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Biomedical subjects

K H Chao

Publications and source records attributed to K H Chao.

At least 37 records · Page 2Linked to original sources

Assisted hatching increases the implantation and pregnancy rate of in vitro fertilization (IVF)-embryo transfer (ET), but not that of IVF-tubal ET in patients with repeated IVF failures.

OBJECTIVE: To assess the effect of augmenting IVF with assisted hatching in the treatment of patients with repeated IVF failures. DESIGN: Prospective randomized study. SETTING: Division of Reproductive Endocrinology and Infertility of National Taiwan University Hospital. PATIENT(S): From July 1993 to February 1996, 49 patients with repeatedly failed IVF were treated with assisted hatching and were compared with 51 control subjects without assisted hatching. INTERVENTION(S): Assisted hatching. MAIN OUTCOME MEASURE(S): Pregnancy rate and implantation rate per embryo after IVF-ET or IVF-tubal ET (TET) were measured. RESULT(S): The pregnancy rate (PR) in the assisted hatching group was found to be 36.7% compared with 19.6% in the control group, but the difference was not significant. When only patients receiving IVF-ET were considered, it was observed that the PR was significantly higher in the assisted hatching group than the control group (42.4% versus 16.1%). With IVF-TET however, the PR was found to be similar in both assisted hatching and control groups (25.0% and 25.0%, respectively). The rate of embryonic implantation in the IVF-ET patients was 11.0%, which was significantly higher than that of control embryos (3.7%). CONCLUSION(S): These results implied that IVF-ET, combined with assisted hatching, may improve the PR and implantation rate in patients with repeated IVF failures, but the same was not true in the case of IVF-TET.

Embryo Implantation↗

Peritoneal interleukin-10 increases with decrease in activated CD4+ T lymphocytes in women with endometriosis.

This study was performed to determine whether peritoneal T cells are suppressed in the CD4+ or CD8+ T cell subpopulation and whether they are Th1 or Th2 predominant in women with endometriosis. Immune cells in the peritoneal fluid (PF) were obtained from women undergoing laparoscopy for endometriosis or tubal ligation. Three-colour flow cytometry was utilized for immunophenotyping of peritoneal fluid mononuclear cells (PFMC). Concentrations of interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) produced by PFMC with and without mitogen stimulation and concentrations of IL-10 and IL-12 were measured in PF. The peritoneal T lymphocytes were predominantly of the Th1 type that produced much more IFN-gamma but less IL-4 or IL-5 in women with or without endometriosis. The decrease in peritoneal lymphocytes was significant in the HLA-DR+ CD4+ CD3+ subpopulation and the concentrations of peritoneal IL-10 and IL-12 were significantly elevated in women with early stage endometriosis. There was impaired IL-5 production by PFMC after phytohaemagglutinin stimulation in women with advanced stage endometriosis. We concluded that the activated peritoneal CD4+ Th1 cells from the women with endometriosis were decreased in number. The suppression of these T cells may be due to the elevation of IL-10 and IL-12 in the peritoneal fluid.

CD4-Positive T-Lymphocytes↗

Paired human chorionic gonadotrophin determinations for the prediction of pregnancy outcome in assisted reproduction.

The aim of this study was to determine the prognostic value of single and paired measurements of serum concentrations of human chorionic gonadotrophin (HCG) for successful pregnancy following in-vitro fertilization (IVF) and tubal embryo transfer (TET). We analysed serum HCG concentrations 15 and 22 days after IVF or TET in 198 conception cycles. Cut-off values of serum HCG were determined by a receiver operating characteristic (ROC) curve. On the basis of single HCG samples on day 15 (HCG15) after transfer, using a cut-off value of HCG15 = 150 mIU/ml, the sensitivity was 71% and the specificity was 77%. The positive predictive value (HCG15 > or = 150 mIU/ml indicating a normal pregnancy) was 89%, while the negative predictive rate (HCG15 < 150 mIU/ml indicating an abnormal pregnancy) was 51%. Patients with HCG15 < 150 mIU/ml but HCG22/HCG15 ratio > or = 15, still had a 90% chance of normal pregnancy. However, in patients with HCG15 < 150 mIU/ml and an HCG22/HCG15 ratio < 15, there was an 84% chance of an abnormal pregnancy. We conclude that a single HCG15 determination combined with the ratio of HCG22 to HCG15 has a higher diagnostic accuracy for prediction of pregnancy outcome than either analysis alone.

