Biomedical subjects

M Dirnfeld

Publications and source records attributed to M Dirnfeld.

At least 37 records · Page 2Linked to original sources

PubMed1993

Outcome of pregnancies inadvertently exposed to gonadotropin-releasing hormone analogues (GnRH-a) in early gestation.

In recent years the down-regulation of pituitary function by GnRH-a, before and during ovarian stimulation for IVF, has been widely used. When GnRH-a are commenced in the luteal phase, it is inevitable that some early human embryos will be exposed. To the best of our knowledge the total number of reported deliveries following exposure is less than 30. We report here a further nine uneventful pregnancies with successful neonatal outcomes and three early miscarriages. It is our belief that the favorable outcome in patients presented here, who inadvertently received GnRH-a in early unsuspected gestation, is related to the use of short-acting analogues (Buserelin nasal spray). This enabled immediate discontinuation of the drug when the presence of pregnancy was suspected. In addition, the routine administration of progesterone supplements is strongly recommended, regardless of the hormonal levels.

Abortion, Spontaneous↗

PubMed1993

Triiodothyronine (T3) modulates hCG-regulated progesterone secretion, cAMP accumulation and DNA content in cultured human luteinized granulosa cells.

Ample clinical evidence indicates that women with thyroid disorders frequently exhibit menstrual disturbances and impaired fertility. In order to characterize the nature of thyroid hormone action in the ovary, the direct effects of triiodothyronine (T3) were investigated in vitro using a culture system of human luteinized granulosa cells. The presence of T3 receptors was also searched in such cells. The cell cultures were maintained in serum-free Ham's F-10 medium in the absence or presence of hCG, with or without graded doses of T3 (10(-11)-10(-7) M), and cell proliferation (assessed by DNA content) as well as cell function (cAMP accumulation and progesterone secretion) determined. T3 alone stimulated cell proliferation. hCG, on the other hand, was anti-mitogenic and T3 combined with hCG inhibited cell growth even further, reaching levels below those reached by either control or hCG alone. Exposure of cells to T3 markedly enhanced hCG-induced cAMP accumulation. Addition of 1-methyl-3-isobutylxanthine (MIX) abolished the cAMP-stimulatory effect elicited by T3, suggesting that the thyroid hormone may act, as MIX, by inhibiting phosphodiesterase. T3 was devoid of any influence on basal progesterone secretion, but inhibited hCG-induced secretion of the steroid. The effects of T3 are not accounted for by changes in cell number since the influence of thyroid hormone on cAMP and steroid secretion were expressed per microgram DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Different morphology and proliferative ability of cumulus and granulosa cells originating from cystic follicles aspirated from stimulated in vitro fertilization patients.

OBJECTIVE: To investigate the morphology and proliferative ability of cumulus and granulosa cells (GCs) originating from cystic follicles and normal-sized follicles after ovarian stimulation. DESIGN: Granulosa cells, cumulus cells, and follicular fluid (FF) were aspirated from cystic follicles and normal-sized follicles from the same ovary. Morphology and proliferative ability of cumulus and GCs were assessed by Giemsa stain and thymidine incorporation, respectively. Cell proliferation was assessed in medium or FF originating from cystic follicles or normal-sized follicles. RESULTS: An oocyte was found in 40% of the cystic follicles versus 68% in the normal-sized follicles. Changes in dispersion and adhesion properties were observed in cystic versus normal aspirated corona cumuli complex. Proliferative ability was consistently lower in GCs originating from cystic follicles versus normal-sized follicles. Proliferation of GCs originating from normal-sized follicles or cystic follicles was inhibited or increased when grown in FF from cystic follicles or FF from normal-sized follicles, respectively. Differences in embryo quality were significantly in favor of oocytes originating from normal-sized follicles. Although the fertilization rate of those oocytes appeared to be higher, the difference was not of statistical significance. CONCLUSIONS: Inhibition of GC proliferation in FF from cystic follicles can be reversed by incubating cells in FF from normal-sized follicles. We conclude that factors in the FF may affect cell proliferation.

Cell Division↗

PubMed1993

Functional differentiation in progesterone secretion by granulosa versus cumulus cells in the human preovulatory follicle and the effect of different induction of ovulation protocols.

