Robert Silver

Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome

Objective To determine whether antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin are associated with recurrent pregnancy loss. Methods Sera from three groups of women were studied: 1) 147 women with recurrent pregnancy loss but no clinical signs or symptoms of autoimmune disease who tested negative for lupus anticoagulant and medium-to-high levels of immunoglobulin G anticardiolipin antibodies; 2) 104 healthy, fertile controls of similar age and gravidity; and 3) 43 women with well-characterized antiphospholipid syndrome. Serum antibody binding against six phospholipids (cardiolipin, phosphatidic acid, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol) was determined using enzyme-linked immunoassays, and results were normalized using an anticardiolipin standard. Results Twenty-six (18%) women with recurrent pregnancy loss and nine (9%) controls tested positive (above the 99th percentile) for antiphospholipid antibodies. Sera from five (3.4%) women with recurrent pregnancy loss and four (3.8%) controls demonstrated binding to phospholipid antigens other than cardiolipin. In contrast, binding to phospholipid antigens was demonstrated in sera from more than 90% of women with antiphospholipid syndrome. Among women testing positive for antiphospholipid antibodies, the median positive value for women in the antiphospholipid syndrome group was significantly higher than for those with recurrent pregnancy loss or normal fertile controls. Conclusions Women with recurrent pregnancy loss are no more likely than fertile controls to have elevated levels of antiphospholipid antibodies once lupus anticoagulant, anticardiolipin, and an obvious clinical history of autoimmune disease have been excluded. Testing for antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin is not clinically useful in the evaluation of recurrent pregnancy loss.

Thyroid autoantibodies are not associated with recurrent pregnancy loss

OBJECTIVE Approximately 1% of all women have recurrent pregnancy loss, defined as >/=3 spontaneous losses of pregnancy; however, a cause is determined in only 50% of cases. Recent studies have associated the presence of thyroid autoantibodies during the first trimester of pregnancy with spontaneous abortion in the current pregnancy among women without a history of recurrent abortion. The objective of this study was to determine whether circulating thyroid autoantibodies were associated with recurrent pregnancy loss. STUDY DESIGN Sera from 74 nonpregnant women with a history of recurrent pregnancy loss and from 75 healthy, fertile control subjects of similar gravidity were tested for thyroglobulin and thyroid peroxidase antibodies by means of radioimmunoassay kits. All women had a third-generation thyroid-stimulating hormone assay performed. Samples were obtained >/=6 months after a pregnancy. RESULTS Twenty-two of the women with a history of recurrent pregnancy loss (29.3%) and twenty-eight of the control subjects (37%) had positive results for either one or both of the thyroid autoantibodies (P >. 05). Mean thyroid-stimulating hormone levels and the proportion of women with abnormal thyroid-stimulating hormone values did not differ between the 2 groups. CONCLUSION Women with a history of recurrent pregnancy loss are no more likely than are fertile control subjects to have circulating thyroid autoantibodies. Testing for antithyroid antibodies is not clinically useful in the evaluation of patients with a history of recurrent pregnancy loss.

Antiphospholipid antibodies and reproduction: The antiphospholipid antibody syndrome

In women who have a diagnosis of APS (both clinical and laboratory criteria) the chance for successful pregnancy is reduced. In these cases, treatment appears to be a clear option, particularly in the case of prior thromboembolic events. The current preference of treatment for women with RPL and aPL antibodies is subcutaneous heparin and aspirin. This treatment should begin with a positive pregnancy test and continue postpartum. It is unclear, at this time, what treatment, if any, is required for women who do not meet all the criteria for diagnosis of APS, but who are known to have aPL antibodies. In some cases, these women were tested because of a prior false-positive test for syphilis, with subsequent identification of aPL antibodies. More recently, women undergoing IVF were tested and found to have an increased incidence of aPL antibodies. It was suggested that aPL antibodies are associated with infertility and failure to implant. However, a summary of published reports indicate that positive aPL antibodies in patients undergoing IVF do not influence ongoing pregnancy rates. This subject, however, remains an area of active investigation because aPL antibodies were shown to interact with the syncytiotrophoblast and cytotrophoblast layers and could, theoretically, after implantation.

