jalali 1389 4 1 gregorian 2010 6 22 4 2 online 1 fulltext

Background: Patients with arrested preterm labor (PTL) are at increased risk for recurrence of preterm birth (PTB). Maintenance tocolysis after arrest of acute PTL is of questionable value. The objective of this study was to evaluate the efficacy of 200 mg vaginal progesterone in order to prevent PTB in women with episodes of threatened PTL. Materials and Methods: This is a randomized double blind clinical trial study.Women with singleton pregnancies between 28-36 weeks of gestation, who were hospitalized for PTL were included. A total of 173 pregnant patients were randomly allocated to receive 200 mg vaginal progesterone suppositories (n=86) or placebo (n=87) daily until the 36th gestational week. The two groups were compared relative to demographic characteristics, incidence of PTB before 34 and 37 weeks, and maternal and neonatal complications. Data were analyzed by chi-square and Fisher’s exact tests. Results: Mean latency until delivery in the cases was longer than the control group (23.88 ± 18.01 vs. 16.67 ± 12.9; p=0.004).Treatment with progesterone was not associated with a reduction in the rate of PTB before 34 weeks [cases: 9 (10.8%) vs. controls: 8 (10%)] and 37 weeks [cases: 45 (54.2%) vs. controls: 33 (41.2%)]. Log rank analysis revealed a significant difference for mean time to delivery between the two groups (p=0.028). There were no significant differences for neonatal and maternal complications in the two groups. Conclusion: Prophylactic administration of 200 mg vaginal progesterone suppositories after successful tocolysis in patients with threatened idiopathic PTL is associated with a longer latency to delivery, but failed to reduce the rate of PTB (Registeration Number: IRCT138706051096N1). Preterm Labor, Preterm Birth, Vaginal Tablet, Progesterone 45 50 Seyede Hajar Sharami, M.D. sharami@gums.ac.ir No Ziba Zahiri, M.D. No Maryam Shakiba, M.Sc No Frozan Milani, M.D. No

Background: To assess the efficacy of luteal phase support (LPS) with vaginal progesterone (P) on pregnancy rates of the stimulated intrauterine insemination (IUI) cycles in couples with unexplained infertility (UEI). Materials and Methods: This was a single-center, prospective, randomized, blinded control trial undertaken at a tertiary care university fertility center between October 2007 and December 2008. A total of 200 couples with UEI underwent 511 consecutive stimulated IUI cycles. Clomiphene citrate (Cc) and human menopausal gonadotropin (hMG) were used for ovulation induction. After IUI, patients were randomized into two groups. The study group (n=98) received intra-vaginal P (Cyclogest) for LPS. The patients randomized into the control group (n=102) received no drug for LPS. The main outcome was the comparison of clinical pregnancy rate (PR) and live birth rate (BR) per cycle and patient between the control and study groups. Results: There were no differences in demographic characteristics between the groups. PR per patient and cycle were similar in the study group (30.6% and 11.5%, respectively) and in the control group [25.5% and 10.03%, respectively] (p>0.05). There were no statistically significant increases in BR per patient and cycle between the study group (19.4% and 7.5%, respectively) and the control group [14.7% and 5.7%, respectively] (p> 0.05). Conclusion: Administration of vaginal P (Cyclogest) for LPS does not improve the reproductive outcome of stimulated IUI cycles (Registeration Number: IRCT1389 01283737N1). Clomiphene Citrate, Human Menopausal Gonadotropin, Progesterone, Infertility 51 56 Mahbod Ebrahimi, M.D maeb214@yahoo.com No Firoozeh Akbari Asbagh, M.D. No Soodabeh Darvish, M.D. No

