Increased Abortion Rate Research Articles

Effects of pregnancy-associated Listeria monocytogenes infection: necrotizing hepatitis due to impaired maternal immune response and significantly increased abortion rate.

The impact of L. monocytogenes infection on maternal immune responses as well as on the outcome of pregnancy was studied in a murine model of pregnancy-associated listeriosis. Mice infected i.v. with L. monocytogenes at day 15 of pregnancy showed a significantly impaired bacterial elimination, which resulted in a severe necrotizing hemorrhagic hepatitis. The aggravated course of the infection could be attributed to a suppressed transcription and production of anti-listerial, pro-inflammatory cytokines and chemokines, namely interferon-gamma, tumor necrosis factor, interleukin-12p40, inducible nitric oxide synthase, murine monokine induced by interferon-gamma, and interferon-gamma-inducible protein-10. In addition, listeriosis significantly increased the abortion rate. Infection of the placenta and fetuses was characterized by placental and fetal necrosis with unrestricted bacterial multiplication. A weak transcription of anti-listerial cytokines in the placenta in the absence of a cellular immune response could not prevent the fatal outcome of pregnancy-associated listeriosis.

RU 486 and Abortion Practices in Europe

Abstract RU 486 has been heralded as “the gentle abortion” by its supporters and vilified by opponents as “the pill of death.” It has been available for a decade to women in France, Britain, and Sweden, and to women in nine other European Union countries since 1999. We explore the impact of this controversial technology on abortion rates and practices in Europe, looking first at the EU region as a whole, then examining more closely the politics of RU 486 in France and Germany. We find no evidence that access to medical abortion with RU 486 has increased abortion rates in Europe. We do find large national differences in the use of medical versus surgical abortions. These abortion practices are shaped by economic incentives, the organization of medical services, bureaucratic accounting rules, and physicians' choices. We conclude that effective implementation, with governmental support, has a critical impact on access to medical abortion services.

Heme oxygenase is downregulated in stress-triggered and interleukin-12-mediated murine abortion.

Heme oxygenases (HOs) are responsible for heme degradation. Besides their enzymatic activities, HOs are involved in tissue protection. Failing upregulation of HOs has been linked to increased necrosis in inflammatory tissues. Interestingly, previously published data indicated that mice exposed to sonic stress during early gestation show an augmented production of decidual inflammatory T-helper 1 (Th1) cytokines, thus resulting in increased abortion rate. No data linked the Th1-inducer interleukin (IL)-12 with the event of abortion. As little is known about the role of HO in pregnancy maintenance, we evaluated the expression of decidual and placental HO-1 and HO-2 in the abortion-prone murine mating combination CBA/J x DBA/2 J with (1) CBA/J female control mice, (2) CBA/J mice exposed to stress during early gestation and (3) CBA/J females injected with recombinant IL-12. Decidual and placental HOs protein expression was analysed by immunohistochemistry and mRNA levels by real time polymerase chain reaction (PCR). As expected, an increased abortion rate was present in mice exposed to stress compared with the control. IL-12 injections also boosted the abortion rate compared with control mice, mimicking the effect of stress. HOs' proteins could be detected in placenta and decidua. Real time PCR revealed lower levels of HO-1 and HO-2 mRNA in stress-triggered and IL-12-injected mice. We conclude that increased Th1-cytokine levels during murine pregnancy may result in low expression of HO-1 and HO-2, thus leading to placental necrosis and foetal rejection.

Reduced Reproduction with Increased Abortion Rate in Transgenic Mice That Overexpress 15-Lipoxygenase

15-Lipoxygenase (15-LOX) is a lipid-oxidizing enzyme that is involved in cell cycle regulation. To evaluate the effect of 15-LOX on reproduction, we studied transgenic mice that overexpress 15-LOX. The transgene was introduced over the genetic background of the low density lipoprotein receptor deficient mice (LDL-R^–/–) and reproduction was compared to LDL-R^–/– mice. We found a lower pregnancy rate in the 15-LOX/LDL-R^–/– mice as compared to the LDL-R^–/– mice (62.74 vs. 79.1%, p < 0.01). Additionally, a remarkably higher number of resorptions per pregnancy was found in the 15-LOX/LDL-R^–/– mice (16.7 vs. 3.27%, p < 0.001) and it was accompanied by a significantly higher activity of the 15-LOX enzyme in these resorptions as compared to other tissues. These findings may implicate a role for 15-LOX in the development of spontaneous abortions.

