Abstract
Objectives
Despite advancements in modern medicine, the effectiveness of in vitro fertilization (IVF) remains low. This study aimed to assess the impact of specific features of T-shaped uterine cavity malformation and its intermediate forms on reproductive function and the effectiveness of assisted reproductive technology (ART), particularly on IVF results and pregnancy outcomes.
Methods
A prospective cohort study included 388 somatically healthy patients undergoing 3D ultrasound (US) examination of the uterine cavity before embryonic transfer for IVF treatment. Patients were evaluated for morphometric parameters using standardized US protocols. Statistical analysis was performed using SPSS statistics.
Results
The study revealed that patients with T-shaped uterus and intermediate forms had higher rates of miscarriages, and unfavorable pregnancy outcomes compared to those with normal uterine cavities. The frequency of pregnancy occurrence in T-shaped and Intermediate groups was statistically similar with the “Normal uterus” group. Morphometric parameters such as T-angle, lateral angle, and myometrial thickness significantly influenced IVF outcomes.
Conclusion
The study highlights the importance of morphometric parameters in predicting IVF success and pregnancy outcomes in patients with T-shaped uterine cavity malformation. These parameters can guide clinical decision-making and may serve as predictors for reproductive outcomes in ART procedures. Further research is warranted to validate these findings and explore additional ultrasound markers for better prediction of reproductive outcomes in patients with uterine cavity malformations.
Keywords
T-shaped uterus, CUME criteria, Three-dimensional ultrasound, Infertility, IVF
Introduction
Despite the advancements in modern medicine, the effectiveness of IVF continues to remain low [1, 2]. The attention of researchers worldwide has more frequently turned to the uterine factor in the pathogenesis of infertility, which comprises 24–62% of the structure of reproductive function impairment in women [3–7].
Uterine development anomalies play a significant role in these impairments. Publications on ART implementation in patients with uterine development malformations are scarce.
It is commonly assumed that pregnancy in women who have congenital uterine developmental anomalies is often complicated by threatened miscarriage, placental insufficiency, and fetal hypoxia [8–11].
The presence of some of the most common congenital uterine cavity malformations is not manifested by any clinical symptoms [12–14].
Routine two-dimensional ultrasound examination, carried out during patient workup in preparation for intrauterine insemination or IVF, does not allow for the study of specific features of uterine cavity structure; hence, its anomalies often remain undiagnosed. For the same reasons, the mentioned malformations can lead to so-called “unexplained infertility”, unsuccessful IVF outcomes, or subsequent miscarriages [15–19].
The true prevalence of congenital uterine anomalies is unknown. It is thought to occurs in 5% of cases in the general population. The frequency of malformations in women with infertility and recurrent miscarriages varies from 8 to 16%, with some authors reporting rates up to 38% [3, 6, 9].
Three-dimensional ultrasound has been widely introduced into reproductive medicine practice in recent years. Three-dimensional ultrasound is a highly informative diagnostic method for uterine cavity disorders with a 100% sensitivity and 92,3% specificity, which allows for the detection of uterine cavity deformities undetectable by two-dimensional echography [20–22].
An updated classification of congenital uterine cavity malformations was proposed by the European Society for Gynaecological Endoscopy and for the European Society of Human Reproduction and Embryology (ESGE/ESHRE) in 2013 [23]. According to this classification, dysmorphic (T-shaped and infantile) uterine abnormalities have been classified into a separate class (U1), while they were previously denoted by the American Society of Reproductive Medicine (ASRM, 2009) as diethylstilbestrol-induced T-shaped malformations.
Two classifications of congenital uterine cavity malformations are widely used at present, ASRM and ESHRE classifications. The T-shaped malformation is distinguished in a separate class in all of these classifications.
The T-shaped congenital uterine cavity malformation, which belongs to class U1a according to the ESHRE/ESGE classification, has variable prevalence, and its diagnosis is largely subjective due to the lack of quantitative ultrasound criteria in the mentioned classification.
The morphometric ultrasound criteria of T-shaped malformation were developed in 2019 by a group of CUME experts [24], who proposed the quantitative US evaluation of this abnormality (Fig. 1).
Based on expert consensus, the following diagnostic criteria of a T-shaped uterus were proposed as reliable: T-angle < 40°, lateral indentation angle 7 mm. According to CUME [24], the diagnosis of a T-shaped uterus can be made in the presence of all three morphometric criteria. If two of 3 signs are present, the uterine shape is classified as borderline.
The proposed criteria will undoubtedly allow systematizing the diagnostic process of the practicing physician in routine clinical practice and unifying scientific research; however, they do not provide an answer to the question as to which particular morphometric parameters of the cavity may have a possible influence on reproductive outcomes because in routine clinical practice, there are encounters with patients who have fulfilled their reproductive function while being diagnosed with T-shaped uterus by 3D examination.
