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.

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.

The impact of soluble HLA-G in IVF/ICSI embryo culture medium on implantation success.

The HLA-G molecule is widely accepted as an important factor for pregnancy success. Its expression has been detected in the extravillous trophoblasts. Soluble HLA-G (sHLA-G) was found in the genital tract, pre-implanted embryos as well as in seminal fluid. In this study, we investigated the concentration of sHLA-G (sHLA-G1 and sHLA-G5) in media from 344 single cultured embryos following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The level of sHLA-G (U/ml) was tested with a sandwich enzyme-linked immunosorbent assay (ELISA) kit. We correlated sHLA-G secretion with ovarian stimulation protocols, the type of embryo transfer (fresh or frozen cycle) and the quality of the embryos. The ovarian stimulation protocol affects the secretion of sHLA-G by the embryo. Embryos obtained from the long agonist protocol secreted more sHLA-G than those originating from the short antagonist protocol (p = 0.0001). Embryos whose transfer resulted in a clinical pregnancy and/or live birth secreted more sHLA-G compared to those whose transfer ended without pregnancy. This was particularly observable in embryos following the long ovarian stimulation protocol and from a frozen embryo cycle. In conclusion, sHLA-G secreted by the embryo has an impact on implantation and live birth and could be a developmental potential marker of the embryo. Its concentration depends on the ovarian stimulation protocol used.

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.

Synthetic Pyrethroids Exposure and Embryological Outcomes: A Cohort Study in Women from Fertility Clinic.

Pyrethroids exposure has been associated with adverse reproductive outcome. However, there is no study that explores the effect of environmental exposure and embryological outcomes. This question was addressed in a prospective cohort of couples undergoing fertility treatment. The study aims to assess the association between urinary metabolites of synthetic pyrethroids and embryological outcomes (MII oocyte count, top quality embryo, fertilization and implantation rate). We included 450 women aged 25−45 undergoing assisted reproductive technology (ART) cycle at Infertility Clinic in Poland. Urine samples were collected at the time of fertility procedure(s) to assess four urinary synthetic pyrethroids concentrations (3-phenoxybenzoic acid (3PBA), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA), cis-2,2-dibromovinyl-2,2-dimethylocyclopropane-1-carboxylic acid (DBCA)) using validated gas chromatography ion-tap mass spectrometry and calculated for each cycle-specific metabolite. To evaluate the effect of environmental exposure to synthetic pyrethroids and embryological outcomes (methaphase II (MII) oocyte yield, top quality embryo, fertilization rate, implantation rate), multivariable generalized linear mixed analyses with random intercepts were prepared. Urinary 3-PBA concentrations decrease MII oocyte count (p = 0.007) in the fourth quartile (>75 percentile) compared to women in the first quartile (≤25 percentile). Additionally, when 3-PBA was treated as continuous variable, the negative association between exposure to pyrethroids and MII oocyte count was also observed (p = 0.012). Exposure to other pyrethroid metabolities (CDCCA, TDCCA, DBCA) was not related to any of the examined embryological outcomes. Exposure to synthetic pyrethroids may be associated with poorer embryological outcome among couples seeking fertility treatments. As this is the first study on this topic, the results need to be confirmed in further studies.

ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure.

The mother's uterine immune system is dominated by uterine natural killer (NK) cells during the first trimester of pregnancy. These cells express killer cell immunoglobulin-like receptors (KIRs) of inhibitory or activating function. Invading extravillous trophoblast cells express HLA-C molecules, and both maternal and paternal HLA-C allotypes are presented to KIRs. Endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) shape the HLA class I immunopeptidome. The ERAPs remove N-terminal residues from antigenic precursor peptides and generate optimal-length peptides to fit into the HLA class I groove. The inability to form the correct HLA class I complexes with the appropriate peptides may result in a lack of immune response by NK cells. The aim of this study was to investigate the role of ERAP1 and ERAP2 polymorphisms in the context of KIR and HLA-C genes in recurrent implantation failure (RIF). In addition, for the first time, we showed the results of ERAP1 and ERAP2 secretion into the peripheral blood of patients and fertile women. We tested a total of 881 women. Four hundred ninety-six females were patients who, together with their partners, participated in in vitro fertilization (IVF). A group of 385 fertile women constituted the control group. Women positive for KIR genes in the Tel AA region and HLA-C2C2 were more prevalent in the RIF group than in fertile women (p/pcorr. = 0.004/0.012, OR = 2.321). Of the ERAP polymorphisms studied, two of them (rs26653 and rs26618) appear to affect RIF susceptibility in HLA-C2-positive patients. Moreover, fertile women who gave birth in the past secreted significantly more ERAP1 than IVF women and control pregnant women (p < 0.0001 and p = 0.0005, respectively). In the case of ERAP2, the opposite result was observed; i.e., fertile women secreted far less ERAP2 than IVF patients (p = 0.0098). Patients who became pregnant after in vitro fertilization embryo transfer (IVF-ET) released far less ERAP2 than patients who miscarried (p = 0.0032). Receiver operating characteristic (ROC) analyses indicate a value of about 2.9 ng/ml of ERAP2 as a point of differentiation between patients who miscarried and those who gave birth to a healthy child. Our study indicates that both ERAP1 and ERAP2 may be involved in processes related to reproduction.

