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.