OBJECTIVE: To investigate P secretion by granulosa cells (GCs) versus cumulus cells derived from human preovulatory follicles. DESIGN: Cells were recovered by aspiration of preovulatory follicles in 44 women participating in an IVF program. Induction of ovulation was performed using clomiphene citrate, hMG and hCG (group I), hMG/hCG (group II), buserelin acetate/hMG/hCG (group III), or Decapeptyl/hMG/hCG (group IV). SETTING: Laboratories of the IVF Unit at the Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel. MAIN OUTCOME MEASURES: Secretion of P was examined after cultures for 96 hours under nonstimulated and hCG stimulated conditions. RESULTS: Progesterone secretion by GCs derived from all four groups was found to be higher compared with the respective cumulus cells. However, although the ratios of P secretion by GCs versus cumulus cells in groups I, II, and III were very similar, a significantly lower value was observed in group IV. The response of GCs to hCG in terms of P secretion was higher with at least one dose of hCG in groups I and IV compared with groups II and III. The response of cumulus cells to hCG was absent regardless of the treatment protocol used in vivo. CONCLUSION: Our results demonstrate that in the human preovulatory follicle, GCs and cumulus cells differ in their capacity to secrete P as well as in their response to hCG. They further suggest that the mode of induction of ovulation affects the relative capacity of GCs and cumulus cells to secrete P and their ability to respond to hCG.

Adult↗

PubMed1993

Pre-ovulatory progesterone growth rate in patients treated with gonadotrophin-releasing hormone agonist and outcome of in-vitro fertilization.

The present study was undertaken to assess whether the increase in serum progesterone concentration following the administration of human chorionic gonadotrophin (HCG) may have predictive value on the in-vitro fertilization (IVF) success rate. Progesterone concentration on the day of HCG administration and the increase in progesterone concentration on the following day were evaluated in 140 consecutive patients undergoing IVF with embryo transfer. Stimulation protocol in all study patients entailed intranasal administration of short-acting gonadotrophin-releasing hormone agonist (GnRHa) buserelin and human menopausal gonadotrophin. A pregnancy rate of 37.2% was achieved when at least three embryos were transferred. The only significant difference between conception and non-conception cycles was found in serum progesterone concentrations after HCG administration (P < 0.01), whereas the mean progesterone concentration on the day of HCG did not differ. No difference in other hormonal or cycle parameters was observed. The increase in progesterone concentration was significantly greater in the group of patients who achieved pregnancy than in the group who did not (2.2 +/- 0.2 versus 1.6 +/- 0.1 ng/ml, respectively; P < 0.01). A critical breakpoint in serum progesterone was arbitrarily determined at 1 ng/ml. An increase in progesterone concentration > or = 1 ng/ml when three or more embryos were transferred was associated with a positive predictive value for pregnancy of 40.4% (sensitivity of 94.7%), whereas a negative predictive value of 86.7% was obtained when this value was < 1 ng/ml. These findings indicate that an adequate rise in serum progesterone following HCG administration provides useful information about the possible outcome of the treated cycle.

Adult↗

PubMed1993

The effect of epidermal growth factor on growth and differentiation of mouse preimplantation embryos in vitro.

The effect of epidermal growth factor (EGF) on embryonic growth, development, attachment and spreading in vitro was studied. EGF was added to 130 embryos at the 4-cell stage; to 128 embryos at the blastocyst stage; and to 147 embryos 24 h following spreading. Development of embryos from the 4-cell to the blastocyst stage, differentiation of the inner cell mass (ICM) and trophectoderm, and the occurrence of attachment and spreading were evaluated. Embryo development was significantly inhibited in cultures supplemented with 100 ng/ml EGF compared to the controls (P < 0.001). Development of 4-cell embryos to blastocysts occurred in 25% of the EGF group compared to 85% of controls. Spreading occurred in 20% of 4-cell embryos and 30% of blastocysts treated with EGF, compared to 80 and 90% of corresponding controls. In embryos developing from the 4-cell stage, massive growth of the ICM and inhibition of the trophectoderm occurred, whereas both ICM and trophectoderm were inhibited by EGF in embryos developing from the blastocyst stage. Following spreading, EGF caused massive growth of the ICM and regression of the trophectoderm. Our preliminary results show that EGF may be involved in the modulation and control of early embryonic growth and differentiation.

Animals↗

PubMed1993

Growth hormone-binding protein (GH-BP) levels in follicular fluid from human preovulatory follicles: correlation with serum GH-BP levels.

