Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease.

OBJECTIVE: To assess the endocrinologic and clinical outcome after laparoscopic ovarian electrocautery because of polycystic reaction to ovarian stimulation in anovulatory infertility patients. DESIGN: Between 1986 and 1989, 133 patients with polycystic ovarian disease underwent laparoscopic electrocoagulation of the ovarian surface in an outpatient clinic after conventional ovarian stimulation had led to polycystic reaction. SETTING: All patients were referred to our outpatient clinic affiliated with the university hospital. RESULTS: The reduction of androgen levels and normalization of cycle length were highly significant. The overall pregnancy rate was 70% (73 of 104), ranging from 27% in smokers to 94% in nonsmoking couples. In 26 second-look operations de novo adhesions were found in 26.9% of the patients. CONCLUSION: Laparoscopic coagulation of the ovarian surface is an effective tool to reduce elevated androgen levels and to improve the intraovarian mechanism of selecting a dominant follicle. A postoperative complication may be adhesion formation.

[Results of treatment with surface cauterization of polycystic ovaries in sterility patients]. / Behandlungsergebnisse mit der Oberflächen-kauterisierung polyzystischer Ovarien bei Sterilitätspatientinnen.

In 39 women with polycystic ovaries (PCO) and a history of sterility, laparoscopic electrocautery of the surface of the ovaries was performed by a technique adapted from Gjoennaess (1984). Previous hormonal treatment with clomiphene and/or human menopausal gonadotropins had been unsuccessful in these patients, whilst 23 of them (59%) conceived within one year after surgery. Electrocautery was followed by a decrease of mean testosterone levels from 0.95 +/- 0.064 ng/ml to 0.48 +/- 0.041 ng/ml and a similar decline of dehydroepiandrosterone sulfate from 2.9 +/- 0.136 g/ml to 1.6 +/- 0.165 g/ml respectively. Laparoscopic ovarian electrocautery is however associated with the risk of postoperative adhesion formation. Therefore we advise this form of surgery only, when hormonal therapy failed or if it presents an unacceptable high risk of hyperstimulation or a multiple pregnancy.

Melatonin and the ovulatory luteinizing hormone surge.

A newly developed 125I-radioimmunoassay allows for the accurate determination of physiological concentrations of plasma melatonin. Melatonin secretion does not change significantly on the day before and the day of the luteinizing hormone (LH) surge when compared with the early follicular phase. In addition, it was confirmed that the beginning of the LH surge frequently occurs in the morning and is associated with low melatonin values (six of nine women). Supraphysiological melatonin concentrations did not decrease the midcycle LH secretion in four women studied.

Influence of melatonin on the sleep-independent component of prolactin secretion.

Sleep has a stimulatory effect on prolactin secretion. Recent studies in the human suggest the hypothesis that prolactin has also an endogenous sleep-independent rhythm, which can be influenced by endogenous melatonin. To investigate this hypothesis, the prolactin response to nighttime exposure to bright light was studied in eight women in detail. Light exposure induces a decrease in nocturnal melatonin secretion. It was demonstrated that exposure to bright light for 2 h at night caused a decrease in prolactin secretion, which surpassed significantly the decline one would expect by sleep deprivation only (P less than 0.01). This was associated with a similar decline in melatonin secretion. Fall and rise of prolactin secretion under these conditions were always preceded by decrease and rise in melatonin levels in all eight women studied. Based on these observations, it is concluded that melatonin is associated with an endogenous circadian component of prolactin secretion. As specific melatonin receptors have been identified in the human nucleus suprachiasmaticus, which is the "master" circadian pacemaker, the observed phenomenon might be mediated through this structure. An alternative explanation of our findings could be based on the fact that melatonin influences dopamine metabolism, which in turn alters prolactin secretion. It can also not be ruled out that melatonin might act via the opioid system, which then could affect prolactin secretion. The total secretory activity for both hormones (area under the curve) did not change under experimental conditions, when compared to a control group. This suggests that acute light exposure and sleep deprivation influence the secretory process rather than the synthesis of these two hormones. This is in agreement with the observation that changes in natural light exposure throughout the year do alter the amplitude, but not the total amount of melatonin secreted. Further studies are needed to answer the question of melatonin storage definitively, as it is commonly believed that melatonin is immediately released after synthesis. It is concluded that melatonin through its external modulator light might entrain the circadian sleep-independent component of prolactin secretion and via its action on prolactin could modulate reproductive processes.

[Rational hormonal diagnosis of oligomenorrhea]. / Rationelle hormonale Diagnostik der Oligomenorrhö.

