Interpretation
Abortion is a common complication of pregnancy. The aetiology of abortion is complex: obesity17, insulin resistance18, hyperandrogenism19, the quality of oocytes and endometrial abnormalities might be associated with the occurrence of abortion 20-22. As reported in prior studies, women with PCOS are associated with an increased risk of abortion23,24. In addition, Wang et al.25 found that the incidence of abortion was increased in women who underwent ART, with a possible mechanism related to corpus luteum insufficiency.
In our study, the incidence of abortion was significantly increased in PCOS phenotypes A and D, and with the coexistence of OA and PCOM in PCOS phenotypes A and D. We speculate that the combination of OA and PCOM might increase the risk of abortion by affecting oocyte quality. A study by Barnes and colleagues reported that oocyte maturation and the fertility rate of anovulatory women were significantly lower than those of regular cycling women; their embryo development ratio followed a similar trend26. Another study of anovulation in cows found that anovulation also leads to major shifts in gene expression in elongated conceptuses during preimplantation stages; transcripts involved with the control of energy metabolism and DNA repair were downregulated, whereas genes linked to apoptosis and autophagy were upregulated27. Furthermore, a recent study revealed decreased oocyte quality in PCOM due to the abnormal activation of one-carbon metabolism and hypermethylation of mitochondrial DNA28. These results support the above conjecture.
Moreover, we also observed that the rate for the presence of a corpus luteum (because of different endometrial preparation protocols for FET) in PCOS phenotypes A and D was significantly lower than that in controls, which might be another reason for the higher rate of abortion. In clinical practice, for PCOS women with OA, clinicians generally adopt a hormone replacement therapy (HRT) cycle to prepared the endometrium for FET29. Recently, Xu et al.30 noticed that HRT cycles were related to a higher abortion rate, which is consistent with the results of a prior study31. The corpus luteum is an important source of hormones in pregnant women12,32, but during endometrial preparation, a corpus luteum is absent in a HRT cycle. Additionally, administering exogenous hormone in a HRT cycle might increase the risk of thromboembolic events and could damage placentation, which may then lead to abortion33,34.
It is generally known that obesity has an undesirable impact on women’s reproduction35. Obesity increases the rate of abortion36 and is an independent risk factor for abortion37,38. Obesity affects follicle development by affecting sex hormone secretion and metabolism35; other studies have found adverse effects of obesity on the quality of the embryo 39 and endometrial receptivity40. In the present study, the BMI in PCOS phenotype A and D groups was significantly higher than that in the control group. Before the initiation of FET, obese women can reduce their weight to optimise pregnancy outcomes41. Interestingly, we also noticed that the age of the women in PCOS phenotypes A and D was lower than that of women in the control group. It is well documented that maternal age increases the incidence of abortion42,43. It is possible that other factors masked the effect of age on abortion. The average age of patients was 30.62 ± 4.07 years in our study, which may have a relatively small impact on abortion. Previous studies found that an advanced age increased the risk of abortion, usually over the age of 35 or 3844,45. In addition, previous studies have suggested that HA is associated with increased rates of abortion46. However, this was not found in our study. A recent systematic review and meta-analysis also showed that HA does not increase the risk of abortion in patients with PCOS18.
Therefore, for women with PCOS phenotypes A and D, lifestyle interventions such as improved diet and increased exercise were used to reduce body weight before FET; natural or ovulation-induced cycles are recommended as a priority for endometrial preparation in FET, and an appropriately increased luteum phase supported. Additionally, pregnancy follow-up after obtaining a clinical pregnancy should be strengthened, and, with any sign of an abortion, treatment should be promptly provided.