The influence of household pets on the composition and quantity of allergenic mite fauna within Irish homes: a preliminary investigation.

Allergenic mites are responsible for inducing hypersensitive reactions in genetically predisposed people worldwide. Mites in dust from 30 Irish homes with pets (dogs, n = 23; cats, n = 7) were compared with those in 30 homes without pets. House dust mites constituted 78% of all mites recorded, with Dermatophagoides pteronyssinus (Acariformes: Pyroglyphidae) representing 57-72% of mites in furniture and mattresses in both home types compared with only 22% of mites in pet beds. Although storage mites accounted for just 13% of all mites recorded, they represented 46% of mites recorded in pet beds. Median levels of the dust mite allergen Der p 1 (µg/g) in dust samples from mattresses in homes without pets were significantly greater than in mattresses from homes with pets, reflecting the greater densities of D. pteronyssinus found in the former home category. Mite species richness was greater in homes with pets (17 species) than in homes without pets (13 species). This suggests that although the presence of pets can result in a wider variety of epidemiologically important mite species within households, increased competition among mite species may result in a more balanced mite fauna in the home, inhibiting the dominance of any one species and hence lowering allergen-associated risks.

Pregnancy rates following frozen embryo transfer (ET) in women failing to conceive despite fresh ET in women using low dosage follicle stimulating hormone (FSH) protocol for follicular maturation of several eggs.

PURPOSE: To determine the pregnancy rate following frozen embryo transfer using embryos derived from low dosage follicle stimulating hormone (FSH) stimulation protocols in women aged < 42 who did not have diminished egg reserve as evidenced by a day 3 serum FSH < or =12 mIU/ml. METHODS: A retrospective review was performed evaluating pregnancy rates on frozen embryo transfers from women who usually had diminished egg reserve and thus used no more than 150 IU of FSH. The pregnancy rates were calculated on the first frozen embryo transfer of women failing to successfully conceive on the fresh embryo transfer. RESULTS: The clinical and live delivered pregnancy rates per transfer were 33.3% (14/42) and 23.8%. The implantation rate was 20.0%. Thirty-one percent of the transfers were in women aged 40-42. CONCLUSIONS: These data show that despite the fact that with minimal stimulation protocols, the remaining frozen embryos are of lesser quality because of de-selection, nevertheless, it is worth transferring these embryos.

Successful pregnancies following embryo transfer despite very thin late proliferative endometrium.

PURPOSE: To determine if successful pregnancies are possible following fresh or frozen embryo transfer despite a maximal endometrial thickness of only < or = 5 mm. METHODS: A retrospective review of all fresh and frozen embryo transfers over a seven-year period was performed. The maximum thickness either on the day of human chorionic gonadotropin injection during fresh embryo transfer or the day before the initiation of progesterone in frozen embryo transfer was performed. All embryo transfers performed with a maximum endometrial thickness of 5 mm were identified and the pregnancy rates were determined. RESULTS: There were 35 embryo transfers performed with a maximum endometrial thickness of <6 mm. There were three clinical pregnancies (8.5% per transfer), two live delivered babies (5.7% pregnancy rates per transfer). One of the live births was a fresh transfer using a minimal stimulation protocol and the endometrial thickness was 5.8 mm and the other a frozen embryo transfer with a maximum thickness of 5.0 mm (1 of 7, 14.2% of frozen embryo transfers resulted in a live delivery despite thin endometria. CONCLUSIONS: Live delivered pregnancies are possible despite thin endometria but the pregnancy rate is poor. Possibly the pregnancy rates may be better without controlled ovarian hyperstimulation.

Fertilization by intracytoplasmic sperm injection with sperm with subnormal morphology using strict criteria results in lower live delivered pregnancy rates following frozen embryo transfer rather than eggs fertilized conventionally.

