J. Blankstein

The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies

We carried out a prospective, randomized, double-blind, placebo-controlled study to investigate the capacity of aspirin to prevent pregnancy-induced hypertension and to alter prostaglandin metabolism. A total of 791 pregnant women with various risk factors for pre-eclamptic toxemia were screened with use of the rollover test (a comparison of blood pressure before and after the woman rolls from her left side to her back) during week 28 or 29 of gestation. Of 69 women with abnormal results (an increase in blood pressure during the rollover test), 65 entered the study and were treated with a daily dose of either aspirin (100 mg; 34 women) or placebo (31 women) during the third trimester of pregnancy. The number of women in whom pregnancy-induced hypertension developed was significantly lower among the aspirin-treated than among the placebo-treated women (4 [11.8 percent] vs. 11 [35.5 percent]; P = 0.024); the same was true for the incidence of preeclamptic toxemia (1 [2.9 percent] vs 7 [22.6 percent]; P = 0.019). The mean ratio of serum levels of thromboxane A2 to serum levels of prostacyclin metabolites after three weeks of treatment decreased by 34.7 percent in the aspirin-treated group but increased by 51.2 percent in the placebo-treated group. No serious maternal or neonatal side effects of treatment occurred in either group. We conclude that low daily doses of aspirin taken during the third trimester of pregnancy significantly reduce the incidence of pregnancy-induced hypertension and pre-eclamptic toxemia in women at high risk for these disorders, possibly through the correction of an imbalance between levels of thromboxane and prostacyclin.

Elective Cervical Suture of Twin Pregnancies Diagnosed Ultrasonically in the First Trimester following Induced Ovulation

The efficiency of elective cervical suture in preventing premature delivery thus reducing neonatal mortality was studied in a group of 50 twin pregnancies. All pregnancies occurred after induction of ovulation and twins were diagnosed early by ultrasound. 25 randomly selected patients underwent elective cervical suture. 22 sutured and 23 non-sutured patients were followed until delivery, while 5 patients aborted in the second trimester. The benefit of suturing on the duration of pregnancy and its outcome were assessed. Of the sutured patients, 10 (45.4%) delivered prematurely and the neonatal death rate was 18.2%. In the non-sutured patients, 11 (47.8%) delivered prematurely and the neonatal death rate was 15.2%. This study demonstrates that elective cervical suture was not effective in prolonging gestation or improving fetal outcome in twin pregnancies following induced ovulation.

The Study of Induction of Ovulation with Menotropins: Analysis of Results of 1897 Treatment Cycles *

Ovulation and the development of a corpus luteum with intact endocrine function is the result of a perfectly balanced interaction among hypothalamic gonadotropin-releasing hormone, pituitary gonadotropins, and ovarian response. Any disturbance in one of these endocrine glands or in the complex feedback mechanism of the closed circuit would result in anovulation. The use of menotropins is appropriate for patients lacking endogenous gonadotropins or for patients having ovaries capable of a normal response but in whom drugs capable of inducing gonadotropin secretion have failed to induce ovulation. This report is based upon computer tabulations of pooled data abstracted from 510 patients to whom 1897 treatment cycles with menotropins were administered during the last 15years. The results of treatment are based upon detailed analyses in different groups of patients to whom the same gonadotropin preparation was administered according to a similar treatment schedule. The percentage of patients who conceived following therapy (the pregnancy rate) in group I (women with negligible endogenous estrogen activity and low gonadotropin levels) was 60.4%; in group II (women with normal gonadotropin levels and distinct endogenous estrogen activity in whom all other treatments had failed) the pregnancy rate was 21.4%. The success rates (the percentages of women who took home at least one living child) were 52.1% in group I and 14.5% in group II. Altogether, 250 children were born to 184 women who conceived following treatment. The mean numbers of treatment cycles per patient were 3.69 in group I and 3.24 in group II. Among women of group I who conceived, 94.1% did so within four treatment cycles and of group II patients 95.2% did so within six treatment cycles. The over-all mild hyperstimulation rate was 4.26% and the severe hyperstimulation rate was 0.36%. The over-all multiple pregnancy rate was 32.5%.

An Unexpectedly High Rate of Ectopic Pregnancy Following the Induction of Orulation with Human Pituitary and Chorionic Gonadotrophin

