Elevtion of serum testosterone in ovarian hyperstimulation syndrome.

Serum testosterone levels were monitored in female subjects who received therapy with human gonadotropins of urinary origin (menotropins) and human chorionic gonadotropin (hCG). Serum testosterone levels were not elevated in those subjects who did not experience side effects with therapy (Group A); among the other 7 subjects (Group B) with either moderate or severe ovarian hyperstimulation, serum testoterone levels rose distinctly (range 1.4 minus 9.0 ng/ml). Total menotropin dosage and serum estradiol-17beta levels were higher in Group B than in Group A. Ovarian hyperstimulation and elevation of serum testosterone were not restricted to patients with the syndrome of polycystic ovaries.

Fetal movements in utero: nature, assessment, prognostic value, timing of delivery.

Fetal movements in utero are an expression of fetal well-being. However, a sudden increase of fetal movements is a sign of acute fetal distress, such as in cases of cord complications or abruptio placentae. Decreased fetal movements are seen in cases of chronic fetal distress such as preeclampsia, hypertension in pregnancy, etc. It was shown that in these cases a pronounced decrease up to cessation of fetal movements occurred before fetal death in utero while fetal heart beats were still audible for at least 12 hours. This situation was called "movements alarm signal" (MAS). This sign points to a severely disturbed fetus and indicates impending intrauterine fetal death. Such a development is an indication for immediate delivery of the fetus, provided it is viable. High-risk pregnant women are instructed to assess and record fetal movements daily as a monitor of fetal condition. A special device which records fetal movements is used to confirm the women's assessment of fetal movement. It was shown that fetal movement monitoring was found to be more reliable than the urinary estriol determination in predicting impending fetal death in utero. It was also shown that in cases of MAS, fetal heart rate (FHR) changes will appear 1 to 4 days after the MAS has appeared. Meconium was found in only 50% of these cases. Increased fetal movements are manifested as a response to various stimuli such as sound, light, touch, and ultrasound. Classification of high-risk pregnancies into 3 groups according to the hormone assays, enzyme assays, ultrasonic cephalometry, fetal movements, and FHR is suggested.

Ovarian hyperstimulation syndrome.

Eighteen patients hospitalized for excessive ovarian hyperstimulation syndrome are reported. In 14 cases the ovarian hyperstimulation was induced by human menopausal -onadotropins and in 4 cases by combined treatment with clomiphene and HCG. In 5 patients the hyperstimulation was associated with conception, which resulted in 1 quintuplet delivery, 1 early quintuplet abortion, 1 twin abortion, 1 normal delivery, and 1 missed abortion. The regimen of treatment was a conservative one. The patients were hospitalized and treated with infusion of plasma expanders. Anticoagulant therapy was administered only in cases that showed clinical evidence of thromboembolic pheomena or laboratory evidence of severe hemoconcentration. The pathogenesis of the ovarian hyperstimulation syndrome, prevention, and management are discussed. This syndrome should be diagnosed early and treated intensively.

Oral contraceptives and serum copper concentration.

PIP: Serum copper concentrations were determined by atomic absorption spectroscopy in 502 women (average age 23.8 years) using oral steroid contraceptives. Mean serum copper level in these women increased substantially (primarily during second or third cycle of treatment), corresponding to levels obtained during the second trimester of pregnancy. An average of 207 g/100 ml was found compared to an average of 129 g/100 ml in normal non-contracepting women. 6.5% of the cases experienced an increase in serum copper beyond the normal range, indicating possible liver dysfunction. Following cessation of oral contraceptives, serum copper level returned to the normal range within 4-6 weeks. The composition and type (combined or sequential) of steroid pills, and duration of treatment made no difference in serum copper levels. Knowledge of serum copper levels may help in selecting suitable subjects for oral contraceptive preparations and deciding when to cease medication in order to prevent early hepatic damage.^ieng

Termination of midtrimester pregnancy by intramniotic injection of urea.

