Publications by authors named "Osamu Ishihara"

96 Publications

International Committee for Monitoring Assisted Reproductive Technologies (ICMART): world report on assisted reproductive technologies, 2013.

Fertil Steril 2021 Apr 26. Epub 2021 Apr 26.

Equal3 Fertility, Cupertino; Stanford University School of Medicine, Palo Alto; and University of California School of Medicine, San Francisco, California.

Objective: To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2013 and assess global trends over time.

Design: Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2013.

Setting: Seventy-five countries and 2,639 ART clinics.

Patient(s): Women and men undergoing ART procedures.

Intervention(s): All ART.

Main Outcome Measure(s): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART).

Result(s): A total of 1,858,500 ART cycles were conducted for the treatment year 2013 across 2,639 clinics in 75 participating countries with a global participation rate of 73.6%. Reported and estimated data suggest 1,160,474 embryo transfers (ETs) were performed resulting in >344,317 babies. From 2012 to 2013, the number of reported aspiration and frozen ET cycles increased by 3% and 16.4%, respectively. The proportion of women aged >40 years undergoing nondonor ART increased from 25.2% in 2012 to 26.3% in 2013. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) was similar to results for 2012. The in vitro fertilization (IVF)/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 24.2% and 22.8%, respectively. In fresh nondonor cycles, single ET increased from 33.7% in 2012 to 36.5% in 2013, whereas the average number of transferred embryos was 1.81-again with wide country variation. The rate of twin deliveries after fresh nondonor transfers was 17.9%; the triplet rate was 0.7%. In frozen ET cycles performed in 2013, single ET was used in 57.6%, with an average of 1.49 embryos transferred and twin and triplet rates of 10.8% and 0.4%, respectively. The cumulative delivery rate per aspiration was 30.4%, similar to that in 2012. Perinatal mortality rate per 1,000 births was 22.2% after fresh IVF/ICSI and 16.8% after frozen ET. The data presented depended on the quality and completeness of the data submitted by individual countries. This report covers approximately two-thirds of world ART activity. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed.

Conclusion(s): Reported ART cycles, effectiveness, and safety increased between 2012 and 2013 with adoption of a better method for estimating unreported cycles.
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http://dx.doi.org/10.1016/j.fertnstert.2021.03.039DOI Listing
April 2021

Cesarean delivery rates for overall and multiple pregnancies in Japan: A descriptive study using nationwide health insurance claims data.

J Obstet Gynaecol Res 2021 Jun 28;47(6):2099-2109. Epub 2021 Mar 28.

Department of Environmental Health Science and Public Health, Akita University Graduate School of Medicine, Akita, Japan.

Aim: Due to the lack of national perinatal registries, population-wide descriptive statistics on cesarean deliveries in Japan are unknown. We aim to describe cesarean deliveries for overall and multiple pregnancies using the Japan National Database of health insurance claims.

Methods: We calculated the national and prefectural cesarean delivery rates for overall and multiple pregnancies in 2014. We described maternal morbidities (e.g., blood transfusion) and the place and type of the institutions providing prenatal and perinatal care.

Results: The national cesarean delivery rates were 18.6% overall and 82.7% for women with multiple pregnancies. Prefectural cesarean delivery rates for overall and multiple pregnancies varied from 12.5% to 24.2% and from 49.2% to 100%, respectively, showing a moderate positive correlation (r = 0.59, p < 0.001). Overall, 1.4% of cesarean patients received an allogeneic blood transfusion, compared to 3.2% for those with multiple pregnancies. In addition, 65.9% of overall cesarean deliveries occurred at hospitals with ≥20 beds, whereas 94.6% of cesarean patients with multiple pregnancies delivered at hospitals. Older patients were more likely to receive their cesarean section at a different institution than their first visit within the same prefecture, but trans-prefectural movement during pregnancy covered by health insurance was most frequent among those in their early thirties: 7.0% overall and 10.7% for multiple pregnancies.

Conclusions: The overall cesarean delivery rate in Japan was optimal, but the rate was high for multiple pregnancies, with large regional differences. Data on patient movement across institutions and areas would help to improve the perinatal care system.
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http://dx.doi.org/10.1111/jog.14772DOI Listing
June 2021

Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial.

Reprod Biomed Online 2021 May 9;42(5):909-918. Epub 2021 Feb 9.

Ferring Pharmaceuticals, Reproductive Medicine & Maternal Health, Copenhagen, Denmark. Electronic address:

Research Question: This study aimed to establish the efficacy and safety of ovarian stimulation with a follitropin delta individualized fixed-dose regimen based on serum anti-Müllerian hormone (AMH) concentration and body weight versus conventional follitropin beta dosing in Japanese women.

Design: This randomized, controlled, assessor-blind, multicentre, non-inferiority trial was conducted in 347 Japanese IVF/intracytoplasmic sperm injection patients. They were randomized to individualized follitropin delta (AMH <15 pmol/l: 12 µg/day; AMH ≥15 pmol/l: 0.10-0.19 µg/kg/day; minimum 6 µg/day; maximum 12 µg/day) or conventional follitropin beta (150 IU/day for the first 5 days, with potential subsequent dose adjustments). The primary end-point was the number of oocytes retrieved with a pre-specified non-inferiority margin (-3.0 oocytes).

Results: The primary trial objective was met, as non-inferiority was established for number of oocytes retrieved for individualized follitropin delta dosing compared with conventional follitropin beta dosing (9.3 versus 10.5; lower boundary of 95% confidence interval -2.3). The occurrence of ovarian hyperstimulation syndrome (OHSS) was reduced to approximately half with individualized compared with conventional dosing, with an incidence of 11.2% versus 19.8% (P = 0.021) for OHSS of any grade and 7.1% versus 14.1% (P = 0.027) for moderate/severe OHSS. The live birth rate per started cycle was 23.5% for individualized dosing and 18.6% for conventional dosing.

