International Journal of Fertility and Sterility

1-12

Authors: Farkhondeh Pouresmaeili , Zahra Fazeli

Premature ovarian failure (POF) is identified as a heterogeneous disorder leading to amenorrhea and ovarian failure before the age of 40 years. The first known symptom of the disease is having irregular menstrual periods. The phenotype appearance of POF depends significantly on the variations in hormones. Low levels of gonadal hormones (estrogens and inhibins) and increased level of gonadotropins [luteinizing hormone (LH) and Follicle stimulating hormone (FSH)] (hypergonadotropic amenorrhea) are well documented as causes of POF. There is an association between the failure of germ cell development and complete ovarian failure, and consistently decreased number of germ cells is more likely associated with partial ovarian failure resulting in secondary amenorrhea. A literature review on recent findings about POF and its association with genomic alterations in terms of genes and chromosomes. POF is a complex heterogeneous disorder. Some of POF cases are carriers of a single gene mutation inherited in an autosomal or X-linked manner while a number of patients suffer from a chromosome abnormality like Turner syndrome in mosaic form and manifest secondary amenorrhea associated with ovarian dysgenesis. Among many of the known involved genes in POF development, several are prove to be positively associated to the disease development in different populations. While there is a promising association between X chromosome anomalies and specific gene mutations with POF, genome-wide analysis could prove a powerful tool for identifying the most important candidate genes that influence POF manifestation.

21-28

Authors: Nasim Charehjooy , Marziyeh Tavalaee , Mohammad Reza Deemeh , Leila Azadi , Abdol Hossein Shiravi , Mohammad Hossein Nasr-Esfahani , Mohammad Hassan Najafi

Background: The intra-cytoplasmic sperm injection (ICSI) technique selects sperm according to morphology and motility. However, these parameters cannot predict the chromatin integrity of sperm. Considering the detrimental effects of DNA-damaged sperm on reproductive outcomes, novel sperm selection procedures have been proposed to circumvent the possibility of inseminating DNA-damaged sperm. It has been shown that different potential hypo-osmotic swelling test (HOST) patterns possess the potential to differentiate between sperm that have intact or damaged chromatin. Therefore, for the first time, this preliminary study evaluates the role of HOST as a sperm selection procedure in a clinical setting. Materials and Methods: In this preliminary prospective clinical trial study, we divided infertile couples diagnosed with male infertility into two groups. In the treatment group (n=39), half of the oocytes were inseminated by sperm selected following density gradient centrifugation (DGC group). The remaining oocytes from the treatment group were inseminated by sperm chosen according to HOST pattern (c, d or e) following DGC processing (HOST group). In the control group (n=63), all oocytes were inseminated by sperm chosen after DGC. Results: There was a significantly higher percentage of embryos that had good quality, implantation, and chemical pregnancy rates in the HOST group compared to the DGC group (p≤0.05). Conclusion: This study has shown that selecting sperm according to membrane functionality (HOST pattern) rather morphology and viability may open a new window in our approach for determining the appropriate sperm for ICSI, particularly in individuals with severe male infertility (Registration Number: IRCT201307087223N2).

35-42

Authors: Dana Mierla , Dumitru Jardan , Veronica Stoian

Background: Chromosomal abnormalities and Y chromosome microdeletions are regarded as two most frequent genetic causes associated with failure of spermatogenesis in the Caucasian population. Materials and Methods: To investigate the distribution of genetic defects in the Romanian population with azoospermia or severe oligozoospermia, karyotype analysis by G-banding was carried out in 850 idiopathic infertile men and in 49 fertile men with one or more children. Screening for microdeletions in the azoospermia factor (AZF) region of Y chromosome was performed by multiplex polymerase chain reaction (PCR) on a group of 67 patients with no detectable chromosomal abnormality. The results of the two groups were compared by a two-tailed Fisher’s exact test. Results: In our study chromosomal abnormalities were observed in 12.70% and 8.16% of infertile and fertile individuals respectively. Conclusion: Our data suggests that infertile men with severe azoospermia have higher incidences of genetic defects than fertile men and also patients from any other group. Infertile men with normal sperm present a higher rate of polymorphic variants. It is important to know whether there is a genetic cause of male infertility before patients are subjected to intracytoplasmic sperm injection (ICSI) or testicular sperm extraction (TESE)/ICSI treatment.

51-58

Authors: Mohammad-Reza Rashidi , Jalal Eisa-Khaje , Laya Farzadi , Masoud Darabi , Alieh Gasemzadeh , Vahideh Shahnazi , Shabnam Fayezi , Amir Mehdizadeh , Reza Haji Hosseini , Mohammad Nouri

Background: Paraoxonase-3 (PON3), as a high density lipoprotein (HDL)-associated lactonase, is capable of preventing the oxidative modification of low density lipoprotein (LDL). PON3 activity in follicular fluid (FF) is three times more than its activity in serum. However, the detailed role of PON3 in women’s fertility remains unknown. The aim of this study was to investigate the correlation between PON3 activity in the FF of women undergoing assisted reproductive technique (ART), in vitro fertilization (IVF), or intra-cytoplasmic sperm injection (ICSI). Materials and Methods: This cross-sectional study consisted of 50 women from couples with male factor infertility (MFI) or with female factor infertility (FFI). The FF samples were obtained during the ART intervention. PON3 activity, HDL cholesterol (HDL C), total antioxidant status (TAS) and the level of malondialdehyde (MDA) were determined. The morphology of the embryo was determined using embryo cell number (ECN) and embryo fragmentation score (EFS). In addition, fertilization rate (FR) was used an oocyte fertilization index. Results: Of 50 women, 20 women belonged to FFI group and the remaining 30 women belonged to MFI group. PON3 activity in FF of women in FFI group was significantly lower (p<0.05) in comparison with corresponding value in MFI group. The value of PON3 activity/MDA in the FFI group was lower than that in MFI group. Moreover, MDA level in the FF of FFI group was significantly higher (p<0.05) than its concentration in MFI group. Meanwhile, no significant difference was found in HDL-C concentration and TAS of both groups. No significant correlation was observed between the ECN and FF biochemical parameters. There was also a negative correlation between FR and MDA (r=-0.42, p=0.02), whereas a positive relation between FR with PON3 activity (r=0.59, p=0.004), HDL-C (r=0.35, p=0.04) and PON3/MDA (r=0.59, p=0.001). Conclusion: According to the results of this study, PON3 activity level as a key component of antioxidant system in FF may directly be associated with the success rate of ART and fertilization rate in women.

