Role of miRNAs in preimplantation embryo development and their potential as embryo selection biomarkers.

CONTEXT: MicroRNAs (miRNAs) play different roles in oocyte fertilisation, degradation of maternal transcripts, embryo development, and implantation. During in vitro fertilisation (IVF), different miRNAs are released from embryos into the spent culture media (SCM) that can potentially reflect the status of the embryo. AIMS: This study is the assessment of miRNAs, which secreted in SCM during the IVF cycles can be used as noninvasive biomarkers to predict an embryo's ability to form a blastocyst, implant, and give live birth. METHODS: Systematic literature search was conducted to review all recent studies about miRNAs as potential non-invasive biomarkers for selecting the best embryos in the assisted reproductive technology (ART) cycle. KEY RESULTS: Studies have shown that levels of some miRNAs in the SCM have an association with the implantation potential and pregnancy outcome of the embryo. CONCLUSIONS: Embryo-secreted miRNAs can be used as potential non-invasive biomarkers for selecting the best embryos in the ART cycle. Unfortunately, few human studies evaluated the association between ART outcomes and miRNAs in SCM. IMPLICATIONS: This review can pave the way for further miRNAs transcriptomic studies on human embryo culture media and introducing a specific miRNA profile as a multivariable prediction model for embryo selection in IVF cycles.

Fatty acids of follicular fluid phospholipids and triglycerides display distinct association with IVF outcomes.

RESEARCH QUESTION: Are triglyceride fatty acids in the follicular fluid associated with either follicular fluid phospholipid fatty acids or IVF outcomes and, if so, how are they associated? DESIGN: In a prospective cross-sectional study, 70 women undergoing intracytoplasmic sperm injection were recruited. Follicular fluid phospholipids and triglycerides were separated by thin-layer chromatography. Fatty acids were measured using gas-liquid chromatography and flame ionization detection system. RESULTS: Significant differences in fatty acid composition were observed between follicular fluid phospholipid and triglyceride fractions. Phospholipid stearic acid and n-3 polyunsaturated fatty acids, particularly alpha-linolenic acid, were negatively associated with the number of mature oocytes and cleaved embryos, whereas arachidonic acid was in direct correlation with cleavage rate per IVF cycle (ß = 0.325, P = 0.022). In the case of triglyceride fraction, total monounsaturated fatty acids, oleic acid in particular, displayed significantly positive associations with the number of oocytes (ß = 0.261, P = 0.043) and embryos (ß = 0.310, P = 0.018). Furthermore, cleavage rate correlated inversely with palmitic acid (ß = -0.359, P = 0.007) and directly with pentadecanoic acid (ß = 0.378, P = 0.005). Most of these associations, however, were not independent of predictive fatty acids belonging to phospholipid fraction, according to multivariate analysis. CONCLUSIONS: Fatty acid compositions of phospholipid and triglyceride fractions from human follicular fluid differentially correlate with IVF cycle parameters.

Investigation of molecular cryopreservation, fertility potential and microRNA-mediated apoptosis in Oligoasthenoteratozoospermia men.

Investigation of the cryo-injury mechanism can provide novel insight into cryopreservation. The objective of this study is to assess the effect of cryopreservation on fertility potential, motility, oxidative stress (OS), DNA fragmentation, microRNAs (miRNAs), and apoptotic target genes in the infertile men compared to the fertile men. All 40 samples were divided into two leading groups of fresh and cryopreserved sperms. Each main group was subdivided into three groups including, Normozoospermia, and Mild, and Severe Oligoasthenoteratozoospermia (OAT). In all collected samples the following were assessed: microRNA-34c (miR-34c) and miR-184, P53 and Caspase9 using Quantitative real-time polymerase chain reaction (RT-PCR), malondialdehyde (MDA), Superoxide dismutase (SOD) using imaging multi-mode reader, and DNA fragmentation using Sperm DNA Fragmentation Assay Test (SDFA). Within the studied groups, immotile spermatozoa were increased due to cryopreservation. We observed an increasing levels of SOD, MDA, and DNA fragmentation. Also, cryopreservation was associated with decreasing the expression of P53, mir-43c, and miR-184 while capase9 was showed enhancing expression after freeze-thawing of sperm cells. During cryopreservation, sperm fertility and motility were influenced via apoptosis cascade-mediated mitochondrial dysfunctions such as caspase9. Also, we found that miR-34c, miR184, and P53 could impact fertility potential. In Addition, there was a meaningful correlations between microRNAs and motility post freeze-thawing process in Severe Oligoasthenoteratozoospermia men.

