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Differential effect of hexoses on hamster embryo development in culture.

The effects of glucose, fructose, and galactose on hamster embryo development in the absence of phosphate were studied in culture. One- and two-cell embryos were cultured to the blastocyst stage in HECM-9 medium without hexose or in medium with increasing concentrations of hexoses. Embryo development, cell number, and cell allocation were assessed in blastocysts. Blastocyst viability was determined by transfer to pseudopregnant recipients. Although 0.25 mM fructose increased mean cell number, low glucose concentrations had no stimulatory effect on development to blastocyst. Both galactose and 5.0 mM glucose were detrimental to embryos. Addition of 0.5 mM glucose increased implantation and fetal viability as compared with controls. Compared with 0.5 mM glucose, treatment with 0.25 mM fructose gave similar implantation and fetal viability, whereas 5.0 mM glucose tended to decrease implantation and significantly decreased fetal development. These data demonstrate that morphology is a poor indicator of embryo viability and that exposure of preimplantation embryos to glucose or fructose is important for embryo viability post-transfer. Although no difference in blastocyst viability was detected between embryos cultured with 0.25 mM fructose and those cultured with 0.5 mM glucose, increased cell numbers obtained with fructose suggest that fructose may be more appropriate than glucose for inclusion in culture medium.

Animals↗

Development of the placental villous tree and its consequences for fetal growth.

Co-ordinated development of the fetal villous tree of the placenta is necessary for continued fetal growth and well-being. Before fetal viability, blood vessel development within the developing immature intermediate villi (IIV) is characterized by branching angiogenesis, such that the placenta expands to produce 10-16 generations of stem villi. Once fetal viability is attained, a developmental switch occurs to form large numbers of gas-exchanging terminal villi (TV) by non-branching angiogenesis in mature intermediate villi (MIV). Several growth factors, including vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), angiopoietins, and angiostatins are produced within the villi and act locally, via their receptors, to control angiogenesis. Their relative contributions to placental vascular development are not fully understood at the present time. Severe early-onset intrauterine growth restriction (IUGR) is characterized by absent/reversed end-diastolic flow velocity (ARED) in the umbilical arteries, leading to fetal hypoxia, acidosis and a substantial rise in perinatal mortality and morbidity. The placentas from such cases show a deficit in peripheral villous development, which may be perpetuated by the effects of oxygen (delivered by maternal blood into the intervillous space) upon VEGF-directed angiogenesis, the so-called 'placental hyperoxia' theory of villous maldevelopment. Trophoblast apoptosis is a significant feature of early-onset IUGR and may explain poor flow-independent transfer of nutrients to the fetus. Finally, since transgenic mouse studies highlight the importance of trophoblast-derived transcription factors for placental villous (labyrinth) development, it is possible that the villous trophoblast controls the orderly development of the underlying mesoderm and blood vessels into the fetal villi.

Animals↗

Medroxyprogesterone acetate, but not progesterone, protects against inflammation-induced parturition and intrauterine fetal demise.

OBJECTIVE: This study was undertaken to determine whether progestational agents can prevent inflammation-induced preterm parturition and fetal demise. STUDY DESIGN: The activation of contractile and inflammatory pathways in response to localized intrauterine inflammation was investigated by using quantitative polymerase chain reaction (PCR). Serum progesterone (P4) levels and alterations in progesterone receptor-B (PR-B) were determined with radioimmunoassay and quantitative PCR, respectively. With our in vivo model of intrauterine inflammation, animals were randomly assigned to pretreatment with P4 or medroxyprogesterone acetate (MPA) before intrauterine lipopolysaccharide (LPS). Animals were observed for preterm delivery. The number of live pups 48 hours after intrauterine LPS was recorded for each treatment group. The ability of MPA to alter signal transduction pathways leading to preterm parturition were investigated by quantitative PCR and histochemical studies. RESULTS: Intrauterine inflammation is associated with decreased serum progesterone levels and decreased transcription of PR-B. Preterm delivery rates were 100% for LPS alone, 63% for LPS+P4, and 0% for LPS+MPA. No live pups remained at 48 hours in the LPS or LPS+P4 groups. Pretreatment with MPA significantly preserved fetal viability. MPA suppressed activation of contraction-associated genes and inflammatory mediators and prevented cervical ripening in response to intrauterine inflammation. CONCLUSION: MPA, with its progestational and anti-inflammatory properties, prevented inflammation-induced preterm parturition and significantly preserved fetal viability.

Animals↗

Ameltolide. I: Developmental toxicology studies of a novel anticonvulsant.

