Francisco Carmona

Obstetrical outcome of pregnancy in patients with systemic Lupus Erythematosus. A study of 60 cases

OBJECTIVE To analyze the course of maternal diseases and the outcome of pregnancy in patients with systemic Lupus Erythematosus (SLE). STUDY DESIGN During a period of 11 years we prospectively followed 60 pregnancies in 46 SLE patients in a tertiary care center in Barcelona (Spain). The management protocol included: (1) planning of conception when disease was inactive; (2) frequent follow-up visits by an internist-obstetrician team; (3) use of sequential ultrasonographic, Doppler and fetal echocardiographic examinations; (4) serial evaluations of maternal immunological condition; and (5) low dose aspirin from 1 month before attempting conception and throughout pregnancy was added in women with antiphospholipid antibodies. From 1985 until 1994 prednisone prophylaxis was used in all lupus patients during the last month of pregnancy and during the first month of the puerperium; from 1995 onwards this regime was abandoned. RESULTS The mean (S.D.) age of patients was 28.6 (4.8) years (range 20 to 42) and the mean (S.D.) previous duration of SLE was 6.25 (4.8) years (range 0 to 17). SLE was diagnosed during the pregnancy in two cases (3.3%) and the disease was active at conception in four cases (6.7%); at that time nine patients (15%) were taking prednisone. Antiphospholipid antibodies were positive in 16 patients (30.4%) and there were 10 (16.7%) pregnancies in patients having lupus nephropathy. There were three first-trimester miscarriages (5%) and four (6.7%) voluntary abortions. Obstetric complications in the remaining 53 pregnancies included: preterm delivery, 11 cases (20.8%); intrauterine growth retardation, five cases (9.4%); hypertension, 10 patients (18.9%), five of them fulfilling the criteria of preeclampsia; premature rupture of membranes, four patients (7.5%); finally, 13 neonates had a birthweight lower than 2500 g. There were 15 lupus flares (28.3%), giving a flare rate of 0.044 per patient/month. There were five neonatal deaths (perinatal mortality rate, 94 per thousand): one because of complete heart block, three due to severe hyaline membrane disease resulting from extreme prematurity and one intrauterine death in a patient having the Leiden mutation. CONCLUSION Pregnancy in patients with SLE should not be regarded as an unacceptable high-risk condition for the mother or her baby provided that conception is accurately planned and patients are managed according to a careful multidisciplinary treatment schedule.

Clinical study and follow-up of 100 patients withthe antiphospholipid syndrome

Abstract Objectives: To study the clinical characteristics at diagnosis and during follow-upof patients with the antiphospholipid syndrome (APS) and to analyze the influence of treatment on their outcome. Patients: One hundred patients with APS were included (86% female and 14%male; mean age, 36 years). Sixty-two percent had primary APS and 38% had APS associated with systemic lupus erythematosus (SLE). The median length of follow-up was 49 months. Results: Fifty-three percent of the patients had thromboses, 52% had thrombocytopenia, and 60% of the women had pregnancy losses. Patients with APS associated with SLE had a higher prevalence of hemolytic anemia ( P = .02), thrombocytopenia (platelet count lower than 100 × 10 9 /L) ( P = .004), antinuclear antibodies ( P = .0002), and low complement levels. Fifty-three percent of the patients with thrombosis had recurrent episodes (86% in the same site as the previous thrombotic event). Recurrences were observed in 19% of the episodes treated with long-term oral anticoagulation, in 42% treated prophylactically with aspirin, and in 91% in which anticoagulant/antiaggregant treatment was discontinued ( P = .0007). Multivariate analysis showed that prophylactic treatment and older age had an independent predictive value for rethrombosis. Prophylactic treatment during pregnancy (usually with aspirin) increased the live birth rate from 38% to 72% ( P = .0002). Conclusions: Patients with APS have a high risk of recurrent thromboses. Long-term oral anticoagulation seems to be the best prophylactic treatment to prevent recurrences. Prophylactic treatment with aspirin during pregnancy reduced the rate of miscarriages remarkably.

Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial

BACKGROUND Studies in macaques have indicated that androgens have some synergistic effects with FSH on folliculogenesis. This study investigated the usefulness of pretreatment with transdermal testosterone in low-responder IVF patients. METHODS Randomized clinical trial including 62 infertile women who had a background of the first IVF treatment cycle cancelled because of poor follicular response. Patients were randomized in two treatment groups in their second IVF attempt. In patients in Group 1 (n = 31), transdermal application of testosterone preceding standard gonadotrophin ovarian stimulation under pituitary suppression was used. In Group 2 (n = 31 patients), ovarian stimulation was carried out with high-dose gonadotrophin in association with a minidose GnRH agonist protocol. The primary end-point was the incidence of low-responder patients. The main secondary outcome was the incidence of patients reaching ovum retrieval. RESULTS The percentage of cycles with low response was significantly lower in Group 1 than in Group 2 (32.2 versus 71% 95% confidence interval for the difference, 15.7-61.6; P < 0.05). The number of patients with ovum retrieval tended to be higher in Group 1 than in Group 2 (80.6 versus 58.1% P = 0.09), the difference reaching statistical significance (81.2 versus 41.1%; P < 0.05) when only patients having normal basal FSH levels (16 and 17 patients in Groups 1 and 2, respectively) were considered. CONCLUSIONS Pretreatment with transdermal testosterone may improve the ovarian sensitivity to FSH and follicular response to gonadotrophin treatment in previous low-responder IVF patients. This approach leads to an increased follicular response compared with a high-dose gonadotrophin and minidose GnRH agonist protocol.

Risk Factors Associated with Fetal Losses in Treated Antiphospholipid Syndrome Pregnancies: A Multivariate Analysis

PROBLEM: Pregnancies in women with antiphospholipid syndrome (APS) are associated with obstetric complications despite treatment. The present study analyzes risk factors and evaluates fetal outcome in a large sample of treated APS pregnancies.
 METHOD OF STUDY: Seventy‐seven pregnancies in 56 women were included. Twelve selected variables potentially related to the outcome of treated pregnancies were analyzed in a multivariate logistic regression model.
 RESULTS: Treated women delivered 65 live infants at 24–41 weeks gestation (mean 36.7±0.5) but two neonatal deaths occurred. There were seven first‐trimester miscarriages (9%) and five intrauterine fetal demises (6.5%). Thus, the probability of having a live baby under treatment was 82% (95% CI 71.3–89.6%), a figure significantly greater (P<0.001) than that observed before therapy (25.7%; 95% CI 18.7–33.7%). Variables related with fetal outcome in the multivariate model were: preconceptional use of aspirin and abnormal umbilical artery Doppler velocimetry at 23–26 weeks gestation.
 CONCLUSIONS: The present report shows that in treated APS pregnancies: i) aspirin treatment started preconceptionally is an independent and significant prognostic factor associated with favorable fetal outcome; and ii) abnormal velocity waveforms in the umbilical artery predict adverse outcome of pregnancy.

Severe ovarian hyperstimulation syndrome: role of peripheral vasodilation

Objective To investigate the pathogenesis of the systemic hemodynamic disturbance and the renal production of vasodilator prostaglandins (PGs) in the ovarian hyperstimulation syndrome. Design Prospective longitudinal study. Setting Assisted Reproduction Unit of the Hospital Clinic i Provincial in Barcelona. Patients Five in vitro fertilization patients with ascites because of severe ovarian hyperstimulation syndrome. Main Outcome Measures Measurement during the syndrome and 4 weeks after recovery of the following: cardiac output, arterial pressure, estimated peripheral vascular resistances, hematocrit, standard renal function tests, plasma renin activity, plasma aldosterone, norepinephrine and antidiuretic hormone concentrations, and urinary excretion of PGE 2 and 6-keto-PGF 1α . Results During the syndrome, all patients showed arterial hypotension (74.2±3.8 versus 85.8±1.0mm Hg), tachycardia, increased cardiac output (6.4±0.2 versus 4.4±0.1L/min), low peripheral vascular resistance (929±52 versus 1,568±51dyn/sec per cm −5 ), high plasma levels of renin (72±25 versus 0.5±0.1ng/mL per h −1 ), norepinephrine (639±141 versus 203±21pg/mL) and antidiuretic hormone (6.1±1.6 versus 1.5±0.1pg/mL), and increased urinary excretion of PGE 2 (551±152 versus 106±44pg/min) and 6-keto-PGF 1α (470±76 versus 99±11pg/min). No evidence of hemoconcentration, as assessed by hematocrit, was observed in any patient. Conclusions (1) Severe ovarian hyperstimulation syndrome is related to marked arteriolar vasodilation that leads to underfilling of the arterial vascular compartment and stimulation of endogenous vasoconstrictor systems and (2) the increased urinary excretion of PGs probably represents a homeostatic response to antagonize the renal effects of these systems.