Environmental Factors and Endometriosis.

Endometriosis is a common disease, affecting up to 60-80% of women, with pelvic pain or/and infertility. Despite years of studies, its pathogenesis still remains enigmatic. Genetic, hormonal, environmental, and lifestyle-related factors may be involved in its pathogenesis. Thus, the design of the review was to discuss the possible role of environmental factors in the development of endometriosis. The results of individual studies greatly differ, making it very difficult to draw any definite conclusions. There is no reasonable consistency in the role of environmental factors in endometriosis etiopathogenesis.

Updating the recommendations of the Working Group for the Preservation of Fertility in Oncological and Hematological Patients and Other Patients Treating Gonadier Therapies "ONCOFERTILITY" (GROF) of the Polish Society of Oncological Gynecology regarding cryopreserves and autologous transplant.

Update of the recommendations of the Fertility Preservation Working Group in Oncological, Hematological and Other Patients Treated with Gonadotoxic Therapies "ONCOFERTILITY" (GROF) of the Polish Society of Oncological Gynecology regarding cryopreservation and autologous ovarian tissue transplantation. The Fertility Preservation Working Group in Oncological, Hematological and Other Patients Treated with Gonadotoxic Therapies "ONCOFERTILITY" (GROF) of the Polish Society of Oncological Gynecology has developed current clinical guidelines and recommendations to improve the quality of healthcare provision in the area of reproductive health in patients undergoing therapy that may impair their reproductive potential. The guidelines are based on current scientific evidence available at the time of writing this document. In the absence of scientific evidence on some aspects, a consensus was reached among GROF stakeholders. The purpose of the guidelines is to assist healthcare professionals in making decisions in specific clinical situations regarding the selection of an appropriate and effective diagnostic and therapeutic process. The document provides practical guidelines for the management of cryopreservation and autologous ovarian tissue transplantation.

Urinary Bisphenol A Concentrations and Parameters of Ovarian Reserve among Women from a Fertility Clinic.

BACKGROUND: Human exposure to environmentally widespread endocrine disruptors, especially bisphenol A (BPA), has been suggested to affect reproductive health. Animal studies indicate that BPA may play a role in the process of reproduction and impact on maturing oocytes, meiotic cell division or fertilization rate. Nevertheless, data regarding the effects of exposure to BPA on women's ovarian function are still limited. Therefore, the aim of the current study is to assess the effects of environmental exposure to BPA on ovarian reserve. METHODS: The study participants consisted of 511 women in reproductive age (25-39 years) who attended an infertility clinic for diagnosis, due to the couples' infertility. BPA urinary concentrations were assessed by the validated gas chromatography ion-trap mass spectrometry method. The ovarian reserve was assessed using ovarian reserve parameters: Hormones concentrations: E2 (estradiol), FSH (follicle stimulating hormone), AMH (anti-Müllerian hormone), and AFC (antral follicle count). RESULTS: In the present study, the negative association between BPA urinary concentrations and AMH (p = 0.02) and AFC (p = 0.03) levels was found. Exposure to BPA was not related to other examined parameters of ovarian reserve (FSH, E2). CONCLUSIONS: Our results suggest that BPA exposure may affect women ovarian reserve parameters and reduce ovarian reserve. As this is one of the first studies of its kind, the findings need confirmation in a further investigation.

Assisted reproductive medicine in Poland, 2013-2016: Polish Society of Reproductive Medicine and Embryology (PTMRiE) and Fertility and Sterility Special Interest Group of the Polish Society of Gynaecologists and Obstetricians (SPiN PTGiP) report.