Ameltolide, a novel anticonvulsant agent, has been shown in animal models to be effective in controlling seizures. The developmental toxicity of ameltolide was evaluated in two species. Naturally mated rats and rabbits were dosed once daily by gavage on gestation days (GD) 6-17 and 6-18, respectively. Rats were given doses of 0, 10, 25, or 50 mg/kg; rabbits were given 0, 25, 50, or 100 mg/kg. Laparotomy was performed on rats on GD 20 and on rabbits on GD 28. In rats, maternal toxicity was indicated at the 25- and 50-mg/kg dose levels by depressed body weight gain. Fetal body weight was depressed at the 50-mg/kg dose level. Fetal viability and morphology were not affected. The no-observed effect levels (NOEL) for adult and developmental toxicity in the rat were 10 and 25 mg/kg, respectively. In rabbits, maternal toxicity was indicated by a net loss in body weight at the 50- and 100-mg/kg dose levels. Fetal viability and body weight were depressed at the 100 mg/kg dose level. Shortened digits occurred on the right forepaw of one fetus at the 50-mg/kg dose level (in conjunction with severe maternal toxicity) and on the hindpaws of two fetuses from separate litters at the 100-mg/kg dose level. Incomplete ossification of the phalanges occurred on the forepaws of nine fetuses from four litters at the 100-mg/kg dose level. Ameltolide was weakly teratogenic in the rabbit. The NOEL for adult and developmental toxicity in the rabbit was 25 mg/kg.

Abnormalities, Drug-Induced↗

Developmental toxicology studies of fluoxetine hydrochloride administered orally to rats and rabbits.

Pregnant Fischer 344 rats were given fluoxetine orally at dose levels of 0, 2, 5, or 12.5 mg/kg on Gestation Days (GD) 6-15; pregnant Dutch Belted rabbits were given 0, 2.5, 7.5, or 15 mg/kg orally on GD 6-18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated at 12.5 mg/kg by depression of weight gain and food consumption. Fetal viability, weight, and morphology were not affected at any dose level. Maternal and developmental No Observed Adverse Effect Levels (NOAELs) in the rat were 5 and 12.5 mg/kg, respectively. In rabbits, weight loss occurred at 2.5, 7.5, and 15 mg/kg. Food consumption was also depressed at 7.5 and 15 mg/kg; abortions and maternal mortality occurred secondarily to anorexia and cachexia at 15 mg/kg. Fetal viability, weight, and morphology were not affected at any dose level. A NOAEL for maternal effects was not established in the rabbit; the NOAEL for developmental effects in the rabbit was 15 mg/kg. Based on these data, fluoxetine did not exhibit any toxicity toward the developing rat or rabbit conceptus at doses that were maternally toxic.

Administration, Oral↗

Developmental toxicology studies of vancomycin hydrochloride administered intravenously to rats and rabbits.

Pregnant CD rats were given vancomycin intravenously in doses of 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6-15; pregnant New Zealand white rabbits were given 0, 40, 80, or 120 mg/kg intravenously on GD 6-18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated in the 120- and 200-mg/kg treatment groups by cortical tubular nephrosis. Maternal body weight gain and food consumption and fetal viability, weight, and morphology were not adversely affected by vancomycin. Maternal and developmental no observed adverse effect levels (NOAELs) in the rat were 40 and 200 mg/kg, respectively. In rabbits, maternal toxicity was indicated by cortical tubular nephrosis in the 80- and 120-mg/kg treatment groups; a single death and depression of body weight gain and food consumption occurred in the 120-mg/kg treatment group. Developmental toxicity was indicated by depression of fetal weight in the 120-mg/kg treatment group; fetal viability and morphology were not adversely affected by vancomycin. Maternal and developmental NOAELs in the rabbit were 40 and 80 mg/kg, respectively. Based on these data, vancomycin did not exhibit selective toxicity toward the developing rat or rabbit conceptus.

Animals↗

The diagnosis of fetal hydrocephalus before viability.

A diagnosis of fetal hydrocephalus was made before viability. The diagnosis was indicated by a discrepancy between the sonographic fetal head size, the uterine size by both clinical and sonographic examination, and x-ray films. An abortion was performed by hysterotomy.

Adolescent↗

Successful outcome of advanced abdominal pregnancy with exclusive omental insertion.

We report the case of an advanced abdominal pregnancy with exclusive omental insertion whose extrauterine location was not established until delivery by Cesarean section at 35 weeks' gestation. It is hard to believe that omental placentation alone would be sufficient to sustain a pregnancy beyond a gestation where the fetus is viable. However, this report challenges such myths and opens the debate as to what represents the minimal placental maternal viscus contact necessary to achieve fetal viability. The case also demonstrates the continuing difficulty in diagnosing this rare but serious condition despite advances in obstetric imaging, and advocates methods to avoid missing the diagnosis, which could be easily incorporated at booking and mid-trimester scans. Apart from this case, few reports describe normal umbilical artery Doppler velocimetry in advanced abdominal pregnancy. There is a paucity of research on suitable clinical investigations prognostic for abdominal pregnancy, although this case provides further evidence for the use of Doppler as a useful surveillance tool in such cases. Finally, this case propagates the ethical and clinical controversy that exists in managing abdominal pregnancy, particularly when diagnosed late after attaining fetal viability. Expectant management may represent a feasible alternative to surgical termination provided the woman is fully informed of the attendant risks and close surveillance of the pregnancy is undertaken.

