Mid-Secretory Uterine Artery Doppler Indices and Endometrial Thickness in Patients with Unexplained Recurrent Pregnancy Loss

INTRODUCTION

Recurrent loss of pregnancy known as 2 or more sequential fetal losses before twenty weeks from the total gestational age.¹ Potential uterine predictors for implantation measurable by ultrasound include; endometrial thickness and volume, endometrial pattern, as well as blood flow in the uterine and sub-endometrial arteries.²

Chromosomal aberrations were observed in 3.2% of RPL cases. Chromosome analysis is an important etiological study in couples with RPL.³ Balanced translocations are the most common chromosomal aberrations found in these pairs. Therefore, these couples are the best candidates for prenatal genetic diagnosis, leading to better reproductive outcomes.⁴

Hormones such as progesterone, human chorionic gonadotropin, normal thyroid levels, and prolactin

levels play an important role in preventing RPL.⁴ Endocrine causes of LPR include luteal phase deficiency, untreated hypothyroidism, hyperprolactinemia, hyperandrogenism, insulin resistance, and decreased ovarian reserve. While diagnostic criteria for LPD remain controversial, treatment of LPD and LPD patients with a progestogen in early pregnancy is the most commonly used treatment, although its role is controversial. Hyperprolactinaemia, polycystic ovarian syndrome, and overt or subclinical hypothyroidism with or without the presence of thyroid antibodies are associated with poor obstetric outcomes and should be treated.⁵

Congenital malformations of the uterus, including scalloped, scalloped, one-horned, bicorneal, and uterine dysplasia, are more common in women who have lost a pregnancy than in the general population.⁵ Recurrent pregnancy loss 4.6% compared to women with 9% primary recurrent pregnancy loss. Acquired uterine abnormalities such as uterine fibroids, endometrial polyps, intrauterine adhesions, or Asherman syndrome may be associated with an increased risk of miscarriage.⁶

The quality of the gametes and embryos and the good viability of the endometrium form the basis for a pregnancy that can last until childbearing. The receptivity of the endometrium has been widely recognized through extensive research in recent years. 3D Doppler ultrasound measurements of endometrial volume and central muscle vascular flow parameters can be used to predict miscarriage.⁶

Potential uterine indices of implantation that can be measured by ultrasound include endometrial thickness and size, endometrial pattern and uterine blood flow and endometrial arteries.⁶ However, the vascular changes associated with RPL have not been sufficiently studied. While defects in the ovum, sperm, embryo, and systemic or local factors have been noted, the role of endometrial sensory defects in unexplained and often unexplained recurrent pregnancy loss has not been well studied.⁷

Therefore; this study purpose to evaluate endometrial thickness and uterine artery blood flow using transvaginal color Doppler ultrasound during the midluteal phase of the menstrual-cycle for female with unexplained recurrent pregnancy loss (RPL).

PATIENTS AND METHODS

This study is prospective controlled clinical trial that conducted a total number of 90 non pregnant female 45 with history of unexplained RPL and 45 normal fertile (control group) retrieved from Gynaecology clinic of Al-Azhar university hospital during a period  from Januray 2021 to December  of the same year.

The study approved by Ethics Committee of   AL-Azhar University (Assuit) faculty of medicine , an informed written consent was obtained from all participants. The study is conducted in accordance with Helsinki standards as revised in 2013.

All studied  female undergoe Proper history taking (personal, menstrual history ,obstetric history, past history, surgical history and present history),Examinations: general, abdominal and PV examination and routine investigations (CBC, chemistry) and Trans vaginal 2-D ultrasound scan for assessment of uterus (including measuring of endometrial thickness) and adnexa Uterine artery Doppler study assessment of uterine-blood-flow during the mid-secretory phase of the menstrual cycle using 7.5 MHz trans-vaginal convex probe (voloson E 6 ultrasound machine). The uterine arteries were identified lateral to cervix trans-vaginally and measurements. The pulsatility index, resistance index and Systole/Diastolic ratio were calculated

Non pregnant women age; 20-35 years. With history of 2 or more successive spontaneous abortion. Unexplained recurrent pregnancy loss  with normal serum PRL, normal thyroid function, normal HbA1c, normal pelvic ultrasound, normal HSG or hystroscopy , negative tests for antiphospholipid antibody syndrome (ACL, Lupus anticoagulant and anti B2 glycoprotein 1) were included. Induced abortion , Less than 2 successive spontaneous abortion or patient refused to participate in the study  were excluded.  All findings of this study was statistically calculated using SPSS (V. 20, Echosoft Corp., USA). Statistical analyzed data were calculated and  tabulated as quantitative and qualitative with percentage for catgorized data.

