International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010.

STUDY QUESTION: What were utilization, outcomes and practices in assisted reproductive technology (ART) globally in 2008, 2009 and 2010? SUMMARY ANSWER: Global utilization and effectiveness remained relatively constant despite marked variations among countries, while the rate of single and frozen embryo transfers (FETs) increased with a concomitant slight reduction in multiple birth rates. WHAT IS KNOWN ALREADY: ART is widely practised in all regions of the world. Monitoring utilization, an approximation of availability and access, as well as effectiveness and safety is an important component of universal access to reproductive health. STUDY DESIGN, SIZE, DURATION: This is a retrospective, cross-sectional survey on utilization, effectiveness and safety of ART procedures performed globally from 2008 to 2010. PARTICIPANTS, SETTING, METHODS: Between 58 and 61 countries submitted data from a total of nearly 2500 ART clinics each year. Aggregate country data were processed and analyzed based on forms and methods developed by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). Results are presented at country, regional and global level. MAIN RESULTS AND THE ROLE OF CHANCE: For the years 2008, 2009 and 2010, >4 461 309 ART cycles were initiated, resulting in an estimated 1 144 858 babies born. The number of aspirations increased by 6.4% between 2008 and 2010, while FET cycles increased by 27.6%. Globally, ART utilization remained relatively constant at 436 cycles/million in 2008 and 474 cycles/million population in 2010, but with a wide country range of 8-4775 cycles/million population. ICSI remained constant at around 66% of non-donor aspiration cycles. The IVF/ICSI combined delivery rate (DR) per fresh aspiration was 19.8% in 2008; 19.7% in 2009 and 20.0% in 2010, with corresponding DRs for FET of 18.8, 19.7 and 20.7%. In fresh non-donor cycles, single embryo transfer increased from 25.7% in 2008 to 30.0% in 2010, while the average number of embryos transferred fell from 2.1 to 1.9, again with wide regional variation. The rates of twin deliveries following fresh non-donor transfers were, in 2008, 2009 and 2010, 21.8, 20.5 and 20.4%, respectively, with a corresponding triplet rate of 1.3, 1.0 and 1.1%. Fresh IVF and ICSI carried a perinatal mortality rate per 1000 births of 22.8 (2008), 19.2 (2009) and 21.0 (2010), compared with 15.1, 12.8 and 14.6/1000 births following FET in the same periods of observation. The proportion of women aged 40 years or older undergoing non-donor ART increased from 20.8 to 23.2% from 2008 to 2010. LIMITATIONS, REASON FOR CAUTION: The data presented are reliant on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of the world ART activity. WIDER IMPLICATIONS OF 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 and embryo transfer practices warrant attention by clinicians and policy makers. STUDY FUNDING/COMPETING INTERESTS: The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART 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; Government of Canada (Research grant), Ferring Pharmaceuticals (Grant unrelated to World Reports). TRIAL REGISTRATION: not applicable.

International Committee for Monitoring Assisted Reproductive Technologies (ICMART) world report: assisted reproductive technology 2004.

STUDY QUESTION: Have changes in assisted reproductive technology (ART) practice and outcomes occurred globally between 2003 and 2004? SUMMARY ANSWER: Globally, ART practice has changed with an increasing prevalence of the use of ICSI rather than conventional IVF. In 2004, a small but increasing number of countries are incorporating single embryo transfer. There remain unacceptably high rates of three or more embryo transfers in select countries resulting in multiple births and adverse perinatal outcomes. WHAT IS KNOWN ALREADY: World data on the availability, effectiveness and safety of ART have been published since 1989. The number of embryos transferred is a major determinant of the iatrogenic increase in multiple pregnancies and is highly correlated with the likelihood of multiple birth and excess perinatal morbidity and mortality. STUDY DESIGN, SIZE, DURATION: Cross-sectional survey of countries and regions undertaking surveillance of ART procedures started in 2004 and their corresponding outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of total, 2184 clinics from 52 reporting countries and regions. Number of ART clinics, types of cycles and procedures, pregnancy, delivery and multiple birth rates and perinatal outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 954 743 initiated cycles resulted in an estimated 237 809 babies born. This was a 2.3% increase in the number of reported cycles from 2003. The availability of ART varied by country and ranged from 14 to 3844 treatment cycles per million population. Over one-third (37.2%) of ART clinics performed <100 cycles per year with only 19.9% performing ≥ 500 cycles per year. Of all cycles, 60.6% were ICSI. Frozen embryo transfers (FETs) represented 31% of the initiated cycles. The overall delivery rate per fresh aspiration for IVF and ICSI was 20.2% compared with 16.6% per FET. The average number of embryos transferred was 2.35. Single (16.3%) and double embryo transfers accounted for 73.2% of cycles. The overall proportion of deliveries with twins and triplets from IVF and ICSI was 25.1 and 1.8%, respectively, but varied widely by country and region. The proportion of premature deliveries per fresh aspiration for IVF and ICSI was 33.7% compared with 26.3% per FET. The perinatal death rate was 25.8 per 1000 births for fresh aspiration for IVF and ICSI compared with 14.2 per 1000 births per FET. LIMITATIONS, REASONS FOR CAUTION: Data are incomplete with seven countries not providing data to the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in 2004 that had in 2003. The validity of data reflects current data collection practice. In 2004, 79.3% of the clinics in participating countries reported to their national or regional registries and to ICMART. In addition, the number of ART cycles per million population is a measure which is affected by a country's government policy, regulation, funding and the number of service providers. WIDER IMPLICATIONS OF THE FINDINGS: ART practice, effectiveness and outcomes vary markedly internationally. Notably, the increasing proportion of cycles that are FET, the change in practice to single embryo transfer and the cessation of the transfer of three or more embryos in some countries has resulted in improved perinatal outcomes with minimal impact on pregnancy rates. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives financial support from ASRM, ESHRE, FSA, Japan Society for Reproductive Medicine, REDLARA, MEFS and SART.

