Preimplantation genetic testing using comprehensive genomic copy number analysis is beneficial for balanced translocation carriers.

Balanced chromosomal translocation is one of chromosomal variations. Carriers of balanced chromosomal translocations have an increased risk of spontaneous miscarriage. To avoid the risk, preimplantation genetic testing (PGT) using comprehensive genomic copy number analysis has been developed. This study aimed to verify whether and how embryos from couples in which one partner is a balanced translocation carrier have a higher ratio of chromosomal abnormalities. A total of 894 biopsied trophectoderms (TEs) were obtained from 130 couples in which one partner was a balanced translocation carrier (Robertsonian translocation, reciprocal translocation, or intrachromosomal inversion) and grouped as PGT-SR. Conversely, 3269 TEs from 697 couples who experienced recurrent implantation failure or recurrent pregnancy loss were included in the PGT-A group. The transferable blastocyst ratio was significantly lower in the PGT-SR group, even when bias related to the sample number and patient age was corrected. Subgroup analysis of the PGT-SR group revealed that the transferable blastocyst ratio was higher in the Robertsonian translocation group. Because the PGT-SR group had a higher proportion of untransferable embryos than the PGT-A group, PGT using comprehensive genomic copy number analysis was more beneficial for balanced translocation carriers than for infertility patients without chromosomal translocations. The frequencies of de novo aneuploidies were further analyzed, and the frequency in the PGT-SR group was lower than that in the PGT-A group. Therefore, we could not confirm the existence of interchromosomal effects in this study.

Educating patients with upper limb dysfunction on self-adjustment of the CPAP/NPPV mask: A case series.

We share our experiences of instructing three patients with severe upper limb dysfunction on how to self-adjust CPAP/NPPV masks. In Case 1, we simplified the procedure by suturing a part of the headband as the left forearm was amputated. In Case 2, the patient had congenitally short limbs with short stature; thus, we provided an additional belt to the headband to maintain the headband's configuration while wearing the mask. In Case 3, the patient had left hemiplegia due to stroke and, repetitive coaching was conducted during the recovery phase rehabilitation program. Difficulties with self-adjusting NPPV/CPAP masks can occur whenever there is limited hand mobility above the head, including upper limb dysfunction. Simplifying procedures and providing sufficient time for instruction could help achieve independence. There have been no previous reports describing similar training details. We believe that sharing this knowledge will be helpful to both patients and healthcare professionals.

Comparison of 1-year cumulative live birth and perinatal outcomes following single blastocyst transfer with or without preimplantation genetic testing for aneuploidy: a propensity score-matched study.

PURPOSE: We evaluated whether preimplantation genetic testing for aneuploidy (PGT-A) could increase the cumulative live birth rate (CLBR) in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). METHODS: The clinical records of 7,668 patients who underwent oocyte retrieval (OR) with or without PGT-A were reviewed for 365 days and retrospectively analyzed. Using propensity score matching, 579 patients in the PGT-A group were matched one-to-one with 7,089 patients in the non-PGT-A (control) group. Their pregnancy and perinatal outcomes and CLBRs were statistically compared. RESULTS: The live birth rate per single vitrified-warmed blastocyst transfers (SVBTs) significantly improved in the PGT-A group in all age groups (P < 0.0002, all). Obstetric and perinatal outcomes were comparable between both groups regarding both RIF and RPL cases. Cox regression analysis demonstrated that in the RIF cases, the risk ratio per OR was significantly lower in the PGT-A group than in the control group (P = 0.0480), particularly in women aged < 40 years (P = 0.0364). However, the ratio was comparable between the groups in RPL cases. The risk ratio per treatment period was improved in the PGT-A group in both RIF and RPL cases only in women aged 40-42 years (P = 0.0234 and P = 0.0084, respectively). CONCLUSION: Increased CLBR per treatment period was detected only in women aged 40-42 years in both RIF and RPL cases, suggesting that PGT-A is inappropriate to improve CLBR per treatment period in all RIF and RPL cases.

