Double vs. single intrauterine insemination per cycle: use in gonadotropin cycles and in diagnostic categories of ovulatory dysfunction and male factor infertility

OBJECTIVE: To evaluate the effectiveness of offering double intrauterine insemination (IUI) to clients in our fertility program. STUDY DESIGN: In this prospective, nonrandomized study, 595 couples with ovulatory dysfunction, endometriosis, male factor, unexplained, tubal factor and combined diagnoses utilizing clomiphene citrate-hCG (CC-hCG), CC-gonadotropin-hCG (CC-Gn-hCG), Gn-hCG, lupron-Gn-hCG (L-Gn-hCG) or luteinizing hormone (LH) surge monitoring of natural cycles were offered single or double IUI in a total of 1276 cycles. Single IUIs were performed at 36 hours following hCG or the day following LH surge; double IUIs were performed 18 and 36 hours following hCG or the day of and day following LH surge. Single versus double IUI clinical pregnancy outcomes were compared between ovarian stimulation protocols and diagnostic categories. RESULTS: One hundred ten clinical pregnancies occurred for 508 couples in 999 single IUI cycles (fecundity, 11.0%); 45 clinical pregnancies for 174 couples occurred in 277 double IUI cycles (16.2%, p < 0.004). The single IUI group was younger than the double IUI group (32.8 vs. 33.7, p < 0.004). Differences for fecundity were noted regarding diagnostic categories between single and double IUI groups (ovulation dysfunction, 12.9% vs 19.5%, p < 0.048, and male factor, 7.9% vs. 17.5%, p < 0.030) and ovulation protocols (CC-Gn-hCG, 13.0% vs. 21.3%, p < 0.031, and L-Gn-hCG, 4.2% vs. 25.0%, p < 0.002). CONCLUSION: Double IUI is superior to single IUI overall, especially when comparing Gn-containing ovarian stimulation protocols or within the ovulatory dysfunction and male factor diagnostic categories.     

Intrauterine insemination results in couples requiring extended semen transport time

PURPOSE: The purpose of the present study is to compare intrauterine insemination (IUI) pregnancy rates (PR) as a function of diagnosis and ovulation protocol utilizing an extended semen transport time. This allowed clients to conveniently collect IUI specimens in the comfort and privacy of their home. A single IUI per treatment cycle was performed. BASIC PROCEDURES: Three-hundred-ten consecutive infertilty couples having unexplained, male factor, ovulatory dysfunction, endometriosis, tubal factor or combined diagnostic factors receiving a total of 584 cycles of IUI were included. Ovulation protocols included LH surge, clomiphene citrate (CC)-hCG, CC-gonadotropins(Gn)-hCG, Gn-hCG or leuprolide acetate (L)-Gn-hCG followed 36-42 hours by a single IUI. Pregnancy rates per cycle (fecundity) and per couple (fertility) as a function of diagnosis, ovulation protocol and cycle number were evaluated. In each cycle the couples processed the specimen by adding sperm washing medium at room temperature to the specimen 30 min following collection and allowed it to incubate for two hours prior to IUI during transport. MAIN FINDINGS: Overall, fecundity was 11.8% (69/584) and fertility was 22.3% (69/310); respectively by diagnosis was: unexplained 22.6%, 38.8%; male factor 18.8%, 42.9%; ovulatory dysfunction 12.4, 22.6%; endometriosis 5.3%, 11.1%; tubal factor 7.6%,13.3%; and combined factors 9.7%, 20.0%. Unexplained vs endometriosis (P < 0.0001, P < 0.005), tubal factor (fecundity P < 0.008) and ovulatory dysfunction (fecundity P < 0.027) was statistically different. Male factor vs endometriosis (P < 0.011, P < 0.036) was significantly different. Ovulatory dysfunction vs endometriosis was significantly different (fecundity P < 0.027). Pregnancies by ovulation protocol: LH surge 4.5%,10.5%; CC-hCG 9.4%,14.9%; CC-Gn-hCG 13.7%, 23.7%; Gn-hCG 17.5%, 45.3%; L-Gn-hCG 3.5%, 6.7%. For Gn-hCG vs L-Gn-hCG (P < 0.009, P < 0.030) and LH surge (fecundity P < 0.033). CC-Gn-hCG vs CC-hCG (fertility P < 0.050) and L-Gn-hCG (P < 0.033, P < 0.034). Gn-hCG vs CC-hCG (fecundity P < 0.043). CONCLUSIONS: We conclude that IUI is effective when utilizing an extended transport time allowing most couples to collect the specimen at home and is most effective when utilizing Gn-hCG therapy. Based on our analysis, endometriosis, tubal factor and combined diagnostic categories should proceed earlier to higher level assisted reproductive technologies.     

