TGFß Gene Members and Their Regulatory Factors in Granulosa Compared to Cumulus Cells in PCOS: A Case-Control Study.

OBJECTIVE: Transforming growth factor-beta (TGF-ß) superfamily and its members that include bone morphogenetic protein 15 (BMP15), anti-Mullerian hormone (AMH), growth /differentiation factor-9 (GDF9), and their respective receptors: BMPR1A, BMPR1B, and BMPR2 have been implicated as key regulators in various aspects of ovarian function. The abnormal function of the ovaries is one of the main contributing factors to polycystic ovarian syndrome (PCOS), so this study aimed to investigate the mRNA expression profile of these factors in granulosa (GCs) and cumulus cells (CCs) of those patients. MATERIALS AND METHODS: The case-control research was conducted on 30 women (15 infertile PCOS and 15 normo-ovulatory patients, 22≤age ≤38 years old) who underwent ovarian stimulation for in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) cycle. GCs/CCs were obtained during ovarian puncture. The expression analysis of the aforementioned genes was quantified using real-time polymerase chain reaction (PCR). RESULTS: AMH and BMPR1A expression levels were significantly increased in GCs of PCOS compared to the control group. In contrast, GDF9, BMP15, BMPR1B, and BMPR2 expressions were decreased. PCOS' CC showed the same expression patterns. GDF9 and AMH were effectively expressed in normal CCs, and BMP15 and BMPR1B in normal GCs (P<0.05). CONCLUSION: Differential gene expression levels of AMH and its regulatory factors and their primary receptors were detected in granulosa and cumulus cells in PCOS women. Since the same antagonist protocol for ovarian stimulation was used in both PCOS and control groups, the results were independent of the protocols. This diversity in gene expression pattern may contribute to downstream pathways alteration of these genes, which are involved in oocyte competence and maturation.

Methylprednisolone for prevention of ovarian hyperstimulation syndrome in patients with polycystic ovarian syndrome undergoing in-vitro fertilisation: a randomised controlled trial.

This study aimed to evaluate the effect of methylprednisolone on prevention of ovarian hyperstimulation syndrome (OHSS) in polycystic ovarian syndrome (PCOS) patients undergoing in-vitro fertilisation (IVF). This randomised controlled trial was carried out between November 2009 and December 2013. A total of 219 eligible patients were randomly allocated for treatment (n = 108) or control groups (n = 111). The treatment group received oral methylprednisolone starting from the first day of stimulation. These patients also received an intravenous dose of methylprednisolone on the days of egg collection and embryo transfer. The control group received no glucocorticoid treatment to prevent OHSS. Nineteen percent of patients (18/93) who received methylprednisolone developed OHSS compared with 16.5% (15/91) in the control group and no significant difference was found (p = .61). There were no significant differences between treatment and control groups in the rates of implantation (10% versus 11%, p = .77) and clinical pregnancy (23.2% versus 17.7%, p = .46). Methylprednisolone did not reduce the incidence and severity of OHSS in PCOS patients undergoing IVF and no improvement in clinical outcomes was observed. Impact statement No significant differences were found in OHSS incidence and clinical outcomes between women who received methylprednisolone and control group. There seems to be no benefit for the routine use of glucocorticoids in IVF/ICSI treatments.

Bacterial vaginosis and the risk of early miscarriage in women undergoing intracytoplasmic sperm injection cycles: a prospective cohort study.

This study aimed to assess the possible association of bacterial vaginosis (BV) and early miscarriage in 408 women undergoing intracytoplasmic sperm injection (ICSI) for reasons of male infertility. A vaginal sample was obtained before oocyte retrieval and evaluated for BV-associated bacteria using the Nugent scoring system. The primary outcome was early miscarriage and the secondary outcomes included implantation, pregnancy, late miscarriage, preterm delivery and live birth rates. Chi-square, ANOVA, relative risk and odds ratio were used for data analysis where appropriate. The prevalence of BV was estimated as 7.3%. From 336 patients who had embryo transfer, 138 patients (41.1%) conceived. A total of 17% (n = 23) of pregnant women miscarried during the first trimester: 15 patients (15%) were normal, 4 (17.4%) were intermediate and 4 (26.7%) patients had BV (p = 0.52). The relative risk of early miscarriage in BV patients compared to the non-BV and intermediate group was 1.77 (0.68-4.64, 95% CI). Implantation, pregnancy, preterm delivery and live birth rates were comparable between groups. We conclude that BV does not appear to have an adverse impact on outcomes in women being treated with ICSI for male factor infertility and is not associated with miscarriage and preterm birth.

Accuracy of Two-Dimensional Transvaginal Sonography and Office Hysteroscopy for Detection of Uterine Abnormalities in Patients with Repeated Implantation Failures or Recurrent Pregnancy Loss.

