International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014†.

STUDY QUESTION: What were the utilization, effectiveness and safety of practices in assisted reproductive technologies (ART) globally in 2014 and what global trends could be observed? SUMMARY ANSWER: The estimated total number of ART cycles conducted in 76 participating countries in 2014 was 1.93 million representing ∼66% of global activity, with 5-year trends including an increase in success rates and proportion of frozen embryo transfer (FET) cycles, improvement in cumulative live birth rates per aspiration, a continued increase in single embryo transfer (SET) and thus a reduction in multiple birth rates, an increase in preimplantation genetic testing and stabilization in the use of intracytoplasmic sperm injection (ICSI). WHAT IS KNOWN ALREADY: ART is widely practiced throughout the world but continues to be characterized by significant disparities in utilization, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report series provides an important instrument for tracking trends in ART treatment and for providing clinical and public health data to ART professionals, health authorities, patients and the general public. STUDY DESIGN, SIZE, DURATION: A retrospective, cross-sectional survey on ART procedures performed globally during 2014 was carried out. A new method for calculating ART utilization rates and number of babies born was introduced in this latest ICMART world report. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 76 countries and 2 746 ART centres submitted data through national and regional ART registries on ART cycles performed during 2014 and their treatment and pregnancy outcomes. ART cycles and outcomes are described at a country level, regionally and globally. Aggregate country data are processed and analyzed based on methods developed by ICMART. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1 629 179 ART cycles were reported for the treatment year 2014. After imputing data for missing values and non-reporting centres in reporting countries, an estimated 1 929 905 cycles resulted in >439 039 babies in reporting countries. From 2010 to 2014, the number of reported non-donor aspirations and FET cycles increased by 37.3% and 67.5%, respectively. The proportion of women aged ≥40 years undergoing non-donor ART increased from 23.2% in 2010 to 27.0% in 2014. ICSI, as a percentage of non-donor aspiration cycles, remained relatively stable at 64.8%. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycle were 19.9% and 24.3%, respectively. In fresh non-donor cycles, SET increased from 30.0% in 2010 to 40.0% in 2014, while the average number of transferred embryos decreased from 1.95 to 1.73-but with wide country variation. The rate of twin deliveries following fresh non-donor transfers continued to decrease, from 20.4% in 2010 to 16.2% in 2014, and the triplet rate decreased from 1.1% to 0.5%. In FET non-donor cycles in 2014, the SET rate was 61.6%, with an average of 1.43 embryos transferred, resulting in twin and triplet rates of 10.1% and 0.2%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 32.1% in 2014. The overall perinatal mortality rate per 1 000 births was 19.4 following fresh IVF/ICSI cycles and 9.5 following FET cycles. Among reporting countries, oocyte donation cycles represented 7.3% of all embryo transfers (89 751 transfer cycles) and resulted in 39 278 babies. LIMITATIONS, REASONS FOR CAUTION: The data presented are dependent 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. China is a major contributor of global cycles missing from this report. Continued efforts to improve the quality and consistency of ART data reported by registries are still needed, including the use of internationally agreed standard definitions (The International Glossary of Infertility and Fertility Care). A new method was introduced in this report to calculate ART utilization and number of babies born following ART; therefore, these results are not directly comparable with previous reports. 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 effectiveness and safety continue to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policymakers. The new method for estimating ART utilization and number of babies born provided more conservative estimates compared to the previuos method. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives unrestricted grants from Abbott and Ferring Pharmaceuticals. ICMART also acknowledges financial support from the following organizations: American Society for Reproductive Medicine; Asia Pacific Initiative on Reproduction; European Society of Human Reproduction and Embryology; Fertility Society of Australia and New Zealand; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproducción Asistida; and the Society for Assisted Reproductive Technology. S.D. reports industry sponsorship for attendance of conference from Ferring, and research grants to support African Network and Registry of ART from Ferring and Merck outside the submitted work. F.Z.-H. reports lectures at organized webinars for Ferring and Merck. O.I. reports honoraria for consulting from Ferring, Merck and ObsEva, as well as honoraria for lectures from Ferring and Merck. G.M.C., J.d.M., M.B., M.S.K. and G.D.A. have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

The protective effects of Terminalia laxiflora extract on hepato-nephrotoxicity induced by fipronil in male rats.

