Assisted Reproductive Technologies Reported in Israel National Registry, 1995 and 1996

V. Insler, O. Gonnen, D. Levran, Y. Lotan, B. Fish, G. Potashnik, A. Kogosovsky, R. Ron-El

Committee of the Israel National Registry Assisted Reproductive Technologies*

National registration of the results of assisted reproductive technology (ART) is maintained by many countries. The Israel Committee for Registry of ART asked 19 in-vitro fertilization (IVF) units in 1995 and 20 in 1996 to report on their activities and results.

Data were collected by questionnaires and analyzed by computer. The most common ovarian stimulation was the combination of GnRH agonist and gonadotropins. There were 10,89 treatment cycles in 1995, of which 45% were with intracytoplasmic sperm injection (ICSI). In 1996, of 12,72 cycles, 54% were with the ICSI procedure. Embryos were transferred into the uterine cavity in 90% of the conventional IVF cycles and in 95% of the ICSI cycles. The overall pregnancy rate was 22% per embryo transfer in the conventional IVF and ICSI cycles. The delivery rate was 13.7% and 15.4% per embryo transfer in the conventional IVF and ICSI cycles, respectively. The rates for abortion and tubal pregnancy were 24% and 1.3%, respectively.

These results are better than in previous years and are comparable with results in some western European countries. Efforts are being made to convert the registry into a real-time computerized system.

Committee of the Israel National Registry of ART.

Folic Acid for Preventing Neural Tube Defects

Ziv Gil, Adi Aran, Orna Friedman, Liana Beni-Adani, Shlomo Constantini

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba; Division of Pediatric Neurosurgery, Dana Children's Hospital, Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv

Spina bifida and anencephaly are the most common, serious malformations in neural tube defects (NTD). Randomized trials in the last 2 decades have demonstrated that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We investigated the use of folic acid and multivitamins containing folic acid in childbearing women.

Of 221 women interviewed, 67 (30%) regularly took pills containing 0.4 mg folic acid. Women with higher educational levels were more likely to take multivitamins with folic acid than were the less educated (p=0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid tablets, before and during their pregnancy. The rest used multivitamins containing folic acid. The 5 women who took folic acid separately were college-educated and nonreligious, and they took multivitamins in addition (p>0.05).

Of the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them took pills containing folic acid on a regular basis. This percentage is higher than that in the Jewish women in the study who took folic acid for prevention of NTD (17%; p=0.038).

Most of the women took folic acid after the first trimester. Only a minority took daily periconceptional folic acid. Multivitamins containing 0.4 mg of folic acid were more popular than folic acid tablets alone. This study emphasizes the need for continuing efforts to increase consumption of folic acid and awareness of its benefits among women of childbearing age.

Atrophic Gastritis Presenting with Pulmonary Embolism

Muhammad A. Abdul-Ghani, Rima Feldman, Moshe Shai, Jacob Varkel

Dept. of Medicine C, Western Galilee Hospital, Naharia

Atrophic gastritis is an autoimmune gastropathy in which there is destruction of gastric parietal cells. This results in intrinsic factor deficiency and disturbance in vitamin B12 absorption. Its clinical manifestationa are therefore the consequences of B12 deficiency and include anemia and neurological defect. In addition, lack of B12 results in metabolic changes, including disturbances of methionine metabolism and accumulation of homocysteine.

In recent years, there has been increasing evidence suggesting that hyperhomocysteinemia is a risk factor for thrombo-embolic disease. We describe a 51-year-old man with atrophic gastritis, severe B12 deficiency and hyperhomocystein-emia. The initial clinical manifestation was pulmonary embolism, without either anemia or neurological signs. B12 deficiency should therefore be considered in patients being investigated for hypercoagulability.

