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Biomedical subjects

V Insler

Publications and source records attributed to V Insler.

At least 55 records · Page 3Linked to original sources

Luteinizing hormone: its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase.

OBJECTIVE: To review studies that have examined the role of LH, its mechanism of action, and its detrimental effects when hypersecreted during the follicular phase. DESIGN: Important published studies related to this topic were identified through a computerized bibliographic search. PATIENTS, PARTICIPANTS: Review of the need for LH during the follicular phase is based on animal models and women with hypogonadotropic hypogonadism. The association of hypersecretion of LH during the follicular phase with low rates of fertilization and high rates of pregnancy loss is based on clinical studies conducted in patients treated by IVF and ET and by induction of ovulation. The possible mechanism by which the effects occur is based on in vitro studies. RESULTS: The results of the studies cited in this review are consistent with the two-cell two-gonadotropin hypothesis implying that synergistic action of both FSH and LH is required for appropriate steroidogenesis. It also seems that, whatever the underlying mechanism, a raised serum LH concentration during the follicular phase confers a substantial risk of infertility and early pregnancy loss. CONCLUSION: By reviewing the literature it appears that LH exhibits an important role in the development of the growing follicle and maturation of the oocyte. It also seems that hypersecretion of LH during the follicular phase implies adverse effects on the fertility process. To further test this hypothesis, we now need systemic assessment of the methods of therapy used for treating patients with polycystic ovary syndrome, in relation to LH secretion and outcome of pregnancy.

Animals↗

Polycystic ovaries in non-obese and obese patients: possible pathophysiological mechanism based on new interpretation of facts and findings.

This study was designed to investigate the basic concentrations of different hormones in obese and non-obese patients with polycystic ovarian disease (PCOD). Eight women with PCOD, of whom four were obese with body mass index (BMI, kg/m2) of > 25 and four were non-obese with BMI < 25, volunteered to participate in this study. Serum samples were taken every 20 min over an 8 h period, starting at 2300 h, on day 5 of a spontaneous or gestagen-induced cycle. Basic insulin concentration was found to be significantly higher in the obese women compared with their non-obese counterparts (P < 0.0001). Serum concentrations of insulin-like growth factor binding protein (IGFBP-I) and sex hormone binding globulin (SHBG) were found to be significantly lower (P < 0.001 for both hormones) in the obese compared with the non-obese women. Serum concentrations of insulin-like growth factor I (IGF-I) did not differ between the two groups. The non-obese women had significantly higher serum concentrations of luteinizing hormone (LH) (P < 0.001) and of growth hormone (GH) (P < 0.002) than their obese counterparts. Based on these results, two models of the development of PCOD were suggested. In obese women, hyperinsulinaemia causes an excessive production of androgens through the enhancement of IGF-I receptors which, in synergism with LH, causes increased activity of cytochrome P-450c 17a. In non-obese patients, relative increase of GH concentration stimulates excessive ovarian IGF-I production. At this point synergism with LH results in excessive production of androgens by the same mechanism as in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Follicular development and its control.

The female reproductive cycle is based on a co-ordinated function of several regulatory elements and signalling systems. Of the approximately 7 million oocytes present in the human fetal ovary, only 475 will eventually ovulate. In the human, the development of a primordial follicle into a dominant one takes about 10 weeks. Approximately 300 follicles are recruited initially for growth and development, 30 of them are likely to become gonadotropin-dependent and enter competition for dominance and, finally, only one will achieve ovulation. The mechanisms by which follicle stimulating hormone, luteinizing hormone, growth factors and steroids may promote or disrupt follicular development are discussed in detail. Possible implications of these new facts on diagnosis and treatment of ovulatory disturbances are described.

Female↗

Vaginal delivery of breech-vertex twins.

The safety of vaginal birth for breech-vertex twins has not been addressed directly before. We retrospectively compared the perinatal outcome of two groups of breech-vertex twins: 24 delivered vaginally and 35 delivered abdominally. Vaginal delivery was allowed under the same protocol developed for singletons in breech presentation. Both groups had similar maternal and neonatal characteristics except for a significantly higher rate (P = .003) of pregnancies after infertility in the abdominal delivery group. Intergroup differences in perinatal outcome, as measured by Apgar scores and morbidity and mortality cases, were not significant. Our data suggest that if measures for safe vaginal delivery are taken, this route appears to incur no morbidity and mortality for breech-vertex twins.

Adult↗

[Chorionic villi sampling: choice of transcervical or transabdominal routes preferable to use of transcervical route exclusively].

