The rationale for using immunomodulators
- Kwak-Kim J.Y.H.
- Chung-Bang H.S.
- Ng S.C.
- Ntrivalas E.I.
- Mangubat C.P.
- Beaman K.D.
- et al.
- Kwak-Kim J.Y.H.
- Chung-Bang H.S.
- Ng S.C.
- Ntrivalas E.I.
- Mangubat C.P.
- Beaman K.D.
- et al.
- Rubinstein M.
- Marazzi A.
- Polak de Fried E.
- Duvan C.I.
- Ozmen B.
- Satiroglu H.
- Atabekoglu C.S.
- Berker B.
|Hanevik et al. (2012)||Single-center RCT by envelope randomization ratio 3:2, no placebo/blinding.||279 women, <40 y, normal uterine cavity, no hormonal disorders, partner with no azoospermia, only frozen embryos were used.||ASA 75 mg/d from ET to 9 wk of gestation if pregnant and terbutaline 5 mg given 3 h before ET, 6 h after ET, and the following morning.||Clinical pregnancy rate per cycle was 30.5% vs. 42% in the intervention vs. control group, P=.18.|
|Várnagy et al. (2010)||Single-center RCT randomized by paired vs. unpaired social number, no placebo/blinding.||2,425 women undergoing GnRH agonist cycles, unselected. Cycles were divided into high risk and low risk of OHSS.||ASA 100 mg/d from first day of stimulation to menstruation, a negative pregnancy test, or ultrasound-verified embryo heart activity.||Among the high-risk group the intervention group had a lower risk of OHSS (0.25% vs. 8.4%), P<.001. No difference was detected in clinical pregnancy rate between the groups.|
|Dirckx et al. (2009)||Single-center RCT randomized by computer, double blinded.||193 women undergoing first or second cycle of IVF/ICSI, no platelet dysfunction, thrombocytopenia, gastric ulcers, gastritis, aspirin hypersensitivity, or anticoagulation treatment.||ASA 100 mg/d first day in the prior cycle throughout stimulation to gestational age 6+3.||Clinical pregnancy (heart beat/cycle) 32% vs. 31% in the intervention vs. placebo group, respectively. Live-birth rate 25% vs. 28%, respectively, not significantly different.|
|Lambers et al. (2009)||Single-center RCT, randomized by computer, double blinded.||169 women <39 y with >1 failed IVF/ICSI, excluded when body mass index >30 kg/m2, tubal pathology, hypertension, smoking >5 cigarettes/day, systemic disease, or untreated endocrinopathy.||ASA 100 mg/d from first day in the prior cycle throughout stimulation and if pregnant, continued to gestational age 12 wk.||Clinical pregnancy rate (serum hCG >50 IU/L) 40.5% vs. 39.3% in the intervention group vs. placebo group, not significant. All other outcomes not significantly different between the two groups.|
|Revelli et al. (2008)||Single-center RCT, randomized by computer in a ratio 1:3, no blinding or placebo.||395 women, <40 y undergoing the first cycles of IVF/ICSI. No autoantibodies present or autoimmune disease. The women were all normal or good ovarian responders. Only fresh ET's were used.||ASA 100 mg/d and prednisolone 10 mg/d from 1. Day of stimulation, prednisolone was increased to 30 mg 5 d from ET. After that again 10 mg/d throughout 10 wk, if positive pregnancy test.||Women were subdivided in groups with high risk of OHSS and low risk of OHSS. Implantation rate was 31.5% vs. 26.2% in the high-risk group and 19.4% vs. 17.3% in the low-risk group, intervention vs. nothing, respectively.|
|Duvan et al. (2006)||Single-center RCT, lottery randomization, using placebo.||187 women undergoing their first cycle of ICSI; no other criteria were made. Participants were divided into four groups according to treatment regime.||On ET day (A) 100 mg ASA/day, (B) 10 mg prednisolone/day, (C) 100 mg ASA and 10 mg prednisolone/day, and (D) control group with placebo.||Pregnancy and clinical pregnancy rates. No statistically significant results were found between the groups.|
|Päkkilä et al. (2005)||Multicenter RCT, using envelope randomization, double blinded.||374 women with <4 failed IVF/ICSI, <40 y of age, and no contradiction to ASA were included.||ASA 100 mg/d from stimulation to menstruation, negative pregnancy test, or birth of child.||Number of oocytes, quality of embryo, clinical pregnancy rate, and pregnancy rate were outcome measures. No significant difference between the intervention and control group was documented.|
|Waldenström et al. (2004)||Single-center RCT, using alternation by day as randomization, no blinding or placebo.||1,380 cycles in an unselected cohort of women. Excluded if allergy to aspirin.||ASA 75 mg from ET to pregnancy test.||Positive serum hCG: OR, 1.3; CI, 1.0–1.6; clinical pregnancy: OR, 1.3; CI, 1.0–1.6; birth rate: OR, 1.2; CI, 1.0–1.6. All borderline significant.|