Conclusions: Dosing with individualized follitropin delta in Japanese women is non-inferior to conventional dosing with follitropin beta for number of oocytes retrieved. The individualized approach shows a favourable benefit-risk profile, providing a statistically significant and clinically relevant reduction in the incidence of OHSS, without compromising live birth rates.
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http://dx.doi.org/10.1016/j.rbmo.2021.01.023DOI Listing
May 2021

Klebsiella pneumoniae-induced pyogenic liver abscess secondary to oocyte pick-up.

Taiwan J Obstet Gynecol 2021 03;60(2):382-383

Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.

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http://dx.doi.org/10.1016/j.tjog.2020.11.033DOI Listing
March 2021

Assisted reproductive technology in Japan: A summary report for 2018 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Reprod Med Biol 2021 Jan 20;20(1):3-12. Epub 2020 Nov 20.

Department of Obstetrics and Gynecology Faculty of Medicine The University of Tokyo Tokyo Japan.

Purpose: Since 2007, the Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle-based data for assisted reproductive technology (ART) in an online registry. Here, we present the characteristics and treatment outcomes of ART cycles registered during 2018.

Methods: The Japanese ART registry consists of cycle-specific information for all ART treatment cycles implemented at 621 participating facilities. We conducted descriptive analyses for such cycles registered for 2018.

Results: In total, 454 893 treatment cycles and 56 979 neonates were reported in 2018: both increased from 2017. The mean maternal age was 38.0 years (standard deviation ± 4.7). Of 247 402 oocyte retrievals, 118 378 (47.8%) involved freeze-all-embryos cycles; fresh embryo transfer (ET) was performed in 50 463 cycles: a decreasing trend since 2015. A total of 199 914 frozen-thawed ET cycles were reported, resulting in 69 357 pregnancies and 49 360 neonates born. Single ET (SET) was performed in 82.2% of fresh transfers and 83.4% of frozen-thawed cycles, with singleton pregnancy/live birth rates of 97.2%/97.2% and 97.0%/97.2%, respectively.

Conclusions: Total ART cycles and subsequent live births increased in 2018. SET was performed in over 80% of cases, and the mode of ET has shifted continuously from using fresh embryos to frozen-thawed ones compared with previous years.
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http://dx.doi.org/10.1002/rmb2.12358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812461PMC
January 2021

Randomized, assessor-blind, antimüllerian hormone-stratified, dose-response trial in Japanese in vitro fertilization/intracytoplasmic sperm injection patients undergoing controlled ovarian stimulation with follitropin delta.

Fertil Steril 2021 Jun 4;115(6):1478-1486. Epub 2020 Dec 4.

Ferring Pharmaceuticals, Reproductive Medicine & Maternal Health, Copenhagen, Denmark. Electronic address:

Objective: To establish the relationship between follitropin delta doses (recombinant follicle-stimulating hormone produced from the human cell line PER.C6) and ovarian response in Japanese women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment and to evaluate the influence of initial antimüllerian hormone (AMH) levels.

Design: Randomized, controlled, assessor-blind, AMH-stratified (low 5.0-14.9 pmol/L; high 15.0-44.9 pmol/L) dose-response trial.

Setting: Reproductive medicine clinics.

Patient(s): A total of 158 Japanese women (20-39 years of age).

Intervention(s): Controlled ovarian stimulation with 6, 9, or 12 μg/d of follitropin delta or 150 IU/d follitropin beta as a reference arm in a gonadotropin-releasing hormone antagonist cycle.

Main Outcome Measure(s): Number of oocytes retrieved.

Result(s): Among all women who started stimulation, the mean number (± standard deviation) of oocytes retrieved in the 6 μg/d, 9 μg/d, and 12 μg/d follitropin delta groups was 7.0 ± 4.1, 9.1 ± 5.6, and 11.6 ± 5.6, respectively, and a significant dose-relation was established, which also remained significant within each AMH strata. Significant dose-responses also were observed for serum estradiol, inhibin A, and progesterone at end-of-stimulation with follitropin delta. The vital pregnancy rate per started cycle with follitropin delta was 19% for 6 μg/d, 20% for 9 μg/d, and 25% for 12 μg/d. The rate of early moderate/severe ovarian hyperstimulation syndrome with follitropin delta was 8% for 6 μg/d, 8% for 9 μg/d, and 13% for 12 μg/d, with 82% of the cases in the high AMH stratum.

Conclusion(s): This trial establishes the dose-response relationship between follitropin delta and ovarian response in Japanese women.

Clinical Trial Registration Number: NCT02309671.
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http://dx.doi.org/10.1016/j.fertnstert.2020.10.059DOI Listing
June 2021

Ovarian stimulation increases the risk of ectopic pregnancy for fresh embryo transfers: an analysis of 68,851 clinical pregnancies from the Japanese Assisted Reproductive Technology registry.

Fertil Steril 2020 12 17;114(6):1198-1206. Epub 2020 Oct 17.

Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.

Objective: To evaluate the risk of ectopic pregnancies (EPs) for fresh cycles according to different ovarian stimulation protocols.

Design: Registry-based retrospective cohort study.

Setting: Not applicable.

Patient(s): A total of 68,851 clinical pregnancies after fresh single embryo transfer between 2007 and 2015.

Intervention (s): None MAIN OUTCOME MEASURE(S): Ectopic pregnancies. Odds ratios and 95% confidence intervals for EPs were calculated by using generalized estimating equations adjusted for potential maternal and treatment characteristics.

Result(s): Among 68,851 clinical pregnancies, 1,049 (1.46%) cases of EP were reported. Compared with natural cycles, all ovarian stimulation protocols were associated with a significantly increased risk of EP. Ovarian stimulation with clomiphene (CC) demonstrated the highest odds ratios for EPs. Significant associations between ovarian stimulation protocols and EP compared with natural cycles were prominent when the number of retrieved oocytes was low (1-3) to moderate (4-7), but there were no significant associations when the number of retrieved oocytes was high (≥8).

