Study area and Design
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.
Patients Selection
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[21]. 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 (Figure 1).
4D-HyCoSy
A Voluson E8 Expert (GE Healthcare, Zipf, Austria) With RIC5-9-D volume probe (5–9 MHz) was used. 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 2.5ml SonoVue solution was aspirated and diluted it into a 15ml 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 five 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 (15ml) 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].
Criteria for tubal patency[14] (Figure 2)
Fallopian tube patency: the contrast agent filled the whole uterine cavity that quickly flowed into the fallopian tube and sprayed at the fimbria of the tube. In addition, the passage of the tube was soft and naturally directed downward.
Poor patency of fallopian tube: the entire fallopian tube and the spillage at the fimbria of the tube were visible, but the passage of the tube was stiff, discontinuous, filamented, angled, circuitous, and directed upward.
Fallopian tube obstruction: Resistance built-up following the injection of the contrast agent. We could not see the entire passage of the tube or the spillage at the fimbria.
Classification of fallopian tube
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.
Outcomes
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.
Statistical analysis
All statistical analyses were conducted with SPSS version 23.0 software for windows (SPSS Inc, Chicago, IL, USA). The data were expressed as ± 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.