Clinical characteristics and laboratory data of pre-eclampsia patients with and without in vitro fertilization embryo transfer treatment

doi:10.21203/rs.3.rs-1518857/v1

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Clinical characteristics and laboratory data of pre-eclampsia patients with and without in vitro fertilization embryo transfer treatment

https://doi.org/10.21203/rs.3.rs-1518857/v1

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Background

Pre-eclampsia affects around 2-10% pregnancies in the world. In vitro fertilization embryo transfer (IVF) pregnancies are associated with a 2.7-fold risk of pre-eclampsia.

Methods

In our retrospective study, 20 pre-eclampsia patients with IVF treatment (PE with IVF group) and 20 matched pre-eclampsia controls with spontaneous conception (PE group) were enrolled. We also collected several fresh decidua tissue and cord blood specimens to determine functional changes of innate immune cells at maternal-fetal interface using flow cytometry assays.

Results

There were no obvious differences in pregnancy outcomes between 2 groups. However, maternal prealbumin (PA) level was significantly decreased while creatinine (Cr) and uric acid (UA) levels were significantly elevated in PE with IVF group. Although levels of maternal alkaline phosphatase (ALP) and cystatin C (CysC) did not differ between 2 groups, they were both abnormally elevated, exceeding the normal reference range. Moreover, significant elevations of IFN-γ and TNF-α secretions were observed in both decidual NK cells and γδT cells of pre-eclampsia patients with IVF treatment. In cord blood, productions of IFN-γ and TNF-α were only increased in the NK cells of pre-eclampsia patients with IVF treatment.

Conclusion

The close surveillance for clinical features of this special pre-eclampsia population is strongly warranted.

Pre-eclampsia

IVF treatment

Clinical characteristic and laboratory data

Pro-inflammatory response

Pre-eclampsia is a multisystem pregnancy complication characterized by variable degrees of placental mal-perfusion, with release of excess anti-angiogenic factors into maternal circulation [1, 2]. These factors can lead to hypertension and multi-organ injury [3]. Pre-eclampsia affects 2-10% of pregnancies around the world and accounts for 15-20% of maternal mortality in developed countries [4, 5]. Therefore, identifying pregnancies at risk for pre-eclampsia is of great value. Previous research has demonstrated that women with prior pre-eclampsia, chronic hypertension, pregestational diabetes, multifetal pregnancy, antiphospholipid antibody syndrome, pre-pregnancy body mass index (BMI) > 30, systemic lupus erythematosus, previous stillbirth, nulliparity, previous placental abruption and the use of assisted reproductive technology (ART), chronic kidney disease, maternal age > 35/40 years and fetal growth restriction are several prominent risk factors of pre-eclampsia [1, 6] (Figure 1).

Since the first IVF pregnancy in the 1980s, this successful treatment for infertility has become popular [7]. However, recent evidence shows that, as compared with the general population, IVF pregnancies are associated with higher risks of adverse obstetric and perinatal complications, including preterm delivery (PTD), low birth weight (LBW), intrauterine growth restriction (IUGR), and pre-eclampsia [8, 9]. Several reasons have been brought up to explain this phenomenon, such as multiple gestation, advanced age at first ongoing pregnancy, and diminished responsiveness of ovaries to FSH stimulation in the IVF cycle [10, 11].

During gestation, maternal body would undergo series of adaptive anatomical and physiological changes, such as endocrine, metabolic, and inflammation [12-14]. These changes are essential for fetal growth and delivery. However, the situation is complicated by the pre-eclampsia [14-16]. Several studies have already summarized the clinical characteristics of the general pre-eclampsia population [17, 18]. It is noteworthy that, in recent years, we have observed the pre-eclampsia patients with IVF treatment experience present in a high proportion of the whole pre-eclampsia population in the clinical setting. However, the clinical laboratory features and characteristics of this special pre-eclampsia population are still not properly understood.

Our study demonstrates the differences in the birth outcomes, maternal hepatic and renal status, glucose and lipid profiles between the PE group and the PE with IVF group. We have also collected fresh decidua and cord blood specimens of several pre-eclampsia patients with and without IVF treatment to determine the secretions of classical pro-inflammatory factors including interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in their decidual and blood natural kill (NK) cells and γδT cells, respectively (Figure 1). We propose that greater focuses on the clinical laboratory features and some functional changes of innate immune cells of this special subset pre-eclampsia population are critical for the clinical management and the prevention of severer pregnancy complications.