Bow shock formation in a complex plasma.

A bow shock is observed in a two-dimensional supersonic flow of charged microparticles in a complex plasma. A thin conducting needle is used to make a potential barrier as an obstacle for the particle flow in the complex plasma. The flow is generated and the flow velocity is controlled by changing a tilt angle of the device under the gravitational force. A void, microparticle-free region, is formed around the potential barrier surrounding the obstacle. The flow is bent around the leading edge of the void and forms an arcuate structure when the flow is supersonic. The structure is characterized by the bow shock as confirmed by a polytropic hydrodynamic theory as well as numerical simulation.

The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology, 2009.

BACKGROUND: Many definitions used in medically assisted reproduction (MAR) vary in different settings, making it difficult to standardize and compare procedures in different countries and regions. With the expansion of infertility interventions worldwide, including lower resource settings, the importance and value of a common nomenclature is critical. The objective is to develop an internationally accepted and continually updated set of definitions, which would be utilized to standardize and harmonize international data collection, and to assist in monitoring the availability, efficacy, and safety of assisted reproductive technology (ART) being practiced worldwide. METHOD: Seventy-two clinicians, basic scientists, epidemiologists and social scientists gathered together at the WHO headquarters in Geneva, Switzerland in December, 2008. Several months in advance, three working groups were established which were responsible for terminology in three specific areas: clinical conditions and procedures, laboratory procedures and outcome measures. Each group reviewed the existing ICMART glossary, made recommendations for revisions and introduced new terms to be considered for glossary expansion. RESULTS: A consensus was reached on 87 terms, expanding the original glossary by 34 terms, which included definitions for numerous clinical and laboratory procedures. Special emphasis was placed in describing outcome measures such as cumulative delivery rates and other markers of safety and efficacy in ART. CONCLUSIONS: Standardized terminology should assist in analysis of worldwide trends in MAR interventions and in the comparison of ART outcomes across countries and regions. This glossary will contribute to a more standardized communication among professionals responsible for ART practice, as well as those responsible for national, regional and international registries.

A complex plasma device of large surface area.

A novel complex plasma device (YCOPEX) to create two-dimensional monolayer plasma crystals of a large surface area of 15x90 cm2 is described. The YCOPEX, in which a plasma is produced by a rf discharge of argon gas, is designed to utilize gravitational force to study fundamental physics of complex plasmas. The device may be used for observation of spatial change of a phase state, propagation of waves, and collisions of flowing dust particles with an obstacle. As an example of experiments, neutral drag forces on microspheres are measured using the gravitational force on those particles. The obtained neutral drag force agrees reasonably with the values estimated from Epstein's formula.

An algorithm for the management of coagulopathy from postpartum hemorrhage, using fibrinogen concentrate as first-line therapy.

