Introduction

Pregnancy involves not only anatomical but also a myriad of intricate molecular and cellular changes in the maternal body to support this complex physiological process from implantation to the development and growth of the fetus [1]. The corpus luteum is a temporary endocrine structure that develops in the ovary after release of a mature ovum. It plays a crucial role in early pregnancy by keeping the uterine environment favorable for conception, placentation and preservation of pregnancy until the placenta takes over this function. The structural and functional integrity of it, therefore is of paramount importance during the early stages of pregnancy [1–4].

The first trimester of pregnancy is a considered as a very critical period as it is characterized by rapid embryonic growth and organogenesis. Any deviations in the cascade of normal physiological events taking place during this stage can lead to serious complications, including abortions and anembryonic pregnancies. Although fetal chromosomal abnormalities or increasing maternal age have been described as the major risk factors of early spontaneous abortions, it is not uncommon to attribute such adverse event to the corpus luteum insufficiency also known as luteal phase defect [1, 5].

Obstetrical sonographic evaluation has emerged as a valuable tool providing detailed insights into the early stages of pregnancy beside clinical evaluation and biochemical markers which have traditionally been used to assess the viability of pregnancies. This study aimed to compare sonographic characteristics between normal and abnormal pregnancies. There have been a few studies on the topic with contentious findings as some reporting significant differences [6, 7] in sonographic characteristics between normal and abnormal pregnancies while the results of the others suggesting vice versa [8–10]. This study was therefore planned with an intention to reconfirm these controversial findings. Understanding these sonographic differences could provide valuable insights into the early detection and prediction of adverse pregnancy outcomes, allowing for timely clinical interventions and improved patient care.

Materials and methods

Sonographic imaging

Aplio 500 Platinum series ultrasound system (Canon Medical Systems Corporation, Ōtawara, Tochigi, Japan) with Doppler features was used to scan the participants. All pregnant women were examined with an empty bladder in the lithotomy position. The transvaginal ultrasound probe (Toshiba PVT- 675 MV Transducer 2.8–7.2 MHz) was gently introduced into the vagina. Routine first trimester obstetrical ultrasound was carried out using the grayscale mode. The gestational age was determined using gestational sac mean diameter (average of the three orthogonal measurements of the gestational sac) or crown rump length. Corpus luteum was then identified and characterized on the basis of appearances described by Durfee et al. [11] either as a simple thin-walled anechoic cyst, thick-walled anechoic cyst with or without internal echoes or as a hypoechoic to isoechoic region in any of the ovaries. Color and spectral Doppler were then used to identify the vascular pattern around it. The sampling gate was placed at the most vivid of the vessels in the ring of fire around corpus luteum to measure Pulsatility Index (PI), Resistive Index (RI) and Systolic to Diastolic (SD) ratio after acquiring more than three consecutive spectra (Fig. 1). Three measurements were recorded for each parameter and average value was then used as representative value.

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Doppler indices were acquired by placing the sample gate in the vessel around corpus luteum in the right ovary of a woman with normal viable pregnancy of 8 weeks

Citation: Imaging 2024; 10.1556/1647.2024.00206

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Results

Corpus luteum was present in all of the normal pregnancies and in 55 of 78 (70.5%) abnormal pregnancies. It wasn't seen in the remaining 23 (29.5%) cases with abnormal pregnancy of which 7 (9%) were of missed while 16 (20.5%) were of threatened abortion. On sonographic assessment, 49 (62.8%) of the normal viable pregnancies it appeared as thick-walled cysts with anechoic center either without (n = 34) or with internal echoes (n = 15), followed by simple cystic or hypoechoic appearances in 17 (21.8%) and 12 (15.4%) cases respectively. There was no significant difference between sonographic appearances of normal with cases of missed and threatened abortion. The details of the sonographic characteristics in each category of subjects are shown in Table 1. PI, RI and SD ratio showed significant difference between normal and cases of missed and threatened abortion (Table 2). On ROC curve analysis PI, RI and SD ratio showed cut-off values of 0.58, 0.49, and 1.9 with P values of <0.0001, 0.002 and 0.006 respectively between normal and missed abortion. The cut – off values in the same order of indices for normal pregnancies and threatened abortion were 0.6, 0.47 and 1.9 with P values of <0.0001 each. See Fig. 2 and Table 3 for the details of ROC analysis.

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Figure shows Areas Under Curve for Pulsatility index between normal pregnancies and cases of missed abortion (A) and threatened abortion (D), for Resistive Index between normal pregnancies and cases of missed abortion (B) and threatened abortion (E) and for SD ratio between normal pregnancies and cases of missed abortion (C) and threatened abortion (F)

Citation: Imaging 2024; 10.1556/1647.2024.00206

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Additionally, it was observed that the corpus luteum was absent in 12 (63.2%) out of 19 threatened abortion cases that ultimately did not survive, in contrast to only 4 (12.1%) out of 33 cases that remained viable. The seven remaining non-viable cases, which showed the presence of the corpus luteum, had even higher values of RI (mean = 0.87 vs 0.54) and PI (mean = 0.99 vs 0.71) compared to those in pregnancies that survived.

