Abstract
Obesity appears to be associated with female reproductive dysfunction and infertility.
Women with obesity undergoing in vitro fertilization (IVF) had poor oocyte quality,
decreased embryo development, and poor pregnancy outcome. However, the mechanism linking
obesity to poor reproductive outcomes is still unclear. Obesity is frequently accompanied
with elevated leptin levels. Here we aimed to evaluate the effect of high leptin level
in follicular fluid (FF) on the proliferation and apoptosis in granule cells and correlate
these findings with poor reproductive outcomes in infertile women with overweight
or obesity who underwent IVF treatment. We investigated clinical and ongoing pregnancy
rates in 189 infertile women who underwent IVF. Leptin levels were quantified in peripheral
blood and FF as well. In vitro cell model was used to explore the potential effect
of high leptin on the proliferation and apoptosis in granulosa cells. Results showed
reduced clinical and ongoing pregnancy rates in overweight/obesity women who underwent
IVF compared to control with normal BMI. On the other hand, leptin levels presented
significant increase in peripheral blood and FF in overweight/obese women. Leptin
level in FF was negatively correlated to good quality embryo rate. Importantly, in
vitro study showed that leptin inhibited cells proliferation and promoted apoptosis
by upregulation of caspase-3 and downregulation of Bcl-2 in granulosa cells in a dose
dependent manner. These observations suggest that leptin may acts as a local mediator
to attenuate embryo development and reduce fertility in obese patients.
Key words
obesity - leptin - good quality embryo - pregnancy rate - granule cells