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Aim: The main purpose of our study is to determine the current research status of assisted reproductive technology (ART) and birth defects by means of co‐word analysis, to explore the hot spots and weak points of current research, and to provide ideas and opinions for follow‐up researchers. Methods: The PubMed database was used to investigate the knowledge structures of the applied words ART and birth defects. The published literature was searched until December 31, 2018. The extracted MeSH terms were quantified using the Bibliographic Item Co‐Occurrence Matrix Builder and the high‐frequency MeSH terms were determined. According to the MeSH term‐source article matrix, hierarchical cluster analysis was performed using SPSS 19.0. The high frequency MeSH term co‐occurrence matrix was constructed to support strategic diagram and social network analysis (SNA). Results: According to the search strategy, 1635 papers were included. Of all the extracted MeSH terms, 105 high frequency MeSH terms were identified and the hotspots were classified into nine categories. In the strategic diagram, research on the effects of prenatal diagnosis methods and ART on the development of offspring has been well developed. In contrast, research on reproductive ethics, epigenetics, and epidemiology is relatively immature, indicating the need for future research. For SNA results, the position status of each component is described by the center value. Conclusions: By providing a quantitative bibliometric study, it can help with the overall command of the latest topic and guide researchers in their new projects. [ABSTRACT FROM AUTHOR]

Aim: Obstetrical guidelines were established in Japan in 2008, and obstetrical diagnoses and treatments were subsequently standardized nationally. We examined changes in the preterm birth rate (PTBR) and extremely preterm birth rate (EPTBR) following the introduction of such guidelines. Methods: Information on 50 706 432 live births in Japan between 1979 and 2021, including Japanese reproductive medicine, the childbearing age of pregnant women, and the employment status of reproductive‐age women between 2007 and 2020, were obtained from the Japanese government and academic societies. Regression analysis was used to compare chronological changes nationally and those of eight Japanese regions. Regional and national average PTBRs and EPTBRs from 2007 to 2020 were compared by using a repeated measures analysis of variance. Results: From 1979 to 2007, PTBRs and EPTBRs in Japan increased significantly. However, from 2008, the national PTBR and EPTBR decreased until 2020 (p < 0.001) and 2019 (p = 0.02), respectively. From 2007 to 2020, overall PTBR and EPTBR were 5.68% and 0.255%, respectively. A significant difference in the PTBR and EPTBR existed between the eight Japanese regions. During this period, the number of pregnancies using assisted reproductive technology increased from 19 595 to 60 381, pregnant women became older, the employment rate of those of reproductive age increased, and nonregular employment was 54%, which was 2.5 times higher than for men. Conclusions: In Japan, after obstetrical guidelines were enacted in 2008, PTRBs decreased significantly even under the pressure of increasing preterm births. Countermeasures may be necessary for regions showing high PTBRs. [ABSTRACT FROM AUTHOR]

Aim: To investigate the therapeutic effect of co‐administration of tacrolimus (TAC) and low‐molecular‐weight heparin (LMWH) or LMWH only on pregnancy outcomes in the female with a history of implantation failure and elevated peripheral blood natural killer (pNK) cell proportion in frozen‐thawed embryo transfer cycles. Methods: To evaluate the pregnancy parameters for 249 patients with ≥2 implantation failures and pNK cell proportion ≥12% by analyzing a retrospective observational cohort study. Sixty patients had received the co‐administration TAC and LMWH (TAC & LMWH group), 85 others had only taken LMWH (LWMH group), and the rest did not take any particular drugs (control group). Results: The experimental finding indicated that the TAC & LMWH group and the LMWH group showed higher clinical pregnancy rates than the control group (p < 0.05), and TAC & LMWH group had a much higher live birth rate. According to the binary logistic regression analysis, the combination of TAC and LMWH was conducive to clinical pregnancy and live birth rate and reduced the possibility of miscarriage. It would not affect the result of spontaneous abortion and live birth, although the LMWH was only beneficial to clinical pregnancy. In addition, these findings were similar for these three groups' obstetrical and neonatal outcomes. Conclusions: The combination of TAC and LMWH can improve clinical pregnancy and live birth rates and reduce the risk of spontaneous miscarriage in patients with a history of implantation failure and elevated pNK ratio. LMWH is also beneficial to clinical pregnancy. [ABSTRACT FROM AUTHOR]

The article offers information on clinical practice guidelines for endometriosis in Japan. It examines fundamental knowledge in clearly elaborating current perspectives on the review of the diagnosis and treatment, in addition to the advance over the last 10 years, as of December 2022. It further explores therapeutic strategies.