Conclusion(s): Ovarian stimulation protocols were significantly associated with an increased risk of EP. In particular, ovarian stimulation with CC had the highest risk of EP compared with other stimulation protocols. Further studies are essential to investigate possible confounding factors for different ovarian stimulation protocols, especially CC, and the risk of EP.
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http://dx.doi.org/10.1016/j.fertnstert.2020.06.032DOI Listing
December 2020

High stretch cycling inhibits the morphological and biological decidual process in human endometrial stromal cells.

Reprod Med Biol 2020 Oct 20;19(4):378-384. Epub 2020 Jul 20.

Department of Obstetrics and Gynecology Saitama Medical University Iruma-gun Japan.

Purpose: Subendometrial myometrium exerts wave-like activity throughout the menstrual cycle, and uterine peristalsis is markedly reduced during the implantation phase. We hypothesized that abnormal uterine peristalsis has an adverse effect on the endometrial decidualization process. We conducted an in vitro culture experiment to investigate the effect of cyclic stretch on the morphological and biological endometrial decidual process.

Methods: Primary human endometrial stromal cells (HESCs) were isolated from hysterectomy specimens and incubated with or without 8-bromo-cyclic adenosine monophosphate (8-br-cAMP) and medroxyprogesterone acetate (MPA) for 3 days. After decidualization, cultures were continued for 24 hours with or without cyclic stretch using a computer-operated cell tension system.

Results: Cyclic stretch significantly repressed expression of decidual markers including insulin-like growth factor-binding protein 1 (), prolactin (), forkhead box O1 (), and on decidualized HESCs. In addition, cyclic stretch of decidualized HESCs affected the decidual morphological phenotype to an elongated shape. The alternation of F-actin localization in decidualized HESCs was not observed in response to cyclic stretch.

Conclusions: These data suggest that cyclic stretch inhibits the morphological and biological decidual process of HESCs. Our findings imply that uterine abnormal contractions during the implantation period impair endometrial decidualization and contribute to infertility.
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http://dx.doi.org/10.1002/rmb2.12341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542020PMC
October 2020

Identifying suitable indicators of access to infertility care - a discussion.

Reprod Biomed Online 2020 12 17;41(6):1158. Epub 2020 Sep 17.

Clinica las Condes and Program of Ethics and Public Policies in Human Reproduction, University Diego Portales, Santiago, Chile.

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http://dx.doi.org/10.1016/j.rbmo.2020.09.009DOI Listing
December 2020

International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology 2012†.

Hum Reprod 2020 08;35(8):1900-1913

Equal3 Fertility, Cupertino, CA, USA.

Study Question: What was the utilization, effectiveness and safety of practices in ART globally in 2012 and what global trends could be observed?

Summary Answer: The total number of ART cycles increased by almost 20% since 2011 and the main trends were an increase in frozen embryo transfers (FET), oocyte donation, preimplantation genetic testing and single embryo transfers (SET), whereas pregnancy and delivery rates (PR, DR) remained stable, and multiple deliveries decreased.

What Is Known Already: ART is widely practiced throughout the world, but continues to be characterized by significant disparities in utilization, availability, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report provides a major tool for tracking trends in ART treatment for over 25 years and gives important data to ART professionals, public health authorities, patients and the general public.

Study Design, Size, Duration: A retrospective, cross-sectional survey on the utilization, effectiveness and safety of ART procedures performed globally during 2012 was carried out.

Participants/materials, Setting, Methods: Sixty-nine countries and 2600 ART clinics submitted data on ART cycles performed during the year 2012, and their pregnancy outcome, through national and regional ART registries. ART cycles and outcomes are described at country, regional and global levels. Aggregate country data were processed and analyzed based on methods developed by ICMART.

Main Results And Role Of Chance: A total of 1 149 817 ART cycles were reported for the treatment year 2012. After imputing data for missing values and non-reporting clinics in reporting countries, 1 948 898 cycles (an increase of 18.6% from 2011) resulted in >465 286 babies (+17.9%) in reporting countries. China did not report and is not included in this estimate. The best estimate of global utilization including China is ∼2.8 million cycles and 0.9 million babies. From 2011 to 2012, the number of reported aspirations and FET cycles increased by 6.9% and 16.0%, respectively. The proportion of women aged 40 years or older undergoing non-donor ART increased from 24.0% in 2011 to 25.2% in 2012. ICSI, as a percentage of non-donor aspiration cycles, increased from 66.5% in 2011 to 68.9% in 2012. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycles were 19.8% and 22.1%, respectively. In fresh non-donor cycles, SET increased from 31.4% in 2011 to 33.7% in 2012, while the average number of transferred embryos decreased from 1.91 to 1.88, respectively-but with wide country variation. The rates of twin deliveries following fresh non-donor transfers decreased from 19.6% in 2011 to 18.0% in 2012, and the triplet rate decreased from 0.9% to 0.8%. In FET non-donor cycles, SET was 54.8%, with an average of 1.54 embryos transferred and twin and triplet rates of 11.1% and 0.4%, respectively. The cumulative DR per aspiration increased from 28.0% in 2011 to 28.9% in 2012. The overall perinatal mortality rate per 1000 births was 21.4 following fresh IVF/ICSI and 15.9 per 1000 following FET.

Limitations, Reasons For Caution: The data presented depend on the quality and completeness of data submitted by individual countries to ICMART directly or through regional registries. This report covers approximately two-thirds of` world ART activity, with a major missing country, China. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed, including the use of internationally agreed standard definitions (International Glossary of Infertility and Fertility Care).

