International Collaboration and Commercial Involvement in Randomized Controlled Trials From 10 Leading Countries, 1997 Through 2019.

Randomized controlled trials (RCTs) affect clinical decisions and their number is increasing. However, trends in international collaboration on RCTs and involvement of healthcare-related industries, the latter of which may contribute to bias, are not known. The objectives were to identify concerns surrounding RCTs, and to quantify changes in (1) the numbers of RCT articles in journals of high clinical importance, (2) international collaboration, and (3) commercial involvement in RCTs by authors in countries that contribute the most to the scientific literature. This was not a systematic review of the medical literature. It is a descriptive study of trends during the past two decades. We extracted RCT articles from MEDLINE data (1997-2019). When grouped by authors' country, the analyses were limited to the 10 leading countries in the natural sciences, as defined by the Nature Index 2019 Annual Tables. The Core Clinical Journals (CCJ) filter in PubMed was used to identify journals that were likely to be highly relevant to clinical practice. RCT articles that included authors from multiple countries were used as examples of international collaboration, and RCTs in which at least one author's affiliation was corporate were considered to have commercial involvement. The annual number of RCT articles more than doubled (from 10,360 to 22,384), but the number published in the CCJ was essentially unchanged (from 2,245 to 2,346). The vast majority of RCT articles had US-based authors. International collaboration increased in nine of the 10 countries studied, and it was particularly common among researchers in Europe, Canada, and Australia. In contrast, international collaboration decreased in China. Regarding commercial involvement, between 1997 and 2019 the proportion of single-country RCTs with commercial involvement decreased (from 12.4% to 3.8% for the United States, and from 2.5% to 0.0% for Europe-Canada-Australia). In contrast, the proportion of international-collaborative RCTs with commercial involvement increased (from 9.2% to 17.6% for the United States, and from 17.9% to 21.3% for Europe-Canada-Australia). The largest change in commercial involvement was the 12-fold increase in Japan: from 3% to 36% (1997-2019). Japan was also noteworthy for its 28-percentage-point decrease in first-authorship of RCT articles from 2012 to 2019. In conclusion, recent increases in the number of RCT articles have occurred almost exclusively outside the CCJ. Thus, many newer RCT articles might have relatively low clinical relevance or impact. International collaboration has generally increased, along with commercial involvement. The latter has become particularly common in Japan, increasing the potential for sponsorship bias. The effects of ongoing attempts to reverse that trend should be evaluated.

Difference in the prevalence of gestational diabetes mellitus according to gestational age at 75-g oral glucose tolerance test in Japan: The Japan Assessment of Gestational Diabetes Mellitus Screening trial.

AIMS/INTRODUCTION: To evaluate the differences in the results of 75-g oral glucose tolerance tests (OGTTs) according to gestational age in Japan. MATERIALS AND METHODS: In this prospective cohort study, 2,578 pregnant women were divided into three categories based on their gestational age during the 75-g OGTT: <14 weeks' gestation, 14-23 weeks' gestation and 24-32 weeks' gestation. The association between gestational age and the results of the 75-g OGTT were evaluated using multivariable analysis. RESULTS: Early gestational age was associated with high fasting plasma glucose levels at the time of the 75-g OGTT, and low corresponding 1-h and 2-h plasma glucose levels. Compared with women with a gestational age of 24-32 weeks, women who had undergone the 75-g OGTT at <14 weeks' gestation had significantly higher odds of gestational diabetes mellitus diagnosis based on the currently used criteria in Japan (adjusted odds ratio 1.42, 95% confidence interval 1.07-1.90). CONCLUSIONS: The results of the 75-g OGTT varied by gestational age. The use of the same 75-g OGTT cut-off values for the diagnosis of gestational diabetes mellitus, regardless of gestational age, might lead to increases in the prevalence of gestational diabetes mellitus diagnosis in Japan.

Maternal body mass index is a better indicator of large-for-gestational-age infants compared with a 75-g oral glucose tolerance test in early pregnancy: The JAGS trial.

