Rui Alberto Ferriani

Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome

A longitudinal prospective study was conducted in 21 women with polycistic ovary syndrome (PCOS), aged 27.20 ± 5.02 years and treated with metformin (1500 mg/day) for 8 weeks. The patients were assessed for spontaneous menstruation, weight, body mass index (BMI), waist circumference, waist/hip ratio (WHR), glucose and insulin concentrations under fasting conditions and after a 75-g glucose tolerance test, lipid profile, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF)-I. Spontaneous menstruation was observed in 81% of the women treated with metformin, with no changes in weight or BMI. Waist measurement and the WHR were reduced. The quantitative insulin sensitivity check index (QUICKI) improved from 0.33 ± 0.03 to 0.35 ± 0.04 (p < 0.005), and serum total cholesterol and low-density lipoprotein-cholesterol were reduced, while high-density lipoprotein-cholesterol was increased. Serum testosterone concentrations were also reduced. There were no differences in serum triglycerides, SHBG or IGF-I. The occurrence of spontaneous menstruation and changes in the pattern of body fat distribution, the reduction in serum testosterone concentrations, the improvement in lipid profile and the reduction of insulinemia with the use of metformin permit us to conclude that treatment with this drug is of benefit to women with PCOS.

The impact of examining the meiotic spindle by polarization microscopy on assisted reproduction outcomes

OBJECTIVE To examine the effect of submitting oocytes to polarization microscopy (PM) before intracytoplasmic sperm injection (ICSI). DESIGN Retrospective observational study. SETTING University hospital in Brazil. PATIENT(S) Couples undergoing ICSI. INTERVENTION(S) PM before ICSI (PM group) compared with no PM before ICSI (No-PM group) MAIN OUTCOMES MEASURE(S) Fertilization and cleavage rates, formation of top-quality embryos (TQEs), and implantation, clinical pregnancy, miscarriage, and live-birth rates. RESULT(S) The PM group consisted of 1,000 consecutive oocytes from 201 couples submitted to PM during the year of 2008. The No-PM group consisted of 1,400 oocytes from 249 couples: 700 consecutive oocytes were retrieved before we started using PM and 700 consecutive oocytes were retrieved after we stopped using PM. In the PM group, we observed an increased fertilization rate (79.7% vs. 72.5%, PM group vs. No-PM group, respectively) but reduced cleavage rate (86.2% vs. 92.5%) and TQE formation (33.1% vs. 49.9%). Implantation (18.7% vs. 20.6%), clinical pregnancy (31.8% vs. 33.3%), miscarriage (21.9% vs. 15.7%), and live-birth (24.9% vs. 28.1%) rates were not significantly different between groups. CONCLUSION(S) Use of PM was associated with increased fertilization rate but reduced cleavage rate and TQE formation; no significant difference was observed for implantation, clinical pregnancy, or live-birth rates.

Involvement of Bone Morphogenetic Proteins (BMPs) in Ovarian Function and Infertility

Advances in assisted reproduction techniques and the treatment of diseases known to be correlated with infer- tility such as polycystic ovary syndrome and premature ovarian failure require a better understanding of ovarian physiol- ogy. Despite the enormous quantity of information produced over the last two decades, the mechanisms controlling fol- licular development are not fully understood. Ovarian function is regulated by interactions between gonadotropins, follicle stimulating hormone, luteinizing hormone and local ovarian factors such as inhibins, activins, bone morphogenetic pro- tein-15 (BMP-15) and growth differentiation factor-9 (GDF-9), all members of the transformation and growth factor-� (TGF-� ) superfamily. There is evidence of a functional ovarian BMP system with countless genes involved in normal fol- licular development and in fertility. The present review summarizes the ligands of the TGF-� superfamily, their receptors and signaling pathways and discusses the ovarian functions of the BMPs secreted by the oocytes as critical regulators of fertility.

Three-dimensional ultrasound imaging of an intrauterine device showing copper corrosion.

A few years after the initial insertion a woman’s IUD cord was not visualized during subsequent examinations and annual scans. Seven years later transvaginal sonography (TVS) suggested that the IUD’s copper wire was fragmented and three-dimensional ultrasound imaging confirmed this. Concerned about the IUD’s efficacy doctors decided to remove it because the cord was not visible and there were concerns about the possibility of perforation and fragmentation during removal.

Cardiovascular risk markers among obese women using the levonorgestrel-releasing intrauterine system: A randomised controlled trial

According to international guidelines, women with obesity without other comorbidities can safely use any hormonal contraceptive (HC). However, limited information is available about contraceptive safety for women with obesity since obesity is an exclusion criterion of most contraceptive clinical trials. As such little is known about the possible risks of HC exposure for women with obesity without comorbidities. One way to assess possible long-term risks in this population, even prior to the development of any clinical disease, is to measure alterations in subclinical atherosclerosis markers. We evaluated the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on subclinical markers of cardiovascular risk in women with obesity. This is a randomised clinical trial in which 106 women with obesity [body mass index (BMI)≥30kg/m2] were randomised to the LNG-IUS (n=53) or to non-hormonal methods (n=53) and followed for 12 months. We evaluated waist circumference (WC), blood pressure, blood glucose, insulin, lipid profile, and endothelial function markers (carotid intima-media thickness, brachial artery flow-mediated dilation, and carotid arterial stiffness). At 12 months, BMI (p=0.005), WC (p=0.045), and glucose levels (p=0.015) were significantly lower in the LNG-IUS group than in the control group. We did not find any clinically relevant changes in subclinical markers of cardiovascular risk among with obesity women at 12 months after LNG-IUS placement compared to users of non-hormonal contraceptive methods.

