ERAP/HLA-C and KIR Genetic Profile in Couples with Recurrent Implantation Failure.

Proper embryo implantation depends on the tolerance of the maternal immune system to the fetus and its foreign paternal antigens. During implantation and early pregnancy, the dominant leukocytes in the uterus are uterine NK cells, expressing killer immunoglobulin-like receptors (KIR). KIRs recognize human leukocyte antigens (HLA-C) on the human trophoblast inherited from the father and mother. The antigenic peptides presented by the HLA are formed via their cleavage by endoplasmic reticulum aminopeptidases ERAP1 and ERAP2. The aim of this study was to assess the association of combined KIR genes and their HLA-C ligands, as well as ERAP1 and ERAP2 polymorphisms with recurrent implantation failure after in vitro fertilization (RIF). We tested 491 couples who underwent in vitro fertilization (IVF) and 322 fertile couples. Genotype CC rs27044 ERAP1 in female with a male's HLA-C1C1 or HLA-C1C2 protected from RIF (p/pcorr. = 0.005/0.044, OR = 0.343; p/pcorr. = 0.003/0.027, OR = 0.442, respectively). Genotype TT rs30187 ERAP1 in female with a male's HLA-C1C2 genotype increased the risk of RIF. Summarizing, in the combination of female ERAP1 and an HLA-C partner, the rs30187 C>T and rs27044 C>G polymorphisms play an important role in implantation failure.

Parameters of ovarian reserve in relation to urinary concentrations of parabens.

BACKGROUND: Parabens are synthetic chemicals commonly used in cosmetics, pharmaceuticals, food and beverage processing as antimicrobial preservatives. In experimental animals, parabens exposure was associated with adverse effects on female reproduction. Despite the widespread use of parabens little is known about their effect on female fecundity. The objective of the current analysis was to evaluate the associations of urinary parabens concentrations with parameters of ovarian reserve among women undergoing treatment in a fertility clinic. METHODS: Five hundred eleven female aged 25-39 years who attended the infertility clinic in central region of Poland for diagnostic purposes were recruited between September 2014 and February 2019. Urinary concentrations of parabens were measured by a validated gas chromatograohy ion-tap mass spectrometry method. Parameters of ovarian reserve were: antral follicle count (AFC), anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and estradiol (E2) levels. RESULTS: The geometric mean of specific gravity adjusted urinary concentrations of methyl (MP), ethyl (EP), propyl (PP), butyl (BP) and izobutyl paraben (iBuP) were 107.93 µg/L, 12.9 µg/L, 18.67 µg/L, 5.02 µg/L and 2.80 µg/L. Urinary concentrations of PP in the third quartile of exposure ((50-75] percentyl) were inversely associated with antral follicle count (p = 0.048), estradiol level (p = 0.03) and positively with FSH concentration (p = 0.026). MP, EP, BP and iBuP parabens were not associated any with parameters of ovarian reserve. CONCLUSIONS: Chronic exposure to PP may potentially contributing to reduced fecundity and impair fertility. As this is one of the first study to investigate the potential effect of parabens on ovarian reserve further epidemiological studies with longer duration of observation are needed.

KIR and HLA-C genes in male infertility.

