We described a woman with mosaic TS who got twin pregnancy following IVF with oocyte donation. In addition to cardiopulmunary arrest, she had some postpartum complications such as prolonged fever, aspiration pneumonia, lung abscess, and endometritis, which were in line syndrome of COVID-19. According to the literature, many studies have been carried out on IVF in TS, few studies have focused on postpartum events [7,8]. Aspiration of small amounts of oropharyngeal secretions is common even to healthy individuals and usually resolves without detectable sequelae. Sensitive tests show that at least one-half of healthy adults’ aspirate during sleep. Thus, most episodes of aspiration are subclinical and/or rapidly resolve without clinical manifestations. The small fraction of aspiration events that do proceed to clinically manifest disease appear to depend upon the volume and contents of the inoculum as well as failures of host defense mechanisms [9]. There are many factors that was made aspiration pneumonia in our case, such as, emergency hysterotomy and anesthesia. But one of the causes of developing lung abscess and prolonged fever following aspiration pneumonia may be attributable to defects of immune responses in these patients.

Moreover, TS may be associated with immune abnormalities. TS patients have been reported to have immune alterations in T cell and immunoglobulin subsets. These include decreased levels of circulation T and B lymphocytes, reduced levels of serum IgG and IgM, and increased IgA [10]. However, other studies did not find major immunological deficiencies in TS subjects [11]. A total of 1169 unique genes showed different expression in TS peripheral blood mononuclear cells (PBMCs) including 35 on the X chromosome. In particular, ubiquitously transcribed tetratricopeptide repeated on chromosome X (UTX) was among the top 10 X-linked genes with the largest decrease in expression and the only gene among these candidates that escapes X inactivation. TS patient immune cells express decreased UTX, a Histone-Modifying Enzyme. UTX Deficiency in T cells prevents T follicular helper (Tfh) differentiation and eradication of chronic infection. TS patients have decreased Tfh cells [10]. In our case, there were aspiration pneumonia, pneumonitis, endometritis, and prolonged fever. It is supposed that lower immunoglobulins, immune cell deficiency and failure of defense mechanisms in women with TS predispose them to these situations. Therefore, treatment with intravenous immunoglobulins (IVIG) could be effective. According to study of Bradly J et al, decreased Tfh cells in TS suggested impaired response to viruses and vaccines [10]. We're living in COVID-19 era and TS patients are a part of the society, thus, it is recommended to design a study to evaluate which type of vaccine and how many doses of vaccines are needed to vaccinate these women.

Due to inherent cardiovascular abnormalities associated with TS, these women are at the increased risk of dying from aortic dissection or rupture owing to the increased cardiovascular demands of pregnancy. These demands are further increased in multiple gestations, which are often an unfortunate consequence of ART. For this reason, it is imperative that any woman with TS who is undergoing treatment with IVF or donor oocyte has only a single embryo transferred [12] which is in line with Bouet et al’s study [13]. Due to small uterine size of women with TS even after hormonal therapy, Folsom et al also recommended that only one embryo should be transferred per IVF cycle to prevent undue complications [14]. Data of Calanchini et al. confirmed that IVF–oocyte donation with double embryo transfer is associated with miscarriages and poor maternal and fetal outcomes [15], so in our case if one embryo had transferred, maybe PPROM and the following complications wouldn't have happened.

In sum, any pregnancy in woman with TS must be considered as high risk of innately cardiovascular risk related to structural cardiac anomalies that this population predisposed to. However, TS is not an absolute contraindication to pregnancy, but there are no screening methods to divide the potential population into those individuals whose underlying cardiovascular risks are too high to allow pregnancy and those who might reasonably be monitored and guided by a skilled perinatologist through a high-risk pregnancy [16]. Despite these risks for a pregnancy, there is a tendency to oocyte donation to achieve a pregnancy, so, it seems logical to transfer one embryo instead of two, to mitigate pregnancy and postpartum complications. Finally, as the best option, use of gestational surrogate is recommended for women considering use of donor eggs for eliminating these risks and to be a biological parenting.

Disclosure

The authors declare no conflict of interest.