|Stern et al. (2003)||Multicenter RCT, using computer randomization and double blinding.||143 women, total of 300 cycles, with ≥10 failed IVF/ICSI and ≥1 autoantibody present, normal uterus, no hemophilia or thrombotic disorders, no osteoporosis.||ASA 100 mg/d and 5,000 IU heparin from ET until results of serum hCG were available.||Positive pregnancy test, implantation rate, and live birth rate. No significant difference was found between intervention and placebo group in all main outcomes.|
|Urman et al. (2000)||Single-center RCT, randomizing by computer and only blinding of the physician||300 unselected women undergoing ICSI because of male factor infertility.||ASA 80 mg from stimulation to fetal heart activity was detected. Treatment was stopped if pregnancy test was negative.||Implantation rate/ET (15.6% vs. 15.1%) and pregnancy rate (39.6% vs. 43.4%) in the intervention vs. control group, respectively.|
|Rubinstein et al. (1999)||Single-center RCT, using envelope randomization and double blinding||298 women undergoing IVF because of tubal factor||ASA 100 mg/d from 21st day of the preceding menstrual cycle through to 12 wk if tested pregnant.||Ovarian responsiveness was measured with three individual indicators; all were significantly increased in the treatment group, implantation rate (17.8% vs 9.2%), P<.05, and pregnancy rate (45% vs. 28%), P<.05.|
|Fawzy et al. (2014)||Single-center RCT, quasi-randomized by alternation, no blinding, or placebo.||295 women contributed with one cycle. All had one or two prior ICSI failures, <39 y, normal uterus, no hormonal disorders, no contradiction to planned treatment.||20 mg prednisolone/day and heparin 1 mg/kg/d from oocyte retrieval to 8 wk. Treatment was stopped if the pregnancy test was negative.||Total pregnancy (42.8 vs. 30.3), P=.028; clinical pregnancy (40.7% vs. 27.5%), P=.018; ongoing pregnancy (38.6% vs. 24.6%), P=.016; and implantation rates (23.9% vs. 14.7%), P<.001, treatment vs. control, respectively.|
|Noci et al. (2011)||Single-center pilot RCT, randomized by computer, no blinding or placebo.||172 women undergoing their first IVF/ICSI cycle. All <40 y, normal tuba and uterus, no endocrine, coagulation, or chronic disorders.||2,500 IU SC fragmin from oocyte retrieval to 9 wk pregnant. Treatment was stopped if tested negative or no live pregnancy was found.||Live-birth rate/ET (21% vs. 16%), clinical pregnancy rate/ET (26% vs. 20%), implantation rate (15% vs. 12%) in the treatment vs. controls, respectively. All results not significant.|
|Berker et al. (2011)||Single-center, randomization dependent on which physician participants saw, no blinding or placebo.||219 women with ≥2 prior ICSI failures, normal uterus, no endocrine, coagulation, or autoantibody disorder.||4,000 IU Clexane from oocyte retrieval to 12 wk of gestation. Treatment was discontinued if pregnancy test was negative.||Clinical pregnancy rate (34.6% vs. 33.9%), live-birth rate (30.7% vs. 29.1%), and implantation rate (22.6% vs. 21.1%) treatment vs. control, respectively. All results not significant.|
|Urman et al. (2009)||Single-center pilot RCT, randomized by computer, no blinding or placebo.||150 women with ≥2 prior IVF/ICSI failures, age ≤38, no hormonal, immunological, or coagulatory diseases, and a normal uterus were included.||1mg/kg/d from oocyte retrieval to 12 wk of gestation if tested positive 12 d after ET.||Clinical pregnancy (45.3% vs. 38.7%), implantation (24.5% vs. 19.8%), ongoing pregnancy (>20 wk; 37.3% vs. 26.7%), and live birth rates (34.7% vs. 26.7%) in the treatment vs. control group, respectively. All results not significant.|
|Qublan et al. (2008)||Single-center RCT, randomized by random table, only blinding of subjects, placebo used.||83 women with ≥3 prior IVF/ICSI failures and ≥1 coagulation disorder, age between 19 and 35 y, normal ovarian response, no systemic or hormonal diseases, no endometriosis, no family history of thrombosis, and a normal uterus were included.||Enoxaparin 40 mg/d from ET to end of pregnancy. Treatment was discontinued if negative pregnancy test 14 d after ET or fetal diminish was diagnosed.||Implantation rate (19.8% vs. 6.1%), P<.001; pregnancy rate (fetal heart activity) (31.0% vs. 9.6%), P<.05; and live-birth rate (23.8 vs. 2.4), P<.01 in the treatment vs. control group, respectively.|
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M.M.H. has nothing to disclose. N.M. has nothing to disclose.