- Academic Editor
Background: To evaluate the value of transvaginal three-dimensional
power Doppler ultrasound (3D-PD-US) in quantitative assessment of early
diminished ovarian reserve (DOR) among perimenopausal women. Methods: A
total of 166 perimenopausal women with DOR were selected from February 2019 to
December 2022, including 63 in the early stage and 103 in the mid-to-late stage.
Ovarian reserve was assessed by biochemical testing and 3D-PD-US imaging.
Biochemical indicators included antimüllerian hormone (AMH), basal serum
follicle stimulating hormone (FSH) and estradiol (E
Among all female organs, the ovaries are the earliest to undergo functional decline or even failure [1]. The time point for the ovaries to diminish their reserve varies significantly among individuals [2, 3, 4]. Diminished ovarian reserve (DOR) is insidious and progressive [3]. With unknown etiology, DOR is influenced by such factors as age, genetic factors, and iatrogenic factors such as surgery, radiotherapy, and chemotherapy [5, 6, 7]. Currently, no treatments can effectively restore ovarian function [4, 6, 8]. Therefore, early detection of DOR is of great significance for introducing safe and non-invasive measures to delay DOR, thus improving quality of life of perimenopausal women [4, 6, 7, 9].
As recommended by the Practice Committee of the American Society for
Reproductive Medicine, ovarian reserve can be assessed by both biochemical tests
and ultrasound imaging [10]. Their usefulness has been verified, but ideal
markers of ovarian reserve have not been explored [7, 10, 11]. Biochemical
indicators of ovarian reserve include antimüllerian hormone (AMH), follicle
stimulating hormone (FSH) and estradiol (E
The purpose of the study was to evaluate the value of 3D-PD-US in quantitative
assessment of early-stage DOR of perimenopausal women whose FSH is “normal”
(
This study is a retrospective cross-sectional observational study. This study
was approved by the local Ethics Committee of the hospital. Informed consensus
was obtained from every subject for the anonymous use of clinical data. A total
of 166 cases of perimenopausal women diagnosed with DOR were collected in our
hospital from February 2019 to December 2022. Inclusion criteria were as follows:
(1) 3D-PD-US and serum AMH, FSH and E
All ultrasound scans were performed using a Voluson E8 (GE Healthcare Austria GmbH & Co OG, Tiefenbach, Zipf, Austria) and a transvaginal RIC5-9-D volume probe (5–9 MHz) that has 3D power Doppler ultrasound scanning modes. Following the procedures previously described by other authors, follicles ranging from 2 mm to 10 mm were labeled and counted. Using 3D-PD-US OV, AFC, VI, FI, and VFI were measured with Sonography-based Virtual Organ Computer Aided Analysis Imaging Program (GE Healthcare Austria GmbH & Co OG, Tiefenbach, Zipf, Austria). 3D-PD-US was as set at the following parameters: frequency low, smooth 5/5, ensemble 12, line density 6, power Doppler map 5, sweep angle 30°, quality middle 2, wall motion filter low 2, and velocity range 0.9 kHz.
The vocal was manually controlled to cover the whole 3D volume of the ovary with a 30° rotation step; accordingly, 6 contour planes covering 180° were analyzed for each ovary.
Vascularization index (VI) was measured to show the number of blood vessels in the ovary (color voxels) and was expressed as a percentage (%) of the ovarian volume. Flow index (FI) was measured to represent the average intensity of flow inside the ovary. Vascularization flow index (VFI) was calculated by multiplying VI and FI to show vascularization and flow.
For each subject, 3–5 mL of blood was collected from the forearm elbow vein
blood on an empty stomach. The levels of serum AMH, FSH and E
Statistical analyses were run on SPSS v26.0 (IBM, Armonk, NY, USA). For
categorical data, the
A total of 308 perimenopausal women with DOR were screened from February 2019 to December 2022. According to the exclusion and inclusion criteria, 142 patients were excluded, including 49 disapproving the anonymous use of clinical data; 27 having a history of hormone therapy within previous 3 months; 4 having a history of radiotherapy; 3 having a history of ovarian surgery; 15 having endocrine diseases (7 of PCOS, 8 of diabetes); 6 having autoimmune diseases (1 of SLE, 3 of RA, 1 of CD, 1 of AS); 9 being treated with endocrine therapy after breast cancer surgery; 12 showing ovarian cysts; 4 having other ovarian tumor besides cyst; 13 patients were unclearly showed and failure to obtain ovarian volume or blood flow (11 with unilateral ovary, 2 with bilateral ovaries). Finally, 166 subjects were enrolled (63 patients in the early stage group, 103 patients in the mid-to-late stage group).
