Endocrine Mucin-Producing Sweat Gland Carcinoma and Primary Cutaneous Mucinous Carcinoma: A Case Series.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are rare low-grade neoplasms thought to arise from apocrine glands that share many histological features and are proposed to be on a single histopathologic continuum, with EMPSGC as the in situ form that may progress to the invasive PCMC. Management involves a metastatic workup and either wide local excision (WLE) with greater than 5 mm margins or Mohs micrographic surgery (MMS) in anatomically sensitive areas. We present 2 cases of EMPSGC and 3 cases of PCMC and review their clinical and histopathologic features, differential diagnoses, and treatment.

Photodynamic ablation of a selected rat embryo: a model for the treatment of extrauterine pregnancy.

BACKGROUND: To test the feasibility of photodynamic therapy (PDT)-based ablation of rat embryos as a model for PDT of extrauterine pregnancy (EUP) in humans. METHODS: A controlled pre-clinical study. Selected rat embryos [one per litter, n = 30, embryonic day 14 (E14)] were subjected to placental injection of a Palladium-bacteriochlorophyll derivative and illuminated to achieve selective photo-ablation. Histopathology studies were performed 48 h after treatment (E16). Parturition (E21) and breeding (approximately 12 weeks) after treatment were also evaluated. RESULTS: Using direct placental injection, nearly 80% of the treated rat embryos were selectively photo-ablated, leaving the remaining litter unharmed to achieve normal parturition. Treated animals retained fertility and normally implanted in both treated and untreated uterine horns attesting to the confined toxicity inherent to this approach. CONCLUSIONS: Although requiring respective adaptation to clinical application in terms of treatment protocols and designated hardware, photodynamic interventions using novel bacteriochlorophyll-based photosensitizers may prove applicable to treatment of EUP, as well as other gynecological pathologies and malignancies in a safe, minimally invasive manner.

Role of vascular endothelial growth factor in ovarian physiology and pathology.

OBJECTIVE: To review the current literature on the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in ovarian physiology and pathology. DESIGN: A computerized search was conducted to identify relevant in vitro and in vivo studies published in English. MEDLINE, Current Contents, and the Index Medicus were searched for studies published before January 2000. RESULT(S): VEGF/VPF is an angiogenic factor and a potent mitogen for vascular endothelium. During reproductive life, VEGF/VPF plays a role in the cyclic growth of ovarian follicles and corpus luteum development and maintenance, mediating ovarian angiogenesis. VEGF/VPF expression and secretion are induced by both FSH and LH/hCG receptor-activated pathways. CONCLUSION(S): VEGF/VPF expression and production within the ovary are critical for normal reproductive function. Defects in angiogenesis may contribute to a variety of disorders including anovulation and infertility, pregnancy loss, ovarian hyperstimulation syndrome, and ovarian neoplasms.

Autoimmunity and reproduction.

OBJECTIVE: To review the association between autoimmunity and reproductive failure. DESIGN: A MEDLINE search done from 1965 to 1996. More than 300 original and review articles were evaluated, from which the most relevant were selected. RESULT(S): Autoimmune processes now are accepted widely as one of the possible mechanisms of many human diseases. The presence of autoimmune disorders has been associated repeatedly with reproductive failure. On the other hand, reproductive failure may be the first manifestation of autoimmune disorders. CONCLUSION(S): When abnormal autoantibody levels are present in women with reproductive failure, the reproductive failure alone should be considered as one of the possible clinical expressions of autoimmune disorders. Two relevant questions of whether these patients should be treated for autoimmunity remain unsolved. A prospective, placebo-controlled trial is necessary to evaluate the importance of any treatment.

Intrauterine insemination before transfer of frozen-thawed embryos may improve the pregnancy rate for couples with unexplained infertility: preliminary results of a randomized prospective study.