Adult↗

Insulin-like growth factors promote DNA synthesis and support cell viability in fetal hemopoietic tissue by paracrine mechanisms.

There is significant evidence that the insulin-like growth factors (IGF) play a role in both murine and human hemopoiesis. In order to better define the nature and mechanisms of these effects, we have used a serum-free system to examine DNA synthesis and cell replication in murine hemopoietic cells. Cell preparations from 13-day fetal mice livers were incubated in serum-free DMEM alone or with erythropoietin (Epo) 0.5 U/ml, recombinant human IGF-I, purified IGF-II, or recombinant human growth hormone (GH) in various doses, and [3H]thymidine added for the last 3 hr of 21-hr incubation. Cell distribution was over 80% erythroid or erythroblasts. IGF-I and IGF-II promoted thymidine incorporation into cells at a half-maximal dose of 3 and 1 nM respectively, IGF-II with a maximum potency 65% of IGF-I; insulin stimulated at a half-maximum dose of 100 nM, with similar maximum effect to IGF-I, and their effects were not additive. GH was stimulatory at 1 microM. Epo was 2-9 times as effective as IGF-I and their effects were not additive. A monoclonal antibody to IGF-I reduced the effect of IGF-I by 50-80%, had no effect on Epo, and abolished the GH effect. Separation of erythroid cells and precursors from accessory and other liver cells did not alter the response to IGF-I. Cell counts increased in response to IGF-I or Epo, and cell viability was maintained by IGF-I compared to control medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prolongation of gestation in the rat and hamster by naproxen.

Administration of naproxen by once or twice daily subcutaneous injection, or orally in the drinking water, was found not to routinely prevent parturition in either the rat or the hamster. However, the duration of labor was prolonged and associated with poor pup viability. The prolonged labor and fetal mortality were thought to be due to suppression of myometrial activity after onset of labor and caused by the episodic administration regimens. Thus fetal deaths could result from asphysia due to suppression of uterine contractions, after partial or total placental separation had occurred. Naproxen was, therefore, administered on a more continuous basis by subcutaneous implantation of pellets in rat and hamster, or orally every four hours in the rat. Either of these regimens was then able to postpone parturition beyond the range of deliveries in control animals. In such naproxen treated rats there was no sign of placetal detachment, even out to day 25 of pregnancy. Fetal viability was preserved and fetuses continued to gain weight. These observations are consistent with a true prolongation of gestation by naproxen rather than merely an interference with the process of labor.

Administration, Oral↗

Maternal - offspring HLA-DRB1 compatibility in multiple sclerosis.

Major histocompatibility complex (MHC) compatibility has been reported to facilitate the long-term tolerance of fetal or maternally derived stem cells exchanged during pregnancy. Furthermore, such compatibility has been suggested to play a role in fetal viability. An increase in maternal - fetal human leukocyte antigen (HLA) compatibility for class II DR alleles has previously been observed in the autoimmune disease scleroderma. Here, we examined the hypothesis that increased maternal - fetal MHC class II DR compatibility was associated with multiple sclerosis (MS) risk. HLA-DRB1 typing was performed in 2170 affected individuals and 2894 unaffected relatives from 1006 families with MS in at least two members. We found no evidence for increased HLA compatibility between affected individuals and their mothers, compared with unaffected individuals and their mothers, nor compared with affected individuals and their fathers. We also observed no excess of homozygosity of mothers compared with fathers of individuals with MS. In families in which the father shared exactly one allele with the mother, we found no excess in transmission of this allele to affected or unaffected offspring. These findings do not support a role for an excess maternal - fetal HLA-DRB1 compatibility in MS susceptibility.

Alleles↗

Forensic implications and medical-legal dilemmas of maternal versus fetal rights.

