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Biomedical subjects

B Lunenfeld

Publications and source records attributed to B Lunenfeld.

At least 73 records · Page 4Linked to original sources
PubMed1991

Synergistic effect of growth hormone and gonadotropins in achieving conception in "clonidine-negative" patients with unexplained infertility.

Based on preliminary reports by others and by us of a potentiating effect of growth hormone (GH) on human menopausal gonadotropin (hMG)-induced ovulation, a study using a randomized, prospective, cross-over protocol between GH + hMG/human chorionic gonadotropin (hCG) and hMG/hCG was undertaken. The study included patients with long-standing (2-11 years) unexplained infertility with a negative or reduced GH response to clonidine (up to 150 micrograms of clonidine orally). The first cycle was randomly assigned between GH/hMG/hCG (study cycle) and hMG/hCG alone (control cycle), and after an interval cycle the patient's treatment was crossed over. All patients who completed the study had previously undergone 1-20 attempts at ovulation induction for in vitro fertilization (IVF) and 5-40 cycles of ovulation induction for in vivo fertilization at three different medical centers. Three patients conceived on the combined GH/hMG cycle, with diminution in the hMG consumption needed for ovulation induction in the study cycles. Another patient with long-standing mechanical infertility underwent 11 abortive attempts at ovulation induction with hMG for IVF but has never achieved egg retrieval. On the GH/hMG/hCG ovulation induction cycle, three mature ova were retrieved as opposed to no response and cancellation of the "hMG only" cycle. Another patient with 11 years of primary infertility who had undergone 21 previous attempts at ovulation induction and had reached follicular aspiration in only three of those cycles conceived spontaneously on the first cycle after the GH/hMG/hCG IVF/ET cycle. All four pregnancies that have been achieved by now in seven GH/hMG-treated patients ended in cesarean deliveries of four normal male neonates. No correlation was found between the follicular fluid levels of insulin-like growth factor I (IGF-I) and the fertilization rate in vitro. The peripheral IGF-I levels were significantly higher during the follicular phase of the study cycles than during the respective stage of the control cycles or the luteal phase of either cycle. A study of serum GH-binding protein (GH-BP) levels revealed gradual increases in the late follicular phase, in the luteal phase, and in early pregnancy. On the basis of this study and in keeping with earlier reports, we conclude that the addition of GH to hMG/hCG may serve as a contributory adjunct in selected patients. However, in contrast to others who could not find a correlation between the response to acute tests for GH release and the ovarian response to combined treatment, we conclude that the clonidine test can play a discriminatory role in identifying patients who may benefit from this innovative combination.

Adult↗
PubMed1991

Ovulatory dysfunction.

Ovulation is the result of a perfectly balanced and coordinated function of endocrine, paracrine, and autocrine systems. Any disruption in the delicately coordinated interaction between the integrated components of the hypothalamic-pituitary-ovarian axis may lead to ovulatory dysfunction, a multifactorial entity. The widening scope of knowledge regarding physiology of the reproductive processes as well as rapid development of new diagnostic methods and therapeutic procedures necessitates the continued reassessment and identification of factors leading to ovulatory dysfunction and the design of safe therapy for this condition. The combined use of serial ultrasonography and estradiol measurements should be the standard method of ovulation induction monitoring. The identification of high-risk groups prior to the initiation of ovulation induction regimens must also be taken into consideration if we want to improve pregnancy rate and reduce the incidence of hyperstimulation to a minimal level.

Abnormalities, Drug-Induced↗
PubMed1990

A clinical evaluation of nuclear estrogen receptors combined with cytosolic estrogen and progesterone receptors in breast cancer.

