Oocytes affected by smooth endoplasmic reticulum aggregates: to discard or not to discard?

Purpose: Oocytes containing smooth endoplasmic reticulum aggregates (SERa) have been associated with reduced fertilization and clinical pregnancy rates as well as compromised neonatal outcomes. It was therefore recommended by an Alpha-ESHRE Consensus to discard oocytes presenting this dysmorphism. The data in the literature are nevertheless conflicting and healthy babies have recently been obtained from affected oocytes.

Vitrification of blastocysts derived from fair to poor quality cleavage stage embryos can produce high pregnancy rates after warming.

Purpose: This study investigates whether certain embryos considered unsuitable for cryopreservation on day 3 might nevertheless have the potential to develop into worthwhile blastocysts that could be vitrified in the same cycle.

Methods: Retrospective study: between 2010 and 2011, embryo transfers and cryopreservation took place mainly on day 3 in our centre. Supernumerary embryos of intermediate to poor quality were reassessed on days 5/6 and any good quality blastocysts were vitrified.

New R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(phenylaminothiocarbonylamino)-2H-1-benzopyrans structurally related to (+/-)-cromakalim as tissue-selective pancreatic beta-cell K(ATP) channel openers.

The present work was aimed at exploring a series of R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(phenylaminothiocarbonylamino)-2H-1-benzopyrans structurally related to (+/-)-cromakalim and differently substituted at the 4- and 6-positions. The biological effects of these putative activators of ATP-sensitive potassium channels (K(ATP)) were characterized in vitro on the pancreatic endocrine tissue (inhibition of insulin release) and on the vascular smooth muscle tissue (relaxation of aorta rings). The biological activity of these new dimethylchroman derivatives was further compared to that of (+/-)-cromakalim, (+/-)-pinacidil, diazoxide and BPDZ 73.

KATP channel openers: tissue selectivity of original 3-alkylaminopyrido- and 3-alkylaminobenzothiadiazine 1,1-dioxides.

The present study was designed to further evaluate the biological effects and tissue selectivity of new 3-alkylaminobenzo- and 3-alkylaminopyridothiadiazine 1,1-dioxides bearing identical branched alkylamino chains at the 3-position. These original compounds were compared with their parent molecules; namely the K(ATP) channel openers diazoxide and pinacidil. All tested 3-alkylamino-substituted derivatives provoked a marked, concentration-dependent inhibition of the glucose-induced insulin secretion from rat pancreatic islets.

Outcome of conventional IVF and ICSI on sibling oocytes in patients suffering from teratospermia.

Objective: To compare the outcomes of conventional IVF and ICSI on sibling oocytes.

Design: Retrospective analysis.

Methods: Performance of ICSI on part of the oocytes and IVF on the remaining portion during the same cycle (sibling oocytes).

Ovarian response to stimulation of HIV-positive patients during IVF treatment: a matched, controlled study.

Background: Our aim was to compare the ovarian response of HIV-positive and -negative patients during IVF.

Methods: Setting - HIV and IVF reference university hospital. Twenty-seven HIV-infected patients who had undergone IVF between March 2000 and March 2005 were matched with 77 HIV-negative patients for age, aetiology of infertility, whether it was primary or secondary infertility, duration of infertility, history of pelvic surgery and type of pituitary inhibition.

3-Alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides as ATP-sensitive potassium channel openers: effect of 6,7-disubstitution on potency and tissue selectivity.

A series of 6,7-disubstituted 4H-1,2,4-benzothiadiazine 1,1-dioxides bearing a short alkylamino side chain in the 3-position were synthesized. These compounds were tested on rat pancreatic islets and on rat aorta rings. In vitro data indicated that in most cases substitution in the 6 and the 7 positions increased their activity as inhibitors of insulin secretion, while the myorelaxant potency of the drugs was maintained or enhanced according to the nature of the substituent in the 7-position.

Effect on K(ATP) channel activation properties and tissue selectivity of the nature of the substituent in the 7- and the 3-position of 4H-1,2,4-benzothiadiazine 1,1-dioxides.

The present work explored 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides diversely substituted in the 7-position. Those compounds, structurally related to previously described potassium channel openers such as the benzothiadiazine dioxide BPDZ 73, were tested as putative K(ATP) channel activators on the pancreatic endocrine tissue and on the vascular smooth muscle tissue. The nature of the substituent introduced in the 7-position as well as the nature of the alkylamino side chain in the 3-position strongly affected both potency and tissue selectivity of 4H-1,2,4-benzothiadiazine 1,1-dioxides.

4,6-Disubstituted 2,2-dimethylchromans structurally related to the K(ATP) channel opener cromakalim: design, synthesis, and effect on insulin release and vascular tone.

Five series (ureas, thioureas, carbamates, sulfonylureas, and amides) of 4,6-disubstituted-2,2-dimethylchromans structurally related to cromakalim were prepared and evaluated, as putative ATP-sensitive potassium channel activators, on rat pancreatic islets and rat aorta rings. The biological data indicate that most compounds were, like the reference molecule cromakalim, more active on the vascular smooth muscle tissue (myorelaxant effect on 30 mM KCl induced contractions of rat aorta rings) than on the pancreatic tissue (inhibition of 16.7 mM glucose induced insulin release from rat pancreatic islets).

Blockade of calcium entry in smooth muscle cells by the antidepressant imipramine.

The present study was designed to evaluate the effects of antidepressants on smooth muscle contractile activity. In rat aortic rings, the antidepressants imipramine, mianserin and sertraline provoked concentration-dependent inhibitions of the mechanical responses evoked by K+ (30 mM) depolarization. These myorelaxant effects were not modified by the presence of glibenclamide or 80 mM K+ in the bathing medium.

Toward tissue-selective pancreatic B-cells KATP channel openers belonging to 3-alkylamino-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides.

3-(Alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides were synthesized, and their activity on rat-insulin-secreting cells and rat aorta rings was compared to that of the K(ATP) channel activators diazoxide and pinacidil. Structure-activity relationships indicated that an improved potency and selectivity for the pancreatic tissue was obtained by introducing a fluorine atom in the 7-position and a short linear (preferably ethyl) or cyclic (preferably cyclobutyl) hydrocarbon chain on the nitrogen atom in the 3-position. By contrast, strong myorelaxant activity was gained by the introduction of a halogen atom different from the fluorine atom in the 7-position and a bulky branched alkylamino chain in the 3-position.

2-alkyl-3-Alkylamino-2H-Benzo- and pyridothiadiazine 1,1-dioxides: from K+ATP channel openers to Ca++ channel blockers?

A series of 2-alkyl-3-alkylamino-2H-benzo- and 2-alkyl-3-alkylamino-2H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides, structurally related to BPDZ 44 and BPDZ 73, two potent pancreatic B-cells K+ATP channel openers, were synthesized and tested on rat pancreatic islets (endocrine tissue) as well as on rat aorta rings (vascular smooth muscle tissue). Alkylation of the 2-position led to double bond tautomerization and formation of compounds with a 2H-conformation. In contrast to the previously described pyridothiadiazine dioxides, such as BPDZ 44, and 7-chlorobenzothiadiazine dioxides, such as BPDZ 73, the 2-alkyl-substituted analogs were found to be poorly active on the insulin releasing process although most drugs exhibited a vasorelaxant activity.