PubMed Health⌕ Search

Biomedical subjects

L Nebel

Publications and source records attributed to L Nebel.

At least 19 recordsLinked to original sources

Congenital malformations after immunotherapy for habitual abortion: is there an increase?

The risk of congenital malformations as assessed in infants born to women who underwent immunotherapy for habitual abortion. One hundred and eighty women were immunized with paternal mononuclear cells and 85 were not. Of 135 pregnancies in immunized patients, 27 (20%) were miscarriages, and 4 of the remaining 108 had congenital malformations. Two (encephalocele and common AV canal) were diagnosed in the 20th and 21st week of gestation. A case of esophageal atresia and Fallot's tetralogy were diagnosed at birth. Of 65 pregnancies in the non-immunized group 38 (58.5%) were miscarriages, and of the remaining 27, 1 case of Down's syndrome occurred. In a subgroup of 7 habitually aborting couples with parental balanced chromosomal anomalies, the balanced translocation was transferred to the infant in 1 case. No other congenital anomalies were found in either group. Consequently, these anomalies are probably not the result of abnormal pregnancies retained as a result of immunization.

Abortion, Habitual↗

Lupus anticoagulant. Significance in habitual first-trimester abortion.

Therapy with steroids and aspirin has been reported to benefit pregnancies in patients with lupus anticoagulant (LA). In this study, habitual first-trimester aborters with LA using steroids and aspirin were compared to a control group of untreated habitual aborters without LA. In habitual aborters with LA, 12 of 24 (50%) pregnancies reached the second trimester as compared to 8 of 22 pregnancies (36%) in the control group. Since the treated group did no better than the control group, LA probably is not a cause of first-trimester abortion. However, once the second trimester is reached, a 50% incidence of growth retardation was found, and 42% of fetuses died in the second or third trimester in treated LA patients. Treatment with steroids and anti-platelet aggregating agents may be necessary despite the attendant risks to prevent those sequelae in the second and third trimesters. There was a 29% live birth rate in treated LA patients; the rate was 36% in control patients. However, this rate was produced only by early intervention, which was unnecessary in the control patients.

Abortion, Habitual↗

A correlation between the structure of myocardial cells and prolonged Q-T interval in young rats.

In the present study, we examined the electrocardiogram and the structure of myocardial cells in young rats at different postnatal ages. The offspring of rats were sacrificed on different postnatal days following electrocardiographical recordings, and sections of their hearts were examined microscopically. In a number of newborns, we observed definite prolongation of the Q-T interval in the electrocardiogram on the first day of life. Normal shortening of the Q-T interval with age was demonstrated in the majority of the offspring while, in some of them, the Q-T interval remained prolonged. In the "affected" offspring, which exhibit a typical pattern of Q-T prolongation with clear ST segment, definite retardation of histological differentiation of the myocardium was found at various ages. In these cases, there were large numbers of "myoblasts" scattered between normal myocytes in different parts of the ventricular walls and septum. These myoblasts were rarely identified in newborns and offspring with a normal Q-T interval. Our results clearly show a correlation between the ratio of persistence of undifferentiated myoblasts at any age and the typical prolonged Q-T pattern in the electrocardiogram (r = 0.9). Due to the possible clinical significance, the hearts of patients with prolonged Q-T syndrome should be examined so as to reach for abnormal differentiation of the myocytes.

Animals↗

Aging of endometrium and oocytes: observations on conception and abortion rates in an egg donation model.

OBJECTIVE: To assess the comparative contribution of endometrial and oocytic aging to the decline in fertility with age. DESIGN: Retrospective analysis of conception and abortion rates in an egg donation program, with respect to donor and recipient ages. PATIENTS: All oocyte recipients had ovarian failure. Donors were women undergoing in vitro fertilization who contributed up to a third of retrieved oocytes. INTERVENTIONS: None. RESULTS: Thirty pregnancies (28 intrauterine) were recorded in 169 reception cycles originating from 91 donation cycles. Women who conceived were younger than those who did not (median age 31 versus 37; P less than 0.046), with no difference in age of donors. There was a significant difference in spontaneous abortion rate by age of donor rather than by age of recipient. Donors to successful pregnancies were younger than donors to aborted pregnancies (median age 27.5 versus 33; P less than 0.0211), but the 11 women with aborted pregnancies did not differ in age from the 17 women with successful pregnancies. CONCLUSIONS: In women, endometrial function as expressed by conception rate in the recipients declines with age, whereas it is oocyte age that primarily influences risk of abortion.

