The possibility of the immunological factor as an etiological cause of infertility was investigat... more The possibility of the immunological factor as an etiological cause of infertility was investigated in 50 infertile couples. Of these, 31 couples were considered as an "unexplained sterility" group, while in the other 19 couples a variety of disorders were diagnosed. In vitro, leucocyte migration inhibition test (LMIT) was used for the detection of female cell-mediated immunity against sperm antigens. Sperm immobilization test (SIT) and sperm toxicity tests (STT) were used for the detection of antisperm antibodies in the cervical mucus. Out of the 31 "unexplained sterility" cases, six revealed a positive LMIT (5.3%). In 26 couples with an abnormal postcoital test (PCT), 10 cases had a positive SIT and STT (38.5%). However, out of the group of 16 couples with a normal PCT only in one case was a positive SIT and STT found (6.2%). The potential role of immunological reactions in infertility will be discussed.
To study the role of tumor necrosis factor (TNF) in the male reproductive systems by examining th... more To study the role of tumor necrosis factor (TNF) in the male reproductive systems by examining the occurrence, source, and possible functional significance of soluble TNF receptors in seminal fluids of normal and infertile men. Concentrations of soluble TNF receptors (p55-sTNF-R and p75-sTNF-R) were measured by ELISA in human sera, seminal fluids, prostatic fluid and fluid obtained from an epididymal spermatocele. The level of p55-sTNF-R in seminal fluids of normospermic men was approximately equal to 20-fold higher than in normal serum (13.9 +/- 6.9 ng./ml. versus 0.7 +/- 0.2 ng./ml.). In contrast, p75-sTNF-R, which occurs in serum at amounts higher than p55-sTNF-R, was almost indiscernible in the seminal fluids (<0.18 +/- 0.28 ng./ml. versus 1.9 +/- 0.6 ng./ml. in sera). Concentrations of p55-sTNF-R in seminal fluids of oligoasthenospermic and azoospermic men were similar to those of normospermic men (15.6 +/- 8.5 ng./ml. and 14.9 +/- 6.5 ng./ml., respectively). Higher p55-sTNF-R concentrations were found in prostatic fluids and first split ejaculates (39.8 +/- 1.2 ng./ml. and 32 +/- 1.7 ng./ml., respectively), while second split ejaculates and the fluid from an epididymal spermatocele were found to contain p55-sTNF-R at lower levels (10.8 +/- 1 ng./ml. and 1 ng./ml., respectively). These findings suggest intense local biosynthesis of p55-sTNF-R in the prostate occurring independently of spermatogenesis. Possible functional implications are: 1) shielding of spermatozoa from the inhibitory effect of TNF in the female reproductive tract; 2) a role for TNF in the normal physiology of the prostate; and 3) blocking TNF-mediated immune response in the prostate, which may have bearings on the development of prostatic hypertrophy or cancer.
Several parameters affecting survival and implantation of frozen-thawed embryos were studied. Of ... more Several parameters affecting survival and implantation of frozen-thawed embryos were studied. Of 386 embryos frozen in dimethylsulfoxide (DMSO) or in 1,2 propanediol (PROH), the survival rate was 63.5% (245/386). Three different methods of cycle preparation were compared prior to thawed embryo replacement. The pregnancy rate was 16.1% (9/56) in spontaneous cycles; 11.4% (5/44) in an ovarian stimulation protocol; and 9.5% (4/42) with estrogen and progesterone substitutional therapy (p = NS). There was no difference in the estradiol/progesterone ratio among the three different protocols during the early luteal phase of the cycle, which may indicate that implantation of thawed embryos could be related to their developmental potential rather than to the endometrial environment. In the spontaneous cycles, when endometrium was synchronized or advanced to embryonic stage up to 32h, implantation rate was 29.2%.
