Study design
This retrospective case–control study was conducted at the Center for Reproductive Medicine, Tianjin Central Hospital of Gynaecology Obstetrics from January 1, 2014 to June 30, 2021, through the analysis of our electronic records. Before the treatment, all patients were required to undergo TVS and diagnostic hysteroscopy; more than one ultrasonography was performed to observe the change in the myoma before embryo transfer. All TVS and diagnostic hysteroscopic examinations were performed by professional clinicians. The inclusion criteria for the type 3 fibroid group and the hysteroscopic myomectomy group were as follows: 1) age ≤ 40 years at the time of commencement of IVF-ICSI treatment; 2) diagnosis of type 3 fibroids or accepted for hysteroscopic resection for type 3 fibroids; and 3) SD or TD > 2.0 cm. The following exclusion criteria were used: 1) oocyte donor treatment cycles; 2) presence of chromosomal abnormalities (including chromosome polymorphism); 3) history of other uterine surgery (including endometrial polyps, cesarean section, etc.); 4) presence of intracavitary lesions, including SM fibroids; 5) single fibroid > 5.0 cm; 6) cervical fibroids; 7) unclear ultrasound description of fibroids; 8) preimplantation genetic testing was performed; and 9) congenital or acquired uterine malformations.
The patients were divided into a type 3 fibroid group (nonsurgery group) and a hysteroscopic myomectomy group (surgery group) according to whether they underwent a hysteroscopic myomectomy. The control group in our study was selected from patients who were treated with IVF only because of fallopian tube factors. According to the age of the nonsurgery group and surgery group, random sampling was carried out in patients between 25 and 47 years old to determine a control group. The nonsurgery group and surgery group patients were assessed for the treatment of hysteroscopic myomectomy, according to each patient’s condition and their personal wishes. All patients underwent controlled ovarian stimulation (COS) using a routine protocol (long, short, GnRH antagonist protocol, or other protocol, including ultralong protocol, mini-stimulation protocol, natural protocol, etc.) at our centre. One experienced surgeon (who had performed more than 500 operative hysteroscopies per year for more than 10 years as a resident) performed all of the procedures.
Outcomes
The outcomes measured in our retrospective study included the average transfer times to live birth(s), cumulative clinical pregnancy rate (CCPR), and cumulative live birth rate (CLBR). The clinical pregnancy rate was defined as the presence of a gestational sac seen on transvaginal ultrasound per embryo transfer cycle. The live birth rate was defined as the delivery of a live birth(s) (≥ 20 completed weeks of gestational age.) per embryo transfer cycle [13]. The CCPR was calculated as the first gestational sac observed and the CLBR was calculated as the live births achieved after all cycles of embryo transfer (cycles using fresh embryos and all frozen-thawed embryos) among both groups [14]. The analysis of the transfer and pregnancy outcomes of the patients in the hysteroscopic myomectomy group started from the first transfer after the operation. Furthermore, we conducted a self-controlled case series study of the surgery group to compare the transfer and pregnancy outcomes before and after the operations.
Surgeries
Operative hysteroscopy was performed using a 26Fr hysteroscope equipped with a 30-degree lens (Endoskope; Karl Storz GmbH and Co., Tuttlingen, Germany). Saline solution (0.9%) (China Otsuka Pharmaceutical Co., Ltd.) was used as the distention medium with a fluid management system (Richard-Wolf, Germany). The dilatation pressure was 80-100 mmHg (1 mmHg = 0.133 kPa), and the electric power was 80w. All operations were performed under general anesthesia.
The surgeon searched for the location of the fibroids in combination with ultrasound examination, measured the thickness of the fibroids from the uterine serosa, and confirmed that they are type 3 fibroids again. Hysteroscopic resection for type 3 myoma began with an incision of the endometrium covering the myoma with bipolar energy (Olympus, Japan). Under ultrasound guidance, the uterine mucosa and myometrium were cut longitudinally with needle electrodes to reveal type 3 fibroids. Intravenous infusion of 10 IU oxytocin (Shanghai Harvest Pharmaceutical Co., Ltd.) in 500 ml of saline solution (0.9%) (China Otsuka Pharmaceutical Co., Ltd.) at a rate of 120 ml/h causes fibroids to bulge and the needle electrode was used to excise the tumor nucleus to avoid injury to the endometrium and normal muscle wall tissue. The excision was performed only on the tumor nucleus of the fibroid, and the pressure of the uterine distended uterus was gradually reduced to remove the type 3 fibroids completely (Figs. 3, 4, 5). At the same time, pay attention to the amount of fluid in and out to prevent complications such as hysteroscopic hyperhydration syndrome. The whole process of resection was carried out under ultrasound monitoring until ultrasound showed no fibroids remained, and the thickness of the tumor fossa from the uterine serosa was measured after surgery. If the diameter of the fibroids is large, the number is too big, or the location is not good enough to be removed at one time, two-stage surgery should be considered.
Postoperative, all patients received oral continuous combined 2 mg 17-β oestradiol and 10 mg dydrogesterone (Femoston®, Abbott Biologicals B.V.) for 2 cycles to promote the recovery of the endometrium. All of the women had a postoperative office hysteroscopy and TSV to control the completeness of the hysteroscopic resection after a rest period of 2 menstrual cycles after surgery.
Statistical analysis
Statistical analysis was performed using SPSS 25.0. Student’s t test, the chi-square test, Fisher’s exact test, Kruskal–Wallis test, or the Mann–Whitney U test were used to compare the groups according to the data distribution. A P value of < 0.05 was considered to indicate statistical significance. Values are presented as the mean ± SD or median (lower quartile, upper quartile) according to the data distribution. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated before and after adjusting for confounding variables, including age, infertility duration, body mass index (BMI), average endometrial thickness in the transfer cycle, and average high-quality embryo rate.
Ethics statement
This study was approved by the Institutional Review Board (IRB) of Tianjin Central Hospital of Gynaecology Obstetrics (No: ZY2021010) and performed in accordance with the Helsinki Declaration. Written informed consent was obtained from the participants when they presented for IVF-ICSI treatment.