Comparison of the Application Value of 4-Dimensional Hysterosalpingo-Contrast Sonography and X-Ray Hysterosalpingography in Intrauterine Insemination

A total of 725 cases clinical data were reviewed. According to the method of hysterosalpingography, they were divided into 535 cases in the HSG group and 190 cases in the 4D‐HyCoSy group. In Tables  1 and 2 we reported the general data and infertility factors. The mean age of female in HSG group was 29.8 years and 31.0 years in 4D‐HyCoSy group. Most patients were nulliparous (53.4%). Endometrial polyps were identified by ultrasound in 12 patients in the HSG group and 9 patients in the 4D‐HyCoSy group. During the routine pre‐hysterosalpingography ultrasound examination, upon detection, hysteroscopic polypectomy was performed, after which IUI was carried out. No cavity abnormalities were found on either procedure and no patients required corrective surgery prior to IUI. In HSG group 9 cases had 1 tubes patent and 526 cases had both tubes patent, in 4D‐HyCoSy group 6 cases had 1 tubes patent and 184cases had both tubes patent. The proportions of infertility attributable to male factors (including ejaculatory dysfunction, oligoasthenozoospermia, eratozoospermia etc.) were compared between the 2 groups. There were 35.32% male factor infertility in HSG group and 40.5% in 4D‐HyCoSy group in total. Comparison of General Data of Patients in the HSG Group and the 4D‐HyCoSy Group (x¯ ± s) Infertility Factors in the HSG Group and the 4D‐HyCoSy Group, n (%) There was no statistically significant difference in general data and infertility factors between the HSG group and the 4D‐HyCoSy group. We reported the results in (Table  3 ) that the clinical pregnancy rates after IUI were (104/535) 19.43% in the HSG group and (34/190) 17.89% in the 4D‐HyCoSy group. The number of IUI cycles required for clinical pregnancy was 1.55 ± 0.65 in the HSG group and 1.62 ± 0.79 in the 4D‐HyCoSy group. Of these, (3/104) 2.8% had ectopic pregnancy in the HSG group, (1/34) 2.9% in the 4D‐HyCoSy group, (10/535) 1.9% in the HSG group, and (3/190) 1.6% in the 4D‐HyCoSy group had a biochemical pregnancy, (12/104) 11.5% in the HSG group, and (5/190) 14.7% in the 4D‐HyCoSy group ended in miscarriage. All the differences were not statistically significant. Comparison of Clinical Pregnancy Outcomes Between the HSG Group and the 4D‐HyCoSy Group, (x¯ ± s), n (100%)

In this cohort of women who underwent HSG or 4D‐HyCoSy for tubal patency test prior to IUI, we found comparable reproductive outcomes regardless of the initial tubal assessment method, suggesting that 4D‐HyCoSy represented a viable alternative to HSG. The comparable outcomes observed in both groups were likely multifactorial. First, both HSG and 4D‐HyCoSy shared a common mechanism of transcervical tubal cannulation and fluid instillation. This process was thought to exert a therapeutic ‘flushing effect’, potentially dislodging subtle debris or mucous plugs that could impede ovum or sperm transport, thereby transiently improving tubal function. 9 Additionally 4D‐HyCoSy and HSG demonstrated high efficacy in fallopian tube evaluation and showed comparable accuracy in diagnosing tubal obstruction, while 4D‐HyCoSy was associated with a lower incidence of pain and fewer adverse reactions. 7 Our findings were in line with the study of Hardel, A.S, who also reported similar pregnancy rates after IUI following either HSG or 4D‐HyCoSy. 10 However, another retrospective study pointed out that 4D‐HyCoSy was not as effective as HSG in increasing the pregnancy rate through the flushing effect. 11 This discrepancy could be attributed to differences in patient population, ovarian stimulation protocols, or sample size. Many studies had reported increased spontaneous pregnancy rates after these 2 contrast imaging methods independently. 12 , 13 While some studies indicated higher pregnancy rates in the HSG group compared with the 4D‐HyCoSy group, 14 , 15 others found no significant difference between the 2 group. 16 These inconsistencies may have arisen because earlier studies often did not adjust for male factors such as age and sperm motility, focused primarily on spontaneous conception rates, which are more susceptible to confounding, and lacked follow‐up within structured assisted reproductive technology settings. It was noteworthy that literature directly comparing these 2 modalities in relation to IUI outcomes remained limited, with most previous studies emphasizing diagnostic accuracy rather than therapeutic implications. The advantages of 4D‐HyCoSy were considerable. HSG was associated with low‐dose radiation exposure, potential iodine allergy, and a risk of postoperative infection, 17 whereas 4D‐HyCoSy involved no radiation, used saline as the contrast medium, and carried a very low risk of hypersensitivity reactions. The risk of infection with saline infusion sonohysterography (SIS) was 0.095%. 