Does embryo categorization by existing artificial intelligence, morphokinetic or morphological embryo selection models correlate with blastocyst euploidy rates?

RESEARCH QUESTION: Does embryo categorization by existing artificial intelligence (AI), morphokinetic or morphological embryo selection models correlate with blastocyst euploidy? DESIGN: A total of 834 patients (mean maternal age 40.5 ± 3.4 years) who underwent preimplantation genetic testing for aneuploidies (PGT-A) on a total of 3573 tested blastocysts were included in this retrospective study. The cycles were stratified into five maternal age groups according to the Society for Assisted Reproductive Technology age groups (<35, 35-37, 38-40, 41-42 and >42 years). The main outcome of this study was the correlation of euploidy rates in stratified maternal age groups and an automated AI model (iDAScore® v1.0), a morphokinetic embryo selection model (KIDScore Day 5 ver 3, KS-D5) and a traditional morphological grading model (Gardner criteria), respectively. RESULTS: Euploidy rates were significantly correlated with iDAScore (P = 0.0035 to <0.001) in all age groups, and expect for the youngest age group, with KS-D5 and Gardner criteria (all P < 0.0001). Additionally, multivariate logistic regression analysis showed that for all models, higher scores were significantly correlated with euploidy (all P < 0.0001). CONCLUSION: These results show that existing blastocyst scoring models correlate with ploidy status. However, as these models were developed to indicate implantation potential, they cannot accurately diagnose if an embryo is euploid or aneuploid. Instead, they may be used to support the decision of how many and which blastocysts to biopsy, thus potentially reducing patient costs.

Preimplantation Genetic Testing for Aneuploidy for Recurrent Pregnancy Loss and Recurrent Implantation Failure in Minimal Ovarian Stimulation Cycle for Women Aged 35-42 Years: Live Birth Rate, Developmental Follow-up of Children, and Embryo Ranking.

This study was aimed at exploring the benefits of preimplantation genetic testing for aneuploidy (PGT-A) in ensuring a successful pregnancy in patients with recurrent pregnancy loss (RPL) caused by an abnormal number of chromosomes in the embryo and recurrent implantation failure (RIF). Thirty-two patients who underwent PGT-A (18 in the RIF protocol and 14 in the RPL protocol) were enrolled in the study, and 2556 patients who did not undergo PGT-A during the same in vitro fertilization (IVF) treatment period were enrolled as controls. All patients underwent minimal stimulation cycle IVF. In the RPL protocol, the live birth rate per embryo transfer (ET) and that per patient were higher with PGT-A (80.0% each) than without it (0% each; P = 0.0050), and the rate of miscarriages was lower with PGT-A than without it (20.0% vs. 100.0%, P = 0.0098). In the RIF protocol, there were no significant differences in the live birth rate per ET and in the rate of miscarriages between groups with and without PGT-A-90.0% vs. 69.2% (P = 0.2313) and 0% vs. 10.0% (P = 0.3297), respectively. None of the children whose mothers underwent PGT-A presented adverse findings at a 1.5-year developmental check-up. In conclusion, PGT-A in RPL is advantageous for improving the live birth rate per ET and that per patient in minimal stimulation cycle IVF; it reduces the rate of miscarriages. In addition, PGT-A might be more beneficial for embryo selection than the existing morphological grades of blastocysts, resulting in earlier conception.

Endometrial preparation and maternal and obstetrical outcomes after frozen blastocyst transfer.