67-76

Authors: Aygül Akyüz , Gönül Şahiner , Memnun Seven , Bilal Bakır

Background: The aim of this study was to determine the relationship between marital violence and distress level among women with a diagnosis of infertility. Materials and Methods: This cross-sectional study consisted of 139 married women diagnosed as primary infertile who applied to an in vitro fertilization (IVF) center in Turkey, between September and December 2009. A descriptive information questionnaire developed by the researcher was used for data collection. In addition, an infertility distress scale (IDS) for determining the severity effect of infertility and the scale for marital violence against women (SDVW) for determining level of marital violence against the women were used. Results: The total IDS score of the study sample was 37.76 ± 10.53. There was no significant relationship between the age and education level of the women and the total IDS score. The total IDS score was higher in women who did not work and those being treated for infertility for more than three years. The total SDVW score of the study sample was 67.0 ± 8.26. The total SDVW score was higher in women who had been trying to have a child for more than six years and had received infertility treatment for longer than three years. The employment status of the women and physical, emotional, and sexual violence scores had a statistically significant relationship with the IDS scores. The emotional violence score was found to have the highest significance among the variables affecting total IDS score. Conclusion: Marital violence is a factor increasing the distress of infertile women. Healthcare staff serving infertile couples should consider the possibility of domestic violence against women as a factor affecting the psychological infertility distress level.

85-90

Authors: Mahbod Ebrahimi , Firoozeh Akbari Asbagh

Ovarian pregnancy is a rare form of extra uterine pregnancy. Serous cyst adenoma is a benign variant of epithelial cell tumors of ovary. The coexistence of a cyst adenoma with an ovarian pregnancy in the same ovary is extremely rare. Some studies suggested that infertility or ovulation-inducing drugs can be involved in increased risk of ovarian tumors and ovarian pregnancies. A 28-year-old infertile woman presented with a ruptured ovarian pregnancy following ovulation induction with metformin. She had a concurrent benign serous cyst adenoma in the same ovary. Resection of both ovarian pregnancy and tumoral mass were performed. The ovary was preserved. Removal of gestational tissue and preservation of the involved ovary are the best options for management of ovarian pregnancy in young patient. Although there is an association between infertility/ovulation inducting medications and ovarian gestation, their connections with serous cyst adenoma are undetermined.

95-98

Authors: Ariane Sadr-Nabavi , Morteza Saeidi

The rearrangement of chromosome 14 is a rare cytogenetic finding. Changes in the number or structure of chromosome 14 can have a variety of effects, such as delayed growth and development, and distinctive facial features. The human chromosome 14 plays an important role in imprinting events importunes of a structural rearrangement is specifically when a phenotype is caused by imprinting, whereby the interpretation of genotype-phenotype correlation becomes extremely difficult. In this study, we examined a 3 year-old mentally impaired girl with unusual facial features. G-banding showed terminal duplication of chromosome 14 in the karyotype of the patient. In this particular case, we explained a phenotype genotype correlation in a patient with a dup (14) rearrangement, thus emphasizing the importance of prenatal diagnosis for pregnancies with an abnormal nuchal translucency.

225-226

Authors: Mohammad Hossein Nasr Esfahani

Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole (1). This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported (2). There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes-a "core outcomes set"-for all trials in a specific clinical area (1). Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women’s health have come together to support The CROWN (CoRe Outcomes in WomeN’s health) Initiative (Box 1).Development of consensus is required around a set of well-defined, relevant and feasible outcomes for all trials concerning particular obstetric and gynaecologic health conditions, such as preterm birth, incontinence, infertility and menstrual problems. With so many subspecialties involved, this is no easy task. Duplication of effort can be avoided by working with the Core Outcome Measures in Effectiveness Trials (COMET) Initiative, which is working towards core data sets for all medical specialties (3). Production of trustworthy core outcome sets will require engagement with patients, healthcare professionals, researchers, industry and regulators, and the employment of scientifically robust consensus methods (1). The data for these core outcome sets, once agreed upon, should be collected in trials and reported in publications as standard practice in the future. Journal editors now invite researchers to take the lead in beginning this work. What will we do as editors to support them and their colleagues? First, we are drawing wide attention to The CROWN Initiative by publishing this editorial in the journals listed below. We shall ensure that the global research community, which includes our many reviewers, is aware of the need for core outcome sets. Submissions which describe development of core outcome sets, if deemed acceptable after peer review, will be effectively disseminated. Our collaboration is not for enforcing harmony at the expense of innovation. To quote from the COMET home page (www.comet-initiative.org): "The existence or use of a core outcome set does not imply that outcomes in a particular trial should be restricted to those in the relevant core outcome set. Rather, there is an expectation that the core outcomes will be collected and reported, making it easier for the results of trials to be compared, contrasted and combined as appropriate; while researchers continue to explore other outcomes as well." We also expect that as new or superior ways of capturing outcomes emerge, core outcome setswill themselves need updating. Producing, disseminating and implementing core outcome sets will ensure that critical and important outcomes with good measurement properties are incorporated and reported. We believe this is the next important step in advancing the usefulness of research, in informing readers, including guideline and policy developers, who are involved in decision-making, and in improving evidence-based practice.