Aberrant methylation of donor genome in cloned bovine embryos.

Despite recent successes in cloning various animal species, the use of somatic cells as the source of donor nuclei has raised many practically relevant questions such as increased abortion rates, high birth weight and perinatal death. These anomalies may be caused by incomplete epigenetic reprogramming of donor DNA. Genome-wide demethylation occurs during early development, 'erasing' gamete-specific methylation patterns inherited from the parents. This process may be a prerequisite for the formation of pluripotent stem cells that are important for the later development. Here, we provide evidence that cloned bovine embryos may have impaired epigenetic reprogramming capabilities. We found highly aberrant methylation patterns in various genomic regions of cloned embryos. Cloned blastocysts closely resembled donor cells in their overall genomic methylation status, which was very different from that of normal blastocysts produced in vitro or in vivo. We found demethylation of the Bov-B long interspersed nuclear element sequence in normal embryos, but not in cloned embryos, in which the donor-type methylation was simply maintained during preimplantation development. There were also significant variations in the degree of methylation among individual cloned blastocysts. Our findings indicate that the developmental anomalies of cloned embryos could be due to incomplete epigenetic reprogramming of donor genomic DNA.

Effect of chemically altered and modified-live infectious bovine rhinotracheitis vaccines on fetal retention in beef replacement heifers during the first four months of gestation

The objective of this study was to determine whether vaccination of pregnant heifers with either chemically altered or modified live infectious bovine rhinotracheitis (IBR) vaccine would cause abortion when previously vaccinated with a chemically altered IBR vaccine. During pre-weaning processing and at weaning, 202 crossbred Brangus heifers were administered chemically altered infectious bovine rhinotracheitis virus (IBR) vaccines. At 60 to 120 days of gestation after first fall breeding, heifers were administered either a modified live virus (MLV) or a chemically altered IBR vaccine. Heifers at 60 to 90 days gestation, and those greater than 90 and up to 120 days gestation, were assigned by gestation category to one of three treatments: (1) a single IM injection of chemically altered IBR vaccine; (2) a single IM injection of modified live IBR vaccine; or (3) controls - no injections. Heifers were palpated 56 days after treatment to determine potential fetal loss. Subsequent calving information was used to confirm post-treatment palpation data. One heifer in each group aborted after treatment; these numbers did not differ among treatments (p=1.0) nor between gestation categories (p=1.0). Calving numbers verified that no fetuses were lost after post-treatment palpation. We concluded that a single dose of these vaccines in pregnant replacement heifers did not cause increased abortion rates compared to unvaccinated control heifers.

Histologic Architecture and Vascularization of Hysteroscopically Excised Intrauterine Septa

Study Objective To investigate histologic structures of intrauterine septa resected hysteroscopically. Design Prospective, consecutive study (Canadian Task Force classification II-2). Setting University-affiliated hospital. Patients Seventy-six women evaluated for uterine septa and infertility. Interventions All patients with diagnosis of uterine septum detected by transvaginal color Doppler (TVCD) underwent operative hysteroscopy in which the most prominent part of the septum was encircled with a hysteroscopic loop electrode and removed. Specimens were sent for histopathologic evaluation. The rest of the septum was divided by monopolar needle electrode until the uterine cavity assumed a globular shape. Measurements and Main Results In 63 women (82.8%) preoperative TVCD revealed septal vascularity typical for radial arteries with mean resistance flow of 0.64 ± 0.06, and enlarged sunusoidal and capillary spaces. Histopathologic results revealed fibromuscular tissue with moderately more connective tissue in 55 cases (72.3%) and myometrial tissue in 21 (27.6%). There was no statistically significant difference (p >0.05) in frequency of septa between patients with primary and secondary infertility. Conclusion Intrauterine septa consisted of the same type of tissue as normal myometrium, with many muscular fibers. We suspect that muscular tissue within the uterine septum is a potential cause of irregular contractility and consequently increased abortion rate in these patients.

