J. Jaroslav Stern

Frequency of abnormal karyotypes among abortuses from women with and without a history of recurrent spontaneous abortion

OBJECTIVE To compare the frequency of chromosomal abnormalities in products of conception from women with and without a history of recurrent spontaneous abortion. DESIGN Retrospective analysis of prospectively collected material. SETTING Private practice at the Genetics and IVF Institute, Fairfax, Virginia and Grupo de Reproducción AGY Asociados, México City, México. PATIENTS Women with (n = 94) and without (n = 130) a history of recurrent spontaneous abortion who had a spontaneous abortion between January 1, 1992 and November 1, 1994. INTERVENTION Chromosomal analysis performed on products of conception using standard G-banding technique. MAIN OUTCOME MEASURE The percentage of chromosomal abnormalities among products of conception from women with and without recurrent spontaneous abortion was compared. RESULTS Among products of conception from women with recurrent spontaneous abortion, 57% (54/94) had abnormal and 43% (40/94) had normal chromosome analyses. Products of conception from women without recurrent spontaneous abortion had abnormal chromosome analyses in 57% (74/130) and normal results in 43% (56/130). CONCLUSIONS No differences in frequency of abnormal karyotype were observed in products of conception from women with recurrent spontaneous abortion compared with women without recurrent spontaneous abortion.

Validation of an Embryotoxicity Assay

PROBLEM: Culture of mouse blastocysts has served as a tool for identifying various embryotoxic factors in human serum. While inactivated, sera from recurrently aborting women inhibit mouse blastocyst development in vitro. Variation in results from individual serum samples has limited the usefulness of this assay in establishing a new classification of idiopathic recurrent spontaneous abortion (RSA).

Color Doppler ultrasonography assessment of tubal patency: a comparison study with traditional techniques

OBJECTIVE To compare the results of color Doppler ultrasonic hysterosalpingography (color US-HSG) and x-ray-HSG with chromoperturbation at the time of laparoscopy. DESIGN Open, uncontrolled study of women seeking evaluation for infertility from August 1989 to July 1991. SETTING Clinical environment. PATIENTS Two hundred thirty-eight infertile women. INTERVENTION Saline was administered transcervically during transvaginal color Doppler sonography in 238 women. Traditional x-ray-HSG was performed in 89 women. Laparoscopy with chromoperturbation was done in 121 women. Forty-nine women had all three procedures performed. MAIN OUTCOME MEASURES The frequency of diagnosis of bilateral tubal patency, bilateral tubal occlusion, and unilateral tubal patency after color US-HSG and x-ray-HSG was compared with chromoperturbation. The diagnostic efficacy of color US-HSG and x-ray-HSG was compared with chromoperturbation. RESULTS Correlation between color US-HSG and x-ray findings with chromoperturbation occurred in 81% versus 60% (P = 0.0008) of all women studied. In 49 women who had all three procedures performed, color US-HSG results correlated with chromoperturbation more often than x-ray-HSG (82% versus 57%, P = 0.0152). CONCLUSION Color US-HSG is an alternative technique to x-ray-HSG in diagnosing tubal occlusion as a cause of infertility.

REVIEW: Immunology of Ovarian Failure

Ovarian failure is the result of depletion of ovarian follicles. Naturally occurring ovarian failure usually takes place around 50 years of age in the human. Premature ovarian failure occurs in 1% of women and is the result of acceleration of rate of ovarian follicular depletion in the majority of cases. Cytokines are involved in the mechanisms of ovarian follicular atresia, whether it occurs at a normal or accelerated rate. It is the balance between the actions of TGF alpha and TGF beta upon the granulosa cell that determines the fate of a nonluteinized follicle and between LH and INF gamma that determines destiny of a luteinized follicle. When granulosa cells express MHC antigens in response to IFN gamma or genetic stimulus, an autoimmune reaction ensures resulting in follicular atresia. If the immune processes proceed continuously rather than cyclically, premature ovarian failure occurs. Thus, not only do the immunologic and endocrinologic systems need to communicate to allow normal ovarian function, evidence exists to support the concept that they interact in the pathophysiology of ovarian failure.

Current status of immunologic recurrent pregnancy loss.

Normal mammalian pregnancy is confronted with a great number of self (autoimmune) and foreign (alloimmune) antigens that modulate the immune system of the mother. When maternal immune response is affected, recurrent pregnancy loss can result. Recurrent pregnancy loss affects 2% to 5% of reproducing couples. Half of these failures can be explained by genetic, hormonal, infectious, and anatomic factors. Eighty percent of the unexplained failures are proposed to have an immunologic cause. HLA typing, mixed lymphocytotoxic antibody tests, mixed lymphocyte culture reactions, lupus anticoagulant tests, and antiphospholipid antibody determination are methods used to study and differentiate between auto- and alloimmune response. Experimental therapies, including leukocyte immunization, seminal plasma suppositories, intravenous immunoglobulin, aspirin and prednisone, and heparin, have been tried to manage this condition. Results of randomized placebo-controlled clinical trials will aid in the choice of treatment for recurrent pregnancy loss. New assays to diagnose auto- and alloimmune factors in recurrent pregnancy loss are being investigated.