235-242

Authors: Fatemeh Foroozanfard, Hamidreza Saberi, Seyed Alireza Moraveji, Fatemeh Bazarganipour

Background: To assess the efficacy of luteal phase support (LPS) using intravaginal progesterone (P) on pregnancy rate in Iranian women with polycystic ovarian syndrome (PCOS) who used a combination for ovulation induction consisting of letrozole or clomiphene citrate (CC) and human menopausal gonadotropin (HMG). Materials and Methods:This was a randomized clinical trial undertaken in a fertility clinic in Kashan, Isfahan Province, Iran. A total of 198 patients completed treatment and follow up. Base on chosen ovulation induction programs, they were divided into two following group: i. CC group (n=98) used a combination consisting of CC (100 mg×5 day) and HMG (150 IU×5 day) and ii. letrozole group (n=100) used a combination consisting of letrozole (5 mg×5 day) and HMG (150 IU×5 day). After human chorionic gonadotropin (hCG) administration (5000 IU), the patients (n=122) who randomly received intravaginal P (Cyclogest, 400 mg daily) were included in LPS group, while the rest (n=123) were included in non-P cycles group. The outcome was the comparison of chemical pregnancy rate between the groups. Results: Our findings showed that LPS was associated with a 10% higher pregnancy rate than in non-P cycles, although this difference did not reach statistical significant (p=0.08). LPS improved pregnancy rate in both CC (4%) and letrozole (6%) groups. In addition, patients who used letrozole for ovulation induction along with intravaginal P showed higher pregnancy rates than CC group. Conclusion: Administration of vaginal P for LPS may improve the pregnancy rate in women with PCOS using letrozole or CC in combination with HMG for ovulation induction (Registration Number: IRCT201206072967N4).

249-254

Authors: Nasrin Saharkhiz,Roshan Nikbakht,Saghar Salehpour

Background: Embryo transfer (ET) is one of the most important steps in assisted reproductive technology (ART) cycles and affected by many factors namely the depth of embryo deposition in uterus. In this study, the outcomes of intracytoplasmic sperm injection (ICSI) cycles after blind embryo transfer and embryo transfer based on previously measured uterine length using vaginal ultrasound were compared. Materials and Methods: This prospective randomised clinical trial included one hundred and forty non-donor fresh embryo transfers during January 2010 to June 2011. In group I, ET was performed using conventional (blind) method at 5-6cm from the external os, and in group II, ET was done at a depth of 1-1.5 cm from the uterine fundus based on previously measured uterine length using vaginal sonography. Appropriate statistical analysis was performed using Student’s t test and Chi-square or Fisher’s exact test. The software that we used was PASW statistics version 18. A p value <0.05 was considered statistically significant. Results: Chemical pregnancy rate was 28.7% in group I and 42.1% in group II, while the difference was not statistically significant (p=0.105). Clinical pregnancy, ongoing pregnancy and implantation rates for group I were 21.2%, 17.7%, and 12.8%, while for group II were 33.9%, 33.9%, and 22.1, respectively. In group I and group II, abortion rates were 34.7% and 0%, respectively, indicating a statistically significant difference (p<0.005). No ectopic pregnancy occurred in two groups. Conclusion: The use of uterine length measurement during treatment cycle in order to place embryos at depth of 1-1.5cm from fundus significantly increases clinical and ongoing pregnancy and implantation rates, while leads to a decrease in abortion rate (Registration Number: IRCT2014032512494N1).

261-266

Authors: Amita Attlee,Asma Nusralla,Rashida Eqbal,Hanaa Said,Mona Hashim,Reyad Shaker Obaid

Background: The aim of this study was to assess the occurrence of polycystic ovary syndrome (PCOS) and its association with body composition among students in University of Sharjah (UOS). Materials and Methods: This cross-sectional study included a total sample size of 50 female students registering in undergraduate programs at the University of Sharjah using convenience sampling technique. A pretested interview schedule was administered to elicit information pertaining to personal background and medical history related to PCOS. A diagnostic ultrasound scan was performed for determining PCOS along with a body composition analysis using bioelectrical impedance analysis (BIA) technology. Results: Twenty percent (10 out of 50 participants) were diagnosed with PCOS, of whom only 4 individuals were previously diagnosed with PCOS and aware of their conditions, while the reports showed 16% with oligomenorrhea, 4% with polymenorrhea, and none with amenorrhea. A positive family history was indicated as reported by 22% of the total participants. Significant difference between the body weights of participants having PCOS (66.7 kg) and those without it (58.8 kg) were noted (p=0.043, t=2.084). On the other hand, the body composition related variables including waist-hip ratio (WHR), fat-free mass (FFM), percent body fat (PBF) and visceral fat area (VFA) were relatively higher in participants having PCOS than those without it. However, there was no statistical significance of differences. Comparatively, the participants with PCOS had lower bone mineral density (BMD) than those without it, whereas the difference was statistically non-significant. Conclusion: The occurrence of PCOS in the present study is consistent with the global prevalence. Comparatively, the body composition of PCOS females is different from the normal females. Further studies are required in the Middle East region on larger sample sizes and broader aspects of health including lifestyle and dietary components to understand these differences.

273-280

Authors: Fatemeh Bazarganipour,Saeideh Ziaei,Ali Montazeri,Fatemeh Foroozanfard,Anoshirvan Kazemnejad,Soghrat Faghihzadeh

Background: This study aimed to assess sexual functioning among women with polycystic ovary syndrome (PCOS) in Iran. Materials and Methods: A cross-sectional study was conducted to ascertain factors related to sexual functioning in 300 PCOS patients attending to the private practice centers in Kashan, Isfahan Province, Iran, from May to October 2012. The Female Sexual Function Index (FSFI) was used to measure sexual functioning. Moreover, the socio-demographic details and clinical information of PCOS including obesity, hirsutism, acne, menstrual cycle disturbances, infertility and endocrine profile were recorded for each patient. Results: Overall the prevalence of female sexual dysfunction (FSD) was 16.6%. In particular patients indicated poorer sexual functioning for the desire (48.3%) and the arousal (44.7%) subscales. Multiple logistic regression analysis suggested patients with lower educational level (OR: 2.94; 95% CI: 1.46-5.92) and irregular menstrual status (OR: 4.61; 95% CI: 1.93-11) were more likely to report sexual dysfunction. Conclusion: The findings suggest that desire and arousal were the most prevalent sexual disorders reported in this patient population. In addition, findings suggested that women with limited or no formal education and a history of menstrual irregularities were the most likely to report female sexual dysfunction. Further investigations are needed to examine female sexual functioning among women with PCOS, to educate their health care providers, and to develop therapeutic interventions.