The present study was led to investigate the defensive role of Terminalia laxiflora extract (TLE) on fipronil (FPN) induced hepatotoxicity and nephrotoxicity in male rats. Rats were administered with TLE (100 mg/kg) against the renal toxicity and hepatotoxicity induced by administration of FPN (10.5 mg/kg) for 30 days. At the end of the experimental period, the serum, liver, and kidneys were harvested and assessed for subsequent analysis. FPN administration to rats resulted in a significant elevation of serum transaminases, urea, and creatinine. Also, FPN-treated groups exhibited a marked reduction in total protein and albumin levels. Compared with the control group, the level of malondialdehyde (MDA) was elevated in groups treated with FPN, whereas superoxide dismutase (SOD), catalase (CAT) activities, and glutathione levels were distinctly reduced in this group. Significant increases in genomic DNA fragmentation and the expression level of the caspase-3 gene were also recorded. The biochemical result was supported by histopathological findings. Co-administration of TLE along with FPN significantly diminished the liver and kidney function tests decreased the level of lipid peroxidation, and enhanced all the antioxidant enzymes, while also diminishing the expression of caspase-3 and DNA laddering, indicating amelioration of DNA damage. These results indicate that TLE plays a vital role in diminishing FPN-induced hepatotoxicity and nephrotoxicity.

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

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.

The effect of early administration of rectal progesterone in IVF/ICSI twin pregnancies on the preterm birth rate: a randomized trial.

BACKGROUND: The rate of multiple pregnancies in IVF/ICSI ranges from 20 to 30%. The incidence of preterm birth in multiple pregnancies is as high as 60% and is even higher in pregnancies conceived after IVF & ICSI. The effect of progesterone on prevention of preterm birth in twins is controversial. Our group has proven a positive effect in reduction of preterm birth, by starting progesterone from the mid-trimester, in exclusively IVF/ICSI singleton pregnancies but not twins. The purpose of our current study was to explore the effect of earlier administration of natural progesterone, in IVF/ICSI twin pregnancies starting at 11-14 weeks for prevention of preterm birth. METHODS: This is a double-blind, placebo controlled, single center, randomized clinical trial. Women with dichorionic twin gestations, having an IVF/ICSI trial were randomized to receive natural rectal progesterone (800 mg daily) vs placebo, starting early from 11 to 14 weeks. They also received oral and vaginal antimicrobial agents as part of our routine treatment for vaginitis and urinary tract infection. They were randomized regardless of cervical length and had no previous history of preterm birth or known Mullerian anomalies. The primary outcome was spontaneous preterm birth rate before 37 weeks. The secondary outcome was; spontaneous preterm birth before 34, 32, 28 weeks and neonatal outcome. RESULTS: A total of 203 women were randomized to both groups, final analysis included 199 women as 4 were lost to follow up. The base line characteristics as well as gestational age at delivery were not significantly different between the study and the placebo group (34.7 ± 3.6 vs 34.5 ± 4.5, P = 0.626). Progesterone administration was not associated with a significant decrease in the spontaneous preterm birth rates before 37 weeks (73.5% vs 68%, P = 0.551), before 34 (20.6% vs 21.6%, P = 0.649), before 32 (8.8% vs 12.4%, P = 0.46) & before 28 (4.9% vs 3.1%, P = 0.555) weeks. CONCLUSIONS: Rectal natural progesterone starting from the first trimester in IVF/ICSI twin pregnancies did not reduce spontaneous preterm birth. TRIAL REGISTRATION: The trial was registered on 31 January 2014 at www.ISRCTN.com, number 69810120.

