Fibrous Histiocytoma-like Spindle-Cell Proliferation in the Nipple After Body-Piercing.

We report the case of a 19-year-old pregnant woman who presented with a nipple tumor. The lesion consisted in a spindle-cell proliferation with histologic features similar to those of fibrous histiocytoma, with a highly vascularized stroma. Although it showed low mitotic activity, scattered marked atypical cells with prominent nucleoli were identified, thus raising concern about the benign nature of the tumor. Immunohistochemical evaluation revealed that the spindle cells were diffusely positive for vimentin, focally positive for CD68, and negative for all the other tested antibodies. The patient had a total excision of the lesion and she is free of disease after 30 months. To our knowledge this is the first reported case of a lesion of this type in the nipple after body-piercing.

Circulatory dysfunction in asymptomatic in vitro fertilization patients. Relationship with hyperestrogenemia and activity of endogenous vasodilators.

Severe ovarian hyperstimulation syndrome (OHSS) is consistently associated with a circulatory dysfunction characterized by arterial hypotension, low peripheral vascular resistance, and increased activity of the renin-aldosterone system. To investigate whether circulatory dysfunction also occurs in asymptomatic patients undergoing controlled gonadotropin ovarian hyperstimulation under pituitary suppression for in vitro fertilization (IVF), 12 women without clinical manifestations of OHSS underwent sequential blood, urine, and hemodynamic measurements at five study points: the 7th day of the menstrual cycle preceding IVF (study point 1 or baseline), the day when pituitary suppression was shown (study point 2), the day of hCG ovulatory injection (study point 3), the day after hCG was injected (study point 4), and 7 days after hCG administration (study point 5). Mean arterial pressure, cardiac output, peripheral vascular resistance, plasma concentrations of estradiol (E2) and aldosterone, and plasma renin activity (PRA) were measured at each study point in all women. Serum levels of nitrite/nitrate, and plasma concentration of atrial natriuretic peptide, norepinephrine, adrenomedullin, and cyclic guanosine 3'5'-monophosphate were measured in samples obtained at study points 1 and 5. Multiple follicular development during ovarian stimulation associated with increased plasma E2 concentration (mean peak plasma E2 level, 2430 +/- 428 pg/mL, range 1630-3840 pg/mL) were observed in each woman. All patients developed a significant increase in cardiac output and decrease in arterial pressure and peripheral vascular resistance, and a marked elevation in PRA and aldosterone, all indicating the development of arteriolar vasodilation. Changes in circulatory measurements were temporarily related with the increase in E2 both being detected at study points 3-5. In contrast, there was a clear chronological dissociation between the increase in plasma E2 concentration and the stimulation of the renin-aldosterone system. PRA and aldosterone only reached abnormal levels at study point 5 in association with a significant increase in plasma norepinephrine concentration. Serum levels of nitrite/nitrate and plasma concentrations of atrial natriuretic peptide, adrenomedullin, and cyclic GMP were similar at study points 1 and 5. It is concluded that the circulatory dysfunction that characterizes severe OHSS is a universal event in patients undergoing controlled ovarian hyperstimulation for IVF. Although the increase in E2 levels during IVF cycles is associated with significant circulatory changes, the circulatory dysfunction that characterizes severe OHSS is clearly unrelated to the onset of hyperestrogenemia. Arteriolar vasodilation during IVF cycles was not associated with an increased activity of the vasodilator substances atrial natriuretic peptide, adrenomedullin, and nitric oxide.

Endometrial cytosolic and nuclear progesterone receptors in the luteal phase defect.

