FSH administration at 12-hour intervals for the first 2 days, combined with mandatory GnRH-agonist trigger and blastocyst vitrification in women (<80Kg) with high AMH levels, results in higher cumulative live birth rates and is safer.

We aimed to determine if a programme change to 12 hourly injections of FSH (150 IU per injection) for the first 2 days of stimulation in women with high ovarian reserve (AMH ≥ 30 pmol/L), followed by 24 hourly injections, would elicit increased earlier follicular recruitment, higher egg yields and blastocyst embryos for cryopreservation, leading to potential higher cumulative pregnancy rates, than conventional daily injections throughout. For safety reasons, the approach required mandatory cryopreservation of all blastocysts (mFET group; n = 74), after ovulation trigger with GnRH-agonist, in GnRH-antagonist controlled cycles. The 'Comparator group' (n = 91) comprised women with the same high AMH levels treated with the same base dose of FSH, with the aim of fresh blastocyst transfer and cryopreservation of supernumerary embryos, treated over the preceding 2 years. There was no difference in age, AMH, weight or BMI between the groups. The mFET group achieved higher egg (17.7 versus 11.7; p < 0.001) and embryo (10.9 versus 7.2; p < 0.001) yields and fewer cases with sub-optimal embryo yields (7% versus 22%; p = 0.018). The cumulative live birth rate was superior in the mFET group (73% versus 43%), as was the safety profile, and negligible rate of treatment plan modification.

The Promising Epigenetic Regulators for Refractory Epilepsy: An Adventurous Road Ahead.

The attribution of seizure freedom is yet to be achieved for patients suffering from refractory epilepsy, e.g. Dravet Syndrome (DS). The confined ability of mono-chemical entity-based antiseizure drugs (ASDs) to act directly at genomic level is one of the factors, combined with undetermined seizure triggers lead to recurrent seizure (RS) in DS, abominably affecting the sub-genomic architecture of neural cells. Thus, the RS and ASD appear to be responsible for the spectrum of exorbitant clinical pathology. The RS distresses the 5-HT-serotonin pathway, hypomethylates genes of CNS, and modulates the microRNA (miRNA)/long non-coding RNA (lncRNA), eventually leading to frozen molecular alterations. These changes shall be reverted by compatible epigenetic regulators (EGR) like, miRNA and lncRNA from Breast milk (BML) and Bacopa monnieri (BMI). The absence of studious seizure in SCN1A mutation-positive babies for the first 6 months raises the possibility that the consequences of mutation in SCN1A are subsidized by EGRs from BML. EGR-dependent-modifier gene effect is likely imposed by the other members of the SCN family. Therefore, we advocate that miRNA/lncRNA from BML and bacosides/miRNA from BMI buffer the effect of SCN1A mutation by sustainably maintaining modifier gene effect in the aberrant neurons. The presence of miRNA-155-5p, -30b-5p, and -30c-5p family in BML and miR857, miR168, miR156, and miR158 in BMI target at regulating SCN family and CLCN5 as visualized by Cystoscope. Thus, we envisage that the possible effects of EGR might include (a) upregulating the haploinsufficient SCN1A strand, (b) down-regulating seizure-elevated miRNA, (c) suppressing the seizure-induced methyltransferases, and (d) enhancing the GluN2A subunit of NMDA receptor to improve cognition. The potential of these EGRs from BML and BML is to further experimentally strengthen, long-haul step forward in molecular therapeutics.

Clinical adjuncts in in vitro fertilization: a growing list.

A growing list of clinical adjuncts are being used during in vitro fertilization (IVF) treatment. Most of these IVF add-ons (such as growth hormone, aspirin, heparin, dehydroepiandrostenedione, testosterone, male and female antioxidants, and screening hysteroscopy) are being introduced into routine clinical practice in a hurried manner without any clear evidence of benefit in most cases. These add-ons make the IVF more complicated and increase the overall cost for the treatment, which is borne by the couples and health care providers. Our current review found no high-quality evidence to support the use of these IVF add-ons in routine practice. Large, well-designed, randomized trials must be conducted to evaluate the effectiveness and safety of these interventions. There is also a pressing need to develop an evidence-dictated mechanism for introducing newer interventions into routine clinical settings.

Iron overload directly affecting the ovaries in a patient with Diamond-Blackfan anaemia: a case report.