Our study aimed to assess the impact of specific features of T-shaped uterine cavity malformation and its borderline forms, particularly their morphometric parameters on the reproductive function as a whole and the effectiveness of ART, in particular on IVF results and pregnancy outcomes in one embryonic transfer cycle with the transfer of one frozen-thawed embryo.
Methods
Our prospective cohort study included 388 somatically healthy patients who underwent a 3D US examination of the uterine cavity as a part of their evaluation before embryonic transfer. These patients further received treatment for infertility by IVF method from 2013 to 2020 in 4 reproductive centers in Yerevan.
The study excluded patients with uterine myomas, uterine cavity deformities resulting from uterine surgeries, synechiae or adenomyosis; uterine polyps; history of ovarian surgeries, genetic thrombophilia; hydrosalpinx, as well as class 2 or 3 obesity (BMI > 35 kg/m2).
Ultrasound examination was performed using Voluson 730 Expert, E10 (GE), and Accuvix A 30-Samsung/Medison devices with three-dimensional multi-frequency vaginal 7–9 MHz probe twice, once in the first and once in the second phase of the menstrual cycle. Scanning was done by 2 ultrasound specialists with more than 5 years of work experience. The evaluation of uterine cavity shape and sizes was conducted with a three-dimensional reconstruction of the uterine cavity in a standard coronal VCI plane with a 90° volume insonation angle. All stored volumes were coded and saved on the scanner hard drives. The analysis of uterine cavity morphology was performed in the same standardized coronal plane with the identification of uterine external contour and the interstitial part of uterine tubes as the reference point. The classification of uterine shape was done based on a consensus between two expert ultrasound specialists with more than 20 years of practical experience.
When defining the morphometric parameters of the uterine cavity we followed the same rules, i.e. performed obligatory measurement of the following: T-angle (Ta), lateral angle (La), and myometrial thickness in the area of the lateral angle (h) (Fig. 2a, b, c).
Figure 3 depicts for comparison echograms of normal uterine cavity (a), T-shaped uterus (b), and the intermediate type (c) according to the CUME classification.
In addition, we measured the distance between uterine tube ostia (Dist 1) and the width of the cavity in lateral angle area (Dist 2) according to the method proposed by C. Exacoustos et al., 2015 [26], as well as the distance between the tubal angle and internal orifice area (L) and the surface of the uterine cavity by manually outlining the uterine cavity in coronal plane with three-dimensional cavity reconstruction, as shown on Fig. 2c.
The value of the L line, in our opinion, can connect the thickness of lateral indentation, h with the other morphometric parameters of a T-shaped uterus, and the ratio h/L can denote the “severity” of the T-shaped cavity, which determines the impact on reproductive outcomes, i.e. be a criterion of clinical relevance.
To demonstrate the point, we hereby show three T-shaped cavities that fulfill all 3 CUME criteria but have different values of h/L and different surface areas of cavities. (Fig. 4).
The ultrasound morphology of uterine cavity in the study patients was as follows: 266/388 (68.6%) had normal cavity, U0; 27/388 (7.0%) had dysmorphic uterus (Class U1) subtype U1a, T-shaped; 73/388 (18.8%) patients who had previously been classified as having T-shaped malformation were diagnosed with an intermediate type of T-shaped anomaly; and 22 (5.7%) of 388 patients had different other malformations of uterine cavity, 11—Class U1c, 5—Class U2a, 2—Class U2b, 3—Class U3b, and one—Class U5.
The patients were aged 20–40 years (mean age 31.7 ± 0.3 years), and the duration of infertility was 7.7 ± 0.2 years.
The embryonic transfer in the IVF cycle was implemented in all patients after evaluating the endometrial thickness and US morphology, in cases with M-echo thickness 9,8 ± 0,06 mm, endometrial homogenous three-layer structure, and satisfactory vascularization (grade A/B endometrium with vascularization in zones 3–4). If endometrium was thin (< 7 mm) but three-layered, as well as in the cases of its satisfactory thickness (8–12 mm) but lacked of three-layer structure, or if there was only vascularization in zones 1–2, embryonic transfer was not done.
The patients involved in the study had their gonadotropic hormones and sex steroids measured in serum on days 2–3 and 21–22 of the cycle.
Statistical analysis
Statistical analysis was performed by using a package of applied programs by SPSS statistics. Descriptive characteristics were calculated, including mean, standard deviation, and standard error of mean for quantitative variables and proportions for qualitative variables. When defining the significance of differences in proportions or percentages for variables characterized by alternative distribution, we used the χ2 criterion, and χ2 criterion with Yates correction in cases when the frequency of the parameter was lower than the limit of the criterion. Student’s t-criterion was used when assessing the significance of mean differences, and the difference was considered significant in p < 0.05.