Aim: This study aimed to investigate the developmental outcomes of Japanese babies conceived through assisted reproductive technology (ART), born at ages 48 and 60 months. Methods: Data were collected from 725 children in a hospital‐based cohort study conducted in Japan. The children's level of development was assessed using the Kinder Infant Development Scale, a parent‐rated questionnaire that consists of nine developmental domains. We compared the development between children conceived through ART (N = 189) and those conceived naturally (N = 536) by conducting analyses of covariance. For the analyses, we controlled for the effects of maternal age, family income, parental education, and multiple births. Results: At 48 months, no significant difference was found between children conceived through ART and those conceived naturally, except for the development of receptive language (F(1, 718) = 4.869, p = 0.028)), which was found only for boys. The mean developmental age of receptive language was 60.1 for the children conceived through ART and 57.5 for those conceived naturally. At 60 months, no significant difference was found between children conceived through ART and those conceived naturally, in all domains. Conclusion: At ages 48 and 60 months, no significant difference was found between the children conceived through ART and those conceived naturally in nine developmental domains, except for boys' receptive language at 48 months. [ABSTRACT FROM AUTHOR]

Aim: We present two cases of triplet pregnancy with complete hydatidiform mole (CHM) in contrasting outcomes and discuss the complications of mothers and outcomes of fetuses through a literature review, raising an important issue on the management of this special pregnancy. Methods: We share our manage experience for two cases of triplet pregnancy with CHM and retrospectively analyze 18 similar pregnancies reported previously with different pregnancy outcomes. Results: In our cases, one case receiving Clomiphene ovulation induction delivered two live fetuses by cesarean section at 30+ weeks without GTN (gestational trophoblastic neoplasia), unfortunately, the other case following ICSI‐ET terminated the pregnancy in the setting of complications at 18+ weeks without GTN. No severe complications were detected during pregnancy and no pGTD was developed after delivery in neither of the pregnant. Conclusions: Co‐existing complete hydatidiform mole in multiple pregnancies may become more common owing to the spreading use of ART. The decision for whether continue pregnancy depending on the personalized conditions including the complications of the pregnancy, the outcomes of the fetuses, the gestational age for delivery, and the potential progression of persistent gestational trophoblastic disease (pGTD). Furthermore, close monitor is necessary for the pregnant with triplet pregnancy with CHM who want to continue pregnancy. [ABSTRACT FROM AUTHOR]

Cervical pregnancy (CP) is a rare form of ectopic pregnancy (EP) in which the embryo implants and grows inside the endocervical canal. Heterotopic cervical pregnancy is an even rare form of EP, in which at least two embryos are simultaneously implanted in different sites and only one in the uterine cavity. Although many treatment approaches are available, the ideal management remains unclear. Here, we describe two cases of CP caused by assisted reproductive technologies (ART). One case underwent fertilization with intracytoplasmic sperm injection (ICSI) for male factor infertility, and the other was frozen–thawed embryo transfer (FET) following conventional in vitro fertilization (IVF). Both cases were successfully treated with ultrasound‐guided cervical pregnancy aspiration, and intrauterine pregnancies were effectively protected. To the best of our knowledge, these two were rare case reports use aspiration without additional methods and intrauterine pregnancy achieved live birth. [ABSTRACT FROM AUTHOR]

Objective: This study aims to determine the effects of early and late onset estrogen supplementation on the immature oocyte retrieval, fertilization and clinical pregnancy rates in follicle stimulating hormone (FSH) and human chorionic hormone (hCG) primed in vitro maturation (IVM) cycles of the patients with polycystic ovary syndrome (PCOS). Methods: This is a retrospective analysis of 161 patients with PCOS who underwent FSH and hCG primed IVM. Group 1 included 120 patients who received early onset estrogen supplementation while group 2 consisted of 41 patients who had late onset estrogen supplementation in primed IVM cycles. Immature oocyte (germinal vesicle and/or metaphase I) retrieval and fertilization rates were the primary outcomes, whereas clinical pregnancy and live rates were the secondary outcomes. Results: Group 1 patients had significantly higher body mass index and more previous IVF attempts (p = 0.001 and p = 0.008, respectively). All of the retrieved oocytes from the PCOS patients were either germinal vesicle or metaphase I oocytes and there were no metaphase II oocytes among the retrieved oocytes. Both groups had statistically similar numbers of metaphase I and fertilized oocytes (p > 0.05 for both). However, group 1 patients had significantly lower number of germinal vesicle oocytes but significantly higher number of metaphase II oocytes (p = 0.001 for both). Both groups had statistically similar fertilization (85.0% vs 78.0%), clinical pregnancy (49.2% vs 43.9%) and live birth (37.5% vs 39.0%) rates (p > 0.05 for all). Conclusion: Early onset estrogen supplementation appears to improve the quality of retrieved immature oocytes and contribute to the maturation of oocytes in stimulated IVM cycles. [ABSTRACT FROM AUTHOR]