Breast cancer tissue from 95 women was simultaneously assayed for three receptors: cytosolic estrogen (CER), cytosolic progesterone (CPR), and nuclear estrogen (NER). The main objective was to determine whether the addition of NER assay to the currently accepted practice with only CER and CPR could improve the predictive capacity of receptors. Forty-two patients were studied for response to hormone therapy and 95 patients were studied for survival; the median follow-up period was 73 months (range, 8 to 300 months). The incidence of CER+, CPR+, and NER+ was 74%, 70%, and 52%, respectively. Each receptor appeared more frequently, although not significantly so, in higher age groups. Forty percent of tumors had all three receptors positive and 14% had all negative; the remaining tumors showed all possible combinations of receptors. Both the rate of response and survival curves among 70 patients with CER+ did not show any significant difference whether NER was positive or negative. Also, among 38 patients with CER+, CPR+, and NER+, there was no significant difference in the clinical outcome as compared to 17 patients with CER+, CPR+, and NER-. Among 25 patients with CER- the rare occurrence of NER+ in only three patients did not suggest any clinical implication. It is concluded, therefore, that on overall clinical grounds the current series does not support the addition of NER assay whenever data is available on both CER and CPR.

Age Factors↗
PubMed1990

Comparison of the physical properties of the nuclear progesterone receptor, bound to antiprogestin RU 486 or progestin ORG 2058, following limited proteolysis.

The susceptibility of the progesterone receptor, liganded either by the antiprogestin RU 486 or by the progestin ORG 2058, to chymotrypsin and trypsin degradation was investigated. The nuclear fraction was isolated from T47D cells previously exposed either to 0.1 microM [3H]RU 486 or to 0.1 microM [3H]ORG 2058. The proteolytic digestion was performed on the micrococcal nuclease hydrolysate. The molecular weights of the receptor fragments were calculated, in high salt buffer, from the sedimentation coefficients determined on a sucrose gradient and from the Stokes radii estimated by gel filtration on an Agarose A-0.5 m column. Micrococcal nuclease solubilized receptor forms with molecular weights of 80,000 and 75,000 for the antiprogestin- or progestin-liganded receptor, respectively. Chymotrypsin degraded these receptor forms to fragments with molecular weights of 23,000 either for the antiprogestin- or progestin-liganded receptor. Similar molecular weights of 23,000 were calculated for the progesterone receptor liganded either by the antiprogestin RU 436 or the progestin ORG 2058 following trypsin cleavage. We conclude that the degradation pattern of the progesterone receptor liganded either by the antiprogestin RU 486 or the progestin ORG 2058 following chymotrypsin or trypsin digestion seems to be similar.

Cell Line↗
PubMed1990

Can growth hormone increase, after clonidine administration, predict the dose of human menopausal hormone needed for induction of ovulation?

Recent observations claimed that growth hormone (GH) administration increased the sensitivity of the ovary to gonadotropin stimulation. These findings prompted us to assess whether ovarian response to human menopausal gonadotropin (hMG) is correlated to GH reserve. Before hMG administration, 25 patients were tested for GH reserve by administration of clonidine. Of the 25 patients, 8 showed a significant increase in GH (9.2 +/- 4.5 ng/mL) and needed a significantly lower dose of hMG/human chorionic gonadotropin to elicit a good ovarian response than the 17 patients who did not respond to clonidine administration may help to estimate the initial dose range of hMG necessary for induction of ovulation.

Administration, Oral↗
PubMed1990

Can premature luteinization in superovulation protocols be prevented by aspiration of an ill-timed leading follicle?

In 12 patients stimulated for in vitro fertilization and embryo transfer (IVF-ET), a single leading follicle developed, whereas the other follicles were 6 mm smaller. In 7 patients chosen at random (group A), the leading follicle was aspirated, whereas in the other 5 the leading follicle was allowed to continue growing (group B). Comparison of the hormonal pattern of both groups showed that a premature luteinizing hormone (LH) surge was avoided only in group A, and only in this group a second follicle aspiration for IVF-ET was done, and two pregnancies were achieved. In group B, aspiration for IVF-ET was canceled because of premature LH surge. It is suggested that aspiration of a single leading follicle during ovulation induction may be an efficient method to avoid premature LH surge enabling other follicles to develop up to the preovulatory stage.

Adult↗
PubMed1990

Induction of ovulation: historical aspects.