Results
The clinical characteristics of the patients are shown in Table 1.
Table 1.
| Characteristics | Normal (1), n = 266 |
T-shaped (2), n = 27 |
Intermediate (3), n = 73 |
|||
|---|---|---|---|---|---|---|
| Mean | Standard Error of Mean | Mean | Standard Error of Mean | Mean | Standard Error of Mean | |
| Age | 31.63 | 0.28 | 32.59 | 1.06 | 32.16 | 0.63 |
| BMI | 24.46 | 0.27 | 24.37 | 0.66 | 25.09 | 0.52 |
| Endometrial thickness on day of embryonic transfer | 7.6 | 0.3 | 6.6 | 1.1 | 8.2 | 0.5 |
| Previous pregnancies | 1.5 | 0.1 | 1.0 | 0.0 | 1.9 | 0.3 |
| Deliveries | 1.1 | 0.1 | 0.0 | 0.0 | 1.0 | 0.0 |
| Miscarriages | 1.4 | 0.2 | 1.6 | 0.6 | 2.0 | 1.0 |
| AMH | 1.4 | 0.2 | 1.5 | 0.3 | 1.5 | 0.4 |
| FSH | 8.2 | 0.1 | 8.4 | 0.3 | 7.9 | 0.2 |
BMI body mass index, AMH anti-Müllerian hormone, FSH follicle stimulating hormone
*P12 < 0.05, P23 < 0.05
No differences were detected between the comparison groups in the quality of transferred blastocysts (Table 2).
Table 2.
| Characteristics | Normal (1) n = 266 |
T-shaped (2) n = 27 |
Intermediate (3) n = 73 |
|---|---|---|---|
| Good | 105 (39.5%) | 11 (40.7%) | 29 (39.7%) |
| Fair | 135 (50.8%) | 14 (51.9%) | 38 (52.1%) |
| Poor | 26 (9.8%) | 2 (7.4%) | 7 (9.6%) |
*P > 0.05
We evaluated IVF outcomes after 1 cycle of embryonic transfer, including biochemical pregnancies (positive test for pregnancy or HCG in serum), and clinical pregnancies (US-confirmed finding of a gestational sac in the uterine cavity) (Table 3).
Table 3.
| Characteristics | Normal (1) n = 266 |
T-shaped (2) n = 27 |
Intermediate (3) n = 73 |
P values |
|---|---|---|---|---|
| Biochemical pregnancies | 156 (58.6%) | 14 (51.9%) | 38 (52.1%) | P > 0.05 |
| Clinical pregnancies | 121 (45.4%) | 11 (40.7%) | 31 (42.5%) | P > 0.05 |
The rates of biochemical pregnancy in groups “Normal”, “T-shaped” and “Borderline” was 58.6%, 51.9%, and 52.1%, respectively (p < 0.05). The frequency of clinical pregnancies was 45.4% in the normal group, 40.7% in the T-shaped group, and 42.5% in the Borderline group (Table 3).
Miscarriages, unfavorable pregnancy outcomes, extrauterine pregnancies, and live births are presented across all groups in Table 4. The data from the table indicate that premature births and miscarriages were more frequent in the groups of patients with T-shaped uterus and borderline uterine forms, compared to the patient group with normal uterine cavities (p < 0.05). The rate of full-term deliveries was highest in the “Normal” group, 38.3%, which was statistically significantly higher than in the “T-shaped” and “Intermediate” groups (p < 0.05).
Table 4.
| Characteristics | Normal (1) n = 266 |
T-shaped (2) n = 27 |
Intermediate (3) n = 73 |
P values |
|---|---|---|---|---|
| Term deliveries | 102 (38.3%) | 2 (7.4%) | 14 (19.2%) |
P12 <0.05 P13 <0.05 P23 <0.05 |
| Pre-term deliveries | 10 (3.8%) | 4 (14.8%) | 8 (11.0%) |
P12 <0.05 P13 <0.05 |
| Miscarriages | 7 (2.6%) | 4 (14.8%) | 7 (9.6%) |
P12 <0.05 P13 <0.05 P23 <0.05 |
| Ectopic pregnancy | 2 (0.8%) | 1 (3.7%) | 2 (2.7%) |
P12 <0.05 P13 <0.05 |
To study the possible impact of morphometric features of the T-shaped uterine cavity and its Borderline forms on IVF outcomes in detail, we conducted a comparative characterization of the above-mentioned parameters in 27 patients with T-shaped malformation and 73 patients with intermediate forms of the same malformation. The mean age of patients with these uterine form types was 32.3 ± 0.5 years, and the duration of infertility was 7.7 ± 0.4 years.
