M.G. Vega

Systemic Inflammation and Autoimmunity in Women with Chronic Endometritis.

To determine in women with recurrent pregnancy loss (RPL) and/or implantation failure (RIF) the prevalence of chronic endometritis (CE), systemic inflammation and autoimmunity, and whether they relate.

Anti-mullerian hormone levels decline with the presence of antiphospholipid antibodies.

Autoimmunity is thought to be an important cause of premature ovarian senescence, characterized by abnormal ovarian reserve markers. Anti‐Mullerian hormone (AMH) has emerged as the most reliable marker for ovarian reserve. We here investigated whether non‐specific immune markers are associated with a low age‐specific AMH.

IVF outcomes in average- and poor-prognosis infertile women according to the number of embryos transferred

Outcome measures of IVF success, which account for effectiveness of IVF and perinatal outcome risks, have recently been described. The association between number of embryos transferred in average and poor-prognosis IVF patients, and the chances of having good or poor IVF and perinatal outcomes, was investigated. Good IVF and perinatal outcome was defined as the birth of a live, term, normal-weight infant (≥2500 g). Poor IVF and perinatal outcome was defined as no live birth or birth of a very low weight neonate (<1500 g) or severe prematurity (birth at <32 weeks gestation). Each neonate was analysed as a separate outcome. A total of 713 IVF cycles in 504 average and poor-prognosis patients from January 2010 to December 2013 were identified. The odds of having good IVF and perinatal outcomes increased by 28% for each additional embryo transferred. The odds of poor IVF and perinatal outcome decreased by 32% with an additional embryo transferred. The likelihood of live birth with good perinatal outcome in average- and poor-prognosis patients after IVF increases with additional embryos being transferred. These data add to recently reported evidence in favour of multiple embryo transfer in older women and those with average or poor IVF prognosis.

Mosaicism: throwing the baby out with the bath water?

With the advent of next-generation sequencing (NGS), cytogenetic laboratories now have the ability to detect low-level mosaicism in the trophectoderm of blastocysts [1]. An abstract presented by Dagan Wells, PhD, and his collaborators at the European Society for Human Reproduction and Embryology (ESHRE) Meeting titled: BEvidence that differences between embryology laboratories can influence the rate of mitotic errors, leading to increased chromosomal mosaicism, with significant implications for IVF success rates,^ was well-received. In this study, the authors retrospectively analyzed 623 blastocysts from seven fertility clinics and suggested that under different laboratory conditions, the same embryo can have different mosaicism rates ranging from 32 to 60 % [2]. The abstract focuses on mosaicism-introduced post-fertilization (mitotic non-disjunction of the embryo) and therefore during laboratory culture, rather than due to meiotic nondisjunction of the oocyte. The concept that laboratory conditions may cause postfertilization aneuploidy or mosaicism in embryos is provocative. This could explain the large dissimilarities seen in aneuploidy rates among different clinical trials and why some embryology laboratories see a decrease in their live birth rates per cycle start when performing preimplantation genetic screening (PGS) due to no euploid embryo being available for transfer [3–5]. Munne et al. first described a possible increase in postfertilization mosaicism when comparing different embryology laboratories [6]. More recently, it has been shown that embryos with better morphological scores have fewer chromosomal errors [7, 8]. What specific embryo culture conditions can impact embryomorphology and possibly ploidy status? According to a recent systematic review and meta-analysis of randomized controlled trials (RCTs), culture at 5 % vs. 20 % oxygen concentration increased the number of high/top morphology embryos at the cleavage stage (RR = 1.2, 95 % CI 1.1–1.3) [9]. Different culture media with different recommended pH ranges support blastocyst development in culture, but the optimal pH level has not been established [10, 11]; animal models suggest that strict control of pH at different developmental stages improves embryo quality [12]. A recent RCT showed that embryos cultured at 37 °C have higher blastulation rates (60.1 vs. 51.6 %, p 0.03) and form more usable blastocysts (48.1 vs. 41.2 %, p 0.03) when compared to embryos cultured at 36 °C [13], indicating the need for strictly controlled temperature of incubators and heated surfaces in the laboratory. If we follow this same principle, variations in the biopsy technique such as location of biopsy in the trophectoderm, due to segregation of abnormal cell lines, and/or number of cells removed, may impact the level of mosaicism reported [14]. We know that controlling for these variables by strict adherence to protocols and training of staff lead to comparable and reproducible outcomes with no difference in aneuploidy rates [15]. If indeed there is variation among embryology laboratories of embryos being reported as mosaic, we need to ask ourselves at what stage is the insult occurring and what is its clinical significance? There is evidence that aneuploid cells proliferate more slowly than euploid cells, and if we diagnose an embryo Capsule Causes and clinical implications of mosaicism detected by preimplantation genetic screening (PGS) have yet to be fully established. This commentary suggests possible evidence-based approaches to diagnosing and reporting mosaicism.