Association of recurrent implantation failure and recurrent pregnancy loss with peripheral blood natural killer cells and interferon-gamma level.

OBJECTIVE: Fetal uterine survival depends on maintaining an immune balance between the mother and fetus. This study aimed to investigate the correlation of blood peripheral natural killer (NK) cells and interferon-gamma (IFN-γ) with recurrent recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). METHODS: In this case-control study, peripheral blood samples were obtained from three groups of RPL, RIF, and parous women without a history of abortion or infertility problems and analyzed by lymphocyte-based flow cytometry. Afterward, the levels of NK cells and IFN-γ were determined. All data were analyzed using one-way analysis of variance and nonparametric Kruskal-Wallis tests. RESULTS: The level of IFN-γ in the RPL group was significantly higher than that in parous women and the RIF group (P<0.05), whereas its level in the RIF group was not significantly different from the control group (P>0.05). A significant correlation was found between the levels of IFN-γ and NK cells in the RPL group (r=0.481; P=0.02). However, no significant correlation was found between the levels of IFN-γ and the active NK cells in the RPL group (P=0.08). Moreover, no significant correlation was found between the levels of NK cells (whether activated or not) and IFN-γ in the RIF patients (P>0.05). CONCLUSION: Immune dysfunction may not be involved in implantation failure during IVF but may be involved in recurrent miscarriage, probably by increasing IFN-γ levels.

Comparison of psychological disorders during and after pregnancies caused by assisted reproductive treatments and spontaneous pregnancies.

INTRODUCTION: Mental disorders during pregnancy are one of the major public health problems because of its effect on both mother and child, but the prevalence of psychiatric disorders in infertile women is largely unknown to compare psychiatric disorders during and after pregnancies with assisted reproductive therapies (ART) and spontaneous pregnancies. METHODS: This cross-sectional study was conducted on pregnant women referring to midwifery centers in Ahvaz City in 2022. Pregnant women were included in two groups of either pregnancy caused by ART (n= 84) or spontaneous pregnancy (n= 256). The Symptom Checklist-90-R (SCL90-R) was used to assess psychiatric disorders during and after pregnancies. RESULTS: A high percentage of women with spontaneous pregnancy (74.6%) and ART (91.7%) had some degree of psychological disorders. The severity of psychological disorders in both groups was higher during pregnancy than after pregnancy (P<0.001). The intensity of various psychological disorders during and after pregnancy in the ART pregnancy group was significantly higher than the control group (P<0.001). An increased risk of psychiatric disorders during pregnancy was associated with the history of psychiatric disorders [odd ratio (OR): 12.393; P= 0.022], family history of psychiatric disorders (OR:26.168; P<0.001), history of infertility (OR: 19.00; P<0.001), primary infertility (OR: 12.714; P=0.004), infertility duration more than three years (OR: 43.424; P<0.001), and frequency of embryo transfer (OR: 18.939; P=0.045). CONCLUSION: Psychiatric disorders were prevalent among pregnant women in the study area especially in pregnant women with ART. Regular screening programs for mental health problem should be included in an antenatal care service especially in this high-risk group.

Evaluation of CD3+ T Cell Percentage, Function and its Relationship with Serum Vitamin D Levels in Women with Recurrent Spontaneous Abortion and Recurrent Implantation Failure.

BACKGROUND: Women afflicted with recurrent spontaneous abortion (RSA) and repeated implantation failure (RIF) may have immune abnormalities. The role of vitamin D has been demonstrated in the function of the immune system. OBJECTIVE: To assess the percentage and function of CD3+ T cells and their relationship with the level of the serum vitamin D or 1,25-dihydroxy vitamin D3 (the active form of the vitamin) in women with RSA and RIF. METHODS: In this case-control study, peripheral blood was obtained from the patient and the healthy control groups. The ratio of CD3+T cell and activated CD3+ CD69+T cell was investigated using flow cytometry. The serum levels of Interferon-γ (IFN-γ) and vitamin D were measured by ELISA. RESULTS: The mean proportion of CD3+T cells in women with RSA increased significantly compared with the healthy control group (p<0.04). However, no significant difference was observed in RIF women compared with the control group. There was no significant difference in the ratio of activated CD3+CD69+T cells between the patient and the healthy control groups. Serum IFN-γ levels in women with RSA showed a significant increase compared to the control group (p<0.031); however, no significant difference was observed between women with RIF and the control group. Serum levels of vitamin D showed a significant reduction in both RSA (p<0.01) and RIF (p<0.04) groups in comparison with the control. CONCLUSION: An increase in the percentage and inflammatory function of T cells was associated with RSA. Decreased vitamin D levels may contribute to immune dysfunction and pregnancy loss.