PURPOSE: Approximately 50% of men reporting to clinics for assisted reproduction have abnormal sperm parameters; we therefore considered whether they differ from fertile males in terms of the frequency of KIR and HLA-C genes, suggesting the involvement of NK cells and some T cells in the inflammatory reaction that can occur in the testes, vas deferens, or epididymis. METHOD: We tested a total of 1064 men: 445 of them were patients who, together with their female partners, participated in in vitro fertilization (IVF), 298 men whose female partners suffered from recurrent spontaneous abortion. Three hundred twenty-one fertile men constituted the control group. KIRs were genotyped using KIR Ready Gene kits and HLA-C by PCR-SSP methods. RESULTS: We found differences in KIR gene frequencies between men who became fathers via natural conception and men who participated in in vitro fertilization for KIR2DL2 (p/pcorr. = 0.0015/0.035, OR = 1.61), KIR2DL5 gr.2 (p/pcorr. = 0.0023/0.05, OR = 1.64), KIR2DS2 (p/pcorr. = 0.0019/0.044, OR = 1.59), and KIR2DS3 (p/pcorr. = 0.0016/0.037, OR = 1.67). KIRs in Cen AA region were significantly overrepresented in fertile males than in IVF males (p/pcorr. = 0.0076/0.03, OR = 0.67), whereas Cen AB + Cen BB frequency was higher in IVF males than in fertile males (p/pcorr. = 0.0076/0.03, OR = 1.50). We also observed a limited association in KIR-HLA-C combinations. CONCLUSION: Fertile men differ in profile of KIR genes and KIR-HLA-C combinations from men participating in IVF.

Radiosurgery or hypofractionated stereotactic radiotherapy after craniospinal irradiation in children and adults with medulloblastoma and ependymoma.

PURPOSE: To assess the results and tolerance of radiosurgery/hypofractionated stereotactic radiotherapy performed after craniospinal irradiation for recurrent tumor. METHODS: Fourteen patients aged 3-46 years, diagnosed with medulloblastoma (10), anaplastic ependymoma (3), and primitive neuroectodermal tumor (1). All patients had craniospinal irradiation (CSI) with the total dose of 30.6-36 Gy and boost to 53.9-60 Gy either during primary or during second-line treatment. Twelve patients were irradiated with a single dose of 6-15 Gy (median 14.5 Gy). One received three fractions of 5 Gy and one six fractions of 5 Gy. In statistical analysis, the Kaplan-Meier method and log-rank test were used. The overall survival was calculated from the date of the end of stereotactic radiosurgery to the date of death or last contact. RESULTS: Recurrences were diagnosed after the median time of 16 months after the end of primary treatment. Eleven patients died during the follow-up. The follow-up for the 3 patients still alive was 6.7, 40.5, and 41.4 months, respectively. One- and 2-year overall survival (OS) was 70% and 39%. Patients who had ECOG performance status of 0 at the time of diagnosis of the disease trended to have better 2-year OS compared to those evaluated as ECOG 1 (p = 0.057). Treatment results were evaluable in 12 patients. Local control (stabilization or regression of the lesion) was achieved in 9 (75%). Overall disease progression was 67%. No patient developed radiation-induced necrosis. The treatment was well tolerated and no serious adverse effects were observed. Eleven patients were given steroids as a prevention of brain edema and four of them needed continuation of this treatment afterwards. In 7 patients, symptoms of brain edema were observed during the first weeks after reirradiation. CONCLUSIONS: Stereotactic radiosurgery or hypofractionated stereotactic radiotherapy is an effective treatment method of the local recurrence after CSI and can be performed safely in heavily pre-treated patients.

The impact of HLA-G, LILRB1 and LILRB2 gene polymorphisms on susceptibility to and severity of endometriosis.

Endometriosis is a disease in which endometriotic tissue occurs outside the uterus. Its pathogenesis is still unknown. The most widespread hypothesis claims that ectopic endometrium appears as a result of retrograde menstruation and its insufficient elimination by immunocytes. Some reports have shown expression of non-classical HLA-G molecules on ectopic endometrium. HLA-G is recognized by KIR2DL4, LILRB1 and LILRB2 receptors on natural killer (NK) and other cells. These receptors are polymorphic, which may affect their activity. In this study we investigated whether HLA-G, KIR2DL4, LILRB1 and LILRB2 polymorphisms may influence susceptibility to endometriosis and disease progression. We used polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and allelic discrimination methods with TaqMan SNP Genotyping Assays for typing of 276 patients with endometriosis and 314 healthy fertile women. The HLA-G rs1632947:GG genotype was associated with protection against the disease and its severe stages; HLA-G rs1233334:CT protected against progression; LILRB1 rs41308748:AA and LILRB2 rs383369:AG predisposed to the disease and its progression. No effect of KIR2DL4 polymorphism was observed. These results support the role of polymorphisms of HLA-G and its receptors LILRB1 and LILRB2 in susceptibility to endometriosis and its progression.