Sir, McBain et a1 reported an incidence of ectopic pregnancies of 3 1 % after hPG-hCG induced ovulation. This rate is higher than in the general population, and occurred in the absence of predisposing factors. Two of their six cases were combined with intrauterine pregnancy. They found an association between ectopic pregnancy and elevated urinary total oestrogens (>200 pg/24 hours) around the time of the ovulation. On reviewing our data we could not confirm such a high incidence. In the infertility clinic of the Sheba Medical Center, Tel-Hashomer we have treated over 800 women with hMG-hCG (Pergonal) in over 3000 cycles. Three women had 4 ectopic pregnancies, a rate of I .14% (4:350 pregnancies), This rate is slightly higher than in our general population, but the incidence of ectopic pregnancy in our hospital has increased over the last 4 years from an overall rate of 0.82% (1:121 pregnancies) to 1.17% (1:85 pregnancies). This increased rate might be due to an increased rate of pelvic inflammatory disease and also to improved methods of diagnosis of the early or clinically uncertain ectopic pregnancy such as ultrasound, laparoscopy and particularly serum hCCi beta subunits. On reviewing the laparoscopies of those three women, we found that two of the three had a mechanical factor. Only in one case did the tubal pregnancy occur without any known tubal pathology. Urinary total oestrogens on the day of hCG administration in all four cases of ectopic pregnancy was between 80-160 ygj24 hours, which is the optimal range (100-200 pg/24 hours). If high oestrogen levels are associated with ectopic pregnancy, the incidence should be higher in cycles with hyperstimulation. We have a 19.8 % hyperstimulation rate in those cycles resulting in pregnancy. This syndrome is mainly associated with high oestrogen levels. In view of the 10% ectopic pregnancy rate reported by McBain in cycles with urinary oestrogens above 200 pg/24 hours it is expected that there would be at least 8 ectopic pregnancies in our hyperstimulated patients, but there were none. Although it has been postulated that high oestrogen levels during ovulation might accelerate tubal transport, and. low levels cause delay of tubal transport or locking, these are more likely to result in degeneration of the ovum (Burdick and Pincus, 1935) rather than ectopic pregnancy. We feel therefore that McBain’s results, although interesting, are not supported by our data.

Lack of association between ovarian follicular size and number and the occurrence of multiple pregnancies in menotropin cycles

A high rate of ovarian multifollicular development and resulting multiple pregnancy remains the main problem of ovulation induction with human menopausal gonadotropins. The aim of this study was to examine a possible correlation between the number and size of ovarian follicles at the time of human chorionic gonadotropin (hCG) administration and to find parameters that can predict the occurrence of multiple pregnancies. Sixty-eight intrauterine pregnancies, 53 singletons and 15 multiple pregnancies in 51 patients, were included in this study. We found no significant difference in the mean estradiol levels, the total number of pre-ovulatory follicles, or the mean number of large, intermediate or small follicles at the time of hCG administration between women who had singleton pregnancies and those with multiple pregnancies. Our study demonstrates that estradiol levels and ovarian ultrasonography do not provide criteria for the prediction of the occurrence of multiple pregnancies in menotropin cycles.

Failure to Improve Ovarian Response by Combined Gonadotropin-Releasing Hormone Agonist and Gonadotropin Therapy

Nineteen women were treated with the gonadotropin-releasing hormone (GnRH) agonist buserelin in order to suppress the pituitary prior to gonadotropin treatment. Eight women were oligomenorrheic, 6 had polycystic ovarian disease (PCOD) and 5 women had normal cycles. Buserelin was administered for 3 weeks before ovarian stimulation, and the pituitary down-regulation was proven by provocative tests. Ovarian stimulation was then achieved by human menopausal gonadotropin (hMG) 2 ampules a day. Several abnormal responses to the combined buserelin/hMG treatment were noted in some patients. This included a sudden decrease in E2 level without LH surge (2 patients), induced follicular growth with buserelin instead of ovarian suppression (2 patients) and ovarian hyperstimulation syndrome in 3 patients with PCOD. From this we conclude that although pituitary suppression can easily be achieved by GnRH analog administration, this does not ensure the prevention of unwanted responses. It is possible that the common denominator for these abnormal responses is that they are ovarian in origin, hence they occur in spite of pituitary down-regulation. Close monitoring of the suppression and stimulation stages will detect most cases of such failures. Furthermore it is possible that not all patients are suitable for the combined treatment of gonadotropin and GnRH agonist.

Observations on effects of analgetic drugs on mother and fetus: comparison between systemic and local drug application during labor.

When determining the efficiency of a drug, one must consider its ability to give the desired effect, the side effects and the dangers inherent in its administration. These criteria must be evaluated when examining the various analgetics used during labor. In this case, however, we must not forget that we are dealing with two patients — the mother and the fetus. Thus, evaluation of all drugs given during labor must include the following considerations: 1. the influence of the drug on the mother; 2. the influence on the course of labor; 3. the influence on the fetus and/or the neonate.

Programmed Oocyte Retrieval for IVF: Clinical and Biological Effects of Different Protocols of Pituitary Suppression and Follicular Stimulation

The day of oocyte retrieval is the most important day in vitro fertilization (IVF) programs. It involves the coordination of the clinical, surgical and laboratory staff, thereby allowing only a limited number of cases to be performed daily. The day of retrieval depends on the day of menstruation and the individual ovarian response to medication, hence it is variable and can usually be anticipated only in the last few days of treatment. Some of these disadvantages can be overcome by fixing the day of retrieval in advance as in a “programmed cycle”. Programmed IVF cycles include; suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives or gonadotropin releasing hormone (GnRH) analogues and a predetermined day for ovum pick-up. The method has been shown to be technically feasible and logistically desirable and can result in a clinical pregnancy rate equivalent to the more conventional individualized approaches to ovulation induction [1–6].