Aim: Maternal diabetes adversely retards the development of preimplantation embryos. Quercetin is a flavonoid belonging to phytoestrogens family and may be useful in treatment of reproductive disorders. The aim of this study was investigation of the ameliorative effects of quercetin administration on preimplantation embryo development in diabetic pregnancy. Methods: Diabetic and healthy female mice were treated with 30 mg/kg/day quercetin 4 weeks before conception. Blastocysts were recovered at the 4th day of pregnancy for protein and mRNA expression changes. Plasma sex‐steroid levels were also analyzed. Results: Quercetin significantly decreased blood glucose levels in diabetic mice. Embryos retrieved from diabetic mice exhibited a considerable delay in morphological development. In diabetic mice with quercetin treatment, morphological distribution was shifted considerably to the well‐developed stages. Serum estradiol level reduced in diabetic mice but, treatment with quercetin significantly increased serum estradiol level. While IGF1R, integrin αvβ3, and Cox2 mRNA expression in the blastocyst of diabetic mice decreased significantly, quercetin treatment caused increasing expression levels of these genes. Expression of the Caspase3 gene increased dramatically in the collected blastocysts from diabetic mice and reduced following quercetin treatment. Besides, the inactive β‐catenin protein level in the blastocysts of diabetic mice was higher than that in normal mice, while treatment with quercetin decreased the level of inactive β‐catenin protein in the blastocyst of diabetic mice. Conclusion: Quercetin protects preimplantation embryos from destructive effects of diabetes. The amelioration of sex hormones disturbance in early pregnancy may help to treat reproductive disorders in diabetic women. Quercetin can be considered as a novel solution to the improvement of reproductive disorders in the diabetic females. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association between use of assisted reproductive technology (ART) and mother‐to‐infant bonding. Methods: Using nationwide birth cohort study with periodical follow‐ups for mothers and children during pregnancy and at 1 year after delivery, mothers were classified following three groups; infertility group with ART: 2792 mothers; infertility group with non‐ART treatment (ovulation induction and intrauterine insemination): 3835 mothers and unaided pregnancy group: 78 726 mothers. Data on maternal and child health as well as basic characteristics were collected via medical records and self‐administered questionnaires. The Japanese version of Mother‐to‐Infant Bonding Scale was used to evaluate maternal bonding style. To evaluate the association between ART and maternal bonding toward babies, multivariate analysis was used with adjustment for potential confounders such as babies' sex, socio‐economic status and history of maternal mental disorders. Results: Multivariate logistic regression analysis indicated that ART was slightly but significantly associated with an increased risk of maternal lack of affection toward their newborn (adjusted odds ratio 1.10, 95% confidence interval 1.02–1.20), while non‐ART was significantly associated with both maternal lack of affection and anger/rejection toward the newborn. No substantial association was observed between ART and overall Mother‐to‐Infant Bonding Scale score (adjusted odds ratio 1.03, 95% confidence interval 0.94–1.12). Very slight negative correlations were observed between poor mother‐to‐infant bonding and good infant mental and physical development at both 6 months and 1 year. Conclusion: ART may exert a negative influence on maternal emotion after delivery, but this does not have strong correlation with child development evaluated by mothers. [ABSTRACT FROM AUTHOR]

Aim: The cryopreservation of embryos is essential for assisted reproductive technology field. The aim of the present study is to examine the efficacy and ease of use of a new vitrification device, Kitasato Vitrification System (KVS), in cryopreservation of human embryos. Methods: Human embryos at the cleavage or blastocyst stage were vitrified and warmed by KVS or Cryotop (control device). The survival of cleavage‐ and blastocyst‐stage embryos and the developmental competence of cleavage‐stage embryos were evaluated. Four individuals inexperienced in vitrification and warming embryos tested both KVS and Cryotop. The vitrification time and the detachment time of the embryos were evaluated. Results: At the cleavage stage, there were no significant differences in the survival rate and the development rate to the blastocyst stage between KVS and Cryotop (100 vs 96.8% and 63.3 vs 61.3%, respectively). At the blastocyst stage, there was no significant difference in the re‐expansion rate between KVS and Cryotop (100 vs 88.9%). The vitrification time was shorter for KVS than Cryotop. There was no significant difference in the detachment time between KVS and Cryotop. Conclusion: Kitasato Vitrification System is easy to operate, even for inexperienced users, and the viability of human embryos vitrified by KVS is comparable to that of Cryotop, a widely used vitrification device. [ABSTRACT FROM AUTHOR]

