Cycle outcomes of dual trigger (GnRH agonist+hCG) versus human chorionic gonadotropin trigger alone in POSEDION group 3-4 poor-responders and normo-responders: A prospective randomized study.

INTRODUCTION: Recently, dual trigger was proposed in an attempt to improve in vitro fertilization (IVF) cycle outcomes in poor and normo-responder patients (PR and NR, respectively). The study's aim was to compare cycle outcomes of dual trigger versus human chorionic gonadotropin (hCG) trigger in NRs and POSEIDON group 3/4 (PG 3/4) PRs. MATERIAL AND METHODS: A prospective randomized controlled trial included PG 3/4 PRs and NRs undergoing IVF using a gonadotropin-releasing hormone (GnRH) antagonist protocol. PRs and NRs were divided into two subgroups: (1) study groups in both arms received dual trigger and (2) control groups received only HCG. RESULTS: Two-hundred twenty-five women participated in the study. The mean patient age was significantly higher in the dual trigger group versus the HCG trigger group in PG 3/4 PRs. The number of retrieved oocytes and MII oocytes and the number of patients with good quality embryos were comparable between groups and live birth rates (LBR) per embryo transfer (ET) were significantly higher in the HCG group versus the dual trigger group in PG3/4 PRs (39.2% versus 19.2%; p = 0.026). NR dual trigger and HCG trigger groups were comparable in terms of patient age and LBR per ET did not significantly differ between these groups. The number of patients with good quality embryos was significantly higher in the dual trigger group versus the HCG group in NRs CONCLUSION: Dual trigger does not seem to add additional benefits in terms of live birth rates in PG3/4 PRs and NRs. Nonetheless, considering the age difference and lack of homogenity in the number and day of embryos transferred in PG 3/4 PRs, major conclusion that can be drawn from the study is that dual trigger is not systematically useful even in poor responders since the number of mature oocytes is comparable between groups. Larger scale studies are required for additional potential implications.

A novel prenatal index predicting the probability of neonatal intensive care in pregnants: amnion progesterone receptor to alfa fetoprotein rate.

INTRODUCTION: Amniocentesis (AC) is the most used interventional procedure for prenatal diagnosis. The study aims to evaluate the pregnancy outcomes undergoing AC and the potential of amnion progesterone receptor (aPR) to alfa fetoprotein (AFP) rate for predicting the probability of neonatal intensive care unit (NICU). MATERIAL AND METHODS: This prospective cross-sectional study population consisted of 85 pregnant women who underwent mid-trimester AC. All cases were screened by ultrasound before AC. Maternal venous and amniotic samples were obtained simultaneously to evaluate the serum progesterone (sPRG), aPR, and aAFP and analyzed with patient results. RESULTS: Unlike sPRG and aAFP, aPR showed a positive correlation with NICU and a negative correlation with parity. In linear regression, the aPR-AFP rate showed strong linearity with NICU and parity. In an aPR-AFP rate analysis, we saw a strong predictivity for NICU compared to the other three parameters. It presented 73.4% specificity and 79% sensitivity at 0.0075 cut-off (AUC: 0.78; p = 0.003; 95% CI: 0.608-0.914). CONCLUSIONS: Evaluating the PR either alone or in a rational combination with AFP will provide physicians with valuable information about the advanced process of pregnancy and postpartum complications. The physicians might use the aPR-AFP rate to predict NICU potential for pregnancy and need further studies to make more vital predictions on postpartum complications.

Pregnancy outcome of freeze thaw cycles of polycystic ovary syndrome patients regarding the anti-Müllerian hormone percentile.