Wider Implications Of The Findings: The ICMART world reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment continues to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policy makers. With the increasing practice of SET and of freeze all and resulting increased proportion of FET cycles, it is clear that PR and DR per aspiration in fresh cycles do not give an overall accurate estimation of ART efficiency. It is time to use cumulative live birth rate per aspiration, combining the outcomes of FET cycles with the associated fresh cycle from which the embryos were obtained, and to obtain global consensus on this approach.

Study Funding/competing Interest(s): The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART gratefully acknowledges financial support from the following organizations: American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Reproductive Technology; Ferring Pharmaceuticals and Abbott (both providing ICMART unrestricted grants unrelated to world reports).

Trial Registration Number: NA.
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http://dx.doi.org/10.1093/humrep/deaa090DOI Listing
August 2020

Septic Shock Caused by Fusobacterium Necrophorum after Sexual Intercourse during Recovery from Infectious Mononucleosis in an Adolescent: A Case Report.

J Pediatr Adolesc Gynecol 2020 Oct 26;33(5):566-569. Epub 2020 Jun 26.

Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.

Background: Infectious mononucleosis (IM) develops after primary infection with Epstein-Barr virus. We report a case of septic shock from pelvic inflammatory disease caused by Fusobacterium necrophorum in an adolescent after sexual intercourse during recovery from IM.

Case: A 17-year-old girl with a 7-day history of fever was diagnosed with IM. During follow-up, she developed lower abdominal pain and high fever after sexual intercourse and was transferred to our hospital. She was in shock and had a right ovarian abscess. Emergency laparotomy, drainage, and right adnexectomy were performed. F necrophorum was subsequently detected in blood and abscess cultures.
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http://dx.doi.org/10.1016/j.jpag.2020.06.018DOI Listing
October 2020

ART utilization: an indicator of access to infertility care.

Reprod Biomed Online 2020 07 14;41(1):6-9. Epub 2020 Mar 14.

Clinica las Condes and Program of Ethics and Public Policies in Human Reproduction, University Diego Portales, Santiago, Chile.

This commentary outlines the importance of utilizing assisted reproductive technology (ART) as an indicator of access to infertility care and provides a standard way of reporting utilization to facilitate international comparisons. Factors that influence ART utilization as well as underlying inequalities and inequities in access to care are discussed. The relevance of a marker that can inform and evaluate policy initiatives, monitor progress and document change is emphasized.
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http://dx.doi.org/10.1016/j.rbmo.2020.03.007DOI Listing
July 2020

Assisted reproductive technology in Japan: A summary report for 2017 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Reprod Med Biol 2020 Jan 21;19(1):3-12. Epub 2019 Nov 21.

Department of Urology Graduate School of Medicine Chiba University Chiba Japan.

Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle-based assisted reproductive technology (ART) data in an online registry since 2007. Herein, we present the characteristics and treatment outcomes of ART cycles registered during 2017.

Methods: We collected cycle-specific information for all ART cycles implemented at participating facilities and performed descriptive analysis.

Results: In total, 448,210 treatment cycles and 56,617 neonates (1 in 16.7 neonates born in Japan) were reported in 2017, increased from 2016; the number of initiated fresh cycles decreased for the first time ever. The mean patient age was 38.0 years (standard deviation 4.6). A total 110,641 of 245,205 egg retrieval cycles (45.1%) were freeze-all cycles; fresh embryo transfer (ET) was performed in 55,720 cycles. A total 194,415 frozen-thawed ET cycles were reported, resulting in 66,881 pregnancies and 47,807 neonates born. Single ET (SET) was performed in 81.8% of fresh transfers and 83.4% of frozen cycles, with singleton pregnancy/live birth rates of 97.5%/97.3% and 96.7%/96.6%, respectively.

Conclusions: Total ART cycles and subsequent live births increased continuously in 2017, whereas the number of initiated fresh cycles decreased. SET was performed in over 80% of cases, and ET shifted from using fresh embryos to frozen ones.
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http://dx.doi.org/10.1002/rmb2.12307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955594PMC
January 2020

Successful treatment of severe acute respiratory distress syndrome due to Group A streptococcus induced toxic shock syndrome in the third trimester of pregnancy-effectiveness of venoarterial extracorporeal membrane oxygenation: A case report.

J Obstet Gynaecol Res 2020 Jan 8;46(1):167-172. Epub 2019 Oct 8.

Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.

We report a case of Group A streptococcal infection-induced toxic shock syndrome (GAS-TSS) with severe acute respiratory distress syndrome (ARDS), successfully treated with venoarterial extracorporeal membrane oxygenation (V-A ECMO). A 31-year-old woman was transferred due to high fever, continuous uterine contractions and fetal bradycardia at 31 weeks of gestation. She was in a shock status on arrival, and as fetal heart beat disappeared, we canceled the cesarean section and took priority in maternal rescue. At 21 h after the admission, pulseless ventricular tachycardia occurred, and V-A ECMO was introduced after defibrillation, which dramatically improved her respiratory and circulatory conditions. On the 3rd day, GAS was isolated from blood culture. The patient was freed from V-A ECMO on the 5th day and was discharged on the 25th day without permanent impairment. V-A ECMO should be considered as an effective therapeutic option against ARDS and circulation failure in GAS-TSS during pregnancy.
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http://dx.doi.org/10.1111/jog.14138DOI Listing
January 2020

Endometrial preparation methods for frozen-thawed embryo transfer are associated with altered risks of hypertensive disorders of pregnancy, placenta accreta, and gestational diabetes mellitus.

Hum Reprod 2019 08;34(8):1567-1575

Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo 157-8535, Japan.

Study Question: What were the risks with regard to the pregnancy outcomes of patients who conceived by frozen-thawed embryo transfer (FET) during a hormone replacement cycle (HRC-FET)?