Basal body temperature profiles, serial serum progesterone levels, and serial endometrial biopsies were studied in 15 infertile women during 21 ovulatory cycles. Ten cycles (in 9 women) demonstrated luteal phase defects (LPD), diagnosed by a histological lag in endometrial maturation, normal luteal phase length, and normal luteal phase serum progesterone levels. Both normal and LPD cycles had a maximum amount of endometrial cytosolic progesterone receptor (PgR) on days 13-15, with a significant decline thereafter. LPD cycles had significantly lower endometrial nuclear PgR concentrations than did normal cycles during the proliferative phase, but luteal phase endometrial nuclear PgR levels were similar in both groups. In 2 LPD women treated with dydrogesterone, normal endometrial maturation and a decline in endometrial cytosolic PgR concentrations in the late luteal phase were found. Therefore, with the exception of endometrial nuclear PgR concentrations during the proliferative phase, we found no evidence for a major abnormality in endometrial PgR levels in LPD cycles with a lag in endometrial histology.

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Two-year prospective and comparative study on the effects of tibolone on lipid pattern, behavior of apolipoproteins AI and B.

OBJECTIVE: To investigate long-term lipid and lipoprotein changes in postmenopausal women treated with tibolone in a prospective study using appropriate control groups. DESIGN: Seventy-six of 105 postmenopausal women initially selected for this study completed the 2-year follow-up. Patients were allocated into three groups. The first received 2.5 mg/day tibolone continuously (n = 27; group T), the second received 0.625 mg/day conjugated equine estrogen plus 2.5 mg/day of medroxyprogesterone (group E-P) continuously (n = 25), and a third group contained an additional 24 women who did not receive replacement therapy; these constituted the untreated control group (group C). Plasma lipids and lipoproteins were determined in all patients before joining the study and also at 12 and 24 months after being included. RESULTS: Women treated with tibolone experienced the greatest decreases in cholesterol, both total and high density lipoprotein (HDL), and triglycerides (TG), whereas the highest increase in HDL was observed in the group E-P. A decrease in low density lipoprotein levels was detected in both therapy groups, whereas a significant increase was observed in the control group. TG were increased after E-P therapy. In all the groups, apolipoprotein AI showed parallel trends to HDL and apolipoprotein B to low density lipoprotein. CONCLUSIONS: Both therapy groups, tibolone and E-P, induced changes in levels of plasma lipids, lipoproteins and apolipoproteins. Long-term tibolone treatment is associated with a marked and significant decrease in HDL apolipoprotein AI and TG, an effect that defines the major difference with standard HRT. Clearly, further studies are necessary to establish the definite risk/benefit ratio of tibolone with respect to its overall effect on lipid metabolism.

Long-term compliance with estrogen replacement therapy in surgical postmenopausal women: benefits to bone and analysis of factors associated with discontinuation.

OBJECTIVE: To evaluate prospectively the effects of long-term estrogen replacement therapy (ERT) on bone density in surgical postmenopausal women treated for 5 years with two different modalities and to determine the factors associated with discontinuation of ERT. DESIGN: We included in the present study 165 women (mean age, 46.8 +/- 4.6 years) who had undergone surgical menopause. ERT was prescribed immediately after surgery, and bone mineral density was measured at the lumbar spine before the women entered the study and at 12, 24, 36, 48, and 60 months after being included. Treated patients were assigned at random to one of two groups. The first group received conjugated equine estrogens 0.625 mg/day continuously, and the second group received transdermal 17beta-estradiol 50 mg/day continuously. Treated groups were compared with a nontreated control group. RESULTS: Our data showed that although ERT clearly protected against bone loss in women who had experienced surgical menopause, only one third of the treated patients continued ERT at the end of follow-up. The main reason for discontinuation was fear of cancer (36.1 % of cases). In addition, no differences were observed between oral and transdermal groups of treatment. CONCLUSIONS: Long-term ERT may have a protective effect against bone loss in surgically postmenopausal women; however, two thirds of treated patients discontinued therapy after 5 years and 43% of them presented a negative balance on bone mass in one or more bone density assessments. For this reason, enhancing compliance and monitoring treatment are mandatory.

Use of gonadotropin-releasing hormone analog with tibolone to prevent cyclic attacks of acute intermittent porphyria.