Chorionic Gonadotropin↗

Total antioxidant status and nitric oxide do not increase in peritoneal fluids from women with endometriosis.

To explore the role of nitric oxide (NO) and oxidative stress in the pathogenesis of adhesion formation and in endometriosis-associated infertility, we examined the peritoneal total antioxidant status (TAS) and the concentrations of products of NO metabolism in women with endometriosis (early stage, n = 12; advanced stage, n = 12) and in fertile women without endometriosis (n = 10). Peritoneal CA 125 and oestrogen and progesterone concentrations were also measured to examine their contributions to TAS and the production of NO. We failed to demonstrate any significant difference in TAS and in the products of NO metabolism in peritoneal fluids among women with early and advanced stages of endometriosis compared with fertile women without endometriosis during the early follicular phase. TAS and the concentration of the products of NO metabolism were not related to concentrations of CA 125, oestrogen or progesterone. The concentration of CA 125 in serum, but not in peritoneal fluid, was positively correlated with the severity of endometriosis. The volume of peritoneal fluid and the progesterone concentration were significantly increased in the group with advanced endometriosis. TAS and the concentration of the products of NO metabolism did not increase in peritoneal fluids from women with endometriosis during the early follicular phase. Their role in the pathophysiology of endometriosis needs to be explored further.

Antioxidants↗

KTP laser and neutral red phototherapy of human squamous cell carcinoma.

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 microg/ml NR in the absence of light. However, cells incubated with greater than 0.5 microg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.

Antineoplastic Agents↗

Serum estradiol level and oocyte number in predicting severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a relatively common and potentially life-threatening complication of ovarian stimulation, the pathogenesis of which remains unclear. To clarify the predictive values of serum estradiol levels and oocyte number in severe OHSS, and to investigate the impact of high serum estradiol levels on pregnancy outcome, we retrospectively analyzed clinical data from 431 cycles of ovarian stimulation for assisted reproduction performed from 1993 through 1995. Receiver operating characteristic plots were used to estimate the predictive power of the measured variables. The overall frequency of severe OHSS was 5.5%. Using a serum estradiol level of 3,600 pg/mL as the minimum cut-off value, the sensitivity was 58%, with a specificity of 92%, a positive predictive value of 29%, and a negative predictive value of 97%. The predictive power was similar when a cut-off point of 20 oocytes retrieved was used. The two criteria together gave a sensitivity of 33%, a specificity of 92%, a positive predictive value of 40%, and a negative predictive value of 98%. One of seven oocyte donors developed severe OHSS. The pregnancy rate was higher in patients with severe OHSS than in patients who did not develop this syndrome (73.9% vs 32.5%) but the pregnancy outcomes were not significantly different. We conclude that elevated estradiol concentrations and oocyte number appear to be helpful in predicting severe OHSS, but neither parameter by itself is predictive. This syndrome is rare in the absence of luteal hCG support, either exogenous or pregnancy-derived; when it occurs, there are usually extremely high preovulatory estradiol concentrations and numerous oocytes retrieved. High serum estradiol levels are unlikely to have adverse effects on pregnancy outcome in patients with severe OHSS.

Adult↗

Long GnRH-agonist protocol in an IVF program. Is it appropriate for women with normal FSH levels and high FSH/LH ratios?

OBJECTIVE: To determine whether subjects with an elevated ratio of follicle-stimulating hormone (FSH) to luteinizing hormone (LH) but normal basal FSH levels should be regarded as poor responders to controlled ovarian hyperstimulation. STUDY DESIGN: One hundred twenty-five women undergoing in vitro fertilization (IVF) for the first time were recruited in this retrospective cohort study. Women over 40 years old or having serum basal FSH > 10 mIU/mL were excluded. RESULTS: Various cutoff values for the FSH/LH ratio were chosen, and the ratio demonstrated that pregnancy rates were apparently higher in patients with the long protocol than with the short one if they had an FSH/LH ratio < 3.0 (48.5% vs. 25.8%, P = .034), < 2.5 (53.3% vs. 28.6%, P = .030) or < 2.0 (57.8% vs. 21.7%, P = .005). Pregnancy rates were similar with the long and short protocols in patients with FSH/LH > or = 3.0 (57.1% vs. 70%, P = .521), FSH/LH > or = 2.5 (40% vs. 53.8%, P = .435) or FSH/LH > or = 2.0 (40% vs. 55.6%, P = .281). CONCLUSION: This study failed to demonstrate that FSH/LH was a useful parameter for predicting reproductive outcome in IVF programs and for patient selection for the long or short gonadotropin-releasing hormone agonist protocol.