Patients with polycystic ovary syndrome display increased levels of anti-Müllerian hormone. Frozen-thawed embryo transfer (FET) prevents ovarian hyperstimulation and results in better pregnancy outcome in PCOS patients. Therefore, we aimed to evaluate the effect of serum AMH levels on the pregnancy outcome of FET cycles in PCOS patients. 110 infertile women with PCOS who were recommended for embryo cryopreservation followed by FET. The patients' AMH levels were evaluated, and the age-related AMH percentiles were determined. The patients were then grouped according to AMH percentiles, namely, 75th-90th percentile (Group 1) and higher than the 90th percentile (Group 2).A total of 110 PCOS patients who conceived in Frozen Embryo Transfer (FET)-In-vitro Fertilisation (IVF) cycles were included in this study. The preterm delivery rates in FET cycles were higher in the group of PCOS patients with AMH levels greater than the 90th percentile than in patients in the 75th-90th percentile group (50% vs 28.8%, p = .024). In conclusion, PCOS patients with AMH levels higher than the 90th percentile had substantially higher preterm delivery rates than those with AMH levels at the 75th-90th percentile, suggesting the need for closer follow-up. Further studies are needed to elucidate the underlying mechanisms behind this correlation.IMPACT STATEMENTWhat is already known on this subject? The association of AMH levels with the risk of adverse pregnancy outcomes has been previously investigated. In women with PCOS, substantially elevated AMH levels were significantly associated with preterm birth.What do the results of this study add? Results showed that the PCOS patients with higher AMH levels and underwent assisted reproductive treatment demonstrated an increased risk of preterm labour than the PCOS patients with lower AMH levels.What are the implications of these findings for clinical practice and/or further research? In women with PCOS, substantially elevated AMH levels were significantly related to preterm birth, suggesting the need for closer follow-up in this population and the need for further studies to elucidate the underlying mechanisms behind this correlation.

The ratio of anterior anogenital distance to posterior anogenital distance: A novel-biomarker for polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. The etiopathogenesis of the disease remains uncertain. Additionally, a full consensus has not been reached regarding PCOS diagnostic criteria. Several attempts have been made to diagnose PCOS with a simple clinical biomarker, but most of them failed. This study aims to investigate the possible association between PCOS and anogenital distance (AGD), which is an important sign of intrauterine androgen exposure. METHODS: A prospective cohort study was conducted on 130 women. The study group contained 65 women with PCOS whereas 65 healthy women were recruited for the control group, all between 18 and 40 years in age. The groups were compared in terms of demographics and clinical and laboratory parameters. Both anterior and posterior AGDs and associated ratios were recorded for each woman. RESULTS: The mean ratio of anterior AGD to posterior AGD for the PCOS and control group were 4.4 ± 1.0 and 4.9 ± 1.0, respectively (p = 0.003). Regression analysis demonstrated that this ratio significantly and positively correlated with the waist to hip ratio and negatively correlated with the free androgen index. CONCLUSION: AGD was initially used to define sexual differentiation of animals. Subsequent human studies showed that boys have longer AGDs than girls. Recent studies supporting the hypothesis that extreme prenatal androgen exposure contributes to PCOS found that AGD in adult PCOS patients was longer than control PCOS patients. However, a novel biomarker other than AGD needs to be identified to standardize these measurements. This work represents the first study to evaluate the ratio of anterior AGD to posterior AGD in PCOS patients. In this study, AGD anterior and posterior measurements were longer in PCOS patients than in controls. However, the strongest predictor of PCOS is the ratio of anterior to posterior AGD.

Identification of Polycystic Ovary Syndrome (PCOS) Specific Genes in Cumulus and Mural Granulosa Cells.

Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disorder which affects women of reproductive age with prevalence of 8-18%. The oocyte within the follicle is surrounded by cumulus cells (CCs), which connect with mural granulosa cells (MGCs) that are responsible for secreting steroid hormones. The main aim of this study is comparing gene expression profiles of MGCs and CCs in PCOS and control samples to identify PCOS-specific differentially expressed genes (DEGs). In this study, two microarray databases were searched for mRNA expression microarray studies performed with CCs and MGCs obtained from PCOS patients and control samples. Three independent studies were selected to be integrated with naive meta-analysis since raw meta-data from these studies were found to be highly correlated. DEGs in these somatic cells were identified for PCOS and control groups. This study enabled us to reveal dysregulation in MAPK (mitogen activated protein kinase), insulin and Wnt signaling pathways between CCs and MGCs in PCOS. The meta-analysis results together with qRT-PCR validations provide evidence that molecular signaling is dysregulated through MGCs and CCs in PCOS, which is important for follicle and oocyte maturation and may contribute to the pathogenesis of the syndrome.