Embryo quality and developmental potential is compromised by age.

The aim of this retrospective study was to assess whether and how the age of the woman affects the quality and developmental potential of the oocytes and embryos in an ART program. A total of 878 IVF cycles was included as a consecutive series of single transfers (n=292), dual transfers (n=366) and triple transfers (n=220), where all the transferred embryos in each cycle were of identical quality score and identical cleavage stage. We found a highly significant decrease in oocyte recovery with increasing age with about one oocyte per 2.3 years (95% CI 1.8 years to 3.1 years, p<0.0001). Further, we found that the number of oocytes that cleaved declined significantly with increasing age with one per 3.7 years (95% CI 2.7 years to 5.5 years, p<0.0001). This decline was mainly due to the decline in number of oocytes retrieved as the ratio of aspirated oocytes that cleaved with increasing age (approx. -0.04/10 year 95% CI: -0.10; +0.009) was not significantly different (p=0.10). The percentage of transfers using fragmented embryos did not increase significantly with increasing age (p=0.08). The odds of fragmentation increased by 3% per year. The average number of embryos transferred decreased significantly (p=0.03) with age from approximately 2.1 at the age of 25 to approximately 1.8 at the age of 40. In a selected subgroup of embryos all consisting of good quality embryos, a significant decrease was found in implantation rate with increasing age (approx. -0.08/10 years, 95% CI: -1.6; +0.00, p=0.05). Of the 357 pregnancies achieved in this study we found a significantly decreased ongoing pregnancy rate and a significantly increased abortion rate with increasing age (p=0.03). The decrease in the rate of ongoing pregnancies was almost linear, decreasing by approximately 1.5% per year. We conclude that age has an impact throughout a woman's reproductive life and that it is important to realize that the age-related decline in fertility may start already in the late twenties and not in the mid-thirties as is generally assumed.

Embryo quality and developmental potential is compromised by age

Aims. The aim of this retrospective study was to assess whether and how the age of the woman affects the quality and developmental potential of the oocytes and embryos in an ART program. Method and material. A total of 878 IVF cycles was included as a consecutive series of single transfers (n=292), dual transfers (n=366) and triple transfers (n=220), where all the transferred embryos in each cycle were of identical quality score and identical cleavage stage. Results. We found a highly significant decrease in oocyte recovery with increasing age with about one oocyte per 2.3 years (95% CI 1.8 years to 3.1 years, p<0.0001). Further, we found that the number of oocytes that cleaved declined significantly with increasing age with one per 3.7 years (95% CI 2.7 years to 5.5 years, p<0.0001). This decline was mainly due to the decline in number of oocytes retrieved as the ratio of aspirated oocytes that cleaved with increasing age (approx. −0.04/10 year 95% CI: −0.10; +0.009) was not significantly different (p=0.10). The percentage of transfers using fragmented embryos did not increase significantly with increasing age (p=0.08). The odds of fragmentation increased by 3% per year. The average number of embryos transferred decreased significantly (p=0.03) with age from approximately 2.1 at the age of 25 to approximately 1.8 at the age of 40. In a selected subgroup of embryos all consisting of good quality embryos, a significant decrease was found in implantation rate with increasing age (approx. −0.08/10 years, 95% CI: −1.6; +0.00, p=0.05). Of the 357 pregnancies achieved in this study we found a significantly decreased ongoing pregnancy rate and a significantly increased abortion rate with increasing age (p=0.03). The decrease in the rate of ongoing pregnancies was almost linear, decreasing by approximately 1.5% per year. Conclusions. We conclude that age has an impact throughout a woman’s reproductive life and that it is important to realize that the age-related decline in fertility may start already in the late twenties and not in the mid-thirties as is generally assumed.

