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Biomedical subjects

M L Polan

Publications and source records attributed to M L Polan.

At least 91 records · Page 5Linked to original sources
PubMed1984

The periovulatory and luteal phase of conception cycles following in vitro fertilization and embryo transfer.

The pattern of periovulatory and luteal phase levels of serum estradiol (E2) and progesterone (P) were compared between 8 conception and 28 nonconception cycles of patients undergoing in vitro fertilization (IVF). Ten additional women served as control subjects and did not undergo follicular aspiration. Follicle growth was induced with an individualized Pergonal (human menopausal gonadotropin) regimen, and laparoscopy was performed 36 hours after human chorionic gonadotropin administration. The length of the luteal phase did not differ significantly among the three groups and was between 14 and 15 days in duration. When IVF conception cycles were compared with nonconception cycles, although no difference in the number of large follicles was observed (4.25 +/- 0.45 versus 3.6 +/- 0.25), the patterns of E2 and P differed significantly. Daily serum E2 levels tended to be higher in the periovulatory phase in conception cycles when compared with nonconception cycles, and were significantly (P less than 0.05) higher in the early, mid, and late luteal phases. Serum P levels were significantly higher (P less than 0.05) in conception cycles from the midluteal phase onward. A decline in both serum E2 and P in the midluteal phase in conception cycles suggested some degree of corpus luteum deficiency. It is suggested that high E2 levels in the periovulatory phase may be an indicator of better follicular development under human menopausal gonadotropin stimulation and that the deficiency observed in the late luteal phase is overcome with the establishment of pregnancy.

Adult↗
PubMed1984

The relationship between follicular fluid steroid concentration and successful fertilization of human oocytes in vitro.

Follicular fluids (FF) and their matched oocytes were obtained from 64 follicles of 28 women who failed to conceive after in vitro fertilization ( IVF ) and 33 follicles of 8 women who successfully conceived after the procedure. Ovulation was induced with human menopausal gonadotropin, and follicular aspiration was performed 36 hours after human chorionic gonadotropin administration. The concentration of 17 beta-estradiol, progesterone, testosterone, dihydrotestosterone, and androsterone was correlated with the morphology of the oocyte-corona-cumulus complex ( OCCC ), oocyte fertilization, the rate of cleavage, and the incidence of pregnancy after embryo transfer. In both groups of women, FF progesterone was lowest in follicles containing immature OCCCs . However, follicles aspirated from women who conceived after IVF which contained intermediate and mature OCCCs had significantly higher FF estradiol levels than similar follicles from women who failed to conceive after the procedure. Fertilized oocytes and 4- to 6-cell stage embryos which were obtained from follicles of pregnant women contained significantly higher FF estradiol levels than fertilized oocytes and similar embryos from nonpregnant women. It appears that higher FF estradiol levels correlate well with successful fertilization and an enhanced cleavage rate of oocytes associated with pregnancy following IVF .

Adult↗
PubMed1984

Delaying human chorionic gonadotropin administration in human menopausal gonadotropin-induced cycles decreases successful in vitro fertilization of human oocytes.

Correct timing of human chorionic gonadotropin (hCG) administration in induced cycles for in vitro fertilization is of crucial importance to oocyte maturation and normal luteal function. The purpose of this work was to compare the effect of hCG timing on follicular development, oocyte maturation, and fertilization in vitro, as well as on the pattern of luteal phase hormone secretion. Ovulation was induced in 32 normally cycling women by human menopausal gonadotropin (hMG)/hCG administration. In the first group (17 women) 10,000 IU hCG was administered 24 hours after the last injection of hMG and in the second group (15 women) 48 to 72 hours after the last hMG injection. Serum estradiol levels prior to oocyte aspiration were similar in both groups, as were the numbers of large follicles on the day of hCG administration (4.5 +/- 2.3 versus 4.1 +/- 1.9 follicles/woman, respectively). The distribution of oocyte-corona-cumulus complexes was similar in both groups and was comprised of 11% immature, 43% intermediate, and 45% mature complexes. The fertilization rate, however, was significantly (P less than 0.001) reduced in the group treated by delayed hCG injection (57% versus 84%), and the percentage of degenerated oocytes was increased (9% versus 1%). Luteal phase length as well as progesterone and estradiol levels were comparable in both groups. It is concluded that an interval longer than 24 hours between the last injection of hMG and the administration of an ovulatory dose of hCG does not affect follicular and luteal phase serum steroid patterns but may result in a decreased oocyte fertilization rate, possibly due to atretic changes in the follicles.