Buserelin↗

Activation status of T and NK cells in the endometrium throughout menstrual cycle and normal and abnormal early pregnancy.

Endometrial lymphocytes were studied at all stages throughout the menstrual cycle and early pregnancy by flow cytometry to examine different lymphocyte subpopulations and the expression of the T- and NK-cell activation markers. After pregnancy, CD8+CD3+ lymphocytes were decreased in the decidua. In both endometrium and decidua, more T cells expressed CD69, CD71, HLA-DR, and CD38 antigens than in peripheral blood. After pregnancy, CD71+CD3+ lymphocytes were further increased. CD25+CD3+ lymphocytes decreased significantly in the endometrium and decidua of ectopic pregnancies, but not in the decidua of normal pregnancies. These findings indicate that T cells are regionally activated in the first trimester, and it may be the result of the stimulation by fetal antigens. NK cells were the most abundant cell type in the decidua, which expressed the phenotype CD16- CD56+, and CD57-CD56+. The proportion of activated decidual NK cells was increased in anembryonic pregnancies more than in normal pregnancies, although the total NK subpopulation was similar in both groups. This might result in increased NK cytotoxicity in anembryonic pregnancies. In conclusion, T cells are activated, but NK cytotoxicity is decreased in the decidua of early normal pregnancies. This might be important in the control of trophoblast growth and placental development.

Abortion, Induced↗

Decrease in interferon gamma production and impairment of T-lymphocyte proliferation in peritoneal fluid of women with endometriosis.

OBJECTIVE: Our purpose was to verify regional immune modulations and to test the effect of gonadotropin-releasing hormone agonist in women with endometriosis. STUDY DESIGN: Concentrations of peritoneal cytokines, including interleukin-1 beta, interleukin-2, soluble interleukin-2 receptor, interleukin-6, granulocyte-monocyte colony-stimulating factor, interferon gamma, and tumor necrosis factor-alpha were compared in women with and without endometriosis. Peritoneal cytokine and interleukin-2 production were examined by adding various mitogens to peritoneal fluid mononuclear cells of women with advanced endometriosis before and after gonadotropin-releasing hormone agonist treatment. RESULTS: A significant increase in peritoneal interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha and a decrease in interferon gamma were noted in women with endometriosis. After gonadotropin-releasing hormone agonist treatment interleukin-6 decreased and interferon gamma increased. A significant impairment of interleukin-2 production of peritoneal fluid mononuclear cells by phytohemagglutinin and pokeweed mitogen stimulation was demonstrated in endometriosis, and production could be restored after gonadotropin-releasing hormone agonist treatment. CONCLUSION: These results indicate that regional immunologic dysfunction might be invoked in the disease process of endometriosis.

Ascitic Fluid↗

The value of human growth hormone as an adjuvant for ovarian stimulation in a human in vitro fertilization program.

The purpose of this study was to evaluate whether the combined treatment of growth hormone (GH) and gonadotropins can improve ovulation stimulation in previously poor responders. Twelve patients who, had suboptimal responses in previous in vitro fertilization cycle were enrolled. They underwent 1 cycle with gonadotropin-releasing hormone analogue (GnRH-a) and gonadotropins and another cycle with GnRH-a, gonadotropins, and GH. Serum gonadotropins, insulin-like growth factor-1 (IGF-1), and sex steroids, including estradiol (E2), progesterone (P4), testosterone, and androstenedione were measured on Day 2 and during ovulation induction. The serum IGF-1 level was higher in the GH cycle. There were no significant differences in the levels of the serum luteinizing hormone, E2, P4, testosterone, and androstenedione between the 2 cycles, so was IGF-1, E2 and P4 in follicular fluid. Co-treatment with GH did not improve the ovarian response. However, the GH cycles had better performance in terms of the number of oocytes fertilized and the pregnancy rate.

