It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child ...

https://www.physiology.org/doi/pdf/10.1152/physrev.00017.2015

Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility

Study question: What are the European trends and developments in ART and IUI in 2014 as compared to previous years? 

Summary answer: The 18th ESHRE report on ART shows a continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries. 

What is known already: Since 1997, ART data generated by national registries have been collected, analysed by the European IVF-monitoring (EIM) Consortium and reported in 17 manuscripts published in Human Reproduction. 

Study design, size, duration: Continuous collection of European data by the EIM for ESHRE. The data for treatments performed in 2014 between 1 January and 31 December in 39 European countries were provided by national registries or on a voluntary basis by clinics or professional societies. 

Participants/materials, setting, methods: From 39 countries and 1279 institutions offering ART services, a total of 776 556 treatment cycles, involving 146 148 with IVF, 362 285 with ICSI, 192 027 with frozen embryo replacement (FER), 15 894 with PGT, 56 516 with egg donation (ED), 292 with IVM and 3404 with frozen oocyte replacement (FOR) were reported. European data on IUI using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1364 institutions offering IUI in 26 countries and 21 countries, respectively. A total of 120 789 treatments with IUI-H and 49 163 treatments with IUI-D were included. 

Main results and the role of chance: In 14 countries (17 in 2013), where all institutions contributed to their respective national registers, a total of 291 235 treatment cycles were performed in a population of ~208 million inhabitants, corresponding to 1925 cycles per million inhabitants (range: 423-2978 per million inhabitants). After treatment with IVF the clinical pregnancy rates (PR) per aspiration and per transfer were marginally higher in 2014 than in 2013, at 29.9 and 35.8% versus 29.6 and 34.5%, respectively. After treatment with ICSI the PR per aspiration and per transfer were also higher than those achieved in 2013 (28.4 and 35.0% versus 27.8 and 32.9%, respectively). After FER with own embryos the PR continued to rise, from 27.0% in 2013 to 27.6% in 2014. After ED a similar trend was observed with PR reaching 50.3% per fresh transfer (49.8% in 2013) and 48.7% for FOR (46.4% in 2013). The delivery rates (DR) after IUI remained stable at 8.5% after IUI-H (8.6% in 2013) and at 11.6% after IUI-D (11.1% in 2013). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 34.9, 54.5, 9.9 and in 0.7% of all treatments, respectively (corresponding to 31.4%, 56.3, 11.5% and 1% in 2013). This evolution in embryo transfer strategy in both IVF and ICSI resulted in a singleton, twin and triplet DR of 82.5, 17.0 and 0.5%, respectively (compared to 82.0, 17.5 and 0.5%, respectively, in 2013). Treatments with FER in 2014 resulted in a twin and triplet DR of 12.4 and 0.3%, respectively (versus 12.5 and 0.3% in 2013). Twin and triplet DR after IUI were 9.5 and 0.3%, respectively, after IUI-H (in 2013:9.5 and 0.6%) and 7.7 and 0.3% after IUI-D (in 2013: 7.5 and 0.3%). 

Limitation, reasons for caution: The method of data collection and reporting varies among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution. 

Wider implications of the findings: The 18th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART, the report gives detailed information about ongoing developments in the field. 

Study funding/competing interest(s): The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

ART in Europe, 2014: results generated from European registries by ESHRE: The European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE).

Background Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. Methods In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. Results Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, −2.6 percentage points; 95% confidence interval [CI], −15.0 to 9.9; aspirin only vs. placebo, −6.2 percentage points; 95% CI, −18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, −10.8 to 15.0; aspirin alone vs. placebo −5.4 percentage points; 95% CI, −18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. Conclusions Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.)

/pdf/aspirin-plus-heparin-or-aspirin-alone-in-women-with-37dqr7qmu6.pdf

Aspirin plus Heparin or Aspirin alone in women with recurrent miscarriage

Internationally, ovarian cancer is the 7th leading cancer diagnosis and 8th leading cause of cancer mortality among women. Ovarian cancer incidence varies by region, particularly when comparing high vs. low-income countries. Temporal changes in reproductive factors coupled with shifts in diagnostic criteria may have influenced incidence trends of ovarian cancer and relative rates by histologic subtype. Accordingly, we evaluated trends in ovarian cancer incidence overall (1973-1977 to 2003-2007) and by histologic subtype (1988-1992 to 2003-2007) using volumes IV-IX of the Cancer Incidence in Five Continents database (CI5plus) and CI5X (volume X) database. Annual percent changes were calculated for ovarian cancer incidence trends, and rates of histologic subtypes for individual countries were compared to overall international incidence. Ovarian cancer incidence rates were stable across regions, although there were notable increases in Eastern/Southern Europe (e.g., Poland: Annual Percent Change (APC) 1.6%, p = 0.02) and Asia (e.g., Japan: APC 1.7%, p = 0.01) and decreases in Northern Europe (e.g., Denmark: APC -0.7%, p = 0.01) and North America (e.g., US Whites: APC -0.9%, p < 0.01). Relative proportions of histologic subtypes were similar across countries, except for Asian nations, where clear cell and endometrioid carcinomas comprised a higher proportion of the rate and serous carcinomas comprised a lower proportion of the rate than the worldwide distribution. Geographic variation in temporal trends of ovarian cancer incidence and differences in the distribution of histologic subtype may be partially explained by reproductive and genetic factors. Thus, histology-specific ovarian cancer should continue to be monitored to further understand the etiology of this neoplasm.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.30676

International patterns and trends in ovarian cancer incidence, overall and by histologic subtype.