PURPOSE: To determine if fertilization by intracytoplasmic sperm injection (ICSI) lowers pregnancy rates following frozen embryo transfer compared to conventional insemination similar to findings with fresh embryo transfer. METHODS: Clinical and live delivered pregnancy and implantation rates were compared according to whether the eggs were fertilized by conventional oocyte insemination vs ICSI over a 10-year period in women whose husbands had normal semen parameters except for having normal strict morphology between 2-5%. RESULTS: The clinical and live delivered pregnancy rates were 40.9% and 31.9, respectively, with ICSI vs. 44.2% and 38.3% for women having conventional insemination. The difference in live delivered pregnancy rates approached statistical significance. CONCLUSIONS: Choosing ICSI for subnormal morphology may not only possibly lower the chance of successful pregnancy following fresh embryo transfer but possibly also following frozen embryo transfer.

Effect of fertilization by intracytoplasmic sperm injection versus conventional insemination on embryo cleavage rates.

PURPOSE: To determine if fertilization by conventional oocyte insemination vs intracytoplasmic sperm injection (ICSI) causes any difference in the maximum number of blastomeres of fresh or frozen thawed embryos transferred. METHODS: Retrospective evaluation of all in vitro fertilization (IVF) cycles over a 10-year period in cycles having a 2 embryos transferred where the semen analysis was normal except for strict morphology which was allowed to be 2-5% normal. The percentage of the maximum number of blastomeres in any transfers was compared according to the method of insemination. RESULTS: There were no differences in the maximum blastomere numbers in cycles where there was conventional insemination vs ICSI. CONCLUSIONS: Though higher pregnancy rates have been found following the transfer of embryos derived from conventional oocyte insemination vs ICSI, and higher pregnancy rates were found following single embryo day 3 transfers with embryos with more blastomeres, the beneficial effect of conventional insemination does not seem to be related to forming embryos with more rapid cleavage.

Support for the hypothesis that successful immunotherapy of various cancers can be achieved by inhibiting a progesterone associated immunomodulatory protein.

A hypothesis was proposed that cancer cells may utilize a pre-existing mechanism that pregnant mammals use to avoid natural killer cell immune surveillance of the fetus. The hypothesis suggested that those cancer cells that are able to proliferate may have found a way to cause the expression of the immunomodulatory protein known as the progesterone induced blocking factor (PIBF). The cancer cells could find an alternate pathway to make this protein that does not require progesterone secretion, or the cancer cells may actually utilize progesterone and thus make PIBF in a similar fashion to normal pregnancy. If the former mechanism was operational, then one could develop monoclonal antibody type therapy directed to this unique protein not needed for normal body functions. However, if the latter pathway involving progesterone secretion is operational, then there would be drugs already on the market, e.g., the progesterone receptor antagonist mifepristone that could be used to treat these cancers. In vitro data has shown that 100% of human leukemia cell lines express mRNA for the PIBF protein. Some leukemia cell lines have been found that actually express the PIBF protein. In fact adding progesterone to the culture media upregulated PIBF protein expression and mifepristone inhibited it. Controlled studies in various murine spontaneous cancers not known to be associated with progesterone receptors showed increased length and quality of life following mifepristone therapy. Anecdotal improvement in advanced widely metastatic human cancers has also been found. Thus there is now experimental data to support this hypothesis and a new door to a completely different type of cancer therapy has been opened.

Successful pregnancy with frozen embryo transfer into a gestational carrier from eggs obtained from a woman in premature menopause.

