Association of miRNA-145 with the occurrence and prognosis of hydrosalpinx-induced defective endometrial receptivity.

MiR-145 is reported to facilitate inflammation and is also associated with unsuccessful embryonic implantation. Whether miR-145 mediates inflammatory response underlying hydrosalpinx-induced defective endometrial receptivity (ER) remains unclear, and this study attempted to clarify this point. Endometrium samples were collected from hydrosalpinx patients (case, n = 243) and patients with tubal patency/obstruction (control, n = 187). The peripheral blood samples of cases and controls were collected to determine the genotypes of miR-145 SNPs. The value of miR-145 expression in the diagnosis and prognostic estimation of hydrosalpinx was assessed using ROC curve and regression analysis, respectively. Lipopolysaccharide (LPS) cell model was established with endometrial cells, and cells were transfected with miR-145 mimic, inhibitor, or negative control. MiR-145 and cytokine levels were quantified by quantitative reverse transcription PCR or western blot. MiR-145 expression was significantly higher in hydrosalpinx compared to control group, and high miR-145 expression was significantly associated with moderate/severe tube lesion, high pulsatility index (>1.06), and high resistance index (>0.61) in hydrosalpinx patients. ROC curve analysis indicated that monitoring miR-145 expression may be useful for the diagnosis of hydrosalpinx (AUC = 0.704). A alleles of rs41291957 (G>A) and rs353292 (G>A) were significantly associated with an increased risk of hydrosalpinx compared to G allele (p < 0.05), yet the mutant allele of rs353291 (A>G) and rs4705343 (T>C) significantly reduced susceptibility to hydrosalpinx compared to the wild type allele. Treatments with miR-145 mimic and LPS in endometrial cells significantly increased the levels of transforming growth factor-ß1, tumor necrosis factor -α, interleukin (IL)-6, and IL-8 compared to negative control, while treatment with miR-145 inhibitor decreased the cytokine levels. In conclusion, abnormally expressed miR-145 may be involved in hydrosalpinx-induced ER defects by regulating the inflammatory response.

Integrated analysis of mRNA and protein expression profiling in tubal endometriosis.

Tubal endometriosis (tubal EM) is a subtype of endometriosis (EM) associated with fallopian tube impairments and infertility. Since the molecular mechanism underlying tubal EM is not clear, we assume that an aberrant transcriptome of fallopian tube epithelium and microenvironment changes caused by cytokines in tubal fluid are possible causes. The aim of this study was to identify potential hub mRNAs/proteins of tubal EM through integrated transcriptomic and proteomic analyses and to elucidate significant pathways, cellular functions, and interaction networks during the initiation and progression of tubal EM. We obtained human fallopian tube epithelium and tubal fluid samples from patients with and without tubal EM. Tubal epithelia were analyzed using microarray, and tubal fluid was analyzed using quantitative label-free LC-MS/MS. We identified differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) and determined common mRNAs/protein. We observed 35 commonly deregulated mRNAs/proteins, and IPA indicated that cellular movement, inflammatory response, and immune cell trafficking were significantly activated during the pathogenesis of tubal EM. We also identified acute phase response signaling pathway activation as a unique pathogenesis signature of tubal EM. Our results demonstrate that an integrated analysis of the transcriptome and proteome has the potential to reveal novel disease mechanisms at a molecular level.

The impact of HSF on endometrium

Summary Objective: We conducted the research in order to explore the impact of hydrosalpinx fluid (HSF) on endometrium. Method: HSF group: 261 patients with HSF scheduled to undergo laparoscopic surgery 3 to 7 days after menstruation in our center. Hysteroscopy would also be performed in order to observe the endometrial morphology during the surgery. Sixty (60) patients would be randomly selected for endometrial biopsy in order to detect the inflammatory cytokines TNF-a and IL-2 mRNA. Non-HSF group: 210 patients with no evidence of HSF due to chronic salpingitis or pelvic adhesion. IVF-ET treatment was performed after eliminating the factor of male infertility and hysteroscopy was conducted before the treatment. Fifty (50) patients underwent endometrial biopsy in order to detect TNF-a and IL-2 mRNA. Results: Hysteroscopy was performed in 261 patients with HSF and 210 patients without HSF. The incidence rate of endometritis manifestation among these two groups of patients was 37.2% (97/261) and 20.5% (43/210), respectively. The incidence rate of endometritis in the patients with HSF is significantly higher than in the patients without HSF (p<0.05). Sixty (60) patients from the HSF group and 50 patients from the non-HSF group were regrouped according to inflammatory and normal manifestation after the endometrial biopsy. There were 49 patients in the inflammatory manifestation group and 61 patients in the normal manifestation group. RT-PCR technology was adopted to detect the expression of inflammatory cytokines TNF-a and IL-2 mRNA in endometrial tissue. The level of TNF-a mRNA expression in endometrial tissues with inflammatory manifestation was higher than in normal endometrium (76.75±11.95 vs. 23.45±9.75, p<0.01). There are significant differences between them. The level of IL-2 mRNA expression in endometrial tissues with inflammatory manifestation was higher than that found in normal endometrium (80.56±13.35 vs. 35.12±8.35, p<0.01). There are significant differences between them. Conclusion: Chronic endometritis is related to HSF and may therefore affect endometrial receptivity.