AIMS: There is no previous study comparing the predictive ability of maternal pre-pregnancy body mass index (BMI) versus a 75-g oral glucose tolerance test (OGTT) in early pregnancy for large-for-gestational-age (LGA) infants. METHODS: This multi-institutional prospective cohort study included 966 pregnant Japanese women. A multiple logistic regression model was applied to compare the effect size of pre-pregnancy BMI, fasting plasma glucose (PG), and 1- and 2-h PG levels after a 75-g OGTT performed before 22weeks gestation for LGA. After these variables were included separately into the model as per continuous variables 1 standard deviation (SD) increase, they were included simultaneously. RESULTS: When pre-pregnancy BMI, fasting PG, and 1- and 2-h PG after a 75-g OGTT were separately included in the model, the adjusted odds ratios (ORs) for LGA per 1 SD increase in pre-pregnancy BMI, fasting, and 1- and 2-h PG were 1.55 (95% confidence interval [CI]: 1.26-1.91), 1.26 (95% CI: 1.03-1.54), 0.99 (95% CI: 0.78-1.25), and 1.17 (95% CI: 0.93-1.49), respectively. When these variables were included simultaneously, the adjusted ORs per 1 SD increase in pre-pregnancy BMI, fasting, and 1- and 2-h PG were 1.52 (95% CI: 1.23-1.88), 1.19 (95% CI: 0.96-1.46), 0.77 (95% CI: 0.57-1.03), and 1.30 (95% CI: 0.96-1.76), respectively. CONCLUSIONS: Maternal pre-pregnancy BMI was more strongly associated with LGA compared with a 75-g OGTT in early pregnancy. Health-care providers should recognize that women with a higher pre-pregnancy BMI carry a higher risk for having LGA infants regardless of the results of a 75-g OGTT.

Pregnancy outcomes in women with type 1 and type 2 diabetes mellitus in a retrospective multi-institutional study in Japan.

The present study was performed to evaluate pregnancy outcomes in women with type 1 and type 2 diabetes mellitus (DM) in Japan. This multi-institutional retrospective study was conducted in 40 general hospitals in Japan during 2003-2009. We evaluated 369 and 579 pregnant women with type 1 and type 2 DM, respectively, and compared pregnancy outcomes between the two groups. Glycosylated hemoglobin levels in the first trimester did not differ significantly between the studied groups. Gestational weight gain was lower in type 2 DM than in type 1 DM. Although there were no significant differences in perinatal outcomes between the groups, the primary cesarean section rate was higher in type 2 DM than in type 1 DM. Multiple logistic regression analysis revealed that primigravida status, pre-gestational body mass index (BMI), gestational weight gain, chronic hypertension, and microvascular disease including diabetic retinopathy or nephropathy were associated with onset of pregnancy-induced hypertension. Further, pre-gestational BMI was associated with the need for primary cesarean section. This study demonstrated that no differences were observed in the rates of perinatal mortality and congenital malformation between pregnant women with type 1 DM and type 2 DM; however, women with type 2 DM displayed a higher risk of primary cesarean section.

Pregnancy outcomes of gestational diabetes mellitus according to pre-gestational BMI in a retrospective multi-institutional study in Japan.

The aim of this study was to determine the effects of pre-gestational body mass index on pregnancy outcomes of women with gestational diabetes in Japan. A multi-institutional retrospective study was performed. We examined pregnant women who met the former criteria for gestational diabetes in Japan, receiving dietary intervention with self-monitoring of blood glucose with or without insulin therapy. Women with gestational diabetes were divided into three groups according to pre-gestational body mass index: body mass index <25 (control group), 25 ≤ body mass index <30 (overweight group), body mass index ≥30 (obese group). Data from a total of 1,758 eligible women were collected from 40 institutions. Participants included 960 controls, 426 overweight women, and 372 obese women with gestational diabetes. Gestational weight gain was highest in the control and lowest in the obese group. The prevalences of chronic hypertension and pregnancy induced hypertension were higher in the overweight and obese groups than in the control group. Multiple logistic regression analysis revealed pre-gestational body mass index, gestational weight gain, chronic hypertension, and nulliparity to be associated with the onset of pregnancy induced hypertension, while the 75-g OGTT results were unrelated to pregnancy induced hypertension. The prevalence of large-for-gestational age was lower in infants born to obese women than in those born to overweight or control women. The present results suggest that medical interventions for obese women with gestational diabetes may contribute to reducing the prevalence of large-for-gestational age but would not achieve marked reductions in maternal complications.

Analysis on the promoter region of human decidual prolactin gene in the progesterone-induced decidualization and cAMP-induced decidualization of human endometrial stromal cells.