Androstenedione↗

The suppression of peritoneal cellular immunity in women with endometriosis could be restored after gonadotropin releasing hormone agonist treatment.

PROBLEM: Our previous study reported that peritoneal natural killer (NK) cytotoxicity and CD3+CD25+ lymphocyte subpopulation were suppressed in women with advanced endometriosis. Whether these phenomena are general for all stages of endometriosis and whether these alterations could be restored by long-term use of gonadotropin releasing hormone agonist (GnRHa) are further tested in this study. METHOD: Lymphocyte subpopulations (B cells, NK cells, T cells, and T-cell activation markers such as CD69, HLA-DR, and CD25) and NK cell cytotoxicity of peripheral blood and peritoneal fluid by dual-color flow cytometry and 51Cr release assay in 30 cases of endometriosis were compared with those in 26 controls. We also compared these changes before and after 6-month treatment with GnRHa for advanced endometriosis. RESULTS: Compared with the controls, only those women with advanced endometriosis showed lower NK cytotoxicity in peritoneal fluid mononuclear cells (PFMC). The CD3+CD69+ lymphocyte subpopulation decreased in peripheral blood mononuclear cells (PBMC) of advanced endometriosis, while the CD3+CD25+ lymphocyte subpopulation decreased in both PBMC and PFMC of mild and advanced endometriosis. After GnRHa treatment, the CD3+CD69+ lymphocyte subpopulation increased in both PBMC and PFMC and the CD3+CD25+ lymphocyte subpopulation increased in PFMC, but not in PBMC. CONCLUSION: Impaired local immunological function in the PF of endometriosis was confirmed by this study and the impairments could be restored after long-term GnRHa therapy.

Ascitic Fluid↗

How many embryos should be transferred in in vitro fertilization and tubal embryo transfer?

In order to achieve higher pregnancy rates, more than one embryo is usually transferred in in vitro fertilization (IVF) programs. Tubal embryo transfer (TET) produces an even higher pregnancy rate. However, the number of embryos that should be transferred in TET programs remains to be clarified. We studied a series of 241 consecutive TET cycles and analyzed their clinical characteristics, embryo numbers, cumulative embryo score (CES), and pregnancy outcomes. The results demonstrated that 1) four embryos was an adequate number to obtain a satisfactory pregnancy rate and fewer multiple pregnancies, 2) older patients and cases with male factor had less chance of pregnancy and more than four embryos could be transferred, and 3) CES values > 40 were preferred, but for young patients with unusually high anxiety about multiple pregnancies, a CES of 21 to 40 was optimal. A policy of transfer that limits transfer to a maximum of two, three or four embryos is not suitable in all cases and other factors (eg, repeated IVF failure or older age) should be individually considered. Therefore, two equations utilizing CES, age and failure of previous TET as the factors were developed to help practitioners to evaluate how many embryos should be transferred on an individual basis.

Adult↗

Comparison between a two-layer discontinuous Percoll gradient and swim-up for sperm preparation on normal and abnormal semen samples.

PURPOSE: This work was to compare the effects of Percoll gradient and swim-up treatments for sperm preparation on the percentage of progressive motility, recovery of motile sperm, removal of debris, percentage of normal forms according to strict criteria, and movement characteristics of sperm using computer-assisted velocity analysis. RESULTS: In total, 50 semen samples from 50 patients were tested and divided into two groups: a normal group (n = 27) with normal parameters and an abnormal group (n = 23) with abnormal parameters. The results in both the normal and abnormal groups revealed that the sperm concentration in the Percoll samples was significantly greater than that in the swim-up samples. Although the percentage of progressive motility was greater in the swim-up samples than in the Percoll samples, the number of motile sperm, reflecting the percentage of motile sperm recovery, was till greater in the Percoll samples. The debris of semen was equally removed by both methods and the percentage of normal forms was also similar in the samples treated according to these two procedures. Both curvilinear velocity (VCL) and straight-line velocity (VSL) of sperm were significantly greater in the swim-up samples than in the Percoll samples. Sperm from the swim-up procedure also showed a greater mean amplitude of lateral head displacement than that from the Percoll gradient procedure, but the distinction was insignificant. CONCLUSION: The Percoll gradient technique, by recovering more motile sperm, may be applied to prepare oligospermic samples. The swim-up method may become the standard choice to prepare normal semen which could obtain sufficiently motile sperm, due to its simplicity and recovered sperm with superior motility.