Developmental and endocrine aspects of normal ovarian aging

Supplies of follicles are established during early fetal life and decrease exponentially thereafter by a process called atresia. Subfertility only starts at a mean age of about 30–31 years, when the remaining follicle reserve has become a fraction of its original number. Thereafter, a further decrease in both oocyte quantity and quality dictates the subsequent reproductive events including decrease of fertility, increased abortion rate, the end of fertility, the beginning of cycle irregularity and, when almost no follicles are left, the occurrance of menopause. The same remarkable variation of age at menopause almost certainly is also present for the preceding reproductive events. When quantity and quality of antral follicles drop below a critical threshold, there is a subsequent drop in inhibine B resulting in the selective FSH rise at a mean age of 37–38 years. This FSH rise explains the accelerated follicle depletion, the increased proportion of growing follicles reaching the selectable stage, the shortening of the follicular phase and the increased incidence of dizygotic twinning. The concurring decrease of oocyte quality is in line with the increased incidence of abortions and chromosomal aberrations after age 35.

Endometriosis and spontaneous abortion rate: a cohort study in infertile women

Objective: To ascertain if there is an association between endometriosis and spontaneous abortion. Design: Prospective cohort study. Setting: Medical School Hospital. Population: 174 infertile women laparoscopically diagnosed with endometriosis and 174 infertile women in which endometriosis was ruled out by laparoscopy, in the same period of time. Main outcome measure: Spontaneous abortion. Non-progressive gestational sac and/or histological study. Results: Per woman abortion rate was 7.47% (13/174) in the endometriosis group, similar to 5.74% (10/174) in the infertile women without endometriosis (RR=1.32; CI=0.53–3.36). Nor were there any differences in the per pregnancy abortion rate: 20.96% (13/62) in endometriosis vs. 16.94% (10/59) in non-endometriosis (RR=1.3; CI=0.47–3.57). The abortion rate was similar in the different AFS stages: 22.86% (8/35) in stage I, 16.67% (3/18) in II, 25% (1/4) in III and 20% (1/5) in IV. In stage I no differences were observed in patients who were managed expectantly or with medical treatment. Conclusion: Endometriosis is not associated with an increased abortion rate. The severity of disease expressed by AFS staging is not associated with an increase in the abortion rate. In stage I the treatment of endometriosis did not decrease abortion rates.

The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.

The morphological normality of a spermatozoon is considered to be an important factor in relation to its ability to fertilize an oocyte. We examined the influence of morphology (strict criteria) on the rates of fertilization, pregnancy and spontaneous abortion obtained following conventional in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in our clinical programme. We found our fertilization cut-off values for conventional IVF to be slightly different from those of the Kruger group (10 and 5%, compared to 14 and 5%). We also found the pregnancy rate per transfer to be as good or better in the groups with < 5% normal forms: 36% of these men had a fertilization rate > 50% using conventional IVF, showing that fertilization capacity is not necessarily impaired even in this 'poor prognosis' group. With the exception of the ICSI group with 5-9% normal forms, the rate of spontaneous abortion in this study was similar to or lower than in our IVF/ICSI programme overall. When the 5-9% normal spermatozoa group was divided into those with teratozoospermia as the only factor and those with additional sperm factors, the increased abortion rate was found in the group with multiple sperm factors (67% spontaneous abortions).

"Increased Number of Induced Abortions in Norway after Media Coverage of Adverse Vascular Events from the Use of Third-generation Oral Contraceptives."

Abstract After the press release in Lancet (October 18, 1995) of increased risks for adverse vascular events in users of pills containing desogestrel and gestodene, the total sales of oral contraceptives dropped over a two-month period by 17%, while sales of the only desogestrel brand available (Marvelon) dropped by over 70% in Norway. From sales, we can estimate that more than 45,000 women either changed from Marvelon to a second- or first-generation brand or stopped using OCs. In total, more than 25,000 women discontinued OC use in Norway during November and December of 1995. Abortion data from one Norwegian county, representing 6–7% of the Norwegian population, show no statistically significant changes in the total number of induced abortions from the first quarter of 1996 as compared with that of the first quarter in preceding years. However, abortion rates that had been steadily decreasing from 1992 through 1995 in women 24 years old or younger, were promptly interrupted by a significant 36% increase during the first quarter of 1996. Most of the additional cases were found among single, childless studients. The observed increased abortion rate among younger women is most probably linked to changes in contraceptive use during the pill scare of late October through December of 1995, during which time these women conceived.

