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.

Further evidence that culture media affect perinatal outcome: findings after transfer of fresh and cryopreserved embryos.

Background: We have previously shown that the medium used for culturing IVF embryos affects the birthweight of the resulting newborns. This observation with potentially far-reaching clinical consequences during later life, was made in singletons conceived during the first IVF treatment cycle after the transfer of fresh embryos. In the present study, we hypothesize that in vitro culture of embryos during the first few days of preimplantation development affects perinatal outcome, not only in singletons conceived in all rank order cycles but also in twins and in children born after transfer of frozen embryos.

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.

Effect of in vitro culture of human embryos on birthweight of newborns.

Background: In animal models, in vitro culture of preimplantation embryos has been shown to be a risk factor for abnormal fetal outcome, including high and low birthweight. In the human, mean birthweight of singletons after in vitro fertilization (IVF) is considerably lower than after natural conception, but it is not known whether culture conditions play a role in this.

Methods: We compared pregnancy rates and perinatal outcomes from singleton pregnancies resulting from a total of 826 first IVF treatment cycles in which oocytes and embryos were randomly allocated to culture in either of two commercially available sequential media systems.

Cost-effectiveness of seven IVF strategies: results of a Markov decision-analytic model.

Background: A selective switch to elective single embryo transfer (eSET) in IVF has been suggested to prevent complications of fertility treatment for both mother and infants. We compared seven IVF strategies concerning their cost-effectiveness using a Markov model.

Methods: The model was based on a three IVF-attempts time horizon and a societal perspective using real world strategies and data, comparing seven IVF strategies, concerning costs, live births and incremental cost-effectiveness ratios (ICERs).

Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis.

Besides the established selection criteria based on embryo morphology and blastomere number, new parameters for embryo viability are needed to improve the clinical outcome of IVF and more particular of elective single-embryo transfer. Genome-wide gene expression in cumulus cells was studied, since these cells surround the oocyte inside the follicle and therefore possibly reflect oocyte developmental potential. Early cleavage (EC) was chosen as a parameter for embryo viability.

eSET irrespective of the availability of a good-quality embryo in the first cycle only is not effective in reducing overall twin pregnancy rates.

Introduction: In several clinics, elective single-embryo transfer (eSET) is applied in a selected group of patients based on age and the availability of a good-quality embryo. Whether or not eSET can be applied irrespective of the presence of a good-quality embryo in the first cycle, to further reduce the twin pregnancy rate, remains to be elucidated.

Methods: In patients <38 years two transfer strategies were compared, which differed in the first cycle only: group A (n = 141) received eSET irrespective of the availability of a good-quality embryo, and group B (n = 174) received eSET when a good-quality embryo was available while otherwise they received double embryo transfer (DET; referred to as eSET/DET transfer policy).

Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial.

Background: Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population.

In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial.

Background: Elective single embryo transfer (eSET) in a selected group of patients (i.e. young patients with at least one good quality embryo) reduces the number of multiple pregnancies in an IVF programme.

Growth rate of human preimplantation embryos is sex dependent after ICSI but not after IVF.

Background: There is concern that IVF and/or ICSI might have an adverse effect on embryonic development via epigenetic alterations. Such alterations might also be involved in the sex-related growth differences in preimplantation embryos found in some animal species. In the present study we analysed cell numbers of human male and female surplus embryos that developed to the blastocyst stage after either IVF or ICSI in order to investigate possible sex-dependent differential growth rates.

Elective single embryo transfer (eSET) policy in the first three IVF/ICSI treatment cycles.

Background: Elective single embryo transfer (eSET), applied in the first or second IVF cycle in young patients with good quality embryos, has been demonstrated to lower the twin pregnancy rate, while the overall pregnancy rate is not compromised. It is as yet unclear whether eSET could be the preferred transfer policy in all treatment cycles, or that it should be restricted to the first or first two cycles.

Methods: eSET policy (when two or more embryos were available, at least one of them being of good quality) was offered to patients younger than 38 years in the first three treatment cycles.