Novel modifications to the C-terminus of LTB that facilitate site-directed chemical coupling of antigens and the development of LTB as a carrier for mucosal vaccines

To facilitate site-directed chemical coupling of antigens to the heat labile enterotoxin B subunit of Escherichia coli (LTB), a series of genetically modified fusion proteins of LTB were constructed. The LTB fusion proteins had modified versions of a short (14 amino acid) spacer epitope called the Pk tag attached at their C termini. The LTB-Pk.cys mutants differed from each other in the position of a single cysteine residue within the Pk tag. The presence of a cysteine residue at any position within the Pk spacer tag did not prevent the LTB-Pk.cys proteins from forming pentamers or binding to GM1 gangliosides, but the position of the cysteine had variable impact on the yield of the fusion proteins. Following site-directed chemical coupling of antigens to the cysteine residue within the Pk tag, the LTB antigen conjugates retained their ability to bind GM1 on the surface of eukaryotic cells. Intranasal immunisation of mice with an experimental antigen (HRP) chemically linked to LTB-Pk.cys induced high levels of anti-HRP antibodies that could be detected in the serum, saliva and nasal and lung washes. No antibody responses to HRP were detected when HRP was co-administered with, but not linked to, LTB-Pk.cys.     

Histochemical localization of aldehyde dehydrogenase in the respiratory tract of the Fischer-344 rat

Acetaldehyde, a nasal carcinogen and respiratory tract irritant, is metabolized by aldehyde dehydrogenase. The localization of aldehyde dehydrogenase in individual cells of the nasal passages, trachea, and lungs of the Fischer-344 rat was determined histochemically using a cold glycol methacrylate embedding procedure. Aldehyde dehydrogenase activity was detected principally in the nasal respiratory epithelium, especially in the supranuclear cytoplasm of ciliated epithelial cells while olfactory epithelium was almost devoid of enzyme activity. Epithelial cells of the trachea demonstrated little detectable aldehyde dehydrogenase activity, however, the Clara cells of the lower bronchioles showed remarkably high activity. These results corroborate previous biochemical findings and extend them by histochemically identifying particular aldehyde dehydrogenase-positive cell types within the nasal respiratory epithelium. The distribution of nasal lesions induced by acetaldehyde correlated with regional aldehyde dehydrogenase deficiencies suggesting that regional susceptibility to the toxic effects of acetaldehyde may be due, at least in part, to a lack of aldehyde dehydrogenase in the susceptible regions. Furthermore, aldehyde dehydrogenase activity in the Clara cells indicates a possible site for metabolism of aldehydes which penetrate to the lower airways.     

A nucleic acid amplification test‐based strategy does not help inform return to work for healthcare workers with COVID‐19

ObjectiveThe objective of this study is to assess the utility of a nucleic acid amplification test‐based approach to shorten isolation of healthcare workers (HCWs) with COVID‐19 in the setting of the highly transmissible omicron variant.MethodsBetween December 24, 2021, and January 5, 2022, HCWs who tested positive for SARS‐CoV‐2 were retested with PCR at least 5 days since onset of symptoms.ResultsForty‐six sequential fully COVID‐19 vaccinated HCWs who had tested positive for SARS‐CoV‐2 underwent follow‐up testing. All the samples were confirmed as omicron variants and only four (8.7%) were negative in the follow‐up test performed at a median of 6 (range 5–12) since onset of symptoms.ConclusionsImplementation of a test‐based strategy is logistically challenging, increases costs, and did not lead to shorter isolation in our institution.     

Evidence That Intravenous Vasopressors Can Affect Rostral Spread of Spinal Anesthesia in Pregnancy

Background: The authors have previously observed an apparent association between rostral spread of spinal anesthesia and choice of intravenous vasopressor given to maintain maternal systolic arterial pressure during cesarean delivery. This study tested the hypothesis that an intravenous infusion of phenylephrine can reduce rostral spread of spinal anesthesia in pregnancy, compared with ephedrine.

Methods: The study was randomized and double blind. It compared phenylephrine 100 [mu]g/ml (phenylephrine group, n = 30), and ephedrine 3 mg/ml (ephedrine group, n = 30), given by infusion, to prevent maternal hypotension during combined spinal-epidural anesthesia for cesarean delivery. Two ml intrathecal plain levobupivacaine, 0.5%, combined with 0.4 ml intrathecal fentanyl, 50 [mu]g/ml, and 10 ml epidural saline was given with the patient in the sitting position. The upper level of neural blockade to cold and light touch sensation was recorded at 10 and 20 min postspinal. Epidural space pressure was recorded at 5, 10, 15, and 20 min.

Results: At 20 min, the upper dermatome blocked to cold sensation was median T3 (interquartile range, T2-T4) for the phenylephrine group, compared with T1 (T1-T2) for the ephedrine group (P = 0.001). At 20 min, the upper dermatome blocked to light touch sensation was median T5 (T4-T8) for the phenylephrine group, compared with T3 (T2-T6) for the ephedrine group (P = 0.009). The mean epidural space pressure in the phenylephrine group was 16 (13-19) mmHg, compared with 16 (13-18) mmHg in the ephedrine group (P = 0.63).