Epigenetic aberration of FMR1 gene in infertile women with diminished ovarian reserve

Objective: The diminished ovarian reserve [DOR] is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone [FSH] levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between the FMR1 premutation [50-200 CGG repeats] and the premature ovarian failure [POF] suggests that epigenetic disorders of FMR1 can act as a risk factor for the DOR as well. The aim of this study was to analyze the mRNA expression and epigenetic alteration [histone acetylation/methylation] of the FMR1 gene in blood and granulosa cells of 20 infertile women

Materials and Methods: In this case-control study, we analyzed the mRNA expression and epigenetic altration of the FMR1 gene in blood and granulosa cells of 20 infertile women. These women were referred to the Royan Institute, having been clinically diagnosed as DOR patients. Our control group consisted of 20 women with normal antral follicle numbers and serum FSH level. All these women had normal karyotype and no history of genetic disorders. The number of CGG triplet repeats in the exon 1 of the FMR1 gene was analyzed in all samples

Results: Results clearly demonstrated significantly higher expression of the FMR1 gene in blood and granulosa cells of the DOR patients with the FMR1 premutation compared to the control group. In addition, epigenetic marks of histone 3 lysine 9 acetylation [H3K9ac] and di-metylation [H3K9me2] showed significantly higher incorporations in the regulatory regions of the FMR1 gene, including the promoter and the exon 1, whereas tri-metylation [H3K9me3] mark showed no significant difference between two groups

Conclusion: Our data demonstrates, for the first time, the dynamicity of gene expression and histone modification pattern in regulation of FMR1 gene, and implies the key role played by epigenetics in the development of the ovarian function

coasting valuable in all patients with any cause of infertility?

Objectives: This study aimed to assess the influence of coasting duration on the number and quality of oocytes and fertilization rate in male factor infertile women and those with polycystic ovary syndrome [PCOS]

Methods: In this prospective observational follow-up study, 114 patients undergoing coasting [53 women with male factor infertility and 61 women with PCOS] were evaluated at the Royan Institute Research Center, Iran, between 2010 and 2012

Results: The results were analyzed according to the coasting periods of 1-4 days. In normal females, the number of oocytes retrieved was significantly reduced after the second day [p = 0.004]. In addition, a statistically significant drop was observed in the number of metaphase II oocytes and fertilization rate after the third day [p = 0.006 and p = 0.006, respectively]. No significant differences were observed in the number and quality of oocytes retrieved and fertilization rate with regard to coasting days in PCOS patients

Conclusion: Coasting with duration of more than three days should be performed with caution in normal females who are at risk of developing ovarian hyperstimulation syndrome

Increasing the number of embryos transferred from two to three, does not increase pregnancy rates in good prognosis patients

To compare the pregnancy outcomes after two embryos versus three embryos transfers [ETs] in women undergoing in vitro fertilization [IVF] intracytoplasmic sperm injection [ICSI] cycles. This retrospective study was performed on three hundred eighty seven women with primary infertility and with at least one fresh embryo in good quality in order to transfer at each IVF/ICSI cycle, from September 2006 to June 2010. Patients were categorized into two groups according to the number of ET as follows: ET2 and ET3 groups, indicating two and three embryos were respectively transferred. Pregnancy outcomes were compared between ET2 and ET3 groups. Chi square and student t tests were used for data analysis. Clinical pregnancy and live birth rates were similar between two groups. The rates of multiple pregnancies were 27 and 45.2% in ET2 and ETS groups, respectively. The rate of multiple pregnancies in young women was significantly increased when triple instead of double embryos were transferred. Logistic regression analysis indicated two significant prognostic variables for live birth that included number and quality of transferred embryos; it means that the chance of live birth following ICSI treatment increased 3.2-fold when the embryo with top quality [grade A] was transferred, but the number of ET had an inverse relationship with live birth rate; it means that probability of live birth in women with transfer of two embryos was three times greater than those who had three ET. Due to the difficulty of implementation of the elective single-ET technique in some infertility centers in the world, we suggest transfer of double instead of triple embryos when at least one good quality embryo is available for transfer in women aged 39 years or younger. However, to reduce the rate of multiple pregnancies, it is recommended to consider the elective single ET strategy

effect of flutamide on ovulation induction in PCOS patients

Polycystic ovary syndrome [PCOS] is a disorder that affects various body organs and requires comprehensive long term evaluation and management. The aim of this study was to evaluate effect of Flutamide on ovulation induction in PCOS patients. This prospective study applied triple blind method, a simple convenience sampling method, to induce ovulations of the ninety six PCOS patients. Patients were divided into two groups; group A included 53 subjects [received Flutamide + Clomiphene Citrate] and group B included 43 subjects [received placebo + Clomiphene Citrate]. Ultrasound was carried to determine the size of follicles and growth rate of them during follicular phase of the menstrual cycle. Also, progesterone levels were measured on days 19 and 21 of the menstrual cycle. In this study, ninety six PCOS patients, in two treatment and control groups, were evaluated regarding to body mass index [BMI], cycle irregularity, age and number of dominant follicles, duration of stimulation, endocrine profile and score of hirsutism. The obtained results revealed no significant differences between two groups. Flutamide does not affect ovulation improvement in PCOS patients undergoing induction

Pregnancy outcome with intracytoplasmic sperm injection method in a woman with prosthetic heart valves

There is an increased risk of thromboembolism, anticoagulant-related hemorrhage, fetal-wastage and congestive cardiac failure in pregnant women with mechanical heart valves. In order to have a good outcome, the care of such patients must necessarily be multidisciplinary and in a well- equipped centre with adequate support services. One such patient who had mechanical mitral and aortic valves replacement in 2000 receiving warfarin anticoagulant therapy, presented with a first trimester pregnancy by ICSI method in 2006. She remained in stable homodynamic state and went through pregnancy without event. Delivery was done by caesarian section at 37 weeks gestation age. With considering use of warfarin during pregnancy, use of stimulation protocol during ICSI and delivering normal neonate ultimately, this interesting case is presented here