Abortion, Spontaneous↗

Pregnancy potential of human oocytes--the effect of cryopreservation.

BACKGROUND: In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a routine procedure for the treatment of infertility. Even though there are embryos available for transfer in about 85 percent of the treatment cycles, the rate of pregnancy rarely exceeds 25 percent per cycle. We designed this study to investigate two questions: Does this high rate of failure result from inadequate technique, or does it simply reflect the maximal potential of a cohort of aspirated eggs to produce a pregnancy? And to what extent does cryopreservation affect the capacity for implantation of embryos? METHODS: The study was conducted among patients enrolled in an egg-donation program. Aspirated eggs from a given cohort were distributed to the donor herself and a few recipients. The recipients were prepared by a standard protocol of hormone replacement and were assigned at random to the transfer of either fresh or frozen and thawed embryos. The donors received only fresh embryos. RESULTS: Forty cycles of donation were studied. In 25 cycles (63 percent) pregnancy was established in the donor, in the recipient (or recipients), or in both. Of the fresh embryos that were transferred to the recipients, 24 percent were successfully implanted, as compared with only 7.7 percent of the frozen and thawed embryos (P less than 0.01). A pregnancy success rate of 37 percent per recipient cycle was observed in the recipients of fresh embryos, as compared with a rate of only 16 percent in those receiving frozen and thawed embryos (P less than 0.05). CONCLUSIONS: The majority of egg cohorts evidently possess the potential to produce a pregnancy, but cryopreservation of human embryos significantly reduces their capacity for implantation.

Adult↗

Transvaginal sonographic measurement of fetal kidneys in the first trimester of pregnancy.

Fetal renal size late in the first trimester of pregnancy was evaluated by transvaginal ultrasonography in 50 patients not at risk for congenital kidney disease and whose pregnancies resulted in a normal outcome. Both kidneys were reliably identified in all patients scanned at 12 weeks, 13 weeks, and 14 weeks, menstrual age. Kidney diameter measurements obtained in this study are presented for reference in evaluating patients in late first trimester whose fetuses are at risk for kidney abnormalities.

Adolescent↗

Selection of patients with habitual abortion for paternal leucocyte immunization.

After potentiation of the immune response in habitual aborters 75-85% of subsequent pregnancies are claimed to result in healthy term infants. However, all publications to date have either been based on the authors concept of the immune processes involved or an attempt to demonstrate the efficacy of treatment either empirically or by matched trials. As immunization is coming into wider clinical use, it is necessary to determine which patients will benefit from this form of treatment. This paper presents our experience with paternal leucocyte immunization over the period 1985-1988. 207 patients were classified on a clinical basis and by immunological testing. 143 patients have been immunised, 129 pregnancies have occurred in 108 patients. The vast majority of our patients have recurrent missed abortions. Only six women habitually aborted live fetuses. Two had subsequent live births. Secondary aborters seem to do well in subsequent pregnancies, whether immunized or not. The patient most likely to benefit from immunization is the Primary missed aborter who does not possess antipaternal antibody (APCA), but is induced to produce APCA by immunization. Using these criteria, 75% success rates are observed in the subsequent pregnancy. This success rate is irrespective of HLA antigen sharing or in-vitro mixed lymphocyte reactivity.

Abortion, Habitual↗

Immunization by paternal leukocytes for prevention of primary habitual abortion: results of a matched controlled trial.

Habitual abortion is a difficult clinical problem, as no cause can be found for abortion in over 50% of patients. At the habitual abortion clinic of the Sheba Medical Center, immunological activity is tested and patients who are considered suitable are offered immunopotentiation with paternal leukocytes. Patients are only treated if they have no other cause for habitual abortion, no lupus anticoagulant and no antipaternal complement-dependent antibodies (APCA). Immunization is thought to potentiate the maternal immune response to paternal antigens encountered on the trophoblast. The production of APCA antibody indicates that an immune response has occurred. Of the 156 patients so far immunized, 109 have developed these antibodies. To date, 79 of these 156 patients have become pregnant. Sixty-seven patients (with 3-12 miscarriages each) belong to the antibody-positive group. Sixty-four of the 89 subsequent pregnancies have been carried past their previous dates of abortion. Forty-seven live births have occurred. By contrast, 12 patients have been pregnant in the antibody-negative group, of the 16 subsequent pregnancies only 6 were successful. A control group is available for comparison. This consists of patients suitable for immunization, but not immunized. Of these patients, only 11 of 30 pregnancies have been carried to term.