In a study, conducted by two clinics in Berlin and Hamburg, specializing in reproductive endocrinology, the anamnestic, clinical, and laboratory data of 170 oligomenorrheic patients (menstrual intervals between 35 and 90 days) were evaluated in order to determine the frequency of possible causes of oligomenorrhea. Pathological hormone levels were found in two thirds of all patients. The order of frequency of abnormal hormone levels was as follows: hyperandrogenemia (testosterone and/or DHEA-sulfate) in 41.8%, hyperprolactinemia in 25.9%, abnormal thyroid function (TSH and/or TRH-induced TSH) in 21.7%, and hypergonadotropic FSH levels in 3.5% of all patients. There was an overlap of between two or more pathological conditions in one third of all patients. This study confirms results of a previous study in amenorrheic patients (Moltz et al., 1987 - see reference list), documenting hyperandrogenemia as the most frequent abnormality found in this group, followed by hyperprolactinemia. As can be expected, the percentage of women with no discernible abnormality was higher in oligomenorrheic patients when compared with the amenorrheic group (32.3% vs 7.7%). Furthermore, overweight patients were overrepresented in the oligomenorrheic group, while underweight patients were seen more frequently in the amenorrheic group. In view of these results of our study we recommend a detailed diagnostic follow-up in all younger patients with ovarian disorders who need to preserve their reproductive potential. This follow-up should include hyperprolactinemia, hypo-/hyperthyroidism, hyperandrogenemic and hypoestrogenemic states and exclusion of primary ovarian failure. In contrast to recommendations of WHO, issued in 1976, such diagnostic work allows an etiology oriented therapy decision and a therapy risk assessment in subgroups of patients, such as hyperandrogenemic patients, who receive clomiphene or gonadotropin treatment. Furthermore, it permits prophylactic considerations, for prevention of hirsutism and polycystic ovarian disease, struma and osteoporosis prophylaxis.

Buserelin suppression of endogenous gonadotropin secretion in infertile women with ovarian feedback disorders given human menopausal/human chorionic gonadotropin treatment.

Fifty infertile women with oligomenorrhea, anovulation, or luteal phase defects were selected for a combined therapy consisting of a gonadotropin-releasing hormone analog (Buserelin Hoechst AG, Frankfurt/Main, FRG) and human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG). Serving as their own controls, these women had been subjected to a total of 238 hMG/hCG treatment cycles with no pregnancy observed (average, 4.7 cycles; range 2 to 14). Of these 238 hMG/hCG cycles, only 98 (41.1%) appeared normal, while the others showed symptoms consistent with inadequate follicle maturation, luteal phase defects, and premature luteinization. In contrast, 89 cycles from 133 combined buserelin/hMG/hCG treatment cycles (66.9%) appeared to be normal, with no evidence of premature luteinization, and 21 patients became pregnant. These data indicate that the likelihood of group II World Health Organization (WHO) patients becoming pregnant with hMG/hCG therapy may be enhanced when endogenous gonadotropin secretion is suppressed at the same time.

Human placental lactogen and unconjugated estriol concentrations in twin pregnancy: monitoring of fetal development in intrauterine growth retardation and single intrauterine fetal death.

Human placental lactogen and unconjugated estriol concentrations in maternal serum were evaluated in 100 uneventful twin pregnancies, and these values were compared with those observed in 16 twin pregnancies associated with intrauterine growth retardation or single intrauterine fetal death. In pregnancies associated with intrauterine growth retardation (n = 8), human placental lactogen levels were at the lower limit of normal range for singleton pregnancies, whereas estriol levels were normal in most cases. When one of the fetuses had died before week 33 of pregnancy (n = 5), both human placental lactogen and estriol levels were low and they were almost at the levels in singleton pregnancy. When intrauterine fetal death occurred after week 36 of pregnancy (n = 3), both hormone levels remained normal until term. Thus human placental lactogen rather than estriol is a good indicator of intrauterine growth retardation in twin pregnancy. Both human placental lactogen and estriol are useful for the monitoring of the surviving fetus in the case of single intrauterine fetal death.

Different hormonal patterns in human menopausal gonadotropin-treated, clomiphene citrate-treated, and untreated conception cycles.

Serum concentrations of seven different hormones were analyzed during 189 singleton conception cycles. One hundred nine women were treated with human menopausal gonadotropin (hMG), 52 women received clomiphene citrate (CC), and 28 became pregnant spontaneously. Serum progesterone (P) levels in hMG-treated women started to increase on day 18 of the cycle and reached peak concentrations between days 28 and 32 of the cycle. Serum estradiol (E2) concentrations paralleled the P patterns. In hMG-treated women, there were significant correlations between serum E2 and P concentrations and the number of the mature follicles observed before ovulation (both P less than 0.01). CC-treated and spontaneous conception cycles revealed significantly lower serum levels of P, E2, testosterone, 17 alpha-hydroxyprogesterone, and prolactin, compared with hMG-treated cycles (P less than 0.05). Elevations of the gonadal steroids in hMG-treated women possibly reflect the multiple corpora lutea formed after multiple ovulations.

Preliminary report about a modified gonadotropin (human menopausal gonadotropin/human chorionic gonadotropin) treatment in infertile patients with premature luteinization.

Premature luteinization is a frequent phenomenon observed in infertile women undergoing human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) therapy for corpus luteum insufficiency or anovulatory cycles. By inducing hyperprolactinemia in these women with sulpiride, we intended to create a dysfunctional state in these women, which supposedly induces a better reaction to hMG/hCG therapy. The rationale behind this combined treatment was the observation that hyperprolactinemic amenorrheic patients have a much higher pregnancy rate under hMG/hCG treatment than the above group. Three cases are reported in detail, illustrating the altered ovarian response to combined sulpiride-hMG/hCG treatment. Of 60 infertile women with repeated premature luteinization, 12 conceived after sulpiride-hMG/hCG therapy. Their expected pregnancy rate would have been very low (5% or less) if conventional hMG/hCG treatment had been continued.

