Absence of autoantibodies to human chorionic gonadotropin in women with a history of habitual abortion.

OBJECTIVE: To determine if immunization to human chorionic gonadotropin (hCG) has occurred in women with habitual abortion. DESIGN: Comparisons between nonpregnant patients with a history of at least three consecutive miscarriages (n = 48) and normal controls (n = 38). In addition, 28 habitual aborters were compared, while pregnant, with 37 pregnant control women. Antibodies to hCG were assessed by a solid-phase immunometric assay using europium-labeled antihuman immunoglobulin (Ig)G as tracer; this method is capable of detecting antibodies toward hCG in serum of patients immunized with beta-hCG-tetanus toxoid conjugate. SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. RESULTS: Three patients (1 primary and 2 secondary aborters, 1 both while pregnant and not pregnant) showed evidence of Ig binding to hCG, but the binding was not inhibited by an excess of hCG. CONCLUSIONS: Antibodies against endogenous hCG may not be responsible for habitual abortion.     

Endocrinology: Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation in patients undergoing IVF: a randomized comparative study

One-hundred women undergoing ovarian stimulation with gonadotrophin-releasinghormone agonist (GnRH-a) and a human menopausal gonadotrophin(HMG) for in-vitro fertilization (IVF) participated in thisrandomized comparative study. The effectiveness of long-actings.c. goserelin (Zoladex depot; 49 patients) and intranasally(i.n.) administrated buserelin acetate (Suprefact; 51 patients)for pituitary down-regulation was compared. Treatment with s.c.goserelin (3.6 mg) or i.n. buserelin acetate (200 µg;6 times/day) was started on day 21–23 of the cycle. Stimulationwith 150 IU of HMG/day was started after at least 11 days ofGnRH-a treatment. There were no differences in the time requiredfor follicular development nor in the clinical outcome betweengroups treated with either goserelin or buserelin. The numberof oocytes recovered in the goserelin group was 6.7 ±5.0 versus 6.3 ± 4.9 in the buserelin group. There were11 pregnancies after the use of goserelin (22.4%) and 12 pregnanciesin those given buserelin (24.0%). The number of HMG ampoulesneeded for follicular maturation was higher in the goserelingroup (27.9 ± 7.8) than in the buserelin group (24.6± 7.8, P < 0.05). The patients given buserelin sufferedsignificantly more from tiredness, depression, headache andabdominal pain than those receiving goserelin, whereas therewere no differences between the groups in experiencing mentalirritability, nausea and swelling. Subcutaneous goserelin depotinjection offers a useful alternative for pituitary down-regulationin IVF stimulation.     

Screening for coeliac disease in women with a history of recurrent miscarriage or infertility

Because subclinical coeliac disease may decrease fertility or complicate pregnancy, we screened women with recurrent miscarriage of unknown aetiology (   n = 63  ), unexplained infertility (   n = 47  ) and infertility with a known cause (   n = 82  ), for anti-endomysium antibodies in serum to find undiagnosed coeliac disease. One woman (1.6%) with recurrent miscarriage, another woman (2.1%) with unexplained infertility and one woman (2.0%) in the control group (   n = 51  ), were considered to have coeliac disease. We could not demonstrate a higher frequency of coeliac disease in women with infertility or recurrent miscarriage, but suggest that undiagnosed coeliac disease is common in women.     

Fear of childbirth and pregnancy-related anxiety in women conceiving with assisted reproduction

OBJECTIVE: To compare the prevalence and predictors of severe fear of childbirth and pregnancy-related anxiety in groups of assisted reproduction treatment (ART) and spontaneously conceiving women with singleton pregnancies. METHODS: The ART group (n = 367, nulliparous 260) represented a cohort from five Finnish infertility clinics in 1999. The control group (n = 379, nulliparous 135) was enrolled in this study by consecutive sampling the same year. Fear of childbirth was assessed by means of the revised version of the Fear-of-Childbirth Questionnaire and pregnancy-related anxiety by means of the Pregnancy Anxiety Scale at gestational week 20 +/- 3.2 (mean+/-standard deviation). RESULTS: The frequency of severe fear of childbirth and anxiety (classified as total scores in the 90th percentile or higher in the revised Fear of Childbirth Questionnaire and Pregnancy Anxiety Scale) did not differ between the groups. Nulliparity was associated with more frequent severe anxiety only in the controls. In nulliparous participants, a partnership of more than 5 years decreased the risk of severe fear of childbirth (odds ratio 0.3, 95% confidence interval 0.2-0.7). In the nulliparous ART group, a long duration of infertility (7 or more years) increased the risk of severe fear of childbirth (odds ratio 4.4, 95% confidence interval 1.2-16.9). CONCLUSION: Women conceiving after ART do not experience severe fear of childbirth or pregnancy-related axiety more often than spontaneously conceiving controls. However, a long duration of infertility is an independent risk factor regarding severe fear of childbirth. LEVEL OF EVIDENCE: II-2.     