Table 5 presents the morphometric parameters of T-shaped uteri and intermediate forms grouped by IVF outcomes in one embryonic transfer cycle.
Table 5.
| Reproductive outcomes | Characteristics | T-shaped (2), n = 27 | Intermediate (3), n = 73 | P23 values | ||
|---|---|---|---|---|---|---|
| Mean | Standard Error of Mean | Mean | Standard Error of Mean | |||
| No pregnancy (A) | Dist1, mm | 45.23 | 2.18 | 42.11 | 0.79 | > 0.05 |
| Dist2, mm | 10.31 | 0.62 | 13.91 | 0.33 | < 0.05 | |
| Dist1-Dist2, mm | 34.93 | 2.17 | 28.20 | 0.68 | < 0.05 | |
| Dist1/Dist2 | 4.54 | 0.34 | 3.06 | 0.06 | 0.05 | |
| Uterine surface S (cm2) | 5.98 | 0.55 | 5.69 | 0.16 | > 0.05 | |
| Angle T,° | 33.49 | 1.26 | 40.58 | 0.62 | < 0.05 | |
| Angle Lat,° | 115.75 | 1.67 | 126.81 | 0.79 | < 0.05 | |
| h, mm | 11.42 | 0.67 | 8.82 | 0.21 | 0.05 | |
| h/L | 0.273 | 0.016 | 0.214 | 0.004 | 0.05 |
| Dist2, mm | 10.77 | 0.66 | 12.66 | 0.61 | > 0.05 | |
| Dist1-Dist2, mm | 24.73 | 3.08 | 24.8 | 0.79 | > 0.05 | |
| Dist1/Dist2 | 2.93 | 0.73 | 3.01 | 0.16 | > 0.05 | |
| Uterine length, mm | 34.43 | 2.15 | 35.39 | 0.83 | > 0.05 | |
| Uterine surface S (cm2) | 4.36 | 0.71 | 4.89 | 0.17 | > 0.05 | |
| Angle T,° | 33.27 | 0.72 | 42.74 | 0.52 | 0.05 | |
| h, mm | 8.43 | 0.68 | 7.81 | 0.30 | > 0.05 | |
| L, mm | 37.87 | 1.69 | 38.3 | 0.85 | > 0.05 | |
| h/L | 0.222 | 0.011 | 0.204 | 0.007 | > 0.05 | |
| Clinical pregnancy (C) | Dist1, mm | 37.51 | 1.32 | 38.74 | 0.64 | > 0.05 |
| Dist2, mm | 10.85 | 0.21 | 14.55 | 0.39 | 0.05 | |
| Dist1/Dist2 | 3.46 | 0.12 | 2.71 | 0.08 | 0.05 | |
| Uterine surface S (cm2) | 4.49 | 0.27 | 5.17 | 0.15 | > 0.05 | |
| Angle T,° | 33.62 | 1.03 | 38.74 | 0.65 | > 0.05 | |
| Angle Lat,° | 120.26 | 1.19 | 130.14 | 0.76 | < 0.05 | |
| h, mm | 8.42 | 0.23 | 7.42 | 0.09 | 0.05 | |
| h/L | 0.215 | 0.007 | 0.189 | 0.003 | < 0.05 | |
|
PAB < 0.05 for: Dist1-Dist2 < 0.05 PAC < 0.05 for: Dist1; Dist1-Dist2; Angle Lat; h; h/L; S |
PAB < 0.05 for: Dist1; Dist1-Dist2; Uterine length, L; S PAC < 0.05 for: Dist1; Dist1-Dist2; Dist1/Dist2; S; Angle T, Angle Lat; h; L; h/L PBC < 0.05 for: Dist2; Angle T; Angle Lat |
As a result of the analysis of morphometric parameters of the uterine cavity in subgroups A, B, and C with different IVF outcomes. Our analysis revealed the following:
A significant difference of mean values in T-shaped uterine malformation between subgroups A (no pregnancy) and C (clinical pregnancy) was observed in parameters characterizing the “degree” of T-shape (Dist 1; Dist1 – Dist 2; h; h/L; S and Angle Lat), while in biochemical pregnancy there was only a significant difference of the parameters Dist1 and Angle Lat, due to the small sample size B);
In intermediate uterine shape forms, the difference between A and C subgroups was not significant only for the parameters Dist 2, length of the uterine cavity, and distance L; subroups A and B had significantly different parameters Dist 1; Dist1 – Dist 2; L; uterine cavity length and surface area; and the comparison of subgroups B and C revealed significant differences for parameters Dist 2; Angle T and Angle Lat.
It is notable that in the subgroups with no pregnancy (A) both for T-shaped and intermediate forms the parameters h and h/L ratio had higher values, depicting the “severity” of the malformation.