[Diagnostic value of the prolactin stimulation test in infertile women with galactorrhea]. / Die diagnostische Wertigkeit eines Prolaktin-Stimulationstestes bei infertilen Frauen mit Galaktorrhoe.

In infertile women breast secretion may be provoked in approximately 11%, although basal prolactin serum levels are only elevated (greater than 12 ng/ml) in 30% of the cases. This casts doubt on the diagnostic value of a single determination of prolactin serum concentrations in women with galactorrhea and/or infertility. Introduction of a dynamic function test of prolactin secretion into the endocrine work-up of such patients improves our diagnostic tools as can be seen by the fact that approximately two thirds of the patients with galactorrhea exhibited an exaggerated response of prolactin to metoclopramide despite normal baseline levels of prolactin.

Polymorphism of human pituitary lutropin (LH). Effect of the seven isohormones on mouse Leydig cell functions.

The effect of the 7 different molecular forms of human pituitary lutropin (LH) on mouse Leydig cells as a model of a target organ were studied. The hormone functions have been characterized by receptor binding, cAMP accumulation and testosterone production. One important finding was the similar intrinsic in vitro biological activity for all isohormones. Quantitatively, however, the potencies of the 7 hormone forms did not correlate with the activities obtained by radioimmunoassay: there was a dramatic decrease of receptor binding activity and biological activity compared to immunoactivity from the more alkaline to the more acidic LH isohormones.

Polymorphism of human pituitary lutropin (LH). Isolation and partial characterization of seven isohormones.

The complete microheterogeneous system of human pituitary lutropin was demonstrated by gel isoelectric focusing. In addition 7 LH isohormones could be isolated by preparative column focusing and characterized with respect to physicochemical, biological and immunological properties. The in vivo biopotencies ranged from 4.50-11.50 IU/mg, the in vitro bioactivity was from 1.20-10.10 IU/mg, and the immunological activity was from 3.10-7.55 IU/mg. The sialic acid content was found to be 1.8-3.2%. Treatment with neuraminidase resulted in a shift of all bands to the alkaline region, however the 7 LH forms were still present.

Gonadotropin therapy of female infertility. Analysis of results in 416 cases.

This report is based on 416 infertile female patients who were treated for 1,033 cycles with gonadotropins. 28.6% of the patients conceived after hMG/hCG treatment in 79.8% of these pregnancies, healthy children were born. Spontaneous abortion or premature birth occurred in 20.2% of the cases. The twin rate was 28.6%, the triplet rate 5.5%. Most of the abortions occurred in the first trimester (52.2%). No malformations were seen. The pregnancy rate showed striking differences in the various diagnostic groups: hypogonadotropic amenorrhea 44.4%, normogonadotropic amenorrhea 50%, anovulatory cycles 22%, corpus luteum insufficiency 14.8%. The abortion rates for these four groups were as follows: hypogonadotropic amenorrhea 25%, normogonadotropic amenorrhea 14.7%, anovulatory cycles 4.8%, corpus luteum insufficiency 36.3%. A detailed analysis of the treatment cycles is given for the four groups: the number of ampoules of hMG/hCG increased from 21.4 ampoules in patients with corpus luteum insufficiency to 47.7 ampoules in patients with hypogonadotropic amenorrhea. The inactive phase increased from 5.6 days in patients with corpus luteum insufficiency to 8.5 days in patients with hypogonadotropic amenorrhea. Estrogen values around the time of ovulation and in the corpus luteum phase were much lower in patients with spontaneous uterine bleedings. Hyperstimulation syndrome occurred less frequently in these patients. The percentage of pregnancies decreased in patients with corpus luteum insufficiency from 8.1% in the first treatment cycle to 4.8% in the following treatment cycles, whereas it increased from the first to the following cycles in the other diagnostic groups. Patients with anovulatory cycles and corpus luteum insufficiency respond differently to hMG/hCG treatment than patients with normogonadotropic amenorrhea. The inactive and active phase are important parameters for the evaluation of ovulation induction with hMG/hCG, hMG/hCG treatment is of little value in patients with corpus luteum insufficiency.

Isolation of highly purified sex hormone binding globulin (SHBG): evidence for microheterogeneity.

Highly purified sex hormone binding globulin (SHBG) was isolated in milligram amounts from a human serum fraction (Cohn IV-4). The final preparation was homogeneous by the criteria of polyacrylamide-gel electrophoresis. Immunological evidence for purity could be given by double diffusion according to Ouchterlony. However, following gel isoelectric focusing highly purified SHBG displayed four different bands, as could be demonstrated by staining as well as by a photoscan of the [3H]5alpha-dihydrotestosterone-SHBG complex. After incubation with neuraminidase the microheterogeneity of SHBG disappeared and the asialo-SHBG showed only one band.