Increased number of induced abortions in Norway after media coverage of adverse vascular events from the use of third-generation oral contraceptives

After the press release in Lancet (October 18, 1995) of increased risks for adverse vascular events in users of pills containing desogestrel and gestodene, the total sales of oral contraceptives dropped over a two-month period by 17%, while sales of the only desogestrel brand available (Marvelon) dropped by over 70% in Norway. From sales, we can estimate that more than 45,000 women either changed from Marvelon to a second- or first-generation brand or stopped using OCs. In total, more than 25,000 women discontinued OC use in Norway during November and December of 1995. Abortion data from one Norwegian county, representing 6–7% of the Norwegian population, show no statistically significant changes in the total number of induced abortions from the first quarter of 1996 as compared with that of the first quarter in preceding years. However, abortion rates that had been steadily decreasing from 1992 through 1995 in women 24 years old or younger, were promptly interrupted by a significant 36% increase during the first quarter of 1996. Most of the additional cases were found among single, childless studients. The observed increased abortion rate among younger women is most probably linked to changes in contraceptive use during the pill scare of late October through December of 1995, during which time these women conceived.

Linking Herbivory and Pollination: Defoliation and Selective Fruit Abortion in Lindera Benzoin

It has been predicted that plants will selectively mature fruit from flowers in which there has been the most intense pollen tube competition. The degree of this selectivity should increase as resources become more constrained and fruit abortion rates increase. One way in which resources could become more constrained is through defoliation by herbivores. The effect of defoliation on selective fruit abortion was tested by examining fruit set and pollen tube numbers in naturally pollinated flowers on defoliated and control branches of Lindera benzoin. Defoliating branches after fruit initiation significantly increased subsequent fruit abortion. Flowers that matured fruit had significantly more pollen tubes per style than those that initiated but then aborted fruit, but greater levels of pollen competition did not result in the production of larger seeds. On undefoliated control branches, selective abortion occurred only among flowers opening during the second half of the flowering season. On defoliated branches selective abortion occurred throughout the entire flowering season. Although defoliation increased abortion rate, it did not increase selectivity based on pollen tube number. When resources were depleted at the branch level, the position of the flower along the branch influenced whether a flower matured a fruit. Floral phenology was unrelated to position. The influence of position on fruit abortion was likely due to the patterns of resource acquisition and use.

Effects of aging on the female reproductive system.

There is an evident decline in human fertility with age. The fundamental physiological question is whether the ovary, the uterus, or both are affected by the changes induced within the body by senescence. Based on clinical studies performed in in-vitro fertilization (IVF) laboratories, there is no doubt that age affects the oocyte. However, the effect of age on the remaining cellular components of the preovulatory follicle have yet not been fully elucidated. In addition, whether the ability of the uterus to have normal implantation of human embryos is age-related is also a matter of controversy. In this review, we analyse the results of our studies that were conducted in order to answer these relevant questions. In the first series of experiments we tested the hypothesis that the function of granulosa cells is affected in older patients (> or = 40 years). In these experiments, we cultured in vitro granulosa-luteal cells from 15 women aged < 40 years and 18 patients aged > or = 40 years undergoing IVF. Immunoreactive alpha-inhibin and progesterone were measured after 48 and 96 h in culture. The measurements showed a significantly higher secretion of inhibin (P < 0.01) after 48 h, and progesterone (P < 0.05) after 48 and 96 h, in the younger as compared to the older group. In addition, we tested the ability of the uterus to sustain normal implantation by an analysis of our oocyte donation programme. In the first approach, we divided all the transfer cycles according to the age of the recipient. We found no differences among groups with regard to pregnancy, implantation or abortion rates. We explored this fundamental question further by performing oocyte donation cycles in which oocytes from the same donor were distributed into a recipient aged < 40 years and another recipient of > or = 40 years. An analysis of 45 cycles in each group of recipients showed a significant (P < 0.05) increase in abortion rates in older as compared to younger patients. When the serum oestradiol concentrations were followed in those women who carried normal single ongoing pregnancies, we found that a significant increase in blood oestradiol concentrations (which probably represents the luteo-placental shift) was detected 2 weeks earlier in younger than in older patients, suggesting a defective vasculature of the uterus that could ultimately be the cause of an increased abortion rate in patients aged > or = 40 years. In conclusion, we firmly believe that senescence affects both the ovary (oocyte and granulosa cells) and the uterus, and these observations should be taken into account in order to advise our patients.