Conservative management of morbidly adherent placenta: expert review

Over the last century, the incidence of placenta accreta, increta, and percreta, collectively referred to as morbidly adherent placenta, has risen dramatically. Planned cesarean hysterectomy at the time of cesarean delivery is the standard recommended treatment in the United States. Recently, interest in conservative management has resurged, especially in Europe. The aims of this review are the following: (1) to provide an overview of methods used for conservative management, (2) to discuss clinical implications for both clinicians and patients, and (3) to identify areas in need of further research.

Subclinical Hypothyroidism and Thyroid Autoimmunity Are Not Associated With Fecundity, Pregnancy Loss, or Live Birth

CONTEXT Prior studies examining associations between subclinical hypothyroidism and antithyroid antibodies with early pregnancy loss and live birth suggest mixed results and time to pregnancy (TTP) has not been studied in this patient population. OBJECTIVE This study sought to examine associations of prepregnancy TSH concentrations and thyroid autoimmunity with TTP, pregnancy loss, and live birth among women with proven fecundity and a history of pregnancy loss. DESIGN AND SETTING This was a prospective cohort study from a large, randomized controlled trial that took place at four medical centers in the United States. PATIENTS OR OTHER PARTICIPANTS Healthy women, ages 18-40 y, who were actively attempting to conceive and had one or two prior pregnancy losses and no history of infertility were eligible for the study. INTERVENTION There were no interventions. MAIN OUTCOME MEASURE TTP, pregnancy loss, and live birth. RESULTS Women with TSH ≥ 2.5 mIU/L did not have an increased risk of pregnancy loss (risk ratio, 1.07; 95% confidence interval [CI], 0.81-1.41) or a decrease in live birth rate (risk ratio, 0.97; 95% CI, 0.88-1.07) or TTP (fecundability odds ratio, 1.09; 95% CI, 0.90-1.31) compared with women with TSH <2.5 mIU/L after adjustment for age and body mass index. Similar findings were observed for women with thyroid autoimmunity and after additional adjustment for treatment assignment. CONCLUSIONS Among healthy fecund women with a history pregnancy loss, TSH levels ≥ 2.5 mIU/L or the presence of antithyroid antibodies were not associated with fecundity, pregnancy loss, or live birth. Thus, women with subclinical hypothyroidism or thyroid autoimmunity can be reassured that their chances of conceiving and achieving a live birth are likely unaffected by marginal thyroid dysfunction.

Morbidly adherent placenta: The need for standardization

Morbidly adherent placenta (MAP) can be associated with major maternal morbidity, and is increasing in frequency. Determination of optimal management has not yet been satisfactory. We identify problems with lack of uniformity and the need for standardized nomenclature for the diagnosis, treatment and research of MAP. We suggest potential solutions and identify areas of future work.

Complications and safety of preconception low-dose aspirin among women with prior pregnancy losses

OBJECTIVE: To evaluate complications and safety of preconception low-dose aspirin in 1,228 U.S. women (2007–2011). METHODS: Evaluation of the safety of low-dose aspirin in the participants and their fetuses was a planned secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial, a multicenter, block-randomized, double-blind, placebo-controlled trial investigating the effect of low-dose aspirin on the incidence of live birth. Women aged 18–40 years with a history of one to two pregnancy losses trying to conceive were randomized to daily low-dose aspirin (81 mg, n=615) or placebo (n=613) and were followed for up to six menstrual cycles or through gestation if they became pregnant. Emergency care visits and possible aspirin-related symptoms were assessed at each study follow-up using standardized safety interviews. In addition, complications for both the participant and her fetus or neonate were captured prospectively using case report forms, interviews conducted during pregnancy and postpartum, and medical records. RESULTS: The proportion of women with at least one possible aspirin-related symptom during the trial was similar between treatment arms (456 [74%] low-dose aspirin compared with 447 [73%] placebo, P=.65) as was the proportion with at least one emergency care visit (104 [17%] low-dose aspirin compared with 99 [16%] placebo, P=.76). Maternal complications were evenly distributed by treatment arm with the exception of vaginal bleeding, which was more commonly reported in the low-dose aspirin arm (22% compared with 17%, P=.02). The distribution of fetal and neonatal complications—which included three stillbirths, three neonatal deaths, and 10 neonates with birth defect(s)—was similar between treatment arms. CONCLUSION: Although rare but serious complications resulting from low-dose aspirin cannot be ruled out, preconception low-dose aspirin appears to be well tolerated by women trying to conceive, women who become pregnant, and by their fetuses and neonates.