A prospective study to evaluate the gender prediction of blastocysts by using cell-free DNA within a culture medium.

Background: Preimplantation genetic diagnosis (PGD) has been used as an option for couples with the possibility of having a baby with a genetic disorder. The common method for performing this test involves isolating 1 cell from day 3 or a few cells from day 5 embryos and performing genetic studies on the cell-extracted DNA. This method is invasive and can cause abortion after implantation in the uterus. Because of this, 2 noninvasive methods for performing a PGD have been studied: PGD using blastocyst fluid and PGD using embryo culture medium. Objective: The aim of this study is to determine the sensitivity of the polymerase chain reaction (PCR) technique to detect the Y chromosome using cell-free DNA within a culture medium for gender prediction of blastocysts. Materials and Methods: In this study, the gender of 30 embryos on day 5 was determined using embryonic DNA extraction from the culture medium and the PCR technique to evaluate the sex-determining region Y and fragile X mental retardation genes. Then, the accuracy was assessed using ultrasound. Results: The results of the PCR technique showed that 7 embryos were male, but an ultrasound revealed that 13 were male. Conclusion: The given results indicated that, because of the low amount of DNA extracted from the culture medium, the diagnosis of the existence of the Y chromosome by this method is still not accurate enough for detecting the gender of the embryo.

Correlation between assisted reproductive technology-induced pregnancy and fetal cardiac anomalies.

OBJECTIVE: To investigate the incidence of fetal heart defects in assisted reproductive technology (ART)-induced pregnancies compared to natural pregnancies as well as to detect their fetal and maternal risk factors associated with ART. METHODS: In this retrospective cohort study, we collected data from the medical records belonging to 2877 pregnant women's fetuses, who underwent fetal echocardiography for various reasons, including ART, over the last 3 years. RESULTS: There were no major cardiac anomaly in the ART-induced pregnancies, while it was seen in 1.32% of natural pregnancies; so, ART did not increase the risk of major cardiac anomalies. However, the incidence of fetal mild cardiac anomalies among fetuses derived from ART-induced pregnancies (51.43%) was significantly higher than that of natural pregnancies (44.43%, p=0.03). None of the ART-induced pregnancies had a history of a child with cardiac disease (vs. 7.56% in natural pregnancies). Also, the increased nuchal thickness (NT) and extra-cardiac anomalies were significantly more prevalent among natural pregnancies, indicating a significant negative correlation between ART and these two risk factors [χ2=10.24, r: -0.06, 95% CI(-0.0974 to -0.0221) and χ2=47.25, r: -0.129, 95% CI(-0.1656 to -0.0913), p<0.01, respectively]. The adjusted odds ratio of developing fetal mild cardiac anomalies were 1.37 times higher greater for ART-induced pregnancies compared to natural pregnancies [95% CI(1.072-1.769), p=0.01]. CONCLUSIONS: Although the likelihood of developing fetal mild cardiac anomalies was 1.37 times higher for ART-induced pregnancy compared to natural pregnancy, ART did not increase the risk of major cardiac anomalies Although the likelihood of developing fetal mild cardiac anomalies was 1.37 times higher for ART-induced pregnancy compared to natural pregnancy, ART did not increase the risk of major cardiac anomalies.

The Effect of Different Doses of Melatonin on in Vitro Maturation of Human Follicular Fluid-Derived Oocyte-Like Cells.