Adult↗
PubMed1984

Fallopian tubal patency assessed by ultrasound following fluid injection. Work in progress.

The ability of ultrasound to detect patency of at least one fallopian tube by demonstrating free fluid in the cul-de-sac was evaluated in 35 infertile women. The results were compared with conventional hysterosalpingograms, which had been obtained simultaneously. Ultrasound demonstrated bilateral occlusion with a sensitivity of 100%, and showed tubal patency with a specificity of 96%. The ability to diagnose tubal occlusion or patency using this ultrasound technique, which the authors have designated "sonosalpingography," eliminates unnecessary exposure of the female pelvis to ionizing radiation and avoids the use of iodinated contrast material.

Fallopian Tube Diseases↗
PubMed1984

Gonadotropin and prolactin levels in follicular fluid of human ova successfully fertilized in vitro.

Follicular fluid (FF) and oocytes were obtained from 94 follicles of 36 women for fertilization in vitro. Ovulation was induced with human menopausal gonadotropin, and follicular aspiration was performed 36 h after an ovulatory injection of hCG. The concentrations of immunoreactive hCG, FSH, and PRL were correlated with the degree of maturation of the oocyte-corona-cumulus complex mass (OCCC), fertilization, rate of cleavage, and the incidence of pregnancy after embryo transfer. Immature OCCC were derived from follicles that contained significantly lower levels of FSH than those from which intermediate and mature OCCC were derived (5.2 +/- 0.6 vs. 11.1 +/- 1.2 mlU/ml; P less than 0.05). FF from oocytes that were successfully fertilized contained higher levels of both hCG and FSH than FF surrounding oocytes that did not fertilize (136.7 +/- 8.7 vs. 108.5 +/- 10.3 mlU/ml hCG; 10.55 +/- 0.6 vs. 5.3 +/- 0.8 mIU FSH, respectively). There was no correlation between early embryonic growth rate and FF concentrations of FSH, hCG, and PRL. Ova reaching the two-cell stage 40 h after fertilization in vitro were associated with the same FF concentrations of FSH, hCG, and PRL as those that cleaved to the four-cell stage. The PRL concentration in FF was significantly higher in mature fertilized ova and in fertilized ova that were associated with a successful pregnancy. It is suggested that the intrafollicular concentration of FSH is associated with the degree of mucification of the OCCC, but FF levels of both FSH and hCG are associated with successful fertilization. High levels of PRL in FF were associated with successful pregnancy and may imply a role of this hormone in oocyte maturation.

Adult↗
PubMed1984

The association between granulosa cell aromatase activity and oocyte-corona-cumulus-complex maturity from individual human follicles.

The steroidogenic capability of granulosa cells isolated from 12 preovulatory human follicles was correlated with the stage of maturation of the corresponding oocyte-corona-cumulus-complex ( OCCC ). Individual follicles from human menopausal gonadotropin (hMG) stimulated cycles were aspirated 36 h after administration of hCG. Granulosa cells were cultured for 150 min and corresponding OCCC were evaluated for maturity before fertilization with human sperm. Granulosa cell aromatase activity was measured using 1 beta-3H-testosterone as substrate by quantitating the amount of 3H2O produced. Progesterone production by the granulosa cells was measured as was follicular fluid levels of combined hCG and LH activity and FSH and PRL. Follicular fluid concentrations of combined hCG plus LH activity decreased somewhat while FSH levels increased as OCCC matured. PRL levels did not vary. Granulosa cell progesterone production did not change with maturity of OCCC . However, aromatase activity decreased as OCCC matured with levels from granulosa cells with immature OCCC vs. intermediate and mature OCCC of 260 +/- 148 vs. 129 +/- 53 (SE) pg E2/10(5) cells, respectively (P less than 0.07). Although granulosa cells responded variably to hMG stimulation from individual to individual, and the response was not predictable from peripheral serum estradiol levels, follicles isolated from the same patient had a definite diminution in aromatase activity with OCCC maturation. From these preliminary results, aromatase activity in immediately preovulatory granulosa cells declined as OCCC matured in hMG/hCG stimulated cycles.