The overall success of human reproduction, either spontaneously or after IVF, is highly dependent upon maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte/embryo competence due to aging insults, especially concerning an increased incidence of aneuploidies and possibly decreased mitochondrial activity. Age-related chromosomal abnormalities mainly arise because of meiotic impairments during oogenesis, following flawed chromosome segregation patterns such as non-disjunction, premature separation of sister chromatids, or the recent reverse segregation. In this review, we briefly discuss the main mechanisms putatively impaired by aging in the oocytes and the deriving embryos. We also report the main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences.

/pdf/impact-of-maternal-age-on-oocyte-and-embryo-competence-4ekvojyhsc.pdf

Impact of Maternal Age on Oocyte and Embryo Competence

Fertility preservation is a key component of cancer management in young people. The Fourth Evian Annual Reproduction Workshop Meeting was held in April 2009 to discuss cancer and fertility in young adults. Specialists in oncology, assisted reproduction, embryology and clinical genetics presented published data and ongoing research on cancer and fertility, with particular focus on strategies to preserve fertility. This report is based on the expert presentations and group discussions, supplemented with publications from literature searches and the authors' knowledge. Fertility preservation should be considered for all young people undergoing potentially gonadotoxic cancer treatment. A variety of options are required to facilitate safe and effective fertility preservation for individual patients. Sperm banking is a simple and low-cost intervention. Embryo cryopreservation is the only established method of female fertility preservation. Oocyte cryopreservation offers a useful option for women without a male partner. Emergency ovarian stimulation and cryopreservation of ovarian tissue (followed by tissue transplantation or in-vitro maturation of oocytes) are experimental techniques for women who require urgent cancer treatment. Further prospective studies are required to validate cryopreservation of oocytes and ovarian tissue, in-vitro maturation of oocytes and new vitrification techniques and to identify any long-term sequelae of slow freezing of embryos.

https://www.rbmojournal.com/article/S1472-6483(10)00716-9/pdf

Cancer and fertility: strategies to preserve fertility.

BACKGROUND: Sexual reproduction provides the means for preserving genetic identity and in turn, genetic variability may affect the ability to reproduce. This review aims to summarize current research on genetic diagnosis and genetic causes of reproductive disorders. METHODS: Searches were done by subject in Medline and other databases, and each subject summary was presented to the Workshop Group and omissions or disagreements were resolved by discussion. RESULTS: Single-gene defects are most likely to be found among patients with hypogonadotropic hypogonadism, which may be due to defects in the KAL genes or the gonadotrophin-releasing hormone receptor genes. With premature ovarian failure there is an increased risk of having a premutation of the Fragile X syndrome gene. Complex genetic inheritance may explain the variable familial links in polycystic ovary syndrome and endometriosis, but no definitive genetic pathways are as yet known. With recurrent miscarriage, genetic defects causing thrombophilias are 2-fold more likely. Chromosome abnormalities account for similar to 60% of all spontaneous abortions, and the most common type, trisomy, is closely associated with advanced maternal age. Three percent of couples have a balanced chromosome abnormality, but live birth rates are better with natural conception than with preimplantation genetic diagnosis. CONCLUSIONS: Understanding of the methods used for genetic diagnosis and research is becoming a standard requirement for the clinical practice of reproductive medicine.

Genetic aspects of female reproduction

INTRODUCTION: Although fertility rates are falling in many countries, Europe is the continent with the lowest total fertility rate (TFR). This review assesses trends in fertility rates, explores possible health and social factors and reviews the impact of health and social interventions designed to increase fertility rates. 

METHODS: Searches were done in medical and social science databases for the most recent evidence on relevant subject headings such as TFR, contraception, migration, employment policy and family benefits. Priorities, omissions and disagreements were resolved by discussion. 

RESULTS: The average TFR in Europe is down to 1.5 children per woman and the perceived ideal family size is also declining. This low fertility rate does not seem directly caused by contraception since in Northern and Western Europe the fertility decline started in the second half of the 1960s. Factors impacting on lower fertility include the instability of modern partnerships and value changes. Government support of assisted human reproduction is beneficial for families, but the effect on TFR is extremely small. Government policies that transfer cash to families for pregnancy and child support also have small effects on the TFR. 

CONCLUSIONS: Societal support for families and for couples trying to conceive improves the lives of families but makes no substantial contribution to increased fertility rates.

Europe the continent with the lowest fertility

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Cancer and fertility: strategies to preserve fertility.

Genetic aspects of female reproduction

Europe the continent with the lowest fertility