OBJECTIVE: Human follicular fluid (FF) contains different cell populations including mesenchymal stem cells. Studies tried to improve their differentiation to oocyte and use them in infertility treatments. Using an antioxidant may improve the quality of these cells. The present study investigated the effects of different doses of melatonin on FF-derived cells grown to oocyte-like cells (OLC). METHODS: Cell viability (MTT assay), flow cytometry, and ICC staining were utilized to evaluate CD105 and CD34 expression; colony forming unit assay (CFU-F) capability, qRT-PCR were used to investigate ZP1, ZP2, ZP3, GDF9, and SCP3 expression. AMH, Estradiol and Progesterone levels in the supernatant were measured. Morphological characteristics of fibroblast-like cells changing to a round shape were seen specifically in the group treated with melatonin 10-7M after 2 weeks. RESULTS: There was no difference between control and treatment groups for MTT and CFU assays. ICC staining was positive for CD105 marker and negative for CD34 hematopoietic stem cell marker. qRT-PCR results indicated that ZP1, ZP2, GDF9, and SCP3 expression increased in the group treated with melatonin 10-7M in Week 2, while ZP3 decreased in this group. Progesterone and AMH were detected in differentiation medium. CONCLUSIONS: Melatonin may improve in vitro formation of OLCs.

Pregnancy outcomes following in vitro fertilization using fresh or frozen embryo transfer.

OBJECTIVE: The aim of this study was to investigate the pregnancy outcomes in women undergoing IVF using fresh and/or frozen embryo transfer. METHODS: In this retrospective patient record study, we reviewed 2,872 infertile women's files, who were candidates for IVF. The patients were classified into two groups, including those who underwent fresh embryo transfer (n=1628) and/or frozen embryo transfer (FET) (n=1244). RESULTS: Fertility was achieved in 313 (19.23%) and 356 (28.62%) patients, who underwent fresh ET and FET, respectively. The rates of clinical pregnancy, ongoing pregnancy, and live births were significantly higher in the FET group than the fresh ET group. The incidence of multiple pregnancies, perinatal mortality, abortion in the first trimester, preterm delivery, and low birth weight were significantly higher among fresh ET group [38 (35.51%), 15 (14.50%), 72 (23.01%), 26 (8.30%), and 33 (10.54%), respectively] than in the FET group [25 (15.33%), 6 (6.87%), 63 (17.69%), 14 (3.93%), and 20 (5.61%); p<0.05]. In addition, the incidence of ectopic pregnancies, abortion in the second trimester, gestational diabetes, preeclampsia, and placenta previa were higher in the fresh ET group, but not significantly so (p>0.05). CONCLUSIONS: Women who underwent IVF via FET showed more successful fertility and pregnancy outcomes compared to those who underwent IVF by fresh ET.

The comparison of predictive value of cervical length in singleton spontaneous preterm labor with in vitro fertilization pregnancies: A cohort study.

BACKGROUND: Preterm labor (PTL) is one of the most important factors in neonatal mortality. Some studies have revealed a reverse relationship between cervical length (CL) and PTL, however, further evidence is needed to confirm it. OBJECTIVE: To investigate the predictive value of CL in spontaneous and in vitro fertilization (IVF) pregnancies. MATERIALS AND METHODS: This prospective cohort study was performed on 154 pregnant women from 16-26 wk of gestation with singleton fetus in spontaneous delivery (n = 77) and IVF pregnancies (n = 77) and followed up until delivery. Women with multiple pregnancy, placenta previa, cerclage, and congenital anomalies were excluded from study. The cut-off determination was done according to the Roc analysis. RESULTS: The mean CL in term delivery and PTL groups were 37 ± 7 mm and 31 ± 6 mm, respectively (p < 0.001). The frequency of PTL in spontaneous and IVF pregnancies were 7.8% and 23.27%, respectively (p = 0.007). According to the Roc analysis, the best cut-off for normal pregnancy was ≤ 36 mm with the negative predictive value of 97.9%, the positive predictive value of 11.4%, sensitivity 83.3%, and specificity of 46.5%. While for the IVF group, the cut off was ≤ 30 mm, with a negative predictive value of 88.4%, positive predictive value of 57.8%, sensitivity of 63.2%, and specificity of 86%. CONCLUSION: In this study, IVF had a significant direct correlation with PTL. CL also had a significant indirect relationship with PTL.