The cornerstone of the conquest of infertility was laid in the beginning of this century. It took, however, nearly 80 years of work of many scientists from all over the globe to slowly unravel the puzzle of nature's most guarded secret, the control of the reproductive processes. The estimated population size of women between the ages 19 and 34 years in the developed world in 1990 will be about 130 million. If we assume that at least 8% will be infertile, then the pool of the infertile population will be above 10 million, with about 700,000 new patients entering this pool every year between the years 1990 and 1995. In the past only about 40% of infertile patients benefited from ovulation induction regimens. With the advent of assisted reproduction this population increased to about 80%. With the use of gonadotrophins for induction of superovulation in normally ovulating women conceptual changes in treatment regimens and monitoring schemes had to be introduced. It is obvious that the primary task of infertility clinics is to diagnose the main cause (or causes) of infertility in each couple in order to be able to institute appropriate therapy within a reasonable time. We have attempted to review briefly the regulation of follicular development, particularly with regard to new findings demonstrating the potentiating effect of growth hormone and/or various growth factors on ovarian sensitivity to FSH. This new knowledge, as well as availability of potent GnRH analogues, will evidently refine our clinical approach to treatment of functional infertility. Continuous advances in the understanding of mechanisms regulating reproductive processes and the better recognition of underlying causes of infertility will lead to the optimal choice of first-, second- and third-line routine therapies which will apply to the majority of patients. Furthermore, it will become possible to design tailor-made ovulation-inducing protocols for specific patients who do not respond properly to the routine treatment.

Adult↗
PubMed1990

Hormonal profiles following clomiphene citrate therapy in conception and nonconception cycles.

The hormonal profiles following clomiphene citrate (CC) administration during a single cycle were compared in infertile women who conceived and in those who did not. Of 41 treated patients, ovulation was assumed to have occurred in 28 and was confirmed by clinical pregnancy in five. In the 28 women who presumably ovulated, two distinct patterns of hormonal secretion were observed. A normal response was exhibited by 17 patients (including the five who became pregnant). The other 11 patients exhibited an abnormal response, characterized by significantly higher luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios than in the normal response group from day 9 until the occurrence of the LH peak (days 9 and 10, P less than 0.05; days 11 and 12, P less than 0.001), and significantly higher oestradiol (E2) levels throughout the cycle (P less than 0.01). In addition, in comparison with the normal response group their LH levels during the follicular phase were significantly higher (P less than 0.05) but their LH peaks at ovulation were significantly lower (P less than 0.02). Moreover, their progesterone levels, in contrast to those in the normal response group, began to increase prior to the LH peak and remained high during the early and mid-luteal phases. None of the women who exhibited this abnormal gonadotrophin response to CC therapy achieved a clinical pregnancy. Exposure to high LH levels in the follicular phase following CC therapy seems to reduce the rate of fertilization and/or to contribute to early embryonic loss.

Clomiphene↗
PubMed1990

Steroid secretion by granulosa cells isolated from a woman with 17 alpha-hydroxylase deficiency.

Steroid synthesis in luteal/granulosa cells harvested after follicular aspiration in a patient with 17 alpha-hydroxylase deficiency was investigated. Follicular stimulation with purified FSH after the suppression of ACTH and gonadotropin secretion by corticoid analogs and superactive GnRH agonist permitted ovum pick-up and the study of steroid synthesis in the obtained granulosa cells. Progesterone synthesis was elevated while 17 alpha-hydroxy progesterone, testosterone, androstenedione, and estrogen production was minimal. Aromatase activity was retained in these cells, as demonstrated by the 100-fold increase in estrogen levels after the addition of androgens. Progesterone levels in follicular fluids were in the normal range, while estrogen, 17 alpha-hydroxy progesterone, and androgen levels were minimal. These results provide in vitro evidence of 17 alpha-hydroxylase deficiency in the granulosa cells of this patient.

Adrenal Hyperplasia, Congenital↗
PubMed1990

Addition of exogenous estrogens to improve cervical mucus following clomiphene citrate medication. Patient selection.

