The Efficacy of Vitamin D Supplement in the Expression and Protein Levels of Endometrial Decidualization Factors in Women with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is a challenging situation for infertility specialists, and its treatment is introduced as a difficult case in the field of assisted reproductive technology (ART). Vitamin D (VD) is one of the supplements that have been suggested to improve the implantation process. In the present study, the effect of VD on the expression and protein levels of VD receptor (VDR), progesterone receptor (PR), prolactin (PRL), insulin-like growth factor binding protein-1 (IGFBP-1), and homeobox protein A10 (HOXA10) in the endometrial cells of unknown RIF women with and without VD deficiency were assessed by qRT-PCR and immunohistochemistry. Twelve women with unknown RIF and VD deficiency (≤ 20 ng/ml) and twelve women with unknown RIF without VD deficiency (≥ 30 ng/ml) from 2021 to 2022 were identified. Endometrial specimens were collected in the mid-luteal stage before treatment or pregnancy. In the group with VD deficiency, oral medication of VD 50,000 units was prescribed for 2 to 3 months and their serum levels of VD were re-measured, then an endometrial biopsy at the same stage of the menstrual cycle was performed. The expression and protein levels of VDR, PR, PRL, IGFBP1, and HOXA10 in RIF patients with VD deficiency were lower than the RIF patients without VD deficiency (P value < 0.05). Our findings suggest that VD can play a key role in the pregnancy process, especially during embryo implantation and decidualization of the endometrial cells.IRCT registration number: IRCT20220528055006N1, Registration date: 2022-10-15, Registration timing: retrospective.

Protective Effects of Fisetin in the Mice Induced by Long-Term Scrotal Hyperthermia.

Exposure to heat in the male reproductive system can lead to transient periods of partial or complete infertility. The current study aimed to examine the beneficial effects of  Fisetin against spermatogenic disorders in mice affected by long-term scrotal hyperthermia. For this purpose, hyperthermia was induced daily by exposure to the temperature of 43 °C for 20 min for 5 weeks. Except for the Healthy group, six other groups were exposed to heat stress: two treated groups including Preventive and Curative which received oral administration of fisetin (10 mg/kg/day) starting immediately before heat exposure and 15 consecutive days after the end of the heat exposure, respectively. And for each treated group, two groups including Positive Control (Pre/Cur+PC group) and vehicle (Pre/Cur+DMSO group) were considered. Our results showed that the testicular volume; the density of spermatogonia, primary spermatocyte, round spermatid, and Sertoli and Leydig cells; and sperm parameters, as well biochemical properties of the testis tissue, were remarkably higher in both Preventive and Curative groups compared to the other hyperthermia-induced groups and were highest in Preventive ones. Unlike the c-kit gene transcript which was significantly increased in the  Fisetin treatment groups (specially the Preventive group), the expression of HSP72 and NF-kß genes, Caspase3 protein, and DFI in sperm cells were significantly more decreased in Preventive and Curative groups compared to other hyperthermia-induced groups and were lowest in Preventive ones. Overall,  Fisetin exerts preventive and curative effects against spermatogenic disorders induced by long-term scrotal hyperthermia.

The Relationship between HLA-G Gene Polymorphisms and Repeated Implantation Failure in Infertile Couples Undergoing Assisted Reproductive Technique.

 HLA-G is a tolerogenic molecule that expresses in cytotrophoblast cells and plays an important role in immune response suppression in maternal decidua. Interactions between the extracellular domains of the HLA-G protein with cell receptors of the immune system are well-known.This study investigated the association between HLA-G  gene  polymorphism  with repeated implantation failure (RIF). We used PCR followed by the sequencing technique for exons 2, 3, and 4, as well as intron 2 of the HLA-G gene in 100 couples with histories of two or more failed assisted reproductive technique (ART) attempts. The data were compared with the results of our previous study.The results indicated that some alleles of the HLA-G gene such as: 0106, 010106, 01010106 and 0105N (null) alleles were significantly higher in the patient group compared to the control group (p<0.05). There were higher SNPs at the +482 T/C and +506 -/C positions in failed ART couples compared to controls (p=0.03; p=0.01, respectively).HLA-G gene polymorphisms do not clearly affect the risk for implantation failure in most couples who undergo ART. However allelic variations, particularly in exons 3 and 4, and intron 2 of the HLA-G gene can lead to ART failure in human embryos.

HLA-G allele and haplotype frequencies in a healthy population of Iran.

The human leukocyte antigen (HLA)-G molecule is expressed in cytotrophoblast cells, adult thymic epithelial cells, erythroblasts, pancreatic islets and mesenchymal stem cells. Although, HLA-G expression in allotransplanted patients is correlated with a better allograft acceptance, it is associated with an advanced grade of the tumor in cancer. In addition to the role on the immune system, HLA-G is also involved in successful pregnancy through the embryo implantation, fetal survival and the initial steps of hematopoiesis and angiogenesis. The aim of this study was determination of HLA-G allele frequencies in a healthy population of Iran. In this research, we selected 100 samples from healthy Iranian individuals and henceforth, we used polymerase chain reaction (PCR) followed by sequencing technique for exon 2, 3, 4 and intron 2 of the gene for evaluating the HLA-G alleles frequencies. Investigation of intronic (intron 2) variation is the novelty of our study. The obtained results indicated thirteen alleles of HLA-G in Iranian individuals including G*01:01:01:01, G*01:06, G*01:01:01:06, G*01:01:02, G*01:01:03, G*01:01:05, G*01:01:06, G*01:01:07, G*01:01:08, G*01:03, G*01:04:01, G*01:04:03, and G*01:04:04. According to this study, the most prevalent alleles in the Iranian population were G*01:01:01:01 (52.5%), G*01:01:02 (16%) and G*01:04:03 (14.5%) and also the lowest alleles regarding the frequency were G*01:01:01:06 (0.5%) and G*01:03 (0.5%). The results of G*01:01:01:01 and G*01:04:01 frequencies showed some similarities with the polish population. Our results were similar to the north Indian population for the frequencies of G*01:06 and G*01:01:02.