Summary Answer: The patients who conceived by HRC-FET had increased risks of hypertensive disorders of pregnancy (HDP) and placenta accreta and a reduced risk of gestational diabetes mellitus (GDM) in comparison to those who conceived by FET during a natural ovulatory cycle (NC-FET).

What Is Known Already: Previous studies have shown that pregnancy and live-birth rates after HRC-FET and NC-FET are comparable. Little has been clarified regarding the association between endometrium preparation and other pregnancy outcomes.

Study Design, Size, Duration: A retrospective cohort study of patients who conceived after HRC-FET and those who conceived after NC-FET was performed based on the Japanese assisted reproductive technology registry in 2014.

Participants/materials, Setting, Methods: The pregnancy outcomes were compared between NC-FET (n = 29 760) and HRC-FET (n = 75 474) cycles. Multiple logistic regression analyses were performed to investigate the potential confounding factors.

Main Results And The Role Of Chance: The pregnancy rate (32.1% vs 36.1%) and the live birth rate among pregnancies (67.1% vs 71.9%) in HRC-FET cycles were significantly lower than those in NC-FET cycles. A multiple logistic regression analysis showed that pregnancies after HRC-FET had increased odds of HDPs [adjusted odds ratio, 1.43; 95% confidence interval (CI), 1.14-1.80] and placenta accreta (adjusted odds ratio, 6.91; 95% CI, 2.87-16.66) and decreased odds for GDM (adjusted odds ratio, 0.52; 95% CI, 0.40-0.68) in comparison to pregnancies after NC-FET.

Limitations, Reasons For Caution: Our study was retrospective in nature, and some cases were excluded due to missing data. The implication of bias and residual confounding factors such as body mass index, alcohol consumption, and smoking habits should be considered in other observational studies.

Wider Implications Of The Findings: Pregnancies following HRC-FET are associated with higher risks of HDPs and placenta accreta and a lower risk of GDM. The association between the endometrium preparation method and obstetrical complication merits further attention.

Study Funding/competing Interest(s): No funding was obtained for this work. The authors declare no conflicts of interest in association with the present study.

Trial Registration Number: Not applicable.
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http://dx.doi.org/10.1093/humrep/dez079DOI Listing
August 2019

Male subfertility and the risk of major birth defects in children born after in vitro fertilization and intracytoplasmic sperm injection: a retrospective cohort study.

BMC Pregnancy Childbirth 2019 Jun 3;19(1):192. Epub 2019 Jun 3.

Division of Reproductive Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.

Background: Children born after intracytoplasmic sperm injection (ICSI) are at increased risk of specific major birth defects compared with children born after in vitro fertilization (IVF). However, whether this risk is due to the treatment itself (i.e., IVF or ICSI) or underlying male subfertility is unknown. This study investigated the associations between male subfertility and the risk of major birth defects in children born after IVF and ICSI.

Methods: We conducted a retrospective cohort study using data from the Japanese assisted reproductive technology registry between 2007 and 2014. Fresh embryo transfer cycles registered from 2007 to 2014 that resulted in singleton live births, still births, or selective terminations were included (n = 59,971). Major birth defects were defined by the US Centers for Disease Control and Prevention guidelines, excluding chromosomal abnormalities. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using generalized estimating equations adjusting for potential confounders.

Results: Major birth defects were reported in 626/59,971 (1.04%) cases. Among IVF cycles, male subfertility was associated with significantly greater risks of hypospadias (3/3163 [0.09%] vs 4/28,671 [0.01%], adjusted OR = 6.85, 95% CI 2.05-22.9, P = 0.002) and atrial septal defects (4/3163 [0.13%] vs 9/28,671 [0.03%], adjusted OR = 3.98, 95% CI 1.12-14.1, P = 0.03) compared with fertile men. Subgroup analysis using sperm parameters showed that oligozoospermia (i.e., sperm concentrations < 15 million/mL) was significantly associated with a greater risk of ventricular septal defects compared with normal sperm concentrations in IVF pregnancies (5/868 [0.58%] vs 60/28,090 [0.21%], adjusted OR = 2.68, 95% CI 1.15-6.27, P = 0.02), and severe oligozoospermia (i.e., sperm concentrations < 5 million/mL) was significantly associated with an increased risk of hypospadias compared with normal sperm concentrations in ICSI pregnancies (5/3136 [0.16%] vs 5/16,865 [0.03%], adjusted OR = 3.88, 95% CI 1.14-13.2, P = 0.03).

Conclusions: The results of this exploratory study suggest that underlying male subfertility may play a role in the risk of major birth defects related to ICSI and IVF. Further research, including systematic reviews adjusting for confounders, is required to confirm the associations between male subfertility and major cardiac and urogenital birth defects.
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http://dx.doi.org/10.1186/s12884-019-2322-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547560PMC
June 2019

Heparin prevents oxidative stress-induced apoptosis in human decidualized endometrial stromal cells.

Med Mol Morphol 2019 Dec 16;52(4):209-216. Epub 2019 Mar 16.

Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan.

Clinical trials have shown that administering heparin during the luteal phase has beneficial effects on implantation and live birth rates. Heparin exerts direct effects on decidual human endometrial stromal cells (HESCs), which are independent of its anticoagulant effect. However, the accurate effects of heparin on the decidualization process remain unidentified. Here, we demonstrate that HESCs become dramatically resistant to oxidative stress upon decidualization, and we hypothesize a possible direct action of heparin on the decidualization of HESCs, which would lead to improved implantation. To test this hypothesis, we established primary HESC cultures and propagated them, and then we decidualized confluent cultures with 8-bromo-cAMP, with medroxyprogesterone acetate, and with or without heparin. We treated the cells with hydrogen peroxide (HO) as a source of reactive oxygen species (ROS). Adding heparin to decidualized HESCs induced prolactin secretion. Decidualized HESCs treated with heparin were prevented from undergoing apoptosis induced by oxidative stress. Heparin induced nuclear accumulation of the forkhead transcription factor FOXO1 and expression of its downstream target, the ROS scavenger superoxide dismutase 2. These results demonstrate that heparin-treated decidualized HESCs acquired further resistance to oxidative stress, suggesting that heparin may improve the implantation environment.
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http://dx.doi.org/10.1007/s00795-019-00220-xDOI Listing
December 2019

Extracellular matrix signaling activates differentiation of adult ovary-derived oogonial stem cells in a species-specific manner.

