Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight.

Children conceived through assisted reproductive technologies (ART) have an elevated risk of lower birthweight, yet the underlying cause remains unclear. Our study explores mitochondrial DNA (mtDNA) variants as contributors to birthweight differences by impacting mitochondrial function during prenatal development. We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or after ovarian stimulation (OS) and find that ART individuals carried a different mtDNA genotype than SC individuals, with more de novo non-synonymous variants.

The prevalence and clinical course of shoulder injury related to vaccine administration (SIRVA) after COVID-19 vaccines in Dutch hospital workers.

Introduction: Shoulder Injury Related to Vaccine Administration (SIRVA) is a rare disorder characterized by persistent shoulder pain and limited range of motion presenting within 48 h after vaccine administration. With the widespread distribution of the COVID-19 vaccine, the incidence of SIRVA is expected to rise. This sudden rise in vaccine administration presents an ideal opportunity to estimate the prevalence of SIRVA and to better characterize SIRVA.

ESHRE PGT Consortium data collection XXI: PGT analyses in 2018.

Study Question: What are the trends and developments in preimplantation genetic testing (PGT) in 2018 as compared to previous years?

Summary Answer: The main trends observed in this 21st dataset on PGT are that the implementation of trophectoderm biopsy with comprehensive whole-genome testing is most often applied for PGT-A and concurrent PGT-M/SR/A, while for PGT-M and PGT-SR, single-cell testing with PCR and FISH still prevail.

What Is Known Already: Since it was established in 1997, the ESHRE PGT Consortium has been collecting and analysing data from mainly European PGT centres. To date, 20 datasets and an overview of the first 10 years of data collections have been published.

At age 9, the methylome of assisted reproductive technology children that underwent embryo culture in different media is not significantly different on a genome-wide scale.

Study Question: Can we detect DNA methylation differences between ART children that underwent embryo culture in different media?

Summary Answer: We identified no significant differences in site-specific or regional DNA methylation between the different culture medium groups.

What Is Known Already: Embryo culture in G3 or K-SICM medium leads to differences in embryonic, neonatal and childhood outcomes, including growth and weight. The methylome may mediate this association as the period of in vitro culture of ART treatments coincides with epigenetic reprogramming.

Methylome-wide analysis of IVF neonates that underwent embryo culture in different media revealed no significant differences.

A growing number of children born are conceived through in vitro fertilisation (IVF), which has been linked to an increased risk of adverse perinatal outcomes, as well as altered growth profiles and cardiometabolic differences in the resultant individuals. Some of these outcomes have also been shown to be influenced by the use of different IVF culture media and this effect is hypothesised to be mediated epigenetically, e.g.

Endometrial factors in the implantation failure spectrum: protocol of a MUltidisciplinary observational cohort study in women with Repeated Implantation failure and recurrent Miscarriage (MURIM Study).

Introduction: Women with repeated implantation failure (RIF) and unexplained recurrent miscarriage (RM) are proposed to be at opposite ends of the implantation spectrum, with RM representing an overly receptive endometrium (implantation of genetically aberrant or poor-quality embryos) versus RIF representing an overly selective endometrium (no implantation even with good quality embryos). In both cases, often no explanation for reproductive failure can be found and although promising add-on treatments have been introduced, therapeutic options are frequently limited to supportive care. Both RM and RIF are multifactorial and research indicates that the interplay between steroidogenesis, uterine natural killer (uNK) cells and the microbiome determine the capacity of the endometrium to be a biosensor for invading embryos.

Lifestyle intervention prior to IVF does not improve embryo utilization rate and cumulative live birth rate in women with obesity: a nested cohort study.

Study Question: Does lifestyle intervention consisting of an energy-restricted diet, enhancement of physical activity and motivational counseling prior to IVF improve embryo utilization rate (EUR) and cumulative live birth rate (CLBR) in women with obesity?

Summary Answer: A 6-month lifestyle intervention preceding IVF improved neither EUR nor CLBR in women with obesity in the first IVF treatment cycle where at least one oocyte was retrieved.

What Is Known Already: A randomized controlled trial (RCT) evaluating the efficacy of a low caloric liquid formula diet (LCD) preceding IVF in women with obesity was unable to demonstrate an effect of LCD on embryo quality and live birth rate: in this study, only one fresh embryo transfer (ET) or, in case of freeze-all strategy, the first transfer with frozen-thawed embryos was reported. We hypothesized that any effect on embryo quality of a lifestyle intervention in women with obesity undergoing IVF treatment is better revealed by EUR and CLBR after transfer of all fresh and frozen-thawed embryos.