To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregn... more To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregnancy rates (PRs) in patients with repeated failure of implantation in IVF-ET cycles. A case-control study. Criteria for patient selection included male factor or unexplained infertility, normal uterine cavity, and at least three failures of implantation in IVF-ET cycles in which at least three embryos were placed per transfer. Data on 70 patients who underwent 92 ZIFT cycles are presented. A control group consisted of patients with the same selection criteria who underwent an additional standard IVF-ET cycle during the same time period. Ovulation induction consisted of down-regulation with GnRH analogue followed by ovarian stimulation with FSH and hMG. Intracytoplasmic sperm injection was performed on the oocytes of all patients with male factor infertility. Zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after oocyte retrieval. Implantation rates and PRs in the ZIFT and control groups were compared. The PRs and implantation rates were significantly higher in the ZIFT group than in the control group: 34.2% (24/70) and 8.7% (29/333) versus 17.1% (12/70) and 4.4% (13/289), respectively (P = 0.002 and P = 0.04). The cumulative conception rate for two ZIFT cycles was 59.3%. Zygote intrafallopian transfer should be considered a beneficial mode of treatment for patients with repeated failure of implantation in IVF and transcervical ET. More prospective randomized studies are needed to support this observation.
Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oes... more Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1.09 and 0.92 multiples of the normal gestation-specific median (MOM) based on a total of 34582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1.05 MOM) and a significant decrease when Pergonal was used (0.93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0.92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Down's syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.
Evaluation of the intracellular signalling mechanisms of follicle stimulating hormone (FSH) and i... more Evaluation of the intracellular signalling mechanisms of follicle stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) was performed in luteinized and non-luteinized human granulosa cells. A severalfold increase in estradiol production from androstenedione was induced by both hormones in these cells, while only FSH led to a concomitant increase in cAMP. IGF-I bound specifically to its receptor in these cells. Specific tyrosine kinase inhibitors (tyrphostins) blocked the effects of both FSH and IGF-I on aromatase activity without altering FSH-induced cAMP accumulation. These findings demonstrate an involvement of a tyrosine kinase pathway in the intracellular signalling mechanism of the IGF-I effect on aromatase activity. Furthermore, since FSH induction of aromatase activity can be blocked by a tyrosine kinase inhibitor without affecting the level of cAMP production, it can be suggested that tyrosine kinase(s) act downstream of cAMP production and protein kinase A activation.
The possibility of the immunological factor as an etiological cause of infertility was investigat... more The possibility of the immunological factor as an etiological cause of infertility was investigated in 50 infertile couples. Of these, 31 couples were considered as an "unexplained sterility" group, while in the other 19 couples a variety of disorders were diagnosed. In vitro, leucocyte migration inhibition test (LMIT) was used for the detection of female cell-mediated immunity against sperm antigens. Sperm immobilization test (SIT) and sperm toxicity tests (STT) were used for the detection of antisperm antibodies in the cervical mucus. Out of the 31 "unexplained sterility" cases, six revealed a positive LMIT (5.3%). In 26 couples with an abnormal postcoital test (PCT), 10 cases had a positive SIT and STT (38.5%). However, out of the group of 16 couples with a normal PCT only in one case was a positive SIT and STT found (6.2%). The potential role of immunological reactions in infertility will be discussed.
To study the role of tumor necrosis factor (TNF) in the male reproductive systems by examining th... more To study the role of tumor necrosis factor (TNF) in the male reproductive systems by examining the occurrence, source, and possible functional significance of soluble TNF receptors in seminal fluids of normal and infertile men. Concentrations of soluble TNF receptors (p55-sTNF-R and p75-sTNF-R) were measured by ELISA in human sera, seminal fluids, prostatic fluid and fluid obtained from an epididymal spermatocele. The level of p55-sTNF-R in seminal fluids of normospermic men was approximately equal to 20-fold higher than in normal serum (13.9 +/- 6.9 ng./ml. versus 0.7 +/- 0.2 ng./ml.). In contrast, p75-sTNF-R, which occurs in serum at amounts higher than p55-sTNF-R, was almost indiscernible in the seminal fluids (<0.18 +/- 0.28 ng./ml. versus 1.9 +/- 0.6 ng./ml. in sera). Concentrations of p55-sTNF-R in seminal fluids of oligoasthenospermic and azoospermic men were similar to those of normospermic men (15.6 +/- 8.5 ng./ml. and 14.9 +/- 6.5 ng./ml., respectively). Higher p55-sTNF-R concentrations were found in prostatic fluids and first split ejaculates (39.8 +/- 1.2 ng./ml. and 32 +/- 1.7 ng./ml., respectively), while second split ejaculates and the fluid from an epididymal spermatocele were found to contain p55-sTNF-R at lower levels (10.8 +/- 1 ng./ml. and 1 ng./ml., respectively). These findings suggest intense local biosynthesis of p55-sTNF-R in the prostate occurring independently of spermatogenesis. Possible functional implications are: 1) shielding of spermatozoa from the inhibitory effect of TNF in the female reproductive tract; 2) a role for TNF in the normal physiology of the prostate; and 3) blocking TNF-mediated immune response in the prostate, which may have bearings on the development of prostatic hypertrophy or cancer.