The impact of HSF on endometrium.

OBJECTIVE: We conducted the research in order to explore the impact of hydrosalpinx fluid (HSF) on endometrium. METHOD: HSF group: 261 patients with HSF scheduled to undergo laparoscopic surgery 3 to 7 days after menstruation in our center. Hysteroscopy would also be performed in order to observe the endometrial morphology during the surgery. Sixty (60) patients would be randomly selected for endometrial biopsy in order to detect the inflammatory cytokines TNF-a and IL-2 mRNA. Non-HSF group: 210 patients with no evidence of HSF due to chronic salpingitis or pelvic adhesion. IVF-ET treatment was performed after eliminating the factor of male infertility and hysteroscopy was conducted before the treatment. Fifty (50) patients underwent endometrial biopsy in order to detect TNF-a and IL-2 mRNA. RESULTS: Hysteroscopy was performed in 261 patients with HSF and 210 patients without HSF. The incidence rate of endometritis manifestation among these two groups of patients was 37.2% (97/261) and 20.5% (43/210), respectively. The incidence rate of endometritis in the patients with HSF is significantly higher than in the patients without HSF (p<0.05). Sixty (60) patients from the HSF group and 50 patients from the non-HSF group were regrouped according to inflammatory and normal manifestation after the endometrial biopsy. There were 49 patients in the inflammatory manifestation group and 61 patients in the normal manifestation group. RT-PCR technology was adopted to detect the expression of inflammatory cytokines TNF-a and IL-2 mRNA in endometrial tissue. The level of TNF-a mRNA expression in endometrial tissues with inflammatory manifestation was higher than in normal endometrium (76.75±11.95 vs. 23.45±9.75, p<0.01). There are significant differences between them. The level of IL-2 mRNA expression in endometrial tissues with inflammatory manifestation was higher than that found in normal endometrium (80.56±13.35 vs. 35.12±8.35, p<0.01). There are significant differences between them. CONCLUSION: Chronic endometritis is related to HSF and may therefore affect endometrial receptivity.

MUC1 expression in fallopian tubes of women with hydrosalpinx.

OBJECTIVE: To analyze the expression of MUC1 in Fallopian tubes with or without hydrosalpinx, using four different types of antibody. STUDY DESIGN: In a case-control study, immunohistochemical expression of MUC1 was examined in Fallopian tubes derived from women with hydrosalpinx (n=10) and normal controls (n=10). Four different antibodies were used for the detection of both extracellular (214D4, HMFG1, VPM654) and intracellular (EPR1023) MUC1 epitopes. Staining intensity was measured with ImageJ software. Expression of MUC1 mRNA was quantified by quantitative RT-PCR. Statistical analysis was performed with Student t-test (mean ± SD) and Mann-Whitney U-test (median [range]). RESULTS: The mean (±SD) and median [range] intensity of MUC1 in controls vs. hydrosalpinx were: 214D4-67.5 ± 11.3 vs. 74.8 ± 14.69 (P=0.22); HMFG1-95.3 [642-1079] vs. 97.0 [502-1550] (P=0.91); VPM654-41.1 [314-914] vs. 46.0 [390-1424] (P=0.1); EPR1023-24.7 ± 7.3 vs. 57.4 ± 31.3 (P=0.01). MUC1 mRNA was 0.16 [008-05] vs. 0.09 [005-019] (P=0.06). Ectodomains and mRNA of MUC1 are unchanged in tubes from hydrosalpinx patients. In contrast, immunodetection of the MUC1 cytoplasmic tail is enhanced in tubes from hydrosalpinx. CONCLUSION: Fallopian tubes with hydrosalpinx have a selective accumulation of MUC1 cytoplasmic tail, but not difference in the ectodomain.

