Unexplained Infertile Women Research Articles

New Immunological Indexes for the Effect of Systemic Inflammation on Oocyte and Embryo Development in Women With Unexplained Infertility: Systemic Immune Response Index and Pan-Immune-Inflammation Value.

Predicting the impact of systemic inflammation on oocyte and embryonic development in unexplained infertile women using the new immunological indexes. This retrospective cohort study was conducted using the records of the In Vitro Fertilization Department of Ankara Gülhane Training and Research Hospital. After reviewing the records of patients who had undergone in vitro fertilization (IVF) for unexplained infertility (UI) and excluding all known factors that could cause systemic immune inflammation, the systemic immune response index (SIRI), and pan-immune score were calculated from the pre-treatment hemogram parameters between the embryo arrest (EA) group and the embryo transfer group. It was investigated whether there was a statistical difference between the two groups and whether an SIRI value affecting embryo quality was found. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off values for inflammatory markers to predict EA. The 108 EA group (embryos that were arrested during their development and could not be transferred) and the 140 embryo transfer group showed statistically significant differences in the parameters of systemic inflammatory index (SII), SIRI, pan-immune inflammation value (PIV), and neutrophil/lymphocyte ratio (NLR) (p < 0.05). These inflammatory parameters, which were examined before ovulation induction, also correlated positively with the required total dose of gonadotropin and negatively with the ovarian sensitivity index (OSI). SII, SIRI, PIV, and NLR have specific cut-off values with ROC analysis and determine the effect of the inflammatory status of the environment in which the oocyte develops on EA (p < 0.005). In women with UI, high levels of systemic immune inflammation have a negative impact on oocyte and embryo development, and treatments to suppress inflammation may improve IVF success.

Effect of endometrial injury on pregnancy outcomes in infertile women undergoing intrauterine insemination.

One of the most common treatments for infertility is intrauterine insemination (II). The objective of this study was to determine the effect of endometrial injury on pregnancy outcomes in unexplained infertility in women undergoing II. In this randomized clinical trial, 122 women with unexplained infertility who were referred to Shariati Hospital from 2018 to 2020 were enrolled. They underwent ovulation induction using letrozole and gonadotropins. On day 9 of stimulation, they were randomly assigned to two similar groups of the same size. The first group underwent endometrial local injury by pipelle endometrial sampling, and the second group (control group) received no intervention. Only 1 II cycle was performed for each patient. Patients with negative pregnancy outcomes were followed up for 3 months. Endometrial thickness, dominant follicle count, chemical and clinical pregnancy rate, miscarriage rate, and spontaneous pregnancy rate after the II cycle were compared between the two groups. Endometrial thickness, dominant follicle count, chemical and clinical pregnancy rate, and miscarriage rate in the same II cycle were not different between the two groups (p>0.05). However, the spontaneous pregnancy rate after the II cycle was significantly higher in the endometrial injury group (p=0.02). Endometrial injury increases pregnancy rates in later cycles but not in the same II cycle.

Evaluation of ovarian reserve in unexplained ınfertile cases: a case-controlled study

BackgroundThe aim of this study was to evaluate the effectiveness of current ovarian reserve tests in unexplained infertile cases.Material and methodsThis case–control study was conducted on 70 unexplained infertile women who were included in a tertiary university hospital. Both groups of basal FSH, estradiol, antimullerian hormone (AMH), inhibin B, ovarian volume, total antral follicle count (AFC), ovarian volume, and ovarian stromal blood flow (peak systolic velocity (PSV), S/D (systole and diastole ratio), resistance index (RI), and pulsatility index (PI)) values were compared.ResultsThe mean AMH, inhibin B, PSV, and stromal blood flow values of the control group patients were higher than those in the unexplained infertility group. However, the values of the means of RI and PI of the cases in the control group were lower than those in the infertility group. When PI’s value was ≥ 2.00, its sensitivity was 65.7%, and its specificity was 64.3%. In the case of the RI, its value was ≥ 0.745, its sensitivity was 65.7%, and its specificity was 62.9%. In order to show ovarian reserve in unexplained infertile cases, the sensitivity values can be sorted from high to low as follows: PI > RI > estradiol > FSH > ovarian volume > AFC > inhibin B > stromal blood flow > PSV > S/D.ConclusionIn the unexplained infertile patient group with normal ovarian reserve test results, basal estradiol, decreased PI, and RI values may be used as good ovarian reserve predictors.