2.1 Clinical study

A clinical retrospective case-control study was conducted and enrolled 20 pre-eclampsia patients with IVF treatment experience (PE with IVF group) and 20 matched pre-eclampsia patients with spontaneous conception (PE group) in West China Second Hospital from 2020 September to 2022 January. Pre-eclampsia was defined as blood pressure ≥ 140/90 mmHg accompanied by proteinuria after 20 gestational weeks [1]. Our exclusion criteria include: (1) abnormal chromosome karyotype; (2) infection of viruses or bacteria; (3) other serious pregnancy complications; (4) male infertility. Both 2 groups were matched for maternal age, BMI, gestational age, and disease severity. In this study, we only enrolled singleton pregnancies to avoid the effects of twins. All pregnancies performed the routine pregnancy examinations in our hospital, and they were all diagnosed of pre-eclampsia in the third trimester and finally delivered by cesarean section. The clinical information of enrolled patients was collected from the medical records during their clinical course. The laboratory data presented in tables referred to the results from the fresh blood samples of pregnancies obtained at the admission for pre-eclampsia. The liver function tests, renal function tests and glucose/lipid tests were determined with the Siemens ADVIA 2400 chemistry analyzer.

2.2 Cord blood/decidua samples collection

We also collected fresh delivery specimens (decidua tissue and cord blood) from 16 pre-eclampsia patients with or without IVF treatment experience. All specimens were obtained from the obstetrics and gynecology department of the West China Second Hospital, between October 2021 and January 2022. The fresh decidua tissue was immediately collected into a separate sterile tube (Corning, USA) after cesarean-section delivery, and transported to our laboratory for further processing. Matched 3 mL cord blood was simultaneously collected in a heparin anti-coagulated vacutainer tube (BD Pharmingen, USA). The protocol of specimen collection was approved by the Medical Ethics Committee of West China Second Hospital of Sichuan University [Record number: 2020 (029)], and written informed consents were obtained from all fresh delivery specimen donors.

2.3 DICs and CBMCs isolation

Decidual immunocytes (DICs) were isolated following a previous methodology [19]. Briefly, the fresh decidual tissues were firstly rinsed several times with ice-cold PBS. Then, decidua tissue specimens were cut into small pieces, digested with 1 mg/mL Collagenase IV (Sigma, United States), and 150 U/mL of DNase I (Applichem, Germany) for 45 min gentle agitation at 37℃, and stopped by adding 3 mL fetal calf serum (Hyclone, United States). After digestion, the cells were filtered through 70 and 40 μm cell strainers (BD, USA), centrifuged at 600 g for 10 min, and resuspended in 3 mL of 10% FBS RPMI-1640 medium. The single-cell suspension was loaded on a Percoll gradient (3 mL of 20% Percoll, 3 mL of 40% Percoll, and 3 mL of 60% Percoll), and centrifuged at 600 g for 20 min. The DICs were collected on the interface fraction between 40% and 60% Percoll. The Percoll with 1.130 g/mL density was purchased from the GE Healthcare.

For cord blood mononuclear cells (CBMCs) isolation, the 3 mL cord blood was carefully added onto the Ficoll (Tbdscience, Tianjin, China) layer (Blood: Ficoll = 1:1) and centrifuged at 450 g for 20 min with brake off. The mononuclear layer was obtained and washed by PBS.

2.4 Hematoxylin and eosin (HE) staining

HE staining assay was conducted by Servicebio company (Wuhan, China), and the image was captured by an inverted microscope (Olympus, U-HGLGPS, Japan).

2.5 Flow Cytometry

Briefly, approximately 1x10⁶ cells were first stained for live/dead discrimination by using Zombie Aqua fixable viability kit (BioLegend, USA). Subsequently cells were stained with anti-human CD45, CD3, CD56, and γδ TCR antibodies (listed in the SI Table 1) for 20 min in the dark at room temperature (RT) after 10 min of incubation with Fc-Block (BioLegend, USA).

Intracellular cytokine concentrations were measured by flow cytometry using anti-human IFN-γ and anti-human TNF-α, purchased from BioLegend (SI Table 1). In specific, cells were stimulated with 2 μL Cell Activation Cocktail (BioLegend, USA) for 4 h, and the addition of protein transport inhibitors, including brefeldin A (BioLegend, USA) and monensin (BioLegend, USA) was necessary. Flow cytometry data acquisition was performed using a FACS Celesta flow cytometer (BD, USA), and analyzed using the FlowJo software V.10. All of flow cytometry data was compensated in FlowJo software V.10 by using single stained controls.