PIP: The use of intraamniotic injection of hypertonic solutions for termination of pregnancy during the second trimester has been generally adopted. Because of side effects in such treatment with other agents, it was decided to use intraamniotic instillation of urea solution (Urevert) to induce midtrimester therapeutic abortion in 38 patients. The method was successful in 35 patients (92%) with a mean injection/abortion interval of 26.1 hours, shorter than that with the use of hypertonic saline or hypertonic glucose solutions. The side effects of headache, nausea, and vomiting were mild, and an endometritis in 1 patient responded well to antibiotic treatment. Intravenous oxytocin drip was necessary in patients with hypotonic contractions or in those who failed to react within 36 hours after injection. In 3 cases of missed labor, the urea solution injected induced labor within 5-8 hours, with no side effects. The mean in-patient hospital time was 4.3 days.^ieng

Serum prolactin in normal and pathologic pregnancy.

Serum prolactin values in normal pregnant women showed a progressive increase from a mean value of 50 ng/ml in the 12th week to 270 ng/ml at term, with the range at term being 100-600 ng/ml. There was a fairly good correlation (r = 0.7) between the values of 24-hour urine estriol in 138 determinations and in the serum prolactin in 133 pregnant women. The regression lines of serum hPRL values with time of gestation in cases of intrauterine growth retardation (IUGR) and diabetes mellitus were less steep than those seen in normal pregnancy. The serum hPRL value of patients with preeclamptic toxemia, latent diabetes, premature rupture of membranes, or multiple pregnancies were found not to differ significantly from the values observed in normal pregnancy. The results indicate that prolactin determinations in pathologic pregnancies are not useful as an aid in their evaluation.

Ovarian implantation into the uterus (Estes operation): clinical and experimental evaluation.

Ovairan implantation into the uterus was performed in 27 women, none of whom conceived during the 4- to 6-year follow-up period. Bypassing the fallopian tube may, in itself, explain the disappointing results of this procedure in our series as well as in those reported in the literature. Experimental ovarian implantation into the uterus of rats supplied information regarding additional factors underlying the low success rate of this operation. It is concluded that this surgical intervention has been made superfluous in view of the poor results and the modern methods for extracorporal fertilization at present being developed.

PIP: Clinical and experimental data which may help to explain the high rate of failure of ovarian implantation into the uterus is presented. During the 1973-1975 period, 27 patients underwent implantation of the pedicled ovary into the uterine cavity in the Department of Obstetrics and Gynecology of the Hadassah University Hospital in Israel. 19 of the women had primary infertility and 8 had secondary infertility. Among the 8 women with secondary infertility, 2 had living children. 6 of these 8 women had previously undergone bilateral salpingectomy for tubal pregnancy. Implantation of the ovary into the uterus was performed according to a modification of the Estes technique. Experimental ovarian implantation into the uterus of 10 rats provided information concerning additional factors underlying low success rate of this operation. The 27 patients were followed for 4-6 years, and some of the group conceived. There were only 2 cases of postoperative complications -- urinary tract infections. The poor results may be explained by the fact that the fallopian tubes are bypassed in this technique. Both the poor results and the modern methods for extracorporal fertility now being developed suggest that this surgical intervention technique is superfluous.

Leukocyte alkaline phosphatase relative score and basal body temperature as indicators of ovulation during menstrual cycles terminated by normal full-term pregnancies.

PIP: Leukocyte alkaline phosphatase relative score (LAP-RS) and basal body temperature (BBT) as indicators of ovulation during menstrual cycles terminated by normal full-term pregnancies were assessed in 5 cycles terminated by full-term pregnancies. For 3 of the cycles the LAP-RS appeared on the day of luteinizing hormone (LH) surge and 24 hours after the day of maximal total estrogen excretion. For the remaining 2 cycles the LAP-RS peak occurred the day before the LH surge. A wide range of absolute basal and peak LAP values was observed but the ratio between the basal and peak determination was similar (5.8). This suggested that ovulation may be predicted by a sudden increase of LAP-RS to mean values 5 times higher than the basal preovulatory level. BBTs indicated ovulation more than 24 hours after the LH surge in 2 of 5 cycles, indicating that this test is unsatisfactory for the purpose of predicting and pinpointing ovulation. These data were supported by a 2nd group of 6 women who were monitored by LAP-RS throughout their menstrual cycles, and conceived after insemination and administration of human chorionic gonadotropin.^ieng

Uterine skin grafts and fertility control in the rat.

