Efficacy of intrauterine injection of granulocyte colony stimulating factor [G-CSF] on treatment of unexplained recurrent miscarriage: a pilot RCT study

Background: Endometrium undergoes several changes in structure and cellular composition during pregnancy. Granulocyte Colony-stimulating Factor [GCS-F] is an important cytokine with critical role in embryo implantation and pregnancy. The aim of the present study was to evaluate the impact of intrauterine injection of G-CSF in patients who suffer from unexplained recurrent miscarriage [RM]

Methods: In the present randomized clinical trial, a total of 68 patients were randomly allocated into two study groups including intrauterine G-CSF [n=23, 300mg] injection and control group [n=27, no G-CSF injection]. Eighteen out of 68 patients were excluded from the final analysis due to different reasons. All patients were in Ovulation Induction [I/O] cycle. In G-CSF group, intrauterine injection of G-CSF was done twice in the cycle. All enrolled patients were under 40 years old and had at least two unexplained pregnancy losses. Pregnancy was evaluated by titer of bhCG, presence of gestational sac [implantation] and fetal heart rate [clinical pregnancy] was assessed by vaginal ultrasonography. Student's T test and Mann-Whitney U were used for analysis. The p

Results: No significant differences were observed between the two study groups when the rates of chemical pregnancy [26.1%vs.29.6%, p=0.781], implantation [26.1%vs.22.2%, p=0.750], clinical pregnancy [17.4% vs.11.1%, p=0.689] and abortion [33%vs.37.5%, p=0.296] were compared

Conclusion: In our study, no significant difference was observed between the two study groups when the rates of chemical pregnancy, implantation, clinical pregnancy and abortion were compared

Effect of administration of single dose GnRH agonist in luteal phase on outcome of ICSI-ET cycles in women with previous history of IVF/ICSI failure: a randomized controlled trial

GnRH agonist administration in the luteal phase has been suggested to beneficially affect the outcome of intracytoplasmic sperm injection [ICSI] and embryo transfer [ET] cycles. This blind randomized controlled study evaluates the effect of GnRH [Gonadotropine Releasing Hormone] agonist administration on ICSI outcome in GnRH antagonist ovarian stimulation protocol in women with 2 or more previous IVF/ICSI-ET failures. One hundred IVF failure women who underwent ICSI cycles and stimulated with GnRH antagonist ovarian stimulation protocol, were included in the study. Women were randomly assigned to intervention [received a single dose injection of GnRH agonist [0.1 mg of Decapeptil] subcutaneously 6 days after oocyte retrieval] and control [did not receive GnRH agonist] groups. Implantation and clinical pregnancy rates were the primary outcome measures. Although the age of women, the number of embryos transferred in the current cycle and the quality of the transferred embryos were similar in the two groups, there was a significantly higher rate of implantation [Mann Whitney test, p=0.041] and pregnancy [32.6% vs. 12.5%, p=0.030, OR=3.3, 95%CI, 1.08 to 10.4] in the in-tervention group. Our results suggested that, in addition to routine luteal phase support using progesterone, administration of 0.1 mg of Decapeptil 6 days after oocyte re-trieval in women with previous history of 2 or more IVF/ICSI failures led to a signif-icant improvement in implantation and pregnancy rates after ICSI following ovarian stimulation with GnRH antagonist protocol

Cytokine profile in the endometrium of normal fertile and women with repeated implantation failure

Repeated Implantation Failure [RIF] is one of the most intricate obstacles in assisted reproduction. The cytokine and chemokine composition of uterine cavity seem to play important roles in the implantation process. To compare the cytokine profile in the endometrium of normal fertile women and those with repeated implantation failure. After enzymatic digestion of endometrial tissues, whole endometrial cells and endometrial stromal cells from RIF and normal fertile women were cultivated and stimulated for cytokine secretion. The levels of IL-10, TGF-beta, IFN-gamma, IL-6, IL-8 and IL-17 in culture supernatants of the two groups were assayed by ELISA and compared together. Endometrial stromal cells and whole endometrial cells of normal fertile women produced higher levels of IL-6, IL-8 and TGF-beta compared to RIF group, although this difference was statistically significant only in endometrial stromal cells [p=0.005, 0.002 and 0.001, respectively]. In addition, endometrial stromal cells of normal fertile women produced lower levels of IL-10 in comparison with RIF group [p<0.005]. Disturbances in cytokine production at the feto-maternal interface could be a cause of implantation failure. A pro-inflammatory cytokine milieu seems to be pivotal for successful implantation

Thyroid autoantibodies in euthyroid women with recurrent abortions and infertility