Infertility trial outcomes: healthy moms and babies

Traditionally, the primary outcome of infertility trials has been a positive pregnancy test or a clinically recognized pregnancy. However, parents desire a healthy baby that grows up to be a healthy adult, rather than a positive pregnancy test. Too often results of infertility trials are lacking in crucial obstetric details. This is problematic because treatments for infertility have the capacity to increase the risk for a variety of adverse obstetric outcomes. This review will outline important obstetric variables that should be included when reporting infertility research. The rationale for including these data, precise definitions of the variables, and cost-effective strategies for obtaining these obstetric details will be highlighted.

Fetoscopic Amniotic Band Release in a Case of Chorioamniotic Separation: An Innovative New Technique

Introduction Fetoscopic release of amniotic bands has proved its life- and limb-saving potential. Rupture of the amnion and separation of chorion from the amnion and uterine wall can however preclude the standard fetoscopic approach to release the amniotic bands using a single port. Methods and Materials A 28-year-old G1P0 woman was referred to our unit at 19 weeks due to amniotic band syndrome involving the left ankle, the infrapatellar region of the right leg, and the umbilical cord. Of note, part of the fetus was seen outside the amniotic cavity by ultrasonography and the left ankle and foot were severely swollen. The patient underwent a laparotomy and fetoscopic release of the amniotic bands as well as partial amnionectomy using two uterine ports and CO2 as distention. Results The surgery and postoperative recovery course were uneventful. At 341/7 weeks the patient went into labor, which was augmented resulting vaginal delivery of a 2,460-g male infant. The infant was noted to have a shallow skin indentation on the left lower extremity near the ankle. The infant was discharged in excellent condition. Conclusion In those cases where release of an amniotic band is impossible due to membrane separation, surgery in a CO2-filled uterus offers an option.

Unusual pleuro‐amniotic shunt complication managed using a 2‐port in‐CO2 fetoscopic technique: Technical and ethical considerations

We report a case of fetal upper arm constriction by a pleuroamniotic shunt, treated fetoscopically using a two-port, in-CO2 gas technique. A 35-year-old, gravida six, para four woman presented at 21 + 4 weeks’ gestation with a fetus with bilateral pleural effusions and non-immune hydrops, which resolved after bilateral double pigtail catheters were inserted. At 28 weeks, one of the shunts was seen encircling the fetal left upper arm. Over 2 weeks this progressed to a deep indentation with distal arm edema (Figure 1). A plastic surgeon recommended release of the constriction to prevent superficial nerve damage and possible vascular consequences. An extensive anterior placenta prevented percutaneous access to the amniotic cavity. At 30 + 2 weeks’ gestation, after extensive counseling regarding her options, a laparotomy under deep general anesthesia was performed and the uterus was exteriorized. Vecuronium and fentanyl were given into the fetal left arm intramuscularly as an anesthetic. A 12 F vascular cannula was then inserted into the amniotic space using the Seldinger technique and sutured in place, and a pediatric cystoscope (Storz, Tuttlingen, Germany) with a 1-mm Storz grasper was used to attempt to unwind the shunt (which exited the fetal chest in the left armpit). There was a film of tissue growing over the shunt making it impossible to unwind the device. Approximately 60 mL of amniotic fluid was then removed and replaced with 200 mL CO2 gas (0.5 L/min, 12 mmHg). A second 12 F port was placed under direct vision and sutured in place. The CO2 allowed excellent visualization of the fetal upper body and area of interest. A 3-mm laparoscopic grasper introduced via the second 12 F port was used to slowly unwind the shunt from the fetal arm (Videoclip S1). Using the 1-mm hysteroscopic grasper we stabilized the shunt and cut it 1 cm from the chest wall with 3-mm laparoscopic scissors, placed through the second port (Figure 2). A pediatric cardiologist continuously monitored the fetal heart rate and cardiac function, which remained normal. There were no signs of maternal hypercarbia or fetal acidosis. At completion of the surgery, the gas was slowly removed and replaced with warmed saline and the ports were closed with 2/0 vicryl sutures. Operative time was 42 min. Repeat ultrasound on a weekly basis revealed resolution of the left arm swelling and minimal residual indentation. At 38 + 2 weeks’ gestation the patient presented with spontaneous rupture of membranes, and following pitocin augmentation she had an uncomplicated spontaneous vaginal delivery. The right shunt was removed without Figure 1 Preoperative ultrasound image showing constriction of fetal left arm by shunt (double pigtail catheter).