OBJECTIVE: To evaluate whether a combination of IUI and frozen-thawed embryo transfer (FT-ET) with ovulation induction would improve the PR in couples with unexplained infertility. DESIGN: Prospective, randomized study. SETTING: In Vitro Fertilization Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): Sixty-two patients with unexplained infertility were assigned into two groups. The study group was composed of 32 women (38 cycles) who received ovulation induction followed by IUI and FT-ET. The control group was composed of 30 women (33 cycles) who received ovulation induction followed by FT-ET. INTERVENTION(S): Clomiphene citrate (CC) and hCG, IUI, and FT-ET. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) per cycle, PR per ET. RESULT(S): In the study group, the PR per cycle and per ET were 36.8% (14 of 38) and 40.6% (13 of 32), respectively. In the control group, the PR per cycle and per ET were 12.1% (4 of 33) and 14.3% (4 of 28), respectively. Statistically significant differences were found between the two groups in the PR per cycle (P=.02) and PR per ET (P=.03). No statistically significant difference was found between the groups for the stage in which the embryos were cryopreserved, the survival cleavage rates after thawing, grading of thawed embryos, and number of embryos transferred. CONCLUSION(S): In couples with unexplained infertility, the PR may be improved by combining IUI and FT-ET with ovulation induction. Performing IUI before thawing may prevent treatment cancellation in cycles with no surviving embryos.

Elevated levels of interleukin-6 in the follicular fluid at the time of oocyte retrieval for in vitro fertilization may predict the development of early-form ovarian hyperstimulation syndrome.

OBJECTIVE: To determine the possible predictive role of interleukin-2 (IL-2), IL-6, and tumor necrosis factor (TNF-alpha) in the development of early-form ovarian hyperstimulation syndrome (OHSS). DESIGN: Nested, case-control study. SETTING: An IVF unit, university-based program. PATIENT(S): Follicular fluid (FF) was obtained from 322 high responders. The study group and control group comprised 10 patients who developed early, severe OHSS and 10 who did not develop OHSS, respectively. An additional control group included 10 low-responder patients who did not develop OHSS. INTERVENTION(S): Ovulation induction with hMG combined with GnRH analogue. MAIN OUTCOME MEASURE(S): All FF samples were tested for IL-2, IL-6, and TNF-alpha. The patient's serum was tested for mean E2 and P concentrations. RESULT(S): Interleukin-6 levels in the FF were significantly higher in the OHSS group than in the two control groups, whereas no differences were found in IL-2 and TNF-alpha. No correlation was found between the FF concentrations of IL-2, IL-6, and TNF-alpha and the mean serum E2 levels or the number of oocytes retrieved. CONCLUSION(S): Elevated levels of IL-6 in the preovulatory FF at the time of oocyte retrieval for IVF may predict the development of early-form OHSS in high responders.

Patients with stages III and IV endometriosis have a poorer outcome of in vitro fertilization-embryo transfer than patients with tubal infertility.

OBJECTIVE: To evaluate the outcome of IVF in patients with stages III and IV endometriosis. DESIGN: Retrospective study. SETTING: The Sara Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Israel. PATIENT(S): Fifty-eight patients with stages III and IV endometriosis and 60 patients with tubal infertility. INTERVENTION(S): IVF-ET for all couples. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and birth rates. RESULT(S): The comparison between patients with endometriosis and those with tubal infertility indicated that the former had a poor IVF outcome in terms of reduced fertilization rate (40% vs. 70%), reduced pregnancy rate per cycle (10.6% vs. 22.4%), and reduced birth rate per cycle (6.7% vs. 16.6%). The differences were statistically significant. CONCLUSION(S): The results show an unfavorable outcome of IVF-ET in patients with endometriosis when compared with those who have tubal infertility.

Circulating autoimmune antibodies may be responsible for implantation failure in in vitro fertilization.