2.6 Statistical analysis

The SPSS software, version 21.0 (IBM Inc., Chicago, IL) was applied to analyze the statistical data. The Student’s t-test or Mann-Whitney test were used to assess differences between groups. Nonnormally distributed data were expressed as median (interquartile range), and normally distributed data were described as means (SEM). All the P values were two-sided and statistical significance level was at P ＜ 0.05.

3.1 There was no significant differences in pregnancy outcomes between PE group and PE with IVF group

The 2 groups were closely matched for maternal age, maternal BMI, gestational age, and the disease severity. Table 1 showed the baseline characteristics of enrolled patients for the retrospective study. No significant differences in maternal age, maternal BMI, gestational age, blood pressure, and the number of patients with mild/severe pre-eclampsia were found between the 2 groups. We observed that women in the PE group presented a higher number of deliveries when compared to the PE with IVF group. This happened, because the pre-eclampsia patients in the PE with IVF group were not successfully impregnated or could not complete pregnancy. For IVF treatments condition, since the treatments that our patients received were carried out at different hospitals, the details of IVF for each patient were difficult to obtain. Therefore, we only investigated the use of fresh or frozen embryos in the PE with IVF group. Among the 20 women, 7 received the fresh embryo transfer and 9 received the frozen embryo transfer and 4 missed the data. For pregnancy outcome, 4 (4/20) mothers in the PE group and 3 (3/20) mothers in the PE with IVF group were admitted to the intensive care unit (ICU) for observation after cesarean section. Although the newborns in PE with IVF group showed a slight advantage in birth length, there were no significant differences in the birth weight, placenta weight, Apgar scores between the 2 groups (Table 1). Taken together, our data indicated that IVF experience may be not associated with the worse birth outcome in the pre-eclampsia population.

3.2 Worse results of biochemical blood tests for maternal renal and liver function in the PE with IVF group

The results of liver and kidney function tests obtained at the admission for pre-eclampsia were presented in the Table 2. Prealbumin (PA) was reported to be a sensitive marker for protein-energy and nutritional status [20, 21]. Elevation of maternal serum PA was observed in our PE with IVF group when compared to PE group (P = 0.02). Of note, the level of maternal PA in the PE with IVF group was below the lower limit of the normal reference range, suggesting that these pre-eclampsia patients with IVF treatment experience might have higher likelihood of malnutrition. The results of renal functional assay showed that, the levels of maternal creatinine (Cr) (P = 0.04), and uric acid (UA) (P = 0.03) in the PE-IVF group were significantly higher than those in the PE group. In addition, the UA level in the PE with IVF group exceeded the upper limit of the normal reference range (Table 2). Although there were no significant differences in maternal alkaline phosphatase (ALP) and Cystatin C (CYSC) between the 2 groups, they exhibited anomalies with elevated concentrations in both 2 groups, which were outside the normal range.

3.3 Glucose and lipid metabolism were not significantly different between PE group and PE with IVF group

The maternal glucose and lipid profiles obtained at the admission for pre-eclampsia of each group were summarized in the Table 3. Of interest, no significant differences were noted between the 2 groups for glucose, total triglycerides (TC), total cholesterol (TG), high-density lipoprotein cholesterol (HDL-C), L-density lipoprotein cholesterol (LDL-C) and apolipoproteins with the majority of ApoA1 and B. However, it was noteworthy that the levels of TC in both 2 groups exceeded its normal ranges. This observation was in accordance with previous findings that the pre-eclampsia women population has a higher level of TC than that in the normotensive group [14]. Serum homocysteine (HCY) has been reported to be a predict marker of pre-eclampsia and associated with IVF outcome [22, 23]. In this research, although we observed an elevation of HCY level in the PE with IVF group in comparison to the PE group (P = 0.04), HCY levels in our 2 groups were both in the normal range. Overall, we did not discover significant differences with clinical significance in measures of glucose and lipid profiles between the PE group and the PE with IVF group.