Correlation between overexpression of transforming growth factor-beta 1 in occluded fallopian tubes and postsurgical pregnancy among infertile women.

OBJECTIVE: To compare the expression profiles of transforming growth factor-beta 1 (TGF-ß1) and its receptors in occluded tubes of infertile women with those of control patients and to evaluate the potential correlation with postsurgical pregnancy outcome. METHODS: The expression profiles of TGF-ß1, TGF-ß1R1, and TGF-ß1R2 in occluded fallopian tubes were compared using immunohistochemistry between 60 infertile patients with adhered tubes and 60 control patients with normal tubes; potential correlations with postsurgical fertility were evaluated at 2-year follow up. RESULTS: Immunostainings of TGF-ß1, TGF-ß1R1, and TGF-ß1R2 were all significantly elevated in patients with adhered tubes compared with normal specimens (P<0.001). In adhered specimens, correlation analyses showed positive correlations between TGF-ß1 and TGF-ß1R1 (P=0.008), and TGF-ß1 and TGF-ß1R2 (P=0.035). At 2-year follow up, 32 of the 60 infertile women had achieved normal pregnancies, 5 had had ectopic pregnancies, and 23 remained infertile. Correlation analysis showed that TGF-ß1 expression level was negatively correlated with pregnancy outcome (r=-0.445, P<0.001), independent of adhesion severity or patient age. CONCLUSION: TGF-ß1 expression was independently correlated with the postsurgical pregnancy outcome among infertile women.

TLR4 in Chlamydia trachomatis infections: knockout mice, STD patients and women with tubal factor subfertility.

Chlamydia trachomatis is the most prevalent sexually transmitted bacterium in the world with almost 100 million new cases each year, some of which will develop tubal pathology. Clear differences in its clinical course of infections have been observed, and recently it has been shown that 40% is based on host genetic factors. We used an integrated approach based on infection of Toll-like receptor 4 (TLR4) knockout mice and immunogenetic analysis of female sexually transmitted disease (STD) patients (susceptibility) and women with C. trachomatis-associated tubal factor subfertility (severity). The results in TLR4 knockout mice suggest that the protection against reinfection is more solid in normal as compared to the TLR4-deficient mice. In humans the functional TLR4 single nucleotide polymorphism studied was not involved in the susceptibility to infection. However, C. trachomatis immunoglobulin (Ig) G-positive subfertile women with tubal pathology were more than twice as likely to be carriers of the mutant TLR4 +896 G allele as compared to those without tubal pathology; however this observation did not reach statistical significance. In conclusion, both the murine model and the human immunogenetics studies show a slight effect upon TLR4 deficiency in the severity of infection but not in the susceptibility to infection.

Analyses of polymorphisms in the inflammasome-associated NLRP3 and miRNA-146A genes in the susceptibility to and tubal pathology of Chlamydia trachomatis infection.

Susceptibility to Chlamydia trachomatis infections is 40% host based. microRNA-146a is a negative regulator of Tolllike receptor (TLR) signaling and possesses functional polymorphisms which decrease the production of premiR-146a and mature miR-146a. Single nucleotide polymorphisms (SNPs) in NLRP3 are associated with decreased NLRP3 expression and hypoproduction of interleukin (IL)-1beta. We investigated whether the SNPs miR-146a G>C (rs2910164), NLRP3 C>T (rs4925663) and G>A (rs12065526) are associated with the susceptibility to and severity of C. trachomatis infection. The genotypes of three SNPs were tested in two cohorts: cohort 1 consists of Dutch women (n = 318) attending a sexually transmitted disease (STD) clinic and cohort 2 (n = 277) consists of subfertile (n = 184) and healthy Finnish women (n=93). While in cohort 1 the analyzed SNPs were not associated with the susceptibility to C. trachomatis infections (C. trachomatis-positive vs. C. trachomatis-negative), we showed in C. trachomatis-positive women that the NLRP3 mutant AG and AA genotypes were a risk factor for the development of symptoms (P = 0.047, OR = 2.9) and more specifically for having lower abdominal pain (genotype AA: P = 0.022, OR = 31.3). In the Finnish tubal pathology group versus the control group no statistical significant differences in the incidences of the SNPs studied were found, nor for the degree of tubal pathology. In conclusion, the mutant NLRP3 A allele is a risk factor for the development of symptoms, specifically lower abdominal pain, after a C. trachomatis infection in women attending an STD clinic.

