Spontaneous conception outcome in infertile women after four-dimensional hysterosalpingo-contrast-sonography

This retrospective study was approved by the Ethics Committee of Guangdong Second Provincial General Hospital (2018-CSkWZ-009). All participants had signed informed consent before examinations.

All the records of the seven hundred and eleven (711) patients who underwent the 4D-HyCoSy in our center between December 2014 and October 2017 were extracted for in depth analysis. Basic clinical data extracted from the records included age, duration of infertility, type of infertility, multipara, previous pelvic inflammatory disease, previous pelvic surgery, previous intrauterine surgery and abortions. In order to determine the spontaneous conception of infertile women after 4D-HyCoSy, it was necessary to select patients who conformed to two major criteria: 1. the patient’s husband showed no evident cause for infertility [16]. 2. No clinical interventions (IVF or hysteroscopy and laparoscopic surgery) were given after 4D-HyCoSy. To conform to these criteria, the exclusion criteria were as follows: women did not conceive without contraception less than a year (35 patients), semen abnormalities (according to WHO 2010 guideline) or no semen examination (213 patients), hydrosalpinx by ultrasound examination (29 patients), hysteroscopy and laparoscopic surgery (103 patients) or in vitro fertilization (IVF) (4 patients) within a year after 4D-HyCoSy, According to the exclusion criteria, 327 patients were enrolled in our follow-up study (Fig. 1).

A Voluson E8 Expert (GE Healthcare, Zipf, Austria) With RIC5–9-D volume probe (5–9 MHz) was used. Equipment settings for 4 dimensional contrast sonography were as follows: volume box angle at 179°, volume angle at 120°, quality at low, direction at up/down, render mode at gradient light and threshold, Low at < 20, adjusted according to the image [14, 17]. The contrast agent was prepared by adding 5 ml of 0.9% sterile saline solution to 59 mg of SF6 Sonovue freeze-dried powder (Bracco International BV, Amsterdam, the Netherlands), then 2.5 ml SonoVue solution was aspirated and diluted it into a 15 ml suspension with the 0.9% of saline solution.

The 4D-HyCoSy was performed within 3 to 10 days after menstruation. Each examination was performed by an experienced physician with more than 5 years of ultrasonographic diagnosis. The patient was in lithotomy position with her vulva and cervix routinely disinfected with an iodinated solution (Effective iodine content: 0.45–0.55%, Shanghai Likang Disinfection Technology Co., Ltd). The condition of the uterus, ovaries and pelvic cavity was evaluated by 2-dimensional transvaginal sonography and the results were recorded (uterine fibromyoma, uterine cavity lesions such as endometrial polyps or adhesions and polycystic ovaries). Next the 4D-HyCoSy was performed. An appropriate initial plane was selected by positioning the vaginal probe at the level of the sectional plane of the uterus, with slight adjustment to allow visualization of bilateral uterine horns and surrounding tissues. 4D-HyCoSy was activated while keeping the probe at the same position with the region of interest as wide as possible. Fifteen millimeters (15 ml) of the contrast agent earlier prepared was then insufflated and adjusted in accordance with the development in the fallopian tube(s) such as spillage at the fimbriae of the contrast in the pelvis. The contrast agent was passed through the catheter into the uterine cavity, following which the flow of the contrast agent in the fallopian tube and the overflow at the tubal fimbriae were observed. The dynamic enhanced volume images were saved and analyzed after the injection of the contrast medium [2, 11, 14].

According to the bilateral tube patency, patients were divided into six categories: type I, defined as bilateral fallopian tubes obstruction; type II, defined as one obstructed fallopian tube with poor patency in the other; type III, defined as one obstructed fallopian tube with patent in the other; type IV, defined as bilateral fallopian tube poor patency; type V, defined as one fallopian tube poor patency with patent in the other; type VI, defined as bilateral fallopian tubes patent.

The outcome of spontaneous conception defined as conception by sexual intercourse and a sonographically visible fetal sac within the uterine cavity. Patients were followed up once a month by telephone, clinical, ultrasound examinations after 4D-HyCoSy. The follow-up lasted for 12 months or till the patient succeeded in the first spontaneous conception.

