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.

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.

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.

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.

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.

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.

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: 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.

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.

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles.

BACKGROUND: For the last few decades urinary human chorionic gonadotrophin (hCG) has been used to induce final oocyte maturation triggering in in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) cycles. Recombinant technology has allowed the production of two drugs that can be used for the same purpose, to mimic the endogenous luteinizing hormone (LH) surge. This allows commercial production to be adjusted according to market requirements; the removal of all urinary contaminants; and the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice the effectiveness of the recombinant drugs should be known compared to the currently used urinary human chorionic gonadotrophin (uhCG). OBJECTIVES: To assess the efficacy and safety of subcutaneous recombinant hCG (rhCG) and high dose recombinant LH (rLH) compared with intramuscular uhCG for inducing final oocyte maturation triggering in IVF and ICSI cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010), MEDLINE (1966 to January 2010) and EMBASE (1980 to January 2010). SELECTION CRITERIA: Two review authors independently scanned titles and abstracts and selected those that appeared relevant for collection of the full paper. Only truly randomised controlled trials comparing rhCG and rLH with urinary hCG for final oocyte maturation triggering in IVF and ICSI cycles for treatment of infertility in normo-gonadotropic women were included. DATA COLLECTION AND ANALYSIS: Assessment for inclusion or exclusion, quality assessment and data extraction were performed independently by two authors. Discrepancies were discussed in the presence of a third author and consensus reached. Quality assessment included method of randomisation, allocation concealment, blinding of participants and assessors, reporting of a power calculation and intention-to-treat analysis. MAIN RESULTS: Fourteen RCTs (n = 2306) were identified; 11 compared rhCG with uhCG and three compared rhLH with uhCG. There was no evidence of a statistically significant difference between rhCG and uhCG regarding the ongoing pregnancy or live birth rate (6 RCTs: OR 1.04, 95% CI 0.79 to 1.37; P = 0.83, I(2) = 0%). There was no significant difference in the incidence of ovarian hyperstimulation syndrome (OHSS) between rhCG and uhCG (3 RCTs: OR 1.5, 95% CI 0.37 to 4.1; P = 0.37, I(2) = 0%). There was no evidence of statistically significant difference between rhLH and uhCG regarding the ongoing pregnancy or live birth rate (OR 0.94, 95% CI 0.50 to 1.76) and incidence of OHSS (OR 0.82, 95% CI 0.39 to 1.69). These results leave open the possibility of strong differences in favour of either treatment for both ongoing pregnancy and OHSS. AUTHORS' CONCLUSIONS: We conclude that there is no evidence of difference between rhCG or rhLH and uhCG in achieving final follicular maturation in IVF, with equivalent pregnancy rates and OHSS incidence. According to these findings uHCG is still the best choice for final oocyte maturation triggering in IVF and ICSI treatment cycles.

A simple and relatively painless technique for hysterosalpingography, using a thin catheter and closing the cervix with the vaginal speculum: a pilot study.

OBJECTIVE: To evaluate the use of a thin catheter for hysterosalpingography (HSG) for reducing the pain experienced during the procedure. METHODS: Infertile women undergoing tubal patency tests were randomised into two groups. In the study group (n=66) a thin catheter originally designed for intrauterine insemination was used to inject the dye. Leakage of the dye was prevented using a vaginal speculum to press on the portiovaginalis of the cervix. The control group (n=23) underwent HSG using the standard metal cannula. Visual analogue scale (VAS) was used to evaluate the level of pain immediately after the procedure. The main outcome measures were the level of pain experienced by the patient during the procedure and the efficacy of the new technique. RESULTS: The mean (±SD) VAS was 11.2±3.1 in the study group and 54.7±10.1 in the metal cannula group (p<0.0001). During the dye injection, the VAS was 10.3±5.2 in the study group compared to 64.1±17.3 in the metal cannula group (p<0.0001). The new technique was successful in filling the uterine cavity with the dye and studying the fallopian tubes. CONCLUSIONS: Using a thin catheter for HSG and pressing on the cervix with the vaginal speculum to prevent leakage of the dye is a successful method to study the uterine cavity and fallopian tubes, and it significantly reduces the pain as compared to a metal cannula.