Between November 1985 and June 1990 we performed 400 first trimester chorionic villi samplings (CVS). In the first 107 cases only transcervical CVS was performed, regardless of placental location. Later, 163 transcervical and 130 transabdominal CVS were performed, depending on placental location. Anterior and fundal placentas were approached transabdominally and posterior placentas transcervically. Multiple pregnancies were excluded. Successful results were obtained in 394 out of 400 cases. There were 5 failures in the first set of cases and 1 in the second (p < 0.05). In 14 cases (3.5%) fetuses with normal karyotypes were spontaneously aborted, 5 of these in the first period (4.7%) and 9 (3.1%) in the second. The spontaneous abortions in the second period followed transabdominal CVS in 4 cases out of 130 (3.1%) and the transcervical route in 5 cases out of 163 (3.105%). The average attempts per case in the first period was 1.44 (SD 0.66) while in the second it was 1.17 (SD 0.44, p < 0.0001) for the transcervical route and 1.06 (SD 0.2, p < 0.002) for the transabdominal route. In our experience choosing between transabdominal and transcervical CVS according to placental location is preferable to the sole use of transcervical CVS in terms of lower failure rate and fewer attempts per case. Proficiency in both techniques is mandatory for optimal results.

Abdomen↗

Endometrial morphology and hormonal profiles in in vitro fertilization patients.

Endometrial biopsy was performed in 27 infertile women participating in the IVF program. Their mean age was 31.8 years, 33% of the women being over 35 years old. The average duration of infertility was 6.9 years. The superovulation protocol consisted of hMG/hCG in 5 cases, of combined GnRH analog/gonadotropin therapy in 20 women, and 2 patients received combined contraceptive pill/gonadotropin treatment. Judging by hormonal profiles, follicular growth rate and number of oocytes retrieved, the response to stimulation was normal. The mean estradiol (E2) levels increased from 132.7 pg/ml on day -5 (SEM = 9.67) to 1272 pg/ml (SEM = 103.7) on the day of hCG administration and to 1813 pg/ml (SEM = 209.6) 1 day later. One day before the hCG application, the mean progesterone and LH levels were 1.34 ng/ml and 8.38 IU/ml, respectively. Only one patient had clinical hyperstimulation syndrome. Ova were harvested in all women, the mean number of oocytes being 7.7 (SEM = 0.83) per patient. In all 27 cases lack of fertilization or faulty ovum cleavage were observed. Thus, an endometrial biopsy (EB) was performed 72 h after oocytes retrieval. The mean estrogen and progesterone levels on the EB day were 610.9 pg/ml (SEM = 78.44) and 45.4 ng/ml (SEM = 7.53), respectively. Histologic examination of the endometrium showed normal secretory endometrium consistent with day 16-17 of spontaneous ovulatory cycle. Two women who received combined contraceptive pills/gonadotropin therapy showed inactive endometrium with subnuclear vacuoles and decidual reaction in the stroma similar to that observed in women on estrogen-progestin birth control medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Flow velocity analysis of umbilical and uterine artery flow in pre-eclampsia treated with propranolol or pindolol.

In a double blind study, 20 gravidas with pre-eclampsia were randomly allocated to treatment with either propranolol 120 mg/day or pindolol 15 mg/day for 7 days. Flow velocimetry was performed before and after treatment to assess the influence of these two regimens of beta blocker on the feto-placental circulation. A continuous wave Doppler unit was used to measure umbilical and uterine artery flow velocity waveforms. The systolic/diastolic (A/B) ratio and the systolic minus diastolic divided by systolic (A-B)/A ratio (resistance index) were used as indexes of blood flow resistance in the umbilical and uterine arteries, respectively. A resistance to flow in the uteroplacental circulation was significantly less in patients treated with pindolol compared to those treated with propranolol (P less than 0.01). The same pattern was also found in umbilical velocimetry, although the statistical significance was borderline (P = 0.06). Although both drugs were equally effective in reducing blood pressure at rest, their effect on the peripheral resistance was different. Pindolol appears to act in part through a peripheral vascular mechanism. Our data support this assumption because the flow in the uteroplacental bed, as reflected by a decrease in resistance index, improved when patients were treated with the drug pindolol.

Adult↗

Early pregnancy termination: an improved technique for 'menstrual regulation' with ultrasound assistance.

We performed aspiration of early pregnancy on 100 women requesting termination, using a low caliber angled catheter under sonographic guidance, without analgesia or anesthesia. The sonographic inclusion criteria for the study were: (1) mean gestational sac diameter less than 30 mm, or (2) crown rump length less than 10 mm when an embryo was visualized. The uterine content was successfully evacuated in all cases and none needed an additional curettage. Two women developed mild endometritis which responded to antibiotic therapy. This refinement of this 'menstrual regulation' technique seems to be safer when compared with the reported results of the original technique.