Aromatase↗
PubMed1984

Human chorionic gonadotropin and prolactin modulation of early luteal function and luteinizing hormone receptor-binding activity in cultured human granulosa-luteal cells.

These studies were undertaken to explore the roles of both hCG and PRL in the modulation of early luteal function in the human. Human granulosa-luteal cells isolated during cycles stimulated by human menopausal gonadotropin hCG were obtained at the time of follicle aspiration and cultured to determine the effects of hCG and PRL on both progesterone and hCG receptor binding. Progesterone production by hCG-stimulated granulosa-luteal cells was increased 3.5-fold over unstimulated levels after 120 h, with maximal stimulation at hCG concentrations greater than 1 IU/ml. [125I]hCG binding to granulosa luteal cells was increased 3-fold in cells cultured with hCG (10 IU/ml) after both 48 h (P less than 0.03) and 96 h (P less than 0.02) in culture. hCG (1 IU/ml) stimulated a significant increase in progesterone production above basal levels after 72 h of culture, which continued to increase until 96 h of culture; 20 alpha-dihydroprogesterone (20 alpha-OH progesterone) production also was increased by hCG (1 IU/ml) at 72 h of culture, but unlike progesterone production, showed no further increase. In both the presence and absence of hCG, granulosa-luteal cells cultured with PRL (100 ng/ml) produced significantly more 20 alpha-OH progesterone (P less than 0.04 and P less than 0.02, respectively) after several days than cells cultured without PRL. In addition, progesterone production in the presence of hCG (10 IU/ml) decreased significantly (P less than 0.04) as 20 alpha-OH progesterone levels increased. Equivalent amounts of [125I]hCG were bound by human granulosa-luteal cells cultured with and without PRL (100 ng/ml). These results show that cultured human granulosa-luteal cells are responsive to hCG, with parallel increases in both progesterone production and [125I]hCG receptor binding. The presence of PRL (100 ng/ml) had no effect on [125I]hCG binding. In both the presence and absence of hCG, PRL resulted in an increase in 20 alpha-OH progesterone production and, in the presence of hCG (10 IU/ml), a decrease in progesterone production after several days in culture.

Cells, Cultured↗
PubMed1984

17 beta-estradiol and progesterone production by human granulosa-luteal cells isolated from human menopausal gonadotropin-stimulated cycles for in vitro fertilization.

The production of 17 beta-estradiol and progesterone (Prog) by human granulosa-luteal cells obtained from 24 aspirated follicles of 11 women undergoing laparoscopy in an in vitro fertilization program was studied. Follicular growth was stimulated with an individualized human menopausal gonadotropin regimen begun on either day 1 (group I; n = 5) or day 3 (group II; n = 6) of the menstrual cycle, and laparoscopy was performed 36 h after hCG administration. Granulosa-luteal cells were cultured for 2 h in culture medium alone or in the presence of either pregnenolone (10(-7) M) or testosterone (10(-7) M). Aromatase activity was present in the granulosa-luteal cells, as evidenced by a significant (P less than 0.001) increase in E2 production in the presence of testosterone. The addition of pregnenolone did not augment Prog production. Granulosa-luteal cells derived from Group II patients produced significantly (P less than 0.001) more Prog than those derived from group I patients. In addition, group II granulosa-luteal cells associated with mature oocyte-coronacumulus complexes produced significantly (P less than 0.001) more Prog than those in group I. Fertilization and pregnancy correlated with Prog production, in that granulosa-luteal cells associated with oocytes that were fertilized produced significantly (P less than 0.001) less Prog than those associated with nonfertilized oocytes. Granulosa-luteal cells from the 2 patients in this series who conceived demonstrated a further significant (P less than 0.02) reduction in Prog production. It appears that administration of human menopausal gonadotropin early (day 1) in the follicular phase results in incomplete maturation of the granulosa cells. Furthermore, the optimal oocyte, in terms of successful fertilization, may be one derived from a follicle that has undergone appropriate stimulation resulting in adequate maturation, but has not surpassed that point.