Air pollution from natural and anthropic sources and male fertility.

Exposure to air pollution has been clearly associated with a range of adverse health effects, including reproductive toxicity. However, a limited amount of research has been conducted to examine the association between air pollution and male reproductive outcomes, specially semen quality. We performed a systematic review (up to March 2017) to assess the impact of environmental and occupational exposure to air pollution on semen quality. Epidemiological studies focusing on air pollution exposures and male reproduction were identified by a search of the PUBMED, MEDLINE, EBSCO and TOXNET literature bases. Twenty-two studies were included which assess the impact of air pollutants (PM2.5, PM10, SO2, NOx, O3, PAHs) on main semen parameters (sperm concentration, motility, morphology), CASA parameters, DNA fragmentation, sperm aneuploidy and the level of reproductive hormones. The number of studies found significant results supporting the evidence that air pollution may affect: DNA fragmentation, morphology and motility.In summary, most studies concluded that outdoor air pollution affects at least one of the assessed semen parameters. However the diversity of air pollutants and semen parameters presented in the studies included in the review and different study design caused lack of consistency in results and difficulties in comparison.

Environmental exposure to parabens and sperm chromosome disomy.

Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and beverage processing due to their board spectrum of activity, inertness, and low cost. The study population consisted of 156 men under 45 years of age who attended the infertility clinic for diagnostic purposes with normal semen concentration of 15-300 mln/ml. Participants were interviewed and provided a semen sample. The parabens concentrations: ethyl paraben (EP), butyl paraben (BP), methyl paraben (MP), and iso-butyl paraben (iBuP) were analyzed in the urine using a validated gas chromatography ion-tap mass spectrometry method. The positive association was found between urinary level of BP and XY18 disomy (p = 0.045) and PP and disomy of chromosome 13 (p = 0.007). This is the first study to examine these relationships, and replication of our findings is needed before the association between parabens concentration in urine and aneuploidy can be fully defined. These findings may be of concern due to increased parabens use.

Exposure to ambient air pollution--does it affect semen quality and the level of reproductive hormones?

BACKGROUND: Ambient air pollution has been associated with a variety of reproductive disorders. However, a limited amount of research has been conducted to examine the association between air pollution and male reproductive outcomes, specifically semen quality. AIM: The present study was designed to address the hypothesis that exposure to fluctuating levels of specific air pollutants adversely affects sperm parameters and the level of reproductive hormones. SUBJECTS AND METHODS: The study population consisted of 327 men who were attending an infertility clinic in Lodz, Poland for diagnostic purposes and who had normal semen concentration of 15-300 mln/ml. All participants were interviewed and provided a semen sample. Air quality data were obtained from AirBase database. RESULTS: The statistically significant association was observed between abnormalities in sperm morphology and exposure to all examined air pollutants (PM10, PM2.5, SO2, NOX, CO). Exposure to air pollutants (PM10, PM2.5, CO, NOx) was also negatively associated with the level of testosterone. Additional exposure to PM2.5, PM10 increase the percentage of cells with immature chromatin (HDS). CONCLUSIONS: The present study provides suggestive evidence of an association between ambient air pollution and sperm quality. Further research is needed to explore this association in more detail. Individual precise exposure assessment would be needed for more detailed risk characterization.

Successful autotransplantation of cryopreserved ovarian tissue with recovery of the ovarian function.