3.4 Dynamic changes of abnormal laboratory data in the 2 groups at the different pregnancy stages of enrolled pre-eclampsia patients

Since our enrolled pregnancies performed the routine examinations during gestation in our hospital, we further investigated the dynamic changes of above abnormal clinical biochemical indexes (ALP, PA, Cr, UA and CYSC) at multiple timepoints of pregnancy, including the results of routine blood tests in the first trimester, the second trimester, and the third trimester of pregnancy. In particular, the third trimester laboratory data referred to the results from the fresh blood samples obtained at their admissions for pre-eclampsia (Figure 2). We discovered that the levels of maternal ALP, PA, Cr, UA and CYSC were all well within the normal range in their early pregnancy. In the second trimester of pregnancy, the levels of maternal ALP, UA and CYSC in both 2 groups were higher than those in the first trimester pregnancy. Of note, the maternal CYSC level in the PE with IVF group that already exceeded the normal range in second trimester of pregnancy, suggesting the minor abnormalities of kidney function might arise before their diagnosis of pre-eclampsia. When women were identified with pre-eclampsia and hospitalized for treatments/cesarean section in the third trimester of pregnancy, almost all above blood indicators exhibited significant changes compared to the second trimester of pregnancy. In addition, the abnormally increased ALP and CYSC levels were discovered in both 2 groups. However, the elevated level of UA, which was over the upper limit of the normal range, and the decreased level of PA, which was below the lower limit of the normal range were only found in the PE with IVF group. Furthermore, representative dynamic alterations (especially including the data from the postpartum period) of these abnormal biochemical indicators of 1 pre-eclampsia patient with spontaneous conception and 3 pre-eclampsia patients who underwent IVF treatment, were shown in the Figure 3. The levels of ALP, PA and CYSC in all 4 patients were back to normal during postpartum recovery period. However, the serum Cr level in 1 pre-eclampsia patient with IVF treatment and serum UA levels in 2 pre-eclampsia patients with IVF treatment and 1 pre-eclampsia patient without IVF treatment still remained in the abnormal range. Although the postpartum recovery data was far more limited, it still indicated that the reassessment of physical condition of mothers would be extremely clinically valuable. Collectively, clinical practitioners should monitor the above indicators to track pre-eclampsia progression and guide personalized treatment of pre-eclampsia.

3.5 Increased NK/γδT cells-derived IFN-γ and TNF-α were at maternal-fetal interface of pre-eclampsia patients who underwent IVF treatment

Generalized activation of the inflammatory response is reported to play a critical role in the pathogenesis of pre-eclampsia [24]. Low-grade pro-inflammatory responses may start in the first trimester pregnancy and excessively increase in women who develop pre-eclampsia [25].To examine the pro-inflammatory cytokine secretion of 2 classical innate immune cells (NK and γδT cells) in our 2 groups, we collected several fresh decidua tissues enriched in lymphocytes (Figure 4) and cord blood specimens of pre-eclampsia patients with and without IVF treatment for flow cytometry assays, and the gating strategy identifying NK cells and γδT cells was presented in the Figure 4. The results showed that the ratios of both decidual and cord blood γδT cells in the CD3+ T cell population were significantly higher in the PE with IVF group (Figure 5). Besides, statistically significant elevations of IFN-γ and TNF-α secretions were observed in both decidual NK and γδT cells of pre-eclampsia patients who underwent IVF treatment. However, in the matched umbilical cord blood samples, the productions of IFN-γ and TNF-α were only increased in the NK cells of pre-eclampsia patients with IVF treatment when compared to pre-eclampsia patients conceived naturally (Figure 6).

Overall, the clinical laboratory data and charaterastcs including pregnancy outcomes, hepatic and renal status, glucose and lipid profiles of pre-eclampsia patients with and without IVF treatment experience were summarized. Data suggested that the pregnancy outcomes of pre-eclampsia patients who underwent IVF treatment were similar to the matched pre-eclampsia patients with natural conception. However, the blood results on the admissions of enrolled patients indicated the mothers in the PE with IVF group exhibited worse results of liver and renal function tests (significant decrease in PA level, and significant increases in Cr and UA levels) when compared to the mothers in the PE group. We next sought to define the dynamic changes in above abnormal blood indexes during the multiple timepoints of pregnancy. The level of CYSC in the pre-eclampsia patients with IVF treatment was found to have already abnormally increased in the second trimester of (before the diagnosis of pre-eclampsia) and the aberrant elevations of Cr and UA levels might persist until their postpartum recovery period. Taken together, increased attention should be paid to the monitoring of liver and kidney function and nutritional status of pre-eclampsia patients with IVF treatment experience, so as to achieve better clinical managements.

