Abstract
Studies have focused on uterine peristalsis and endometrial development, whereas knowledge is limited on cyclical changes in the uterocervical angle (the angle formed between the uterine corpus and cervix) during the menstrual cycle. Here, these dynamic changes were investigated. We conducted a retrospective analysis of 99 freeze-thawed blastocyst transfer cycles in 2020 and a prospective analysis of 192 cycles between 2022 and 2023. Transvaginal ultrasonography was performed to measure the uterine angle during the menstrual, ovulatory, and implantation periods. In the prospective study, conditions were standardized by instructing patients to empty their bladders and avoid uterine compression during scanning. In the retrospective analysis, the uterine angle significantly differed between the menstrual and ovulatory periods (141.1â±â33.5° vs. 147.7â±â40.9°, pâ=â0.04), but no correlation with serum estradiol or progesterone levels was observed. The prospective analysis confirmed significant differences in uterine angle between the menstrual and ovulatory periods and between the ovulatory and implantation periods (135.1â±â27.7°, 141.5â±â30.9°, and 136.8â±â28.7°, respectively; both pâ<â0.01), without hormonal correlation. These findings suggest that the uterine angle varies throughout the menstrual cycle, becoming more anteverted during the menstrual and implantation periods and straightening around ovulation.
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Introduction
The number of patients experiencing infertility is increasing1, and the need for fertility treatments is growing. Despite remarkable advances in technology, including in vitro fertilization2, the success rate of assisted reproductive technology (ART) remains at approximately 30%, and further breakthroughs are required. A deep understanding of physiological phenomena, such as follicular development, fertilization, and implantation, is necessary for the advancement of ART. In this study, we propose that the uterus changes its angle and position throughout the menstrual cycle.
In most cases, the uterus is anteverted and anteflexed in the pelvis toward the bladder. In clinical practice, uterine tilt often changes during the menstrual cycle, even in the same patient. Therefore, as preliminary data, we obtained MRI images of a fertile patient (28 years old, one parity, 28-day menstrual cycle) with no organic disease of the uterus or bilateral adnexa throughout the menstrual period (day 3 after the start of menstruation), ovulation period (day 14), and implantation period (day 21), as shown in Fig. 1. The uterus was strongly anteverted at the time of menstruation, shifted to an upright position during ovulation, and then anteverted again around the implantation period, although there was no evidence of adhesion to the pelvis or urinary retention in the bladder (Fig. 1). However, because the results were obtained from a single case using MRI, whether changes in the uterine angle occur throughout the menstrual cycle in other cases remains to be determined.
Pelvic MRI images of the same patient at different phases of the menstrual cycle. Pelvic MRI scans of the same volunteer (28 years old, parityâ=â1, regular 28-d cycle) were obtained three times during the menstrual cycle. (a) Day 3: menstrual period; (b) Day 14: ovulatory period; (c) Day 21: implantation period. Note the small angle and strong anteversion during the menstrual and implantation periods [(a) red line; (c) green line] and the larger angle with an upright shift during the ovulatory period [(b) yellow line].
Studies have described dynamic uterine movements, such as peristalsis and changes in endometrial receptivity, but little attention has been paid to positional changes in the uterus. The uterocervical angle, defined as the angle between the uterine corpus and cervix, may play a crucial role in embryo transfer efficiency and implantation success. However, cyclical variations throughout the menstrual cycle remain largely unexplored.
We hypothesized that the uterine angle changes physiologically during the menstrual cycle to facilitate processes, such as sperm transport and implantation. Therefore, we aimed to investigate whether the uterine angle varies across different phases of the cycle and to explore its potential physiological and clinical significance.
The objective of this study was to determine whether the uterine angle changes during the menstrual cycle. The uterine angle included both the angle between the cervix and uterine body and uterine tilt in the pelvis (which is the angle between the uterine body and horizontal axis of the ground). For the purposes of this study, the uterine angle was defined as the angle between the uterine cervix and body.