Fertil Steril 2019 04 11;111(4):794-805. Epub 2019 Mar 11.

Laboratory of Aging and Infertility Research, Department of Biology, Northeastern University, Boston, Massachusetts. Electronic address:

Objective: To test if ovarian microenvironmental cues affect oogonial stem cell (OSC) function in a species-specific manner.

Design: Animal and human study.

Setting: Research laboratory.

Patient(s)/animal(s): Human ovarian cells obtained from cryopreserved ovarian cortical tissue of reproductive-age women, and ovarian cells and tissues from female C57BL/6 mice.

Intervention(s): Mouse ovarian tissue, mouse OSCs (mOSCs) and human OSCs (hOSCs) were analyzed for extracellular matrix (ECM) protein expression, and OSCs isolated from adult mouse and human ovaries were cultured in the absence or presence of ECM proteins without or with an integrin signaling inhibitor.

Main Outcome Measure(s): Gene expression and in vitro derived (IVD) oocyte formation.

Result(s): Culture of mOSCs on a collagen-based ECM significantly elevated the rate of differentiation of the cells into IVD oocytes. Mouse OSCs expressed many integrins, including Arg-Gly-Asp (RGD)-binding subunits, and ECM-mediated increases in mOSC differentiation were blocked by addition of integrin-antagonizing RGD peptides. In comparison, hOSCs expressed a different pattern of integrin subunits compared with mOSCs, and hOSCs were unresponsive to a collagen-based ECM; however, hOSCs exhibited increased differentiation into IVD oocytes when cultured on laminin.

Conclusion(s): These data, along with in silico analysis of ECM protein profiles in human ovaries, indicate that ovarian ECM-based niche components function in a species-specific manner to control OSC differentiation.
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http://dx.doi.org/10.1016/j.fertnstert.2018.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462309PMC
April 2019

Neonatal outcomes following different ovarian stimulation protocols in fresh single embryo transfer.

Sci Rep 2019 02 28;9(1):3076. Epub 2019 Feb 28.

Division of Reproductive Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.

Previous studies suggested ovarian stimulation was associated with lower birth weight and higher risk of preterm delivery (PTD) from fresh embryo transfers (ETs). However, whether the increased risk differs between distinct ovarian stimulation protocols remains unknown. A retrospective cohort study of 38,220 singleton deliveries after fresh single ETs from 2007 to 2013 was conducted. Main outcomes were birth weight and gestational length. Compared with the natural cycle, all ovarian stimulation protocols were associated with a significantly increased risk for PTD, low birth weight (LBW) and small for gestational age (SGA). In subgroup analysis of maternal age under 35 years, luteal support using progesterone, and early cleavage ETs, the significant associations remained for LBW and SGA in gonadotropin-releasing hormone (GnRH) antagonist protocol and for LBW in GnRH agonist protocol. Ovarian stimulation using clomiphene citrate (CC) had the highest increased risks for LBW (Adjusted odds ratio [AOR], 1.58, 95% confidence interval [95% CI], 1.43-1.73) and SGA (AOR, 1.65, 95% CI, 1.50-1.82) compared with natural cycles, and was further associated with PTD and cesarean section. These findings suggest ovarian stimulation was associated with lower birth weight, and CC may have adverse effect on neonatal outcomes in fresh cycles.
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http://dx.doi.org/10.1038/s41598-019-38724-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395801PMC
February 2019

Association of the hypoxia-inducible factor-1α (HIF-1α) gene polymorphisms with prognosis in ovarian clear cell carcinoma.

J Ovarian Res 2019 Jan 24;12(1). Epub 2019 Jan 24.

Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan.

Background: Ovarian clear cell carcinoma (OCCC) is the second most common ovarian cancer after serous carcinoma in Japan. OCCC has a more unfavorable clinical outcome due to a poor response to platinum-based chemotherapy, compared with serous carcinoma. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of cellular response to hypoxia and plays an important role in tumor growth, and HIF-1α gene single-nucleotide polymorphisms (SNPs) adversely affect the outcome in some cancers. Herein, we investigated the association of the HIF-1α gene SPNs with clinical outcome in OCCCs. Eighty-nine patients with OCCC were recruited in whom pathological diagnosis was confirmed with surgically resected specimen.

Results: The SNPs of C1772T and G1790A in the HIF-1α gene occurred in 23.6 and 3.3% of the patients, respectively. In the univariate analysis, overall survival was associated with stage and surgical residual tumor but not with the SNPs C1772T, G1790A, C1772T and/or G1790A. In the multivariate survival analysis, a significant association was observed between outcome and FIGO stage and/or surgical residual tumor; however, no association was obtained between HIF-1α gene SNPs and these factors.

Conclusion: In conclusion, unlike the other cancers in which HIF-1α gene SNPs were demonstrated to be associated with the outcome, OCCC prognosis may not be affected by HIF-1α gene SNPs. Further studies need to be performed to clarify the association of HIF-1α expression with the unfavorable prognosis in OCCCs, in terms of transcriptional/translational activity, nuclear translocation of the protein, and protein degradation.
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http://dx.doi.org/10.1186/s13048-019-0481-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345011PMC
January 2019

Assisted reproductive technology in Japan: A summary report for 2016 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Reprod Med Biol 2019 Jan 29;18(1):7-16. Epub 2018 Nov 29.