Evaluation of vitamin E levels, antioxidant enzymes and malondialdehyde in women with unexplained infertility

Unexplained infertility is a perplexing disorder. 30% of infertile couples are diagnosed with unexplained infertility with all standard fertility investigations normal. Oxidative stress has been shown to have a negative impact on reproductive function in women with endometriosis and (PCOS) polycystic ovarian syndrome. In another study antioxidant supplementation improved OS induced infertility. Many studies have demonstrated an increase in Malondialdehyde in serum of women with infertility and vitamin E as a protective antioxidant in the body with positive effect on the fertility. There is growing evidence linking OS and unexplained infertility.Based on this knowledge the specific group of unexplained infertile women were chosen to assess their levels of serum antioxidant enzymes, Vitamin E and lipid peroxidation marker. To compare the Levels of Malondialdehyde, Antioxidant enzymes and Vitamin E in the serum of women with unexplained infertility and control group.: Case control study.70 normal ovulatory women who conceived within 12 months of contraceptive free intercourse, and with no history of miscarriage were recruited in the control group. 70 women with unexplained infertility were recruited as study group. All participants included in the study were between 28 and 38 years of age. Serum levels of MDA, Antioxidant enzymes (GST, SOD, Catalase) and Vitamin E concentrations were compared between two groups. Vitamin E concentrations were determined by using High performance liquid chromatography. Antioxidant enzymes and MDA were measured by standard spectrophotometric assay.: Data was analysed using SPSS Software. Continuous parameters were analysed using Mann Whitney U test. There is a significant decrease in the vitamin E levels 3.80 ug/ml) in the unexplained infertile group as compared to controls 6.0 ug/ml). All women in the study group showed significantly (P&amp;#60;0.05) higher levels of MDA and lower levels of antioxidant enzymes such as GST, SOD and Catalase as compared to the fertile women. This decrease was found to be significant with p value of &amp;#60;0.05. The study group have a higher oxidative stress status and low level of antioxidants compared to control group. Serial measurement of oxidative stress biomarkers and their defense system may help to understand the aetiology of unexplained infertility and to enhance their chances of conception.

Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women-a single-cell RNA transcriptome study during the implantation window.

Autoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the endometrial receptivity remains to be elucidated. In this study, we used single-cell RNA sequencing (scRNA-seq) to dissect immune microenvironment in endometrium of AITD patients during window of implantation (WOI). We collected CD45+ immune cell populations of endometrium samples of unexplained infertile women with AITD (n=3), as well as samples of AITD- controls (n=3). The cells were then processed with 10X Genomics Chromium for further analysis. We characterized 28 distinct immune cell subtypes totally, and uncovered differences in the composition and gene expression patterns between AITD patients and controls. The proportions of T CD4+, cNK, ILC3, T CD8+ GZMK+, T CD8+ Cytotoxic and ILC3 CD3E - cells were increased, and CD366+ uNK1 was decreased in AITD+ patients. And the abnormal expression of GNLY and chemokines was observed in AITD patients. In addition, uNK and T CD8+ Cytotoxic cells showed lower cytotoxicity but activation of immune response. Genes enriched in cell adhesion of ILC3 and Tregs were downregulated, while the number of ILC3 and Tregs were increased. Immune imbalance exists in endometrium during WOI, which may impact embryo implantation.