Abortion, Habitual↗

Development of human embryos in the presence of a copper intrauterine device.

This study was designed to examine the teratogenic potential of copper releasing intrauterine contraceptive devices on the developing embryo. The tissues and organs of 11 whole embryos between 7 and 12 weeks of gestation were histologically examined for copper absorption after exposure to a copper intrauterine device in utero. The findings were not significantly different when compared with a control group of 7 embryos. No malformation or copper aggregates were observed in the various organs and placentas. The observations in this small sample would suggest that the copper-releasing intrauterine device has no deleterious effects on fetal development. The question remains whether malformations reported in some cases are associated with copper deposits in the tissues or with free copper ions in the fetal circulation. The implications are discussed.

Adult↗

Fetal intracranial anatomy in the first trimester of pregnancy: transvaginal ultrasonographic evaluation.

The normal values and ranges of fetal intracranial structures were studied by high resolution transvaginal ultrasonic scan at 12, 13 and at 14 weeks' gestation. The data including measurements of crown rump length (CRL), bi-parietal diameter (BPD), head circumference (HC), hemispheric width (HW), lateral ventricle width (LVW), LVW/HW ratio, thalamus and cerebellum may be useful in determining deviations from the normal and also in expanding the range of prenatal diagnoses of fetal structural abnormalities in early pregnancy.

Brain↗

Selective reduction in multiple gestations: pregnancy outcome after transvaginal and transabdominal needle-guided procedures.

Selective fetal reduction was performed in the first trimester of pregnancy in 20 women with multifetal gestations after ovulation induction with human menopausal gonadotropin (hMG). In 10 women (group A) reduction was performed transabdominally, and in 10 women (group B) the transvaginal approach was used. The transvaginal technique achieved penetration of several gestational sacs without withdrawing the needle from the uterus. Fetal termination using either procedure occurred with intrafetal injection of potassium chloride. Six (60%, group A) and eight (80%, group B) patients delivered healthy newborns. One patient (group B) is at 30 weeks' gestation. Four (40%, group A) and one (10%, group B) aborted 1 day to 8 weeks after the procedure (1 septic abortion, each group). Our results suggest that transvaginal fetal reduction offers a better outcome, with minimal complications, to patients referred for selective continuation of pregnancy.

Abdomen↗

Cyclosporin-induced embryotoxicity in mice.

Pregnant ICR mice were injected daily with 30 mg cyclosporin (CS)/kg body weight on days 6-8 or 10-12 of gestation. In parallel, control mice were administered saline injections on the same gestational days. The mice were sacrificed on days 12, 15, 17 or 19 of gestation. The number of resorption sites counted, the embryos and placentae were carefully separated, weighed and examined macro- and microscopically, along with various other maternal organs. It was found that 30 mg CS/kg body weight, when administered to pregnant ICR mice in 3 successive injections, did not raise the maternal mortality rate. Histological examination of maternal organs revealed pathological alterations in the thymus, liver, kidney and spleen; most changes had disappeared by 1 week following the last injection. CS reduced the number of viable embryos and increased the number of embryos resorbed. Microscopic examination of the embryos showed that organogenesis was not affected by the drug. However, CS, in the administered dose, had a clear embryotoxic effect.

Animals↗

Fetal demise associated with lupus anticoagulant: clinical features and results of treatment.

There are many reports in the literature associating lupus anticoagulant with fetal death. Successful pregnancies have been reported following suppression of the antibody by prednisone and the addition of antiaggregants and possibly anticoagulants. This report describes our experience treating such patients and the outcome of subsequent pregnancies. The results are less successful than the figures in the literature, 13 live births out of 27 pregnancies in 19 patients. This may be due to lupus anticoagulant being diagnosed as the cause for a wide variety of clinical presentations including habitual first trimester abortion, mid trimester fetal death, intrauterine growth retardation and placental dysfunction in the third trimester. Our experience shows that steroids and antiaggregants have a definite place in cases of second and third trimester fetal death and in cases of clinical systemic lupus erythematosus. However, lupus anticoagulant is one of a spectrum of autoantibodies whose pathophysiology has not been fully elucidated. It is questionable whether this regimen of treatment has a place in patients with no previous fetal loss or in cases of primary habitual abortion.

Adult↗

Programmed oocyte retrieval: clinical and biological effects of oral contraceptives administered before in vitro fertilization.