Results
To investigate whether the uterine angle changes during the menstrual cycle, we conducted both retrospective and prospective studies using transvaginal ultrasonography. In both studies, the uterine angle was defined as the angle formed by the line connecting the external and internal cervical os (Fig. 2A) and line connecting the internal os and uterine fundus (Fig. 2B). In the prospective study, patients were instructed to void their bladders before the examination to reduce variability, and the ultrasound probe was inserted without applying pressure to the uterus.
Retrospective study
This retrospective study included 99 patients. The uterine angle was 141.1â±â33.5° (meanâ±âstandard deviation) during the menstrual period, 147.7â±â40.9° during the ovulatory period, and 145.7â±â31.9° during the implantation period. There was a significant difference in the angles between the menstrual and ovulatory periods (pâ=â0.04) (Table 1).
We investigated whether there was a correlation between the uterine angleâincluding its change during the ovulatory and implantation periodsâand serum Eâ and Pâ values, but no significant correlation was observed (Supplementary Figs. S1â3).
Prospective study
This prospective study included 192 chemotherapy cycles. In all cases, to eliminate the confounding effect of bladder contents on the angle, patients were instructed to void immediately before the ultrasound examination, ensuring an empty bladder. The uterine angle was 135.1â±â27.7° during the menstrual period, 141.5â±â30.9° during the ovulatory period, and 136.8â±â28.7° during the implantation period. Significant differences were observed between the angles during the menstrual and ovulatory periods and between the ovulatory and implantation periods (both pâ<â0.01) (Table 2).
The results of the stratified analyses according to age, gravidity, and parity are presented in Supplementary Table S1.
There was no correlation between changes in the uterine angle and serum levels of Eâ and Pâ during the ovulatory and implantation periods (Supplementary Figs. S4â6). Although the difference was not statistically significant, a trend was observed in which the uterine angle decreased and the anteflexion increased as Pâ concentrations rose from the ovulatory to the implantation period.
Subsequently, in this prospective study, we examined the changes in the angle in cases where there was a significant change and in those where little change was observed. Based on the interquartile range of angle changes from the menstrual to the ovulatory period, we classified the cases into four groups: Group A (+â21.8° to +â98.8°), Group B (+â4.5° to +â20.2°), Group C (ââ10.2° to +â4.4°), and Group D (ââ66.7° to ââ10.5°). We similarly examined the changes in the angle from the ovulatory to the implantation period. The groups were classified as follows: Group A (ââ91.3° to ââ17.5°), Group B (ââ16.5° to ââ1.2°), Group C (ââ1.1° to +â12.9°), and Group D (+â14.1° to +â66.1°). Group A comprised patients with the most significant dynamic changes. There were 21 cases that were classified as Group A during both the menstrual-to-ovulatory and ovulatory-to-implantation periods. Figure 3 shows the angle changes for these 21 cases. Supplementary Fig. S7 shows the angle changes for all 192 cases.
Graph of changes in the uterine angle. Graph showing uterine angle changes in cases with significant variation from the menstrual to the ovulatory period and from the ovulatory to the implantation period. The Y-axis represents the uterine angle; the X-axis represents the menstrual, ovulatory, and implantation periods.
Discussion
In the present study, we found that the uterine angle was smallerâindicating a more anteverted uterusâduring the menstrual and implantation periods, whereas it increased and straightened during the ovulatory period. This straightening during ovulation may represent an adaptive mechanism that facilitates sperm ascent and efficient passage to the fallopian tubes, thereby aiding conception. Our study found that the uterine angle changed by approximately 6â7° from the menstrual to the ovulatory period, suggesting that this change might be a crucial process for fertilization. The uterus exhibits peristaltic movements from the cervical side toward the fundus during the ovulatory period3. The synchronization between these peristaltic movements and uterine straightening may support sperm transport, potentially contributing to fertilization.