Fractalkine and apoptotic/anti-apoptotic markers in granulosa cells of women with polycystic ovarian syndrome.

Owing to the role of fractalkine in regulating cellular apoptosis/proliferation, we investigated fractalkine effects on apoptosis/proliferation signaling of granulosa cells in polycystic ovarian syndrome (PCOS) patients through in vitro and in vivo experiments. In vivo, granulosa cells were collected from 40 women undergoing oocyte retrieval (20 controls and 20 PCOS). The expression levels of fractalkine, BAX, Bcl2, Bcl2-XL, Bad, and TNF-α were assessed using RT-PCR. In vitro, we determined the effect of different doses of fractalkine on the expression of the above mentioned genes in GCs of both groups. We found that the expression levels of fractalkine and Bcl-2 were significantly lower in the GCs of PCOS patients compared to the control group (p < 0.05). In contrast, the expression levels of TNF-α and BAX were higher in the patient's group than in the control group. The results suggested that expression levels of fractalkine were negatively and positively correlated with the number of oocytes and fertilized oocytes respectively. Moreover, fractalkine could dose-dependently increase fractalkine and decrease BAD, BAX, Bcl-xl, and TNF-α expressions in the control GCs. In contrast, GCs collected from PCOS patients revealed an increase in expression of BAD, BAX, and Bcl-xl following fractalkine treatment. Our findings indicated that insufficient expression of fractalkine in PCOS patients is related with elevated apoptotic and inflammatory markers and reduced anti-apoptotic genes in the GCs.

Influence of cryopreservation on structure and function of mammalian spermatozoa: an overview.

Cryopreservation is a useful approach to preserve male fertility for assisted reproduction technique and other evaluations. In spite of extensive development in the cryopreservation field, there are biological and biochemical points including DNA fragmentation and antioxidant which should be illuminated to preserve fertility in safe form. Several molecular markers such as coding and noncoding RNAs are transferred from spermatozoa into oocyte via fertilization. These biomarkers affect fertility potential during the cryopreservation. Despite its impact, sperm cryopreservation has some destructive effect including loss of sperm motility and viability, acrosomal damage, mitochondrial membrane depolarization, plasma membrane permeability alteration even nuclear, and DNA damage. There is a growing concern about the impact of sperm cryopreservation on biological factors which can interrupt successful fertility procedures such as in vitro fertilization. Additionally, cryo-damage can decrease embryonic development extent. Promoting cryopreservation method via investigating the wide range of non-invasive factors may be increasingly important to have access to safe approach of freezing. Therefore, the aim of this study is the assessment of biological factors which can penetrate the fertility potential during the freezing procedure, explicate innovative methods in fertility preservation.

NK cell frequency and cytotoxicity in correlation to pregnancy outcome and response to IVIG therapy among women with recurrent pregnancy loss.

BACKGROUND: Recurrent miscarriage (RM) has a multifactorial etiology mainly due to chromosomal abnormalities and immunological factors. Treating RM has remained to be a challenging issue and the role of intravenous immunoglobulin (IVIG) in treating RM is still controversial. MATERIALS AND METHODS: This study aimed to evaluate the changes in natural killer (NK) cells' frequency and cytotoxicity in patients with RM who received the IVIG therapy. A total of 78 women with a history of three or more recurrent miscarriages were included and their peripheral blood was drawn in case of positive pregnancy test. On the same date, 400 mg/kg of IVIG was administrated intravenously in 38 women and it continued every four weeks through weeks 30-32 of gestation. The remaining 40 patients with RM were included to be the untreated control group. Then, the effects of IVIG on NK cell frequency, cytotoxic activity, and the expression of inhibitory and activating receptors in the patients with RM, pre and posttreatment were assessed. RESULTS: NK cells percentage and cytotoxicity were significantly reduced in the IVIG-treated patients after 32 weeks of gestation (p < 0.0001). Expression levels of inhibitory receptors was increased, however, the expression levels of activating receptors were significantly decreased after the IVIG therapy. Pregnancy outcome after the treatment was significantly higher (86.8%) in the IVIG-treated patients than controls (45%; p = 0.0006). CONCLUSION: Our results suggested that women with RM may benefit from IVIG as a therapeutic approach and the frequency and functional status of peripheral NK cells may serve as a valuable predictive factor of therapy response.