A 25-year-old woman with a 10-year history of recurrent attacks of acute abdominal pain just before menstrual periods had acute intermittent porphyria (AIP) diagnosed when she was 23.5 years old. Many acute attacks required hospitalization. Suppression of the menstrual cycle with a gonadotropin-releasing hormone analog (GnRHa; triptorelin) and tibolone administration as add-back therapy resulted in absence of acute porphyric attacks. The patient had no acute attacks over a 1-year follow-up period. This case suggests that long-term GnRHa therapy with tibolone add-back may be a therapeutic option for patients with AIP.

Effects of HLA antibodies on pregnancy.

To investigate the effect of maternal HLA antibodies on the evolution of pregnancy, we tested sera from 187 pregnant women for the presence of lymphocytotoxic antibodies (anti-HLA-A, -B, and -C and anti-B lymphocytes or anti-HLA-DR). Patients were studied before 20 weeks, between 21 and 30 weeks, and between 31 and 40 weeks' gestation. No correlation was found between the presence of such antibodies and obstetric complications, fetal wastage, placental weight, or infant birth weight. Patients with anti-DR antibodies delivered more female than male infants by a 3:1 ratio.

Prolactin in the evaluation of luteal phase in infertility.

Hyperprolactinemia was detected in 15 of 130 infertile patients (11.5%) with regular menstrual cycles and no galactorrhea who underwent luteal phase evaluation by basal body temperature (BBT), plasma estradiol (E2), and progesterone (P) determination, and endometrial biopsy (repeated in a later cycle when the first was defective). Luteal phase length and plasma levels of P and E2 were similar in the hyperprolactinemic and normoprolactinemic patients. Moreover, a significantly higher incidence of inadequate luteal phase, histologically documented, was found in the normoprolactinemic group. It is concluded that the usefulness of plasma prolactin (PRL) determination in the evaluation of luteal function in infertility is scanty and that most histologically documented cases of luteal phase defects occur with euprolactinemia.

Luteal function after delayed ovulation.

Thirty-three infertile patients presenting spontaneous ovulatory cycles with long follicular phases (greater than or equal to 20 days) underwent a luteal function evaluation by basal body temperature, plasma progesterone (P), estradiol, and prolactin determination, and endometrial biopsy study. An endometrial luteal phase deficiency (LPD) was detected in 13 patients (39.4%), although in 10 of them (77%) P levels were normal. This study shows a high incidence of endometrial LPD among cycles with delayed ovulation and that in cases of LPD related to abnormal folliculogenesis, the endometrium is a better indicator than plasma P.

Histocompatibility in in vitro fertilization couples.

Major histocompatibility differences between mother and fetus may facilitate implantation and maintenance of pregnancy. Thus, we have investigated the compatibility of HLAs in couples with three successive failed IVF-ET cycles. The study couples (n = 15) shared a statistically greater number of HLAs than IVF couples achieving a viable pregnancy with their first IVF-ET attempt (n = 15) and a control group of 100 fertile couples. No difference between fertile and infertile control couples was observed regarding HLA sharing. Thus, we conclude that some cases of unsuccessful ETs after IVF might be caused by underlying close histocompatibility between partners.

The effect of postovulatory administration of dehydrogesterone on plasma progesterone levels.

The effect of dehydrogesterone upon corpus luteum function as reflected by plasma progesterone levels was investigated in eight healthy women. No significant difference was found between control cycles and treated cycles when dehydrogesterone, 20 mg daily, was given orally for 10 days after ovulation.

Dehydrogesterone treatment of endometrial luteal phase deficiency after ovulation induced by clomiphene citrate and human chorionic gonadotropin.

Twenty infertile patients being treated with clomiphene citrate (CC) and human chorionic gonadotropin (hCG) for induction of ovulation, with a defective endometrial secretory pattern despite normal plasma levels of progesterone, estradiol, and prolactin, were entered into treatment plans on a random basis involving the following: CC-hCG plus dehydrogesterone (group 1), and CC-hCG (group 2). Success rates were similar in both groups (20% and 30%, respectively), based on a corrected endometrial defect during the second treated cycle. It is concluded that progestational agents are of low therapeutic value in endometrial luteal phase deficiency induced by CC.