During the menstrual period in the retrospective and prospective studies, and during the implantation period in the prospective study, the uterine angle appeared smaller than during the ovulatory period. During menstruation, a more anteverted uterine position may help retain menstrual blood and prevent excessive bleeding, allowing clot formation when necessary. Additionally, during implantation, a smaller angle may support embryo retention within the uterine cavity and promote successful implantation.
The concept that the uterine angle changes during the menstrual cycle is novel, and to our knowledge, no previous reports have addressed the clinical significance of these changes. As mentioned previously, changes in the uterine angle may occur purposefully throughout a patientâs reproductive life. Understanding the relation between such changes and pregnancy outcomes could enhance our understanding of reproductive physiology and perinatal health, potentially improving infertility treatment success and reducing complications.
However, several questions remain unanswered: (1) The present study included only ART cases; therefore, applicability to non-ART cases remains unknown. (2) Do uterine angle changes during the menstrual cycle exhibit intra-patient reproducibility? (3) What mechanisms underlie these angle changes? (4) How do these changes manifest in patients with uterine retroversion? It is challenging to distinguish between physiological retroversion4 and retroversion caused by pathological conditions, such as pelvic adhesions5, which may limit uterine mobility. Considering that uterine adhesions may restrict changes in uterine angulation, we included only patients with anteverted uteri in this study. Some reports have associated retroverted and retroflexed uteri with clinical manifestations, such as severe dysmenorrhea6, recurrent miscarriage7, and an increased incidence of uterine prolapse8. However, further studies are needed to confirm and validate these associations. Another limitation is that the statistical power of the subgroup analyses was not formally evaluated.
In addition to the angle between the cervix and uterine body, the tilt of the uterus in the pelvisâdefined as the angle between the uterine body and horizontal axis of the groundâmay also vary (Fig. 1). One limitation of the current study is that uterine tilt was not assessed; this parameter warrants separate investigation.
Recent studies have demonstrated that the uterus exhibits not only anatomical but also dynamic physiological changes, including uterine peristalsis and structural alterations in the junctional zone9,10,11. Cine MRI studies have shown that these contractions fluctuate throughout the menstrual cycle and are influenced by hormonal changes, particularly in estrogen and progesterone levels9,12. Peristaltic movements originating in the junctional zone are believed to support sperm transport and embryo implantation and improve in vitro fertilization outcomes13,14. The uterine angle changes observed in our study may represent an additional manifestation of these dynamic uterine behaviors and contribute to a more comprehensive understanding of uterine receptivity.
From a clinical perspective, it is necessary to determine whether changes in the uterine angle are associated with pregnancy outcomes, including implantation and live birth rates, as well as perinatal complications, such as placenta previa and preterm birth. A steep or acutely angled uterus may complicate intrauterine insemination or embryo transfer by making catheter insertion technically difficult, which could negatively affect treatment outcomes. Future studies that integrate uterine angle assessment with other dynamic parameters, such as peristaltic activity, may help identify optimal sites for cannulation or embryo placement, ultimately improving fertility treatment outcomes and perinatal prognosis.
In conclusion, we found that the uterine angle changes throughout the menstrual cycle. Further investigation is necessary to elucidate the mechanisms underlying these changes and their clinical significance.
Methods
This study was approved by the Ethics Committee of the University of Yamanashi under ethics approval number 2584, granted on 1/11/2022, and both the retrospective and prospective components were conducted in accordance with institutional guidelines and regulations. For the retrospective component, informed consent was obtained via an opt-out method by publicly disclosing the study details on the hospital website. For the prospective component, based on the ethical committeeâs approval and in accordance with institutional guidelines for observational studies of minimal risk, informed consent was also obtained via an opt-out method through electronic disclosure. All participants were provided with the opportunity to decline participation.