Association of MICA gene polymorphisms with Chlamydia trachomatis infection and related tubal pathology in infertile women.

BACKGROUND: The course and morbidity of Chlamydia trachomatis infections are determined by host genetic factors, virulence of the micro-organism and environmental factors. Major histocompatibility complex class I chain-related A (MICA) gene is highly polymorphic as a potential host genetic candidate. The aim of this study was to investigate the association of polymorphic extracellular domains of MICA with C. trachomatis infection and related tubal factor infertility. METHODS: Effect of MICA on the susceptibility to C. trachomatis infection and its association with tubal pathology were investigated in 214 infertile women recruited during the period from 2004 to 2007. Subjects were tested for C. trachomatis antibodies, and were further divided into two groups: those with (n = 42) and without (n = 59) tubal pathology based on laparoscopy results. The relationship between prevalence of C. trachomatis, tubal pathology and MICA allele polymorphisms was analysed. RESULTS: Women with tubal infertility more often had antibodies to C. trachomatis [66.7 versus 39.1%; odds ratio (OR): 3.12, 95% CI: 1.68-5.78, P = 0.004] than infertile women without tubal pathology. Moreover, allele 008 had a highly negative correlation with C. trachomatis infection (P(c) = 0.0036, OR: 2.14), while other allele polymorphisms showed no significant association with the disease. No statistically significant differences were found in the MICA allele frequencies of C. trachomatis-positive women with or without tubal pathology. CONCLUSIONS: The association of a specific MICA allele with C. trachomatis IgG antibodies among women with infertility suggests that the MICA locus might modify host susceptibility to C. trachomatis infection.

Chronic isolated fallopian tube torsion.

OBJECTIVE: To describe a case of chronic isolated fallopian tubal torsion in a woman without identifiable risk factors and discuss the difficulty of diagnosis. DESIGN: Case report. SETTING: University-based reproductive endocrinology and infertility center. PATIENT(S): Multiparous woman with no risk factors of torsion of the fallopian tube presenting with chronic right lower quadrant pain. INTERVENTION: Laparoscopy with subsequent salpingectomy. MAIN OUTCOME MEASURE(S): Resolution of symptoms. Preservation of ovary and future fertility. RESULT(S): Patient's symptoms resolved after salpingectomy. Information regarding future fertility is pending. CONCLUSION(S): Isolated fallopian tube torsion is rare and often difficult to diagnose. Despite ultrasonographic evidence of arterial and/or venous flow to the adnexa, adnexal torsion cannot be ruled out. If clinical suspicion for torsion is high, early diagnosis and treatment via laparoscopy is encouraged as a means of preserving fallopian tube integrity and maintaining fertility, especially in reproductive-age women.

Survivin gene expression in granulosa cells from infertile patients undergoing in vitro fertilization-embryo transfer.

OBJECTIVE: To evaluate survivin gene expression in granulosa cells from infertile patients and examine the relationship between survivin gene expression and infertile clinical background. DESIGN: Prospective study. SETTING: IVF-ET program at Osaka Medical College. PATIENT(S): Twenty-eight patients underwent ovulation induction for IVF-ET performed because of tubal infertility, male factor infertility, or endometriosis. INTERVENTION(S): Granulosa cells obtained at oocyte retrieval were examined for survivin gene expression by quantitative reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURE(S): Hormone environment, number of oocytes, fertilization rate, high-quality embryo rate, pregnancy rate, and expression of survivin genes. RESULT(S): Survivin gene expression was detected in all granulosa cells. The gene expression levels of survivin in patients with endometriosis were significantly lower than those in patients with male factor infertility. The gene expression levels of survivin in total pregnant patients were higher than those in total nonpregnant patients and than those in the male factor infertility group, and there was no correlation between gene expression level and serum E(2) level. CONCLUSION(S): Survivin may be used as an indicator of the success of IVF-ET, and the existence of endometriosis may elevate the apoptosis of granulosa cells.

The CD14 functional gene polymorphism -260 C>T is not involved in either the susceptibility to Chlamydia trachomatis infection or the development of tubal pathology.