PURPOSE: To describe a unique case of a successful gestational carrier pregnancy in a woman with premature ovarian failure using her own oocyte. METHODS: Despite amenorrhea, failure to have menses to progesterone withdrawal and resistance to gonadotropin stimulation, ovulation induction was attempted by restoring down-regulated follicle stimulating hormone (FSH) receptors by lowering the elevated serum FSH and allowing stimulation by endogenous or exogenous gonadotropins. Oocyte retrieval was attempted if a mature follicle was obtained. GnRH antagonist was used to prevent premature oocyte release. Tapering prednisone was used for the first five days of the cycle due to patient's history of autoimmune disease (vasculitis and Crohn's disease). IVIG was given 8/2003 for vasculitis. RESULTS: The patient underwent a total of 19 attempted retrievals during continuous natural cycles from 3/2003 to 2/2007. Oocyte retrieval required traversing the uterus with the retrieval needle because of ovarian position after multiple surgeries for bilateral endometriomas and Crohn's disease. Empty follicle syndrome was encountered in four retrieval attempts. In 15 attempts, an oocyte was obtained. The sole attempt at natural fertilization failed. ICSI and assisted hatching were used in all subsequent attempts, and were successful in all but one attempt which led to a 3 pronuclei embryo which was discarded. The first four single embryos retrieved (7, 4, 6 cells and morula) were all A1 or A2 and transferred fresh to the patient, but no pregnancy resulted. All subsequent embryos were cryopreserved. The transfer of four embryos (6-cell and 7-cell and 3-cell and 8-cell) in two cycles to two different gestational carriers resulted in a successful delivery of a full-term healthy female infant 3.3 kg. Genetic testing confirmed maternal identity to be the patient, not the carrier. CONCLUSIONS: This is the first reported case of a successful gestational carrier pregnancy after reversing ovarian failure, inducing ovulation, and transferring a frozen-thawed embryo.

Modified diadenosine tetraphosphates with dual specificity for P2Y1 and P2Y12 are potent antagonists of ADP-induced platelet activation.

BACKGROUND: Diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A), a natural compound stored in platelet dense granules, inhibits ADP-induced platelet aggregation. Ap(4)A inhibits the platelet ADP receptors P2Y(1) and P2Y(12), is a partial agonist of P2Y(12), and is a full agonist of the platelet ATP-gated ion channel P2X1. Modification of the Ap(4)A tetraphosphate backbone enhances inhibition of ADP-induced platelet aggregation. However, the effects of these Ap(4)A analogs on human platelet P2Y(1), P2Y(12) and P2X1 are unclear. OBJECTIVE: To determine the agonist and antagonist activities of diadenosine tetraphosphate analogs towards P2Y(1), P2Y(12), and P2X1. METHODS: We synthesized the following Ap(4)A analogs: P(1),P(4)-dithiotetraphosphate; P(2),P(3)-chloromethylenetetraphosphate; P(1)-thio-P(2),P(3)-chloromethylenetetraphosphate; and P(1),P(4)-dithio-P(2),P(3)-chloromethylenetetraphosphate. We then measured the effects of these analogs on: (i) ADP-induced platelet aggregation; (ii) P2Y(1)-mediated changes in cytosolic Ca(2+); (iii) P2Y(12)-mediated changes in vasodilator-stimulated phosphoprotein phosphorylation; and (iv) P2X1-mediated entry of extracellular Ca(2+). RESULTS: Ap(4)A analogs with modifications in the phosphate backbone inhibited both P2Y(1) and P2Y(12), and showed no agonist activity towards these receptors. The dithio modification increased inhibition of P2Y(1), P2Y(12), and platelet aggregation, whereas the chloromethylene modification increased inhibition of P2Y(12) and platelet aggregation, but decreased P2Y(1) inhibition. Combining the dithio and chloromethylene modifications increased P2Y(1) and P2Y(12) inhibition. As compared with Ap(4)A, each modification decreased agonist activity towards P2X1, and the dual modification completely eliminated P2X1 agonist activity. CONCLUSIONS: As compared with Ap(4)A, tetraphosphate backbone analogs of Ap(4)A have diminished activity towards P2X1 but inhibit both P2Y(1) and P2Y(12) and, with greater potency, inhibit ADP-induced platelet aggregation. Thus, diadenosine tetraphosphate analogs with dual receptor selectivity may have potential as antiplatelet drugs.