Scorpion stings in pregnancy: an analysis of outcomes in 66 envenomed pregnant patients in Iran.

BACKGROUND: Scorpionism is one of the most important health problems in tropical regions, which unfortunately results in thousands of deaths annually. Pregnant women are potential victims in areas with high scorpion-sting prevalence. Limited medical data are available on the effects of scorpion envenomation in pregnant women. This study aimed to examine the effect of scorpion envenomation on pregnancy outcomes in 66 cases. METHODS: The present descriptive/analytical cross-sectional study was performed on 66 scorpion-envenomed pregnant women referred to the clinical toxicology unit of Ahvaz Razi Hospital in Iran during 2015-2017. The variables assessed in all cases, via questionnaire and hospital medical records, were: age, patient residency, gestational week, status of the fetus, laboratory anomalies, clinical severity of envenomation, sting site and scorpion species. Pregnancy outcome (miscarriage, stillbirth, preterm birth, normal delivery) and status of the newborns were also evaluated. Data were analyzed using SPSS ® software (version 24.0). RESULTS: The following pregnancy outcomes were recorded from envenomed pregnant women: miscarriage = 1.5% (n = 1), stillbirth = 4.5% (n = 3), preterm birth = 10.6% (n = 7), normal birth = 83% (n = 55). Among participants whose pregnancy led to birth, 11(17.7%) cases had prenatal-neonatal complications. Neonatal complications, including Apgar score less than 8 points at 5 min, were found in 7 (11.3%) preterm birth cases and in 4 (6.4%) normal birth cases, along with birth weight below 2500 g in normal births. A significant relationship was found between adverse pregnancy outcomes and bite location, as well as scorpion species, but no relationship was found with other variables. CONCLUSION: Envenomation significantly contributes to preterm birth. Moreover, the location of bites and the type of scorpion species have a decisive role in the pregnancy outcome of scorpion-envenomed pregnant women.

Insulin Resistance and Free Androgen as Predictors for Ovarian Hyperstimulation Syndrome in Non-PCOS Women.

We evaluated the effect of insulin resistance and free androgen index (FAI) in non-PCOS (polycystic ovary syndrome) infertile women following controlled ovarian hyperstimulation. A prospective study was done on 144 infertile non-PCOS women with regular menstrual cycle. At first, insulin resistance (IR), free androgen index (FAI), PCOM (polycystic ovary morphology), AFC (antral follicle count), and AMH (anti-Müllerian hormone) were assessed. The patients underwent assisted reproductive technology (ART), and then preovulatory follicles and oocytes retrieved were recorded. The variables of the study were compared between two groups of patients with ovarian hyperstimulation syndrome (OHSS) (n=66) and non-OHSS patients (n=78). Of the 9 variables: BMI, HOMA-IR, FAI, AFC, AMH, PCOM, and preovulatory follicles were risk factors, while the age and retrieved oocytes were not. The 7 variables that showed significance in the univariate analyses were determined as independent variables included in the multivariable logistic regression analysis, as a result, a total of 5 risk factors, BMI, HOMA-IR, FAI, PCOM, and preovulatory follicles entered the equation. The maximum contribution was HOMA-IR followed by PCOM, FAI, preovulatory follicles and BMI. Patients with OHSS had higher chance to have ovaries with polycystic morphology (74%), about three times more than patients who did not develop OHSS (29%) (p<0.001). The best cut-points for IR, FAI, AFC, AMH, and preovulatry follicles were 2.36, 3.9, 8, 3.3 ng/ml, and 10, respectively. Patients with a higher value of BMI, FAI, HOMA-IR, and preovulatory follicles and the presence of PCOM are more likely to develop OHSS, which are not confined to PCOS patients.

Evaluating Chronic Endometritis in Women with Recurrent Implantation Failure and Recurrent Pregnancy Loss by Hysteroscopy and Immunohistochemistry.