OBJECTIVE: To investigate the role of autoimmune factors as a possible cause for implantation failure as manifested by chemical pregnancy after IVF and ET. DESIGN: Anticardiolipin, anti-double-stranded DNA (dsDNA), antinuclear antibody, lupus anticoagulant, and rheumatoid factor serum levels were examined in patients with chemical pregnancies and in matched controls. SETTING: An IVF unit, university-based IVF program. PATIENTS: The study group included 21 patients who had one or more chemical pregnancies and no deliveries. The control group consisted of 21 patients who had conceived and delivered after IVF-ET treatment, without any history of fetal wastage, matched for age, type and duration of infertility, and number of previous IVF cycles. RESULTS: The incidence of circulating autoimmune antibodies in the study group was 33.3% (7/21). Three patients (14.2%) were positive for anticardiolipin, two (9.5%) were positive for antidsDNA, one (4.7%) for antinuclear factor, and one (4.7%) for rheumatoid factor. Autoimmune antibodies were not detected in any of the control group. CONCLUSION: Autoimmunity may play a role in implantation failure in IVF-ET. Circulating autoimmune antibody screening is therefore recommended after chemical pregnancy.

Analysis of 104 twin pregnancies conceived with assisted reproductive technologies and 193 spontaneously conceived twin pregnancies.

OBJECTIVE: To evaluate pregnancy outcome of assisted reproductive technology (ART)-conceived twin pregnancies. DESIGN: Retrospective study. SETTING: A tertiary obstetric care center. PATIENT(S): All twin pregnancies delivered > or = 24 weeks of gestation from January 1, 1996, to December 31, 1997. INTERVENTION(S): Maternal and neonatal record review. MAIN OUTCOME MEASURE(S): Pregnancy and perinatal outcome. RESULT(S): The study group comprised 104 ART-conceived twin pregnancies, and 193 non-ART-conceived pregnancies served as controls. Mean maternal age, the proportion of nulliparae, and the percentage of women who delivered before 34 weeks' gestation was higher among the study women, whereas mean gestational age was younger. The incidences of pregnancy-induced hypertension, uterine bleeding, premature contractions, intrauterine growth retardation, fetal death, discordance, and cesarean section were significantly higher in the study group. Correspondingly, in the study group, the mean birth weight of both twins was lower; more neonates weighed < 1, 500 g, more had Apgar scores of < 7 at 5 minutes, more were admitted to the intensive care unit, and more second twin neonates died. The outcome of twin pregnancies conceived spontaneously was comparable with those conceived by ovulation induction. CONCLUSION(S): Assisted reproductive technology-conceived twin pregnancies are at greater risk than non-ART-conceived ones for pregnancy complications and adverse perinatal outcome.

The ratio between carcinoma antigen-125 levels in the seminal plasma and serum may be a marker for fertilization in intracytoplasmic sperm injection.

OBJECTIVE: To assess the relationship between tumor marker carcinoma antigen-125 levels in seminal plasma and serum and fertilization rates in an IVF program, using intracytoplasmic sperm injection (ICSI). DESIGN: A prospective study. SETTING: IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): Twenty-five infertile patients with severe oligo-terato-asthenospermia syndrome and 25 fertile male donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum and seminal plasma carcinoma antigen-125 concentrations and fertilization rate per cycle. RESULT(S): In the infertile group, the seminal plasma carcinoma antigen-125 levels ranged from 22.0 to 1,284.0 U/mL (mean level +/- SD, 229.9 +/- 274.2 U/mL). In the normospermic fertile male donors, the seminal plasma carcinoma antigen-125 concentrations ranged from 12.2 to 336.7 U/mL (mean level +/- SD, 110.1 +/- 91.6 U/mL). This difference was statistically significant. The mean +/- SD ratio between the seminal plasma/serum carcinoma antigen-125 levels differed significantly between the infertile group (47.9 +/- 61.3) and the fertile male donors (5.7 +/- 3.5). In the infertile group, the ratio between the seminal plasma/serum carcinoma antigen-125 levels was found to be negatively correlated with the oocyte fertilization rate. CONCLUSION(S): The ratio between carcinoma antigen-125 levels in the seminal plasma and serum may be an indirect marker for male infertility and fertilization rate in IVF treatment using ICSI.

The effect of antioxidant treatment on human spermatozoa and fertilization rate in an in vitro fertilization program.

