Material & Method
This was a retrospective cohort study. The study was conducted at Uludag University School of Medicine, ART center. The research ethics committee of Uludag University approved the study protocol (2017-1/52). Electronic database between Jan 2012 / Jan 2017 was screened to identify patients who have endometriosis.
Women aged >40 years, who had male infertility, chronic systemic diseases (diabetes mellitus, hypertension, etc.), and suspicion of malignancy were excluded from study. The enrolled patients’ IVF&ICSI cycles were compared in three endometriosis phenotypes; superficial endometriosis (SUP), ovarian endometrioma (OMA), deep infiltrating endometriosis(DE). If a patient had two phenotypes together, was enrolled in the more severe group. Superficial endometriosis was diagnosed during laparoscopic surgery, which has done for other indications like tubal factor infertility, unexplained infertility. It is defined as the presence of endometriotic lesions on the peritoneum. Ovarian endometrioma is defined as homogenous, usually unilocular, focal lesions in the ovary with low-level echoes in ultrasound imaging and with shading sign in magnetic resonance imaging.(10) DE was diagnosed by bimanual pelvic examination (palpable rectovaginal endometriotic nodule), by transvaginal ultrasound and MRI or diagnosed during endometriosis surgery as infiltrating type of endometriosis. (11,12)
Adenomyosis was defined as ingrowths of the endometrial cells into the myometrium. Patients were screened by transvaginal ultrasound and presence of two of the listed criteria was defined as adenomyosis. 1-No distinction of the endometrial-myometrial junction; 2-Asymmetry of the anterior and posterior myometrium; 3-Subendometrial myometrial striations; 4-Myometrial cysts and fibrosis; and 5-Heterogeneous myometrial echotexture. (13)
All patients were stimulated either by ultralong protocol, long protocol, antagonist protocol, micro-dose flare up or natural protocol. Goserelin acetate 3.6 mg monthly depot form was injected for 3 months or daily leuprolide acetate 0.1 mg / daily injection was applied for 3 months for pituitary desensitization in ultra-long protocol. Daily injections of leuprolide acetate were started on the 21th day of cycle in long protocol. After pituitary desensitization, daily gonadotropin injection with 150-600 IU/day was started and daily antagonist (certrorelix-ganirelix 0.25 mg) injections were applied after reaching 12-14 mm follicle in short antagonist protocol. Trigger (recombinant hCG or Leuprolide acetate) was given when >3 follicles greater than 17 mm. Oocyte retrieval was done 34-36 hours after hCG injection. Luteal phase was supported with vaginal %8 progesterone gel, two times a day, starting on the evening of oocyte retrieval and continued until a negative pregnancy test or detection of fetal cardiac activity. Day of embryo transfer was decided based on the number of available embryos, embryo quality.
Three types of cycle cancellation were defined.
Type A is identified as no follicular development despite the maximum dose of gonadotropin injections.
Type B is identified as full fertilization failure.
Type C is identified as maturation arrest and is defined whenever the maturation of embryo stopped. (Table -1)
All cycles were compared as 2 groups. First group was consisted of cancelled cycles (CC); the second group was consisted of the embryo transferred (ET) cycles. Both of the groups were divided in three subgroups depending on the phenotype of endometriosis. Factors associated with cycle cancellation depending on the phenotype of the disease were found. We further investigated independent risk factors associated with cycle cancellation with logistic regression analysis. Also we analyzed the effects of presence of adenomyosis and laparoscopy or laparotomy on ovarian reserve.
Kolmogorov Smirnov test was used for assessing whether the variables follow a normal distribution or not. Variables were reported as mean±standard and median (minimum:maximum) deviation values. According to the normality test result, independent samples t-test was used for between-group comparisons. Categorical variables were reported as n(%) and compared by Pearson Chi-square test or Fisher-Freeman-Halton-Test. In order to determine the independent risk factors that affect IVF cycle cancellation, binary logistic regression analysis with backward selection was performed. SPSS (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) was used for performing statistical analysis and the level of significance was set at α=0.05.