Effect of miRNA-99a along with TGF-?1(C/G +915) in female with secondary unexplained infertility

Background: Women infertility is a big health problem worldwide and the genetic disorders considered underling causes of unexplained female infertility. Objective: to find out the role of miR-99a and TGF-?1 SNP (G/C +915) in development of secondary unexplained infertility in women and prognostic of miR-99a. To achieve this goal, investigate the fold change of miR-99a and possibility to use them as biomarker. Also identification of TGF-?1(G/C +915)SNP by ARMS- PCR. Material and methods: case control study have been conducted, blood samples had been collected from population (patients 50) and (control 50) living in the north area of Thi-Qar province The samples collected during the period from November 2021 to July 2022. The genomic RNA and DNA were extracted from serum and blood respectively for molecular assay. Results: the mean of miR-99a fold change in patients group 3.70 ±1.18 versus 0.84 ±0.34 in control group and p&lt; 0.001. TGF-?1 SNP +915(GC) genotype CC was more frequent significantly in patients group than in control group (p &lt; 0.001) and the odds ratio was 19.06, and no significant difference in frequency rate of genotype GC between study groups p = 0.106. Genotype GG was less frequent significantly in patients group than in control group p = 0.046 and the odds ratio was 0.22. Conclusion: we can get a diagnostic and prognostic as biomarker, using the miR-99a which show high sensitivity 100%, specificity 98% and accuracy 100% in secondary unexplained infertility, also TGF? (+915 G/C) SNP as predisposing risk factor for developing of secondary unexplained infertility.

Cervical fluid pH, electrolytes and osmolarity changes and expression of ion transporters (ENaC, CFTR and AQP) in cervix of women with primary unexplained infertility.

Unexplained infertility could arise from a defect in the cervix. However, the contribution of abnormal cervical fluid microenvironment to this problem still needs to be identified. Therefore, this study identifies the changes in the cervical fluid microenvironment, i.e., pH, electrolytes and osmolarity as well as expression of ion transporters in the cervix including ENaC, CFTR and AQP in fertile women and in women suffering from primary unexplained infertility. Fertile women and women with unexplained infertility but having regular 28-day menstrual cycles were chosen in this study, Day-22 serum progesterone levels were determined. In the meantime, serum FSH and LH levels were determined on day 2 while, cervical flushing was performed at day 14 to analyse changes in the cervical fluid pH, osmolarity, Na+ and Cl- levels. Meanwhile, cells retrieved from cervical fluid were subjected to mRNA expression and protein distribution analysis for CFTR, AQP and ENaC by qPCR and immunofluorescence, respectively. No significant changes in serum progesterone, FSH and LH levels were observed between the two groups. However, cervical fluid pH, osmolarity, Na+ and Cl- levels were significantly lower in primary unexplained infertile group when compared to fertile group. Expression of CFTR and AQP (AQP 1, AQP 2, AQP 5 and AQP 7) in endocervical cells was lower and expression of β-ENaC was higher in primary unexplained infertile women (p < 0.05 when compared to fertile group). Alterations in the cervical fluid microenvironment linked to the defective ion transporter expression in the cervix might contribute towards the unfavourable condition that accounts for unexplained infertility in women.

Comparative Evaluation of Sildenafil Citrate and Estrogen as an Adjuvant Therapy for Treatment of Unexplained Infertility in Women.

Uterine blood flow determines endometrial thickness. This study examined how vaginal sildenafil citrate and estradiol valerate altered endometrial thickness, blood flow, and fertility in infertile women. This study observed 148 infertile women whose infertility was unexplained. Group 1 comprised 48 patients who received oral estradiol valerate (Cyclo-Progynova 2 mg/12 h white tablets) from day 6 till ovulation was initiated with clomiphene citrate. A number of 50 participants in group 2 received oral sildenafil (Respatio 20 mg/12 h film-coated tablets) for 5 days starting the day after their previous menstrual period and finishing on the day they ovulated with clomiphene citrate. Group 3 was the control group, with 50 patients receiving clomiphene citrate (Technovula 50 mg/12 h tablets) ovulation induction from the 2nd to 7th day of cycle. All patients had transvaginal ultrasounds to determine ovulation, follicle count, and fertility. Miscarriage, ectopic pregnancy, and multiple pregnancies were monitored for three months. The three groups' mean ETs differed statistically at p = 0.0004. A statistically significant difference was found between the three groups in terms of the number of follicles, with 69% of patients in group 1 having one and 31% having two or more, 76% of patients in group 2 having one and 24% having two or more, and 90% of patients in the control group having one and 10% having two or more (p = 0.038). The clinical pregnancy rates of the three groups were 58%, 46%, and 27%, respectively (p = 0.005). The distribution of all side effects was not statistically different between the three groups. It is possible to claim that adding oral estrogen to clomiphene citrate therapy as an adjuvant therapy can improve endometrial thickness and, as a result, increase the pregnancy rates in unexplained infertility compared to sildenafil, especially in cases where the infertility has lasted less than two years. Most people who take sildenafil end up with a mild headache.

