Interpretation
In the present study, patients in the HRT-FET group were more likely to
have a higher prepregnancy BMI and complicate with PCOS, which would
increase the probability of combining insulin resistance, metabolic
abnormalities and obesity, and lead to preeclampsia. According to
Versen-Höynck,5 the risk of preeclampsia and severe
preeclampsia would increase in pregnant women without a corpus luteum
compared with those with one or more corpus lutea; moreover, a subgroup
analysis of patients receiving FET indicated that an HRT cycle may lead
to an increased risk of preeclampsia compared with a natural cycle.
Compared NC-FET with a normal corpus luteum, HRT-FET cases are at
increased risk of preeclampsia due to suppression of their own
follicular function, resulting in lack of many vasoactive substances
secreted by the corpus luteum, and reduced vascular
compliance.6 The results of the present study indicate
that for patients who have hypertension diagnosed before pregnancy, a
previous history of preeclampsia or a family history of hypertension,
the selection of fresh embryo transfer and NC-FET rather than HRT-FET is
recommended. For those who have already received HRT-FET, their blood
pressure, urine protein and weight gain need to be well monitored to
prevent preeclampsia.
Studies have shown that high levels of oestradiol are a risk factor for
low birth weight infants. Animal experiments have also found that high
levels of oestrogen in early pregnancy inhibit extravillous trophoblasts
from infiltrating the spiral arterioles of the uterus, resulting in poor
placental angiogenesis, which eventually leads to adverse pregnancy
outcomes.7 It is speculated that the weight of
newborns may be related to the use of a super physiological dose of
oestradiol for ovarian hyperstimulation. In addition, previous studies
have reported that the embryo freezing process of FET may affect the
early epigenetic changes in embryos and then affect the growth potential
of newborns. Mainigi et al. used mouse models to study the effect of
ovulation induction on the growth of the placenta and foetus and
suggested that VEGF affects the formation of the placenta. VEGF also
upregulates the expression of the negative growth regulatory gene Grb10,
a differentially methylated gene of the placenta, whose expression is
markedly upregulated in trophoblasts in the labyrinth zone of the mouse
placenta (the major site of maternal-foetal material exchange in the
mouse placenta), but there was no significant difference in the foetal
mouse.8,9 It is speculated that multiple factors may
be jointly involved in influencing foetal weight in different
transplantation protocols.
Previous studies have shown that among singleton pregnant women,
patients with PCOS have a higher risk of cervical insufficiency than
non-PCOS patients. Higher prepregnancy BMI increased the risk of
cervical insufficiency.10 At the same time, cervical
insufficiency may be related to insulin resistance and hyperandrogenism.
In this study, compared with the NC-FET and fresh embryo transfer
groups, the HRT-FET group had a higher prepregnancy BMI , a higher
proportion of PCOS and intrauterine operation histories. These factors
increased the risk of cervical insufficiency in this group of patients.
The results of this study suggest that in the choice of embryo transfer
method, for the combination of PCOS, obesity, insulin resistance and
other risk factors for cervical insufficiency, the prioritization of
fresh embryo transfer or NC-FET can reduce the risk of premature birth
and cervical insufficiency. Ultrasound regularly monitors the length of
the cervix uteri during pregnancy and obstetric examination to alert
patients to the occurrence of cervical insufficiency.
It is speculated that the incidences of placental increta and placenta
accreta may be related to the supraphysiological dose of oestrogen
caused by controlled ovarian hyperstimulation (COH) in the fresh embryo
transfer protocol and the thinner endometrium on the day of hCG
injection/transformation in the HRT-FET group. Aberdeen et al indicated
that supraphysiological doses of oestrogen lead to a significant
reduction in the pregnancy-associated protein A (PAPP-A) produced by the
placenta and decidua, affecting the infiltration of trophoblasts and
embryonic development and adhesion.11 Senapati et al
showed that COH affects the expression of key genes that mediate
endometrial remodelling in early embryo implantation, which may affect
the infiltration of trophoblasts and vascular remodelling. In this
research, the incidence of placenta previa was higher in the fresh
embryo transfer group, which may be related to asynchrony in endometrial
development and interference with placenta formation caused by the
effect of supraphysiological doses of oestrogen on the endometrium. The
postpartum haemorrhage rate of the HRT-FET group was higher than that of
the fresh embryo transfer and NC-FET group, which may be related to the
higher proportion of placenta accreta and placental adhesion in the FET
hormone replacement cycle. After the foetus is delivered, due to
placental adhesion and placenta accreta, the placenta cannot be
delivered smoothly, which affects uterine contraction and increases the
risk of postpartum haemorrhage. Therefore, for women who undergo
HRT-FET, clinicians should be more vigilant about postpartum haemorrhage
during delivery, the maternal physical condition should be fully
assessed and blood resources should be prepared; for patients with
previous intrauterine operations, especially those with a history of
multiple intrauterine operations, HRT-FET needs to be selected with
caution. If HRT-FET treatment is performed, more attention should be
given to evaluating the severity of placenta accreta, and the mode of
delivery should be fully evaluated to reduce the risk of postpartum
haemorrhage and the serious maternal and foetal complications caused by
placenta accreta.