Is premature ovarian ageing a cause of unexplained recurrent miscarriage?

Recurrent miscarriage is often unexplained. In our study, we test the hypothesis that unexplained recurrent miscarriage is associated with premature ovarian ageing by comparing the basal follicle-stimulating hormone (FSH) level between women with recurrent miscarriage and a control group of subjects in two different ethnic centres: one in Guangzhou, China and the other in Sheffield, UK. The subjects were stratified into three different age groups, and all of them were under the age of 40 years. We found no significant difference in basal FSH level between the subjects and the control groups, and the proportion of women with high FSH (>10 IU/l) was higher in the Guangzhou cohort but not in the Sheffield cohort. Our observation suggests that premature ovarian ageing is not a significant contributory factor of recurrent miscarriage, but a study on the ethnic variation in the aetiology of recurrent miscarriage is needed.     

Is there a role for assisted reproductive technology in recurrent miscarriage?

Unexplained recurrent miscarriage (RM) is a significant health problem for which no effective treatment is available yet. In only 50% of couples with RM a cause can be found. In clinical practice, a frequently asked question is whether assisted reproductive technology (ART) is a treatment option. The scientific rationale and the chances of success for ART in couples with unexplained RM are still controversial. Presently, there is not enough evidence to justify IVF or intrauterine insemination (IUI) as a treatment option. Research on oocyte donation has been reported in one article. It is questionable whether couples with unexplained RM would undergo the potential risks and emotional aspects of ART. There is insufficient data on whether preimplantation genetic diagnosis improves the live birthrate in carriers of a structural chromosome rearrangement with a history of RM. No randomized controlled trials are available for preimplantation genetic screening (PGS) for unexplained RM. A recently published review concluded that the live birthrate for IVF/PGS and natural conception groups appears to be quite similar. Because evidence is lacking, we recommend refraining from ART in couples with recurrent miscarriage.     

Do women with recurrent miscarriage constitute a high-risk obstetric population?

The aim of this study was to examine if women with history of recurrent miscarriage have a higher risk of maternal and foetal complications in future pregnancies. This was a retrospective case control study that analysed data collected prospectively between 2001 and 2007 from 400 women with history of recurrent miscarriage who achieved pregnancies progressing beyond 24 weeks gestation compared to 39,860 deliveries from the general obstetric database within the same time period. Results showed that women with recurrent miscarriage had significantly increased odds of low Apgar scores at one (odds ratios (OR) 1.57, 95% CI 1.20–2.05) and five?minutes (OR 2.0, 95% CI 1.23–3.27), small for gestational age (OR 1.96, 95% CI 1.12–3.43), preterm delivery (OR 1.64, 95% CI 1.22–2.19) and antepartum haemorrhage (OR 7.67, 95% CI 4.23–13.91). The risks were increased in the presence of a male foetus but no difference was observed between primary and secondary miscarriage patients. In conclusion, women with recurrent miscarriage have an increased risk of several maternal and foetal complications and therefore may require closer monitoring during the antenatal period particularly when pregnant with a male foetus.     

Internet forums following a miscarriage: a place for women in particular pain?

Objective: Miscarriage is a frequent event, but one which might be particularly difficult to cope with. The main aim of this study was to explore the features of the women using Internet forums following a miscarriage. Methods: A sample of 211 women who experienced miscarriage and who use the Internet completed an online questionnaire. Sociodemographic data were gathered and three scales were completed: the Hospital Anxiety and Depression Scale, the Texas Grief Inventory adjusted to miscarriage and the Dyadic Adjustment Scale. Results: Our results show that these women reported a great amount of pain compared to a more standard sample. Interestingly, our findings show that while women reported wishing to be supported, only a few of them sought such support. Conclusion: Further study focusing on support for women who experience miscarriage must be developed and Internet-based programmes are warranted.     

Is a Chlamydia vaccine a reality?