A prospective study of 63 couples with a history of recurrent spontaneous abortion: contributing factors and outcome of subsequent pregnancies

To evaluate the possible causes of recurrent spontaneous abortion(RSA) and to elucidate the prognosis for subsequent pregnancies63 RSA patients were studied. Parental karyo-typing revealedchromosomal aberrations in six of the 63 couples (4.8%). Therate of increased concentrations of antibodies against cardiolipinwas comparable in the patients (10.0%) and in 30 parous controls(6.7%), as was also the occurrence of other autoantibodies (43.3and 36.7%, respectively). Hysteroscopy revealed uterine cavityabnormalities in 11 of the 55 patients studied (20.0%). Altogether,for 35 RSA women (55.4%) investigations resulted in entirelynormal findings; abnormal findings were more frequently encounteredin primary aborters (56.8%) than in secondary aborters (26.9%,P < 0.05). During the follow-up period of 24.1 ± 15.4months, 48 patients became pregnant a total of 65 times, andthe cumulative live birth rate was 62.5%. A living fetus wasseen in ultrasound examination in 46 pregnancies (70.7%), whereasa blighted ovum was diagnosed in nine pregnancies (13.8%). Anadditional nine pregnancies aborted so suddenly that no ultrasoundexamination was performed, and one ectopic pregnancy was treatedlaparoscopically. Of the initially viable pregnancies, 13 (28.3%)ended in miscarriage and two were terminated due to fetal anomalies.Normal findings in the investigations were associated with asmaller risk for abortion (40.0%) than were abnormal findings(65.5%, P < 0.05). Of the 30 babies, six (20.0%, with babiesfrom one twin pregnancy excluded) were growth-retarded, 9.7%were born before 37 weeks of gestation, and 22.8% of the mothershad impaired glucose tolerance during pregnancy. Thus pregnanciesin RSA women were accompanied by increased risk for fetal growthretardation, preterm delivery and impaired glucose toleranceand needed, therefore, to be followed carefully.     

Screening for coeliac disease in women with a history of recurrent miscarriage or infertility.

Because subclinical coeliac disease may decrease fertility or complicate pregnancy, we screened women with recurrent miscarriage of unknown aetiology (n = 63), unexplained infertility (n = 47) and infertility with a known cause (n = 82), for anti-endomysium antibodies in serum to find undiagnosed coeliac disease. One woman (1-6%) with recurrent miscarriage, another woman (2.1%) with unexplained infertility and one woman (2.0%) in the control group (n = 51), were considered to have coeliac disease. We could not demonstrate a higher frequency of coeliac disease in women with infertility or recurrent miscarriage, but suggest that undiagnosed coeliac disease is common in women.     

The immunolocalization of bcl-2 at the maternal-fetal interface in healthy and failing pregnancies

Programmed cell death by apoptosis occurs in both fetal and maternal tissues during early pregnancy. To investigate a role for apoptosis at the maternal-fetal interface, we have immunolocalized the bcl-2 protein in formalin-fixed decidual and placental tissue collected from women undergoing surgical termination of pregnancy (n = 22), from women undergoing a sporadic miscarriage (n = 16) and from women with a history of recurrent pregnancy loss (more than three consecutive pregnancy losses; n = 22) undergoing a further miscarriage. In all three groups, bcl-2+ cells were found in aggregates and dispersed in the stroma, and immunoreactivity was observed in glandular epithelium. Double immunostaining revealed that a majority of stromal bcl-2+ cells were CD56+ large granular lymphocytes. A computerized image analysis revealed no significant differences in percentage area of bcl-2 or CD56+ immunostaining. Significantly more biopsies from the surgical termination group (4/10) had > 20% positive immunostaining for CD56 compared with 0% in the other two groups combined (0/20; P < 0.05). Bcl- 2 immunoreactivity was observed in the villi syncytiotrophoblast, and staining intensity was consistently greater in the surgical termination group. The possible roles of bcl-2 at the maternal-fetal interface are discussed.      

Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production

Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti- aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto- PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.      

Deficient syncytiotrophoblast tumour necrosis factor-alpha characterizes failing first trimester pregnancies in a subgroup of recurrent miscarriage patients

Pregnancy failure in mice has been associated with increased placental concentrations of the pro-inflammatory cytokine tumour necrosis factor- alpha (TNF-alpha). To investigate the role of uterine TNF-alpha in human first trimester miscarriage, we have collected human decidual and trophoblast tissue from women (i) undergoing surgical termination of pregnancy (n = 27), (ii) undergoing a sporadic miscarriage (n = 20) and (iii) with a history of recurrent pregnancy loss [>3 consecutive pregnancy losses (n = 26)] undergoing a further miscarriage. Formalin fixed tissues were examined for TNF-alpha mRNA (in-situ hybridization) and protein (immunohistochemistry). In decidua from all three groups, TNF-alpha protein and mRNA were co-localized to the decidual stroma, the luminal surface of some maternal vessels and to the glandular epithelium. Chorionic villi from the normal pregnancy and the sporadic miscarriage group exhibited co-localized TNF-alpha protein and mRNA in the syncytiotrophoblast and cytotrophoblast. In the recurrent miscarriage group, however, 63.6% of the biopsies showed positive immunostaining in only the cytotrophoblast, compared with 4.0% of women undergoing surgical termination of pregnancy and 0.0% of women with a sporadic failed pregnancy (P < 0.001). TNF-alpha mRNA was also localized exclusively to this layer. This may be a secondary effect caused by a different mechanism of pregnancy loss unique to this subgroup.