Adult↗
PubMed1983

Purine modulation of LH action in gonadal cells.

A rapid and marked amplification of LH and FSH-stimulated cyclic AMP accumulation and steroid secretion is produced by adenosine in luteal and granulosa cells, respectively, of both the rat and the human ovary. The rat Leydig cell response to LH, however, was unaffected by adenosine. In the luteal cell, adenine nucleotides and adenosine were equipotent with decreasing activity shown by inosine, adenine and hypoxanthine--guanosine, guanine, xanthine and pyrimidines were inactive. Both an extracellular and intracellular site appears to be involved in adenosine amplification of LH--the extracellular site accounted for about 20% of the response and may be a catalytic receptor site. The intracellular site was directly related to an increase in luteal cell ATP levels in which adenosine appears to serve as a selective prosubstrate for hormone activated adenylate cyclase. The luteal antigonadotropic action of PGF2 alpha was blocked by adenosine and these modulators were shown to be competitive antagonists of LH-stimulated cyclic AMP accumulation. Due to the ubiquitous nature of both adenosine and PGF2 alpha, (conditions have been described in other systems for their rapid release,) it is suggested that they may serve as important local humoral modulators of gonadotropin action for regulation and control of ovarian function.

Adenosine↗
PubMed1983

The use of high-dose human menopausal gonadotropin in an in vitro fertilization program.

Sixty-three normal ovulatory women suffering from obstructive tubal disease not corrected by previous surgery were enrolled in an in vitro fertilization (IVF) program. To achieve a large number of mature follicles, a relatively high dose of human menopausal gonadotropin (hMG) was administered (19 +/- 4 ampules/cycle). Monitoring consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin (10,000 IU) was administered when more than two large follicles (1.6 to 1.8 cm in diameter) were visualized. Fifty-five laparoscopies for oocyte retrieval were performed. A mean of 4.3 follicles per woman were aspirated, and 3.2 oocytes per woman were recovered. The oocytes were preincubated for 8 or 24 hours according to the morphologic degree of mucification and dispersal of the oocyte-corona-cumulus complex. Seventy-seven percent of the oocytes were fertilized and were transferred into the uterus 38 to 40 hours after insemination. Fifty-two women received one to eight embryos (mean, 3.5 +/- 1.9), and 9 (17%) conceived. This regimen of high-dose hMG precludes the need for serum or urine luteinizing hormone monitoring, because the occurrence of spontaneous ovulation is low. It is valuable in increasing the number of fertilizable oocytes, the percentage of women undergoing embryo transfer, and compensates with multiple oocyte transfer for the high embryonic loss involved in IVF.

Adult↗
PubMed1983

Adenosine amplifies follicle-stimulating hormone action in granulosa cells and luteinizing hormone action in luteal cells of rat and human ovaries.

It is known that adenosine amplifies LH-stimulated cAMP accumulation and progesterone production in rat luteal cells. The aim of this study was to investigate the effect of adenosine on cAMP and steroid production in short term cultures of rat and human luteal cells in the presence of LH and in rat and human granulosa cells in the presence of FSH. In rat luteal cells, the maximal cAMP response to LH and adenosine amplification of this response occurred in the midluteal phase and was decreased in both early and late luteal cells. In humans, adenosine (50 microM) increased cAMP and and progesterone accumulation by 100% and 40%, respectively, in periovulatory granulosa cells. Adenosine also amplified cAMP accumulation in response to increasing hCG concentrations by 2- to 3-fold in human luteal cells. The ability of the human luteal cell to respond to hCG with cAMP accumulation and the ability of adenosine to amplify this cAMP response appeared to be inversely related to human luteal cell age. In isolated preparations of rat granulosa cells, adenosine amplified cAMP accumulation in response to FSH, and cAMP accumulation was inversely proportional to the duration of follicular development. In human periovulatory granulosa cells, adenosine (100 microM0 increased cAMP accumulation by 2-fold and amplified FSH-stimulated cAMP accumulation by 25%. These studies suggest that in both the rat and human, adenosine may physiologically affect gonadotropin function in both follicular and luteal ovarian tissue.