Chlamydia trachomatis is a leading cause of sexually transmitted bacterial infections with severe sequelae such as tubal factor infertility and ectopic pregnancy; infections can also be asymptomatic. So far no vaccine has been developed but studies that may lead to the development of a highly warranted vaccine have been performed. The first attempt to vaccinate children with a whole-cell vaccine initially resulted in protection but the protection was short-lived. In animal models whole-cell vaccination resulted in hypersensitivity reactions, so that new strategies were devised. The first immunogenic molecule described was the major outer membrane protein (MOMP), and this molecule has therefore been studied in great detail as a candidate vaccine. Even though complete protection was not obtained, reduced shedding was observed and vaccine trials in animal models using naked DNA as a vaccine resulted in stimulation of both the humoral and cellular immune response, indicating progress in the development of a vaccine.     

Could platelet distribution width be a predictive marker for unexplained recurrent miscarriage?

Purpose

The aim of our study was to evaluate the platelet function in unexplained recurrent miscarriage and to investigate whether any hematologic changes detectable by simple complete blood count have a diagnostic value for the prediction of unexplained recurrent miscarriage.

Methods

A prospective study based on the comparison of 74 patients with unexplained recurrent first-trimester pregnancy loss with 208 control subjects matched for age. The two groups were compared in terms of platelet indices.

Results

There was a significant difference in platelet distribution width in patients with unexplained recurrent miscarriage compared to healthy control subjects. Platelet distribution width values in the patient group were statistically higher (P < 0.001) than the control group.

Conclusion

Our study provides an evidence that platelet distribution width gradually increases in women with recurrent miscarriage compared to control group. Patients with unexplained recurrent miscarriage have significantly increased platelet aggregation. This data may provide an empirical rationale for the use of anticoagulants in the management of this clinical condition.     

Is adenovirus a fetal pathogen?

OBJECTIVES: The purpose of this study was to test the relationship between adenovirus genetic material in the amniotic fluid and adverse pregnancy outcome. STUDY DESIGN: This was a prospective, observational study of women who were referred in the second trimester of gestation for either genetic amniocentesis or evaluation of fetal malformation. A 2-mL aliquot of amniotic fluid was subjected to multiplex polymerase chain reaction for a panel of viruses that included adenovirus and human genome controls. Fetuses with an abnormal karyotype were excluded from analysis. RESULTS: The prevalence of adenovirus was similar in normal (39/652) and anomalous fetuses (23/364; chi(2) test, P=.376). There was significant seasonal variation in the prevalence in both normal and anomalous fetuses (chi(2) exact test, P<.001), but no significant difference between groups. The monthly proportion of patients who underwent amniocentesis remained constant throughout the year (mean, 8.3%; chi(2) test, P=.67). Central nervous system anomalies and echogenic liver foci were significantly more common among fetuses with positive amniotic fluid polymerase chain reaction results for adenovirus (P<.005, respectively). CONCLUSION: Adenovirus is found in a similar prevalence and seasonal variation in sonographically normal and abnormal pregnancies. Although a specific fetal presentation was not identified, echogenic liver lesions with or without hydrops and neural tube defects were significantly more common in the presence of adenovirus. The significance of these findings deserves further study.     

Is rectovaginal endometriosis a progressive disease?

OBJECTIVE: The purpose of this study was to observe the natural history of untreated asymptomatic rectovaginal endometriosis. STUDY DESIGN: This was a prospective, observational study. Eighty-eight patients with untreated asymptomatic rectovaginal endometriosis were followed for 1 to 9 years. Pain symptoms and clinical and transrectal ultrasonographic findings were evaluated before and every 6 months after diagnosis. RESULTS: Two patients had specific symptoms that were attributable to rectovaginal endometriosis that was associated with an increase in lesion size and underwent surgery. In 4 other patients, the size of the endometriotic lesions increased, but the patients remained symptom free. The estimated cumulative proportion of patients with progression of disease and/or appearance of pain symptoms that were attributable to rectovaginal endometriosis after 6 years of follow up was 9.7%. For the remaining patients, the follow-up period was uneventful, with no detectable clinical nor echographic changes of the lesions and with no appearance of new symptoms. CONCLUSION: Progression of the disease and appearance of specific symptoms rarely occurred in patients with asymptomatic rectovaginal endometriosis.     

Is fetal pain a real evidence?

