Progestogens and pregnancy loss.

Progestational agents are often prescribed to prevent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Progestogens have therefore been used at all stages of pregnancy including luteal-phase support prior to pregnancy, threatened miscarriage, recurrent miscarriage, and to prevent preterm labor. In luteal support, a Cochrane review reported that progestogens were associated with a higher rate of live births or ongoing pregnancy in the progesterone group (odds ratio 1.77, 95% confidence interval (CI) 1.09-2.86). Evidence suggests that progestogens are also effective for treating threatened miscarriage. Again, in a Cochrane Database review, progestogens were associated with a reduced odds ratio of 0.53 (95% CI 0.35-0.79) when progestogens were used. In recurrent miscarriage, progestogens also seem to have a beneficial effect. A meta-analysis of progestational agents showed a 28% increase in the live birth rate (relative risk 0.72, 95% CI 0.53-0.97). For the last 30 years, progestogens have been used to prevent preterm labor. Recent meta-analyses also report beneficial effects. This review summarizes the literature and the author's experience using progestogens to prevent pregnancy loss.

Recurrent miscarriage and hCG supplementation: a review and metaanalysis.

Human chorionic gonadotropin (hCG) has been used to prevent subsequent miscarriages after previous recurrent miscarriages. In addition to the luteotrophic effects, hCG has uterine immune and autocrine actions. hCG also affects cytokine expression. A Cochrane database systematic review has indicated that hCG seems to prevent further miscarriages, (OR for miscarriage = 0.26, 95% CI 0.14-0.52). However, the trials in the Cochrane database were not matched for the number of miscarriages, 1°, 2° or 3° aborter status, maternal age, etc. and no account was made for chromosomally abnormal pregnancies. All of these impact on the subsequent prognosis and may confound the results. The previous trials in the literature all assessed urinary (u-hCG) rather than recombinant hCG (r-hCG), raising the question whether the effect on pregnancy outcome is due to hCG itself, or other urinary proteins present in u-hCG. A new trial is indicated in which r-hCG is compared to u-hCG and the most effective compared to placebo. Treatment and placebos arms should be stratified for the prognostic factors above and the results corrected for fetal chromosomal aberrations. Until such a trial is carried out, the use of hCG supplementation is empiric.

Autoantibodies as predictors of pregnancy complications.

Certain autoantibodies which are found in autoimmune diseases including CTDs can impair fertility. Reproductive failure may present as pregnancy loss, either as miscarriage, intrauterine fetal death or stillbirth. There are also late obstetric complications such as intrauterine growth restriction, pre-eclampsia and pre-term birth. This review summarizes the possible influences of autoantibodies in reproductive failure, and particularly their predictive value (if available). The aPLs detectable by lupus anticoagulant, anti-cardiolipin or anti-beta2 glycoprotein I assays are associated with pregnancy loss and have a positive predictive value (PPV) of 75%. In spite of the general consensus on the management of pregnant aPL-positive women, few well-designed clinical trials have been reported and there is also insufficient data about the PPV of treatment. Anti-thyroid antibodies have been associated with pregnancy loss, and indeed have a PPV of 40%. However, no antibody is pathognomic for pregnancy loss. It may be more appropriate to assess a combination of antibodies rather than one antibody. However, a large meta-analysis of published trials is required in order to determine the prevalence of each particular autoantibody and different combinations of antibodies in different forms of reproductive failure.

Anti-phospholipid antibodies and infertility.

Antiphospholipid syndrome (APS) or the presence of antiphospholipid antibodies (aPL), usually presents as pregnancy loss. However, aPL have also been reported to affect implantation, placentation, and early embryonic development. The binding of aPl to beta2GP1 may lead to breakdown of the phospholipid adhesion molecules between different elements of trophoblast. As aPL affect placental growth and function, aPl may prevent implantation presenting as infertility. Lupus anticoagulant and anticardiolipin antibody have been implicated in the prothrombotic effects of APS. Antibodies to other phospholipids such as anti-phosphatidylserine, phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl Inositol etc. may be more relevant in infertility. Their role remains to be clarified. There is theoretical evidence from animal models and clinical infertility practice that aPL has a role in infertility. However, a large-scale meta-analysis has failed to confirm the association. To determine whether infertility or even pregnancy loss is associated with aPL, it is necessary to know that the embryo is chromosomally normal. Pregestational diagnosis has shown that up to 60% of embryos may be chromosomally aneuploid in failed in vitro fertilization (IVF); hence, may confound our understanding concerning the association between aPL and infertility, failed IVF or even pregnancy loss.