We also compared the above-mentioned parameters between T-shape and intermediate forms in each of the subgroups A, B, and C with different IVF outcomes (Table 5, P23 values).
A similar analysis for reproductive outcomes in the same groups compared the subgroups a, b, c, and d in each of the groups by the same parameters (Table 6). The following results were found:
The only difference of mean values between subgroups a and b in T-shaped uterine malformation was found for the Dist 2, h and h/L parameter. Notably, the mean lateral angle was 126.05 ± 1.45° in the group “a” and 119,83 ± 1,58° in pre-term deliveries group; however, despite the obvious smaller value of lateral angle, the difference was not significant due to the small number (2) of term deliveries. There were significant differences between subgroups “a” and “c” for parameters Dist.2, Angle Lat, h, and h/L;
In intermediate uterine shapes significant differences were also found between the subgroups, mainly for parameters characterizing the “degree” of T-shape.
Table 6.
| Repr. outcomes | Characteristics | T-shaped (2), n = 27 | Intermediate (3), n = 73 | P23 values | ||
|---|---|---|---|---|---|---|
| Mean | Standard Error of Mean | Mean | Standard Error of Mean | |||
| Full-term pregnancies (a) | Dist1, mm | 37.9 | 0.5 | 38.66 | 0.88 | > 0.05 |
| Dist2, mm | 12.05 | 0.05 | 15.0 | 0.54 | 0.05 | |
| Dist1/Dist2 | 3.15 | 0.03 | 2.61 | 0.09 | 0.05 | |
| Uterine surface S (cm2) | 4.98 | 0.02 | 5.39 | 0.16 | > 0.05 | |
| Angle T,° | 32.60 | 1.56 | 36.19 | 0.76 | > 0.05 | |
| Angle Lat,° | 126.05 | 1.45 | 132.37 | 1.18 | > 0.05 | |
| h, mm | 7.15 | 0.05 | 6.96 | 0.06 | > 0.05 | |
| L, mm | 40.00 | 1.90 | 40.61 | 0.72 | > 0.05 | |
| h/L | 0.179 | 0.010 | 0.173 | 0.003 | > 0.05 | |
| Pre-term deliveries (b) | Dist1, mm | 38.35 | 3.73 | 38.00 | 1.42 | > 0.05 |
| Dist2, mm | 10.73 | 0.26 | 14.80 | 0.85 | 0.05 | |
| Dist1/Dist2 | 3.57 | 0.31 | 2.61 | 0.14 | 0.05 | |
| Uterine surface S (cm2) | 4.61 | 0.63 | 5.26 | 0.35 | > 0.05 | |
| Angle T,° | 32.25 | 2.55 | 39.44 | 1.17 | < 0.05 | |
| Angle Lat,° | 119.83 | 1.58 | 128.76 | 0.91 | 0.05 | |
| L, mm | 39.5 | 1.30 | 39.38 | 0.79 | > 0.05 | |
| h/L | 0.209 | 0.003 | 0.198 | 0.003 | > 0.05 | |
| Miscarriages (c) | Dist1, mm | 36.95 | 1.19 | 40.16 | 1.54 | > 0.05 |
| Dist2, mm | 10.48 | 0.18 | 13.61 | 0.99 | 0.05 | |
| Dist1/Dist2 | 3.53 | 0.14 | 3.03 | 0.22 | > 0.05 | |
| Uterine length, mm | 34.63 | 1.21 | 35.8 | 1.44 | > 0.05 | |
| Uterine surface S (cm2) | 4.39 | 0.34 | 5.02 | 0.44 | > 0.05 | |
| Angle T, | 34.88 | 1.05 | 42.36 | 0.49 | < 0.05 | |
| Angle Lat,° | 118.33 | 1.72 | 126.63 | 0.58 | < 0.05 | |
| h, mm | 8.93 | 0.12 | 7.76 | 0.04 | 0.05 | |
| h/L | 0.232 | 0.008 | 0.207 | 0.005 | > 0.05 | |
| Extrauterine pregnancies (d) | Dist1, mm | 35.60 | – | 37.25 | 1.65 | – |
| Dist2, mm | 10.40 | – | 13.7 | 0.5 | – | |
| Dist1-Dist2, mm | 25.20 | – | 23.55 | 1.15 | – | |
| Dist1/Dist2 | 3.42 | – | 2.72 | 0.02 | – | |
| Uterine length, mm | 33.6 | – | 34.90 | 1.30 | – | |
| Uterine surface S (cm2) | 3.48 | – | 4.34 | 0.58 | – | |
| Angle T,° | 36.1 | – | 41.15 | 2.05 | – | |
| Angle Lat,° | 122.2 | – | 132.35 | 4.75 | – | |
| h, mm | 9.2 | – | 8.00 | 0.20 | – | |
| L, mm | 37.2 | – | 38.05 | 0.85 | – | |
| h/L | 0.247 | – | 0.210 | 0.010 | – | |
|
Pab < 0.05 for: h; Dist2; h/L Pac < 0.05 for: Dist2; Angle Lat; h; h/L For extrauterine pregnancies, n = 1 (values are given) |
Pab < 0.05 for: Angle Lat; h; h/L Pac < 0.05 for: AngleT; Angle Lat; h; L; h/L Pad < 0.05 for: S, AngleT; h; h/L Pbc < 0.05 for: AngleT; |
We also compared the above-mentioned parameters between T-shaped and intermediate forms in each of the subgroups a, b, c, and d, with different pregnancy outcomes (Table 6, P23 values).