Early follicular phase follicle-stimulating hormone treatment of endometrial luteal phase deficiency.

Fifteen infertile women with inadequate luteal phase, histologically documented in at least two separate cycles, and normal midluteal plasma levels of progesterone (greater than or equal to 10 ng/mL), estradiol (70 to 300 pg/mL), and prolactin (less than 20 ng/mL) received "pure" follicle-stimulating hormone (pFSH), 150 IU intramuscularly, for 4 days (days 1 to 4 of the cycle). The endometrial defect was corrected in 7 of the 15 (46.7%) patients during the first treated cycle. Hormonal levels were similar in control and treatment cycles. Two of 5 patients with no additional infertility factors except luteal phase deficiency (LPD) became pregnant and carried to term singleton pregnancies. In 5 additional infertile patients with normal luteal function as assessed by endometrial histological study (2 cycles) and hormone measurements (first study cycle), a third biopsy was performed in a consecutive cycle under pFSH administration. In no case was the normal secretory pattern impaired. It is concluded that (1) some forms of LPD may be successfully treated by early follicular pFSH therapy and (2) pFSH does not alter the normal endometrial secretory pattern.

Immunoreactive endothelin plasma levels in severe ovarian hyperstimulation syndrome.

OBJECTIVE: To determine the plasma levels of immunoreactive endothelin in patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective longitudinal study. SETTING: Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona, a tertiary care setting. PATIENTS: Sixteen IVF patients with severe OHSS. MAIN OUTCOME MEASURES: Measurement during the syndrome and 4 to 5 weeks after recovery of the following: mean arterial pressure, hematocrit, plasma renin activity, plasma aldosterone, norepinephrine, antidiuretic hormone, atrial natriuretic peptide, and immunoreactive endothelin concentrations. RESULTS: During the syndrome patients showed decreased mean arterial pressure (70.0 +/- 1.1 versus 85.2 +/- 1.6 mm Hg), increased mean hematocrit values (45.5% +/- 1.1% versus 38.1% +/- 0.4%), oliguria (630.6 +/- 40.7 versus 1,306.2 +/- 43.9 mL/d), and very high plasma levels of renin (36.0 +/- 9.1 versus 1.2 +/- 0.08 ng/mL per hour), aldosterone (190.6 +/- 28.4 versus 14.8 +/- 1.5 ng/dL), norepinephrine (602.1 +/- 91.0 versus 220.5 +/- 12.1 pg/mL), antidiuretic hormone (4.1 +/- 0.7 versus 1.0 +/- 0.1 pg/mL), and atrial natriuretic peptide (10.9 +/- 1.6 versus 4.7 +/- 0.2 fmol/mL). Immunoreactive endothelin plasma levels were increased significantly during OHSS (8.9 +/- 0.9 versus 3.9 +/- 0.2 pg/mL) and all patients had elevated values during the syndrome. CONCLUSIONS: Circulating plasma levels of immunoreactive endothelin are elevated in patients with severe OHSS in parallel with other neurohormonal vasoconstrictor systems. It may represent a homeostatic response to maintain blood pressure.

Intravenous immunoglobulin preceding in vitro fertilization-embryo transfer for patients with repeated failure of embryo transfer.

OBJECTIVE: To determine the effectiveness of immunotherapy with high-dose IV immunoglobulin preceding IVF-ET for patients with repeated failure of ET. DESIGN: Prospective, observational. SETTING: Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona, a tertiary care setting. PATIENTS: Twelve consecutive tubal infertility patients experiencing repeated unexplained IVF-ET failure including at least three ETs replacing three to four fresh embryos each. Two women shared three or more human leukocyte antigens (HLA) with the husband. INTERVENTION: During the subsequent new IVF-ET cycle, each patient received 400 mg/kg IV immunoglobulin daily for 5 days during ovarian stimulation, that is, 5 to 7 days before ET. MAIN OUTCOME MEASURES: Clinical pregnancies. RESULTS: No implantation occurred. There were no side effects. CONCLUSIONS: High-dose IV immunoglobulin is not a useful tool for IVF-ET failure.