ART utilization: an indicator of access to infertility care.

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.

Human-stimulated oocyte extract induces genetic and mitochondrial reprogramming of mesenchymal stromal cells.

SUMMARY: Reprogramming autologous adult cells to pluripotent cells allows for relatively safe cell replacement therapy. This can be achieved by nuclear transfer, cell fusion, or induced pluripotent stem cell technology However, the epigenetic memory of the cell is considered as a great challenge facing the complete reprograming of cells by these methods. Introducing oocyte-specific factors into differentiated cells may present a promising approach by mimicking cellular reprogramming during fertilization. METHODS: Human bone marrow mesenchymal stromal cells (hBM-MSCs) were cultured with different concentrations of human metaphase II (M II) oocyte extract (0.1, 1, 5, 10, 30 ng/µl). Reprogramming was assessed at various exposure times (1, 4, 7 days). Cells were tested for their proliferation rate, morphological changes, expression of pluripotency markers, expression of mesenchymal to epithelial transition markers, and mitochondrial rejuvenation. (mitochondrial localization, morphological changes, bioenergetics, transmembrane potential, and levels of reactive oxygen species, ROS). RESULTS: Treatment of human BM-MSCs with 10 ng/µl oocyte extract resulted in increased cell proliferation, which was associated with the upregulation of the pluripotency genes OCT-4, NANOG, and SOX-2 and a concomitant downregulation of mesenchymal-specific genes. MSCs exhibited small, immature round mitochondria with few swollen cristae localized proximal to the cell nucleus. This was accompanied by morphological cell changes, a metabolic shift towards oxidative phosphorylation, a high mitochondrial membrane potential, and increased ROS production. CONCLUSION: These data show that treatment with 10 ng/µl human MII-phase oocyte extract induced genetic and mitochondrial reprogramming of human BM-MSCs to a more embryonic phenotype.

Triple-arm trial of pH (Tri-pH) effect on live birth after ICSI in Egyptian IVF facilities: protocol of a randomised controlled trial.

INTRODUCTION: One potential stressor that can affect preimplantation and postimplantation embryonic growth after in vitro fertilisation (IVF) is the pH of the human embryo culture medium, but no evidence exists to indicate which pH level is optimal for IVF. Based on anecdotal evidence or mouse models, culture media manufacturers recommend a pH range of 7.2 to 7.4, and IVF laboratories routinely use a pH range of 7.25 to 7.3. Given the lack of randomised trials evaluating the effect of pH on live birth rate after IVF, this trial examines the effect of three different pH levels on the live birth rate. METHODS AND ANALYSIS: This multicentre randomised trial will involve centres specialised in IVF in Egypt. Eligible couples for intracytoplasmic sperm injection (ICSI) will be randomised for embryo culture at pH 7.2, 7.3 or 7.4. The study is designed to detect 10 percentage points difference in live birth rate between the best and worst performing media with 93% power at a 1% significance level. The primary outcome is the rate of live birth (delivery of one or more viable infants beyond the 20th week of gestation) after ICSI. Secondary clinical outcomes include biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage, preterm births, birth weight, stillbirth, congenital malformation and cumulative live birth (within 1 year from randomisation). Embryo development outcomes include fertilisation, blastocyst formation and quality, and embryo cryopreservation and utilisation. ETHICS AND DISSEMINATION: The study was reviewed and approved by the Ethics Review Boards of the participating centres. Eligible women will sign a written informed consent before enrolment. This study has an independent data monitoring and safety committee comprised international experts in trial design and in vitro culture. No plan exists to disseminate results to participants or health communities, except for the independent monitoring and safety committee of the trial. TRIAL REGISTRATION NUMBER: NCT02896777.

Oocyte Aging: The Role of Cellular and Environmental Factors and Impact on Female Fertility.