Since the analysis of mean values of uterine cavity parameters revealed significant differences between groups for the following parameters: Dist1- Dist2; Angle Lat; Angle T; h; Dist1/Dist2 and h/L, the sensitivity and specificity were measured by ROC analysis for the same parameters in all clinical groups.
In the “T-shaped” group the parameter Dist1-Dist2 had 100% sensitivity and 41.7% specificity for 25.3 mm cutoff; Angle Lat had 100% sensitivity and 91.7% specificity for 123.5° cutoff; for h the respective values were 91.7% and 50% for 7.15 mm cut-off; Dist1/Dist2 had 91.7% sensitivity and 50% specificity for 3.13 cutoff, and h/L had 100% sensitivity and 100% specificity for 0.196 cutoff.
In the “Intermediate” group, the parameter Dist1-Dist2 had 64.3% sensitivity and 25% specificity for 22.5 mm cutoff; Angle Lat had 100% sensitivity and 50% specificity for 127.5° cutoff; for h the respective values were 95.8% and 50% for 7.05 mm cutoff; Dist1/Dist2 had a 70.8% sensitivity and 42.9% specificity for 2.54 cutoff, and h/L had 100% sensitivity and 85.7% specificity for 0.180 cutoff.
When we combined the T-shaped and “intermediate” groups as if we were to classify the cavities according to the ESHRE criteria, the results changed towards decreased sensitivity and specificity for most of the parameters: Dist1-Dist 2 had 56.3% sensitivity and 33.3% specificity for 23.55 mm cutoff; Angle Lat had 93.8% sensitivity and 33.0% specificity for 127.5° cutoff; for h the respective numbers were 88.8% and 100% for 7.25 mm cutoff; for Dist1-Dist2 the sensitivity was 75.8% and specificity was 50.0% for 2.62 cutoff; and h/L had 100% sensitivity and 81.2% specificity for 0.180 cutoff value.
Interestingly, the mean values of T-angle were not different among the groups of full-term pregnancies and pre-term deliveries (Fig. 4).
Based on these results, it is important to stress yet again the necessity of strict adherence to the morphometric parameters proposed by us to classify a uterine cavity in the appropriate group.
Regarding the mean values of uterine cavity surface area across the groups, our analysis revealed somewhat unexpected findings. Despite the logically justified, expected reduction of the uterine surface in T-shaped malformation due to the myometrium thickening in lateral walls, the comparison of the mean values of uterine surface found no significant differences between T-shaped and intermediate-form groups. With a detailed examination of this parameter, it became evident that higher values of surface area were due to the larger interostial space rather than the width of the cavity in its middle and lower parts, which could possibly explain this paradox (Fig. 5).
Discussion
As a result of this study, we established a certain dependence of the occurrence and outcome of pregnancy on the morphometric parameters of uterine cavity, which deserves a more detailed evaluation in larger groups due to the relative rarity of the discussed malformation and the necessity of more scrutinized identification of “pure” and intermediate forms of T-shaped malformation.
Our results indicate that women with T-shaped uterus have a higher probability of pre-term delivery compared to women with normal uterus. This result is in line with findings in other studies [27, 28].
Women with T-shaped uterus have a higher risk of miscarriage (14.8% versus 3.8% in normal uterus, p < 0.05) and extrauterine pregnancy (3.7% versus 0.8% in normal uterus, p < 0.05). According to our study results, the frequency of pregnancy occurrence in T-shaped and Intermediate groups was statistically similar with the “Normal uterus” group. Similar results were recorded by other authors [29].
The importance of our study is shown by the fact that it is the first large prospective cohort study following the dependence of reproductive outcomes on the morphometric parameters in women with T-shaped cavity malformation.
When evaluating the US morphology of uterine cavity in T-shaped malformation we noticed that even in the presence of all 3 criteria, the uterine cavities had considerable differences in coronal plane length, width in the uterine tube ostia area, width in the lateral angle area and myometrial width in the lateral angle area.