18 Although this might be due to the small sample sizes of individual studies and insufficient ability to detect uncommon complications. Moreover, 4D‐HyCoSy offered a comprehensive, real‐time assessment of the pelvic organs, allowing for the simultaneous evaluation of the uterine myometrium and ovaries, which HSG cannot provide. Discomfort associated with 4D‐HyCoSy was also reported to be significantly milder compared with HSG in a study by Van Weilie et al. 19 Thus, our study contributed uniquely by linking a diagnostic modality directly to a key treatment endpoint. The primary clinical implication of our study was that 4D‐HyCoSy can be confidently recommended as a first‐line test for tubal patency in the workup for IUI. Several limitations of our study warranted consideration. Firstly, its retrospective and single‐center design may have introduced selection bias. Although our sample size was sufficient for the primary outcome, it may have been underpowered to detect small differences in secondary outcomes, such as ectopic pregnancy rates. Despite statistical adjustments for known confounders, residual confounding from unmeasured factors (eg, specific infertility sub‐types) could not be entirely excluded. Finally, the accuracy of 4D‐HyCoSywas operator‐dependent, which may have affected the generalizability of our results to centers with less experience in this technique. In summary, our study demonstrated that 4D‐HyCoSy and HSG yielded equivalent IUI success rates. Future prospective, randomized controlled trials with larger sample sizes are needed to confirm these findings. Further research could also explore the cost‐effectiveness of these strategies and investigate their role in specific patient subgroups, such as those with suspected endometriosis.

No significant differences were observed in clinical pregnancy rates, number of IUI cycles required to achieve pregnancy, or adverse pregnancy outcomes—including ectopic pregnancy, biochemical pregnancy rates, and the early miscarriage rates between women who underwent HSG and 4D‐HyCoSy for tubal patency testing. 4D‐HyCoSy offers distinct advantages over HSG, primarily by eliminating radiation exposure and providing a comprehensive, 1‐stop diagnostic evaluation of the uterine cavity, myometrium, ovaries, and pelvic environment in a single session. Therefore, it is recommended that HSG be phased out in favor of adopting 4D‐HyCoSy as the first‐line diagnostic test for tubal patency in pre‐IUI evaluation.

A retrospective study was performed on 725 infertile couples who underwent IUI treatment in the Department of Reproductive and Genetic Medicine, Ganzhou Maternal and Child Health Hospital (Ganzhou, China) from January 2023 to June 2024. All procedures were performed in a similar manner by the same group of doctors in a single center. This research was approved by the Ethics Committee of the Ganzhou Maternal and Child Health Hospital (No. 2025‐LSL‐150). All participants had signed an informed consent form before the imaging examination. They all met the following criteria for the procedure: (1) Patient has normal sexual activity without taking contraceptive measures, has not been pregnant for more than 1 year, and meets the diagnostic criteria for infertility. (2) Patients who underwent IUI after 4D‐HyCoSy or HSG examination. (3) The age of the couples ranged from 20 to 38 years old. (4) The ovarian reserve function of the female was normal. (1)The endometrial thickness on the ovulation day was ≤5 mm. (2) IUI cycle was canceled due to luteinization of the follicle. (3)Either the husband or the wife had chromosomal abnormalities. (4) The female had uterine adhesions, pelvic adhesions, or uterine tumors, severe uterine malformations such as uterine septum and unicorn uterus. (5) Absence of motile spermatozoa on the day of IUI and unknown outcome following IUI. Patients undergoing investigation for subfertility underwent 4D‐HyCoSy during the proliferative phase of the menstrual cycle. Routine scanning of the uterus and adnexa, pelvic basic condition, and pelvic activity of the uterus and adnexa. After accurate cleaning of the cervix and vagina with an iodinated solution, an 8‐Fr catheter was introduced transcervical. A Resona6T (Mindray, China) ultrasound system with coded contrast imaging was used. The mechanical index of the instrument was set at 0.12–0.18. An V11‐3HU transvaginal volume transducer with a frequency range of 5.0–9.0 MHz and scanning angles from 0° to 179° was used in the examinations. An SF6 microbubble agent (Sono Vue, Bracco International BV, Amsterdam, the Netherlands) was used to prepare the contrast medium for injecting into the uterine cavity. Then use a vaginal volume probe to determine the position of both ovaries, 3 modes of HyCoSy were completed in sequence: 4D‐HyCoSy, 2D‐HyCoSy, and second harmonic imaging (SHI). We started with a 2D‐HyCoSy using saline as contrast medium and ultrasound performed on the 2D setting and B mode. Five milliliter of sterile saline were first injected into the uterine cavity to determine whether there were any intracavitary abnormalities. With