ESHRE PGT Consortium data collection XIX-XX: PGT analyses from 2016 to 2017.

Study Question: What are the trends and developments in pre-implantation genetic testing (PGT) in 2016-2017 as compared to previous years?

Summary Answer: The main trends observed in this 19th and 20th data set on PGT are that trophectoderm biopsy has become the main biopsy stage for PGT for aneuploidies (PGT-A) and that the implementation of comprehensive testing technologies is the most advanced with PGT-A.

What Is Known Already: Since it was established in 1997, the ESHRE PGT Consortium has been collecting and analysing data from mainly European PGT centres. To date, 18 data sets and an overview of the first 10 years of data collections have been published.

ESHRE PGT Consortium data collection XVI-XVIII: cycles from 2013 to 2015.

Study Question: What are the trends and developments in preimplantation genetic testing (PGT) in 2013-2015 as compared to previous years?

Summary Answer: The main trends observed in the retrospective data collections 2013-2015, representing valuable data on PGT activity in (mainly) Europe, are the increased application of trophectoderm biopsy at the cost of cleavage stage biopsy and the continuing expansion of comprehensive testing technology in PGT for chromosomal structural rearrangements and for aneuploidies (PGT-SR and PGT-A).

What Is Known Already: Since it was established in 1997, the ESHRE PGT Consortium has been collecting data from international PGT centres. To date, 15 data sets and an overview of the first 10 years of data collections have been published.

Comparison of DNA methylation patterns of parentally imprinted genes in placenta derived from IVF conceptions in two different culture media.

Study Question: Is there a difference in DNA methylation status of imprinted genes in placentas derived from IVF conceptions where embryo culture was performed in human tubal fluid (HTF) versus G5 culture medium?

Summary Answer: We found no statistically significant differences in the mean DNA methylation status of differentially methylated regions (DMRs) associated with parentally imprinted genes in placentas derived from IVF conceptions cultured in HTF versus G5 culture medium.

What Is Known Already: Animal studies indicate that the embryo culture environment affects the DNA methylation status of the embryo. In humans, birthweight is known to be affected by the type of embryo culture medium used.

Erratum: Increased blood pressure and impaired endothelial function after accelerated growth in IVF/ICSI children.

[This corrects the article DOI: 10.1093/hropen/hoz037.].

Reduced oxygen concentration during human IVF culture improves embryo utilization and cumulative pregnancy rates per cycle.

Study Question: Do different oxygen levels during human IVF embryo culture affect embryo utilization, cumulative IVF success rates per cycle and neonatal birthweight?

Summary Answer: After 2 days of culture, a lower oxygen level (5%) leads to more good-quality embryos and more embryos that can be cryopreserved, and thereby to a higher cumulative live birth rate per cycle when compared to embryo culture in 20% oxygen, while birthweights are similar.

What Is Known Already: Several studies have compared IVF outcome parameters after embryo culture in a more physiological level of 5% oxygen and the atmospheric level of 20%. Although there is consensus that embryo development improves in 5% oxygen, effects on pregnancy and live birth rates are mainly seen in blastocyst, but not cleavage-stage transfers.

Increased blood pressure and impaired endothelial function after accelerated growth in IVF/ICSI children.

Study Question: What is the effect of growth velocity (height and weight) in early infancy on metabolic end-points and endothelial function in children born after ART?

Summary Answer: Neonatal, infant and childhood growth is positively related to blood pressure in 9-year-old IVF/ICSI offspring, while growth in childhood was negatively associated with endothelial function.

What Is Known Already: Offspring of pregnancies conceived after ART are at risk for later cardiometabolic risk factors. It is well established that early growth is related to numerous later cardiometabolic risk factors such as high blood pressure.

Anti-oxidative function of follicular fluid HDL and outcomes of modified natural cycle-IVF.

High density lipoproteins (HDL) are the main cholesterol carriers in follicular fluid (FF), the natural environment of oocyte development. Additionally, HDL have critical biological functions such as anti-oxidative capacity, which have not been studied in reproduction. Therefore, this study aimed to investigate whether the anti-oxidative function of FF-HDL is associated with fertility outcomes.