STUDY OBJECTIVE: The identification of less invasive methods with acceptable diagnostic value for evaluating intrauterine abnormalities can improve the satisfaction of patients and physicians. Although hysteroscopy plus biopsy has favorable predictive and diagnostic values, limited studies have evaluated its value, and the exact value of this method is not completely understood. The aim of this study was to evaluate the prevalence of chronic endometritis in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) by hysteroscopy and immunohistochemistry. DESIGN: A cross-sectional study. SETTING: An infertility clinic at Jundishapur University Hospital, Ahvaz, Iran. PATIENTS: Women with RIF after IVF and RPL. INTERVENTIONS: Hysteroscopy on the third to fifth day after finishing the menstruation cycle and then a biopsy for immunohistochemistry by a specific monoclonal antibody against the CD138 marker. MEASUREMENTS AND MAIN RESULTS: In total, 85 patients with a mean age of 36.08 ± 5.76 years underwent hysteroscopy on the third to fifth day after finishing the menstruation cycle. At the end of hysteroscopy, a biopsy was taken and assessed using immunohistochemistry by a specific monoclonal antibody against the CD138 marker. Immunohistochemical staining findings of >5 plasma cells per 20 high-power fields were considered the gold standard. The prevalence of chronic endometritis (CE) in both groups and the diagnostic value of hysteroscopy were evaluated. All data were analyzed using the Fisher exact test and analysis of variance. The prevalence of RIF-related CE was 23.4% (11); 21.3% (10) of the cases were diagnosed by hysteroscopy. The prevalence of RPL-related CE was 36.8% (14) and 31.6% (12) based on hysteroscopy and immunohistochemistry staining, respectively. Subsequently, 10 patients (RIF/RPL-related CE with a positive hysteroscopic outcome) were selected randomly for in vitro fertilization therapy, and 3 (30%) of them eventually became pregnant. The sensitivity, specificity, and positive and negative predictive values of hysteroscopy in diagnosing CE were 86.36%, 87.30%, 70.37%, and 94.82%, respectively. CONCLUSION: Hysteroscopy is a reliable diagnostic technique in patients with RIF after in vitro fertilization and RPL that can reliably diagnose chronic endometritis.

Scorpion stings in pregnancy: an analysis of outcomes in 66 envenomed pregnant patients in Iran

Scorpionism is one of the most important health problems in tropical regions, which unfortunately results in thousands of deaths annually. Pregnant women are potential victims in areas with high scorpion-sting prevalence. Limited medical data are available on the effects of scorpion envenomation in pregnant women. This study aimed to examine the effect of scorpion envenomation on pregnancy outcomes in 66 cases. Methods: The present descriptive/analytical cross-sectional study was performed on 66 scorpion-envenomed pregnant women referred to the clinical toxicology unit of Ahvaz Razi Hospital in Iran during 2015-2017. The variables assessed in all cases, via questionnaire and hospital medical records, were: age, patient residency, gestational week, status of the fetus, laboratory anomalies, clinical severity of envenomation, sting site and scorpion species. Pregnancy outcome (miscarriage, stillbirth, preterm birth, normal delivery) and status of the newborns were also evaluated. Data were analyzed using SPSS ® software (version 24.0). Results: The following pregnancy outcomes were recorded from envenomed pregnant women: miscarriage = 1.5% (n = 1), stillbirth = 4.5% (n = 3), preterm birth = 10.6% (n = 7), normal birth = 83% (n = 55). Among participants whose pregnancy led to birth, 11(17.7%) cases had prenatal-neonatal complications. Neonatal complications, including Apgar score less than 8 points at 5 min, were found in 7 (11.3%) preterm birth cases and in 4 (6.4%) normal birth cases, along with birth weight below 2500 g in normal births. A significant relationship was found between adverse pregnancy outcomes and bite location, as well as scorpion species, but no relationship was found with other variables. Conclusion: Envenomation significantly contributes to preterm birth. Moreover, the location of bites and the type of scorpion species have a decisive role in the pregnancy outcome of scorpion-envenomed pregnant women.(AU)

The Effect of Tranexamic Acid on Preventing Post-partum Hemorrhage Due to Uterine Atony: A Triple-blind Randomized Clinical Trial.