Background: It is important to evaluate ovarian reserves prior to intracytoplasmic sperm injection (ICSI) treatment. The aim of this study is to determine the accuracy of anti-mullerian hormone (AMH) as a marker for ovarian reserve and to compare it with day-3 serum follicle-stimulating hormone (FSH) levels. Materials and Methods: In this analytic, corss-sectional study, sequential sampling was done on 70 infertile women who underwent ICSI treatment at Imam Khomeini Hospital, Ahvaz, Iran. Initially, 5cc of venous blood was drawn from each patient to measure serum AMH and FSH levels on the day-3 cycle. Patients were divided into two subgroups according to the numbers of oocytes retrieved. Patients were classified as good responders if there were four or more oocytes retrieved, whereas patients with less than four oocytes were poor responders. Results: The basal AMH level correlated with the number of oocytes retrieved (linear Pearson correlation coefficient=0.599), however the basal FSH level had a weakly reverse correlation (correlation coefficient = -0.11). AMH levels had a sensitivity of 85% and specificity of 61.5%, with a cutoff value equal to 2.3 ng/ml which was higher than FSH. Conclusion: AMH serum levels are good predictors of ovarian reserve in comparison with FSH. AMH, FSH, ICSI 57 60 Roshan Nikbakht, M.D gita_yazdani@yahoo.com No Mehrdad Borhani, M.D No Gita Yazdani Sarvestani, M.D No

Background: Photodynamic therapy (PDT) is a promising new cancer treatment strategy which inactivates tumor cells by simultaneoulsy using light and a photosensitizer. The similarity between tumors and newly implanted embryos is notable. Extrauterine pregnancy (EUP) does not have a definite treatment and previous therapeutic options (medical and surgical) have not been effective or suitable. Therefore, PDT is suggested as a possible treatment for EUP. Materials and Methods: The photosensitizer, hematoporphyrin, was injected locally into the placenta of one selected embryo from a pregnant Wistar rat (E15). Then, a laser beam was illuminated at the same point and 48 hours later, changes in the embryo and placenta were investigated. Furthermore, the integrity of the uterus was examined by macroscopic evaluation and sonographic images. Results: Sections obtained from treated and control groups demonstrated that the embryo and placenta were damaged in the PDT group, whereas the control ones were intact. Furthermore, macroscopic observations and sonographic images during the second parturition after treatment showed that the uterus was intact and fertility was preserved. Conclusion: Successful ablation of the treated embryo with no clear damage to the uterus attests to the success of this approach. The successful use of hematoporphyrin, as a first generation photosensitizer, should be further investigated for its possible clinical applications. Photodynamic Therapy (PDT), Ectopic Pregnancy, Embryo, Placenta, Fertility 61 66 Mohammad Nabiuni, Ph.D. nabiuni@tmu.ac.ir No Mohammad Hossein Majles Ara, Ph.D No Azar Sheikholeslami, M.Sc No

Background: Letrozole is an aromatase inhibitor which can decrease estrogen production in peripheral tissues and endometriosis. Danazol, as an androgen, inhibits estrogen production in ovaries and recently has been introduced as an aromatase inhibitor. This study was designed to compare the effects of Danazol with Letrozole on endometriosis symptom relief. Materials and Methods: This study was a randomized clinical trial in which 105 patients with confirmed endometriosis were randomly assigned to one of three groups. Group 1 received Letrozole tablets (2.5 mg/day), calcium (1000 mg/day) and vitamin D (800 IU/day). Group 2 received Danazol tablets (600 mg/day), calcium (1000 mg/day) and vitamin D (800 IU/day). Group 3 (placebo group) were assigned to take two calcium tablets daily (500 mg/tablet) and vitamin D (800 IU/day). Pelvic pain, dysmenorrhea and dyspareunia were assessed in participants at baseline and monthly during the study for a total of six months. Data were analyzed via SPSS version 15 software with Freidman and Wilcoxon tests. Results: Mean age in three groups has no significant difference. Of the 105 participants who were enrolled in this study, 38 patients were assigned to group 1 (Letrozole group), 37 patients in group 2 (Danazol group) and 31 patients were placed in group 3 (placebo group). This study showed that the mean scores for chronic pelvic pain, dysmenorrhea and dyspareunia for the Letrozole group were less than the Danazol and placebo groups. Conclusion: This study showed that Letrozole can be more effective than Danazol for reducing chronic pelvic pain, dyspareunia and dysmenorrhea in patients suffering from recurrent endometriosis (Registeration Number: IRCT138812043414N1). Letrozole, Danazol, Endometriosis, Laparoscopy 62 72 Mohamad Ali Roghaei, M.D taherian@med.mui.ac.ir No Hatav Ghasemi Tehrany, M.D. No Aliakbar Taherian, M.D. No Navid Koleini, M.D. No