Vasa previa: a major complication and its management.

Vasa previa is an extremely rare condition. Consequently it is not often considered in the differential diagnosis of antepartum or intrapartum hemorrhage. Rupture of a fetal vessel may lead to sudden fetal death from exsanguination; therefore, this condition should be suspected in any antepartum or intrapartum hemorrhage. The blood that is lost should be tested for the presence of fetal hemoglobin. Other diagnostic tests to assess the degree of fetal distress are described. Four patients showing unusual presentations of vasa previa are reported. These cases demonstrate that fetal vessel rupture may occur independently of membrane rupture.

What is the minimal uterine cavity needed for a normal pregnancy? An extreme case of Asherman syndrome.

There are no reports on the subsequent anatomic findings in women with intrauterine adhesions who conceived and delivered after therapy, but our experience indicates that most of these women menstruate and conceive normally. The recurrence of intrauterine adhesions, together with preserved fertility in this patient, suggest that fertility, while usually correlated with subsequent resumption of normal menstruation and anatomy, may sometimes be independent of these features.

Effect of diclofenac on implantation and embryonic development in the rat.

Recent evidence suggests that decidualization can be considered a modified inflammatory reaction. In this work we intended to determine whether the prostaglandin inhibitor diclofenac could affect implantation. Rat blastocysts were cultured in diclofenac in vitro, then implanted to host mothers on day 5 of pseudopregnancy. Large doses of diclofenac in culture were toxic. Smaller doses had a profound effect on implantation. Another group of host mothers received diclofenac i.p., one hour prior to transfer of untreated blastocysts. The results were compared to parallel controls without diclofenac treatment. Control animals had a 72% implantation rate, whereas there was only a 35-41% implantation rate after in vitro diclofenac treatment. In the treated host mothers only 7% of embryos were normal, while 34% were growth-retarded. More normal embryos were found when the blastocysts were cultured with diclofenac. The observations indicate that diclofenac administered to the mother inhibits the ongoing process of implantation and placentation, whereas following in vitro exposure the embryo can recover from the insult. The implications for a better understanding of the process of implantation are discussed.

Nonoperative management of ectopic pregnancy. A preliminary report.

The incidence of ectopic pregnancy is increasing throughout the Western world; at present it is uncertain how much of this increase is due to the disease and/or its antecedents and how much due to better means of diagnosis. That the treatment of the obvious or ruptured ectopic pregnancy should be surgical is beyond doubt. However, in view of the natural tendency of some ectopic pregnancies to terminate in tubal abortion or complete resorption, it is questionable whether surgery is always necessary in every early case or whether some patients can be monitored by means of rising or falling levels of beta subunits of human chorionic gonadotropin (HCG) until tubal abortion or resorption occurs. This may be the best means of preserving tubal function and fertility.

Fertility after nonsurgical treatment of ectopic pregnancy.

There is no question that the treatment of choice for ectopic pregnancy is surgery. However, since some ectopic pregnancies terminate in tubal abortion or complete resorption, it is questionable whether surgery is necessary in every case. Some patients can be managed by monitoring rising or falling levels of beta-human chorionic gonadotropin (beta-HCG) until tubal abortion or resorption occurs. This approach, which may be the best means of preserving tubal function and fertility, was used in 14 patients who fulfilled extremely selective criteria. In some of the patients, surgery later proved to be necessary, but in 11 nonsurgical management was followed by a fall in beta-HCG levels, and there were no further untoward effects. Three of these patients subsequently developed intrauterine pregnancies, and one patient had a repeat ectopic.

Features of shoulder dystocia in a busy obstetric unit.