BACKGROUND: We constructed an algorithm for the management of coagulopathy from massive postpartum hemorrhage. Fibrinogen concentrate was administered preferentially, and the dose of both fibrinogen concentrate and fresh frozen plasma given was determined by the plasma fibrinogen concentration and prothrombin time. The efficacy of the algorithm and the amount of fibrinogen concentrate and fresh frozen plasma transfused were determined. METHODS: The study was conducted in a single teaching perinatal center. Nineteen patients were included between April 2011 and March 2014 (patient group). For a historical comparison group, we retrospectively analyzed the records of 19 patients who had been treated for coagulopathy from massive postpartum hemorrhage between April 2006 and March 2011 (control group). RESULTS: Blood loss was significantly lower in the patient group. No adverse events were associated with this management in either group. The dose of fibrinogen concentrate administered was significantly higher and that of fresh frozen plasma administered was significantly lower in the patient group. CONCLUSION: This algorithm appeared to help reduce blood loss and the total amount of fresh frozen plasma transfused when treating coagulopathy from postpartum hemorrhage, and may represent another strategy for achieving hemostasis in this setting.

Electromagnetic wave band structure due to surface plasmon resonances in a complex plasma.

The dielectric properties of complex plasma containing either metal or dielectric spherical inclusions (macroparticles, dust) are investigated. We focus on surface plasmon resonances on the macroparticle surfaces and their effect on electromagnetic wave propagation. It is demonstrated that the presence of surface plasmon oscillations can significantly modify plasma electromagnetic properties by resonances and cutoffs in the effective permittivity. This leads to related branches of electromagnetic waves and to the wave band gaps. The conditions necessary to observe the band-gap structure in laboratory dusty plasma and/or space (cosmic) dusty plasmas are discussed.

Effects of the placement of endosseous implants in vascularized bone grafts on bone union in beagle dogs.

Recently, reconstructive surgery with revascularized osteocutaneous flaps has been used to restore function in patients with bone defects caused by surgery for oral cancer. However, few basic studies have addressed problems such as the union of bone segments after osteotomy, the effects of dental implant placement on blood flow, and bone formation at the bone:implant interface in grafted bone. Nine adult beagle dogs were divided into three groups of three dogs each. Each group received osteotomized vascularized tibial grafts, osteotomized tibial grafts with implants (implants placed in contralateral limbs as control), or simple (non-vascularized) tibial grafts. The development of bone around the implants was studied by histological examination, contact micro-radiography (CMR), and fluorescent bone labeling. In the dogs receiving osteotomized vascularized tibial grafts, bone bridging was confirmed at both the medial and distal junctions of the bone segments after 4 weeks. Additional newly formed bone was observed after 8 weeks, and bone union at the surface of the segments was completed after 12 weeks. In contrast, bone formation was clearly delayed in dogs receiving simple (non-vascularized) tibial grafts. Histologically, no difference in bone union was evident between limbs with dental implants in tibial bone and control limbs without implants, suggesting that implant placement does not negatively affect revascularization. Fluorescent bone labeling technique confirmed high vascularity of the vascularized tibial bone grafts but not of the simple (non-vascularized) tibial bone grafts early after the procedure. Our results suggest that osseointegration occurred around dental implants placed at the same time as reconstruction with osteotomized vascularized bone grafts in this animal model.

Synthesis of 12-hydroxyeicosatetraenoic acid by human endometrium and decidua.

In order to clarify the possible involvement of lipoxygenase metabolites of arachidonic acid (AA) in implantation, monohydroxylic acid production was examined using human endometrium and decidua in early pregnancy. As 14C-AA was mainly converted to 12-hydroxyeicosatetraenoic acid (12-HETE) as well as prostaglandins (PGs) by the microsomal fraction of the endometrium, a subsequent study was carried out on the endometrium (at various stages) and decidua in early pregnancy using tissue incubation and high performance liquid chromatography (HPLC) analysis for 12-HETE. The amounts of 12-HETE released into the culture medium by proliferative and secretory endometrium were 165.1 +/- 123.4 (ng/mg.protein/24 h, mean +/- SD) and 502.3 +/- 127.2, respectively, whereas, decidua produced a smaller amount of 12-HETE that declined as gestation progressed. This lipoxygenase product as well as PGs might have a role in implantation.

An inhibitor of prostaglandin biosynthesis from human decidua: partial purification and properties.

An inhibitor of prostaglandin synthetase which catalyzes the conversion of arachidonic acid into prostaglandin E2 was partially purified from the 105,000 x g supernatant fraction of the human decidual cell homogenate. By means of ammonium sulfate fractionation, Mono Q ion-exchange chromatography, and gel filtration chromatography, the inhibitor was purified about 15-fold, giving a preparation with a molecular weight of 55-60 KDa. The 50% inhibitory concentration of the purified substance was approximately 0.2 mg/ml. The inhibitor may play a role in suppression of prostaglandin production by decidua in early pregnancy.