Background: Sperm DNA fragmentation is known as an important cause of male infertility. The influence of sperm DNA damage on reproductive potential has been subject of many studies indicating various results and remaining the subject controversial. In this study, we investigated differences of the semen parameters and intracytoplasmic sperm injection (ICSI) outcome according to sperm DNA fragmentation levels (DFLs) of patients. Materials and Methods: The DFLs were determined by Halosperm, a new improved sperm chromatin dispersion (SCD) test. Patients were grouped as low DNA fragmentation group (LFG ≤30%) and high fragmentation group (HFG >30%). Results: Our analysis showed that semen parameters including concentration of untreated sperm and motility of prepared semen were low in HGF, whereas other parameters were not different. Sperm DNA fragmentation levels decreased in both groups after semen preparation by density gradient technique. Conclusion: No difference was detected on ICSI outcomes (fertilization, embryo development, embryo cleavage, embryo quality and pregnancy rates) between two group. Asisted Reproductive Technique, DNA Fragmentation, ICSI, Sperm 73 78 Seda Yılmaz, M.Sc. seda2410@yahoo.com No Asuman Demiroglu Zergeroğlu, Ph.D No Elif Yılmaz, B.Sc No Kenan Sofuoglu, M.D. No Nuri Delikara, M.D No Pelin Kutlu, M.Sc. No

Background: Assisted reproductive techniques (ART) are used with increasing frequency worldwide. The present research was conducted to determine the effects of ART on hearing defects and ear abnormalities. Materials and Methods: In a descriptive, cross-sectional, non-randomized study, the status of hearing and ear abnormalities was assessed in 300 newborns conceived by ART at Royan Institute, Tehran, Iran. This study was performed over a sixteen month period. Data were collected from parents, otoscopic examinations and transiently evoked otoacoustic emissions (TEOAE) tests of the newborns. The external ear was assessed by otoscopic examination, followed by the TEOAE test (an objective test that does not need the infant’s collaboration) which was performed by an audiologist. In this test, the OAE wave was registered after a click (stimulus) at 5-20 millisecond intervals with an 82 dB SPL altitude. Data were analyzed by statistical tests. Results: Of the 300 cases examined by otoscopy, two cases (0.66%) had bilateral malformation in the auricle, two (0.66%) had unilateral perforation of the tympanic membrane, five (1.66%) had unilateral retraction of the tympanic membrane, eight (2.66%) had bilateral retraction of the tympanic membrane, one (0.33%) had unilateral tympanic membrane inflammation, one (0.33%) had bilateral tympanic membrane inflammation and one case (0.33%) had wax obstruction of the external ear canal. A total of 289 out of 300 newborns undewent the TEOAE test. Of these, three cases (1.03%) did not have a bilateral registered wave and were diagnosed with bilateral hearing loss. Conclusion: This study shows that hearing and ear screening in newborns conceived by ART is contemplative and emphasizes the profitability of continual check up in these infants. Newborn, Assisted Reproductive Techniques, Hearing, Ear 79 84 Seyed Ebrahim Ahmadi, M.Sc ahmadi@Irmed.org No Mohammad Reza Nateghi, M.D. No Hamid Gourabi, Ph.D. No Ramin Mozafari Kermani, M.D No Farnoush Jarollahi, M.Sc. No Sodabeh Afsharpour, B.Sc No Jalil Kouhpayehzadeh, M.D. No