BACKGROUND: We sought to compare diagnostic values of two-dimensional transvaginal sonography (2D TVS) and office hysteroscopy (OH) for evaluation of endometrial pathologies in cases with repeated implantation failure (RIF) or recurrent pregnancy loss (RPL). MATERIALS AND METHODS: This prospective study was performed at Royan Institute from December 2013 to January 2015. TVS was performed before hysteroscopy as part of the routine diagnostic work-up in 789 patients with RIF or RPL. Uterine biopsy was performed in cases with abnormal diagnosis in TVS and/or hysteroscopy. We compared the diagnostic accuracy values of TVS in detection of uterine abnormalities with OH by receiver operating characteristic (ROC) curve analysis. RESULTS: TVS examination detected 545 (69%) normal cases and 244 (31%) pathologic cases, which included 84 (10.6%) endometrial polyps, 15 (1.6%) uterine fibroids, 10 (1.3%) Asherman's syndrome, 9 (1.1%) endometrial hypertrophy, and 126 (15.9%) septate and arcuate uterus. TVS and OH concurred in 163 pathologic cases, although TVS did not detect some pathology cases (n=120). OH had 94% sensitivity, 95% specificity, 62% positive predictive value (PPV), and 99% negative predictive value (NPV) for detection of endometrial polyps. In the diagnosis of myoma, sensitivity, specificity, PPV, and NPV were 100%. TVS had a sensitivity of 50% and specificity of 98% for the diagnosis of myoma. For polyps, TVS had a sensitivity of 54% and specificity of 80%. Area under the ROC curve (AUROC) was 70.69% for the accuracy of TVS compared to OH. CONCLUSION: TVS had high specificity and low sensitivity for detection of uterine pathologies in patients with RIF or RPL compared with OH. OH should be considered as a workup method prior to treatment in patients with normal TVS findings.

Novel +90G>A Intronic Polymorphism of CYP2D6.

OBJECTIVE: CYP2D6, an enzyme, metabolizes a large number of commonly prescribed drugs. Variations in CYP2D6 gene encoding this enzyme have been associated with individual differences in drug metabolism rates. The purpose of our study was to identify some allelic variants of CYP2D6 gene and to detect defective CYP2D6 alleles, as part of a pharmacogenetic screening program. MATERIALS AND METHODS: A prospective study was done on 120 participants referred to Royan Institute in 2013. Allele and genotype frequencies for polymorphism of CYP2D6 gene in exons 1 and 4 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sequencing on PCR products, respectively. RESULTS: We identified a novel variant of the gene encoding cytochrome P450 2D6 (CYP2D6) at position +90 of intron 4 by sequencing method. This novel polymorphism of CYP2D6 has been deposited in GeneBank(®) under the accession number KF225465 in Jun 2013. CONCLUSION: In the current study, we identified novel polymorphism in intron 4. This single nucleotide polymorphism (SNP) is known as +90G>A in the fourth intron.

No relationship between most polymorphisms of steroidogenic acute regulatory (StAR) gene with polycystic ovarian syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine women's disorders in reproductive age. Hyperandrogenism has a critical role in the etiology of PCOS and it can cause fault in Steroidogenesis process. During steroidogenesis, steroidogenic acute regulatory protein (StAR) seems to increase the delivery of cholesterol through mitochondrial membrane. Therefore, polymorphisms of StAR might effect on this protein and play a role in the etiology of PCOS. OBJECTIVE: The aim of this study was to investigate the association between StAR SNPs with PCOS. Thus, seven polymorphisms in this gene: rs104894086, rs104894089, rs104894090, rs137852689, rs10489487, rs104894085 were detected. MATERIALS AND METHODS: In this case control study, 45 PCOS women, 40 male factor/unexplained infertile women, and 40 fertile women as two control groups were participated from 2008-2012. Polymorphisms were detected using restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Heterozygote genotyping for rs137852689 SNP (amino acid 218 C > T) was only seen in seven PCOS patients, one in normal ovulatory women, and five in male factor/unexplained infertile women (15.5%, 2.5%, 12.5%, respectively) (p= 0.12). While, it has shown no association between other SNPS with PCOs. CONCLUSION: The RFLP results for seven chosen SNPs, which located in exon 5 and 7 showed normal status in three groups, it means no heterozygous or homozygous forms of selected SNPs were observed. So, it seems evaluation of the active amino acid sites should be investigated and also the study population should be increased.

Risk factors for ectopic pregnancy: A case-control study.

