The Risk of Major Birth Defects after Intracytoplasmic Sperm Injection and in Vitro Fertilization

126

The influence of seminal plasma on the cytokine and immune uterine environment is well characterised in mice and humans, while the effects of disruption to uterine seminal plasma exposure on pregnancy and offspring health is becoming more clearly understood. The cellular and molecular environment of the uterus during the pre-and peri-implantation period of early pregnancy is critical for implantation success and optimal foetal and placental development. Perturbations to this environment not only have consequences for the success of pregnancy and neonatal health and viability, but can also drive adverse health outcomes in the offspring after birth, particularly the development of metabolic disorders such as obesity, hypertension and insulin resistance. It is now reported that an absence of seminal plasma at conception in mice promotes increased fat accumulation, altered metabolism and hypertension in offspring. The evidence reviewed here demonstrates that seminal plasma is not simply a transport medium for sperm, but acts also as a key regulator of the female tract environment providing optimal support for the developing embryo and benefiting future health of offspring.

Section: Seminal Plasma and Assisted Reproductionmentioning

confidence: 99%

Seminal fluid and reproduction: much more than previously thought

Bromfield

2014

126

“…The details of the meta-analysis-including the literature search, the study selection and the data extraction processes-are described there. We found 19 studies [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] for inclusion in the meta-analysis and found that ART increased the risk of MM with an odds ratio of 1.29 (95% CI 1.01-1.67). Our major conclusion was that the risk we found may be inflated by the fact that none of the studies used the most appropriate control group, namely subfertile couples conceiving spontaneously.…”

Section: Introductionmentioning

confidence: 99%

A meta-analysis of the impact of IVF and ICSI on major malformations after adjusting for the effect of subfertility

Rimm

Katayama

Katayama³

2011

Objective To estimate the effect of assisted reproductive technology (ART) on major malformation (MM) rate in ART offspring independent of the effect of subfertility on MM. Design Meta-analysis. Methods This meta-analysis is based on our previously published meta-analysis of observational studies evaluating the relationship between ART treatment and MM rates, as well as recent research by Zhu et al. to estimate the impact of subfertility alone on MM in subfertile couples conceiving spontaneously. Results The overall odds ratio for MM in our original metaanalysis, in which all studies used apparently inappropriate control groups of "normal" populations, was 1.29 (95% CI 1.01-1.67). Here we attempted to estimate the risk of subfertility and used this estimate to perform an adjusted meta-analysis. Zhu et al. found that about 40% of the odds of MM was due to subfertility. When we took Zhu's finding into account, the adjusted odds ratio in the meta-analysis was 1.01 (95% CI 0.82-1.23). Conclusions Our study suggests ART does not increase the risk of MM as much as previously reported. More research is needed to quantify the underlying risk of subfertility and separate it from the risk associated with ART. Physicians who counsel subfertile couples should recognize that previous studies of MM rates in ART patients probably overestimated the risk.

“…Major birth defect rates were 3.2 % and 2.7 % for ART and naturally conceived children respectively, but the significance of the difference disappeared after adjustment for maternal age, parity and ethnicity. Hansen et al [35] compared major birth defects in IVF children (8.6 %), ICSI children (9.0 %) and naturally conceived children (4.2 %) respectively. The difference between the ART children and the latter group was significant, but the study was criticised since the group of mothers of naturally conceived children was younger, had a higher parity and was of an ethnically more varied composition.…”

Section: Congenital Malformationsmentioning

confidence: 99%

“…It has been shown that deletions of the Y chromosome are transmitted from father to son [40]. Also the increased incidence of hypospadias in boys born after ICSI has been linked to inherited paternal subfertility factors [35].…”

Section: Congenital Malformationsmentioning

confidence: 99%

Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report

Albertini

Evers²,

Geraedts³

et al. 2014

Purpose Assisted Reproduction Treatment (ART) is here to stay. This review addresses the parental background of birth defects, before, during and after conception and focuses both on the underlying subfertility and on the question whether ART as a treatment is an additional contributing factor. Methods Searches were performed in Medline and other databases. Summaries were discussed in a Delphi panel set-up by the European Society of Human Reproduction and Embryology (ESHRE). Results Several birth defects and adult diseases arise during the earliest stages of ovarian development and oocyte differentiation: this is the case of cleft palate disorders in offspring from female rat exposed to Dioxin during fetal life or the polycystic ovary diseases in female offspring (primates) exposed to elevated androgen concentration during fetal life. Human oocytes and embryos often fail to stop the propagation of aneuploid cells but maintain their ability to repair DNA damages including those introduced by the fertilizing sperm. There is a 29 % increased risk of birth defects in the newborns spontaneously conceived by subfertile couples and the risk is further increased (34 %) when conception is achieved by treating infertlity with ART (Danish IVF Registry). Periconceptional conditions are critical for ART babies: their birth weight is in general smaller (Norvegian Registry) but a more prolonged culture time doubled the number of large babies (Finnish Registry). Conclusion The long-term developmental effects of ART on child and subsequent health as an adult remains a subject worthy of futher monitoring and investigation. Capsule Remaining mindful of the growing body of evidence showing that during gamete production, genetic and epigenetic changes influence offspring health, serves to reinforce the need to continue to monitor ART children.