International Journal of

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Background: Premature ovarian failure (POF) is a common condition; its incidence is estimated to be as great as 1 in 100 by the age of 40 years. Physiologic replacement of ovarian steroid hormones seems rational until the age of normal menopause. Temporary return of ovarian function and pregnancy may occur rarely in women with POF. We report a case of POF who conceived during hormone replacement therapy.
Case: A 30 years-old woman with confirmed POF after pelvic surgery and sever emotional stress conceived spontaneously.
Conclusion: Return of ovarian function and achievement of pregnancy is possible in women with POF.

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 Background: Controlled ovarian hyperstimulation and intrauterine insemination (IUI) cycle is an ideal protocol for some subfertile patients. So, we decided to try this therapeutic protocol for the patients with unilateral tubal blockage diagnosed by hysterosalpingography (HSG).       
Objective: To evaluate the effect of unilateral tubal blockage diagnosed by HSG on cumulative pregnancy rate (CPR) of the stimulated IUI cycles.          
Materials and Methods: A cross-sectional analysis was performed between October 2006 and October 2009 in an academic reproductive endocrinology and infertility center. Two groups of patients undergoing stimulated IUI cycles were compared. Sixty-four infertile couples with unilateral tubal blockage diagnosed by HSG as the sole cause of infertility in the group (І), and two hundred couples with unexplained infertility in the group (II). The patients underwent 3 consecutive ovarian hyperstimulation (Clomiphen citrate and human menopausal gonadotropin) and IUI cycles. The main outcome measurements were the CPRs per patients for 3 consecutive stimulated IUI cycles.                                            
Results: Cycle characteristics were found to be homogenous between the both groups. CPRs were similar in group І (26.6%) and group II (28%) (p=0.87; OR=1.075; 95% CI: 0.57 -2.28).
Conclusion: Unilateral tubal blockage (diagnosed on HSG) has no effect on success rate of stimulated IUI cycles, so COH and IUI could be recommended as the initial therapeutic protocol in these patients.

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Background: Clomiphene citrate (CC) an agonist and antagonist of estrogen, is the first line treatment in ovarian stimulation. Anti-estrogenic effect of CC in endometrial thickness and cervical mucus has negative effect on pregnancy rate. Letrozole is an Aromatase Inhibitor has been seen that has acceptable pregnancy rate compared to CC.
Objective: The aim of this study was to compare the efficacy of letrozole and clomiphene citrate (CC) with gonadotropins for ovarian stimulation in women candidate for intrauterine insemination (IUI).
Materials and Methods: One hundred sixty patients eligible to IUI therapy enrolled in this study. Patients randomized to two groups: group A (received letrozole-gonadotropin) and group B (received CC-gonadotropin). In group A (n=80) letrozole was given on days 3-7 of the menstrual cycles. In group B clomiphen citrate was given like letrozole combined with human menopausal gonadotropin (hMG) administered every day starting on day 8. Ovulation was triggered with urinary HCG when the leading follicle (s) reached 18 mm in diameter. A single IUI was performed 36-40 hours later. The ovarian stimulation response (E2 levels and number of follicles, clinical pregnancy and endometrial thickness) was primary outcome.
Results: Both groups were similar in demographic characteristics. There was a significantly lower peak serum E2 level in the letrozole group compared with CC. (236±86 Vs. 283±106 pg/mL, respectively; p<0.002). The number of mature (>18 mm) preovulatory follicles was significantly higher in CC group than letrozole group (2.2±.68 Vs. 2.02±0.63 respectively; p=0.025). Endometrial thickness measured at the time of hCG administration was significantly higher in letrozole group. (9.08±1.2 mm Vs. 8.1±1.9 mm; p=0.0001). The clinical pregnancy rate was comparable between two groups.
Conclusion: Letrozole is a good and cost-effective alternative to CC in IUI cycles.

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Background: Fetal growth in diabetic pregnancies is a complex process and probably abnormalities in other metabolic pathways such as protein and lipid, as well as carbohydrate are responsible for delivering of macrosomic newborn.
Objective: The purpose of this study was to investigate the association between fetal growth and different maternal metabolic parameters in women with gestational diabetes mellitus (GDM) in comparison to control group.
Materials and Methods: This was a prospective cohort study conducted between March 2011 and May 2012, on 112 pregnant women with GDM and 159 healthy pregnant women. In order to determine of lipids or lipoproteins changes during pregnancy and to investigate any possible effects on fetal growth, lipid components, glucose and insulin levels were obtained in maternal serum three times in third trimester.
Results: Maternal serum glucose, total cholesterol (TC), low and high density lipoprotein (LDL-c, HDL-c) levels did not show any significant difference between two groups. While insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and triglyceride (TG) values were detected to be significantly higher in the GDM cases especially after 32 weeks of gestation (p<0.001). After adjustment for confounding variables, maternal hypertriglyceridemia remained as a significant risk factor for delivering large for gestational age (LGA) newborns (p=0.04); and according to spearman test the increase of TG level was correlated with increase of insulin resistance and HOMA-IR (p<0.001, CI: 0.312).
Conclusion: Due to positive correlation of hypertriglyceridemia and hyperinsulinemia with newborn weight, it is possible to assume that elevated TGs levels in GDM cases is a reflection of variation in maternal insulin levels.