Where does the embryo implant after embryo transfer in humans?

OBJECTIVE: To investigate where human embryos implant after ET. DESIGN: Prospective analysis. SETTING: University hospital. PATIENT(S): Sixty infertile women without uterine fibroids, a major uterine anomaly, or a history of cesarean section. INTERVENTION(S): Transabdominal and transvaginal three-dimensional ultrasound examinations. MAIN OUTCOME MEASURE(S): The location of ET-associated air bubbles in the uterine cavity and the location of the resultant gestational sac. RESULT(S): Sixty ETs resulted in 22 pregnancies, and 32 gestational sacs were located. Twenty-six of the 32 embryos were within or between the area in which the catheter tip was situated and the area over which air bubbles had spread immediately after ET. CONCLUSION(S): In cases of pregnancy achieved through ET, approximately 80% of embryos implant in areas to which they initially are transferred and approximately 20% implant in other areas.

Basilar artery occlusion in a case of Duchenne muscular dystrophy.

This is a report of a case of Duchenne muscular dystrophy (DMD), with multiple infarcts in the territories of the basilar artery. He developed abrupt vomiting and transient left hemiparesis at the age of 4 years. The episodes were seen 3 times between 4-year-1-month to 5-year-1-month old. Transaxial computerized tomography (CT) revealed multiple, well-defined but irregularly marginated areas of low density centered in the mid- and upper pons, right cerebral peduncle and thalamus. A right vertebral angiogram illustrated the narrowed basilar artery. The rectus femoris muscle was biopsied at the age of 4-year-1-month which showed marked variation in fiber size, myonecrosis with phagocytosis, central nuclei, and adipose and connective tissue proliferation, which were consistent with those seen in DMD. It remains unknown whether the basilar artery occlusion was an incidental event in this particular case or closely related to the disease process of DMD.

Multiple ring enhancement in a case of acute reversible demyelinating disease in childhood suggestive of acute multiple sclerosis.

A 5-year-old Japanese boy was admitted to our hospital because of progressive visual disturbance and quadriplegia. Computed tomography (CT) revealed multiple low density areas in the cerebral white matter, and intravenous injection of contrast medium resulted in ring enhancement around these areas. Exploratory aspiration of one of the low density areas gave a xanthochromic, viscous fluid. Pathologic examination of the drained fluid demonstrated small pieces of brain tissue with necrotizing lesions surrounded by demyelinating areas. The patient has been followed up for 3 years with corticosteroid treatment, and marked improvement has been achieved both in neurological examination and CT findings. From these clinicopathological findings an acute form of multiple sclerosis (MS) in childhood was suspected.

A pilot study on the anticonvulsive effects of a thyrotropin-releasing hormone analog in intractable epilepsy.

In 1981, Inanaga et al reported on the efficacy of DN-1417 (a TRH analog) in the treatment of degenerative myoclonus epilepsy and other forms of intractable epilepsy. Following this report, we studied the efficacy and safety of DN-1417 treatment in 10 intractable epileptic children ranging in age from 6 months to 11 years (mean 4 years), including 7 with Lennox syndrome (LS), 2 with West syndrome (WS) and 1 with degenerative myoclonus epilepsy (DME). The daily dose was from 0.02 to 0.05 mg/kg, initially, and then was increased to 0.05 mg/kg. Complete control of seizures was achieved in 2 patients with LS, a 50% or greater decrease in seizure frequency was observed in one patient each with LS and DME and a less than 50% decrease in 1 with LS and 2 with WS. There was no change in 2 LS cases, and 1 LS case became worse. Activation of psychic activities, such as psychomotor activity, facial expression and motivation, was also noted in 7 of the 10 patients. Furthermore, improvement of motor function was noted in 5 patients. Electroencephalographic abnormalities improved in 2 completely seizure free patients with LS in which EEG ameliorated along with clinical seizure control.

Functional reconstruction of a bilateral maxillectomy defect using a fibula osteocutaneous flap with osseointegrated implants.

We have achieved functional reconstruction for a bilateral upper alveolar bone, gingival, and palatal defect that has various problems originating from instability of the prosthesis using the fibula osteocutaneous flap with osseointegrated implants. The flap had three bone segments and two skin paddles. The combined bone segments created the upper alveolar arch, and the skin paddles closed the palatal defect. Nine months later, prosthodontic treatment was performed successfully. Our procedure restored the patient to masticatory function of the upper jaw, intelligible speech, and natural facial appearance. As a result, quality of life of the patient was extremely improved.

[A case of famotidine-induced aseptic meningitis].