First, as a retrospective study, we targeted patients who underwent freeze-thawed blastocyst transfer at our hospital in 2020. This retrospective study used archived data, which were fully anonymized before access. Data analysis was conducted from 1/1/2023 to 31/3/2023. For routine clinical care, transvaginal ultrasonography was performed at three time points during the embryo transfer cycle: (1) menstrual period: second or third day of menstruation; (2) ovulatory period: the day before the start of progesterone preparations in hormone replacement cycles or the day before ovulation in natural cycles; and (3) implantation period: the day of embryo transfer (Fig. 4). Using medical records, the uterine angle was evaluated using transvaginal ultrasonography (Voluson P8; GE Healthcare, Canada) at each specified time. The uterine angle was defined as the angle formed by the line connecting the external and internal cervical os (A) and line connecting the internal os and uterine fundus (B) (Fig. 2). We hypothesized that changes in the uterine angle would differ between patients with anteverted and retroverted uteri; therefore, this study focused only on patients with an anteverted uterus.
Schedule of frozen-thawed embryo transfer. (a) Menstrual period: second or third day of menstruation; (b) Ovulatory period: the day before the start of progesterone preparations in hormone replacement cycles or day before ovulation in natural cycles; (c) Implantation period: the day of embryo transfer. Ultrasonography was performed at all three time points. Serum hormone measurements (estradiol and progesterone) were obtained during the ovulatory (b) and implantation (c) periods.
Additionally, because the uterine angle may vary depending on bladder content and the pressure applied by the ultrasound probe, we conducted a prospective study to observe changes under standardized conditionsâimmediately after bladder emptying and using a consistent probe insertion method. The probe was inserted to avoid exerting pressure on the uterus. Ultrasound examinations were conducted by three gynecologists at our hospital following a standardized protocol that involved measuring the uterine angle without pressing the probe against the uterus. All angle measurements were performed by a single experienced observer (T.Y.) to ensure consistency and reduce interobserver variability. The observer was blinded to the identity of the sonographer who performed each scan at the time of measurement.
In this prospective study, we targeted patients who underwent freeze-thawed blastocyst transfer between 1/12/2022 and 31/12/2023. This study was approved by the Ethics Committee of our hospital. The uterine angle was measured using the same method as in the retrospective study. Sample size calculation indicated that at least 71 participants were required to detect a 5° difference in uterine angle between two phases of the menstrual cycle (paired design, standard deviationâ=â15°, αâ=â0.05, powerâ=â0.80). Both cohorts in this study exceeded this threshold.
We compared the uterine angles within each embryo transfer cycle. Given the possibility that changes in the uterine angle are influenced by fluctuations in serum hormone levels, we examined the relation between serum estradiol (Eâ) and progesterone (Pâ) levels during the ovulatory and implantation periods.
Statistical analyses were performed using JMP (version 17.2.0). Data are presented as meanâ±âstandard deviation. Wilcoxonâs signed-rank test was used to assess changes in the uterine angle across the cycle, and simple regression analysis was used to evaluate the relation between the uterine angle and serum hormone levels. A p-valueâ<â0.05 was considered statistically significant.
Data availability
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to their containing information that could compromise the privacy of research participants.
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We would like to thank Editage (www.editage.jp) for providing English language editing services.
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Tatsuya Yoshihara and Osamu Yoshino conceived and designed this study.Tatsuya Yoshihara, Dai Miyashita, Tatsuyuki Ogawa, and Maki Ogi contributed to data acquisition and analysis.Tatsuya Yoshihara, Yosuke Ono, and Osamu Yoshino drafted the manuscript.Maki Ogi, Dai Miyashita, Kota Tanaka, Yuri Tada, Tomohiko Fukuda, and Yasuhiko Okuda contributed to manuscript revision.All authors read and approved the final submitted version of this manuscript.
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The Ethics Committee of the University of Yamanashi (approval No. 2584; November 1, 2022) authorized the research. All procedures were carried out in accordance with relevant guidelines and regulations and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Yoshihara, T., Ogi, M., Ono, Y. et al. Uterine angle changes during the in vitro fertilization treatment cycle. Sci Rep 15, 25798 (2025). https://doi.org/10.1038/s41598-025-11258-6
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DOI: https://doi.org/10.1038/s41598-025-11258-6