Evaluation of serum VEGF-A and interleukin 6 as predictors of angiogenesis during peri-implantation period assessed by Transvaginal Doppler Ultrasonography amongst women of prior reproductive failure: a cross-sectional analytical study.

Background: Infertility is a wide spectrum of disorder affecting many couples and is defined as the inability of a couple to achieve pregnancy. A series of investigations are required to know the reason behind infertility, yet a small percentage (08-37%) of couples exist, in which no obvious cause is delineated. Different hormones, growth factors and interleukins are responsible for successful ovulation, implantation and further growth of embryo. Endometrial receptivity is an important predictor of the outcome of implantation and further growth of embryo. Methods: The study would be conducted in a tertiary care centre over a period of two years from July 2022 till July 2024 on non-pregnant unexplained infertile women (63) who will undergo In vitro Fertilisation and Embryo Transfer (IVF-ET) in the following cycle and the result will be compared with the fertile women (21) with same demographic features. The levels of serum Vascular Endothelial Growth factor–A, interleukin-6 will be measured on day 21 of the menstrual cycle in both the group, simultaneously, transvaginal ultrasonography and doppler findings will be measured in both groups to see for endometrial receptivity. The values will be compared for any significance. A new Scoring system will be generated of these three parameters PREDICGIO scoring system after pilot study on ten patients. The values of Serum VEGF-A, IL6 and Doppler findings will be compared between fertile and infertile group to see for significant difference. Conclusion: The current study helps in determining the suboptimal vasculogenesis and angiogenesis in women with failure in reproduction. It will also help to a great extent in managing patients of reproductive failure with immunomodulator drugs thus providing external angiogenic factors to help in conceiving and carrying pregnancy till term.

Interplay of “leukemia inhibitory factor receptor gene” (rs3099124) polymorphism, leukemia inhibitory factor and ovarian steroids with unexplained infertility

Objective of the study To explore the association of leukemia inhibitory factor receptor (LIFR) gene variant rs3099124, ovarian steroids, and leukemia inhibitory factor with unexplained infertility in Pakistani females. Methodology A case–control investigation in which eighty-one (81) females with unexplained infertility and one hundred and sixty-two (162) fertile counterparts (age and body mass index compared) were recruited between October 2016 and 2018. Ten milliliters of venous blood was collected from all participants. “Genomic DNA” was taken out from lymphocytes in peripheral blood samples. “Tetra Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS-PCR)” was constructed through software “Primer-I”. Amplification was carried out by “T-ARMS-PCR” followed by subsequent sequencing for confirmation and extensive consonance. Estradiol, Progesterone and Leukemia Inhibitory Factor (LIF) were measured in serum by ELISA. Results Statistically significant difference was noticed in genotype frequency in “LIFR-gene variant; rs3099124” (χ2 = 28.222, P value < 0.01) between research participants. Although, rs “3099124” “AA” (OR = 0.000; 95%CI = 0–0) and “GA” genotypes (OR = 0.525; 95%CI = 0.226–1.22) showed non-significant safety/protection against unexplained infertility yet minor/risk allele “A” frequency was greater in women with unexplained infertility suggesting a possible explanation of implantation failure. LIF concentration varied between fertile and infertile groups (χ2 = 9.857, P < 0.05) revealing significant threat of unexplained infertility in women with decreased LIF concentration (OR = 2.316, 95%CI = 1.214–4.416). Progesterone was significantly related to unexplained infertility in both study groups (χ2 = 20.347, P < 0.05). High progesterone reduced the possibility of unexplained infertility (OR = 0.306; 95% CI = 0.166–0.567). Conclusion LIFR gene variation (rs3099124) and reduced LIF secretion may cause implantation failure in women with unexplained infertility.