PURPOSE: To elucidate the promoter region of human decidual prolactin (dPRL) gene in the human endometrial stromal cells (ESC). METHODS: Various segments of the human dPRL promoter that direct the expression of the secreted alkaline phosphatase (SEAP) reporter gene were transfected into human ESC decidualized by estrogen (E) + progesterone (P) or cyclic AMP (cAMP) to identify E + P or cAMP responsive elements. RESULTS: The region between nucleotides -2038 and -1605 relative to the transcriptional initiation site includes two activator protein-1 (AP-1) sites, which both provided maximal response to E + P or cAMP in decidualized cells. When either AP-1 site was mutated, response in the promoter activity to both E + P or cAMP response showed a decrease compared with control. The region between -310 and -285 that contains consensus-binding sequences for transcription factors of CCAAT/Enhancer-binding proteins (C/EBP) contributed to E + P and cAMP response in decidualized cells. Also, the 5'-flanking region that extends 79 base pairs upstream, including an imperfect cAMP response element (CRE), contributed to E + P and cAMP response. In cells treated with E + P or cAMP for 10 days, mutant of C/EBP-binding site showed an increase in promoter activity comparing to dPRL-2038. In contrast, treatment with PKI showed a decrease in promoter activity in cells treated with E + P or cAMP alone. CONCLUSIONS: These results suggest that cAMP-induced region of the human dPRL promoter resides between -1862 and -1856, -1703 and -1697, -310 and -285, and that the sequences between -1862 and -1856, -1703 and -1697 of the promoter display E + P-induced promoter activity. Furthermore, the current study indicates that E + P or cAMP cooperatively regulate the dPRL gene transcription through some transcriptional factors such as C/EBP, CREB, and other cofactor(s), and that some repressor(s) or corepressor(s) may be involved in the C/EBP-binding site of the human dPRL promoter.

Ureteral obstruction associated with pelvic inflammatory disease in a long-term intrauterine contraceptive device user.

We report herein a case of ureteral obstruction associated with pelvic inflammatory disease in a long-term intrauterine contraceptive device (IUD) user. A 62-year-old woman presented with a 2-week history of left flank pain and high fever, but no abdominal pain. She had forgotten the use of an IUD. Retrograde pyelography showed a stricture in the lower third of the left ureter. Magnetic resonance showed swelling of the uterus wall and left parametria, but did not reveal the presence of an IUD. Subtotal hysterectomy, bilateral salpingo-oophorectomy and left nephronureterectomy was performed. The IUD was then found in the uterine cavity. The results of pathological and bacteriological findings for Actinomyces infection were negative. Therefore we diagnosed this case as ureteral obstruction associated with pelvic inflammatory disease. Ureteral obstruction associated with pelvic inflammatory disease in a long-term IUD user is extremely rare.

Expression of matrix metalloproteinase-3 in mouse endometrial stromal cells during early pregnancy: regulation by interleukin-1alpha and tenascin-C.

During the peri-implantation period, the endometrium undergoes tissue remodeling and cellular rearrangement. To clarify the involvement of matrix metalloproteinases (MMPs) in endometrial remodeling, we isolated total RNAs from the endometrium of non-pregnant and pregnant mice on days 3 to 5 and evaluated mRNA expression of MMP-2, -3, -9, -11 and -13 using reverse transcription-polymerase chain reaction (PCR). Prompt increases in MMP-3 and -13 mRNA were found on day 4 of pregnancy. Quantitative real-time PCR showed that expression of MMP-3 and -13 increased significantly on day 4, up to 8.4 +/- 2.7 times and 3.4 +/- 1.5 times, respectively, the level in non-pregnant endometrium (p < 0.05). On day 4, immunohistochemistry demonstrated MMP-3-positive endometrial stromal cells. At the same time, tenascin-C (TN-C) mRNA increased 11.1 +/- 4.0 times from the level in non-pregnant endometrium (p < 0.004). To clarify regulation of MMP-3 expression, we examined the effects of interleukin-1alpha (IL-1alpha) and TN-C on MMP-3 mRNA in cultured mouse endometrial stromal cells. Both substances resulted in a dose-dependent increase in MMP-3 mRNA (6.1 +/- 1.8-fold at 1 ng/ml of IL-1alpha and 3.9 +/- 1.8-fold at 10 mug/ml of TN-C). This study shows that MMP-3 expression is upregulated in endometrial stromal cells of the peri-implantation period and may be controlled by IL-1alpha and TN-C.