OBJECTIVES: The aim of the study was autotransplantation of cryopreserved ovarian tissue to a patient suffering from premature ovarian failure caused by aggressive oncological therapy. MATERIAL AND METHODS: A 28-year-old woman, GII PI, was diagnosed with invasive adenocarcinoma of the cervix at 18 weeks of gestation. At 31 weeks of gestation, a cesarean section was performed, resulting in the delivery of a healthy male newborn, followed by simultaneous, radical hysterectomy with bilateral salpingo-oophorectomy and lymphadenectomy. Half of each ovary was cryopreserved. The patient was scheduled for radiochemotherapy, supplemented with brachytherapy. After the intervention, the patient experienced menopausal symptoms. The basal hormonal levels were: estradiol - 2 pg/ml, FSH - 96.52 IU/ml, LH - 37.55 IU/ml, AMH - 0.03 ng/ml. Thirteen months after surgery, the peritoneal pocket was formed on the anterior abdominal wall during laparoscopy and heterotrophic autotransplantation of the frozen-thawed ovarian tissue was performed, replacing 59% of the tissue. RESULTS: Nine weeks after transplantation, symptom resolution, an increase in estradiol (53 pg/ml), and a decrease in FSH (64.89 IU/ml) and LH (33.39 IU/ml) levels were noted. Twenty-four weeks after transplantation, high estradiol levels (269 pg/ml), normal level of FSH (5.92 IU/ml) and LH (4.09 IU/ml), and an increase in AMH (0.37 ng/ml) were observed. Follicular development in the transplanted ovarian tissue was confirmed. CONCLUSIONS: Cryopreservation and transplantation of ovarian tissue allowed to restore the ovarian function. It could offer an alternative physiological solution to treating premature ovarian failure caused by oncological therapy.

Human sperm aneuploidy after exposure to polycyclic aromatic hydrocarbons.

The purpose of this cross-sectional study was to investigate whether environmental exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with sperm aneuploidy. A sample of 181 men who attended an infertility clinic for diagnostic purposes and who had a normal semen concentration of 20-300×106 spermatozoa mL-1 or slight oligozoospermia (semen concentration of 15-20×106 spermatozoa mL-1;

Integral dose: Comparison between four techniques for prostate radiotherapy.

AIM: Comparisons of integral dose delivered to the treatment planning volume and to the whole patient body during stereotactic, helical and intensity modulated radiotherapy of prostate. BACKGROUND: Multifield techniques produce large volumes of low dose inside the patient body. Delivered dose could be the result of the cytotoxic injuries of the cells even away from the treatment field. We calculated the total dose absorbed in the patient body for four radiotherapy techniques to investigate whether some methods have a potential to reduce the exposure to the patient. MATERIALS AND METHODS: We analyzed CyberKnife plans for 10 patients with localized prostate cancer. Five alternative plans for each patient were calculated with the VMAT, IMRT and TomoTherapy techniques. Alternative dose distributions were calculated to achieve the same coverage for PTV. Integral Dose formula was used to calculate the total dose delivered to the PTV and whole patient body. RESULTS: Analysis showed that the same amount of dose was deposited to the treated volume despite different methods of treatment delivery. The mean values of total dose delivered to the whole patient body differed significantly for each treatment technique. The highest integral dose in the patient's body was at the TomoTherapy and CyberKnife treatment session. VMAT was characterized by the lowest integral dose deposited in the patient body. CONCLUSIONS: The highest total dose absorbed in normal tissue was observed with the use of a robotic radiosurgery system and TomoTherapy. These results demonstrate that the exposure of healthy tissue is a dosimetric factor which differentiates the dose delivery methods.

Live birth of monochorionic triamniotic triplets after in vitro fertilization and blastocyst transfer: case report and review of the literature.

