Medical induction prior to surgical evacuation of hydatidiform mole: is there a greater risk of persistent trophoblastic disease?

A retrospective study was undertaken to assess whether stimulation of uterine contractility prior to surgical evacuation of a molar pregnancy will lead to an increased frequency of persistent trophoblastic disease. Forty-seven patients treated with chemotherapy for persistent trophoblastic disease after a hydatidiform mole between 1971 and 1988 were evaluated. The use of medical methods in this study group was compared to a control group of 219 patients with hydatidiform mole not requiring further treatment. A medical method, mainly treatment with prostaglandins, was used in 61.7% in the study group compared to 35.2% in the control group. This difference was, however, due to different stage distribution in the groups. Persistent disease was significantly correlated to uterine size and medical methods were mainly used in patients where uterine size corresponded to 15 weeks gestation or more. In this subset of patients, a medical method was used in the same frequency in both groups. Thus, large uterine size seems to be an independent risk factor. We conclude that stimulation of uterine contractility, which in Sweden is frequently used before surgical evacuation of the uterus in patients with hydatidiform mole and large uteri, carries no additional risk.

Choriocarcinoma of the fallopian tube associated with induced superovulation in an IVF program; a case report.

The authors present a case of choriocarcinoma of the fallopian tube. The patient was enrolled in an IVF program and to our knowledge this is the first report of a choriocarcinoma following treatment with clomiphene citrate and hMG. The possible role of superovulation in inducing the tumour is discussed. The patient was treated by conservative surgery only and is in remission 1.5 years after the event.

Twenty years' experience of treating gestational trophoblastic neoplasia in Sweden.

Experience gathered during the last 20 years in the treatment of gestational trophoblastic neoplasia (GTN) is presented. Fifty-eight cases were treated at the Karolinska Hospital during the period of 1966-86. This number accounts for approximately 50% of the cases in Sweden during this period of time. Thirty-four patients developed their malignancy after a molar pregnancy. Thirty-three patients were nonmetastatic and of the 25 metastatic cases, 6 patients were staged to a high-risk group. Chemotherapy was given to all patients except one who had a primary choriocarcinoma in an ectopic pregnancy. Surgery was performed in elective cases or when chemotherapy failed. Surgical procedures were also performed in a few emergency situations. Since 1978 all patients were started on methotrexate--folinic acid ad modum Goldstein. When this medication failed, either the CHAMOMA (vincristine, methotrexate--folinic acid, actinomycin D, melphalan, adriamycin) or later the EMA/CA (etoposide, methotrexate--folinic acid, actinomycin D, cyclophosphamide, adriamycin) regimen ad modum Bagshawe was given. An overall remission rate of 96.5% was achieved. The minimum period of follow-up was 2 years. The 2 patients who died (in 1966 and 1982) were referred to our department in a late stage. Five patients had a late recurrence and all but one were successfully treated.

Antibody to human chorionic gonadotropin detected choriocarcinoma.

Persistently elevated levels of serum human chorionic gonadotropin (hCG) in women call for a tumor investigation, if pregnancy can be ruled out. We present a case of increased hCG concentrations for 1 1/2 years. Radiolabelled antibody directed against the hCG molecule indicated the source of production to be a choriocarcinoma. The patient was cured by multiagent chemotherapy.

The value of endometrial curettage in the follow-up of hydatidiform mole.

Multiple curettages in the follow-up of patients with hydatidiform mole are often performed in Sweden. Of 36 patients developing trophoblastic neoplasia after molar evacuation, 24 underwent one or more endometrial curettages. The objective was generally to verify a diagnosis of malignant disease. However, in only one patient was a histopathological proof of choriocarcinoma obtained. In 3 other patients, malignancy could not be ruled out. It is demonstrated that development of malignancy after hydatidiform mole is rarely proven by endometrial curettage.

The effect of a prostaglandin synthetase inhibitor on the hormonal profile and the endometrium in women.