Serum GH-binding protein (GH-BP), which is identical with the extracellular domain of the GH-receptor, has important implications for the distribution and physiological activity of GH and may enable evaluation of GH-receptor function. Recent studies suggest that GH plays an important role in the modulation of ovarian function and GH-receptors/BPs are found in the female reproductive system. The purpose of the present study was to investigate the presence of GH-BP in human follicular fluid (FF) and compare the levels of FF GH-BP with those detectable in serum, in 46 women undergoing in vitro fertilization. Levels of GH-BP were determined by incubation of [125I]hGH with 50 microL FF or serum, in the absence or presence of excess hGH and specific binding was expressed as a percentage of the total counts per min incubated. The mean GH-BP level in patient FF was 12.39 +/- 0.63% (mean +/- SE) and this correlated significantly with serum GH-BP levels (r = 0.82; P < 0.001). The binding of hGH to FF was dose dependent, highly specific, and of high affinity and low capacity. The affinity constants (Ka) obtained by Scatchard analysis for hGH binding to patient's FFs and sera were not significantly different. Furthermore, we have analyzed the sodium dodecyl sulfate gel electrophoretic pattern of GH-BP in FF and serum by both the ligand-blot technique and after cross-linking with [125I]hGH. Our results show that there is close similarity between serum and FF GH-BPs. Significantly lower FF GH-BP levels were measured in patients older than 36 yr compared to younger women (P < 0.05), whereas increased values were obtained both in patients with elevated E2 concentrations in serum (> 7000 pmol/L) and in FF (> 2200 nmol/L), (P < 0.02 and P < 0.05, respectively). This first demonstration of GH-BP in FF is expected to increase our understanding of the possible direct effect of GH on ovarian steroidogenesis, and suggests a possible regulatory role for GH-BP in folliculogenesis.

Adult↗

PubMed1993

Gamete intrafallopian transfer. An overview.

Gamete intrafallopian transfer involves a direct transfer of both human gametes, sperm and oocytes, into the fallopian tube. Since the first report of a successful pregnancy following the use of this technique by Asch et al in 1984, its role in the treatment of infertile women with patent tubes has been established. Recent data demonstrate a 34.4% clinical pregnancy rate, with the highest pregnancy rate achieved in infertile women due to endometriosis or unexplained infertility.

Aftercare↗

PubMed1992

Spontaneous fetal reduction in multiple gestations assessed by transvaginal ultrasound.

OBJECTIVE: To assess the occurrence of disappearance of one or more of the fetuses in pregnancies which start as multiple gestation. DESIGN: Observational study. SETTING: Infertility section, Rambam Hospital, Haifa. SUBJECTS: 88 women with multiple gestations, established after ovulation induction (54 twin, 26 triplet, five quadruplet, and three quintuplet) and diagnosed by transvaginal ultrasound at 5-6 weeks, in all of whom absorption of at least one gestation sac was detected at follow-up ultrasound scan. INTERVENTIONS: Follow-up by serial transvaginal and later abdominal ultrasound scan throughout pregnancy. RESULTS: Of the 54 twin gestations, 51 ended in the birth of a singleton and three in miscarriage. Of the 26 pregnancies starting as triplets, 12 ended in singleton births, 12 in twins and two miscarried. The five quadruplet gestations resulted in one singleton birth, one set of twins, two triplets, and one ended in late miscarriage. Of the three quintuplet pregnancies, two resulted in the birth of triplets, one of them after spontaneous, the other after iatrogenic fetal reduction. In the third quintuplet pregnancy, one fetus vanished spontaneously and another was subject to iatrogenic reduction, two fetuses survived and were liveborn. Of the 221 fetuses identified 107 (48%) vanished spontaneously. CONCLUSION: Iatrogenic fetal reduction should be delayed until 12 weeks gestation in quadruplet or higher multiple gestations, but is probably not indicated in twin and triplet gestations.

Adult↗

PubMed1991

The impact of sonographic assessment of the endometrium and meticulous hormonal monitoring during natural cycles in patients with failed donor artificial insemination.