Increased induced monocyte tissue factor expression by plasma from patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To investigate whether monocyte expression of tissue factor is increased by plasma from patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective longitudinal study. SETTING: Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona, a tertiary care setting. PATIENTS: Nine IVF patients with severe OHSS. INTERVENTIONS: Pretreatment with leuprolide acetate was followed by gonadotropin treatment for ovarian follicular stimulation. After administration of hCG, a standard IVF-ET procedure was performed. MAIN OUTCOME MEASURES: Measurement during the syndrome and 4 to 5 weeks after recovery of induced monocyte tissue factor expression. RESULTS: In each of the nine patients, plasma obtained during the syndrome induced a significantly higher proportion of monocytes expressing tissue factor and a significantly higher intensity of tissue factor expression on monocytes than plasma obtained after recovery and control plasma. CONCLUSIONS: Procoagulant activity of blood monocytes, which is mediated principally by tissue factor expression, is increased in patients with severe OHSS. This fact may be important in thrombotic events associated with the syndrome.

Prevalence of human immunodeficiency virus in an infertile population.

OBJECTIVE: To assess the prevalence of human immunodeficiency virus (HIV) antibody in infertility. DESIGN: Prospective cross-sectional blind study. SETTING: An infertility clinic in Barcelona. PATIENTS: Three hundred thirty-five consecutive patients (308 infertile women and 27 spontaneous recurrent aborters) were seen between January 1989 and May 1990. MAIN OUTCOME MEASURE: Human immunodeficiency virus serostatus. RESULTS: The rate of seropositivity in the group of patients studied was 0.3% (95% confidence interval 0% to 0.9%). CONCLUSION: Further studies are desirable to establish the value of routine HIV testing in infertility patients as a population of women actively seeking 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 Clínic 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 PGE2 and 6-keto-PGF1 alpha. RESULTS: During the syndrome, all patients showed arterial hypotension (74.2 +/- 3.8 versus 85.8 +/- 1.0 mm Hg), tachycardia, increased cardiac output (6.4 +/- 0.2 versus 4.4 +/- 0.1 L/min), low peripheral vascular resistance (929 +/- 52 versus 1,568 +/- 51 dyn/sec per cm-5), high plasma levels of renin (72 +/- 25 versus 0.5 +/- 0.1 ng/mL per h-1), norepinephrine (639 +/- 141 versus 203 +/- 21 pg/mL) and antidiuretic hormone (6.1 +/- 1.6 versus 1.5 +/- 0.1 pg/mL), and increased urinary excretion of PGE2 (551 +/- 152 versus 106 +/- 44 pg/min) and 6-keto-PGF1 alpha (470 +/- 76 versus 99 +/- 11 pg/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.

The comparison of two gonadotropin-releasing hormone agonists in an in vitro fertilization program.

OBJECTIVE: To compare two gonadotropin-releasing hormone agonists (GnRH-a), buserelin acetate and leuprolide acetate [LA], used in combination with gonadotropins in ovarian stimulation for in vitro fertilization (IVF). DESIGN: Randomized prospective study. SETTING: Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona. PATIENTS: Thirty-five pairs of IVF patients who were matched on age, indication, and number of attempts. These women were randomized to receive either buserelin acetate plus gonadotropins (group B) or LA plus gonadotropins (group L). MAIN OUTCOME MEASURES: Luteolysis, ovarian response, and IVF outcome. RESULTS: The mean time for total ovarian arrest and the total dose of gonadotropins and estradiol levels on the day of human chorionic gonadotropin administration were similar in the two groups of patients. The number of follicles punctured, the number of oocytes retrieved, and the percentage of mature oocytes in group L were significantly higher. The number of embryos suitable for replacement and cryopreservation was higher in group L compared with group B approaching statistical significance. CONCLUSION: Our results warrant further studies to compare different GnRH-a as therapeutic tools in IVF.