BACKGROUND: Two types of endometrial preparation protocols are used for frozen embryo transfers in current practice: hormone replacement and the natural cycle. Endometrial preparation in the natural cycle reportedly increases the chances of live birth and decreases early pregnancy loss compared with that in the hormone replacement cycle. However, the influence of endometrial preparation on maternal and neonatal health remains unclear. OBJECTIVE: This study aimed to investigate whether the differences between hormone replacement cycle and natural cycle influence perinatal outcomes and risk of congenital anomalies in frozen-thawed blastocyst transfer fetuses or births. STUDY DESIGN: Perinatal outcomes and congenital abnormalities were compared between the natural and hormone replacement cycles. According to the timing of ovulation, frozen-thawed blastocyst transfers in the natural cycle were classified into 2 patterns: on day 4.5 (ovulation 4.5) or day 5 (ovulation 5.0) after ovulation. When the serum luteinizing hormone level was not increased on the day of the trigger, a single vitrified-warmed blastocyst transfer was performed on day 7 after the trigger (ovulation 5.0). When the luteinizing hormone level was slightly increased on the day of trigger, single vitrified-warmed blastocyst transfer was performed on day 6 after the trigger (ovulation 5.0). In total, 67,018 cycles (ovulation 4.5, 29,705 cycles; ovulation 5.0, 31,995 cycles; hormone replacement, 5318 cycles) of frozen-thawed blastocyst transfer between January 2008 and December 2017 at Kato Ladies Clinic were retrospectively analyzed. During the study period, embryo cryopreservation was performed using a vitrification method in all cycles. RESULTS: Hormone replacement cycles were associated with a higher occurrence of hypertensive disorders of pregnancy (adjusted odds ratio, 2.16; 95% confidence interval, 1.66-2.81) and placenta accreta (adjusted odds ratio, 4.14; 95% confidence interval, 1.64-10.44) compared with the natural cycle. The risks of cesarean delivery (adjusted odds ratio, 1.93; 95% confidence interval, 1.78-2.18), preterm birth (adjusted odds ratio, 1.55; 95% confidence interval, 1.25-1.93), and low birthweight (adjusted odds ratio, 1.42; 95% confidence interval, 1.18-1.73) were also higher for hormone replacement cycles. No significant difference in the risk of congenital anomalies was observed between the 2 cycles. CONCLUSION: The risk of hypertensive disorders of pregnancy, placenta accreta, cesarean delivery, preterm delivery, and low birthweight was higher in hormone replacement cycles than in natural cycles, whereas the risk of congenital anomalies was similar between both cycles. Further follow-up is needed to investigate these risks and to explore alternative endometrial preparation methods.

Perinatal outcomes and congenital anomalies associated with letrozole and natural cycles in single fresh cleaved embryo transfers: A single-center, 10-year cohort study.

Objective: To investigate and compare the safety of letrozole and natural cycles in fresh early embryo transfers. Design: A retrospective cohort study. Setting: A large fertility treatment center. Patients: Women who underwent natural and letrozole cycles during fresh early embryo transfer at Kato Ladies Clinic between January 2008 and December 2017. Interventions: None. Main Outcome measures: Perinatal complications and congenital anomalies. Results: No significant differences were observed in pregnancy complications, gestational age, birth weight, small for gestational age, large for gestational age, and congenital anomalies between the the women who underwent natural and letrozole cycles. Conclusions: The perinatal outcomes and congenital anomaly rates associated with letrozole and natural cycles in fresh early embryo transfers were comparable. Therefore, our data support the safe use of letrozole in fresh early embryo transfers in assisted reproductive technology.

Maternal and obstetric outcomes are influenced by developmental stage and cryopreservation of transferred embryos after clomiphene citrate-based minimal stimulation IVF.