Cystic fibrosis (CF), the most common life-shortening, hereditary disease in whites, manifests itself principally in childhood. Patients presenting with CF as adults appear to be different when compared to patients diagnosed with CF during childhood. Often these patients have been previously diagnosed with asthma, chronic bronchitis or emphysema. We present a case of a woman diagnosed with CF at age 37 years. We noticed her finger clubbing during her son’s hospital admission for CF decompensation. Taking a thorough history, she complained of chronic productive cough and was treated for hyper reactive airway disease for many years. A Computed Tomography scan was performed which showed bronchiectasis, atelectasis and the presence of a honey comb pattern in her lung fields. Two sweat tests were performed, both of which were strongly positive. Her CF diagnosis was confirmed. The clinical course of patients receiving a diagnosis of CF in adulthood is largely unknown, but frequently they have milder disease and a more favorable prognosis. The proportion and number of patients with CF diagnosed in adulthood has increased. A large number of these patients present with subtle symptoms or single-organ disease. Since the majority have pulmonary disease CF should be included in the differential diagnosis of chronic respiratory symptoms in adults. Cystic Fibrosis, Clubbing, Infertility, Pregnancy 85 87 Alireza Nikzad Jamnani, M.D alirezanikzad@yahoo.com No Mehri Najafi Sani, M.D No Armen Malekiyan, M.D. No

To the Editor We are interested the article by Niknejadi et al. (1) highly scientific and provocative however there seem to be a lack of clarity on some of the methodological issues; 1. In the materials and methods section, it was mentioned that: “in cases that had normal endometrial findings on transvaginal sonography (TVS), a hysteroscopy was not scheduled due to ethical considerations” whereas in the results, a total of 466 cases with negative TVS were presented. It is not mentioned how these patients were found. If they have other indications for hysteroscopy, it may add bias to your research which may affect the results (verification bias). The bias would be present since both the TVS positive and negative patients would come from different patient populations that have different indications as a result of their various medical conditions. For example, most likely the TVS negative patients in this study came from patients who presented with in vitro fertilization (IVF) failure, intrauterine insemination (IUI) failure and abnormalities seen in clinical exams, to name a few. The TVS positive cases would beare the people diagnosed during routine TVS for infertility evaluation. Although your research is retrospective, it would be better to consider such differences between subjects (2-6). 2. Considering that TVS negative patients do not routinely undergoto hysteroscopies; therefore one can conclude that TVS is a highly sensitive test, thus positive patients will not be missed. Laparoscopy is a highly specific test needed solely for confirming the diagnosed problem and can 88 Royan Institute International Journal of Fertility and Sterility Vol 4, No 2, Jul-Sep 2010 filter out healthy patients (2). It seems that in your report, the sensitivity of TVS is not very high. On the other hand, if we assume that there are some degrees of verification bias in your study, the real sensitivity even will be lower than calculated. References 1. Niknejadi M, Ahmadi F, Zafarani F, Khalili M, Ghaderi F, Rashidi Z. Diagnostic accuracy of transvaginal sonography in infertile patients with endometrial polyps. International Journal of Fertility and Sterillity (IJFS). 2010; 3 (4): 157-160. 2. Berek JS. Berek & Novak's Gynecology. 14th ed. Philadelphia: Lippincott Williams & Wilkins; 2007; 787. 3. Ringham BM, Alonzo TA, Grunwald GK, Glueck H. Estimates of sensitivity and specificity can be biased when reporting the results of the second test in a screening trial conducted in series. BMC Med Res Methodol. 2010; 10:3. 4. Buzoianu M, Kadane JB. Adjusting for verification bias in diagnostic test evaluation: a Bayesian approach. Stat Med. 2008; 27(13): 2453-2473. 5. Zhou XH.Correcting for verification bias in studies of a diagnostic test's accuracy. Stat Methods Med Res. 1998; 7(4): 337-353 6. Cronin AM, Vickers AJ. Statistical methods to correct for verification bias in diagnostic studies are inadequate when there are few false negatives: a simulation study. BMC Med Res Methodol. 2008; 8: 75. 88 88 Mona Oudi, B.Sc. monaoudi@royaninstitute.org No Reza Omani Samani, M.D. No

