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.

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.

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.

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.

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.

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.

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.

Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT.

Study Question: Does embryo culture medium influence pregnancy and perinatal outcome in IVF?

Summary Answer: Embryo culture media used in IVF affect treatment efficacy and the birthweight of newborns.

What Is Known Already: A wide variety of culture media for human preimplantation embryos in IVF/ICSI treatments currently exists. It is unknown which medium is best in terms of clinical outcomes.

Differences in Strength and Timing of the mtDNA Bottleneck between Zebrafish Germline and Non-germline Cells.

We studied the mtDNA bottleneck in zebrafish to elucidate size, timing, and variation in germline and non-germline cells. Mature zebrafish oocytes contain, on average, 19.0 × 10(6) mtDNA molecules with high variation between oocytes.

Ammonium accumulation in commercially available embryo culture media and protein supplements during storage at 2-8°C and during incubation at 37°C.

Study Question: Does ammonium accumulate in commercially available culture media and protein supplements used for in vitro development of human pre-implantation embryos during storage and incubation?

Summary Answer: Ammonium accumulates in ready-to-use in vitro fertilization (IVF) culture media during storage at 2-8°C and in ready-to-use IVF culture media and protein supplements during incubation at 37°C.

What Is Known Already: Both animal and human studies have shown that the presence of ammonium in culture medium has detrimental effects on embryonic development and pregnancy rate. It is, therefore, important to assess the amount of ammonium accumulation in ready-to-use IVF culture media under conditions that are common in daily practice.

Differences in gene expression profiles between human preimplantation embryos cultured in two different IVF culture media.

Study Question: Is gene expression in human preimplantation embryos affected by the medium used for embryo culture in vitro during an IVF treatment?

Summary Answer: Six days of in vitro culture of human preimplantation embryos resulted in medium-dependent differences in expression level of genes involved in apoptosis, protein degradation, metabolism and cell-cycle regulation.

What Is Known Already: Several human studies have shown an effect of culture medium on embryo development, pregnancy outcome and birthweight. However, the underlying mechanisms in human embryos are still unknown.

Age of G-1 PLUS v5 embryo culture medium is inversely associated with birthweight of the newborn.

Study Question: Does age of G-1 PLUS v5 embryo culture medium affect IVF outcome?

Summary Answer: Birthweight of singletons born after IVF showed an inverse association with age of the embryo culture medium, while no association was found between age of culture medium and fertilization rate, embryonic development or ongoing pregnancy.

What Is Known Already: It has been reported that IVF culture media can deteriorate during storage, which suggests that the capacity of culture media to support optimal embryo development decreases over time. Some animal studies showed an effect of storage time on embryo development, in contrast to other studies, while the effect of aging culture medium on IVF outcome in humans is unknown.

Does the type of culture medium used influence birthweight of children born after IVF?

Study Question: Do culture media influence birthweight of children born after IVF?

Summary Answer: Some studies have observed a significant effect of culture media on birthweight, while others have not, but since most studies compared different culture media, conventional meta-analysis was not possible.

What Is Known Already: Animal studies suggest that in vitro culture of embryos can have a significant effect on the birthweight of offspring when compared with in vivo developed embryos. The type of culture medium (or certain components of the medium) used is one of the causal factors.

Altered gene expression in human placentas after IVF/ICSI.

Study Question: Is gene expression in placental tissue of IVF/ICSI patients altered when compared with a spontaneously conceived group, and are these alterations due to loss of imprinting (LOI) in the case of imprinted genes?

Summary Answer: An altered imprinted gene expression of H19 and Pleckstrin homology-like domain family A member 2 (PHLDA2), which was not due to LOI, was observed in human placentas after IVF/ICSI and several biological pathways were significantly overrepresented and mostly up-regulated.

What Is Known Already: Genomic imprinting plays an important role in placental biology and in placental adaptive responses triggered by external stimuli. Changes in placental development and function can have dramatic effects on the fetus and its ability to cope with the intrauterine environment.

Impact of maternal cholesterol metabolism on ovarian follicle development and fertility.

The relationship among maternal lipid metabolism, fetal development, and adult disease of the offspring represents an emerging topic of high epidemiological relevance. The present review highlights the very early aspects of this process. Recent data suggest a link between lipid metabolism and reproduction/fertility, not only on the systemic level, but also locally on the level of the ovary that maintains its own sterol metabolism, likely in a self-regulated fashion.

IVF culture medium affects post-natal weight in humans during the first 2 years of life.

Study Question: Is post-natal growth during the first 2 years of life in IVF singletons affected by type of medium used for culturing human embryos during an IVF treatment?

Summary Answer: The in vitro culture of human embryos in medium from Cook resulted in singletons with a lower weight during the first 2 years of life compared with singletons born after embryo culture in medium from Vitrolife.

What Is Known Already: In a previous study, we reported that type of medium used for culturing human IVF embryos during the first few days after fertilization until fresh embryo transfer significantly affects fetal growth and consequently birthweight of the resulting singletons.

Study Design, Size, Duration: From July 2003 to December 2006, a total of 1432 IVF treatment cycles with fresh embryo transfer were randomly allocated to have all embryos cultured in medium from Vitrolife AB (n = 715) or from Cook (n = 717).

IVF culture medium affects human intrauterine growth as early as the second trimester of pregnancy.

Study Question: When does a difference in human intrauterine growth of singletons conceived after IVF and embryo culture in two different culture media appear?

Summary Answer: Differences in fetal development after culture of embryos in one of two IVF media were apparent as early as the second trimester of pregnancy.

What Is Known Already: Abnormal fetal growth patterns are a major risk factor for the development of chronic diseases in adult life. Previously, we have shown that the medium used for culturing embryos during the first few days after fertilization significantly affects the birthweight of the resulting human singletons.

Placentas from pregnancies conceived by IVF/ICSI have a reduced DNA methylation level at the H19 and MEST differentially methylated regions.

Study Question: Does IVF/ICSI have an effect on the epigenetic regulation of the human placenta?

Summary Answer: We found a reduced DNA methylation level at the H19 and MEST differentially methylated regions (DMRs), and an increased RNA expression of H19 in placentas from pregnancies conceived by IVF/ICSI when compared with placentas from spontaneous conception.

What Is Known Already: Changes in fetal environment are associated with adverse health outcomes. The placenta is pivotal for intrauterine environment.

During IVF treatment patient preference shifts from singletons towards twins but only a few patients show an actual reversal of preference.

Background: Knowledge of patients' preferences for elective single embryo transfer (eSET) or double embryo transfer (DET) and for singletons or twins is of great importance in counselling for embryo transfer (ET) strategies. In this study, the stability of IVF patients' preferences over time for either a healthy single child or healthy twins was measured and we investigated which factors could explain preference shifts.

Methods: Infertile women (n = 177) who participated in an RCT comparing one cycle eSET with one cycle DET were included.

Epigenetics and the placenta.

Background: The placenta is of utmost importance for intrauterine fetal development and growth. Deregulation of placentation can lead to adverse outcomes for both mother and fetus, e.g.