Adenosine↗
PubMed1983

Hysteroscopic management of intrauterine lesions and intractable uterine bleeding.

Müllerian fusion defects, submucous myomas, and intractable uterine bleeding have been managed traditionally by major surgical intervention. However, the cystoscope-resectoscope provides the operative versatility allowing transvaginal surgical management of these situations. Forty women underwent hysteroscopy and treatment with the cystoscope-resectoscope at the Yale-New Haven Hospital. Those patients treated for septate müllerian defects also underwent concomitant laparoscopy. Therapeutic surgical use of the cystoscope-resectoscope resulted in no immediate or long-term complications. Of 11 patients with uterine anomalies treated in this fashion, 9 carried to term without difficulty. Fourteen women with space-occupying intrauterine lesions were treated and resumed normal cyclical menses for a minimum of 1 year. In all 11 patients with intractable uterine bleeding hemorrhage was controlled immediately and 6 women remained amenorrheic for a sustained period. The use of the cystoscope-resectoscope for the management of these entities provides several advantages: 1) A transcervical approach obviates the necessity for abdominal surgery, and 2) the instrument is rapidly and easily accessible to the practicing gynecologist.

Colposcopy↗
PubMed1983

Abdominal myomectomy and subsequent fertility.

The role of myomectomy in subsequent fertility was evaluated. Of 50 patients undergoing myomectomy, 25 subsequently conceived. The most important correlation with subsequent fertility was surgical indication, 68 per cent of the women who underwent exploration for a pelvic mass having conceived, whereas only 16 per cent of women with a normal infertility evaluation conceived. In addition, women more than 30 years of age who became pregnant had fewer and smaller fibroid tumors than those who did not. It is concluded that myomectomy itself may decrease fertility, probably on the basis of adhesion formation and may be unjustified in women with otherwise negative infertility evaluations.

Age Factors↗
PubMed1982

Abnormal ovarian cycles as diagnosed by ultrasound and serum estradiol levels.

A significant portion of human infertility is presumably due to defective ovulation, including patients who fail to conceive despite medical induction of ovulation, those who fail despite repeated timely donor inseminations, and those with "infertility of unknown etiology". All point out the inadequacy of standard criteria for normal ovulation. This investigation correlates preovulatory serum estradiol and gonadotropin concentrations with dominant follicle growth measured ultrasonographically and serum progesterone levels. The data indicate a 35% incidence of cycles with significantly abnormal serum estradiol levels, decreased dominant follicle size, and abnormal progesterone levels despite biphasic basal body temperature curves and normal cycle length. If these cycles represent inadequate or abnormal ovulation, they can be distinguished from adequate cycles prior to follicle rupture and may benefit the treatment of human infertility.

Adult↗
PubMed1981

Prolactin-stimulated ovarian androgen metabolism.

Activities of 5 alpha, 3 alpha, and 3 beta reductases were studied with the use of microsomal fractions isolated from the ovaries of immature female rats after treatment with pregnant mares' serum (PMS) followed by human chorionic gonadotropin (hCG). The effect of exogenous prolactin treatment was similarly assessed by comparing enzymic activity in prolactin-treated rat ovaries to that in control rat ovaries, after pretreatment with PMS. With the use of 3H-testosterone as substrate, reductase activities were determined by measuring the production of dihydrotestosterone and the 3 alpha- and 3 beta-epimers of androstanediol. The rate of formation of tritiated androstanediol from radiolabeled testosterone was ten times higher than that of tritiated dihydrotestosterone during the follicular phase. After ovulation, the metabolism of testosterone to both androstanediol and dihydrotestosterone decreased markedly. Negligible amounts of estrogen and androsterone were formed, and most of the androstanediol was found to be 5 alpha-androstane-3 beta, 17 beta-diol. The Michaelis-Menten constant (Km) for 5 alpha-reductase was 1.3 x 10(-5)M. During the follicular phase, the sum of 3H-dihydrotestosterone and 3H-androstanediol produced from radiolabeled testosterone was found to be 30% greater in prolactin-treated animals than in control animals. Implication of increased ovarian androgen metabolism as a consequence of hyperprolactinemia are discussed.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