A prostaglandin synthetase inhibitor, naproxen, was given continuously throughout the menstrual cycle at a dose of 250 mg twice daily to 10 healthy fertile women (group 1) and at a dose of 1000 mg per day to eight women in the secretory phase (group 2). Blood samples were withdrawn three times a week during a control cycle and during the treatment cycle. Luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol, and progesterone were analyzed. Endometrial biopsies were taken in the secretory phase of the control cycle and in the treatment cycle of group 1 and on the first day of menstruation of group 2. Naproxen treatment did not suppress ovulation in any cycle and did not affect the corpus luteum function either in group 1 or in group 2. In only one of the endometrial samples taken in the secretory phase (group 1) was the density of the lysosomes increased in the treatment cycle compared to the control cycle. The specimen taken during the early menstrual period (group 2) showed an increase in glandular epithelium and height following naproxen treatment. Furthermore, a significant increase in the number of plasmolemmal vesicles per square micrometer was observed in the capillary endothelial cells after the administration of 1000 mg of naproxen per day. This suggests that the transcellular exchange of water-soluble molecules in the endothelial cells was more active after the administration of a prostaglandin synthetase inhibitor than in the control group. In spite of the significant morphologic changes observed in the naproxen-treated material the onset of menstrual bleeding could not be prevented. The mechanism of the onset of menstruation needs to be further investigated.

Relief of primary dysmenorrhea by transcutaneous electrical nerve stimulation.

In this study we describe the use of high-frequency transcutaneous electrical nerve stimulation (TENS) (100 Hz) and low-frequency TENS (lf-TENS) (2 Hz trains) as compared with placebo-TENS (p-TENS) in a group of 21 patients suffering from primary dysmenorrhea. Naloxone, a relatively pure opiate antagonist, was an additional test administered to 6 volunteer patients who had experienced an alleviation of pain with TENS. As will be seen, 14 out of 21 patients receiving high-frequency TENS (hf-TENS) experienced a pain reduction exceeding 50% of its original intensity. During lf-TENS or p-TENS, only 7 and 5 patients, respectively, obtained pain relief exceeding 50%. In 4 out of 6 volunteer patients, the relief of pain obtained with lf-TENS was counteracted by naloxone, whereas the relief experienced with hf-TENS in the same patients was, in general, unaffected by naloxone.

Self-monitoring of blood glucose by diabetic women during the third trimester of pregnancy.

The clinical value of self-monitoring blood glucose in diabetic pregnancy at home was compared with hospital care in the thirty-second to thirty-sixth week of pregnancy in a prospective randomized study including 100 pregnancies in 97 patients (White's class B, 38; C, 25; D, 28; and F, 9) of which 54 were in the home group and 46 in the hospital group. The duration of pregnancy was not significantly different in two treatment groups, with a median duration of 266.0 days in the home group and 266.5 days in the hospital group. The mean blood glucose values during the study period were 5.9 mmol/L in the home group and 6.0 mmol/L in the hospital group, thus there were no significant group differences. There were no significant group differences in pregnancy complications; however, 10 of 54 (19%) had to interrupt home-monitoring because of pregnancy complications. The perinatal morbidity was not significantly different in the two treatment groups, with the following percentages of complications in the combined series: 4% idiopathic respiratory distress syndrome, 7% transient tachypnea, 2% symptomatic hypoglycemia, 16% hyperbilirubinemia, 22% feeding problems, and 10% erythrocytosis.

Diurnal variation of uterine contractility.

The diurnal uterine activity in four normal women in the secretory phase of their menstrual cycles and one woman suffering from dysmenorrhea were studied in relation to concomitant hormone levels in blood (progesterone, hGH, prolactin, cortisol, vasopressin, and 15-keto-13,14-dihydro-PGF2 alpha). In the four normal women uterine activity decreased after midnight, unrelated to circulating levels of 15-keto-13,14-dihydro-PGF2 alpha. But during a dysmenorrheic episode the uterine hypercontractility pattern correlated well with levels of the PGF2 alpha-metabolite, indicating a role of endogenous-produced PGF2 alpha in this condition. The results demonstrate a diurnal rhythm, possibly related to the wake-sleep cycle. No simple associations were seen between vasopressin, cortisol, prolactin, hGH, the PGF2 alpha-metabolite, and uterine activity.

The effect of intravenous and intrauterine administration of prostacyclin on non-pregnant uterine contractility in vivo.