OBJECTIVE: To study the possible influence of antioxidant treatment on human spermatozoa and the fertilization rate in an IVF program. DESIGN: Prospective study. SETTING: In Vitro Fertilization Unit, Serlin Maternity Hospital, and the Laboratory of Male Fertility, Bar-Ilan University, Ramat-Gan, Israel. PATIENTS: Fifteen fertile normospermic male volunteers who had low fertilization rates in their previous IVF cycles. INTERVENTIONS: Vitamin E (alpha-tocopherol) 200 mg daily by mouth for 3 months. MAIN OUTCOME MEASURES: Lipid peroxidation potential (amount of malondialdehyde [MDA]), quantitative ultramorphologic analysis of spermatozoa, and fertilization rate per cycle. RESULTS: The high MDA levels significantly decreased from 12.6 +/- 9.4 nmol/10(8) spermatozoa to normal levels of 7.8 +/- 4.2 nmol/10(8) spermatozoa after 1 month of treatment. The fertilization rate per cycle increased significantly from 19.3 +/- 23.3 to 29.1 +/- 22.2 after 1 month of treatment. No additional effects on MDA levels and fertilization rate were observed after completion of treatment. With regard to the quantitative ultramorphologic analysis, none of the sperm cell subcellular organelles were affected significantly by vitamin E treatment. CONCLUSION: Vitamin E may improve the fertilization rate of fertile normospermic males with low fertilization rates after 1 month of treatment, possibly by reducing the lipid peroxidation potential, and with no change of the quantitative ultramorphologic analysis of subcellular organelles.

Second-trimester multifetal pregnancy reduction facilitates prenatal diagnosis before the procedure.

OBJECTIVE: To evaluate the pregnancy outcome of selective second-trimester multifetal pregnancy reduction (MFPR) compared to first-trimester MFPR. DESIGN: Cohort analysis. SETTING: In Vitro Fertilization Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): The study groups comprised 38 and 70 patients who underwent selective second-trimester MFPR (group 1) and first-trimester MFPR (group 2) at mean gestational ages of 19.7 +/- 3.3 weeks and 11.7 +/- 0.7 weeks, respectively. INTERVENTION(S): Ultrasonographically guided intracardiac injection of potassium chloride (KCl) solution. MAIN OUTCOME MEASURE(S): Pregnancy outcome and obstetric complications. RESULT(S): No statistically significant difference was found between group 1 and group 2 regarding mean gestational age at delivery (35.4 +/- 3.4 weeks and 35.9 +/- 3.1 weeks, respectively); mean birth weight (2,318.9 +/- 565.7 g and 2, 138.1 +/- 529.4 g); and the incidence of obstetric complications. These complications included pregnancy loss (5.2% and 15.7%), pregnancy-induced hypertension (0 and 10%), discordancy (12% and 18. 4%), intrauterine growth restriction (0 and 40%), and gestational diabetes (0% and 6%). However, the rate of all pregnancy complications was lower among second-trimester MFPR patients. CONCLUSION(S): Selective second-trimester MFPR is associated with favorable perinatal outcome and may facilitate detection of structural and chromosomal anomalies before the procedure and selective reduction of the affected fetus.

Levels of vascular endothelial growth factor are elevated in patients with ectopic pregnancy: is this a novel marker?

OBJECTIVE: To determine serum levels of vascular endothelial growth factor (VEGF) and evaluate their capacity to serve as a marker for the diagnosis of ectopic pregnancy (EP). DESIGN: Prospective, case-controlled study. SETTING: A tertiary care center. PATIENT(S): Twenty women with EP, 10 women with normal intrauterine pregnancy, and 10 women with abnormal intrauterine pregnancy, all at comparable stages of gestation. INTERVENTION(S): Serum samples were obtained from all women. MAIN OUTCOME MEASURE(S): All samples were analyzed for VEGF, progesterone, and beta-hCG by specific methods. RESULT(S): Women with EP had higher serum levels of VEGF than women with normal intrauterine pregnancy and women with abnormal intrauterine pregnancy (median levels, 226.8 pg/mL, 24.4 pg/mL, and 59.4 pg/mL, respectively). With a cutoff level of 200 pg/mL, serum VEGF could distinguish intrauterine from extrauterine pregnancy with a sensitivity of 60%, specificity of 90%, and positive predictive value of 86%. CONCLUSION(S): The increased serum VEGF levels in women with EP may facilitate this challenging diagnosis and reduce maternal morbidity and mortality.