UNLABELLED: Monozygotic triplet pregnancies are very rare, even after in vitro fertilization (IVF). We present a case of a live birth of triplets from a monochorionic triamniotic pregnancy after blastocyst transfer. A 29-year-old woman underwent intracytoplasmic sperm injection (IVF-ICSI). Her medical history included a 4-year infertility treatment with ovarian stimulation, three cycles of intrauterine insemination, hysteroscopy and an unsuccessful attempt at IVF. During the second IVF attempt, the patient underwent ovulation simulation according to the long GnRH agonist protocol. Eleven metaphase II (MII) oocytes were injected with spermatozoa, resulting in four expanded blastocysts. In the end, two blastocysts (4AA) were transferred into the uterine cavity. Ultrasound examination performed at 7 weeks of gestation showed an ongoing triamniotic triplet pregnancy. Regular uterine contractions began at 33 weeks of gestation and a cesarean section was performed, resulting in a birth of three healthy girls, weighing 2060g (Apgar 7), 1860g (Apgar 6), 2000g (Apgar 6). After 13 days of hospitalization the infants and the mother were discharged home. CONCLUSION: The causes of monozygotic multiple gestations in spontaneous and ART pregnancies are poorly understood. They seem to occur more often after IVF. Any definitive relationship between particular stages of the IVF procedure and monozygotic multiple pregnancies remains controversial.

[An ongoing twin pregnancy after embryo time laps monitoring in a patient with a history of IVF failures--case report and literature review]. / Zywa ciaza blizniacza otrzymana za pomoca metody ciaglego monitorowania zarodków u pacjentki z niepowodzeniami IVF-ET--opis przypadku i przeglad pismiennictwa.

INTRODUCTION: A standard assessment of embryo morphology at given time points does not always allow to transfer the embryo with the highest implantation potential. The effect of transfer of an improper embryo results in a lack of pregnancy or a miscarriage and, as a consequence, exposes the patient to unnecessary emotional stress and necessity to perform yet another transfer of frozen embryos. We present a case of a patient with earlier IVF failures. The use of time-lapse technique in this case helped to choose two good embryos. The transfer resulted in ongoing twin pregnancy. MATERIAL AND METHODS: A 35-year-old woman with history of IVF-ET treatment failure was deemed eligible for an ICSI procedure because of the male factor. Ovarian stimulation was performed according to the agonist long protocol. Eight MII oocytes were fertilized and seven embryos were obtained. Continuous embryo monitoring was performed with the use of Primo Vision system. Forty-four hours after fertilization only 2 correctly developing embryos were identified. They were transferred on day 3. The development of the remaining 5 embryos was arrested. These embryos did not achieve the blastocyst stage on day 5-6 after fertilization. Forty days after embryo transfer a twin pregnancy, confirmed with fetal heart rate of both fetuses, was revealed on ultrasound examination. Currently the patient is at 27 weeks of ongoing twin gestation. CONCLUSIONS: The system of continuous embryo monitoring introduces new criteria for the examination of embryo development. These new parameters can be useful in clinical practice. However prospective randomized studies are necessary to provide data confirming the usefulness of time-lapse technique in IVF treatment.

Clinical examples of 3D dose distribution reconstruction, based on the actual MLC leaves movement, for dynamic treatment techniques.

AIM: To present practical examples of our new algorithm for reconstruction of 3D dose distribution, based on the actual MLC leaf movement. BACKGROUND: DynaLog and RTplan files were used by DDcon software to prepare a new RTplan file for dose distribution reconstruction. MATERIALS AND METHODS: FOUR DIFFERENT CLINICALLY RELEVANT SCENARIOS WERE USED TO ASSESS THE FEASIBILITY OF THE PROPOSED NEW APPROACH: (1) Reconstruction of whole treatment sessions for prostate cancer; (2) Reconstruction of IMRT verification treatment plan; (3) Dose reconstruction in breast cancer; (4) Reconstruction of interrupted arc and complementary plan for an interrupted VMAT treatment session of prostate cancer. The applied reconstruction method was validated by comparing reconstructed and measured fluence maps. For all statistical analysis, the U Mann-Whitney test was used. RESULTS: In the first two and the fourth cases, there were no statistically significant differences between the planned and reconstructed dose distribution (p = 0.910, p = 0.975, p = 0.893, respectively). In the third case the differences were statistically significant (p = 0.015). Treatment plan had to be reconstructed. CONCLUSION: Developed dose distribution reconstruction algorithm presents a very useful QA tool. It provides means for 3D dose distribution verification in patient volume and allows to evaluate the influence of actual MLC leaf motion on the dose distribution.