Intravenous administration of prostacyclin at a dose of 10 ng/min/kg bodyweight for 10 minutes did not have any effect on non-pregnant human contractility in three subjects. Higher doses were not given due to side effects. Intrauterine administration of PGI2 at doses of 0.3-0.6 micrograms resulted in a gradual stimulation of the myometrial activity. Whether this response is a secondary effect of the vasodilation caused by PGI2 or a direct effect on the myometrium could not be established in these experiments.

Treatment of primary dysmenorrhea.

The management of primary dysmenorrhea is discussed, firstly from the viewpoint of the adolescent girl and secondly of the adult woman. Sexually active girls wishing to use contraceptive agents are recommended low-dose oral contraceptives (OC). Teenagers with severe dysmenorrhea who do not require OC are prescribed a prostaglandin synthetase inhibitor. The adult woman has first the choice between OC and prostaglandin synthetase inhibitor as well. When all these are ineffective, secondary causes of dysmenorrhea must be sought and specific treatment eventually required. When no medication affords pain relief, however, and no organic cause can be found, the patient is referred for pain consultation. Hysterectomy is discussed as the final solution for the elderly woman.

Naproxen in the treatment of OC-resistant primary dysmenorrhea. A double-blind cross-over study.

The efficacy of oral contraceptives (OC) in the treatment of primary dysmenorrhea in controlled studies varies from 50 to 80%. The addition of a prostaglandin synthetase inhibitor, naproxen, was found to afford pain relief to a further 70% of women with OC-resistant dysmenorrhea in a double-blind cross-over study comprising 39 patients. This effect was shown to be statistically significant at p = 0.0005. Our recommendation is that low-dose OCs should be the first choice as contraceptive agents for women with dysmenorrhea and that a prostaglandin synthetase inhibitor should be given when OCs are ineffective.

The possible roles of prostaglandins and related compounds in endometrial bleeding. A mini-review.

This mini-review summarizes some aspects of hemostatic defects, with particular reference to endometrial bleeding, both the normal menstruation and some bleeding disorders of the uterus. Two cell types are of particularly great interest in the hemostatic mechanism, viz. the platelet and the vascular endothelial cell. We will therefore start with a brief survey of the roles of platelets and vascular endothelium in hemostasis, and the underlying biochemical events will be discussed, particularly the participation of the arachidonate metabolites: the prostaglandins, the thromboxanes and the leukotrienes. This section is then followed by a brief description of some histological findings in the menstruating endometrium; the normal as well as the pathologically bleeding tissue. The possible roles of arachidonate metabolites in these events will be discussed. Several clinical studies have been published, in which various attempts have been made to treat excessive endometrial bleeding with inhibitors of prostaglandin biosynthesis. The findings in these studies are described. The relevance of this approach and its possible effects on other areas of arachidonic acid metabolism will be discussed. Finally, some studies will be summarized in which various attempts have been made to quantitate and endometrial prostaglandins in different physiological and pathological conditions.

The effect of a prostaglandin synthetase inhibitor on the hormonal profile and the endometrium in women.

A prostaglandin synthetase inhibitor, naproxen, was given continuously throughout the menstrual cycle at a dose of 250 mg b.i.d. to 10 healthy fertile women. Blood samples were drawn three times a week during an earlier control cycle and during the treatment cycle and analyzed for LH, FSH, prolactin, estradiol and progesterone. Endometrial biopsies were taken in the secretory phase. Naproxen treatment did not suppress ovulation in any of the cycles and did not affect the corpus luteum function. In only one of the endometrial samples taken was the density of the lysosomes increased in the treatment cycle compared with the control cycle.

A new prostaglandin E2-gel for pretreatment of the cervix in nulliparous patients having a late first trimester termination of pregnancy.

A new PGE2-gel, based on a cross-linked starch powder, has been developed. This gel seems to have solved several of the pharmaceutical and practical problems connected with local administration of prostaglandins. In a three-center study 120 nulliparous patients were given 0.5 mg PGE2 in 2.2 ml gel intracervically prior to dilatation of the cervix and evacuation of the uterus in late first trimester. Considerable cervical dilatation was obtained within 15 h. The frequency of side effects, including pain and gastro-intestinal discomfort was low. The technique can be recommended for outpatients.