The ex utero intrapartum treatment (EXIT) procedure in giant fetal neck masses.

Giant fetal neck masses can cause airway obstructions with potential poor fetal prognosis after delivery. The relationship between the fetal neck mass and airway structure can be defined prenatally with ultrasound and magnetic resonance imaging (MRI). The ex utero intrapartum treatment (EXIT) procedure is an available technique to obtain a fetal airway while feto-maternal circulation is preserved. We present a case in which prenatally a giant fetal neck mass was diagnosed on ultrasound and MRI, and a successful EXIT procedure could be performed.

Expression of neuropeptide Y is increased in murine endometrial epithelium during the peri-implantation period under regulation by sex steroids.

Oligopeptide hormones are involved in cell-cell interaction during embryonal implantation and neuropeptide Y (NPY) is expressed in the human placenta and decidual cells in the third trimester of pregnancy. However, there is no report regarding the intrauterine localisation and the functions of NPY during the peri-implantation period. In the present study, the spatiotemporal changes in NPY expression in the murine uterus during the peri-implantation period were investigated using reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and immunohistochemical techniques, as were the effects of sex steroids on NPY mRNA expression in primary cultured murine uterine epithelial cells. Neuropeptide Y mRNA was increased in the pregnant murine uterus, as well as in the pseudopregnant murine uterus, during the peri-implantation period. Immunohistochemical analysis revealed increases in NPY expression in luminal and glandular epithelial cells and decidualised stromal cells. Neuropeptide Y mRNA expression was strongly induced in cultured epithelial cells in response to sex steroids. The data suggest that NPY is involved in cell-cell interactions during embryonic implantation.

A pilot study of neoadjuvant chemotherapy with mitomycin C, etoposide, cisplatin, and epirubicin for adenocarcinoma of the cervix.

BACKGROUND: To evaluate the efficacy and toxicity of the combination of mitomycin C, etoposide, cisplatin, and epirubicin (MEPA) as neoadjuvant therapy for patients with cervical adenocarcinoma. METHODS: Fourteen patients with cervical adenocarcinoma received neoadjuvant MEPA therapy followed by radical hysterectomy. The International Federation of Gynecology and Obstetrics stage was: IB1 in 2 patients, IB2 in 5, and IIB in 7. The MEPA regimen consisted of mitomycin C (15 mg/m2) on day 1, etoposide (70 mg/m2) on days 1 to 3, cisplatin (15 mg/m2) on days 1 to 5, and epirubicin (30 mg/m2) on day 1, with this course being repeated every 4 weeks. After two or three courses of chemotherapy, all patients underwent radical hysterectomy. Postoperative radiotherapy was given to 6 patients who showed risk factors at surgery. RESULTS: Of the 14 patients, 7 had complete remission (CR) clinically, 6 had partial remission, and only 1 showed no change. Examination of surgical material revealed no residual disease in 6 patients, and microscopic residual disease (<5 mm) in 2 patients. The patients who had no residual disease or microscopic disease in their hysterectomy specimens showed a significantly longer survival than those with macroscopic residual disease (P = 0.012). The dose-limiting toxicity was myelosuppression. Of the 33 treatment cycles administered, leukopenia of grade 3 or more occurred in 70%,and thrombocytopenia of grade 3 or more occurred in 79%. There were no therapy-related deaths. CONCLUSION: Although severe myelosuppression was also observed, there was a satisfactory response rate to MEPA therapy, which showed a good pathological CR rate.

Screening tests for gestational diabetes in Japan in the 1st and 2nd trimester of pregnancy.

The objective of this study was to investigate the utility and characteristics of various screening procedures for gestational diabetes mellitus (GDM) in Japan during the first trimester and between 24 and 28 weeks of pregnancy. The subjects were 749 pregnant women who came to our hospitals. A 50-g oral glucose challenge test (GCT), casual plasma glucose measurements, fasting blood glucose measurements, and glycosylated hemoglobin measurements were performed in the first trimester. Subjects with no abnormalities were tested again at 24-28 weeks of gestation. Of the 749 subjects, 22 (2.9%) tested positive for GDM. Of those 22 patients, 14 were diagnosed with GDM in the first trimester (63.6%) and eight in the second trimester (36.4%). This finding suggests the importance of screening for glucose intolerance in the first trimester. Furthermore, it appears that the GCT has the most utility for GDM screening; the other screening methods tested were not as useful because of their low sensitivity, particularly in the second trimester.