289-298

Authors: Aygul Akyuz,Nese Sever,Emre Karasahin,Gulten Guvenc,Suzan Cek

Background: There are various treatment options for infertility, and new techniques are also being developed as it is an important healthcare problem affecting approximately 15-20% of married couples. The purpose of this study was to evaluate the level of information of fertile and infertile Turkish women on oocyte donation in order to understand their awareness of the legal, ethical, social and religious issues regarding this technique and to compare these two groups in terms of these variables. Materials and Methods: This cross-sectional study included infertile women being treated at the assisted reproductive technologies (ART) program of a university hospital and women who had presented at the gynecology outpatients department of the same university for routine check-ups and who had no previous history of infertility. After consulting with specialists in the field and searching the related literature, a data collection form having 22 questions for infertile women and 18 questions for fertile women was prepared. Results: The women were asked whether they would use the oocytes of another woman if necessary. The results showed that 67.6% of the fertile women said they would never want to use this method, while 63.9% of the infertile women stated they may accept to use this method under certain conditions (two distinct answers appeared in the answers, some women stated they would prefer donated oocytes from close relatives, while others stated they would prefer oocytes from total strangers), such as from a close relative or from someone they do not know at all. Conclusion: Infertile women mentioned that they could use illegal routes if necessary to have a child at much higher rates than stated by fertile women. This shows that desire to have a child is a strong source of motivation in Turkey.

303-314

Authors: Kubra Erdem,Serap Ejder Apay

Background: Studies conducted on infertile women in the literature investigated some features such as depression, anxiety, loneliness, and social support. However, there has been no study examining the relationship between levels of perceived social support and depression in infertile women. Considering this deficiency, the study was conducted to determine the relationship between perceived social support and depression in infertile women. The purpose of this study is to determine the relationship between perceived social support and depression in infertile women. Materials and Methods: This descriptive and sectional study was conducted between 16 April and 31 October 2012 in in vitro fertilisation (IVF) Centre of Fırat University Research Hospital. Sampling formula was used in cases when the number of elements in the population was not known to calculate minimum sample size required to be included in the study. A total of 238 women who applied to the relevant centre between the specified dates constituted the sample group of the study. A Questionnaire Form, Beck Depression Inventory (BDI) and the Multidimensional Scale of Perceived Social Support (MSPSS) were used to collect the data. A pilot study was carried out on nine infertile women. As a result of the pilot study, we formed the final version of the Questionnaire Form. The data of these nine women were not involved in the research. The data obtained from the study was assessed using Statistical Package for the Social Sciences (SPSS; SPSS Inc., Chicago, IL, USA) version 15.0. Percentage distribution, mean, t test, one-way analysis of variance (One-Way ANOVA), and Pearson correlation analysis were used to evaluate the data. Results: The women’s total mean score on the BDI was 12.55 ± 8.07. Scores obtained by women on the MSPSS was 15.75 ± 8.53 for the subscale of friend, 21.52 ± 8.20 for the subscale of family, and 15.62 ± 8.45 for the subscale of significant others. The women’s total MSPSS score was 52.89 ± 21.75. Conclusion: A significant, negative relationship was found between total BDI score with subscale and total mean scores of MSPSS (r= -0.596, p<0.01). Symptoms of depression decreased as the women’s perceived social support increased.

325-332

Authors: Kamran Dorostkar,Sayed Mortaza Alavi Shoushtari,Amir Khaki

Background: The objective of the study was to investigate the effects of in vitro zinc sulphate additive to semen extender on sperm parameters (progressive motility, viability, membrane integrity and DNA stability) after cryopreservation. Materials and Methods: In this Prospective longitudinal laboratory study, semen samples of 5 buffalo bulls of 3-5 years old were collected at 5 different occasions from Iran, Urmia during summer and autumn 2011, 25 samples were used in each treatment. Sperm progressive motility, viability and abnormal morphology were measured before and at 0.5 (T0), 1(T1) and 2(T2) hours after diluting semen(1:10 v/v) in Tris-citric acid based extender (without egg yolk and glycerol) at 37˚C containing none (control group), 0.072, 0.144, 0.288, 0.576 and 1.152 mg/L zinc sulphate to investigate dose and time effects. Next, a Tris-citric acid-egg yolk-glycerol extender (20% egg yolk and 7% glycerol) containing the same amount of zinc sulphate was prepared, diluted semen (1:10 v/v) was cooled and kept into a refrigerated chamber (4˚C) for 4 hours to equilibrate. Sperm progressive motility, viability, abnormal morphology, membrane integrity and DNA damage were estimated.The equilibrated semen was loaded in 0.5 ml French straws and frozen in liquid nitrogen. Later, the frozen semen was thawed and the same parameters as well as total antioxidant capacity (TAC) of the frozen-thawed semen were determined. Results: The results showed that zinc sulphate additive at the rate of 0.288 mg/L gave a higher protection of sperm progressive motility (53.7 ± 1.8% vs. 40.5 ± 1.7%), viability (70.8 ± 1.8% vs. 60.1 ± 1.5%), membrane integrity (67.3 ± 1.6% vs. 56.6 ± 1.7%), DNA stability (10.1 ± 0.47% vs. 11.8 ± 0.33% damaged DNA) through the process of dilution, equilibration and freeze-thawing and caused a higher TAC level (81 ± 3.3% vs. 63 ± 3.2 μmol/L) after freez-thawing compared to the control group. Adding 0.576 and 1.152 mg/L zinc sulphate, however, was deleterious to the sperm and significantly reduced the studied sperm parameters. Conclusion: Adding 0.288 mg/L zinc sulphate to the extender, compared to the control group, gives a better sperm preservation upon freezing processes which in turn, may results in higher semen fertility. But, addition of higher zinc sulphate concentrations (0.576 and 1.152 mg/L) are detrimental to buffalo spermatozoa.

