state of peripheral blood natural killer cells and cytotoxicity in women with recurrent pregnancy loss and unexplained infertility

Background: The prognostic value of peripheral natural killer [pNK] cells, as a screening test in women with recur- rent pregnancy loss [RPL] and unexplained infertility, is still a matter for discussion. The purpose of this study was to compare the percentage of circulating CD56+NK cells, CD69 and perforin markers between women with unexplained infertility and RPL with the healthy control group

Materials and Methods: In this case-control study, the percentage of CD56+NK cells and activation markers [CD69 and perforin levels] in the peripheral blood were measured in 25 women with unexplained infertility, 24 women with idiopathic RPL and 26 women from the healthy control group, using specific monoclonal antibodies by flow cytometry

Results: The percentage of CD56+NK cells was significantly higher in patients with infertility in comparison with the healthy control group [P=0.007]. There were not significant differences either in the total number of CD56+cells between the RPL group and the control group [P=0.2] or between the RPL group and the infertile group [P=0.36]. The percentage of CD69+lymphocytes in RPL group was significantly higher than in the infertility group [P=0.004]. There was a statistically significant difference in Perforin levels between RLP and control [P=0.001] as well as RPL and infertile [P=0.002] groups

Conclusion: An increased percentage of CD56+NK cells in patients with unexplained infertility, an elevated expression of CD69 on NK cells in patients with RPL and infertility and a high level of perforin on CD56+cells in the RPL group might be considered as immunological risk factors in these women

Vaginal progesterone on the prevention of preterm birth and neonatal complications in high risk women: a randomized placebo-controlled double-blind study

Background: Preterm birth is the major cause of neonatal mortality and morbidity

Objective: The aim of this study was to evaluate the effect of prophylactic vaginal progesterone on decreasing preterm birth rate and neonatal complications in a high-risk population

Materials and Methods: A randomized, double-blind, placebo-controlled study was performed on 100 high-risk singleton pregnancies. Vaginal suppository progesterone [400 mg] or placebo was administered daily between 16-22 wks to 36 wks of gestation. Progesterone [n=50] and placebo [n=50] groups were compared for incidence of preterm delivery and neonatal complications

Results: The preterm birth rate was 52%. Preterm birth rate before the 37 wks of gestation [68% vs. 36%: RR=1.89, 95% CI: 1.25-2.86] and also before the 34 wks of gestation [42% vs. 18%: RR=2.33, 95% CI: 1.19-4.58] in placebo group was significantly higher than progesterone group. Our study also showed that the administration of vaginal progesterone was associated with a significant reduction in the risk of birth weight

Conclusion: Prophylactic vaginal progesterone reduced the rate of preterm delivery, the risk of a birth weight

[Predictors of single-dose methotrexate treatment failure in ectopic pregnancy]

Background: The use of Methotrexate [MTX] is a good and common practice for the treatment of women who were diagnosed early with ectopic pregnancy [EP]

The aim of this study is to determine the predictors of treatment failure with a single dose of MTX injection

Methods: In this quasi-experimental research, we studied 70 women with ectopic pregnancies who were treated with MTX, according to a single dose protocol from 2010 to 2013. EP was diagnosed whenever an intrauterine gestational sac was not identified by transvaginal ultrasonography [TVUS], accompanied by an abnormal rise or plateau in human chorionic gonadotropin [PHCG] concentration. Briefly, women with ectopic pregnancies were considered candidates for MTX treatment if they were hemodynami-cally stable; did not desire surgical therapy, agreed to weekly follow-up; and did not have hepatic, hematologic, or renal disease

A Patient was considered a treatment success [group 1] if her pHCG levels decreased <10 m lU/ml after the first dose of MTX. Treatment failure [group 2] was defined as the need for a second or a third dose of MTX or surgery. The following risk factors were compared between the two groups: serum pHCG on the days 1 and 4, a > 15% decrease in serum pHCG between the days 1-4 of the treatment, age, parity, gravidity, the size of the ectopic mass and the endo-metrial thickness

Results: The success rate of MTX treatment was 77.1%. There were no significant differences between the two groups in regard to the age, parity, gravidity, the size of ectopic mass and the endometrial thickness in vaginal sonography, but the mean serum pHCG concentration on days 1 and 4 was lower in the success group than the failure group. We also observed a > 15% decrease in serum PHCG in 80.9% of the women from the success group and in 38.5% of the cases whose treatment had failed. The presence of fetal heart activity was seen in only one patient and this patient's treatment failed. Two patients had previous history of ectopic pregnancy and the treatment of both ended in failure

Conclusion: Among women with ectopic pregnancies who were candidates for MTX treatment, a high serum PHCG concentration on the days 1-4 and also a < 15% fall in serum pHCG between the days 1-4 treatment, are the most important factors associated with the failure of the treatment with a single dose MTX protocol. It is better to use these factors for making decisions about the initiation of the treatment or the continuation of it