Associations between dietary patterns and parameters of ovarian reserve in Polish women of reproductive age.

OBJECTIVES: Research investigating the association between reproductive health and diet has predominantly focused on the antenatal and prenatal periods, as well as childbirth in women, and semen quality in men. There is a limited amount of research addressing female fertility assessed as ovarian reserve in relation to diet. The main aim of this study was to evaluate the association between dietary patterns and the parameters of ovarian reserve, such as antral follicle count (AFC), anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2) - predictors of reproductive health in women of childbearing age. MATERIAL AND METHODS: Women aged 24-39 years (N = 511) were enrolled from fertility clinic in central Poland. The count of antral follicles was determined using ultrasonography (USG), FSH and E2 levels were measured using a chemilumi- nescence method and for determination of AMH level, an enzyme-linked immunosorbent assay method was employed. Diet was assessed according to food frequency questionnaire and dietary patterns were identified by factor analysis. Women were classified into 3 groups according to scores of each dietary pattern: Western, mixed, prudent. RESULTS: Higher adherence to the prudent dietary pattern in obese women was associated with significantly higher AFC (p = 0.03) and AMH (p = 0.05) as compared to participants with the Western dietary pattern. The results were adjusted for age, BMI, smoking and duration of fertility. Increased consumption of mixed dietary pattern was not statistically significant associated with any of examined ovarian reserve parameters. CONCLUSIONS: The prudent dietary pattern is positively associated with ovarian reserve in a cohort of women seeking fertility care. Continued research in this area will provide nutritional guidance for clinicians and their patients and provide novel insight on potential modifiable lifestyle factors which can be associated with ovarian reserve. Int J Occup Med Environ Health. 2024;37(4).

Exposure to air pollution and ovarian reserve parameters.

Exposure to air pollution is associated with many different health effects, especially cardiovascular and respiratory diseases. Additionally, highly significant links between exposure to air pollution and fertility, particularly male fertility was observed, however the studies regarding exposure to selected air pollutants and female fertility assessed by ovarian reserve are rare. Hence, the main aim of the study was to analyze relationship between exposure to ambient air pollution and ovarian reserve parameters among Polish women. The study population consisted of 511 women, who attended to infertility clinic because of diagnostic purposes. Participants filled in the questionnaire about social-demographic, lifestyle and health factors. Infertility specialists assessed ovarian parameters such as: antral follicle count (AFC) and concentration of hormones: Anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH) and estradiol (E2). The air pollutants level (sulfur dioxide, nitrogen dioxide, carbon monoxide, ozone, particulate matters) were obtained via National Environmental Protection Inspectorate database. Significant negative association between PM2,5 and AHM (p = 0.032) as well as AFC (p = 0.044) was observed. Moreover, SO2 concentrations decrease AFC (p = 0.038). The results also suggest that PM10, PM2.5, SO2 exposure on antral follicle count may be more pronounced among women with a female factor infertility diagnosis. Additionally, exposure to PM2.5 and NOx on AFC and AMH was stronger among older women (> 35 years of age). To conclude, the present study found that air pollution could lead to decrease in follicle antral count and Anti-Müllerian hormone level, especially exposure to PM2,5 and SO2 thus the evidence suggest negative impact to ovarian reserve.

IL-18 and IL-18 binding protein concentration in ovarian follicular fluid of women with "tubal factor" subjected to in vitro fertilization.

