Уважаемые коллеги,
В виду определенного профессионального интереса к обследованиям при планировании беременности а так же собственного по вопросам тромбофилии и невынашивания хочется запостить недавний Ланцетовский семинар о проблемах диагностики и лечения привычного невынашивания (ПДФ файл могу переслать любому на мыло, так как здесь только текстовый фрагмент без ссылок и рисунков):
Seminar
Recurrent miscarriage
Raj Rai MD and Prof Lesley Regan MD,
Department of Obstetrics and Gynaecology, St Mary's Campus, Imperial College London, Mint Wing, South Wharf Road, London W2 1PG, UK
Available online 10 August 2006
Causes of recurrent miscarriage
Historically, recurrent miscarriage has been attributed to either genetic, structural, infective, endocrine, immune, or unexplained causes. Thrombophilic disorders are now thought to play a part in the cause of recurrent pregnancy loss, which widens the scope of investigations and management options for recurrent miscarriage.
Genetic abnormalities
Fetal aneuploidy is the most important cause of miscarriage before ten weeks' gestation.31 At least 50–60% of all miscarriages are associated with cytogenetic abnormalities, the most frequent being trisomy, followed by polyploidy and monosomy X.4, 5, 32 and 33 Most human aneuploidies arise from errors in the first meiotic division of the oocyte, which is initiated prenatally and is not complete until ovulation. An increased rate of sperm chromosome abnormalities has also been reported in couples with recurrent miscarriage,34 but only 7% of fetal trisomies have been shown to arise from paternal meiotic errors.35 Despite the recognised association between advancing maternal age and fetal aneuploidy, little is known about the underlying mechanisms. One hypothesis is that women have a limited oocyte pool, and that increasing age results in a relative scarcity of oocytes at optimum stages of maturation.36 Thus women who have lost at least one trisomic fetus have been reported to have a diminished ovarian reserve and to enter the menopause at an earlier age than those with no such history.37 and 38 Some women with recurrent miscarriage might be more prone to heterotrisomy—ie, recurrence of a different trisomy after a trisomic pregnancy.39 One screening study of couples with recurrent miscarriage undergoing in-vitro fertilisation showed that they had more abnormal embryos than an age-matched control group with no history of recurrent miscarriage.40
In about 4% of couples with recurrent miscarriage one partner carries either a balanced reciprocal translocation, in which there is an exchange of two terminal segments from different chromosomes, or a Robertsonian translocation, in which there is centric fusion of two acrocentric chromosomes.16 Carriers of a balanced reciprocal translocation are phenotypically normal, but 50–70% of their gametes and hence embryos are unbalanced, because of abnormal segregation at meiosis. The reproductive risk conferred by chromosome rearrangements is dependent on the type of rearrangement and whether it is carried by the woman or her male partner.41 The livebirth rate in couples with a structural chromosome abnormality who conceive spontaneously is higher (50–65%)42 than that currently achieved after in-vitro fertilisation and preimplantation genetic screening, which is 29% per oocyte retrieval and 38% per embryo transfer.43
Structural abnormalities
Transcervical embryoscopy has shown that aneuploid embryos have disordered growth and development (such as anencephaly and facial and limb dysplasia), and that similar abnormalities are found in up to 18% of euploid pregnancies ending in miscarriage.44
The frequency of congenital uterine abnormalities (uterine septae and bicornuate uterus) in the general population is unknown, but in women with recurrent miscarriage it has been reported to be between 1·8% and 37·6%.45, 46 and 47 This wide range reflects differences in diagnostic criteria and the imaging techniques used. A retrospective review of patients with uncorrected abnormalities suggests that they undergo high rates of miscarriage and preterm delivery.45 However, the benefits of surgical correction (open or hysteroscopic) on pregnancy outcome have not yet been assessed by a randomised trial.
Uterine fibroids are present in up to 30% of women, but their effect on reproductive outcome is controversial.48 Most studies report that implantation failure after in-vitro fertilisation is linked to either intramural or submucosal fibroids, but this finding could indicate publication bias. The mechanism or mechanisms by which fibroids could cause early pregnancy loss are unclear. Traditionally, researchers have postulated that uterine fibroids have a mechanical or space-occupying effect that impedes embryonic implantation. The expression of HOX10, a gene that controls differentiation and is involved in implantation, has now been shown to be lower in uteri with fibroids than in those without.49
A diagnosis of cervical incompetence, based on a history of late miscarriage preceded by spontaneous rupture of membranes or painless cervical dilatation, is frequently cited as a cause of midtrimester recurrent miscarriage.16 and 50 However, no objective tests can reliably identify women with cervical weakness in the non-pregnant state. A Cochrane review identified no conclusive evidence that prophylactic cervical cerclage reduces the risk of recurrent midtrimester miscarriage.51 Therefore, the value of serial ultrasound assessments of cervical shortening and the insertion of a rescue cerclage for prevention of late miscarriage and preterm delivery are questionable.52 and 53 In our experience, the success of cerclage is determined by detailed clinical history, treatment of coexistent thrombophilic disorders and prophylactic antibiotics. More important is the skill and experience of the surgeon, and their ability to bury the suture material under the vaginal mucosa to keep vaginal discharge to a minimum.54 Abdominal cerclage has been advocated for selected women with previous failed vaginal cerclage. However, a systematic review comparing the two techniques concluded that although abdominal cerclage might reduce perinatal death, it is associated with a higher risk of serious operative complications.55
Infection
Infective causes of recurrent miscarriage remain speculative. For any infective agent to be implicated, it must be capable of persisting in the genital tract undetected and must cause few maternal symptoms. Because toxoplasmosis, rubella, cytomegalovirus, herpes, and listeria infections do not meet these criteria, routine screening for these diseases has now been abandoned.56 The evidence for bacterial vaginosis as a cause of early miscarriage secondary to endometritis is inconsistent,57 and 58 but the presence of bacterial vaginosis during the first trimester of pregnancy has been repeatedly reported as a risk factor for late miscarriage and early preterm birth.59 One randomised controlled trial in a low-risk obstetric population showed that the risk of late miscarriage and preterm birth is reduced by screening women for bacterial vaginosis in early pregnancy and treating with oral clindamycin.60 However, investigators in no less than eight randomised trials concluded that there is no benefit in screening and treating all pregnant women for bacterial vaginosis to prevent preterm birth. By contrast, the Cochrane review suggested that detection and treatment of bacterial vaginosis early in pregnancy might prevent preterm delivery in women with a history of preterm birth.61