The present study was undertaken to determine whether the sonographic characteristics of the endometrium in the proliferative phase of the natural cycle combined with meticulous hormonal monitoring would have an impact on the prediction of conception. Fourteen women with regular ovulatory cycles were examined daily, from day 8 of the cycle, by transvaginal ultrasound through 16 unstimulated cycles. All patients had had at least four previous unsuccessful donor artificial insemination cycles scheduled by basal body temperature records. During the study, donor artificial insemination was meticulously timed by hormonal and sonographic monitoring. Four clinical pregnancies occurred with a success rate of 29% per patient, or 25% per cycle. The endometrial thickness at the mid-proliferative phase (day 8) was significantly smaller in patients who conceived in comparison with patients who failed to conceive (0.33 +/- 0.07 cm vs. 0.59 +/- 0.03 cm; p < 0.01). The endometrial thickness on the day of the luteinizing hormone (LH) peak was not significantly different between the two groups. However, the amount of endometrial growth between day 8 of the cycle and the day of the LH peak was significantly greater in conception than non-conception cycles (0.55 +/- 0.05 cm and 0.24 +/- 0.06 cm; p < 0.01). No difference in hormonal parameters was observed either on day 8 of the cycle or on the day of the LH peak between conception and non-conception cycles. On the day of the LH peak, an endometrium with typical triple line appearance and thickness of 0.6 cm or more was seen significantly more often in conception than non-conception cycles (p < 0.05). No pregnancy occurred with an endometrium < 0.6 cm at the time of ovulation. The presence of the favorable endometrial pattern in the periovulatory phase was associated with a positive predictive value for pregnancy of 50% (sensitivity of 100% and specificity of 67%), whereas the negative predictive value of the hyperechoic pattern at the time of ovulation was 100%. Our data show negative correlation between early growth of the endometrium and pregnancy in unstimulated cycles, suggesting that the amount of endometrial growth during the cycle up to ovulation may have an important role in implantation. The sonographic image of the endometrium in natural cycles provides useful information about the possible outcome of the treated cycle.

Journal Article↗

PubMed1991

A randomized prospective study on the effect of short and long buserelin treatment in women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response.

Fifty four women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response to stimulation with human menopausal gonadotropins (hMG) participated in this study. They were randomized to receive either gonadotropin releasing hormone agonist (GNRHa), Buserelin, prior to and during induction of ovulation by hMG (Group I--long protocol), or GnRHa starting on the first day of the cycle together with induction of ovulation by hMG (Group II--short protocol). Mean follicular phase serum luteinizing hormone (LH) and progesterone (P) levels were significantly lower in Group I than in Group II (P less than 0.01). Cancellation rate was significantly lower in Group I than in Group II (P less than 0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos transferred per patient, and a higher pregnancy rate. Significantly more hMG ampoules and more treatments days were required in the long GNRHa protocol. Our data demonstrate that the use of GNRHa prior to and during ovarian stimulation with hMG offers a very good alternative for patients with repetitive unsuccessful IVF cycles due to inadequate response.

Adult↗

PubMed1991

The use of long-acting gonadotropin-releasing hormone agonist (GnRH-a; decapeptyl) and gonadotropins versus short-acting GnRH-a (buserelin) and gonadotropins before and during ovarian stimulation for in vitro fertilization (IVF).

The efficiency of two ovarian stimulation protocols using different gonadotropin-releasing hormone agonists (GnRH-a) for in vitro fertilization (IVF) was examined and compared with human menopausal gonadotropin (hMG)-only stimulation. Fifty-four patients who had 57 aspiration cycles were treated with protocol 1, which consisted of long-acting GnRH-a D-Trp6 (Decapeptyl Depot) and hMG. Protocol 2 entailed intranasal administration of short-acting GnRH-a (Buserelin) and human menopausal gonadotropin (hMG) in 66 women who underwent 70 aspiration cycles. Fifty-five patients who had 59 ovum pickups (OPU) treated with hMG only served as a control. No differences were observed in cycle parameters and hormonal concentrations among the three groups. The total clinical pregnancy rates per OPU for patients receiving protocols 1 and 2 were 12.3 and 27.1%, respectively (P less than 0.05). The pregnancy loss was significantly lower in protocol 2 than in protocol 1 (26.3 versus 71.4%; P less than 0.05). Our data show superiority of short-acting GnRH-a over the long-acting agents in achievement of pregnancy and its outcome, though neither was significantly different from the hMG-only protocol.

Adult↗

PubMed1991

Does the choice of catheter for embryo transfer influence the success rate of in-vitro fertilization?