We reported a 50-year-old woman with a history of mixed connective tissue disease. She had two episodes of meningitis-like symptoms after taking famotidine and tiquizium bromide for treatment of gastric ulcer. From CSF findings (elevated pressure, increase of protein, polymorphonuclear pleocytosis, negative culture) and result of famotidine challenge test, we diagnosed her as a drug induced aseptic meningitis. Because she had taken tiquizium bromide several times previously without any side effects, we concluded that famotidine was a causative drug. She was recovered without sequelae within a few days following cessation of these drugs. This is the first report of H2-blocker induced aseptic meningitis. When we encounter a patient with aseptic meningitis who presents polymorphonuclear pleocytosis in CSF, we should suspect drug induced aseptic meningitis and take a history of drug medication including H2-blocker.

[Familial Creutzfeldt-Jakob disease with the heterozygous point mutation at codon 200 of the prion protein gene (Glu-->Lys)--report of CJD200 brothers of Yamanashi Prefecture origin].

We report two brothers with familial Creutzfeldt Jakob disease (CJD) having a heterozygous point mutation at codon 200 of the prion protein gene (Glu-->Lys): CJD200. The brothers were born in Kitakoma-gun, Yamanashi Prefecture. Patient 1, a 62-year-old man, developed CJD in 1995 and died nine months later. Patient 2, his brother, developed CJD200 at the age of 58 in 1982 and died 13 months later. They both exhibited rapidly progressive dementia with myoclonus and periodic synchronous discharges on electroencephalograms and became bedridden with three or four months. DNA analysis of peripheral blood cells of patient I showed a point mutation in the prion protein gene at codon 200: GAG-->AAG (Glu-->Lys). Five families with CJD200, 11 patients, have been reported in Japan to date, and nine of the patients from four families were born in Yamanashi Prefecture and vicinity. Our patients were born in the same area. We suspect that there is a cluster of CJD200 in Yamanashi Prefecture and vicinity. In Europe and America the phenotype of CJD200 has been reported to be heterogeneous, whereas the clinical features in Japanese cases are fairly homogeneous. We suspect that these patients have a common ancestor with a codon 200 mutation, and that that explains why the phenotypes are homogeneous.

[Efficacy of chemotherapy for clear cell adenocarcinoma of the ovary].

In line with various protocols for chemotherapy of ovarian carcinoma, we used EP (etoposide-cisplatin or carboplatin) therapy in 10 patients with clear cell adenocarcinoma as the first line chemotherapy. Four of these cases were in advanced stage at IIIc, and had residual tumor after the operation. One of these patients with measurable tumor responded to semi-high dose treatment, and 5-days of continuous infusion of etoposide resulted in CR. Three cases of a patient at the stages of Ic and IIc are in disease free status after two years of standard-dose EP therapy. Therefore, high-dose EP therapy might be an effective chemotherapy for some patients with ovarian clear cell adenocarcinoma.

[A case of ovarian malignant Sertoli-Leidig cell tumor treated with CBDCA, etoposide and epirubicin chemotherapy].

A 49-year-old female presented with a low abdominal tumor. Before operation, she had neither evidence of androgen excess nor abnormal tumor marker values, but US, CT and MRI findings strongly suggested the possibility of a malignant ovarian tumor. Her operative findings were as follows: a goose egg-sized main tumor in the low abdomen, with a walnut-sized tumor in the right side, which grew around the right ureter, causing right non-functional kidney. Pathological examination revealed her tumor was a very rare type of malignant Sertoli-Leidig cell tumor with pelvic lymph nodes metastases. Most patients with this disease usually have good prognoses, but with metastasis or recurrence, no therapy is as effective as in epithelial ovarian cancer. In this case, we selected a new combination chemotherapy of CBDCA, Etoposide and Epirubicin, considering current changes in the chemotherapy for ovarian germ cell tumors and Sertoli-Leidig cell tumors of testis. Now, 1 year and 4 months after operation, she has no evidence of recurrence or metastasis. This study proposes a new, presumably more effective chemotherapy for an ovarian malignant Sertoli-Leidig cell tumor.

[Minute carcinoid tumor in the rectum with liver metastasis].

A 65-year-old woman was admitted to our hospital for evaluation of multiple liver tumors following endoscopic polypectomy for rectal polyp a year earlier. The polypectomy specimen was reexamined and showed inclusion of a carcinoid tumor 3 mm in diameter. The perirectal lymph node was palpated by digital examination on readmission. The patient died one mouth after readmission due to liver failure. Autopsy revealed metastatic carcinoid tumor in the liver and perirectal nodes.