341-346

Authors: Emre Goksan Pabuccu,Salih Taskin,Cem Atabekoglu,Murat Sonmezer

Severe pelvic infections following ultrasound-guided transvaginal oocyte retrieval (TVOR) are rare but challenging. Ovarian abscess formation is one of the consequences and management of such cases as highly debated in pregnant patients. In this case report, an early fetal loss following laparoscopic management of ovarian abscess is described and possible etiologies are discussed.

105-112

Authors: Thomas Ebner , Omar Shebl , Peter Oppelt , Richard Bernhard Mayer

Although intracytoplasmic sperm injection (ICSI) allows proper fertilization in most cases of male sub fertility, it is one of the most unphysiological techniques in assisted reproductive technologies (ART). Thus, over the last decade, researchers have tried to improve sperm observation with higher-resolution microscopy techniques such as the intracytoplasmic morphologically selected sperm injection (IMSI) technique. In order to identify literatures for this review, the PubMed database was searched from 2000 onwards using the terms IMSI, motile sperm organelle morphology examination (MSOME) and sperm vacuole. Approximately 10 years after the introduction of the MSOME and IMSI procedures, several questions related to the prevalence, origin, location, and clinical consequences of sperm vacuoles have not yet been clarified. It seems that IMSI as a routine application is not state of the art and the only confirmed indications for IMSI are recurrent implantation failure following ICSI and severe male factor.

119-128

Authors: Ebrahim Cheraghi , Malek Soleimani Mehranjani , Mohammad Ali Shariatzadeh , Mohammad Hossein Nasr Esfahani , Zahra Ebrahimi

Background: Studies have demonstrated the efficacy of metformin (MTF ) in reducing insulin resistance and N-acetyl cysteine (NAC) in inhibiting oxidative stress which are involved in the pathogenesis of polycystic ovarian syndrome (PCOS). We aimed to compare the effects of MTF and NAC combination on serum metabolite and hormonal levels during the course of ovulation induction in PCOS individual candidates of intracytoplasmic sperm injection (ICSI). Materials and Methods: In this prospective randomized clinical trial, placebo controlled pilot study, 80 patients of polycystic ovarian syndrome at the age of 25-35 years were divided into 4 groups (n=20): i. NAC=treated with N-acetyl cysteine (600 mg three times daily), ii. MTF=treated with metformin (500 mg three times daily), iii. MTF+NAC=treated with N-acetyl cysteine plus metformin (the offered doses) and iv. placebo (PLA). A total number of 20 patients (6 from MTF group, 4 from NAC group, 6 from MTF+NAC group and 4 from PLA group) were dropped of the study. The drugs were administrated from day 3 of menses of previous cycle until ovum pick-up. Results: Serum levels of luteinizing hormone (LH), total testosterone, cholesterol and triglyceride, insulin and leptin significantly reduced in the MTF and NAC groups compared to the placebo (p<0.01). But levels of LH, total testosterone, cholesterol and triglyceride had no significant reduction in the MTF+NAC groups compared to the placebo. The serum levels of malonyldialdehyde (MDA), insulin and leptin reduced significantly after treatment in the MTF+NAC group compared to the placebo (p<0.05). Conclusion: Considering the adverse effect of combination therapy, we proposed the conadministration might have no beneficial effect for PCOS patient during course of ovulation induction of ICSI (Registration Number: IRCT201204159476N1).

135-142

Authors: Rosane Santana , Amanda Souza Setti , Luiz Guilherme Maldonado , Fernanda Montenegro Valente , Carla Iaconelli , Assumpto Iaconelli Jr , Edson Borges Jr

Background: The objective of this retrospective cohort study was to evaluate whether the length of pituitary blockage with gonadotrophin-releasing hormone (GnRH) antagonists or the stimulation period influence intracytoplasmic sperm injection (ICSI) outcomes in patients older than 36 years of age. Materials and Methods: In this retrospective study, a total of 138 couples with maternal age >36 years undergoing ICSI with an antagonist protocol were included. The influences of stimulation and suppression length on the response to ovarian stimulation and ICSI outcomes were investigated. Receiver operating characteristic curve (ROC) analysis was performed to assess the predictive value of the stimulation period for achievement of implantation and pregnancy. Results: The gonadotrophin stimulation length negatively influenced the implantation rate (RC: -4.200; p=0.023). The area under ROC curve (AUC) could distinguish between women with positive and negative implantation (AUC: 0.611; CI: 0.546-0.673) and pregnancy (AUC: 0.593; CI: 0.528-0.656). The threshold value demonstrated a high negative predictive value on likelihood of implantation (p=0.0032, 90% sensitivity) and pregnancy (p=0.0147, 87.1% sensitivity) when patients underwent more than 10 days of stimulation. Conclusion: The stimulation period negatively influences the implantation rate in women older than 36 years. A stimulation interval greater than 10 days is associated with a negative predictive value for the chance of implantation and pregnancy.

147-154

Authors: Shayesteh Parashi , Somayeh Moukhah , Mahnaz Ashrafi

Background: Although the risk factors of ectopic pregnancy have been determined in previous studies, the main risk factors of ectopic pregnancy are different in various countries due to different cultural and social characteristics. Determination of main risk factors of ectopic pregnancy leads to a rapid diagnosis and an improvement in strategies for its prevention. The purpose of this study was to determine the main risk factors of ectopic pregnancy in a sample of Iranian women. Materials and Methods: We designed a case-control study to include 150 cases and 300 controls and to compare them by the following factors: socio-demographic characteristics, contraceptive methods, prior tubal surgery, tubal pathology, prior ectopic pregnancy, prior caesarean section, prior abortion, prior infertility, and prior abdominal/pelvic surgery. Results: The case and control groups were significantly similar in term of education and parity. There was an association between ectopic pregnancy and age which was disappeared after controlling for the main risk factors (adjusted OR=2.45, 95% CI: 0.86-6.97). There was no statistically significant relation between ectopic pregnancy and prior tubal surgery, tubal pathology, prior abortion, prior infertility, assisted reproductive technology, and oral contraceptive method (p>0.05). However, there was a significant association between prior ectopic pregnancy, prior tubal ligation, use of intrauterine device, and prior abdominal/pelvic surgery with ectopic pregnancy (p<0.05). The risk of ectopic pregnancy increased with the use of intrauterine device and tubal ligation, whereas decreased with use of oral contraception. Conclusion: This study identified prior ectopic pregnancy, prior tubal ligation, use of intrauterine device, and prior pelvic/abdominal surgery as the main risk factors for ectopic pregnancy in a sample of Iranian women. Our findings can be useful for early diagnosis of ectopic pregnancy and for improvement in strategies of its prevention through medical therapy instead of unnecessarily surgical treatment.