According to our results, T-shaped uterus and intermediate types of this malformation influenced the occurrence of pregnancy in one embryonic transfer cycle with one frozen thawed embryo transfer, mainly depending on the degree of malformation reflected by values of the following parameters, Dist 1; Dist1 – Dist 2; h; h/L and Angle Lat.
In the case of pregnancy occurrence, patients in the second and third clinical groups had a higher frequency of pre-term delivery and miscarriage, as well as pregnancy complications, compared to the patients with a normal ultrasound morphology of the uterine cavity.
In our opinion, defining the mentioned morphometric parameters with their cutoff values can be promising in terms of predicting the successful occurrence of pregnancy and full-term pregnancy, as well as could probably setting clear indications for metroplasty in T-shaped uterine cavity malformation. Further research is warranted to validate these findings.
Evaluation of the impact of T-shaped uterus on ART outcomes (IUI and IVF) and of the accuracy of three-dimensional ultrasound in VCI mode in search of ultrasound markers that might serve as predictors of reproductive outcomes in T-shaped uterus appear relevant.
Funding
None.
Declarations
Conflict of Interest
The authors declare that there is no conflict of interest.
Ethical approval
Study was approved by the Ethics Committee and complied with Declaration of Helsinki principles.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Maheshwari A, Bari V, Bell JL et al (2022) Transfer of thawed frozen embryo versus fresh embryo to improve the healthy baby rate in women undergoing IVF: the E-Freeze RCT. Health Technol Assess 26(25):1–142. 10.3310/AEFU1104 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Calhaz-Jorge C, de Geyter C, Kupka MS, de Mouzon J, Erb K, Mocanu E et al (2016) Assisted reproductive technology in Europe, 2012: results generated from European registers by ESHRE. Hum Reprod 31(8):1638–1652 [DOI] [PubMed] [Google Scholar]
- 3.Grimbizis GF, Camus M, Tarlatzis BC, Bontis JN, Devroey P (2001) Clinical implications of uterine malformations and hysteroscopic treatment results. Hum Reprod Update 7(2):161–174 [DOI] [PubMed] [Google Scholar]
- 4.Rackow BW, Arici A (2007) Reproductive performance of women with müllerian anomalies. Curr Opin Obstet Gynecol 19(3):229–237 [DOI] [PubMed] [Google Scholar]
- 5.Di Spiezio SA, Florio P, Nazzaro G, Spinelli M, Paladini D, Di Carlo C et al (2015) Hysteroscopic outpatient metroplasty to expand dysmorphic uteri (HOME-DU technique): a pilot study. Reprod Biomed Online 30(2):166–174 [DOI] [PubMed] [Google Scholar]
- 6.Hassan MAM, Lavery SA, Trew GH (2010) Congenital uterine anomalies and their impact on fertility. Womens Health Lond Engl. 6(3):443–461 [DOI] [PubMed] [Google Scholar]
- 7.Puente JM, Fabris A, Patel J, Patel A, Cerrillo M, Requena A, et al. Adenomyosis in infertile women: prevalence and the role of 3D ultrasound as a marker of severity of the disease. Reprod Biol Endocrinol [DOI] [PMC free article] [PubMed]
- 8.Propst AM, Hill JA III (2000) Anatomic factors associated with recurrent pregnancy loss. Semin Reprod Med. 18(4):341–350 [DOI] [PubMed] [Google Scholar]
- 9.Saravelos SH, Cocksedge KA, Li T-C (2008) Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal. Hum Reprod Update 14(5):415–429 [DOI] [PubMed] [Google Scholar]
- 10.Oppelt P, von Have M, Paulsen M, Strissel PL, Strick R, Brucker S et al (2007) Female genital malformations and their associated abnormalities. Fertil Steril 87(2):335–342 [DOI] [PubMed] [Google Scholar]
- 11.Kowalik CR, Emanuel MH, Bongers MY, Spinder T, de Kruif JH, Bloemenkamp KWM, et al., 2018 The randomized uterine septum transsection trial (TRUST): design and protocol. BMC Womens Health [Internet] [DOI] [PMC free article] [PubMed]