Ghrelin is involved in the decidualization of human endometrial stromal cells.

Successful implantation involves a complex interaction between the endometrium and the embryo. It is well known that several neuropeptides are expressed in the endometrium and placenta during embryonal implantation, suggesting an important role as chemical mediators of the feto-maternal relationship. Ghrelin has recently been identified as the endogenous ligand for the GH secretagogue receptor. Ghrelin is a peptide hormone with many physiological functions, and its expression in the human placenta has been reported. To investigate the involvement of ghrelin in embryonal implantation, we assessed the spatio-temporal expression pattern of ghrelin and its receptor in the human endometrium and placenta through the normal menstrual cycle and in early pregnancy. We also examined the effect of ghrelin on the decidualization of endometrial stromal cells (ESC). Weak expression of ghrelin mRNA was detected in the nonpregnant endometrium, and it was dramatically increased in the decidualized endometrium. A GH secretagogue receptor mRNA was detected in the endometrium throughout the normal menstrual cycle and in early pregnancy, but not in the first trimester placenta. Immunohistochemical analysis using an antighrelin antibody revealed strong signals in decidual cells and extravillous trophoblast cells. Coculture with first trimester placenta up-regulated ghrelin mRNA expression by primary cultured ESC, although sex steroids and 8-bromo-cAMP had no effect. In addition, ghrelin enhanced the decidualization of ESC induced by 8-bromo-cAMP (8-Br-cAMP) in vitro. Thus, ghrelin is a novel paracrine/autocrine factor that is involved in cross-talk between the endometrium and embryo during embryonal implantation.

PPAR-gamma, TNF-alpha messenger RNA levels and lipase activity in the pregnant and lactating rat.

Dramatic alternations in maternal metabolism occur during gestation and lactation, especially glucose and fat metabolism. For example, in rats, the amount of body fat mass increases during gestation, then decreases just prior to delivery, and remains low after parturition. To investigate the factors involved in such changes in maternal fat mass, messenger ribonucleic acid (mRNA) levels of adipocytokines, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and tumor necrosis factor-alpha (TNF-alpha), were examined in the intraabdominal adipose tissue of non-pregnant rats, pregnant rats and postpartum rats. We also examined the issue of whether apoptosis, which could be promoted by PPAR-gamma and TNF-alpha, is involved in any of the changes in maternal fat mass The activity of lipoprotein lipase (LPL) and hormone sensitive lipase (HSL) in adipose tissue was also measured. PPAR-gamma and TNF-alpha mRNA levels remained constant during the gestational and postpartum periods. Apoptosis was not detected at any time as evidenced by DNA laddering and in situ staining. LPL activity was significantly increased at day 5 and remained elevated until day 14 of gestation. HSL activity was significantly increased at day 10 of gestation and then decreased after delivery, at day 10 of lactation. In conclusion, during the gestational and postpartum period of rats, changes in maternal fat mass did not directly correlate with the levels of expression of PPAR-gamma and TNF-alpha mRNA. Apoptosis also does not appear to influence on fat mass change. The changes in LPL and HSL activities during gestation suggest that these enzymes might be regulators of maternal adipose tissue level.

Validity of trans-rectal ultrasound-guided embryo transfer against retroflexed uterus.

Background: Embryo transfer is one of the most critical steps affecting the success of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer. It has been reported that uterine contraction caused by touching the uterine fundus at the time of embryo transfer decreased the pregnancy rate. It was demonstrated that there is a significant rise in the pregnancy rate by adequate positioning of embryos. Transabdominal ultrasound-guided embryo transfer has been reported to improve the pregnancy rate compared with the clinical touch method. The improvement of the pregnancy rate under ultrasound guidance can be attributed to the accurate positioning of the embryos aided by good visualization without touching the uterine fundus. However, sometimes difficulties are encountered when visualizing the tip of the catheter in cases where the patient has a retroflexed uterus. Methods: In the present study, we investigated the difference in the pregnancy rates and in the implantation rates between transabdominal ultrasound-guided group and trans-rectal ultrasound-guided group in retroflexed cases. Results and Conclusion: We found that the pregnancy rate and the implantation rate were higher among the trans-rectal group compared with the transabdominal group in retroflexed cases. The difference between the two groups was statistically significant. (Reprod Med Biol 2003; 2: 159-163).

