Chemoprevention and prophylactic surgery in ovarian carcinoma

Introduction

Ovarian cancer is the leading cause of death from gynaecological malignancy, especially because of late diagnosis. The objective of the study was to provide the clinician with current concepts regarding prevention of ovarian cancer.

Material and methods

A computerized search of articles published was performed using the Medline database We performed a review of the literature (PubMed, Embase) using the following search terms (MeSH and non-MeSH): prevention, chemoprevention, chimioprevention, ovarian cancer, ovarian, ovary, carcinoma, tumor, tumour.

Results

Oral contraceptive and acetaminophen use may provide substantial protection against ovarian cancer, whereas aspirin, carotenoids and non-steroidal anti-inflammatory agents do not decrease the risk. However, to date, there is no recommendation concerning low risk population. At the opposite, young women (< 35–40 years old) presenting with BRCA1 or 2 mutation or Lynch syndrome may be counseled for chemoprevention using oral contraceptive. For high risk women over 35–40 years old, prophylactic bilateral salpingo-oophorectomy should be performed. Indeed, it has been showed that prophylactic surgery significantly decrease mortality rates in high risk women.

Conclusion

Large randomized studies are required to assess the efficacy of ovarian cancer chemoprevention in low risk women. High-risk women over 35–40 years old should be counseled for prophylactic salpingo-oophorectomy or for chemoprevention using oral contraceptive.     

Length difference between equine <Emphasis Type="Italic">ZFX</Emphasis> and <Emphasis Type="Italic">ZFY</Emphasis> genes and its application for molecular sex determination

Purpose  

We analyzed the sex chromosome-encoding ZFX-ZFY genes and tested molecular sexing using the amplification patterns of intron 9 of ZFX-ZFY in the horse.     

Lack of association between genetic polymorphisms in three folate-related enzyme genes and male infertility in the Chinese population

PurposeThis study explored the possible association of four single nucleotide polymorphisms (SNPs) of the three folate-related enzyme genes: MTHFR C677T and A1298C, MTR A2756G and MTRR A66G, with male infertility in the Chinese population.MethodsThe polymorphic distributions of the four SNPs (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G) were investigated by the method of SNaPshot in a Chinese cohort including 296 idiopathic infertile males with azoospermia or oligozoospermia and 204 fertile males.ResultsWe found no evidence for an association between any of these variants (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G) and male infertility.ConclusionsThere is no evidence for an association between male infertility and polymorphism of the three folate-related enzyme genes in the Chinese population.     

Meta-analysis of the association of AhR Arg554Lys,AhRR Pro185Ala,and ARNT Val189Val polymorphisms and endometriosis risk in Asians

PurposeSeveral studies have suggested an association between the polymorphisms AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val and endometriosis, but results have been inconclusive. The aim of the present study was to assess these associations by meta-analysis.MethodsEligible literatures were retrieved from PubMed, ISI Web of Science, Elsevier Science Direct, and several Chinese databases. The pooled odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were calculated with a random or fixed-effect model.ResultsA total of six eligible studies were included. Regarding the AhR Arg554Lys and ARNT Val189Val polymorphisms, no obvious associations were found in either overall analysis or subgroup analysis based on the country, source of control, sample size, and genotyping method. For the AhRR Pro185Ala polymorphism, overall results suggested a marginal association with endometriosis susceptibility under the dominant model (OR = 1.65, 95 % CI = 1.00–2.72). Furthermore, a significantly increased risk for endometriosis was found in the subgroups which used the TaqMan method for genotype analysis or had a sample size ≥200.ConclusionsThis meta-analysis suggested that the polymorphisms of AhR Arg554Lys and ARNT Val189Val are not associated with endometriosis, while the AhRR Pro185Ala polymorphism may be associated with endometriosis risk. However, further case–control studies with larger sample sizes are needed to confirm our results.     

The association of PTPN22 polymorphism with endometriosis: effect of genetic and clinical factors

Objective

To investigate the possible effect of clinical and genetic variables on the association between PTPN22 and endometriosis.

Methods

PTPN22, ACP₁ and p53 codon 72 genetic polymorphisms and duration of previous pharmacological treatment were studied. The study sample consisted of 132 women hospitalized for endometriosis diagnosed by laparoscopic intervention and histologically confirmed: 359 healthy blood donors were studied as controls. PTPN22, ACP₁ and p53 codon 72 genotypes were determined by DNA analysis. Discriminant statistical analysis, logistic regression analysis, chi square of independence, power test and linear correlation were performed using SPSS programs.