The performance of two different transfer catheters has been evaluated in 193 consecutive embryo transfers. Forty pregnancies were achieved, corresponding to a pregnancy rate of 21% of all embryo transfers. The Frydman catheter was used in 123 attempts whereas 70 embryo transfers were performed with the Tom Cat catheter. The Tom Cat catheter yielded a significantly higher pregnancy rate than the Frydman catheter (28% versus 16%; P = 0.03). The mean number of embryos transferred per attempt was similar in the two groups (2.9 +/- 0.1 and 3.0 +/- 0.1 in the Tom Cat and Frydman groups respectively) as was the quality. When more than three embryos were transferred, a pregnancy rate of 37% per embryo transfer was achieved using the Tom Cat versus 20% using the Frydman catheters (P = 0.03). A higher frequency of difficult transfer procedures was observed when the Frydman catheter was used while the Tom Cat performed much better in difficult cases. An alternate use of the two catheters suggests a significantly better performance of the Tom Cat catheter in relation to the efficiency of establishing pregnancy.

Adult↗

PubMed1990

The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome.

Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins.

Drug Therapy, Combination↗

PubMed1989

Treatment of hirsutism with cimetidine: a prospective randomized controlled trial.

Cimetidine (Tagamet, Smith Klein, Brussels, Belgium) the histamine receptor type 2 blocker, has been suggested as a possible treatment of hirsutism. In a prospective randomized controlled trial, cimetidine 1.5 gm a day was given for 3 months to 12 moderately or severely hirsute women, while 8 other women were randomized to serve as a control group. There was no significant change in the hair growth rate in either group as measured by two assessment methods. This finding suggests that cimetidine, given in the recommended dose for a period of 3 months, does not have a beneficial effect on hirsutism.

Adolescent↗

PubMed1989

The fertilization and cleavage rates of eggs recovered from the cul-de-sac.

Five hundred ninety-one oocytes were laparoscopically recovered in 93 consecutive stimulated cycles. Fifty-three of the 591 oocytes were collected from the cul-de-sac in 39 cycles. The cul-de-sac-originated oocytes had fertilization and cleavage rates of 72 and 79%, respectively; these rates were similar to those achieved in oocytes originating from follicles. A significant decrease in the fertilization rate of cul-de-sac-originated oocytes was noticed in oocytes collected from the cul-de-sac 60 minutes or more after the beginning of the procedure. Oocytes collected from the cul-de-sac yielded 21% of the embryos transferred in cycles where some of the oocytes were recovered from the cul-de-sac. These findings indicate that repeated aspirations of the cul-de-sac may increase the number of embryos transferred.

Body Fluids↗

PubMed1989

Oral contraceptive pills and follicular fluid hormones in an in vitro fertilization program.

Fluids were collected from 136 ovarian follicles of 35 women undergoing in vitro fertilization and embryo transfer (IVF-ET). Fifteen women (76 follicles) received oral contraceptive pills (OCs) prior to ovulation induction. All women received human menopausal gonadotropins (hMG) for ovulation induction and in all cases follicular aspiration was performed 32 to 34 hours after an injection of human chorionic gonadotropin (hCG). The concentrations of follicular-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and 17 beta-estradiol (E2) in the follicular fluids (FF) were measured by radioimmunoassay (RIA). FSH concentration in the FF of the OCs group (15 women, 76 follicles) was significantly lower (2.1 mIU/mL) as compared to the FSH (15.9 mIU/mL) in the FF of the control group (20 women, 60 follicles). The LH FF concentrations after hCG injection were similar in the two groups. The E2/P ratio in the OCs group (9.6) was significantly lower than the E2/P ratio in the control group (20.6). OCs given to patients before induction of ovulation with hMG results in lower E2/P ratios and lower FSH concentration in the FF.

Chorionic Gonadotropin↗

PubMed1988

Pregnancies following the interval double-transfer technique in an in vitro fertilization-embryo transfer program.

In 16 women undergoing IVF-ET, with more than four embryos available, two transfers were performed (24 hr apart), instead of one. The pregnancy rate was 25%, as compared with a pregnancy rate of 6.2% in 16 women having fewer than four embryos available and in whom one conventional transfer was performed. Since in our IVF-ET program, we do not freeze the extra embryos available, the purpose of the double transfer was to use all the embryos available and to improve the chances of finding the "implantation window" open. It is our feeling that multiple transfers may be beneficial to improve the pregnancy rate in an IVF-ET program without freezing facilities. However, a larger controlled clinical trial is necessary, in order to establish the advantages of multiple transfers in terms of pregnancy rate in comparison with the potential disadvantages.

Embryo Transfer↗