Female aging is one of the most important factors that impacts human reproduction. With aging, there is a natural decline in female fertility. The decrease in fertility is slow and steady in women aged 30-35 years; however, this decline is accelerated after the age of 35 due to decreases in the ovarian reserve and oocyte quality. Human oocyte aging is affected by different environmental factors, such as dietary habits and lifestyle. The ovarian microenvironment contributes to oocyte aging and longevity. The immediate oocyte microenvironment consists of the surrounding cells. Crosstalk between the oocyte and microenvironment is mediated by direct contact with surrounding cells, the extracellular matrix, and signalling molecules, including hormones, growth factors, and metabolic products. In this review, we highlight the different microenvironmental factors that accelerate human oocyte aging and decrease oocyte function. The ovarian microenvironment and the stress that is induced by environmental pollutants and a poor diet, along with other factors, impact oocyte quality and function and contribute to accelerated oocyte aging and diseases of infertility.

Characterization of embryonic cells obtained from multifetal reduction.

The multifetal reduction (MFR) procedure is usually reserved for high-order multiple pregnancies, and aspirated tissues are typically discarded. In this study, cells obtained from MFR tissue (termed multifetal reduction embryonic cells (MFR-ECs)), were characterized in vitro by genotypic and phenotypic analyses and tested in vivo by injection under the kidney capsule of nude mice. MFR-ECs were highly proliferative in culture and showed a normal karyotype by microarray CGH. Immunohistochemical analysis at day zero showed positive focal staining for desmin, S-100 protein, synaptophysin and chromogranin. Histology examination showed a mixture of cells from the three germ layers at different stages of differentiation. Markers of these stages included important developmental transcription factors, such as beta three-tubulin (ectoderm), paired box 6 (ectoderm) and alpha-smooth muscle actin (mesoderm). Quantitative polymerase chain reaction (qPCR) showed down-regulation of the mRNAs of cancer-related genes such as TP53. In vivo transplantation in nude mice showed a typical hyaline cartilage plate and no teratoma formation. Thus, MFR-ECs represent a rich, unique source for studying stem cell development, embryogenesis and cell differentiation.

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

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.

Increased insulin resistance in men with unexplained infertility.

This prospective case-control study aimed to test the presence of insulin resistance (IR) in men with unexplained infertility. We included two groups: the study group including 160 infertile men with unexplained oligozoospermia (sperm count <10 × 106/ml) and normal hormonal profile, and the control group of 79 men with proven fertility within the preceding year. A fasting blood test measured IR, FSH, LH, total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides. Insulin level was significantly higher in the study group (13.67 ± 10.44) compared with the control group (5.46 ± 3.15), P < 0.0001, and IR was significantly higher in the study group, P < 0.0001. FSH was significantly (P < 0.0001) higher in the study group (4.71 ± 2.57) than the control group (3.15 ± 1.92). LH was significantly higher in the study group (4.98 ± 2.41) compared with the control group (3.15 ± 1.12), P < 0.0001. Total cholesterol was significantly higher in the study group (198.29 ± 37.52) than the control group (182.45 ± 35.92), P < 0.05. In conclusion, IR in men with unexplained infertility may be a cause of reproductive and metabolic abnormalities. The benefit of insulin-sensitizing agents for these patients should be tested.

Does intrauterine injection of low-molecular-weight heparin improve the clinical pregnancy rate in intracytoplasmic sperm injection?

