RESEARCH QUESTION:What is the association of endometrial thickness with pregnancy losses and live births in IVF treatment and the optimal threshold that optimizes the IVF outcome?DESIGN:Data were analysed from 25,767 IVF cycles from centres of the CARE Fertility Group in the UK between 2007 and 2016. Transvaginal ultrasound was conducted to measure the maximum endometrial thickness during gonadotrophin stimulation. Live birth rates were per embryo transfer. Pregnancy loss rates included the combination of biochemical and clinical pregnancy losses.RESULTS:The live birth rate was 15.6% with 5 mm or less endometrial thickness and gradually increased to 33.1% with an endometrial thickness of 10 mm. On the other hand, the pregnancy loss rate was 41.7% with 5 mm or less endometrial thickness and gradually decreased to 26.5% with an endometrial thickness of 10 mm. Statistical modelling for optimal endometrial thickness threshold found 10 mm or more maximized live births and minimized pregnancy losses. This association was independent after adjusting for confounders such as age, oocyte number, number of transferred embryos, ovarian stimulation protocol and embryo quality for live births (crude RR 1.27; 95% CI 1.21 to 1.33; Adjusted RR 1.18; 95% CI 1.12 to 1.23) and pregnancy losses (crude RR 0.83; 95% CI 0.77 to 0.89; adjusted RR 0.86; 95% CI 0.8 to 0.92).CONCLUSIONS:Endometrial thickness is strongly associated with pregnancy losses and live births in IVF, and the optimal endometrial thickness threshold of 10 mm or more maximized live births and minimized pregnancy losses.

Thrombophilia and impaired placental vasculature are a major cause of adverse pregnancy outcome. In 2007, a new hereditary factor for obstetric complications and recurrent pregnancy loss (RPL) was identified as a sequence variation in the core promoter of the annexin A5 gene, ANXA5, called the M2 haplotype. M2 carriership has been demonstrated in couples with recurrent miscarriage and its origin is embryonic rather than specifically maternal, confirmed by subsequent papers. The M2 haplotype is the first report of a hereditary factor related to pregnancy pathology caused by embryonic-induced anticoagulation. It has been demonstrated that couples with RPL had equal and significantly increased M2 carriership and that maternal and paternal carriership confers equal risk. Given its importance for patients with RPL, and potentially implantation failure, this study assessed the incidence of carrier status for the M2 ANXA5 haplotype in both the male and female of couples attending five CARE IVF centres. In 314 patients (157 couples), 44% of couples (one or both partners), 24% of females, 26% of males and 37% of couples with unexplained infertility were M2 carriers. This high incidence has provoked further urgent studies on specific patient populations and on the value of post embryo-transfer therapy.

Thrombophilia and impaired placental vasculature are a major cause of adverse pregnancy outcome. In 2007, a new hereditary factor for obstetric complications and recurrent pregnancy loss (RPL) was identified as a sequence variation in the core promoter of the annexin A5 gene, ANXA5, called the M2 haplotype. M2 carriership has been demonstrated in couples with recurrent miscarriage and its origin is embryonic rather than specifically maternal, confirmed by subsequent papers. The M2 haplotype is the first report of a hereditary factor related to pregnancy pathology caused by embryonic-induced anticoagulation. It has been demonstrated that couples with RPL had equal and significantly increased M2 carriership and that maternal and paternal carriership confers equal risk. Given its importance for patients with RPL, and potentially implantation failure, this study assessed the incidence of carrier status for the M2 ANXA5 haplotype in both the male and female of couples attending five CARE IVF centres. In 314 patients (157 couples), 44% of couples (one or both partners), 24% of females, 26% of males and 37% of couples with unexplained infertility were M2 carriers. This high incidence has provoked further urgent studies on specific patient populations and on the value of post embryo-transfer therapy.