STUDY QUESTION: Is the embryo transfer (ET) method associated with maternal and perinatal outcomes after minimal stimulation IVF using clomiphene citrate (CC)? SUMMARY ANSWER: The incidence of pregnancy complications and adverse perinatal outcomes was influenced by the developmental stage (cleavage versus blastocyst stages) and cryopreservation (fresh versus vitrified) of the transferred embryos. WHAT IS KNOWN ALREADY: Pregnancies resulting from IVF are associated with higher risks of adverse perinatal outcomes compared to natural conceptions; therefore, the next focus in reproductive medicine should be to assess whether these increased risks are attributable to IVF. Pregnancy complications and perinatal outcomes should be considered in addition to pregnancy outcomes when selecting the ET method, however, studies that describe the influence of transfer methods on perinatal and maternal outcomes are limited. STUDY DESIGN SIZE DURATION: This study retrospectively analysed a large single-centre cohort. The clinical records of 36 827 women who underwent oocyte retrieval (during a CC-based minimal stimulation cycle) followed by their first ET at the fertility treatment centre between January 2008 and December 2017 were retrospectively analysed. The patients underwent a single fresh cleavage-stage ET (SFCT), single vitrified-warmed cleavage-stage ET (SVCT) or single vitrified-warmed blastocyst transfer (SVBT). This study only included one cycle per patient. PARTICIPANTS/MATERIALS SETTING METHODS: Oocyte retrieval was performed following CC-based minimal ovarian stimulation. The embryos were transferred 2-3 days after retrieval or vitrified at the cleavage or blastocyst stage. The vitrified embryos were then warmed and transferred within the natural cycles. Pregnancy complications and perinatal outcomes were stratified according to the transfer methods used. Multivariate logistic regression analysis was performed to evaluate the effect of ET methods on the prevalence of pregnancy complications and congenital anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: The rates of clinical pregnancy and delivery were significantly different among the groups. We analysed pregnancy complications in 7502 singleton births (SFCT, 3395 cycles; SVCT, 586 cycles; and SVBT, 3521 cycles). Multivariate logistic regression analysis revealed that the adjusted odds ratio (AOR) for hypertensive disorders in pregnancy was significantly lower in the SVBT group than in the SFCT group [AOR, 0.72; 95% CI, 0.56-0.92]. The AOR for low-lying placenta was lower in the SVBT group than in the SFCT group (AOR, 0.34; 95% CI, 0.19-0.60). The AOR for placenta previa was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.21; 95% CI, 0.07-0.58 versus AOR, 0.53; 95% CI, 0.38-0.75, respectively). A total of 7460 follow-up data on neonatal outcomes was analysed. The AOR for preterm delivery was lower in the SVBT group than in the SFCT group (AOR, 0.78; 95% CI, 0.64-0.94). The AOR for low birthweight was significantly lower after SVCT and SVBT than after SFCT (AOR, 0.68; 95% CI, 0.46-0.98 versus AOR, 0.57; 95% CI, 0.48-0.66, respectively). The AOR for small for gestational age was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.68; 95% CI, 0.46-0.98 versus AOR, 0.44; 95% CI, 0.36-0.55, respectively). The AOR for large for gestational age babies was higher in the SVBT group than in the SFCT group (AOR, 1.88; 95% CI, 1.62-2.18). The incidence of each congenital anomaly was similar among the groups. LIMITATIONS REASONS FOR CAUTION: The study data were collected through self-reported parental questionnaires on maternal and neonatal outcomes. Our findings were not compared with the incidence of pregnancy complications and congenital anomalies in natural pregnancies. Furthermore, this study was retrospective in nature; therefore, further studies are required to ascertain the generalizability of these findings to other clinics with different protocols and/or different patient demographics. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated reassuring outcomes for SVBT (in terms of a lower incidence of pregnancy complications) compared to SFCT. Our findings provide valuable knowledge that will help improve perinatal and maternal outcomes in CC-based stimulation and inform couples of the possible benefits and risks of each type of ET method. STUDY FUNDING/COMPETING INTERESTS: This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Establishment of day 7 blastocyst freezing criteria using blastocyst diameter for single vitrified-warmed blastocyst transfer from live birth outcomes: a single-center, large cohort, retrospectively matched study.