Preservation of the Larynx in Advanced Cancer

Edward Rosenblatt, Nava Siegelmann-Danieli, Jemal Zidan, Nisim Haim, Abraham Kuten

Oncology Dept., Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

The effectiveness of sequential chemo-radiotherapy in preserving the larynx in advanced laryngeal carcinoma was assessed. 4 Unselected patients (19 men and 2 women, mean age 60 years) with advanced squamous cell carcinoma of the larynx (T3-4/N0-3) received induction chemotherapy consisting of 2-3 cycles of cisplatin (100 mg/m²) and 5-flourouracil (1000 mg/m²/day) as a continuous infusion on days 1-5 followed by definitive radiotherapy: 50 Gy to the whole neck, 70 Gy to the larynx and clinically involved nodes, using a combination of 6 MV photons and 9-12 MeV electrons.

19 of The 21 patients responded to combined therapy but there was no response to induction therapy in 2 (10%) and 2 did not complete therapy due to severe toxicity. At a mean follow-up of 40 months, 7 had undergone total laryngectomy (33%), for an overall 5-year laryngeal preservation rate of 66%. Reasons for total laryngectomy in 2 patients were no response and in 5 tumor recurrence.

Mean survival was 39 months (range 11-46 months); at last follow-up 17 of 21 were alive and disease-free, 11 of whom had a functional larynx (65% of survivors). 2 died due to disease progression and 1 due to a cardiovascular event. Sequential chemo-radiation allows laryngeal preservation in about 2/3 of surviving patients without compromising survival.

Testicular Cancer: Self-Awareness and Testicular Self-Examination in Soldiers and Military Physicians

Thomas Tichler, Rony Weitzen, Aharon Feinstone, Raoul Orvieto, Marian Moskovitz, Adam Singer

Depts. of Oncology and Medicine B, Sheba Medical Center, Tel Hashomer; Medical Corps, Israel Defence Forces; Gynecology Dept., Hasharon Medical Center, Petah Tikvah; and Medical Dept. B, Fleaman Hospital, Haifa

Testicular cancer is the most common malignancy in young men. To evaluate knowledge and awareness of that cancer, and of the practice of testicular self-examination (TSE), we developed a questionnaire which was distributed to 717 male soldiers and 200 of their military physicians.

21% of the soldiers had received some explanation of the importance of TSE, but only 16% were actually instructed how to perform TSE, and only 2% practiced it regularly. 24% had never examined their testicles before, 185 only rarely, and 6% often. With increased age, TSE frequency increased, but previous education, type of military unit, and ethnic origin had no affect. 99% of military physicians had been taught how to examine breasts, but only 70% had been taught routine testicular examination. 22% performed it, but 27% never did. 84% had never taught their soldiers the importance of TSE, although 51% taught female soldiers breast self-examination.

There was a significant lack of awareness of the importance of regular practice of TSE among both soldiers and their army physicians.

Gastrointestinal Hemorrhage of Obscure Origin

Yoel Siegel, David Ergaz, Oscar Liphshitz, Felix Gottesfeld, Zev Sthoeger

Depts. of Medicine B and Surgery, and Gastroenterology Unit, Kaplan Medical Center, Rehovot (Associated with Hebrew University-Hadassah Medical School, Jerusalem)

Gastrointestinal bleeding of obscure origin consists of recurrent bouts of acute or chronic bleeding for which no definite source is discovered in routine endoscopic and barium contrast studies of the upper and lower gastrointestinal tracts. Usually its cause is angiodysplasia of the intestine, but many cases are due to tumors, mostly of the small bowel, which may be malignant.

In patients under the age of 50, the proportion with malignancy is relatively high (up to 14%) as compared to older patients. We describe a 45-year-old woman who suffered from gastrointestinal bleeding for 3 years. The cause of bleeding was not found despite extensive work-up.

In her last admission for acute gastrointestinal hemorrhage she was given a total of 30 units of blood. A tumor of the small intestine found by angiography was excised and found to be a stromal tumor of uncertain malignant potential. 1 year after operation she is asymptomatic without bleeding and her hemoglobin is stable without treatment.