Centrifugation, Density Gradient↗

Synchronous primary carcinomas of the endometrium and ovary.

OBJECTIVES: Synchronous carcinomas of the endometrium and ovary may indicate either independently developing neoplasms or metastatic disease. The clinical implications and prognosis of these two categories are quite different. The objectives of this study were to identify and evaluate the empirical criteria and significant therapeutic implications. METHOD: The National Taiwan University Hospital Cancer Registry records and pathological reports from 1977 to 1994 were reviewed. Empirical criteria were used to identify synchronous primary cancers. RESULTS: A total of 322 patients had endometrial cancer and 421 patients had ovarian cancer in our Cancer Registry records. Eleven patients had simultaneous cancer involvement of both the endometrium and ovary. Six cases fulfilled the criteria of synchronous primary carcinomas of the endometrium and ovary. Of these, five were alive and free of disease for 35-144 months (median 94.2 months). The disease-free survival rates between patients with synchronous primary and metastatic cancers of different histologic types showed a statistically significant difference (P = 0.013). No statistical significance was noted for different histologic types (P > 0.5). CONCLUSIONS: The empirical criteria used here were useful in identifying synchronous primary cancers of the endometrium and ovary. The favorable clinical outcome may relate to early detection of early-stage disease and low-grade malignancy with an indolent growth rate. Surgical management with or without adjuvant therapy has a satisfactory outcome in our experience.

Adult↗

Peritoneal natural killer cytotoxicity and CD25+ CD3+ lymphocyte subpopulation are decreased in women with stage III-IV endometriosis.

We examined the lymphocytes of peripheral blood (PB) and peritoneal fluid (PF) of women with or without endometriosis to investigate the alteration of cytotoxic activity of natural killer (NK) cells and activation of T cells in the peritoneal cavity of women with endometriosis. A total of 16 control women and 14 patients with stage III-IV endometriosis were selected on the basis of laparoscopic examination in National Taiwan University Hospital. The lymphocyte subpopulations (B cell, NK cell and T cell), including T-cell activation markers (CD69, CD25, HLA-DR), in PB and PF were analysed by dual-colour flow cytometry. The NK cytotoxicity of PB and PF mononuclear cells was evaluated by 51Cr release assay. There was a significant decrease of NK cytotoxicity and CD25+ CD3+ lymphocyte subpopulation in PF of women with endometriosis compared with those without endometriosis. However, there was no difference in the proportion of NK cells in both PB and PF between women with and without endometriosis. Therefore, the decreased NK cytotoxicity in PF of women with endometriosis was due to the functional defect, but not quantitative defect, of NK cells. The concomitant reduction of activated T cells in women with endometriosis might suggest its possible role in the defect of NK cytotoxicity.

Ascitic Fluid↗

Gonadotropin releasing hormone (GnRH) agonist induces down-regulation of the CD3+CD25+ lymphocyte subpopulation in peripheral blood.

PROBLEM: To test whether GnRH agonist could alter in vivo human immune cells and whether the alteration is related to the success of pregnancy in an in vitro fertilization-embryo transfer (IVF-ET) program. METHODS: Thirty-six infertile patients were enrolled under the long protocol of GnRH agonist (buserelin acetate) and superovulation with gonadotropin from our IVF-ET program. Peripheral B cells, NK cells, CD4+ and CD8+ T cells, and the expression of CD69, CD25, HLA-DR, and CD71 antigens on the T cells were serially examined by dual-color flow cytometry. RESULTS: B cells, NK cells, CD8+ T cells, and CD71+ T lymphocyte subpopulations were not changed throughout the whole course of treatment. CD4+ T cell and CD25+ T cell subpopulations were significantly down-regulated when the GnRH agonist was used for approximately 2 wk. CD3+CD69+, CD3+CD25+, and CD3+DR+ lymphocyte subpopulations were increased at 7 days (during implantation) and at 14 days after embryo transfer in pregnant patients, but not in patients who failed to get pregnant. CONCLUSIONS: The GnRH agonist had a transiently immunosuppressive effect on CD4+ and CD25+ T cells, but CD69+, CD25+, and HLA-DR+ T cells were activated during and after successful implantation.