Which pretreatment patient variables have an effect on live birth rates following assisted conception?The predictors in the final multivariate logistic regression model found to be significantly associated with reduced chances of IVF/ICSI success were increasing age (particularly above 36 years), tubal factor infertility, unexplained infertility and Asian or Black ethnicity.The two most widely recognized prediction models for live birth following IVF were developed on data from 1991 to 2007; pre-dating significant changes in clinical practice. These existing IVF outcome prediction models do not incorporate key pretreatment predictors, such as BMI, ethnicity and ovarian reserve, which are readily available now.In this cohort study a model to predict live birth was derived using data collected from 9915 women who underwent IVF/ICSI treatment at any CARE Centres for Assisted Reproduction) clinic from 2008 to 2012. Model validation was performed on data collected from 2723 women who underwent treatment in 2013. The primary outcome for the model was live birth, which was defined as any birth event in which at least one baby was born alive and survived for more than 1 month.Data were collected from 12 fertility clinics within the CARE consortium in the UK. Multivariable logistic regression was used to develop the model. Discriminatory ability was assessed using the area under receiver operating characteristic (AUROC) curve, and calibration was assessed using calibration-in-the-large and the calibration slope test.The predictors in the final model were female age, BMI, ethnicity, antral follicle count (AFC), previous live birth, previous miscarriage, cause and duration of infertility. Upon assessing predictive ability, the AUROC curve for the final model and validation cohort was (0.62; 95% confidence interval (CI) 0.61-0.63) and (0.62; 95% CI 0.60-0.64) respectively. Calibration-in-the-large showed a systematic over-estimation of the predicted probability of live birth (Intercept (95% CI) = -0.168 (-0.252 to -0.084), P < 0.001). However, the calibration slope test was not significant (slope (95% CI) = 1.129 (0.893-1.365), P = 0.28). Due to the calibration-in-the-large test being significant we recalibrated the final model. The recalibrated model showed a much-improved calibration.Our model is unable to account for factors such as smoking and alcohol that can affect IVF/ICSI outcome and is somewhat restricted to representing the ethnic distribution and outcomes for the UK population only. We were unable to account for socioeconomic status and it may be that by having 75% of the population paying privately for their treatment, the results cannot be generalized to people of all socioeconomic backgrounds. In addition, patients and clinicians should understand this model is designed for use before treatment begins and does not include variables that become available (oocyte, embryo and endometrial) as treatment progresses. Finally, this model is also limited to use prior to first cycle only.To our knowledge, this is the first study to present a novel, up-to-date model encompassing three readily available prognostic factors; female BMI, ovarian reserve and ethnicity, which have not previously been used in prediction models for IVF outcome. Following geographical validation, the model can be used to build a user-friendly interface to aid decision-making for couples and their clinicians. Thereafter, a feasibility study of its implementation could focus on patient acceptability and quality of decision-making.None.

Success rates for IVF among women from different ethnic groups have been inconclusive. In this study, the relationship between ethnicity and IVF outcome was investigated. Results of a cohort study analysing 13,473 first cycles were compared with the results of meta-analysed data from 16 published studies. Adjustment was made for age, body-mass index, cause of infertility, duration of infertility, previous live birth, previous spontaneous abortion and number of embryos transferred. Black and South Asian women were found to have lower live birth rates compared with White women: Black versus White (OR 0.42 [0.25 to 0.70]; P = 0.001); South Asian versus White (OR 0.80 [0.65t o 0.99]; P = 0.04). Black women had significantly lower clinical pregnancy rates compared with White women (OR 0.41 [0.25 to 9 0.67]; P < 0.001). The meta-analysed results also showed that Black and South Asian women had statistically significant reduced odds of live birth (OR 0.62 [0.55 to 0.71); P < 0.001 and OR 0.66 [0.52 to 0.85); P = 0.001, respectively). Black and South Asian women seem to have the poorest outcome, which is not explained by the commonly known confounders. Future research needs to investigate the possible explanations for this difference and improve IVF outcome for all women.

Thrombophilia and impaired placental vasculature are a major cause of adverse pregnancy outcome. In 2007, a new hereditary factor for obstetric complications and recurrent pregnancy loss (RPL) was identified as a sequence variation in the core promoter of the annexin A5 gene, ANXA5, called the M2 haplotype. M2 carriership has been demonstrated in couples with recurrent miscarriage and its origin is embryonic rather than specifically maternal, confirmed by subsequent papers. The M2 haplotype is the first report of a hereditary factor related to pregnancy pathology caused by embryonic-induced anticoagulation. It has been demonstrated that couples with RPL had equal and significantly increased M2 carriership and that maternal and paternal carriership confers equal risk. Given its importance for patients with RPL, and potentially implantation failure, this study assessed the incidence of carrier status for the M2 ANXA5 haplotype in both the male and female of couples attending five CARE IVF centres. In 314 patients (157 couples), 44% of couples (one or both partners), 24% of females, 26% of males and 37% of couples with unexplained infertility were M2 carriers. This high incidence has provoked further urgent studies on specific patient populations and on the value of post embryo-transfer therapy.

Background: Meiosis 1 errors are believed to be the largest single cause of clinical embryo failure and early miscarriage. Following the failure of FISH technology and concerns over embryo mosaicism, our aim was to assess paired chromosome status and error rates, and predict oocyte aneuploidy using the metaphase2 polar body with a novel Array CGH platform as a means to select embryos for couples with multiple IVF failures. Methods: The PB1 was removed from metaphase 2 oocytes using a laser-assisted breech of the zona pellucida to effect the biopsy. Reliable 23-paired chromosome analysis was obtained, and in time for fresh embryo transfer. It was a non- randomised investigation in patients seeking this technology as a result of previous multiples failures of IVF. Results: 134 couples presented for 150 cycles of array CGH with a median age of 41.0. 861 polar bodies were evaluated, 67.4% and 32.6% were aneuploid and euploid, respectively. 19,803 paired chromosomes were analysed, 3.5% and 3.4% of chromosome errors resulted in either a gain or loss, respectively. There was a positive correlation between female age and aneuploidy, but no correlation with numbers oocytes harvested. 26% of cycles (n=39) failed to achieve embryo transfer (ET) as none of the oocytes were euploid. The live birth rate per ET and implantation was 24.1% and 27.7%, respectively, and 5.2% of chemical pregnancies (1.9% of transfers) resulted in a dizygotic multiple pregnancy. Conclusion: Array CGH was proven to generate robust chromosome information. Chromosome segregation error rates were found to be inversely proportional to chromosome length and proportional to the G/C base content. Clinically, the transfer of a single embryo after PB 1 array CGH analysis appeared to generate improved implantation rates in women with very poor prognosis, whilst reducing the risk of a multiple pregnancy.