BACKGROUND: Ectopic pregnancy (EP) is a condition presenting as a major health problem for women of childbearing age. This study aimed to identify potential risk factors for EP and to evaluate the contribution of the risk factors associated to EP. MATERIALS AND METHODS: This retrospective nested case-control study was conducted from 2006 to 2011. In case group, there were a total of 83 women diagnosed with EP, while in the control group; there was a total of 340 women who gave birth. The basic recorded information included surgical, gynecological, obstetrics, sexual, contraceptive, and infectious histories; demographic characteristics; smoking habits; fertility markers; as well as reproductive outcome after EP. The association between EP and the factors studied was analyzed by logistic regression. RESULTS: The findings reveal that the following factors were associated with increased risk of EP, including: Maternal age (odds ratio [OR] =1.11, confidence interval [CI] [1.06-1.16], P < 0.0001), spouse's cigarette smoking (OR = 1.73, CI [1.05-2.85], P = 0.02), gravidity (OR = 1.50, CI [1.25-1.80], P < 0.0001), prior spontaneous abortions (OR = 1.93, CI [1.11-3.36], P = 0.01), history of EP (OR = 17.16, CI [1.89-155.67], P = 0.01), tubal blockage (OR = 10.85, CI [2.02-58.08], P = 0.01), use of intrauterine device (IUD) (OR = 4.39, CI [1.78-10.81], P = 0.001), tubal damage (OR = 2.704, CI [1.26-5.78], P = 0.01), first pregnancy interval (OR = 1.01, CI [1.00-1.02], P < 0.0001) and history of infertility (OR = 6.13, CI [2.70-13.93], P < 0.0001). CONCLUSION: By identifying risk factors being amenable to modification, such as cigarette smoking and use of IUD and first pregnancy interval the effective risk-reduction strategies can be devised.

Comparison of two dimensional and live three dimensional ultrasounds for the diagnosis of septated uterus.

BACKGROUND: Traditionally, septate uterus was diagnosed with invasive method like hysterosalpingography and hysteroscopy. Nowadays transvaginal ultrasonography was reported to be a sensitive tool for detection of septate uterus too. OBJECTIVE: The objective of the present study was to evaluate the application of two dimensional ultrasound (2-DUS) and real time three dimensional ultrasound (3-DUS) in differentiating various type of septated uterus. Hysteroscopy confirmation was assigned as the gold standard. MATERIALS AND METHODS: This retrospective study was performed among 215 infertile women with suspected septate uterus from October 2008 to July 2012. An inclusion criterion was septated uterus based on HSG or experiencing abortion, preterm labor, or recurrent IVF failure. Fusion anomalies were excluded from the study (unicornuate, bicornuate and didelphys anomalies). The results of 3D and 2D sonographies were compared, while they were confirmed by hysteroscopy result in detection of septated uterus. Kappa index for agreement between 2DUS and hysteroscopy, as well as 3-DUS and hysteroscopy in detection of septate uterus was carried out. By receiver operating characteristic (ROC) curve, cut off points for predicting the kind of anomalies were proposed. RESULTS: The women were evaluated by 2-DUS (n=89) and (II) 3-DUS (n=126). All women underwent hysteroscopy, following 2-DUS and 3-DUS at the same or subsequent cycle. The results of kappa (K) index were 0.575 and 0.291 for 3-DUS and hysteroscopy, as well as 2-DUS and hysteroscopy, respectively. Also, the cutoff points were 27% for arcuate and subseptate, and 35% for differentiating septate and subseptate. CONCLUSION: Real time 3-DUS has better ability for visualization both uterine cavity and the fundal uterine, so it has higher agreement in detection of septate uterus than 2-DUS.

Comparison of the outcomes between reduced and nonreduced triplet pregnancies achieved by Assisted Reproductive Technology.

BACKGROUND: In recent years, the significant increase in multiple pregnancies as a result of assisted reproductive technology (ART) has introduced the concept of multifetal reduction techniques. However, it is still unclear whether there are significant advantages of using this technique. AIM: To compare the outcomes of triplet pregnancies achieved by ART managed expectantly with those receiving fetal reduction interventions. MATERIALS AND METHODS: In this retrospective study of 115 triplet pregnancies, 57 pregnancies were reduced to twins while 58 were managed expectantly. RESULTS: The fetal loss rate before 24 weeks did not differ between reduced and nonreduced pregnancies (12.3% vs 12.1%). However, the results of those using fetal reduction techniques showed a lower incidence of preterm labour (26.3% vs 50%, P = 0.009), higher mean gestational age at delivery (35.1 ± 2.6 vs 32.4 ± 3.6 weeks, P = 0.002) and higher mean birthweights compared with the control group (2188 ± 547 vs 1674 ± 546 g, P < 0.001). The perinatal mortality rate was significantly lower in reduced triplets compared with those expectantly managed (6% vs 17.6%, P = 0.007). The rate of live birth was 94% in reduced and 82.4% in nonreduced pregnancies (P = 0.007). The percentages of neonates admitted to the neonatal intensive care unit (NICU) were 27.7 and 62.7% in reduced and nonreduced pregnancies, respectively (P < 0.001). CONCLUSIONS: In this observational cohort study reduction of triplets to twins decreased prematurity and increased birthweight without an increase in fetal loss. Additionally, there was a lower perinatal mortality, higher live birth rate and lower NICU admission.

The Survival of a 580 g Infant Conceived by In vitro.

With recent improvements in maternal fetal medicine and neonatal intensive care, the survival rates of extremely low birth weight infants have been improved. In this report we describe the case of an extremely low birth weight infant due to preeclampsia, who was conceived by in vitro fertilization and is in complete physical and mental health after a one - year follow - up.