Hospitalization for Renal Colic: Epidemiological Features and Clinical Manifestations

Yahav Oron, Amir Shahar, Eran Dolev

Sheba Medical Center, Tel Hashomer; Israel Defense Forces Medical Center; Meir General Hospital, Sapir Medical Center, Kfar Saba; and Dept. of Medicine H, Sourasky-Tel Aviv Medical Center

The medical records of all patients referred to the emergency department (ED) of Sheba Medical Center for renal colic during 1996 were analyzed. Patients discharged from the ED and those hospitalized were compared.

There was no significant difference between the 2 groups with regard to average age or sex distribution. Statistically significant differences were found with regard to frequency of chills and fever, history of renal colic, referral for renal colic during that year or hospitalization for renal colic or nephrolithiasis, previous positive imaging, stone removal by surgery or extracorporeal shock wave lithotripsy, fever exceeding 37.5^o and administration of fluids, pethidine or pramin in the ED, prolonged stay in the ED and previous appendectomy.

A conditional regression model tested the predictive value of each of those factors. Inclusion of independent variables into the model led to an overall correct classification rate of 84.43%, with 44.83% sensitivity and 93.16% specificity. There were correlations between referrals for renal colic, overall renal colic rate and average monthly temperature, so there was no pure correlation between average monthly temperature and referrals to the ED for renal colic.

The major indications for hospitalization were actually the clinical ones, indicating either an active metabolic disease or suspected obstruction of the urinary tract. Treatment in the ED and duration of the visit indicated disease severity.

Relationship between Occupation and Clinical Characteristics during Pregnancy and Recommendation to Stop Working

S. Gazit-Nissim, E. Sheiner, M. Mazor, I. Shoham-Vardi

Depts. of Epidemiology and Health Services Evaluation, and of Obstetrics and Gynecology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer Sheba

We examined the relationship between occupation and clinical characteristics during pregnancy and medical recommendations to stop working. Using a case-control design, we compared 58 working women who had preterm births, with 126 who had delivered at term. All women were interviewed postpartum while still in hospital.

There were no differences between the groups with regard to physical activity outside the home, weekly work hours, nor duration of work. Only a small proportion had been exposed to unusually difficult working conditions, to hazardous agents or to a very uncomfortable working environment. Women who had had preterm births were advised more often to leave their jobs or modify their working patterns. Multivariate analysis revealed that the physician's decision to recommend cessation of work was influenced primarily by complications during the current pregnancy.

It appears that our patients at risk for preterm birth are probably correctly identified, and receive appropriate guidelines as to working patterns. It is possible that a poor obstetric history or previous abortions may paradoxically have a protective effect, as they influence the physician to recommend cessation of work.

Physicians' Reminders Promote Annual Fecal Occult Bloodtesting Compliance

Shlomo Vinker, Vardina Shumla, Eliezer Kitai

Family Medicine Dept., Sackler Faculty of Medicine, Tel Aviv University

Screening for the early detection of colorectal cancer using the fecal occult blood test has been shown to be effective in reducing mortality. In Israel family physicians recommend that their patients, aged 50-75, have the test performed annually. But compliance with testing in the general population has been poor.

We therefore studied this issue in 3 primary care facilities, in 384 patients, average age 62.7‏6.9 years; 81 (21.1%) performed the fecal occult blood test. Performance rates were significantly lower (13.9%) in those aged 50-59 (p = 0.0003), as compared wh those aged 60-69 and 70-75 (24.3% and 24.7%, respectively). Compliance rates of the patients of different physicians varied as well.

Recommendation of family physicians led to overall compliance of 21.1%. Additional efforts are needed to increase compliance in order to decrease colorectal cancer morbidity and mortality in Israel.