PURPOSE: To establish blastocyst freezing criteria for day 7 blastocyst (day 7 BL) for single vitrified-warmed blastocyst transfer (SVBT) by examining the diameter of blastocysts. METHODS: Patients who underwent day 7 BL transfer cycles (1143 cycles, mean age: 38.5 ± 3.5) and randomly selected patients after 1:1 matching who underwent day 6 BL transfer cycles and day 2-single-embryo transfer (SET) cycles were used for analysis. Comparison of the miscarriage (per clinical pregnancy) and live birth rates were made among day 2-SET, day 7 BL, and day 6 BL. These blastocyst groups were stratified into six groups based on blastocyst diameter, namely, 180 µm, 190 µm, 200 µm, 210 µm, over 220 µm, and hatched, for making the freezing criteria. RESULTS: For each diameter, 180 µm, 190 µm, 200 µm, 210 µm, over 220 µm, and hatched, the live birth rates of day 7 BL after SVBT were 9.0%, 11.9%, 11.5%, 15.6%, 20.0%, and 19.9%, respectively. Compared with the 14.6% live birth rate of the day 2-SET group, the live birth rate of 220 µm day 7 BL was significantly higher (P < 0.05) and was around the same in other diameter groups. CONCLUSION: Our study demonstrates that sufficient live birth rates can be obtained after SVBT even from blastocysts on day 7 when blastocysts were vitrified at expanded blastocyst stage of over 180 µm of diameter or at hatched blastocyst stage and were transferred at the optimal time. This is the first study to establish a day 7 blastocyst freezing criteria using blastocyst diameter, which is an objective assessment way.

Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure.

STUDY QUESTION: Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)? SUMMARY ANSWER: PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups. WHAT IS KNOWN ALREADY: PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40-50% and 5-25% in patients with RPL, respectively. STUDY DESIGN, SIZE, DURATION: A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35-36, 37-38, 39-40 or 41-42 years) were selected for PGT-A groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted. MAIN RESULT AND THE ROLE OF CHANCE: There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16-13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28-10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02-0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03-0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients. LIMITATIONS, REASONS FOR CAUTION: The sample size was too small to find any significant advantage for improving the live birth rate and reducing the clinical miscarriage rate per patient. Further study is necessary. WIDER IMPLICATION OF THE FINDINGS: A large portion of pregnancy losses in the RPL group might be due to aneuploidy, since PGT-A reduced the overall incidence of pregnancy loss in these patients. Although PGT-A did not improve the live birth rate per patient, it did have the advantage of reducing the number of embryo transfers required to achieve a similar number live births compared with those not undergoing PGT-A. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Japan Society of Obstetrics and Gynecology and grants from the Japanese Ministry of Education, Science, and Technology. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Cryostorage duration does not affect pregnancy and neonatal outcomes: a retrospective single-centre cohort study of vitrified-warmed blastocysts.

A retrospective cohort study of 8736 autologous single vitrified-warmed blastocyst transfer cycles was conducted in a single centre to investigate the effect of cryostorage on clinical and neonatal outcomes. Cryostorage duration was classified into three groups: (A) 0-2 months (n = 4702); (B) 2-13 months (n = 2853) and (C) 13-97 months (n = 1181). Blastocysts were vitrified using the Cryotop method. No significant differences were observed in live birth rates: (A) 37.3%; (B) 34.9%; (C) (35.2%). Gestational period was significantly shorter in group C: (A) 38.7 ± 1.8; (B) 38.6 ± 1.6; (C) 38.1 ± 1.7; P < 0.05. This was clinically unimportant as the average gestational age was more than 38 weeks. No significant differences between groups were observed in birth weight: (A) 3060 ± 455 g; (B) 3052 ± 449 g; (C) 2992 ± 445 g, or congenital malformation rates: (A) 2.2%; (B) 1.9%; (C) 1.8%. The limitation of this study was that maximum storage duration was 8 years; most blastocysts were in cryostorage for much shorter periods. Long-term storage of blastocysts that are vitrified using an open device vitrification system has no negative effect on pregnancy and neonatal outcomes.

Cytogenetic analysis of the retained products of conception after missed abortion following blastocyst transfer: a retrospective, large-scale, single-centre study.