Table 1 summarizes both groups’ data about age, body mass index (BMI), marital
status, menstrual history, menstrual blood volume, dysmenorrhea, AMH, E
Early stage group | Mid-to-late stage group | t/ |
p | ||
n | 63 | 103 | |||
Age (years) | 42.02 |
43.18 |
4.301 |
0.040 | |
N, |
4 (6.3%) | 22 (21.4%) | 5.579 |
0.018 | |
BMI (kg/m |
22.11 |
23.33 |
1.132 |
0.289 | |
Marital status | |||||
Married | 62 (98.41%) | 100 (97.09%) | 0.292 |
0.589 | |
Unmarried | 1 (1.59%) | 3 (2.91%) | |||
Menstrual history | |||||
Menstruation menarche (years) | 13.37 |
13.29 |
0.099 |
0.754 | |
Menstrual cycle (days) | 28.16 |
28.37 |
0.095 |
0.758 | |
Menstrual period (days) | 4.24 |
4.18 |
1.257 |
0.264 | |
Menstrual blood volume | |||||
Less than normal | 1 (1.59%) | 0 (0%) | 3.182 |
0.364 | |
Normal | 4 (6.35%) | 3 (2.91%) | |||
More than normal | 47 (74.60%) | 77 (74.76%) | |||
Menopause | 11 (17.46%) | 23 (22.33%) | |||
Dysmenorrhea | |||||
Yes | 11 (17.46%) | 19 (%) | 0.026 |
0.873 | |
No | 52 (82.54%) | 84 (%) | |||
Biochemical indexes | |||||
AMH (ng/mL) | 1.09 |
0.38 |
23.547 |
0.000 | |
E |
63.49 |
59.28 |
1.721 |
0.191 | |
FSH (mIU/mL) | 7.90 |
31.53 |
78.601 |
0.000 |
Item | OV (cm |
AFC (Units) | VI | FI | VFI |
r | –0.342 | –0.381 | –0.179 | –0.123 | –0.175 |
p | 0.000 |
0.000 |
0.001 |
0.025 |
0.001 |
Group | OV (cm |
AFC (Units) | VI | FI | VFI |
Early stage group | 4.56 |
4.71 |
6.66 |
30.29 |
2.18 |
Mid-to-late stage group | 3.15 |
2.59 |
4.60 |
28.40 |
1.48 |
t | 5.921 | 8.14 | 3.197 | 2.626 | 2.91 |
p | 0.000 |
0.000 |
0.002 |
0.009 |
0.004 |
The incidence of cardiovascular and metabolic diseases increases among perimenopausal women, with the decline of ovarian reserve function [2, 9]. Early diagnosis is essential for delay DOR and improve the quality of life among perimenopausal women [2, 9, 18]. DOR is first manifested by a decrease in AMH, followed by a feedback to the increase in FSH [5]. A higher FSH indicates a larger decrease in reserve function [10, 11, 12, 13]. Clinical diagnosis of DOR mainly relies on AMH, FSH, ultrasound, and symptoms [2, 9, 10]. But DOR is insidious in its early stage, and some medical institutions do not provide measurement of AMH level in China. So, delayed diagnosis may lead to loss of an optimal treatment time. Therefore, based on FSH, we defined those with a normal FSH as the early stage DOR group, and those with elevated FSH as the mid-to-late stage DOR group. For the first time, we here clarified that 3D-PD-US could increase the accuracy rate of early assessment for DOR.
Our study found significant differences in AMH between the two groups. The AMH
in the mid-to-late stage group was lower than that in the early stage group,
which is consistent with previous studies [10, 11, 19]. AMH reflects the size of
the antral follicular pool. Older ovaries exhibit more pronounced decreases in
both the quantity and quality of oocytes [19]. Previous studies have confirmed
that age is an independent risk factor for DOR [1, 3], and negatively correlated
with the ovarian reserve function [2, 3]. In our study, we found significant
between-group differences (all p
3D-PD-US can display the 3D shape of the ovaries more intuitively, evaluate the
blood flow of the ovaries quantitatively, monitor changes in ovarian morphology,
functionality and hemodynamics dynamically and comprehensively. It is recommended
by the Practice Committee of the American Society for Reproductive Medicine for
evaluating ovarian reserve function. Previous studies have shown that the OV,
AFC, VI, FI, and VFI of 3D-PD-US are effective parameters for predicting ovarian
reserve function, with high sensitivity and specificity [6, 7, 8, 9]. In this study, the
coefficients of Spearman’s test showed statistical associations of FSH with OV
(–0.342), AFC (–0.381), VI (–0.179), FI (–0.123) and VFI (–0.175), respectively
(all p
Furthermore, all 3D-PD-US indicators showed significant differences between the
early stage group and the mid-to-late stage group (all p
3D-PD-US has a high diagnostic value for ovarian reserve function in perimenopausal women and may be replicated in clinical early detection of DOR.
The data for this study is publicly available. You can request data from the author (Yunfei Ma) through email (439925904@qq.com).
YM and YW designed the research study. YM and YW performed the research. YM analyzed the data. Both authors contributed to editorial changes in the manuscript. Both authors read and approved the final manuscript. Both authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
According to the regulation of National Health Commission- “Ethical Review of Life Sciences and Medical Research Involving Human Beings”, the study using anonymized data is exempt from ethical review. This study is a retrospective cross-sectional Observational study. Although our research can be exempted from ethical review, we fully respect the wishes of the research subjects by phone. 49 patients were excluded who didn’t approve the anonymous use of clinical data.
We would like to express our gratitude to all those who helped us during the writing of this manuscript. Thanks to all the peer reviewers for their opinions and suggestions.
This research received no external funding.
The authors declare no conflict of interest.
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