OBJECTIVES: The purpose of this publication is to present data on the results and complications associated with infertility treatment using assisted reproductive technology (ART) and intrauterine insemination (IUI) in Poland between 2013 and 2016. MATERIAL AND METHODS: The report was prepared by the Polish Society of Reproductive Medicine and Embryology (PTMRiE) and the Fertility and Sterility Special Interest Group of the Polish Society of Gynaecologists and Obstetrics (SPiN PTGiP) as a part of the European IVF Monitoring program (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Reporting was voluntary and the data was not subject to external control. The report presents the availability and structure of infertility treatment services, the number of procedures, their effectiveness and complications. RESULTS: Between 2013 and 2016, a total of 106,718 treatment cycles using ART [64,413 classical in vitro fertilization and in vitro fertilization with intracytoplasmic sperm injection (IVF + ICSI), 36,041 frozen embryo replacements (FER)] and 51,405 IUI were recorded. The clinical pregnancy rates per embryo transfer in IVF, ICSI and FER were 38.3%, 38.1% and 32.4%, respectively. The effectiveness of IUI with husband/partner's semen (IUI-H) was 11.1% and with donor semen (IUI-D) 16.7%. Multiple delivery rates were 11.3% and 6.2% in IVF + ICSI and IUI, respectively. The most common complication was the ovarian hyperstimulation syndrome (OHSS) (0.34%). CONCLUSIONS: PTMRiE and SPiN PTGiP report is the only national study documenting Polish reproductive medicine. The results of infertility treatment effectiveness in Poland are comparable with the European data, complications are less frequent than in other countries. The low percentage of multiple pregnancies, and so perinatal complications, is especially valuable. However, due to the lack of a central database and register, the possibility of external control and monitoring of pregnancies and births is limited. Thus, a fully reliable assessment of the treatment quality in our country is not possible.

Tandem autologous hematopoietic cell transplantation with sequential use of total marrow irradiation and high-dose melphalan in multiple myeloma.

The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose of 12 Gy (4 Gy on days -3, -2, and -1) and melphalan 200 mg/m2 for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional "boosts" (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41-64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patients. Grade 3 infections were reported in 30% patients. Other toxicities were rare. Proportion of patients who achieved at least very good partial response increased from 46% before the first auto-HCT to 82% after tandem transplantation. Complete remission rates changed from 10% to 42%, respectively. The probabilities of overall and progression-free survival at 5 years were 74% and 55%, respectively. No patient died without progression. We conclude that conditioning with TMI ± PET-guided "boosts" represents personalized treatment approach in MM and is characterized by very good toxicity profile. Tandem auto-HCT using TMI in sequence with high-dose melphalan appears safe with encouraging early efficacy.

The Association of HLA-G Gene Polymorphism and Its Soluble Form With Male Infertility.

Successful reproduction depends on many factors. Male factors contribute to infertility in approximately 50% of couples who fail to conceive. Seminal plasma consists of secretions from different accessory glands containing a mixture of various cytokines, chemokines, and growth factors, which together can induce a local immune response that might impact on a male's as well as a female's fertility. Human leukocyte antigen (HLA)-G expression has been suggested as an immunomodulatory molecule that influences pregnancy outcome. The HLA-G gene encodes either membrane-bound or/and soluble proteins. The aim of this study was the evaluation of HLA-G polymorphisms and their impact on soluble HLA-G (sHLA-G) production. We tested the HLA-G polymorphism in three positions: rs1632947: c.-964G>A; rs1233334: c.-725G>C/T in the promoter region; rs371194629: c.∗65_∗66insATTTGTTCATGCCT in the 3' untranslated region. We tested two cohorts of men: 663 who participated in in vitro fertilization (test material was blood or sperm), and 320 fertile controls who possessed children born after natural conception (test material was blood). Since 50% of men visiting assisted reproductive clinics have abnormal semen parameters, we wondered if men with normal sperm parameters differ from those with abnormal parameters in terms of HLA-G polymorphism and secretion of sHLA-G into semen. We found that certain rs1632947-rs1233334-rs371194629 HLA-G haplotypes and diplotypes were associated with male infertility, while others were protective. Normozoospermic men with the A-C-del haplotype and A-C-del/A-C-del diplotype secreted the most sHLA-G into semen (574.1 IU/mL and 1047.0 IU/mL, respectively), while those with the G-C-ins haplotype and G-C-ins/G-C-ins diplotype - the least (80.8 IU/mL and 75.7 IU/mL, respectively). Men with the remaining haplotypes/diplotypes secreted sHLA-G at an intermediate level. However, only in one haplotype, namely G-C-ins, did we observe strong significant differences in the concentration of sHLA-G in the semen of men with teratozoospermia compared to men with normal sperm parameters (p = 0.009). In conclusion, fertile men differ in the profile of HLA-G polymorphism from men participating in IVF. Among all HLA-G haplotypes, the most unfavorable for male fertility is the G-C-ins haplotype, which determines the secretion of the lowest concentration of the soluble HLA-G molecule. This haplotype may reduce sperm parameters.