Evidences suggest an association between the prevalence of thyroid peroxidase [anti-TPO] and anti thyroglobulin [anti-Tg] with recurrent abortions and infertility. Iodine deficiency was once endemic in Iran and little data is available about the prevalence of these antibodies in different groups of fertile or infertile individuals. This case control study was designed to compare the presence of anti-TPO and anti-Tg in four groups of women to reveal their role in the etiology of recurrent abortion and infertility. Four groups of euthyroid women referring to Avicenna Infertility Clinic in Tehran were selected; 95 cases as fertile controls and 70, 78 and 137 cases with male and female factor infertility and recurrent abortion respectively. TSH, anti-TPO and anti-Tg were evaluated by chemiluminescent immunoassay. The prevalence of the above mentioned autoantibodies in euthyroid controls was about 25% and the percentage of people with an anti-Tg >500 was two times bigger in the abortion group compared to the control group [p<0.05] and the proportion of people with an anti-Tg>500 in younger cases in the abortion group was significantly higher than the rest of the cases [p<0.05]. Anti-TPO distribution had no significant differences. There were no statistically significant differences among four groups. It seems that more comprehensive studies are needed to reach a common conclusion about thyroid autoantibodies in women with recurrent abortions in different groups and different parts of Iran. In addition, dividing the recurrent abortion and infertility groups on the basis of their etiologies could be effective

Serum leptin levels in women with immunological recurrent abortion

Recurrent abortion [RA] may be a consequence of aberrant expression of immunological factors during pregnancy. Although the relative importance of immunological factors in human reproduction remains controversial, substantial evidence suggests that autoantibodies contribute to reproductive failure. Production of such antibodies is under the control of cytokines; and leptin, besides its role in reproductive success, has a profound effect on directing the cytokine profile toward Th[1] [cellular] pattern. Therefore, the present study was performed to assess serum leptin levels in women with immunological recurrent abortion. In this prospective study, 250 women who attended Avicenna Infertility Clinic with RA were screened for known causes of abortion from July to December 2008 in Tehran, Iran. Eighty-one patients with normal karyotypes and hormonal profile with normal ovaries and uterus and no signs of infection were categorized as patients with immunological [IRA, n = 39] or unexplained [URA, n = 42] recurrent abortion based on presence or absence of autoantibodies. After blood sampling, levels of anti-nuclear antibody [ANA], anti-double stranded DNA antibody [anti-dsDNA], lupus anti-coagulant antibody [LACAb], anti-phospholipid antibody [APA], anti-cardiolipin antibody [ACA], anti-thyroglobulin antibody [TgAb], anti-thyroperoxidase antibody [TPOAb] and anti-thrombin III antibody [ATIIIAb] were measured by enzyme-linked immunosorbent assay [ELISA] or chemiluminescent enzyme immunoassay [CLEIA]. In IRA group, 9 [23.1%], 24 [61.5%], 25[64.1%] and 1 [2.6%] women were above the normal cut-off point for ANA, TgAbs, TPOAbs and AT-III Abs, respectively. IRA patients had normal values of LACAbs, APA and ACA. With normal level of fasting blood sugar [FBS], IRA and URA groups had similar serum leptin levels [23.7 +/- 13.2 ng/ml vs. 22.7 +/- 12.5 ng/ml, respectively]. Serum leptin concentrations showed a positive correlation with weight and BMI in both groups. This study suggests that serum leptin levels are higher in IRA and URA patients than normal women. The findings of this study suggest the need for a more comprehensive study and comparison of leptin levels in IRA and URA patients to women with no history of miscarriages

comparative study of GnRH antagonist and GnRH agonist in PCO patients undergoing IVF/ICSI cycles

Polycystic ovarian syndrome [PCOS] patients are prone to premature LH surge and ovarian hyperstimulation syndrome [OHSS]. Long GnRH analogue protocol and GnRH antagonist protocol are two methods utilized for induction ovulation in patients undergoing IVF/ICSI. The aim of this study was to compare the effects of GnRH agonists and antagonists in PCOS patients. A total of 60 PCOS patients under 35 years old were enrolled in this study. The patients have no history of thyroid disorder and hyperprolactinemia. All patients received OCP [LD] before starting the treatment. Then patients randomly divided into two groups. The agonist group underwent st and ard long GnRH analogue protocol. In antagonist group, HMG [150 IU/day] was started from third day of cycle. Then GnRH antagonist [0.25mg] was administered from 6th day after HMG initiation [LH /= 18mm, serum estradiol level on 6[th] day of HMG initiation and HCG injection time, fertilization and pregnancy rate between two groups. However there were significant differences regarding duration of treatment, duration of HMG usage, LH level at the initiation of HMG, OHSS rate and number of Metaphase II oocytes between two groups [p<0.05]. Usage of the GnRH antagonist may have more advantages such as the shorter duration of treatment and less gonadotrophin requirement. Furthermore, the incidence of OHSS can be reduced in GnRH antagonist comparing to agonist. For decreasing the risk of OHSS and abortion rate, we recommend long term use of OCP before starting the treatment