Association of Thyroid Dysfunction with Unexplained Infertility in Women of Karachi Pakistan

Background: Thyroid autoimmunity and thyroid dysfunction is predominant in women of procreative age and has been linked with hostile fertility. Objective: To evaluate the association of thyroid dysfunction with unexplained infertility (UI). Material and Methods: A case-control study was performed by the department of Physiology Basic Medical Sciences Institute in collaboration with Jinnah Postgraduate Medical Centre, Karachi from May 2018 to June 2019. A sample size of 88 subjects; Group A (44 healthy fertile controls) and Group B (44 UI women) was calculated. Study variables included height, weight, body mass index, serum Triiodothyronine (T3), Thyroxine (T4), Thyroid-stimulating Hormone (TSH), Thyroid Binding Globulin (TBG), and Anti-thyroid peroxidase antibody (Anti -TPO). Results: UI females had high TSH concentration without any disturbance in T3 and T4 in comparison with controls, 40% of women with UI had TSH levels higher than 2.5 mIU/L as compared to 4% in controls. The mean TSH was 2.47±1.97mIU/L in UI females as compared to 1.10±2.14 mIU/L in controls. Both logistic regression models adjusted for age and body mass index showed that fertile controls were significantly less likely to be found with higher TSH (aOR=0.71, 95% CI: 0.52-0.98, p=0.040) and TBG (aOR=088, 95% CI: 0.81-0.95, p=0.002) as compared to females with UI. Conclusion: Minimal deviation of TSH (increased), raised anti-thyroid antibodies with slightly low T3 and T4 levels was observed in UI females. Mild variations in TSH within the normal range may contribute to some cases of UI therefore a direct need for thyroid profile assessment in all infertile females is recommended.

Serum copper, zinc and selenium levels in women with unexplained infertility in Ibadan Nigeria: A cross-sectional analytical study.

Infertility is a global public health issue affecting couples. Trace metals have been implicated in effective reproductive functions in males but less studied in females. To compare the serum levels of copper (Cu), zinc (Zn), selenium (Se) and copper/zinc ratio in women with unexplained infertility and fertile women. This was a cross-sectional analytical study that compared 75 consenting women who had unexplained infertility with 74 fertile women that were controls. Both groups were seen within 1 year of delivery and were recruited from the family planning unit, at the University College Hospital, Ibadan. Data were obtained through a semi-structured questionnaire, after which 10 mL of venous blood was collected. Analysis of selected trace elements were done by atomic absorption spectrophotometry. IBM SPSS version 23 was utilized for data analysis and the levels of statistical significance was set at <0.05. The mean (± SD) serum concentrations of Cu (93.11 ± 16.55 μg/dL), Zn (72.04 ± 15.03 μg/dL) and Se (28.28 ± 8.33 μg/dL) amongst the women with unexplained infertility were lower when compared to the control group (all with P < 0.001). The serum Cu/Zn ratio was higher among the fertile women, though not statistically significant (P < 0.62). Age of <35 years was associated with normal serum levels of Cu (P < 0.01), while women with normal body mass index had low serum concentrations of Cu (P = 0.04), amongst the fertile group. Serum copper, zinc and selenium concentrations are significantly lower in women with unexplained infertility, therefore diets or supplements containing these trace elements may be helpful in their management.