Heavy metal and trace element concentrations in blood and follicular fluid affect ART outcome.

OBJECTIVES: To assess the effects of heavy metal and trace element concentrations in blood and follicular fluid on assisted reproductive technology cycle outcome. STUDY DESIGN: A prospective study was conducted between January 2012 and July 2012 in a university hospital infertility clinic. One hundred and one patients with unexplained infertility who underwent intracytoplasmic sperm injection using GnRH-antagonist protocol were recruited. Concentrations of four toxic metals (Cd, Pb, Hg, As) and three trace elements (Cu, Zn, Fe) were measured both in blood and follicular fluid specimens. Patients were evaluated in two groups; the study group consisted of patients with ongoing pregnancy (n=20) and the reference group consisted of patients experienced assisted reproductive technology failure, miscarriage or biochemical pregnancy (n=81). RESULTS: Demographics and cycle parameters were comparable between the groups except for median number of day 3 Grade A embryos. Statistically significant negative correlations were found between blood Pb levels and number of MII oocytes, implantation, clinical pregnancy and ongoing pregnancy rates. Results of the log binomial regression revealed 2.2% lower risk for ongoing pregnancy for each 1µg/dL higher blood Pb concentration while holding the other variables in the model constant (RR 0.978; 95% CI 0.956-0.998; P=.041). Also, the results revealed 71.9% lower risk for ongoing pregnancy for each 1µg/dL higher follicular fluid Cu concentration while holding the other variables in the model constant (RR 0.288; 95% CI 0.085-0.92; P=.039). CONCLUSION: Blood concentrations of Pb and follicular fluid concentrations of Cu seem to have significant impacts on assisted reproductive technology cycle outcome.

Controlled ovarian hyperstimulation with sequential letrozole co-treatment in normo/high responders.

OBJECTIVE: To investigate the effect of co-administration of letrozole in an ovarian stimulation protocol using recombinant FSH and GnRH antagonists for ICSI in normo/high responders. METHODS: Computerized data of 320 antagonist ICSI/ET cycles with or without letrozole were retrospectively analyzed. In 105 cases, letrozole (5 mg/day) was started at the second day of the cycle continued for 5 days. At the second day of letrozole, gonadotropins were added. The remaining 215 cases were stimulated with recombinant FSH only. In all cases on day 6, GnRH antagonist was started. Ovarian stimulation protocols with or without letrozole were compared for cycle outcome parameters. RESULTS: In cycles with letrozole, significantly lower gonadotropin consumption and lower peak estradiol levels were found. In cycles with letrozole, mean number of metaphase II and fertilized oocytes retrieved were significantly higher compared to cycles without letrozole. The pregnancy and clinical pregnancy rates were similar. CONCLUSION: Should the number of oocytes retrieved being higher in letrozole group might indicate that letrozole might contribute to successful ovarian stimulation with a lower dosage of gonadotropins. Despite the lower peak estradiol levels, pregnancy rates being similar to other group also support the idea that letrozole can contribute to normal potential of implantation.

Congenital cytomegalovirus infections and glycoprotein B genotypes in live-born infants: a prevalence study in Turkey.

BACKGROUND: Cytomegalovirus (CMV) infections are the leading cause of infectious hearing loss and central nervous system disease among children worldwide. In this study, we aimed to determine the birth prevalence of congenital CMV infection in live-born infants in Turkey. METHODS: In total, 944 consecutive live-born infants born from 926 pregnant women were included in this study. CMV-DNA was investigated in saliva samples of all newborns within the first 3 days after birth using TaqMan-based real-time PCR. RESULTS: The birth prevalence of congenital CMV infection in live-born infants was 1.91% (18/944), and all congenitally infected infants were asymptomatic at birth. The prevalence of congenital CMV infection was 16.7% (3/18) in twin pregnancies and 1.32% (12/908) in single pregnancies (p = 0.002). Genotyping analysis showed glycoprotein B-1 (gB1) to be the most frequently detected genotype at 83.3%. CONCLUSION: The study results suggest that the majority of congenital CMV infection in Turkey occurs following nonprimary maternal infection. We believe that congenital CMV infection and its long-term effects have been underestimated in our country, as infected infants are usually asymptomatic at birth.