The purpose of this paper is to review the issue of fetal rights from primarily a legal perspective, with consideration of morals and professional ethics. The practice of medicine is fraught with numerous bioethical dilemmas. These dilemmas often leave the physician wondering if he has made the correct decision. A physician's morals and professional ethics may influence his or her decision in resolving bioethical dilemmas. The case example is a 34-year-old female with a 41-week intra-uterine pregnancy. The mother was refusing induction of labor. Without the labor induction, the fetus may die. Despite this risk, the mother desired to pursue a vaginal delivery. The AMA's ethics state that a competent, pregnant mother's wishes should prevail and the court should not be involved unless there are unusual circumstances. The mother in the case example was competent and informed consent was provided. Case law does not specifically address the dilemma of the case example. However, there is case law regarding court-ordered cesarean sections which reveals different opinions. The difference in court opinion encompasses the relative degree of weight given to the fetus's right to be born healthy and alive versus the mother's privacy rights. Some courts describe this "balancing test," whereas others state that the mother's privacy rights prevail unless there are exceptional circumstances, which will be extremely rare. The fetus has acquired rights in other areas of the law; for example, abolishment of the intra-family immunity doctrine and the definition of murder in most states. In considering the legal arena of fetal versus maternal rights, a decision tree is presented to assist physicians in assessing cases of a pregnant mother refusing medical treatment. There is no precise demarcation in assessing fetal and maternal rights. The greater the degree of fetal viability, the greater degree of fetal rights. Consideration must also be given to the relative degree of invasiveness to the mother for the proposed procedure; the more invasive, the greater degree of maternal rights. Each case must be evaluated on an individual basis and the decision tree can assist a clinician with this process.

Adult↗

Relationship of small-for-dates sac size to crown-rump length and spontaneous abortion in patients with a known date of ovulation.

Spontaneous abortion after established sonographic viability is rare. This study prospectively evaluated 39 late first-trimester abortions after fetal viability was established by ultrasound. The average crown-rump length measurement and mean sac diameter in this group were determined and compared with predicted values based on known conception dates, and the discrepancy between actual and predicted measurements was noted. The same calculations were then made on 39 prospectively matched non-aborting controls. We also determined the difference between sac size and crown-rump length in both groups. Significant differences were found for all three measures. Small-for-dates sac size and small-for-dates crown-rump length were defined as having a discrepancy score greater than 1 standard deviation (SD) above normal. Small-for-dates sac/crown-rump length was defined as having a discrepancy score less than 1 SD below normal. A high percentage of aborters was correctly predicted by a mean sac diameter (82%) or crown-rump length (77%) that was greater than +1 SD, with few false positives (12.8 and 5.1%, respectively). The cutoff for differences of sac minus crown-rump length measurements (10.1 mm) was less sensitive (56%), but just as specific (82%). When both the mean sac diameter and crown-rump length were smaller than expected (according to known date of ovulation), the ability to predict abortion was 71% with few false positives (3.5%).

Abortion, Spontaneous↗

Complete hydatidiform mole coexisting with a live fetus after gamete intrafallopian transfer. A case report.

BACKGROUND: Molar pregnancy with a coexisting live fetus is a rare occurrence. We report the only known case with a surviving coexistent fetus after gamete intrafallopian transfer (GIFT). CASE: After GIFT, a 28-year-old primary infertility patient was diagnosed as having a complete hydatidiform mole coexisting with a live fetus at 13 weeks of gestation. At 36 weeks of gestation, a cesarean section was performed due to elevated serum human chorionic gonadotropin (hCG) levels, and a male infant with a normal appearance and weighing 2,688 g was delivered. CONCLUSION: If the patient desires to try to carry the fetus to viability after counseling on the possible associated risks of malignancy, it is possible to achieve fetal viability if (1) there is decline in the serum hCG level after it peaks before the second trimester, (2) ultrasound reveals degeneration of the molar part, and (3) there are no complications of pregnancy.

Adult↗

Legal abortion: the impending obsolescence of the trimester framework.

Women who wish to terminate a pregnancy, and physicians willing to perform abortions, are subject to increasing harassment from groups which challenge the constitutional abortion right upheld by the Supreme Court in Roe v. Wade. Their vulnerability, in fact, parallels the vulnerability of the abortion right. This Article analyzes the inherent weakness and impending obsolescence of the trimester framework established in Roe. Present medical evidence of maternal health risks and fetal viability demonstrates that the trimester framework is inconsistent with current medical knowledge, and will likely be rendered obsolete by developments in medical technology. The Article suggests that adoption of an alternative constitutional basis for legal abortion is necessary to preserve the abortion right, and explores the utility of two arguments grounded in the equal protection doctrine. Finally, it discusses means of preserving legal abortion within the confines of the trimester framework established in Roe v. Wade.

Abortion, Illegal↗

Congenital abnormalities in legal abortions at 20 weeks' gestation or later.

A study of late abortions by the Royal College of Obstetricians and Gynaecologists made possible estimation of the number of abortions carried out for various types of confirmed congenital defects at or after 20 completed weeks of gestation. A reduction in the legal age of fetal viability to 24 weeks, in the absence of any other change in practice, would have stopped an estimated 26 abortions for confirmed serious fetal defects other than anencephaly in 1982; a reduction to 22 weeks would have stopped 77 such abortions.

Aborted Fetus↗