the same catheter, we diluted 3 mL of Sono Vue with 20 mL of saline and used 5–20 mL of the final solution for each patient. The diagnosis of tubal patency for saline and B‐mode ultrasound was obtained when the following criteria were met: (1) visualization of the flow of contrast media in the tubes without dilatation of the lumen; (2) appearance of contrast media in the peritoneal cavity near the ovaries (hyperechoic image). The diagnosis of tubal patency for Sono Vue was obtained with the direct display of the contrast medium first in the uterine cavity and immediately thereafter in the tubes. Patients in the X‐HSG group were instructed to empty their bladder and assume the lithotomy position prior to the examination. Following routine disinfection of the vulva and vagina, air was removed from the infusion tube, and a hysterography catheter was gently advanced into the uterine cavity. The balloon was then inflated with 2 mL of normal saline to secure the catheter within the cervical canal, preventing dislodgement. Under fluoroscopic guidance using a Siemens DR digital gastrointestinal system, 20 mL of Iohexol injection (Jiangsu Hengrui Pharmaceuticals Co., Ltd.) was slowly administered into the uterine cavity. Morphological visualization of the uterus and fallopian tubes was monitored throughout the procedure. Radiographs were acquired at the following intervals: when the contrast agent had fully opacified the uterus and fallopian tubes but had not yet entered the pelvic cavity; during injection, when satisfactory filling of the uterine cavity and fallopian tubes was achieved; after the contrast agent had dispersed into the pelvic cavity, to assess its distribution pattern within the pelvis. Diagnostic criteria for HSG: (1) Unobstructed fallopian tubes: The contrast agent has a good imaging effect, and a large amount of contrast agent diffuses from the fallopian tubes to the pelvic cavity. (2) Partially unobstructed fallopian tubes: The contrast agent is filled in the fallopian tubes, but in some local areas of the fallopian tubes, the contrast agent is agglutinated and unevenly dispersed. (3) Fallopian tube obstruction: The fallopian tubes are not visualized at all or only a very small part can be visualized, or no contrast agent diffusion is found in the pelvic cavity. The couples scheduled for IUI were randomized to IUI with or without ovarian stimulation (OS). Women in the OS group received 2.5 mg to 5 mg oral letrozole daily starting from cycle days 3 to 5 for 5 days. Intramuscular injection of human menopausal gonadotropin (HMG, Lebode, Livzon, Zhuhai, China) 75–150 IU was given every alternate day starting from day 10 and titrated according to the response. When no more than 3 follicles with a diameter of 17–18 mm were present, final oocyte maturation was induced by intramuscular administration of 10000 U human chorionic gonadotropin (HCG, Gonlong, Qingdao, China) and 24 hours later IUI was performed. Women in the natural cycle IUI group did not receive any ovarian stimulation before IUI. General information (age of the couples, body mass index [BMI], total motile sperm in millions of the male, previous pregnancies, duration of infertility, infertility factors [ejaculatory dysfunction, oligoasthenozoospermia, eratozoospermia], ovulatory disorders, unexplained factors, unilateral or both tubal patency, endometrial polyp and insemination outcomes) was recorded. Clinical pregnancy was defined as the ultrasound visualization of an intrauterine gestational sac with the presence of fetal cardiac activity, confirmed at 4–6 weeks following IUI. Ectopic pregnancy was defined as pregnancy in which a fetus develops outside of the uterus confirmed by ultrasound. Biochemical pregnancy was defined as a peripheral blood β‐HCG level of ≥15 U/L measured 14 days after IUI and with no visible gestational sac on ultrasound at 4–6 weeks following IUI. The early miscarriage was defined as spontaneous abortion before 12 weeks. The main observation indicators were determined as follows: clinical pregnancy rate = number of clinical pregnancy cycles/total number of IUI cycles × 100%. Secondary observation indicators included the number of IUI cycles required to reach clinical pregnancy. Adverse pregnancy outcomes: ectopic pregnancy rate = number of ectopic pregnancy cycles/clinical pregnancy cycles × 100%, biochemical pregnancy rate = number of biochemical pregnancy cycles/total number of IUI cycles × 100%, early miscarriage rate = number of early miscarriage cycles/clinical pregnancy cycles × 100%. SPSS version 26.0 (IBM Corp Armonk, NY, USA) was used for statistical analysis. Continuous variables were presented as means ± standard deviations (SD). Statistical analyses were performed using the Chi‐square test or Fisher's exact test for comparing categorical variables, and the student's t ‐test or the non‐parametric Wilcoxon‐Mann–Whitney rank‐sum test for quantitative variables. Variables with a p ‐value <.05 (2‐tailed) were considered statistically significant.