Ultrasonographic findings of pregnancy losses after treatment for recurrent pregnancy loss: intravenous immunoglobulin versus placebo

OBJECTIVE To describe the ultrasonographic findings of pregnancies that terminated in repeat abortion in women participating in an ongoing randomized placebo-controlled clinical trial evaluating the efficacy of intravenous (IV) immunoglobulin (Ig) in the treatment of recurrent spontaneous abortion (SA). DESIGN A prospective descriptive study of ultrasonographic findings of pregnancies from 27 women experiencing repeated recurrent SAs after entry into a clinical trial. SETTING Clinical practice at the Genetics & IVF Institute in Fairfax, Virginia. PATIENTS Women experiencing two or more consecutive recurrent SAs received either 500 mg/kg per mo IV Ig or placebo (albumin). To date 90 women have been enrolled in the clinical trial and 52 have achieved pregnancy. The outcome of the 52 pregnancies include 16 deliveries, 9 ongoing pregnancies, and 27 losses. INTERVENTIONS Ultrasonographic examinations performed in 27 women experiencing pregnancy loss are the subject of this study. MAIN OUTCOME MEASURES The frequency of ultrasonographic findings of empty gestation sac (blighted ovum) and intrauterine fetal demise (IUFD) is compared between patients receiving IV Ig and placebo. RESULTS Ultrasonographic findings of the 27 pregnancies losses included 11 blighted ova and 16 IUFDs. Of 11 blighted ova, 8 (73%) were in women receiving IV Ig and 3 (27%) were receiving placebo. Sixteen IUFDs were observed: 3 (19%) in women receiving IV Ig and 13 (81%) in women receiving placebo. Of 11 pregnancy losses occurring in women receiving IV Ig, 8 (73%) were blighted ova, 3 (27%) were IUFDs. Sixteen pregnancy losses occurred in women receiving placebo: 3 (19%) were blighted ova and 13 (81%) were IUFDs. The differences in frequency of blighted ova between IV Ig- and placebo-treated women was significant. CONCLUSION IV Ig is not effective in preventing blighted ova and may be effective in preventing IUFDs.

Mechanism of recurrent spontaneous abortion: I. Ultrasonographic findings

OBJECTIVES Our objective was to study the mechanisms of early pregnancy loss with ultrasonographic findings in pregnancies that terminated in repeat abortion in women with recurrent spontaneous abortion compared with patients with spontaneous abortion with no previous spontaneous abortion and with women with recurrent spontaneous abortion who had viable pregnancies. STUDY DESIGN A prospective, unselected study of 83 pregnancies followed from 4 to 12 weeks of gestation. Weekly transvaginal ultrasonography.among 43 pregnancies terminating in abortion were compared with 40 pregnancies ending in live birth with the Fisher exact test with a p value of significance assigned at less than 0.05. RESULT A significant difference in the presence of fetal heart activity was observed at 6 weeks +/- 5 days among women who subsequently aborted when recurrent spontaneous abortions were compared with no history of abortion (55% and 14%, p less than 0.02). Fetal pole size was small in 86% of pregnancies lost after fetal heart activity. CONCLUSION Ultrasonographic examination at 6 weeks can diagnose impending abortion with a sensitivity of 85%, specificity of 93%, positive predictive value of 92%, and negative predictive value of 87% among women with recurrent spontaneous abortion.

Anti-Endothelial Cell Antibodies: Another Cause for Pregnancy Loss?

PROBLEM: Previous studies demonstrated that unique tissue‐specific antigens expressed on vascular endothelial cells can serve as immunogens, and the apparent association between transplant rejection and antiendothelial cell (EC) antibodies is well established. A common feature of some placentas from women with recurrent pregnancy loss is the diffuse formation of microthrombi associated with changes in thromboresistant properties of endothelial cells, similar to the findings in rejected organs. Therefore, the prevalence of anti‐EC antibodies in patients with recurrent pregnancy loss and the role of these antibodies in cultured human endothelial cells from umbilical cord vein were studied.

Serum progesterone and estradiol concentrations in the early diagnosis of ectopic pregnancy after in vitro fertilization-embryo transfer

To determine if discriminatory P or E2 concentrations can be established for early diagnosis of EP after IVF, 282 pregnancies were studied 11, 13, 15, and 17 days after ET. Receiver-operator characteristic analysis of P and E2 indicated no clinically useful threshold value for EP. No significant differences in P or E2 was seen when intrauterine and extrauterine pregnancies or viable and nonviable pregnancies were compared. All EPs had P < 50 ng/mL and E2 < 500 pg/mL at 11 days after ET. Serum P and E2 cannot differentiate EPs from intrauterine pregnancies nor viable from nonviable pregnancies resulting from IVF.