Different immune responses in different parts of the cycle.
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Biomedical subjects
Publications and source records attributed to J H Check.
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PURPOSE: To determine if production of the immunomodulatory protein, progesterone induced blocking factor (PIBF), requires merely progesterone or whether other factors made by the corpus luteum are required. METHODS: The percentage of peripheral lymphocytes expressing PIBF was determined by obtaining a blood sample from women 9-12 days after embryo transfer. The embryos were either fresh ones following hyperstimulation and oocyte retrieval or were frozen-thawed embryos. Preparation for frozen embryo transfer required corpus luteum suppression with exogenous estrogen. The percentage of lymphocytes expressing PIBF was determined by an immunocytochemistry method. RESULTS: PIBF expression (>1%) was found in 20.5% of COH and 13.3% of frozen embryo transfer cycles. There either was a significant difference or a trend for higher pregnancy rates when PIBF expression was detected. CONCLUSIONS: These data corroborate previous conclusions that PIBF is detected in a minority of women in the late luteal phase. A corpus luteum is not required for its expression.
The hypo-osmotic swelling (HOS) test measures the functional integrity of the sperm membrane. Although, the sperm membrane is essential for the fertilization of oocytes, several clinical studies suggest that abnormally low HOS test scores do not predict poor or failed fertilization in human in-vitro fertilization trials. However, in-vivo and in-vitro studies clearly demonstrate that a low HOS score is associated with poor pregnancy rates suggesting this sperm defect causes implantation problems rather than fertilization problems. The problem of implantation could be caused by the supernumerary sperm attached to the zona pellucida. Supporting evidence for this theory was demonstrated by finding high pregnancy and implantation rates despite low HOS scores following intracytoplasmic sperm injection which avoids the presence of supernumerary sperm on the zona pellucida. These data thus support theories that some sperm abnormalities may reduce fertility potential by causing implantation disorders rather than problems with fertilization.
Attempts to treat various cancers by immunotherapy have been tried for about 50 years. Most studies have focused on improving cytotoxic T lymphocyte (CTL) responses against various tumors. Immunotherapy has been both active and passive, and results have been modest at best. Spontaneous abortion (SAB) of pregnancies could in some ways resemble remission of a tumor. Both tumors and conceptusses are faced with a similar problem -- how to grow in a host in a vascular rich area, and yet escape immune surveillance despite both entities being an allogenic stimulus. In general, the fetus is far more immunogenic than a spontaneous tumor, and yet abortuses seem to avoid CTL responses but are sometimes invaded by natural killer (NK) cells. There are data suggesting that SAB will occur if there is inhibition of production of an immunosuppressive protein called progesterone-induced blocking factor (PIBF). This protein inhibits NK cell cytolysis and influences TH2 cytokine dominance over TH1. If some tumors avoid NK cell destruction through a PIBF mechanism, perhaps an active rejection of these tumors could be achieved by inhibiting PIBF production by treating with a progesterone receptor antagonist. Passive immunization could also be considered by conjugative radionuclide or toxic chemical to a PIBF antibody which may be tumor specific since PIBF is not produced in normal tissue. The first step should be to see if PIBF can be detected in the peripheral circulation in patients with certain tumors.
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BACKGROUND: Recipients of donor oocytes need to be synchronized to the donor's cycle if fresh embryos are to be transferred on the cycle of oocyte retrieval. It would be much easier to merely retrieve the oocytes from the donor, fertilize the oocytes with the recipient's male partner's spermatozoa, cryopreserve the embryos, then transfer on an oestrogen/progesterone treatment programme. METHODS: The IVF outcomes of all patients enrolled in a shared oocyte programme from January 1997 to June 1999 were reviewed. Pregnancy and implantation rates were computed and statistically analysed. RESULTS: There was a significantly higher clinical pregnancy rate for recipients who had a fresh embryo transfer compared with recipients whose first embryo transfer consisted of frozen/thawed embryos (63.4 versus 43.6%). CONCLUSIONS: Conception is more likely after fresh than frozen embryo transfer with recipients but is similar to donor conception rates. If a uterine defect, per se, even without the use of the controlled ovarian stimulation regimen, could explain the difference between fresh pregnancy and implantation rates in donors versus recipients, then these same differences would have been seen when comparing frozen transfers, but they were, in fact, similar.