- 12.Zhu Y, Cheng Z, Wang J, Liu B, Cheng L, Chen B et al (2017) A novel mutation of HOXA11 in a patient with septate uterus. Orphanet J Rare Dis 12:1–6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Hammoud A, Gibson M, Peterson C, Kerber R, Mineau G, Hatasaka H (2008) Quantification of the familial contribution to müllerian anomalies. Obstet Gynecol 111(2):378–384 [DOI] [PubMed] [Google Scholar]
- 14.Hofstetter G, Concin N, Marth C, Rinne T, Erdel M, Janecke A (2008) Genetic analyses in a variant of Mayer-Rokitansky-Kuster-Hauser syndrome (MURCS association). Wien Klin Wochenschr 120(13):435 [DOI] [PubMed] [Google Scholar]
- 15.Iverson RE, DeCherney AH, Laufer MR (2007) Clinical manifestations and diagnosis of congenital anomalies of the uterus. In: Rose BD (ed) UpToDate. Waltham, MA, USA [Google Scholar]
- 16.Salim R, Jurkovic D (2004) Assessing congenital uterine anomalies: the role of three-dimensional ultrasonography. Best Pract Res Clin Obstet Gynaecol 18(1):29–36 [DOI] [PubMed] [Google Scholar]
- 17.Lavergne N, Aristizabal J, Zarka V, Erny R, Hedon B (1996) Uterine anomalies and in vitro fertilization: what are the results? Euro J Obstetr Gynecol Reprod Biol 1(68):29–34 [DOI] [PubMed] [Google Scholar]
- 18.Guirgis RR, Shrivastav P (1990) Gamete intrafallopian transfer (GIFT) in women with bicornuate uteri. J In Vitro Fert Embryo Transf 7(5):283–284 [DOI] [PubMed] [Google Scholar]
- 19.Marcus S, Al-Shawaf T, Brinsden P (1996) The obstetric outcome of in vitro fertilization and embryo transfer in women with congenital uterine malformation. Am J Obstet Gynecol 175(1):85–89 [DOI] [PubMed] [Google Scholar]
- 20.Valenzano MM, Mistrangelo E, Lijoi D, Fortunato T, Lantieri PB, Risso D et al (2006) Transvaginal sonohysterographic evaluation of uterine malformations. Euro J Obstetr Gynecol Reprod Biol 124(2):246–249 [DOI] [PubMed] [Google Scholar]
- 21.Valenzano MM, Mistrangelo E, Lijoi D, Fortunato T, Lantieri PB, Risso D et al (2005) Transvaginal sonohysterographic evaluation of uterine malformations. Eur J Obstet Gynecol Reprod Biol 124(2):246–249 [DOI] [PubMed] [Google Scholar]
- 22.Makris N, Skartados N, Kalmantis K, Mantzaris G, Papadimitriou A, Antsaklis A (2007) Evaluation of abnormal uterine bleeding by transvaginal 3-D hysterosonography and diagnostic hysteroscopy. Eur J Gynaecol Oncol 28(1):39–42 [PubMed] [Google Scholar]
- 23.Grimbizis GF, Gordts S, Di Spiezio SA, Brucker S, De Angelis C, Gergolet M, Li TC, Tanos V, Brolmann H, Gianaroli L, Campo R (2013) The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies. Hum Reprod 28:2032–2044 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Ludwin A, Coelho Neto MA, Ludwin I, Nastri CO, Costa W, Acién M et al (2019) Congenital uterine malformation by experts (CUME): T-shaped uterus. Ultrasound Obstet Gynecol 51:102293 [DOI] [PubMed] [Google Scholar]
- 25.Fernandez H, Garbin O, Castaigne V, Gervaise A, Levaillant J-M (2011) Surgical approach to and reproductive outcome after surgical correction of a T-shaped uterus. Hum Reprod 26(7):1730–1734 [DOI] [PubMed] [Google Scholar]
- 26.Exacoustos C, Romeo V, Zizolfi B, Cobuzzi I, Spiezio AD, Zupi E (2015) Dysmorphic uterine congenital anomalies: a new lateral angle and a cavity width ratio on 3D ultrasound coronal section to define uterine morphology. J Minim Invasive Gynecol 22(6):S73 [DOI] [PubMed] [Google Scholar]
- 27.Venetis CA, Papadopoulos SP, Campo R, Gordts S, Tarlatzis BC, Grimbizis GF (2014) Clinical implications of congenital uterine anomalies: a meta-analysis of comparative studies. Reprod Biomed Online 29:665–683 [DOI] [PubMed] [Google Scholar]
- 28.Woelfer B, Salim R, Banerjee S, Elson J, Regan L, Jurkovic D (2001) Reproductive outcomes in women with congenital uterine anomalies detected by three-dimensional ultrasound screening. Obstet Gynecol 98(6):1099–1103 [DOI] [PubMed] [Google Scholar]
- 29.Pleş L, Alexandrescu C, Ionescu CA, Arvătescu CA, Vladareanu S, Moga MA (2018) Three-dimensional scan of the uterine cavity of infertile women before assisted reproductive technology use. Medicine (Baltimore) 97:e12764. 10.1097/MD.0000000000012764 [DOI] [PMC free article] [PubMed] [Google Scholar]
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