Comparing clomiphen citrate plus HMG with clomiphen citrate plus rFSH in IUI cycles in couples with unexplained or male factor infertility: a prospective randomized study

Different protocols are used for controlled ovarian hyper stimulation [COH], but the optimal method has not yet been determined. The aim of this study was to compare the outcome of controlled ovarian stimulation [COS] using clomiphen citrate [CC] plus HMG versus CC plus rFSH in intra uterine insemination cycles [IUI]. 144 women with unexplained or male factor infertility undergoing IUI cycles were randomized [72 patients in CC plus rFSH group and 72 patients in CC plus HMG group] and included in this single blind study from October 2006 to June 2010. The primary outcomes were clinical and ongoing pregnancy rates. The number of dominant follicles, mean of follicular size, endometrial thickness on the day of HCG administration, total dose of gonadotropins and duration of stimulation with gonadotropins were secondary outcomes. Clinical and ongoing pregnancy rates were not significantly different in the two groups .There was a significant higher multiple pregnancy rate in CC plus rFSH group [33.3%] versus CC plus HMG group [12.5%; p<0.005]. There were no statistically significant differences in the secondary outcomes between the two groups. According to our results it seems that CC plus HMG is a more suitable and cost-effective regimen than CC plus rFSH in IUI cycles in patients with unexplained or male factor infertility

Effects of simvastatin pretreatment on clomiphene response in clomiphene - resistant women with polycystic ovary syndrome

Objective: The aim of this study is to determine if simvastatin pretreatment would change Clomiphene response in Clomiphene citrate-resistant [CC-R] women with [PCOS]

Materials and methods: This quasi experimental study included twenty five Clomiphene resistant women with PCOS. All patients received cyclic oral contraceptives pills [OCR] [SOpg of ethinyl estradiol and 150microg of desogestrol] from the 5th day of their spontaneous or progesterone [P] induced menstrual cycle; in addition, they received simvastatin [20mg/day] from the first day of cycle for two consecutive months. Then, patients were given 100 mg Clomiphene citrate [CO] [Iran Hormone, Iran] for five days starting from day three of their menstrual cycles. The primary outcome measures were ovulation and pregnancy rates. The change in body mass index [BMI], the mean number of follicles > 18 mm, the mean of follicular size and endometrial thickness on the day of human chorionic gonadotropin [HOG] administration were secondary outcome measures

Results: Ovulation occurred in 5 out of 25 [20 %] patients, but none of the patients conceived in this study. No important change in BMI was observed after using simvastatin [0.28+1.13; p=0.228]. In all patients with ovulation, the number of follicles > 18mm was one. The mean follicular size and endometrial thickness on the day of HCG administration were 19.67 +/- 2.04 and 7.00 +/-1.34, respectively

Conclusion: In this study, we did not observe the favorable effect on ovulation and pregnancy rates with CC following of simvastatin pretreatment in CC-resistant PCOS women. So, further studies with a larger number of patients, higher doses of CC and more cycles are necessary to make this obvious

Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphen-resistant women with polycystic ovary syndrome

Clomiphen citrate [CC] is the first line therapy for women with infertility and poly cystic ovary syndrome [PCOS]. However, 20-25% of women are resistant to CC and do not ovulate. The objective of this study was to evaluate the efficacy of sequential treatment of metformin and incremental doses of letrozole in induction of ovulation in cases of CC-resistant PCOS patients. In this prospective before-after study, we enrolled 106 anovulatory PCOS women who failed to ovulate with CC alone from Amir-Almomenin University Hospital in Semnan, Iran. After an initial 6-8 weeks of metformin treatment, they received 2.5 mg letrozole daily on days 3-7 after menes. If they did not ovulate with 2.5 mg letrozole, the doses were increased to 5 to 7.5 mg daily in subsequent cycles. The main outcomes were ovulatory rate, pregnancy rate and cumulative pregnancy rate. 13.33% of patients conceived with metformin alone. Ovulation occurred in 83 out of remaining 91 patients [91.2%]. 78.02% of patients responded to lower doses of letrozole. Cumulative pregnancy rate was 60/105 [57.14%]. We suggest that treatment in CC-resistant PCOS patients should begin at first with lower doses of letrozole and could increase to the higher dose depending on the patient response before considering more aggressive therapeutic alternatives such as gonadotropins

[Comparaing the causes of abortion in patients with two or more than two consecutive miscarriages]