Multifetal pregnancy reduction: a possible risk factor for periventricular leukomalacia in premature newborns.

OBJECTIVE: To investigate the possible role of multifetal pregnancy reduction as a risk factor for the development of periventricular leukomalacia, which has been associated with prematurity and twin pregnancies. DESIGN: A case-control study. SETTING: In Vitro Fertilization Unit and Intensive Care Nursery of the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): A total of 1,401 consecutive preterm infants who were born between January 1, 1994, and December 31, 1995. INTERVENTION(S): Cranial ultrasonographic evaluation of each infant within 3 days of birth. MAIN OUTCOME MEASURE(S): Premature infants who developed periventricular leukomalacia (cases) were compared with premature infants who did not develop this disorder (controls) when multifetal pregnancy reduction was considered. RESULT(S): Fourteen premature infants developed periventricular leukomalacia. Of these, 28.6% (4 infants) were exposed to multifetal pregnancy reduction, compared with 1.9% of the controls, giving an odds ratio (OR) of 20.9 (95% confidence interval [CI] 5.5-79.4). Adjustment of this OR for IVF treatment (OR, 18.6; 95% CI, 1.8-140.3), twinning (OR, 6.3; 95% CI, 1.3-30.3), and for both IVF treatment and twinning simultaneously (OR, 8.5; 95% CI, 1.7-42.2) did not explain all the observed associations between periventricular leukomalacia and multifetal pregnancy reduction. CONCLUSION(S): Our data suggest that multifetal pregnancy reduction may be an additional risk factor for periventricular leukomalacia among premature infants, regardless of twinning.

Levels of soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 are increased in women with ovarian hyperstimulation syndrome.

OBJECTIVE: To determine whether plasma and peritoneal fluid levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) are altered in women with ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective, case-control study. SETTING: Lis Maternity Hospital and the Sara Racine IVF Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): The study group comprised 16 women with severe OHSS. The control groups comprised 10 women treated with controlled ovarian hyperstimulation and 8 women with normal findings at diagnostic laparoscopy. INTERVENTION(S): Plasma samples were obtained from the study group and the first control group. Peritoneal fluid samples were obtained during paracentesis from the study group and during diagnostic laparoscopy from the second control group. MAIN OUTCOME MEASURE(S): Samples were assayed by specific ELISA for sVCAM-1 and sICAM-1. RESULT(S): The mean peritoneal fluid levels of sVCAM-1 and sICAM-1 and the mean plasma levels of sVCAM-1 were significantly higher in the women with OHSS than in the control groups. However, the mean plasma levels of sICAM-1 were comparable. A positive correlation was demonstrated between the levels of sVCAM-1 and plasma E2 at the time of hCG administration and between the levels of sICAM-1 and number of ova retrieved. CONCLUSION(S): Our findings suggest that soluble cell adhesion molecules may have a role in the pathogenesis and progression of OHSS.

Role of angiopoietins in reproductive tract angiogenesis.

UNLABELLED: Components of the female reproductive system undergo a number of programmed angiogenic processes coupled with cyclic evolution and decline of ovarian, endometrial, and placental structures. The development of a new vascular network requires a remarkable degree of coordination between different cell types undergoing complex changes. This implies that the expression of the inciting angiogenic factors are hormone dependent. Recently, a second family of vascular endothelial growth factors was identified, the angiopoietins. Angiopoietins are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis, after the induction of new capillaries by vascular endothelial growth factor (VEGF). There are four known angiopoietins, and their specificity for the vascular endothelium results from the restricted expression pattern of their tyrosine kinase receptor, Tie2. In this review, we discuss the molecular characterization and mechanism of action of angiopoietin-1 and angiopoietin-2 in reproductive tract angiogenesis. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the angiogenic process and specifically explain the role of angiopoietics in reproductive tract angiogenesis and compare the differences between the various proteins that are involved in angiogenesis.