163-166

Authors: Fakhrolmolouk Yassaee , Masoumeh Farahani , Ali Reza Abadi

Background: Maternal subclinical hypothyroidism during pregnancy is associated with various adverse outcomes. Recent consensus guidelines advocate universal thyroid function screening during pregnancy. There are no data from Iran about the prevalence of thyroid hypofunction in pregnancy. This study aims to find the prevalence of thyroid dysfunction. Materials and Methods: In this descriptive cross sectional study, thyrotropin (TSH) was measured in 3158 pregnant women irrespective of gestational age from October 2008-March 2012. If TSH was more than 2.5 mIU/L in the first trimester or more than 3 mIU/L in the second or third trimester, free T4 was measured to diagnose subclinical / overt hypothyroidism. If serum free T4 was in the normal range (0.7-1.8 ng/dl) the diagnosis was subclinical hypothyroidism and if below the normal range, overt hypothyroidism was diagnosed. Results: A total of 3158 pregnant women were evaluated. One hundred forty seven of them were diagnosed as hypothyroidism. Subclinical hypothyroidism and overt hypothyroidism were present in 131 (89.1%) and 16 (10.9%) women respectively. Prevalence of subclinical hypothyroidism was 4.15%. Most of the subclinical and overt hypothyroidism cases were diagnosed in the first trimester. Conclusion: It appears logical to check TSH during pregnancy due to the observed prevalence of subclinical hypothyroidism.

175-182

Authors: Ashraf Kazemi , Fatemeh Ramezanzadeh , Mohammad Hosein Nasr Esfahani , Ali Akbar Saboor-Yaraghi , Saharnaz Nejat , Abbas Rahimi-Foroshani

Background: This study evaluated the impact of body mass index (BMI), total calorie intake and physical activity (PA) as energy expenditure related factors on oxidative stress (OS) in follicular fluid (FF). Materials and Methods: This prospective study conducted on 219 infertile women. We evaluated patients’ BMI, total calorie intake and PA in their assisted reproduction treatment cycles. Malondialdehyde (MDA) and total antioxidant capacity (TAC) in pooled FF at oocyte retrieval were additionally assessed. Results: There was no relation between OS biomarkers to total calorie intake and PA. The TAC levels in FF adjusted for age, duration of infertility, etiology of infertility, number of used gonadotrophin and PA showed a positive relation to BMI (p=0.001). The number of used gonadotrophin and PA had a negative relation to duration of infertility (p=0.03) and anovulation disorder as an etiology of infertility. The MDA level in FF had a positive association with anovulation disorder as the etiology of infertility (p=0.02). MDA in FF was unaffected by BMI. Conclusion: Increasing age, BMI and PA do not affect OS in FF. In women with longtime infertility and those with anovulation disorder as an etiology of infertility, decreased potent antioxidant defense in the follicular microenvironment may contribute to ovarian function. Therefore antioxidant supplements may be beneficial for these groups of women.

193-206

Authors: Sara Mostafapour , Samad Zare , Rajab Ali Sadrkhanlou , Abbas Ahmadi , Mazdak Razi

Background: The prevalence of hyperprolactinemia following administration of conventional antipsychotic drugs requires further investigation. The current study is designed to evaluate the effect of sulpiride (SPD)-induced hyperprolactinemia on alterations to ovarian follicular growth, gonadotropins, and ovarian hormones and to analyze the extent of potential problems in mammary glands. Materials and Methods: A total of 40 albino Wistar rats were divided into four groups: control (no treatment), control-sham (0.3 ml olive oil), low dose SPD (20 mg/kg) and high dose SPD (40 mg/kg). All compounds were intraperitoneally (IP) administered for a period of 28 days. Results: After 28 days, we dissected the rats’ ovarian tissues, uterine horns and mammary glands which were sent for histological analyses. We counted the numbers of normal, atretic follicles and corpora lutea (CL). Serum levels of prolactin (PRL), estradiol, progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were evaluated. SPD-administered animals showed sporadic follicular atresia in different sizes associated with higher numbers of CL on the ovaries. The mammary glands exhibited features of galactorrhea. There was remarkable (p<0.05) elevation in SPD-administered animals’ uterine horn endometrium, myometrium and perimetrium thicknesses. The serum levels of PRL and progesterone significantly (p<0.05) increased, while the serum concentration of estradiol, LH and FSH notably (p<0.05) decreased according to the SPD administered dose. No histological and biological changes occurred in control-sham animals. SPD-induced animals had unsuccessful attempts at mating and decreased pregnancy rates. Conclusion: The present findings suggest that SPD-induced disturbances depend on PRL level. In addition, an increased PRL level is largely dependent on the administered doses of SPD.