Preconceptional Maternal Bile Acids and Birth Weight of Neonates.

Preconceptional maternal bile acid species are significantly associated with birth weight of the offspring.

Growth, health, and motor development of 5-year-old children born after preimplantation genetic diagnosis.

Objective: To evaluate the growth, health, and motor development of children born after preimplantation genetic diagnosis (PGD).

Design: Observational cohort study and comparison of 5-year-old children born after PGD to similar aged children born after IVF/intracytoplasmic sperm injection (ICSI) and children from families with a genetic disorder born after natural conception (NC).

Setting: University hospital.

No effect of IVF culture medium on cognitive development of 9-year-old children.

Study Question: Do embryo culture media used during an IVF/ICSI treatment have an effect on cognitive development of singleton IVF children at 9 years of age?

Summary Answer: Cognitive development of children born after culture in two different embryo culture media is comparable.

What Is Known Already: Previously, we have shown that the culture medium used in an IVF/ICSI treatment affects birthweight and weight at 2 years of age after alternating assignment to embryo culture in either K-SCICM (Cook) or G1™ Version 3 (Vitrolife). Children with low birthweight are known to have an increased risk for learning disabilities.

The choice for invasive prenatal tests after subfertility.

The aim of this study was to test whether women who conceived after a period of subfertility are less likely to undergo invasive prenatal testing (IPT) and determine factors of influence in that decision. We conducted a retrospective study at the Maastricht University Medical Centre (MUMC+) to compare the rates of IPT following abnormal results of combined first trimester screening (cFTS) or second trimester screening (STS), or because of advanced maternal age among women tested for the effect of type and duration of subfertility and history of fertility investigations and/or treatment. We included 977 women who underwent IPT between January 2010 and December 2013.

Differential miRNA Expression Profiles in Cumulus and Mural Granulosa Cells from Human Pre-ovulatory Follicles.

Background: Mural Granulosa Cells (MGCs) and Cumulus Cells (CCs) are two specialized cell types that differentiate from a common progenitor during folliculogenesis. Although these two cell types have specialized functions and gene expression profiles, little is known about their microRNA (miRNA) expression patterns.

Objective: To describe the miRNA profile of mural and cumulus granulosa cells from human preovulatory follicles.

Perinatal follow-up of children born after preimplantation genetic diagnosis between 1995 and 2014.

Purpose: We aim to evaluate the safety of PGD. We focus on the congenital malformation rate and additionally report on adverse perinatal outcome.

Methods: We collated data from a large group of singletons and multiples born after PGD between 1995 and 2014.

Association of culture medium with growth, weight and cardiovascular development of IVF children at the age of 9 years.

Study Question: Is embryo culture media used during an IVF/ICSI treatment associated with differences in growth, body composition and cardiovascular development as determined in 9-year-old singleton IVF children?

Summary Answer: The choice of in vitro culture medium for human embryos is associated with differences in body weight, BMI, truncal adiposity, waist circumference and waist/hip ratio at the age of 9, while no significant differences were observed in cardiovascular development.

What Is Known Already: Children born after IVF/ICSI have an increased risk of low birthweight, which is correlated with a higher risk of cardiovascular diseases. Some studies show that IVF children exhibit a significantly higher systolic and diastolic blood pressure and higher fasting glucose levels compared to naturally conceived children.

Recent developments in genetics and medically assisted reproduction: from research to clinical applications.

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing.

Recent developments in genetics and medically-assisted reproduction: from research to clinical applications.

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively-parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing.

The treatment of post-hysterectomy vaginal vault prolapse: a systematic review and meta-analysis.

Introduction And Hypothesis: The treatment of post-hysterectomy vaginal vault prolapse (VVP) has been investigated in several randomized clinical trials (RCTs), but a systematic review of the topic is still lacking. The aim of this study is to compare the effectiveness of treatments for VVP.

Methods: We performed a systematic review and meta-analysis of the literature on the treatment of VVP found in PubMed and Embase.

BRCA1 mutation carriers have a lower number of mature oocytes after ovarian stimulation for IVF/PGD.

Purpose: The aim of this study was to determine whether BRCA1/2 mutation carriers produce fewer mature oocytes after ovarian stimulation for in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD), in comparison to a PGD control group.

Methods: A retrospective, international, multicenter cohort study was performed on data of first PGD cycles performed between January 2006 and September 2015. Data were extracted from medical files.