RESULTS

The mean ± SD age of cases were27.87 ±3.87 and mean ±SD of control 28.53 ± 4.5 p value 0.455, regard to body mass index, Endometrium thickness was no statistically significant between both group. Mean ±SD (11.5 ± 1.67 mm versus 12.08 ± 1.8 mm ) for cases and control respectively.  Parity were significant between both groups cases and control respectively > 0.001 . As regard to Doppler blood flow studies of right and left uterine arteries we found that : systole / diastole ratio (S/D) for both uterine arteries higher in patients  group (7.23 ± 1.05 & 6.8 ± 1.8) for right and left uterine arteries for patients group  versus ( 4.7± 1.15 &4.7 ±1) for control group respectively  (p-value < 0.001). Resistance index (RI) for both uterine arteries higher in patients group (0.86 ± 0.06 & 0.86 ± 0.7) for right and left uterine arteries for patients group  versus ( 0.75± 0.05 &0.76±0.06 ) for control group respectively  (p-value < 0.001). Pulsatility index for both uterine arteries was statistically significantly in patients group (2.21 ± 0.09 & 2.2 ± .08) for right and left uterine arteries for patients group  versus ( 1.65± 0.03 &1.69 ±0.03) < 0.001. Diagnostic performance right/ left uterine arteries S/D ratio at a cutoff level of (> 6.2 & > 5.7) with sensitivity (84.4% & 90.9 % ), specificity (93.3% &80%) , PPV (92.6%&82 %) , NPV (85.7%&89.8% )  and AUC ( 0.94& &0.93 ) for right and left uterine arteries respectively   p-value < 0.001). As regard to diagnostic performance of right and left uterine arteries RI at a cutoff level of (> 0.81 & > 0.78) with sensitivity (66.7% & 80 % ), specificity (88.9% &75.6%) , PPV (85.7%&76.6 %) , NPV (72.7%&79.1% )  and AUC ( 0.87& 0.84 ) for right and left uterine arteries respectively ( p-value < 0.001). As regard to diagnostic performance of right and left uterine arteries PI at a cutoff level of (> 1.95 & > 1.89) with sensitivity (66.7% & 68.9 % ), specificity (95.6% &91.1%) , PPV (93.8%&88.6 %) , NPV (74.2%&74.6% )  and AUC ( 0.78& &0.77 ) for right and left uterine arteries respectively ( p-value < 0.001).

Table 1 : Sociodemographic characteristics of the studied groups

Table 2: Obstetric data of the studied groups.

Table 3: Comparison between studied groups as regard to endometrial thickness.

Table 4: Comparison between studied groups as regard to right and left uterine arteries S/D ratio

Table 5 : Comparison between studied groups as regard to right and left uterine arteries RI

Table 6: Comparison between studied groups as regard to right and left uterine arteries PI.

Table 7: Diagnostic performance of right and left uterine arteries S/D ratio in discrimination of cases & control groups

Table 8: Diagnostic performance of right and left uterine arteries resistance index in discrimination of cases & control groups

Table 9: Diagnostic performance of  right and left uterine arteries pulsatility index in discrimination of cases & control groups                                

Fig. 1: ROC curve of systole /diastole(S/D) (AUC = 0.94 & p-value < 0.001).

Fig. 2: ROC curve Rt. uterine artery RI (AUC = 0.87 & p-value < 0.001) and left uterine artery resistance index (AUC = 0.84 & p-value < 0.001)

Fig. 3: ROC curve of right uterine artery PI (AUC = 0.78 & p-value < 0.001). and Lt. uterine artery PI (AUC = 0.77 & p-value < 0.001).