Autologous intrauterine skin grafting was studied as a method of fertility control in the rat. Skin taken from the ear was grafted onto the right horn in 52 rats. All skin grafts "took" and developed into one of three forms: (1) replacement of endometrium over a wide area, (2) polypoid formations, or (3) skin bridges. Curettage before the skin grafting did not affect the "take" or subsequent course of the graft. After mating, no pregnancy occurred in skin-grafted horns, whereas control horns behaved like those in control rats. Results obtained in rat uteri indicate another approach to the treatment of uterine bleeding and possibly to contraception.

Leukocyte alkaline phosphatase monitoring of ovarian function in normal and clomiphene-treated cycles.

PIP: Daily leukocyte alkaline phosphatase activity (LAP), basal body temperature (BBT), fern test (FT) and serum luteinizing hormone (LH) were determined during 15 normal menstrual cycles and 10 cycles treated with clomiphene citrate. A rise in LAP activity, as determined by LAP-relative score (LAP-RS), was observed during the midcycle period. This rise reached peak values on the day of serum LH surge in 60% of cycles. In the remaining cycles, LAP-RS showed peak values 1 day before (8%) or after (32%) LH peak. The mean LAP-RS peak value in clomiphene treated cycles was 13.2, 5-6 times higher than the basic value. The low point of the BBT coincided with the LH SURGE in only 32% of cycles. In 32% the span was more than 1 day before or after LH peak. The day of ovulation as determined by FT corresponded to the LH surge in only 40% of cycles. In 20% of cases, the ovulatory FT reponse occurred more than 1 day before or after LH surge. The results in this study indicated that LAP-RS is a rapid, simple and reliable test for timing of ovulation when carried out daily. It may be valuable in monitoring follicular activity during human chorionic gonadotropin therapy.^ieng

The effect of oral contraceptives on serum lipids.

PIP: In the latter part of pregnancy total lipids, cholesterol, triglycerides, phospholipids, and free fatty acids increase progressively. A study involving 375 women aged 19-30 taking various oral contraceptives, both combined and sequential, showed a mean value of 712 mg/100 ml blood of total lipids as contrasted with 596 mg/100 ml for controls. Serum triglycerides also showed marked elevation -- 122 mg/100 ml as compared with 70 mg/100 ml for controls. However, there was no significant change in the level of cholesterol. There was no significant difference between the combined and sequential users or between users of pills of different steroid composition. Total serum lipids and triglyceride levels were similar to those seen in the last 2 trimesters of pregnancy; however, in pregnancy the cholesterol level also increases. Estrogens are known to elevate serum triglycerides, and in hypercholesteremic subjects, estrogen administration lowers serum cholesterol concentrations.^ieng

Hyperprolactinemic male infertility.

Serum prolactin was studied in 25 fertile and 127 infertile men. The latter included 91 oligospermic, 27 azoospermic, and 9 hypogonadotropic hypogonadal men. The mean prolactin level in all three groups of infertile men was significantly above that of the fertile group. There was no correlation among serum levels of follicle-stimulating hormone, luteinizing hormone, sperm count, and serum prolactin values. Hyperprolactinemia was found in five patients (two oligospermic, one azoospermic, and two hypogonadotropic hypogonadal men). Bromocriptine, 2.5 mg twice daily, suppressed hyperprolactinemia. In one man with hyperprolactinemic oligospermia, treatment with bromocriptine yielded significant improvement in sperm count (to normal values).

Serotonin and 5-hydroxyindoleacetic acid in fertile and subfertile men.

High levels of serotonin and 5-HIAA were found in the urine of a group of 102 oligospermic and azoospermic men. These levels were significantly higher than those of normal fertile men.

Prevention of postpartum venous thrombosis with low doses of heparin.

Postpartum superficial and deep venous thrombosis were found in 22.3% and 5.3% of women with varicose veins who delivered vaginally, or by cesarean section. The preventive use of low doses of heparin (5,000 U every 12 h injected subcutaneously) in 116 parturients with varicose veins reduced significantly the incidence of postpartum venous thrombosis. None of the 26 women with previous thrombosis who received preventive treatment, developed such an event.

Conservative management of suspected prolactin secreting pituitary adenoma during pregnancy.