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Background: The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established.
Case: High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy.
Conclusion: Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy.

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Premature ovarian failure (POF) is a heterogeneous syndrome with several causative factors. Autoimmune mechanisms are involved in pathogenesis of 4-30 % of POF cases. The present review focuses on the role of autoimmunity in the pathophysiology of POF. The evidences for an autoimmune etiology are: demonstration of ovarian autoantibodies, the presence of lymphocytic oophoritis, and association with other autoimmune disorders. Several ovarian antigenic targets have been identified in POF patients. The oocyte seems to be the most often targeted cell. Lymphocytic oophoritis is widely present in POF associated adrenal insufficiency. Addisonۥs disease is one of the most common autoimmune disorders associated with POF. Early detection of this potentially life threatening disease was recommended in several studies. The gold standard for detecting autoimmune POF is ovarian biopsy. This procedure is not recommended due to unknown clinical value, expense, and risks. Several immunoassays have been proposed as substitute diagnostic tools. Nevertheless, there is no clinically proven sensitive and specific serum test to confirm the diagnosis of autoimmune POF or to anticipate the patient’s chance of developing POF or associated diseases. Some authors suggested the possible effects of immuno-modulating therapy on the resumption of ovarian function and fertility in a selected group of autoimmune POF patients. However, in most instances, this treatment fails to reverse the course of the disease. Numerous studies illustrated that standard treatment outcome for infertility is less effective in the presence of ovarian autoimmunity. The antibody-induced damage could be a pathogenic factor. Nevertheless, the precise cause remains obscure.

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Background: Recurrent pregnancy loss (RPL) defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) genes are closely related to fibrinolytic process, embryonic development and pregnancy success.
Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes.
Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two) were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I) polymorphism was determined by PCR-RFLP.
Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%), and 5 controls (5%) (p=0.006) so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84). In addition, 7 patients (7 %), and no one from the control group, were homozygote (I/I) for ACE polymorphism (p=0.034), suggesting no significant associations between ACE D allele or DD genotype and RPL.
Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL.

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Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is the most common cause of infertility due to anovulation. There is no single criterion for the diagnosis of this syndrome.
Objective: The purpose of this study was to investigate the prevalence of PCOS and its associated complications in Iranian women using meta-analysis method.
Materials and Methods: Prevalence of PCOS was investigated from the SID, Goggle scholar, PubMed, Magiran, Irandoc, and Iranmedex, and weighting of each study was calculated according to sample size and prevalence of the binomial distribution. Data were analyzed using a random-effects model meta-analysis (Random effects model) and the software R and Stata Version 11.2.
Results: 30 studies conducted between the years 2006 to 2011 were entered into meta-analysis. The total sample size was 19, 226 women aged between 10-45 years. The prevalence of PCOS based on National institute of child health and human disease of the U.S was, 6.8% (95 % CI: 4.11–8.5), based on Rotterdam was 19.5% (95 % CI: 2.24-8.14), and based on ultrasound was 4.41% (95% CI: 5.68-4.14). Also, the prevalence of hirsutism was estimated to be 13%, acne 26%, androgenic alopecia 9%, menstrual disorders 28%, overweight 21%, obesity 19%, and infertility 8%.
Conclusion: The prevalence of PCOS in Iran is not high. However, given the risk of complications such as heart disease - cardiovascular and infertility, prevention of PCOS is important; we suggest that health officials must submit plans for the community in this respect.

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Background: So far, non-invasive diagnostic approaches such as ultrasound, magnetic resonance imaging, or blood tests do not have sufficient diagnostic power for endometriosis disease. Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis.
Objective: The present study focuses on the identification of predictive biomarkers in serum by pattern recognition techniques and uses partial least square discriminant analysis, multi-layer feed forward artificial neural networks (ANNs) and quadratic discriminant analysis (QDA) modeling tools for the early diagnosis of endometriosis in a minimally invasive manner by 1H- NMR based metabolomics.
Materials and Methods: This prospective cohort study was done in Pasteur Institute, Iran in June 2013. Serum samples of 31 infertile women with endometriosis (stage II and III) who confirmed by diagnostic laparoscopy and 15 normal women were collected and analyzed by nuclear magnetic resonance spectroscopy. The model was built by using partial least square discriminant analysis, QDA, and ANNs to determine classifier metabolites for early prediction risk of disease.
Results: The levels of 2- methoxyestron, 2-methoxy estradiol, dehydroepiandrostion androstendione, aldosterone, and deoxy corticosterone were enhanced significantly in infertile group. While cholesterol and primary bile acids levels were decreased. QDA model showed significant difference between two study groups. Positive and negative predict value levels obtained about 71% and 78%, respectively. ANNs provided also criteria for detection of endometriosis.
Conclusion: The QDA and ANNs modeling can be used as computational tools in noninvasive diagnose of endometriosis. However, the model designed by QDA methods is more efficient compared to ANNs in diagnosis of endometriosis patients.