Aim: To evaluate obstetric outcomes in embryo transfer (ET) during estrogen with progestin hormone replacement therapy (HRT) cycles using assisted reproductive technology (ART). Methods: Of the 118 singleton pregnancies conceived with ART and delivered between January 2015 and December 2017, we reviewed the data of 87 cases that had information on HRT at the time of ET. Data on pregnancy outcomes included the presence of small for gestational age fetuses, hypertensive disorders of pregnancy, placenta previa (including low‐lying placenta), placental abruption and placenta accreta spectrum (including placenta accreta, placenta increta and placenta percreta). We investigated the relationship between HRT cycles and adverse placental outcomes (placenta accreta spectrum, placental abruption, placenta previa, hypertensive disorders of pregnancy and small for gestational age fetuses). We then analyzed the associations that correlated with adverse placental outcomes. Results: Patients with ET during HRT cycles were more likely to have placenta accreta spectrum. During the study period, 87 out of 118 singleton live births using ART had information on HRT (60 HRT cycles and 27 ovulation cycles). The incidence of placenta accreta spectrum was significantly higher in the HRT cycle group than in the ovulation cycle group (HRT cycle, 31.7% [19 of 60] vs ovulation cycle, 7.4% [2 of 27]; P < 0.01). Conclusion: The obstetric outcomes occurring in pregnancies involving HRT use may differ among ET cycles. ET during HRT cycles were associated with adverse obstetric outcomes due to placenta accreta spectrum. The potential interaction between HRT cycles and adverse placental events is novel and warrants further investigation. [ABSTRACT FROM AUTHOR]

Abstract: It has been more than 15 years since the measurement of serum anti‐Müllerian hormone (AMH) first allowed the quantitative assessment of ovarian reserve. Meanwhile, the clinical implication of serum AMH has been expanding. The measurement of serum AMH has been applied in various clinical fields, including assisted reproduction, menopause, reproductive disorders and assessment of ovarian damage/toxicity. Well‐known findings about the usefulness of serum AMH revealed by numerous studies executed in the early era include decline with aging, a good correlation with oocyte yield in assisted reproduction, upregulation in polycystic ovarian syndrome and a decrease on ovarian surgery and toxic treatment. More intensive research, including a meta‐analysis, cutting‐edge clinical trial and advances in AMH assays, has yielded newer findings and firmer clinical interpretations in serum AMH in the past few years. Variations in the AMH decline trajectory in the general population do not support the accurate prediction of menopause. The ability to predict pregnancy in infertility treatment and natural conception is poor, while a nomogram integrating serum AMH as a stimulation protocol is useful for avoiding poor and/or hyper‐responses. On the other hand, improvements in measuring very low concentrations of serum AMH may be capable of distinguishing women with poor ovarian function. Age‐independent standardization of AMH values may be helpful for comparing ovarian reserves among women at different ages. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We evaluated whether maintenance tocolysis (intravenous ritodrine hydrochloride and/or magnesium sulfate) was effective in cases of spontaneous preterm labor with intact membranes. Methods: One hundred and thirty preterm labor patients who reached 36 weeks of gestation by maintenance tocolysis were selected. Immediate delivery (ID) after ceasing maintenance tocolysis was defined as an ‘effective case’. The correlated factors between ID and no immediate delivery (NID) were statistically analyzed. Results: Thirty‐six patients delivered < two days after ceasing maintenance tocolysis (27.7%) and were defined as effective cases. Multiple logistic regression analysis revealed that amniotic fluid interleukin‐8 at admission (≥ 2.3 ng/mL; odds ratio [OR] 5.6, 95% confidence interval [CI] 2.1–17.6; P < 0.001), pre‐pregnancy body mass index (≤ 21.4; OR 5.3, 95% CI 2.0–16.2; P < 0.001) and cerclage (OR 3.6, 95% CI 1.1–11.8; P = 0.028) were independent factors correlated with ID (< 2 days). Conclusion: Maintenance tocolysis may be effective in limited cases with mild intra‐amniotic inflammation, in lean women and in cerclage cases. Maintenance tocolysis should be ceased in cases without these clinical factors when clinical symptoms disappear. [ABSTRACT FROM AUTHOR]