Diabetes and Premature Delivery: Etiology and Risk Factors 

Avi Beigelman, Arnon Wiznitzer, Ilana Shoham-Vardi, Hilel Vardi, Gershon Holtcberg, Moshe Mazor

Depts. of Obstetrics and Gynecology and of Epidemiology and Health Services Evaluation, Soroka Medical Center and Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheba

Preterm birth is the leading cause of perinatal morbidity and mortality, while preterm labor and delivery in diabetes mellitus (DM) carries an increased risk of perinatal complications. We investigated the hypothesis that DM (gestational and pregestational) is an independent risk factor for preterm birth and evaluated the hypothesis that the risk factors for preterm birth in diabetics are different from those in non-diabetics.

The study population consisted of all singleton deliveries at this hospital between 1990-1997. Excluded were those of mothers who had not had prenatal care, or who had only partial care or multiple gestations. There were 3 subgroups: 834 women with pregestational DM, 3,841 with gestational DM, and 66,253 non-diabetics.

The combined spontaneous and induced preterm delivery rate was determined in each subgroup. Potential risk factors for spontaneous preterm deliveries were assessed by a univariate model. A logistic regression model was used to assess the unique contribution of DM (gestational and pregestational) to preterm delivery in the presence of the other risk factors, and to compare risk factors for preterm delivery between subgroups.

The prevalence of spontaneous preterm delivery was: 7.1% in non-diabetics, 10.0% in those with gestational DM and 25.5% in those with pregestational DM. When adjusted by a multivariate model for other risk factors for preterm delivery, DM still remained an independent risk factor for spontaneous preterm delivery (gestational DM: odds ratio 1.28, 95% CI: 1.1-1.48; pregestational diabetes: odds ratio 3.4, 95% CI: 2.65-4.36).

The main difference in risk factors for preterm birth between the 3 subgroups was the amount of amniotic fluid. Polyhydramnios was an independent risk factor for preterm delivery in non-diabetics and in pregestational DM, but not in gestational DM. On the other hand, oligohydramnios was associated with a higher risk for preterm delivery only in gestational DM compared to non-diabetics.

DM (gestational and pregestational) is an independent risk factor for spontaneous preterm delivery. Polyhydramnios is an independent risk factor for preterm delivery in pregestational but not in gestational DM. Oligohydramnios is a greater risk factor for preterm delivery in gestational DM compared to non-diabetics.

Thallium Scan and Pulmonary Carcinoma 

Adam Mor, Amit Segev, Rami Herskoviz, Yoseph A. Mekori

Dept. of Medicine B, Meir General Hospital, Kfar Saba Affiliated with Sackler Faculty of Medicine, Tel Aviv

A 70-year-old man was admitted for exacerbation of congestive heart failure. In his assessment thallium scan of the heart was performed. An incidental finding was a focus of absorption in the right lung. The lesion was later diagnosed as adenocarcinoma based on the cytological findings.

Tacrolimus does not Accentuate Hepatic Damage due to Hypoperfusion 

Ron Ben Abraham, Ivgeni Isartal, Richard Nakache, Vallery Rudick, Daniel Ogorek, Gideon Paret, Avi Weinbroum

Dept. of Anesthesiology and Critical Care Medicine, Organ Transplantation and Postoperative Care Units, Tel Aviv-Sourasky Medical Center; and Pediatric Intensive Care Units, Sheba Medical Center, Tel Hashomer; and Sackler Faculty of Medicine, Tel Aviv University

Deterioration of hepatic function following liver transplantation is a known complication, sometimes attributed to the use of cyclosporin A. Reaction to tacrolimus (Prograf), a relatively new and effective immunosuppressant drug, is thought to result in a much lower grade of organ dysfunction, especially in the transplanted liver.

Using the ex-vivo rat model of isolated perfused liver, we evaluated hepatocellular damage and oxygen extraction when tacrolimus was administered following liver hypoperfusion. Tacrolimus did not worsen hepatic dysfunction caused by the hypoperfusion. Therefore using tacrolimus in the perioperative period might be safer than cyclosporin A, which tends to worsen hepatic damage in the presence of hypoperfusion.