As is well known, pregnancy poses an immunological challenge [26]. Past few years have seen a rapid expansion of our knowledge of immune regulation in pre-eclampsia, and a hypothesis regarding the etiology of pre-eclampsia is the maladaptation of immune responses [27, 28]. In this study, we wanted to determine whether there are differences in functional changes of innate immune cells between patients with and without IVF treatment. Hence, we examined the secretions of 2 classical pro-inflammatory cytokines, IFN-γ and TNF-α, in the decidual and cord blood NK cells and γδT cells derived from the delivery specimens of our patients. The results revealed that pre-eclampsia patients with IVF treatment experience might display stronger pro-inflammatory responses at maternal-fetal interface than controls, and these effects on the mothers and the fetus required further investigation. Meanwhile, we guessed these increased inflammatory responses were related to IVF experience, since and similar findings have been reported by others. For example, the injection of HCG during assisted reproduction can stimulate the ovaries, thereby activating the inflammatory process [29]. Moreover, previous study has demonstrated that the children born via ART displayed a higher risk of immune dysfunction in childhood [30]. Together, an obvious and attractive speculation is that IVF treatments may influence some of the immunomodulatory properties of innate immune cells at maternal-fetal interface. The underlying mechanisms are still unknown, and associations need to investigate in further study.

There are still several limitations to current study. This study was a single center setting and enrolled a relatively small number of patients. Well-designed large-scale, multi-center clinical retrospective studies will worth further investigation. Additionally, our results merely reflected conditions occurring in the singleton pre-eclampsia patients. However, women treated with assisted reproduction were often transferred more than 1 embryo to increase the chances of pregnancy, and high twin and higher order multiple pregnancy rates still existed in this patient population [31]. The differences in clinical characteristics between pre-eclamptic twin pregnancies with and without IVF treatment are needed to explore. Besides, immune-regulatory mechanisms at the maternal-fetal interface are complex, very limited information is available regarding the change of innate immunity within this study. The etiology of infertility may act as a confounding factor, influencing perinatal outcome of ART treatment [32, 33]. We did not collect adequate clinical data to accurately assign IVF pre-eclampsia patients to aetiologic subgroups in this study. Further subgroup analyses in IVF pre-eclampsia are required.

Overall, although pre-eclampsia patients with IVF treatment did not appear to show more adverse pregnancy outcomes, they might be considered at a higher risk of malnutrition and threatened by reduced liver and kidney function when compared to the naturally conceived pre-eclampsia patients. Besides, they might have stronger pro-inflammatory responses at maternal-fetal interface, and these effects on the mothers and the growth and development of infants required further investigation. To make better clinical management, the close surveillance for the nutritional status, liver and kidney function and of this special pre-eclampsia population and a long follow-up for their infants are strongly warranted.

IVF, In Vitro Fertilization; DICs, Decidual Immunocytes; CBMCs, Cord Blood Mononuclear cells; PA, Prealbumin; Cr, Creatinine; UA, Uric Acid; ALP, Alkaline Phosphatase; CYSC, Cystatin C. NK cells, Natural Kill cells; IFN-γ, Interferon-γ; TNF-α, Tumor Necrosis Factor-α.

Author Contributions

Liman Li performed the clinical data collection and drafted the initial manuscript. Wenjie Zhou, Ying Liu and Shiling Jiang collected the fresh clinical decidual and cord blood samples. Yuan Liu and Ting Feng performed the flow cytometry assays. Rong Zhou and Hong Li were liable for oversight and leadership responsibility for the research activity planning and execution. All authors contributed to the article and approved the submitted version.

Funding

This work was financially supported by the National Natural Science Foundation of China (No. 81971461) and the National Key R&D Program of China (2021YFC2701600).

Acknowledgements

Authors would like to thank Ying Feng, PhD, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, for histological evaluation of HE-stained section.

Availability of data and materials

Literature research results are available from the authors upon reasonable request.