Early sonographically guided amniocenteses with filtration technique: follow-up on 249 procedures.

Fetal and neonatal outcome is reported for 249 consecutive low-risk pregnancies in which early amniocentesis was carried out with filter technique, at a mean gestational age of 12.5 weeks, to improve the yield in cell cultures. Three pregnancies (1.2%) were terminated because of abnormal test results, four stillbirths (1.6%) occurred between weeks 33 and 38, and five pregnancies were lost spontaneously after sampling, corresponding to 2% of unintended fetal losses before 28 weeks of gestation. Of the live-born infants, 2.9% were delivered prematurely, all between weeks 32 and 37. Malformations and orthopedic postural deformities were not associated with leakage after amniocentesis and were found at expected rates. None of the cases was lost to follow-up. The increase in abortion rate caused by early amniocentesis with filter technique is likely to be within the same range as that seen after routine amniocentesis and transabdominal chorionic villus sampling, although the sample is too small for a proper risk evaluation.

Effects of Defoliation on Sex Differentiation in Oil Palm Clones

SUMMARYDefoliation affected inflorescence production by oil palms, causing a decrease in sex ratio (ratio of female inflorescences to total) and an increase in abortion rate. Clones differed in response to defoliation. One of seven clones showed no increase in abortion rate; in one clone there was a tendency for female inflorescences to abort in greater numbers than males. The change in sex ratio occurred much sooner after defoliation in some clones than in others, and comparison of flowering records with dissections done at the time of defoliation indicated that inflorescence sex was affected at more than one stage in development. This has important consequences for attempts to predict yields.

Hepatitis B Vaccine in Pregnancy: Maternal and Fetal Safety

Perinatal transmission of hepatitis B (HB) virus occurs if the mother has had acute HB infection during late pregnancy or in the first months postpartum, or if the mother is a chronic HB antigen carrier. Vertical transmission from chronic carriers exceeds 90% and accounts for up to 40% of the world chronic carriers in endemic areas. Hepatitis in pregnancy is not associated with increased abortion rate, stillbirth, or congenital malformation. However, prematurity seems to be increased if hepatitis is acquired in the last trimester. Sixty percent of pregnant women who acquire acute HB infections at or near delivery will transmit the HB virus to their offspring. Although infection is rarely symptomatic, 70 to 90% of the babies will remain chronically infected into adult life and be prone to cirrhosis and hepatocellular carcinoma. Because of such high risks and the safety and efficacy (seroconversion 90 to 100%) of HB vaccine in preventing HB infection, it is recommended that HB vaccine be given to pregnant women at high risk. However, its safety to the fetus is not well documented. Only one human study reports the safety and efficacy of Heptavax, but only when administered (to 72 pregnant women) in the last trimester of pregnancy when embryopathy cannot occur. We report pregnancy outcome in ten women, mostly health care personnel or patients traveling to endemic areas exposed to the vaccine during the first trimester of pregnancy. No congenital abnormalities were observed and all the infants are physically and developmentally normal for their ages at 2 to 12 months. Although small, this cohort suggests safe use of the vaccine in early pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal diagnosis in multiple gestation: 20 Years' experience with amniocentesis

Three hundred and thirty-nine cases of multiple gestation underwent prenatal diagnosis by amniocentesis. The spontaneous abortion rate (to 28 weeks) in this group was 3.57 per cent compared with our singleton abortion rate of 0.60 per cent. The perinatal mortality rate (PMR) and prematurity rate were not different from the singletons, and compared favourably with the PMR reported in the literature for multiple gestations which did not undergo any intervention during pregnancy. This increased abortion rate following amniocentesis may only represent the increased natural loss rate in multiple gestations, and not indicate any increased risk added by the procedure.