INTRODUCTION: Composition of follicular fluid is also regarded to be linked to quality of oocytes, fertilization and quality of the embryo. The aim of this study was to investigate the concentration of IL-18 and IL18BP in follicular fluid (FF) in a homogeneous group of women with sterility caused by "tubal factor" subjected to in vitro fertilization (IVF) and the relation between concentrate of this cytokine and IVF outcome. MATERIALS/METHODS: The study group consisted of 83 non-smoking women aged 30.9 ± 3.2 (23.0-43.0) with confirmed (hysterosalpingography and/or laparoscopy) bilateral complete tubal impermeability. Follicular fluid levels of IL-18 and IL18BP were evaluated in 83 patients undergoing in vitro fertilization (IVF). Ovarian hormonal stimulation was conducted according to a GnRH antagonist protocol. The measurement of IL-18 and IL18BP in follicular fluid was done using the ELISA method. RESULTS: The mean follicular levels of IL-18 and IL18BP were 468.5 ± 357.4 pg/ml and 8611.3 ± 534 pg/ml. The biochemical pregnancy rate was 39.7% (33/83); 22 women became clinically pregnant (26.5%). The implantation rate was 26.7% (36/135). No significant correlation was found between follicular concentrations of IL-18 and age of the patients (r = 0.13 p>0.05), number of metaphase II oocytes collected (r = -0.11 p>0.05), number of 3-day embryos (r = -0.157 p>0.05), biochemical pregnancies (r = 0.03 p>0.05), or clinical pregnancies (r = -0.06 p>0.05). Also there was no significant correlation between IL18BP and age of the patients (r = 0.21 p>0.05), number of metaphase II oocytes collected (r = 0.08 p>0.05), number of 3-day embryos (r = -0.19 p>0.05), biochemical pregnancies (r = 0.11 p>0.05) and clinical pregnancies (r = -0.34 p>0.05). CONCLUSION: IL-18 and IL18BP are detectable in follicular fluid but do not determine IVF outcome in women with "tubal factor". IL-18 and IL18BP are not promising prognostic markers for IVF success in this subgroup of patients.

Detection of intracavitary lesions in 820 infertile women: comparison of outpatient hysteroscopy with histopathological examination.

OBJECTIVES: The aim of the study was to compare the results of a diagnostic hysteroscopy with a histopathology examination (referential test) in a group of infertile women. MATERIALS AND METHODS: Eight hundred and twenty infertile patients were included in the study The subjects with intracavitary lesions underwent operative hysteroscopy to enable the removal of polyps and intracavitary myomas. Endometrial biopsy was performed in all patients with no pathologies in hysteroscopy. The removed tissue underwent histopathological examination. RESULTS: The mean age was 32.9 +/- 4.1. A total of 648 (79%) patients were diagnosed with primary and 172 (21%) with secondary infertility; 542 (66.1%) hysteroscopies were performed with no anesthesia and 278 (33.9%) hysteroscopies were performed in short total intravenous anesthesia. Sensitivity and specificity accuracy, error positive predictive value (PPV) and negative predictive value (NPV) of hysteroscopy in detecting endometrial lesions were 99.6%, 96.6%, 97.4%, 2.6%, 92.2% (PPV) and 99.8% (NPV), respectively. The agreement between hysteroscopy and pathology report was very high (kappa K = 0.94). In case of normal uterine cavity 562 of the 563 endometrial samples showed evidence of normal endometrium. In all 32 cases of resected submucosal myomas histopathology confirmed the hysteroscopic findings (sensitivity 100%, specificity 100%, accuracy 100%, error 0%, kappa K = 1.0). Both, hysteroscopy and histopathology confirmed the presence of endometrial polyps in 199 cases. The diagnosis of a polyp was not confirmed in histopathological findings (false-positive results) in 20 hysteroscopies. No endometrial polyps were missed during hysteroscopy Sensitivity specificity accuracy error positive and negative predictive values in detecting endometrial polyps were 100%, 96.8%, 97.6%, 2.4%, 90.9% (PPV) and 100% (NPV), respectively. The Kappa coefficient agreement between hysteroscopy and histopathology for endometrial polyps was 0.91. CONCLUSIONS: Hysteroscopy is a method of high sensitivity and specificity in detecting pathologies, but in case of a pathology it cannot replace histological examination. Our result show that a routine endometrial biopsy performed in infertile patients with no pathology in hysteroscopy should not be recommended.