At the outset it is necessary to establish the acronyms that geographically have a different meaning. In the UK and elsewhere it is customary to separate out the screening of chromosomes (Preimplantation Genetic Screening - PGS) from diagnosing a single gene disorder - Preimplantation Genetic Diagnosis (PGD). In some regions, notably the US, both processes PGS and PGD are often included in the over-arching term, PGD. This short article deals only with PGS (perhaps better described as Chromosome Screening). However, it should be noted that with some platforms it is becoming increasingly easier to deliver information on not only the full complement of chromosome information, including a translocation, but also the diagnosis of a monogenic diseased state as well as HLA matching, from a single cell [1] - an exciting prospect indeed.

Copyright: © 2011 Fishel S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. At the outset it is necessary to establish the acronyms that geographically have a different meaning. In the UK and elsewhere it is customary to separate out the screening of chromosomes (Preimplantation Genetic Screening – PGS) from diagnosing a single gene disorder Preimplantation Genetic Diagnosis (PGD). In some regions, notably the US, both processes PGS and PGD are often included in the over-arching term, PGD. This short article deals only with PGS (perhaps better described as Chromosome Screening). However, it should be noted that with some platforms it is becoming increasingly easier to deliver information on not only the full complement of chromosome information, including a translocation, but also the diagnosis of a monogenic diseased state as well as HLA matching, from a single cell [1] – an exciting prospect indeed!

Objective: To ascertain meiotic aneuploidy of the human egg using array comparative genomic hybridization to evaluate the 23-paired chromosome copy number of first polar body as an objective prognosticator of embryo viability for embryo transfer in the same cycle.Design: Case report.Setting: Independent-sector IVF program.Patient(s): A 41-year-old woman with a history of 13 failed cycles of IVF.Intervention(s): Polar body biopsy of metaphase II eggs.Main Outcome Measure(s): Birth.Result(s): Two of the nine eggs were euploid, and the resulting embryos, although morphologically inferior to sibling embryos, were selected for transfer to the uterus, resulting in the birth of a normal healthy baby.Conclusion(s): Selection of euploid eggs, as an objective parameter of subsequent embryo viability and with the opportunity to transfer embryos in the same cycle could maximise the opportunity for live birth after IVF even in cases with poor prognosis. (Fertil Steril (R) 2010; 93: 1006.e7-e10. (C) 2010 by American Society for Reproductive Medicine.)

The most common reason that IVF is unsuccessful is the failure of embryos to implant.Although embryo abnormality may be responsible in many cases, problems relating to abnormalities in a woman's immune system may play a part in a significant proportion of these failures. Evidence is emerging that immunologic and immunophenotypic evidence of local and peripheral natural killer[NK] cell activation and T-helper 1[TH1] dominance may be associated with unexplained repeated embryo implantation failure.We have identified women with these problems and treated them with what we consider appropriate immunotherapy.We present our findings. Retrospective review. 284 women with at least 3 unexplained IVF failures had blood tests for NK assay and TH1/TH2 intracellular cytokine ratios,in addition to other tests fo recurrent embryo implantaion failure.NK abnormalities were treated with intravenous immunoglobulin[IVIg] 25G once between day 8-10 of superovulation, repeated if pregnancy test was positive.TH1/TH2 abnormality with raised TNFalpha: IL10 ratios were treated with antiTNFalpha drugs[Infliximab] 200-300mg before IVF. No abnormalities were found in 13 women.105 women had NK abnormality and had IVIg.9 out of 12 egg recipients[75%]so treated conceived.93 had IVF with own eggs[mean age=37.6yrs, mean no. failed IVF=6.4]-51[54.8%] coceived. 37 women[mean age=37.3yrs,mean no. failed IVF=6.6] had raised TNFalpha/IL10 ratios and were treated with Infliximab.2 out 4 egg recipients so treated[50%]conceived and 20 out of 33 treated with own eggs[60.6%]conceived.49 women have delivered and all babies are fine. A pregnancy rate in the region of 10% would be expected in women with similar IVF profiles. Women with repeated unexplained IVF failures seem to have a high incidence of abnormalities on immunological testing for NK assay and TH1 dominance.Immunotherapy with IVIg and anti TNFalpha drugs seem to improve IVF outcome.More research is however urgently needed on this area.