Color Doppler Imaging of Central Retinal Artery in Retinopathy of Prematurity

Alon Harris, Hanna J. Garzozi, Mira Harris-Izhak, Nir Shoham, Daniel R. Holland

Depts. of Ophthalmology, Indiana University School of Medicine, Indianapolis and of HaEmek Medical Center, Afula; and Eye Health Northwest, Portland, Oregon

Color Doppler imaging (CDI) is a noninvasive technique, combining 2-dimensional brightness-modulated (B-mode) ultrasound evaluation of eye and orbital structures, with simultaneous color-coded Doppler imaging of orbital blood flow. It has been used to characterize various ophthalmic disorders in adults. Currently there is no data describing orbital blood flow parameters in either normal children or in those with ophthalmic disease, such as the retinopathy of prematurity (ROP).

We evaluated blood flow in the central retinal artery of preterm infants undergoing examination for ROP. We also investigated whether useful readings could be obtained on a consistent basis, and the reproducibility of differences in central retinal artery blood flow between subjects with and without ROP (including the influence of "plus" disease).

We obtained hemodynamic readings in 43 of 46 eyes of preterm infants. 13 eyes had no signs of ROP; 18 had ROP (at least stage 1) without "plus" disease, and 12 had ROP with "plus" disease. There were no statistically significant differences in systolic blood flow velocity within the 3 groups. However the average velocity was slower in the "plus" disease group, correlating with the clinical finding of dilated and tortuous blood vessels which characterize the posterior retina of ROP eyes with "plus" disease.

Man in a Hot Climate - Early Studies of the Institute of Military Physiology 

Ezra Sohar, Yair Shapiro, Yoram Epstein

Institute of Military Medicine, Medical Corps, Israel Defense Forces and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer

In the 1950's many IDF soldiers were hospitalized for heat stroke - about 25% of whom died. Analyzing these cases revealed that commanders misinterpreted human ability to perform in the heat and ignored basic concepts of fluid and electrolyte balance and heat load.

In the early 1960's a series of studies was conducted with regard to soldiers' performance in the heat. The first study (1959), which later became a classic, was conducted during a 21-day march from Eilat to Metula, crossing all climatic zones of Israel. The study was followed by other investigations which approached the issues of voluntary dehydration, fluid consumption vs sweat loss, salt additives, and the effect of heat load on performance.

Based on these early studies, proper regulations were issued to field officers. Over the years, the lessons learned from these studies saved many lives. The number of cases of heat stroke and of other climate-related injuries was dramatically reduced, and performance was enhanced.

Acipimox as a Secondary Hypolipidemia in Combined Hypertriglyceridemia and Hyperlipidemia

D. Yeshurun, H. Hamood, N. Morad, J. Naschitz

Hyperlipidemia Clinic, Dept. of Medicine A, Bnai-Zion Medical Center, and Rappaport Faculty of Medicine, Technion, Haifa

32 patients with hypertriglyceridemia, excessive hypertri- glyceridemia, and combined hyperlipidemia, were treated with the nicotinic acid derivative acipimox (Olbetam). First line treatment with bezafibrate, or statins in some with combined hyperlipidemia, had failed. In 10 acipimox was discontinued due to side effects or absence of clinical response. The other 22 completed 6 months of treatment with no side effects.

Acipimox caused a significant 54% decrease in triglyceride levels, a 23% decrease in total cholesterol, and a 12% increase in HDL-cholesterol. LDL-cholesterol was difficult to calculate because of the high triglyceride levels, so no results are presented.

Although acipimox was much better tolerated than nicotinic acid, it also had side effects, but fewer. Acipimox can therefor be used as a second-line drug, mainly in those with combined hyperlipidemia and hypertriglyceridemia.