OBJECTIVE: To assess the incidence and complications of shoulder dystocia and whether those complications could be avoided. STUDY DESIGN: Retrospective analysis of shoulder dystocia between 1996 and 1999 to determine whether macrosomia, diabetes, height of head at full dilatation, length of second stage or instrumental delivery could predict shoulder dystocia. Fetal asphyxia, brachial plexus injury, maneuvers used to free the shoulders and experience of the attendant were also assessed. RESULTS: There were 56 cases of shoulder dystocia in 24,000 births, 59% after spontaneous delivery. McRoberts maneuver was used in 48 deliveries but sufficed as a solitary procedure in nine cases. The addition of suprapubic pressure was sufficient for 25 patients and 27 when bilateral episiotomy was also used. Corkscrew procedures were required in 12 patients. Midwives were involved in 35 cases and required assistance in 27. Macrosomia > 4,000 g was a feature in 20 infants and diabetes in 6. Neither the height of the head nor the length of the second stage was helpful. There were 13 cases of Erb's palsy, seven after vacuum delivery and six after spontaneous delivery. Eight of these cases were associated with McRoberts procedure and suprapubic pressure, two with no procedure and three with the corkscrew procedure. CONCLUSION: If all infants > 4,000 g had been delivered by cesarean section, there still would have been 36 cases of shoulder dystocia. If the ultrasonically estimated weight were used to select patients for cesarean section, seven cases would have been diagnosed. To lessen the degree and incidence of fetal injury, labor ward staff are urged to become as familiar as possible with the techniques of freeing the shoulders.

Lupus anticoagulant. Significance in habitual first-trimester abortion.

Therapy with steroids and aspirin has been reported to benefit pregnancies in patients with lupus anticoagulant (LA). In this study, habitual first-trimester aborters with LA using steroids and aspirin were compared to a control group of untreated habitual aborters without LA. In habitual aborters with LA, 12 of 24 (50%) pregnancies reached the second trimester as compared to 8 of 22 pregnancies (36%) in the control group. Since the treated group did no better than the control group, LA probably is not a cause of first-trimester abortion. However, once the second trimester is reached, a 50% incidence of growth retardation was found, and 42% of fetuses died in the second or third trimester in treated LA patients. Treatment with steroids and anti-platelet aggregating agents may be necessary despite the attendant risks to prevent those sequelae in the second and third trimesters. There was a 29% live birth rate in treated LA patients; the rate was 36% in control patients. However, this rate was produced only by early intervention, which was unnecessary in the control patients.

Successful pregnancy outcome with combination therapy in women with the antiphospholipid antibody syndrome.

Four women with the antiphospholipid syndrome associated with lupus anticoagulant and a poor obstetric history were treated with a combination of glucocorticosteroids, anticoagulants and platelet inhibitor therapy. All patients had at least one previous miscarriage while receiving prednisone and low-dose aspirin. The treatment regimen included: aspirin, dipyridamole, prednisone, and warfarin or heparin. This treatment resulted in a successful pregnancy outcome in all cases, without preeclampsia or recurrence of thrombosis. One patient developed a vertebral compression fracture while receiving heparin and prednisone. Two pregnancies required cesarean delivery for fetal distress at 32 and 34 weeks. All four infant birth weights were appropriate for the gestational age. This regimen may be a therapeutic option for patients with the antiphospholipid antibody syndrome, especially if they have failed other commonly used treatments.

Sixth meeting of the European Forum on antiphospholipid antibodies. How to improve the understanding of the antiphospholipid syndrome?

The main objective of these meetings is to promote international collaboration in various clinical and research projects. This paper is the summary of the 2007 Ljubljana meeting, and offers an overview of the proposed projects. The technical and methodological details of the projects will be published on the forum's web site (http://www.med.ub.es/MIMMUN/FORUM/STUDIES.HTM).

The use of oxytocin after a previous caesarean section--a review and report on a series.

We briefly present our experience with trial labour in the presence of a Caesarean section scar and review some of the literature on the management of such patients.

Immunotherapy of habitual abortion.

Many cases of habitual abortion have been assumed to be due to hyporesponsiveness to the spouse's antigens encountered in pregnancy. Immunization by paternal leukocytes has been used to potentiate the immune response and prevent further miscarriages. This treatment has been highly controversial in terms of efficacy, mode of action, and side effects. More recently immunoglobulin has been used as passive immunization for similar indications. In our experience immunotherapy is effective; 80% of patients have subsequent live births. The most significant results are seen in patients with five or more abortions, in whom 66% of subsequent pregnancies develop normally compared to 20% in a control group. We have used antipaternal complement-dependent antibody (APCA) production after immunization as a marker of immune response. APCA correlates with beneficial outcome in the next pregnancy. APCA may also be associated with cytokines, which may enhance embryonic and trophoblast development. Immunoglobulin may similarly provide the relevant antibodies or cytokines. At present a large scale meta-analysis is being performed to confirm or refute the efficacy of this treatment. This meta-analysis may resolve the controversy.