All statistical analyses were conducted with SPSS version 23.0 software for windows (SPSS Inc., Chicago, IL, USA). The data were expressed as \( \overline{x} \) ± SD or percentage. The chi-square test was used to compare the difference among groups for counting data. Kaplan–Meier method was performed to calculate cumulative conception rates and conception time after 4D-HyCoSy. Log-rank test was performed to evaluate the clinical and ultrasound factors on spontaneous conception that included age, duration of infertility, infertility type, previous pelvic surgery, history of abortion, history of intrauterine surgery, history of pelvic inflammatory disease, multiparas or not, uterine fibromyoma, lesion of uterine cavity (adhesions or/and polyps), polycystic ovary and tubal patency. Next, a stepwise Cox regression was performed to analyze the potential confounding affecting factors associated with spontaneous conception, and a P value < 0.05 was considered significant.

A total of seven hundred and eleven (711) patients performed 4D-HyCoSy in this study, and 327 (327/711,46.0%) met the inclusion criteria, Each case was followed up for a year. A total of 44 patients (44/327,13.5%) were lost follow-up, and 283 patients were finally included in our study (Fig. 1). six patients undergo repeated procedure due to severe venous intravasation. No Patients had a severe vasovagal reaction requiring resuscitation. The age of the participants ranged from 20 to 46 years, with an average age of (30.4 ± 5.4) years. The duration of infertility among patients ranged from 1 to 10 years, with a mean of (2.0 ± 1.7) years.

One hundred sixteen (116) infertile women succeeded in spontaneous conception in a year after 4D-HyCoSy and they were carried to term. Also, an ectopic conception occurred. The cumulative conception rate was 40.9% and the mean conception time was (8.8 ± 0.3) months. The conception rate of 1–3 months,1–6 months,1-9 months and 1–12 months was 21.5%, 30.4%, 38.2%, 40.9%, respectively; and the conception rates of 1–3 months, 4–6 months, 7–9 months and 10–12 months accounted for 52.6, 20.7, 19.8 and 6.9% of the total conception rates, respectively.

The three factors (tubal patency, duration of infertility, uterine cavity lesions) selected by univariate analysis were included in multivariate regression analysis. The results showed that spontaneous conception outcome after 4D-HyCoSy was the result of multiple factors, i.e. the spontaneous conception rates increased with decreasing infertility duration and good tubal patency (Table 2). No significant difference was observed in the age, type of infertility, multiparas, history of pelvic surgery, history of pelvic inflammation, abortion, uterine cavity operation, uterine fibromyomata, and polycystic ovary between conception group and non-conception group after 4D-HyCoSy (P > 0.05) (Table 1).

4D-HyCoSy results suggested that there were 27 cases of type I, 56 cases of type II, 9 cases of type III, 93 cases of type IV, 66 cases of type V, and 32 cases of type VI, respectively. Within a year after 4D-HyCoSy, the spontaneous conception rate was highest in type VI, reaching 62.5%, followed by type IV (46.2%), type III (44.4%), type V (39.4%), type II (33.9%) and type I (14.8%) (P < 0.01) (Figs. 3 and 4). Further comparison between the two groups (Due to the small number of type III, no statistical analysis was performed) showed that the conception rate of type VI significantly exceeded that of type IV and type V. There was no significant difference in conception rate between type IV and type V. Meanwhile, the conception rate of type VI, type IV and type V was significantly higher than that of type I (Fig. 4). Cox regression analysis showed fallopian tube patency was significantly associated with spontaneous conception, and the conception rate of infertile women with type IV and type VI increased significantly after 4D-HyCoSy.The mean conception time was (5.0 ± 2.1) months in type VI, (8.6 ± 0.5) months in type V and (9.0 ± 0.5) months in type IV, respectively.

The conception rate was highest among women who were infertile for less than 2 years (52.5%), followed by duration of infertility ranging 2 to 3 years (29.4%) and the duration of infertility more than or equal to 3 years (22.8%)(P < 0.05) (Table 1 and Fig. 5). Cox regression analysis showed that duration of infertility was significantly associated with spontaneous conception (Table 2). The conception rate of infertile women with duration of infertility less than 2 years increased significantly after 4D-HyCoSy (Table 2). The mean conception time was (8.2 ± 0.4) months in patients with duration of infertility less than 2 years.

The conception rate was significantly low in women with lesion of uterine cavity (endometrial polyp or adhesion of uterine cavity) (Table 1).