Results

A significant increase of PTPN22 *T allele in endometriosis is observed in women carrying ACP₁*C allele, in women carrying p53 codon 72 *Pro allele and in women with prolonged pharmacological treatment.

Conclusions

PTPN22 may not be a primary factor in the etiology of endometriosis but may cooperate with clinical and genetic factors influencing susceptibility and clinical course of disease. These new observations point to a multifactorial origin of endometriosis and help to explain the reported differences between human populations concerning the association between PTPN22 and endometriosis.     

The ovarian response to standard gonadotrophin stimulation depends on FSHR, SHBG and CYP19 gene synergism

Purpose

Follicle stimulating hormone, sex hormone-binding globulin and cytochrome P450 aromatase play crucial roles in the regulation of mammalian reproduction. The synergistic effect of FSHR 307(T/A)/FSHR 680(N/S), SHBG(TAAAA)_n and CYP19(TTTA)_n genotypes on ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction (IVF/ICSI) was explored.

Methods

The study population consisted of 300 women under IVF/ICSI treatment and 300 women with at least with at least one successful child birth as controls. The polymorphisms were genotyped while the follicular size, the follicle and oocyte numbers were recorded during oocyte retrieval.

Results

The genotype analysis, excluding heterozygotes for each particular polymorphism, revealed eight combined homozygotic FSHR/SHBG/CYP19 genotypes. A gradual reduction in the number of follicles and oocytes from FSHR 307Thr/680Asn allele/long SHBG allele/long CYP19 allele homozygotes to FSHR 307Ala/680Ser allele/short SHBG allele/short CYP19 allele homozygotes was observed (20.36 ± 6.74 vs. 8.05 ± 2.47, p < 0.008 and 13 ± 4.63 vs. 6.1 ± 2.32, p < 0.02, respectively).

Conclusions

FSHR/SHBG/CYP19 combined genotypes are associated with ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction.     

Analysis of the DAZ gene family in cryptorchidism and idiopathic male infertility

OBJECTIVE: To investigate whether partial deletions of the DAZ gene family on the Y chromosome are associated with cryptorchidism, similar to that found for complete AZF deletions. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): A total of 193 azoospermic and severely oligozoospermic men: 95 with a history of cryptorchidism and 98 classified as idiopathic. INTERVENTION(S): A two-part study for Y chromosome microdeletions was performed: a polymerase chain reaction (PCR)-based analysis for complete AZF deletions and partial DAZ gene analysis by PCR-restriction digestion assay for single-family variants. MAIN OUTCOME MEASURE(S): Presence and type of AZF deletions and number of DAZ genes present. RESULT(S): The frequency of complete AZF deletions was similar in idiopathic (13.3%) and cryptorchid men (11.6%), but partial DAZ deletions were found only in infertile subjects without cryptorchidism (7.1%). The testicular phenotype was similar in men with complete AZF deletions and partial DAZ deletions, therefore the contribution of the other AZF genes in determining the spermatogenic impairment is still unclear. CONCLUSION(S): Our findings suggest that the loss of only some copies of DAZ is sufficient to lead to severe male infertility, but it is not a frequent finding in cryptorchid men.     

The role of gene defects underlying isolated hypogonadotropic hypogonadism in patients with constitutional delay of growth and puberty

Variation in FGFR1, GNRHR, TAC3, and TACR3 was evaluated in 146 Finnish subjects with constitutional delay of growth and puberty. Although one male subject carried a previously undescribed heterozygous deletion (Phe309del) in GNRHR, which segregated with delayed puberty in his family, mutations in the coding regions of FGFR1, GNRHR, TAC3, and TACR3 are not likely to underlie common constitutional delay of growth and puberty.     

Use of parthenogenetic activation of human oocytes as an experimental model for evaluation of polar body based PGD assay performance

Purpose  

To develop an experimental model to assess the feasibility of polar body preimplantation genetic diagnosis without requiring oocyte fertilization.     

Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage

OBJECTIVE: To identify associations or interrelations between carriage of the methylenetetrahydrofolate reductase (MTHFR) C677T, the MTHFR A1298C, the factor V Leiden G1691A, the factor II prothrombin G20210A, the human platelet antigen (HPA) 1 C12548T, and the apolipoprotein (APO) B R3500Q polymorphisms and idiopathic recurrent miscarriage (IRM). DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred forty-five women with a history of three or more consecutive pregnancy losses before 20 weeks gestation and 101 healthy postmenopausal women with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous punctures. MAIN OUTCOME MEASURE(S): Multiplex polymerase chain reaction was performed to identify the different alleles of six candidate genetic risk factors for IRM (MTHFR C677T, MTHFR A1298C, factor V Leiden G1691A, factor II prothrombin G20210A, HPA 1 C12548T, and the APO B R3500Q). RESULT(S): Allele and genotype frequencies of all polymorphisms were not significantly different between the study and the control groups. Also, no significant associations occurred between combinations of polymorphisms and the occurrence of IRM. CONCLUSION(S): Our data fall short of showing any significant association between single polymorphisms of the MTHFR, the Factor V Leiden, the Factor II Prothrombin, the HPA 1 and APO B genes or combinations of these polymorphisms and the occurrence of IRM.     

Evaluation of vertical transmission of Toxoplasma gondii in Calomys callosus model after reinfection with heterologous and virulent strain

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes a variety of clinical syndromes, but the infection is severe in immunocompromised individuals and during pregnancy due to the possibility of transplacental transmission of the parasite causing congenital toxoplasmosis. Vertical transmission of the parasite usually occurs when females are primarily infected during pregnancy. Calomys callosus is resistant to T. gondii ME49 strain, which presents a moderate virulence and congenital disease occurs only during the acute phase of infection. The aim of this study was to determine whether vertical transmission occurs when females of C. callosus chronically infected with ME49 strain of T. gondii are reinfected with a highly virulent strain (RH, type I). Females were infected with cysts of the ME49 strain. On the 1st day of pregnancy, animals were reinfected with tachyzoites of the RH strain. In the 19th day of pregnancy, placentas and embryos were processed for morphological analysis, immunohistochemistry and for detection of the parasite by PCR and mouse bioassay. Morphological and immunohistochemical analyses revealed the presence of parasites only in placental tissues. Mouse bioassay results showed seroconversion only in mice that were inoculated with placental tissues. Also, T. gondii DNA was detected only in placental samples. Congenital toxoplasmosis does not occur in C. callosus females chronically infected with the moderately virulent ME49 strain of T. gondii and reinfected with the highly virulent RH strain, thus indicating that primary T. gondii infection before pregnancy leads to an effective long-term immunity preventing transplacental transmission to the fetus.     

Transporte intraabdominal y endovaginal de paquetes de droga (body packer y body pusher)

Vaginal smuggling of drug containers (body pusher) is a relatively uncommon subtype of intraabdominal trafficking of illicit substances (body packer). We report two cases of drug smuggling by simultaneous internal (body packer) and vaginal (body pusher) concealment of drug packages. Conservative management, based on laxative treatment, careful extraction of endovaginal packets and close clinical observation —with radiological tests for confirmation— is a safe and useful therapeutic approach for these patients. Early suspicion and treatment of body pusher, with severe potential complications —mainly, acute cocaine intoxication—, remains essential.     

Comparison of early-onset neonatal sepsis caused by Escherichia coli and group B Streptococcus

OBJECTIVE: The purpose of this study was to compare maternal characteristics and neonatal morbidity and mortality rates that are associated with early-onset neonatal sepsis that is caused by group B Streptococcus and Escherichia coli. STUDY DESIGN: This was a retrospective review of newborn infants with a positive blood culture (and/or cerebrospinal fluid) that was positive for either E coli or group B Streptococcus during the first week of life. Data were abstracted from maternal and neonatal medical records. RESULTS: Among 28,659 deliveries during the study period, 102 episodes of early-onset neonatal sepsis were identified, 61 of which were caused by group B Streptococcus and 41 of which were caused by E coli. E coli sepsis cases had a lower birth weight, a higher percentage with 5-minute Apgar score <7, and a longer stay in the hospital neonatal intensive care unit and required mechanical ventilation more frequently. Death after early-onset neonatal sepsis with E coli was also more frequent. CONCLUSION: Early-onset sepsis with E coli is associated with more morbidity and a higher mortality rate compared with early-onset group B Streptococcus.