Seventeen women with prolactin levels of 100 ng/ml and above suspected of harboring prolactin-secreting pituitary adenoma, from the basis of this study. Ten patients had radiological signs of an adenoma while in 7 the radiological criteria for such a diagnosis were not fulfilled. Ovulation and pregnancy were induced with bromocriptine in all 17 patients. They were carefully observed during pregnancy and following delivery. All gave birth to full-term babies after uneventful pregnancies, except for one patient who experienced intrauterine fetal death at 31 wk of gestation. It is our policy that women with suspected intrasellar prolactin-secreting pituitary adenoma be allowed to conceive and give birth without previous surgical intervention. The patient should be closely followed during pregnancy for clinical symptoms of enlargement of the tumor, including periodic visual field examinations. In cases of neurologic or ophthalmologic complications, surgery or bromocriptine administration without interruption of pregnancy is advocated, or if lung maturity is achieved, delivery should be induced.

Fetal heart rate monitoring in cases of decreased fetal movement.

Thirty pregnant women in the third trimester of pregnancy in whom fetal movements were reduced up to cessation, for at least 12 hours, were monitored for FHR. The FHR 12-48 hours after the cessation of fetal movements was pathological in 21 cases and normal in 9 cases. The most frequent pathological FHR changes were loss of beat to beat variation and variable decelerations. In the following 48 hours another four cases showed pathological FHR changes. One to four days before the reduced fetal movements only six out of 15 cases showed pathological FHR changes which were L.B.B.V. Meconium was found in only 50% of the cases. It is suggested that pregnant women, especially high risk cases, should record fetal movements as a screening method. FHR monitoring is also a valuable method for detecting antenatal fetal distress, and should be used as an adjunct to fetal movements recording. When acute fetal distress has been established by MAS alone or with FHR change, the fetus should be promptly delivered.

Fetal heart rate response to maternal hypotension during amniocentesis.

Ten cases of severe fetal heart rate deceleration following maternal vaso-vagal reflex during amniocentesis were presented. The good outcome of these fetuses suggests that this transient phenomenon has no adverse effect on the fetus. This type of FHR response should be recognized so as to avoid unnecessary Caesarian sections done because of severe FHR bradycardia following amniocentesis.

Fetal movements recorder, use and indications.

A new device for recording fetal movements is presented. This device is composed of 2 sensors, incorporating a highly sensitive piezoelectric material. It is sensitive to rapid straining forces such as fetal movements and relatively insensitive to steady, slow movements such as uterine contractions and maternal respiratory movements. In this study of 20 women, the sensors were placed on 2 different zones of the abdomen, usually above the umbilicus. There was a good correlation between fetal movements recorded by the device and those felt by the patients. Seventy percent of all observed fetal movements recorded by the device were registered simultaneously by the women. The device recorded 90.4 percent and the women recorded 79.7 percent of all such movements.

Puerperal endometritis and intrauterine adhesions.

The role of puerperal endometritis in intrauterine adhesion formation was studied by hysterography in 171 women who had cesarean sections. Of 28 patients who developed significant endometritis, only one developed intracervical adhesions. In the control group of 143 cases, there was also only one such case. Endometritis alone apparently does not play a significant role in intrauterine and endocervical adhesion formation. The possible role of placental fibroblasts in preventing endometrial regeneration is discussed.

[Estrogens and endometrial cancer].

PIP: Research dealing with the association between estrogens and endometrial cancer is discussed in this editorial. Three major areas of research are considered: 1) the relationship between endogenous estrogens and endometrial cancer; 2) endometrial cancers produced in experimental animal studies; and 3) the relationship between exogenous estrogens and endometrial cancer in humans. The possibility that endometrial cancer is the final stage of a disruption in endocrine homeostasis is also considered; it is known that continuous, uninterrupted stimulation of estrogen activity causes endometrial hyperplasia, and it is possible that in some cases this may progress to a malignant process. The author concludes that the use of exogenous estrogen preparations presents an increased risk of endometrial cancer only when they have been used for a long duration, such as 5 or 10 years on a continuous basis. He suggests that if a woman accepts the possible risk of developing endometrial hyperplasia, the gynecologist must accept responsibility for prescribing the smallest dose of estrogen which is appropriate, and for stopping estrogen therapy as soon as any hyperplastic changes are observed in the endometrium.^ieng