215-220

Authors: Fariba Mahmoudi , Homayoun Khazali , Mahyar Janahmadi

Background: Kisspeptin and naloxone stimulate the reproductive axis while morphine inhibits its function. We have investigated the effect of central injection of kisspeptin-10 on mean plasma testosterone concentration in morphine or naloxone pretreated rats. Materials and Methods: In this experimental study, 60 male Wistar rats that were divided into 12 groups (n=5 per group) received saline, kisspeptin (1 nmol, ICV), naloxone (2 mg/kg, subcutaneously), morphine (5 or 10 mg/kg, sc) or co-administrations of kisspeptin, morphine and naloxone at 09:00 - 09:30. In the co-administrated groups, kisspeptin was injected 15 minutes following morphine or naloxone injections. Blood samples were collected 60 minutes following injections via the tail vein. Plasma testosterone concentration was measured by a rat testosterone ELISA kit. Results: Central injection of kisspeptin or subcutaneous injection of naloxone significantly increased the mean plasma testosterone concentration compared to saline while subcutaneous injections of different doses of morphine (5 or 10 mg/kg) significantly decreased testosterone compared to saline. The results revealed that morphine significantly attenuated the testosterone increase after kisspeptin injection compared to kisspeptin while a stimulatory additive effect was observed in the kisspeptin/naloxone group compared to either naloxone or kisspeptin. Conclusion: Morphine and kisspeptin systems may interact with each other to control the hypothalamic-pituitary-gonadal (HPG) axis.

245-252

Authors: Firoozeh Ahmadi , Fatemeh Zafarani , Gholam Shahrzad

Female genital tuberculosis (TB) remains as a major cause of tubal obstruction leading to infertility, especially in developing countries. The global prevalence of genital tuberculosis has increased during the past two decades due to increasing acquired immunodeficiency syndrome (AIDS). Genital TB is commonly asymptomatic, and it is diagnosed during infertility investigations. Despite of recent advances in imaging tools, such as computerized tomography (CT) scan, magnetic resonance imaging (MRI) and ultrasongraphy, hysterosalpingography is still the standard screening test for evaluation of tubal infertility and a valuable tool for diagnosis of female genital tuberculosis. Tuberculosis gives rise to various appearances on hysterosalpingography (HSG) from non-specific changes to specific findings. The present pictorial review illustrates and describes specific and non-specific radiographic features of female genital tuberculosis in two parts. Part I presents specific findings of tuberculosis related to tubes such as "beaded tube", "golf club tube", "pipestem tube", "cobble stone tube" and "leopard skin tube". Part II describes adverse effects of tuberculosis on structure of endometrium and radiological specific findings such as "dwarfed" uterus with lymphatic intravasation and occluded tubes, "T-shaped" tuberculosis uterus, "pseudounicornuate" uterus and "Collar-stud abscess", which have not been encountered in the majority of non-tuberculosis cases.

267-270

Authors: Mahboobeh Shirazi , Ezat Abbariki , Ali Hafizi , Fatemeh Shahbazi , Mozhgan Bandari , Ebrahim Dastgerdy

Background: Group B streptococcus colonization in pregnant women usually has no symptoms, but it is one of the major factors of newborn infection in developed countries. In Iran, there is a little information about the prevalence of maternal colonization and newborns infected by group B streptococcus. In order to find the necessary information to create a protocol for prevention and treatment of group B streptococcus infection in newborns, we conducted a study of its prevalence among Iranian pregnant women and its vertical transmission to their newborns. Materials and Methods: This is a cross-sectional descriptive and analytic study performed at Prenatal Care Clinic of the Sarem Hospital from 2009 to 2011. The pregnant women with the gestational age of 35-37 weeks were enrolled in the study. The vaginal culture for group B streptococcus was done for 980 mothers based on our protocol. Among 980 mothers, 48 were shown positive vaginal culture; however, 8 cases among these 48 mothers were positive for both vaginal and urine culture. Babies with mothers showing positive vaginal culture were screened for infection using complete blood count /blood culture (B/C) and C-reactive protein (CRP). Then, a complete sepsis workup was performed for babies with any signs of infection in the first 48 hours after birth, and they received antibiotic therapy if necessary. All collected data were analyzed (SPSS version 15). Results: Among 980 pregnant women with vaginal culture, 48 cases had positive group B streptococcus cultures among which 8 mothers also had positive group B streptococcus urine culture. Our findings revealed that 22 (50%) symptomatic neonates were born from the mothers with positive vaginal culture for group B streptococcus. About 28 of them (63%) had absolute neutrophil count more than normal, and 4 (9.1 %) newborns were omitted from the study. Therefore, 50% of neonates showed clinical feature, whereas para-clinical test was required to detect the infection for the rest of neonates who showed no signs or symptoms. Conclusion: The colonization of group B streptococcus in Iranian women is significant, while 50% of newborns from mother with positive vaginal culture were symptomatic after birth; therefore, screening of newborns for group B streptococcus infection is recommended to become a routine practice in all healthcare centers in Iran.

275-280

Authors: Javad Jamshidi , Farkhondeh Pouresmaeili , Hossein Darvish , Davood Omrani , Eznollah Azargashb , Mohammad Reza Sadeghi , Niknam Lakpour

Background: Fatty acid binding proteins (FABPs) are members of the intracellular lipid binding protein (iLBPs) family and most of them show tissue specific expression. FABP9/PERF15 (Perforatorial15) is the male germ cell-specific fatty acid-binding protein. It was first identified as the major constituent of the murine sperm perforatorium and perinuclear theca. To date, investigations in mice have demonstrated that this protein has a role in the male reproductive system, especially in spermatogenesis. Also, it has been reported that FABP9 can protect sperm fatty acids from oxidative damage. Recently it was shown that it can affect sperm morphology in mice. Based on these findings, we designed a study to evaluate if mutations of this gene can affect sperm morphology in humans. Materials and Methods: In this case-control study, DNA was extracted from peripheral blood of 100 infertile males with normal sperm count but with a number of morphologically abnormal sperms in their semen that was above normal. Four exons and one intron of the FABP9 gene were amplified by polymerase chain reaction (PCR), re-sequenced and then analyzed for mutation detection. Results: We did not detect any mutation in any area of the four exons, intron 3 and splice sites of FABP9 gene in any of the studied 100 samples. Conclusion: There was no mutation in the exonic regions and the poor sperm morphology. However, we didn’t analyze the promoter, intron 1 and 2 to establish conclusions regarding the association of these genic regions and sperm dysmorphology.