Due to the progress in fetal surgery, it is important to acquire data about fetal pain. Material and methods: We performed a Medline research from 1995, matching the following key words: “pain” and “fetus”, with the following: “subplate”, “thalamocortical”, “myelination”, “analgesia”, “anesthesia”, “brain”, “behavioral states”, “substance p”. We focused on: (a) fetal development of nociceptive pathways; (b) fetal electrophysiological, endocrinological and behavioral reactions to stimuli and pain. Results: We retrieved 217 papers of which 157 were highly informative; some reported similar data or were only case-reports, and were not quoted. Most endocrinological, behavioral and electrophysiological studies of fetal pain are performed in the third trimester, and they seem to agree that the fetus in the 3rd trimester can experience pain. But the presence of fetal pain in the 2nd trimester is less evident. In favor of a 2nd trimester perception of pain is the early development of spino-thalamic pathways (approximately from the 20th week), and the connections of the thalamus with the subplate (approximately from the 23rd week). Against this possibility, some authors report the immaturity of the cortex with the consequent lack of awareness, and the almost continuous state of sleep of the fetus. Conclusions: Most studies disclose the possibility of fetal pain in the third trimester of gestation. This evidence becomes weaker before this date, though we cannot exclude its increasing presence since the beginning of the second half of the gestation.     

Blood anti-Müllerian hormone is a possible determinant of recurrent early miscarriage,yet not conclusive in predicting a further miscarriage

Research questionIs blood anti-Müllerian hormone (AMH) concentration a strong determinant of unexplained recurrent early miscarriage (REM)?DesignIn the first part of the study, AMH concentrations measured using an Immunotech ELISA Kit were compared between 188 unselected (mostly fertile) women consecutively referred for three or more miscarriages in the first trimester of pregnancy and 376 age-matched parous women without pregnancy loss. Cases and controls were previously enrolled in an incident case–control study on thrombophilic mutations. Blood samples were collected >2 months after any recognized obstetric event or hormonal treatment. In the second part of the study, a prospective 2-year follow-up of cases was performed.ResultsWhen considering all women irrespective of age, AMH concentration did not significantly differ between cases and controls. However, in the subgroup ≥25 years old (176 cases versus 358 controls of ∼33.5 years), the cases had significantly lower AMH concentrations than the controls (median [interquartile range]: 2.8 [1.4–4.7] versus 3.25 [1.7–5.5], P = 0.046) and the proportion of cases with an AMH concentration <1 ng/ml was significantly higher (17.6% versus 10.6%; odds ratio 1.80; 95% confidence interval 1.07–3.00, P = 0.028). With regard to the subsequent pregnancy, AMH concentration was not correlated with either the conception delay or the miscarriage occurrence. However, increased age and number of previous miscarriages were significantly predictive of a subsequent miscarriage (P = 0.046 and 0.03, respectively).ConclusionAn altered ovarian reserve is a possible determinant of unexplained REM. However, AMH blood concentration predicts neither the delay nor the outcome of a subsequent pregnancy.     

How can we better predict the risk of spontaneous miscarriage among women experiencing threatened miscarriage?

Abstract

This study seeks to establish progesterone and progesterone-induced blocking factor (PIBF) levels as predictors of subsequent completed miscarriage among women presenting with threatened miscarriage between 6 and 10 weeks of gestation. Our secondary objective was to assess the known maternal risk factors, toward development of a parsimonious and clinician-friendly risk assessment model for predicting completed miscarriage. In this article, we present a prospective cohort study of 119 patients presenting with threatened miscarriage from gestation weeks 6 to 10 at a tertiary women’s hospital emergency unit in Singapore. Thirty (25.2%) women had a spontaneous miscarriage. Low progesterone and PIBF levels are similarly predictive of subsequent completed miscarriage. Study results (OR, 95% CI) showed that higher levels of progesterone (0.91, 95% CI 0.88–0.94) and PIBF (0.99, 95% CI 0.98–0.99) were associated with lower risk of miscarriage. Low progesterone level was a very strong predictor of miscarriage risk in our study despite previous concerns about its pulsatile secretion. Low serum progesterone and PIBF levels predicted spontaneous miscarriage among women presenting with threatened miscarriage between gestation weeks 6 to 10. Predictive models to calculate probability of spontaneous miscarriage based on serum progesterone, together with maternal BMI and fetal heart are proposed.