Abortion, Induced↗

Spontaneous ovarian hyperstimulation syndrome concomitant with spontaneous pregnancy in a woman with polycystic ovary disease.

Ovarian hyperstimulation syndrome has been described after treatment with exogenous gonadotropins, clomiphene citrate, and gonadotropin-releasing hormone. Spontaneous ovarian hyperstimulation syndrome has not been described before, except in association with hypothyroidism. We report on a case associated with spontaneous pregnancy, occurring in a woman with polycystic ovary disease.

Adult↗

Corpus luteum defects.

During the review period a number of experimental works dealing with structure and function of different cell populations constituting the corpus luteum have been published. The function of luteinizing hormone receptors and their response to luteinizing hormone stimulation at different phases of the luteal phase have been studied. The synthesis, localization, and levels within the endometrium of a series of proteins such as insulin-like growth factor I, its binding protein, placental protein 14, and CA 125 have been examined. The possible implications of these studies on normal and disturbed corpus luteum functions are briefly discussed. The clinical assessment of corpus luteum function is still neither simple nor accurate. Histologic dating of endometrial biopsy has been reexamined, showing that readings of the same slide by the same evaluator were in exact agreement only in 43.1% of instances, and the dating differences among five various evaluators were even larger. An examination of 28 young, healthy volunteers participating in a 2-month strenuous exercise program indicated that in normal women, exercise, change of living conditions, stress, or other extraneous impacts may result in menstrual disturbances affecting either the entire cycle course or the luteal phase only. However, in the majority of cases, these effects are transient. Another study established that the prolactin secretion characteristics in women with luteal phase deficiency did not differ from those observed in 36 normal, apparently ovulating women. Another clinical study showed that deficient plasma lipoprotein levels are not connected with luteal phase deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer.

From the reviewed data, it appears that CC, hMG-hCG, or the association of these drugs with IVF-ET and GIFT programs do not carry an increased risk for congenital malformations as a whole, nor is there any specific malformation that has an increased incidence or is related in any way with the use of these drugs. Table 7 represents the specific malformation rate per 1,000 births in the general population and in newborns delivered after treatment with CC, hMG-hCG, or IVF-ET and GIFT. The malformation rate in the treated groups does not differ from that of the general population. However, as shown by McIntosh et al., the incidence of congenital malformations often rises with a longer follow-up. Most of the reports about babies born after ovulation induction are based on the initial examination done shortly after birth. Thus, studies including examination of these infants up to at least 12 months of age will be undoubtedly of value. Also, data concerning the reproductive capability of women born after ovulation induction is lacking. With regard to the abortion rate in pregnancies achieved after such treatments and procedures, it can be concluded that it does not appear to be higher than that of the general population, particularly when early pregnancy loss, advanced maternal age, the infertility status, and the increased incidence of multiple pregnancies occurring in these patients are taken into consideration.

Abortion, Spontaneous↗

Pathophysiology of polycystic ovarian disease: new insights.

The incidence of polycystic ovarian disease (PCOD) varies from 0.6 to 92%, depending on the parameters analysed, PCOD has been reported to appear in association with Cushing's Syndrome, adrenal hyperplasia, hypothyroidism, adrenal and ovarian tumours and some genetic abnormalities. The controversy regarding the pathophysiological mechanism underlying the disease still persists. Critical evaluation of old data, assessment of new findings concerning the possible role of insulin, growth factors and their binding proteins, and extrapolation of neuroendocrinological experiments enabled the construction of a concise hypothesis of the pathophysiology of PCOD. According to this hypothesis, PCOD is a multifactorial disease. The sequence of events finally leading to clinical manifestation of the disease (hyperandrogenism, abnormal luteinizing hormone pulsatility pattern and ovulation disturbances) may originate in different organs or be triggered by different mechanisms. It may stem from the adrenals, the hypothalamus or higher central nervous system centres, or from the ovary itself; it may originate from excess of fat tissue usually combined with hyperinsulinism; or may be the result of a net increase in active growth factors. Each of the above disturbances probably appears early in life, much before the clinical signs of the disease are evident. Predisposing factors such as gestational diabetes of the mother, childhood obesity, borderline adrenal hyperplasia and late menarche have to be looked for as early as possible in order to prevent the late consequences of the disease, such as increased risk of infertility, endometrial and breast cancer and cardiovascular disease.

Female↗