Cytogenetic analysis of the retained products of conception (POC) is the most effective test for identifying miscarriage causes. However, there has been no large-scale study limited to blastocyst transfer. This study retrospectively reports the findings of 1030 cases in which POC analysis was performed after missed abortion following single blastocyst transfer performed at the Shinbashi Yume Clinic. We identified 19.4% as normal karyotypes and 80.6% as aneuploid. These cases broke down into: 62.3% trisomy; 7.8% double trisomy; 0.5% triple or quadruple trisomy; 1.3% monosomy 21; 3.2% monosomy X; 0.1% 47,XXY; 1.0% polyploidy; 1.0% mixed; 1.1% embryonic mosaicism; and 2.4% structural anomalies. In samples with normal karyotypes, 49.5% were female while 50.5% were male. The occurrence of trisomy and double trisomy were both significantly more frequent in the ≥38 years group than in the ≤37 years group (P < 0.01). Trisomy was significantly more frequently associated with fetal heartbeat (P < 0.01); double trisomy, polyploidy and normal karyotype were significantly more frequent with no fetal heartbeat (P < 0.01). There was no significant difference in the frequency of chromosomal abnormalities between the number of miscarriages or blastocyst quality. Thus, POC cytogenetic testing is highly valuable for ascertaining the cause of miscarriage.

Reproductive outcomes following preimplantation genetic diagnosis using fluorescence in situ hybridization for 52 translocation carrier couples with a history of recurrent pregnancy loss.

Forty-six reciprocal and six Robertsonian translocation carrier couples who experienced recurrent pregnancy loss underwent fluorescence in situ hybridization-based preimplantation genetic diagnosis (PGD) for the presence of the two translocated chromosomes. Out of 52 couples, 17 (33%) were undergoing infertility treatment. In total, 239 PGD cycles as oocyte retrieval (OR) were applied. The transferrable rate of negatively diagnosed embryos at the cleavage stage was 26.3%; 71 embryos were transferred as single blastocysts. The clinical pregnancy rate per transfer was 60.6%. We obtained 41 healthy live births with 3 incidences of miscarriage (7.0%). The average cumulative live birth rate was 76.9% during 4.6 OR cycles using a mild ovarian stimulation strategy. The outcomes were classified into four groups based on carrier gender and maternal age (young (<38 years) or advanced). PGD was performed for 52 couples of which the average number of OR cycles was 4.1, 2.1, 6.7 and 4.5 in young female and male carriers and female and male carriers of advanced age; the live birth rate for a primiparity was 77.8, 72.7, 66.7 and 50.0% in those groups. These results suggest that the final live birth rate might be influenced by maternal age regardless of the gender of the carrier.

Synthesis and Biological Evaluation of Cyclopentaquinoline Derivatives as Nonsteroidal Glucocorticoid Receptor Antagonists.

The steroidal glucocorticoid antagonist mifepristone has been reported to improve the symptoms of depression. We report the discovery of 6-(3,5-dimethylisoxazol-4-yl)-2,2,4,4-tetramethyl-2,3,4,7,8,9-hexahydro-1H-cyclopenta[h]quinolin-3-one 3d (QCA-1093) as a novel nonsteroidal glucocorticoid receptor antagonist. The compound displayed potent in vitro activity, high selectivity over other steroid hormone receptors, and significant antidepressant-like activity in vivo.

The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function.

The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs). MSCs were shown to be capable of inducing angiogenesis and restoring the number of ovarian follicles and corpus lutea in ovaries. No deformities, tumor formation or deaths were observed in F1 and F2 rats, indicating that the local injection of MSCs into the ovary did not have any obvious side effects. In addition, the localization of the Y chromosome was investigated using the fluorescent in situ hybridization method by injecting male A-MSCs into the ovaries; as a result, the Y chromosomes were localized not in the follicles, but in the thecal layers. ELISA revealed that A-MSCs secreted higher levels of vascular endothelial cell growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) than tail fibroblast cells. Quantitative real-time PCR and immunohistochemistry showed that higher expression levels of VEGF, IGF-1 and HGF were observed in CTX-treated ovaries after A-MSC transplantation. These findings suggest that MSCs may have a role in restoring damaged ovarian function and could be useful for regenerative medicine.

Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified versus fresh single embryo transfer.

OBJECTIVE: To compare neonatal outcome between children born after vitrified versus fresh single-embryo transfer (SET). STUDY DESIGN: Retrospective, single-centre cohort study of 6623 delivered singletons following 29,944 single-embryo transfers. Patients underwent minimal ovarian stimulation/natural cycle IVF followed by SET of fresh or vitrified-warmed (using Cryotop, Kitazato) cleavage-stage embryos or blastocysts. Outcome measures were gestational age at delivery, birth weight, birth length, low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA) infants, perinatal mortality and minor/major birth defects (evaluated by parent questionnaire). RESULTS: Gestational age (38.6 ± 2 versus 38.7 ± 1.9 weeks) and preterm delivery rate (6.9% versus 6.9%, aOR: 0.96 95%CI: 0.76-1.22) in singletons born after the transfer of vitrified embryos were comparable to those born after the transfer of fresh embryos. Children born after the transfer of vitrified embryos had a higher birth weight (3028 ± 465 versus 2943 ± 470 g, p<0.0001) and lower LBW (8.5% versus 11.9%, aOR: 0.65 95%CI: 0.53-0.79) and SGA (3.6% versus 7.6% aOR: 0.43 95%CI: 0.33-0.56) rates. Total birth defect rates (including minor anomalies) (2.4% versus 1.9%, aOR: 1.41 95%CI: 0.96-2.10) and perinatal mortality rates (0.6% versus 0.5%, aOR: 1.02 95%CI: 0.21-4.85) were comparable between the vitrified and fresh groups. CONCLUSIONS: Vitrification of embryos/blastocysts did not increase the incidence of adverse neonatal outcomes or birth defects following single embryo transfer.

Relationship between educational programs offered at midsize hospitals in Japan and novice nurses' anxiety levels.

BACKGROUND: This article describes training methods for novice nurses in midsize hospitals and examines how preceptorship is related to their anxiety levels. METHODS: Questionnaires were sent to nurse managers in 15 hospitals; completed questionnaires were received from 11 hospitals. Sixty-three novice nurses evaluated the educational programs, and their anxiety levels were determined using the State-Trait Anxiety Inventory. RESULTS: Ten hospitals performed group orientation. Among these, 8 hospitals had a preceptorship program. The novice nurses in hospitals with a preceptorship program reported that preceptorship offered learning opportunities. CONCLUSION: It is important that novice nurses receive appropriate education, which will reduce their anxiety.

Rubeosis iridis after bilateral cataract surgery and its spontaneous regression in a patient with myotonic dystrophy.

A 49-year-old cataract patient with myotonic dystrophy had phacoemulsification and intraocular lens implantation in both eyes. Rubeosis iridis developed bilaterally 10 days later and began to regress without treatment 2 weeks after the surgery. It was completely absent 1 year after the surgery. These findings indicate that surgeons should be aware that rubeosis iridis can develop in myotonic patients after cataract surgery.

Alterations in retinal nerve fiber layer thickness following indirect traumatic optic neuropathy detected by nerve fiber analyzer, GDx-N.

PURPOSE: To evaluate changes in the retinal nerve fiber layer following traumatic optic neuropathy. DESIGN: Observational case report. METHODS: A patient presented with visual loss after an accident. Scanning laser polarimetry was performed. RESULTS: Thickness of the retinal nerve fiber layer increased immediately after the trauma but then progressively decreased. Severe loss was observed at day 90 and then ceased. Enlargement of the optic disk cup was also observed. CONCLUSIONS: This is the first report documenting early transient increase followed by progressive loss of the retinal nerve fiber layer in traumatic optic neuropathy.