PURPOSE: To assess the ability of twice frozen/thawed multi-cell embryos to implant in the human uterus. METHOD: Fourteen frozen embryo transfer (ET) cycles, in which at least one twice-frozen embryo was thawed for transfer, were matched to frozen ET cycles in which no twice-frozen embryos were thawed. The number of embryos thawed at the pronuclear stage and at the multi-cell stage were matched. RESULTS: Multi-cell embryos frozen once had a 76.3% survival rate after thaw and those frozen twice had a 74.0% survival rate. For frozen ET cycles that had no twice-frozen embryos, the viable pregnancy and implantation rates were 58.3% and 29.8%, respectively. The corresponding rates for cycles involving at least one twice-frozen embryo were 50.0% and 25.5%, respectively. CONCLUSION: The inclusion of twice-frozen embryos in the embryo pool did not reduce the implantation rate.
PURPOSE: To determine if pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) correlate with the presence or not of luteinizing hormone (LH) in the gonadotropins used for stimulation. Furthermore to see if the early follicular phase serum LH level affects pregnancy outcome according to the type of gonadotropins used. METHODS: The type of gonadotropins were prescribed randomly according to finances and convenience. Serum LH was obtained on day 2 or 3 of the menstrual cycle. RESULTS: When LH was > the median, significantly higher pregnancy rates were obtained in those treated with the follicle stimulating hormone (FSH)/human menopausal gonadotropin combination. When LH was < or = the median, significantly more oocytes were retrieved with FSH exclusively. No confounding variables were found to explain the data. CONCLUSIONS: Considering concerns of published studies that LH may have a toxic effect on pregnancy outcome, and if LH is suppressed too low, gonadotropins with exclusive FSH may not stimulate sufficient oocytes, the results were opposite to expectations.
PURPOSE: To see if pregnancies can be achieved after performing intracytoplasmic sperm injection (ICSI) of in vitro matured metaphase I or germinal vesicle stage oocytes and then cryopreserving them at the 2 pronuclear stage. METHODS: Transfer of frozen/thawed hatched day 3 embryos to two women. All embryos were a result of in vitro maturation of immature oocytes followed by ICSI. RESULTS: Both women conceived. One has delivered and one has successfully completed the first trimester. CONCLUSION: These two cases represent only the second and third reported cases of pregnancies following frozen embryo transfer where the embryos resulted from fertilizing immature oocytes by ICSI.
PURPOSE: To determine if unilateral salpingectomy for hydrosalpinx can improve fecundity in a woman with many cycles of failure to conceive despite the fertilization of donor oocytes and subsequent embryo transfer. METHODS: Salpingectomy performed after failure to conceive despite IVF-ET with the patient's own oocytes (n=5) or transfer of donor embryos (n=2) or embryo transfer cycles as a donor oocyte recipient (n=5). RESULTS: The patient conceived three of four times following salpingectomy. Transfer of four frozen-thawed donor embryos and two frozen-thawed embryos of her own led to a successful delivery. In one of two cycles as a donor oocyte recipient she had a successful delivery and subsequently, the transfer of cryopreserved/thawed embryos from a previous donor oocyte cycle led to a chemical pregnancy. CONCLUSION: Unilateral hydrosalpinx can be a cause of recalcitrant failure to conceive despite assisted reproductive technology. Salpingectomy can restore fecundity.
PURPOSE: To evaluate pregnancy and implantation rates following fresh and frozen embryo transfer (ET) according to blastomere number. METHODS: A retrospective study from 1/1/97 to 9/30/98 including all cycles with ETs irrespective of age. RESULTS: 65% of fresh transfers had at least one 8-cell embryo vs only 39.6% for frozen ET. The clinical pregnancy and implantation rates were higher when one 8-cell embryo was transferred (64% and 24%) vs a 5-7 cell embryo (41% and 14.5%) for fresh transfers. There was less of a difference with frozen ETs (46% and 19% for 8-cell vs 38% and 17% for 5-7 cell). CONCLUSIONS: Since mostly only 8-cell embryos at day 3 reach the blastocyst stage, these data raise questions as to whether the quest to attain the highest pregnancy rate per transfer through blastocyst transfer, may be at the expense of overall pregnancy rate (fresh and frozen) from a given oocyte harvest.