BACKGROUND: Postpartum haemorrhage (PPH) is an important cause of early maternal death which needs to be controlled. OBJECTIVE: This study was designed to compare the effect of intravenous tranexamic acid (TXA) and prostaglandin analogue on reducing PPH resulted from uterine atony in women undergoing C section or vaginal delivery. METHOD: A randomized, triple-blind, placebo-controlled study was conducted on 248 pregnant women with PPH due to uterine atony who were randomly assigned into two groups of TXA as the intervention group (n=124) and prostaglandin analogue as the control group (n=124). The intervention group received 4 g TXA for an hour and then 1 g over 6 hours infusion intravenously and the control group received prostaglandin analogue. RESULTS: Postoperative bleeding did not significantly differ between the two groups (68.2±6.1 ml and 69.1±175.73 ml, respectively, P =0.6). Moreover, hemoglobin declines were 1±0.4 g/dl and 1.2±0.5 g/dL in TXA and prostaglandin group respectively, indicating that the difference was not statistically significant (P =0.7). CONCLUSION: The results of the present study showed that administrating intravenous TXA had comparable effects with prostaglandin analogue on reducing PPH in women with uterine atony and in those undergoing C section or vaginal delivery. Therefore, TXA can be used instead of prostaglandin in managing such patients.

A new look at tamoxifen: co-administration with letrozole in intrauterine insemination cycles.

OBJECTIVE: To assess the effectiveness of tamoxifen administration with letrozole in the context of intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: This prospective double-blinded study included 130 patients. After randomization, 65 patients in group A received letrozole + tamoxifen and human menopausal gonadotropin (HMG), whereas 65 patients in group B received placebo instead of tamoxifen. In both groups, the parameters recorded were total number of follicles with ≥16 and 18 mm diameter, endometrial thickness and appearance, and total HMG administered. The results were compared between groups after single-stage IUI was performed. RESULTS: Total dominant follicles in both groups were similar (mean number of follicles with diameter ≥16 and 18 mm was 1.5 ± 1.4 and 1.6 ± 1.1, respectively, in group A and 1.5 ± 1.1 and 1.6 ± 1, respectively, in group B; at the same time with less HMG usage in group A (255 ± 167 vs. 313 ± 174 IU), and higher pregnancy rate in group A (18.7 vs. 11.7 %); but none of them was statistically significant). Surprisingly, endometrial thickness was significantly higher in group A (7.7 ± 1.5 vs. 7 ± 1.3 mm; P value 0.008). CONCLUSION: In addition to the efficacy of tamoxifen in co-administration with clomiphene citrate, it has promising effects with letrozole in induction of ovulation cycles with or without IUI.

Evaluation of nuchal translucency measurement in first trimester pregnancy.

BACKGROUND: A significant number of pregnancies, particularly in women with previous histories of infertility, are associated with fetal abnormalities. Methods such as the nuchal translucency (NT) measurement enable us to identify more pregnancies with chromosomal abnormalities. MATERIALS AND METHODS: This analytic cross-sectional study was performed in 446 pregnant women at 11-14 weeks gestation, from 2009 to 2010 in the Fetal Medicine Unit of Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences. All NT measurements were performed by a certified sonographer using the Fetal Medicine Foundation (FMF) recommended protocol. FMF first trimester software was used for primary and secondary (adjusted) risk calculation. RESULTS: The average maternal age was 28.5 years and 15% of mothers were ≥35 years of age. The average crown rump length (CRL), gestational age and NT thickness were 61.7, 12.4 weeks and 1.75 mm, respectively. There were 20 cases with increased adjusted risk (4.04%) and 4 cases of documented abnormal karyotype. CONCLUSION: In our study increased adjusted risk was 4.04%.Documented abnormal karyotype were 0.9% and 28% of total and high-risk groups who accepted amniocentesis, respectively. In this study, 50% of women with high-risk results and about half of those with abnormal karyotypes were seen in women under age 35. Knowing these risks is of utmost importance in pregnancy, particularly in patients with infertility histories.