Iron is a 'one-way' element and the primary point of regulation of body iron stores is at the level of intestinal iron absorption. Repeated blood transfusions for congenital anaemias bypass this regulatory checkpoint and inevitably lead to iron overload in the long-term. Iron overload causes multi-organ dysfunction of the heart, liver, pancreas and joints. It also causes reproductive toxicity primarily through its damaging effect on the anterior pituitary leading to hypogonadotrophic hypogonadism. Another less understood mechanism of reproductive toxicity is direct gonadal damage of excess free iron. In this article, we present the case of a 24-year-old woman with Diamond-Blackfan anaemia who presented to our unit seeking fertility assistance. The evaluation revealed a combination of hypogonadotrophic hypogonadism and reduced ovarian reserve along with evidence of severe iron overload. A literature search along with input from clinical experts has allowed us to counsel the patient to help her make an informed choice. A multi-disciplinary approach which would include initial optimization of pre-conceptional health with aggressive iron chelation therapy and subsequent ovulation induction with gonadotrophins has been planned, failing which, egg donation may be the only viable alternative.

Microsurgical anatomy of the superior sagittal sinus and draining veins.

BACKGROUND: The superior sagittal sinus and the draining cerebral veins are often encountered during the surgery for parasagittal and falx meningiomas and during the interhemisperic transcallosal approaches. A knowledge about the variations from the normally described anatomy helps in anticipating and avoiding problems related to these structures during surgery. AIM: The normal variations in the disposition of the superior sagittal sinus and the number and direction of the draining veins in the Indian population have been studied. SETTINGS AND DESIGN: This is an anatomical study in the fresh cadavers. MATERIALS AND METHODS: Sixty fresh cadavers were examined in the autopsy theatre of the Forensic Medicine Department of the Hospital between March 2011 and February 2013. STATISTICAL ANALYSIS USED: Epi-Info, MS-Excel, and the Statistical Package for the Social Sciences (SPSS) were used for data analysis. RESULTS: The position of the superior sagittal sinus was variable and was up to within 1cm on either side of the sagittal suture. The origin of the superior sagittal sinus varied from the level of foramen caecum to a little posterior from the foramen caecum. The total length of the superior sagittal sagitttal sinus varied from 321 mm to 357 mm (average length 338.77mm); vertical compartments of the sinus were found in three-fourth of the cases studied. Tributaries were found in the herringbone pattern and varied from 13 to 19 on the right and 14 to 19 on the left. The Rolandic vein was the largest draining vein in most of the cases. The superior sagittal sinus drained predominantly to the right transverse sinus in three-fourth of the cases studied. The position of the torcula was variable; often towards the right side and at a higher level. The central sulcus was 49.93 mm posterior to the coronal suture and 130.78 mm anterior to the lambdoid suture. CONCLUSIONS: This is the first study of its kind in Indian population studying the anatomical variations in the anatomy of the superior sagittal sinus that may have a significant bearing on the neurosurgical approaches adopted.

Use of granulocyte-colony stimulating factor in assisted reproductive technology: A systematic review and meta-analysis.

Granulocyte-colony stimulating factor (G-CSF), a glycoprotein, has been used in women undergoing Assisted Reproductive Technology (ART). We decided to undertake a systematic review to evaluate the effectiveness of G-CSF in women with thin endometrium and recurrent implantation failure (RIF) undergoing ART. The outcomes included an increase in endometrial thickness, live birth, clinical pregnancy rates and adverse effects. We included two trials evaluating women with thin endometrium and another two trials evaluating women with RIF. The pooled data did not reveal statistically significant increase in endometrial thickness following G-CSF in women with thin endometrium (mean difference 0.47, 95% CI -1.36-2.31; I2 82%). However significantly higher clinical pregnancy rate was noted (RR 2.43, 95% CI 1.09-5.40; I2 0%) following G-CSF compared to no intervention and quality of evidence for both these outcomes was very low. In RIF population, the administration of G-CSF was associated with a significantly higher clinical pregnancy rate compared to no intervention with pooled risk ratio of 2.51 (95% CI 1.36-4.63; I2 0%) and quality of evidence being low. Findings of current review suggest a possible benefit of G-CSF in women with thin endometrium undergoing ART and RIF. However these findings need to be further validated in larger trials before G-CSF can be used in routine clinical practice.