Several parameters affecting survival and implantation of frozen-thawed embryos were studied. Of ... more Several parameters affecting survival and implantation of frozen-thawed embryos were studied. Of 386 embryos frozen in dimethylsulfoxide (DMSO) or in 1,2 propanediol (PROH), the survival rate was 63.5% (245/386). Three different methods of cycle preparation were compared prior to thawed embryo replacement. The pregnancy rate was 16.1% (9/56) in spontaneous cycles; 11.4% (5/44) in an ovarian stimulation protocol; and 9.5% (4/42) with estrogen and progesterone substitutional therapy (p = NS). There was no difference in the estradiol/progesterone ratio among the three different protocols during the early luteal phase of the cycle, which may indicate that implantation of thawed embryos could be related to their developmental potential rather than to the endometrial environment. In the spontaneous cycles, when endometrium was synchronized or advanced to embryonic stage up to 32h, implantation rate was 29.2%.
To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregn... more To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregnancy rates (PRs) in patients with repeated failure of implantation in IVF-ET cycles. A case-control study. Criteria for patient selection included male factor or unexplained infertility, normal uterine cavity, and at least three failures of implantation in IVF-ET cycles in which at least three embryos were placed per transfer. Data on 70 patients who underwent 92 ZIFT cycles are presented. A control group consisted of patients with the same selection criteria who underwent an additional standard IVF-ET cycle during the same time period. Ovulation induction consisted of down-regulation with GnRH analogue followed by ovarian stimulation with FSH and hMG. Intracytoplasmic sperm injection was performed on the oocytes of all patients with male factor infertility. Zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after oocyte retrieval. Implantation rates and PRs in the ZIFT and control groups were compared. The PRs and implantation rates were significantly higher in the ZIFT group than in the control group: 34.2% (24/70) and 8.7% (29/333) versus 17.1% (12/70) and 4.4% (13/289), respectively (P = 0.002 and P = 0.04). The cumulative conception rate for two ZIFT cycles was 59.3%. Zygote intrafallopian transfer should be considered a beneficial mode of treatment for patients with repeated failure of implantation in IVF and transcervical ET. More prospective randomized studies are needed to support this observation.
Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oes... more Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1.09 and 0.92 multiples of the normal gestation-specific median (MOM) based on a total of 34582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1.05 MOM) and a significant decrease when Pergonal was used (0.93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0.92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Down's syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.
Evaluation of the intracellular signalling mechanisms of follicle stimulating hormone (FSH) and i... more Evaluation of the intracellular signalling mechanisms of follicle stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) was performed in luteinized and non-luteinized human granulosa cells. A severalfold increase in estradiol production from androstenedione was induced by both hormones in these cells, while only FSH led to a concomitant increase in cAMP. IGF-I bound specifically to its receptor in these cells. Specific tyrosine kinase inhibitors (tyrphostins) blocked the effects of both FSH and IGF-I on aromatase activity without altering FSH-induced cAMP accumulation. These findings demonstrate an involvement of a tyrosine kinase pathway in the intracellular signalling mechanism of the IGF-I effect on aromatase activity. Furthermore, since FSH induction of aromatase activity can be blocked by a tyrosine kinase inhibitor without affecting the level of cAMP production, it can be suggested that tyrosine kinase(s) act downstream of cAMP production and protein kinase A activation.
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Papers by J. Dor