Medication with Clomiphene Citrate and its effects on the quality of cervical mucus and the addition of exogenous estrogens in order to suppress abnormal mucus secretion are controversial issues. We have prospectively studied a group of 19 anovulatory women who were treated with clomiphene citrate in order to characterize those patients most likely to respond to the addition of exogenous estrogens. On day 14 of the cycle, 17 beta estradiol and cervical score were measured and 1 mg estradiol benzoate was injected intramuscularly. Cervical scores were below 7 in 12 out of the 19 patients before estradiol benzoate administration. In these patients, 17 beta estradiol rose from 751 +/- 541 to 1321 +/- 648 pg/ml (p less than 0.03), and cervical scores rose from 3.75 +/- 2.1 to 7.1 +/- 3.7 (p less than 0.01), after estradiol benzoate administration. Patients with cervical scores of 8-12 did not improve significantly. In the 12 patients with cervical scores below 7, those (n = 6) with 17 beta estradiol below 600 pg/ml experienced a significant improvement in cervical score, in contrast to those (n = 6) with 17 beta estradiol above 600 pg/ml who had no improvement. The reduction in cervical mucus accomplished with clomiphene citrate can be further improved by adding exogenous estrogens, mainly in patients who have low 17 beta estradiol levels concomitant with low cervical score.

Anovulation↗
PubMed1990

Luteal rescue in in vitro fertilization-embryo transfer.

The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization (IVF) program were compared. A control group (group I) consisted of 28 women (28 cycles) who received our standard ovulation induction regimen (no luteal phase support). The treatment group (group II) consisted of 40 women (42 cycles) who were prospectively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin (hCG) 5 days after the initial hCG dose. The groups were matched for age and cause of infertility. Estradiol (E2) and progesterone (P) were measured on the day of embryo transfer and every 3 to 4 days thereafter. Luteal phase hCG support significantly augmented (1) E2 and P levels in the conception cycles of group II compared with group I and (2) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II. An ongoing pregnancy rate of 19% was achieved in group II. This was not statistically different from the 13% ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our standard ovulation induction regimen during the period of the study. In summary, the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG. It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri-implantation hormonal milieu.

Adult↗
PubMed1989

The assessment of a cycle with clomiphene as an indicator for further treatment.

A group of 15 anovulatory women was treated during one single cycle with clomiphene citrate (CC) 100 mg daily, starting on day 5 of the cycle for 5 days, (group A). Eleven ovulatory patients represent a control group (group B). Serum levels of follicular stimulating hormone (FSH) and luteinizing hormone (LH) were determined on day 5 and 9 of the cycle. Follicular growth was assessed by ultrasound from day 9 until presumed ovulation. Estradiol levels and cervical mucus characteristics were measured on day 14 and progesterone assessed on day 23 of the cycle. In the clomiphene induced cycles FSH and LH values on day 9 were significantly above pretreatment levels (p less than 0.001 and p less than 0.0001, respectively), and above those of day 9 of the control group (p less than 0.0001). In comparison to the control group under CC treatment, an excessive production of estradiol was observed (p less than 0.0001) corresponding to significant increase in number of follicles (over 15 mm in diameter), p less than 0.04. Inspite this elevated estradiol, the cervical score was significantly lower (p less than 0.004) than in the control group. Three patients out of the 15 were characterized by a discrepancy between elevated estradiol levels and a poor mucus score. The rational of the CC assessment cycle is to identify those patients who may need an alternative treatment such as HMG/HCG or pulsatile GnRH.

Adult↗
PubMed1989

Severe ovarian hyperstimulation syndrome: a reevaluated therapeutic approach.