Recurrent miscarriage is defined as the loss of three or more pregnancies. Recurrent Pregnancy Loss [RPL] is traditionally investigated after three or more consecutive losses. Although some believe that the investigation must be launched after two miscarriages, there is not enough compelling evidence to draw conclusion. In this cross-sectional study, we studied 58 women with two or more consecutive abortions [37 women with two and 21 women with three or more miscarriages] from 2005 to 2009. The following risk factors were analyzed and compared between the two groups: endocrine dysfunctions, genetic abnormalities, uterine anomalies, infections, thrombophilia, polycystic ovary syndrome, autoimmune disorders, sperm characteristics, and advanced maternal age. We did not find any known factor for pregnancy losses in 18 [31.03%] patients but in the rest, the most common cause of Recurrent pregnancy loss was endocrine disorders [41.4%]. The other causes were uterine abnormalities [12.1%], infections [12.1%], maternal age more than 35 years [12.1%], thrombophilia [8.6%], abnormal semen analysis [8.6%], genetic defects [6.9%] and autoimmune disorders [1.7%]. There were no significant differences between the two groups in regards with the causes of abortion except uterine abnormality [P=0.039] which was more frequent in women with three or more three miscarriages [23.8%] relative to women with two abortions [5.4%]. There were no significant differences between women with two or women with three or more three abortions in regards with the causes of abortion except uterine anomalies. Therefore, it seems quite reasonable and perhaps beneficial to start the investigation in patients with two abortions

Comparison of pregnant and non-pregnant women with clomiphene resistant polycystic ovary syndrome in treatment with metformin and letrozole

Polycystic ovary syndrome [PCOS] is one of the most common causes of anovulatory infertility. Clomiphen citrate [CC] is the first line therapy for women with infertility and PCOS. These patients usually respond to clomiphene citrate in doses between 50-100 mg/day. However, failure of the patient to respond to a dosage of 150 mg/day of clomiphene citrate is considered as clomiphene resistant. The aim of this study was to compare between pregnant and non-pregnant women in cases of PCOS patients with CC resistant. Meanwhile, we evaluated ovulatory rate, pregnancy rate and live birth rates. We studied 106 CC-resistant PCOS patients who attended to Amir-Al-Momenin Hospital [Semnan, Iran] during the years 2005-2008. After an initial 6-8 weeks of metformin [1500mg daily: 500mg q8h], they received 2.5mg letrozole for 5 days starting on cycle day 3. If they failed to show ovluation with 2.5mg letrozole, doses were increased to 5 and 7.5 mg daily in the subsequent cycles. One patient developed generalized rash with metformin and excluded from the study. 14 of 105 patients [13.33%] conceived with metformin alone. Overall, ovulation rate was 83.91 [91.2%]. Overall, pregnancy rate was 60/105 [57.14%] with 45 [74.9%] full term pregnancies, 10 [16.7%] abortions and 5 [8.3%] preterm births. The only significant difference between the responder and non-responder was found in the age of patients [P=0.008]. No significant differences were found in BMI, period of infertility, menstrual pattern, hirsutism, pictures of PCO in one or two ovaries in sonography, LH, and FSH or LH/FSH ratio. Combination of metformin with incremental doses of letrozole associated with a good pregnancy rate in CC-resistant PCOS patients. The treatment seems especially more effective in young weman

Association of bacterial vaginosis, trichomonas vaginalis, and vaginal acidity with outcome of pregnancy

Bacterial vaginosis and Trichomons vaginalis are believed to be the risk factors for preterm labor birth and preterm prelabor rupture of membranes. The objective of this study was to investigate the association between bacterial vaginosis, T.vaginalis, and vaginal pH with preterm labor birth and preterm prelabor rupture of membranes after excluding other known risk factors. In this cohort study, we enrolled 1223 pregnant women with gestational age of 16 - 36 weeks from Amir-Almomenin G eneral Hospital in Semnan, Iran, who had no known medical risk factors for preterm labor birth. Bacterial vaginosis and T.vaginalis were determined on the basis of vaginal pH, saline wet mount, and Amsel tests. The principal outcome was delivery before 37 weeks of gestation and preterm prelabor rupture of membranes. Bacterial vaginosis and T.vaginalis were detected in 16.0% and 5.5% of these women, respectively. Bacterial vaginosis was positive in 65 [33.1%] patients at 16 - 20 weeks of gestation and in 134 [66.9%] patients at 36 weeks of gestation or during labor [developing preterm labor birth or preterm prelabor rupture of membranes]. The frequencies for T.vaginalis were 20 [29.9%] and 47 [70.1%] patients, respectively. All patients with bacterial vaginosis and T.vaginalis had a vaginal pH >/= 5. There was a significant correlation between bacterial vaginosis and vaginal pH >/= 5, with preterm labor birth [OR: 5.99; CI: 3.79 - 9.49] and preterm prelabor rupture of membranes [OR: 2.34; CI: 1.07 - 4.99]. Moreover, a significant correlation was found between vaginal pH >/= 5 with preterm labor birth [OR: 5.82; CI: 2.96 - 11.39] and preterm prelabor rupture of membranes [OR: 4.11; CI: 1.62 - 10.12]. There was no significant correlation between T.vaginalis with preterm labor birth [OR: 0.73; CI: 0.22 - 2.17] and preterm prelabor rupture of membranes [OR: 1.22; CI: 0.29 - 5.05]. The presence of bacterial vaginosis or vaginal pH ?5 at 16 - 36 weeks of gestation is associated with an increased risk of preterm labor birth and preterm prelabor rupture of membranes