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To compare the efficacy of gradient and swim-up semen preparation techniques on pregnancy rates in couples undergoing intrauterine insemination (IUI) cycles with low dose gonadotropin stimulation with the diagnosis of unexplained or mild male subfertility.Two hundred and twenty three couples were randomized into swim up or gradient technique groups for sperm preperation. The clinical and on going pregnancy rates per cycle and per patient were evaluated.Both clinical and ongoing pregnancy rates per cycle were significantly higher in the "gradient" group (19% and 16.9%) in comparision with the "swim up" group (9.7% and 6.9%) (p 0.05). Clinical pregnancy and on-going pregnancy rates per patient were higher in the "gradient" group (26.1% and 23.4%) when compared to the "swim up" group (15.2% and 10.7%), (p 0.05). In the subgroup of 191 unexplained subfertile couples with 290 cycles; the "gradient" group also revealed significantly higher clinical and ongoing pregnancy rates per cycle (21.6% and 17.9%) when compared with the "swim up" group (10.3% and 7.1%) (p 0.05). In total of 48 treatment cycles upon 32 couples with mild male factor subfertility no significant difference were found between the two sperm preparation techniques in terms of clinical (% 5.3 vs %6.9, p 0.05) and ongoing (% 5.3 vs %6.9, p 0.05) pregnancy rates per cycle.The gradient technique significantly improves clinical outcome in IUI cycles of unexplained subfertile couples when compared to swim up technique. In male subfertile patients, both techniques yield similar clinical outcomes.

Background: Inflammation, neurogenic inflammation and pain remain challenging to treat in sickle cell disease (SCD). Alternative therapies including acupuncture have been used for centuries to reduce pain and ameliorate underlying pathobiology of many disorders. We examined the mechanisms underlying acupuncture therapy in sickle mice. To prevent the influence of anesthetics and constraint on the pathobiology we developed electroacupuncture (EA) treatment for awake/conscious freely moving mice to simulate treatment conditions in patients, and then examined the peripheral and central mechanisms of neuroinflammation and nociception. Methods: HbSS-BERK sickle and HbAA-BERK control mice were treated with four EA treatments (every 3rd day, frequency: 4 or 10 Hz, pulse width: 100 microsecond, duration: 30 min) at acupoint GB30. Untreated and sham-EA treated (acupuncture without electrical stimulation) were used as controls. Hyperalgesia was evaluated daily by determining mechanical threshold, deep tissue hyperalgesia and thermal hyperalgesia using von Frey filaments, grip force, and cold plate, respectively. Blood and tissues were collected for analysis after four sessions of treatment. Skin biopsies were incubated overnight and culture medium was analyzed for mast cell activation marker tryptase, and neuromodulatory marker substance P. Results: Varied analgesic response to EA treatment was observed in sickle mice. About 86% treated mice equally showed positive (>50% pain relief) or moderate (20-30% pain relief) response and 14% were non-responsive ( Conclusions: EA treatment on conscious free-moving mice simulates clinical conditions in patients and excludes the potential influence due to restraint or anesthetics. EA leads to peripheral and central neuromodulation and anti-inflammatory response by attenuating mast cell activation, substance P, and cytokine release in the periphery and by abrogating spinal nociceptive signaling of p38MAPK and inflammation. Together, these molecular and cellular effects lead to EA-induced attenuation of neurogenic inflammation and hyperalgesia in sickle mice. Importantly, these data explain the cause of variable effectiveness of EA in SCD. Disclosures No relevant conflicts of interest to declare.

Patients experiencing chronic and/or recurrent pain show a correlative decline in health and lifespan. In turn, declining health and sensory effects may contribute to persistent pain and poor response to analgesia. We therefore hypothesized that dietary alterations to improve health and stress reduction by mating may reduce chronic pain in male sickle mice. Methods. We used male HbSS-BERK (sickle) mice, which show hyperalgesia as compared to and HbAA-BERK (control) mice (Kohli et al., Blood 2010). Breeders and pups up to 12 wks of age were fed Sickle Mouse Diet (59M3, TestDiet) and 18% Protein Rodent Diet (2018, Harlan), thereafter, called ‘sickle’ and ‘rodent’ diet. Sickle diet contained 26.4% Protein, 11.1% fat and 27.5% and 26% kcal/g of each, respectively. Rodent diet contained 18.6% protein and 6.2% fat, and 24% and 18% kcal/g of each, respectively. Vitamins were about 2-fold higher in sickle as compared to rodent diet. Sickle mice showing hyperalgesia were recruited and treated as follows: [A] Rodent diet without mating (RD/M-); [B] Sickle diet with mating (SD/M+); [C] Rodent diet with mating (RD/M+); [D] Sickle diet without mating (SD/M-) and [E] mice on SD and mating for 4 weeks, were deprived of SD and mating and fed RD. Control mice which do not show hyperalgesia were fed RD without mating. Sensory testing was performed at baseline (BL) at recruitment and weekly, to evaluate mechanical hyperalgesia with von Frey filaments, thermal hyperalgesia in response to heat/cold and grip force for musculoskeletal/deep tissue hyperalgesia. Following the treatments, release of cytokines from skin biopsies was analyzed by cytokine arrays as described by us earlier (Vincent et al., Blood 2013), and spinal cords were analyzed for nociceptive signaling. Results. We did not observe difference in the body weight of mice between different groups at any time. White blood cell counts and spleen weight were significantly increased in group E following the withdrawal of SD and mating as compared to group C on SD/M+ (p Disclosures No relevant conflicts of interest to declare.