Inhibin, follicle-stimulating hormone, and age as predictors of ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment.

OBJECTIVE Our purpose was to determine the relative power of basal inhibin and follicle-stimulating hormone (defined before treatment) and the womans age both as single and combined predictors of ovarian response in an in vitro fertilization program where pituitary desensitization was routinely used. STUDY DESIGN The study was a retrospective analytic investigation of 120 women undergoing the first cycle of in vitro fertilization. Forty consecutive cycles canceled because of poor follicular response were initially selected. As a control group, the nearest completed in vitro fertilization cycles before and after each canceled cycle (i.e., the closest cycles in temporal relationship to the index cycle) were used. RESULTS The mean age and basal follicle-stimulating hormone level were significantly higher in the canceled than in the control group, whereas the basal inhibin level was significantly higher in the latter. Follicle-stimulating hormone and inhibin alone, with an accuracy (predictive value of ovarian response) of 70%, were better predictors of cancellation than age was. Any two or all three of these variables studied did not improve the predictive value of follicle-stimulating hormone or inhibin alone. CONCLUSION Age is a poorer predictor than pretreatment basal follicle-stimulating hormone and inhibin levels for ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment. Basal follicle-stimulating hormone and inhibin have similar predictive properties and could therefore be used interchangeably.

Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction

At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH.

Ovarian cystectomy versus laser vaporization in the treatment of ovarian endometriomas: a randomized clinical trial with a five-year follow-up

OBJECTIVE To investigate the effect of two laparoscopic techniques for treatment of ovarian endometriomas on recurrence rate. DESIGN Prospective randomized clinical trial. SETTING University teaching hospital. PATIENT(S) Ninety women with ovarian endometriomas. INTERVENTION(S) Patients were randomly selected to undergo either laparoscopic cystectomy (group 1) or laser vaporization (group 2) of ovarian endometrioma. MAIN OUTCOME MEASURE(S) Recurrence, evaluated by ultrasound scan examination, was assessed at 12 and 60 months of follow-up. RESULT(S) Endometrioma recurrence rate was higher, though not significantly different, in group 2 at 60 months of follow-up. Nevertheless, at 12 months of follow-up recurrences were statistically higher in group 2. CONCLUSION(S) The comparison between laparoscopic laser ablation and laparoscopic cystectomy for ovarian endometriomas after long-term follow-up showed earlier recurrences and a higher recurrence rate in the laser group, although at 5 years of follow-up there were no statistically significant differences.

Class III–IV Proliferative Lupus Nephritis and Pregnancy: A Study of 42 Cases

Problem:  A growing number of women with lupus nephritis wish pregnancy. Our aim was to analyze maternal and fetal outcome in pregnancies with the most severe forms (proliferative or class III–IV) of lupus nephritis.

Pregnancy outcome in systemic lupus erythematosus: good news for the new millennium.

Systemic lupus erythematosus (SLE) is the autoimmune disease that most commonly compromises pregnancy. Moreover, the relationship between SLE and pregnancy is in both directions. However, in the recent years there has been a great change in the perception of the effects of pregnancy on SLE flares and of SLE on pregnancy outcome (both fetal and maternal). The current experience indicates that pregnancy in patients with SLE should not be regarded as an unacceptable high risk condition for the mother or her baby provided that careful planning of conception and multidisciplinary monitoring and treatment are carried out.