PURPOSE: Follow-up of a woman with a serum CA-125 level > 1000 U/mL where laparoscopy only found endometriosis. METHODS: Case report-- re-evaluation several years later. RESULTS: Extensive clear-cell carcinoma of ovary with metastases leading to death. CONCLUSION: This case suggests that bilateral oophorectomy should be performed in women not desiring any more children if the serum CA- 125 level is very high even if only endometriosis is found initially.
PURPOSE: To determine if the presence of uterine fibroids adversely affect in vivo conception rates. METHODS: Pelvic ultrasound evaluation of the presence or absence of fibroids in consecutive infertility patients not treated with assisted reproductive technology in a two-year period. Conception outcome noted. Data analyzed according to the presence or absence of fibroids. RESULTS: No difference in cumulative probability of pregnancy after five months was seen in patients with or without the presence of fibroids. There were no confounding variables found that could have skewed the pregnancy rates in one direction or the other. CONCLUSION: In general the presence of fibroids do not adversely affect conception outcome for in vivo pregnancies. However, since the majority of the fibroids were small (< 6 cm) and were not submucosal and did not compress the endometrial cavity, larger studies are needed to address specific subtypes and circumstances on pregnancy outcome.
PURPOSE: To evaluate the longest interval that embryos can remain frozen and still result in a viable pregnancy after thaw and transfer. METHODS: Case report. RESULTS: A 42-year-old woman conceived and successfully completed the first trimester after transfer of frozen donated embryos from a 32-year-old woman whose eggs had been cryopreserved for over nine years. CONCLUSIONS: Patients can now be informed that there is anecdotal evidence that embryos can survive and result in successful pregnancies even after nine years of cryopreservation. This information may affect legislative decisions in requiring destruction of these stored embryos.
PURPOSE: To determine if maternal/paternal sharing of DQ alpha major histocompatibility (MHC) type II antigens is associated with reduced pregnancy and implantation rates following in vitro fertilization-embryo transfer (IVF-ET). METHODS: Prospective study with type II MHC DQ alpha alleles detected by polymerase chain reaction (PCR) technology using Perkin Elmer Amyli-type HLA DQ alpha PCR amplification and typing kit. The tests were only performed on patients having their first IVF cycle. RESULTS: No difference was found in clinical pregnancy rates per transfer between those couples sharing DQ alpha I alleles and those who did not (43.7% vs 40%). There were no spontaneous abortions in the group sharing DQ alpha I alleles. CONCLUSION: Maternal/paternal sharing of DQ alpha I antigens does not reduce fecundity following IVF-ET.
PURPOSE: To evaluate in the modern era of in vitro fertilization (IVF) cumulative probability of pregnancy for the first four embryo transfers (ET) irrespective of whether the embryos were fresh or frozen. METHODS: Retrospective review over a 2 1/2 year period. Cumulative probability of pregnancy for four consecutive cycles of either fresh or frozen ETs divided into four age groups. RESULTS: The cumulative clinical and viable pregnancy rates after four ETs were 92% and 88%; 87% and 82%; 83% and 69%; and 68% and 52% for age groups <30, 30-34, 35-39, and 40-44. The cumulative rates decline with age. CONCLUSIONS: Pregnancy rates per transfer for the first four ETs regardless of age are similar even in IVF centers that emphasize frozen ETs.
Too often infertile patients are given a "herd type" fertility investigation which ultimately leads to expensive, time consuming, and risky in vitro fertilization. However, attention to certain simple details available by non-invasive methods, e.g., checking for premature luteinization, luteinized unruptured follicle syndrome, or performing the post-coital test at the appropriate interval, can lead to a quick solution of the infertility problem. Caution about persistent infertility related to iatrogenic factors, e.g., development of poor post-coital tests or excessively thin endometrium from clomiphene citrate, or development of luteinized unruptured follicle syndrome or premature luteinization by taking follicle maturing drugs, or creating a hostile environment from taking follicle maturing drugs when the woman already made a mature follicle (and would have had a higher success rate with luteal phase support with progesterone) will help achieve pregnancies without necessarily proceeding to the most expensive and invasive procedure of in vitro fertilization. Finally, many wasted cycles of treatment could be avoided by including the simple but very important hypo-osmotic swelling test and measurement of sperm autoantibodies with the first initial semen analysis.