A comparison between uterine artery blood flow in fertile and unexplained infertile women by Doppler ultrasound using pulsatility index and resistance index

Background and objectives: Infertility is inability to conceive after one year of regular unprotected intercourse. Unexplained infertility is present if the basic fertility investigations are normal. The objective of this study is to investigate the use of uterine artery blood flow as a cause of unexplained infertility (using pulsatility index, resistance index) and compare them to fertile women. Methods: A prospective cohort study was performed on 70 patients (35 fertile and 35 with unexplained infertility patients) in Sulaymaniyah Maternity Teaching Hospital, Kurdistan Region, Iraq, during October 2016 to December 2017. Transvaginal color Doppler ultrasound was done in the mid luteal phase (day 21 - 24) for uterine artery by using pulsatility index and resistance index. Results: The age of the patients ranged from 20 - 39 years. The uterine artery pulsatility index was significantly higher in the unexplained infertile women (mean ± SD = 2.78 ± 0.615) than fertile women (mean ± SD = 2.42 ± 0.325). The uterine artery blood flow resistance index was significantly higher in unexplained infertile group (mean ± SD = 0.899 ± 0.066) than fertile women (mean ± SD = 0.83 ± 0.054). Conclusions: Unexplained infertility is associated with decreased uterine artery blood flow and increase uterine artery resistance (pulsatility index and resistance index) when compared with fertile women.

Hormonal changes in consecutive clomiphene citrate stimulation cycles and their effect on pregnancy rates.

Objective:To determine the relationship between the cumulative effect of sequential clomiphene citrate (CC) treatments in unexplained infertile women with intercycle and intracycle serum hormone changes.Materials and Methods:Patients who received CC 50 mg in the first cycle (group I, n=34) as ovulation induction and those who received CC 50 mg in the second consecutive cycle (group II, n=18) were compared. Basal (cycle days 2-5) and trigger day (the day that recombinant human chorionic gonadotropin is given) levels of gonadotropin and steroid hormones were measured.Results:The 17OHP increase on trigger day was found to be statistically significantly higher in group II compared to the basal day (p=0.083). The testosterone (T) response on the trigger day of the patients in group II was found to be statistically significantly higher than that in group I (p=0.023). The number of selected follicles was negatively correlated with a follicle-stimulating hormone decrease and positively correlated with an estradiol increase. Endometrial thickness was positively correlated with a luteinizing hormone increase, and cycle cancelation was positively correlated with decreased estradiol.Conclusion:Based on this study, it was concluded that the reason for the increased efficiency rate in successive cycles of CC may be the cumulative increase in T and 17OHP levels. However, this result was found not to affect the clinical pregnancy rate.

Association of glutathione s-transferase pi (GSTP1) gene polymorphism in unexplained infertile women

15–20 million people in India are affected by infertility.Among them, 34% of the couples are shown to have unexplained infertility (UEI). Both genetic and environmental factors influence UEI. Data from various studies show that oxidative stress plays an important role in unexplained infertility. The genes of the phase II detoxification enzyme, Glutathione s-transferase family are upregulated in humans as a defense mechanism opposing the adverse effects of oxidative stress and play important role during pregnancy. Since all investigations for infertility work-up are normal evaluating the causes for UEI will have impact on the treatment protocol. In this study the association between GSTP1 variations and unexplained infertility are discussed. To compare the association of GSTP1 polymorphism in women with unexplained infertility and a control group.: This is a case control study with 70 normal ovulatory women who conceived within 12 months of contraceptive free intercourse, and with no history of miscarriage were recruited in the control group and 70 women with unexplained infertility were recruited as study group. All participants included in the study were between 28 and 38 years of age. The association of GSTP1 polymorphism were studied using real-time PCR with the Light Cycler instrument (Roche Applied Science).: GSTP1 variant allele frequencies were 0.39 and 0.41for control and cases respectively. The results of this study indicate GSTP1 genetic polymorphisms did not show a significant association with unexplained infertile group.