Polycystic ovary syndrome treated with laparoscopic ovarian drilling with a harmonic scalpel. A prospective, randomized study.

OBJECTIVE: To evaluate the endocrinologic profile and reproductive outcome after laparoscopic drilling using a harmonic scalpel for polycystic ovarian syndrome (PCOS) in clomiphene-resistant infertile women. STUDY DESIGN: We performed a prospective, randomized study of 34 infertile women with PCOS. Group A (17 women) underwent laparoscopic ovarian drilling using a harmonic scalpel laser. Group B (control group, 17 women) underwent laparoscopic ovarian drilling using a neodymium-yttrium-aluminum-garnet laser. Change in the hormonal profile after surgery, ovulation rate and pregnancy rate were compared between groups A and B. RESULTS: LH and testosterone serum levels and the LH-FSH ratio showed a statistically significant reduction after surgery, and the spontaneous ovulation rate was 94% in both groups. The cumulative pregnancy rates within two years of follow-up were 77% in group A and 60% in group B. CONCLUSION: Laparoscopic ovarian drilling using a harmonic scalpel is an effective treatment for PCOS in clomiphene-resistant, anovulatory women: it results in ovulation and conception without major complications.

Spinal intradural hemorrhage due to a neurinoma in an early puerperal woman.

A spinal intradural hemorrhage due to a neurinoma is very rare and requires emergency surgery. We report the first case of a spinal intradural hemorrhage due to a neurinoma in an early puerperal woman. The patient had a history of intermittent episodes of lower back pain for 3 years. The antenatal course to that time had been uneventful. Two days after a normal vaginal delivery, she presented with sudden onset of spinal lesion with severe symptoms and an emergency laminectomy was performed to remove an intradural hemorrhagic lesion due to a neurinoma. In this case, we speculate that clots in the intratumoral vessels spontaneously occurred during pregnancy and obstructions of these vessels followed by necrosis and hemorrhage of distal tissues occurred in the early postpartum stage. Moreover, the change in posture caused by the change in the maternal center of gravity following delivery, as well as the frequent bending required for the care of the newborn, may have been contributing factors. Mild but repetitive traction force caused by the change in posture and frequent bending may have created exertion on the vascular attachment to the nerve roots, causing the intradural hemorrhage.

The effect of RANTES on human sperm chemotaxis.

BACKGROUND: Follicular fluid (FF) is a powerful stimulator of human sperm hyperactivation and the acrosome reaction. FF causes sperm accumulation by way of chemotaxis. The chemoattractant in FF has not yet been identified in the human. It is well known that some types of chemokine such as RANTES (Regulated on Activation Normal T Expressed and Secreted Chemokine) exist in genital tract fluids (for example, FF, seminal plasma and uterine fluid). Few reports appear to exist concerning the direct effect of chemokines on the function of human sperm. METHODS: The chemotactic effect of RANTES on human sperm were investigated by capillary and double-chamber assays, while the chemokinetic effect was investigated using computer-assisted sperm analysis. RESULTS: Both the capillary and double-chamber assays demonstrated a significant chemotactic effect of RANTES on human sperm. Anti-RANTES rabbit IgG partially neutralized the chemotactic effect of FF. In contrast, no statistically significant chemokinetic effect was observed in any motility parameter. CONCLUSIONS: Here, it was demonstrated that mRNA for the RANTES receptors CCR-1 and CCR-5 are present in human sperm. Furthermore, RANTES is involved in the chemotactic effect of FF in vitro.

Autoimmune hepatitis complicated with antiphospholipid syndrome in pregnancy.

PROBLEM: There are few reports on the association between autoimmune hepatitis (AIH) and antiphospholipid syndrome; only five reports were found on a MEDLINE search between 1966 and 2001. Therefore, the etiology and the optimal treatment of them are not clear. METHOD OF STUDY: We encountered a case of AIH complicated by antiphospholipid syndrome in pregnancy. We present the clinical course and treatment of this case, and discuss some problems in managing such a patient. RESULTS: The patient received low-dose prednisolone and low-dose aspirin and delivered a live-born infant at term without any adverse effects. CONCLUSION: In this case, there was no relation between the variation of alanine aminotransferase (ALT) and the one of beta2-glycoprotein I (GPI)-dependent anticardiolipin antibody. It is supposed that there was no relation between the activity of AIH and the one of antiphospholipid syndrome, and it is also supposed that one is not secondary to the other.