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.