Division of Reproductive Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine National Center for Child Health and Development Tokyo Japan.

Purpose: The Japan Society of Obstetrics and Gynecology started an online cycle-based assisted reproductive technology (ART) registry system in 2007. This report presents the characteristics and treatment outcomes of ART registered for the cycles practiced during 2016.

Methods: Cycle-specific information for all ART cycles implemented in participating ART facilities were collected. A descriptive analysis was conducted for the registry database of 2016.

Results: In total, 447 790 treatment cycles and 54 110 neonates (one in 18.1 neonates born in Japan) were reported in 2016. The mean patients' age was 38.1 years (SD = 4.5). Among the egg retrieval cycles, 104 575 of 251 399 (41.6%) were freeze-all cycles without fresh embryo transfers (ET), while fresh ET was performed in 64 497 cycles (58.4%). A total of 187 132 frozen-thawed ET cycles were reported, resulting in 62 432 pregnancies and 44 484 neonates born. Single ET was selected for 81.0% of fresh transfers and 82.7% of frozen cycles, resulting in singleton pregnancy/live birth rates of 97.0%/96.4% and 96.7%/96.4%, respectively.

Conclusion: The total ART cycles and subsequent live births continued to increase in 2016. Single ET was performed more than 80%, and ET has shifted from using fresh embryos to frozen ones.
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http://dx.doi.org/10.1002/rmb2.12258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332769PMC
January 2019

International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011.

Fertil Steril 2018 11;110(6):1067-1080

Department of Obstetrics & Gynaecology Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Objective: To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2011 and assess global trends over time.

Design: Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2011.

Setting: Sixty-five countries and 2,560 ART clinics.

Patient(s): Women and men undergoing ART procedures.

Intervention(s): All ART.

Main Outcome Measure(s): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART).

Result(s): A total of 1,115,272 ART cycles were reported for the treatment year 2011. Imputing data for nonreporting clinics, 1,643,912 cycles resulted in >394,662 babies, excluding People's Republic of China. The best estimate of global utilization including People's Republic of China is approximately 2.0 million cycles and 0.5 million babies. From 2010 to 2011, the number of reported aspiration and frozen ET cycles increased 13.1% and 13.8%, respectively. The proportion of women aged ≥40 years undergoing nondonor ART increased from 23.2% in 2010 to 24.0% in 2011. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) decreased slightly from 67.4% in 2010 to 66.5% in 2011. The IVF/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 19.8% and 21.4%, respectively. In fresh nondonor cycles, single ET increased from 30.0% in 2010 to 31.4% in 2011, whereas the average number of transferred embryos decreased from 1.95 in 2010 to 1.91 in 2011-again with wide country variation. The rates of twin deliveries after fresh nondonor transfers decreased from 20.4% in 2010 to 19.6% in 2011; the triplet rate decreased from 1.1%-0.9%. In frozen ET cycles performed in 2011, single ET was 51.6%, with an average of 1.59 embryos transferred and twin and triplet rates were 11.1% and 0.4%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 28.0% in 2011. Fresh IVF/ICSI carried a perinatal mortality rate per 1,000 births of 21.0 in 2010 and 16.3 in 2011. This compared with a perinatal mortality rate after frozen ET of 14.6 per 1,000 births in 2010 and 8.6 in 2011. The data presented depend on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of'world ART activity.

Conclusion(s): Global ART utilization, effectiveness, and safety increased between 2010 and 2011.
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http://dx.doi.org/10.1016/j.fertnstert.2018.06.039DOI Listing
November 2018

Loss of high-mobility group N5 contributes to the promotion of human endometrial stromal cell decidualization.

Reprod Med Biol 2018 Oct 16;17(4):493-499. Epub 2018 Aug 16.

Department of Obstetrics and Gynecology Saitama Medical University Saitama Japan.

Purpose: High-mobility group N (HMGN) proteins are the only non-histone proteins that specifically bind within the nucleosome between core histones and DNA. Among them, HMGN5 is one of the candidates that could participate in mouse endometrial decidualization; however, the specific role of HMGN5 remains to be clarified in human endometrial stromal cells (HESCs).

Methods: Primary HESCs were isolated from hysterectomy specimens and incubated with or without 8-bromo-cyclic adenosine monophosphate (8-br-cAMP) and medroxyprogesterone acetate (MPA).

Results: We demonstrated that HMGN5 expression in decidualized HESCs stimulated by 8-br-cAMP and MPA decreased significantly. The inhibition of HMGN5 expression by small interfering RNA (siRNA) induced the major decidual marker genes expression, including (insulin-like growth factor binding protein 1) and (prolactin). In addition, microRNA-542-3p (miR-542-3p), which was identified as a regulatory miRNA of during decidualization, was significantly suppressed by HMGN5 siRNA. However, the expression of HMGN5 was not alternated by miR-542-3p overexpression.

Conclusions: These findings suggest that the down-regulation of HMGN5 plays a role in the promotion of human endometrial stromal decidualization and acts upstream of miR-542-3p.
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http://dx.doi.org/10.1002/rmb2.12226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194248PMC
October 2018

Quantitative Proteomic Profiling of the Human Ovary from Early to Mid-Gestation Reveals Protein Expression Dynamics of Oogenesis and Folliculogenesis.

Stem Cells Dev 2018 06 29;27(11):723-735. Epub 2018 May 29.