The risk of fragile X premutation expansion is lower in carriers detected by general prenatal screening than in carriers from known fragile X families.

The Fragile X syndrome is the most common cause of inherited mental retardation. For a female premutation carrier, the risk of having a child with a full mutation is positively correlated with the size of the premutation. The current study was performed to evaluate the risk of premutation expansion in the offspring of average-risk carriers detected by general prenatal screening. Over a 4-year period, 9,660 women underwent DNA screening for FMR1 mutation/premutation at the Tel Aviv Sourasky Medical Center. A premutation was defined as a CGG repeat number >50 in the 5' untranslated region (UTR) of exon 1 in the FMR1 gene. The study included only individuals with no family history of X-linked mental retardation or known FMR1 mutations. A premutation was found in 85 women (1 in 114), 68 of whom consented to have prenatal diagnoses in 74 pregnancies. The abnormal allele was transmitted to the offspring in 44 pregnancies. Of these, no change in allele size was noted in 35 pregnancies (79.6%), and expansion within premutation range was evident in 4 pregnancies (9%). In 5 pregnancies (11.4%), expansion to the full mutation was noted. This occurred only in carriers having more than 90 repeats. We conclude that the likelihood of Fragile X premutation expansion to full mutation is significantly lower in individuals ascertained by general prenatal carrier testing than in those from known Fragile X families.

Rectal carcinoma during pregnancy: a reminder and updated treatment protocols.

Rectal carcinoma is rare during pregnancy. Prognosis is usually unfavorable due to late diagnosis, and management, especially regarding the mode of delivery, is controversial. Current treatment of rectal carcinoma includes neoadjuvant chemoradiotherapy, which may influence obstetrical management. We present a case report and discuss obstetrical management in view of updated knowledge and therapeutic approaches.

Anaerobic glycolysis. The metabolism of the preovulatory human oocyte.

OBJECTIVES: The aim of the study was to investigate the process of glycolysis in gonadotropic, hyperstimulated, human ovarian follicles. STUDY DESIGN: Follicular fluid (FF) lactate and glucose concentrations were measured in 26 patients with tubal factor infertility undergoing in vitro fertilization treatment. RESULTS: The mean FF lactate and glucose concentrations were 3.17+/-0.90 mM with positive, and 3.39+/-0.91 mM with negative correlations to follicular size. FF lactate concentration correlated negatively to glucose levels. CONCLUSIONS: Our study confirms in vivo the anaerobic glycolysis in gonadotropic, hyperstimulated human ovarian follicles.

Morphologic and histopathologic characteristics of placentas from twin pregnancies spontaneously conceived and from reduced and nonreduced assisted reproductive technologies.

OBJECTIVE: To prospectively evaluate morphologic and histopathologic characteristics of placentas from twin pregnancies obtained by assisted reproductive technologies (ART) and non-ART and to evaluate the influence of previous fetal reduction on placental features. STUDY DESIGN: Fifty-five placentas from consecutive deliveries of ART-obtained and 50 placentas from consecutive deliveries of non-ART-conceived twin pregnancies were investigated by one pathologist, who was blinded to specimen origins. The patients' demographic and clinical data were also recorded. RESULTS: The mean maternal and gestational ages were similar in both groups. ART-obtained pregnancies were associated with an increased incidence of pregnancy complications and lower mean birth weight. Placentas from ART-obtained pregnancies were mostly of the dichorionic type and were thinner, weighed less and had more infarctions as compared to non-ART-conceived pregnancies. Placental characteristics of reduced ART-obtained twin pregnancies were comparable to those of nonreduced ones. The second twin's placenta in all groups weighed less and had a higher incidence of anomalous umbilical cord insertion. CONCLUSION: Placentas from ART-obtained twin pregnancies appear to have more pathologic features as compared to those of non-ART-conceived ones. Fetal reduction does not significantly affect the remaining placentas.