Adult↗

Decidual natural killer cytotoxicity decreased in normal pregnancy but not in anembryonic pregnancy and recurrent spontaneous abortion.

PROBLEM: The natural killer (NK) cell activity is depressed in the decidua of early normal pregnancy. Recently Morii et al. (Am J Reprod Immunol 1993;29:1-4) found that all early intradecidual CD3+ T cells expressed either T cell receptor (TCR) alpha/beta or gamma/delta but that the expression of the CD3+/TCR complex was down-regulated. METHOD: To test whether these changes in decidual cellular immunity are different among normal pregnancy, anembryonic pregnancy and recurrent spontaneous abortion, we examined the immune cell subpopulations in the decidua from these three types of pregnancy using flow cytometry and an NK cytotoxicity assay. RESULTS: Intradecidual CD3+ T cells expressed either TCR alpha/beta or gamma/delta, and the level of expression of the CD3/TCR complex was down-regulated in normal pregnancy, anembryonic pregnancy, and recurrent spontaneous abortion. Although the relative proportion of decidual NK cells was increased to approximately the same extent in all three types of pregnancy, decidual NK activity was higher in anembryonic pregnancies and in recurrent spontaneous abortions than it was in normal pregnancies. CONCLUSION: Decidual NK cell responses are different in anembryonic pregnancies and in recurrent spontaneous abortions than in normal pregnancies. Whether this difference is pathogenic or is the response to a dead embryo remains to be elucidated.

Abortion, Habitual↗

Interleukin-1 beta (IL-1 beta) is increased in the follicular fluids of patients with premature luteinization.

PROBLEM: Most, but not all, studies indicate that premature luteinization correlates with poor pregnancy outcome in in-vitro fertilization (IVF) programs. It remains unclear whether cytokines (IL-1 beta, TNF alpha), the established immune mediators, play a role in regulation or initiation of an abnormal follicular or embryo development in patients with premature luteinization. METHODS: Levels of cytokines (IL-1 beta, TNF alpha), estradiol (E2) progesterone (P4), and androstenedione (A'ione) were examined in 18 preovulatory follicular fluid (FF) samples from patients with premature luteinization (group 1) and 3 FF samples from patients without premature luteinization (group 2). The number of oocytes recovered, fertilization rate, and pregnancy outcome were evaluated in these two groups. RESULT: IL-1 beta (25.4 +/ 11.9 pg/ml, mean +/ SD) and TNF alpha (13.4 +/ 10.7 pg/ml) were present in these FF samples. The mean level of IL-1 beta in group 1 was significantly higher than that in group 2 (37.3 +/ 12.3 vs. 20.0 +/ 7.6 pg/ml; P < 0.00001) and the mean level of E2 was significantly lower in group 1 than that in group 2 (1064 +/ 686 vs. 1570 +/ 641 ng/ml; P = 0.02). The levels of TNF alpha, P4, and A'ione showed no distinction between these two groups. There was no correlation between the levels of either IL-1 beta or TNF alpha and P4, E2 or A'ione. The fertilization rate in group 1 (62/77; 80%) was similar to that in group 2 (124/160; 78%). Five of 7 patients in group 1 and seven of 20 patients in group 2 achieved pregnancy following embryo transfer. One of five pregnancies in group 1 aborted. CONCLUSION: The exaggerated levels of IL-1 beta in patients with premature luteinization may arise from accumulation of this cytokine owing to sustained high LH stimulation, and this may be a protective response to the abnormal LH surge and function to inhibit prematurely increased secretion of P4. These data indicate the important role of LH in the induction of IL-1 beta secretion and the possible regulatory action of IL-1 beta in luteinization. According to the diminution of E2 in group 1, there may be a subtle atretic process progressing in follicles primed with prematurely elevated LH. However, the detrimental effect of premature luteinization, if it exists, may work at the stage ¿during or after implantation.

Abortion, Spontaneous↗