Discussion
Main
findings and Interpretations
In the current study, elevated BMI was associated with fewer mature
oocytes and available embryos in younger women, but we did not observe a
statistically significant decline in blastocyst formation rate, HQE
rate, and TQE rate in overweight and obese individuals versus
normal-weight controls, which is inconsistent with the research results
of Ioanna et al. 9. Despite previous studies reporting
that elevated BMI can be associated with poor pregnancy outcomes of
fresh IVF cycles, no significant effects of maternal BMI on implantation
rate, CPR, OPR, and LBR in all groups and subgroups were observed in
fresh cycles. This finding may be related to the lack of differences in
the number of HQE and TQE, which could also explain the absence of
statistical differences in the abortion rates of fresh cycles. Unlike
the recent study demonstrated that obesity was associated with
spontaneous abortion19, compared to women with normal
weight, the odds of early miscarriage were 1.45
times higher among obese women20.
CLBR was significantly lower among younger women with high BMI relative
to the normal BMI group; this may be due to a reduced number of
available embryos at cleavage and blastocyst stages in the high BMI
group. Nevertheless, the decrease in the number of
embryos was triggered by a reduction in the number of retrieved oocytes
and mature oocytes, which was statistically different for younger women
among different BMI groups. Thus, we speculated that the obesity
microenvironment has a greater adverse effect on oocyte maturation and
development in younger women than in older
women.
Previous animal studies have indicated that obesity adversely affects
oocyte maturation and embryonic development 21-25.
This could be due to direct damage of the oocytes and indirect effects
of dysfunctional systemic maternal endocrinology and metabolism. Murine
models fed a high-fat diet (HFD-mice) were used to mimic the effects of
obesity and metabolic dysfunction observed in obese humans. In addition
to the body weight gain of the HFD-mice, hypercholesterolemia,
elevations in glucose, insulin, or free fatty acids, and changes in
adipokines may affect oocyte quality21. The adverse
effects of maternal obesity have been observed as early as the oocyte
and two-cell embryo stages, and there are more apoptotic follicles and
smaller and fewer mature oocytes in obese mice compared with control
mice26. Oocytes from HFD-mice tend to have meiotic
aneuploidy, spindle and chromosome alignment defects, and mitochondrial
abnormalities, which are a major cause of early embryonic
loss23, 24. In addition, bidirectional communication
of the oocyte with the surrounding cells is critical for oocyte
development, and several studies have attempted to evaluate the impact
of obesity on these ovarian cells. HFD-mice exhibited increased
anovulation and decreased fertilization rates in vivo, which is
accompanied by remarkably increased apoptosis, endoplasmic reticulum
stress, lipid accumulation, and mitochondrial dysfunction in granulose
and cumulus cells27. Increased apoptosis of granulose
cells might explain the low peak estradiol levels among
obese women of any age, despite the increased Gn dose for younger women.
But research evidence from human studies is limited, Jungheim et al.
demonstrated that obesity does not affect IVF outcomes in women using
donor oocytes28. Recent study using the Time-Lapse
system indicated that human oocytes from overweight and obese women were
smaller and less likely to complete fertilization; the resulting embryos
were more likely to reach the morula stage, and the trophectoderm of
blastocysts had fewer
cells29.
Thus, the adverse effect of elevated BMI on oocyte quality rather than
endometrial receptivity may be the major factor impairing IVF/ICSI
outcomes. However, further research is needed to confirm and consolidate
the above ideas.
Moreover, the long-term adverse effects of obesity are mainly reflected
in the birth safety and health of the offspring. In the present study,
maternal HDP and fetal macrosomia were more likely to occur among
younger women with high BMI. Liu et al.30 also
reported that obesity might raise the risk of some poor prenatal
outcomes through the development of GDM and HDP. Therefore, the fetus is
more likely to be exposed to an adverse intrauterine environment,
resulting in an increased incidence of fetal macrosomia and cesarean
delivery, which, in turn, increases the risk of childhood and adult
obesity. In addition, no significant difference in
congenital defects between different
BMI groups except for cleft lip and
cleft palate in younger women was observed in our study.
Interestingly, our findings indicate no significant differences in
pregnancy outcomes, obstetric and neonatal complications, and congenital
defects between different BMI groups among older women (≥ 38y), whether
undergoing fresh cycles or subsequent FET cycles. Therefore, we believe
that age is still a major factor affecting IVF/ICSI outcomes. Obesity
has a greater adverse impact on younger women (< 38y) compared
to older women (≥ 38y). Kort et al.31 showed that 10%
weight loss could enhance LBR in overweight/obese women. Liu et
al.30 also suggested a 10%–15% reduction in
pre-pregnancy maternal BMI for obese women and a 5% reduction for
overweight women to lower the incidence of prenatal outcomes. Based on
the above evidence, younger women with elevated BMI
should
consider losing weight before pregnancy, but older women do not have to
delay pregnancy to achieve weight loss as they need to balance against
the risk of age-related fertility decline. Notably, our weight loss
recommendations are based on age boundaries. However, it remains to be
tested whether weight management interventions could improve the short-
and long-term outcomes of IVF/ICSI treatment.