BACKGROUND: The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women. METHODS: The different CD14 -260 C>T genotypes were assessed by PCR-based RFLP analysis in three cohorts: 1) A cohort (n = 576) of women attending a STD clinic, 2) a cohort (n = 253) of women with subfertility, and 3) an ethnically matched control cohort (n = 170). The following variables were used in the analysis: In cohort 1 the CT-DNA status, CT IgG serology status, self-reported symptoms and in cohort 2, the CT IgG serology status and the tubal status at laparoscopy. RESULTS: In the control cohort the CC, CT and TT genotype distribution was: 28.2%, 48.2%, and 23.5% respectively. No differences were found in the overall prevalence of CD14 -260 genotypes (28.1%, 50.7%, and 21.2%) in cohort 1 when compared to the control cohort. Also no differences were observed in women with or without CT-DNA, with or without serological CT responses, with or without symptoms, or in combinations of these three variables. In subfertile women with tubal pathology (cohort 2, n = 50) the genotype distribution was 28.0%, 48.0%, and 24.0% and in subfertile women without tubal pathology (n = 203), 27.6%, 49.3% and 23.2%. The genotype distribution was unchanged when CT IgG status was introduced in the analyses. CONCLUSION: The CD14 -260 C>T genotype distributions were identical in all three cohorts, showing that this polymorphism is not involved in the susceptibility to or severity of sequelae of C. trachomatis infection.

Increased cystic fibrosis transmembrane conductance regulator (CFTR) expression in the human hydrosalpinx.

BACKGROUND: Hydrosalpinx (HSP), characterized by abnormal fluid accumulation in the Fallopian tube, is one of the main causes of infertility in women; however, the mechanism underlying the formation of hydrosalpinx fluid (HF) remains elusive. The present study investigated the possible involvement of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, in the pathogenesis of hydrosalpinx. METHODS: Masson's trichrome staining was used to characterize epithelial transformation in human HSP; RT-PCR, immunohistochemistry and immunofluorescence staining were used for CFTR expression and localization. RESULTS: Masson's trichrome staining showed areas of epithelial transformation, focally attenuated and pseudostratified. Immunostaining showed enhanced CFTR immunoreactivity in the focally attenuated and pseudostratified areas of HSP epithelium. RT-PCR revealed that CFTR expression in HSP was significantly greater than that in normal Fallopian tubes. CONCLUSIONS: These results indicate that HSP epithelium undergoes epithelial transformation with elevated CFTR expression, which may lead to increased transepithelial electrolyte and fluid secretion resulting in HF formation. The present findings may lead to the development of new treatment strategies for infertile patients with HSP.

Interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms are not associated with tubal pathology and Chlamydia trachomatis-related tubal factor subfertility.

BACKGROUND: Chlamydia trachomatis infections have been associated with tubal pathology. However, not all C.trachomatis-infected women actually develop tubal pathology. Recently, host genetic factors such as the interleukin-1 gene cluster have been linked to inflammatory and infectious diseases. METHODS: Dutch Caucasian women were investigated for (i) the role of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms in tubal pathology (group 1); and (ii) the presence of these gene polymorphisms in C.trachomatis IgG-positive women with and without tubal pathology (group 2). Group 1 consisted of women with (n = 40) or without (n = 95) tubal pathology, respectively, and group 2 of C.trachomatis IgG-positive women of whom 28 had tubal pathology at laparoscopy and 47 did not. IL-1B-511 and IL-1B+3954 gene polymorphisms were assessed by PCR-restriction fragment length polymorphism (RFLP), and the variable number of tandem repeats (VNTR) of the IL-1RN gene were assessed by a PCR-based assay. RESULTS: Neither IL-1B-511, IL-1B+3954 nor IL-1RN genotypes, allele or carrier frequencies showed significant association with tubal pathology or C.trachomatis post-infection-based tubal pathology. CONCLUSIONS: The data obtained suggest that specific IL-1 gene polymorphisms are not associated with the tubal pathology risk or to the development of C.trachomatis-based post-infectious severe sequelae.

Hydrosalpinx fluid diminishes endometrial cell HOXA10 expression.

