https://www.fertstert.org/article/S0015-0282(14)02371-1/pdf

Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health

There is conflicting evidence regarding the effect of raised body mass index (BMI) on the outcome of assisted reproductive technology In particular, there is insufficient evidence to describe the effect of BMI on live birth rates We carried out a systematic review and meta-analysis of studies to evaluate the effect of raised BMI on treatment outcome following IVF/ICSI treatment Subgroup analysis on overweight and obese patients was performed Literature searches were conducted on MEDLINE, EMBASE and the Web of Science from 1966 to 2010 Thirty-three studies including 47,967 treatment cycles were included Results indicated that women who were overweight or obese (BMI ≥ 25) had significantly lower clinical pregnancy (RR=090, P<00001) and live birth rates (RR=084, P=00002) and significantly higher miscarriage rate (RR=131, P < 00001) compared to women with a BMI < 25 following treatment A subgroup analysis of overweight women (BMI ≥ 25-299) revealed lower clinical pregnancy (RR=091, P=00003) and live birth rates (RR=091, P=001) and higher miscarriage rate (RR=124, P < 000001) compared to women with normal weight (BMI < 25) In conclusion, raised BMI is associated with adverse pregnancy outcome in women undergoing IVF/ICSI treatment, including lower live birth rates This effect is present in overweight as well as obese women

https://www.rbmojournal.com/article/S1472-6483(11)00422-6/pdf

Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis

Over-nutrition in females causes altered fetal growth during pregnancy and permanently programs the metabolism of offspring; however, the temporal and mechanistic origins of these changes, and whether they are reversible, are unknown. We now show that, in obese female mice, cumulus-oocyte complexes exhibit endoplasmic reticulum (ER) stress, high levels of intracellular lipid, spindle abnormalities and reduced PTX3 extracellular matrix protein production. Ovulated oocytes from obese mice contain normal levels of mitochondrial (mt) DNA but have reduced mitochondrial membrane potential and high levels of autophagy compared with oocytes from lean mice. After in vitro fertilization, the oocytes of obese female mice demonstrate reduced developmental potential and form blastocysts with reduced levels of mtDNA. Blastocysts transferred to normal weight surrogates that were then analyzed at E14.5 showed that oocytes from obese mice gave rise to fetuses that were heavier than controls and had reduced liver and kidney mtDNA content per cell, indicating that maternal obesity before conception had altered the transmission of mitochondria to offspring. Treatment of the obese females with the ER stress inhibitor salubrinal or the chaperone inducer BGP-15 before ovulation increased the amount of the mitochondrial replication factors TFAM and DRP1, and mtDNA content in oocytes. Salubrinal and BGP-15 also completely restored oocyte quality, embryo development and the mtDNA content of fetal tissue to levels equivalent to those derived from lean mice. These results demonstrate that obesity before conception imparts a legacy of mitochondrial loss in offspring that is caused by ER stress and is reversible during the final stages of oocyte development and maturation.

/pdf/mitochondrial-dysfunction-in-oocytes-of-obese-mothers-31snisjnrw.pdf

Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors

The prevalence of obesity and overweight are increasing and have become an epidemic worldwide. Obesity has detrimental influences on all systems, including reproductive health. The prevalence of obesity in infertile women is high, and it is well known that there is an association between obesity and infertility. The relationship between obesity and reproductive functions is still being explored. Overweight women have a higher incidence of menstrual dysfunction and anovulation. Overweight and obese women are at a high risk for reproductive health. The risk of subfecundity and infertility, conception rates, miscarriage rates, and pregnancy complications are increased in these women. They have poor reproductive outcomes in natural as well as assisted conception. These poor reproductive outcomes include assisted reproduction such as ovulation induction, in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), and ovum donation cycles. Weight loss has beneficial effects on the reproductive outcomes in these patients.

Impact of obesity on infertility in women.

BackgroundSmall lifestyle-intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcomes, but large randomized, controlled trials are lacking. MethodsWe randomly assigned infertile women with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 29 or higher to a 6-month lifestyle intervention preceding treatment for infertility or to prompt treatment for infertility. The primary outcome was the vaginal birth of a healthy singleton at term within 24 months after randomization. ResultsWe assigned women who did not conceive naturally to one of two treatment strategies: 290 women were assigned to a 6-month lifestyle-intervention program preceding 18 months of infertility treatment (intervention group) and 287 were assigned to prompt infertility treatment for 24 months (control group). A total of 3 women withdrew consent, so 289 women in the intervention group and 285 women in the control group were included in ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1505297

Randomized trial of a lifestyle program in obese infertile women

BACKGROUND Debate exists regarding the effect of raised BMI on the outcome of pregnancies after assisted reproduction technology. We assessed the effect of BMI on the risk of miscarriage in women conceiving following single blastocyst transfer (SBT) after controlling for confounding factors. METHODS Fresh and cryo-thawed cycles of SBT that resulted in a pregnancy between January 2006 and March 2010 were included. Patients with BMI < 18.5 kg/m(2) or older than 40 years were excluded. Patients were grouped according to their BMI at the start of treatment cycle. The main outcome measure was the miscarriage rate before 23 weeks gestation. Confounding variables examined included female age, duration and cause of infertility, previous miscarriage, smoking status and quality of blastocyst replaced. RESULTS A total of 413 women conceived following SBT in fresh (n = 325) or cryo-thawed (n = 88) IVF cycles, of whom 244 had a normal BMI (18.5-24.9) and 169 had a raised BMI of ≥ 25. Overall, 27% (113/413) of women miscarried before 23 weeks gestation. Women with a BMI of ≥ 25 had more than double the risk of miscarriage compared with women who had normal BMI [38 versus 20%, odds ratio (OR): 2.4, 95% confidence interval (CI) 1.6-3.8, P < 0.001, respectively]. After adjusting for confounding variables, having a BMI of ≥ 25 significantly increased the risk of clinical miscarriage before 23 weeks gestation in both fresh (adjusted OR = 2.7, 95% CI 1.5-4.9, P = 0.001) and cryo-thawed IVF cycles (OR = 6.8, 95% CI 1.5-31.1, P = 0.012). CONCLUSIONS Raised BMI is independently associated with higher miscarriage rate after IVF treatment.

Influence of BMI on risk of miscarriage after single blastocyst transfer

Obesity contributes to worse outcomes following treatment using assisted reproductive technology (ART), including lower pregnancy and live birth rates and a higher miscarriage rate. This could be mediated through a detrimental effect on oocyte and embryo quality. Oocyte donation studies have suggested that endometrial changes also play a significant role. Endocrine changes associated with obesity, including hyperandrogenism and insulin resistance, as well as changes in local levels of IGFs, cytokines and leptin are thought to underlie the relationship between raised BMI and adverse ART outcomes. This review aims to highlight these underlying mechanisms.

The impact of raised BMI on the outcome of assisted reproduction: current concepts.

/pdf/session-18-miscarriage-treatment-and-prognostic-factors-3r87a7hj0n.pdf

S. Sobaleva

Papers

Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis

Influence of BMI on risk of miscarriage after single blastocyst transfer

The impact of raised BMI on the outcome of assisted reproduction: current concepts.

Session 18: Miscarriage: Treatment and Prognostic Factors