Frozen thawed embryo transfer cycles; A comparison of pregnancy outcomes with and without prior pituitary suppression by GnRH agonists: An RCT

Background: To perform an in-vitro fertilization cycle, pretreatment with gonadotropin-releasing hormone (GnRH) agonist is widely used as a part of controlled ovarian hyper-stimulation protocols to prevent endogenous luteinizing hormone surge and spontaneous ovulation. GnRH agonist pretreatment is relatively costly and there is a risk of hypo estrogenic side effect. It would also lengthen the preparation period until pituitary desensitization occurs. Objective: Our study is aimed at evaluating the pregnancy outcome rate of frozen thawed embryo transfer with and without GnRH agonists pretreatment. Materials and Methods: Women with documented infertility who were candidate for frozen thawed embryo transfer were recruited and randomly assigned to two groups. In group A (n=100), patients received GnRH agonist, Buserelin, to induce pituitary desensitization prior to endometrial preparation and embryo transfer. Individuals in group B (n=100) received steroid manipulation without prior down-regulation of the pituitary. Chemical pregnancy, implantation rate, clinical pregnancy and ongoing pregnancy were measured and statistically compared between the two groups. Results: None of the outcome measures including clinical and chemical pregnancy rates, implantation rate, and ongoing pregnancy rate showed significant difference between the two groups. Similarly, the rate of miscarriage did not vary between the two groups. Conclusion: In this study, we found that removing the GnRH agonists pretreatment from the programmed cycles did not negatively influence the pregnancy outcome or implantation rate. Moreover, it will cause a considerable reduction in cost of assisted reproductive technology as well as adverse effects relate

HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers.

HIV posttreatment controllers (PTCs) represent a natural model of sustained HIV remission, but they are rare and little is known about their viral reservoir. We obtained 1,450 proviral sequences after near-full-length amplification for 10 PTCs and 16 posttreatment noncontrollers (NCs). Before treatment interruption, the median intact and total reservoir size in PTCs was 7-fold lower than in NCs, but the proportion of intact, defective, and total clonally expanded proviral genomes was not significantly different between the 2 groups. Quantification of total but not intact proviral genome copies predicted sustained HIV remission as 81% of NCs, but none of the PTCs had a total proviral genome greater than 4 copies per million peripheral blood mononuclear cells (PBMCs). The results highlight the restricted intact and defective HIV reservoir in PTCs and suggest that total proviral genome burden could act as the first biomarker for identifying PTCs. Total and defective but not intact proviral copy numbers correlated with levels of cell-associated HIV RNA, activated NK cell percentages, and both HIV-specific CD4+ and CD8+ responses. These results support the concept that defective HIV genomes can lead to viral antigen production and interact with both the innate and adaptive immune systems

HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers.

HIV posttreatment controllers (PTCs) represent a natural model of sustained HIV remission, but they are rare and little is known about their viral reservoir. We obtained 1,450 proviral sequences after near-full-length amplification for 10 PTCs and 16 posttreatment noncontrollers (NCs). Before treatment interruption, the median intact and total reservoir size in PTCs was 7-fold lower than in NCs, but the proportion of intact, defective, and total clonally expanded proviral genomes was not significantly different between the 2 groups. Quantification of total but not intact proviral genome copies predicted sustained HIV remission as 81% of NCs, but none of the PTCs had a total proviral genome greater than 4 copies per million peripheral blood mononuclear cells (PBMCs). The results highlight the restricted intact and defective HIV reservoir in PTCs and suggest that total proviral genome burden could act as the first biomarker for identifying PTCs. Total and defective but not intact proviral copy numbers correlated with levels of cell-associated HIV RNA, activated NK cell percentages, and both HIV-specific CD4+ and CD8+ responses. These results support the concept that defective HIV genomes can lead to viral antigen production and interact with both the innate and adaptive immune systems.National Institutes of Health/National Institute of Allergy and Infectious Diseases [AI125109]; Harvard University Center for AIDS Research [5P30AI060354-08, 5P30AI060354-14]; Michael Smith Foundation for Health Research; [UM1AI068634]; [UM1AI068636]; [UM1AI106701]; [UM1AI126617]; [UM1AI069423]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies.

BackgroundHIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized.MethodsPosttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks. Viral load and CD4+ cell dynamics were compared between posttreatment controllers and noncontrollers.ResultsOf the 67 posttreatment controllers identified, 38 initiated ART during early HIV infection. Posttreatment controllers were more frequently identified in those treated during early versus chronic infection (13% vs 4%, P < .001). In posttreatment controllers with weekly viral load monitoring, 45% had a peak posttreatment interruption viral load of ≥1000 copies/mL and 33% had a peak viral load ≥10000 copies/mL. Of posttreatment controllers, 55% maintained HIV control for 2 years, with approximately 20% maintaining control for ≥5 years.ConclusionsPosttreatment control was more commonly identified amongst early treated individuals, frequently characterized by early transient viral rebound and heterogeneous durability of HIV remission. These results may provide mechanistic insights and have implications for the design of trials aimed at achieving HIV remission

The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies.

BackgroundHIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized.MethodsPosttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks. Viral load and CD4+ cell dynamics were compared between posttreatment controllers and noncontrollers.ResultsOf the 67 posttreatment controllers identified, 38 initiated ART during early HIV infection. Posttreatment controllers were more frequently identified in those treated during early versus chronic infection (13% vs 4%, P < .001). In posttreatment controllers with weekly viral load monitoring, 45% had a peak posttreatment interruption viral load of ≥1000 copies/mL and 33% had a peak viral load ≥10000 copies/mL. Of posttreatment controllers, 55% maintained HIV control for 2 years, with approximately 20% maintaining control for ≥5 years.ConclusionsPosttreatment control was more commonly identified amongst early treated individuals, frequently characterized by early transient viral rebound and heterogeneous durability of HIV remission. These results may provide mechanistic insights and have implications for the design of trials aimed at achieving HIV remission