Ethics approval and consent to participate

The Medical Ethics Committee of West China Second Hospital of Sichuan University [Record number: 2020 (029)] has proved our study (approval number: 81971461). All fresh specimens we collected from clinical patients have provided their written informed consent to participate in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Table 1. Baseline subject characteristics
Parameter	PE (n = 20)	PE with IVF (n = 20)	P value
Maternal age, year	34.10 (0.48)	36.85 (1.33)	0.06
BMI, m/kg²	27.71(0.56)	28.52 (0.79)	0.41
Gestational age, week	37.62 (0.47)	37.46 (0.28)	0.78
Blood pressure SBP, mmHg DBP, mmHg	141.95 (3.09) 90.58 (2.20)	144.20 (5.25) 93.20 (3.94)	0.72 0.57
Mild/severe^&	6/14	6/14	/
Gravidity	2 (1-4)	1 (1-3)	0.25
Parity	1 (0-1)	0 (0-1)	<0.0001
Embryo, fresh/frozen	/	7/9*	/
ICU admission	25.00 %	15.00 %	/
Birth weight, g	2690.00 (155.89)	3016.5 (124.67)	0.11
Birth length, cm	46.74 (0.76)	48.75 (0.52)	0.03
Placenta weight, g	488.83 (24.28)	525.63 (17.94)	0.23
Apgar score
1 min	10 (10-10)	10 (10-10)	0.23
5 min	10 (10-10)	10 (10-10)	/
10 min	10 (10-10)	10 (10-10)	/

^&Mild pre-eclampsia or severe pre-eclampsia.

*Among the 20 women, 7 received the fresh embryo transfer and 9 received the frozen embryo transfer and 4 missed the data.

Table 2. Liver and renal functions of enrolled pre-eclampsia patients
Parameter	Reference range	PE (n = 20)	PE with IVF (n =20)		P value
Liver function
ALT, U/L	＜49.0	16.50 (12.25-25.00)	22.00 (15.50-46.50)	0.17
AST, U/L	＜40.0	25.50 (19.25-31.00)	27.50 (22.25-33.00)	0.27
TBIL, μmol/L	5.0-23.0	8.35 (6.18-11.10)	8.75 (6.13-10.08)	0.93
DBIL, μmol/L	＜8.0	1.72 (0.18)	1.93 (0.20)	0.43
IDIL, μmol/L	＜17.0	7.58 (0.82)	6.84 (0.48)	0.45
TP, g/L	57.0-85.0	58.94 (1.25)	55.77 (2.14)	0.21
ALB, g/L	34.0-55.0	35.11 (0.76)	32.77 (1.18)	0.10
GLB, g/L	20.0-40.0	23.75 (22.33-25.60)	23.25 (19.20-24.88)	0.22
γ-GT, U/L	＜45.0	17.50 (12.00-37.75)	17.50 (11.25-26.25)	0.63
ALP, U/L	35-129	142.70 (10.48)	131.11 (11.25)	0.46
LDH, U/L	120-246	220.00 (188.25-272.25)	204.50 (177.00-295.50)	0.79
PA, mg/L	180-350	191.50 (10.42)	153.95 (12.14)	0.02
ADA, U/L	4-24	7.35 (0.76)	7.46 (0.50)	0.91
Renal function
Urea, mmol/L	2.6-7.5	4.50 (3.53-5.45)	4.91 (3.81-5.93)	0.54
Cr, μmol/L	30.4-73	51.90 (2.37)	59.84 (3.02)	0.04
UA, μmol/L	184-420	384.25(22.24)	456.30 (21.48)	0.03
CYSC, mg/L	＜1.02	1.20 (0.06)	1.28 (0.06)	0.29

P values of normally distributed data and nonnormally distributed data were derived from the Student’s t-test or Mann-Whitney test, respectively. Normally distributed data were described as means (SEM) and nonnormally distributed data were expressed as median (interquartile range).

Table 3. Glucose and lipid profiles of enrolled pre-eclampsia patients
Parameter	Reference range	PE (n = 20)	PE with IVF (n = 20)	P value
Glucose, μmol/L	3.9-11.1	4.93 (0.33)	4.58 (0.22)	0.37
TC, mmol/L	＜5.18	6.28 (1.66)	6.05 (0.34)	0.66
TG, mmol/L	＜1.7	4.30 (0.43)	3.82(0.36)	0.41
HDL-C, mmol/L	＞1.0	1.82 (1.55-2.17)	1.84 (1.27-2.05)	0.36
LDL-C, mmol/L	＜3.3	3.20 (2.3-3.70)	3.20 (2.05-4.38)	0.82
ApoA1, g/L	0.76-2.14	1.86 (0.09)	1.74 (0.07)	0.29
ApoB, g/L	0.46-1.42	1.20 (0.08)	1.20 (0.09)	0.99
HCY, μmol/L	5-15	6.44 (0.30)	7.58 (0.48)	0.04

No competing interests reported.

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Clinical characteristics and laboratory data of pre-eclampsia patients with and without in vitro fertilization embryo transfer treatment

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