During the 10 years 1978 to 1987, 33 patients were hospitalized because of moderate and severe ovarian hyperstimulation syndrome (OHSS) in 39 treatment cycles. Twenty-five treatment cycles ended in moderate OHSS (group A), 7 had severe OHSS without a significant amount of ascites (group B1), and 7 had severe OHSS with ascites (group B2). Groups A and B1 received intravascular volume expander, electrolytes replacement, and indomethacin up to 300 mg/day. The patients in group B2 had significant clinical and biochemical improvement after abdominal paracentesis. Urinary output and creatinine clearance improved significantly, and a decrease in hematocrit, blood osmolarity, and weight reduction were achieved. A strategy for treatment of OHSS based on consecutive ultrasonographic examination, clinical and biochemical evaluation, and abdominal paracentesis in severe OHSS with clinically significant ascites is suggested.

Abortion, Missed↗
PubMed1989

Hormonal therapy and pubertal development in boys with selective hypogonadotropic hypogonadism.

The authors have compared the effects of treatment with weekly injections of human chorionic gonadotropin (hCG) with those of monthly testosterone (T) injections in males with hypogonadotropic hypogonadism. There was no significant difference in pubertal development as measured by progression through the Tanner stages, final height, or bone age, with the two treatment regimens. The final testicular volume in patients treated with 5,000 U/week of hCG (14.0 +/- 2.0 ml) was significantly greater than that in patients treated with 250-mg monthly T injections (4.3 +/- 1.8 ml) (P less than 0.01). This study shows that weekly injections of hCG are effective in achieving virilization in hypogonadotropic hypogonadic males, leading to a greater testicular growth than T preparations. Therefore, hCG treatment may have an advantageous effect on the eventual induction of fertility with human menopausal gonadotropin.

Adolescent↗
PubMed1989

The potentiating effect of growth hormone on follicle stimulation with human menopausal gonadotropin in a panhypopituitary patient.

A hypogonadotropic patient with primary pituitary insufficiency who has been previously treated for four cycles with hMG/hCG for ovulation induction is described. The hMG consumption was 76 to 96 ampules/cycle. Addition of GH (16 to 24 units/cycle) to hMG treatment was associated with a significant diminution in hMG consumption (35 to 36 ampules/cycle). The patient conceived on the second cycle of combined hMG/GH/hCG treatment. The possible role of GH as an adjunct to gonadotropin treatment is discussed, as well as the possible mechanisms of GH effects on the ovary.

Adult↗
PubMed1989

Human chorionic gonadotropin, estradiol, and progesterone profiles in conception and nonconception cycles in an in vitro fertilization program.

In 22 consecutive in vitro fertilization cycles stimulated with purified follicle-stimulating hormone, human chorionic gonadotropin (hCG), estradiol (E2), and progesterone (P) were measured every 3 days during the luteal phase. All serum measurements were normalized to the day of hCG administration (day 0). There was a total of nine pregnancies; two were biochemical pregnancies, whereas 7 of the 22 women had clinical pregnancies (31.8%). Of these, two miscarried and five had term pregnancies (three singleton, two twin). Conception cycles could be differentiated from nonconception cycles by serum E2 levels on day 8 (P = 0.035), by hCG levels on day 11 (P = 0.03), and by P levels on day 14 (P = 0.001). From days 8 to 11, hCG levels plateaued in conception cycles and decreased in nonconception cycles. However, during that period, E2 and P fell in both groups of women. This decline in sex steroids, which was observed in both conception and nonconception cycles, may well negatively influence endometrial development during the peri-implantation period and compromise conception, resulting in failure to conceive, biochemical pregnancy, and early miscarriage.

Adult↗
PubMed1989

In vitro fertilization and primary embryonic cleavage are possible in 17 alpha-hydroxylase deficiency despite extremely low intrafollicular 17 beta-estradiol.

Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency in genotypic females is characterized by primary amenorrhea and the absence of sexual maturation due to inadequate biosynthesis of ovarian androgens and estrogens. We induced ovarian follicular development in a woman with this syndrome. Ovum pick-up, in vitro fertilization, and primary embryonic development were achieved despite undetectable plasma estradiol and extremely low ovarian androgen concentrations and minute concentrations of these hormones in the ovarian follicular fluid.

Adrenal Hyperplasia, Congenital↗