Granulocyte colony stimulating factor (GCSF) did not affect the fertility outcomes in women with unexplained infertility after intrauterine insemination: a randomised clinical trial

This study aimed to evaluate the effect of granulocyte colony stimulating factor (GCSF) on fertility outcomes in women with unexplained infertility after intrauterine insemination (IUI). This study is a randomised clinical trial that was conducted on unexplained infertile women referred to infertility Clinic in Yasuj, Iran. All participants were stimulated by letrozole, clomiphene and HMG during the cycle. When at least one follicle was greater than 18 mm, 5000 IU hCG intramuscularly was administered for ovulation induction and then IUI was performed 34–36 hours later. In GCSF group, 300 μg GCSF subcutaneously administrated in two days after IUI. Control group received routine IUI. The main outcome measures were biochemical pregnancy, clinical pregnancy, abortion and ongoing pregnancy rate. Our results showed no statistically significant difference in the biochemical pregnancy (16.3% vs. 12.2%; P=.56), clinical pregnancy (16.3% vs. 8.2%; P=.21), abortion (0 vs. 2.04%; P=.55) and ongoing pregnancy rates (8.2% vs. 14.2%; P=.32) between the control and the G-CSF groups. The results of the current study suggest that systemic administration of 300 μg GCSF in the two days after receiving IUI in patients with unexplained infertility does not offer any beneficial clinical related implantation, and pregnancy rates. IRCT registration number: IRCT20160524028038N4 Impact statement What is already known on this subject? Unexplained infertility means to the inability of couples in pregnancy after a year without obvious male and female infertility factors. Some patients have not been justified in endometrial function, which leads to the defect of the dialogue between the foetus and endometrium and may lead to implantation failure. Granulocyte colony stimulating factor is produced at the maternal-foetal interface during embryo implantation and is the main part of the uterine-cytokine network that is needed to create and maintain pregnancy. What do the results of this study add? The current study suggests that systemic administration of 300 μg granulocyte colony stimulating factor in the two days after receiving IUI in patients with unexplained infertility does not offer any beneficial clinical related implantation and pregnancy rates. What are the implications of these findings for clinical practice and/or further research? These results may not be generalised to all patients and more randomised controlled trials are needed for the comparison of granulocyte colony stimulating factor effects on women with thin and normal endometrial thickness, efficacy, side effects, and pregnancy outcomes of the intrauterine perfusion versus systemic subcutaneous administration of granulocyte colony stimulating factor in unexplained infertility treated with intrauterine insemination.

Human papillomavirus prevalence in unexplained infertile women with chronic endometritis

Introduction: This study investigates unexplained infertile women with or without chronic endometritis (CE) and examines the prevalence of the human papillomavirus (HPV) in this population.&#x0D; Material and Method: This study was done with a cross-sectional and retrospective method. The prevalence of HPV infection and related cases in the participants were examined. In this study, 15 infertile women with CE and 64 infertile women without CE were and analyzed from four perspectives: negative HPV, low-risk HPV, probable high-risk HPV, and the presence of high-risk HPV. &#x0D; Results: The participants have mean age of 32.89 years ±3.95. High-risk HPV infection was detected in 3 (20%) and 11 (17%) of the patients with and without CE, respectively (p&gt;0.05). The negative HPV (2 (13%) and 17 (26%)), low-risk HPV (3 (20%) and 20 (31%)), and probable high-risk HPV (7 (46%) and 16 (25%)) in infertile women with CE and infertile women had no significantly different prevalence (p&gt;0.05). The two studied groups had no significantly different mean age, body mass index (BMI), and Infertility duration were not in (P=0.08, P=0.932, and P=0.283, respectively). &#x0D; Conclusion: HPV has no significantly different prevalence in unexplained infertile women with and without CE. It is recommended that this study be repeated with more unexplained infertile women with CE.

CD55 is upregulated by cAMP/PKA/AKT and modulates human decidualization via Src and ERK pathway and decidualization-related genes.