Triclosan exposure and in vitro fertilization treatment outcomes in women undergoing in vitro fertilization.

Triclosan (TCS) is a widespread environmental endocrine-disrupting chemical. Animal and in vitro studies suggested that triclosan may affect homesostasis of sex and thyroid hormones and impact on reproduction. Due to limited data derived from human epidemiological studies, this study was performed to examine the association between urinary concentration of triclosan and in vitro reproductive outcomes (methaphase II (MII) oocyte yield, top quality embryo, fertilization rate, implantation rate, and clinical pregnancy) among women from infertility clinic. The study participants were enrolled in an Infertility Center in Poland. A total of 450 women aged 25-45 (n = 674 IVF cycles) provided urine samples. The urinary concentrations of triclosan were evaluated using validated gas chromatography ion-tap mass spectrometry method. Clinical outcomes of IVF treatment were abstracted from patients electronic chart records. Triclosan was detected in urine of 82% of women with geometric mean 2.56 ± 6.13 ng/mL. Urinary concentrations of triclosan were associated with decrease implantation rate (p = 0.03). There were no association between other examined IVF outcomes: MII oocytes, embryo quality, fertilization rate, and exposure to triclosan. As this is one of the first study on this topic, studies among larger and more diverse population are needed to confirm the results.

Exposure to pyrethroid pesticides and ovarian reserve.

INTRODUCTION: Synthetic pyretroids are among the most common pesticides currently used worldwide. Animal studies suggest that exposure to pyrethroids could dysregulated the function of the ovary, mainly follicular development and/or synthesis of the reproductive hormone. Nevertheless data regarding the effect of exposure on female ovarian function is limited. So the aim of the present study is to assess the effect of exposure to synthetic pyrethroids on ovarian reserve. MATERIALS AND METHODS: The study population consists of 511 females aged 25-39 years attending infertility clinics for diagnostic purposes, because of couples' infertility. Validated gas chromatography ion-tap mass spectrometry method was used to assess the urinary concentrations of pyrethroid metabolites (CDDCA (cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid), TDDCA (trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid), 3PBA (3-phenoxybenzoic acid) and DBCA (cis-2,2-dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid)). Ovarian reserve was assessed using parameters of ovarian reserve (antral follicle count and concentrations of hormones: AMH (anti-Mullerian hormone), FSH (follicle stimulating hormone) and E2 (estradiol)). RESULTS: In the present analysis the association was found between urinary concentrations of 3-PBA and levels of AMH (p = 0.03), FSH (p = 0.04) and antral follicle count (p = 0.02). Urinary level of CDCCA, TDCCA and DBCA was not associated with any examined parameters of ovarian reserve. CONCLUSIONS: Synthetic pyrethroids may affect female ovarian reserve. As this is the first, preliminary study the results need confirmation in a further detailed investigations.

Urinary bisphenol A concentrations and in vitro fertilization outcomes among women from a fertility clinic.

Bisphenol A (BPA) is a widespread environmental endocrine disrupting chemical. Although many animals and in vitro studies reported that BPA may affect female fertility through the effect on maturing oocytes and meiotic cell division, but the data from human studies are limited and inconclusive. The study was conducted to examine the association between urinary BPA concentration and in vitro reproductive outcomes (metaphase II (MII) oocyte yield, top quality embryo, fertilization rate, implantation rate and clinical pregnancy) among women from an infertility clinic. The study participants were enrolled in the Infertility Center in Poland. 450 women aged 24-44 (n = 674 IVF cycles) provided urine samples. The urinary concentrations of BPA were evaluated using validated gas chromatography ion-tap mass spectrometry method. Clinical outcomes of IVF treatment were abstracted from patients electronic chart records. To assess the relationship between urinary BPA concentrations early examined reproductive outcomes generalized linear mixed models were used. The detection rate of BPA in urine samples was 98% and the geometric mean 1.59 ± 2.15 ng/ml. A significant decrease was observed between urinary concentration of BPA and implantation (p = 0.04) and decreased MII oocyte count (p = 0.03). There was no association between other examined IVF outcomes: embryo quality, fertilization rate and clinical pregnancy and BPA exposure. Exposure to BPA may have a negative effect during the early stages of human development. The studies among the larger and more diverse population are needed to confirm the results.

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.

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.