OBJECTIVE: Heparin can modulate proteins, and influence processes involved in implantation and trophoblastic development. This study aimed to assess the improvement of clinical pregnancy and implantation rates after local intrauterine injection of low-molecular-weight heparin (LMWH) in patients undergoing intracytoplasmic sperm injection (ICSI). METHODS: A randomised case/control design was followed in women scheduled for ICSI. The study arm was injected with intrauterine LMWH during mock embryo transfer immediately following the ovum pickup procedure, while the control arm was given an intrauterine injection with a similar volume of tissue culture media. Side effects, the clinical pregnancy rate, and the implantation rate were recorded. RESULTS: The pregnancy rate was acceptable (33.9%) in the LMWH arm with no significant reported side effects, confirming the safety of the intervention. No statistically significant differences were found in the clinical pregnancy and implantation rates between both groups (p=0.182 and p=0.096, respectively). The odds ratio of being pregnant after intrauterine injection with LMWH compared to the control group was 0.572 (95% confidence interval [CI], 0.27-1.22), while the risk ratio was 0.717 (95% CI, 0.46-1.13; p=0.146). No statistical significance was found between the two groups in other factors affecting implantation, such as day of transfer (p=0.726), number of embryos transferred (p=0.362), or embryo quality. CONCLUSION: Intrauterine injection of LMWH is a safe intervention, but the dose used in this study failed to improve the outcome of ICSI. Based on its safety, further research involving modification of the dosage and/or the timing of administration could result in improved ICSI success rates.

GnRH agonist plus vaginal progesterone for luteal phase support in ICSI cycles: a randomized study.

In this prospective randomized study, the effect of daily gonadotrophin-releasing hormone agonist (GnRHa) in the luteal phase on IVF and intracytoplasmic sperm injection (ICSI) outcomes was assessed. Women (n = 446) were counselled for IVF-ICSI, and randomized on the day of embryo transfer to group 1 (daily 0.1 mg subcutaneous GnRHa until day of beta-HCG) (n = 224) and group 2 (stopped GnRHa on day of HCG injection) (n = 222). Both groups received daily vaginal progesterone suppositories. Primary outcome was clinical pregnancy rate. Secondary outcome was ongoing pregnancy rate beyond 20 weeks. Mean age, oestradiol on day of HCG, number of oocytes retrieved, number of embryos transferred, and clinical and ongoing pregnancy rates were 28.9 ± 4.5 years, 2401 ± 746 pg/mL; 13.5 ± 6.0 oocytes; 2.6 ± 0.6 embryos, and 36.2% and 30.4% consecutively in group 1 compared with 29.7 ± 4.7 years, 2483 ± 867 pg/mL, 13.7 ± 5.5 oocytes, 2.7 ± 0.6 embryos, 30.6% pregnancy rate, and 25.7% ongoing pregnancy rate in group 2. No significant difference was found between the groups. Subcutaneous GnRHa during the luteal phase of long GnRHa protocol cycles does not increase clinical or ongoing pregnancy rates after IVF-ICSI.

International committee for monitoring assisted reproductive technologies: world report on assisted reproductive technologies, 2007.

OBJECTIVE: To analyze information on assisted reproductive technology (ART) performed worldwide, and trends in outcomes over successive years. DESIGN: Cross-sectional survey on access, efficiency, and safety of ART procedures performed in 55 countries during 2007. SETTING: Not applicable. PATIENT(S): Infertile women and men undergoing ART globally. INTERVENTION(S): Collection and analysis of international ART data. MAIN OUTCOME MEASURE(S): Number of cycles performed, by country and region, including pregnancies, single and multiple birth rates, and perinatal mortality. RESULT(S): Overall, >1,251,881 procedures with ART were reported, and resulted in 229,442 reported babies born. The availability of ART varied by country, from 12 to 4,140 treatments per million population. Of all aspiration cycles, 65.2% (400,617 of 614,540) were intracytoplasmic sperm injection. The overall delivery rate per fresh aspiration was 20.3%, and for frozen-embryo transfer (FET), 18.4%, with a cumulative delivery rate of 25.8%. With wide regional variations, single-embryo transfer represented 23.4% of fresh transfers, and the proportion of deliveries with twins and triplets from fresh transfers was 22.3% and 1.2%, respectively. The perinatal mortality rate was 19.9 per 1,000 births for fresh in vitro fertilization using intracytoplasmic sperm injection, and 9.6 per 1,000 for FET. The proportion of women aged ≥40 years increased to 19.8% from 15.5% in 2006. CONCLUSION(S): The international trend toward <3 transferred embryos continued, as did the wider uptake of FET. This was achieved without compromising delivery rates. The application of ART for women aged >40 years was a major component of ART services in some regions and countries.