Pro- and anti-inflammatory cytokines and growth factors in patients undergoing in vitro fertilization procedure treated with prednisone.

Embryo implantation is a key moment in pregnancy. Abnormal production of pro- and anti-inflammatory cytokines, their receptors and other immune factors may result in embryo implantation failure and pregnancy loss. The aim of this study was to determine the profile of selected pro- and anti-inflammatory factors in the blood plasma of patients undergoing in vitro fertilization (IVF) and control women who achieved pregnancy after natural conception. The examined patients were administered steroid prednisone. We present results concern the plasma levels of IFN-ɣ, BDNF, LIF, VEGF-A, sTNFR1 and IL-10. We found that IVF patients receiving steroids differed significantly from patients who were not administered such treatment in terms of IFN-γ and IL-10 levels. Moreover, IVF patients differed in secretion of all tested factors with the fertile controls. Our results indicated that women who secrete at least 1409 pg/ml of sTNFR1 have a chance to become pregnant naturally and give birth to a child, while patients after IVF must achieve a concentration of 962.3 pg/ml sTNFR1 in blood plasma for successful pregnancy. In addition, IVF patients secreting VEGF-A above 43.28 pg/ml have a greater risk of miscarriage or a failed transfer in comparison to women secreting below this value. In conclusion, fertile women present a different profile of pro- and anti-inflammatory cytokines, and growth factors compared to patients with recurrent implantation failure (RIF).

Urinary concentration of selected nonpersistent endocrine disrupting chemicals-reproductive outcomes among women from a fertility clinic.

Parabens and benzophenones are compounds widely used in cosmetics and personal care products. Although human exposure is widespread there is a limited number of epidemiological studies assessing the relationship between exposure to these chemicals and female reproductive health. The aim of the study is to explore the relationship between paraben and benzophenone concentrations and reproductive outcomes among women attending a fertility center. This prospective cohort included 450 women undergoing in vitro treatment (IVF) at fertility clinic in Poland. The validated gas chromatography ion-tap mass spectrometry to assess concentrations of parabens in urine (methyl (MP), ethyl (EP), propyl (PP), butyl paraben (BP)) and benzophenone-3 (BP-3) was used. To explore the relationship between concentrations of examined chemicals and reproductive outcomes (methaphase II (MII) oocyte yield, total oocyte yield, implantation rate, fertilization rate, clinical pregnancy, live births), multivariable generalized linear mixed model was used for the analysis. Increased exposure to butyl paraben was associated with a significant decrease in MII oocyte count (p = 0.007) when exposure to BP was treated as the continuous variable. Additionally, the exposure to BP in the highest quartile of exposure also decreases MII oocyte count (p = 0.02) compared to the lowest quartile. Urinary concentrations of BP were not related to total oocyte count, fertilization and implantation rate, clinical pregnancy, and live birth when the exposure variable was continuous variable or in the quartiles of exposure. Exposure to MP, EP, PP, the sum of examined parabens, and benzophenone-3 were not related to any of the examined reproductive outcomes. Exposure to butyl paraben was associated with a decrease in MII oocyte count among women attending fertility clinic rinsing concerns that exposure may have a potential adverse impact on embryological outcomes. The results emphasize the importance to reduce chemicals in the environment in order to minimize exposure. As this is the first study showing such an association, further research is needed to confirm these novel results in other populations.