S100 protein family and embryo implantation.

It is well known that embryo implantation is a critical process in which embryo should be able to reach and attach to endometrium. Until now, various types of factors are involved in the regulation of this process. S100 proteins are calcium-binding proteins, which have vital roles in embryo implantation and have been considered as possible candidate markers for endometrial receptivity. However, studies regarding mode of actions of these proteins are scarce and more mechanistic insights are needed to clarify exact roles of each one of the S100 protein family. Understanding of function of these proteins in different compartments, stages, and phases of endometrium, could pave the way for conducting studies regarding the therapeutic significance of these proteins in some disorders such as recurrent implantation failure. In this review, we outlined roles and possible underlying mechanisms of S100 protein family in embryo implantation.

Endothelins and their receptors in embryo implantation.

As a critical stage of pregnancy, the implantation of blastocysts into the endometrium is a progressive, excessively regulated local tissue remodeling step involving a complex sequence of genetic and cellular interplay executed within an optimal time frame. For better understanding the causes of infertility and, more importantly, for developing powerful strategies for successful implantations and combating infertility, an increasing number of recent studies have been focused on the identification and study of newly described substances in the reproductive tree. The endothelins (ET), a 21-aminoacidic family of genes, have been reported to be responsible for the contraction of vascular and nonvascular smooth muscles, including the smooth muscles of the uterus. Therefore, this review aims to comprehensively discuss the physiological role of endothelins and signaling through their receptors, as well as their probable involvement in the implantation process.

Distinct effect of fetal bovine serum versus follicular fluid on multipotentiality of human granulosa cells in in vitro condition.

This study aimed to develop an appropriate medium for preservation of multipotentiality in human granulosa cells. To compare the possible effect of different media supplemented with follicular fluid or fetal bovine serum, granulosa cells were cultured in vitro over a period of 14 days. Stemness feature and any alteration in the cell phenotype were monitored using colony count assay and flow cytometry analysis by monitoring the expression of Oct3/4 and GATA-4 factors. Transcript expression level of Sox-2, Klf-4, and Nanog were investigated using quantitative real-time PCR analysis. Cells were cultured in the medium supplement with follicular fluid showed normal cell morphology and epithelial-like appearance, however, cells treated with fetal bovine serum, exhibited the clonogenic potential of granulosa cells which was increased after exposure to follicular fluid after 14 days (p < 0.05). Flow cytometry analysis revealed a significant reduction in the protein level of GATA-4 in cells cultured in presence of follicular fluid compared with cells received fetal bovine serum (p < 0.001). Quantitative real-time PCR analysis disclosed reduction of Sox-2, Klf-4 and Nanog levels in cells exposed to fetal bovine serum. Our experiment showed the exposure of human granulosa cells to follicular fluid efficiently preserves the stemness characteristics of the cells.

Incorporating bioactive glass nanoparticles in silk fibroin/bacterial nanocellulose composite scaffolds improves their biological and osteogenic properties for bone tissue engineering applications.

Blend polymers composed of natural polymers are a ubiquitous biomaterial class due to their suitable mechanical and biological characterization. In the present study, composite scaffolds based on bacterial cellulose (BC)/silk fibroin (SF) with bioactive glass nanoparticles (BGNPs) were developed to enhance osteogenesis in human adipose derived stem cells (hASCs). The scanning electron microscopy (SEM) results of BGNPs indicated a spherical morphology and size ranging from 15 to 30 nm. The presence of BC and BGNPs reduced the pore diameter of SF scaffolds to about 210 ± 10 µm and 205 ± 10 µm, respectively, while increasing their compressive strength and compressive modulus. FTIR analyses proved the presence of BGNPs, BC and SF in the scaffolds. Flow cytometry data confirmed the surface markers for hASCs. The results also showed that BC and BGNPs addition to BC/SF scaffolds decreased degradation and swelling rate. The gene expression (Runx2, alkaline phosphatase and osteocalcin) studies signified the osteogenic potential of BGNPs in BC/SF scaffolds on hASCs. Eventually, the increased cell adhesion, viability and differentiation in the BC/SF and BC/SF/BGNPs composite scaffolds drawn from MTT, SEM, Alizarin red staining and alkaline phosphatase activity confirmed that these scaffolds promise to serve as a therapeutic candidate for bone defects.