Reply of the Authors We welcome the opportunity to respond to the letter of Dr. Samani and colleague: 1. A common problem of diagnostic research in clinical medicine is that due to ethical or cost considerations, only a small proportion of participants with negative results may receive the gold standard test. Therefore, the results for diagnostic reference tests are more available in patients with positive results. In this situation it is very common to use the information that is available from diagnostic tests in verified participants. Data from such studies are prone to verification bias (also called ‘work-up bias’). As you are aware, we can not ethically prescribe an invasive procedure, such as a hysteroscopy, for humans without a reasonable indication. Therefore we could not perform both diagnostic tests (TVS and hysteroscopy) on all patients. Instead, in our study, we attempted to find subjects who had both results of TVS and hysteroscopy in their medical records. We know that there is an inevitable source of verification bias in our results because of the subject selection strategy. However, studies in this field often have a similar selection strategy. There are some new techniques for correcting verification bias and currently we are analyzing our data to adjust for verification bias (1-3). 2. The sensitiviy of our study is 88.3% which is higher than similar studies in other countries (4, 5). This sensitivity is based on the hysteroscopic 89 Royan Institute International Journal of Fertility and Sterility Vol 4, No 2, Jul-Sep 2010 results as the gold standard, which is discussed in our article. Hysteroscopy has some limitations; therefore a prospective study should be planned utilizing pathology as the gold standard. References 1. Gaffikin L, McGrath J, Arbyn M, Blumenthal PD. Clin Trials. Avoiding verification bias in screening test evaluation in resource poor settings: a case study from Zimbabwe. Clin Trials. 2008; 5(5): 496-503. 2. de Groot JA, Janssen KJ, Zwinderman AH, Moons KG, Reitsma JB Multiple imputation to correct for partial verification bias revisited. Stat Med. 2008; 27(28): 5880-5889. 3. Buzoianu M, Kadane JB. Adjusting for verification bias in diagnostic test evaluation: a bayesian approach. Stat Med. 2008; 27(13): 2453-2473. 4. Soares SR, Barbosa dos Reis MM, Camargos AF. Diagnostic accuracy of sonohysterography, transvaginal sonography, and hysterosalpingography in patients with uterine cavity diseases. Fertil Steril. 2000; 73(2): 406-411. 5. Loverro G, Nappi L, Vicino M, Carriero C, Vimercati A, Selvaggi L. Uterine cavity assessment in infertile women: comparison of transvaginal sonography and hysteroscopy. Eur J Obstet Gynecol Reprod Biol. 2001; 100(1): 67-71. 89 89 Maryam Niknejadi M.D. mniknejadi@royaninstitute.org No

After twenty years Computer Aided Sperm Analysis has developed considerably and is now routinely used in many laboratories across the world. The advantage of the CASA methodology available is twofold: Analysis of particularly sperm concentration, sperm motility, sperm morphology and vitality is quantified in an Background manner. Secondly, most of the CASA analysis with the exception of sperm morphology, is rapid and literally takes a few seconds. These two factors allow scientists to produce data in an Background and consistent manner and also make experiments possible that would otherwise have had too many time constraints. In this paper emphasis will be placed on quantitative sperm motility and its multiple uses in assessing sperm function in general fertility studies; testing the effect of a vast range of substances (peptides, hormones, toxicology) on sperm function. Two approaches will be described. In each instance either sperm washing, swim-up or differential centrifugation were used. When sperm were placed in media supporting sperm function and largely simulate the composition of follicular fluid after washing, a certain percentage of sperm would become hyperactive. In good quality sperm usually more than 20% of sperm become hyperactivewhen CASA parameters are set at VCL>150; LIN7. Unfortunately sperm from different individuals exhibit maximum hyperactivation at different time intervals over three hours. However, in cases where a specific strategy is required for a particular patient, additional tests such as “the hyperactivation test” may be useful. Also, the ability of a sperm sample to become hyperactivated can be used to assess the effect of substances such as pesticides and hormones on functional integrity. A second useful CASA functional test that has been developed in our laboratory, and used in certain hormone assays is the percentage rapid moving sperm in a sample and a cut-off point of VCL>100 to 120 was found most useful when washed samples were employed. In conclusion, CASA now provides us with tools which are reliable and consistent to study sperm function as related to fertility and toxicology in a quantitative and Background way. 0 0 van der Horst G raj.duggavathi@mcgill.ca No