A Randomized Clinical Trial Study of the Effects of Varicocelectomy on Sperm Clinical Analysis and DNA Fragmentation: A Preliminary Data

2Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil *Corresponding author Rosana Maria dos Reis, PhD Sector of Human Reproduction Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo Av. Bandeirantes, 3900 Bairro Monte Alegre, Ribeirão Preto SP 14049-900, Brazil Tel. +55 16 3602-2926 E-mail: romareis@fmrp.usp.br

EP27.02: Ultra-high magnification (IMSI) vs standard sperm selection (ICSI) for assisted reproduction

The development of Mullerian duct anomalies can be explained by two theories: the classical unidirectional caudal to cranial fusion theory and the alternative bidirectional theory suggesting that fusion proceeds simultaneously in both caudal and cranial directions. In the literature case reports inconsistent with the traditional unidirectional theory can be found. We present an uncommon case which supports the alternative theory. A 38-year-old nulligravida presented in our centre for assisted reproductive treatment because of infertility. Considering her personal history, she underwent laparoscopy with hysteroscopy in 2002 where uterus didelphys was suspected and longitudinal vaginal septum was resected. However, another laparoscopy in 2014 revealed the uterus of a normal shape. We decided to perform hysterosalpingo-foam sonography (HyFoSy) with contrast ExEmFoam®. After acquiring a 3D volume of the uterus, two catheters were placed into both external cervical canals and ExEmFoam® was continuously administered first into the left cervical canal and subsequently into the right one. The progress through uterine cavities and tubes was observed in real-time with ultrasound. Finally, a 3D volume of the uterus with contrast foam was acquired. Frontal views of the uterine cavity from 3D volume were rendered. We observed both tubes patent. As for the uterus, we found normal uterine fundus without indentation with symmetrical corns. The cavity was separated with wide septum starting from the fundus and going downwards between the cervices with the lower half of the septum relatively thin. Interestingly, the distinctive oval communication of size 5.5 x 7 mm between both uterine cavities was observed at the level of an upper and middle third of the septum. The final diagnosis of complete septate uterus with double cervix and communication between both cavities is inconsistent with the traditional embryonic theory and suggests the bidirectional theory is more probable.

Effects of clomiphene citrate on pituitary luteinizing hormone and follicle‐stimulating hormone release in women before and after treatment with ethinyl estradiol

OBJECTIVE To evaluate the effects of clomiphene citrate (CC) on pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in hypoestrogenic women and in the same women after treatment with ethinyl estradiol (EE2). DESIGN The study was of a prospective nature and was conducted on selected patients. SETTING Volunteer women were studied in a tertiary care public hospital. PATIENTS The 10 patients studied were selected on the basis of hypogonadal status (menopause, premature ovarian failure, or gonadal dysgenesis and Turner phenotype) and no hormonal treatment. INTERVENTIONS Gonadotropin-releasing hormone (GnRH) was continually infused at the dose of 0.2 micrograms/min for 4 hours before and after the use of CC and/or EE2. MAIN OUTCOME MEASURE The study was performed with the objective of determining the effect of estrogen (E) levels on the action of CC on in vivo gonadotropin release. RESULTS In the presence of hypoestrogenic conditions, CC had no pituitary action. However, after EE2 treatment CC promoted greater FSH release and a significant inhibition of LH release from the pituitary. CONCLUSION Clomiphene citrate needs a basal E level to be able to act on the pituitary. In normoestrogenic states and under GnRH stimulation, CC preferentially promotes FSH release while presenting a predominantly inhibitory effect on LH release.

Progesterone alters the pituitary response to luteinizing hormone releasing hormone in postmenopausal women previously treated with estradiol

The effect of luteinizing hormone-releasing hormone (LHRH) on LH release was studied in 5 menopausal women injected with progesterone. Each patient received 2 x 100 micrograms doses of LHRH administered intravenously 120 minutes apart under the following conditions: without any previous treatment (test 1); 16 hours after intramuscular injection of 10 mg progesterone (test 2); after 3-4 weeks of oral treatment with 50 micrograms/day of ethinyl estradiol (EE2) (test 3); 16 hours after intramuscular injection of 10 mg progesterone following treatment with 50 micrograms/day oral EE2 for 3-4 weeks (test 4). The interval between tests was at least 1 month. Progesterone decreased the total plasma hormonal increment (PHIt) of hypogonadal women, with a reduction in plasma hormonal increment both after the 1st stimulus (PHI1) and after the 2nd stimulus (PHI2), whereas estradiol increased PHIt, mainly due to an increase of PHI2. The administration of progesterone to hypogonadal women previously treated with EE2 maintained the increased PHIt caused by the latter, but not owing to a greater increase in PHI1.