Advanced Glycation End-Products of Follicular Fluid are Associated with Embryo Morphokinetic Parameters and ART Outcomes.

Advanced glycation end products (AGEs) can disrupt antioxidant system and steroidogenesis, resulting in detrimental effects on assisted reproductive technology (ART) outcomes. This study aimed to investigate the association of AGEs in follicular fluid (FF) with morphokinetic parameters of embryos and ART outcomes. Fifty women undergoing ART treatment were studied. AGEs, glucose, 25(OH) vitamin D, malondialdehyde (MDA) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were evaluated in FF. The expression of 3ßHSD, CYP11A1, and CYP19A1 genes were analyzed in granulosa cells (GCs) by qRT-PCR technique. Morphokinetic parameters were evaluated using time-lapse technology. The FF level of AGEs was reversely associated with CAT, SOD, and GPX activities, and total and mature oocytes number, blastocyst formation rate, and high-grade embryos number, while it showed positive correlations with the FF MDA levels, the expression of steroidogenesis genes, number of immature oocytes, morphokinetic parameters, and number of low-grade embryos. Furthermore, the level of vitamin D in FF had an inverse association with AGEs and positive correlations with ART outcomes and morphokinetic parameters. Comparison between the those with positive and negative biochemical pregnancy showed no significant differences in terms of FF factors and just the expression of 3ßHSD, CYP11A1, and CYP19A1 genes were higher in pregnant women (p < 0.05). AGEs could delay blastomere division and lead to an increase in the number of low-quality embryos, while vitamin D have an adverse effect on AGEs and a protective function against AGEs negative effects.

A treatment approach of severe vulvar edema in ovarian hyperstimulation syndrome patient: A case report.

Background: Ovarian hyperstimulation syndrome (OHSS) is a serious life-threatening complication of infertility treatment. Vulvar edema is a disease with various causes and frequent phenomena seen in physiological and pathologic conditions like pregnancy, inflammatory disorders, tumors, idiopathic reasons, and most importantly, in the severe form of OHSS. Case Presentation: Here, we report a 26-yr-old woman with severe OHSS, recombinant follicle-stimulating hormone therapy. 8 days later, we observed a mild and asymmetrical swelling of the vulva with severe edema in the right labia. Due to the worsening of the vulvar edema even after 15 days of conservative treatment, hand massage and compressive bandaging of the vulva were performed, which caused rapid recovery within 20 min of the case. Conclusion: Treatment with a hand massage with lubricant gel followed by compressive bandaging resolved the vulvar edema immediately; it is an easy procedure without any adverse events.

Intraovarian Injection of Autologous Platelet-Rich Plasma Improves Therapeutic Approaches in The Patients with Poor Ovarian Response: A before-after Study.

In this article published in Int J Fertil Steril, Vol 16, No 2, April-June 2022, Pages: 90-94, the authors found that this sentence "Also, AMH level was not statistically significantly different after PRP treatment (0.38 ± 0.039) in comparison with before of treatment (0.39 ± 0.04, Fig.1C)" was incorrect. The corrected one is "Also, AMH level was not significantly different before PRP treatment (0.38 ± 0.039) in comparison with after of treatment (0.39 ± 0.04, Fig.1C)" in the first paragraph of the result section.
The authors would like to apologies for any inconvenience caused.

Follicular fluid advanced glycation end products in assisted reproduction: A systematic review.

Follicular fluid (FF) advanced glycation end products (AGEs) have been associated with low oocyte quality and number, low fertilization rate, impaired embryonic development and low pregnancy rate. These findings are especially relevant in women undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), ie, assisted reproductive technology (ART). A systematic literature search was conducted to examine various AGEs including pentosidine, carboxymethyl-lysine (CML), methylglyoxal 5-hydro-5-methylimidazolones (MG-H1), toxic AGE (TAGE), and soluble receptor for AGE (sRAGE) with ART outcomes. Studies showed that total AGEs and sRAGE in FF were associated with the ovarian response, follicle number, retrieved oocyte number, mature (MII) oocyte number, fertilization rate, embryo number, embryo quality, and successful pregnancy. Although FF AGEs could be considered predictive biomarkers, population heterogeneity and differences in ovulation induction protocols make the findings less clear. This review highlights important role of AGEs in ART and necessity of evaluating AGEs in serum vs with FF to better predict ART outcomes.