291-300

Authors: Irene Molina , María del Carmen Gonzalvo , Ana Clavero , Miguel Ángel López-Ruz , Juan Mozas , Juan Pasquau , Antonio Sampedro , Luis Martínez , José Antonio Castilla

Background: Assisted reproductive technology (ART) with washed semen can achieve pregnancy with minimal risk of horizontal and vertical transmission of chronic viral diseases (CVD) such as human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) among serodiscordant couples. However, few studies have been made of the use made by these couples of ARTs or of the obstetric results achieved. Materials and Methods: In this retrospective study, 93 men who were seropositive for HIV, HCV or HBV and who underwent assisted reproduction treatment at our centre (Hospital Universitario Virgen de las Nieves, Granada, Spain) were included. Washed semen was tested to detect viral particles. Non-infected women were tested before and after each treatment, as were the neonates at birth and after three months. Results: A total of 62 sperm samples were washed, and none were positive for the detection of viral molecules. Semen samples from 34 HBV positive males were not washed since the female partner had immunity to hepatitis B. In total, 38 clinical pregnancies were achieved (22% per cycle and 40.9% per couple) out of 173 cycles initiated, and 28 births were achieved (16.2% per cycle and 30.1% per couple), producing 34 live births. The rate of multiple pregnancies was 21.4%. Obstetric and neonatal results were similar in the groups of couples studied. At follow-up, no seroconversion was detected in the women or neonates. Conclusion: Sperm washing and intracytoplasmic sperm injection are shown to be a safe and effective option for reducing the risk of transmission or super infection in serodiscordant or concordant couples who wish to have a child. Pregnancies obtained by ART in couples when the male is CVD infected achieve good obstetric and neonatal results.

313-322

Authors: Shiva Nasiraei-Moghadam , Kazem Parivar , Abolhasan Ahmadiani , Mansoureh Movahhedin , Mohammad Reza Vaez Mahdavi

Background: The goals of the study are evaluation the effects of food deprivation and isolation situation as a social stress on fertility; and in the following, investigation of the improving effect of melatonin as an antioxidant component. Materials and Methods: In this experimental study, We investigated histopathological and serological effects of melatonin and social stress (food deprivation and isolation) on different features of sperm and testicular tissue among 42 male rats in 7 groups including control, sham, melatonin received (M), food deprivation (FD), Food deprivation and melatonin treatment (FDM), Food deprivation and isolation situation (FDi), and Food deprivation and melatonin treatment and isolation situation (FDMi) groups. Epididymal sperms of all rats were also counted. Histopathological evaluation of the testes was done under a light microscopy to determine the number of spermiogenic cells. Serological evaluation of testosterone, corticosterone, and melatonin was performed, as well. For statistical analysis, one-way ANOVA and Tukey’s post hoc test were used, and the value of p≤0.05 was considered statistically significance. Results: The result showed that food deprivation increased the number of abnormal, immotile, and dead sperms, while decreased the number of normal sperms (p<0.05). Isolation could improve sperm motility and viability, while enhanced the number of spermatogenic cells. Melatonin had a protective effect on sperm count, motility, and viability, while reduced sperm abnormality. Conclusion: Our results demonstrated that melatonin treatment and isolation situation improve the parameters related to epididymal sperms and spermatogenic cells after food deprivation.

331-336

Authors: Yunus Yildiz , Gülnur Ozaksit , Bekir Serdar Unlu , Emre Ozgu , Hasan Energin , Metin Kaba , Mustafa Ugur

Background: To investigate the relationship between adiponectin, metabolic and hormonal parameters, and insulin resistance in patients with non-treated polycystic ovary syndrome. Materials and Methods: In this cross-sectional observational study, 81 patients admitted to out-patient clinic with complaints of menstrual irregularity, hirsutism and obesity were enrolled. Serum adiponectin, biochemical and hormonal parameters, and 75 gram oral glucose tolerance test (OGTT) were measured. Spearman’s correlation coefficient was used for statistical analysis. Results: We observed inverse correlations between serum adiponectin level and body mass index, homeostasis model assessment insulin-resistance score, insulin level, fasting glucose level, and prolactin level (p=0.001, p=0.02, p=0.04, p=0.02, and p=0.005, respectively). No significant correlations were found between serum adiponectin level and age, height, weight, Ferriman-Gallwey score, 2 hours OGTT test value and free testosterone level (p=0.3, p=0.6, p=0.2, p=0.8, p=0.9, and p=0.01, respectively). Conclusion: The present study demonstrated that in polycystic ovary syndrome patients, when serum adiponectin level decreased, degree of insulin resistance increased. Our findings indicate that serum adiponectin level is likely to be an adequate marker for determination of the degree of insulin resistance, and may be a predictor of diseases, such as type 2 diabetes mellitus (T2DM) and metabolic syndrome, which develop on the basis of insulin resistance.

345-348

Authors: Funda Gungor Ugurlucan , Burcin Karamustafaoglu , Ahmet Cem Iyibozkurt , Isin Kilicaslan , Yasar Caliskan , Mehmet Ozsurmeli , Ercan Bastu , Faruk Buyru

We report a case that developed nephrotic syndrome during hospitalization for severe ovarian hyperstimulation syndrome without history of acute renal failure. During hospitalization, she developed persistent ascites and respiratory distress. The 24 hours urine protein analysis revealed significant proteinuria and renal biopsy showed global and segmental sclerosis in glomeruli, mesangial arteritis, proliferations in visceral epithelial cells (IgA nephropathy). To the best of our knowledge, such a complication will be presented for the first time in the literature.

353-356

Authors: Levent Verim

Disorders of sexual development (DSD) are congenital anomalies due to atypical development of chromosomes, gonads and anatomy. Complete androgen insensitivity syndrome (CAIS), also known as testicular feminization (TF) is a rare DSD disease. The majority of CAIS patients apply to hospital with the complaint of primary amenorrhea or infertility. Given that CAIS patients are all phenotypically female while having 46, XY karyotypes, CAIS diagnosis should be disclosed in an age-appropriate manner preferably by a mental health professional. Cases are reported here for three 46XY siblings consistent with CAIS.