Prospective randomized study for hydrotubation versus no hydrotubation before intrauterine insemination in unexplained infertility.

The purpose of the study was to investigate the value of hydrotubation before intrauterine insemination (IUI). In 228 patients with the diagnosis of unexplained infertility, ovarian stimulation was performed before IUI, using 100mg of clomiphine citrate for 5 days from day 3 of the cycle and one ampoule of human menopausal gonadotrophin for 5 days from day 6 of the cycle. Folliculometry and determination of LH concentration in urine were performed daily until LH became positive, then randomization for hydrotubation before IUI versus no hydrotubation was performed. Fifteen patients were cancelled from the study due to poor response or stimulation of three or more follicles. A total of 213 patients were randomized as follows: 103 patients undergoing hydrotubation using 50 ml of saline and 110 patients with no hydrotubation. IUI was performed the following day and ongoing pregnancy occurred in 13 patients (12.6%) in the hydrotubation group and nine patients (8.2%) in the non-hydrotubation group with no significant difference (OR 1.66; 95% CI 0.62-4.63). In conclusion, hydrotubation before IUI does not improve pregnancy rate.

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.

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.

World collaborative report on Assisted Reproductive Technology, 2002.

The International Committee for Monitoring Assisted Reproductive Technology's (ICMART) Eighth World Report analyzes assisted reproductive technology (ART) practice and results for the year 2002 from 53 countries by type of ART, women's age, number of embryos transferred and multiple births. Over 601,243 initiated cycles resulted in a delivery rate (DR) per aspiration of 22.4% for conventional IVF, 21.2% for ICSI and a DR per transfer of 15.3% for frozen embryo transfer. For conventional IVF and ICSI, there was an overall twin rate of 25.7% per delivery and a triplet rate of 2.5%. The number of babies born worldwide through ART in 2002 was estimated to range between 219,000 and 246,000. There were wide variations in availability, DRs and multiple birth rates across the countries. Compared with the previous report (year 2000), there was a large increase in the number of cycles and a slight increase in the DR. There was a marginal decline in the mean number of embryos transferred and in the multiple DRs.

Ultrasound cervical measurement and prediction of spontaneous preterm birth in ICSI pregnancies: a prospective controlled study.

A prospective controlled study was performed in which transvaginal ultrasound measurement of cervical length was compared in 222 twin ICSI pregnancies, 122 singleton ICSI pregnancies and 51 spontaneous singleton pregnancies. Preterm birth was defined as

Highly purified hMG achieves better pregnancy rates in IVF cycles but not ICSI cycles compared with recombinant FSH: a meta-analysis.

OBJECTIVE: Human menopausal gonadotropin (hMG) was demonstrated to be superior to recombinant FSH (rFSH) regarding clinical outcomes. It is not clear whether this change in the evidence was due to the introduction of highly purified (HP) hMG. DESIGN: Systematic review of properly randomised trials comparing HP-hMG vs. rFSH in women undergoing in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI). A meticulous search was performed using electronic databases and hand searches of the literature. RESULTS: Six trials (2371 participants) were included. Pooling of the trials demonstrated that the probability of clinical pregnancy following HP-hMG administration was higher than rFSH and reached borderline significance (odd ratio (O.R) = 1.21, 95% confidence interval (CI) = 1.00 to 1.45), but the ongoing pregnancy/live-birth rate was not statistically different between the two drugs, although it showed strong trends towards improvement with HP-hMG (O.R = 1.19, 95% CI = 0.98 to 1.44). Subgroup analysis comparing both drugs in IVF cycles demonstrated a statistically significant better ongoing pregnancy/live-birth rate in favour of HP-hMG (O.R = 1.31, 95% CI = 1.02 to 1.68). On the other hand, there was almost an equal ongoing pregnancy/live-birth rate in ICSI cycles (OR = 0.98, 95% CI = 0.7 to 1.36). CONCLUSIONS: HP-hMG should be preferred over rFSH in women undergoing assisted reproduction, especially if IVF is the intended method of fertilisation.