Investigating the efficacy of ultrasound-guided ethanol retention technique for endometrioma sclerotherapy and its effect on pro-inflammatory cytokine levels: A single-arm clinical trial.

BACKGROUND: Endometriosis is a chronic inflammatory disease affecting about 10% of women of reproductive age. Endometrioma is the most common presentation of endometriosis in ovaries. OBJECTIVES: Herein, the authors study the effect of the ultrasound-guided ethanol retention technique for endometrioma sclerotherapy and its effect on the plasma levels of pro-inflammatory cytokines. MATERIALS AND METHODS: Each endometrioma was aspirated and washed with 0.9% saline until clearance and then 2/3 of the cyst volume was filled with ethanol 98%. Patients were followed for 3 months. After that, changes in their cyst diameter, dyspareunia, dysmenorrhea, and antral follicular count were assessed. Also, the sera levels of Interleukin 1ß (IL-ß), IL-6, and IL-8 were assayed before and after the treatment. The primary sera levels were also compared with a control group. RESULTS: In the treatment and control groups, 23 and 25 individuals (respectively) with a matched mean age (p-value = 0.680) were enrolled in the study. Among the laboratory variables, IL-1ß (p-value = 0.035), as well as AMH (p-value = 0.002), were lower, and IL-6 (p-value = 0.011) was higher in the endometriosis group compared to the controls. Following the treatment, dysmenorrhea, dyspareunia, and the mean diameter of all cysts were significantly (p-values < 0.001) decreased in the treatment group. Also, right (p-value = 0.022) and left (p-value = 0.002) ovaries' antral follicular counts were increased following the treatment. No significant change was found among any of the investigated laboratory levels (p-value > 0.05). CONCLUSION: Ethanol retention method is proven to be safe and could improve the clinical status of patients with endometrioma. Although further studies are necessary.

microRNAs in the blastocoel fluid as accessible indicators of chromosomal normality.

MicroRNAs (miRNAs) derived from the pre-implantation blastocoel fluid (BF) have attracted interest as accessible biomarkers indicative of embryonic health in ongoing IVF cycles. Therefore, we investigated expression levels of some aneuploidy-associated miRNAs and implantation-related mRNAs as predictive markers for embryo chromosomal normality. In this study, the BF of 25 blastocysts that had been checked for aneuploidy (aneuploid=17 and euploid=8) was aspirated and the expression of 10 miRNAs (miR-20a, miR-30c, miR-661, miR-372, miR-142, miR-191, miR-345, miR-339, miR-141, and miR-27b) and four genes (ERBB4, SELL, ITGB3, ITGAV) were evaluated using real time-PCR. Results showed that the levels of miR-661 and miR-20a were significantly higher in the BF of the aneuploid embryos compared to the euploid group (p = 0.0017 and 0.004, respectively). A comparison of the mRNA levels between the aneuploid and euploid groups also demonstrated a significant difference in ITGAV (p = 0.013) and SELL (p = 0.0317) levels. In the euploid group, a negative correlation was found between ITGB3 and miR-30c (r = -0.71, p = 0.08), and in the aneuploid group, a positive correlation was found between ERBB4 and miR-345 (r = 0.71, p = 0.02). It can be suggested that miR-20a, miR-661, and ITGAV levels of BF could be used as less-invasive biomarkers to evaluate embryonic health. Moreover, aneuploidy-related miRNA levels were associated with levels of genes involved in embryo implantation.

Intraovarian Injection of Autologous Platelet-Rich Plasma Improves Therapeutic Approaches in The Patients with Poor Ovarian Response: A Before-After Study.