1 Department of Biology, Laboratory for Aging and Infertility Research, Northeastern University , Boston, Massachusetts.

The in vivo gene networks involved in coordinating human fetal ovarian development remain obscure. In this study, quantitative mass spectrometry was conducted on ovarian tissue collected at key stages during the first two trimesters of human gestational development, confirming the expression profiling data using immunofluorescence, as well as in vitro modeling with human oogonial stem cells (OSCs) and human embryonic stem cells (ESCs). A total of 3,837 proteins were identified in samples spanning developmental days 47-137. Bioinformatics clustering and Ingenuity Pathway Analysis identified DNA mismatch repair and base excision repair as major pathways upregulated during this time. In addition, MAEL and TEX11, two key meiosis-related proteins, were identified as highly expressed during the developmental window associated with fetal oogenesis. These findings were confirmed and extended using in vitro differentiation of OSCs into in vitro derived oocytes and of ESCs into primordial germ cell-like cells and oocyte-like cells, as models. In conclusion, the global protein expression profiling data generated by this study have provided novel insights into human fetal ovarian development in vivo and will serve as a valuable new resource for future studies of the signaling pathways used to orchestrate human oogenesis and folliculogenesis.
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http://dx.doi.org/10.1089/scd.2018.0002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985909PMC
June 2018

Assisted reproductive technology in Japan: a summary report for 2015 by The Ethics Committee of The Japan Society of Obstetrics and Gynecology.

Reprod Med Biol 2018 01 29;17(1):20-28. Epub 2017 Nov 29.

Department of Obstetrics and Gynecology Graduate School of Biomedical Sciences Tokushima University Tokushima Japan.

Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) implemented an assisted reproductive technology (ART) registry system in 1986. Here are reported the characteristics and treatment outcomes of ART cycles that were registered in 2015.

Methods: JSOG has requested all participating ART facilities to register cycle-specific information for all ART cycles since 2007. A descriptive analysis was performed by using the registry database for 2015.

Results: In total, 424 151 cycles and 51 001 neonates (1 in 19.7 neonates born in Japan) were registered in 2015. The patients' mean age was 38.2 years (standard deviation = 4.5). Among the fresh cycles, 94 158 of 244 718 (38.5%) egg retrieval cycles were cycles with freeze-all embryos or oocytes, while fresh embryo transfer (ET) was performed in 70 254 cycles, signaling a decrease from 2014. There were 169 898 frozen-thawed ET cycles, resulting in 56 355 pregnancies and 40 599 neonates. Single ET was performed at a rate of 79.7% for fresh and 81.8% for frozen cycles and the singleton pregnancy/live birth rates were 96.9%/96.5% and 96.8%/96.4% for the respective cycles.

Conclusion: The total ART cycles and live births resulting from ART has been increasing in Japan. Single ET was performed at a rate of almost 80% and ET cycles have shifted from fresh to frozen cycles.
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http://dx.doi.org/10.1002/rmb2.12074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768979PMC
January 2018

Weight reduction using a formula diet recovers menstruation in obese patients with an ovulatory disorder.

Reprod Med Biol 2017 07 7;16(3):268-275. Epub 2017 Jul 7.

Department of Obstetrics and Gynecology Graduate School of Biomedical Sciences Tokushima University Tokushima Japan.

Aim: To determine the effectiveness of a formula diet in weight reduction and the recovery of menstruation in obese patients with ovulatory disorders.

Methods: After the enrollment of 39 obese women with ovulatory disorders, they replaced one or two of their three normal meals with a microdiet (MD) (240 kcal/meal) for 24 weeks. Physical, endocrinological, and biochemical tests were conducted before and at 12 and 24 weeks of the study. Of the 39 women enrolled, 26 were not taking clomiphene. They were divided into three groups according to their body weight outcomes and then analyzed for menstruation recovery.

Results: A weight reduction of ≥5% was observed in 31 (81.5%) of the 39 women. There were significant decreases in the body weight and Body Mass Index during the study. Menstruation returned in 18 (69%) of the 26 patients without clomiphene treatment, with the recovery being significantly more prevalent in the groups (totally 81.0%) that exhibited a 5%-10% weight reduction and ≥10% weight reduction, compared to the group with a <5% weight reduction.

Conclusion: The use of a formula diet effectively reduced the patients' body weight and led to the recovery of menstruation in these obese patients with ovulatory disorders.
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http://dx.doi.org/10.1002/rmb2.12034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715880PMC
July 2017

Overexpression of microRNA-542-3p attenuates the differentiating capacity of endometriotic stromal cells.

Reprod Med Biol 2017 04 26;16(2):170-178. Epub 2017 Mar 26.

Department of Obstetrics and Gynecology Saitama Medical University Moroyama Japan.

Aim: Endometriosis is defined as the presence of endometrial glandular and stromal cells outside of the uterine cavity. A previous study reported that microRNA (miR)-542-3p plays a critical role in eutopic endometrial decidualization. This study aims to clarify the potential role of miR-542-3p and the target gene, (insulin-like growth factor-binding protein 1), in the impairment of the decidualizing capacity of human ectopic endometrial stromal cells (HEcESCs).

Methods: In vitro analysis of primary undifferentiated and decidualizing human eutopic endometrial stromal cells (HEuESCs) and HEcESCs was conducted. The primary HEuESCs or HEcESCs were expanded in culture and decidualized with 8-bromo-cyclic adenosine monophosphate (8-bromo-cAMP) and medroxyprogesterone acetate (MPA).

Results: The morphological and biological differentiating capacities of the HEcESCs were markedly impaired. In contrast to the HEuESCs, the HEcESCs that were treated with the decidual stimulus retained the mesenchymal phenotype and capacity for migration. The down-regulation of miR-542-3p in the HEcESCs treatment with 8-bromo-cAMP and MPA was much weaker than that of the HEuESCs. High expression of miR-542-3p led to a significant decrease in the expression of IGFBP1 in the HEcESCs.

Conclusion: Impairment of the differentiating capacity by the overexpression of miR-542-3p could influence the capacity for migration and invasion of endometriotic cells in an ectopic environment.
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http://dx.doi.org/10.1002/rmb2.12028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661816PMC
April 2017