Decidualization is an essential process for embryo implantation and maintenance of pregnancy, and abnormal decidualization contributed to several pregnancy disorders like a miscarriage. The objective of this study was to explore the regulation and function of CD55 in human decidualization. By immunohistochemical staining, it was found that CD55 expression was higher in first-trimester decidua than in the endometrium. In both primary endometrial stromal cells and immortalized cell line T-hESCs, CD55 was upregulated by induction of in vitro decidualization with medroxyprogesterone acetate (MPA) and 8-Br-cAMP. During decidualization in vitro, CD55was stimulated by 8-Br-cAMP in a time- and concentration-dependent manner, which was reversed by a PKA inhibitor H89 and partially by an AKT activator SC79. Knocking down CD55 expression diminished the expression of decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1), accompanied by inhibition of Src, aberrant activation of ERK and decreased expression of several decidualization-related genes, including FOXO1, EGFR, and STAT3. Furthermore, the decidua of unexplained miscarriage women and the endometrium of unexplained infertile women both exhibited decreased CD55 expression. Collectively, these findings revealed that 8-Br-cAMP promotes CD55 expression via PKA activation and AKT dephosphorylation, and decreased CD55 impairs decidualization by inactivation of Src, aberrant activation of ERK pathway, and compromised expression of decidualization-related genes, indicating that CD55 deficiency may contribute to the pathogenesis of spontaneous miscarriage and infertility.

Relationship between growth hormone levels and ovarian reserves

Purpose: The aim of this study was to investigate the relationship between serum anti mullerian hormone levels and serum growth hormone levels in patients with diminished ovarian reserve and unexplained infertility who are planned for in vitro fertilization.&#x0D; Materials and Methods: This prospective cohort study includes 154 women and comprises three study groups which include infertile women with diminished ovarian reserve (Group I), women with unexplained infertility (Group II) and healthy women (Group III) as control group. Prospectively recorded patient data comprehended age, body mass index (BMI), antral follicle count (AFC), gravidity and parity, education, occupation, smoking and alcohol use, and laboratory results (Anti-Mullerian hormone (AMH), Growth Hormone (GH), Follicle-Stimulating hormone, Luteinizing Hormone and Estradiol). &#x0D; Results: The study population consisted of 154 subjects, 52 in Group-I, 52 in Group-II, and 50 in Group-III. The mean women age was higher in DOR group than the other two groups (Respectively with quartiles; 35.5(25-40), 29.5(20-38), 33(19-39)). The other demographic parameters were similar between the groups. Median serum AMH levels was lower in DOR group. Growth hormone levels were similar between the groups.. &#x0D; Conclusion: Our results show that growth hormone has no relationship between ovarian reserve markers. Although lack of relation with ovarian reserve, it’s widely known that GH plays major role in granulosa cell function.

Does Coronavirus Disease-19 Infection Affect Ovarian Reserve in Infertile Women? A Retrospective Study.

Previous studies have revealed menstrual changes following coronavirus disease-19 (COVID-19) disease. The potential impact of COVID-19 on female reproductive organs, ovary in particular, has not been investigated thoroughly. The aim of this study was to evaluate changes in serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH) and oestradiol (E2) following COVID-19 disease as a surrogate for the detection of ovarian vulnerability to SARS-CoV-2 infection. In this retrospective study, hospital records of unexplained infertile women between 21 and 40 years old who have attended our institution's reproductive medicine unit for evaluation and/or treatment of infertility have been evaluated. Menstrual cycle day 2-5 serum follicle-stimulating hormone, luteinising hormone and E2 levels of 28 infertile women have been studied both before and after the COVID-19 disease to evaluate ovarian reserve before the ovulation induction treatment cycle. The demographic characteristics and hormonal results of these 28 unexplained infertile women have been compared. The Shapiro-Wilk test has been used to evaluate the normal distribution of variables. Comparison of ovarian reserve markers which were established before and after COVID-19 infection has been performed using paired samples t-test. All patients except one have shown mild COVID-19 symptoms and their infection courses have resulted in uneventful recovery. Serum FSH, LH and E2 levels of 24 (85%) and serum anti-Müllerian hormone (AMH) levels of 4 (15%) patients have been evaluated before and after COVID-19 disease is statistically similar. COVID-19 disease or inflammatory response of the infection itself does not seem to affect pituitary gonadotropins and ovarian hormones in infertile women based on menstrual cycle day 2-5 serum FSH, LH, E2 and AMH levels. Further studies including higher patient numbers are urgently needed to clarify the potential effects of COVID-19 disease on the gonadal function of women.