to assess the relationships between uterine kinetics and infertility.

Impact of single embryo transfer policy on perinatal outcomes in fresh and frozen cycles-analysis of the Japanese Assisted Reproduction Technology registry between 2007 and 2012.

OBJECTIVE: To investigate whether the introduction of single embryo transfer (SET) policy in Japan has improved perinatal outcomes. DESIGN: A retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 140,718 live births and 510 stillbirths (after 22 weeks of gestation) conceived by assisted reproductive technology in Japan between 2007 and 2012 were reviewed. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm birth (PTB), low birth weight (LBW), very low birth weight (VLBW), small for gestational age (SGA), large for gestational age (LGA), perinatal mortality, and other pregnancy complications. RESULT(S): The rate of SET increased significantly from 52.2% in 2007 to 82.6% in 2012, while the rate of multiple pregnancy decreased significantly from 10.7% to 4.1% over the same period. The rates of PTB, LBW, and SGA decreased significantly, while that of LGA increased. Perinatal mortality decreased from 0.70% to 0.40% in fresh cycles, while that of frozen cycles did not change. Double ET or more was associated with a significantly increased risk for multiple pregnancy, placenta accreta, preterm premature rupture of membrane, cesarean section (CS), PTB, LBW, SGA, and early neonatal death compared with SET. Compared with before the SET policy was launched, the risks of multiple pregnancy, CS, early PTB before 32 weeks, LBW, VLBW, and SGA were significantly decreased after the policy was launched, with significant interactions of fresh/frozen status. CONCLUSION(S): The results suggest that the SET policy improved perinatal outcomes in Japan. The impact of SET policy was different in fresh and frozen cycles for several perinatal outcomes.

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.

Efficacy, safety, and trends in assisted reproductive technology in Japan-analysis of four-year data from the national registry system.

PURPOSE: This study aimed to evaluate the efficacy, safety, and trends in assisted reproductive technology (ART) in Japan. METHODS: Data pertaining to treatment cycles, pregnancy rate, live birth rate, age distribution, single embryo transfer rate, and multiple pregnancy rate were analyzed for patients registered in the national ART registry system of Japan from 2007 to 2010. RESULTS: The total number of treatment cycles was 161,164, 190,613, 213,800, and 242,161 in 2007, 2008, 2009, and 2010, respectively. The number of ART treatments administered to patients aged ≥40 years was 31.2 %, 32.1 %, 33.4 %, and 35.7 %, respectively, showing an increasing trend from 2007 to 2010. In each of these years, the total pregnancy rate per embryo transfer was 24.4 %, 21.9 %, 22.3 %, and 21.9 % for fresh cycles, respectively, and 32.0 %, 32.1 %, 32.5 %, and 33.7 % for frozen cycles, respectively. The single embryo transfer rate was 49.9 %, 63.6 %, 70.6 %, and 73.0 %, respectively, showing an increasing trend, while the multiple pregnancy rate was 11.5 %, 6.8 %, 5.3 %, and 4.8 %, respectively, showing a decreasing trend. CONCLUSIONS: From 2007 to 2010 in Japan, the number of ART treatment cycles, number of elderly patients treated, and the single embryo transfer rate increased, while the multiple pregnancy rate decreased. However, the overall pregnancy rate remained stable during the study period.

Implications of assisted reproductive technologies on term singleton birth weight: an analysis of 25,777 children in the national assisted reproduction registry of Japan.

OBJECTIVE: To evaluate the implications of assisted reproductive technologies (ART) on neonatal birth weight. DESIGN: A retrospective study using analysis of covariance and multiple logistic regression analysis of the Japanese ART registry. SETTING: Japanese institutions providing ART treatment. PATIENT(S): A total of 25,777 singleton neonates reaching term gestation following ART during the years 2007-2008, with 11,374 achieved through fresh embryo transfers (fresh ET) and 14,403 achieved through frozen-thawed embryo transfers (FET). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Birth weight. RESULT(S): The mean birth weight after FET was significantly higher compared with fresh ET and all Japanese births (3,100.7 ± 387.2 g, 3,009.8 ± 376.8 g, and 3,059.6 ± 369.6 g, respectively). The risk for low birth weight in FET was significantly lower compared with fresh ET. In fresh ET, ovarian stimulations were associated with about twofold risk of low birth weight compared with natural cycle. Regarding to the duration of embryonic culture, the risks resulting from a shorter culturing time were significantly higher compared with a longer culturing time in fresh ET. CONCLUSION(S): The best method of embryo transfer for fetal growth was FET after extended culturing until blastocyst stage. However, further investigations should be performed to understand the safety of ART treatment.

Insulin resistance/hyperinsulinemia and reproductive disorders in infertile women.

Obesity, which disturbs lipid and glucose metabolism, is a recent medical concern. It threatens human health and also has adverse effects on reproductive functions by causing insulin resistance/hyperinsulinemia, especially in women with polycystic ovary syndrome (PCOS). For PCOS patients to prevent these adverse effects, it is important to take into account improving their lifestyles by exercise and proper diets. The relationship between insulin resistance/hyperinsulinemia and reproductive disorders should be understood as fully as possible in order to provide effective treatment. It is well known that insulin resistance and compensatory hyperinsulinemia can be triggered by obesity with visceral fat accumulation. Hyperinsulinemia affects granulosa cells in small follicles and theca cells. This condition induces early response to luteinizing hormones on granulosa cells of small follicles and causes premature differentiation of these cells, which eventually results in anovulation. For improvement of anovulation because of hyperinsulinemia, insulin-sensitizing agents (biguanide and thiazolidinedione derivatives) are useful. Hyperinsulinemia may adversely affect the endometrial functions and environment, and evoke implantation disturbance. Treatment with an insulin-sensitizing agent (metformin) improves the levels of glycodelin, insulin-like growth factor binding protein 1, and blood flow in spiral arteries during the peri-implantation period. It supports endometrial function, improves the endometrial environment, and facilitates embryo implantation. The rate of early pregnancy loss during the first trimester is 30-50% in women with PCOS, which is threefold higher than for normal women. Metformin treatment improves the levels of insulin, the homeostasis model assessment for insulin resistance, and plasminogen activator inhibitor activity, and decreases early pregnancy loss. It goes without saying that lifestyle change is fundamental for improving reproductive performance in addition to treatment with insulin-sensitizing agents.