International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2006.

STUDY QUESTION: What are the access, effectiveness and safety of assisted reproductive technology (ART) worldwide in 2006? SUMMARY ANSWER: ART access, effectiveness and safety vary markedly among countries. Overall, there was an increase in the use of ICSI, single embryo transfer (SET) and frozen embryo transfer (FET). There was a decline in the multiple delivery rate (DR) and preterm birth rate. WHAT IS KNOWN ALREADY: ART is widely practiced worldwide and there is a need for its continuous monitoring to improve the comprehensiveness and quality of ART data and services. STUDY DESIGN, SIZE, DURATION: This is a retrospective, cross-sectional survey of ART cycles undertaken worldwide in 2006. PARTICIPANTS, SETTING, METHODS: A total of 2352 clinics in 56 countries provided data. Data were analyzed at a country and regional level. The forms for data collection were developed by the International Committee Monitoring Assisted Reproductive Technologies (ICMART) and sent to each country or regional ART register. MAIN RESULTS AND THE ROLE OF CHANCE: A total of >1,050,300 initiated cycles resulted in an estimated >256,668 babies. The overall pregnancy rates (PRs) and DRs per aspiration for IVF were 30.7 and 22.8%, respectively, and for ICSI 29.7 and 20.0%, respectively. The PRs and DRs for FETs were 26.4 and 17.8%, respectively. Multiple DR per PR were 22.2% for twins and 1.5% for triplets following fresh IVF/ICSI and 16.4% for twins and 0.8% for triplets for FETs. Ovarian hyperstimulation syndrome complicated >4585 cycles (0.6%). Access to ART varied from 11 to 3988 cycles per million population. ICSI comprised 66.0% of all initiated cycles, FET 27.4% and SET 20.7%. Perinatal mortality rate was 25.2 per 1000 births for fresh IVF/ICSI and 17.5 per 1000 for FETs. LIMITATIONS, REASONS FOR CAUTION: 44.6% of the countries provided incomplete data. Quality of data varies among individual countries and is dependant on the policy of the local regulatory authority for monitoring ART clinics. Continuous efforts are needed to improve comprehensiveness and quality of data collected. WIDER IMPLICATIONS OF THE FINDINGS: Adopting the policy of SET, FET and the cessation of transferring more than two embryos should be widely applied. ICMART will continue helping countries and regions to establish their own ART registries. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives financial support from medical societies: European Society for Human Reproduction and Embryology (ESHRE), American Society for Reproduction Medicine (ASRM), Fertility Society of Australia (FSA), Japan Society for Reproductive Medicine (JSRM), Latin American Network for Reproductive Medicine (REDLARA) and Middle East Fertility Society (MEFS) and Society for Assisted Reproductive Technology (SART). All authors have no conflict of interest in relation to this work. We declare no support or financial relationship with any organizations or any activities that could appear to have influenced the submitted work.

Three new flavonol glycosides from Suaeda maritima.

Three new flavonol glycosides isolated from the 70% methanol extract of Suaeda maritima (Chenopodiaceae) were characterized based on spectroscopic and chemical methods as quercetin 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-ß-d-glucopyranosyl(1″″' â†’ 2″″)-glucopyranoside, kaempferol 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-ß-d-glucopyranosyl(1″″' â†’ 2″″)-glucopyranoside, and kaempferol 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-(2″″'-O-trans-feruloyl)-ß-d-glucopyranosyl-(1″″' â†’ 2″″)-ß-d-glucopyranoside. In addition, four known compounds, namely, quercetin and kaempferol, methyl cis, trans-ferulate, and methyl trans-ferulate were identified. The plant extract and these compounds showed cytotoxic activity against the human tumor cell lines MCF7, HCT116, and HEPG2.