Background: Advanced age is associated with a decline in the natural oocytes, low oocyte yield, and also increases the assisted reproductive technology (ART) failure rate, and consequently resulted in a pregnancy rate decrease. Platelet-rich plasma (PRP) is one of the proposed therapeutic strategies for women with poor ovarian response (POR). Because of the autologous source of PRP, the lowest risks of disease transmission, immunogenic and allergic reactions have been expected. This study aimed to evaluate the single-dose intraovarian injection of autologous PRP in poor ovarian reserve. Materials and Methods: We conducted a clinical trial study in the Al-Zahra hospital and Milad Infertility Clinic, Tabriz, Iran (April and May, 2021). A total of thirty-five women with a POR and mean age 40.68 ± 0.34 enrolled in this study. After injection of autologous PRP into the ovaries, the number of oocytes, antral follicles, and level of estradiol, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteal hormone (LH), FSH/LH ratio also were evaluated while, these parameters were evaluated before PRP administration. Results: At the 2-month follow-up, women treated with PRP showed a significant elevation in the number of oocytes (3.68 ± 0.24, P=0.0043) and embryos (3.17 ± 0.14, P=0.0001), as well as in the estradiol levels (404.1 ± 16.76 vs. 237.7 ± 13.14, P=0.0003). Conclusion: Single PRP injection is effective and might be a promising therapeutic approach in the patients with POR to conceive with their own oocytes, although further evidence is required to assess the influence of PRP on the live birth rate.

The effect of cognitive-behavioral therapy on stress and anxiety of women with premature ovarian insufficiency: A randomized controlled trial.

TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N64. Date of registration: 14/02/2021. URL: https://en.irct.ir/user/trial/52024/view; date of first registration: 17/02/2021.

Role of endometrial microRNAs in repeated implantation failure (mini-review).

MicroRNAs (miRNAs) play various roles in the implantation and pregnancy process. Abnormal regulation of miRNAs leads to reproductive disorders such as repeated implantation failure (RIF). During the window of implantation, different miRNAs are released from the endometrium, which can potentially reflect the status of the endometrium for in vitro fertilization (IVF). The focus of this review is to determine whether endometrial miRNAs may be utilized as noninvasive biomarkers to predict the ability of endometrium to implant and provide live birth during IVF cycles. The levels of certain miRNAs in the endometrium have been linked to implantation potential and pregnancy outcomes in previous studies. Endometrial miRNAs could be employed as non-invasive biomarkers in the assisted reproductive technology (ART) cycle to determine the optimal time for implantation. Few human studies have evaluated the association between ART outcomes and endometrial miRNAs in RIF patients. This review may pave the way for more miRNA transcriptomic studies on human endometrium and introduce a specific miRNA profile as a multivariable prediction model for choosing the optimal time in the IVF cycle.

Oncostatin M and its receptor in women with polycystic ovary syndrome and association with assisted reproductive technology outcomes.

The role of adipokines in ovarian-related disorders such as polycystic ovary syndrome (PCOS) has been reported. However, the involvement of Oncostatin M (OSM), a recently identified adipokine, in ovarian function is unknown. Therefore, we investigated the association of the OSM signaling pathway with ovarian functions and PCOS pathogenesis. This case-control study enrolled 30 PCOS and 30 healthy women who underwent the intracytoplasmic sperm injection procedure. OSM and OSM receptor (OSMR) levels were evaluated in the follicular fluid (FF). Moreover, the expression of insulin receptor substrates (IRS1 and IRS2), OSM, OSMR, suppressor of cytokine signaling 3 (SOCS3), and androgen receptor (AR) genes were analyzed in the isolated cumulus cells (CCs). For the in-vitro experiment, the effect of recombinant OSM on the expression of related genes in isolated CCs was analyzed. Follicular concentrations of OSM and OSMR were significantly lower in PCOS (123.91±48.58 pg/ml and 0.93±0.35 ng/ml, respectively) compared to control women (283.53 ± 96.62 pg/ml and 1.45 ± 0.18 ng/ml, respectively; p < 0.001) and were positively correlated with the oocyte maturation (r = 0.611 and r = 0.611, respectively) and fertilization (r = 0.592 and r = 0.627, respectively) rates in the PCOS group. Furthermore, the SOCS3 expression was upregulated about eight times in PCOS patients compared to the controls (p < 0.05). The treatment of cells with recombinant OSM significantly increased SOCS3, OSMR, IRS-1, and -2 expression and decreased AR expression. The decreased levels of OSM and its receptor in PCOS patients, possibly mediated by SOCS3, could negatively affect oocyte maturation and fertilization rates.