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Background: Premenstrual syndrome (PMS) is among the most unfavorable problems in women in reproductive age; however its pathophysiology is still not fully confirmed. Vitamin D as an immunomodulator could prevent inflammatory state before and during menstruation.
Objective: The aim was to investigate whether there is any relationship between serum vitamin D levels and PMS.
Materials and Methods: In total, 82 women participate in this case-control study which was conducted in Shahid Akbar-abadi hospital from November 2013 to March 2015. Categorization was based on an Iranian version of the premenstrual symptoms screening tool (PSST). Levels of 25 hydroxy-vitamin D3 (25OHD) were determined by using 25-OH Vitamin D ELISA kit in luteal phase. Characteristics of participants and vitamin D levels were compared between two groups by using independent sample t-test.
Results: Menarche age of women with PMS was significantly lower than normal women (p=0.04). Body mass index was not statistically different between groups. We observed a high rate of vitamin D deficiency and also its severe deficiency in both PMS and non-PMS groups. However, our study demonstrated no significant difference in the levels of serum 25OHD between the two groups.
Conclusion: It seems there is no association between PMS and serum levels of vitamin D3; however, the high rate of vitamin D deficiency amon

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Background:Gonadotropin-releasing hormone (GnRH) antagonist protocol has been proposed as a potentially proper option for the patients with limited ovarian reserve. Nevertheless, there is no significant difference in terms of clinical pregnancy between the GnRH antagonist and agonist cycles. The use of aromatase inhibitors such as letrozole was suggested by some studies.
Objective: The object of this study was to evaluate the efficacy of letrozole co-treatment with GnRH-antagonist protocol in ovarian stimulation of poor responder patients undergoing intracytoplasmic sperm injection.
Materials and Methods: A double-blinded randomized control trial was conducted on 70 infertile women with poor ovarian response based on Bologna criteria in two groups: letrozole+GnRH-antagonist (LA) group and placebo+GnRH-antagonist (PA) group (n=35/each). The LA group involved at letrozole 2.5 mg daily over 5 days and recombinant human follicle stimulating hormone 225 IU/daily. The PA group received placebo over 5 days and recombinant human follicle stimulating hormone at the same starting day and dose, similar to LA group. GnRH-antagonist was introduced once one or more follicle reached ≥14 mm. The main outcome measures were the number of oocytes retrieved, fertilization rate, implantation rate, cycle cancellation rate, and clinical pregnancy rate.
Results: There were no significant differences in demographic characteristics between groups. There were no significant differences between groups regarding the number of oocytes retrieved (p=0.81), number of embryos transferred (p=0.82), fertilization rate (p=0.225), implantation rate (p=0.72), total cycle cancelation rate (p=0.08), and clinical pregnancy rate (p=0.12).
Conclusion: The use of letrozole in GnRH-antagonist cycles does not improve clinical outcomes in poor responder patients undergoing intracytoplasmic sperm injection.

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Background: Uncontrolled increase of C-section is one of the major problems in Iranian health system, such that C-section is the most common surgical procedure in the entire country’s hospitals in Obstetrics and Gynecology sections. A variety of complications also come along with cesarean.
Objective: The aim of this study was to evaluate the prevalence, causes, and complications of cesarean in Iran.
Materials and Methods: forty-one articles were considered with respect to certain criteria and were included in a systematic review to perform a meta-analysis study. The systematic review’s search was conducted on SID, Iranmedx, Magiran, Medlib, PubMed, and Science Direct databases published between1999-2016. The weight of each included study was calculated according to its sample size and the reported prevalence of binomial distribution. A random-effects model using R and STATA (Version 11.2) software was utilized for analyzing data
Results: The total number of the sample was 197514 pregnant women with a mean age of 26.72 yr. The prevalence of cesarean in Iran was estimated at 48%. The main reasons for the prevalence of cesarean in this study were mothers’ higher education, previous cesarean, and doctor recommendation. The most frequent complication in women undergoing cesarean was the muscular pain, and the most common fetal complications in newborns by caesarean delivery was transient tachypnea.
Conclusion: The prevalence of C-section in Iran is much higher than what WHO recommends. It is essential, to decrease such a phenomenon, making the mothers aware of the risks of cesarean delivery, and establishing counselling sessions as well to eliminate the mothers’ fear of vaginal delivery.