OBJECTIVE: To determine the effect of hydrosalpinx fluid on the expression of HOXA10, an essential regulator of endometrial receptivity. DESIGN: In vitro study. SETTING: Academic medical center. PATIENT(S): Patients with unilateral or bilateral hydrosalpinx. INTERVENTION(S): Hydrosalpinx fluid was aspirated from 10 patients at laparoscopy. The fluid was serially diluted in minimum essential medium. Ishikawa cells (an endometrial adenocarcinoma cell line, representative of endometrial epithelium) were incubated with this fluid at concentrations of 10% and 50% for 48 hours. Cells were also incubated in undiluted minimum essential medium (MEM) and in 10% serum as controls. After incubation, the cells were lysed in Trizol, and total RNA was extracted and analyzed by Northern blot using a 32P-labeled HOXA10 riboprobe. A 32P-labeled G3PDH probe was used as a control for loading. MAIN OUTCOME MEASURE(S): HOXA10 mRNA expression. RESULT(S): HOXA10 mRNA expression in endometrial cells decreased with increasing concentrations of hydrosalpinx fluid. Densitometric analysis of the northern blot revealed that HOXA10 mRNA expression was different from control at both concentrations (P<.007). CONCLUSION(S): HOXA10 is necessary for implantation in the murine model. HOXA10 expression is diminished by hydrosalpinx fluid. This effect on HOXA10 is a potential molecular mechanism by which implantation rates are diminished in women with hydrosalpinges.

Expression of cytokine genes in adhesions on uterine tubes.

We studied expression of genes of interleukins, interferon-gamma, tumor necrosis factor-alpha, and transforming growth factor-beta(2) in adhesions on uterine tubes. In tubal adhesions the intensity of production of mRNA for proinflammatory cytokines, antiinflammatory cytokine interleukin-10, and regulator of cell proliferation surpassed that in normal tissues by 2.5-7.4, 2.2, and 50.2 times, respectively. Correlations were found between production of mRNA for tumor necrosis factor-alpha and transforming growth factor-beta(2), interleukin-12, and interferon-gamma and interleukin-12 and transforming growth factor-beta(2). Our results suggest that expression of these genes during adhesion formation is regulated by the feedback mechanism.

Allelic polymorphism and chromosomal localization of the human oviductin gene (MUC9).

OBJECTIVE: To determine if the gene coding for human oviductin (the estrogen-dependent, oviduct-specific glycoprotein with an affinity for the zona pellucida) shows length polymorphism in the region of tandem repeats. To determine the frequencies of the length alleles in health and disease. DESIGN: Descriptive fundamental and clinical studies. SETTING: Fertility clinic and research center, university teaching hospital. PATIENT(S): Fertile women, women with a history of ectopic pregnancy or tubal disease, and women with stage I or II endometriosis. INTERVENTION(S): Blood samples were drawn for DNA analysis. MAIN OUTCOME MEASURE(S): Length and sequence of the region of tandem repeats. RESULT(S): Four different length alleles of the human oviductin gene were identified. Their relative frequencies in pathologic cases were not statistically significant compared with those found in normal fertile women. The human genome contains a single copy of the oviductin gene located on chromosome 1p13. CONCLUSION(S): The human oviductin gene codes for a glycoprotein that shares the characteristics of epithelial mucins. Because eight epithelial mucin genes have been identified so far, we therefore propose to name this gene MUC9. The biologic function of the protein is likely to include protection of the early embryo and of the fallopian tube itself.

The chromosomal normality of unfertilized oocytes from patients with polycystic ovarian syndrome.

The present study was designed to compare the cycle characteristics of in-vitro fertilization (IVF) and the chromosomal normality of oocytes in patients with polycystic ovarian syndrome (PCOS) with those of patients with tubal factor infertility. In all, 28 cycles of 24 PCOS patients and 55 cycles of 31 patients with tubal factor infertility (control) were investigated. Although a significantly greater number of oocytes were retrieved from PCOS patients (mean +/- SD: 15.6 +/- 6.4 versus 9.0 +/- 4.0, PCOS versus control group, P < 0.05), the percentage of fertilized oocytes was significantly lower in the PCOS group compared with controls (40.1 versus 73.8%, P < 0.01). The pregnancy rate per embryo transfer did not differ between the two groups. Cytogenetic analysis was performed on 74 oocytes from PCOS patients and 73 oocytes from control patients. In the PCOS group, 10 of the 74 oocytes (13.5%) demonstrated aneuploidy, four (5.4%) oocytes were diploid and six (8.1%) oocytes were metaphase II with a prematurely condensed sperm chromosome (PCC). In the tubal infertility group, nine of the 73 (12.3%) oocytes showed aneuploidy, four (5.5%) oocytes were diploid and five (6.8%) oocytes were found to have PCC. There was no significant difference in the aneuploidy, diploidy and PCC rates between the two groups. These results suggest that the reduced fertilization observed in PCOS is not attributable to chromosomal aberrations or immaturity of oocytes recruited from patients with PCOS.