Impact of antimüllerian hormone assays on the outcomes of in vitro fertilization: a prospective controlled study.

OBJECTIVE: To assess the value of routine antimüllerian hormone (AMH) assays in patients considered high risk for cancellation. DESIGN: Prospective controlled study. SETTING: A private IVF center, Cairo, Egypt. PATIENT(S): In total 4,917 patients received counseling before starting IVF/intracytoplasmic sperm injection (ICSI). They were comprised of group A1 (n = 1,335), who were considered to be at risk for cancellation after ovarian stimulation, and group A2 (n = 3,582), who were considered low risk for cancellation. A control group, B (n = 4,639), included group B1 (n = 1,248) and group B2 (n = 3,391) based on the same criteria as groups A1 and A2. INTERVENTION(S): An AMH assessment was performed for group A1. All of the patients were stimulated using the long GnRH agonist protocol. Patients with low AMH levels received the flare-up protocol. MAIN OUTCOME MEASURE(S): The cancellation of IVF/ICSI cycles before or after stimulation, as well as the pregnancy rates (PR) in relation to AMH levels. RESULT(S): The group A1 patients (6.4%) did not start IVF due to low AMH, and some (6.6%) had their cycles canceled due to poor responses, compared with 2.6% in group A2 and 13.2% in group B1. The clinical PR was 42% in patients with normal AMH and 20% in patients with low AMH. The differences among these three groups were highly significant. CONCLUSION(S): The AMH assays reduced the cancellations, cost, and stress experienced by couples.

International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2005.

OBJECTIVE: To analyze information on assisted reproductive technology (ART) performed worldwide and trends in outcomes over successive years. DESIGN: Cross-sectional survey on access, effectiveness, and safety of ART procedures performed in 53 countries during 2005. SETTING: A total of 2,973 clinics from national and regional ART registries. PATIENT(S): Infertile women and men undergoing ART globally. INTERVENTION(S): Collection and analysis of international ART data. MAIN OUTCOME MEASURE(S): Number of cycles performed by country and region, including pregnancies, single and multiple birth rates, and perinatal mortality. RESULT(S): Overall, 1,052,363 ART procedures resulted in an estimated 237,315 babies born. The availability of ART varied by country from 15 to 3,982 cycles per million of population. Of all initiated fresh cycles, 62.9% were intracytoplasmic sperm injection. The overall delivery rate per fresh aspiration was 19.6% and for frozen embryo transfer 17.4%, with a cumulative delivery rate of 23.9%. With wide regional variations, single embryo transfer represented 17.5% of cycles, and the proportion of deliveries with twins and triplets from fresh transfers was 23.6% and 1.5%, respectively. CONCLUSION(S): Systematic collection and dissemination of international ART data allows patients, health professionals, and policy makers to examine and compare the impact of reproductive strategies or lack of them as markers of reproductive health.

The use of vaginal natural progesterone for prevention of preterm birth in IVF/ICSI pregnancies.

The aim of this study was to evaluate the effect of vaginal natural progesterone on the prevention of preterm birth in IVF/intracytoplasmic sperm injection (ICSI) pregnancies. A single-centre prospective placebo-controlled randomized study was performed. A total of 313 IVF/ICSI pregnant patients were randomized into two groups for either treatment with daily 400 mg vaginal natural progesterone or placebo, starting from mid-trimester up to 37 weeks or delivery. Amongst the patients, there were 215 singleton and 91 twin pregnancies. There was no significant difference in risk of preterm birth among all patients (OR 0.672, 95% CI 0.42-1.0. There was a significantly lower preterm birth rate in singleton pregnancies in the natural progesterone arm (OR 0.53, 95% CI 0.28-0.97) and no significant difference between both arms in twin pregnancies (OR 0.735, 95% CI 0.36-2). In conclusion, the administration of 400 mg vaginal natural progesterone from mid trimester reduced the incidence of preterm birth in singleton, but not in twin, IVF/ICSI pregnancies.