Discussion

Spontaneous abortions are not very uncommon occurrence with frequency of early pregnancy spontaneous abortions to be up to 15% of known and as high as 30% of the clinically recognized pregnancies [7]. in this study, we sought to discover sonographic and Doppler features of the CL that could be linked to first-trimester spontaneous pregnancy loss. Presence, echogenic characteristics as well as Doppler indices of the corpus luteum were evaluated and compared in both normal and abnormal pregnancies.

Absence of CL in 29.5% of the abnormal pregnancies on the contrary to its presence in 100% of the viable pregnancies was one of the salient features in or study. The finding was in agreement with Nafea et al. [12] who reported presence of CL in all of their controls and absence in 21.4 % of their cases of threatened abortion which later on, upon follow up actually ended up in loss of pregnancy. They did not included cases of missed abortion in their study. Glock et al. [13] also found that five of six (83%) women in their study in whom a corpus luteum was sonographically undetectable resulted in termination of pregnancy.

Rowan K et al. [14] observed that the CL was more common (56%) on the right side. This was in contrast to our study as we noted to be more common on the left side both in normal and abnormal pregnancies without any significant difference in laterality in both of these groups. The frequency of sonographic appearances of the CL we found in our study in normal and in cases of missed abortion are in agreement with Gupta et al. [15] who also reported CL as a thick-walled cyst to be the most frequent appearance. They however found simple cystic appearance only in 12.82 % of the cases in contrast to our study where it was the second most common appearance found in 21.8 % of all the normal pregnancies. They did not report the statistical comparison of these appearances between the two groups. Cases of threatened abortion were not included in their study. Durfee et al. [11] on the other hand found hypoechoic appearance in 34% followed by thick-walled appearance in 27% of the normal viable pregnancies. In short there is no consensus on what is the most common normal sonographic appearance in all of the reported studies or could these predict the viability of pregnancy or not till date. The reason might be explained by the findings of Glock et al. [12], which suggested that the appearance of the CL either cystic or partially cystic did not affect plasma progesterone or 17-hydroxyprogesterone levels nor was predictive of the pregnancy outcome.

In the absence of any remarkable demarcation of the grey-scale features between normal and abnormal pregnancies the Doppler indices (RI, PI and EDV) recorded from the vascular ring around CL were significantly different in normal viable pregnancies than those in cases of both missed and threatened abortion in our study. These findings are in agreement with most of the previously available reports [7, 10, 12, 15] In addition even higher values of RI and PI in cases of aborted cases compared to continued ones are also in agreement with the results of Abd-elfatah et al. [16] Alcazar et al. [17] also compared RI and found increased blood flow impedance in cases of missed abortion but not in threatened abortion and anembryonic pregnancy compared to normal pregnancies used as control. Despite reports of a few other researchers suggesting no significant association between the Doppler flow parameters and poor early pregnancy outcomes [8, 9] it is widely accepted that the rapid growth of blood vessels across the basement membrane between theca and granulosa layers is essential to sustain development and functioning of the CL [6, 18] In other words, adequate perfusion of CL is required for maintaining the serum progesterone levels and thus for viability of the pregnancy. CL gets highest perfusion per unit tissue than any other organ, even accounting for more than 20% of its total volume. It allows it to obtain enough oxygen, nutrients, and hormone precursors necessary to synthesize and release large amounts of progesterone [7, 19, 20].

Small sample size and cross-sectional study design were the limitations of our study. A longitudinal study design with follow up of the subjects included in the normal pregnancy group could have confirmed the preservation of pregnancy afterwards. Additionally, the failure to acquire and incorporate information about genetic testing and hormonal profiles with the sonographic appearances was another limitation; the presence of such information could have added a lot to this study.

However, the findings of study lead us to conclude that the first trimester adverse pregnancy outcomes are associated with differences in blood flow Doppler characteristics of corpus luteum. It is therefore recommended that corpus luteum should be evaluated at least for high-risk pregnancies in first trimester sonography as a routine.

Authors Contribution

Hina Shabbir: Data Collection, manuscript writing; Zareen Fatima: Project development, manuscript writing, data analysis; Abdul Wahab: Data Collection, manuscript writing; Kashif Azeem Zafar: Data Collection; Muhammad Ansar: Manuscript writing; Mahrukh Latif: Manuscript writing; Sabar Butt: Manuscript review.

Funding Resources

No funding disclosure has to be made.

Ethical Statement

The study was carried out after ethical approval from Institutional Research Ethical Committee of The University of Lahore under reference number Ref No: REC-UOL-/120-05/2022. Written informed consents were acquired from all of the participants.

Conflict of Interest

Authors declare no conflicts of interest.