We have prospectively compared two regimens of suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives (OCs) for 15 or 30 days and two ovarian stimulation protocols. The latent phase, which represents a period of ovarian insensitivity, was prolonged and directly correlated to the duration of suppression. Thirty days' suppression, compared with 15 days', resulted in the cancellation of more cycles and a lower fertilization and pregnancy percentage. No significant increase in either serum progesterone or luteinizing hormone was noted in suppressed cycles. It is concluded that if programming is desired, OCs should be used for the shortest period possible. The variation in the length of the follicular phase indicates that there is a different 'fixed' day for retrieval for each suppression-stimulation protocol and this day should be established prospectively.

Adult↗

Effect of diclofenac on implantation and embryonic development in the rat.

Recent evidence suggests that decidualization can be considered a modified inflammatory reaction. In this work we intended to determine whether the prostaglandin inhibitor diclofenac could affect implantation. Rat blastocysts were cultured in diclofenac in vitro, then implanted to host mothers on day 5 of pseudopregnancy. Large doses of diclofenac in culture were toxic. Smaller doses had a profound effect on implantation. Another group of host mothers received diclofenac i.p., one hour prior to transfer of untreated blastocysts. The results were compared to parallel controls without diclofenac treatment. Control animals had a 72% implantation rate, whereas there was only a 35-41% implantation rate after in vitro diclofenac treatment. In the treated host mothers only 7% of embryos were normal, while 34% were growth-retarded. More normal embryos were found when the blastocysts were cultured with diclofenac. The observations indicate that diclofenac administered to the mother inhibits the ongoing process of implantation and placentation, whereas following in vitro exposure the embryo can recover from the insult. The implications for a better understanding of the process of implantation are discussed.

Animals↗

The role of early post-implantation beta-HCG levels in the outcome of pregnancies following in-vitro fertilization.

Daily plasma beta-HCG levels from days 11 to 18 after ovum retrieval (OR) were evaluated in a group of 73 women who became pregnant following in-vitro fertilization and embryo replacement (IVF-ER). The 47 patients who had a normal ongoing pregnancy could be distinguished from the 26 patients with a pathological pregnancy (pre-clinical abortion, clinical abortion and tubal pregnancy) by the mean daily beta-HCG levels, their mean daily increase and the intercept and slope of the beta-HCG regression analysis. The mean daily beta-HCG levels of the normal pregnancies were significantly higher than: (i) pre-clinical abortions on days 12-18 after OR; (ii) clinical abortions on days 12-16; and (iii) tubal pregnancies on days 12-17. Using quadratic discriminant analysis, normal and pathological pregnancies could also be distinguished by their absolute beta-HCG levels on day 13 after OR with 27.6 mIU/ml being the cut-off point. Our results indicate that the outcome of pregnancy following IVF-ER could be predicted with a high degree of probability by monitoring daily beta-HCG levels within the first 2 weeks following OR.

Adult↗

Protocols for induction of ovulation. The concept of programmed cycles.

Programmed oocyte retrieval which includes suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives or GnRH analogue and predetermined ("fixed") day for ovum pick-up has been demonstrated to yield a pregnancy rate that is comparable to that achieved by the conventional individualized approach to follicular maturation. We have prospectively compared two regimens of suppression (the pill and GnRH analogue) followed by two ovarian stimulation protocols (clomiphene citrate + human menopausal gonadotropin [CC + hMG] and pure follicle-stimulating hormone + human menopausal gonadotropin [pure FSH + hMG]). Sixteen patients were studied in each group. It was found that the latent phase, which represents a period of ovarian insensitivity, was prolonged and directly correlated to the duration of suppression, and that suppression with the GnRH analogue was associated with a shorter latent phase than that with the pill. Suppression with the pill for 30 days compared with 15 days resulted in a greater cancellation of laparoscopic oocyte retrieval, a lower fertilization rate, and a lower pregnancy rate. The numbers of oocytes recovered, fertilized, and cleaved were similar in both stimulation protocols. The use of the GnRH analogue for 30 days compared with 15 days was associated with a lower pregnancy rate, even though the number of oocytes that were recovered and fertilized were similar. Ovarian stimulation with pure FSH + hMG resulted in a shorter latent phase than did stimulation with CC + hMG, but the results of treatment with both protocols were similar. It is concluded that both the pill and GnRH analogue are acceptable means of manipulating the cycle and the day of oocyte retrieval. However, they should be used for the shortest periods possible because prolonged use is associated with some unwarranted effects. For each suppression-stimulation protocol there seems to be a different fixed day for retrieval that should be established prospectively.

Chorionic Gonadotropin↗